ESMO 2026 GI Cancer Slides

[Slide 1] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Future work • Who benefits most? Identify biomarkers—gene driver, VEGF and immune signature • Can we move to earlier? Explore ivonescimab in the perioperative and adjuvant setting • Can we improve outcomes further? Investigate combinations with targeted therapy and ADCs • What's next for bispecific antibodies? Emerging approaches targeting DLL4/VEGF, PD-1/TIGIT, and HER2 in late-stage testing; many more on the way. James J. Harding James Harding Invited Discussant LBA8 ALICANTE AUDITORIUM - HALL 6 [Slide 2] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN HARMONi GI1: Broadly similar population, with some geographic and etiologic differences Demographics | ABC-02 GemCis | Topaz-1 GemCis + Durva | Keynote-966 GemCis + Pembro | HARMONI-G1 GemCis +Ivonescimab Study Population | United Kingdom | Global | Global | China iCCA | 60% | 56 | 60% | 58% HBV | NR | 24% | 31% | 59.6% Global testing planned—NCT07765433 first-line ECOG ACRIN; NCT05615818 second line SAFIR-ABC10 Zhu et al. J Hepatology 2026; Deng et al. Hepatology 2023 Valle et al. NEJM 2010, Oh et al. NEJM Evidence 2022; Kelley et al. Lancet 2023; Vogel et al. ASCO 2022; Chan et al.CCR 2026; Zhou et al. ESMO 2026 LBA #8 James J. Harding James Harding Invited Discussant LBA8 ALICANTE AUDITORIUM - HALL 6 [Slide 3] Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN HARMONi-GI1 met primary OS endpoint [KM curve inset] Ivonescimab + chemo | Durvalumab + chemo mOS (95% CI), months | 14.9 (12.9, NE) | 12.1 (11.0, 13.4) Stratified HR (95% CI) | 0.75 (0.61, 0.92) P-value | 0.0031 (one-side) The one-sided P-value boundary for significance was [illegible] 12-month rate [illegible] | 18-month rate [illegible] Number at Risk [illegible] mOS, median overall survival; HR, hazard ratio; CI, confidence interval; NE, not estimable. • Balanced arms • Control arm performance similar to historic • Similar treatment intensity • D/C'd (Any, ICI): 12.7%, 3.5% vs 10%, 5.6% • Median GemCis duration: 5.7 vs 5.5 months • Post protocol treatment > durvalumab arm • Ivonescimab 31.8% vs Durvalumab 45.9% • Interim analysis 81.6% maturity Zhou et al. ESMO 2026 LBA #8 James J. Harding James Harding Invited Discussant LBA8 ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: Overall survival Ivonescimab + chemo | 14.9 | 12.9, NE Durvalumab + chemo | 12.1 | 11.0, 13.4 HR: 0.75 HR CI: 0.61, 0.92 P: 0.0031 (one-sided) [Slide 4] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Ivonescimab adds toxicity • Δ 10% Grade 3/4 TEAE favoring ivonescimab— ↑ Grade 3/4 thrombocytopenia and neutropenia • Antiangiogenic effect evident—credentials mechanism of action • HTN Any 15%, Grade ≥ 3 5.6% • Proteinuria Any: 32.2% vs 11.8% • Hemorrhage and thrombosis—similar between arms • Hemorrhage: 9.8% (Gr≥3 1.5%) vs 6.5% (Gr≥3 1.8%) • VTE: 2.7% vs 1.5% / ATE: 0.3% vs 1.5% • IrAE comparable to TOPAZ-1/Keynote-966 • QoL data pending Zhou et al. ESMO 2026 LBA #8 James J. Harding James Harding Invited Discussant LBA8 ALICANTE AUDITORIUM - HALL 6

[Slide 1] Proffered Paper session LBA8 - Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1) Speakers Jian Zhou (Shanghai, China) Lecture Time 17:42 - 17:54 Abstract Background Durvalumab plus chemotherapy (chemo) is the standard first-line treatment for advanced biliary tract cancer (BTC). In the current phase 3 study conducted in China, we evaluated the efficacy and safety of ivonescimab, a PD-1/VEGF bispecific antibody, plus chemo versus durvalumab plus chemo as first-line treatment for advanced BTC. Here we report the results from the preplanned interim analysis. [Slide 2] Results 682 patients were randomized (ivonescimab: 340; durvalumab: 342). Baseline characteristics were balanced between arms. Median follow-up was 14.3 months. The primary endpoint was met. Median OS was significantly improved with ivonescimab plus chemo versus durvalumab plus chemo (14.9 vs. 12.1 months; HR 0.75, 95% CI 0.61-0.92, P = 0.0031). Median PFS was 8.4 vs. 5.8 months (HR 0.61, 95% CI 0.51-0.72, P <0.0001). The ORR was 53.8 % vs. 32.5 % (P <0.0001). Treatment-related adverse events were generally well tolerated, with a manageable safety profile. The most common treatment-emergent adverse events (TEAEs) were haematological toxicity. No new safety signals were identified for ivonescimab. Conclusions Ivonescimab plus chemo significantly improved OS, PFS and ORR in patients with advanced BTC compared with durvalumab plus chemo, with a manageable safety profile. These results support ivonescimab plus chemo as a potential new first-line standard of care for advanced BTC. [Slide 3] Methods Eligible patients with unresectable locally advanced or metastatic BTC were stratified by disease status (locally advanced vs. metastatic) and primary tumor location (intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancer), and randomized 1:1 to receive ivonescimab or durvalumab plus gemcitabine and cisplatin (Q3W, 8 cycles), followed by ivonescimab or durvalumab maintenance therapy. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

[Slide 1] HARMONi-GI1 Study Design • A randomized, controlled, double-blinded phase 3 trial Key Eligibility Criteria • Locally advanced or metastatic BTC • Initially unresectable or recurrent after curative surgery • No prior systemic therapy1 • ECOG PS 0 or 1 Stratification Factors • Disease status: locally advanced vs. metastatic • Primary tumor location: intrahepatic vs. extrahepatic vs. gallbladder R 1:1 | N=682 Ivonescimab 20 mg/kg, Q3W + Chemo2 up to 8 cycles -> Ivonescimab Q3W /Placebo Q4W Durvalumab 1500 mg, Q3W + Chemo2 up to 8 cycles -> Durvalumab Q4W /Placebo Q3W Primary endpoint: • Overall survival (OS) Key secondary endpoints3: • Progression-free survival (PFS) • Objective response rate (ORR) 1Neoadjuvant or adjuvant therapy was permitted if it was completed ≥6 months before disease progression. 2Chemo: gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2, Days 1 and 8, Q3W. 3PFS and ORR were investigator-assessed per RECIST v1.1. ECOG, Eastern Cooperative Oncology Group; PS, performance status; VS., versus; R, randomization; Chemo, chemotherapy; QnW, every n weeks. Jian Zhou, MD, PhD [Slide 3] Key Secondary Endpoint: PFS • Ivonescimab with chemotherapy significantly improved PFS 6-month rate: 68.7% (Ivonescimab+chemo) | 49.3% (Durvalumab+chemo) 9-month rate: 49.3% (Ivonescimab+chemo) | 31.7% (Durvalumab+chemo) | Ivonescimab + chemo | Durvalumab + chemo mPFS (95% CI), months | 8.4 (7.5, 9.3) | 5.8 (5.6, 7.2) Stratified HR (95% CI) | 0.61 (0.51, 0.72) P-value | <0.0001 (one-side) PFS was investigator-assessed per RECIST v1.1. mPFS, median progression-free survival; HR, hazard ratio; CI, confidence interval. Number of Risk (months 0-20) Ivonescimab+chemo: 340 | 334 | 311 | 286 | 280 | 254 | 218 | 206 | 155 | 148 | 114 | 93 | 49 | 46 | 23 | 13 | 12 | 3 | 3 | 3 | 0 Durvalumab+chemo: 342 | 326 | 275 | 241 | 227 | 207 | 163 | 151 | 107 | 100 | 61 | 49 | 24 | 22 | 11 | 6 | 6 | 2 | 1 | 1 | 0 Jian Zhou, MD, PhD Survival table Endpoint: PFS (investigator-assessed, key secondary) Arm | N | Median | Median CI Ivonescimab + chemo | 340 | 8.4 | 7.5, 9.3 Durvalumab + chemo | 342 | 5.8 | 5.6, 7.2 HR: 0.61 (stratified) HR CI: 0.51, 0.72 P: <0.0001 (one-sided) Landmark rates: 6 months: Ivonescimab + chemo 68.7% | Durvalumab + chemo 49.3% 9 months: Ivonescimab + chemo 49.3% | Durvalumab + chemo 31.7% [Slide 4] Key Secondary Endpoint: ORR △=21.3% P<0.0001 | Ivonescimab + chemo (N=340) | Durvalumab + chemo (N=342) ORR (95% CI), % | 53.8 (48.4, 59.2) | 32.5 (27.5, 37.7) DCR (95% CI), % | 91.5 (88.0, 94.2) | 77.8 (73.0, 82.1) ORR in primary tumor location subgroup ORR (95% CI), % | iCC | eCC | GBC Ivonescimab+chemo | 54.0 (46.8, 61.1) | 47.7 (35.1, 60.5) | 58.4 (46.6, 69.6) Durvalumab+chemo | 30.1 (23.8, 37.0) | 36.4 (24.9, 49.1) | 35.0 (24.7, 46.5) ORR was investigator-assessed per RECIST v1.1. ORR, objective response rate; DCR, disease control rate; CI, confidence interval; iCC, intrahepatic cholangiocarcinoma; eCC, extrahepatic cholangiocarcinoma; GBC, gallbladder cancer. Jian Zhou, MD, PhD

Summary of Safety and Treatment Exposure • Ivonescimab plus chemo showed a manageable safety profile, with longer treatment exposure | Ivonescimab plus chemo (N=339) | Durvalumab plus chemo (N=339) Duration of exposure, median (range), months Ivonescimab/durvalumab | 7.8 (0.4, 19.9) | 5.7 (0.2, 19.8) Gemcitabine | 5.7 (0.4, 9.2) | 5.5 (0.2, 8.3) Cisplatin | 5.7 (0.4, 9.2) | 5.5 (0.2, 8.3) TEAEs, n(%) Any grade | 339 (100.0) | 335 (98.8) Grade 3 or 4 | 278 (82.0) | 245 (72.3) Serious | 147 (43.4) | 148 (43.7) Leading to discontinuation of any drug | 43 (12.7) | 34 (10.0) Leading to discontinuation of ivonescimab/durvalumab | 12 (3.5) | 19 (5.6) Leading to death | 11 (3.2) | 13 (3.8) Leading to death (related to ivonescimab/durvalumab) | 3 (0.9) | 6 (1.8) Grade ≥3 immune-related | 14 (4.1) | 14 (4.1) Safety was assessed per NCI CTCAE v5.0. TEAE, treatment-emergent adverse event. Jian Zhou, MD, PhD

LBA8 - Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1) Speakers Jian Zhou (Shanghai, China) Lecture Time 17:42 - 17:54 Background Durvalumab plus chemotherapy (chemo) is the standard first-line treatment for advanced biliary tract cancer (BTC). In the current phase 3 study conducted in China, we evaluated the efficacy and safety of ivonescimab, a PD-1/VEGF bispecific antibody, plus chemo versus durvalumab plus chemo as first-line treatment for advanced BTC. Here we report the results from the preplanned interim analysis. Methods Eligible patients with unresectable locally advanced or metastatic BTC were stratified by disease status (locally advanced vs. metastatic) and primary tumor location (intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancer), and randomized 1:1 to receive ivonescimab or durvalumab plus gemcitabine and cisplatin (Q3W, 8 cycles), followed by ivonescimab or durvalumab maintenance therapy. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). Results 682 patients were randomized (ivonescimab: 340; durvalumab: 342). Baseline characteristics were balanced between arms. Median follow-up was 14.3 months. The primary endpoint was met. Median OS was significantly improved with ivonescimab plus chemo versus durvalumab plus chemo (14.9 vs. 12.1 months; HR 0.75, 95% CI 0.61-0.92, P = 0.0031). Median PFS was 8.4 vs. 5.8 months (HR 0.61, 95% CI 0.51-0.72, P <0.0001). The ORR was 53.8 % vs. 32.5 % (P <0.0001). Treatment-related adverse events were generally well tolerated, with a manageable safety profile. The most common treatment-emergent adverse events (TEAEs) were haematological toxicity. No new safety signals were identified for ivonescimab. Conclusions Ivonescimab plus chemo significantly improved OS, PFS and ORR in patients with advanced BTC compared with durvalumab plus chemo, with a manageable safety profile. These results support ivonescimab plus chemo as a potential new first-line standard of care for advanced BTC.

[Slide 1] HARMONi-GI1 met primary OS endpoint Overall Survival Rate (%) Ivonescimab+chemo Durvalumab+chemo 12-month rate 59.7% 50.7% 18-month rate 44.0% 32.5% Ivonescimab + chemo | Durvalumab + chemo mOS (95% CI), months 14.9 (12.9, NE) | 12.1 (11.0, 13.4) Stratified HR (95% CI) 0.75 (0.61, 0.92) P-value 0.0031 (one-side) The one sided P-value boundary for significance was 0.0[illegible] Time (months) Number of Risk mOS, median overall survival; HR, hazard ratio; CI, confidence interval; NE, not estimable. • Balanced arms • Control arm performance similar to historic • Similar treatment intensity • D/C'd (Any, ICI): 12.7%, 3.5% vs 10%, 5.6% • Median GemCis duration: 5.7 vs 5.5 months • Post protocol treatment > durvalumab arm • Ivonescimab 31.8% vs Durvalumab 45.9% • Interim analysis 81.6% maturity Zhou et al. ESMO 2026 LBA #8 James J. Harding Survival table Endpoint: Overall survival (interim analysis) Arm | N | Median | Median CI Ivonescimab + chemo | 340 | 14.9 mo | 12.9, NE Durvalumab + chemo | 342 | 12.1 mo | 11.0, 13.4 HR: 0.75 (stratified) HR CI: 0.61, 0.92 P: 0.0031 (one-side) 12-month rate: 59.7% vs 50.7% 18-month rate: 44.0% vs 32.5% [Slide 3] Key Take Aways • Compelling and convincing efficacy: HARMONi-GI1 demonstrates a clinically meaningful OS benefit with ivonescimab plus gemcitabine and cisplatin. • Manageable added toxicity: Increased hematologic and VEGF-related adverse events; QoL data awaited. • Potentially practice-changing: Longer follow-up will clarify durability of benefit, while global phase III testing will assess broader applicability. James J. Harding [Slide 4] Ivonescimab adds toxicity • Δ 10% Grade 3/4 TEAE favoring ivonescimab— ↑ Grade 3/4 thrombocytopenia and neutropenia • Antiangiogenic effect evident—credentials mechanism of action • HTN Any 15%, Grade ≥ 3 5.6% • Proteinuria Any: 32.2% vs 11.8% • Hemorrhage and thrombosis—similar between arms • Hemorrhage: 9.8% (Gr≥3 1.5%) vs 6.5% (Gr≥3 1.8%) • VTE: 2.7% vs 1.5% / ATE: 0.3% vs 1.5% • IrAE comparable to TOPAZ-1/Keynote-966 • QoL data pending Zhou et al. ESMO 2026 LBA #8 James J. Harding

Key takeaway points Ivonescimab is the worldwide first PD-1/VEGF dual-target bispecific antibody and has been approved in China in three lung indications since 2024 Ivonescimab plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in advanced biliary tract cancer as first-line treatment compared with durvalumab plus chemotherapy HARMONi-GI1 supports ivonescimab plus chemotherapy as a new standard of care for first-line BTC Jian Zhou, MD, PhD

[Slide 1] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Primary Endpoint: OS • Ivonescimab with chemotherapy significantly improved OS 12-month rate: 59.7% | 50.7% 18-month rate: 44.0% | 32.5% | Ivonescimab + chemo | Durvalumab + chemo mOS (95% CI), months | 14.9 (12.9, NE) | 12.1 (11.0, 13.4) Stratified HR (95% CI) | 0.75 (0.61, 0.92) P-value | 0.0031 (one-side) mOS, median overall survival; HR, hazard ratio; CI, confidence interval; NE, not estimable. Number of Risk Ivonescimab+chemo 340 337 330 322 314 304 292 281 266 253 238 221 180 146 101 66 42 32 22 9 1 0 Durvalumab+chemo 342 336 329 316 309 297 275 259 240 217 199 186 151 119 77 45 33 24 14 3 1 0 Jian Zhou, MD, PhD Jian Zhou — Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1) ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: Overall survival (primary) Arm | N | Median | Median CI Ivonescimab + chemo | 340 | 14.9 mo | 12.9, NE Durvalumab + chemo | 342 | 12.1 mo | 11.0, 13.4 HR: 0.75 (stratified) HR CI: 0.61, 0.92 P: 0.0031 (one-side) Landmark rates: 12 months: Ivonescimab + chemo 59.7% | Durvalumab + chemo 50.7% 18 months: Ivonescimab + chemo 44.0% | Durvalumab + chemo 32.5% [Slide 4] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Treatment-Emergent Adverse Events (Incidence≥15%) • The most common adverse events of any grade and grade 3 or 4 were haematological toxicity, and no new safety signals were identified AE | Ivonescimab+chemotherapy all grades | Ivonescimab+chemotherapy grade 3 or 4 | Durvalumab+chemotherapy grade 3 or 4 | Durvalumab+chemotherapy all grades Total | 100.0 | 82.0 | 72.3 | 98.8 Anaemia | 82.9 | 24.5 | 24.5 | 80.8 Neutrophil count decreased | 82.0 | 54.6 | 41.3 | 67.8 White blood cell count decreased | 81.4 | 34.5 | 27.4 | 68.7 Platelet count decreased | 72.0 | 36.0 | 22.1 | 58.7 Aspartate aminotransferase increased | 33.6 | 5.0 | 1.5 | 28.0 Proteinuria | 33.6 | 2.4 | 0.3 | 11.8 Weight decreased | 28.3 | 1.8 | — (no grade 3-4 value shown) | 24.2 Hypoalbuminaemia | 28.0 | 0.3 | — (no grade 3-4 value shown) | 20.1 Nausea | 28.0 | 0.3 | — (no grade 3-4 value shown) | 28.0 Alanine aminotransferase increased | 27.7 | 2.1 | 1.5 | 22.7 Vomiting | 25.7 | 0.6 | 2.1 | 29.2 Decreased appetite | 23.0 | 1.8 | 0.9 | 24.8 Asthenia | 18.0 | 2.1 | 1.8 | 17.1 Rash | 17.7 | 0.9 | 0.3 | 12.7 Blood creatinine increased | 16.5 | — (no grade 3-4 value shown) | — (no grade 3-4 value shown) | 12.1 Constipation | 16.2 | 0.3 | — (no grade 3-4 value shown) | 18.3 Blood bilirubin increased | 15.9 | 6.2 | 5.6 | 16.8 Hypothyroidism | 15.9 | 0.3 | — (no grade 3-4 value shown) | 6.8 Pyrexia | 15.6 | 1.2 | 0.6 | 18.9 Hypertension | 15.0 | 5.9 | 0.6 | 2.4 Hyponatraemia | 13.3 | 2.4 | 2.4 | 18.6 Patients (%) Jian Zhou, MD, PhD ALICANTE AUDITORIUM - HALL 6

MADRID 2026 ESMO congress Ivonescimab plus chemotherapy versus durvalumab plus chemotheray as first-line treatment for advanced biliary tract cancer: a randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1) Jian Zhou¹, Tongsen Zheng², Jia Fan¹, Guoming Shi¹, Caiqi Liu², Xiaoyong Huang¹, Hong Zhao³, He Tian⁴, Jia Luo⁵, Li Peng⁶, Xianglin Yuan⁷, Yong Zha⁸, Xiong Chen⁹, Haitao Zhao¹⁰, Yefu Liu¹¹, Tao Peng¹², Wei Cheng¹³, Jun Zhou¹⁴, Yufeng Yuan¹⁵, Michelle Xia¹⁶ ¹Zhongshan Hospital, Shanghai, China; ²Harbin Medical University Cancer Hospital, Harbin, China; ³National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; ⁴Shandong Cancer Hospital & Institute, Jinan, China; ⁵Hunan Cancer Hospital, Changsha, China; ⁶The Fourth Hospital of Hebei Medical University, Shijiazhuang, China; ⁷Tongji Hospital Tongji Medical College of HUST, Wuhan, China; ⁸Yunnan Cancer Hospital, Kunming, China; ⁹Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; ¹⁰Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; ¹¹Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, China; ¹²The First Affiliated Hospital of Guangxi Medical University, Nanning, China; ¹³People's Hospital of Hunan Province, Changsha, China; ¹⁴Beijing Tsinghua Changgung Hospital, Beijing, China; ¹⁵Zhongnan Hospital of Wuhan University, Wuhan, China; ¹⁶Akeso Biopharma, Inc., Zhongshan, China. Presenter: Jian Zhou, MD, PhD 25 October 2026

Preferred First-line: GemCis + Anti-PD1/L1 Antibodies TOPAZ-1 (N = 685) Gemcitabine Cisplatin plus Durvalumab mOS 12.8 vs 11.5 months HR 0.80 ORR = 26.7% 12-month OS 54.1% 24-month OS 24.9% Durva / Placebo Overall Survival (%) / Months No biomarker (MSI ~1%) Subsequent Therapy: 42.5 to 49.5% Keynote-966 (N = 1069) Gemcitabine Cisplatin plus Pembrolizumab mOS 12.7 vs 10.9 months HR 0.83 ORR = 29% 12-month OS 52% 24-month OS 25% Pembro / Placebo Overall Survival, % / Months No biomarker (MSI ~1%) Subsequent Therapy: 47 to 49% Oh et al. NEJM Evidence 2022; Oh et al. EASL 2026; Kelley et al. Lancet 2023; Ueno et al. eClinicalMedicine 2026 James J. Harding James Harding Invited Discussant LBA8 Survival table Endpoint: Overall survival (two separate trials shown side by side: TOPAZ-1 and KEYNOTE-966) TOPAZ-1: Gemcitabine Cisplatin plus Durvalumab | 12.8 months TOPAZ-1: Placebo | 11.5 months KEYNOTE-966: Gemcitabine Cisplatin plus Pembrolizumab | 12.7 months KEYNOTE-966: Placebo | 10.9 months HR: 0.80 (TOPAZ-1); 0.83 (KEYNOTE-966) TOPAZ-1 12-month OS 54.1% TOPAZ-1 24-month OS 24.9% KEYNOTE-966 12-month OS 52% KEYNOTE-966 24-month OS 25%

OS in Prespecified Subgroups Events/Number of Patients: Ivonescimab + chemo | Durvalumab + chemo | HR (95% CI) Favors ivonescimab + chemo Favors durvalumab + chemo Overall | 166/340 | 197/342 | 0.75 (0.61, 0.92) Age <65 years | 108/219 | 128/228 | 0.80 (0.62, 1.03) ≥65 years | 58/121 | 69/114 | 0.67 (0.47, 0.95) Sex Male | 94/182 | 103/172 | 0.78 (0.59, 1.03) Female | 72/158 | 94/170 | 0.71 (0.53, 0.97) ECOG 0 | 51/103 | 48/89 | 0.88 (0.59, 1.30) 1 | 115/237 | 149/253 | 0.71 (0.56, 0.91) Disease status Locally advanced | 11/32 | 20/32 | 0.42 (0.20, 0.88) Metastatic | 155/308 | 177/310 | 0.79 (0.64, 0.98) Primary tumor location Intrahepatic | 89/198 | 119/196 | 0.63 (0.48, 0.83) Extrahepatic | 31/65 | 30/66 | 0.94 (0.57, 1.55) Gallbladder | 46/77 | 48/80 | 0.95 (0.63, 1.42) ≥ 3 metastatic sites Yes | 43/66 | 38/55 | 0.73 (0.47, 1.13) No | 123/274 | 159/287 | 0.72 (0.57, 0.91) Extent of disease Recurrent | 12/34 | 15/38 | 0.78 (0.37, 1.67) Initially unresectable | 154/306 | 182/304 | 0.74 (0.60, 0.92) Jian Zhou, MD, PhD

Conclusions • HARMONi-GI1 met its primary endpoint and all key secondary endpoints • Ivonescimab plus chemotherapy significantly improved OS, PFS and ORR in previously untreated advanced BTC compared with durvalumab plus chemotherapy ➢ mOS: 14.9 vs. 12.1, HR 0.75 (95% CI: 0.61, 0.92), P=0.0031 ➢ mPFS: 8.4 vs. 5.8, HR 0.61 (95% CI: 0.51, 0.72), P<0.0001 ➢ ORR: 53.8% vs. 32.5%, P<0.0001 • The safety profile was manageable, with no unexpected adverse events, low rate of discontinuation, no increase in grade ≥3 haemorrhage and no increase in irAEs • HARMONi-GI1 is the first phase 3 trial in BTC to show statistically significant and clinically meaningful improvement in OS over durva+chemo in Chinese population HARMONi-GI1 supports ivonescimab plus chemotherapy as a new standard of care for first-line BTC Jian Zhou, MD, PhD

Ivonescimab plus chemotherapy versus durvalumab plus chemotheray as first-line treatment for advanced biliary tract cancer: a randomized, controlled, double-blinde[d] phase 3 trial (HARMONi-GI1) Jian Zhou1, Tongsen Zheng2, Jia Fan1, Guoming Shi1, Caiqi Liu2, Xiaoyong Huang1, Hong Zhao3, He Tian4, Jia Luo5, Li Peng6, Xianglin Yuan7, Yong Zha8, Xiong Chen9, Haitao Zhao10, Yefu Liu11, Tao Peng12, Wei Cheng13, Jun Zhou14, Yufeng Yuan15, Michelle Xia16 1Zhongshan Hospital, Shanghai, China; 2Harbin Medical University Cancer Hospital, Harbin, China; 3National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 4Shandong Cancer Hospital & Institute, Jinan, China; 5Hunan Cancer Hospital, Changsha, China; 6The Fourth Hospital of Hebei Medical University, Shijiazhuang, China; 7Tongji Hospital Tongji Medical College of HUST, Wuhan, China; 8Yunnan Cancer Hospital, Kunming, China; 9Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 10Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 11Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, China; 12The First Affiliated Hospital of Guangxi Medical University, Nanning, China; 13People's Hospital of Hunan Province, Changsha, China; 14Beijing Tsinghua Changgung Hospital, Beijing, China; 15Zhongnan Hospital of Wuhan University, Wuhan, China; 16Akeso Biopharma, Inc., Zhongshan, China. Presenter: Jian Zhou, MD, PhD 25 October 2026

[Slide 1] Study design: CLARITY-Gastric01 (NCT06346392) Randomised, open-label, sponsor-blinded, global Phase 3 study comparing the efficacy and safety of sonesitatug vedotin (Sone-Ve) to investigator's choice of therapy in patients with 2L+ advanced gastroesophageal carcinoma (GEC) expressing CLDN18.2 STUDY POPULATION: N=594; 2L+ GEC expressing CLDN18.2 (≥25% tumour cells with any intensity membranous staining) STRATIFIED BY: • Region • Prior gastrectomy • Treatment line DOSE SELECTION: R 1:1:1* → Sone-Ve 2.2 mg/kg Q3W (n=267); Investigator's choice of therapy (n=265) [R 1:1]; Sone-Ve 1.8 mg/kg Q3W (n=62): closed to enrolment MULTIPLE TESTING PROCEDURE: DUAL-PRIMARY — PFS in ITT 0.1% initial alpha; OS in 3L+ 4.9% initial alpha; 2-sided α recycling → OS in ITT Investigator's choice of therapy — 2L: • Ramucirumab + paclitaxel • Paclitaxel (contraindication to ramucirumab only) • Docetaxel (contraindication to ramucirumab only); 3L+: • Irinotecan • TAS-102 (except China) • Apatinib (China only) Endpoints — DUAL PRIMARY: • OS (3L+)† • PFS by BICR (ITT [all 2L+])‡; KEY SECONDARY: • OS (ITT); ADDITIONAL SECONDARY / EXPLORATORY: • PFS by BICR (3L+) • ORR and DoR by BICR (ITT, 3L+) • Safety • OS by CLDN18.2 expression (ITT) • PFS, ORR and DoR by Investigator (ITT, 3L+) • OS in prespecified subgroups (ITT, 3L+) *Patients were randomised 1:1:1 to Sone-Ve 2.2 mg/kg Q3W, Sone-Ve 1.8 mg/kg Q3W, or investigator's choice of therapy. As of January 2025, the optimal Sone-Ve monotherapy dose was determined to be 2.2 mg/kg IV Q3W and the 1.8 mg/kg arm was closed to enrollment. Randomisation continued in a 1:1 ratio Sone-Ve 2.2 mg/kg Q3w or investigator's choice of therapy. †All randomised patients who had received ≥2 prior lines of systemic therapy; ‡All randomised patients who had received ≥1 prior line of systemic therapy. PFS, ORR and DoR determined per RECIST v1.1. Rui-Hua Xu CLARITY-Gastric01 [Slide 2] OS in 3L+ Dual-primary endpoint: OS in 3L+ | Sone-Ve 2.2 mg/kg (n=178) | Investigator's choice of therapy (n=177) Median OS (95% CI), months | 10.0 (7.2–11.4) | 5.0 (4.2–6.4) HR (95% CI) | 0.47 (0.36–0.62) P-value | <0.000001 12-month OS: 38.1% vs 18.1% No. patients at risk (0–27 mo by 3) Sone-Ve 2.2 mg/kg | 178 146 95 59 19 7 3 1 0 0 Investigator's choice of therapy | 177 117 58 24 14 6 2 2 1 0 Sone-Ve significantly improved OS versus investigator's choice of therapy in the 3L+ population The HR and CI were estimated from a stratified Cox proportional-hazards model with ties = Efron. Stratification variables were geographical region, prior gastrectomy and line of therapy. The CI was calculated using a profile likelihood approach. A HR of less than 1 favours Sone-Ve. Tick marks indicate censored observations. CI, confidence interval; HR, hazard ratio. Rui-Hua Xu CLARITY-Gastric01 Survival table Endpoint: OS in 3L+ (dual primary) Arm | N | Median | Median CI Sone-Ve 2.2 mg/kg | 178 | 10.0 | 7.2–11.4 Investigator's choice of therapy | 177 | 5.0 | 4.2–6.4 HR: 0.47 HR CI: 0.36–0.62 P: <0.000001 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 38.1% | Investigator's choice of therapy 18.1% [Slide 3] OS subgroup analysis in ITT Subgroup | Sone-Ve 2.2 mg/kg | Investigator's choice of therapy | Hazard ratio (95% CI) No. of events/total no. of patients All patients | 139/267 | 174/265 | 0.58 (0.47–0.73) Age ≥18–<65 years | 96/191 | 123/192 | 0.60 (0.46–0.78) Age ≥65 years | 43/76 | 51/73 | 0.64 (0.42–0.96) Sex Female | 52/117 | 62/106 | 0.58 (0.40–0.84) Sex Male | 87/150 | 112/159 | 0.64 (0.48–0.85) Region Japan & S. Korea | 22/55 | 33/54 | 0.52 (0.30–0.89) Region Other Asia | 59/107 | 83/106 | 0.46 (0.33–0.64) Region RoW | 58/105 | 58/105 | 0.92 (0.64–1.33) ECOG PS 0 | 43/88 | 46/92 | 0.80 (0.53–1.22) ECOG PS 1 | 96/179 | 128/173 | 0.53 (0.40–0.69) Primary tumour location Gastric | 106/213 | 133/194 | 0.52 (0.40–0.67) Primary tumour location GEJC/EAC | 33/54 | 41/71 | 1.08 (0.68–1.71) No. of organ metastases 0–2 | 84/179 | 112/185 | 0.63 (0.47–0.83) No. of organ metastases 3 | 55/88 | 62/80 | 0.53 (0.37–0.77) Liver metastasis Yes | 40/66 | 55/74 | 0.60 (0.40–0.90) Liver metastasis No | 99/201 | 119/191 | 0.62 (0.47–0.81) Peritoneal metastasis Yes | 87/163 | 108/148 | 0.50 (0.37–0.66) Peritoneal metastasis No | 52/104 | 66/117 | 0.78 (0.54–1.12) Prior gastrectomy Yes | 49/110 | 70/111 | 0.45 (0.31–0.65) Prior gastrectomy No | 90/157 | 104/154 | 0.76 (0.57–1.01) Line of therapy 2L | 54/89 | 52/88 | 0.88 (0.60–1.30) Line of therapy 3L+ | 85/178 | 122/177 | 0.47 (0.36–0.62) Favours Sone-Ve 2.2 mg/kg | Favours Investigator's choice of therapy OS HR point estimates favoured Sone-Ve versus investigator's choice of therapy across most clinically relevant subgroups in the ITT population All subgroups were prespecified in the protocol. The analysis was based on the Kaplan-Meier technique and was performed using an unstratified Cox proportional hazards model. The overall HR was calculated using a stratified Cox proportional hazards model, adjusting for Interactive Response Technology strata, including prior gastrectomy, region and line of therapy and using an implemented pooling strategy per the statistical analysis plan with treatment as the only covariate. Ties were handled by the Efron approach. CIs were calculated using a profile likelihood approach. A HR below 1 favours Sone-Ve. Because PFS and OS were the only endpoints that were part of the multiple testing procedure, the widths of the CIs for subgroups have not been adjusted for multiplicity and may not be used in place of hypothesis testing. EAC, oesophageal adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; GEJC, gastroesophageal junction adenocarcinoma; RoW, rest of world. Rui-Hua Xu CLARITY-Gastric01 [Slide 4] PFS by BICR in ITT and in 3L+ Dual-primary endpoint: PFS by BICR in ITT | Sone-Ve 2.2 mg/kg (n=267) | Investigator's choice of therapy (n=265) Median PFS (95% CI), months | 4.2 (3.5–5.3) | 3.8 (3.0–4.2) HR (95% CI) | 0.77 (0.62–0.96) P-value | 0.053193 No. of patients at risk (0–24 by 3): Sone-Ve 267 133 76 39 15 4 3 0 0; Investigator's choice 265 114 45 23 10 2 1 0 0 Secondary endpoint: PFS by BICR in 3L+ | Sone-Ve 2.2 mg/kg (n=178) | Investigator's choice of therapy (n=177) Median PFS (95% CI), months | 4.1 (3.0–5.3) | 2.7 (2.4–3.0) HR (95% CI) | 0.56 (0.43–0.74) No. of patients at risk (0–24 by 3): Sone-Ve 178 82 46 24 7 2 2 0 0; Investigator's choice 177 53 13 5 1 1 0 0 0 In the ITT population, Sone-Ve showed a positive trend for PFS by BICR, but did not meet the threshold for statistical significance In the 3L+ population, Sone-Ve improved PFS by BICR versus investigator's choice of therapy* *Not formally tested. The HR for event or death and CI were estimated from a stratified Cox proportional-hazards model with ties = Efron. Stratification variables were geographical region, prior gastrectomy and line of therapy. The CI was calculated using a profile likelihood approach. A HR of less than 1 favours Sone-Ve. Tick marks indicate censored observations. BICR, blinded independent central review. Rui-Hua Xu CLARITY-Gastric01 Survival table Endpoint: PFS by BICR (ITT dual primary; 3L+ secondary) Arm | N | Median | Median CI ITT: Sone-Ve 2.2 mg/kg | 267 | 4.2 | 3.5–5.3 ITT: Investigator's choice | 265 | 3.8 | 3.0–4.2 3L+: Sone-Ve 2.2 mg/kg | 178 | 4.1 | 3.0–5.3 3L+: Investigator's choice | 177 | 2.7 | 2.4–3.0 HR: ITT 0.77; 3L+ 0.56 HR CI: ITT 0.62–0.96; 3L+ 0.43–0.74 P: ITT 0.053193 (not significant); 3L+ not formally tested

Summary of results: CLARITY-Gastric01i Sone-Ve | Investigator's choice 3L+ (n=178) | (n=177) OS Number of deaths, n | 85 | 122 Median OS (95% CI) (in months) | 10.0 (7.2–11.4) | 5.0 (4.2–6.4) HR (95% CI)ii | 0.47 (0.36–0.62) p-value | p<0.000001 OS rate at 12 months (%) | 38.1 | 18.1 ITT (2L+) (n=267) | (n=265) OS Number of deaths, n | 139 | 174 Median OS (95% CI) (in months) | 10.6 (9.1–12.0) | 6.4 (5.8–7.6) HR (95% CI)ii | 0.58 (0.47–0.73) p-value | p<0.000004 HR, CLDN18.2 ≥75% (95% CI)ii, iii | 0.59 (0.45–0.78) HR, CLDN18.2 ≥25–<75% (95% CI)ii, iii | 0.63 (0.42–0.94) OS rate at 12 months (%) | 42.6 | 27.8 PFS by BICR Median PFS (95% CI) (in months) | 4.2 (3.5–5.3) | 3.8 (3.0–4.2) HR (95% CI)ii | 0.77 (0.62–0.96) p-value | p=0.053193 PFS by investigatoriv Median PFS (95% CI) (in months) | 4.4 (3.8-5.7) | 3.0 (2.7-4.1) HR (95% CI)ii | 0.59 (0.48-0.73) i OS and PFS data cut-off was 31 May 2026 ii Estimated from a stratified Cox proportional-hazards model with ties = Efron. The CI was calculated using a profile likelihood approach iii Tumour cells with membranous staining at any intensity iv Exploratory endpoint

Response and disease control in ITT ORR risk difference estimate (95% CI): 10.2 (2.68–17.83) ORR 23.3% (Sone-Ve) | ORR 13.8% (Investigator's choice) [stacked CR/PR bars] Disease control rate 70.4% | Disease control rate 55.6% | Sone-Ve 2.2 mg/kg | Investigator's choice of therapy Patients with measurable disease at baseline | 189 | 189 Confirmed ORR, n (%) | 44 (23.3) | 26 (13.8) Complete response, n (%) | 7 (3.7) | 1 (0.5) Disease control rate, n (%) | 133 (70.4) | 105 (55.6) Median duration of response, months (95% CI)* | 8.5 (5.8–NC) | 6.8 (2.9–NC) Sone-Ve demonstrated higher response and disease control rates, and longer duration of response versus investigator's choice of therapy More participants achieved complete response with Sone-Ve versus investigator's choice of therapy *Duration of response by BICR is calculated in all randomised patients in each arm (Sone-Ve n=267; Investigator's choice of therapy, n=265). BICR, blinded independent central review; CR, complete response; NC, not calculated; ORR, objective response rate; PR, partial response. Rui-Hua Xu CLARITY-Gastric01

OS in 3L+ Dual-primary endpoint: OS in 3L+ Sone-Ve 2.2 mg/kg (n=178) | Investigator's choice of therapy (n=177) Median OS (95% CI), months: 10.0 (7.2–11.4) | 5.0 (4.2–6.4) HR (95% CI): 0.47 (0.36–0.62) P-value: <0.000001 12-month OS: 38.1% (Sone-Ve) | 18.1% (Investigator's choice) No. patients at risk (months 0,3,6,9,12,15,18,21,24,27) Sone-Ve 2.2 mg/kg: 178 | 146 | 95 | 59 | 19 | 7 | 3 | 1 | 0 | 0 Investigator's choice of therapy: 177 | 117 | 58 | 24 | 14 | 6 | 2 | 2 | 1 | 0 Survival table Endpoint: OS in 3L+ (dual-primary) Arm | N | Median | Median CI Sone-Ve 2.2 mg/kg | 178 | 10.0 | 7.2–11.4 Investigator's choice of therapy | 177 | 5.0 | 4.2–6.4 HR: 0.47 HR CI: 0.36–0.62 P: <0.000001 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 38.1% | Investigator's choice of therapy 18.1%

OS by CLDN18.2 expression levels in ITT CLDN18.2 ≥75% expression | Sone-Ve 2.2 mg/kg (n=183) | Investigator's choice of therapy (n=194) Median OS (95% CI), months | 10.6 (8.1–13.5) | 6.4 (5.6–8.0) HR (95% CI) | 0.59 (0.45–0.78) No. of patients at risk (0–27 by 3): Sone-Ve 183 152 107 70 31 17 9 4 0 0; Investigator's choice 194 146 85 48 27 9 5 2 0 0 CLDN18.2 ≥25% to <75% expression | Sone-Ve 2.2 mg/kg (n=83) | Investigator's choice of therapy (n=71) Median OS (95% CI), months | 10.5 (7.1–12.4) | 6.2 (4.3–8.8) HR (95% CI) | 0.63 (0.42–0.94) No. of patients at risk (0–27 by 3): Sone-Ve 83 74 51 37 18 9 5 2 1 0; Investigator's choice 71 51 29 19 10 5 3 3 1 0 OS benefit with Sone-Ve vs investigator's choice of therapy was consistent across CLDN18.2 expression levels The HR and CI were estimated from a stratified Cox proportional-hazards model with ties = Efron. Stratification variables were geographical region, prior gastrectomy and line of therapy. The CI was calculated using a profile likelihood approach. A HR of less than 1 favours Sone-Ve. Tick marks indicate censored observations. Rui-Hua Xu CLARITY-Gastric01 Survival table Endpoint: OS by CLDN18.2 expression (ITT) Arm | N | Median | Median CI ≥75%: Sone-Ve 2.2 mg/kg | 183 | 10.6 | 8.1–13.5 ≥75%: Investigator's choice | 194 | 6.4 | 5.6–8.0 ≥25% to <75%: Sone-Ve 2.2 mg/kg | 83 | 10.5 | 7.1–12.4 ≥25% to <75%: Investigator's choice | 71 | 6.2 | 4.3–8.8 HR: ≥75%: 0.59; ≥25-<75%: 0.63 HR CI: ≥75%: 0.45–0.78; ≥25-<75%: 0.42–0.94

[Slide 1] Proffered Paper session LBA7 - CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) Speakers Rui-Hua Xu (Guangzhou, China) Lecture Time 17:18 - 17:30 Abstract Background CLDN18.2 is a validated therapeutic target in advanced GEC. Sone-Ve, a CLDN18.2-targeting monomethyl auristatin E–based antibody drug conjugate, demonstrated clinical activity in phase 1/2 studies of advanced GEC. [Slide 2] Methods CG-01 is a randomised, open-label, global, phase 3 study of Sone-Ve vs investigator's choice of therapy (INV) after ≥1 prior therapy for GEC expressing CLDN18.2 in ≥25% tumour cells with membranous staining at any intensity. Participants (pts) with 2L+ unresectable, locally advanced/metastatic CLDN18.2-positive GEC (intent-to-treat population: ITT) were initially randomised 1:1:1 to Sone-Ve 1.8 mg/kg, Sone-Ve 2.2 mg/kg or INV. Post-dose selection, pts were randomised 1:1 to Sone-Ve 2.2 mg/kg or INV (2L: ramucirumab + paclitaxel, paclitaxel, or docetaxel; 3L+: irinotecan, trifluridine/tipiracil, or apatinib [China only]). Randomisation was stratified by region, prior gastrectomy and line of therapy. Dual primary endpoints are OS in 3L+ and progression-free survival (PFS) by BICR in ITT. Key secondary endpoint is OS in ITT. [Slide 3] Proffered Paper session | 3L+ Sone-Ve (n=178) | INV (n=177) Median OS (95% CI), mo | 10.0 (7.2–11.4) | 5.0 (4.2–6.4) HR (95% CI) | 0.47 (0.36–0.62) | p-value | <0.001 | | ITT (2L+) (n=267) | (n=265) Median OS (95% CI), mo | 10.6 (9.1–12.0) | 6.4 (5.8–7.6) HR (95% CI) | 0.58 (0.47–0.73) | p-value | <0.001 | Median PFS by BICR (95% CI), mo | 4.2 (3.5–5.3) | 3.8 (3.0–4.2) HR (95% CI) | 0.77 (0.62–0.96) | p-value | 0.05 | | SAS* (n=261) | (n=252) TRAE, n (%) | | Any | 224 (85.8) | 205 (81.3) Grade ≥3 | 95 (36.4) | 113 (44.8) Gastrointestinal toxicity | 29 (11.1) | 16 (6.3) Haematology | 20 (7.7) | 40 (15.9) Leading to death | 3 (1.1) | 2 (0.8) Leading to discontinuation | 8 (3.1) | 11 (4.4) *SAS, safety analysis set; all pts who received ≥1 dose. TRAE, treatment-related adverse event. [Slide 4] Conclusions CG-01 showed a significant OS benefit with Sone-Ve vs INV in 3L+ and ITT, with a manageable safety profile. These findings support Sone-Ve as a potential 2L+ treatment for a broad patient population with advanced CLDN18.2-positive GEC.

[Slide 1] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN OS in 3L+ Dual-primary endpoint: OS in 3L+ | Sone-Ve 2.2 mg/kg (n=178) | Investigator's choice of therapy (n=177) Median OS (95% CI), months | 10.0 (7.2–11.4) | 5.0 (4.2–6.4) HR (95% CI) | 0.47 (0.36–0.62) P-value | <0.000001 12-month OS: 38.1% vs 18.1% No. patients at risk (0–27 mo by 3) Sone-Ve 2.2 mg/kg | 178 146 95 59 19 7 3 1 0 0 Investigator's choice of therapy | 177 117 58 24 14 6 2 2 1 0 Sone-Ve significantly improved OS versus investigator's choice of therapy in the 3L+ population Rui-Hua Xu CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: OS in 3L+ (dual primary) Arm | N | Median | Median CI Sone-Ve 2.2 mg/kg | 178 | 10.0 | 7.2–11.4 Investigator's choice of therapy | 177 | 5.0 | 4.2–6.4 HR: 0.47 HR CI: 0.36–0.62 P: <0.000001 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 38.1% | Investigator's choice of therapy 18.1% [Slide 2] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN PFS by BICR and PFS by investigator in ITT Dual-primary endpoint: PFS by BICR in ITT | Sone-Ve 2.2 mg/kg (n=267) | Investigator's choice of therapy (n=265) Median PFS (95% CI), months | 4.2 (3.5–5.3) | 3.8 (3.0–4.2) HR (95% CI) | 0.77 (0.62–0.96) P-value | 0.053193 No. of patients at risk (0–24 by 3): Sone-Ve 267 133 76 39 15 4 3 0 0; Investigator's choice 265 114 45 23 10 2 1 0 0 Exploratory endpoint: PFS by investigator in ITT | Sone-Ve 2.2 mg/kg (n=267) | Investigator's choice of therapy (n=265) Median PFS (95% CI), months | 4.4 (3.8–5.7) | 3.0 (2.7–4.1) HR (95% CI) | 0.59 (0.48–0.73) No. of patients at risk (0–24 by 3): Sone-Ve 267 151 91 48 20 7 4 1 0; Investigator's choice 265 111 44 23 12 2 1 0 0 PFS assessment by investigator showed a more pronounced treatment effect (HR 0.59) than BICR, consistent with the observed OS benefit Rui-Hua Xu CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: PFS in ITT by BICR (dual primary) and by investigator (exploratory) Arm | N | Median | Median CI BICR: Sone-Ve 2.2 mg/kg | 267 | 4.2 | 3.5–5.3 BICR: Investigator's choice | 265 | 3.8 | 3.0–4.2 Investigator-assessed: Sone-Ve 2.2 mg/kg | 267 | 4.4 | 3.8–5.7 Investigator-assessed: Investigator's choice | 265 | 3.0 | 2.7–4.1 HR: BICR 0.77; investigator 0.59 HR CI: BICR 0.62–0.96; investigator 0.48–0.73 P: BICR 0.053193; investigator-assessed exploratory, no p [Slide 3] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Response and disease control in ITT ORR risk difference estimate (95% CI): 10.2 (2.68–17.83) ORR 23.3% (CR, PR) | ORR 13.8% (CR, PR) Disease control rate 70.4% | Disease control rate 55.6% | Sone-Ve 2.2 mg/kg | Investigator's choice of therapy Patients with measurable disease at baseline | 189 | 189 Confirmed ORR, n (%) | 44 (23.3) | 26 (13.8) Complete response, n (%) | 7 (3.7) | 1 (0.5) Disease control rate, n (%) | 133 (70.4) | 105 (55.6) Median duration of response, months (95% CI)* | 8.5 (5.8–NC) | 6.8 (2.9–NC) Sone-Ve demonstrated higher response and disease control rates, and longer duration of response versus investigator's choice of therapy More participants achieved complete response with Sone-Ve versus investigator's choice of therapy *Duration of response by BICR is calculated in all randomised patients in each arm (Sone-Ve n=267; Investigator's choice of therapy, n=265). BICR, blinded independent central review; CR, complete response; NC, not calculated; ORR, objective response rate; PR, partial response. Rui-Hua Xu CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) ALICANTE AUDITORIUM - HALL 6 [Slide 4] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Most common adverse events Most common AEs of any Grade (Sone-Ve n=261 | Investigator's choice of therapy n=252) Nausea 54.4% | 26.6% Decreased appetite 43.3% | 24.2% Vomiting 41.0% | 24.6% Anemia 29.9% | 40.9% Weight decreased 28.0% | 11.9% Constipation 24.5% | 13.1% Fatigue 24.1% | 19.8% Neutropenia 23.8% | 39.7% Diarrhea 23.0% | 25.4% Hypoalbuminemia 21.8% | 14.7% Most common Grade ≥3 AEs Neutropenia 10.3% | 25.4% Decreased appetite 9.6% | 1.6% Anemia 8.4% | 11.1% Nausea 6.9% | 2.8% Neutrophil count decreased 6.9% | 18.7% Vomiting 6.1% | 2.8% Fatigue 4.2% | 3.6% Pulmonary embolism 4.2% | 1.6% Pneumonia 3.4% | 2.8% Weight decreased 3.4% | 0.8% Lymphocyte count decreased 3.1% | 3.2% Higher rates of GI-related AEs were observed with Sone-Ve versus investigator's choice of therapy Lower rates of haematologic toxicity were observed with Sone-Ve versus investigator's choice of therapy Safety was assessed in the Safety Analysis Set, defined as all patients who received ≥1 dose of treatment. [...] Any Grade peripheral neuropathy occurred in 56 (21.5%) patients in the Sone-Ve arm and 36 (14.3%) patients in the investigator's choice of therapy arm; Grade ≥3 peripheral neuropathy occurred in 2 (0.8%) patients in the Sone-Ve arm and 1 (0.4%) patients in the investigator's choice of therapy arm. Any Grade alopecia occurred in 13 (5.0%) of patients in the Sone-Ve arm and 36 (14.3%) in investigator's choice of therapy arm. Rui-Hua Xu CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) ALICANTE AUDITORIUM - HALL 6

[Slide 1] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN Conclusions CLARITY-Gastric01 is the first global, Phase 3 trial to demonstrate a statistically significant OS benefit and a manageable safety profile with a CLDN18.2 targeting antibody-drug conjugate in patients with previously treated advanced or metastatic CLDN18.2-positive GEC (defined as ≥25% tumour cells with membraneous staining at any intensity) Sone-Ve showed a statistically significant and clinically meaningful improvement in OS versus investigator's choice of therapy • Median OS was doubled to 10 months in the 3L+ population and improved by over 4 months to 10.6 months in the ITT (2L+) population • OS benefit was maintained across CLDN18.2 expression subgroups PFS by BICR in ITT (HR 0.77) did not reach the threshold for statistical significance • PFS by BICR in 3L+ was improved with Sone-Ve versus investigator's choice of therapy (HR 0.56) • Assessment of PFS by investigator in ITT showed a more pronounced treatment effect (HR 0.59) than by BICR Sone-Ve demonstrated a differentiated and manageable safety profile versus investigator's choice of therapy Sone-Ve is a potential new standard of care in the 2L+ setting for patients with advanced or metastatic CLDN18.2-positive gastroesophageal carcinoma 2L, second- or later-line; 3L+, third- or later-line; BICR, blinded independent central review; CLDN18.2, Claudin18 isoform 2; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PFS, progression-free survival; Sone-Ve, sonesitatug vedotin. Rui-Hua Xu CLARITY-Gastric01 ALICANTE AUDITORIUM - HALL 6 [Slide 2] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN My Conclusions Sone-Ve represents an important therapeutic advance in gastroesophageal carcinoma. • ≥3L: Impressive efficacy in a setting of high unmet need. • 2L: Potential benefit, but more data needed, particularly versus ramucirumab/paclitaxel. • Study design: Combining 2L and ≥3L complicates clinical interpretation. • Safety: Manageable, but GI toxicity remains relevant. • Future: First-line trials ongoing; curative setting should be a next step Salah-Eddin Al-Batran ALICANTE AUDITORIUM - HALL 6 [Slide 3] 16:30 - 18:15 Presidential Symposium II CHAIRS: GIUSEPPE CURIGLIANO, YELENA JANJIGIAN OS in ITT Key secondary endpoint: OS in ITT Sone-Ve 2.2 mg/kg (n=267) | Investigator's choice of therapy (n=265) Median OS (95% CI), months: 10.6 (9.1–12.0) | 6.4 (5.8–7.6) HR (95% CI): 0.58 (0.47–0.73) P-value: 0.000004 12-month OS: 42.6% (Sone-Ve) | 27.8% (Investigator's choice) No. of patients at risk (months 0,3,6,9,12,15,18,21,24,27) Sone-Ve 2.2 mg/kg: 267 | 227 | 159 | 107 | 49 | 26 | 14 | 6 | 1 | 0 Investigator's choice of therapy: 265 | 197 | 114 | 67 | 37 | 14 | 8 | 5 | 1 | 0 Sone-Ve significantly improved OS versus investigator's choice of therapy in the ITT population The HR and CI were estimated from a stratified Cox proportional-hazards model with ties = Efron. Stratification variables were geographical region, prior gastrectomy and line of therapy. The CI was calculated using a profile likelihood approach. A HR of less than 1 favours Sone-Ve. Tick marks indicate censored observations. Rui-Hua Xu CLARITY-Gastric01 ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: OS in ITT (key secondary) Arm | N | Median | Median CI Sone-Ve 2.2 mg/kg | 267 | 10.6 | 9.1–12.0 Investigator's choice of therapy | 265 | 6.4 | 5.8–7.6 HR: 0.58 HR CI: 0.47–0.73 P: 0.000004 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 42.6% | Investigator's choice of therapy 27.8%

Background • CLDN18.2, a tight junction protein that is expressed in 40–80% of gastroesophageal carcinomas depending on [the] threshold for positivity assessed, has emerged as a validated therapeutic target1–3 • In the 2L setting, median OS is <10 months with ramucirumab plus paclitaxel, whereas single chemotherapeu[tic] options in the 3L+ setting are associated with an OS benefit of <6 months4,5 • No CLDN18.2-targeted therapies are approved globally for 2L+ therapy • Sone-Ve is a first-in-class CLDN18.2-targeted antibody-drug conjugate comprised of a CLDN18.2-directe[d] antibody conjugated to the microtubule-disrupting payload MMAE via a protease cleavable linker6 Here, we present the results of the global Phase 3 CLARITY-Gastric01 trial (NCT06346392) evaluat[ing] Sone-Ve versus investigator's choice of therapy in patients with 2L+ advanced or metastatic CLDN18.2 (≥25% tumour cells with membranous staining at any intensity) gastroesophageal carcinoma [references illegible] Rui-Hua Xu

[Slide 1] Congratulations on This Important Achievement! CLARITY-Gastric01: a Phase 3 study of sonesitatug vedotin (Sone-Ve, AZD0901) in second or later-line advanced or metastatic Claudin 18.2-positive gastroesophageal carcinoma Rui-Hua Xu,1 Yelena Janjigian,2 Ming-Huang Chen,3 Jeeyun Lee,4 Jun Zhang,5 Elena Elimova,6 Elizabeth Smyth,7 Thorsten Oliver Goetze,8 Weijian Guo,9 Mitsuhiro Furuta,10 Keun-Wook Lee,11 Giang Nguyen,12 Filippo Pietrantonio,13 Maria Carmen Riesco Martinez,14 Anthony Turpin,15 Dani Castillo,16 Jiabu Ye,17 Silver Liu,17 Nicola Valeri,18 Kohei Shitara19 [Affiliations - small print, partially legible: Sun Yat-sen University Cancer Center; Memorial Sloan Kettering Cancer Center; Taipei Veterans General Hospital; Samsung Medical Center; Ruijin Hospital; Princess Margaret Cancer Centre; Churchill Hospital, Oxford; University Cancer Center Frankfurt; Fudan University Shanghai Cancer Center; Kanagawa Cancer Center; Seoul National University Bundang Hospital; Vietnam National Cancer Hospital; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Hospital Universitario 12 de Octubre, Madrid; CHU Lille; City of Hope; AstraZeneca R&D China, Shanghai; AstraZeneca Oncology R&D, Cambridge; National Cancer Center Hospital East, Kashiwa] Final Publication Number: LBA7 [Slide 2] Primary Endpoint: OS in 3L+ Population Median OS: 10.0 vs 5.0 months (Sone-Ve vs ICT) HR 0.47; p<0.001 12-month OS: 38.1% (Sone-Ve 2.2 mg/kg) | 18.1% (Investigator's choice of therapy) No. patients at risk (months 0,3,6,9,12,15,18,21,24,27) Sone-Ve 2.2 mg/kg: 178 | 146 | 95 | 59 | 19 | 7 | 3 | 1 | 0 | 0 Investigator's choice of therapy: 177 | 117 | 58 | 24 | 14 | 6 | 2 | 2 | 1 | 0 Impressive OS Benefit: median survival doubled This is good news for our patients in a difficult-to-treat setting Salah-Eddin Al-Batran Survival table Endpoint: OS in 3L+ (primary) Sone-Ve 2.2 mg/kg | 178 | 10.0 Investigator's choice of therapy | 177 | 5.0 HR: 0.47 P: <0.001 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 38.1% | Investigator's choice of therapy 18.1% [Slide 3] Key Secondary Endpoint: OS in 2L+ Population Median OS: 10.0 vs 6.4 months (Sone-Ve vs ICT) HR 0.58; p<0.001 Adding the 2L population 12-month OS: 42.6% (Sone-Ve 2.2 mg/kg) | 27.8% (Investigator's choice of therapy) No. of patients at risk (months 0,3,6,9,12,15,18,21,24,27) Sone-Ve 2.2 mg/kg: 267 | 227 | 159 | 107 | 49 | 26 | 14 | 6 | 1 | 0 Investigator's choice of therapy: 265 | 197 | 114 | 67 | 37 | 14 | 8 | 5 | 1 | 0 Salah-Eddin Al-Batran Survival table Endpoint: OS in 2L+ (ITT, key secondary) Sone-Ve 2.2 mg/kg | 267 | 10.0 (as printed on discussant slide) Investigator's choice of therapy | 265 | 6.4 HR: 0.58 P: <0.001 Landmark rates: 12 months: Sone-Ve 2.2 mg/kg 42.6% | Investigator's choice of therapy 27.8%

[Slide 2] Baseline characteristics Characteristic | Sone-Ve 2.2 mg/kg (n=267) | Investigator's choice of therapy (n=265) Median age (range), years | 57 (24 to 82) | 57 (24 to 82) Male sex, n (%) | 150 (56.2) | 159 (60.0) Region, n (%) Japan or South Korea | 55 (20.6) | 54 (20.4) Other Asia | 107 (40.1) | 106 (40.0) Rest of world | 105 (39.3) | 105 (39.6) Primary tumour location, n (%) Stomach | 213 (79.8) | 194 (73.2) Gastroesophageal junction/Esophagus | 54 (20.2) | 71 (26.8) Peritoneal metastasis, Yes, n (%) | 163 (61.0) | 148 (55.8) CLDN18.2 expression,* n (%) <25% | 1 (0.4)‡ | 0 ≥25–<75% | 83 (31.1) | 71 (26.8) ≥75% | 183 (68.5) | 194 (73.2) Prior gastrectomy, Yes, n (%) | 98 (36.7) | 93 (35.1) Line of therapy,† n (%) 2L | 90 (33.7) | 88 (33.2) 3L+ | 177 (66.3) | 177 (66.8) Prior anti-CLDN18.2 mAb, n (%) Zolbetuximab | 10 (3.7) | 7 (2.6) Other | 8 (3.0) | 1 (0.4) Demographics and baseline disease characteristics were generally balanced across treatment arms in the ITT population *Expression in tumour cells with membranous staining at any intensity; †Line of therapy data are from the clinical reporting form and the number of patients in the sonesitatug vedotin arm differs from the equivalent data in the IRT due to mis-stratification in the clinical reporting form (IRT: 2L, n=89); ‡One patient had negative CLDN18.2 result but was randomised. IRT, interactive reporting technology software; mAb, monoclonal antibody. Rui-Hua Xu CLARITY-Gastric01 [Slide 4] OS subgroup analysis in 3L+ Subgroup | Sone-Ve 2.2 mg/kg (No. of events/total no. of patients) | Investigator's choice of therapy | Hazard ratio (95% CI) All patients | 85/178 | 122/177 | 0.47 (0.36–0.62) Age: ≥18–<65 years | 60/130 | 90/132 | 0.45 (0.32–0.62) Age: ≥65 years | 25/48 | 32/45 | 0.57 (0.34–0.98) Sex: Female | 30/79 | 46/72 | 0.42 (0.26–0.66) Sex: Male | 55/99 | 76/105 | 0.53 (0.37–0.74) Region: Japan & S. Korea | 13/40 | 25/41 | 0.39 (0.19–0.77) Region: Other Asia | 38/74 | 58/73 | 0.42 (0.28–0.63) Region: RoW | 34/64 | 39/63 | 0.61 (0.38–0.97) ECOG PS: 0 | 24/58 | 33/61 | 0.50 (0.29–0.85) ECOG PS: 1 | 61/120 | 89/116 | 0.45 (0.32–0.63) Primary tumour: Gastric | 63/141 | 95/137 | 0.43 (0.31–0.59) Primary tumour: GEJC/EAC | 22/37 | 27/40 | 0.63 (0.36–1.11) No. of organ metastases: 0–2 | 49/117 | 73/120 | 0.50 (0.34–0.71) No. of organ metastases: ≥3 | 36/61 | 49/57 | 0.40 (0.25–0.61) Liver metastasis: Yes | 27/47 | 41/54 | 0.53 (0.32–0.85) Liver metastasis: No | 58/131 | 81/123 | 0.46 (0.32–0.64) Peritoneal metastasis: Yes | 55/117 | 77/100 | 0.31 (0.22–0.45) Peritoneal metastasis: No | 30/61 | 45/77 | 0.80 (0.50–1.27) Prior gastrectomy: Yes | 31/78 | 51/79 | 0.33 (0.21–0.52) Prior gastrectomy: No | 54/100 | 71/98 | 0.61 (0.43–0.87) Favours Sone-Ve 2.2 mg/kg <- 1 -> Favours Investigator's choice of therapy OS HR point estimates favoured Sone-Ve versus investigator's choice of therapy across all clinically relevant subgroups in the 3L+ population All subgroups were prespecified in the protocol. The analysis was based on the Kaplan-Meier technique and was performed using an unstratified Cox proportional hazards model. The overall HR was calculated using a stratified Cox proportional hazards model, adjusting for Interactive Response Technology strata, including prior gastrectomy, region and line of therapy and using an implemented pooling strategy per the statistical analysis plan with treatment as the only covariate. Ties were handled by the Efron approach. CIs were calculated using a profile likelihood approach. A HR below 1 favours Sone-Ve. Because PFS and OS were the only endpoints that were part of the multiple testing procedure, the widths of the CIs for subgroups have not been adjusted for multiplicity and may not be used in place of hypothesis testing. EAC, oesophageal adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; GEJC, gastroesophageal junction adenocarcinoma; RoW, rest of world. Rui-Hua Xu CLARITY-Gastric01

[Slide 1] MADRID 2026 ESMO congress CLARITY-Gastric01: a Phase 3 study of sonesitatug vedotin (Sone-Ve, AZD0901) in second or later-line advanced or metastatic Claudin 18.2-positive gastroesophageal carcinoma Rui-Hua Xu,1 Yelena Janjigian,2 Ming-Huang Chen,3 Jeeyun Lee,4 Jun Zhang,5 Elena Elimova,6 Elizabeth Smyth,7 Thorsten Oliver Goetze,8 Weijian Guo,9 Mitsuhiro Furuta,10 Keun-Wook Lee,11 Giang Nguyen,12 Filippo Pietrantonio,13 Maria Carmen Riesco Martínez,14 Anthony Turpin,15 Dani Castillo,16 Jiabu Ye,17 Silver Liu,17 Nicola Valeri,18 Kohei Shitara19 Final Publication Number: LBA7 A copy of these slides [and] plain language summar[y can] be accessed via this qu[ick] response (QR) code [Slide 2] ESMO congress ADCs in PDAC Claudin 18.2 as a target Sonesitatug vedotin (Sone-Ve) is an ADC that targets CLDN 18.2 with a MMAE as a payload. CLARITY-PanTumor01: A phase 2 trial of the claudin 18.2-specific antibody-drug conjugate AZD0901 (CMG901) in patients with CLDN18.2-expressing advanced solid tumors. NCT06219941 Raufi et al, presented at 2024 ASCO Meeting [Arm schematic text illegible]

[Slide 1] AZUR-1: Phase 2 Study A single-arm, open label study of dostarlimab monotherapy in participants with untreated stage 2/3 MMR-D/MSI-H locally advanced rectal cancer. Inclusion criteria1 • Adults aged ≥ 18 years • Histologically confirmed stage II–III (T3–T4, N0, or T any, N+), locally advanced rectal cancer • Radiologically and endoscopically evaluable disease • ECOG PS 0–1 • Tumor that can be categorized as dMMR or MSI-H by local or central assessment Exclusion criteria1 • Distant metastatic disease • Prior radiation therapy, systemic therapy, or surgery for the management of rectal cancer • Tumor-caused symptomatic bowel obstruction • Participant has any history of interstitial lung disease or pneumonitis • Any irAE of Grade ≥ 3, immune-related severe neurologic events, exfoliative dermatitis of any grade, or myocarditis from prior immunotherapy • Malignancy that has progressed or required active treatment ≤ 2 years Overview of Study Design Phase 2, open-label, single-arm study1-2 (N = 150) Dostarlimab 500 mg IV Q3W × 9 cycles → EOT response assessment → < cCR: SoC, +/− surgery (if needed); cCR: Non-operative management 6 weeks | 12 weeks Disease assessments: • 6 weeks, 12 weeks, EOT, then – Q4 months in Years 1–3 – Q6 months in Years 4–5 Endpoints1 Primary: • Proportion who sustain cCR for 12 months by ICR Secondary: • Sustained cCR24 by ICR for 24 and 36 months • EFS by INV at 3 years • cCR by INV at 12, 24, and 36 months • ORR by ICR at post-intervention disease assessment • Organ preservation rate at 3 years • DSS and DSS at 5 years • OS and OS at 5 years • Safety (AE, SAE, irAE, study discontinuations, and deaths) • PK parameters • Antidrug antibodies against dostarlimab [Slide 2] AZUR-1: the rationale Non-operative management (NOM) of dMMR tumours DOSTARLIMAB: BASELINE | 6 WEEKS | 3 MONTHS | 6 MONTHS | FU2 / 14 MONTHS | FU3 / 18 MONTHS | FU4 / 22 MONTHS ENDOSCOPY | MRI RECTUM | PET/CT [Waterfall: Tumor Response SD, PR, nCR, cCR; Rectal (100%)] • 49 patients with rectal adenocarcinoma • 9 cycles of dostarlimab • Median follow-up of 30 months • 100% cCR • RFS at 2 years was 96% Prof David Tougeron | ESMO Congress 2026 Cercek A et al. NEJM 2025

LBA87 - Clinical complete response with dostarlimab monotherapy in dMMR/MSI-H locally advanced rectal cancer (LARC): First results from the global registrational AZUR-1 trial Speakers Andrea Cercek (New York, United States of America, NY) Lecture Time 11:00 - 11:10 Abstract Background Multimodal treatment with chemotherapy, radiation and surgery is a standard of care (SOC) for LARC associated with significant toxicity/morbidity. After TNT, the range of clinical complete response (cCR) is 21–41%. dMMR/MSI-H tumours are exceptionally responsive to PD-1 blockade: in a small study, neoadjuvant dostarlimab treatment led to durable cCRs and eliminated the need for SOC in most patients (pts) with LARC. AZUR-1 (NCT05723562) is a global single-arm trial and the first registrational study evaluating the clinical benefit of dostarlimab monotherapy in pts with dMMR/MSI-H LARC. Methods Dostarlimab 500 mg was administered IV every 3 weeks for 9 cycles. Key endpoints include rate of sustained cCR for 12 months (cCR12) following end of treatment (EOT) with dostarlimab alone by investigator (INV) and independent central review (ICR), and composite rate of cCR12 (INV) + pathological CR (pCR). Results At data cutoff (DCO, 20 April 2026), 154 pts were enrolled and median follow-up was 26.3 months (range 2–36). Of 144 pts with ≥12 months follow-up, 68% achieved cCR12 (INV). Of 15 pts who underwent surgery after dostarlimab alone, 12 (80%) had pCR, resulting in a cCR12+pCR rate of 76%. Fewer pts were cCR12-evaluable by ICR, primarily due to cCR being confirmed later by ICR after initial EOT evaluation. Of pts evaluable by ICR, 47% (54/116) achieved cCR12, with 38 pts in cCR and being followed for cCR12 at DCO. 98% of pts who achieved cCR remained in cCR for ≥12 months by INV or ICR, with no recurrences to date for pts who achieved cCR or pCR. Overall, 93% of patients are in surveillance with no evidence of disease progression after treatment (dostarlimab ± SOC) and 71% achieved this outcome with dostarlimab alone. The safety profile was acceptable: 88% of pts completed all 9 cycles of dostarlimab and Grade ≥3 immune-mediated AEs occurred in 4 pts. Conclusions In this AZUR-1 interim analysis, 68% of pts achieved cCR12 and 76% achieved cCR12+pCR with dostarlimab alone with no disease recurrences to date. These durable responses indicate the potential to eliminate the need for chemotherapy, radiation and surgery, and redefine the curative-intent treatment paradigm for pts with dMMR/MSI-H LARC.

EOT response assessment: cCR | nCR | PR | SD | NA | PD *Assessments after EOT response assessment: cCR | pCR with dostarlimab alone Y-axis: cCR/pCR, nCR, PR, SD, NA, PD cCR12 (INV): 98/144 68% (95% CI: 60–76) cCR12 (ICR): 54/116 47% (95% CI: 37–56) Legend: cCR12 responder | Non-evaluable for cCR12 | cCR12-non-responder (pCR with dostarlimab alone) | cCR12 non-responder

[Slide 1] Durable responses were observed in patients who achieved cCR Patients achieving cCR (INV) after dostarlimab monotherapy among patients with ≥12 months follow-up (n=100) cCR (n=100) 98% of cCRs were durable with no recurrences (2 patients with cCR elected for surgery and had pCR) Legend: Time from enrolment to start of cCR12 follow-up; In follow up with sustained cCR; Ongoing follow up (further response assessment pending); cCR reported prior to EOT; EOT; Patients with cCR who elected for surgery Months (0-40) cCR, clinical complete response; cCR12, clinical complete response for ≥12 months; EOT, end of treatment; INV, investigator; pCR, pathological complete response Dr Andrea Cercek [Slide 2] High rate of cCR12 was observed with dostarlimab alone cCR12 = Patients who achieved cCR after dostarlimab monotherapy and maintained for ≥12 mo with no additional treatment Legend: cCR with <12 mo follow-up (n=10); cCR with ≥12 mo follow-up (n=98); Non-cCR12 (n=46); Late cCR (n=8) 2 patients who achieved a cCR at EOT response assessment elected for surgery (both pCR) so could not achieve cCR12 Y axis: cCR/pCR, nCR, PR, SD, N/A†, PD cCR with <12 mo follow-up (n=10) | cCR with ≥12 months follow-up* (n=98) | Non-cCR12 (n=46) Patients evaluable for cCR12 = 144 cCR12 by INV: 68% (98/144) *Sufficient follow-up for cCR12 analyses required 12 months of follow-up and adequate disease assessments according to the scheduled assessment plan (i.e., a patient with a cCR may have completed 12 months of follow-up but would still not be cCR12-evaluable if the required disease assessments were not performed). †Patients who were not evaluable (n=4) have been pooled with those who were N/A (n=6): four patients did not reach end of treatment response assessment and did not initiate SOC treatment; six patients did not undergo end of treatment response assessment but were recorded as continuing on study and received SOC. cCR, clinical complete response; cCR12, clinical complete response for ≥12 months; EOT, end of treatment; mo, months; N/A, not available; nCR, near complete response; pCR, pathological complete response; PD, progressive disease; PR, partial response; SD, stable disease; SOC, standard of care. Dr Andrea Cercek [Slide 3] Assessment of response: Clinical complete response (cCR) Clinical complete response (cCR): concordant examination, endoscopy and MRI Clinical examination + Endoscopy ✓ Normal digital rectal examination ✓ No visible residual rectal tumor + Rectal MRI ✓ No residual diffusion restriction on DWI; scar on T2-weighted imaging ✓ Target lymph nodes decrease to <5 mm in short-axis diameter* [Images: Endoscopy and MRI, Baseline → Complete response] *The <5 mm threshold is source-specific and should be applied within the study assessment protocol, not treated as a standalone universal guarantee of nodal sterilization. cCR, clinical complete response; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging. Dr Andrea Cercek [Slide 4] AZUR-1 trial design Global Phase 2 single-arm study of dostarlimab monotherapy for dMMR/MSI-H locally advanced rectal cancer Patients with dMMR/MSI-H LARC → Dostarlimab treatment → EOT response assessment → Post-dostarlimab management based on INV assessment → Efficacy endpoints for interim analysis ✓ Stage II to III (T3–T4, N0, or T any, N+) ✓ dMMR/MSI-H by local or central assessment ✓ No prior treatment for rectal cancer ✓ No tumour-caused symptomatic bowel obstruction N=154 Dostarlimab 500 mg IV Q3W x 9 cycles Endoscopy and MRI/CT 21 days after last dose (+7 days) cCR → NOM† (surveillance without further treatment) <cCR → NOM† (surveillance without further treatment) or SOC (ChT/RT/surgery) (per investigator discretion) iCR/nCR* (second assessment loop) Primary/secondary: cCR12 by ICR/ cCR12 by INV Exploratory: cCR12 (INV) + pCR Note, cCR12 and pCR achieved after dostarlimab alone *Patients with near CR (nCR; defined as those with significant reduction in tumour burden but with some residual disease) or incomplete CR (iCR; defined as all responses less than nCR that are not progressive disease, including those with PR and SD) will have the option for a second clinical response evaluation 4–8 weeks after the initial evaluation, at the discretion of the investigator and the patient. If the patient reaches cCR, they may enter the nonoperative management period; if the response is less than cCR, patients will either proceed with SOC or surveillance without further treatment per investigator discretion. †Endoscopy, rectal MRI, and CT CAP Q4M in Years 1–2 and Q6M in Years 3–5. cCR12, clinical complete response for ≥12 months; iCR, incomplete clinical response; ICR, independent central review; INV, investigator; nCR, near complete response; NOM, nonoperative management. Dr Andrea Cercek

[Slide 2] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ High rate of clinical complete responses (cCR) was observed after dostarlimab alone Legend: cCR (n=102); Late cCR (n=8)*; nCR (n=9); PR (n=15); SD (n=10); N/A (n=10); PD (n=8) Y axis: cCR, nCR, PR, SD, N/A†, PD cCR: 66% (n=102) | nCR: 6% (n=9) | PR: 10% (n=15) | SD: 6% (n=10) | N/A: 7% (n=10)† | PD: 5% (n=8) End of treatment response (N=154) cCR 71% (110/154) *8 patients converted from nCR/PR to cCR at any time; †Patients who were not evaluable (n=4) have been pooled with those who were N/A (n=6): four patients did not reach end of treatment response assessment and did not initiate SOC treatment; six patients did not undergo end of treatment response assessment but were recorded as continuing on study and received SOC. cCR, clinical complete response; N/A, not available; nCR, near complete response; pCR, pathological complete response; PD, progressive disease; PR, partial response; SD, stable disease. Dr Andrea Cercek ALMERIA AUDITORIUM - HALL 9 [Slide 3] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ High rate of cCR12 + pCR was observed with dostarlimab alone cCR12 = Patients who achieved cCR after dostarlimab monotherapy and maintained for ≥12 mo with no additional treatment Legend: cCR with 12 months follow up (n=98); pCR after dostarlimab alone (n=12); nCR (n=3); PR (n=13); SD (n=10); N/A (n=10); PD (n=8); Late cCR (n=8); cCR with <12 months follow up (n=10) cCR with <12 mo follow-up (n=10) | cCR with ≥12 months follow-up* (n=98) | Non-cCR12 (n=46) End of treatment response (N=154) cCR12 (n=98) + pCR (n=12): 76% (110/144) [Footnotes: N/A pooling and abbreviations, small print] Dr Andrea Cercek ALMERIA AUDITORIUM - HALL 9 [Slide 4] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ Safety profile was consistent with prior studies of dostarlimab Dostarlimab median number of cycles 9 (range 2–9) N=154 AEs (≥10% of patients) | Gr 1–2 | ≥Gr 3 Any dostarlimab-related AE, n (%) | 98 (64) | 15 (10) Pruritus | 21 (14) | 0 Hypothyroidism | 19 (12) | 0 Fatigue | 16 (10) | 1 (<1) Immune-mediated AEs (≥2% of patients) | Gr 1–2 | ≥Gr 3 Any immune-mediated AE, n (%) | 32 (21) | 4 (3)|| Hypothyroidism | 12 (8) | 0 Arthralgia | 3 (2) | 0 Hyperthyroidism | 3 (2) | 0 SAEs* | Any causality | Dostarlimab related† Any treatment-emergent SAE, n (%) | 31 (20) | 8 (5) SAEs of clinical interest Intestinal obstruction‡ | 3 (2) | 0 Rectal stenosis | 2 (1) | 0 Intestinal perforation§ | 2 (1) | 0 Among adverse events related to dostarlimab: • 3 (2%) patients discontinued treatment¶ • No fatal AEs DCO 20 April 2026. [Footnotes small print: SAE definition; AEs considered related at investigator discretion; obstruction at primary tumour site in 2 patients with response; perforation includes large intestinal perforation (n=1) and procedural intestinal perforation (n=1); ≥Gr3 immune-mediated includes Grade 3 adrenal insufficiency (n=1), Grade 4 diabetic ketoacidosis (n=1), Grade 3 lichen planus (n=1) and Grade 3 hepatitis (n=1); discontinuations: hepatitis (n=1), amylase increase (n=1) and lichen planus (n=1) - partially legible] Dr Andrea Cercek ALMERIA AUDITORIUM - HALL 9

EOT response assessment: cCR | nCR | PR | SD | NA | PD *Assessments after EOT response assessment: cCR | pCR with dostarlimab alone cCR/pCR, nCR, PR, SD, NA, PD cCR12 (INV): 98/144 68% (95% CI: 60–76) cCR12 (ICR): 54/116 47% (95% CI: 37–56) cCR12 responder | Non-evaluable for cCR12 | cCR12-non-responder (pCR with dostarlimab alone) | cCR12 non-responder

Patient disposition Assessed for eligibility N=165 Screening failures (n=11) • Ineligible (n=10) • Withdrew (n=1) Received dostarlimab monotherapy N=154 (full analysis set) • Completed (n=136) • Discontinued prematurely (n=18)* Did not reach response assessment (n=4) • Withdrew (n=3) • Died (n=1) NOM after dostarlimab 71% (110/154) Additional SOC treatment after dostarlimab 26% (40/154) Lost to follow-up post SOC (n=5) • Withdrew (n=1) • Died (n=4)† On study and in follow-up 94% (145/154) PD post SOC (n=2) On study with no evidence of PD after dostarlimab ± SOC 93% (143/154)‡ *Premature discontinuations included adverse event (n=4), physician decision (n=6), PD (n=6), withdrawal by patient (n=1), other (n=1). †One patient refused SOC and died without evidence of having received any additional treatment. ‡Two patients refused SOC, as recommended after EOT disease assessment, had local progression and then received additional treatment (immunotherapy n=1; CRT n=1); no further PD noted during or following additional treatments. CRT, chemoradiotherapy; DCO, data cut-off; EOT, end of treatment; NOM, non-operative management; PD, progressive disease; SOC, standard of care. Dr Andrea Cercek

Investigator-assessed cCR is achieved earlier than by central review cCR12 (INV): 98/144 68% cCR12 (ICR): 54/116 47% Legend: cCR with <12 mo follow-up | cCR with ≥12 mo follow-up | Non-cCR/pCR cCR12 by INV 94% mature cCR12 by ICR 75% mature *No subsequent systemic treatment or radiotherapy after completing dostarlimab. cCR, clinical complete response; cCR12, clinical complete response for ≥12 months; ICR, independent central review; INV, investigator; mo, months; nCR, near complete response; pCR, pathologic complete response. Dr Andrea Cercek

[Slide 1] Clinical Complete Response With Dostarlimab Monotherapy in dMMR/MSI-H Locally Advanced Rectal Cancer: First Results From the Global Registrational AZUR-1 Trial Andrea Cercek1, Jean-Baptiste Bachet2, Gunnar Folprecht3, Hideaki Bando4, Jenny Seligmann5, Naureen Starling6, María del Carmen Riesco Martínez7, Pilar García Alfonso8, Denis Smith9, Lisa Salvatore10,11, Encarna Gonzalez Flores12, Emmanuel Mitry13, Eric Chen14, Jaume Capdevila15, Federica Morano16, Susana Roselló Keränen17, Neda Stjepanovic18, Zsolt Szijgyarto19, Luis A. Diaz, Jr1, Jeanine M.L. Roodhart20 1Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Sorbonne University, Pitié Salpêtrière Hospital, Paris, France; 3Technical University Dresden/Medical Faculty Carl Gustav Carus, Dresden, Germany; 4National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan; 5University of Leeds, Leeds, UK; 6Royal Marsden NHS Foundation, London, UK; 7Hospital Universitario 12 de Octubre, Madrid, Spain; 8Hospital General Universitario Gregorio Marañón, Faculty of Medicine, Complutense University of Madrid, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; 9CHU Haut Lévêque, Pessac, France; 10Università Cattolica del Sacro Cuore, Rome, Italy; 11Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy; 12Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria IBS, Granada, Spain; 13Institut Paoli-Calmettes, Marseille, France; 14Princess Margaret Cancer Centre, Toronto, Canada; 15Vall Hebron University Hospital and Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain; 16Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 17Hospital Clínico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; 18GSK, Baar, Switzerland; 19GSK, London, UK; 20University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands [Slide 3] High rate of cCR12 + pCR was observed with dostarlimab alone cCR12 = Patients who achieved cCR after dostarlimab monotherapy and maintained for ≥12 mo with no additional treatment Legend: cCR with 12 months follow up (n=98) | nCR (n=3) | SD (n=10) | PD (n=8) | Late cCR (n=8) | *pCR after dostarlimab alone (n=12) | PR (n=13) | N/A (n=10) | cCR with <12 months follow up (n=10) cCR with <12 mo follow-up (n=10) | cCR with ≥12 months follow-up* (n=98) | Non-cCR12 (n=46) End of treatment response (N=154) cCR12 (n=98) + pCR (n=12): 76% (110/144) †Patients who were not evaluable (n=4) have been pooled with those who were N/A (n=6): four patients did not reach end of treatment response assessment and did not initiate SOC treatment; six patients did not undergo end of treatment response assessment but were recorded as continuing on study and received SOC. cCR, clinical complete response; cCR12, clinical complete response for ≥12 months; mo, months; N/A, not available; nCR, near complete response; pCR, pathological complete response; PD, progressive disease; PR, partial response; SD, stable disease; SOC, standard of care. Dr Andrea Cercek

Figure 2. Response after dostarlimab treatment EOT response assessment: cCR; nCR; PR; SD; NA; PD *Assessments after EOT response assessment: cCR; pCR with dostarlimab alone cCR12 (INV): 98/144 68% (95% CI: 60-76) cCR12 (ICR): 54/116 47% (95% CI: 37-56) Legend: cCR12 responder; Non-evaluable for cCR12; cCR12-non-responder (pCR with dostarlimab alone); cCR12 non-responder Clinical response is shown for each patient at EOT response assessment and at further follow-up to date. cCR, clinical complete response; cCR12, clinical complete response at 12 months; CI, confidence interval; ICR, independent central review; INV, investigator-assessed; NA, not applicable; nCR, near-complete response; NR, no response; pCR, pathologic complete response; PD, progressive disease; PR, partial response; SD, stable disease.

[Slide 2] High rate of clinical complete responses (cCR) was observed after dostarlimab alone Legend: cCR (n=102) | Late cCR (n=8)* | nCR (n=9) | PR (n=15) | SD (n=10) | N/A (n=10) | PD (n=8) cCR: 66% (n=102) | nCR: 6% (n=9) | PR: 10% (n=15) | SD: 6% (n=10) | N/A: 7% (n=10)† | PD: 5% (n=8) End of treatment response (N=154) cCR 71% (110/154) [Footnote, small/blurred:] *8 patients converted from nCR/PR to cCR at any time; †Patients who were not evaluable (n=4) have been pooled with those who were N/A (n=6): four patients did not reach end of treatment response assessment and did not initiate SOC treatment; six patients did not undergo end of treatment response assessment but were recorded as continuing on study and received SOC. cCR, clinical complete response; N/A, not available; nCR, near complete response; pCR, pathological complete response; PD, progressive disease; PR, partial response; SD, stable disease. Dr Andrea Cercek [Slide 3] High rate of cCR12 + pCR was observed with dostarlimab alone cCR12 = Patients who achieved cCR after dostarlimab monotherapy and maintained for ≥12 mo with no additional treatment Legend: cCR with 12 months follow up (n=98) | pCR after dostarlimab alone (n=12) | nCR (n=3) | PR (n=13) | SD (n=10) | N/A (n=10) | PD (n=8) | ↓ Late cCR (n=8) | cCR with <12 months follow up (n=10) cCR with <12 mo follow-up (n=10) | cCR with ≥12 months follow-up* (n=98) | Non-cCR12 (n=46) End of treatment response (N=154) cCR12 (n=98) + pCR (n=12): 76% (110/144) [Footnote, small/blurred: patients not evaluable (n=4) pooled with N/A (n=6) ...; abbreviations] Dr Andrea Cercek

High rate of cCR12 was observed with dostarlimab alone cCR12 = Patients who achieved cCR after dostarlimab monotherapy and maintained for ≥12 mo with no additional treatment Legend: cCR with <12 mo follow-up (n=10); cCR with ≥12 mo follow-up (n=98); Non-cCR12 (n=46); Late cCR (n=8) cCR with <12 mo follow-up (n=10) | cCR with ≥12 months follow-up* (n=98) | Non-cCR12 (n=46) Patients evaluable for cCR12 = 144 cCR12 by INV: 68% (98/144) [Footnotes as on the sharper copy: sufficient follow-up definition; N/A pooling (n=4 not evaluable + n=6 N/A); abbreviations] Dr Andrea Cercek

[Slide 1] Abstract Proffered Paper session LBA78 - Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) Speakers Sanjiv S. Gangaram-Panday (Rotterdam, Netherlands) Lecture Time 13:40 - 13:50 Abstract Background The Surgery As Needed for Oesophageal cancer (SANO)-trial demonstrated that active surveillance is non-inferior to standard surgery in terms of two-year overall survival in patients with a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). Active surveillance resulted in improved quality of life. Here, we report 5-year outcomes. [Slide 2] Methods From 2017 to 2021, a multicentre stepped-wedge cluster-randomised non-inferiority trial was conducted. Patients with locally advanced oesophageal cancer who achieved complete clinical response (defined as no tumour detected on endoscopic biopsies, -ultrasound, or PET-CT) underwent active surveillance or standard surgery. Cox regression was used to compare 5-year overall and disease-free survival, and the cumulative incidence of distant metastases was estimated using competing risk analysis. [Slide 3] Results A total of 309 patients were included, 198 underwent active surveillance and 111 underwent standard surgery. Median follow-up was 76 months (IQR 67–86). Five-year overall survival was not statistically significantly different between active surveillance and standard surgery (50%, 95%CI 34-57 vs. 54%, 95%CI 46-64; HR 1.17, 95%CI 0.77-1.77) with similar results across histologic subtypes. Disease-free survival was not statistically significantly different (HR 1.39, 95% CI 0.94-2.06). The cumulative incidence of distant metastases at five years was significantly higher in the active surveillance group compared to the standard surgery group (46%, 95%CI 39-53 vs. 29%, 95%CI 21-37; P<.01). Overall, 85 of 198 patients (43%) were spared non-beneficial oesophagectomy, including those with sustained complete clinical response at last follow-up or distant metastases detected within six months after nCRT. Conclusions Overall survival at 5 years is not statistically significantly different between active surveillance and standard surgery in patients with oesophageal cancer and a complete clinical response after nCRT, despite a higher incidence of distant metastases in the active surveillance group. These findings support active surveillance as a feasible treatment strategy in these patients.

Background The Surgery As Needed for Oesophageal cancer (SANO)-trial demonstrated that active surveillance is non-inferior to standard surgery in terms of two-year overall survival in patients with a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). Active surveillance resulted in improved quality of life. Here, we report 5-year outcomes. Methods From 2017 to 2021, a multicentre stepped-wedge cluster-randomised non-inferiority trial was conducted. Patients with locally advanced oesophageal cancer who achieved complete clinical response (defined as no tumour detected on endoscopic biopsies, -ultrasound, or PET-CT) underwent active surveillance or standard surgery. Cox regression was used to compare 5-year overall and disease-free survival, and the cumulative incidence of distant metastases was estimated using competing risk analysis. Results A total of 309 patients were included, 198 underwent active surveillance and 111 underwent standard surgery. Median follow-up was 76 months (IQR 67–86). Five-year overall survival was not statistically significantly different between active surveillance and standard surgery (50%, 95%CI 34-57 vs. 54%, 95%CI 46-64; HR 1.17, 95%CI 0.77-1.77) with similar results across histologic subtypes. Disease-free survival was not statistically significantly different (HR 1.39, 95% CI 0.94-2.06). The cumulative incidence of distant metastases at five years was significantly higher in the active surveillance group compared to the standard surgery group (46%, 95%CI 39-53 vs. 29%, 95%CI 21-37; P<.01). Overall, 85 of 198 patients (43%) were spared non-beneficial oesophagectomy, including those with sustained complete clinical response at last follow-up or distant metastases detected within six months after nCRT. Conclusions Overall survival at 5 years is not statistically significantly different between active surveillance and standard surgery in patients with oesophageal cancer and a complete clinical response after nCRT, despite a higher incidence of distant metastases in the active surveillance group. These findings support active surveillance as a feasible treatment strategy in these patients.

[Slide 1] Methods Design • Phase III, stepped-wedge, cluster-randomised trial • Non-inferiority design Patients • Locally advanced oesophageal cancer • nCRT according to the CROSS regimen • cCR at 12 weeks after nCRT (CRE-2) [Slide 2] Cause-specific mortality Legend: Active surveillance (red); Surgery (blue); death by oesophageal cancer (solid); death by other cause (dashed) Y axis: Cumulative incidence (%); X axis: Time (months) 0-60 End-of-curve labels at 60 months: 40%, 30%, 15%, 10% death by oesophageal cancer: sHR 1.67, 95%CI 1.02-2.73, p=0.04 death by other cause: sHR 0.49, 95%CI 0.22-1.09, p=0.08 Number at risk Active surveillance: 198 178 150 120 106 98 Surgery: 111 97 78 70 63 60 Survival table Endpoint: Cause-specific mortality (cumulative incidence; competing risks) Active surveillance | 198 Surgery | 111 HR: sHR 1.67 (death by oesophageal cancer); sHR 0.49 (death by other cause) HR CI: 1.02-2.73; 0.22-1.09 P: 0.04; 0.08 Landmark rates: 60 mo: Active surveillance - death by oesophageal cancer 40% | Surgery - death by oesophageal cancer 30% | Surgery - death by other cause 15% | Active surveillance - death by other cause 10% [Slide 3] Distant dissemination rate Legend: Active surveillance; Surgery Y axis: Cumulative incidence (%); X axis: Time (months) 0-60 End-of-curve labels at 60 months: 46% (active surveillance), 29% (surgery) sHR 2.04, 95%CI 1.25-3.34, p < 0.01 Number at risk Active surveillance: 198 156 123 98 94 85 Surgery: 111 88 69 63 60 56 Survival table Endpoint: Distant dissemination (cumulative incidence) Active surveillance | 198 Surgery | 111 HR: sHR 2.04 HR CI: 1.25-3.34 P: < 0.01 Landmark rates: 60 mo: Active surveillance 46% | Surgery 29% [Slide 4] Conclusions • 5-year overall survival was not statistically significantly different • Distant metastases were significantly higher with active surveillance • 43% of patients avoided oesophagectomy • These findings support the concept of active surveillance after nCRT

13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Conclusions • 5-year overall survival was not statistically significantly different • Distant metastases were significantly higher with active surveillance • 43% of patients avoided oesophagectomy • These findings support the concept of active surveillance after nCRT Sanjiv Gangaram-Panday Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) ALMERIA AUDITORIUM - HALL 9

Active surveillance | Surgery Overall survival (%) Time (months) Number at risk (number censored) (months 0, 12, 24, 36, 48, 60) Active surveillance | 198 (0) | 178 (0) | 150 (0) | 120 (1) | 106 (1) | 98 (1) Surgery | 111 (0) | 97 (0) | 78 (0) | 70 (0) | 63 (0) | 60 (0) [Watermark: Pre-proof] Survival table Endpoint: Overall survival Active surveillance | 198 Surgery | 111

[Slide 1] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Disease-free survival Legend: Active surveillance / Surgery HR 1.39, 95% CI 0.94-2.06, p = 0.10 Y-axis: Disease-free survival (%); X-axis: Time (months) 0-60 Number at risk (number censored) (months 0, 12, 24, 36, 48, 60) Active surveillance: 198 (0) 156 (0) 118 (0) 97 (1) 91 (1) 82 (1) Surgery: 111 (0) 87 (0) 67 (0) 62 (0) 59 (0) 55 (0) Sanjiv Gangaram-Panday Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: Disease-free survival Active surveillance | 198 Surgery | 111 HR: 1.39 HR CI: 95% CI 0.94-2.06 P: 0.10 [Slide 2] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Distant dissemination rate Legend: Active surveillance / Surgery sHR 2.04, 95%CI 1.25-3.34, p < 0.01 Y-axis: Cumulative incidence (%); X-axis: Time (months) 0-60 Curve end labels: 46% (active surveillance), 29% (surgery) Number at risk (months 0, 12, 24, 36, 48, 60) Active surveillance: 198 156 123 98 94 85 Surgery: 111 88 69 63 60 56 Sanjiv Gangaram-Panday Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: Distant dissemination (cumulative incidence) Active surveillance | 198 Surgery | 111 HR: sHR 2.04 HR CI: 95% CI 1.25-3.34 P: <0.01 Landmark rates: 60 mo (curve end label): Active surveillance 46% | Surgery 29% [Slide 3] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Cause-specific mortality Legend: Active surveillance / Surgery / — death by oesophageal cancer / - - death by other cause death by oesophageal cancer: sHR 1.67, 95%CI 1.02-2.73, p=0.04 death by other cause: sHR 0.49, 95%CI 0.22-1.09, p=0.08 Y-axis: Cumulative incidence (%); X-axis: Time (months) 0-60 Curve end labels: 40%, 30% (solid lines, death by oesophageal cancer); 15%, 10% (dashed lines, death by other cause) Number at risk (months 0, 12, 24, 36, 48, 60) Active surveillance: 198 178 150 120 106 98 Surgery: 111 97 78 70 63 60 Sanjiv Gangaram-Panday Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: Cause-specific mortality (cumulative incidence) Active surveillance | 198 Surgery | 111 HR: death by oesophageal cancer sHR 1.67; death by other cause sHR 0.49 HR CI: 1.02-2.73; 0.22-1.09 P: 0.04; 0.08 Landmark rates: 60 mo (curve end label), death by oesophageal cancer: Active surveillance 40% | Surgery 30% 60 mo (curve end label), death by other cause: Surgery 15% | Active surveillance 10% [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Complete clinical responders Active surveillance (n=198): • 16% (n=32) developed distant metastases (11% (n=22) within 6 months post-nCRT) • 51% (n=101) developed locoregional regrowth • 1% (n=1) developed second primary oesophageal tumour • 32% (n=64) maintained CCR Hypothetical 43% avoided oesophagectomy Sanjiv Gangaram-Panday Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) ALMERIA AUDITORIUM - HALL 9

[Slide 1] Overall survival Legend: Active surveillance; Surgery HR 1.17, 95% CI 0.77-1.77, p = 0.46 5-year RMST: -0.32 months 95% CI -6.29 to 5.65, p = 0.92 Overall survival (%); Time (months) Number at risk (number censored) (0, 12, 24, 36, 48, 60): Active surveillance: 198 (0), 178 (0), 150 (0), 120 (1), 106 (1), 98 (1) Surgery: 111 (0), 97 (0), 78 (0), 70 (0), 63 (0), 60 (0) Survival table Endpoint: Overall survival Active surveillance | 198 Surgery | 111 HR: 1.17 HR CI: 0.77-1.77 P: 0.46 [Slide 2] Disease-free survival Legend: Active surveillance; Surgery HR 1.39, 95% CI 0.94-2.06, p = 0.10 Disease-free survival (%); Time (months) Number at risk (number censored) (0, 12, 24, 36, 48, 60): Active surveillance: 198 (0), 156 (0), 118 (0), 97 (1), 91 (1), 82 (1) Surgery: 111 (0), 87 (0), 67 (0), 62 (0), 59 (0), 55 (0) Survival table Endpoint: Disease-free survival Active surveillance | 198 Surgery | 111 HR: 1.39 HR CI: 0.94-2.06 P: 0.10 [Slide 3] Complete clinical responders Active surveillance (n=198): • 16% (n=32) developed distant metastases (11% (n=22) within 6 months post-nCRT) • 51% (n=101) developed locoregional regrowth • 1% (n=1) developed second primary oesophageal tumour • 32% (n=64) maintained CCR Hypothetical 43% avoided oesophagectomy

Proffered Paper session LBA78 - Active surveillance versus standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results of a cluster-randomised controlled trial (SANO) Speakers Sanjiv S. Gangaram-Panday (Rotterdam, Netherlands) Lecture Time 13:40 - 13:50 Abstract Background The Surgery As Needed for Oesophageal cancer (SANO)-trial demonstrated that active surveillance is non-inferior to standard surgery in terms of two-year overall survival in patients with a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). Active surveillance resulted in improved quality of life. Here, we report 5-year outcomes. Methods From 2017 to 2021, a multicentre stepped-wedge cluster-randomised non-inferiority trial was conducted. Patients with locally advanced oesophageal cancer who achieved complete clinical response (defined as no tumour detected on endoscopic biopsies, -ultrasound, or PET-CT) underwent active surveillance or standard surgery. Cox regression was used to compare 5-year overall and disease-free survival, and the cumulative incidence of distant metastases was estimated using competing risk analysis.

[Slide 1] Disease-free survival Legend: Active surveillance — Surgery HR 1.39, 95% CI 0.94-2.06, p = 0.10 Y-axis: Disease-free survival (%) X-axis: Time (months) Number at risk (number censored) Active surveillance (red): 198 (0) | 156 (0) | 118 (0) | 97 (1) | 91 (1) | 82 (1) Surgery (blue): 111 (0) | 87 (0) | 87 (0) | 62 (0) | 59 (0) | 55 (0) (time points 0, 12, 24, 36, 48, 60 months) Survival table Endpoint: Disease-free survival Active surveillance | 198 Surgery | 111 HR: 1.39 HR CI: 0.94-2.06 P: 0.10 [Slide 2] Distant dissemination rate Legend: Active surveillance — Surgery sHR 2.04, 95%CI 1.25-3.34, p < 0.01 Y-axis: Cumulative incidence (%) X-axis: Time (months) End-of-curve labels: Active surveillance 4[illegible]% ; Surgery 2[illegible]% Number at risk Active surveillance (red): 198 | 156 | 123 | 98 | 94 | 85 Surgery (blue): 111 | 88 | 69 | 63 | 60 | 56 (time points 0, 12, 24, 36, 48, 60 months) Survival table Endpoint: Distant dissemination rate (cumulative incidence) Active surveillance | 198 Surgery | 111 HR: sHR 2.04 HR CI: 1.25-3.34 P: <0.01 [Slide 3] Cause-specific mortality Legend: Active surveillance — Surgery — death by oesophageal cancer --- death by other cause death by oesophageal cancer: sHR 1.67, 95%CI 1.02-2.73, p=0.04 death by other cause: sHR 0.49, 95%CI 0.22-1.09, p=0.08 Y-axis: Cumulative incidence (%) X-axis: Time (months) End-of-curve labels: 40% ; 30% ; 15% ; 10% Number at risk Active surveillance (red): 198 | 178 | 150 | 120 | 108 | 98 Surgery (blue): 111 | 97 | 78 | 70 | 63 | 60 (time points 0, 12, 24, 36, 48, 60 months) Survival table Endpoint: Cause-specific mortality (cumulative incidence; death by oesophageal cancer and by other cause) Active surveillance | 198 Surgery | 111 HR: death by oesophageal cancer: sHR 1.67; death by other cause: sHR 0.49 HR CI: 1.02-2.73; 0.22-1.09 P: 0.04; 0.08

[KM figure with shaded confidence bands] Legend: Active surveillance | Surgery Y-axis: Overall survival (%) ; X-axis: Time (months) 0, 12, 24, 36, 48, 60 Number at risk (number censored): Active surveillance: 198 (0), 178 (0), 150 (0), 120 (1), 106 (1), 98 (1) Surgery: 111 (0), 97 (0), 78 (0), 70 (0), 63 (0), 60 (0) Survival table Endpoint: Overall survival Active surveillance | 198 Surgery | 111

[Slide 1] Antitumour Activity of INCB161734 + SoC Chemotherapy in Patients With mPDAC INCB161734 1200 mg qd Response, % (n/N) | GEMNabP (n=26)* | mFOLFIRINOX (n=27)† ORR‡,§ | 69 (18/26) | 89 (24/27) ORR‡ (confirmed + pending) | 58 (15/26) | 81 (22/27) DCR‡,§ | 96 (25/26) | 100 (27/27) [Waterfall plot] Best Percent Change From Baseline; Chemotherapy regimen: GEMNabP / mFOLFIRINOX; → Ongoing; bars labelled SD / PR / CR; Prior lines¶ • Median duration of efficacy follow-up was 7.2 months for INCB161734 + GEMNabP and 5.6 months for INCB161734 + mFOLFIRINOX|| • Plasma ctDNA analysis demonstrated high rates of rapid molecular responses for INCB161734 + GEMNabP (74%) and mFOLFIRINOX (69%)** *1 patient receiving INCB161734 + GEMNabP was included in the efficacy evaluable population but was not included in the waterfall plot due to death before the first scan. †1 patient was removed from the efficacy evaluable population due to an early adverse event. ‡Assessed in patients with a baseline scan and at least 1 of the following: ≥1 postbaseline scan or discontinued treatment due to death or PD. §Data include unconfirmed responses. ¶In the advanced/metastatic setting. ||Calculated by the reverse Kaplan-Meier method. **Molecular response: ≥90% reduction in KRAS G12D VAF by week 8, assessed by ddPCR or NGS (Predicine) for all patients with baseline G12D VAF and week 8 data. CR, complete response; ctDNA, circulating tumour DNA; DCR, disease control rate; ddPCR, droplet digital polymerase chain reaction; GEMNabP, nab-paclitaxel + gemcitabine; mFOLFIRINOX, modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin; mPDAC, metastatic pancreatic ductal adenocarcinoma; NGS, next-generation sequencing; ORR, objective response rate; PD, progressive disease; PR, partial response; qd, daily; SD, stable disease; SoC, standard of care; VAF, variant allele frequency. [Slide 2] Durable Benefit With INCB161734 + SoC Chemotherapy in mPDAC • PFS at 6 months was 80% for INCB161734 + GEMNabP and 90% for INCB161734 + mFOLFIRINOX [Swimmer plot] INCB161734 + GEMNabP / INCB161734 + mFOLFIRINOX; Duration of Treatment (Weeks) Legend: CR, PR, SD, PD, Death, Ongoing Assessed in patients with a baseline scan and at least one of the following: ≥1 postbaseline scan or discontinued treatment due to death or PD. CR, complete response; GEMNabP, nab-paclitaxel + gemcitabine; mFOLFIRINOX, modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin; mPDAC, metastatic pancreatic ductal adenocarcinoma; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; SoC, standard of care. [Slide 3] Safety: INCB161734 in Combination With mFOLFIRINOX | INCB161734 1200 mg qd + mFOLFIRINOX (n=28) Any TRAE, n (%)* | 28 (100) TRAE leading to INCB161734 Interruption | 11 (39) Reduction | 6 (21) Discontinuation | 0 TRAE leading to chemotherapy (any component)† Interruption | 22 (79) Reduction | 16 (57) Discontinuation | 9 (32) RDI, median %‡ INCB161734 | 77 mFOLFIRINOX (cycles 1-4) | 67 mFOLFIRINOX† | 53 INCB161734 1200 mg qd + mFOLFIRINOX (n=28) TRAE, n (%)§ | Any grade | Grade 1/2 | Grade ≥3 Diarrhoea | 19 (68) | 16 (57) | 3 (11) Nausea | 18 (64) | 17 (61) | 1 (4) Vomiting | 16 (57) | 14 (50) | 2 (7) Decreased neutrophil count¶ | 16 (57) | 6 (21) | 10 (36) Fatigue | 15 (54) | 12 (43) | 3 (11) Anaemia | 11 (39) | 8 (29) | 3 (11) Decreased platelet count|| | 9 (32) | 4 (14) | 5 (18) Peripheral sensory neuropathy | 9 (32) | 9 (32) | 0 Decreased appetite | 7 (25) | 7 (25) | 0 Dysgeusia** | 7 (25) | 7 (25) | NA • The safety profile of INCB161734 + GEMNabP or mFOLFIRINOX was broadly consistent with the established profiles of the SoC regimens • No fatal TRAEs were recorded *Assessed in patients who received ≥1 dose of study drug. †Median duration of treatment was 7.0 months. ‡Chemotherapy dose intensity was derived as the minimum RDI among all chemotherapy components. §Includes any-grade TRAEs that occurred in ≥20% of patients. ¶Includes neutropenia and neutrophil count decreased. ||Includes thrombocytopenia and platelet count decreased. **The maximum possible severity per CTCAE for dysgeusia is grade 2. CTCAE, Common Terminology Criteria for Adverse Events; GEMNabP, nab-paclitaxel + gemcitabine; mFOLFIRINOX, modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin; NA, not applicable; qd, daily; RDI, relative dose intensity; SoC, standard of care; TRAE, treatment-related adverse event. [Slide 4] Conclusions • The favourable safety and tolerability profile for INCB161734 1200 mg qd + GEMNabP or mFOLFIRINOX in patients with mPDAC was broadly consistent with the established profiles of the SoC regimens • GI TRAEs were mostly grade 1/2 and improved during treatment • The incidence of TRAEs leading to INCB161734 treatment discontinuation was low • Deep and durable treatment responses were observed • ORR (DCR) was 69% (96%) for INCB161734 + GEMNabP and 89% (100%) for INCB161734 + mFOLFIRINOX • 6-month PFS landmark rates were 80% for INCB161734 + GEMNabP and 90% for INCB161734 + mFOLFIRINOX • Encouraging clinical efficacy supports the ongoing global phase 3 DAWN-303 trial evaluating SoC chemotherapy in combination with INCB161734 or placebo in patients with 1L mPDAC (NCT07522073) • DAWN-303 is actively enrolling globally 1L, first-line; DCR, disease control rate; GEMNabP, nab-paclitaxel + gemcitabine; GI, gastrointestinal; KRAS, Kirsten rat sarcoma; mFOLFIRINOX, modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin; mPDAC, metastatic pancreatic ductal adenocarcinoma; ORR, objective response rate; PFS, progression-free survival; qd, daily; SoC, standard of care; TRAE, treatment-related adverse event.

Antitumour Activity of INCB161734 + SoC Chemotherapy in Patients With mPDAC INCB161734 1200 mg qd Response, % (n/N) | GEMNabP (n=26) | mFOLFIRINOX (n=27) ORR | 69 (18/26) | 89 (24/27) ORR (confirmed + pending) | 58 (15/26) | 81 (22/27) DCR | 96 (25/26) | 100 (27/27) Best Percent Change From Baseline Chemotherapy regimen: GEMNabP; mFOLFIRINOX; Ongoing Prior lines • Median duration of efficacy follow-up was 7.2 months for INCB161734 + GEMNabP and 5.6 months for INCB161734 + mFOLFIRINOX • Plasma ctDNA analysis demonstrated high rates of rapid molecular responses for INCB161734 + GEMNabP (74%) and mFOLFIRINOX (69%)

[Slide 1] RAS mutations distribution PDAC (N=73): KG12D 40%; KG12V 35%; KG12R 11%; RAS Others 14% NSCLC (N=18): KG12D 34%; KG12V 22%; KG12C 11%; RAS others 33% Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China Lung (N=481): G12C 30%; G12D 22%; 19%; 7%; 4%; [smaller slices illegible] Legend: p.G12C, p.G12D, p.G12V, p.G12A, p.G13D, p.Q61H, p.G13C, p.Q61L, p.G12S, p.A146T, p.G12R, p.G12F, p.Q61K, p.Q61R, Other Wu L et al, J Cancer Res Clin Oncol 2025 Francesco Facchinetti [Slide 2] INCB161734 in Combination With Cetuximab Showed Encouraging Antitum[or] Activity in Heavily Pretreated Patients With KRASG12D-Mutated Metastatic C[RC] [title cropped at right edge] % (n/N) | INCB161734 monotherapy (n=24) ORR* | 8 (2/24) DCR* | 79 (19/24) % (n/N) | INCB161734 + cetuximab (n=22) ORR* | 36 (8/22) DCR* | 100 (22/22) Waterfall plots: Best Percent Change From Baseline; Ongoing Prior lines (monotherapy, partial): 2 3 2 2 3 3 4 3 1 4 3 3 4 3 7 1 2 3 3 5 6 2 2 Prior lines (combination, partial): 2 6 2 2 2 3 2 1 2 3 7 2 3 3 2 2 2 *Assessed in patients who received INCB161734 at 1200 mg qd with a baseline scan and at least 1 of the following: >=1 postbaseline scan, study discontinuation due to death or PD. Data include unconfirmed responses. [rest cropped] CR, complete response; CRC, colorectal cancer; DCR, disease control rate; KRAS, Kirsten rat sarcoma; ORR, objective response rate; PD, progressive disease; PR, partial response; qd, daily; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. [Slide 3] Safety: INCB161734 ± Cetuximab in Patients With Metastatic CRC - TRAEs led to INCB161734 dose reductions in 8% of patients with both monotherapy and in combination with cetuximab - No grade 4 or 5 TRAEs were observed with INCB161734 monotherapy or INCB161734 + cetuximab - Higher incidences of rash, fatigue, and electrolyte abnormalities were observed with INCB161734 + cetuximab, consistent with th[e] cetuximab safety profile INCB161734 1200 mg qd | Monotherapy (n=24) | + Cetuximab (n=25) [row label cropped] n (%) [...]AE | 22 (92) | 25 (100) [...] TRAE | 2 (8) | 7 (28) [...]eading to INCB161734 [...]ption | 3 (13) | 8 (32) [...]tion | 2 (8) | 2 (8) [...]tinuation | 0 (0) | 0 (0) [...]ading to cetuximab [...]ption | NA | 10 (40) [...]ion | NA | 3 (12) [...]inuation | NA | 1 (4) TRAEs*†‡ Monotherapy (n=24), % | + Cetuximab (n=25), % Rash§ | 8 | [illegible] Diarrhoea | 67 | [illegible] Nausea | 67 | [illegible] Vomiting | 58 | 60 Fatigue | 4 | 44 Lipase increased | 17 | 24 Hypomagnesemia | 0 | 24 Neutropenia | 8 | 16 Stomatitis | 4 | 16 Dry skin | 0 | 16 Decreased appetite | 21 | 12 Amylase increased | 8 | 12 Hypokalemia | 0 | 12 Paronychia | 0 | 12 Dehydration | 0 | 12 Dysgeusia¶ | 13 | 8 *Assessed in patients who received >=1 dose of study drug. †Related to INCB161734 monotherapy or related to any study drug for combination therapy. ‡Occurring in >=10% of patients in either treatment group. §Includes rash, dermatitis acneiform, rash maculo-papu[lar]... ¶The maximum possible severity per CTCAE for dysgeusia is grade 2. CRC, colorectal cancer; CTCAE, Common Terminology Criteria for Adverse Events; KRAS, Kirsten rat sarcoma; NA, not applicable; qd, daily; TRAE, treatment-related adverse event. [Slide 4] Relevant considerations - First KRAS G12D selective inhibitor with clear activity in colorectal cancer - ON/OFF inhibitor, did lessons from KRAS G12C help to get straight there? - Curious to see the PFS of INCB161734 monotherapy - First-line with FOLFOX! Francesco Facchinetti

CHAIRS: CHIARA BRACONI, MONICA NIGER, ANNA SABOROWSKI Phase 1 Evaluation of INCB161734 Plus SoC Chemotherapy in mPDAC (NCT06179160) Key Eligibility Criteria • Locally advanced or metastatic PDAC with KRAS G12D mutation* • ECOG PS 0 or 1 • No prior treatment with a KRAS G12D selective inhibitor • Dose escalation: ≤1 prior systemic regimen in the metastatic setting† • Dose expansion: no prior regimen in the metastatic setting† Key Endpoints • Safety and tolerability • Efficacy (ORR, DCR, DOR, and PFS) Chemotherapy Regimens GEMNabP: D1, D8, D15 of 28D cycle. Gemcitabine 1000 mg/m², nab-paclitaxel 125 mg/m² mFOLFIRINOX: D1, D15 of 28D cycle. Oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150-180 mg/m², fluorouracil 2400 mg/m² Dose Escalation‡ INCB161734 1200 mg qd + GEMNabP (n=5) INCB161734 600 mg qd + GEMNabP (n=12) INCB161734 1200 mg qd + mFOLFIRINOX (n=7) INCB161734 600 mg qd + mFOLFIRINOX (n=10) Selected RDE Dose Expansion‡ INCB161734 1200 mg qd + GEMNabP (n=21) INCB161734 1200 mg qd + mFOLFIRINOX (n=21) Data cut-off date: July 6, 2026. [illegible footnotes]

Conclusions • The favourable safety and tolerability profile for INCB161734 1200 mg qd + GEMNabP or mFOLFIRINOX in patients with mPDAC was broadly consistent with the established profiles of the SoC regimens – GI TRAEs were mostly grade 1/2 and improved during treatment – The incidence of TRAEs leading to INCB161734 treatment discontinuation was low • Deep and durable treatment responses were observed – ORR (DCR) was 69% (96%) for INCB161734 + GEMNabP and 89% (100%) for INCB161734 + mFOLFIRINOX – 6-month PFS landmark rates were 80% for INCB161734 + GEMNabP and 90% for INCB161734 + mFOLFIRINOX • Encouraging clinical efficacy supports the ongoing global phase 3 DAWN-303 trial evaluating SoC chemotherapy in combination with INCB161734 or placebo in patients with 1L mPDAC (NCT07522073) – DAWN-303 is actively enrolling globally

[Slide 1] Patient Disposition and Baseline Characteristics • As of July 6, 2026, 54 patients with mPDAC received INCB161734 1200 mg qd in combination with chemotherapy • 26 patients received INCB161734 in combination with GEMNabP • Median (range) duration of INCB161734 treatment was 7.6 (0.5, 9.1) months • Treatment ongoing in 16 (62%) • Primary reason for discontinuation was progressive disease (n=8; 31%)* • 28 patients received INCB161734 in combination with mFOLFIRINOX • Median (range) duration of INCB161734 treatment was 7.0 (0.6, 11.7) months • Treatment ongoing in 23 (82%) • Primary reason for discontinuation was progressive disease (n=4; 14%)† INCB161734 1200 mg qd | GEMNabP (n=26) | mFOLFIRINOX (n=28) Age, median (range), years: 62 (35, 77) | 63 (37, 77) ≥65 years, n (%): 11 (42) | 13 (46) ECOG PS, n (%) 0: 13 (50) | 12 (43) 1: 13 (50) | 16 (57) Metastatic disease at diagnosis, n (%): 12 (46) | 25 (89) Liver metastases, n (%): 22 (85) | 24 (86) Prior neoadjuvant/adjuvant therapy, n (%): 10 (38) | 3 (11) Total prior systemic therapy, n (%) 0: 14 (54) | 24 (86) 1: 12 (46) | 3 (11) 2: 0 | 1 (4) Prior lines of systemic therapy in the metastatic setting, n (%) 0: 24 (92) | 26 (93) 1: 2 (8) | 2 (7) *2 patients discontinued with the primary reason of adverse event. †1 patient discontinued with the primary reason of adverse event. ECOG PS, Eastern Cooperative Oncology Group performance status; GEMNabP, nab-paclitaxel + gemcitabine; KRAS, Kirsten rat sarcoma; mFOLFIRINOX, modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin; mPDAC, metastatic pancreatic ductal adenocarcinoma; qd, daily. [Slide 2] Safety: INCB161734 in Combination With GEMNabP INCB161734 1200 mg qd + GEMNabP (n=26) Any TRAE, n (%)*: 26 (100) TRAE leading to INCB161734 Interruption: 19 (73) Reduction: 6 (23) Discontinuation: 1 (4) TRAE leading to chemotherapy (any component)† Interruption: 22 (85) Reduction: 18 (69) Discontinuation: 8 (31) RDI, median %‡ INCB161734: 85 GEMNabP (cycles 1-4): 69 GEMNabP†: 49 TRAE, n (%)§ | Any grade | Grade 1/2 | Grade ≥3 Diarrhoea: 17 (65) | 16 (62) | 1 (4) Nausea: 17 (65) | 16 (62) | 1 (4) Decreased neutrophil count¶: 17 (65) | 2 (8) | 15 (58) Anaemia: 15 (58) | 5 (19) | 10 (38) Vomiting: 12 (46) | 9 (35) | 3 (12) Fatigue: 12 (46) | 7 (27) | 5 (19) Pyrexia: 10 (38) | 9 (35) | 1 (4) Decreased platelet count‖: 9 (35) | 4 (15) | 5 (19) Alopecia: 7 (27) | 7 (27) | 0 Decreased appetite: 7 (27) | 7 (27) | 0 ALT increased: 6 (23) | 6 (23) | 0 Dysgeusia**: 6 (23) | 6 (23) | NA Oedema peripheral: 6 (23) | 6 (23) | 0 Peripheral sensory neuropathy: 6 (23) | 6 (23) | 0 *Assessed in patients who received ≥1 dose of study drug. †Median duration of treatment was 7.6 months. ‡Chemotherapy dose intensity was derived as the minimum RDI among all chemotherapy components. §Includes any-grade TRAEs that occurred in ≥20% of patients. ¶Includes neutropenia and neutrophil count decreased. ‖Includes thrombocytopenia and platelet count decreased. **The maximum possible severity per CTCAE for dysgeusia is grade 2. [Slide 4] Antitumour Activity of INCB161734 + SoC Chemotherapy in Patients With mPDAC INCB161734 1200 mg qd Response, % (n/N) | GEMNabP (n=26)* | mFOLFIRINOX (n=27)† ORR‡,§: 69 (18/26) | 89 (24/27) ORR‡ (confirmed + pending): 58 (15/26) | 81 (22/27) DCR‡,§: 96 (25/26) | 100 (27/27) Best Percent Change From Baseline Chemotherapy regimen: GEMNabP / mFOLFIRINOX / → Ongoing Prior lines¶ • Median duration of efficacy follow-up was 7.2 months for INCB161734 + GEMNabP and 5.6 months for INCB161734 + mFOLFIRINOX‖ • Plasma ctDNA analysis demonstrated high rates of rapid molecular responses for INCB161734 + GEMNabP (74%) and mFOLFIRINOX (69%)** *1 patient receiving INCB161734 + GEMNabP was included in the efficacy evaluable population but was not included in the waterfall plot due to death before the first scan. †1 patient was removed from the efficacy evaluable population due to an early adverse event. ‡Assessed in patients with a baseline scan and at least 1 of the following: ≥1 postbaseline scan or discontinued treatment due to death or PD. §Data include unconfirmed responses. ¶In the advanced/metastatic setting. ‖Calculated by the reverse Kaplan-Meier method. **Molecular response: ≥90% reduction in KRAS G12D VAF by week 8, assessed by ddPCR or NGS (Predicine) for all patients with baseline G12D VAF and week 8 data.

Phase 1 Evaluation of INCB161734 Plus SoC Chemotherapy in mPDAC (NCT06179160) Key Eligibility Criteria • Locally advanced or metastatic PDAC with KRAS G12D mutation* • ECOG PS 0 or 1 • No prior treatment with a KRAS G12D selective inhibitor • Dose escalation: ≤1 prior systemic regimen in the metastatic setting† • Dose expansion: no prior regimen in the metastatic setting† Key Endpoints • Safety and tolerability • Efficacy (ORR, DCR, DOR, and PFS) Chemotherapy Regimens GEMNabP: D1, D8, D15 of 28D cycle. Gemcitabine 1000 mg/m², nab-paclitaxel 125 mg/m² mFOLFIRINOX: D1, D15 of 28D cycle. Oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150-180 mg/m², fluorouracil 2400 mg/m² Dose Escalation‡ INCB161734 1200 mg qd + GEMNabP (n=5) INCB161734 600 mg qd + GEMNabP (n=12) INCB161734 1200 mg qd + mFOLFIRINOX (n=7) INCB161734 600 mg qd + mFOLFIRINOX (n=10) Selected RDE Dose Expansion‡ INCB161734 1200 mg qd + GEMNabP (n=21) INCB161734 1200 mg qd + mFOLFIRINOX (n=21) Data cut-off date: July 6, 2026. *Determined by local testing. †Neoadjuvant or adjuvant therapy may be counted as 1 line of therapy if recurrence/development of metastatic disease occurred within 6 months of the last dose of therapy; patients who received no standard systemic therapy for PDAC may have received ≤1 cycle of GEMNabP or mFOLFIRINOX before enrolling. ‡Treated until start of new anticancer therapy, disease progression, unacceptable toxicity, death, withdrawal of consent, discontinuation or the end of the study.

Introduction [Mechanism illustration] INCB161734; binds GTP-bound KRAS (Active) ON; binds GDP-bound KRAS (Inactive) OFF; INC; GTP; GDP; RAF; MEK; ERK; mFOLFIRINOX or GemNabP; PDAC; 39.5% • PDAC is the sixth leading cause of cancer deaths worldwide1 – 1L chemotherapies for patients with mPDAC have limited benefit2 • PDAC is primarily a KRAS-driven cancer3 – KRAS G12D is the most frequent oncogenic driver, occurring in ~40% of patients • INCB161734 is a potent and selective ON/OFF oral KRAS G12D inhibitor4 • Phase 1 results demonstrated INCB161734 monotherapy efficacy and manageable safety in patients with KRAS G12D solid tumours, including mPDAC5 • INCB161734 1200 mg qd was tolerable when combined with SoC chemotherapy in patients with mPDAC6 • Here, we report updated efficacy and safety data for INCB161734 in combination with SoC chemotherapy in patients with KRAS G12D mPDAC 1. Sung H, et al. CA Cancer J Clin. 2026;76:e70090. 2. Koopman M, et al. ESMO Gastrointest Oncol. 2025;9:100214. 3. Lee JK, et al. NPJ Precis Onc. 2022;6:91. 4. Farren MR, et al. Presented at: AACR 2024; San Diego, CA, USA. Poster 5900. 5. Desai J, et al. Presented at: ESMO 2025; Berlin, Germany. Oral 9160. 6. Wainberg Z, et al. Presented at: ASCO GI 2026; San Francisco, CA, USA. Oral 654.

MADRID 2026 ESMO congress Safety and Efficacy of INCB161734, a Novel Oral KRAS G12D Inhibitor, in Combination With Chemotherapy in Patients With Advanced/Metastatic Pancreatic Ductal Adenocarcinoma Antoine Hollebecque,1 Haeseong Park,2 Jason Henry,3 Davide Melisi,4 Lillian L. Siu,5 Philippe Cassier,6 Eileen M. O'Reilly,7 Mitesh J. Borad,8 Lipika Goyal,9 Rasha Cosman,10 Sabine Tejpar,11 Shigehisa Kitano,12 Manuel Hidalgo,13 Shubham Pant,14 Jayesh Desai,15 Amanda McBride,16 Linda Favre-Kontula,17 Feng Zhou,16 Aidan Gilmartin,16 Zev Wainberg18 Presentation number: 3137RO

[Slide 1] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH RASolute 302 Study Design Key eligibility criteria: - Adults with mPDAC - One prior fluoropyrimidine- or gemcitabine-based regimen in the metastatic setting - ECOG PS 0-1 - Documented tumor RAS mutational status^a by local testing R 1:1 -> Daraxonrasib 300 mg, PO QD Investigator's choice of chemotherapy (1 of 4): GnP, mFOLFIRINOX, NAL-IRI + 5-FU/LV, FOLFOX Dual primary endpoints - OS and PFS (per BICR)^b (RAS G12 population) Key secondary endpoints - OS and PFS (per BICR)^b (overall population^c) - ORR^b (per BICR) (RAS G12 and overall populations) - TTD in PROs^d (RAS G12 and overall populations) Stratification factors: - ECOG PS (0 vs 1) - Metastatic disease at diagnosis (yes vs no) - Liver metastases at baseline (yes vs no) - Tumor RAS mutational status (RAS G12D/V vs other RAS G12 vs RAS G13 or Q61 mutation or no RAS mutation identified) Global enrollment: 59 sites across 6 countries NCT06625320. ^aEither mutant, defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61), or no RAS mutation identified. ^bPer RECIST 1.1. ^cIncluding patients whose tumors harbor RAS G12, G13, or Q61 mutations, or had no RAS mutation identified. ^dTTD in symptom of pain and in global health status/quality of life. Presented by Zev A. Wainberg, MD, MSc [Speaker panel] Zev Wainberg - Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study ALMERIA AUDITORIUM - HALL 9 [Slide 2] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH RASolute 302 Primary Analysis Results - In the Phase 3 RASolute 302 study in patients with previously treated mPDAC, daraxonrasib demonstrated statistically significant and clinically meaningful improvements in OS, PFS, ORR, and quality of life vs SOC chemotherapy in both the RAS G12 and overall populations^1 - Daraxonrasib is approved in the US for patients with mPDAC who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy^2 - Daraxonrasib is recommended in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)^3 - Daraxonrasib also received a positive CHMP opinion in the EU for the treatment of patients with mPDAC who have received at least one prior systemic therapy^4 OS in the Overall Population | | Daraxonrasib (n=248) | Chemo (n=252) | No. of events, n (%) | 79 (32) | 141 (56) mOS, months (95% CI) | 13.2 (10.0-NE) | 6.7 (5.8-8.0) HR (95% CI)^a | 0.40 (0.30-0.53) P-value^b | p=4.6×10^-11 Curve labels at 12 months: 53.2% (daraxonrasib), 17.3% (chemo) No. at risk (Months 0-16) Daraxonrasib: 248 240 237 225 208 188 165 125 90 62 37 24 11 7 4 1 0 Chemo: 252 235 217 193 161 126 108 78 53 35 21 10 5 2 0 ^aHRs and 95% CIs were based on the stratified Cox model with Efron's method of tie handling. ^bP-values were calculated using the stratified log-rank test. 1. O'Reilly EM, et al. N Engl J Med. 2026;395(4):325-337; 2. FDA Press Release. August 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma. Accessed August 27, 2026; 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.4.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed October 5, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. European Medicines Agency. October 15, 2026. CHMP Summary of Positive Opinion for Rasonque (Daraxonrasib). CHMP Ref No. EMADOC-1829012207-72049. Presented by Zev A. Wainberg, MD, MSc [Speaker panel] Zev Wainberg - Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: OS, overall population Arm | N | Median | Median CI Daraxonrasib | 248 | 13.2 months | 10.0-NE Chemo (SOC) | 252 | 6.7 months | 5.8-8.0 HR: 0.40 HR CI: 0.30-0.53 P: 4.6×10^-11 Landmark rates: 12 months: Daraxonrasib 53.2% | Chemo 17.3% [Slide 3] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH PFS by RAS Genotype Subgroups PFS by BICR | PFS by investigator Tumor RAS mutational status^a | Events/N Daraxonrasib | Chemo | PFS HR (95% CI)^c || Events/N Daraxonrasib | Chemo | PFS HR (95% CI)^c Overall | 127/248 | 130/252 | 0.55 (0.43-0.70) || 135/248 | 149/252 | 0.48 (0.38-0.61) RAS G12D | 53/95 | 74/121 | 0.48 (0.33-0.69) || 53/95 | 79/121 | 0.43 (0.30-0.62) RAS G12V | 39/102 | 29/76 | 0.54 (0.33-0.87) || 46/102 | 36/76 | 0.51 (0.33-0.80) RAS G12R | 19/30 | 16/31 | 0.80 (0.41-1.56) || 22/30 | 17/31 | 0.73 (0.38-1.39) Other RAS mutation^b | 9/11 | 7/14 | 1.29 (0.47-3.51) || 7/11 | 9/14 | 0.57 (0.21-1.56) RAS Q61 | 9/11 | 5/11 | 1.55 (0.51-4.69) || 7/11 | 7/11 | 0.63 (0.22-1.83) No RAS mutation identified | 6/9 | 2/7 | 1.92 (0.39-9.52) || 6/9 | 6/7 | 0.62 (0.20-1.94) [axis 0.05 0.5 1.0 5 10; Favors Daraxonrasib | Favors Chemo] PFS results generally favored daraxonrasib versus SOC chemotherapy across RAS genotype subgroups, although treatment-effect estimates differed between BICR and investigator assessments, particularly in smaller subgroups Data cutoff: 10 Feb 2026. ^aLocally determined. Only subgroups with ≥5 patients in at least one treatment arm were included. ^bOther RAS mutations include RAS Q61 and RAS G13. ^cHRs and 95% CIs overall and for subgroups were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc [Speaker panel] Zev Wainberg - Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study ALMERIA AUDITORIUM - HALL 9 [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH OS by Preselected SOC Chemotherapy Regimen^a GnP: Daraxonrasib (n=140) | Chemo (n=141); HR (95% CI)^c 0.45 (0.32-0.65) mFOLFIRINOX/FOLFOX^b: Daraxonrasib (n=30) | Chemo (n=30); HR (95% CI)^c 0.46 (0.23-0.95) NAL-IRI + 5-FU/LV: Daraxonrasib (n=78) | Chemo (n=81); HR (95% CI)^c 0.32 (0.18-0.58) No. at risk (Months 0-16) GnP Daraxonrasib: 140 136 136 127 116 110 94 72 50 32 17 12 3 2 0 GnP Chemo: 141 131 121 110 88 69 59 43 27 19 9 5 3 2 0 mFOLFIRINOX/FOLFOX Daraxonrasib: 30 27 26 25 22 21 20 15 13 8 5 4 3 2 2 0 mFOLFIRINOX/FOLFOX Chemo: 30 28 25 22 18 14 13 8 6 5 4 3 2 0 NAL-IRI + 5-FU/LV Daraxonrasib: 78 77 75 73 70 57 51 38 27 22 15 8 5 3 2 1 0 NAL-IRI + 5-FU/LV Chemo: 81 76 71 61 55 43 36 27 20 11 8 2 0 Data cutoff: 10 Feb 2026. Median (range) follow-up time was 8.5 (3.2-15.9) months. ^aInvestigator's choice of chemotherapy was determined prior to randomization. ^bmFOLFIRINOX and FOLFOX regimens were pooled due to small individual sample sizes. ^cHRs and 95% CIs were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc [Speaker panel] Zev Wainberg - Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: OS by preselected SOC chemotherapy regimen GnP cohort - Daraxonrasib | 140 GnP cohort - Chemo | 141 mFOLFIRINOX/FOLFOX cohort - Daraxonrasib | 30 mFOLFIRINOX/FOLFOX cohort - Chemo | 30 NAL-IRI + 5-FU/LV cohort - Daraxonrasib | 78 NAL-IRI + 5-FU/LV cohort - Chemo | 81 HR: GnP 0.45; mFOLFIRINOX/FOLFOX 0.46; NAL-IRI + 5-FU/LV 0.32 HR CI: GnP 0.32-0.65; mFOLFIRINOX/FOLFOX 0.23-0.95; NAL-IRI + 5-FU/LV 0.18-0.58

[Slide 1] Proffered Paper session LBA82 - Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study Speakers Zev A. Wainberg (Los Angeles, United States of America) Lecture Time 14:22 - 14:32 Abstract Background Multiagent systemic chemo offers limited benefit in mPDAC. Aberrant RAS(ON) signaling drives PDAC; >90% of cases harbor mutant (mut) RAS, and RAS WT PDAC remains dependent on RAS pathway signaling. Daraxonrasib is an oral, RAS(ON) multi-selective, tri-complex inhibitor of active, GTP-bound mut and WT RAS. Daraxonrasib significantly improved OS and PFS vs SOC chemo in pts with previously treated mPDAC overall (with or without an identified tumor RAS mut; mOS 13.2 vs 6.7 mo; HR, 0.40; mPFS 7.2 vs 3.6 mo; HR, 0.49) and in pts with RAS G12 mut mPDAC (OS HR, 0.40; PFS HR, 0.45) with manageable safety in the RASolute 302 primary analysis (NCT06625320). We report additional subgroup analyses from RASolute 302. [Slide 2] OS in subgroups | | n (%) Daraxonrasib n=248 | Chemo n=252 | OS HR (95% CI) | Tumor RAS mut status | G12D | 95 (38) | 121 (48) | 0.49 (0.33-0.74) | | G12V | 102 (41) | 76 (30) | 0.32 (0.19-0.54) | | G12R | 30 (12) | 31 (12) | 0.61 (0.29-1.30) | | RAS Q61 | 11 (4) | 11 (4) | 0.37 (0.09-1.44) | | No RAS mut identified | 9 (4) | 7 (3) | 0.43 (0.09-1.98) | Conclusions Daraxonrasib demonstrated OS benefit vs chemo across clinically relevant subgroups including pts with or without an identified tumor RAS mut. Directionally consistent OS benefit across these subgroups further reinforces the potential for daraxonrasib to be a new SOC for eligible pts with mPDAC. [Slide 3] Methods Pts with previously treated mPDAC were randomized 1:1 to daraxonrasib 300 mg PO QD or investigator's choice of SOC chemo (GnP, mFOLFIRINOX, Nal-IRI+5-FU/LV, or FOLFOX). Dual primary endpoints (EPs) were OS and PFS in the RAS G12 mut population; key secondary EPs included OS and PFS in the overall population. Additional analyses evaluated OS in clinically relevant subgroups by locally determined tumor RAS mut status, preselected chemo regimen, and disease setting of prior treatment. Results At data cutoff (10 Feb 2026), median follow-up was 8.5 mo (range, 3.2-15.9). OS benefit with daraxonrasib vs chemo was observed across all RAS mut subgroups (Table). Daraxonrasib showed a consistent OS treatment effect across preselected chemo subgroups (HRs, 0.32-0.46). OS data by disease setting of prior treatment will also be presented. Table: LBA82

[Slide 2] ORR by RAS Genotype Subgroups Tumor RAS mutational status(b) | ORR by BICR (PR+CR/n(a)), % Daraxonrasib (n=248) | Chemo (n=252) | ORR by investigator (PR+CR/n(a)), % Daraxonrasib (n=248) | Chemo (n=252) Overall | 32% (75/237) | 11% (27/241) | 24% (60/248) | 8% (21/252) RAS G12D | 24% (23/95) | 9% (11/116) | 18% (17/95) | 6% (7/121) RAS G12V | 50% (47/94) | 15% (11/73) | 37% (38/102) | 14% (11/76) RAS G12R | 7% (2/27) | 14% (4/29) | 10% (3/30) | 3% (1/31) Other RAS mutation(c) | 18% (2/11) | 0% (0/14) | 18% (2/11) | 7% (1/14) RAS Q61 | 18% (2/11) | 0% (0/11) | 18% (2/11) | 9% (1/11) No RAS mutation identified | 11% (1/9) | 17% (1/6) | 0% (0/9) | 14% (1/7) Daraxonrasib generally showed ORR improvements compared with SOC chemotherapy across RAS genotype subgroups by both BICR and investigator assessments, with differences seen between assessments Data cutoff: 10 Feb 2026. (a)Patients with measurable disease at baseline were included. (b)Locally determined. Only subgroups with ≥5 patients in at least one treatment arm were included. (c)Other RAS mutations include RAS Q61 and RAS G13. Presented by Zev A. Wainberg, MD, MSc [Slide 3] OS by Preselected SOC Chemotherapy Regimen(a) GnP: Daraxonrasib (n=140) | Chemo (n=141) — HR (95% CI)(c) 0.45 (0.32–0.65) mFOLFIRINOX/FOLFOX(b): Daraxonrasib (n=30) | Chemo (n=30) — HR (95% CI)(c) 0.46 (0.23–0.95) NAL-IRI + 5-FU/LV: Daraxonrasib (n=78) | Chemo (n=81) — HR (95% CI)(c) 0.32 (0.18–0.58) [Three KM panels; y-axis: OS Probability (%); x-axis: Months 0–16] No. at risk (low resolution, monthly 0 onward): GnP — Daraxonrasib: 140 136 136 127 116 110 94 72 50 32 17 12 3 2 0; Chemo: 141 131 121 110 88 69 59 43 27 19 9 5 3 2 0 mFOLFIRINOX/FOLFOX — Daraxonrasib: 30 27 26 25 22 21 20 15 13 8 5 4 3 2 2 0; Chemo: 30 28 25 22 18 14 13 8 6 5 4 3 2 0 NAL-IRI + 5-FU/LV — Daraxonrasib: 78 77 75 73 70 67 51 38 27 22 15 8 5 3 2 1 0; Chemo: 81 76 71 61 55 43 36 27 20 11 8 2 0 Data cutoff: 10 Feb 2026. Median (range) follow-up time was 8.5 (3.2–15.9) months. (a)Investigator's choice of chemotherapy was determined prior to randomization. (b)mFOLFIRINOX and FOLFOX regimens were pooled due to small individual sample sizes. (c)HRs and 95% CIs were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc Survival table Endpoint: Overall survival by preselected SOC chemotherapy regimen (subgroups) GnP subgroup: Daraxonrasib | 140 GnP subgroup: Chemo | 141 mFOLFIRINOX/FOLFOX subgroup: Daraxonrasib | 30 mFOLFIRINOX/FOLFOX subgroup: Chemo | 30 NAL-IRI + 5-FU/LV subgroup: Daraxonrasib | 78 NAL-IRI + 5-FU/LV subgroup: Chemo | 81 HR: GnP 0.45; mFOLFIRINOX/FOLFOX 0.46; NAL-IRI + 5-FU/LV 0.32 HR CI: 0.32–0.65; 0.23–0.95; 0.18–0.58 [Slide 4] OS by Disease Setting of Prior Treatment Metastatic disease <6 months after neoadjuvant/adjuvant therapy(a): Daraxonrasib (n=42) | Chemo (n=34) — HR (95% CI)(b) 0.36 (0.17–0.75) One prior line of therapy for metastatic disease: Daraxonrasib (n=206) | Chemo (n=218) — HR (95% CI)(b) 0.43 (0.32–0.58) [Two KM panels; y-axis: OS Probability (%); x-axis: Months 0–16] No. at risk (monthly from 0): Metastatic <6 mo — Daraxonrasib: 42 41 41 37 37 36 32 27 22 16 9 6 2 2 2 0; Chemo: 34 31 27 24 22 18 17 15 9 4 1 1 1 0 One prior line — Daraxonrasib: 206 199 196 188 171 152 133 98 68 46 28 18 9 5 2 1 0; Chemo: 218 204 190 169 139 108 91 63 44 31 20 9 4 2 0 Data cutoff: 10 Feb 2026. Median (range) follow-up time was 8.5 (3.2–15.9) months. (a)Patients received prior neoadjuvant or adjuvant treatment but were diagnosed with metastatic disease <6 months from the last dose. Under the study criteria, this was considered first-line treatment in the metastatic setting. (b)HRs and 95% CIs were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc Survival table Endpoint: Overall survival by disease setting of prior treatment (subgroups) Metastatic <6 mo after (neo)adjuvant: Daraxonrasib | 42 Metastatic <6 mo after (neo)adjuvant: Chemo | 34 One prior metastatic line: Daraxonrasib | 206 One prior metastatic line: Chemo | 218 HR: Metastatic <6 mo 0.36; One prior line 0.43 HR CI: 0.17–0.75; 0.32–0.58

[Slide 1] RAS Genotype Distribution • Consistent with the expected distribution of RAS mutations in PDAC, RAS G12 variants predominated; G13, Q61, and no RAS mutation identified were uncommon RAS genotypes in PDAC1 Reported real-world prevalence KRAS G12D (39.9%) KRAS G12V (28.6%) KRAS G12R (14.6%) KRAS G12C (1.7%) KRAS Q61 (6.3%) KRAS G13 (0.8%) NRAS (0.2%) RAS WT (8%) RAS genotypes in RASolute 302a RAS G12D (43.2%) RAS G12V (35.6%) RAS G12R (12.2%) Other RAS G12c (0.8%) RAS Q61 (4.4%) RAS G13 (0.6%) No RAS mutation identifiedb (3.2%) aLocally determined at a data cutoff of 10 Feb 2026. bPatients with no identified tumor RAS mutation but with other known driver mutations (eg, BRAF V600E, MSI-H/dMMR, NTRK gene fusion) for which there is local regulatory approval must have received appropriate targeted therapy. cOther RAS G12 includes KRAS G12N, KRAS G12A, KRAS G12C, and KRAS G12L mutations. 1. Pant S, et al. J Clin Oncol. 2025;43:777. Presented by Zev A. Wainberg, MD, MSc [Slide 3] PFS by RAS Genotype Subgroups PFS by BICR | PFS by investigator Tumor RAS mutational statusa | Events/N Daraxonrasib | Chemo | PFS HR (95% CI)c | Events/N Daraxonrasib | Chemo | PFS HR (95% CI)c Overall | 127/248 | 130/252 | 0.55 (0.43–0.70) | 135/248 | 149/252 | 0.48 (0.38–0.61) RAS G12D | 53/95 | 74/121 | 0.48 (0.33–0.69) | 53/95 | 79/121 | 0.43 (0.30–0.62) RAS G12V | 39/102 | 29/76 | 0.54 (0.33–0.87) | 46/102 | 36/76 | 0.51 (0.33–0.80) RAS G12R | 19/30 | 16/31 | 0.80 (0.41–1.56) | 22/30 | 17/31 | 0.73 (0.38–1.39) Other RAS mutationb | 9/11 | 7/14 | 1.29 (0.47–3.51) | 7/11 | 9/14 | 0.57 (0.21–1.56) RAS Q61 | 9/11 | 5/11 | 1.55 (0.51–4.69) | 7/11 | 7/11 | 0.63 (0.22–1.83) No RAS mutation identified | 6/9 | 2/7 | 1.92 (0.39–9.52) | 6/9 | 6/7 | 0.62 (0.20–1.94) [forest plot axis 0.05 0.5 1.0 5 10; Favors Daraxonrasib | Favors Chemo] PFS results generally favored daraxonrasib versus SOC chemotherapy across RAS genotype subgroups, although treatment-effect estimates differed between BICR and investigator assessments, particularly in smaller subgroups Data cutoff: 10 Feb 2026. aLocally determined. Only subgroups with ≥5 patients in at least one treatment arm were included. bOther RAS mutations include RAS Q61 and RAS G13. cHRs and 95% CIs overall and for subgroups were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc [Slide 4] Conclusions • In the Phase 3 RASolute 302 study, daraxonrasib demonstrated significant improvement in OS in the overall patient population (mOS: 13.2 months vs 6.7 months; HR, 0.40 [95% CI: 0.30–0.53]) • OS improvement was observed across all RAS genotype subgroups, regardless of identified tumor RAS mutational status, as expected based on daraxonrasib's mechanism of action • ORR and PFS (by BICR and investigator) generally favored daraxonrasib across subgroups • OS improvement with daraxonrasib was also maintained across preselected standard of care chemotherapy regimens or prior treatment settings, including early metastatic recurrence following perioperative therapy Consistent OS improvement across key patient subgroups reinforces daraxonrasib as a new standard of care for previously treated mPDAC Presented by Zev A. Wainberg, MD, MSc

[phone UI overlay: "1 de 1"] OS by RAS Genotype Subgroups Tumor RAS mutational status^a | Events/N Daraxonrasib | Chemo | OS HR (95% CI)^c Overall | 79/248 | 141/252 | 0.42 (0.32–0.55) RAS G12D | 37/95 | 71/121 | 0.49 (0.33–0.74) RAS G12V | 22/102 | 39/76 | 0.32 (0.19–0.54) RAS G12R | 12/30 | 16/31 | 0.61 (0.29–1.30) Other RAS mutation^b | 3/11 | 10/14 | 0.29 (0.08–1.06) RAS Q61 | 3/11 | 7/11 | 0.37 (0.09–1.44) No RAS mutation identified | 4/9 | 4/7 | 0.43 (0.09–1.98) Axis: 0.05 0.5 1.0 2.0 — Favors Daraxonrasib / Favors Chemo Daraxonrasib showed OS improvement compared with SOC chemotherapy across all RAS genotype subgroups Data cutoff: 10 Feb 2026. ^aLocally determined. ^bOther RAS mutations include RAS Q61 and RAS G13. ^cThe size of diamonds is relative to the size of the population in each subgroup. HRs and 95% CIs overall and for subgroups were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc

OS by RAS Genotype Subgroups Events/N Tumor RAS mutational status(a) | Daraxonrasib | Chemo | OS HR (95% CI)(c) Overall | 79/248 | 141/252 | 0.42 (0.32-0.55) RAS G12D | 37/95 | 71/121 | 0.49 (0.33-0.74) RAS G12V | 22/102 | 39/76 | 0.32 (0.19-0.54) RAS G12R | 12/30 | 16/31 | 0.61 (0.29-1.30) Other RAS mutation(b) | 3/11 | 10/14 | 0.29 (0.08-1.06) RAS Q61 | 3/11 | 7/11 | 0.37 (0.09-1.44) No RAS mutation identified | 4/9 | 4/7 | 0.43 (0.09-1.98) [Forest plot axis: 0.05, 0.5, 1.0, 2.0; Favors Daraxonrasib <- | -> Favors Chemo] Daraxonrasib showed OS improvement compared with SOC chemotherapy across all RAS genotype subgroups Data cutoff: 10 Feb 2026. (a)Locally determined. (b)Other RAS mutations include RAS Q61 and RAS G13. (c)The size of diamonds is relative to the size of the population in each subgroup. HRs and 95% CIs overall and for subgroups were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc

Baseline Demographics and Disease Characteristics Columns: Overall^1: Daraxonrasib (n=248) | Chemo (n=252); Preselected SOC chemo regimen^b: GnP: Daraxonrasib (n=140) | Chemo (n=141); mFOLFIRINOX/FOLFOX^c: Daraxonrasib (n=30) | Chemo (n=30); NAL-IRI + 5-FU/LV: Daraxonrasib (n=78) | Chemo (n=81) Age, median (range), years: 66 (30-88) | 65 (36-86) | 64 (30-85) | 63 (36-86) | 70 (47-88) | 66 (51-82) | 67 (43-87) | 68 (46-86) ECOG PS, n (%) 0: 129 (52) | 118 (47) | 80 (57) | 70 (50) | 13 (43) | 5 (17) | 36 (46) | 43 (53) 1^a: 119 (48) | 134 (53) | 60 (43) | 71 (50) | 17 (57) | 25 (83) | 42 (54) | 38 (47) Metastatic disease at diagnosis, n (%): 154 (62) | 154 (61) | 93 (66) | 102 (72) | 21 (70) | 15 (50) | 40 (51) | 37 (46) Prior 5-FU-based regimen, n (%): 181 (73) | 186 (74) | 139 (99) | 141 (100) | 6 (20) | 9 (30) | 36 (46) | 36 (44) Prior gemcitabine-based regimen, n (%): 110 (44) | 114 (45) | 5 (4) | 4 (3) | 29 (97) | 30 (100) | 76 (97) | 80 (99) Liver metastases at baseline, n (%): 174 (70) | 176 (70) | 105 (75) | 109 (77) | 22 (73) | 21 (70) | 47 (60) | 46 (57) Tumor RAS mutational status, n (%) RAS G12D/V: 197 (79) | 197 (78) | 111 (79) | 109 (77) | 22 (73) | 22 (73) | 64 (82) | 66 (81) Other RAS G12: 31 (13) | 34 (13) | 19 (14) | 24 (17) | 4 (13) | 5 (17) | 8 (10) | 5 (6) RAS G13 or Q61, or no RAS mutation identified: 20 (8) | 21 (8) | 10 (7) | 8 (6) | 4 (13) | 3 (10) | 6 (8) | 10 (12) - Baseline characteristics for patients diagnosed with metastatic disease <6 months from the last dose of neoadjuvant/adjuvant therapy (n=76) and those who received one prior line of therapy for metastatic disease (n=424) were balanced between arms Key baseline characteristics and prognostic factors for subgroups were generally consistent with the overall population and balanced between arms Data cutoff: 10 Feb 2026. ^aThree patients (including 2 patients randomized to the daraxonrasib arm and 1 patient randomized to the chemotherapy arm) had ECOG PS >1 at baseline. These patients were not dosed due to no longer meeting study eligibility criteria. ^bInvestigator's choice of chemotherapy was determined prior to randomization. ^cmFOLFIRINOX and FOLFOX regimens were pooled due to small individual sample sizes. 1. O'Reilly EM, et al. N Engl J Med. 2026;395:325-337. Presented by Zev A. Wainberg, MD, MSc

PFS by RAS Genotype Subgroups Tumor RAS mutational status(a) | PFS by BICR: Events/N Daraxonrasib | Chemo | PFS HR (95% CI)(c) || PFS by investigator: Events/N Daraxonrasib | Chemo | PFS HR (95% CI)(c) Overall: 127/248 | 130/252 | 0.55 (0.43-0.70) || 135/248 | 149/252 | 0.48 (0.38-0.61) RAS G12D: 53/95 | 74/121 | 0.48 (0.33-0.69) || 53/95 | 79/121 | 0.43 (0.30-0.62) RAS G12V: 39/102 | 29/76 | 0.54 (0.33-0.87) || 46/102 | 36/76 | 0.51 (0.33-0.80) RAS G12R: 19/30 | 16/31 | 0.80 (0.41-1.56) || 22/30 | 17/31 | 0.73 (0.38-1.39) Other RAS mutation(b): 9/11 | 7/14 | 1.29 (0.47-3.51) || 7/11 | 9/14 | 0.57 (0.21-1.56) RAS Q61: 9/11 | 5/11 | 1.55 (0.51-4.69) || 7/11 | 7/11 | 0.63 (0.22-1.8[cut off]) No RAS mutation identified: 6/9 | 2/7 | 1.92 (0.39-9.52) || 6/9 | 6/7 | 0.62 (0.20-1.9[cut off]) [Forest plots, axis 0.05-10; Favors Daraxonrasib / Favors Chemo] PFS results generally favored daraxonrasib versus SOC chemotherapy across RAS genotype subgroups, although treatment-effect estimates differed between BICR and investigator assessments, particularly in smaller subgroups Data cutoff: 10 Feb 2026. aLocally determined. Only subgroups with >=5 patients in at least one treatment arm were included. bOther RAS mutations include RAS Q61 and RAS G13. cHRs and 95% CIs overall and for subgroups were based on the unstratified Cox model with Efron's method of tie handling. Presented by Zev A. Wainberg, MD, MSc [Orange hand-drawn annotation circling RAS G12R row]

[Slide 1] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH G-HOPE-001 study design An open-label, phase 3 study conducted in China and Japan (NCT06238843) Key inclusion criteria: - Adults ≥18 years old - ECOG PS 0-1 - Locally advanced unresectable or metastatic G/GEJA - CLDN18.2-positive by central or local immunohistochemistry* - Received and progressed on 2-4 prior therapies which must include fluoropyrimidine, platinum, and a taxane or irinotecan Key exclusion criteria: - Positive HER2(†) - History of treatment with topoisomerase inhibitor-based ADCs R(‡) 1:1 Arcotatug tavatecan (AT) 6 mg/kg Q3W Treatment of physician's choice (TPC): Irinotecan, paclitaxel, trifluridine/tipiracil Treatment continuation until: Completion of 24 months of study treatment; Disease progression and/or lack of clinical benefit(||); Loss of follow-up; Death; Intolerable toxicity; Withdrawal of informed consent Primary endpoints: PFS by IRRC per RECIST v1.1; OS(§) Secondary endpoints included: ORR per RECIST v1.1; Safety *Defined as CLDN18.2 IHC membrane staining intensity ≥2+ in ≥75% of tumour cells. For participants who have previously received any anti-CLDN18.2 therapy, tumour samples were obtained after discontinuation of prior anti-CLDN18.2 therapy. †Defined as IHC 3+, or IHC 2+ and positive by in situ hybridization. ‡Stratification factors include region (China vs. Japan), primary tumour site (stomach vs. gastroesophageal junction) and history of prior gastrectomy (yes vs. no). ||Patients could continue to receive study treatment after disease progression as long as they continued to show clinical benefit. §In Japan the single primary endpoint is OS. ADC, antibody-drug conjugate; CLDN18.2, claudin18.2; ECOG PS, Eastern Cooperative Oncology Group performance status; G/GEJA, gastric or gastroesophageal junction adenocarcinoma; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; IRRC, independent radiological review committee; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks; R, randomisation; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1 [Speaker panel] Kohei Shitara - Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 ... ALMERIA AUDITORIUM - HALL 9 [Slide 2] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Final PFS by IRRC at IA1: primary endpoint | Arcotatug tavatecan (N=203) | TPC (N=205) Event, n (%) | 74 (36.5) | 90 (43.9) Median (95% CI) | 5.5 (4.3, 8.2) | 2.9 (2.6, 3.4) HR (95% CI) | 0.47 (0.34, 0.65) P-value (2-sided) | <0.0001 Curve labels at 6 months: 48.5% (AT); 24.0% (TPC) Y-axis: Progression free survival (%); X-axis: Months (0-15) At risk (censored) at 0/3/6/9/12/15 months: Arcotatug tavatecan: 203 (0), 78 (82), 29 (110), 10 (124), 1 (129), 0 (129) TPC: 205 (0), 43 (92), 7 (111), 2 (113), 1 (114), 0 (115) - AT demonstrated a statistically significant and clinically meaningful improvement in PFS demonstrating a ~53% reduction in risk of progression or death. Consistent benefit was observed by investigator assessment (HR 0.39; 95% CI, 0.30-0.53). ITT population. Median and 95% CI are estimated using Kaplan-Meier method. P-value is from the stratified log-rank test; HR and 95% CI are from stratified Cox proportional hazards model. Median follow-up duration for PFS by IRRC at IA1: AT, 4.2 months (95% CI, 2.9-4.4); TPC, 2.9 months (95% CI, 2.7-3.4). 3L+, third-line or later; CI, confidence interval; CLDN18.2, claudin18.2; G/GEJA, gastric or gastroesophageal junction adenocarcinoma; HR, hazard ratio; IA1, interim analysis 1; IRRC, independent radiological review committee; ITT, intent-to-treat; IA1, interim analysis 1; PFS, progression-free survival; TPC, treatment of physician's choice. [Speaker panel] Kohei Shitara - Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 ... ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: PFS by IRRC at IA1 (primary endpoint, ITT) Arm | N | Median | Median CI Arcotatug tavatecan | 203 | 5.5 mo | 4.3, 8.2 TPC | 205 | 2.9 mo | 2.6, 3.4 HR: 0.47 HR CI: 0.34, 0.65 P: <0.0001 (2-sided) Landmark rates: 6 mo: Arcotatug tavatecan 48.5% | TPC 24.0% [Slide 3] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH OS at IA2: primary endpoint | Arcotatug tavatecan (N=230) | TPC (N=230) Event, n (%) | 122 (53.0) | 159 (69.1) Median (95% CI) | 10.2 (9.1, 12.3) | 6.9 (5.7, 7.8) HR (95% CI) | 0.57 (0.45, 0.73) P-value (2-sided) | <0.0001 Curve labels: 6 months 71.6% (AT), 54.5% (TPC); 12 months 43.2% (AT), 24.7% (TPC) Y-axis: Overall survival (%); X-axis: Months (0-24) At risk (censored) at 0/3/6/9/12/15/18/21/24 months: Arcotatug tavatecan: 230 (0), 218 (0), 149 (16), 88 (52), 43 (78), 14 (98), 7 (103), 1 (107), 0 (108) TPC: 230 (0), 181 (3), 113 (14), 52 (45), 26 (56), 10 (65), 3 (70), 2 (71), 0 (71) - AT demonstrated a statistically significant and clinically meaningful improvement in OS vs. TPC for CLDN18.2+ G/GEJA in the 3L+ setting, demonstrating a ~43% reduction in risk of death ITT population. Median and 95% CI are estimated using Kaplan-Meier method. Median follow-up duration for OS at IA2: AT, 11.1 months (95% CI, 9.8, 12.1); TPC, 11.2 months (95% CI, 9.9, 12.7). 3L+, third-line or later; AT, arcotatug tavatecan; CI, confidence interval; CLDN18.2, claudin18.2; G/GEJA, gastric or gastroesophageal junction adenocarcinoma; HR, hazard ratio; IA2, interim analysis 2; ITT, intent-to-treat; OS, overall survival; TPC, treatment of physician's choice. [Speaker panel] Kohei Shitara - Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 ... ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: OS at IA2 (primary endpoint, ITT) Arm | N | Median | Median CI Arcotatug tavatecan | 230 | 10.2 mo | 9.1, 12.3 TPC | 230 | 6.9 mo | 5.7, 7.8 HR: 0.57 HR CI: 0.45, 0.73 P: <0.0001 (2-sided) Landmark rates: 6 mo: Arcotatug tavatecan 71.6% | TPC 54.5% 12 mo: Arcotatug tavatecan 43.2% | TPC 24.7% [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Conclusions - The phase 3 G-HOPE-001 study evaluating AT vs. TPC in patients with CLDN18.2+ G/GEJA in the 3L+ setting reached prespecified primary endpoints with statistically significant and clinically meaningful improvements in both PFS and OS: - PFS: At IA1, median 5.5 vs. 2.9 months (HR 0.47; 95% CI 0.34, 0.65; p<0.0001); at IA2, median 7.1 vs. 3.1 months (descriptive) - OS: At IA2, median 10.2 vs. 6.9 months (HR 0.57; 95% CI 0.45, 0.73; p<0.0001) - AT demonstrated a favourable safety profile, with manageable GI and haematological toxicities that were consistent with findings from prior studies - These results support arcotatug tavatecan (AT), a novel Fc-silenced CLDN18.2-targeted ADC, as an effective treatment option in the 3L+ setting for patients with CLDN18.2-positive, HER2-negative G/GEJA 3L+, third-line or later; ADC, antibody-drug conjugate; AT, arcotatug tavatecan; CI, confidence interval; CLDN18.2, claudin18.2; Fc, fragment crystallizable; G/GEJA, gastric or gastroesophageal junction adenocarcinoma; GI, gastrointestinal; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IA1, interim analysis 1; IA2, interim analysis 2; OS, overall survival; PFS, progression-free survival; TPC, treatment of physician's choice. [Speaker panel] Kohei Shitara - Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 ... ALMERIA AUDITORIUM - HALL 9

[Slide 2] OS at IA2: primary endpoint [KM curve: Overall survival (%) vs Months] Landmarks printed: 6 mo: AT 71.6%, TPC 54.5%; 12 mo: AT 43.2%, TPC 24.7% Table: Arcotatug tavatecan (N=230) | TPC (N=230) Event, n (%): 122 (53.0) | 159 (69.1) Median (95% CI): 10.2 (9.1, 12.3) | 6.9 (5.7, 7.8) HR (95% CI): 0.57 (0.45, 0.73) P-value (2-sided): <0.0001 At risk (censored), months 0/3/6/9/12/15/18/21/24: Arcotatug tavatecan: 230 (0), 218 (0), 149 (16), 88 (52), 43 (78), 14 (98), 7 (103), 1 (107), 0 (108) TPC: 230 (0), 181 (3), 113 (14), 52 (45), 26 (56), 10 (65), 3 (70), 2 (71), 0 (71) • AT demonstrated a statistically significant and clinically meaningful improvement in OS vs. TPC for CLDN18.2+ G/GEJA in the 3L+ setting, demonstrating a ~43% reduction in risk of death ITT population. Median and 95% CI are estimated using Kaplan–Meier method. Median follow-up duration for OS at IA2: AT, 11.1 months (95% CI, 9.8, 12.1); TPC, 11.2 months (95% CI, 9.9, 12.7). 3L+, third-line or later; AT, arcotatug tavatecan; CI, confidence interval; CLDN18.2, claudin18.2; G/GEJA, gastric or gastroesophageal junction adenocarcinoma; HR, hazard ratio; IA2, interim analysis 2; ITT, intent-to-treat; OS, overall survival; TPC, treatment of physician's choice. Survival table Endpoint: OS (primary endpoint), IA2, ITT Arm | N | Median | Median CI Arcotatug tavatecan | 230 | 10.2 | 9.1, 12.3 TPC | 230 | 6.9 | 5.7, 7.8 HR: 0.57 HR CI: 0.45, 0.73 P: <0.0001 (2-sided) Landmark rates: 6 mo: Arcotatug tavatecan 71.6% | TPC 54.5% 12 mo: Arcotatug tavatecan 43.2% | TPC 24.7% [Slide 3] PFS by IRRC updates at IA2 [KM curve: Progression-free survival (%) vs Months] Landmarks printed: 6 mo: AT 55.2%, TPC 23.1% Table: Arcotatug tavatecan (N=230) | TPC (N=230) Event, n (%): 117 (50.9) | 137 (59.6) Median (95% CI): 7.1 (5.3, 9.7) | 3.1 (2.8, 3.8) HR (95% CI): 0.45 (0.35, 0.58) At risk (censored), months 0/3/6/9/12/15/18: Arcotatug tavatecan: 230 (0), 142 (32), 81 (60), 38 (89), 10 (108), 1 (112), 0 (113) TPC: 230 (0), 82 (54), 16 (85), 6 (90), 3 (93), 1 (93), 0 (93) • The descriptive PFS update at IA2 continued to demonstrate a substantial benefit with AT versus TPC ITT population. Median and 95% CI are estimated using Kaplan–Meier method. Median follow-up duration for PFS by IRRC at IA2: AT, 8.2 months (95% CI, 7.0, 8.5); TPC, 4.4 months (95% CI, 4.2, 5.5). AT, arcotatug tavatecan; CI, confidence interval; HR, hazard ratio; IA2, interim analysis 2; IRRC, independent radiological review committee; ITT, intent-to-treat; PFS, progression-free survival; TPC, treatment of physician's choice. Survival table Endpoint: PFS by IRRC (descriptive update), IA2, ITT Arm | N | Median | Median CI Arcotatug tavatecan | 230 | 7.1 | 5.3, 9.7 TPC | 230 | 3.1 | 2.8, 3.8 HR: 0.45 HR CI: 0.35, 0.58 Landmark rates: 6 mo: Arcotatug tavatecan 55.2% | TPC 23.1% [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH ORR by IRRC at IA2 Confirmed responses in patients with a measurable lesion Arcotatug tavatecan (N=182) | TPC (N=182) Best overall response, n (%) Complete response: 3 (1.6) | 1 (0.5) Partial response: 65 (35.7) | 13 (7.1) Stable disease: 84 (46.2) | 85 (46.7) Progressive disease: 22 (12.1) | 49 (26.9) Not evaluable: 2 (1.1) | 16 (8.8) No post-baseline assessment yet: 6 (3.3) | 18 (9.9) Objective response rate,* n (%): 68 (37.4) | 14 (7.7) 95% CI: (30.3, 44.4) | (3.8, 11.6) Median duration of response,† months: 9.9 | NC‡ 95% CI: 8.1, 12.1 | 3.0, NC Disease control rate,§ n (%): 152 (83.5) | 99 (54.4) 95% CI: (78.1, 88.9) | (47.2, 61.6) • AT demonstrated a higher response rate with durable responses Includes all randomised participants with at least one target/measurable lesion at baseline. *Complete response + partial response. †Duration of response calculated in patients with confirmed objective response: AT, n=68; TPC, n=14; ‡Among AT and TPC responders, duration of response events occurred in 21/68 (30.9%) and 5/14 (35.7%), respectively; 10/68 (14.7%) and 4/14 (28.6%) were censored for subsequent therapy, with remaining responses ongoing at data cutoff; §Complete response + partial response + stable disease. AT, arcotatug tavatecan; CI, confidence interval; IA2, interim analysis 2; IRRC, independent radiological review committee; NC, not calculated; ORR, objective response rate; TPC, treatment of physician's choice. [Speaker video] Kohei Shitara Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 ... ALMERIA AUDITORIUM - HALL 9

Background Arcotatug tavatecan is a novel CLDN18.2-targeted ADC comprising an Fc-silenced antibody designed to reduce on target, off-tumor toxicity and conjugated to an exatecan-derived TOPO I inhibitor payload for selective delivery to tumor cells. Here, we report the prespecified first interim analysis (IA1) of the G-HOPE-001 study. Methods Patients (pts) with unresectable or metastatic G/GEJA, CLDN18.2 IHC ≥2+ in ≥75% of tumor cells who had progressed on 2-4 prior regimens were randomized 1:1 to arcotatug tavatecan 6mg/kg Q3W or TPC (irinotecan, paclitaxel or trifluridine/tipiracil) until progression or unacceptable toxicity. Stratification factors were regions, primary tumor site and prior gastrectomy. Primary endpoints were IRRC-assessed PFS per RECIST v1.1 and OS. The prespecified IA1 included the PFS final analysis and an OS futility analysis, with a data cutoff of February 13, 2026. Results In IA1, 408 pts from China and Japan (male: 62.0%, median age: 58.0, ECOG PS 1: 71.6%, primary tumor at stomach: 81.6%, primary tumor resection: 43.6%) were randomized to arcotatug tavatecan (N=203) and TPC (N=205) arms. IRRC-assessed median PFS was 5.5 months vs 2.9 months (HR: 0.47 [95% CI: 0.34-0.65], p-value <0.0001). With 34.8% of events, median OS was 9.9 months vs 7.4 months (HR: 0.63 [95% CI: 0.45-0.89]). IRRC-assessed ORR was 23.6% in arcotatug tavatecan and 5.3% in TPC. Grade ≥3 (G3+) TEAEs occurred in 45.8% pts with arcotatug tavatecan vs 57.9% pts with TPC. Common gastrointestinal TEAEs (≥10%) with arcotatug tavatecan vs TPC were nausea (38.9% vs 40.6%), vomiting (22.2% vs 28.4%) and diarrhea (12.8% vs 34.5%). Interstitial lung disease was not observed. TRAEs leading to treatment discontinuation occurred in 1.0% of pts in each arm. No TRAE led to death. Conclusions Arcotatug tavatecan demonstrated a statistically significant and clinically meaningful improvement in PFS with a manageable safety profile versus TPC for CLDN18.2+ G/GEJA in the 3L+ setting. OS results will be evaluated at the prespecified IA2.

[Slide 1] ESMO GASTROINTESTINAL CANCERS Annual Congress | MUNICH GERMANY 26-29 JUNE 2024 BACKGROUND Nonmalignant cells: Polarity; Apical membrane; Claudin 18.2; Basolateral membrane; Basement membrane Cancer cells CLDN18.2 expressed aberrantly on tumor cell surface - promising therapeutic target Nakayama et al, Nat Rev Clin Oncol 2024 [ADC structure diagram: Asn297; spacer1; spacer2] Fully human anti-CLDN18.2 Ab with IgG1 Fc silenced | Site specific conjugation and cleavable linker | Exatecan (topoisomerase inhibitor) payload DAR 4 IBI343 ADC Profile targeting CLDN 18.2 • Promising in vivo safety: Fc-silent with no ADCC-mediated GI toxicity • Promising in vivo efficacy: Strong on-target killing effect & "bystander killing effect" ESMO GASTROINTESTINAL CANCERS 2024 Dr Jia (Jenny) Liu [Slide 2] nature medicine | Search | Log in Content | About | Publish articles > article Download PDF Article | Open access | Published: 16 July 2025 CLDN18.2-targeting antibody–drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: a phase 1 trial Jia Liu, Jianwei Yang, Yuping Sun, Jifang Gong, Jinbo Yue, Yueyin Pan, Meili Sun, Rongfeng Song, Xiuying Xiao, Andrea Tazbirkova, Jian Ruan, Zhenyang Liu, Zimin Liu, Zhihua Li, Lili Sheng, Yanru Qin, Jieer Ying, Xianjun Yu, Jian Zhang, Yiping Mou, Chuangxin Lu, Ping Chen, Suyi Li, Jie Li, Xiujuan Qu, Ting Deng, Juan Du, Aiping Zhou, [author list continues] [Slide 4] Overall safety summary at IA2 | | Arcotatug tavatecan (N=230) | TPC (N=222) | Median (range) treatment duration, months | 5.0 (0.7–18.8) | 2.0 (0.5–14.3) Any TEAEs, n (%) | 226 (98.3) | 216 (97.3) Treatment-related | 222 (96.5) | 208 (93.7) Any Grade ≥3 TEAEs, n (%) | 134 (58.3) | 139 (62.6) Treatment-related | 109 (47.4) | 124 (55.9) Any TESAEs, n (%) | 90 (39.1) | 84 (37.8) Treatment-related | 51 (22.2) | 53 (23.9) Any TEAEs leading to dose interruption, n (%) | 109 (47.4) | 114 (51.4) Any TEAEs leading to dose reduction, n (%) | 41 (17.8) | 78 (35.1) Any TEAEs leading to drug discontinuation, n (%) | 8 (3.5) | 5 (2.3) Treatment-related | 4 (1.7) | 3 (1.4) Any TEAEs leading to death, n (%) | 8 (3.5) | 5 (2.3) Treatment-related | 1 (0.4)* | 0 • Treatment-related Grade ≥3 TEAEs and TEAEs leading to dose reduction or interruption were less frequent with AT vs. TPC • Incidence of TESAEs was similar between arms, and treatment-related drug discontinuations were uncommon Includes participants who received ≥1 dose of study drug. Events were graded according to Common Terminology Criteria for Adverse Events version 5.0. *Sudden death of unknown cause AT, arcotatug tavatecan; IA2, interim analysis 2; TEAE, treatment emergent adverse ev[obscured by black bar]choice.

TEAEs in ≥10% of patients at IA2 [Butterfly bar chart; columns: AE | Arcotatug tavatecan any grade | AT grade ≥3 | TPC grade ≥3 | TPC any grade] Anaemia: 66.1 | 20.4 | 13.1 | 54.1 WBC count decreased: 58.3 | 11.7 | 22.5 | 54.5 Neutrophil count decreased: 55.2 | 17.4 | 32.0 | 58.1 Decreased appetite: 44.3 | 3.9 | 2.3 | 35.1 Nausea: 43.9 | 0.9 | 1.8 | 43.7 Hypoalbuminaemia: 40.4 | 0 | 0.5 | 28.4 Weight decreased: 30.9 | 3.0 | 2.3 | 22.5 Platelet count decreased: 28.7 | 6.5 | 5.4 | 18.9 ALT increased: 25.7 | 0.4 | 0 | 13.5 Vomiting: 25.2 | 2.6 | 3.2 | 32.9 AST increased: 22.6 | 1.7 | 1.4 | 14.0 Hypokalaemia: 22.2 | 4.8 | 12.6 | 24.8 GGT increased: 20.9 | 6.1 | 3.6 | 12.2 Constipation: 20.0 | 0 | 0 | 18.0 Hypocalcaemia: 19.1 | 0.4 | 0.9 | 14.4 Lymphocyte count decreased: 18.7 | 7.4 | 10.8 | 21.6 Hyponatraemia: 16.1 | 1.3 | 0.5 | 11.7 Blood ALP increased: 15.7 | 1.7 | 1.8 | 9.5 Diarrhoea: 15.2 | 1.3 | 4.1 | 40.5 Fatigue: 15.2 | 0.9 | 0 | 11.3 Asthenia: 14.3 | 2.2 | 3.6 | 17.6 Hypoproteinaemia: 13.0 | 0 | 0 | 5.9 Malaise: 12.2 | 0 | 0.9 | 10.4 Protein urine present: 10.9 | 0 | 0 | 6.8 Abdominal pain: 10.0 | 2.2 | 1.4 | 11.7 Alopecia: 1.7 | 0 | 0 | 12.6 Patients experiencing TEAEs (%) • GI toxicities such as nausea, vomiting and diarrhoea were comparable or less frequent with arcotatug tavatecan than TPC; haematological events were manageable Includes participants who received ≥1 dose of study drug. Events were graded according to Common Terminology Criteria for Adverse Events version 5.0. Presented in order of overall frequency with arcotatug tavatecan. ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; GI, gastrointestinal; IA2, interim analysis 2; TEAE, treatment emergent adverse event; TPC, treatment of physician's choice; WBC, white blood cell.

[Slide 1] Proffered Paper session LBA77 - Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician's choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 study Speakers Kohei Shitara (Kashiwa, Japan, Chiba) Lecture Time 13:30 - 13:40 [Abstract] Background Arcotatug tavatecan is a novel CLDN18.2-targeted ADC comprising an Fc-silenced antibody designed to reduce on target, off-tumor toxicity and conjugated to an exatecan-derived TOPO I inhibitor payload for selective delivery to tumor cells. Here, we report the prespecified first interim analysis (IA1) of the G-HOPE-001 study. [Slide 2] Results In IA1, 408 pts from China and Japan (male: 62.0%, median age: 58.0, ECOG PS 1: 71.6%, primary tumor at stomach: 81.6%, primary tumor resection: 43.6%) were randomized to arcotatug tavatecan (N=203) and TPC (N=205) arms. IRRC-assessed median PFS was 5.5 months vs 2.9 months (HR: 0.47 [95% CI: 0.34-0.65], p-value <0.0001). With 34.8% of events, median OS was 9.9 months vs 7.4 months (HR: 0.63 [95% CI: 0.45-0.89]). IRRC-assessed ORR was 23.6% in arcotatug tavatecan and 5.3% in TPC. Grade ≥3 (G3+) TEAEs occurred in 45.8% pts with arcotatug tavatecan vs 57.9% pts with TPC. Common gastrointestinal TEAEs (≥10%) with arcotatug tavatecan vs TPC were nausea (38.9% vs 40.6%), vomiting (22.2% vs 28.4%) and diarrhea (12.8% vs 34.5%). Interstitial lung disease was not observed. TRAEs leading to treatment discontinuation occurred in 1.0% of pts in each arm. No TRAE led to death. Conclusions Arcotatug tavatecan demonstrated a statistically significant and clinically meaningful improvement in PFS with a manageable safety profile versus TPC for CLDN18.2+ G/GEJA in the 3L+ setting. OS results will be evaluated at the prespecified IA2. [Slide 3] Methods Patients (pts) with unresectable or metastatic G/GEJA, CLDN18.2 IHC ≥2+ in ≥75% of tumor cells who had progressed on 2-4 prior regimens were randomized 1:1 to arcotatug tavatecan 6mg/kg Q3W or TPC (irinotecan, paclitaxel or trifluridine/tipiracil) until progression or unacceptable toxicity. Stratification factors were regions, primary tumor site and prior gastrectomy. Primary endpoints were IRRC-assessed PFS per RECIST v1.1 and OS. The prespecified IA1 included the PFS final analysis and an OS futility analysis, with a data cutoff of February 13, 2026.

[Slide 1] G-HOPE-001 trial: design and IA1 result An open-label, phase 3 study conducted in China and Japan (NCT06238843) Key inclusion criteria: • ECOG PS 0–1 • Locally advanced unresectable or metastatic G/GEJA • CLDN18.2 IHC 2+/3+ in ≥75% TC • 3L+ • Prior zolbetuximab and irinotecan allowed Key exclusion criteria: • Positive HER2ᵃ • History of treatment with topoisomerase inhibitor-based ADCs R‡ 1:1 Arcotatug tavatecan (AT) 6 mg/kg Q3W Treatment of physician's choice (TPC): irinotecan, paclitaxel, trifluridine/tipiracil ‡Stratification factors include region (China vs. Japan), primary tumour site (stomach vs. gastroesophageal junction) and history of prior gastrectomy (yes vs. no) Cross-over not allowed Dual primary endpoint PFS met! Events maturity: 40% [Embedded KM curve: Progression-free survival (%) vs Months; inset table (Arcotatug tavatecan vs TPC: Event n (%), Median (95% CI), HR (95% CI), P-value) - values too small/blurry to read reliably: illegible] HR 0.47, absolute gain +2.6 months (median)/+25% (@6mos) Filippo Pietrantonio, MD Survival table Endpoint: PFS (dual primary endpoint), IA1 Arcotatug tavatecan TPC HR: 0.47 [Slide 2] Overall survival: the other dual primary endpoint OS at IA2, median follow-up ≈ 11 mos Events maturity: 61% [KM curve: Overall survival vs months 0-24; landmark labels on curve at 6 and 12 months, partly blurry: AT ~71.6% / TPC ~56.6% at 6 mo; AT 43.7% / TPC 24.7% at 12 mo] Arcotatug tavatecan (N=230) TPC (N=230) Event, n (%) 122 (53.0) 159 (69.1) Median (95% CI) 10.2 (9.1, 12.3) 6.9 (5.7, 7.8) HR (95% CI) 0.57 (0.45, 0.73) P-value (2-sided) <0.0001 HR 0.57, absolute gain +3.3 months (median) PFS may be sufficient for regulatory purposes in some settings, but OS and quality of life remain the only endpoints that matter to patients, especially in the 3L+ setting Filippo Pietrantonio, MD Survival table Endpoint: OS (dual primary endpoint), IA2 Arm | N | Median | Median CI Arcotatug tavatecan | 230 | 10.2 mo | 9.1, 12.3 TPC | 230 | 6.9 mo | 5.7, 7.8 HR: 0.57 HR CI: 0.45, 0.73 P: <0.0001 (2-sided) Landmark rates: 12 months: Arcotatug tavatecan 43.7% | TPC 24.7%

[Slide 1] IROCAS study design1 International, academic, multicentre, open-label, randomised phase III trial Key eligibility criteria - R0-resected colon adenocarcinoma - High-risk stage III: pT4 and/or pN2 - Age 18 - 70 years and ECOG PS 0-1 - Age 71-75 years and ECOG PS 0 * - Randomisation within 42 days after surgery - Treatment start 28-56 days after surgery R 1:1 n=398 mFOLFIRINOX 12 cycles every 2 weeks: Oxaliplatin 85 mg/m2 • Irinotecan 180 mg/m2 • Leucovorin 400 mg/m2 • 5-FU 2400 mg/m2 over 46 h n=397 mFOLFOX6 12 cycles every 2 weeks: Oxaliplatin 85 mg/m2 • Leucovorin 400 mg/m2 • 5-FU bolus 400 mg/m2 • 5-FU 2400 mg/m2 over 46 h Adjuvant chemotherapy 6 months Stratification factors - Participating country (France, Canada, Italy) - pT1-3N2 vs pT4aN1 vs pT4bN1 vs T4N2 - Right vs left colon - Perforation or urgent surgery: yes vs no Primary endpoint - 3-year disease-free survival (DFS) - Intention-to-treat population (ITT) Secondary endpoints - 2-year DFS (ITT) - Overall survival - Safety - Treatment delivery and compliance * Following protocol amendment No. 6, patients aged 71-75 years were eligible if ECOG PS 0. 1. Bennouna J, et al. Clinical Colorectal Cancer 2019 Prof. Jaafar Bennouna [Slide 2] Primary endpoint: 3-year DFS in the ITT population mFOLFIRINOX did not improve DFS compared with mFOLFOX6 data cut-off: 6 July 2026; median follow-up 55 months (IQR, 42.6-65.9) | Number of events, n (%) | 3yr-event-free survival rate (95% CI) mFOLFIRINOX | 146 (36.7) | 65.6 (60.6-70.2) mFOLFOX6 | 138 (34.8) | 66.3 (61.4-70.8) HR=1.07 (95% CI, 0.84-1.36) - stratified logrank p=0.61 | mFOLFIRINOX (n=398) | mFOLFOX6 (n=397) 2-year DFS rate (%) (95% CI) | 70.2 (65.4 - 74.5) | 71.8 (67.1 - 76.0) Patients at risk (0, 12, 24, 36, 48, 60, 72 months) mFOLFIRINOX | 398 | 324 | 266 | 227 | 166 | 102 | 0 mFOLFOX6 | 397 | 323 | 278 | 242 | 181 | 117 | 0 Abbreviations: DFS, disease-free survival; HR, hazard ratio; CI, confidence interval. Prof. Jaafar Bennouna Survival table Endpoint: 3-year DFS (ITT) mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 1.07 HR CI: 0.84-1.36 P: 0.61 (stratified logrank) Landmark rates: 3 years: mFOLFIRINOX 65.6 (CI 60.6-70.2) | mFOLFOX6 66.3 (CI 61.4-70.8) 2 years: mFOLFIRINOX 70.2 (CI 65.4-74.5) | mFOLFOX6 71.8 (CI 67.1-76.0) [Slide 3] 3-year OS in the ITT population OS did not differ significantly between treatment groups | Number of events, n (%) | 3yr-overall survival, rate (95% CI) mFOLFIRINOX | 66 (16.6) | 91.2 (87.8-93.6) mFOLFOX6 | 76 (19.1) | 86.7 (82.9-89.7) HR=0.85 (95% CI, 0.61-1.21) - stratified logrank p=0.37 Patients at risk (0, 12, 24, 36, 48, 60, 72 months) mFOLFIRINOX | 398 | 371 | 357 | 319 | 229 | 144 | 0 mFOLFOX6 | 397 | 373 | 355 | 318 | 232 | 145 | 0 Abbreviations: OS, overall survival; NE, not estimable, HR, hazard ratio; CI, confidence interval. Prof. Jaafar Bennouna Survival table Endpoint: Overall survival (ITT) mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 0.85 HR CI: 0.61-1.21 P: 0.37 (stratified logrank) Landmark rates: 3 years: mFOLFIRINOX 91.2 (CI 87.8-93.6) | mFOLFOX6 86.7 (CI 82.9-89.7) [Slide 4] Disease-free survival by prespecified subgroup - ITT population Subgroup | mFOLFIRINOX Events/N (%) | mFOLFOX6 Events/N (%) | Stratified HR (95% CI) | Interaction P value* Age | | | | 0.25 <=70 yr | 138/376 (36.7) | 130/370 (35.1) | 1.03 (0.80, 1.33) 71-75 yr | 8/22 (36.4) | 8/27 (29.6) | 1.90 (0.70, 5.16) Sex | | | | 0.98 Male | 89/240 (37.1) | 88/239 (36.8) | 1.06 (0.78, 1.45) Female | 57/158 (36.1) | 50/158 (31.6) | 1.07 (0.72, 1.59) ECOG performance status | | | | 0.52 PS 0 | 116/326 (35.6) | 112/329 (34.0) | 1.02 (0.78, 1.34) PS 1 | 30/72 (41.7) | 26/68 (38.2) | 1.25 (0.72, 2.17) Primary tumour sidedness | | | | 0.56 Left-sided | 78/222 (35.1) | 70/220 (31.8) | 1.14 (0.81, 1.61) Right-sided | 68/176 (38.6) | 68/177 (38.4) | 0.99 (0.70, 1.40) Pathologic T stage | | | | 0.99 pT1-3 | 64/188 (34.0) | 57/187 (30.5) | 1.06 (0.74, 1.53) pT4a | 68/177 (38.4) | 67/171 (39.2) | 1.06 (0.74, 1.52) pT4b | 14/33 (42.4) | 14/39 (35.9) | 1.05 (0.45, 2.45) Pathologic N stage | | | | 0.22 pT4N1 | 33/112 (29.5) | 32/109 (29.4) | 0.83 (0.48, 1.42) pN2a | 60/164 (36.6) | 45/157 (28.7) | 1.38 (0.93, 2.05) pN2b | 53/122 (43.4) | 60/130 (46.2) | 0.93 (0.63, 1.37) High-risk category T4 | | | | 0.98 pT4 | 82/210 (39.0) | 81/210 (38.6) | 1.06 (0.76, 1.47) pT1-3 | 64/188 (34.0) | 57/187 (30.5) | 1.06 (0.74, 1.53) High-risk category N2 | | | | 0.32 pN2 | 113/286 (39.5) | 106/288 (36.8) | 1.13 (0.86, 1.48) pN1 | 33/112 (29.5) | 32/109 (29.4) | 0.83 (0.48, 1.42) High-risk category T4N2 | | | | 0.44 pT4N2 | 50/100 (50.0) | 49/101 (48.5) | 1.21 (0.80, 1.82) Other | 96/298 (32.2) | 89/296 (30.1) | 0.98 (0.73, 1.33) Tumour perforation | | | | 0.80 Yes | 33/70 (47.1) | 35/70 (50.0) | 1.00 (0.59, 1.70) No | 113/328 (34.5) | 103/327 (31.5) | 1.08 (0.82, 1.43) All patients | 146/398 (36.7) | 138/397 (34.8) | 1.07 (0.84, 1.36) mFOLFIRINOX better | mFOLFOX6 better * P value from the interaction test between treatment and each subgroup unadjusted for multiplicity Prof. Jaafar Bennouna

[Slide 1] ORIGINAL ARTICLE · Articles in Press, October 25, 2026 Download Full Issue A randomised phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III colon cancer: Results of the international IROCAS study. J. Bennouna 1 · T. André 2 · E. Martin 3 · C. Cremolini 4 · S. Gill 5 · T. Asmis 6 · P. Kavan 7 · E. Mitry 8 · S. Hiret 3 · L. Mineur 9 · P. Artru 10 · C. Perret 11 · O. Bouché 12 · Y. Touchefeu 13 · B. Goldenberg 14 · O. Dupuis 15 · S. Lonardi 16 · B. Chibaudel 17 · H. Castanié 18 · C. Coutzac 19 · L. Bauguion 20 · E. Guardiola 21 · A. Benmaziane 22 · J. Barrière 23 · E. Chen 24 · V. Simmet 25 · G. Allegrini 26 · F. Marmorino 4 · V. Pezzella 27 · L. Monard 27 · L. Campion 3 · C. O'Callaghan 28 · J. Taieb 29 Show less Affiliations & Notes [Slide 2] Results Between May 2017 and June 2023, 795 patients were assigned to mFOLFIRINOX (n=398) or mFOLFOX6 (n=397). Median age was 59 years (range 19–75); 39.7% were women, 52.8% had pT4 disease, 72.2% had pN2 disease, and 25.3% had both. At a median follow-up of 55 months (IQR 42.6–65.9), 284 DFS events had occurred: 146 with mFOLFIRINOX and 138 with mFOLFOX6. Three-year DFS was 65.6% versus 66.3%, respectively (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.84–1.36; P=0.61). Although Overall survival (OS) data remain immature, 3-year OS was 91.2% versus 86.7% (HR 0.85, 95% CI 0.61–1.21; P=0.37); no significant treatment-by-subgroup interaction was observed. Grade ≥3 adverse events occurred in 62.2% and 62.1% of patients, respectively. Grade ≥3 diarrhoea (15.6% versus 3.8%) and fatigue (7.3% versus 1.8%) were more frequent with mFOLFIRINOX, whereas grade ≥3 neutropenia was less frequent (18.0% versus 23.9%). G-CSF use was 37.8% versus 19.1%. Conclusion Adjuvant mFOLFIRINOX triplet chemotherapy did not improve DFS compared with standard doublet mFOLFOX6 in patients with high-risk stage III colon cancer. These findings do not support empirical chemotherapy intensification and highlight the need for novel adjuvant strategies.

[Slide 3] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ 3-year OS in the ITT population OS did not differ significantly between treatment groups | Number of events, n (%) | 3yr-overall survival, rate (95% CI) mFOLFIRINOX | 66 (16.6) | 91.2 (87.8-93.6) mFOLFOX6 | 76 (19.1) | 86.7 (82.9-89.7) HR=0.85 (95% CI, 0.61-1.21) - stratified logrank p=0.37 Patients at risk (0, 12, 24, 36, 48, 60, 72 months) mFOLFIRINOX | 398 | 371 | 357 | 319 | 229 | 144 | 0 mFOLFOX6 | 397 | 373 | 355 | 318 | 232 | 145 | 0 Abbreviations: OS, overall survival; NE, not estimable, HR, hazard ratio; CI, confidence interval. Prof. Jaafar Bennouna Jaafar Bennouna IROCAS: A randomized phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III (T4 and/or N2) colon cancer ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: Overall survival (ITT) mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 0.85 HR CI: 0.61-1.21 P: 0.37 (stratified logrank) Landmark rates: 3 years: mFOLFIRINOX 91.2 (CI 87.8-93.6) | mFOLFOX6 86.7 (CI 82.9-89.7) [Slide 4] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ Most common treatment-related adverse events (incidence >=15%) AE | mFOLFIRINOX any grade | mFOLFIRINOX grade >=3 | mFOLFOX6 grade >=3 | mFOLFOX6 any grade Any TRAE | 100 | 62.2 | 62.1 | 99.7 Peripheral sensory neuropathy | 96.6 | 22.4 | 26.0 | 96.7 Diarrhoea | 87.5 | 15.6 + | 3.8 | 61.3 Fatigue | 78.6 | 7.3 + | 1.3 | 68.4 Nausea | 72.4 | 6.3 + | 1.3 | 65.6 Thrombocytopenia | 56.3 | 3.4 | [illegible] | 66.9 Anaemia | 49.5 | 1.3 | [illegible] | 51.1 Neutropenia | 47.1 | 18.0 | 23.9 + | 60.3 Oral mucositis | 46.9 | 1.6 | [illegible] | 47.3 Alopecia | 32.3 | | [illegible] | 16.8 Vomiting | 29.9 | 3.6 + | 1.3 | 18.8 AST increased | 21.9 | 0.5 | [illegible] | 28.2 ALT increased | 24 | 2.3 | [illegible] | 27 Myalgia | 26.8 | 0.8 | [illegible] | 22.6 Constipation | 20.3 | 0.3 | | 24.2 Dysgeusia | 22.1 | | | 23.7 Abdominal pain | 23.7 | 0.5 | [illegible] | 16.8 Anorexia | 22.9 | 1.0 | [illegible] | 21.1 Infections | 22.4 | 3.6 | [illegible] | 20.6 ALP increased | 21.4 | 0.8 | | 15.5 Hypersensitivity reaction | 20.8 | 1.0 | [illegible] | 16 GGT increased | 16.4 | 4.9 | [illegible] | 18.6 Hand-foot syndrome | 9.6 | 1.0 | [illegible] | 16 Legend: mFOLFIRINOX, grade >=3; mFOLFIRINOX, any grade; mFOLFOX6, grade >=3; mFOLFOX6, any grade Patients (%) Prof. Jaafar Bennouna Jaafar Bennouna IROCAS: A randomized phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III (T4 and/or N2) colon cancer ALMERIA AUDITORIUM - HALL 9

[Slide 1] Probability of disease-free survival (%) Number of events, n (%) | 3yr-event-free survival rate (95% CI) mFOLFIRINOX | 146 (36.7) | 65.6 (60.6-70.2) mFOLFOX6 | 138 (34.8) | 66.3 (61.4-70.8) HR=1.07 (95% CI, 0.84-1.36) - stratified logrank p=0.61 Time (months) Patients at risk (0/12/24/36/48/60/72) mFOLFIRINOX | 398 | 324 | 266 | 227 | 166 | 102 | 0 mFOLFOX6 | 397 | 323 | 278 | 242 | 181 | 117 | 0 Survival table Endpoint: Disease-free survival mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 1.07 HR CI: 0.84-1.36 P: 0.61 (stratified logrank) Landmark rates: 3 years: mFOLFIRINOX 65.6 (CI 60.6-70.2) | mFOLFOX6 66.3 (CI 61.4-70.8) [Slide 2] Probability of overall survival (%) Number of events, n (%) | 3yr-overall survival, rate (95% CI) mFOLFIRINOX | 66 (16.6) | 91.2 (87.8-93.6) mFOLFOX6 | 76 (19.1) | 86.7 (82.9-89.7) HR=0.85 (95% CI, 0.61-1.21) - stratified logrank p=0.37 Time (months) Patients at risk (0/12/24/36/48/60/72) mFOLFIRINOX | 398 | 371 | 357 | 319 | 229 | 144 | 0 mFOLFOX6 | 397 | 373 | 355 | 318 | 232 | 145 | 0 Survival table Endpoint: Overall survival mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 0.85 HR CI: 0.61-1.21 P: 0.37 (stratified logrank) Landmark rates: 3 years: mFOLFIRINOX 91.2 (CI 87.8-93.6) | mFOLFOX6 86.7 (CI 82.9-89.7)

[Slide 1] #LBA29 IROCAS : An international randomised phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III colon cancer J. Bennouna1, T. André2, E. Martin3, C. Cremolini4, S. Gill5, T. Asmis6, P. Kavan7, E. Mitry8, S. Hiret3, L. Mineur9, P. Artru10, C. Perret11, O. Bouché12, Y. Touchefeu13, B. Goldenberg14, O. Dupuis15, S. Lonardi16, B. Chibaudel17, H. Castanié18, C. Coutzac19, L. Bauguion20, E. Guardiola21, A. Benmaziane22, J. Barrière23, E. Chen24, V. Simmet25, G. Allegrini26, F. Marmorino4, V. Pezzella27, L. Monard27, L. Campion3, C. O'Callaghan28, J. Taieb29 [Affiliations, small print: Hôpital Foch, Suresnes, France; Hôpital Saint Antoine, Paris, France; ICO Paul Papin/René Gauducheau, Nantes, France; University of Pisa, Pisa, Italy; BC Cancer, Vancouver, Canada; ... UNICANCER, Paris, France; Queen's University, Kingston, Canada; Hôpital Européen Georges Pompidou, Paris, France] 25 October 2026 [Slide 3] Baseline demographic and clinicopathological characteristics Characteristics, n (%) | mFOLFIRINOX (n=398) | mFOLFOX6 (n=397) Age, years, median (range) | 57 (19-74) | 59 (24-75) - age >70 years | 22 (5.5) | 27 (6.8) Sex, male | 240 (60.3) | 239 (60.2) ECOG PS 0 | 326 (81.9) | 329 (82.9) Pathological T stage - pT1-3 | 188 (47.2) | 187 (47.1) - pT4a ; pT4b | 177 (44.5) ; 33 (8.3) | 171 (43.1) ; 39 (9.8) Pathological N stage - pN1 (1-3 positive lymph nodes) | 112 (28.1) | 109 (27.5) - pN2a (4-6 positive lymph nodes) ; pN2b (≥ 7 positive lymph nodes) | 164 (41.2) ; 122 (30.7) | 157 (39.5) ; 130 (32.7) - pN2, not otherwise specified | 0 | 1(0.3) High-risk pathological features - pT4 | 210 (52.8) | 210 (52.9) - pN2 | 286 (71.9) | 288 (72.5) - pT4 and pN2 | 100 (25.1) | 101 (25.4) Primary tumour location – n (%) - Right-sided ; Left-sided | 176 (44.2) ; 222 (55.8) | 177 (44.6) ; 220 (55.4) Tumour perforation at diagnosis, Yes | 70 (17.6) | 70 (17.6) Time from surgery to randomization,weeks, median (range) | 6.6 (3.0-8.9) | 6.4 (3.0-9.4) Two patients randomised to mFOLFIRINOX were subsequently found on pathological review to have pT1-3N1 disease Prof. Jaafar Bennouna

ORIGINAL ARTICLE · Articles in Press, October 25, 2026 Download Full Issue A randomised phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III colon cancer: Results of the international IROCAS study. J. Bennouna 1 · T. André 2 · E. Martin 3 · ... · L. Campion 3 · C. O'Callaghan 28 · J. Taieb 29 ... Show more Affiliations & Notes Article Info

Post-Hoc Analysis: FOLFOXIRI vs FOLFOX/CAPOX Recurrence free survival FOLFOX/CAPOX 51% FOLFOXIRI 47% HR 1.09 (0.78, 1.53), P = 0.662 Time from randomisation - Months (0-48) FOLFOXIRI 65 64 62 57 51 44 36 32 30 29 23 22 20 19 17 16 15 Doublet 169 164 156 144 134 120 103 96 76 67 60 53 47 45 40 35 33 | TDMM/mL, median (IQR) | P FOLFOXIRI | 0.28 (0.06, 1.78) | 0.236 Doublet | 0.15 (0.06, 0.97) | ctDNA Clearance Rate by Regimen ns EoT ctDNA Status (%): Clearance / No Clearance FOLFOXIRI 60% (31/52) Doublet 62% (47/76) 2025 ASCO ANNUAL MEETING #ASCO25 PRESENTED BY: Jeanne Tie, MBChB FRACP MD Jeffrey Meyerhardt, MD, MPH Survival table Endpoint: Recurrence-free survival (post-hoc) FOLFOXIRI | 65 FOLFOX/CAPOX (Doublet) | 169 HR: 1.09 HR CI: 0.78, 1.53 P: 0.662 Landmark rates: 36 months: FOLFOX/CAPOX 51% | FOLFOXIRI 47%

[Slide 1] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER PRABITAS: Study Design A pragmatic, investigator-initiated, open-label, randomized phase 3 trial Japan Registry of Clinical Trials jRCTs041230120 Patients - Histologically confirmed mCRC - Prior regimens including - Fluoropyrimidine, IRI, OX - Anti-VEGF agents - Anti-EGFR antibody (if indicated) - ECOG PS 0-2 Stratification factors ECOG PS (0/1/2), RAS status (wild-type/mutant), Facility Planned N=890 R 1:1 Conventional FTD/TPI+BEV: FTD/TPI 35 mg/m2 BID, days 1-5 and 8-12; BEV 5 mg/kg IV, days 1 and 15; 28-day cycle Biweekly FTD/TPI+BEV: FTD/TPI 35 mg/m2 BID, days 1-5; BEV 5 mg/kg IV, day 1; 14-day cycle Primary endpoint: OS (non-inferiority) Non-inferiority margin: HR 1.25 Secondary endpoints: PFS, TTF, ORR, DCR, safety Pragmatic elements - Broad eligibility criteria - Starting dose, dose modification and CT timing at physician's discretion - Only 10 prespecified AEs, collected twice (first 2 months and whole treatment period) Hiroya Taniguchi Hiroya Taniguchi - Biweekly versus conventional trifluridine/tipiracil plus bevacizumab for refractory metastatic colorectal cancer: The pragmatic phase 3 PRABITAS trial [Slide 2] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Overall Survival (ITT population) | N | Events | Median OS, mo (95% CI) Conventional | 486 | 355 | 10.3 (9.5-11.6) Biweekly | 484 | 336 | 11.3 (10.2-12.5) HR 0.93 (95% CI 0.80-1.08) p<0.0001 for non-inferiority Non-inferiority margin: HR 1.25 Data cutoff: May 20, 2026 Median follow-up: 17.9 mo Time (months): 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 Number at risk Conventional | 486 | 457 | 359 | 265 | 186 | 111 | 61 | 33 | 13 | 0 Biweekly | 484 | 451 | 366 | 288 | 203 | 129 | 63 | 33 | 10 | 0 Hiroya Taniguchi Hiroya Taniguchi - Biweekly versus conventional trifluridine/tipiracil plus bevacizumab for refractory metastatic colorectal cancer: The pragmatic phase 3 PRABITAS trial Survival table Endpoint: Overall survival (ITT) Arm | N | Median | Median CI Conventional FTD/TPI+BEV | 486 | 10.3 mo | 9.5-11.6 Biweekly FTD/TPI+BEV | 484 | 11.3 mo | 10.2-12.5 HR: 0.93 HR CI: 0.80-1.08 P: <0.0001 for non-inferiority [Slide 3] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Progression-Free Survival and Tumor Response Progression-Free Survival | N | Events | Median PFS, mo (95%CI) Conventional | 486 | 466 | 3.9 (3.6-4.4) Biweekly | 484 | 449 | 3.9 (3.6-4.4) HR 0.93 (95%CI 0.81-1.06) Time (months): 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 Number at risk Conventional | 486 | 307 | 148 | 73 | 33 | 16 | 9 | 3 | 0 | 0 Biweekly | 484 | 284 | 161 | 97 | 45 | 26 | 7 | 2 | 2 | 0 Tumor Response | Conventional n=457 | Biweekly n=449 ORR | 2% | 2% DCR | 47% | 52% Patients with measurable disease (RECIST v1.1) Hiroya Taniguchi Hiroya Taniguchi - Biweekly versus conventional trifluridine/tipiracil plus bevacizumab for refractory metastatic colorectal cancer: The pragmatic phase 3 PRABITAS trial Survival table Endpoint: Progression-free survival Arm | N | Median | Median CI Conventional FTD/TPI+BEV | 486 | 3.9 mo | 3.6-4.4 Biweekly FTD/TPI+BEV | 484 | 3.9 mo | 3.6-4.4 HR: 0.93 HR CI: 0.81-1.06 [Slide 4] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Treatment-related Adverse Events Conventional | Biweekly Hematological AEs (Grade >=3) / G-CSF use Neutropenia** | 39% | 13% Leukopenia** | 18% | 7% Febrile neutropenia** | 5% | 1% G-CSF use** | 13% | 3% Non-hematological AEs (Grade >=2) Anorexia** | 26% | 15% Nausea* | 18% | 12% Vomiting | 5% | 3% Fatigue | 17% | 15% Diarrhea** | 10% | 4% Oral mucositis | 5% | 6% Infection | 9% | 9% *p<0.05, **p<0.001 CTCAE v5.0; worst grade: first 2 months for neutropenia/leukopenia, entire treatment period for other AEs. Hiroya Taniguchi Hiroya Taniguchi - Biweekly versus conventional trifluridine/tipiracil plus bevacizumab for refractory metastatic colorectal cancer: The pragmatic phase 3 PRABITAS trial

[Slide 2] Overall Survival (ITT population) | N | Events | Median OS, mo (95% CI) Conventional | 486 | 355 | 10.3 (9.5-11.6) Biweekly | 484 | 336 | 11.3 (10.2-12.5) HR 0.93 (95% CI 0.80-1.08) p<0.0001 for non-inferiority Non-inferiority margin: HR 1.25 Data cutoff: May 20, 2026 Median follow-up: 17.9 mo Time (months): 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 Number at risk Conventional | 486 | 457 | 359 | 265 | 186 | 111 | 61 | 33 | 13 | 0 Biweekly | 484 | 451 | 366 | 288 | 203 | 129 | 63 | 33 | 10 | 0 Hiroya Taniguchi Survival table Endpoint: Overall survival (ITT) Arm | N | Median | Median CI Conventional FTD/TPI+BEV | 486 | 10.3 mo | 9.5-11.6 Biweekly FTD/TPI+BEV | 484 | 11.3 mo | 10.2-12.5 HR: 0.93 HR CI: 0.80-1.08 P: <0.0001 for non-inferiority [Slide 3] Progression-Free Survival and Tumor Response Progression-Free Survival | N | Events | Median PFS, mo (95%CI) Conventional | 486 | 466 | 3.9 (3.6-4.4) Biweekly | 484 | 449 | 3.9 (3.6-4.4) HR 0.93 (95%CI 0.81-1.06) Time (months): 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 Number at risk Conventional | 486 | 307 | 148 | 73 | 33 | 16 | 9 | 3 | 0 | 0 Biweekly | 484 | 284 | 161 | 97 | 45 | 26 | 7 | 2 | 2 | 0 Tumor Response | Conventional n=457 | Biweekly n=449 ORR | 2% | 2% DCR | 47% | 52% Patients with measurable disease (RECIST v1.1) Hiroya Taniguchi Survival table Endpoint: Progression-free survival Arm | N | Median | Median CI Conventional FTD/TPI+BEV | 486 | 3.9 mo | 3.6-4.4 Biweekly FTD/TPI+BEV | 484 | 3.9 mo | 3.6-4.4 HR: 0.93 HR CI: 0.81-1.06 [Slide 4] Treatment-related Adverse Events Conventional | Biweekly Hematological AEs (Grade >=3) / G-CSF use Neutropenia** | 39% | 13% Leukopenia** | 18% | 7% Febrile neutropenia** | 5% | 1% G-CSF use** | 13% | 3% Non-hematological AEs (Grade >=2) Anorexia** | 26% | 15% Nausea* | 18% | 12% Vomiting | 5% | 3% Fatigue | 17% | 15% Diarrhea** | 10% | 4% Oral mucositis | 5% | 6% Infection | 9% | 9% *p<0.05, **p<0.001 CTCAE v5.0; worst grade: first 2 months for neutropenia/leukopenia, entire treatment period for other AEs. Hiroya Taniguchi

Articles 14-day versus 28-day trifluridine–tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan Tomoki Sakakida*, Hiroya Taniguchi*, Masako Asayama*, ... on behalf of the PRABITAS investigators† Summary Background Trifluridine–tipiracil (FTD–TPI) plus bevacizumab is the standard treatment for refractory metastatic colorectal cancer. However, the conventional schedule is frequently associated with haematological and gastrointestinal toxicity, which is clinically significant and relevant to patients. A simplified 14-day schedule has been proposed to reduce toxicity, but whether this treatment preserves survival has not been established in a randomised trial. We therefore aimed to assess whether the 14-day schedule is non-inferior to the conventional schedule for overall survival. Methods PRABITAS was a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial conducted in 178 hospitals in Japan. Patients with refractory metastatic colorectal cancer were randomly assigned (1:1) using a minimisation algorithm, stratified by Eastern Cooperative Oncology Group performance status, RAS mutational status, and institution, to FTD–TPI (35 mg/m² orally twice daily) plus bevacizumab (5 mg/kg intravenously) on either a conventional 28-day (FTD–TPI on days 1–5 and 8–12; bevacizumab on days 1 and 15) or 14-day schedule (FTD–TPI on days 1–5; bevacizumab on day 1). Eligibility criteria were broadened compared with those of conventional explanatory trials, and trial procedures were aligned with routine clinical practice. The primary endpoint was overall survival, analysed in the intention-to-treat population, with a prespecified non-inferiority margin of 1·25. Safety was assessed in all patients who received at least one dose. Missing data were not imputed. This trial is registered with the Japan Registry of Clinical Trials, jRCTs041230120, and is closed to enrolment. Findings Between Dec 26, 2023, and May 20, 2025, we randomly assigned 972 patients, of whom 970 (99%) constituted the intention-to-treat population after two were excluded because they were randomly assigned before site approval (486 [50%] to the 28-day treatment group, 292 [60%] men and 194 [40%] women; and 484 [50%] to the 14-day treatment group, 264 [55%] men and 220 [45%] women). Median follow-up was 17·9 months (IQR 14·3–22·6). Median overall survival was 10·3 months (95% CI 9·5–11·6) in the 28-day group and 11·3 months (10·2–12·5) in the 14-day group (stratified hazard ratio 0·93 [95% CI 0·80–1·08]). The 12-month overall survival rates were 44·0% (95% CI 39·5–48·5) in the 28-day group and 47·5% (42·9–52·0) in the 14-day group. Neutropenia grade 3 or worse was reduced in the 14-day group (13% vs 39%; absolute difference 25 percentage points [95% CI 20–31]), as was anorexia grade 2 or worse (15% vs 26%; absolute difference 11 percentage points [6–16]). Two treatment-related deaths occurred in the 14-day group and none in the 28-day group. Interpretation A 14-day schedule of FTD–TPI plus bevacizumab was non-inferior to the conventional 28-day schedule for overall survival, while reducing haematological and gastrointestinal toxicity. These findings support this simplified schedule as the new standard for FTD–TPI plus bevacizumab in refractory metastatic colorectal cancer. Funding Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Challenging Research (Pioneering). Published Online October 24, 2026 https://doi.org/10.1016/S0140-6736(26)01782-4 See Online/Comment https://doi.org/10.1016/S0140-6736(26)02034-9

Comment Optimising late-line treatment administration in metastatic colorectal cancer: an even brighter SUNLIGHT ... In 2023, the SUNLIGHT study6 was the first randomised trial to show benefit of a combination over an established late-line treatment, showing that the addition of bevacizumab to FTD–TPI significantly improved overall survival, from 7·5 months to 10·8 months (hazard ratio [HR] 0·61 [95% CI 0·49–0·77; p<0·001), ... Tomoki Sakakida and colleagues12 addressed this question in the investigator-initiated, open-label, randomised, phase 3, non-inferiority PRABITAS trial, conducted across 252 Japanese institutions. The study compared the conventional 28-day schedule of FTD–TPI plus bevacizumab with a 14-day schedule consisting of FTD–TPI on days 1–5 and bevacizumab on day 1. The primary endpoint was overall survival in the intention-to-treat population, with a prespecified non-inferiority margin of 1·25 for the upper boundary of the 95% CI of the HR. Sakakida and colleagues randomly assigned 972 patients (after two were excluded) with refractory metastatic colorectal cancer to the 28-day treatment group (486 [50%]) or the 14-day treatment group (484 [50%]). 556 (57%) patients were men and 414 (43%) were women. ... Baseline characteristics were balanced across groups, with a median age of 68 years (IQR 59–74) and RAS-mutated tumours in 576 (59%) patients. After a median follow-up of 17·9 months (IQR 14·3–22·6), median overall survival was 10·3 months (9·5–11·6) within the 28-day treatment group and 11·3 months (10·2–12·5) in the 14-day treatment group (stratified HR 0·93 [95% CI 0·80–1·08]), showing the non-inferiority of the latter. No differences between groups were observed in terms of progression-free survival and objective response rate. As for safety findings, neutropenia of grade 3 or worse decreased from 39% to 13%, febrile neutropenia from 5% to 1%, and G-CSF use from 13% to 3%. Published Online October 24, 2026 https://doi.org/10.1016/S0140-6736(26)02034-9

14-day versus 28-day trifluridine–tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan Tomoki Sakakida*, Hiroya Taniguchi*, Masako Asayama*, Yusuke Suwa, Takaya Shimura, Seiichiro Mitani, Akitaka Makiyama, Hiroyuki Arai, Hiroshi Matsuoka, Mitsuru Yokota, Yoshinao Takano, Kyoko Kato, Hisanobu Oda, Takeshi Kajiwara, Kohei Ogawa, Nobuhiro Shibata, Kentaro Sawada, Takato Yomoda, Toshihiro Kudo, Hiroyuki Okuda, Yuta Okumura, Chihiro Tanaka, Masato Nakamura, Takashi Tsuda, Takahito Kitajima, Hiroshi Tsukuda, Eiji Shinozaki, Mitsuhiro Furuta, Tomomi Kashiwada, Koichi Okuya, Hiroyuki Mushiake, Junichi Hasegawa, Koei Nihei, Takashi Mizushima, Takashi Mine, Takuro Mizukami, Chiho Kudo, Ayako Mishima, Kenta Murotani, Toshiki Masuishi, on behalf of the PRABITAS investigators† Summary Background Trifluridine–tipiracil (FTD–TPI) plus bevacizumab is the standard treatment for refractory metastatic colorectal cancer. However, the conventional schedule is frequently associated with haematological and gastrointestinal toxicity, which is clinically significant and relevant to patients. A simplified 14-day schedule has been proposed to reduce toxicity, but whether this treatment preserves survival has not been established in a randomised trial. We therefore aimed to assess whether the 14-day schedule is non-inferior to the conventional schedule for overall survival. Methods PRABITAS was a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial conducted in 178 hospitals in Japan. Patients with refractory metastatic colorectal cancer were randomly assigned (1:1) using a minimisation algorithm, stratified by Eastern Cooperative Oncology Group performance status, RAS mutational status, and institution, to FTD–TPI (35 mg/m² orally twice daily) plus bevacizumab (5 mg/kg intravenously) on either a conventional 28-day (FTD–TPI on days 1–5 and 8–12; bevacizumab on days 1 and 15) or 14-day schedule (FTD–TPI on days 1–5; bevacizumab on day 1). Eligibility criteria were broadened compared with those of conventional explanatory trials, and trial procedures were aligned with routine clinical practice. The primary endpoint was overall survival, analysed in the intention-to-treat population, with a prespecified non-inferiority margin of 1·25. Safety was assessed in all patients who received at least one dose. Missing data were not imputed. This trial is registered with the Japan Registry of Clinical Trials, jRCTs041230120, and is closed to enrolment. Findings Between Dec 26, 2023, and May 20, 2025, we randomly assigned 972 patients, of whom 970 (99%) constituted the intention-to-treat population after two were excluded because they were randomly assigned before site approval (486 [50%] to the 28-day treatment group, 292 [60%] men and 194 [40%] women]; and 484 [50%] to the 14-day treatment group, 264 [55%] men and 220 [45%] women). Median follow-up was 17·9 months (IQR 14·3–22·6). Median overall survival was 10·3 months (95% CI 9·5–11·6) in the 28-day group and 11·3 months (10·2–12·5) in the 14-day group (stratified hazard ratio 0·93 [95% CI 0·80–1·08]). The 12-month overall survival rates were 44·0% (95% CI 39·5–48·5) in the 28-day group and 47·5% (42·9–52·0) in the 14-day group. Neutropenia grade 3 or worse was reduced in the 14-day group (13% vs 39%; absolute difference 25 percentage points [95% CI 20–31]), as was anorexia grade 2 or worse (15% vs 26%; absolute difference 11 percentage points [6–16]). Two treatment-related deaths occurred in the 14-day group and none in the 28-day group. Interpretation A 14-day schedule of FTD–TPI plus bevacizumab was non-inferior to the conventional 28-day schedule for overall survival, while reducing haematological and gastrointestinal toxicity. These findings support this simplified schedule as the new standard for FTD–TPI plus bevacizumab in refractory metastatic colorectal cancer. Funding Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Challenging Research (Pioneering). Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Introduction Colorectal cancer is a leading cause of cancer-related mortality worldwide, with approximately 1·9 million new cases and 900 000 deaths annually.1 For patients with metastatic colorectal cancer who experience disease progression after fluoropyrimidine-based, oxaliplatin-based, and irinotecan-based chemotherapy, international guidelines recommend sequential use of later-line Sidebar: Published Online October 24, 2026 https://doi.org/10.1016/S0140-6736(26)01782-4 | See Online/Comment https://doi.org/10.1016/S0140-6736(26)02034-9 | *Contributed equally to this work as joint first authors | †Investigators listed in the appendix (p 2) | Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan (T Sakakida MD, H Taniguchi MD, A Mishima, T Masuishi MD); Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T Sakakida); Department of Gastroenterology, Saitama Cancer Center, Kitaadachigun, Japan (M Asayama MD); Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan (Y Suwa MD); Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan (T Shimura MD); Department of Medical Oncology, Kindai University Faculty of Medicine, Sakai, Japan (S Mitani MD); Cancer Center, Gifu University Hospital, Gifu, Japan (A Makiyama MD); Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan (H Arai MD, T Mizukami MD); Department of Surgery, Fujita Health University Hospital, Toyoake, Japan (Prof H Matsuoka MD); www.thelancet.com Published online October 24, 2026 https://doi.org/10.1016/S0140-6736(26)01782-4

28-day schedule 14-day schedule Overall survival (%) Time (months) HR 0·93 (95% CI 0·80–1·08) Number at risk (censored) 28-day schedule 14-day schedule Figure 2: Kaplan–Meier estimates of overall survival in the intention-to-treat population Vertical lines indicate censored data. HRs were estimated from stratified Cox proportional-hazards models with Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2) and RAS mutation status (wild-type vs mutant) as strata. Median survival times and 95% CIs were estimated by the Brookmeyer–Crowley method; 95% CIs for HRs were obtained from the stratified Cox model. The prespecified non-inferiority margin was HR 1·25. HR=hazard ratio. Survival table Endpoint: OS (ITT) 28-day schedule | 486 14-day schedule | 484 HR: 0.93 HR CI: 0.80–1.08

Articles 14-day versus 28-day trifluridine–tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan Tomoki Sakakida*, Hiroya Taniguchi*, Masako Asayama*, Yusuke Suwa, Takaya Shimura, Seiichiro Mitani, Akitaka Makiyama, Hiroyuki Arai, Hiroshi Matsuoka, Mitsuru Yokota, Yoshinao Takano, Kyoko Kato, Hisanobu Oda, Takeshi Kajiwara, Kohei Ogawa, Nobuhiro Shibata, Kentaro Sawada, Takato Yomoda, Toshihiro Kudo, Hiroyuki Okuda, Yuta Okumura, Chihiro Tanaka, Masato Nakamura, Takashi Tsuda, Takahito Kitajima, Hiroshi Tsukuda, Eiji Shinozaki, Mitsuhiro Furuta, Tomomi Kashiwada, Koichi Okuya, Hiroyuki Mushiake, Junichi Hasegawa, Koei Nihei, Takashi Mizushima, Takashi Mine, Takuro Mizukami, Chiho Kudo, Ayako Mishima, Kenta Murotani, Toshiki Masuishi, on behalf of the PRABITAS investigators†

[Slide 1] Study Design ACTICCA-1 is an investigator-initiated, randomised, controlled, phase 3 study. Key inclusion criteria - Age 18 years or older - Histologically confirmed CCA or muscle-invasive gallbladder cancer - Mixed tumour types and ampullary cancers excluded - Macroscopically complete resection with curative intent (R0 and R1) - ECOG 0 or 1 - Adequate renal, haematological, and liver function - Start of adjuvant treatment within 6 to 16 weeks after surgery R 1:1 Stratification - Tumour location - N0 vs. N1 - R0 vs. R1 Group A CisGem (ABC 02): 8 cycles cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and 8 of a 21 days cycle CT or MRI q 3 months for 2 years, imaging q 6 months for 3 additional years Group B Capecitabine (BILCAP): 8 cycles capecitabine 1.250 mg/m2 BID on days 1 through 14 of a 21 days cycle Primary endpoint - Disease-free survival (DFS), i.e. recurrence or death due to any cause Secondary endpoints - Overall survival (OS) - Cumulative Recurrence - Safety (CTCAE version 4.03) - Quality of life (QoL) monitored with EORTC QLQ-C30 and BIL 21 ACTICCA-1 was conducted in 67 hepatobiliary sites in Australia, Austria, Denmark, Germany, Italy, New Zealand, The Netherlands, and the United Kingdom. Henning Wege, LBA21, ACTICCA-1 [Slide 2] Primary Endpoint (DFS) [KM: Disease-free survival probability vs Time since randomization (years)] Group A CisGem / Group B Capecitabine DFS rate at 24 months 52% vs. 44% - Median DFS 25.7 vs. 17.9 months - Log rank p=0.097 - Cox HR 0.82 (95% CI 0.67-1.01), p=0.058 - Non-constant treatment effect (Schoenfeld residuals) Number at risk: Group A 297 191 140 110 75 35 Group B 294 169 122 101 72 30 Henning Wege, LBA21, ACTICCA-1 Survival table Endpoint: Disease-free survival (primary) Group A CisGem | 297 | 25.7 months Group B Capecitabine | 294 | 17.9 months HR: 0.82 (Cox) HR CI: 0.67-1.01 (95% CI) P: Cox p=0.058; log rank p=0.097 Landmark rates: 24 months: Group A CisGem 52% | Group B Capecitabine 44% [Slide 3] Secondary Endpoints (OS & Recurrence) RMST OS (3 years) Δ 1.44 months, p=0.076 [KM: Overall survival probability vs Time since randomization (years)] Number at risk: Group A 297 193 101 2; Group B 294 177 98 1 Median OS 58.1 vs. 48.2 months, Cox HR 0.82, p=0.103 Cumulative incidence of recurrence or disease-related death (Aalen-Johansen estimates) [Curve: Cumulative incidence vs Time since randomization (years)] Group A CisGem / Group B Capecitabine Henning Wege, LBA21, ACTICCA-1 Survival table Endpoint: Overall survival (secondary) Group A CisGem | 297 | 58.1 months Group B Capecitabine | 294 | 48.2 months HR: 0.82 (Cox) P: 0.103 [Slide 4] Safety (Selected Events) Graded via CTCAE version 4.03 Group A CisGem, N=297 | Group B Capecitabine, N=294 | Total, N=591 All events (%), G3/4 (%) 1967 (74.7), 348 (23.2) | 1662 (69.5), 158 (14.3) | 3629 (72.1), 506 Severe 130 | 113 | 243 Related 51 | 47 | 98 Haematology (%), G3/4 577 (25.9), 234 | 180 (6.5), 18 | 757 (16.2), 252 Anaemia 114 | 21 | 135 Neutropenia 233 | 29 | 262 Gastrointestinal (%), G3/4 361 (11.8), 11 | 452 (15.0), 40 | 813 (13.4), 51 Diarrhoea 65 | 139 | 204 Nausea 91 | 85 | 176 Stomatitis 18 | 23 | 41 Skin (%), G3/4 105 (3.0), 1 | 353 (16.0), 44 | 458 (9.5), 45 Alopecia 29 | 9 | 38 PPES 4 | 262 | 266 General (%), G3/4 294 (9.1), 20 | 214 (12.2), 6 | 508 (10.7), 26 Fatigue 167 | 112 | 279 PPE = Palmar-plantar erythrodysestesia syndome Henning Wege, LBA21, ACTICCA-1

[Slide 3] Secondary Endpoints (OS & Recurrence) RMST OS (3 years) Δ 1.44 months, p=0.076 Y-axis: Overall survival probability; X-axis: Time since randomization (years) 0–6 Group A 297 193 101 2 Group B 294 177 99 1 Median OS 58.1 vs. 48.2 months, Cox HR 0.82, p=0.103 Cumulative incidence of recurrence or disease-related death (Aalen-Johansen estimates) Y-axis: Cumulative incidence; X-axis: Time since randomization (years) 0–5 Group A CisGem; Group B Capecitabine Henning Wege, LBA21, ACTICCA-1 Survival table Endpoint: Overall survival (secondary endpoint) Group A CisGem | 297 | 58.1 months Group B Capecitabine | 294 | 48.2 months HR: 0.82 (Cox) P: 0.103 (Cox); RMST OS (3 years) Δ 1.44 months, p=0.076

[Slide 1] Presentation Adjuvant chemotherapy with gemcitabine and cisplatin compared to standard of care after curative intent resection of cholangiocarcinoma and gallbladder carcinoma (ACTICCA-1 trial) Saturday, 24 Oct 2026 10:25 - 10:35 Alicante Auditorium - Hall 6 Save | Note Info Background Despite surgery and adjuvant capecitabine, about 50% of biliary tract cancer (BTC) patients recur or die within two years. Gemcitabine and cisplatin (GC) has been the established chemotherapy regimen in advanced BTC, providing a strong rationale for its evaluation in the adjuvant setting. [Slide 2] Background Despite surgery and adjuvant capecitabine, about 50% of biliary tract cancer (BTC) patients recur or die within two years. Gemcitabine and cisplatin (GC) has been the established chemotherapy regimen in advanced BTC, providing a strong rationale for its evaluation in the adjuvant setting. Methods ACTICCA-1 is a randomized, phase III investigator-initiated trial. Patients were enrolled at 60 sites across 7 countries between September 2017 and January 2023 and randomized to adjuvant GC (arm A) or capecitabine (arm B), both for 24 weeks. The primary endpoint is disease-free survival (DFS) in the full analysis set (FAS). Secondary endpoints include overall survival, safety and tolerability of chemotherapy, quality of life, and patterns of disease recurrence. Results At the data cut-off date of Dec 31, 2025, 591 patients had been randomized. Median follow-up was 4.8 years. Median age was 63, 46.9% were female, and median interval between surgery and enrolment was 67 days. The location was intrahepatic in 28.3%, perihilar in 19%, distal in 36.5%, and gallbladder in 16.2%. N+ was 47.9%. DFS favoured arm A compared to arm B (median 2.14 vs. 1.49 years, log rank p=0.097). As pre-defined in the statistical analysis plan (SAP), due to violation of the proportional hazard assumption Cox model (HR 0.82, 95% CI 0.67-1.01) was not feasible and restricted mean survival time (RMST) was analysed. Patients in arm A experienced on average 2.6 additional DFS months compared to arm B (RMST in the first 3 years p=0.01) and a strong trend in overall survival (p=0.076). Toxicity showed a slightly higher rate of severe adverse events (130 vs. 113 with 51 vs. 47 treatment related) and adverse events rate (74.4% vs. 69.5% of patients) in arm A compared to B. Further endpoints will be displayed at the meeting. Conclusions GC is an adjuvant treatment option for BTC. Clinical trial identification NCT02104882; 2012-005078-70. Legal entity responsible for the study University Medical Center Hamburg Eppendorf.

[Slide 2] Patient Allocation Randomisation 1:1 N=601 Allocated to CisGem N=301 • 297 received allocated intervention • 4 recurrence at inclusion Analysed N=297 Discontinuation reason at cut-off • 96 death • 15 lost to follow-up • 14 withdrawal of consent • 6 patient decision • 3 choice of investigator • 8 other reason • 72 no reason provided Allocated to Capecitabine N=300 • 294 received allocated intervention • 6 recurrence at inclusion Analysed N=294 Discontinuation reason at cut-off • 102 death • 13 lost to follow up • 1 SAE reason • 4 withdrawal of consent • 3 patient decision • 6 choice of investigator • 13 other reason • 81 no reason provided • Recruitment Sep. 2017 until Jan. 2023 • Data cut-off Dec. 31st in 2025 • Median follow-up 4.8 years (95% CI 4.6-4.9) • 591 patients evaluated as modified ITT population (i.e. all randomized patients regardless of treatment received) Henning Wege, LBA21, ACTICCA-1 [Slide 3] Patient Characteristics | Stratification parameters Columns: Group A CisGem, N=297 | Group B Capecitabine, N=294 | Total, N=591 Age in years [range] | 63.0 [27-82] | 63.0 [26-83] | 63.0 [26-83] Male (%) Male | 154 (51.9) | 160 (54.4) | 314 (53.1) ECOG 0 | 172 (58.3) | 179 (58.0) | 342 (58.2) ECOG 1 | 120 (40.7) | 119 (40.6) | 239 (40.6) Localisation (%) Intrahepatic | 85 (28.6) | 82 (27.9) | 167 (28.3) Perihilar | 55 (18.5) | 57 (19.4) | 112 (19.0) Distal | 109 (36.7) | 107 (36.4) | 216 (36.5) Gallbladder | 48 (16.2) | 48 (16.3) | 96 (16.2) T-Status (%) T1 | 49 (16.9) | 52 (17.9) | 101 (17.4) T2 | 134 (46.2) | 141 (48.5) | 275 (47.3) T3 | 95 (32.8) | 90 (30.9) | 185 (31.8) T4 | 11 (3.8) | 6 (2.1) | 17 (2.9) R-Status (%) R0 | 201 (67.7) | 199 (67.7) | 400 (67.7) Lymph node (%) Negative | 155 (52.2) | 153 (52.0) | 308 (52.1) Time since surgery (%) <2 months | 121 (40.7) | 110 (37.4) | 231 (39.1) Henning Wege, LBA21

[Slide 2] Subgroup Analysis • RMST DFS (3 years) of subgroups showed differences with CIs excluding 0* for male, ECOG 1, T3-4, distal CCA, lymph node positive, R0. • In exploratory interaction testing, there were no significant signals of potential effect heterogeneity. Legend: Group A CisGem | Group B Capecitabine Columns: Subgroup | Group A events/n(%) | Group A RMST | Group B events/n(%) | Group B RMST | Difference RMST | Favours CisGem | interaction p-value Sex (interaction p 0.614) f | 83/143 (58.0%) | 23.8 (22.0-25.8) | 76/134 (56.7%) | 21.9 (19.8-24.1) | 2.0 (-0.9-4.8) m | 93/154 (60.4%) | 22.7 (20.9-24.7) | 113/160 (70.6%) | 19.6 (17.8-21.6) | 3.1 (0.5-5.8) * Age (0.825) ≤63 | 100/151 (66.2%) | 22.3 (20.5-24.2) | 102/150 (68.0%) | 19.7 (17.9-21.8) | 2.6 (-0.1-5.3) >63 | 76/146 (52.1%) | 24.4 (22.5-26.4) | 87/144 (60.4%) | 21.5 (19.6-23.7) | 2.8 (0.0-5.6) Type of surgery (0.535) Open | 146/231 (63.2%) | 22.5 (21.0-24.1) | 143/219 (65.3%) | 20.2 (18.6-22.0) | 2.3 (0.0-4.6) Laparoscopic | 23/52 (44.2%) | 26.7 (23.8-29.9) | 33/58 (56.9%) | 23.4 (20.5-26.7) | 3.3 (-1.0-7.6) Robotic | 7/13 (53.8%) | 22.9 (17.0-30.7) | 13/16 (81.2%) | 15.7 (11.0-22.4) | 7.1 (-1.6-15.9) ECOG status (0.085) 0 | 101/172 (58.7%) | 23.1 (21.4-25.0) | 103/170 (60.6%) | 22.0 (20.2-24.0) | 1.1 (-1.5-3.7) 1 | 73/120 (60.8%) | 23.6 (21.6-25.7) | 83/119 (69.7%) | 19.0 (16.9-21.3) | 4.6 (1.6-7.6) * T classification (0.511) T1-2 | 93/183 (50.8%) | 25.5 (23.8-27.2) | 106/193 (54.9%) | 23.5 (21.8-25.4) | 2.0 (-0.5-4.5) T3-4 | 78/106 (73.6%) | 19.2 (17.0-21.6) | 79/96 (82.3%) | 15.2 (13.1-17.7) | 4.0 (0.7-7.2) * L classification (0.709) L0 | 52/117 (44.4%) | 27.1 (25.1-29.2) | 58/116 (50.0%) | 24.3 (22.2-26.7) | 2.7 (-0.3-5.8) L1 | 87/121 (71.9%) | 19.6 (17.6-21.8) | 97/127 (76.4%) | 16.8 (14.9-19.1) | 2.7 (-0.2-5.7) Grading (0.298) G1-G2 | 105/177 (59.3%) | 23.4 (21.6-25.2) | 107/170 (62.9%) | 21.5 (19.7-23.5) | 1.9 (-0.7-4.4) G3-G4 | 45/76 (59.2%) | 22.4 (19.8-25.4) | 61/86 (70.9%) | 18.0 (15.5-20.8) | 4.5 (0.7-8.3) Type of cancer (0.710) intrahepatic (CCA) | 41/85 (48.2%) | 25.5 (23.1-28.1) | 49/82 (59.8%) | 22.2 (19.6-25.1) | 3.3 (-0.3-7.0) perihilar / Klatskin (CCA) | 33/55 (60.0%) | 23.3 (20.4-26.6) | 34/57 (59.6%) | 22.5 (19.5-25.9) | 0.8 (-3.6-5.2) distal extrahepatic (CCA) | 75/109 (68.8%) | 20.9 (18.8-23.2) | 81/107 (75.7%) | 17.2 (15.1-19.6) | 3.7 (0.5-6.8) * muscle invasive gallbladder carcinoma | 27/48 (56.2%) | 24.5 (21.5-28.0) | 25/48 (52.1%) | 23.4 (20.1-27.2) | 1.1 (-3.6-5.9) Lymph node status (0.899) Negative | 74/155 (47.7%) | 26.4 (24.7-28.3) | 80/153 (52.3%) | 24.3 (22.4-26.4) | 2.2 (-0.5-4.9) Positive | 102/142 (71.8%) | 19.8 (17.9-21.9) | 109/141 (77.3%) | 16.6 (14.7-18.8) | 3.2 (0.3-6.0) * Tumor resection (0.109) R0 | 100/201 (49.8%) | 25.7 (24.1-27.4) | 118/199 (59.3%) | 22.0 (20.3-23.9) | 3.7 (1.3-6.2) * R1 | 76/96 (79.2%) | 18.4 (16.2-20.8) | 71/95 (74.7%) | 17.4 (15.1-20.0) | 1.0 (-2.3-4.3) Forest axis 0 5 10 15 Henning Wege, LBA21, ACTICCA-1 [Slide 4] Summary & Conclusions • ACTICCA-1 is the largest RCT in adjuvant BTC comparing two active regimens (CisGem vs. capecitabine). • CisGem did not significantly improve DFS at 24 months (52% vs. 44%, Δ 8%, Cox HR 0.82, p=0.058) and no significant interaction was noted in the subgroup analyses. • Despite a difference in median OS of nearly 10 months (58.1 vs. 48.2 months), the secondary endpoint OS did not show a significant improvement for CisGem compared to capecitabine (Cox HR 0.82, p=0.103). • In the first 3 years, CisGem significantly increased DFS by RMST analysis with Δ 2.6 months (p=0.011). • As expected, CisGem demonstrated an increased (and mainly haematological) toxicity. CisGem should not be considered as a standard of care, however is an adjuvant treatment option for patients with BTC. Henning Wege, LBA21, ACTICCA-1

[Slide 1] Kaplan-Meier curve for the primary endpoint Disease-free survival Legend: CisGem; Capecitabine X-axis: Time since randomization [years]; Y-axis: Disease-free survival probability Number at risk (years 0 | 1 | 2 | 3 | 4 | 5) CisGem Number at risk: 297 | 191 | 140 | 110 | 75 | 35 CisGem Cumulative number censored: 0 | 20 | 24 | 29 | 52 | 87 Capecitabine Number at risk: 294 | 169 | 122 | 101 | 72 | 30 Capecitabine Cumulative number censored: 0 | 14 | 15 | 19 | 41 | 75 Survival table Endpoint: Disease-free survival (primary endpoint) CisGem | 297 Capecitabine | 294 [Slide 2] Overall survival Legend: CisGem; Capecitabine X-axis: Time since randomization [years]; Y-axis: Overall survival probability Number at risk (years 0 | 1 | 2 | 3 | 4 | 5) CisGem Number at risk: 297 | 248 | 193 | 154 | 101 | 49 CisGem Cumulative number censored: 0 | 24 | 33 | 43 | 78 | 122 Capecitabine Number at risk: 294 | 238 | 177 | 142 | 99 | 42 Capecitabine Cumulative number censored: 0 | 24 | 30 | 35 | 64 | 111 Survival table Endpoint: Overall survival CisGem | 297 Capecitabine | 294

Subgroup Analysis • RMST DFS (3 years) of subgroups showed differences with CIs excluding 0* for male, ECOG 1, T3-4, distal CCA, lymph node positive, R0. • In exploratory interaction testing, there were no significant signals of potential effect heterogeneity. Group A CisGem Group B Capecitabine ACTICCA-1 UKE Universitätsklinikum Hamburg-Eppendorf Subgroup | Group A events/n(%) | Group A RMST | Group B events/n(%) | Group B RMST | Difference RMST | Favours CisGem | interaction p-value Sex | | | | | | 0.614 f | 83/143 (58.0%) | 23.8 (22.0 - 25.8) | 76/134 (56.7%) | 21.9 (19.8 - 24.1) | 2.0 (-0.9 - 4.8) m | 93/154 (60.4%) | 22.7 (20.9 - 24.7) | 113/160 (70.6%) | 19.6 (17.8 - 21.6) | 3.1 (0.5 - 5.8) * Age | | | | | | 0.825 ≤ 63 | 100/151 (66.2%) | 22.3 (20.5 - 24.2) | 102/150 (68.0%) | 19.7 (17.9 - 21.8) | 2.6 (-0.1 - 5.3) > 63 | 76/146 (52.1%) | 24.4 (22.5 - 26.4) | 87/144 (60.4%) | 21.5 (19.6 - 23.7) | 2.8 (0.0 - 5.6) Type of surgery | | | | | | 0.535 Open | 146/231 (63.2%) | 22.5 (21.0 - 24.1) | 143/219 (65.3%) | 20.2 (18.6 - 22.0) | 2.3 (0.0 - 4.6) Laparoscopic | 23/52 (44.2%) | 26.7 (23.8 - 29.9) | 33/58 (56.9%) | 23.4 (20.5 - 26.7) | 3.3 (-1.0 - 7.6) Robotic | 7/13 (53.8%) | 22.9 (17.0 - 30.7) | 13/16 (81.2%) | 15.7 (11.0 - 22.4) | 7.1 (-1.6 - 15.9) ECOG status | | | | | | 0.085 0 | 101/172 (58.7%) | 23.1 (21.4 - 25.0) | 103/170 (60.6%) | 22.0 (20.2 - 24.0) | 1.1 (-1.5 - 3.7) 1 | 73/120 (60.8%) | 23.6 (21.6 - 25.7) | 83/119 (69.7%) | 19.0 (16.9 - 21.3) | 4.6 (1.6 - 7.6) * T classification | | | | | | 0.511 T1-2 | 93/183 (50.8%) | 25.5 (23.8 - 27.2) | 106/193 (54.9%) | 23.5 (21.8 - 25.4) | 2.0 (-0.5 - 4.5) T3-4 | 78/106 (73.6%) | 19.2 (17.0 - 21.6) | 79/96 (82.3%) | 15.2 (13.1 - 17.7) | 4.0 (0.7 - 7.2) * L classification | | | | | | 0.709 L0 | 52/117 (44.4%) | 27.1 (25.1 - 29.2) | 58/116 (50.0%) | 24.3 (22.2 - 26.7) | 2.7 (-0.3 - 5.8) L1 | 87/121 (71.9%) | 19.6 (17.6 - 21.8) | 97/127 (76.4%) | 16.8 (14.9 - 19.1) | 2.7 (-0.2 - 5.7) Grading | | | | | | 0.298 G1-G2 | 105/177 (59.3%) | 23.4 (21.6 - 25.2) | 107/170 (62.9%) | 21.5 (19.7 - 23.5) | 1.9 (-0.7 - 4.4) G3-G4 | 45/76 (59.2%) | 22.4 (19.8 - 25.4) | 61/86 (70.9%) | 18.0 (15.5 - 20.8) | 4.5 (0.7 - 8.3) Type of cancer | | | | | | 0.710 intrahepatic (CCA) | 41/85 (48.2%) | 25.5 (23.1 - 28.1) | 49/82 (59.8%) | 22.2 (19.6 - 25.1) | 3.3 (-0.3 - 7.0) perihilar / Klatskin (CCA) | 33/55 (60.0%) | 23.3 (20.4 - 26.6) | 34/57 (59.6%) | 22.5 (19.5 - 25.9) | 0.8 (-3.6 - 5.2) distal extrahepatic (CCA) | 75/109 (68.8%) | 20.9 (18.8 - 23.2) | 81/107 (75.7%) | 17.2 (15.1 - 19.6) | 3.7 (0.5 - 6.8) * muscle invasive gallbladder carcinoma | 27/48 (56.2%) | 24.5 (21.5 - 28.0) | 25/48 (52.1%) | 23.4 (20.1 - 27.2) | 1.1 (-3.6 - 5.9) Lymph node status | | | | | | 0.899 Negative | 74/155 (47.7%) | 26.4 (24.7 - 28.3) | 80/153 (52.3%) | 24.3 (22.4 - 26.4) | 2.2 (-0.5 - 4.9) Positive | 102/142 (71.8%) | 19.8 (17.9 - 21.9) | 109/141 (77.3%) | 16.6 (14.7 - 18.8) | 3.2 (0.3 - 6.0) * Tumor resection | | | | | | 0.109 R0 | 100/201 (49.8%) | 25.7 (24.1 - 27.4) | 118/199 (59.3%) | 22.0 (20.3 - 23.9) | 3.7 (1.3 - 6.2) * R1 | 76/96 (79.2%) | 18.4 (16.2 - 20.8) | 71/95 (74.7%) | 17.4 (15.1 - 20.0) | 1.0 (-2.3 - 4.3) Henning Wege, LBA21, ACTICCA-1

[Slide 1] Camupepimut (ELI-002 7P) Mechanism of Action Targeting the Lymph Nodes with Amphiphile (AMP) to Orchestrate Anti-tumor T cell Response Tissue Injection Site: AMP; Endogenous Albumin; Albumin-bound AMP Lymph Node: Albumin-bound AMP; Antigen Presenting Cell; T Cell APC Activation T Cell Response ↑ Expansion ↑ Persistence ↑ Effector function ↑ Phenotype 1 Subcutaneous injection -> 2 Albumin binding -> 3 Lymph node targeting -> 4 Delivery to immune cells -> 5 T Cell Response Wainberg, O'Reilly, et al. Nature Medicine. 2025; Pant, O'Reilly, et al. Nature Medicine. 2024; Liu, Irvine, et al. Nature. 2014; Moynihan, Irvine, et al. Nature Medicine. 2016; Ma, Irvine, et al. Science. 2019 Eileen M. O'Reilly, MD, FASCO [Slide 2] AMPLIFY-7P Phase 2 Primary Endpoint: DFS endpoint in ITT not met n=144 | Intention-to-Treat: Camupepimut (n=96) Median 23.8 months Observation (n=48) Median 21.2 months HR: 0.85 (0.52-1.41) P=0.5329 Dosing Period (shaded, ~0-4.5 months) Y axis: Disease-free Survival (%); X axis: Months At risk (0,3,...,27 mo): Camupepimut: 96 82 64 50 42 40 24 15 6 0 Observation: 48 36 29 28 24 22 16 10 4 0 Eileen M. O'Reilly, MD, FASCO Primary DFS analyses used stratified Cox model and specified stratified log-rank test; DCO: April 20, 2026 Survival table Endpoint: DFS (primary, ITT) Camupepimut | 96 | 23.8 months Observation | 48 | 21.2 months HR: 0.85 HR CI: 0.52-1.41 P: 0.5329 [Slide 3] Exploratory Analysis: DFS Supervised by mKRAS T Cell Response Strength of mKRAS-specific T cell response significantly correlates to improved RFS / DFS in Phase 1, Phase 2 n=25 | Phase 1: RFS Supervised by T cell Response >=9.17x (n=17) HR: 0.12 (0.02-0.62) Median: Not Reached <9.17x (n=8) P=0.0002 Median: 3.02 months Y axis: Relapse-free Survival (%); X axis: Months At risk: >=9.17x 17 13 10 8 6 6 3 1 0; <9.17x 8 3 1 1 1 1 0 n=90 | Phase 2: DFS Supervised by T cell Response >9.17x (n=74) HR: 0.22 (0.08-0.63) Median: Not Reached <9.17x (n=16) P<0.0001 Median: 6.08 months Y axis: Disease-free Survival (%); X axis: Months At risk: >9.17x 74 68 53 46 40 38 24 15 6 0; <9.17x 16 9 7 3 1 1 0 Eileen M. O'Reilly, MD, FASCO Phase 1 ELI-002-2P: Wainberg, O'Reilly, et al. Nature Medicine. 2025; mKRAS T cell fold-change assessed among n=90 evaluable patients; DCO: April 20, 2026 Survival table Endpoint: Phase 1 RFS / Phase 2 DFS by mKRAS T-cell response fold-change (exploratory) Phase 1 >=9.17x | 17 | Not Reached Phase 1 <9.17x | 8 | 3.02 months Phase 2 >9.17x | 74 | Not Reached Phase 2 <9.17x | 16 | 6.08 months HR: Phase 1 0.12; Phase 2 0.22 HR CI: Phase 1 0.02-0.62; Phase 2 0.08-0.63 P: Phase 1 P=0.0002; Phase 2 P<0.0001 [Slide 4] Pre-specified DFS Analysis: ctDNA Positive vs ctDNA Negative Camupepimut treatment effect was consistent in ctDNA+ and ctDNA- n=119 | Prespecified: ctDNA Positive vs Negative ctDNA: Negative - Camupepimut / Observation: HR: 0.51 (0.25-1.02) P=0.0280 ctDNA: Positive - Camupepimut / Observation: HR: 0.57 (0.22-1.48) P=0.0489 Camupepimut, ctDNA- Median: Not Reached Observation, ctDNA- Median: 21.2 months Camupepimut, ctDNA+ Median: 4.3 months Observation, ctDNA+, Median: 1.9 months Y axis: Disease-free Survival (%); X axis: Months At risk (0,3,...,27 mo): Camupepimut ctDNA-: 62 57 50 42 37 35 21 14 5 0 Observation ctDNA-: 31 24 20 19 17 16 12 8 3 0 Camupepimut ctDNA+: 20 13 7 1 1 1 1 0 0 0 Observation ctDNA+: 6 2 1 1 0 0 0 0 0 0 Eileen M. O'Reilly, MD, FASCO Unstratified analyses, non-adjusted P-values were calculated using two-sided Wilcoxon test; Primary DFS analyses used specified stratified log-rank test; ITT HR 0.85; DCO: April 20, 2026 Survival table Endpoint: DFS by baseline ctDNA status (pre-specified) Camupepimut, ctDNA- | Not Reached Observation, ctDNA- | 21.2 months Camupepimut, ctDNA+ | 4.3 months Observation, ctDNA+ | 1.9 months HR: ctDNA- 0.51; ctDNA+ 0.57 HR CI: ctDNA- 0.25-1.02; ctDNA+ 0.22-1.48 P: ctDNA- P=0.0280; ctDNA+ P=0.0489 (unstratified, non-adjusted, two-sided Wilcoxon)

[Slide 1] AMPLIFY-7P: Randomized Phase 2 Trial in Adjuvant mKRAS+ PDAC NCT05726864 (2:1 Randomized) Testing whether camupepimut (ELI-002 7P) improves DFS following standard locoregional therapy Camupepimut Monotherapy • 7 mKRAS peptide antigens Phase 2: Key Criteria • Includes: mKRAS G12D/R/V/C/A/S/G13D • Resected Stage I-III mKRAS PDAC • Complete R0/R1 resection • Radiographic NED status < 6 months • MRD agnostic (biomarker +/-) • Enrollment Completed 12/2024 R 2:1 — Stratification: Nodal Status N=96 Camupepimut Monotherapy N=48 Standard of Care: Observation Optional crossover @ confirmed PD N=144 pts, 24 U.S. Sites Endpoints Primary Endpoint: Disease Free Survival (DFS) Tumor Biomarker Response Overall Survival, Safety Exploratory: Immunogenicity DFS assessment by iRECIST (new lesions confirmed by biopsy/imaging); R0/R1: Absence or presence of microscopic residual disease; NED: No Evidence of Disease. MRD: Minimal Residual Disease. PD: Progressive Disease Eileen M. O'Reilly, MD, FASCO [Slide 4] Key Takeaways Published Today in Nature Medicine [QR code] George, O'Reilly, et al. Nature Medicine. 2026 Primary Endpoint Not Met • Primary DFS Endpoint: Not met in ITT population (HR: 0.85 P=0.5329) • However, the biologically, clinically relevant signal informs future Phase 3 Clear Clinical Signal in Prespecified Subgroups Consistent treatment effect observed in ctDNA negative (HR: 0.51 P=0.0280), ctDNA positive (HR: 0.57 P=0.0489), no prior radiation (HR: 0.59 P=0.0221) Biological Validation Strong mKRAS-specific T cell response (>9.17x) correlated with DFS (HR: 0.22 P<0.0001) Favorable Safety Camupepimut (ELI-002 7P) maintained a favorable safety profile DFS: Disease-free Survival; ITT: Intention-to-treat Eileen M. O'Reilly, MD, FASCO

[Slide 1] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Key Takeaways Published Today in Nature Medicine | [QR code] George, O'Reilly, et al. Nature Medicine. 2026 Primary Endpoint Not Met | • Primary DFS Endpoint: Not met in ITT population (HR: 0.85 P=0.5329) • However, the biologically, clinically relevant signal informs future Phase 3 Clear Clinical Signal in Prespecified Subgroups | Consistent treatment effect observed in ctDNA negative (HR: 0.51 P=0.0280), ctDNA positive (HR: 0.57 P=0.0489), no prior radiation (HR: 0.59 P=0.0221) Biological Validation | Strong mKRAS-specific T cell response (>9.17x) correlated with DFS (HR: 0.22 P<0.0001) Favorable Safety | Camupepimut (ELI-002 7P) maintained a favorable safety profile Eileen M. O'Reilly, MD, FASCO DFS, Disease-free Survival; ITT, Intention-to-treat [Speaker card] Eileen O'Reilly - Seven-valent mKRAS-specific lymph node targeted amphiphile immunotherapy versus observation in resected pancreatic ductal adenocarcinoma (PDAC): The AMPLIFY-7P randomized phase 2 study ALMERIA AUDITORIUM - HALL 9 [Slide 2] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive [partially cropped] AMPLIFY-7P Phase 2 Primary Endpoint: DFS endpoint in ITT not met n=144 Intention-to-Treat: Camupepimut (n=96) Median 23.8 months Observation (n=48) Median 21.2 months HR: 0.85 (0.52-1.41) P=0.5329 [KM curve; y-axis: Disease-free Survival (%); x-axis: Months 0-30; shaded Dosing Period] At risk (months 0, 3, 6, 9, 12, 15, 18, 21, 24, 27): Camupepimut: 96, 82, 64, 50, 42, 40, 24, 15, 6, 0 Observation: 48, 36, 29, 28, 24, 22, 16, 10, 4, 0 Primary DFS analyses used stratified Cox model and specified stratified log-rank test; DCO: April 20, 2026 Eileen M. O'Reilly, MD, FASCO ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: DFS (primary endpoint, ITT) Camupepimut | 96 | 23.8 months Observation | 48 | 21.2 months HR: 0.85 HR CI: 0.52-1.41 P: 0.5329 [Slide 3] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH AMPLIFY-7P Phase 2 Exploratory Analysis: mKRAS T Cell Response Potent mKRAS-specific T cell responses observed in patients randomized to camupepimut T Cell Response: 99% (89 / 90) Responders; 1% Non-responders T cell Fold Change Over Baseline: 146x Mean; 44x Median; 9.17x [y-axis: Fold-change from baseline 0-1300; Baseline vs Max Response] mKRAS T cell Response >9.17x: 82% (74 / 90) CD4 / CD8: 85% (68 / 80) CD4 + CD8; 9% CD4 Only; 6% CD8 Only mKRAS Variant Specificity (% with Response): G12D 89%; G12R 87%; G12V 82%; G12C 83%; G12A 88%; G12S 89%; G13D 88% [y-axis: Average fold change from baseline; Baseline vs Max Response] Among evaluable patients with assessable baseline and on-treatment samples; DCO: April 20, 2026 Eileen M. O'Reilly, MD, FASCO [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH AMPLIFY-7P Phase 2 Pre-specified DFS Analysis: No Prior Radiation Prior radiation observed to influence response to camupepimut; Treatment effect observed in no prior radiation n=106 Prespecified: No Prior Radiation Camupepimut (n=73) HR: 0.59 (0.33-1.03) Observation (n=33) P=0.0221 Median: 23.8 months [camupepimut] Median: 10.4 months [observation] [KM curve; y-axis: Disease-free Survival (%); x-axis: Months 0-30] At risk (months 0, 3, 6, 9, 12, 15, 18, 21, 24, 27): Camupepimut: 73, 64, 51, 40, 34, 33, 20, 11, 3, 0 Observation: 33, 21, 17, 17, 14, 13, 8, 4, 2, 0 Baseline Lymphocytes: Absolute Lymphocyte Count (x10^9 / L); P < 0.0001; Prior Radiation No vs Yes; Median 1.7 vs 1.2 mKRAS T Cell Response: Fold-change from baseline; P = 0.0011; Prior Radiation No vs Yes; Median 58x vs 15x mKRAS T cell Response >9.17x: OR: 0.21 (0.07-0.64) P=0.005 Unstratified analyses, non-adjusted P-values were calculated using two-sided Wilcoxon test; Primary DFS analyses used specified stratified log-rank test; ITT HR 0.85; DCO: April 20, 2026 Eileen M. O'Reilly, MD, FASCO ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: DFS, pre-specified subgroup: no prior radiation Camupepimut | 73 | 23.8 months Observation | 33 | 10.4 months HR: 0.59 HR CI: 0.33-1.03 P: 0.0221

13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH Primary Endpoint: DFS endpoint in ITT not met [AMPLIFY-7P Phase 2] n=144 | Intention-to-Treat: [KM curve; y-axis: Disease-free Survival (%); x-axis: Months 0-30; shaded Dosing Period] Camupepimut (n=96) Median 23.8 months Observation (n=48) Median 21.2 months HR: 0.85 (0.52-1.41) P=0.5329 At risk (0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30) Camupepimut 96 82 64 50 42 40 24 15 6 0 Observation 48 36 29 28 24 22 16 10 4 0 Eileen M. O'Reilly, MD, FASCO Primary DFS analyses used stratified Cox model and specified stratified log-rank test; DCO: April 20, 2026 [Speaker card] Eileen O'Reilly — Seven-valent mKRAS-specific lymph node targeted amphiphile immunotherapy versus observation in resected pancreatic ductal adenocarcinoma (PDAC): The AMPLIFY-7P randomized phase 2 study ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: DFS (ITT, primary) Camupepimut | 96 | 23.8 months Observation | 48 | 21.2 months HR: 0.85 HR CI: 0.52-1.41 P: 0.5329

[Slide 3] Pre-specified DFS Analysis: 6 Month DFS Rate AMPLIFY-7P Phase 2 n=144 Intention-to-Treat: 6 months Camupepimut: 75.7% Observation: 61.7% [faded legend: Camupepimut (n=96) Median 23.8 months; Observation (n=48) Median 21.2 months; HR: 0.85 (0.52-1.41) P=0.5329] Pre-specified DFS Rate | 6 months Camupepimut 75.7% Observation 61.7% DFS Rate Difference 14.0% P-value 0.0557 Exploratory HR from t0 to 6 months 0.55 Dosing Period At risk (months 0/3/6/9/12/15/18/21/24/27) Camupepimut: 96 82 64 50 42 40 24 15 6 0 Observation: 48 36 29 28 24 22 16 10 4 0 Eileen M. O'Reilly, MD, FASCO Primary DFS analyses used stratified Cox model and specified stratified log-rank test; DCO: April 20, 2026 Survival table Endpoint: DFS (ITT) - pre-specified 6-month DFS rate Camupepimut (ELI-002 7P) | 96 | 23.8 months Observation | 48 | 21.2 months HR: 0.85 HR CI: 0.52-1.41 P: 0.5329 Landmark rates: 6 months: Camupepimut (ELI-002 7P) 75.7% | Observation 61.7% [Slide 4] Methods AMPLIFY-7P is a randomized, open label phase 2 trial in patients (pts) with stages I-III, KRAS-mutated PDAC who received curative-intent therapy and no recurrence at ≤ 6 months. Pts randomized 2:1, stratified by lymph node status (N0 vs N1/2), to 10 doses camupepimut (prime, boost) or observation. Primary endpoint: investigator DFS; secondary: safety, 6-month DFS; success required Hazard Ratio (HR) ≤ 0.70, 2-sided alpha ~0.10. Results From 01-12/2024, 144 pts with mKRAS PDAC; 44.4% G12D, 35.4% G12V, 16.7% G12R: randomized to camupepimut (n=96) or observation (n=48) at 24 centers. Stratification balanced nodal status (N1/N2: 57[59.4%] vs 29[60.4%]) but ctDNA(+) 20[20.8%] vs 6[12.5%]. Primary DFS endpoint not met (HR 0.85, p=0.539), however, pre-specified 6-month DFS advantage of 14% (75.7% vs 61.7%; HR=0.55; p=0.0557) and mKRAS-specific T cells correlated with efficacy (mDFS not reached vs 6.08 mo; HR=0.22; p<0.0001); subgroups promising DFS:. Table: LBA83 Subgroup | n(%) | DFS (mo) | HR | Nominal p ctDNA(-) | 93(65%) | NR vs 21.2 | 0.51 | 0.0280 No radiation | 106(74%) | 23.8 vs 10.4 | 0.59 | 0.0221 Post-hoc multivariate Cox regression analysis DFS: camupepimut adjusted HR=0.45; 95%CI 00.25-0.80; p=0.0064; ctDNA adjusted HR=6.72; 95%CI 3.49-12.94; p<0.0001. Grade ≥ 3 AEs (10.4 vs 14.6%); serious AEs (6.3 vs 8.3%); no new safety signals. Immunogenicity: mKRAS-specific T cell responses 99% (89/90); 85% (68/80) CD8+ and CD4+ T cells and antigen spreading 87% (13/15). Conclusions Prespecified 6-month subgroup DFS increased and DFS associated with mKRAS-specific T cell response, although primary DFS endpoint not met. Baseline ctDNA(+) adversely prognostic/imbalanced. Phase III planned with refined stratification and pt selection factors.

AMPLIFY-7P | Phase 2 Pre-specified DFS Analysis: No Prior Radiation Prior radiation observed to influence response to camupepimut; Treatment effect observed in no prior radiation n=106 Prespecified: No Prior Radiation Disease-free Survival (%) Camupepimut (n=73) HR: 0.59 (0.33-1.03) Observation (n=33) P=0.0221 Median: 23.8 months [Camupepimut] Median: 10.4 months [Observation] Months At risk (0, 3, 6, 9, 12, 15, 18, 21, 24, 27) Camupepimut: 73 64 51 40 34 33 20 11 3 0 Observation: 33 21 17 17 14 13 8 4 2 0 Baseline Lymphocytes Absolute Lymphocyte Count (x10⁹ / L) P < 0.0001 Prior Radiation: No | Yes Median ▸ 1.7 | 1.2 mKRAS T Cell Response Fold-change from baseline P = 0.0011 Prior Radiation: No | Yes Median ▸ 58x | 15x 9.17x [threshold line] mKRAS T cell Response >9.17x OR: 0.21 (0.07-0.64) P=0.005 Unstratified analyses, non-adjusted P-values were calculated using two-sided Wilcoxon test; Primary DFS analyses used specified stratified log-rank test; ITT HR 0.85; DCO: April 20, 2026 Eileen M. O'Reilly, MD, FASCO Survival table Endpoint: DFS - prespecified subgroup: no prior radiation (n=106) Camupepimut | 73 | 23.8 months Observation | 33 | 10.4 months HR: 0.59 HR CI: 0.33-1.03 P: 0.0221 (unstratified, non-adjusted)

[Slide 2] MASTERPLAN: randomised phase II trial KEY ELIGIBILITY CRITERIA • Age ≥18 • ECOG PS 0-1 • One of: ➢ Operable disease with ≥1 high-risk feature ➢ Borderline resectable ➢ Locally advanced Open-label multicentre trial 14 hospitals R (2:1) Australia & New Zealand CHEMOTHERAPY ALONE: 3 months chemotherapy CHEMOTHERAPY + SBRT: 3 months chemotherapy + SBRT 40 Gy in 5 fractions → +/- SURGERY → ADJUVANT/ONGOING CHEMOTHERAPY PRIMARY ENDPOINT: 12-month locoregional recurrence (LRR) SECONDARY ENDPOINTS: PFS, OS, toxicity, (R0) resection rate, post operative complications NCT04089150 • ACTRN12619000409178 • Recruitment: Feb 2020–Jan 2025 4 [Slide 3] B Median overall survival, months (95% CI) Chemotherapy plus SBRT 22·0 (17·5–34·7) Chemotherapy alone 14·0 (8·9–19·2) HR 0·45 (0·25–0·81); logrank p=0·0061 Y-axis: Overall survival (%); X-axis: Time from randomisation (months) Number at risk (censored) at 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 months: Chemotherapy plus SBRT: 49 (0), 47 (2), 47 (2), 45 (2), 37 (2), 35 (3), 26 (6), 20 (8), 17 (9), 16 (9), 14 (10) Chemotherapy alone: 25 (0), 23 (0), 21 (0), 17 (0), 16 (0), 12 (0), 7 (2), 5 (3), 4 (4), 2 (4), 1 (4) Figure 3: Kaplan–Meier curve for progression-free survival (A) and overall survival (B) for the overall population receiving chemotherapy plus SBRT and those receiving chemotherapy alone The p value for overall survival is descriptive. HR=hazard ratio. SBRT=stereotactic body radiotherapy. Survival table Endpoint: Overall survival Arm | N | Median | Median CI Chemotherapy plus SBRT | 49 | 22.0 mo | 17.5-34.7 Chemotherapy alone | 25 | 14.0 mo | 8.9-19.2 HR: 0.45 HR CI: 0.25-0.81 P: 0.0061 (logrank, descriptive) [Slide 4] Perioperative chemotherapy and stereotactic body radiotherapy versus perioperative chemotherapy alone in patients with high-risk, localised pancreatic cancer (MASTERPLAN): an open-label, phase 2, multicentre, randomised trial of the Australasian Gastro-Intestinal Trials Group Andrew Oar, Andrew Kneebone, Katrin M Sjoquist, David Espinoza, Mark Lee, Hien Le, Leily Gholamrezaei, Julie Chu, James Lynam, Girish Mallesara, Dominique Lee, Dinesh Vignarajah, Iain Ward, Jaswinder Samra, Andrew Barbour, Angela Whitehead, Susan Brooks, Anna Nicholson, Tim Wei Wang, Weng Ng, Fathalla Ali, Derrick Siu, Juanita Lopez Gaitan, Olivia Cook, Alisha Moore, Martinus B Oostendorp, Sonia Yip, John Shakeshaft, David Pryor, Nam Nguyen, David Goldstein, on behalf of the Australasian Gastro-Intestinal Trials Group (AGITG) Summary

3136RO - Randomised phase II study of mFOLFIRINOX ± SBRT in patients with high risk, borderline resectable or locally advanced pancreatic cancer: Results of the AGITG MASTERPLAN trial Speakers Andrew Oar (Southport, Australia) Lecture Time 17:14 - 17:19 Abstract Background Stereotactic body radiotherapy (SBRT) delivers high-dose, precision radiotherapy (RT). Despite advances in chemotherapy (CT) for pancreatic cancer (PC), locoregional recurrences (LRR) are frequent and contribute to morbidity/mortality. Methods Eligible pts had operable disease with ≥1 high risk feature (>4 cm, extrapancreatic extension, or node positive), or BRPC, or LAPC. High-risk operable and BRPC pts were classified as potentially operable PC (POPC), while LAPC/medically inoperable pts as inoperable PC (IPC). Staging followed AGITG guidelines with central radiology review. CT was clinician choice: mFOLFIRINOX or gem/nab-paclitaxel. Pts were randomised 2:1 to 3mths of CT+SBRT (I) or to 3mths CT alone (C). SBRT was 40Gy in 5 fractions with fiducial marker guidance and real time RT quality assurance. After CT±SBRT, pts were evaluated for surgery. Following resection pts received 3mths adjuvant CT. Pts unsuitable for resection, continued CT for further 3mths. The primary endpoint was 12mth LRR. Secondary endpoints included resection rate, margin status, toxicity per CTCAE (v5.0), progression-free survival (PFS), and overall survival (OS). Results Across 14 sites 75 pts were enrolled with 1 ineligible, including 48 POPC and 26 IPC. 12mth LRR rates were 20.2 % (95% CI: 9.9-33.2%) v 52.0% (95% CI: 30.3-69.9%) in I and C respectively (p=0.022). In POPC, 12mth LRR rates were 19.7% (95% CI: 7.8–35.6) (I) v 52.9% (95% CI: 25.9–74.1) (C) (p=0.031), and in IPC 21.4% (95% CI: 4.8–45.8) (I) v 50.0% (95% CI: 11.4-80.2) (C) (p=0.16). Overall Grade 3+ toxicity occurred in 70.2% (I) and 64.0% (C) (p=0.27). Median PFS was 11.9 v 6.3 mths (p=0.002) and median OS 22.0 v 14.0 mths (p=0.006) in I and C, respectively. Table: 3136RO Clinicodemographics and outcomes | | C=Control (n=25) | I=Investigational (n=49) | P value | | Demographics | | | | | Median age (IQR) | 66 (55-70) | 65 (58-70) | 0.89 | | % Male | 72% | 51% | 0.08 | | Baseline Ca19.9 (median, IQR) | 340 (60-977) | 180 (34-1152) | 0.60 | | Staging | - | - | | | Operable with ≥1 high-risk feature | 3 (12%) | 1 (2.0%) | - | | BRPC | 14 (56%) | 30 (61%) | - | | IPC | 8 (32%) | 18 (37%) | 0.69 | | cN0 | 60% | 71% | 0.32 | | Treatment | | | | | CT regimen | - | - | - | | mFOLFIRINOX | 23 (92%) | 44 (90%) | - | | Gemcitabine/nab-paclitaxel | 2 (8%) | 3 (6%) | 1.0 | | Withdrawal prior to chemotherapy | 0 (0%) | 2 (4%) | | | SBRT commenced | NA | 39 (80%) | NA | | Surgical Outcomes (POPC only; n=48) | C=Control (n=17) | I=Investigational (n=31) | | | Resection performed n (%) | 10 (59%) | 21 (68%) | 0.54 | | R0 resection (>1mm) | 4/10 (40%) | 13/21 (62%) | 0.44 | Conclusions SBRT improved LRR and PFS without additional toxicity. A significant OS signal was observed in this cohort. Further research to optimise the role of SBRT is required.

THE LANCET Oncology ARTICLES · Online first, October 23, 2026 Perioperative chemotherapy and stereotactic body radiotherapy versus perioperative chemotherapy alone in patients with high-risk, localised pancreatic cancer (MASTERPLAN): an open-label, phase 2, multicentre, randomised trial of the Australasian Gastro-Intestinal Trials Group Andrew Oar, MBBS a · Prof Andrew Kneebone, MBBS b,c · Katrin M Sjoquist, PhD d · David Espinoza, MBioStat d · Mark Lee, MBBS e,f · Prof Hien Le, MBBS g,h · et al. Show more

[Slide 2] Primary outcome: lower 12-month locoregional recurrence (LRR) [Cumulative incidence plot: LRR Cumulative Incidence vs Time from randomisation - months; curves Chemotherapy, Chemotherapy + SBRT] HR: 0.44 (95% CI: 0.22-0.88, p(Gray's)=0.02) Number at risk (0, 3, 6, 9, 12, 15, 18, 21, 24 months) Chemotherapy 25 20 15 7 4 3 2 1 1 SBRT 49 44 38 31 22 17 13 11 10 12-month LRR 20.2% SBRT + chemotherapy 95% CI 9.9–33.1% 12-month LRR 52.0% Chemotherapy alone 95% CI 30.3–69.9% Treatment effect HR 0.44 95% CI 0.22–0.88; p=0.022 Absolute difference ~32% at 12 months Primary endpoint: ITT analysis. LRR includes synchronous LRR + distant progression. Sensitivity analysis for initial/isolated LRR: HR 0.35; p=0.044 Survival table Endpoint: 12-month locoregional recurrence (cumulative incidence) Chemotherapy + SBRT | 49 Chemotherapy alone | 25 HR: 0.44 HR CI: 0.22–0.88 P: 0.022 (Gray's) Landmark rates: 12 months: Chemotherapy + SBRT 20.2% LRR (CI 9.9–33.1%) | Chemotherapy alone 52.0% LRR (CI 30.3–69.9%) [Slide 3] PFS and OS: both favoured the addition of SBRT * PFS: 11.9 vs 6.3 mths HR 0.44 (95% CI 0.26–0.75); (p=0.002) [in-plot] HR: 0.44 (95% CI: 0.26-0.75, p(logrank)=0.002) Number at risk (0, 3, 6, 9, 12, 15, 18, 21, 24 months) Chemotherapy+SBRT 49 44 38 31 23 19 15 12 10 Chemotherapy 25 20 15 7 5 4 2 1 1 OS: 22.0 vs 14.0 mths HR 0.45 (95% CI 0.25–0.81); (p=0.006) [in-plot] HR: 0.45 (95% CI: 0.25-0.81, p(logrank)=0.006) Number at risk (0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 months) Chemotherapy+SBRT 49 47 47 45 37 35 26 20 17 16 14 Chemotherapy 25 23 21 17 16 12 7 5 4 2 1 * Secondary endpoint 8 Survival table Endpoint: PFS and OS (secondary endpoints) Chemotherapy + SBRT (PFS) | 49 | 11.9 mo Chemotherapy (PFS) | 25 | 6.3 mo Chemotherapy + SBRT (OS) | 49 | 22.0 mo Chemotherapy (OS) | 25 | 14.0 mo HR: PFS 0.44; OS 0.45 HR CI: PFS 0.26–0.75; OS 0.25–0.81 P: PFS 0.002; OS 0.006 (log-rank) [Slide 4] CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ Conclusions • MASTERPLAN first prospective randomised trial showing significant benefit of SBRT in high risk localised PDAC • SBRT significantly reduced LRR and improved PFS • SBRT was safe with a low incidence of Grade ≥3 toxicity • Improved OS was observed in MASTERPLAN, however requires further evaluation in adequately powered randomised trials. • Future studies should explore biomarkers, novel systemic treatment agents, treatment intensification including SBRT in patients with high risk localised PDAC 10

PFS and OS: both favoured the addition of SBRT * PFS: 11.9 vs 6.3 mths HR 0.44 (95% CI 0.26–0.75); (p=0.002) [on plot] HR: 0.44 (95% CI: 0.26-0.75, p(logrank)=0.002) Number at risk (0,3,6,9,12,15,18,21,24 months): Chemotherapy+SBRT 49 44 38 31 23 19 15 12 10 Chemotherapy 25 20 15 7 5 4 2 1 1 OS: 22.0 vs 14.0 mths HR 0.45 (95% CI 0.25–0.81); (p=0.006) [on plot] HR: 0.45 (95% CI: 0.25-0.81, p(logrank)=0.006) Number at risk (0,3,6,9,12,15,18,21,24,27,30 months): Chemotherapy+SBRT 49 47 47 45 37 35 26 20 17 16 14 Chemotherapy 25 23 21 17 16 12 7 5 4 2 1 * Secondary endpoint 8 Survival table Endpoint: PFS (secondary) Chemotherapy + SBRT | 49 | 11.9 mo Chemotherapy alone | 25 | 6.3 mo HR: 0.44 HR CI: 0.26-0.75 P: 0.002

Safety and surgical outcomes: no clear increase in clinically important toxicity Grade ≥3 adverse events 70.2% vs 64.0% SBRT + chemotherapy vs chemotherapy alone; p=0.59 SBRT-attributed serious toxicity 1 patient One grade ≥3 SAE attributed to SBRT (pancreatitis) Grade ≥3 GI events None reported No grade ≥3 perforation or GI haemorrhage with SBRT Surgical outcomes Outcome | Chemotherapy + SBRT | Chemotherapy alone Surgical exploration | 29/47 (62%) | 11/25 (44%) Resection - POPC + IPC | 25/47 (53%) | 11/25 (44%) R0 resection – POPC | 13/21 (62%) | 4/10 (40%) 30-day postoperative complications | 4/25 (16.7%) | 4/11 (36.4%) Safety population: all treated participants. Resection figures exclude open-and-close procedures.

Summary and Conclusions Zanidatamab Demonstrated Superiority Over Trastuzumab • At this FFA, zanidatamab + CT demonstrated a statistically significant and clinically meaningful improvement in OS (HR, 0.76) vs trastuzumab + CT • All primary endpoints have been met, showing PFS and OS benefits for both zanidatamab-containing regimens Sustained Long-Term Survival With Zanidatamab + Tislelizumab + CT • With longer follow-up, zanidatamab + tislelizumab + CT sustained a robust OS benefit over trastuzumab + CT, with an improved HR vs IA1 (HR, 0.65 vs 0.72)¹ and a 40% 3-year OS rate vs 23% with trastuzumab + CT • Adding tislelizumab to zanidatamab + CT provided a meaningful trend toward further OS benefit irrespective of PD-L1 status Long-Term Safety and Tolerability • The safety profiles remained manageable with no new safety signals, supporting the tolerability of prolonged treatment These results solidify zanidatamab with chemotherapy ± tislelizumab as the new standard of care in 1L HER2-positive mGEA, replacing trastuzumab-based regimens [QR code] A copy of the presentation can be accessed via the QR code. Copies of this slide deck obtained through QR code are for personal use only and may not be reproduced without written permission from the author of the slides 1L, first-line; CT, chemotherapy; FFA, final formal analysis; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IA1, first interim analysis of OS; mGEA, advanced or metastatic gastro-oesophageal adenocarcinoma; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival. 1. Shitara K, et al. N Engl J Med. 2026;394:2002-14. Kohei Shitara, MD

LBA79 - Zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (TIS) for first-line (1L) HER2-positive (HER2+) advanced/metastatic gastroesophageal adenocarcinoma (mGEA): Second interim analysis (IA) from HERIZON-GEA-01 Speakers Kohei Shitara (Kashiwa, Japan, Chiba) Lecture Time 16:15 - 16:20 [Abstract button] Background In the primary analysis of progression-free survival (PFS) and first IA (IA1) of overall survival (OS) of the phase 3 HERIZON-GEA-01 trial (NCT05152147), zani + CT ± TIS significantly prolonged PFS and, with TIS, provided a significant OS benefit (HR 0.72) vs trastuzumab (tras) + CT (Shitara, et al. NEJM. 2026), supporting the US approval of these regimens in 1L HER2+ mGEA. Here, we present the planned second IA of OS (IA2). Methods Patients (pts) with untreated HER2+ mGEA were randomized 1:1:1 to zani (1800 mg [<70 kg]/2400 mg [≥70 kg] IV every 3 weeks [Q3W]) + CT (capecitabine/oxaliplatin or 5-FU/cisplatin) ± TIS (200 mg IV Q3W) or tras + CT. PFS (by blinded independent central review) and OS were primary endpoints. At IA2, formal OS comparisons were tested in sequence: zani + CT vs tras + CT, then zani + CT + TIS vs zani + CT. Results 914 pts were randomized. With a median follow-up of 35.3 mo (data cutoff: 15 July 2026; 9.4 mo longer than IA1), zani + CT significantly improved OS vs tras + CT (HR 0.76 [95% CI: 0.62–0.93]; P = 0.0088; median OS, 22.9 mo [95% CI: 19.9–27.6] vs 19.6 mo [95% CI: 16.9–22.2]). A 4-mo longer median OS was observed with zani + TIS + CT (27.0 mo [95% CI: 23.7–32.2]) vs zani + CT (HR 0.81 [95% CI: 0.65–1.00]), although the difference was not statistically significant (P = 0.0502). The OS benefit of zani + TIS + CT vs tras + CT observed at IA1 (HR 0.72) was sustained at IA2 with an improved HR (0.65 [95% CI: 0.52–0.80]). Estimated 36-mo OS was 39.8% for zani + CT + TIS, 31.5% for zani + CT, and 22.9% for tras + CT. Median duration of treatment was 46.6 (40.5 for zani) wks with zani + CT + TIS, 31.1 (30.1 for zani) wks with zani + CT, and 30.0 (28.2 for tras) wks with tras + CT. The safety profiles were consistent with IA1. Conclusions At IA2, zani + CT led to a statistically significant and clinically meaningful OS improvement vs tras + CT. With longer follow-up, zani + CT + TIS showed improved OS benefit over tras + CT and there was a meaningful trend for OS improvement vs zani + CT. Unchanged safety profiles support the tolerability of prolonged treatment. These results continue to support zani combined with CT ± TIS as a new HER2-directed 1L standard of care in HER2+ mGEA.

[Slide 1] Zanidatamab + Tislelizumab + CT: OS in the ITT Population Zanidatamab + tislelizumab + CT continued to demonstrate an OS benefit vs trastuzumab + CT, with an improved HR from IA1 Median OS (95% CI), mo: Zanidatamab + tislelizumab + CT 27.0 (23.7-32.2) | Trastuzumab + CT 19.6 (16.9-22.2) HR (95% CI): 0.65 (0.52-0.80)^a Curve annotations: 55.8% (95% CI, 49.8-61.4) [24 mo, zanidatamab + tislelizumab + CT]; 40.7% (95% CI, 34.9-46.5) [24 mo, trastuzumab + CT]; 39.8% (95% CI, 33.2-46.3) [36 mo, zanidatamab + tislelizumab + CT]; 22.9% (95% CI, 17.3-28.5) [36 mo, trastuzumab + CT] Y-axis: Overall survival (%); X-axis: Months from randomisation (0-57); + Censored Patients at risk (0,3,6,...,57 months): Zani + TIS + CT: 302 267 246 228 207 185 168 148 129 101 72 64 53 42 35 28 11 6 2 0 Tras + CT: 308 284 261 227 199 171 147 121 95 70 48 39 33 21 15 12 5 1 1 0 Data cutoff: 15 July 2026. ^aAnalysis was descriptive, as prespecified criteria for significance were previously met. CT, chemotherapy; HR, hazard ratio; IA1, first interim analysis of OS; ITT, intent-to-treat; OS, overall survival; TIS, tislelizumab; Tras, trastuzumab; Zani, zanidatamab. Kohei Shitara, MD Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + tislelizumab + CT | 302 | 27.0 mo | 23.7-32.2 Trastuzumab + CT | 308 | 19.6 mo | 16.9-22.2 HR: 0.65 HR CI: 0.52-0.80 Landmark rates: 24 mo: Zanidatamab + tislelizumab + CT 55.8% (CI 49.8-61.4) | Trastuzumab + CT 40.7% (CI 34.9-46.5) 36 mo: Zanidatamab + tislelizumab + CT 39.8% (CI 33.2-46.3) | Trastuzumab + CT 22.9% (CI 17.3-28.5) [Slide 2] Zanidatamab + Tislelizumab + CT vs Trastuzumab + CT: OS in Key Prespecified Subgroups The OS benefit with zanidatamab + tislelizumab + CT vs trastuzumab + CT was generally consistent across prespecified subgroups, including in patients with PD-L1-negative disease Subgroup | Category | Events/Patients Zanidatamab + tislelizumab + CT | Events/Patients Trastuzumab + CT | OS HR^a (95% CI) All patients | | 157/302 | 212/308 | 0.65 (0.52-0.80) Age | <65 years | 78/163 | 116/162 | 0.56 (0.42-0.74) Age | >=65 years | 79/139 | 96/146 | 0.79 (0.59-1.07) Geographic region | Asia | 70/159 | 111/165 | 0.55 (0.41-0.74) Geographic region | EU/NA | 60/95 | 65/93 | 0.84 (0.59-1.20) Geographic region | ROW | 27/48 | 36/50 | 0.69 (0.42-1.14) ECOG PS | 0 | 53/122 | 67/120 | 0.70 (0.49-1.00) ECOG PS | 1 | 103/179 | 145/188 | 0.64 (0.49-0.82) Prior gastrectomy | Yes | 21/51 | 34/56 | 0.61 (0.36-1.06) Prior gastrectomy | No | 136/251 | 178/252 | 0.65 (0.52-0.82) Anatomical subtype | Gastric | 96/208 | 155/226 | 0.55 (0.43-0.71) Anatomical subtype | GEJ | 51/74 | 45/60 | 0.98 (0.66-1.47) Anatomical subtype | Oesophageal | 10/20 | 12/22 | 0.73 (0.32-1.71) HER2 status | IHC 3+ | 127/251 | 172/255 | 0.65 (0.51-0.82) HER2 status | IHC 2+/ISH+ | 30/51 | 39/52 | 0.70 (0.43-1.13) PD-L1 status | TAP <1% | 47/90 | 75/98 | 0.50 (0.35-0.73) PD-L1 status | TAP >=1% | 90/187 | 121/188 | 0.68 (0.52-0.89) Forest plot axis: 0.1 - 1.0 - 10.0; Favours Zani + TIS + CT | Favours Tras + CT Data cutoff: 15 July 2026. ^aThe widths of the CIs were not adjusted for multiplicity and cannot be used to infer treatment effects. CT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EU, European Union; GEJ, gastro-oesophageal junction; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IHC, immunohistochemistry; ISH, in situ hybridisation; NA, North America; OS, overall survival; PD-L1, programmed death-ligand 1; ROW, rest of the world; TAP, tumour area positivity; TIS, tislelizumab; Tras, trastuzumab; Zani, zanidatamab Kohei Shitara, MD [Slide 3] Zanidatamab + Tislelizumab + CT vs Zanidatamab + CT: OS in the ITT Population A consistent trend toward improved OS was observed irrespective of PD-L1 status Median OS (95% CI), mo: Zanidatamab + tislelizumab + CT 27.0 (23.7-32.2) | Zanidatamab + chemotherapy 22.9 (19.9-27.6) ITT HR (95% CI): 0.81 (0.65-1.00); P = 0.0502 PD-L1 TAP <1% HR (95% CI): 0.76 (0.52-1.10) PD-L1 TAP >=1% HR (95% CI): 0.77 (0.58-1.02) Y-axis: Overall survival (%); X-axis: Months from randomisation (0-57); + Censored Patients at risk (0,3,6,...,57 months): Zani + TIS + CT: 302 267 246 228 207 185 168 148 129 101 72 64 53 42 35 28 11 6 2 0 Zani + CT: 304 278 256 228 202 182 162 142 122 94 71 51 42 28 23 18 5 3 1 0 Data cutoff: 15 July 2026 CT, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PD-L1, programmed death-ligand 1; TAP, tumour area positivity; TIS, tislelizumab; Zani, zanidatamab Kohei Shitara, MD Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + tislelizumab + CT | 302 | 27.0 mo | 23.7-32.2 Zanidatamab + chemotherapy | 304 | 22.9 mo | 19.9-27.6 HR: 0.81 HR CI: 0.65-1.00 P: 0.0502

[Slide 1] Background • Zanidatamab is a bispecific HER2-directed antibody that binds to HER2 ECD 2 and 4 in a trans configuration, facilitating crosslinking associated with the formation of distinct HER2 clusters on the cell surface. It has several key mechanisms of action1: – Increasing HER2 internalisation; reducing phosphorylation of EGFR, HER2, and HER3 and blocking downstream signalling; and inducing immune-mediated effects (CDC, ADCC, and ADCP) • Tislelizumab is a high-affinity ICI targeting PD-1 and is specifically engineered to minimise Fcγ receptor binding on macrophages Adults with untreated, unresectable, locally advanced, recurrent or metastatic GEA • HER2 IHC 3+ or IHC 2+/ISH+ per central testing • ECOG PS 0 or 1 • No prior HER2-targeted agents or immunotherapy in any setting Stratification factors • Geographic region • HER2 status • ECOG PS R 1:1:1 N = 914 Trastuzumab + chemotherapy(a) Zanidatamab(b) + chemotherapy(a) Zanidatamab(b) + tislelizumab(c) + chemotherapy(a) Prophylaxis to prevent IRRs and diarrhoea was mandatory in the zanidatamab-containing arms Treatment until disease progression/death/unacceptable toxicity. Chemotherapy could be discontinued after 6 cycles Tumour imaging(d) Q6W Dual primary endpoints • PFS (per BICR) • OS Data cutoff for IA2: 15 July 2026 Here we report results from the planned second interim analysis of OS (IA2) from HERIZON-GEA-01 (a)Physician's choice of CAPOX (capecitabine plus oxaliplatin) or FP (5-fluorouracil plus cisplatin). Chemotherapy was administered for at least 6 cycles or until disease progression, unacceptable toxicity, or another criterion for treatment discontinuation was met. (b)Zanidatamab 1800 mg (<70 kg) or 2400 mg (≥70 kg) was administered IV Q3W. (c)Tislelizumab 200 mg was administered IV Q3W. (d)Computed tomography/magnetic resonance imaging scans were performed Q6W for the first 54 weeks, then every 9 weeks. ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; BICR, blinded independent central review; CDC, complement-dependent cytotoxicity; ECD, extracellular domain; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; Fcγ, fragment crystallisable-gamma; GEA, gastro-oesophageal adenocarcinoma; HER2, human epidermal growth factor receptor 2; HER3, human epidermal growth factor receptor 3; IA2, planned second interim analysis of OS; ICI, immune checkpoint inhibitor; IHC, immunohistochemistry; IRR, infusion-related reaction; ISH, in situ hybridisation; IV, intravenously; OS, overall survival; PD-1, programmed cell death protein 1; PFS, progression-free survival; Q3W, every 3 weeks; Q6W, every 6 weeks; R, randomisation. 1. Weisser NE, et al. Nat Commun. 2023;14(1):1394. Kohei Shitara, MD [Slide 2] Zanidatamab + Tislelizumab + CT vs Zanidatamab + CT: OS in the ITT Population A consistent trend toward improved OS was observed irrespective of PD-L1 status Zanidatamab + tislelizumab + CT | Zanidatamab + chemotherapy Median OS (95% CI), mo: 27.0 (23.7–32.2) | 22.9 (19.9–27.6) ITT HR (95% CI): 0.81 (0.65–1.00); P = 0.0502 PD-L1 TAP <1% HR (95% CI): 0.76 (0.52–1.10) PD-L1 TAP ≥1% HR (95% CI): 0.77 (0.58–1.02) Y-axis: Overall survival (%); X-axis: Months from randomisation; + Censored Patients at risk (0,3,6,...,57 mo): Zani + TIS + CT: 302 267 246 228 207 185 168 148 129 101 72 64 53 42 35 28 11 6 2 0 Zani + CT: 304 278 256 228 202 182 162 142 122 94 71 51 42 28 22 18 5 3 1 0 Data cutoff: 15 July 2026. CT, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PD-L1, programmed death-ligand 1; TAP, tumour area positivity; TIS, tislelizumab; Zani, zanidatamab. Kohei Shitara, MD Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + tislelizumab + CT | 302 | 27.0 mo | 23.7–32.2 Zanidatamab + chemotherapy | 304 | 22.9 mo | 19.9–27.6 HR: 0.81 HR CI: 0.65–1.00 P: 0.0502 [Slide 3] Safety Summary The AE profile remained consistent with IA1, and no unexpected safety signals were observed Columns: Zanidatamab + tislelizumab + CT (n = 294)(a) | Zanidatamab + CT (n = 305)(a) | Trastuzumab + CT (n = 302) Duration of treatment, weeks Mean (SD): 64.1 (58.0) | 52.6 (52.6) | 42.3 (39.2) Median (IQR): 46.6 (17.6–101.4) | 31.1 (14.3–74.7) | 30.0 (18.1–54.1) Duration of zanidatamab or trastuzumab treatment, weeks Mean (SD): 60.2 (57.4) | 51.0 (52.9) | 40.8 (39.4) Median (IQR): 40.5 (14.4–97.1) | 30.1 (12.1–72.7) | 28.2 (16.3–52.1) Any-grade TEAE, n (%): 293 (99.7) | 301 (98.7) | 297 (98.3) TRAE, n (%): 289 (98.3) | 296 (97.0) | 291 (96.4) Grade ≥3: 213 (72.4) | 180 (59.0) | 181 (59.9) Serious TEAEs, n (%): 176 (59.9) | 155 (50.8) | 131 (43.4) Treatment-related: 124 (42.2) | 87 (28.5) | 62 (20.5) TEAEs leading to death, n (%): 30 (10.2) | 26 (8.5) | 22 (7.3) Treatment-related: 7 (2.4) | 1 (0.3) | 4 (1.3) Discontinuation due to TRAEs, n (%) Any component: 132 (44.9) | 107 (35.1) | 88 (29.1) Zanidatamab or trastuzumab(b): 35 (11.9) | 28 (9.2) | 7 (2.3) Tislelizumab(c): 49 (16.7) | — | — Any-grade diarrhoea, n (%): 244 (83.0) | 241 (79.0) | 161 (53.3) Grade ≥3: 74 (25.2) | 61 (20.0) | 39 (12.9) AESIs(d), n (%): 103 (35.0) | 94 (30.8) | 56 (18.5) IRRs: 74 (25.2) | 77 (25.2) | 40 (13.2) Noninfectious pulmonary toxicities: 22 (7.5) | 5 (1.6) | 4 (1.3) Left ventricular dysfunction: 27 (9.2) | 20 (6.6) | 13 (4.3) Immune-mediated AEs(d), n (%): 118 (40.1) | 44 (14.4) | 32 (10.6) • Diarrhoea occurred primarily in cycles 1 and 2, and the incidence was consistent with IA1 Data cutoff: 15 July 2026. (a)Five patients who were assigned to the zanidatamab + tislelizumab + CT arm did not receive tislelizumab. Data from these patients are summarized in the zanidatamab + CT arm. (b)Zanidatamab- or trastuzumab-related TEAEs that led to discontinuation of zanidatamab or trastuzumab. (c)Tislelizumab-related TEAEs that led to discontinuation of tislelizumab. (d)AESIs for zanidatamab were IRRs, non-infectious pulmonary toxicities, and left ventricular dysfunction; AESIs for tislelizumab were IRRs and immune-mediated AEs. Immune-mediated AEs are excluded from AESIs and reported separately. AESIs for zanidatamab and tislelizumab are reported in all treatment groups, even if the study agent was not administered in that group. AE, adverse event; AESI, AE of special interest; CT, chemotherapy; IA1, first interim analysis of OS; IQR, interquartile range; IRR, infusion-related reaction; TEAE, treatment-emergent AE; TRAE, treatment-related AE. Kohei Shitara, MD [Slide 4] Zanidatamab + CT: OS in the ITT Population Zanidatamab + CT demonstrated a statistically significant and clinically meaningful improvement in OS vs trastuzumab + CT (FFA criteria met) Zanidatamab + CT | Trastuzumab + CT Median OS (95% CI), mo: 22.9 (19.9–27.6) | 19.6 (16.9–22.2) HR (95% CI): 0.76 (0.62–0.93); P = 0.0088(a) Landmark labels: 24 mo: 49.6% (95% CI, 43.6–55.3) [Zani + CT]; 40.7% (95% CI, 34.9–46.5) [Tras + CT] 36 mo: 31.5% (95% CI, 25.4–37.8) [Zani + CT]; 22.9% (95% CI, 17.3–28.9) [Tras + CT] Y-axis: Overall survival (%); X-axis: Months from randomisation; + Censored Patients at risk (0,3,6,...,57 mo): Zani + CT: 304 278 256 228 202 182 162 142 122 94 71 51 42 28 22 18 5 3 1 0 Tras + CT: 308 284 261 227 199 171 147 121 95 70 48 39 33 21 15 12 5 1 1 0 Data cutoff: 15 July 2026. (a)The critical 2-sided alpha was 0.0279. CT, chemotherapy; FFA, final formal analysis; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; Tras, trastuzumab; Zani, zanidatamab. Kohei Shitara, MD Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + CT | 304 | 22.9 mo | 19.9–27.6 Trastuzumab + CT | 308 | 19.6 mo | 16.9–22.2 HR: 0.76 HR CI: 0.62–0.93 P: 0.0088 Landmark rates: 24 mo: Zanidatamab + CT 49.6% (CI 43.6–55.3) | Trastuzumab + CT 40.7% (CI 34.9–46.5) 36 mo: Zanidatamab + CT 31.5% (CI 25.4–37.8) | Trastuzumab + CT 22.9% (CI 17.3–28.9)

Progression-Free Survival in the ITT Population PFS was consistent with the primary analysis (IA1) HERIZON GEA-301 Zanidatamab + Tislelizumab + CT | Zanidatamab + CT | Trastuzumab + CT Median PFS (95% CI), mo | 12.7 (9.8–16.8) | 12.4 (9.8–14.5) | 8.3 (7.0–8.9) HR (95% CI) vs Tras + CT | 0.61 (0.50–0.76) | 0.65 (0.53–0.80) Progression-free survival (%) + Censored Months from randomisation Patients at risk (0, 3, 6, ... 54 months) [low resolution; digits marked [?] are uncertain] Zani + TIS + CT: 302 239 183 151 124 109 90 71 66[?] 49 38 36[?] 28[?] 28[?] 17 14 3 2 0 Zani + CT: 304 231 175 140 115 86[?] 77 63 55 38 29 27 21 15 10 7 1 1 0 Tras + CT: 308 247 168[?] 101 68[?] 49 33 25 19 12 9 8 6[?] 5 4 4 0 Data cutoff: 15 July 2026 CT, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; TIS, tislelizumab; Tras, trastuzumab; Zani, zanidatamab. Kohei Shitara, MD Survival table Endpoint: Progression-free survival, ITT (final formal analysis) Arm | N | Median | Median CI Zanidatamab + Tislelizumab + CT | 302 | 12.7 mo | 9.8–16.8 Zanidatamab + CT | 304 | 12.4 mo | 9.8–14.5 Trastuzumab + CT | 308 | 8.3 mo | 7.0–8.9 HR: 0.61 (zani+tisle+CT vs tras+CT); 0.65 (zani+CT vs tras+CT) HR CI: 0.50–0.76; 0.53–0.80

[Slide 1] Patient Disposition Median follow-up was 35.3 months at IA2, 9.4 months longer than at IA1 Randomised N = 914 Zanidatamab + tislelizumab + CT: n = 302; 299 patients treated^a Ongoing in study, n = 122 (40%): Ongoing study treatment, n = 67; Survival follow-up, n = 55 Discontinued study, n = 180 (60%): Death, n = 157; Withdrawal of consent, n = 20; Lost to follow-up, n = 3 Zanidatamab + CT: n = 304; 300 patients treated^a Ongoing in study, n = 103 (34%): Ongoing study treatment, n = 48; Survival follow-up, n = 55 Discontinued study, n = 201 (66%): Death, n = 178; Withdrawal of consent, n = 19; Lost to follow-up, n = 3; Investigator's decision, n = 1 Trastuzumab + CT: n = 308; 302 patients treated Ongoing in study, n = 75 (24%): Ongoing study treatment, n = 19; Survival follow-up, n = 56 Discontinued study, n = 233 (76%): Death, n = 211; Withdrawal of consent, n = 21; Lost to follow-up, n = 1 Data cutoff: 15 July 2026. ^aTreated includes all randomised patients who received any amount of any study treatment and does not necessarily reflect the safety analysis set. Five patients assigned to the zanidatamab-tislelizumab-CT arm did not receive tislelizumab and are included in the safety analysis set for the zanidatamab-CT arm. CT, chemotherapy; IA1, first interim analysis of overall survival; IA2, planned second interim analysis of overall survival Kohei Shitara, MD [Slide 2] Zanidatamab + CT: OS in the ITT Population Zanidatamab + CT demonstrated a statistically significant and clinically meaningful improvement in OS vs trastuzumab + CT (FFA criteria met) Median OS (95% CI), mo: Zanidatamab + CT 22.9 (19.9-27.6) | Trastuzumab + CT 19.6 (16.9-22.2) HR (95% CI): 0.76 (0.62-0.93); P = 0.0088^a Curve annotations: 49.6% (95% CI, 43.6-55.3) [24 mo, zanidatamab + CT]; 40.7% (95% CI, 34.9-46.5) [24 mo, trastuzumab + CT]; 31.5% (95% CI, 25.4-37.8) [36 mo, zanidatamab + CT]; 22.9% (95% CI, 17.3-28.9) [36 mo, trastuzumab + CT] Y-axis: Overall survival (%); X-axis: Months from randomisation (0-57); + Censored Patients at risk (partly obscured by camera): Zani + CT: [304] 278 256 228 202 182 162 142 122 94 71 51 42 28 22 18 5 3 1 0; Tras + CT: [308] 284 261 227 199 171 147 121 95 70 48 39 33 21 15 12 5 1 1 0 Data cutoff: [15] July 2026. ^aThe critical 2-sided alpha was 0.0279. CT, chemotherapy; FFA, final formal analysis; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; Tras, trastuzumab; Zani, zanidatamab Kohei Shitara, MD [partly obscured] Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + CT | 304 | 22.9 mo | 19.9-27.6 Trastuzumab + CT | 308 | 19.6 mo | 16.9-22.2 HR: 0.76 HR CI: 0.62-0.93 P: 0.0088 (critical 2-sided alpha 0.0279) Landmark rates: 24 mo: Zanidatamab + CT 49.6% (CI 43.6-55.3) | Trastuzumab + CT 40.7% (CI 34.9-46.5) 36 mo: Zanidatamab + CT 31.5% (CI 25.4-37.8) | Trastuzumab + CT 22.9% (CI 17.3-28.9) [Slide 4] Zanidatamab + Tislelizumab + CT vs Zanidatamab + CT: OS in the ITT Population Median OS was 4 months longer with zanidatamab + tislelizumab + CT compared with zanidatamab + CT; however, this OS comparison had limited power for superiority Median OS (95% CI), mo: Zanidatamab + tislelizumab + CT 27.0 (23.7-32.2) | Zanidatamab + chemotherapy 22.9 (19.9-27.6) HR (95% CI): 0.81 (0.65-1.00); P = 0.0502 Curve annotations: 55.8% (95% CI, 49.8-61.4) [24 mo, zani + tis + CT]; 49.6% (95% CI, 43.6-55.3) [24 mo, zani + CT]; 39.8% (95% CI, 33.2-46.3) [36 mo, zani + tis + CT]; 31.5% (95% CI, 25.4-37.8) [36 mo, zani + CT] Y-axis: Overall survival (%); X-axis: Months from randomisation (0-57); + Censored Patients at risk: Zani + TIS + CT: 302 267 246 228 207 185 168 148 129 101 72 64 53 42 35 28 11 6 2 0 Zani + CT: 304 278 256 228 202 182 162 142 122 94 71 51 42 28 22 18 5 3 1 0 Data cutoff: 15 July 2026 CT, chemotherapy; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; TIS, tislelizumab; Zani, zanidatamab Kohei Shitara, MD Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Zanidatamab + tislelizumab + CT | 302 | 27.0 mo | 23.7-32.2 Zanidatamab + CT | 304 | 22.9 mo | 19.9-27.6 HR: 0.81 HR CI: 0.65-1.00 P: 0.0502 Landmark rates: 24 mo: Zanidatamab + tislelizumab + CT 55.8% (CI 49.8-61.4) | Zanidatamab + CT 49.6% (CI 43.6-55.3) 36 mo: Zanidatamab + tislelizumab + CT 39.8% (CI 33.2-46.3) | Zanidatamab + CT 31.5% (CI 25.4-37.8)

14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER CheckMate 8HW Overall survival: NIVO+IPI vs NIVO across all lines Centrally confirmed MSI-H/dMMR | NIVO + IPI (n = 296) | NIVO (n = 286) Events (%) | 78 (26) | 111 (39) Median OS, mo 95% CI | NR (NE-NE) | NR (NE-NE) HR (95% CI) | 0.61 (0.46-0.82) P value | 0.0009a Landmarks (NIVO+IPI / NIVO): 12 mo 90% / 83%; 24 mo 85% / 72%; 36 mo 81% / 69%; 48 mo 77% / 65%; 60 mo 74% / 62% No. at risk (months 0, 3, 6 ... 81) NIVO+IPI 296 279 273 267 264 260 257 255 251 247 245 239 238 226 216 209 199 186 176 166 151 141 114 78 62 31 3 0 NIVO 286 275 263 252 238 228 220 213 207 202 201 199 195 185 176 170 163 151 141 134 122 115 94 57 49 17 3 0 • In patients with centrally confirmed MSI-H/dMMR mCRC, NIVO + IPI demonstrated statistically significant OS benefit vs NIVO across all lines (HR, 0.61, 95% CI, 0.46-0.82, P = 0.0009) – These data are consistent with those observed in the all-randomized population by local testing (HR, 0.64, [95% CI, 0.51-0.81]) – OS results were consistent across most prespecified subgroups Median follow-up for all randomized patients with centrally confirmed MSI-H/dMMR mCRC was 68.1 (range, 37.6-81.4) months. aStatistical boundary for significance, 0.0058. Sara Lonardi Final overall survival results from CheckMate 8HW: Nivolumab plus ipilimumab versus nivolumab or chemotherapy in MSI-H/dMMR metastatic colorectal cancer ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: OS (centrally confirmed MSI-H/dMMR, NIVO+IPI vs NIVO, all lines) Arm | N | Median | Median CI NIVO + IPI | 296 | NR | NE-NE NIVO | 286 | NR | NE-NE HR: 0.61 HR CI: 0.46-0.82 P: 0.0009 Landmark rates: 12 mo: NIVO + IPI 90% | NIVO 83% 24 mo: NIVO + IPI 85% | NIVO 72% 36 mo: NIVO + IPI 81% | NIVO 69% 48 mo: NIVO + IPI 77% | NIVO 65% 60 mo: NIVO + IPI 74% | NIVO 62%

[Slide 1] CheckMate 8HW Study design: CheckMate 8HW • CheckMate 8HW is a randomized, multicenter, open-label phase 3 trial^a Key eligibility criteria: • Histologically confirmed unresectable or metastatic CRC • MSI-H/dMMR status by local testing • Immunotherapy-naïve • ECOG PS 0 or 1 Stratification factors: • Prior lines of treatment (0 vs 1 vs ≥ 2) • Primary tumor location (right vs left) R 2:2:1 n = 353: NIVO 240 mg Q2W for 6 doses, followed by NIVO 480 mg Q4W^b n = 354: NIVO 240 mg + IPI 1 mg/kg Q3W for 4 doses,^c followed by NIVO 480 mg Q4W^b n = 132: Investigator's choice of chemo^d (mFOLFOX6 and FOLFIRI ± bevacizumab or cetuximab) Treatment until disease progression, unacceptable toxicity, withdrawal of consent (all arms), or a maximum treatment duration of 2 years (NIVO and NIVO + IPI arms only) Dual primary endpoints in patients with centrally confirmed MSI-H/dMMR status^e: • PFS by BICR^f (NIVO + IPI vs chemo in 1L) • PFS by BICR^f (NIVO + IPI vs NIVO across all lines) Key secondary endpoints in patients with centrally confirmed MSI-H/dMMR status^e: • PFS by BICR^f (NIVO + IPI vs NIVO in 1L) • ORR • OS Other key endpoints in all treated patients • Safety • At data cutoff (May 28, 2026), median follow-up^g for all randomized patients was 68.1 (range, 37.6–81.4) months across all lines and 63.0 (range, 37.6–80.2) months in the 1L population • The final OS analysis was initiated based on achieving 3 years of minimum follow-up ^aClinicalTrials.gov. NCT04008030. ^bPatients with ≥ 2 prior lines are randomized only to the NIVO or NIVO + IPI arms. ^cPatients can continue NIVO treatment upon early IPI discontinuation. ^dPatients receiving investigator's choice of chemo are eligible to receive NIVO + IPI upon progression (crossover treatment). ^eConfirmed using either immunohistochemistry and/or polymerase chain reaction-based tests. ^fEvaluated using RECIST v1.1. ^gTime between randomization and data cutoff across all 3 treatment arms. 4 [Slide 2] CheckMate 8HW Overall survival: NIVO+IPI vs NIVO across all lines Landmark labels: NIVO+IPI 90% (12 mo), 85% (24), 81% (36), 77% (48), 74% (60); NIVO 83% (12), 72% (24), 69% (36), 65% (48), 62% (60) Centrally confirmed MSI-H/dMMR | NIVO + IPI (n = 296) | NIVO (n = 286) Events (%) | 78 (26) | 111 (39) Median OS, mo 95% CI | NR (NE-NE) | NR (NE-NE) HR (95% CI) | 0.61 (0.46-0.82) P value | 0.0009^a Months: 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 No. at risk NIVO+IPI 296 279 273 267 264 260 257 255 251 247 245 239 238 226 216 209 199 186 176 166 151 141 114 78 62 31 3 0 NIVO 286 275 263 252 238 228 220 213 207 202 201 199 195 185 176 170 163 151 141 134 122 115 94 57 49 17 3 0 • In patients with centrally confirmed MSI-H/dMMR mCRC, NIVO + IPI demonstrated statistically significant OS benefit vs NIVO across all lines (HR, 0.61, 95% CI, 0.46-0.82, P = 0.0009) — These data are consistent with those observed in the all-randomized population by local testing (HR, 0.64, [95% CI, 0.51-0.81]) — OS results were consistent across most prespecified subgroups Median follow-up for all randomized patients with centrally confirmed MSI-H/dMMR mCRC was 68.1 (range, 37.6-81.4) months. ^aStatistical boundary for significance, 0.0058. 7 Survival table Endpoint: OS (centrally confirmed MSI-H/dMMR, all lines) Arm | N | Median | Median CI NIVO + IPI | 296 | NR | NE-NE NIVO | 286 | NR | NE-NE HR: 0.61 HR CI: 0.46-0.82 P: 0.0009 Landmark rates: 12 mo: NIVO + IPI 90% | NIVO 83% 24 mo: NIVO + IPI 85% | NIVO 72% 36 mo: NIVO + IPI 81% | NIVO 69% 48 mo: NIVO + IPI 77% | NIVO 65% 60 mo: NIVO + IPI 74% | NIVO 62% [Slide 3] CheckMate 8HW Efficacy summary: PFS and ORR with extended follow-up Patients with centrally confirmed MSI-H/dMMR | All lines: NIVO + IPI (n = 296) | All lines: NIVO (n = 286) | 1L: NIVO + IPI (n = 171) | 1L: NIVO (n = 170) Median PFS, mo (95% CI) | NR (71.7-NE) | 39.3 (23.0-58.7) | NR (64.3-NE) | 60.8 (32.8-NE) HR (95% CI) | 0.60 (0.47-0.77) [all lines] | 0.68 (0.48-0.96) [1L] ORR, n (%) | 213 (72) | 165 (58) | 127 (74) | 104 (61) CR rate, n (%) | 117 (40) | 89 (31) | 70 (41) | 55 (32) DCR, n (%) | 249 (84) | 218 (76) | 145 (85) | 137 (81) • NIVO + IPI continued to show clinical benefit in PFS, and higher ORR rates compared with NIVO across all treatment lines at extended follow-up (descriptive analyses) • Based on descriptive analysis, 1L NIVO + IPI continued to demonstrated clinically meaningful improvements in PFS (HR, 0.21, 95% CI, 0.14-0.32) and higher ORR (74% vs 27%) and CR (41% vs 7%) rates vs chemo, respectively Median follow-up for all randomized patients was 68.1 (range, 37.6-81.4) months across all lines and 62.8 (range, 37.6-80.2) months in the 1L setting. 9 [Slide 4] CheckMate 8HW Summary • CheckMate 8HW delivers 2 firsts in MSI-H/dMMR mCRC — The first significant OS benefit for an IO regimen over chemo in 1L (HR, 0.37, P < 0.0001) — The first significant OS benefit for dual IO over monotherapy across all lines (HR, 0.61, P = 0.0009) • The 1L NIVO + IPI vs NIVO comparison shows a durable, clinically meaningful, and consistent OS benefit (HR, 0.66, P=0.0432), with 5-year OS rates (77% vs 66%), despite not satisfying its prespecified survival statistical threshold (P = 0.0058) • With longer follow-up, descriptive analyses showed consistent PFS and ORR benefit with NIVO + IPI across all comparisons and treatment lines • The safety profile of NIVO + IPI remained stable with longer follow-up, with low frequency of grade 3/4 toxicity despite numerically higher incidence of any-grade TRAEs with the combination, confirming tolerability alongside efficacy • These results reinforce the durable, long-term clinical benefit of NIVO + IPI across all efficacy endpoints tested, supporting it as a global 1L standard of care in MSI-H/dMMR mCRC 11

A Centrally confirmed MSI-H/dMMR NIVO+IPI (n = 296) NIVO (n = 286) Total censored patients, n 218 175 Median OS, months 95% CI NR NE-NE NR NE-NE HR (95% CI) 0.61 (0.46-0.82) P = 0.0009 (Threshold for significance P < 0.006) Overall survival probability (%) Months No. at risk NIVO+IPI / NIVO B 1L centrally confirmed MSI-H/dMMR NIVO+IPI (n = 171) NIVO (n = 170) Total censored patients, n 132 114 Median OS, months 95% CI NR NE-NE NR NE-NE HR (95% CI) 0.66 (0.44-0.99) P = 0.0432 (Threshold for significance P < 0.006) Survival table Endpoint: Overall survival (centrally confirmed MSI-H/dMMR, all lines; panel A) Arm | N | Median | Median CI NIVO+IPI | 296 | NR | NE-NE NIVO | 286 | NR | NE-NE HR: 0.61 HR CI: 0.46-0.82 P: 0.0009 (threshold for significance P < 0.006) Panel A printed landmarks NIVO+IPI vs NIVO: 12 mo 90% vs 83%; 24 mo 85% vs 72%; 36 mo 81% vs 69%; 48 mo 77% vs 65%; 60 mo 74% vs 62% Panel B (1L, NIVO+IPI n=171 vs NIVO n=170): median NR vs NR; HR 0.66 (0.44-0.99), P = 0.0432 (threshold P < 0.006, not met); 12 mo 90% vs 88%; 24 mo 85% vs 78%; 36 mo 84% vs 73%; 48 mo 80% vs 70%; 60 mo 77% vs 66%

[Slide 1] CheckMate 8HW Overall survival: NIVO+IPI vs chemo in 1L Centrally confirmed MSI-H/dMMR | NIVO + IPI (n = 171) | Chemo (n = 84) Events (%) | 39 (23) | 41 (49) Median OS, mo (95% CI) | NR (NE-NE) | 50.1 (31.7-NE) HR (95% CI) | 0.37 (0.24-0.57) P value | < 0.0001 Landmark labels (12/24/36/48/60 mo): NIVO+IPI 90% | 85% | 84% | 80% | 77%; Chemo 78% | 66% | 57% | 51% | 46% Months: 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 No. at risk NIVO+IPI | 171 161 158 155 154 152 149 148 146 145 145 143 142 132 123 116 108 96 89 80 66 57 43 27 21 10 1 0 Chemo | 84 78 69 66 62 59 55 53 52 50 49 47 45 41 38 35 33 30 26 25 20 18 15 12 [?] 2 0 0 - In patients with centrally confirmed MSI-H/dMMR mCRC, NIVO + IPI demonstrated statistically significant OS benefit vs chemo in the 1L (HR, 0.37, 95% CI, 0.24-0.57, P < 0.0001) - Benefit from 1L NIVO + IPI observed despite 79.8% (n=67/84) of patients treated with chemo receiving subsequent IO therapy Median follow-up for all randomized patients with centrally confirmed MSI-H/dMMR mCRC in the 1L setting was 62.8 (range, 37.6-80.2) months. aStatistical boundary for significance, 0.0059. Survival table Endpoint: Overall survival, 1L, centrally confirmed MSI-H/dMMR Arm | N | Median | Median CI NIVO + IPI | 171 | NR | NE-NE Chemo | 84 | 50.1 mo | 31.7-NE HR: 0.37 HR CI: 0.24-0.57 P: < 0.0001 Landmark rates: 12 mo: NIVO + IPI 90% | Chemo 78% 24 mo: NIVO + IPI 85% | Chemo 66% 36 mo: NIVO + IPI 84% | Chemo 57% 48 mo: NIVO + IPI 80% | Chemo 51% 60 mo: NIVO + IPI 77% | Chemo 46% [Slide 3] CheckMate 8HW Overall survival: NIVO+IPI vs NIVO in 1L Centrally confirmed MSI-H/dMMR | NIVO + IPI (n = 171) | NIVO (n = 170) Events (%) | 39 (23) | 41 (49)[?] Median OS, mo (95% CI) | NR (NE-NE) | NR (NE-NE) HR (95% CI) | 0.66 (0.44-0.99) P value | 0.0432a Landmark labels (12/24/36/48/60 mo): NIVO+IPI 90% | 85% | 84% | 80% | 77%; NIVO 88% | 78% | 73% | 70% | 66% Months: 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 No. at risk NIVO+IPI | 171 161 158 155 154 152 149 148 146 145 145 143 142 132 123 116 108 96 89 80 66 57 43 27 21 10 1 0 NIVO | 170 168 164 160 150 145 139 135 133 129 128 126 123 116 108 102 96 85 75 69 58 52 39 22 17 5 2 0 - OS favored NIVO+IPI vs NIVO in 1L (HR, 0.66, 95% CI, 0.44-0.99, P = 0.0432), however, the prespecified threshold for statistical significance (P < 0.0058) was not met - Lack of statistical significance likely reflects the smaller sample size and fewer events relative to the all-lines comparison - The 5-year OS rates (77% vs 66%) were consistent with the results across all lines (74% vs 62%) Median follow-up for all randomized patients with centrally confirmed MSI-H/dMMR mCRC in the 1L setting was 62.8 (range, 37.6-80.2) months. aStatistical boundary for significance, 0.0058. Survival table Endpoint: Overall survival, 1L, centrally confirmed MSI-H/dMMR Arm | N | Median | Median CI NIVO + IPI | 171 | NR | NE-NE NIVO | 170 | NR | NE-NE HR: 0.66 HR CI: 0.44-0.99 P: 0.0432 (threshold P < 0.0058 not met) Landmark rates: 12 mo: NIVO + IPI 90% | NIVO 88% 24 mo: NIVO + IPI 85% | NIVO 78% 36 mo: NIVO + IPI 84% | NIVO 73% 48 mo: NIVO + IPI 80% | NIVO 70% 60 mo: NIVO + IPI 77% | NIVO 66%

[Slide 2] Dual Checkpoint Blockade, Anti–PD1/PDL1 Monotherapy and Chemoimmunotherapy in dMMR/MSI-H Metastatic Colorectal Cancer: A Kaplan–Meier-Derived Individual Patient Data Meta-Analysis (Abstract 924eP) Matheus de Oliveira Andrade1,2; Gabriela B. E. Silva2; Lucas M. Delgado4; Anderson R. Simoes5; Rafael L. Nohmi6; Rhenan H. Silva2; Barbara Ferreira7; Gustavo Dos Santos Fernandes1 Background Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). The relative efficacy of dual checkpoint blockade, anti–PD1/PDL1 monotherapy, and chemoimmunotherapy strategies remains uncertain. Methods A systematic review and meta-analysis was conducted by searching PubMed, Embase, Cochrane, and major conference proceedings for randomized controlled trials (RCTs) evaluating ICIs in patients with dMMR/MSI-H mCRC. Pooled Kaplan–Meier-derived individual patient data analyses were performed. Outcomes included progression-free survival (PFS), overall survival (OS), and adverse events (AEs). An exploratory frequentist network meta-analysis was performed among patients with BRAF V600E mutation. Results (included studies): KEYNOTE-177 (Phase III; I: 153, C: 154; Pembrolizumab vs CT; First line; BRAF V600E 35/153) | COMMIT (Phase III; I: 41, C: 41; Atezolizumab vs Folfox+Atezolizumab+bevacizumab; First line; I: 10/41, C: 9/41) | CHECKMATE 8HW André 2024 (Phase III; I: 202, C: 101; Nivolumab+ipilimumab vs CT; 52/202) | CHECKMATE 8HW André 2025 (I: 354, C: 353; Nivolumab+ipilimumab vs Nivolumab; First and later lines; I: 85/353, C: 106/354) | SAMCO-PRODIGE (Phase II; I: 61, C: 61; Avelumab vs CT; 2nd line; 25/61) Dual checkpoint blockade achieved the most favorable survival outcomes across evaluated regimens, supporting nivolumab plus ipilimumab as a potentially preferred therapeutic strategy for patients with dMMR/MSI-H mCRC. PFS (pooled KM): Anti-PD1 + Anti-CTLA4 vs. CT: HR 0.34, 95% CI 0.27-0.41, p<0.001 Anti-PD1 + Anti-CTLA4 vs. Anti-PD1/PDL1: HR 0.68, 95% CI 0.56-0.81, p<0.001 Anti-PD1 + Anti-CTLA4 vs. CT+Anti-PDL1+bevacizumab: HR 0.51, 95% CI 0.34-0.76, p=0.001 Anti-PD1/PDL1 vs. CT: HR 0.60, 95% CI 0.51-0.71, p<0.001 Pooled KM curve of PFS including all studies (CheckMate 8HW ITT, KEYNOTE-177, SAMCO, and COMMIT) comparing nivolumab plus ipilimumab, anti-PD-1/PD-L1 monotherapy, CT plus atezolizumab and bevacizumab, and CT. OS (pooled KM): Anti-PD1 + Anti-CTLA4 vs. CT: HR 0.32, 95% CI 0.23-0.44, p<0.001 Anti-PD1 + Anti-CTLA4 vs. Anti-PD1/PDL1: HR 0.49, 95% CI 0.36-0.65, p<0.001 Anti-PD1 + Anti-CTLA4 vs. CT+Anti-PDL1+bevacizumab: HR 0.54, 95% CI 0.29-0.99, p=0.045 Anti-PD1/PDL1 vs. CT: HR 0.65, 95% CI 0.52-0.81, p<0.001 Pooled KM curve of OS including all studies (CheckMate 8HW ITT, KEYNOTE-177, SAMCO, and COMMIT) comparing nivolumab plus ipilimumab, anti-PD-1/PD-L1 monotherapy, CT plus atezolizumab and bevacizumab, and CT. Exploratory frequentist NMA among patients with BRAF V600E mutation (league table, PFS HRs): ICI-ICI vs CT-ICI-AA 0.37 (0.09-1.53); ICI vs CT-ICI-AA 0.23 (0.06-0.88); ICI vs ICI-ICI 0.62 (0.39-0.98); CT vs CT-ICI-AA 0.11 (0.03-0.48); CT vs ICI-ICI 0.30 (0.14-0.62); CT vs ICI 0.48 (0.27-0.86) Grade ≥3 AEs and treatment discontinuation rate: [forest plot values too small to transcribe reliably] Author contact: matheusandrade.ext@americasmed.com.br; @AndradeMO_MD

[Slide 1] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ DEWI Phase II: Study design KEY ELIGIBILITY CRITERIA • ECOG PS of 0-1, • Age ≥18 years, • Pts aged >70 years: G8 score of ≥14 and/or fit for surgery, • Non-metastatic dMMR/MSI-H gastric or GEJ adenocarcinoma, cT2-T4, Nx, M0 after: - CT of the thorax-abdomen-pelvis (TAP-CT), - Echo-endoscopy (EUS), - Optional coelioscopy. PRIMARY OBJECTIVE • To evaluate clinical complete response (cCR) at 1 year, defined as the proportion of Pts who, at 1 year after the start of treatment with dostarlimab, are: - alive, - without tumor resection, - free of disease progression (on endoscopy & Thoraco-Abdo-Pelv CT scan) - with negative biopsies - with complete or near complete at endoscopy (Grade 3 or 4) STATISTICAL ANALYSES: Interim Safety/Futility Analysis • Current design: Simon two-stage, • Planned design: Fleming three-stage, • One-sided type I error: 0.54%, power: 95%, • A total of 80 evaluable Pts with cCR status available at 1 year are required. • A cCR rate at 1 year of 50% (P1) is expected. • Interim analysis: planned after 25 Pts first pts included with 1 year of follow-up. The study will continue if ≥8 Pts (33.3%) achieve cCR at 1 year. ClinicalTrials.gov identifier: NCT06059495 EU CT Number: 2023-506102-39-00 Thierry André Thierry André — Watch-and-wait (W&W) strategy for dostarlimab in localized deficient dMMR/MSI-H gastroesophageal adenocarcinoma (GEA): Results from the first interim analysis of the GERCOR-GONO DEWI phase II study ALMERIA AUDITORIUM - HALL 9 [Slide 2] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ DEWI Phase II: Study Schedule cCR=clinical complete response; W&W=watch-and-wait; PD=disease progression Inclusion -> DOSTARLIMAB 500 mg IV q3w, 4 cycles: C1-C4, W1-W4-W7-W10 Week 12 Evaluation: (1) Biopsy(es) with or without tumoral cells and tumoral regression at endoscopy (stage 2-3) and without PD, W&W -> DOSTARLIMAB 500 mg IV q3w*, 4 cycles: C5-C8, W13-W15-W18-W21 -> Week 24 Evaluation: cCR -> DOSTARLIMAB 1000 mg IV q6w*, 4 cycles: C9-C12 -> cCR: W&W / If PD STOP DOSTARLIMAB** No cCR -> SURGERY with TGR 1a, 1b, 2 (Becker) / SURGERY with TGR 3 (Becker) -> If PD STOP DOSTARLIMAB** (2) cCR, W&W -> DOSTARLIMAB 1000 mg IV q6w*, 2 cycles: C5-C6, W13-W19 -> Week 24 Evaluation: cCR -> DOSTARLIMAB 1000 mg IV q6w*, 4 cycles: C7-C10, W25-W31-W37-W43 -> cCR: W&W / If PD STOP DOSTARLIMAB** No cCR -> SURGERY proposed -> If surgery** (3) Local/loco regional PD and biopsy(es) with tumoral cells -> SURGERY with TGR 1a, 1b, 2 (Becker) -> DOSTARLIMAB 1000 mg IV q6w*, 6 cycles: C5-C10 -> If PD STOP DOSTARLIMAB** SURGERY with TGR 3 (Becker) -> STOP DOSTARLIMAB** First Pt included: Jan 22, 2024 Thierry André Thierry André — Watch-and-wait (W&W) strategy for dostarlimab in localized deficient dMMR/MSI-H gastroesophageal adenocarcinoma (GEA): Results from the first interim analysis of the GERCOR-GONO DEWI phase II study ALMERIA AUDITORIUM - HALL 9 [Slide 3] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ Interim Analysis (15 Jan 2026): 25 Pts with 1 year follow-up and completed 12-Month evaluation (12M) [Pie chart:] cCR at 1 year n=14 (61%); Surgery n=9 (36%); Not treated n=1; Not evaluated at 1 Y n=1 TRG Becker (n=9) TRG 1a: no residual tumor 0 TGR 2: 10% to 50% residual tumor cells 3 (33%) TRG 3: >50% residual tumor cells 6 (67%) •25 Pts enrolled; 1 Pt excluded (Biermer disease, no dostarlimab treatment). •23 Pts reached 1 year evaluation: 14/23 (61%) achieved cCR. •1 Pt after the interim analysis achieved cCR at 1 year • Overall cCR rate: 15/24 (62,5%). •9/24 Pts underwent surgery. •Median cumulative dostarlimab dose during the first 6 months: 4,000 mg. Interim endpoint met: ≥8 Pts (33.3%) achieved cCR at 1 year; study to continue. Thierry André Thierry André — Watch-and-wait (W&W) strategy for dostarlimab in localized deficient dMMR/MSI-H gastroesophageal adenocarcinoma (GEA): Results from the first interim analysis of the GERCOR-GONO DEWI phase II study ALMERIA AUDITORIUM - HALL 9 [Slide 4] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ At Analysis with data cutoff on 1 Sep 2026: 43 Pts treated and with 1 year follow-up and completed 1 year evaluation Median follow-up: 14.9 months (Q1=14 months, Q3=15.7 months) [Pie chart:] cCR at 1 year with organ preservation n=29; Surgery n=14 (32.5%) TRG Becker (n=14) TRG 1a: no residual tumor 1 (7%) TGR 2: 10% to 50% residual tumor cells 6 (43%) TRG 3: >50% residual tumor cells 7 (50%) Among the 29 Pts in cCR under a Watch-and-Wait approach with organ preservation - Median treatment duration: 10 months (range, 3-11). - All Pts in cCR at M6 remained in cCR at 1 year. - No relapse and no death. - One patient refuse Watch and Wait in CCR. Thierry André Thierry André — Watch-and-wait (W&W) strategy for dostarlimab in localized deficient dMMR/MSI-H gastroesophageal adenocarcinoma (GEA): Results from the first interim analysis of the GERCOR-GONO DEWI phase II study ALMERIA AUDITORIUM - HALL 9

[Slide 1] Interim Analysis (15 Jan 2026): 25 Pts with 1 year follow-up and completed 12-Month evaluation (12M) [Pie chart:] cCR at 1 year n=14 (61%); Surgery n=9 (36%); Not treated n=1; Not evaluated at 1 Y n=1 TRG Becker (n=9) TRG 1a: no residual tumor 0 TGR 2: 10% to 50% residual tumor cells 3 (33%) TRG 3: >50% residual tumor cells 6 (67%) •25 Pts enrolled; 1 Pt excluded (Biermer disease, no dostarlimab treatment). •23 Pts reached 1 year evaluation: 14/23 (61%) achieved cCR. •1 Pt after the interim analysis achieved cCR at 1 year • Overall cCR rate: 15/24 (62,5%). •9/24 Pts underwent surgery. •Median cumulative dostarlimab dose during the first 6 months: 4,000 mg. Interim endpoint met: ≥8 Pts (33.3%) achieved cCR at 1 year; study to continue. Thierry André [Slide 2] DEWI phase II: Safety and Outcomes Planned Interim Analysis (15 Jan 2026): 25 Pts with at least 1 year follow-up Median follow-up = 14.06 months in Feb 2026 SAFETY (N=24) •Grade 3-4 dostarlimab-related AEs: 21%. •Treatment interruption for SAE (n=5, 4 Pts had surgery and one had cCR after 8 dostarlimab doses as administered intravenously) •Surgery performed in 9/24 Pts: • 4 fistulas including 2 esophagogastric anastomotic fistulas • 1 postoperative death related to a fistula complications. DISEASE CONTROL AND OVERALL SURVIVAL •1 Pts with metastatic disease progression (sus clav nodes after surgery) •1 death: 1 postoperative death related to a fistula complications. [Slide 3] At Analysis with data cutoff on 1 Sep 2026: 43 Pts treated and with 1 year follow-up and completed 1 year evaluation Median follow-up: 14.9 months (Q1=14 months, Q3=15.7 months) [Pie chart:] cCR at 1 year with organ preservation n=29; Surgery n=14 (32.5%) TRG Becker (n=14) TRG 1a: no residual tumor 1 (7%) TGR 2: 10% to 50% residual tumor cells 6 (43%) TRG 3: >50% residual tumor cells 7 (50%) Among the 29 Pts in cCR under a Watch-and-Wait approach with organ preservation - Median treatment duration: 10 months (range, 3-11). - All Pts in cCR at M6 remained in cCR at 1 year. - No relapse and no death. - One patient refuse Watch and Wait in CCR. Thierry André [Slide 4] Conclusion and Future Directions • Interim analysis met primary endpoint. • About 2/3 of patients in this preliminary results with 43 patients are in CCR at 1 year with organ preservation without relapse or death. • Additional cohort of 20 surgery-unfit Pts (elderly and/or with comorbidities) currently enrolled, 1-year cCR analysis planned in 202. • Target enrollment: 89 surgery-fit and 39 surgery-unfit Pts. • Translational studies (ctDNA and transcriptomic profiling) is ongoing to identify predictive biomarkers to support early selection for surgery versus watch-and-wait management. Thierry André

DEWI Phase II: Study Schedule cCR=clinical complete response W&W=watch-and-wait PD=disease progression Inclusion -> DOSTARLIMAB 500 mg IV q3w 4 cycles: C1-C4 W1-W4-W7-W10 Week 12 Evaluation: - Biopsy(es) with or without tumoral cells and tumoral regression at endoscopy (stage 2-3) and without PD W&W -> DOSTARLIMAB 500 mg IV q3w* 4 cycles: C5-C8 W13-W15-W18-W21 -> Week 24 Evaluation: cCR -> DOSTARLIMAB 1000 mg IV q6w* 4 cycles: C9-C12 -> cCR: W&W / If PD STOP DOSTARLIMAB**; No cCR -> SURGERY with TGR 1a, 1b, 2 (Becker) / SURGERY with TGR 3 (Becker) -> If PD STOP DOSTARLIMAB** - cCR W&W -> DOSTARLIMAB 1000 mg IV q6w* 2 cycles: C5-C6 W13-W19 -> cCR -> DOSTARLIMAB 1000 mg IV q6w* 4 cycles: C7-C10 W25-W31-W37-W43 -> cCR: W&W / If PD STOP DOSTARLIMAB**; No cCR -> SURGERY proposed -> If surgery** - Local/loco regional PD and biopsy(es) with tumoral cells -> SURGERY with TGR 1a, 1b, 2 (Becker) -> DOSTARLIMAB 1000 mg IV q6w* 6 cycles: C5-C10 -> If PD STOP DOSTARLIMAB**; SURGERY with TGR 3 (Becker) -> STOP DOSTARLIMAB** First Pt included: Jan 22, 2024 Thierry André

[Slide 1] Clinical Complete Response: How Much Residual Disease Are We Missing? Clinical response evaluation outcomes per diagnostic modalities and tumour regression grade | TGR1 | TRG2 | TRG3 | TRG4 | p value* Endoscopy with regular biopsies and fine-needle aspiration | | | | | 0·0036 Positive | 4/13 (31%) | 2/11 (18%) | 4/9 (44%) | 14/17 (82%) | .. Negative | 9/13 (69%) | 9/11 (82%) | 5/9 (56%) | 3/17 (18%) | .. Endoscopy with bite-on-bite biopsies and fine-needle aspiration | | | | | <0·0001 Positive | 5/18 (28%) | 17/29 (59%) | 20/24 (83%) | 17/17 (100%) | .. Negative | 13/18 (72%) | 12/29 (41%) | 4/24 (17%) | 0/17 | .. Endoscopic ultrasonography with maximum tumour thickness | | | | | 0·035 Positive | 11/27 (41%) | 13/29 (45%) | 13/20 (65%) | 15/19 (79%) | .. Negative | 16/27 (59%) | 16/29 (55%) | 7/20 (35%) | 4/19 (21%) | .. PET-CT | | | | | 0·191 Positive | 17/27 (63%) | 22/30 (73%) | 17/19 (89%) | 18/22 (82%) | .. Negative | 10/27 (37%) | 8/30 (27%) | 2/19 (11%) | 4/22 (18%) | .. *Calculated with the χ² test. • TRG 2 was missed 41% patients by EGD with bite-on-bite biopsy and FNA • TRG 2 was missed 55% by EUS • TRG2 was missed 27% by PET-CT Accuracy for detecting TRG3–4 does not establish accuracy for excluding all residual viable disease Daniela Molena, MD Noordman B et al. Lancet Oncol 2018 [Slide 2] SANO at 5 Years: Did Delaying Surgery Come at a Cost? pCR rate (i.e. positive predictive value of cCR): 37% TRG1 40% | TRG2 35% | TRG3 13% | TRG4 12% | ypT0N+ 3% Distant dissemination rate Active surveillance — Surgery sHR 2.04, 95%CI 1.25-3.34, p < 0.01 Number at risk [illegible] • 51% had local recurrence • Higher 5-year distant metastasis incidence with active surveillance (46% vs 29%; p<0.01) • Only 32% maintained cCR (64 pts) at a median follow-up 76 months (IQR 67-86) Daniela Molena, MD Sanjiv S. Gangaram-Panday et al , LBA78, EAMO 2026 [Slide 3] MSI-H/dMMR: Do All Patients Still Need Chemotherapy? NEONIPIGA Neoadjuvant nivolumab + ipilimumab 58.6% pCR among 29 patients who underwent surgery Phase II · dMMR/MSI-H gastric/GEJ adenocarcinoma EFS Probability / Time, mo INFINITY — Cohort 1 Neoadjuvant durvalumab + tremelimumab 60% pCR among 15 evaluable operated patients Phase II · dMMR/MSI-H gastric/GEJ adenocarcinoma Disease-Free Survival, % / Time, mo Daniela Molena, MD Andre T et al. J Clin Oncol. 2023 Raimondi A et al. Annals of Oncology. 2025 [Slide 4] Can Immunotherapy Enable Organ Preservation? INFINITY (Phase II) Resectable MSI-H/dMMR gastric/GEJ adenocarcinoma Enrolled / evaluable | 18 / 17 Clinical complete response (cCR) | 76% (13/17) 24-month outcomes • PFS | 94.1% • OS | 100% • Gastrectomy-free survival | 70.6% Events | 1 local regrowth; 4 without cCR DEWI (Phase II, ESMO 2026) Localized MSI-H/dMMR gastric/GEJ adenocarcinoma Enrolled | 43 cCR with organ preservation (1 year) | 67.4% (29/43) Outcomes (median follow-up: 14.9 m) • Relapse | 0 • Deaths | 0 • Remained on watch-and-wait | 29 (67.4%) Daniela Molena, MD Raimondi A et al. Annals of Oncology. 2025 Thierry André et al. 2877RO, ESMO 2026

DEWI phase II Interim Analysis (15 Jan 2026): Pts treated with 1 year follow-up Overall Population (n=24) | n | % Male/Female | 18/6 | 75/25 Age, median (min-max) Yrs | 65 (59-71) | - ECOG PS at baseline 0/1 | 18/6 | 75/25 Tumor localisation Gastric/ Gastro-esophageal Junction | 14/9 | 62.5/37.5 Echo-Endoscopy/scanner stage uT2 | 5 | 21 uT3 | 18 | 75 uT4 | 1 | 4 uN0/uN+/uNx | 9/10/5 | 37/42/21 dMMR (Immunochemistry) | 24/24 | 100 loss of MLH1 and/or PMS2 | 22 | 92 loss of MSH2 and/or MSH6 | 2 | 8 MSI (PCR) | 12/12 | - Lynch syndrome* (Yes Germline) Yes/No (germline)/sporadic or unknown | 1/21/2 | 4/88/8 Thierry André

[Slide 1] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Combination of Temab-A + Bev in Patients With 3L+ CRC in the First-in Human Study (NCT05029882) Key Inclusion Criteria (Part 7) • Adult patients with metastatic CRC, irrespective of c-Met protein expression level • Progression on fluoropyrimidine, oxaliplatin, and irinotecan, and if applicable, anti-EGFR or anti-VEGF monoclonal antibody, or other targeted therapy • Measurable disease per RECIST v1.1 • ECOG PS 0–1 • Hemoglobin ≥ 8 g/dL (with no RBC transfusion in the past 14 days) Key Exclusion Criteria (Part 7) • BRAF V600E mutation • dMMR+/MSI-H • Prior regorafenib or FTD-TPI treatment Part 7: Temab-A and Bev Combination Therapy Safety Lead-In (Part 7a): DL1 (1.6 mg/kg; n=7) | DL2 (2.4 mg/kg; n=8) | Backfill DL3 (2.0 mg/kg; n=5) Temab-A + Bev 7.5 mg/kg IV Q3W Dose Optimization (Part 7b): R (1:1:1) N=66 Arm 1a Temab-A 2.0 mg/kg Q3W + Bevb (n=22) Arm 2 Temab-A 2.4 mg/kg Q3W + Bevb (n=22) Arm 3 Comparator (SOC)c FTD-TPI + Bevd (n=22) Primary Objective (Part 7) • Evaluate the safety, efficacy, and pharmacokinetics of Temab-A in combination with Bev vs FTD-TPI + Bev in patients with 3L+ CRC Data cutoff date: 02March2026. aOne patient withdrew and was not treated. b7.5 mg/kg Q3W. cTwo patients withdrew and were not treated. d5.0 mg/kg Q2W. 3L+, third-line and beyond; Bev, bevacizumab; CRC, colorectal cancer; DL, dose level; dMMR, deficient DNA mismatch pair; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; FTD-TPI, trifluridine/tipiracil; IV, intravenous; MSI-H, microsatellite instability-high; Q3W, every 3 weeks; R, randomization; RBC, red blood cells; RECIST, Response Evaluation Criteria in Solid Tumors; SOC, standard of care; Temab-A, telisotuzumab adizutecan; VEGF, vascular endothelial growth factor. Michael Cecchini Long-term follow-up of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Updated results of a phase 1 study ALICANTE AUDITORIUM - HALL 6 [Slide 2] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER TRAEs Were Primarily Hematologic and Gastrointestinal and Were Manageable Most common TRAEsa Temab-A 2.4 mg/kg + Bev (n=30): Grade ≥3 | Grade 1-2 || FTD-TPI + Bev (n=20): Grade 1-2 | Grade ≥3 Patients (%) Anemia | 53 | 13 || 15 | 15 Neutropenia | 33 | 20 || 30 | 30 Thrombocytopenia | 10 | 23 || 30 | 5 Nausea | – | 57 || 50 | – Fatigue | 7 | 37 || 35 | – Vomiting | – | 40 || 25 | – Decreased appetite | – | 30 || 20 | – Diarrheab | – | 20 || 30 | 5 Management of TRAEs | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Median treatment duration, months (range) | 6.1 (1.4–19.8) | 4.9 (0.9–14.0) Treatment discontinuation, n (%) | 1 (3) | 1 (5) Dose reduction, n (%) | 15 (50) | 6 (30) Dose interruption, n (%) | 22 (73) | 9 (45) • There were no TRAEs leading to death • Adjudicated ILD/pneumonitis rate was 3% (Grade 3: n=1) among 30 patients who received 2.4 mg/kg Temab-A + Bev Data cutoff date: 02March2026. aAny grade reported in ≥20% of patients. bAll events of diarrhea with Temab-A were Grade 1. Bev, bevacizumab; FTD-TPI, trifluridine/tipiracil; ILD, interstitial lung disease; Temab-A, telisotuzumab adizutecan; TRAE, treatment-related adverse event. Michael Cecchini Long-term follow-up of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Updated results of a phase 1 study ALICANTE AUDITORIUM - HALL 6 [Slide 3] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Temab-A 2.4 mg/kg + Bev Shows Promising Efficacy Over FTD-TPI + Bev With a Median PFS of 6.8 Months Median follow-up: 18.2 months (range 0.4–22.8) PFS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 27 (90.0) | 18 (90.0) Median PFS, months (95% CI) | 6.8 (5.4–9.5) | 4.2 (1.8–6.3) HR (95% CI) | 0.48 (0.26–0.89) Legend: Temab-A 2.4 mg/kg + Bev | FTD-TPI + Bev Y-axis: Probability; X-axis: Time (Months) 0–20 Patients at Risk Temab-A 2.4 mg/kg | 30 | 30 | 28 | 26 | 25 | 21 | 19 | 12 | 12 | 11 | 4 | 4 | 4 | 4 | 3 | 2 | 1 | 1 | 1 | 1 | 0 FTD-TPI | 20 | 19 | 15 | 12 | 11 | 9 | 7 | 4 | 4 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 Data cutoff date: 02March2026. Bev, bevacizumab; FTD-TPI, trifluridine/tipiracil; HR, hazard ratio; PFS, progression-free survival; Temab-A, telisotuzumab adizutecan. Michael Cecchini Long-term follow-up of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Updated results of a phase 1 study ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: PFS Arm | N | Median | Median CI Temab-A 2.4 mg/kg + Bev | 30 | 6.8 months | 5.4–9.5 FTD-TPI + Bev | 20 | 4.2 months | 1.8–6.3 HR: 0.48 HR CI: 0.26–0.89 [Slide 4] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Conclusions Temab-A 2.4 mg/kg + Bev showed sustained clinically meaningful improvements in efficacy outcomes, including ORR (30%), median PFS (6.8 months), and median OS (14.7 months; HR=0.62) The safety profile was manageable with low discontinuation rates; hematologic adverse events were managed with dose interruptions and reductions The regimen is being evaluated in the global randomized Phase 3 trial AndroMETa-CRC-560 (NCT07525206) For additional information, refer to the manuscript published concurrently in Annals of Oncology Thank you to the patients, study sites, and investigators who participated in this clinical trial. AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Marianne Pons, PhD, and Phillip Giannopoulos, PhD, CMPP of Bio Connections, LLC, and funded by AbbVie. Bev, bevacizumab; CRC, colorectal cancer; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Temab-A, telisotuzumab adizutecan. Copies of this presentation obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from ESMO or the author of this presentation. Scan QR code to download an electronic version of this presentation. To submit a medical question, please visit www.abbviemedinfo.com Michael Cecchini Long-term follow-up of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Updated results of a phase 1 study ALICANTE AUDITORIUM - HALL 6

Temab-A 2.4 mg/kg + Bev Shows Promising Efficacy Over FTD-TPI + Bev With a Median PFS of 6.8 Months Median follow-up: 18.2 months (range 0.4–22.8) PFS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 27 (90.0) | 18 (90.0) Median PFS, months (95% CI) | 6.8 (5.4–9.5) | 4.2 (1.8–6.3) HR (95% CI) | 0.48 (0.26–0.89) Legend: Temab-A 2.4 mg/kg + Bev; FTD-TPI + Bev Probability ; Time (Months) 0-20 Patients at Risk Temab-A 2.4 mg/kg: 30 | 30 | 28 | 26 | 25 | 21 | 19 | 12 | 12 | 11 | 4 | 4 | 4 | 4 | 3 | 2 | 1 | 1 | 1 | 1 | 0 FTD-TPI: 20 | 19 | 15 | 12 | 11 | 9 | 7 | 4 | 4 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 Survival table Endpoint: PFS Arm | N | Median | Median CI Temab-A 2.4 mg/kg + Bev | 30 | 6.8 mo | 5.4–9.5 FTD-TPI + Bev | 20 | 4.2 mo | 1.8–6.3 HR: 0.48 HR CI: 0.26–0.89

[Slide 1] Temab-A + Bev vs FTD-TPI + Bev for Patients With Recurrent Metastatic CRC • Increased expression of c-Met protein is common in CRC and carries a poor prognosis1,2 • Prior results from this Phase 1 studya (median follow-up: 9.8 months) showed that telisotuzumab adizutecan (ABBV-400, Temab-A) + bevacizumab (Bev) resulted in manageable safety and higher antitumor activity vs SOC (trifluridine/tipiracil [FTD-TPI] + Bev) in 3L+ CRC3 ○ The 2.4 mg/kg Temab-A dose exhibited the most favorable benefit-risk profile versus 2.0 mg/kg ○ cORR with Temab-A 2.4 mg/kg vs FTD-TPI + Bev: 30% vs 0% Mechanism of action of Temab-A Validated c-Met—targeted antibody (telisotuzumab) | Potent Top1i payload (adizutecan) | Stable linker Minimizes free-payload toxicity Tumor cell | c-Met protein | Top1i inhibits DNA replication | Leading to apoptosis Antitumor effect of Temab-A does not rely on c-Met signaling, unlike c-Met protein–targeting TKIs and mAbs With a median follow-up of 18.2 months, we report results from patients randomized to receive either Temab-A 2.4 mg/kg + Bev or FTD-TPI + Bev aNCT05029882. 3L+, third-line and beyond; ADC, antibody-drug conjugate; Bev, bevacizumab; cORR, confirmed objective response rate; CRC, colorectal cancer; FTD-TPI, trifluridine/tipiracil; mAbs, monoclonal antibodies; SOC, standard of care; Temab-A, telisotuzumab adizutecan; TKI, tyrosine kinase inhibitor; Top1i, topoisomerase 1 inhibitor. 1. Lee SJ, et al. Clin Colorectal Cancer. 2018;17(3):165–169. 2. Liu Y, et al. World J Gastroenterol. 2015;21(12):3706–3710. 3. Cecchini M, et al. Oral presentation at ESMO 2025 (Abstract 731MO). [Slide 2] Temab-A 2.4 mg/kg + Bev Shows Promising Efficacy Over FTD-TPI + Bev With a Median PFS of 6.8 Months Median follow-up: 18.2 months (range 0.4–22.8) PFS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 27 (90.0) | 18 (90.0) Median PFS, months (95% CI) | 6.8 (5.4–9.5) | 4.2 (1.8–6.3) HR (95% CI) | 0.48 (0.26–0.89) Legend: Temab-A 2.4 mg/kg + Bev | FTD-TPI + Bev Y-axis: Probability; X-axis: Time (Months) 0–20 Patients at Risk Temab-A 2.4 mg/kg | 30 | 30 | 28 | 26 | 25 | 21 | 19 | 12 | 12 | 11 | 4 | 4 | 4 | 4 | 3 | 2 | 1 | 1 | 1 | 1 | 0 FTD-TPI | 20 | 19 | 15 | 12 | 11 | 9 | 7 | 4 | 4 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 Data cutoff date: 02March2026. Bev, bevacizumab; FTD-TPI, trifluridine/tipiracil; HR, hazard ratio; PFS, progression-free survival; Temab-A, telisotuzumab adizutecan. Survival table Endpoint: PFS Arm | N | Median | Median CI Temab-A 2.4 mg/kg + Bev | 30 | 6.8 months | 5.4–9.5 FTD-TPI + Bev | 20 | 4.2 months | 1.8–6.3 HR: 0.48 HR CI: 0.26–0.89 [Slide 3] Median OS for Temab-A 2.4 mg/kg + Bev Was 14.7 Months and 10.2 Months for FTD-TPI + Bev Median follow-up: 18.2 months (range 0.4–22.8) OS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 22 (73.3) | 17 (85.0) Median OS, months (95% CI) | 14.7 (9.8–17.8) | 10.2 (7.7–14.5) HR (95% CI) | 0.62 (0.33–1.18) Legend: Temab-A 2.4 mg/kg + Bev | FTD-TPI + Bev Y-axis: Probability; X-axis: Time (Months) 0–23 Patients at Risk Temab-A 2.4 mg/kg | 30 | 30 | 29 | 27 | 26 | 25 | 25 | 24 | 24 | 22 | 19 | 19 | 19 | 16 | 15 | 12 | 9 | 9 | 8 | 4 | 1 | 1 | 1 | 0 FTD-TPI | 20 | 19 | 19 | 19 | 19 | 19 | 18 | 16 | 15 | 13 | 10 | 8 | 6 | 6 | 6 | 5 | 3 | 3 | 2 | 1 | 0 | 0 | 0 | 0 Data cutoff date: 02March2026. Bev, bevacizumab; FTD-TPI, trifluridine/tipiracil; HR, hazard ratio; OS, overall survival; Temab-A, telisotuzumab adizutecan. Survival table Endpoint: OS Arm | N | Median | Median CI Temab-A 2.4 mg/kg + Bev | 30 | 14.7 months | 9.8–17.8 FTD-TPI + Bev | 20 | 10.2 months | 7.7–14.5 HR: 0.62 HR CI: 0.33–1.18

A Randomized Phase 1 Study of Telisotuzumab Adizutecan (ABBV-400, Temab-A) in Combination With Bevacizumab Versus Trifluridine-Tipiracil With Bevacizumab in Patients With Metastatic Colorectal Cancer Michael Cecchini, Marcia Cruz-Correa, Sae-Won Han, Kanwal Raghav, Ana Landa-Magdalena, John Strickler, Aitana Calvo, Antoine Hollebecque, Takako Eguchi Nakajima, Gali Perl, Vikram Jain, Zoë Hunter, Edward M. Chan, Martha Blaney, Rui Li, Athan Vasilopoulos, Apurvasena Parikh, Manish R. Sharma BACKGROUND - Temab-A is an ADC composed of the c-Met-directed antibody, telisotuzumab, conjugated to a novel topoisomerase 1 inhibitor - Increased expression of c-Met protein is common in CRC and carries a poor prognosis [Schematic: Validated c-Met-targeted antibody (telisotuzumab); Potent Top1i payload (adizutecan); Stable linker - Minimizes free-payload toxicity; Antitumor effect of Temab-A does not rely on c-Met signaling, unlike c-Met protein-targeting TKIs and mAbs] STUDY DESIGN First in human, phase 1 study of combination Temab-A and bevacizumab in c-Met unselected patients with 3L+ CRC (NCT05029882) Safety lead-in and randomized dose optimization - Median 3 prior lines of therapies - ~90% prior bevacizumab in Temab-A arms Safety Lead-In (Part 7a): DL1 (1.6 mg/kg; n=7) -> DL2 (2.4 mg/kg; n=8); Backfill DL3 (2.0 mg/kg; n=5); Temab-A + Bev 7.5 mg/kg IV Q3W Dose Optimization (Part 7b): R (1:1:1) N=66 -> Arm 1: Temab-A 2.0 mg/kg Q3W + Bev (n=22); Arm 2: Temab-A 2.4 mg/kg Q3W + Bev (n=22); Arm 3 Comparator (SOC): TFD-TPI + Bev (n=22) KEY RESULTS - Selected dose: Temab-A 2.4 mg/kg + Bev; Median follow-up: 18.2 months Safety and Tolerability [Butterfly chart, Patients (%), Temab-A 2.4 mg/kg + Bev (n=30) vs FTD-TPI + Bev (n=20), Grade ≥3 / Grade 1-2: Anemia, Neutropenia, Thrombocytopenia, Nausea, Fatigue, Vomiting, Decreased appetite, Diarrhea - bar values small; see notes] | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Median treatment duration, months (range) | 6.1 (1.4-19.8) | 4.9 (0.9-14.0) Treatment discontinuation, n (%) | 1 (3) | 1 (5) Dose reduction, n (%) | 15 (50) | 6 (30) Dose interruption, n (%) | 22 (73) | 9 (45) - No TRAEs leading to death - Adjudicated ILD/pneumonitis rate was 3% (Grade 3: n=1) in patients treated with 2.4 mg/kg Temab-A + Bev Efficacy ORR 30% vs 0% with FTD-TPI + Bev MEDIAN PFS 6.8 months vs 4.2 months with FTD-TPI + Bev (HR: 0.48) MEDIAN OS 14.7 months vs 10.2 months with FTD-TPI + Bev (HR: 0.62) - c-Met protein expression was detected in the tumors of all patients - Longer survival observed with Temab-A + Bev over FTD-TPI + Bev across c-Met protein expression levels Temab-A 2.4 mg/kg + Bev showed sustained clinically meaningful improvements in efficacy outcomes, and the safety profile was manageable with low discontinuation rates; hematologic adverse events were managed with dose interruptions and reductions. Temab-A 2.4mg/kg is being evaluated in the global randomized Phase 3 trial, AndroMETa-560 (NCT07525206) Bev, bevacizumab; CRC, colorectal cancer; FTD-TPI, trifluridine-tipiracil; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks; TRAE, treatment-related adverse event.

[Slide 1] Efficacy: promising, but… Median follow-up: 18.2 months (range 0.4–22.8) PFS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 27 (90.0) | 18 (90.0) Median PFS, months (95% CI) | 6.8 (5.4–9.5) | 4.2 (1.8–6.3) HR (95% CI) | 0.48 (0.26–0.89) Progression-free survival → Sunlight (N=246) mPFS: 5.6 mos Worse performance of FTD-TPI+Bev due to more heavily pretreated pts? Patients at Risk (0–20 months) Temab-A 2.4 mg/kg | 30 30 28 26 25 21 19 12 12 11 4 4 4 4 3 2 1 1 1 1 0 FTD-TPI | 20 19 15 12 11 9 7 4 4 2 1 1 1 1 0 0 0 0 0 0 0 OS | Temab-A 2.4 mg/kg + Bev (n=30) | FTD-TPI + Bev (n=20) Events, n (%) | 22 (73.3) | 17 (85.0) Median OS, months (95% CI) | 14.7 (9.8–17.8) | 10.2 (7.7–14.5) HR (95% CI) | 0.62 (0.33–1.18) Overall survival → Sunlight (N=246) mOS: 10.8 mos Numerically longer OS, but wide CI HR: is it appropriate? Patients at Risk (0–23 months) Temab-A 2.4 mg/kg | 30 30 29 27 26 25 25 24 24 22 19 19 19 16 15 12 9 9 8 4 1 1 1 0 FTD-TPI | 20 19 19 19 19 19 18 16 15 13 10 8 6 6 6 5 3 3 2 1 0 0 0 0 Prager et al. NEJM 2023 Lisa Salvatore, MD, PhD Survival table Endpoint: PFS and OS: Temab-A 2.4 mg/kg + Bev vs FTD-TPI + Bev (mCRC) Arm | N | Median | Median CI Temab-A 2.4 mg/kg + Bev (PFS) | 30 | 6.8 | 5.4–9.5 FTD-TPI + Bev (PFS) | 20 | 4.2 | 1.8–6.3 Temab-A 2.4 mg/kg + Bev (OS) | 30 | 14.7 | 9.8–17.8 FTD-TPI + Bev (OS) | 20 | 10.2 | 7.7–14.5 HR: PFS 0.48; OS 0.62 HR CI: PFS 0.26–0.89; OS 0.33–1.18 [Slide 2] Efficacy: promising, but… | Temab-A 2.4 (N=40) | Temab-A 2.0+Bev (N=26) | Temab-A 2.4+Bev (N=30) RR | 17.5% | 19% | 30% DCR | 77.5% | 81% | 97% mPFS | 5.3 | 5.6 | 6.8 mOS | 10.7 | 11.2 | 14.7 Sharma et al. JCO 2026; Cecchini et al. ESMO 2025; Cecchini et al. ESMO 2026 Open question #1 • What does really add Bev to Temab-A? Higher RR if Bev is added to Temab-A 2.4, but dose reduction due to AEs in 50% of patients We will never have a direct comparison Temab-A vs Temab-A+Bev Lisa Salvatore, MD, PhD [Slide 3] Efficacy: promising, but… | Temab-A ≥2.4 cMet 3+ ≥10% (N=25) | Temab-A ≥2.4 cMet 3+ <10% (N=50) | Temab-A 2.0/2.4+Bev cMet 3+ ≥10% (N=18) | Temab-A 2.0/2.4+Bev cMet 3+ <10% (N=35) RR | 36% | 12% | 17% | 31% Sharma et al. JCO 2026; Murciano-Goroff et al. ESMO 2025; Cecchini et al. ESMO 2025 | Temab-A 2.4+Bev cMet 3+ ≥10% (N=10) | Temab-A 2.4+Bev cMet 3+ <10% (N=18) mPFS | 9.3 | 6.8 mOS | 15.3 | 13.3 Cecchini et al. ESMO 2026 Open questions #2 • Can cMet expression predict response? Yes if Temab-A alone ??? Temab-A+Bev (no for RR; PFS and OS promising indipendently of c-Met expression) Lisa Salvatore, MD, PhD [Slide 4] Temab-A + Bev: my personal conclusions ✓ Temab-A + Bev is a promising regimen for pretreated mCRC (RR30%, mPFS 6.8 months and mOS 14.7 months). ✓ Pay attention to hematologic toxicity, in particular 53% of G3-4 anemia and 33% of G3-4 neutropenia. High rate of dose interruption and reduction. ✓ Phase III study is ongoing. I hope the study will be sufficiently powered to address the remaining open questions: patient selection and the optimal dose of Temab-A+Bev. Though the added benefit of Bev will remain unknown. Lisa Salvatore, MD, PhD

[Slide 1] COMPANION-002: Phase 3 U.S. Biliary Tract Cancer (BTC) Study KEY ELIGIBILITY Advanced, metastatic or unresectable BTC One prior gemcitabine/platinum containing regimen for advanced disease ≥1 measurable lesion by RECIST v1.1 ECOG PS 0-1 Excluded known actionable mutations if available targeted therapy for second-line R (2:1) N=168 28-day cycles Tovecimig (10 mg/kg) Days 1 & 8 + Paclitaxel (80 mg/m2) Days 1, 8 & 15 N= 111 → Follow-up Q 3 months 28-day cycles Paclitaxel (80 mg/m2) Days 1, 8 & 15 N=57 → Crossover permitted upon BICR confirmed PD → 28-day cycles Tovecimig (10 mg/kg) Days 1 & 8 + Paclitaxel (80 mg/m2) Days 1, 8 & 15 N=31; Follow-up Q 3 months STRATIFICATION FACTORS • Tumor Location - Intrahepatic vs others (extrahepatic, gallbladder or ampullary) • ECOG PS (0 vs 1) • Disease Status - Locally advanced vs metastatic PRIMARY OBJECTIVE • Objective Response Rate (ORR) by blinded independent central review (BICR) SECONDARY OBJECTIVES • Progression free survival (PFS) per BICR • Disease control rate (DCR) • Overall survival (OS) • Duration of response (DoR) • Progression free survival 2 (PFS2) • Safety profile • Quality of Life (EORTC QLQ-C30 and BIL21) Nilofer Azad, MD [Slide 2] COMPANION-002: Tovecimig + Paclitaxel Significantly Improves ORR and DCR Tovecimig + paclitaxel responses were durable: median DoR 4.9 months n (%) | Tovecimig + Paclitaxel (n=111) | Paclitaxel (n=57) ORR (CR + PR) Yes | 20 (18.0) | 3 (5.3) p-value | 0.0228 BOR CR | 1 (0.9) | 0 PR | 19 (17.1) | 3 (5.3) SD | 49 (44.1) | 18 (31.6) Non-CR/non-PD* | 8 (7.2) | 2 (3.5) PD | 18 (16.2) | 25 (43.9) NE** | 16 (14.4) | 9 (15.8) DCR (CR + PR + SD) | 69 (62.2) | 21 (36.8) p-value | 0.0018 [Waterfall plot: Change from Baseline (%) by Patient; legend Tovecimig + Paclitaxel, Paclitaxel] *Non-CR / Non-PD: patients enrolled based on local radiology scan results but displayed no clearly definable target lesions as determined by independent central radiology. ** Not Evaluable: patients who did not receive a Week-8 scan; these patients are not evaluable for response only but will be evaluable for PFS/OS analyses. Nilofer Azad, MD [Slide 3] COMPANION-002: Tovecimig + Paclitaxel Significantly Improves PFS (BICR) Legend: + Censored; Tovecimig + Paclitaxel; Paclitaxel Median PFS, months (95% CI) Tovecimig + Paclitaxel: 4.7 (3.9-5.6) Paclitaxel: 2.6 (1.9-3.6) HR, 0.44 (95% CI, 0.30-0.66) p < .0001 Time (months) Number at Risk (Censored) Tovecimig + Paclitaxel: 111(0) 73 (10) 30 (11) 11 (10) 8 (2) 5 (1) 3 (1) 2 (1) 1 (1) 1 (0) Paclitaxel: 57 (0) 25 (4) 9 (1) 4 (1) 2 (0) 2 (1) Nilofer Azad, MD Survival table Endpoint: PFS (BICR) Arm | N | Median | Median CI Tovecimig + Paclitaxel | 111 | 4.7 months | 3.9-5.6 Paclitaxel | 57 | 2.6 months | 1.9-3.6 HR: 0.44 HR CI: 0.30-0.66 P: <.0001 [Slide 4] COMPANION-002: OS Analysis Confounded by Crossover Paclitaxel alone survival curve includes 31 patients (54%) who crossed over and received tovecimig Legend: + Censored; Tovecimig + Paclitaxel; Paclitaxel Median OS, months (95% CI) Tovecimig + Paclitaxel: 8.9 (7.0-11.2) Paclitaxel: 9.4 (6.5-13.5) HR, 1.05 (95% CI, 0.7-1.5) p = .779 Time (months) Number at Risk (Censored) Tovecimig + Paclitaxel: 111 (0) 95 (2) 72 (1) 53 (0) 34 (1) 26 (0) 22 (1) 13 (6) 9 (3) 5 (4) 2 (4) Paclitaxel: 57 (0) 53 (1) 39 (2) 27 (0) 22 (0) 19 (0) 9 (2) 6 (3) 2 (2) 1 (1) Nilofer Azad, MD Survival table Endpoint: OS Arm | N | Median | Median CI Tovecimig + Paclitaxel | 111 | 8.9 months | 7.0-11.2 Paclitaxel | 57 | 9.4 months | 6.5-13.5 HR: 1.05 HR CI: 0.7-1.5 P: .779

Phase 2/3 COMPANION-002 Conclusions • Tovecimig + paclitaxel met the primary endpoint: ORR 18.0% vs 5.3% (p=0.0228), with durable responses (median DOR 4.9 months) • Disease control rate was also significantly improved: 62.2% vs 36.8% (p=0.0018) • PFS was significantly prolonged: 4.7 vs 2.6 months (HR=0.44, p<0.0001) • Overall survival may have been confounded by crossover, with 54% of paclitaxel patients receiving tovecimig • Addition of tovecimig to paclitaxel in cross-over setting doubled first line paclitaxel only PFS (3.9 vs 1.5 months, HR=0.40, p=0.0035) and those crossover patients survived for a median of 12.8 months. • Safety was manageable and consistent with prior studies and the anti-VEGF class, with no new safety signals • Overall, 28.8% of patients treated with tovecimig + paclitaxel discontinued the treatment regimen due to an adverse event; most TEAEs leading to discontinuation were consistent with known anti-angiogenic and chemotherapeutic toxicities. • Tovecimig + paclitaxel is a promising option for patients with BTC who have been previously treated Nilofer Azad, MD

In summary, this might be what we were looking for Question | My take | My Comments Is this study promising? | YES | • Promising MoA and targets • Low bar in the second line setting Did it meet its primary endpoint? | YES | • ORR 18% vs 5.3% (p=0.0228) • Clear signs of clinical activity PFS HR 0.44 • We need to identify patients who benefit the most Will it change practice? | ? | • We would want a phase III trial with FOLFOX as control arm demonstrating a clear OS benefit • Given the high unmet need of these patients, a formal review by a relevant guideline committee is warranted Sebastián Mondaca, MD, MBA

Tovecimig: Next-generation Angiogenesis Disrupting Bispecific Antibody [Antibody schematic: VEGF-A and DLL4 binding arms; 2x2 target binding valency] Anti-VEGF-A MAb — VEGF/VEGF-R signaling — Disrupts tumor vessel formation (proven anti-angiogenic mechanism) Anti-DLL4 MAb — DLL4-Notch-1 signaling — Targets tumor DLL4 expression and alters perfusion in tumor vessels (novel angiogenesis target) • Dual blockade: VEGF-A – validated target for blockbuster oncology therapeutics (e.g.: Avastin®) DLL4 (Notch-1 ligand) – mediates resistance to anti-VEGF therapies • Bispecific anchors in tumor microenvironment (DLL4) to disrupt angiogenesis • Only DLL4 × VEGF bispecific to demonstrate monotherapy activity in patients with CRC and GC¹ • Preclinical combination activity and an encouraging early BTC response signal supported further development of tovecimig + paclitaxel in Phase 2; the same dose and schedule were subsequently carried forward into COMPANION-002. Nilofer Azad, MD ¹ Lee, J et al. 2021, October 7-10. Plenary Presentation AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics 2 Oh DY, et al. ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023. Abstract 54[illegible]

COMPANION-002: A Randomized Phase 2/3 Trial of Tovecimig Plus Paclitaxel versus Paclitaxel Alone as a Second-line Therapy in Patients with Advanced Biliary Tract Cancer COMPANION-002: randomized, open-label phase 2/3 trial (34 US sites) Advanced BTC progressed on 1L gemcitabine + platinum N = 168 → R 2:1 Tovecimig 10 mg/kg IV D1, D15 + paclitaxel 80 mg/m² D1, D8, D15, q28d (n = 111) Crossover after BICR-confirmed PD: 31/57 (54%) Paclitaxel alone 80 mg/m² D1, D8, D15, q28d (n = 57) Primary endpoint: ORR by BICR (RECIST v1.1) • Key secondary endpoints: PFS, OS, DCR Objective response rate (primary) P = .0228: 18.0% | 5.3% Disease control rate P = .0018: 62.2% | 36.8% Progression-free survival (BICR): Median 4.7 vs 2.6 mo; HR 0.44 (95% CI 0.30–0.66); P < .0001 No. at risk: 111 30 8 3 1 | 57 9 2 Months since randomization Target lesion response [waterfall; 204%; +20% (PD); −30% (PR)]; Individual patients (T+P, n = 88; P, n = 47) Tovecimig + paclitaxel (T+P) | Paclitaxel alone (P) Relevance: The combination of tovecimig, a novel bispecific antibody targeting DLL4/VEGFA, and taxane chemotherapy demonstrated interesting activity in previously treated biliary cancers. Development continues in treatment-naiive biliary cancer.* Relevance statement written by JCO Associate Editor Eileen M. O'Reilly, MD, FASCO. Fig. Design and key efficacy outcomes of COMPANION-002 (NCT05506943), a randomized, open-label phase 2/3 trial. Patients with advanced BTC that progressed on one prior gemcitabine/platinum-based regimen were randomized 2:1 to tovecimig plus paclitaxel (n = 111) or paclitaxel alone (n = 57); crossover was permitted after BICR-confirmed progression. ORR, DCR, and PFS were assessed by BICR per RECIST v1.1 in the ITT population; P values are two-sided. Waterfall plot shows maximum percentage change from baseline in target lesion size (evaluable patients); dashed lines indicate RECIST v1.1 thresholds for PR (−30%) and PD (+20%). 1L, first-line; BICR, blinded independent central review; BTC, biliary tract cancer; D, day; DCR, disease control rate; HR, hazard ratio; ITT, intent-to-treat; ORR, objective response rate; OS, overall survival; PD, progressive disease; PR, partial response; PFS, progression-free survival; q28d, every 28 days; R, randomization. Azad et al. (2026) | Journal of Clinical Oncology | DOI: 10.1200/JCO-26-02188 Journal of Clinical Oncology An American Society of Clinical Oncology Journal

[Slide 1] OS in the ITT population Compared with chemotherapy alone, anbenitamab plus chemotherapy significantly reduced the risk of death by 61% | | Anbenitamab group | Control group | Median OS, mo, 95%CI | 19.6 (16.8,23.4) | 9.6 (7.7,13.7) HR (95% CI) 0.39 (0.28, 0.54) P value 3.97*10^[illegible exponent] [KM curves with landmark labels: Anbenitamab group 67.3% (15 mo), 56.2% (18 mo), 37.0% (24 mo); Control group 56.9% (15 mo), 25.8% (18 mo), 14.0% (24 mo)] Number at risk (events) at 0 / 3 / 6 / 9 / 12 / 15 / 18 / 21 / 24 / 27 / 30 / 33 / 36 / 39 / 42 months Anbenitamab group 125 (0) / 122 (1) / 114 (3) / 101 (3) / 82 (13) / 63 (24) / 48 (29) / 32 (38) / 19 (45) / 15 (47) / 7 (52) / 4 (55) / 2 (57) / 2 (57) / 0 (59) Control group 121 (0) / 108 (0) / 83 (1) / 63 (2) / 45 (10) / 32 (14) / 21 (17) / 13 (20) / 6 (24) / 4 (26) / 3 (27) / 3 (27) / 1 (29) / 0 (30) Ruixing Zhang Survival table Endpoint: Overall survival, ITT population Arm | N | Median | Median CI Anbenitamab + chemotherapy | 125 | 19.6 mo | 16.8-23.4 Placebo + chemotherapy (control) | 121 | 9.6 mo | 7.7-13.7 HR: 0.39 HR CI: 0.28-0.54 P: 3.97*10^[illegible exponent] Landmark rates: 15 months: Anbenitamab 67.3% | Control 56.9% 18 months: Anbenitamab 56.2% | Control 25.8% 24 months: Anbenitamab 37.0% | Control 14.0% [Slide 2] Study design KC-WISE is a multicenter, randomized, double-blind, phase 3 study conducted at 51 sites in China (NCT05427383). Study Population • Centrally confirmed HER2 positive GC/GEJC • Progressed on previous therapy containing trastuzumab • ECOG PS of 0 or 1 R 1:1 → Anbenitamab 30 mg/kg Q3W and chemotherapy* → Placebo and chemotherapy* Primary endpoints: ➢ IRC assessed PFS ➢ OS [boxed] Secondary endpoints: ➢ IRC and investigator assessed ORR, DoR, DCR, investigator assessed PFS, and safety Stratification factors: − Chemotherapy type (taxanes [paclitaxel and docetaxel] or irinotecan) − HER2 expression (IHC 3+ or IHC2+/FISH+) − Previous lines of therapy (1 or ≥2) The second interim analysis was planned when approximate 150 OS events were observed. DCR, disease control rate; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; GC/GEJC, gastric cancer or gastroesophageal junction carcinoma; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; IRC, independent review committee; ORR, objective response, rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks. Ruixing Zhang [Slide 3] IRC and investigator-assessed ORR, DoR and PFS | | Anbenitamab (n=125) IRC-assessed | Anbenitamab Investigator-assessed | Control (n=121) IRC-assessed | Control Investigator-assessed | Best overall response, n (%) Complete response | 0 | 1 (0.8) | 1 (0.8) | 0 Partial response | 70 (56.0) | 65 (52.0) | 16 (13.2) | 22 (18.2) Stable disease | 19 (15.2) | 27 (21.6) | 29 (24.0) | 26 (21.5) Non-CR/Non-PD | 14 (11.2) | 14 (11.2) | 8 (6.6) | 8 (6.6) Progressive disease | 19 (15.2) | 14 (11.2) | 56 (46.3) | 53 (43.8) Not evaluable | 3 (2.4) | 4 (3.2) | 11 (9.1) | 12 (9.9) Objective response rate, %, 95% CI | 56.0 (46.8-64.9) | 52.8 (43.7-61.8) | 14.0 (8.4-21.5) | 18.2 (11.8-26.2) Disease control rate, %, 95% CI | 82.4 (74.6-88.6) | 85.6 (78.2-91.2) | 44.6 (35.6-53.9) | 46.3 (37.2-55.6) Median DoR, mo, 95% CI | 7.9 (5.6-9.7) | 8.6 (6.2-10.6) | 3.6 (2.7-7.8) | 3.4 (2.8-7.7) Median PFS, mo, 95% CI | 7.1 (5.4-9.0) | 8.8 (6.9-10.3) | 2.7 (1.5-3.0) | 2.8 (2.5-3.0) At cutoff date of July 15, 2026, the median follow-up duration was 22.8 months (95% CI, 18.9 to 24.4) in the anbenitamab group and 22.3 months (95% CI, 18.6 to 24.6) in the control group. BOR, best overall response; CI, confidence interval; CR, complete response; DoR, duration of response; IRC, independent review committee; PD, progressive disease. Ruixing Zhang

Subsequent anti-tumor therapy | Anbenitamab(n=125) | Control(n=121) Subsequent therapy | 75 (60.0) | 78 (64.5) Anti-tumor agents | 71 (56.8) | 76 (62.8) Immunotherapy | 30 (24.0) | 28 (23.1) HER2 targeted therapy | 50 (40.0) | 56 (46.3) Radiotherapy | 7 (5.6) | 3 (2.5) Surgery | 3 (2.4) | 3 (2.5) Other therapies | 4 (3.2) | 4 (3.3) Ruixing Zhang

[Slide 2] Anbenitamab (KN026) is a HER2-targeted bispecific antibody with superior binding affinity, inhibitory potency, and HER2 internalization relative to trastuzumab or pertuzumab17; it has recently been approved by the National Medical Products Administration (China) for the second- and later-line treatment of HER2-positive advanced gastric cancer on the basis of the KC-WISE trial.18 HB1801 is an albumin-bound docetaxel. Previous clinical studies showed that HB1801 had improved antitumor activity in advanced gastric cancer.19 [Slide 3] FIGURE 2 A Progression-free Survival as Assessed by Blinded Independent Central Review Anbenitamab plus HB1801 (58.5 at 24 months); THP (34.4 at 24 months) Hazard ratio for disease progression or death, 0.46 (95% CI, 0.37 to 0.56) P<0.001 Months since Randomization No. at Risk Anbenitamab plus HB1801: 445 430 407 345 324 217 173 113 86 38 7 0 THP: 440 410 368 274 232 144 110 75 50 28 5 0 B Subgroup Analysis of Progression-free Survival Subgroup | Anbenitamab plus HB1801 | THP (no. of patients with event/total no. of patients) | Hazard Ratio for Disease Progression or Death (95% CI) All patients | 149/445 | 252/440 | 0.46 (0.38 to 0.57) Age <65 yr | 135/389 | 218/362 | 0.45 (0.37 to 0.56) Age ≥65 yr | 14/56 | 34/78 | 0.47 (0.25 to 0.88) ECOG 0 | 71/251 | 130/236 | 0.38 (0.28 to 0.51) ECOG 1 | 78/194 | 120/202 | 0.59 (0.44 to 0.79) Previous neoadjuvant or adjuvant therapy Yes | 60/165 | 95/161 | 0.49 (0.36 to 0.68) No | 89/280 | 157/279 | 0.45 (0.35 to 0.58) Previous treatment with trastuzumab Yes | 30/81 | 56/91 | 0.47 (0.30 to 0.74) No | 119/364 | 196/349 | 0.46 (0.37 to 0.58) Previous treatment with pertuzumab Yes | 14/29 | 23/32 | 0.46 (0.23 to 0.90) No | 135/416 | 229/408 | 0.46 (0.38 to 0.58) Hormone-receptor status Positive | 95/244 | 150/243 | 0.48 (0.37 to 0.62) Negative | 54/201 | 102/197 | 0.44 (0.31 to 0.61) Visceral metastasis Yes | 114/316 | 190/316 | 0.47 (0.37 to 0.59) No | 35/129 | 62/124 | 0.46 (0.30 to 0.69) Liver metastasis Yes | 57/156 | 111/181 | 0.46 (0.33 to 0.63) No | 92/289 | 141/259 | 0.47 (0.36 to 0.62) Bone metastasis Yes | 85/206 | 119/193 | 0.55 (0.42 to 0.73) No | 64/239 | 133/247 | 0.38 (0.29 to 0.52) No. of distant metastatic sites 1 or 2 | 92/310 | 148/288 | 0.46 (0.36 to 0.60) ≥3 | 56/125 | 98/141 | 0.50 (0.36 to 0.70) HER2 status IHC score of 3+ | 108/374 | 207/385 | 0.43 (0.34 to 0.54) IHC score of 2+ and FISH-positive | 41/71 | 45/55 | 0.44 (0.29 to 0.69) Stage IV disease at initial diagnosis Yes | 85/253 | 139/246 | 0.48 (0.37 to 0.63) No | 64/192 | 113/194 | 0.45 (0.33 to 0.61) Anbenitamab plus HB1801 Better | THP Better Progression-free Survival, Overall and According to Subgroup Analyses (Intention-to-Treat Population). Survival table Endpoint: PFS by BICR (ITT) Anbenitamab plus HB1801 | 445 THP | 440 HR: 0.46 HR CI: 0.37 to 0.56 P: <0.001 Landmark rates: 24 months: Anbenitamab plus HB1801 58.5% | THP 34.4% [Slide 4] TABLE 3 Table 3. Summary of Adverse Events.* Anbenitamab plus HB1801 (N=444) All Grades | Grade ≥3 || THP (N=439) All Grades | Grade ≥3 number of patients (percent) Any adverse event | 444 (100) | 204 (45.9) | 434 (98.9) | 151 (34.4) Common adverse events† Anemia | 330 (74.3) | 21 (4.7) | 250 (56.9) | 15 (3.4) Diarrhea‡ | 236 (53.2) | 10 (2.3) | 176 (40.1) | 5 (1.1) Alopecia | 229 (51.6) | 0 | 172 (39.2) | 0 ALT level increased | 192 (43.2) | 6 (1.4) | 163 (37.1) | 6 (1.4) Leukopenia | 190 (42.8) | 43 (9.7) | 144 (32.8) | 24 (5.5) Neutropenia | 181 (40.8) | 58 (13.1) | 146 (33.3) | 37 (8.4) AST level increased | 175 (39.4) | 6 (1.4) | 158 (36.0) | 6 (1.4) Hypoalbuminemia | 167 (37.6) | 0 | 100 (22.8) | 1 (0.2) Weight loss | 155 (34.9) | 3 (0.7) | 106 (24.1) | 2 (0.5) Hypertriglyceridemia | 152 (34.2) | 14 (3.2) | 154 (35.1) | 12 (2.7) Peripheral edema | 128 (28.8) | 3 (0.7) | 64 (14.6) | 1 (0.2) Asthenia | 119 (26.8) | 4 (0.9) | 85 (19.4) | 2 (0.5) Weight gain | 114 (25.7) | 1 (0.2) | 83 (18.9) | 0 Hypokalemia | 113 (25.5) | 15 (3.4) | 61 (13.9) | 7 (1.6) Urinary tract infection | 103 (23.2) | 2 (0.5) | 85 (19.4) | 2 (0.5) Hyperchloesterolemia | 101 (22.7) | 0 | 122 (27.8) | 0 Nausea | 95 (21.4) | 1 (0.2) | 70 (15.9) | 0 * Listed are adverse events that occurred up to 30 days after the last administration of trial drugs or initiation of new antitumor treatment (whichever occurred first). The events are listed in descending order of frequency in the anbenitamab group. Safety analyses were performed in the safety population, which included all the patients who had undergone randomization and received at least one dose of a trial drug. The adverse events were coded according to the Medical Dictionary for Regulatory Activities, version 28.1, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. ALT denotes alanine aminotransferase, and AST aspartate aminotransferase. † Adverse events that occurred in at least 20% of the patients in either group are reported. ‡ Diarrhea led to dose reduction in five patients (1.1%) in the anbenitamab group and two patients (0.5%) in the THP group and to treatment interruption in two patients (0.5%) and one patient (0.2%), respectively. No patients discontinued treatment owing to diarrhea. Primary prophylaxis for diarrhea was administered to 7.2% of the patients in the anbenitamab group and to 8.0% of those in THP group. Summary of Adverse Events.

16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ OS in the ITT population Compared with chemotherapy alone, anbenitamab plus chemotherapy significantly reduced the risk of death by 61% Anbenitamab group | Control group Median OS, mo, 95%CI: 19.6 (16.8, 23.4) | 9.6 (7.7, 13.7) HR (95% CI): 0.39 (0.28, 0.54) P value: 3.97*10^[illegible] Curve labels - Anbenitamab group: 67.3%, 56.2%, 37.0%; Control group: 56.9%, 25.8%, 14.0% Y-axis: Overall survival (%); X-axis: Time (months) 0-42 Number at risk Anbenitamab group: 125 (0), 122 (1), 114 (3), 101 (3), 82 (13), 63 (24), 48 (29), 32 (38), 19 (45), 15 (47), 7 (52), 4 (55), 2 (57), 2 (57), 0 (59) Control group: 121 (0), 108 (0), 83 (1), 63 (2), 45 (10), 32 (14), 21 (17), 13 (20), 6 (24), 4 (26), 3 (27), 3 (27), 1 (29), 0 (30) Ruixing Zhang Ruixing Zhang Anbenitamab plus chemotherapy for previously treated HER2-positive gastric or gastroesophageal carcinomas (GC/GEJC): Updated overall survival (OS) analysis of KC-WISE ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: Overall survival (ITT) Arm | N | Median | Median CI Anbenitamab group (anbenitamab + chemotherapy) | 125 | 19.6 mo | 16.8, 23.4 Control group (chemotherapy) | 121 | 9.6 mo | 7.7, 13.7 HR: 0.39 HR CI: 0.28, 0.54 P: 3.97*10^[exponent illegible] Landmark rates: 15 mo (vertical line): Anbenitamab group 67.3% 18 mo (vertical line): Anbenitamab group 56.2% 24 mo (vertical line): Anbenitamab group 37.0%

[Slide 1] Confidential Phase 3 KEYNOTE-975 Study Design (NCT04210115) Key Eligibility Criteria • Histologically confirmed ESCC, GEJC, EAC • Tumor staging cTX N+ M0, cT2-T4a NX M0, or cTX N+M1, cervical or upper thoracic esophageal carcinoma with supraclavicular metastases only • Eligible for dCRT • Ineligible for curative surgery • Radiographically evaluable disease • ECOG PS 0-1 • Available tumor tissue R (1:1) N = 703 Pembrolizumab 200 mg Q3W (8 cycles) then 400 mg Q6W (5 cycles) + dCRT (RT + investigator choice of FOLFOX or FP) Placebo Q3W (8 cycles) then Q6W (5 cycles) + dCRT (RT + investigator choice of FOLFOX or FP) Treated until progression, unacceptable toxicity, or withdrawal Stratification • PD-L1 CPS (≥10 vs <10) • Radiation dose (50 Gy vs 60 Gy) • Geographic region and histology (SCC East Asia vs SCC ROW and adenocarcinoma regardless of origin) Endpoints • Primary: EFS and OS in PD-L1 CPS≥10, CPS≥1, all participants • Secondary: Safety and tolerability [Slide 2] Confidential EFS in Participants With PD-L1 CPS ≥10 Tumors | | Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 137 (66%) | 15.2 (11.2 - 19.4) | 0.97 (0.77 - 1.23) | | Placebo + dCRT | 147 (69%) | 14.7 (11.4 - 19.9) | P = 0.399a | Y-axis: Event-free survival (%); X-axis: Time, months 24-mo rate: 39% / 37% 48-mo rate: 30% / 27% No. at Risk Pembrolizumab + dCRT: 209 169 116 101 81 68 59 41 34 22 13 5 3 0 0 Placebo + dCRT: 214 176 127 101 86 63 52 39 33 24 15 11 3 0 0 Data cutoff: Jan 21, 2026. aDid not meet the pre-specified boundary for significance (P = 0.0193) Survival table Endpoint: EFS, PD-L1 CPS ≥10 Arm | N | Median | Median CI Pembrolizumab + dCRT | 209 | 15.2 | 11.2-19.4 Placebo + dCRT | 214 | 14.7 | 11.4-19.9 HR: 0.97 HR CI: 0.77-1.23 P: 0.399 Landmark rates: 24 mo: Pembrolizumab + dCRT 39% | Placebo + dCRT 37% 48 mo: Pembrolizumab + dCRT 30% | Placebo + dCRT 27% [Slide 3] Confidential OS in Participants With PD-L1 CPS ≥10 Tumors | | Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 111 (53%) | 32.2 (24.0 - 48.0) | 1.00 (0.77 - 1.30) | | Placebo + dCRT | 118 (55%) | 35.0 (25.2 - 50.1) | P = 0.500a | Y-axis: Overall survival (%); X-axis: Time, months 24-mo rate: 58% / 59% 48-mo rate: 43% / 44% No. at Risk Pembrolizumab + dCRT: 209 182 163 143 126 109 87 70 64 50 33 17 7 1 0 Placebo + dCRT: 214 196 171 149 135 109 95 75 64 55 41 23 11 2 0 Data cutoff: Jan 21, 2026. aNominal p-value as OS was not tested for statistical significance as did not meet the pre-specified boundary for significance in EFS in PD-L1 CPS ≥10. Survival table Endpoint: OS, PD-L1 CPS ≥10 Arm | N | Median | Median CI Pembrolizumab + dCRT | 209 | 32.2 | 24.0-48.0 Placebo + dCRT | 214 | 35.0 | 25.2-50.1 HR: 1.00 HR CI: 0.77-1.30 P: 0.500 (nominal) Landmark rates: 24 mo: Pembrolizumab + dCRT 58% | Placebo + dCRT 59% 48 mo: Pembrolizumab + dCRT 43% | Placebo + dCRT 44% [Slide 4] Confidential EFS and OS in Key Subgroups in all Participants EFS — Events/Patients, N | HR (95% CI) Overall 468/703 0.94 (0.78-1.12) Age Category: <65 years 210/300 0.95 (0.72-1.25); ≥65 years 258/403 0.94 (0.73-1.20) Sex: Male 349/508 1.00 (0.81-1.23); Female 119/195 0.81 (0.57-1.17) Race: Asian 172/289 1.04 (0.77-1.41); Non-Asian 289/402 0.88 (0.70-1.11) ECOG PS: 0 156/241 0.78 (0.57-1.07); 1 312/462 1.06 (0.85-1.32) Geographic Region and Histology: Adenocarcimona 73/96 0.67 (0.42-1.06); ESCC in East Asia 164/281 1.04 (0.77-1.42); ESCC in Rest of the World 231/326 0.93 (0.72-1.21) Chemotherapy Backbone: FP 216/350 1.11 (0.85-1.46); FOLFOX 252/353 0.81 (0.63-1.04) Radiation Dose: 50 Gy 397/583 0.97 (0.79-1.18); 60 Gy 68/116 0.80 (0.50-1.30) Histology: Adenocarcinoma 73/96 0.67 (0.42-1.06); Squamous Cell Carcinoma 395/607 0.98 (0.80-1.19) Current Disease Stage: II 122/213 0.98 (0.69-1.40); III 278/391 0.96 (0.76-1.22); IV 64/92 0.97 (0.59-1.58) Axis: 0.1 – 1 – 10; Favors pembrolizumab + dCRT ← → Favors placebo + dCRT OS — Events/Patients, N | HR (95% CI) Overall 385/703 0.99 (0.81-1.21) Age Category: <65 years 169/300 1.04 (0.77-1.41); ≥65 years 216/403 0.95 (0.73-1.24) Sex: Male 291/508 1.09 (0.86-1.37); Female 94/195 0.77 (0.51-1.16) Race: Asian 135/289 1.08 (0.77-1.51); Non-Asian 246/402 0.93 (0.72-1.19) ECOG PS: 0 126/241 0.74 (0.52-1.05); 1 259/462 1.15 (0.90-1.47) Geographic Region and Histology: Adenocarcimona 61/96 0.76 (0.46-1.25); ESCC in East Asia 129/281 1.11 (0.79-1.57); ESCC in Rest of the World 195/326 1.00 (0.75-1.33) Chemotherapy Backbone: FP 176/350 1.24 (0.92-1.66); FOLFOX 209/353 0.82 (0.63-1.08) Radiation Dose: 50 Gy 330/583 0.96 (0.78-1.20); 60 Gy 52/116 1.23 (0.71-2.13) Histology: Adenocarcinoma 61/96 0.76 (0.46-1.25); Squamous Cell Carcinoma 324/607 1.04 (0.83-1.29) Current Disease Stage: II 102/213 1.05 (0.71-1.55); III 230/391 1.01 (0.78-1.31); IV 50/92 1.00 (0.57-1.74) Axis: 0.1 – 1 – 10; Favors pembrolizumab + dCRT ← → Favors placebo + dCRT Data cutoff: Jan 21, 2026. Subgroups with fewer than 20 participants were not included in the forest plot.

Confidential EFS and OS in Participants With PD-L1 CPS ≥1 Tumors EFS Table: Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value Pembrolizumab + dCRT: 206 (64%) | 16.9 (12.8 - 19.5) | 0.92 (0.76 - 1.11) Placebo + dCRT: 229 (69%) | 14.7 (11.6 - 18.6) | P = 0.187a 24-mo rate: 40% / 39%; 48-mo rate: 32% / 28% No. at Risk (months 0,5,...,70): Pembro: 324 269 195 165 133 107 92 63 51 30 18 8 5 0 0 Placebo: 331 275 200 158 136 108 85 66 58 43 28 20 9 1 0 OS Table: Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value Pembrolizumab + dCRT: 172 (53%) | 33.2 (25.6 - 46.7) | 0.95 (0.77 - 1.17) Placebo + dCRT: 186 (56%) | 35.0 (25.3 - 43.6) | P = 0.324a 24-mo rate: 59% / 57%; 48-mo rate: 43% / 44% No. at Risk (months 0,5,...,70): Pembro: 324 287 259 232 204 174 137 110 94 72 47 27 12 2 0 Placebo: 331 301 267 226 205 172 145 119 103 88 70 43 18 3 0 Data cutoff: Jan 21, 2026. aNominal p-value as EFS and OS in PD-L1 CPS ≥1 was not tested for statistical significance. Survival table Endpoint: EFS and OS, PD-L1 CPS ≥1 (not formally tested) Arm | N | Median | Median CI EFS: Pembrolizumab + dCRT | 324 | 16.9 mo | 12.8-19.5 EFS: Placebo + dCRT | 331 | 14.7 mo | 11.6-18.6 OS: Pembrolizumab + dCRT | 324 | 33.2 mo | 25.6-46.7 OS: Placebo + dCRT | 331 | 35.0 mo | 25.3-43.6 HR: EFS 0.92; OS 0.95 HR CI: EFS 0.76-1.11; OS 0.77-1.17 P: EFS P = 0.187; OS P = 0.324 (nominal) Landmark rates: 24 mo: EFS Pembro 40% | EFS Placebo 39% | OS Pembro 59% | OS Placebo 57% 48 mo: EFS Pembro 32% | EFS Placebo 28% | OS Pembro 43% | OS Placebo 44%

[Slide 1] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH [Speaker video] Manish Shah Pembrolizumab or placebo plus concurrent definitive chemoradiotherapy in esophageal and gastroesophageal junction (GEJ) cancer: The phase 3 randomized KEYNOTE-975 study ALMERIA AUDITORIUM - HALL 9 Confidential EFS in Participants With PD-L1 CPS ≥10 Tumors | | Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 137 (66%) | 15.2 (11.2 - 19.4) | 0.97 (0.77 - 1.23) | | Placebo + dCRT | 147 (69%) | 14.7 (11.4 - 19.9) | P = 0.399a | Y-axis: Event-free survival (%); X-axis: Time, months 24-mo rate: 39% (pembrolizumab) / 37% (placebo) 48-mo rate: 30% (pembrolizumab) / 27% (placebo) No. at Risk (0,5,...,70 mo) Pembrolizumab + dCRT: 209 169 116 101 81 68 59 41 34 22 13 5 3 0 0 Placebo + dCRT: 214 176 127 101 86 63 52 39 33 24 15 11 3 0 0 Data cutoff: Jan 21, 2026. aDid not meet the pre-specified boundary for significance (P = 0.0183) Survival table Endpoint: EFS, PD-L1 CPS ≥10 Arm | N | Median | Median CI Pembrolizumab + dCRT | 209 | 15.2 | 11.2-19.4 Placebo + dCRT | 214 | 14.7 | 11.4-19.9 HR: 0.97 HR CI: 0.77-1.23 P: 0.399 Landmark rates: 24 mo: Pembrolizumab + dCRT 39% | Placebo + dCRT 37% 48 mo: Pembrolizumab + dCRT 30% | Placebo + dCRT 27% [Slide 2] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH [Speaker video] Manish Shah Pembrolizumab or placebo plus concurrent definitive chemoradiotherapy in esophageal and gastroesophageal junction (GEJ) cancer: The phase 3 randomized KEYNOTE-975 study ALMERIA AUDITORIUM - HALL 9 Confidential OS in Participants With PD-L1 CPS ≥10 Tumors | | Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 111 (53%) | 32.2 (24.0 - 48.0) | 1.00 (0.77 - 1.30) | | Placebo + dCRT | 118 (55%) | 35.0 (25.2 - 50.1) | P = 0.500a | Y-axis: Overall survival (%); X-axis: Time, months 24-mo rate: 58% (pembrolizumab) / 59% (placebo) 48-mo rate: 43% (pembrolizumab) / 44% (placebo) No. at Risk (0,5,...,70 mo) Pembrolizumab + dCRT: 209 182 163 143 126 109 87 70 64 50 33 17 7 1 0 Placebo + dCRT: 214 196 171 149 135 109 95 75 64 55 41 23 11 2 0 Data cutoff: Jan 21, 2026. aNominal p-value as OS was not tested for statistical significance as did not meet the pre-specified boundary for significance in EFS in PD-L1 CPS ≥10. Survival table Endpoint: OS, PD-L1 CPS ≥10 Arm | N | Median | Median CI Pembrolizumab + dCRT | 209 | 32.2 | 24.0-48.0 Placebo + dCRT | 214 | 35.0 | 25.2-50.1 HR: 1.00 HR CI: 0.77-1.30 P: 0.500 (nominal) Landmark rates: 24 mo: Pembrolizumab + dCRT 58% | Placebo + dCRT 59% 48 mo: Pembrolizumab + dCRT 43% | Placebo + dCRT 44% [Slide 3] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH [Speaker video] Manish Shah Pembrolizumab or placebo plus concurrent definitive chemoradiotherapy in esophageal and gastroesophageal junction (GEJ) cancer: The phase 3 randomized KEYNOTE-975 study ALMERIA AUDITORIUM - HALL 9 Confidential EFS and OS in Participants With PD-L1 CPS ≥1 Tumors EFS | | Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 206 (64%) | 16.9 (12.8 - 19.5) | 0.92 (0.76 - 1.11) | | Placebo + dCRT | 229 (69%) | 14.7 (11.6 - 18.6) | P = 0.187a | 24-mo rate: 40% / 39%; 48-mo rate: 32% / 26% No. at Risk: Pembrolizumab + dCRT 324 269 195 165 133 107 92 63 51 30 18 8 5 0 0 Placebo + dCRT 331 275 200 158 136 108 85 66 58 43 28 26 9 1 0 OS | | Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 172 (53%) | 33.2 (25.6 - 46.7) | 0.95 (0.77 - 1.17) | | Placebo + dCRT | 186 (56%) | 35.0 (25.3 - 43.6) | P = 0.324a | 24-mo rate: 59% / 57%; 48-mo rate: 43% / 44% No. at Risk: Pembrolizumab + dCRT 324 287 259 232 204 174 137 110 94 72 47 27 12 2 0 Placebo + dCRT 331 301 267 226 205 172 145 119 103 88 70 43 18 3 0 Data cutoff: Jan 21, 2026. aNominal p-value as EFS and OS in PD-L1 CPS ≥1 was not tested for statistical significance. Survival table Endpoint: EFS and OS, PD-L1 CPS ≥1 Arm | N | Median | Median CI Pembrolizumab + dCRT (EFS) | 324 | 16.9 | 12.8-19.5 Placebo + dCRT (EFS) | 331 | 14.7 | 11.6-18.6 Pembrolizumab + dCRT (OS) | 324 | 33.2 | 25.6-46.7 Placebo + dCRT (OS) | 331 | 35.0 | 25.3-43.6 HR: EFS 0.92; OS 0.95 HR CI: EFS 0.76-1.11; OS 0.77-1.17 P: EFS 0.187; OS 0.324 (nominal) Landmark rates: 24 mo: Pembrolizumab + dCRT (EFS) 40% | Placebo + dCRT (EFS) 39% | Pembrolizumab + dCRT (OS) 59% | Placebo + dCRT (OS) 57% 48 mo: Pembrolizumab + dCRT (EFS) 32% | Placebo + dCRT (EFS) 26% | Pembrolizumab + dCRT (OS) 43% | Placebo + dCRT (OS) 44% [Slide 4] 13:30 - 15:00 Proffered paper 1: Gastrointestinal tumour, upper digestive CHAIRS: FILIPPO PIETRANTONIO, ELIZABETH SMYTH [Speaker video] Manish Shah Pembrolizumab or placebo plus concurrent definitive chemoradiotherapy in esophageal and gastroesophageal junction (GEJ) cancer: The phase 3 randomized KEYNOTE-975 study ALMERIA AUDITORIUM - HALL 9 Confidential EFS and OS in all Participants EFS | | Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 224 (64%) | 16.8 (13.0 - 19.4) | 0.94 (0.78 - 1.12) | | Placebo + dCRT | 244 (69%) | 15.8 (12.1 - 19.3) | P = 0.239a | 24-mo rate: 40% / 40%; 48-mo rate: 31% / 28% No. at Risk: Pembrolizumab + dCRT 349 291 212 178 144 117 101 70 54 33 20 9 6 0 0 Placebo + dCRT 354 296 216 173 149 117 90 71 62 47 32 22 10 0 0 OS | | Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 188 (54%) | 32.5 (25.6 - 41.5) | 0.99 (0.81 - 1.21) | | Placebo + dCRT | 197 (56%) | 35.3 (26.3 - 43.6) | P = 0.445a | 24-mo rate: 58% / 58%; 48-mo rate: 42% / 44% No. at Risk: Pembrolizumab + dCRT 349 311 280 249 217 187 148 118 100 76 51 29 13 2 0 Placebo + dCRT 354 324 287 245 221 186 155 127 109 94 75 47 19 3 0 Data cutoff: Jan 21, 2026. aNominal p-value as EFS and OS in all participants was not tested for statistical significance. Survival table Endpoint: EFS and OS, all participants Arm | N | Median | Median CI Pembrolizumab + dCRT (EFS) | 349 | 16.8 | 13.0-19.4 Placebo + dCRT (EFS) | 354 | 15.8 | 12.1-19.3 Pembrolizumab + dCRT (OS) | 349 | 32.5 | 25.6-41.5 Placebo + dCRT (OS) | 354 | 35.3 | 26.3-43.6 HR: EFS 0.94; OS 0.99 HR CI: EFS 0.78-1.12; OS 0.81-1.21 P: EFS 0.239; OS 0.445 (nominal) Landmark rates: 24 mo: Pembrolizumab + dCRT (EFS) 40% | Placebo + dCRT (EFS) 40% | Pembrolizumab + dCRT (OS) 58% | Placebo + dCRT (OS) 58% 48 mo: Pembrolizumab + dCRT (EFS) 31% | Placebo + dCRT (EFS) 28% | Pembrolizumab + dCRT (OS) 42% | Placebo + dCRT (OS) 44%

Confidential EFS and OS in all Participants EFS | | Events n (%) | Median EFS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 224 (64%) | 16.8 (13.0 - 19.4) | 0.94 (0.78 - 1.12) | | Placebo + dCRT | 244 (69%) | 15.8 (12.1 - 19.3) | P = 0.239a | [KM curve: Event-free survival (%) vs Time, months 0-70] 24-mo rate: 40% / 40%; 48-mo rate: 31% / 28% (pembrolizumab / placebo) No. at Risk (months 0/5/10/.../70): Pembrolizumab + dCRT: 349 291 212 178 144 117 101 70 54 33 20 9 6 0 0 Placebo + dCRT: 354 296 216 173 149 117 90 71 62 47 32 22 10 0 0 OS | | Events n (%) | Median OS (95% CI), mo | HR (95% CI) P-value | | Pembrolizumab + dCRT | 188 (54%) | 32.5 (25.6 - 41.5) | 0.99 (0.81 - 1.21) | | Placebo + dCRT | 197 (56%) | 35.3 (26.3 - 43.6) | P = 0.445a | [KM curve: Overall survival (%) vs Time, months 0-70] 24-mo rate: 58% / 58%; 48-mo rate: 42% / 44% (pembrolizumab / placebo) No. at Risk (months 0/5/10/.../70): Pembrolizumab + dCRT: 349 311 280 249 217 187 148 118 100 76 51 29 13 2 0 Placebo + dCRT: 354 324 287 245 221 186 155 127 109 94 75 47 19 3 0 Data cutoff: Jan 21, 2026. aNominal p-value as EFS and OS in all participants was not tested for statistical significance. Survival table Endpoint: EFS and OS, all participants Arm | N | Median | Median CI Pembrolizumab + dCRT (EFS) | 349 | 16.8 mo | 13.0-19.4 Placebo + dCRT (EFS) | 354 | 15.8 mo | 12.1-19.3 Pembrolizumab + dCRT (OS) | 349 | 32.5 mo | 25.6-41.5 Placebo + dCRT (OS) | 354 | 35.3 mo | 26.3-43.6 HR: EFS 0.94; OS 0.99 HR CI: EFS 0.78-1.12; OS 0.81-1.21 P: EFS P=0.239 (nominal); OS P=0.445 (nominal) Landmark rates: 24 months EFS: Pembrolizumab + dCRT 40% | Placebo + dCRT 40% 48 months EFS: Pembrolizumab + dCRT 31% | Placebo + dCRT 28% 24 months OS: Pembrolizumab + dCRT 58% | Placebo + dCRT 58% 48 months OS: Pembrolizumab + dCRT 42% | Placebo + dCRT 44%

[Slide 1] LEAP-012 Study Design (NCT04246177) Key Eligibility Criteria • Confirmed HCC not amenable to curative treatment • ≥1 measurable HCC lesion per RECIST v1.1 • All lesions treatable with transarterial chemoembolization (TACE) in 1 or 2 sessions • No portal vein thrombosis or extrahepatic disease • Child-Pugh liver class A • ECOG PS of 0 or 1 R 1:1 Lenvatinib 12 mg (BW ≥60 kg) or 8 mg (BW <60 kg) PO QD + Pembrolizumab 400 mg IV Q6W (up to 2 years) + TACE^b Placebo PO QD + Placebo IV Q6W (up to 2 years) + TACE^b Stratification Factors • Study site • Alpha fetoprotein (≤400 ng/mL vs >400 ng/mL) • ECOG PS (0 vs 1) • ALBI grade (1 vs 2 or 3) • Tumor burden score^1,a (≤6 vs >6 but ≤12 vs >12) End Points • Primary: PFS^c and OS – IA1 was the final analysis for PFS – Initial alpha of 0.025 (1-sided) allocated to PFS; passed to OS if PFS is statistically significant • Secondary: ORR,^c,d DOR,^c,d DCR,^c,d TTP,^c,d PFS,^d and safety 1. Wang Q et al. J Hepatol. 2019;70:893-903. ^aLargest tumor in centimeters + number of tumors. ^b2-4 weeks after the start of systemic therapy with a maximum of 2 treatments per tumor (4 total) and no more than 1 treatment per month. ^cPer RECIST v1.1 by BICR. ^dPer mRECIST by BICR. [Slide 2] Objective Response Rate per RECIST v1.1 by BICR Δ14.9% (95% CI, 6.1-23.4)^a P = 0.0005 (nominal) 48.1% (41.6-54.7) 33.7% (27.8-40.1) CR / PR Lenvatinib + pembrolizumab + TACE: PR 44.3%, CR 3.8% Dual placebo + TACE: PR 28.8%, CR 4.9% Objective Response Rate, % | | Lenvatinib + pembrolizumab + TACE n = 237 | Dual placebo + TACE n = 243 | Best overall response, % (95% CI)^b,c Complete response | 3.8 (1.8-7.1) | 4.9 (2.6-8.5) Partial response | 44.3 (37.9-50.9) | 28.8 (23.2-34.9) Stable disease | 41.8 (35.4-48.3) | 47.3 (40.9-53.8) Progressive disease | 6.3 (3.6-10.2) | 15.2 (11.0-20.4) Duration of response, median (range), months | 14.3 (1.3+ to 58.0+) | 12.6 (2.0+ to 51.8+) Disease control rate | 89.9 (85.3-93.4) | 81.1 (75.6-85.8) ^aEstimated from stratified analysis. ^bParticipants with insufficient data for assessment of response: 2.1% in the lenvatinib + pembrolizumab + TACE group and 1.6% in the dual placebo + TACE group. ^cParticipants without postbaseline assessments: 1.7% in the lenvatinib + pembrolizumab + TACE group and 2.1% in the dual placebo + TACE group. Data cutoff date for IA3: August 19, 2025. [Slide 3] Progression-Free Survival per RECIST v1.1 by BICR and Overall Survival^a Progression-Free Survival, % / Months Lenvatinib + pembrolizumab + TACE | Events, n (%) 154 (65.0) | Median (95% CI), months 14.6 (12.6-16.7) Dual placebo + TACE | 162 (66.7) | 10.2 (8.1-12.3) HR, 0.70 (95% CI, 0.56-0.89) nominal P = 0.0018 24 mo: 23.9% / 18.9%; 36 mo: 19.1% / 12.4% Overall Survival, % / Months Lenvatinib + pembrolizumab + TACE | 126 (53.2) | 40.4 (34.4-47.0) Dual placebo + TACE | 127 (52.3) | 40.8 (35.2-45.8) HR, 0.98 (95% CI, 0.76-1.26) P^b = 0.4442 24 mo: 74.4% / 67.5%; 36 mo: 55.3% / 55.4% No. at risk ^aAt the data cutoff, 253 of 318 OS events required for the final analysis had occurred, corresponding to an OS data maturity of 80%. ^bOne-sided P from re-randomization test; threshold P = 0.0104. Data cutoff date for IA3: August 19, 2025. Survival table Endpoint: OS (IA3) Arm | N | Median | Median CI Lenvatinib + pembrolizumab + TACE | 237 | 40.4 | 34.4-47.0 Dual placebo + TACE | 243 | 40.8 | 35.2-45.8 HR: 0.98 HR CI: 0.76-1.26 P: 0.4442 (one-sided, re-randomization test; threshold 0.0104) 24 mo: 74.4% vs 67.5% 36 mo: 55.3% vs 55.4% [Slide 4] Most Common Treatment-Related Adverse Events^a (≥20%) Grade 1 or 2 / 3 or 4 Lenvatinib + pembrolizumab + TACE; Dual placebo + TACE n (%) | Lenvatinib + pembrolizumab + TACE n = 237 | Dual placebo + TACE n = 241 Treatment-related AEs^a | 234 (98.7) | 204 (84.6) Grade 3 or 4 | 167 (70.5) | 75 (31.1) Serious AEs | 81 (34.2) | 31 (12.9) Led to discontinuation of both drugs | 21 (8.9) | 4 (1.7) Led to death (grade 5) | 4 (1.7)^b | 2 (0.8)^c Incidence, % Hypertension, Proteinuria, ALT increased, AST increased, Hypothyroidism, Platelet count decreased, Blood bilirubin increased, Decreased appetite, PPE, Diarrhea, Weight decreased, Fatigue, Dysphonia, Post embolization syndrome ^aRelated to pembrolizumab, lenvatinib, and/or TACE. ^b1 participant each died from hepatic failure, gastrointestinal hemorrhage, myositis, and immune-mediated hepatitis. ^c1 participant each died from brain stem hemorrhage, and multiple organ dysfunction syndrome. Data cutoff date for IA3: August 19, 2025.

[Slide 2] TACE + Immunotherapy in Phase 3 trials: PFS PFS ENDPOINT WAS MET IN ALL PHASE 3 TRIALS EMERALD-11 LEAP-0122 TALENTACE3 EMERALD-34 PFS (months) EMERALD-1: 15.0 vs. 8.2 HR 0.77 LEAP-012: 14.6 vs. 10.2 HR 0.7 TALENTACE: 10.32 vs 6.37 HR 0.64 EMERALD-3: 13.0 vs 9.9, HR 0.7 / 12.9 vs 8.1, HR 0.71 Anna Saborowski 1. Sangro et al. Lancet 2025;405:216-32; 2. Josep Llovet, ESMO 2026, 1678RO; 3. Dong et al. Ann Oncol 2025;36(S1):S62;; 4. Abou-Alfa et al. J Clin Oncol 2026;44 (suppl 17):LBA4000. [Slide 3] TACE + Immunotherapy in Phase 3 trials: OS OS ENDPOINT WAS NOT MET IN ALL PHASE 3 TRIALS EMERALD-11 LEAP-0122 TALENTACE3 EMERALD-34 OS (months) EMERALD-1: 29.9 vs. 33.6 vs. 33.3 HR 1.1 LEAP-012: 40.4 vs. 40.8 HR 0.98 TALENTACE: 34.53 vs 35.38 HR 0.96 (early data) EMERALD-3: 39.5.0 vs 34.7, HR 0.84 / NC vs 32.9, HR 0.7 [illegible] Anna Saborowski 1. Bruno Sangro, ESMO GI 2026; 2. Josep Llovet, ESMO 2026, 1678RO; 3. Dong et al. Ann Oncol 2025;36(S1):S62;; 4. Abou-Alfa et al. J Clin Oncol 2026;44 (suppl 17):LBA4000.

Objective Response Rate per mRECIST1 by BICR Δ21.5% (95% CI, 12.7-30.0)a P < 0.0001 (nominal) 71.3% (65.1-77.0) 49.4% (42.9-55.8) CR PR 16.0% / 55.3% (Lenvatinib + pembrolizumab + TACE) 14.8% / 34.6% (Dual placebo + TACE) Lenvatinib + pembrolizumab + TACE n = 237 | Dual placebo + TACE n = 243 Best overall response, % (95% CI)b,c Complete response 55.3 (48.7-61.7) | 34.6 (28.6-40.9) Partial response 16.0 (11.6-21.3) | 14.8 (10.6-19.9) Stable disease 19.0 (14.2-24.6) | 32.5 (26.7-38.8) Progressive disease 3.0 (1.2-6.0) | 12.3 (8.5-17.2) Duration of response, median (range), months 14.5 (1.0+ to 58.0+) | 12.5 (2.1+ to 58.0+) Disease control rate 90.3 (85.8-93.7) | 81.9 (76.5-86.5) 1. Lencioni R, Llovet JM. Semin Liver Dis. 2010;30:52-60. aEstimated from stratified analysis. bParticipants with insufficient data for assessment of response: 5.1% in the lenvatinib + pembrolizumab + TACE group and 3.7% in the dual placebo + TACE group. cParticipants without postbaseline assessments: 1.7% in the lenvatinib + pembrolizumab + TACE group and 2.1% in the dual placebo + TACE group. Data cutoff date for IA3: August 19, 2025.

Conclusions • LEAP-012 met its primary end point of PFS but did not show OS benefit at IA3 • A median OS of approximately 40 months sets a new benchmark for trial design in unresectable, nonmetastatic HCC • The safety profile of lenvatinib plus pembrolizumab remains consistent with previous reports and earlier analysis of LEAP-012

[Slide 1] Study design Academic proof-of-concept single arm phase II trial, NCT06578559 Key Clinical Eligibility Criteria • ≥18 years of age • ECOG PS ≤ 1 • BRAF-V600E mutant mCRC treated with previous EC (± chemo), with at least PR or SD and PFS ≥ 6 months • One intervening EC-free line of therapy • At least 4 months between the end of EC and retreatment ctDNA analysis* Molecular Eligibility Criteria • BRAF-V600E mutant • RAS wild-type • MAP2K1 wild-type • MET not amplified → Encorafenib + cetuximab re-treatment Primary endpoint: ORR Key Secondary Endpoints: DCR, PFS, OS, safety Fleming single stage design: p0 for ORR = 0.05; p1 for ORR= 0.25; alpha error = 0.05 (two-sided); beta error = 0.20 Target accrual: 16 patients; p0 rejected if ≥ 3 objective responses observed *GUARDANT360 CDx, Guardant Health ECOG PS, Eastern Cooperative Oncology Group Performance Status, mCRC, metastatic colorectal cancer; p0, null hypothesis; p1: alternative hypothesis; PR, partial response; SD, stable disease; ctDNA, circulating tumor DNA; PFS, progression-free survival; ORR, objective response rate; DCR, disease control rate; OS, overall survival Marco Maria Germani, MD [Slide 2] Results, study screening Genomic profile of the 13 molecularly ineligible patients [Oncoprint: MSI status; screening genes BRAF 93%, KRAS 31%, NRAS 7%, MET 7%, MAP2K1 0%] Alteration type: Missense / other SNV; Frameshift indel; Nonsense; Splice-site; Amplification; Wild-type / VUS Microsatellite status: MSI-H; MSS VAF (%) - SNV/indel, log10 (0.05–50); Est. copy number - AMP (2.0–2.8) 2 BRAF-V600E wild-type 7 KRAS mut + 1 KRAS ampl 1 NRAS mut 1 NRAS mut + KRAS mut 1 MET ampl 1 MET ampl + NRAS mut Amp, amplification; mut: mutation; Est, estimated; MSI-H: microsatellite high; MSS, microsatellite stable; mut, mutation; VAF: variant allele fraction; VUS: variance of unknown significance Marco Maria Germani, MD [Slide 3] Results, objective response rate ORR: 0/16 (0%) 95% CI: 0 – 20.6% DCR: 6/16 (37.5%) 95% CI: 15.2 – 64.6% [Waterfall plot of best change in target lesions; legend: Disease Progression / Stable Disease; reference lines +20% and -30%] Two patients were not radiologically assessed for objective response because clinically deteriorated and died before scheduled radiological assessment. Both patients were computed as non-responders. * PD due to non-target lesion progression. ** PD due to occurrence of new lesions CI, confidence interval; DCR, disease control rate; ORR, objective response rate; PD, disease progression Marco Maria Germani, MD

[Slide 1] How do we understand the differences in trial outcomes? 1. Patient selection – in Tridente, only patients with prior CR/PR were included 2. Regimen – could the addition of binimetinib push patients to respond? But actually the clinically important survival interval is very similar between the two studies: mPFS: 2.8 months in TRIDENTE, 2.9 months in BRICKET Rona Yaeger, MD [Slide 2] Rechallenge Trials: TRIDENTE and BRICKET Design TRIDENTE: study design RAS wild-type/BRAF V600E-mutant mCRC -> EC-based therapy -> PD -> ≥1 of SoC -> PD -> ENCO + BINI + CET (N =21) • Encorafenib 300 mg QD • Binimetinib 45 mg BID • Cetuximab initially 400 mg/m2 and subsequently 250 mg/m2 QW Primary endpoint: ORR • CR or PR by RECIST v1.1 • PD within 4 weeks after the last ENCO administration ≥ 4 months Key eligibility criteria • ≥ 20 years of age • ECOG PS 0-1 • Refractory or intolerant to fluoropyrimidine-based chemotherapy including oxaliplatin or irinotecan • Measurable disease per RECIST v1.1 BRICKET: study design RAS wild-type/BRAF V600E-mutant mCRC -> EC-based therapy -> PD -> 1 of SoC (EC free) -> PD -> Molecular Eligibility Criteria -> ENCO + CET (N =16) Molecular Eligibility Criteria • BRAF-V600E mutant • RAS wild-type • MAP2K1 wild-type • MET not amplified • Encorafenib 300 mg QD • Cetuximab initially 400 mg/m2 and subsequently 250 mg/m2 QW Primary endpoint: ORR • PR or SD by RECIST v1.1 • PFS ≥ 6 months ≥ 4 months Key eligibility criteria • ≥ 18 years of age • ECOG PS 0-1 • Measurable disease per RECIST v1.1 Rona Yaeger, MD

[Slide 2] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Results, Survival outcomes Progression-free survival n | Events | Median PFS (mos) | 95% CI 16 | 16 | 2.94 | 2.01 – 3.39 PFS probability ; Months 0-8 Number at risk (number censored): 16 (0) | 13 (0) | 3 (0) | 2 (0) | 0 (0) Overall survival n | Events | Median OS (mos) | 95% CI 16 | 11 | 9.11 | 4.01 – 13.0 OS probability ; Months 0-14 Number at risk (number censored): 16 (0) | 14 (0) | 12 (1) | 8 (2) | 6 (3) | 4 (3) | 3 (4) | 1 (4) CI, confidence interval; mos, months; n, number; PFS, progression free survival; OS, overall survival Marco Maria Germani, MD [Speaker panel] Marco Maria Germani — Circulating tumor DNA (ctDNA)-guided re-treatment (re-tx) with encorafenib and cetuximab (EC) in patients (pts) with chemorefractory BRAFV600E mutated metastatic colorectal cancer (mCRC): The proof-of-concept single arm phase II BRICKET trial by GONO ALICANTE AUDITORIUM - HALL 6 Survival table Endpoint: PFS and OS (single arm) Arm | N | Median | Median CI Encorafenib + cetuximab re-treatment — PFS | 16 | 2.94 mo | 2.01 – 3.39 Encorafenib + cetuximab re-treatment — OS | 16 | 9.11 mo | 4.01 – 13.0 [Slide 3] 14:45 - 16:15 Rapid oral: Gastrointestinal tumours, lower digestive CHAIRS: LISA SALVATORE, KAI-KEEN SHIU, RONA YAEGER Results, objective response rate ORR: 0/16 (0%) 95% CI: 0 – 20.6% DCR: 6/16 (37.5%) 95% CI: 15.2 – 64.6% Legend: Disease Progression; Stable Disease Waterfall reference lines: +20%, -30% Two patients were not radiologically assessed for objective response because clinically deteriorated and died before scheduled radiological assessment. Both patients were computed as non-responders. * PD due to non-target lesion progression ** PD due to occurrence of new lesions CI, confidence interval; DCR, disease control rate; ORR, objective response rate; PD, disease progression Marco Maria Germani, MD [Speaker panel] Marco Maria Germani — Circulating tumor DNA (ctDNA)-guided re-treatment (re-tx) with encorafenib and cetuximab (EC) in patients (pts) with chemorefractory BRAFV600E mutated metastatic colorectal cancer (mCRC): The proof-of-concept single arm phase II BRICKET trial by GONO ALICANTE AUDITORIUM - HALL 6

[Slide 3] Results, Survival outcomes Progression-free survival n | Events | Median PFS (mos) | 95% CI 16 | 16 | 2.94 | 2.01 – 3.39 Number at risk (number censored): 16 (0) [0 mo], 13 (0) [2], 3 (0) [4], 2 (0) [6], 0 (0) [8] Overall survival n | Events | Median OS (mos) | 95% CI 16 | 11 | 9.11 | 4.01 – 13.0 Number at risk (number censored): 16 (0) [0], 14 (0) [2], 12 (1) [4], 8 (2) [6], 6 (3) [8], 4 (3) [10], 3 (4) [12], 1 (4) [14] CI, confidence interval; mos; months; n, number; PFS, progression-free survival; OS, overall survival Marco Maria Germani, MD Survival table Endpoint: PFS and OS (single arm, encorafenib + cetuximab re-treatment) Arm | N | Median | Median CI EC re-treatment (PFS) | 16 | 2.94 mos | 2.01 – 3.39 EC re-treatment (OS) | 16 | 9.11 mos | 4.01 – 13.0 [Slide 4] Results, treatments and survival since LB in eligible and not eligibile patients Eligible, n=16 — Lines post-LB — [swimmer plot] — 6/16 treated after PD to EC (37.5%) Not eligible, n=13 — Lines post-LB — [swimmer plot] — 10/13 treated after LB (76.9%) Time since LB (months) No OS difference since LB detected between eligible and not eligible patients Cohort | Events/Pop | Survival after LB (mos, 95% CI) | 95% CI | HR | 95% CI | p value Not eligible | 9/13 | 5.1 | 2.9 – 12.7 | Ref. | – | Eligible | 11/16 | 9.7 | 4.7 – 13.6 | 0.90 | 0.36 – 2.29 | 0.832 OS probability after liquid biopsy / Months 0-14 Number at risk (number censored) Not eligible: 13 (0), 9 (3), 7 (3), 4 (3), 4 (3), 4 (3), 3 (3), 2 (3) Eligible: 16 (0), 14 (0), 13 (0), 10 (1), 7 (2), 5 (3), 3 (3), 1 (4) CI, confidence interval; FTD/TPI: trifluridine-tipiracil; LB: liquid biopsy; mos; months; n, number; NE: not evaluable; OS, overall survival; PD: progressive disease; SD: stable disease Marco Maria Germani, MD Survival table Endpoint: OS since liquid biopsy (eligible vs not eligible) Arm | N | Median | Median CI Not eligible | 13 | 5.1 mos | 2.9 – 12.7 Eligible | 16 | 9.7 mos | 4.7 – 13.6 HR: 0.90 HR CI: 0.36 – 2.29 P: 0.832

[Slide 1] Study design and Baseline Characteristics An open-label, prospective phase II trial (NCT06587061, NCT07131514). Key eligibility criteria: KRAS G12D mutation; Resectable/ Borderline resectable PDAC; No prior treatment Neoadjuvant (~4 cycles) | Adjuvant (~4 cycles) Cohort 1 N=30 -> HRS-4642+GnP -> Surgery -> HRS-4642+GnP same regimen as neoadjuvant Cohort 2 N=30 -> HRS-4642+Adebrelimab+GnP -> Surgery -> HRS-4642+Adebrelimab+GnP same regimen as neoadjuvant All drugs IV, q3w; A total of 8 cycles of neoadjuvant and adjuvant treatment Primary endpoints: ORR per RECIST v1.1 and safety. Secondary endpoints: R0 resection rate, MPR (CAP Score 0-1) rate, EFS, OS, and exploratory biomarkers. ECOG, Eastern Cooperative Oncology Group; RECIST, Response Evaluation Criteria in Solid Tumors; ORR, objective response rate; MPR, major pathological response; EFS, event-free survival; OS, overall survival. Baseline Characteristics | Cohort 1 (N=30) | Cohort 2 (N=30) Age, median (range) | 64 (47-73) | 64 (39-75) Male, n (%) | 21 (70) | 18 (60) ECOG PS-1, n (%) | 30 (100) | 30 (100) Location, n (%) Head | 12 (40) | 18 (60) Others | 18 (60) | 12 (40) Clinical stage, n I / II / III | 1 / 20 / 9 | 0 / 18 / 12 CA 19-9, n (%) >2xULN | 24 (80) | 23 (77) Data cutoff: Sep 3, 2026. 30 patients were enrolled per cohort; all received neoadjuvant therapy and ≥1 post-treatment assessment. Dr. Chenlei Wen [Slide 2] Tumor Response and Survival ORR: Cohort 1, 63% (19/30); Cohort 2, 87% (26/30). Tumor shrinkage was observed in all patients. Median TTR: Cohort 1, 51 days (range, 42-128); Cohort 2, 49 days (range, 39-97). 6-month EFS: Cohort 1, 87%; Cohort 2, 96%. Survival data remain immature. [Waterfall plot] Best change from baseline (%) — Cohort1 / Cohort2 [Spider plot] Change from baseline in target lesion (%) — Cohort 1 / Cohort 2; Baseline, Week 6, Week 12 ORR, objective response rate; TTR, time to response; EFS, event-free survival. Dr. Chenlei Wen [Slide 3] Surgery and Biochemical Outcomes | Cohort 1 (N=30) | Cohort 2 (N=30) Surgery, n (%) Completed surgery | 23 (77) | 29 (97) - R0 resection | 23/23 (100) | 29/29 (100) Incomplete surgery | 7 (23) | 1(3) - Still receiving neoadjuvant | 4 (13) | 0 - Awaiting surgery | 2 (7) | 0 - Declined surgery | 1 (3) | 1 (3) Pathologic response, n/N (%) pCR | 0 | 1/29 (3) MPR a | 4/23 (17) | 5/29 (17) CA19-9 response b, n/N(%) | 27/27 (100) | 26/26 (100) a MPR, major pathological response, defined as CAP tumor regression score 0-1. b CA19-9 response was assessed in patients with baseline CA19-9 level above the upper limit of normal. pCR, pathological complete response. [Line chart] Change in CA19-9 (%) — Cohort 1 / Cohort 2; Baseline, C2D1, C3D1, C4D1 Dr. Chenlei Wen [Slide 4] Conclusions HRS-4642 plus GnP ± adebrelimab showed a manageable safety profile: • The most common TRAEs were hematologic toxicities; • Perioperative safety was tolerable. Promising neoadjuvant activity and surgery outcomes in resectable/borderline resectable KRAS G12D-mutant PDAC: • Cohort 1: ORR 63%; R0 resection 100%; MPR 17%; • Cohort 2: ORR 87%; R0 resection 100%; MPR 17%; • Survival data were immature in both cohorts. Follow-up is ongoing for long-term efficacy and safety data. Acknowledgements: We are grateful to the patients, their families, and the investigators for their participation. This trial was supported by Ruijin Hospital. Dr. Chenlei Wen

Perioperative Safety TRAEs were generally manageable. The most common TRAEs were hematologic toxicities. No fatal TRAEs or TRAEs precluding surgery occurred. | Cohort 1 (N=30) | Cohort 2 (N=30) Any TRAE, n (%) | 30 (100) | 30 (100) Grade ≥ 3 | 14 (47) | 16 (53) Leading to dose reduction | 2 (7) | 1 (3) Leading to dose discontinuation | 0 | 1 (3) Serious | 0 | 1 (3) Leading to death | 0 | 0 Precluding surgery | 0 | 0 TRAEs occurring in ≥ 20% of patients in either cohort, n (%) | Cohort 1 Any Grade | Cohort 1 Grade ≥3 | Cohort 2 Any Grade | Cohort 2 Grade ≥3 Leukopenia | 24 (80) | 4 (13) | 19 (63) | 5 (17) Neutropenia | 24 (80) | 12 (40) | 21 (70) | 13 (43) Thrombocytopenia | 28 (93) | 3 (10) | 18 (60) | 1 (3) Anemia | 20 (67) | 0 | 29 (97) | 1 (3) LDH increased | 19 (63) | 0 | 25 (83) | 0 ALP increased | 18 (60) | 0 | 23 (77) | 0 ALT increased | 15 (50) | 0 | 18 (60) | 0 γ-GGT increased | 13 (43) | 0 | 18 (60) | 0 Hypercholesterolemia | 13 (43) | 0 | 18 (60) | 0 Uric acid increased | 11 (37) | 0 | 9 (30) | 0 AST increased | 10 (33) | 0 | 17 (57) | 0 Hypertriglyceridemia | 7 (23) | 1 (3) | 17 (57) | 0 LDL increased | 7 (23) | 0 | 8 (27) | 0 Hypoalbuminemia | 3 (10) | 0 | 9 (30) | 0 Hyperglycemia | 3 (10) | 0 | 9 (30) | 0 Rash | 2 (7) | 0 | 6 (20) | 0 TRAE, treatment-related adverse events; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; AST, aspartate aminotransferase; LDL, low-density lipoprotein. Dr. Chenlei Wen

[Slide 1] 3157P - HRS-4642 with dual immunotherapy and chemotherapy for advanced pancreatic cancer: Preliminary results from Arm 1 of a phase II study Wen-Quan Wang1,2,3, Lu Liu1,2,3, Wei Gan1,2,3, Chen-Chen Liu1,2,3, Lin-Hui Tang1,2,3, Yu Li1,2,3, Fei Liang2,4, Qiang Zhou1,2,3, Yao-Lin Xu1,2,3, Yue-Ming Zhang1,2,3, Ning Pu1,2,3, Hua-Xiang Xu1,2,3, Jun-Yi He1,2,3, Lei Zhang1,2,3, Chen-Ye Shi1,2,3, Wen-Chuan Wu1,2,3, Xu-An Wang1,2,3, Jian-Fei Wang5, Liang Liu1,2,3 1Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; 2Cancer Centre, Zhongshan Hospital, Fudan University; 3Department of General Surgery, Zhongshan Hospital, Fudan University; 4Department of Biostatistics, Zhongshan Hospital, Fudan University; 5Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China Background • KRAS G12D inhibitors have shown promising antitumor activity in pancreatic cancer. Studies suggest that combining KRAS inhibitors with immunotherapy may further improve outcomes. • This study assesses the feasibility of combining HRS-4642 (a KRAS G12D inhibitor) and dual immunotherapy (anti-PD-L1 + anti-CTLA-4) with standard chemotherapy (gemcitabine plus nab-paclitaxel) in patients with pancreatic ductal adenocarcinoma (PDAC). Methods • This was an open-label, two-arm, phase 2 trial (NCT06938282). • Arm 1: Unresectable, locally advanced or metastatic PDAC. • Arm 2: Borderline-resectable PDAC (BRPC). • Target enrollment: ~30 patients per arm. Figure 1. Study design Key Eligibility Criteria: • KRAS G12D mutation • Age ≥18 years • ECOG PS: 0-1 • No prior systemic therapy • Measurable disease (≥1 lesion) • Adequate organ function HRS-4642 + Adebrelimab + SHR8068 (280 mg, priming dose) + GnP (Q3W) • Non-surgical: continuous treatment • Surgical: Neoadjuvant → Surgery → Adjuvant + Maintenance therapy Treatment continued until disease progression, unacceptable toxicity • Primary endpoints: safety and objective response rate (ORR) per RECIST v1.1 (Arm 1); 18-month OS rate (Arm 2) • Secondary endpoints: overall survival (OS), progression-free survival (PFS), disease control rate (DCR), resection rate and safety with adverse events summarized using NCI-CTCAE v5.0 Results - Patients • As of April 2026, a total of 12 pts with metastatic PDAC were enrolled in Arm 1 (Table 1). Table 1. Baseline Characteristics | N = 12 Median age, y (range) | 53 (38 - 75) Sex: Male 10 (83.3) | Female 2 (16.7) ECOG PS: 0 7 (58.3) | 1 5 (41.7) Tumor location: Head/neck 6 (50.0) | Others 6 (50.0) Stage IV at enrollment | 12 (100.0) Sites of lesion: Liver 11 (91.7) | Lung 1 (8.3) | Others 3 (25.0) CA19-9: CA19-9>2×ULN 12 (100.0) | CA19-9>1000 U/ml 6 (50.0) Efficacy • Among 10 evaluable patients, the ORR was 80.0% (8 PR, 2 SD), meeting the BOP2 design's stage endpoint of ≥2 responses. • Two PR patients with oligometastases underwent R0/R1 resection and had no recurrence on maintenance at data cutoff. Figure 2. Waterfall plot for treatment response (SD SD PR PR PR PR PR PR PR PR) Safety • Any-grade treatment-related adverse events (TRAEs) occurred in 91.7% of patients, and grade ≥3 TRAEs in 50.0%. • No fatal TRAEs were reported. Figure 3. TRAEs occurring in >2 patients (Anemia, ALP increased, ALT increased, GGT increased, AST increased, Neutropenia, Hyperlipasemia, Lymphopenia, Amylase increased, Leukopenia, Hypertriglyceridemia, Hypercholesterolemia, Fever, Total bile acid increased, Thrombocytopenia, Rash, LDL increased) Conclusions • The combination of HRS-4642, dual immunotherapy, and chemotherapy showed a manageable safety profile and promising efficacy, with the potential to convert unresectable disease to a resectable form. • Based on these results, Arm 2 (BRPC) has commenced enrollment. Correspondence to: Liang Liu, liu.liang@zs-hospital.sh.cn [Slide 2] FPN:3161P Neoadjuvant ivonescimab plus gemcitabine/nab-paclitaxel for borderline resectable pancreatic cancer: a prospective single-arm phase II trial H.Li1,2, H.Yan1, R.Li2, X.Zhang2, J.Yao2, W.Li2, X.Mu2, S.Gao3, Y.Liu1,2, J.Hao3 1.Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; 2.Department of Hepatobiliary and Pancreatic Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin, China; 3.Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China Background • Outcomes for borderline resectable pancreatic cancer (BRPC) remain suboptimal despite perioperative chemotherapy. • Immune checkpoint inhibition alone has limited activity in pancreatic ductal adenocarcinoma, whereas dual PD-1 and VEGF blockade may remodel the tumor microenvironment, improve drug delivery and augment chemotherapy response. • We evaluated neoadjuvant ivonescimab, a PD-1/VEGF bispecific antibody, plus gemcitabine/nab-paclitaxel (AG) in untreated BRPC. Methods This prospective, single-arm, single-center phase II trial (NCT06944106) enrolled patients with histologically confirmed, untreated BRPC and ECOG PS 0-1. Patients received ivonescimab 20 mg/kg Q3W plus gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 for 3 cycles; up to 6 cycles were permitted before radical surgery when feasible. The primary endpoint was R0/R1 resection rate. Secondary endpoints included ORR, DCR, pathological response, TRG, safety, EFS and OS. Fig 1. Research Flow Chart: Safety Run-in Phase n=6 (ivonescimab + Gemcitabine/Nab-paclitaxel) → 28-day observation → Expansion Enrollment n=20 → Curative resection; Primary Endpoint R0 and R1 resection rate; Secondary Endpoints Safety, MPR, TRG, EFS, ORR, DCR, OS Table 1. Patient Characteristics (n=26): Median age (range; years) 65 (38-75); Male 13 (50%); Female 13 (50%); ECOG PS 0 26 (100%), 1 0 (0%); Treatment Exposure (range) 3 (2-5); Head/Uncinate process 19 (73.1%); Body/tail 7 (26.9%) Results Patients: As of April 23, 2026, 26 patients had received treatment (median age 65 years (range, 38-75); 50.0% male; all ECOG PS 0). The median number of treatment cycles was 3 (range, 2-5). Efficacy: Among 18 response-evaluable patients, 8 had PR and 10 had SD; ORR was 44.4% and DCR was 100%, with no radiographic progression in evaluable patients. Thirteen patients proceeded to radical surgery, and all achieved R0 resection (50.0% of treated patients; 72.2% of response-evaluable patients). Among 11 patients with available postoperative pathology, 4 (36.4%) had ≥ 50% tumor regression; no MPR was observed. TRG was 2 in 9 patients and 3 in 2 patients. EFS and OS were immature. Grade ≥ 3 treatment-related adverse events occurred in 7 patients (26.9%), mainly leukopenia (15.4%), hypertension (11.5%) and neutropenia (7.7%). No immune-related adverse events, serious adverse events or treatment-related deaths were reported. Tab 2. Analysis of efficacy evaluation - Objective response indicators (n=18): CR 0 (0%); PR 8 (44.4%); SD 10 (55.6%); PD 0 (0%); ORR (CR+PR) 8 (44.4%); DCR (CR+PR+SD) 18 (100%) Surgical related data: Proceeded to radical surgery, n 13; R0 resection rate 100% (13/13) Pathological Outcomes (n=11): ≥50% tumor regression 4 (36.4%); MPR 0 (0%); TRG 2, n 9; TRG 3, n 2 Fig 2. Best change from baseline in target lesion size (%) n=18 Tab 3. TRAEs of Grade ≥3 n=26: Leukopenia G3 3, G4 1; Hypertension G3 3, G4 0; Neutropenia G3 1, G4 1; Overall grade ≥3 TRAE 7 (26.9%) Conclusions [N]eoadjuvant ivonescimab plus AG showed encouraging disease control, feasible conversion to R0 surgery and [ma]nageable toxicity in BRPC. Continued enrollment and follow-up are needed to confirm pathological and [sur]vival benefit in this ongoing neoadjuvant trial. Corresponding Author: Huikai Li, Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute & Hospital Disclosure statement: All authors have no conflicts of interest to declare. [Slide 3] 3150P - A Phase Ib/II Study of HRS-4642 plus Nimotuzumab in Patients with KRAS G12D-Mutant Advanced Pancreatic Ductal Adenocarcinoma D. Cao1, J. Zhou1, Q. Leng1, H. Xu1, M. Ren1, J. Wang2 1Department of Abdominal Oncology, WestChina Hospital of Sichuan University - Cancer Center, Chengdu, China; 2Department of Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China Conflict of interest: None Background • KRAS G12D mutations occur in ~40% of advanced pancreatic ductal adenocarcinoma (PDAC). Activation of EGFR upstream of KRAS has been identified as a dominant mechanism responsible for resistance to KRAS inhibition. • Combining HRS-4642 (long-acting, non-covalent KRAS G12D inhibitor) with nimotuzumab (anti-EGFR mAb) may produce synergistic effects in advanced KRAS G12D-mutant PDAC patients (pts). Methods • This was a single-arm, open-label, phase Ib/II study (NCT06773130). • Pts received HRS-4642 plus nimotuzumab in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. Figure 1. Study design Key Inclusion Criteria • Age 18-75 years • Histology/cytologically confirmed pancreatic ductal adenocarcinoma • With a confirmed KRAS G12D mutation • Previously treated with ≥1 line of systemic therapy Phase Ib (Safety Lead-in) N=6~12: Nimotuzumab, 400mg (iv), qw + HRS-4642 (iv), q2w 1200mg (RP2D) / 1000mg / 800mg (backup) Phase II (Efficacy Exploration) Simon's II stage: Enroll 9 pts, ≥1 CR/PR → Continue enrollment to 20 pts; ≥4 CR/PR, declare effective Subjects enrolled in the same dosage group during the Phase Ib could also be included in the sample size of Phase II. • Primary endpoints: safety and the recommended phase 2 dose (RP2D) (Phase Ib); objective response rate (ORR) per RECIST v1.1 (Phase II) • Secondary endpoints: safety (phase II only), overall survival (OS), ORR (phase Ib only), disease control rate (DCR), progression-free survival (PFS), and duration of response (DOR) Results - Patients • Up to April 24, 2026, a total of 20 pts were enrolled (Table 1). Table 1. Baseline Characteristics (N=20): Median age (range), yr 61 (42-74); Male sex 17 (85.0); ECOG 0 7 (35.0), 1 13 (65.0); Disease stage IV 20 (100.0); No. of sites of metastatic disease 1 7 (35.0), 2 7 (35.0), ≥3 6 (30.0); Main pancreatic tumor location Head or neck 10 (50.0), Body or tail 10 (50.0); Previous lines of anticancer therapy 1 11 (55.0), ≥2 9 (45.0) Efficacy • At the data cutoff on April 24, 2026, 15 pts were evaluable: 7 PR and 8 SD (ORR 46.7%, DCR 100.0%), and all showed target lesion shrinkage from baseline. Median PFS has not been reached. Figure 2. Waterfall plot for treatment response Figure 3. Duration of treatment and response Safety • In the Phase Ib, HRS-4642 1200 mg q2w plus nimotuzumab 400 mg qw was established as the RP2D, with no DLT observed in 6 pts. • Among the 20 patients, the incidence of TRAEs was 95.0%, with grade 3 TRAEs occurring in 20.0%; no grade ≥4 TRAEs occurred. Table 2. TRAEs occurring in >2 patients (All grade | Grade 3): Hypercholesterolaemia 16 (80.0%) | 2 (10.0%); Lipase increased 10 (50.0%) | 1 (5.0%); Alanine aminotransferase increased 9 (45.0%) | 0 (0.0%); Blood triglycerides increased 9 (45.0%) | 0 (0.0%); Amylase increased 6 (30.0%) | 0 (0.0%); Aspartate aminotransferase increased 6 (30.0%) | 1 (5.0%); Anaemia 4 (20.0%) | 0 (0.0%); Hypoalbuminaemia 4 (20.0%) | 0 (0.0%); Pruritus 4 (20.0%) | 0 (0.0%); Neutrophil count decreased 3 (15.0%) | 0 (0.0%); Asthenia 3 (15.0%) | 0 (0.0%); Gamma-glutamyltransferase increased 2 (10.0%) | 0 (0.0%); White blood cell count decreased 2 (10.0%) | 0 (0.0%); Rash 2 (10.0%) | 0 (0.0%); Proteinuria 2 (10.0%) | 0 (0.0%) Conclusions • Combination of HRS-4642 and nimotuzumab showed encouraging efficacy with well-tolerated toxicities in pts with KRAS G12D-mutant advanced pretreated PDAC. Updated results will be presented. [Slide 4] 3165P: Perioperative HRS-4642, Chemotherapy, and Adebrelimab in KRAS G12D-Mutant Pancreatic Cancer: Preliminary Phase 2 Results Baiyong Shen1, C. Wen1, S. Zou1, F. Li1, Q. Zhan1, T. Wang2, N. Zhu3, L. Gan1, L. Jiang1, W. Chai3, J. Wang4 1Department of General Surgery, Ruijin Hospital - Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Pathology, Ruijin Hospital; 3Department of Radiology, Ruijin Hospital; 4Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China Background • Surgical resection remains the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant and adjuvant therapy strategies are recommended for resectable (particularly those with high-risk factors) and borderline resectable patients (pts), with the aim of achieving R0 resection and improving survival outcomes. • This study evaluates the safety and efficacy of combining HRS-4642 (a KRAS G12D inhibitor) and adebrelimab (an anti-PD-L1 antibody) with standard chemotherapy in pts with early-stage PDAC. Methods • This was an open-label, single-center, phase II trial (NCT07131514). • A Bayesian Optimal Phase II (BOP2) design was used (H0: 20%; H1: 40%), providing 85.86% power under H1. A total of 15-30 pts were planned for enrollment. Figure 1. Study design Key Eligibility Criteria: •KRAS G12D mutation •High-risk/borderline resectable pancreatic cancer •No prior treatment •ECOG: 0-1 Neoadjuvant ~4 cycles: HRS-4642+Adebrelimab+AG, iv, q3w; HRS-4642: 500mg d1, 1200mg d8, Adebrelimab: 1200mg, d1; Nab-Paclitaxel: 125 mg/m2, d1, d8, Gemcitabine: 1000mg/m2, d1, d8 2-4 weeks, radically resectable → Resection → Within 12 weeks → Adjuvant ~4 cycles (same regimen as neoadjuvant) • Primary endpoints: objective response rate (ORR) per RECIST v1.1 and safety • Secondary endpoints: R0 resection rate, major pathological response (MPR) rate (CAP Score 0-1), overall survival Results - Patients • Between July 2025 and March 2026, a total of 30 pts with high-risk resectable and borderline resectable PDAC were enrolled. Table 1. Baseline Characteristics (N = 30): Median age, y (range) 64 (39-75); Male 18 (60.0); Female 12 (40.0); ECOG PS 0: 0, 1: 30 (100.0); Tumor location Head 18 (60.0), Others 12 (40.0); Resectability status High-risk resectable 9 (30.0), Borderline resectable 21 (70.0); Clinical stage I / II / III 0 / 18 / 12; CA 19-9>2×ULN 23 (76.7); CA 19-9≤2×ULN 7 (23.3) Efficacy • Among 25 evaluable patients, the ORR was 88.0% (22 PR, 3 SD), tumor shrinkage was observed in all patients. • 16 pts underwent surgery and had postoperative pathology available, with a 100% (16/16) R0 resection rate and an 18.8% (3/16) MPR rate. Figure 2. Waterfall plot for treatment response Safety • Among all pts, treatment-related adverse events (TRAEs) occurred in 93.3%, and grade 3/4 TRAEs occurred in 46.7%. • No treatment-related deaths were reported. Figure 3. TRAEs occurring in >10% patients [labels illegible] Conclusions • For pts with resectable or borderline resectable PDAC, the triplet of HRS-4642, GnP, and adebrelimab was well tolerated. Encouraging neoadjuvant activity was observed, with high ORR and R0 resection rates, further supported by postoperative pathological findings.

[Slide 1] MADRID 2026 ESMO congress HRS-4642 Plus Chemotherapy ± Adebrelimab as Perioperative Therapy in KRAS G12D-Mutant Pancreatic Cancer: Preliminary Results of a Phase 2 Study Baiyong Shen1,*, Chenlei Wen1, Siyi Zou1, Fanlu Li1, Qian Zhan1, Ting Wang2, Naiyi Zhu3, Lina Gan1, Lingxi Jiang1, Weimin Chai3, Jianfei Wang4 * Principal investigator 1. Department of General Surgery, Ruijin Hospital - Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2. Department of Pathology, Ruijin Hospital - Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3. Department of Radiology, Ruijin Hospital - Shanghai Jiao Tong University School of Medicine, Shanghai, China, 4. Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China [Slide 2] Rational combinations in PDAC KRAS and PRMT5 inhibition as a potential strategy in PDAC Vopimetostat inhibits PRMT5 only in MTAP-del cancer cells when MTA is bound Tumor regression in Murine Models of PDAC with MTAP-Loss Treated with Vopimetostat and Daraxonrasib or Zoldonrasib Vopimetostat + zoldonrasib in MTAPdel , KRAS G2D mut 2/3L PDAC Best Change in Tumor Size from Baseline (%) LoT Line of Therapy BOR, n: CR / PR / SD / PD ORR, % DCR, % [illegible] PD / SD / PR / CR / Ongoing Therapy 1-Spira et al, presented at 2026 ESMO Meeting, poster 3149P [Slide 3] MEK inhibitors in PDAC Atebimetinib is a novel allosteric small molecule inhibitor of MEK1/2 Atebimetinib (320 mg QD) + mGnP DCR: 82% ORR: 36% Phase 2a | Atebimetinib (320 mg QD) + mGnP OS, N=55 OS Probability Months 17.3 mo Participant Population: First-line (1L) metastatic Pancreatic Ductal Adenocarcinoma (PDAC) MAPKeeper First line (1L) PDAC Metastatic setting ECOG PS 0-1 N=255 Atebimetinib + mGnP N=255 Gem/nab-Pac 1L SoC Chemotherapy Primary Endpoints: OS Secondary Endpoints: PFS, DCR, ORR, QoL Chung et al, presented at 2026 ASCO Meeting NCT07562152 Survival table Endpoint: Overall survival, phase 2a single arm Atebimetinib (320 mg QD) + mGnP | 55 [Slide 4] KRAS inhibitors in PDAC Other pan-RAS inhibitors in PDAC ERAS-0015 is an investigational, oral, highly potent pan-RAS molecular glue designed to inhibit RAS signaling with a potential best-in-class profile. Erasca is evaluating ERAS-0015 in the AURORAS-1 Phase 1 trial in patients with RAS-mutant solid tumors. Maximum percentage change from baseline 8 mg QD / 16 mg QD / 24 mg QD / 32 mg QD / 40 mg QD / Treatment Ongoing ERAS-0015 2L+ KRAS G12X PDAC 8 mg QD N=9 | 16 mg QD N=8 | 24 mg QD [illegible] | 32 mg QD [illegible] | 40 mg QD N=2 uORR, n (%): 1 (11) | 0 | [illegible] | [illegible] | [illegible] DCR, n (%): 4 (44) | 8 (100) | [illegible] | 7 (100) | 2 (100) Of the patients treated at RDEs of 24 mg and 32 mg: 27% were 2L 73% were 3L+ AURORAS-1 Phase 1 trial in the U.S: 57% uORR in patients with 2L+ KRAS G12X PDAC receiving ERAS-0015 monotherapy at the recommended dose for expansion of 32 mg once daily.

[Slide 1] CHAIRS: CHIARA BRACONI, MONICA NIGER, ANNA SABOROWSKI First-in-human study design Key Eligibility Criteria • 18-75 years of age • Histologically confirmed GPC3+ HCC • BCLC B/C, Child-Pugh A • Relapsed/progressed/intolerant to HCC systemic therapies (≥1 line) • No active CNS involvement Key Endpoints Primary • Safety and tolerability (incidence and severity of TEAEs including DLTs) Secondary • Investigator-assessed ORR, DCR per RECIST v1.1, and OS Patient Journey PRE-SCREENING | SCREENING | MANUFACTURING | TREATMENT | MAIN FU | LTFU GPC3 IHC Testing; Main screening; Leukapheresis; Manufacturing of AZD7003; Bridging therapy (Optional) Lymphodepletion Cy: 500 mg/m² Flu: 25 mg/m² Days −5, −4, −3 D-7; D0 AZD7003 infusion; D28 End of DLT period Ongoing safety & efficacy assessments for 12 months LTFU for safety up to 15 years Qi Zhang, M.D. [Slide 2] Compelling response rate in a heavily pretreated patient population Change from baseline in target lesion (%) 0.75 × 10^6 cells/kg; 1.5 × 10^6 cells/kg; 2.5 × 10^6 cells/kg; 4.0 × 10^6 cells/kg* RP2D† | 0.75 × 10^6 cells/kg N=1 | 1.5 × 10^6 cells/kg N=6 | 2.5 × 10^6 cells/kg N=18 | 4.0 × 10^6 cells/kg N=11 | Overall N=36 ORR, n (%) | 0 | 3 (50.0) | 7 (38.9) | 6 (54.5) | 16 (44.4) DCR, n (%) | 1 (100) | 5 (83.3) | 18 (100) | 9 (81.8) | 33 (9[illegible] Data cutoff 15 August 2026 Qi Zhang, M.D. *One participant excluded as no post-baseline tumor assessment available. †2.5 [illegible] was determined as the recommended phase 2 dose (RP2D) based on combined [illegible] kinetics, safety and efficacy data. [Slide 3] Encouraging survival signal across dose levels, especially in responders Overall survival (%) / Time post infusion (months) 0.75 × 10^6 cells/kg; 1.5 × 10^6 cells/kg; 2.5 × 10^6 cells/kg; 4.0 × 10^6 cells/kg; All mOS 18.0m (95% CI 11.1-31.4) Responder (cPR) / Non-responder mOS 27.4m (95% CI 12.22–NE) mOS 13.7m (95% CI 8.11–NE) Number at risk | 0.75 × 10^6 cells/kg N=1 | 1.5 × 10^6 cells/kg N=6 | 2.5 × 10^6 cells/kg N=18 | 4.0 × 10^6 cells/kg N=11 | Overall N=36 12-month OS rate (95% CI) | - | 33.3 (4.6, 67.6) | 75.6 (47.3, 90.1) | 72.7 (37.1, 90.3) | 65.4 (47.1, [illegible]) Observed median follow-up time, month (Min, Max) | 7.0 | 10.4 (7.6, 41.5) | 15.9 (4.8, 35.8) | 17.7 (1.7, 30.2) | 14.9 (1.7, [illegible]) Data cutoff 15 August 2026 Qi Zhang, M.D. *1 participant had no post-baseline tumour assessments and was not inc[illegible] cPR, confirmed partial response; mOS, median overall survival; NE, not evaluable Survival table Endpoint: OS Arm | N | Median | Median CI All (overall) | 36 | 18.0 | 11.1-31.4 Responder (cPR) | 16 | 27.4 | 12.22-NE Non-responder | 19 | 13.7 | 8.11-NE 12-month OS rate: overall 65.4% (95% CI 47.1-[illegible]); 1.5x10^6 33.3% (4.6-67.6); 2.5x10^6 75.6% (47.3-90.1); 4.0x10^6 72.7% (37.1-90.3) [Slide 4] Conclusions • In this FIH study in patients with HCC, AZD7003 had a tolerable safety profile with predominately Grade 1/2 CRS and no ICANS or IEC-HS • AZD7003 showed rapid, robust expansion and long-term persistence in peripheral blood • AZD7003 showed encouraging efficacy in heavily pretreated patients: • 44.4% ORR and 91.7% DCR across all dose levels • 65.4% 12-month OS rate (95% CI, 47.1–78.7) • 2.5 × 10^6 cells/kg was determined as the recommended phase 2 dose • These FIH results support further clinical development of AZD7003 in advanced HCC Qi Zhang, M.D.

C-CAR031 (AZD7003): a dnTGFβRII armoured GPC3 CAR-T GPC3 is an ideal HCC target ▪ Glypican-3 (GPC3) is highly expressed in the majority of HCC tumours and virtually absent in normal adult tissues1,2,3 HCC tumour Adjacent normal liver C-CAR031 (AZD7003) design ▪ C-CAR031 is now known as AZD7003 ▪ Affinity-tuned anti-GPC3 scFv enhances safety4 ▪ Co-expression of a dominant negative (dn) receptor protects from TGFβ-driven immunosuppression5,6 GPC3 CAR Second generation CAR with 4-1BB costimulatory domain dnTGFβRII Binds TGFβ but cannot signal Qi Zhang, M.D. 1. Moek KL et al, Am J Pathol. 2018 Sep;188(9):1973-1981; 2. Batra et al, Ca[illegible] Res. 2020 Mar;8(3):309-320; 3. Bergamaschi et al, AACR 2025, Abstract 379[illegible] Torchia ML et al, Cytotherapy. 2022 Jul;24(7):720-732; 5.Tauriello DVF et al, [illegible] 2022 Jan;22(1):25-44; 6. Zhang Q et al, Nature. 657, 495–504 (2026)

[Slide 1] Study Design and Methods Multicenter, single-arm, phase II trial (NCT06640166) Inclusion Criteria • mCRC • BRAF V600E • PD on EC in 2nd line • PS 0-1 • Best response to EC: CR, PR or SD lasting ≥3 months. Encorafenib plus cetuximab in combination with FOLFIRI (EC beyond progression) Experimental treatment • Encorafenib 300 mg (75 mgx4 hard capsules) po qd; • Cetuximab 500 mg/m2 iv Q2W; • FOLFIRI iv Q2W (Irinotecan 180 mg/m2, Folinic Acid 400 mg/m2, 5Fluorouracil 400 mg/m2 iv bolus and 2400 mg/m2 iv continuous infusion over 46-48 hours) Primary endpoint Investigator-assessed 6-month PFS rate in the ITT population. Secondary endpoint • mPFS; mOS; • ORR; DCR (per RECIST V1.1); • Safety. Statistical hypothesis Binomial test (single-stage, one-sided α = 0.05, 80% power) H0=10% H1=30% Required to enroll 25 patients and to observe ≥7 pts alive without progression at 6 months to reject the null hypothesis, supporting further investigation. Maria Alessandra Calegari [Slide 2] Results – Primary Endpoint Investigator-assessed 6-month PFS rate in the ITT population Patients evaluable for 6-month PFS rate (n = 18) PFS > 6 months: 12* | PFS < 6 months: 6 6-month PFS rate 66.7% (12/18) * Positivity threshold ≥7 pts alive without progression at 6 months [Swimmer plot: Individual patients; Progression Free Survival (months) 0-20; dashed line at 6 months; legend: Progressive disease, On treatment ongoing, Evaluable for primary endpoint, Not yet evaluable for primary endpoint] Data cutoff: May 8, 2026 Abbreviations: ITT, intention to treat; PFS, progression free survival; pt, patient Maria Alessandra Calegari [Slide 3] Results – Survivals Progression Free Survival Endpoint | Estimate (95%CI) Median PFS, months | 7.1 (6.2 – NA) 6-month PFS rate | 69.5% (51.7 – 93.6) 12-month PFS rate | 22.8% (8.8 – 59.0) Median FU 16.1 months No. at risk: 25 15 12 3 3 3 2 0 0 Events: 0 4 6 13 13 13 13 14 14 Months 0 3 6 9 12 15 18 21 24 Overall Survival Endpoint | Estimate (95%CI) Median OS, months | NR 6-month OS rate | 94.1% (83.6 – 100.0) 12-month OS rate | 83.7% (64.5 – 100.0) Median FU 7.6 months No. at risk: 25 18 14 10 8 7 4 2 0 Events: 0 0 1 1 2 4 5 5 5 Data cutoff: May 8, 2026 Abbreviations: CI, confidence interval; FU, follow up; NA, not assessable; NR, not reached; PFS, progression free survival; OS, overall survival Maria Alessandra Calegari Survival table Endpoint: PFS and OS (single arm) Encorafenib + cetuximab + FOLFIRI (PFS) | 25 | 7.1 months | 6.2 – NA Encorafenib + cetuximab + FOLFIRI (OS) | 25 | NR Landmark rates: 6-month PFS: EC + FOLFIRI 69.5% (CI 51.7 – 93.6) 12-month PFS: EC + FOLFIRI 22.8% (CI 8.8 – 59.0) 6-month OS: EC + FOLFIRI 94.1% (CI 83.6 – 100.0) 12-month OS: EC + FOLFIRI 83.7% (CI 64.5 – 100.0) [Slide 4] Results – ORR, DCR Waterfall plot Endpoint | Estimate (95%CI) Objective response rate | 15.0% (3.2-37.9) Disease control rate | 80% (56.3-94.3) Best change from baseline, % Pt 5, Pt 21, Pt 11, Pt 17, Pt 18, Pt 9, Pt 2, Pt 7, Pt 3, Pt 1, Pt 4, Pt 12, Pt 14, Pt 13, Pt 6, Pt 20, Pt 16, Pt 15, Pt 10, Pt 8 Best response: PR, SD, PD Spider plot Change from baseline, % / Time from baseline, months (0-21) Best response: PR, SD, PD; ▲ Disease progression; * Surgery Data cutoff: May 8, 2026 Abbreviations: CI, confidence interval; DCR, disease control rate; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease Maria Alessandra Calegari

Conclusions ECLYPse met its primary endpoint, with a 6-month PFS rate of 67% (12/18 pts), a mPFS of 7.1 months, and no new safety signal. Continuing EC beyond progression in combination with ChT appears to extend disease control in this poor-prognosis population. This strategy (EC beyond progression in combination with ChT) should be furtherly assessed in the post-BREAKWATER era (2nd line setting). Maria Alessandra Calegari

[Slide 1] KN035-CN-005 Study Design A multi-center, open-label, randomized phase III trial • Histologically or cytologically confirmed unresectable or metastatic biliary tract cancer (including GBC, iCCA and eCCA) • Received no prior systemic therapy • Patients who relapsed >6 months after completing one regimen of adjuvant or neoadjuvant chemotherapy were eligible • ECOG performance status 0 or 1 (N=472) R 1:1 Envafolimab + GEMOX Envafolimab: 2.5 mg/kg subcutaneously QW (until treatment discontinuation) GEMOX: Gemcitabine: 1,000 mg/m² on D1 and D8; Oxaliplatin: 85 mg/m² on D1, Q3W, up to 6 cycles GEMOX Gemcitabine: 1,000 mg/m² on D1 and D8; Oxaliplatin: 85 mg/m² on D1, Q3W, up to 6 cycles Stratification factors: • Primary tumor site (GBC, iCCA, eCCA) • Disease stage (locally advanced vs metastatic) • Prior treatment (adjuvant chemotherapy vs other) • ECOG performance status (0 vs 1) ◆Primary endpoint: OS ◆Secondary endpoints: PFS, ORR, DCR, DoR, and TTP (RECIST 1.1) Safety and tolerability Pharmacokinetics and immunogenicity of envafolimab Data cutoff: September 10, 2024 Abbreviations: GBC, Gallbladder cancer; iCCA, intrahepatic cholangiocarcinoma; eCCA, extrahepatic cholangiocarcinoma; QW, once per week; D1, Day 1; D8, Day 8; OS, overall survival; PFS, progression-free survival; ORR, objective response rate; DCR, disease control rate; DoR, duration of response; TTP, time to progression Presented by Prof. Shukui Qin [Slide 2] Primary Endpoint: Final Analysis of Overall Survival • The Envafolimab combination regimen demonstrated a durable immune tail effect, with the 36-month OS rate nearly doubled compared to the control arm (12.5% vs 7.7%). Envafolimab+GEMOX / GEMOX 12-month: 44.2% vs 29.9% 24-month: 19.9% vs 10.8% 36-month: 12.5% vs 7.7% Enva+GEMOX (N=232) | GEMOX (N=230) Median OS (95% CI), months: 10.9 (9.2-12.1) | 8.6 (7.6-9.4) Hazard ratio (95% CI): 0.723 (0.585-0.880) P-value: 0.0016 % of Subjects Overall Survival Months Subject at risk Presented by Prof. Shukui Qin Survival table Endpoint: OS Arm | N | Median | Median CI Envafolimab+GEMOX | 232 | 10.9 | 9.2-12.1 GEMOX | 230 | 8.6 | 7.6-9.4 HR: 0.723 HR CI: 0.585-0.880 P: 0.0016 12-month: 44.2% vs 29.9% 24-month: 19.9% vs 10.8% 36-month: 12.5% vs 7.7% [Slide 3] Secondary Endpoint: PFS, ORR and DoR PFS Enva+GEMOX (N=232) | GEMOX (N=230) Events, n (%): 203 (87.5%) | 151 (65.7%) Median PFS (95% CI), months: 5.4 (4.2-5.6) | 4.5 (4.2-5.5) HR (95% CI): 0.802 (0.638-1.007) P-value: 0.058 Tumor Response: ORR Enva+GEMOX (N=232) | GEMOX (N=230) ORR, n (%): 64 (27.6%) | 48 (20.9%) CR, n (%): 5 (2.2%) | 1 (0.4%) PR, n (%): 59 (25.4%) | 47 (20.4%) DCR, n (%): 166 (71.6%) | 165 (71.7%) DoR (Responders Only) Enva+GEMOX (n=64) | GEMOX (n=48) Median DoR (95% CI), months: 5.5 (4.1-7.0) | 4.2 (3.1-6.7) HR (95% CI): 0.587 (0.339-1.018) DoR rate, % ≥6 months: 45.3% | 35.4% ≥12 months: 33.6% | 9.6% ≥24 months: 27.2% | 6.4% 4-month Landmark Analysis of PFS Piecewise Cox proportional hazards model Interval | HR (95% CI) | P-value 0-4 months | 0.988 (0.720, 1.356) | 0.9415 >4 months | 0.650 (0.472, 0.896) | 0.0085 4-month Landmark Analysis of PFS Enva+GEMOX (N=136) | GEMOX (N=110) Cumulative PFS, months: 6.9 | 5.7 Stratified cHR (95% CI): 0.642 (0.465-0.887) Stratified P-value: 0.0068 After excluding early (≤4 months) progression or censoring, patients entering the maintenance phase showed greater benefit with Enva+GEMOX. Presented by Prof. Shukui Qin [Slide 4] Conclusions • KN035-CN-005 is the world's first initiated Phase III trial evaluating an immune checkpoint inhibitor combined with chemotherapy for the first-line treatment of advanced BTC. • The addition of Envafolimab to GEMOX demonstrated a clinically meaningful and robust prolongation of Overall Survival compared to GEMOX alone. • The combination did not exacerbate GEMOX-related adverse events, and no new safety signals were identified compared to the monotherapies. • Envafolimab plus GEMOX provides a highly effective first-line treatment strategy, establishing a compelling new standard of care option for patients with advanced BTC. Presented by Prof. Shukui Qin

[Slide 1] How do patients treated with Olaparib in the Optimum compare to the RW population of BTC on SoC? mOS (22.8mo) 2yr OS from starting maintenance =17.7% mPFS (10.6mo) (4 cycles [1-31]) RR = Not Reported [RWD in N=475 Completed maintenance D] Camera, ESMO Open 2026 With CisGemDurva Chemo (+/-ICI) RR = 27% mPFS (17mo) mOS (29.5mo) [OPTIMUM study Olaparib treated =FAS population] 2yr OS from starting maintenance =41% With Olaparib (+/- Durva) [Slide 2] CLINICAL IMPACT of OPTIMUM trial ➢ Will this study change my clinical practice? Olaparib is not approved in BTC Lack of proper control arm Immunotherapy maintenance is currently SoC Unbalanced cHRD (higher in Olaparib arm) Unbalanced ICI (higher in Olaparib arm) Unknow distribution of MMRd tumours and their response to ICI ➢ What do we gain from this study with regards to Olaparib? Olaparib is an effective treatment in cHRD-altered BTC Do we need a new trial? [Slide 4] CONCLUSION ➢ Will this study change my clinical practice? Extra Validation that Immunocheckpoint inhibitors should be added to chemotherapy in first line GemOx can be considered as an alternative regimen if CisGem is contraindicated ➢ How can we inform the future? s.c. ICI is an appealing option BUT We may need Data of Non-Inferiority with I.V. ICI Data in Non-Chinese population Has this become irrelevant? Ivonescimab In first line

[Slide 1] Study Design Phase 2 randomized open-label, non-comparative, signal-seeking design 1. Locally advanced unresectable or metastatic BTC (intrahepatic, extrahepatic or gallbladder) 2. No progression at least 16 weeks with 1L platinum-based chemotherapy 3. Somatic or germline DDR gene mutations in tissue NGS or ctDNA* R (1:1) N = 62 Olaparib + Durvalumab group Olaparib 300 mg BID Durvalumab 1500 mg IV on D1 Every 4 weeks Olaparib group Olaparib 300 mg BID Every 4 weeks Primary endpoint • 6-month PFS rate Secondary endpoints • OS • ORR • Safety profile Exploratory biomarker analysis • Tumor NGS • ctDNA • scRNAseq Stratification factors • Localization (IH-CCA vs EH-CCA/GBCA) • Best response to platinum-based chemotherapy (CR/PR vs SD) *ATM, ATR, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, GEN1, FANCA, FANCD2, POLE, MLH1, MSH2, MSH6, MRE11A, NBN, PALB2, PMS2, RAD50, RAD51, RAD51C, RAD51D, and XRCC2 Designed to detect an improvement in the 6-month PFS rate from 48.0% (P0) to 69.3% (P1) in either treatment arms. Changhoon Yoo, MD, PhD [Slide 2] Survival outcomes Progression-free survival Progression-free survival (%) Time (months) Overall survival Overall survival (%) Time (months) Post-progression systemic therapy: 9/24 (37.5%) vs. 19/22 (86.4%) Number at risk O+D Olaparib Predefined primary endpoint: 6-mo PFS rate 69.3% Changhoon Yoo, MD, PhD Survival table Endpoint: PFS (6-mo PFS rate primary endpoint) and OS Arm | N | Median | Median CI Olaparib + Durvalumab | 32 | PFS 7.7 mo; OS 16.5 mo | PFS 5.5–11.8; OS 11.8–19.9 Olaparib | 29 | PFS 8.2 mo; OS 29.6 mo | PFS 4.9–14.0; OS 15.7–NE 6-mo PFS rate (one-sided 95% CI): Olaparib + Durvalumab 62.5 (46.8-74.7); Olaparib 62.1 (45.5-74.9) 1yr OS rate (one-sided 95% CI): Olaparib + Durvalumab 64.3 (45.9-77.8); Olaparib 75.9 (58.1-86.9) [Slide 3] Tumor response Olaparib + Durvalumab arm ORR: 30.0% (14.0–50.8) DCR: 93.8% (81.6–98.9) Olaparib arm ORR: 25.0% (10.4–45.6) DCR: 79.3% (63.2–90.6) Best change from baseline in lesion size (%) BOR: CR, PR, SD, PD HRD: cHR, ncHR, Others PrimarySite: Extrahepatic, Gallbladder, Intrahepatic GemCis_BOR: CR or PR, SD Core HRD (cHRD): BRCA1, BRCA2, or PALB2 Non-core HRD (ncHRD): ATM, ATR, BAP1, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FAM175A, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCM, GEN1, MRE11A, NBN, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RBBP8, SLX4, XRCC2, BLM, TP53BP1, and WRN Changhoon Yoo, MD, PhD [Slide 4] Conclusions • Although the primary endpoint was not met (6M PFS rates 62.5% and 62.1% vs. 69.3%), olaparib ± durvalumab was feasible as maintenance therapy following 1L platinum-based chemotherapy. • Durable survival benefit was derived in patients with aBTC harboring cHRD gene mutations, supporting further development of HRD-targeted therapy in aBTC . • Immunological biomarker analysis is ongoing using serial single-cell RNA sequencing of PBMC. Changhoon Yoo, MD, PhD

Patient characteristics | | FAS group n = 61 | Olaparib + Durvalumab arm n = 32 | Olaparib arm n = 29 | Age, median (range) | 67 (38 - 85) | 70 (52 - 85) | 66 (38 - 82) Sex, Male/Female | 34 (55.7)/27 (44.3) | 17 (53.1)/15 (46.9) | 17 (58.6)/12 (41.4) ECOG PS, 0/1 | 20 (32.8)/41 (67.2) | 10 (31.3)/22 (68.8) | 10 (34.5)/19 (65.5) Primary tumor location Intrahepatic | 28 (45.9) | 15 (46.9) | 13 (44.8) Extrahepatic-distal Bile Duct | 10 (16.4) | 7 (21.9) | 3 (10.3) Extrahepatic-perihilar Bile Duct | 11 (18.0) | 3 (9.4) | 8 (27.6) Gallbladder | 12 (19.7) | 7 (21.9) | 5 (17.2) Disease status at the time of 1L therapy Locally Advanced Unresectable | 11 (18.0) | 4 (12.5) | 7 (24.1) Recurrent or metastatic | 50 (82.0) | 28 (87.5) | 22 (75.9) Tumor response to 1L GemCis-containing therapy CR or PR | 27 (44.3) | 14 (43.8) | 13 (44.8) SD | 34 (55.7) | 18 (56.3) | 16 (55.2) Prior treatment with GemCis+ICIs | 12 (1[illegible].7) | 5 (15.6) | 7 (24.1) Core HRD (cHRD) mutations (BRCA1, BRCA2 or PALB2) | 18 (29.5%) | 8 (25.0%) | 10 (34.5%) ctDNA positivity at C1D1 (n = 59) | 34 (57.6%) | 18 (58.1%) | 16 (57.1%) Changhoon Yoo, MD, PhD

[Slide 1] 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive CHAIR: GUILLERMO ARGILES MARTINEZ 1° endpoint - progression-free survival median (95% CI) PFS (months) placebo 12.9 (10.4,16.3) EPA 13.5 (11.8,17.9) Location of CRC recurrence similar Five-year PFS: placebo 24.5% (17.9,31.7) vs EPA 23.6% (16.4,31.5) Analysis population | Hazard Ratio (95% CI) | P-value Intention to treat | 0.89 (0.70, 1.13) | 0.3286 Per protocol | 0.97 (0.71, 1.32) | 0.8572 Favours EPA <- -> Favours Placebo key 2° endpoint - overall survival CRC 51/57 deaths (EPA) CRC 63/73 deaths (placebo) median (95% CI) OS (months) placebo 59.0 (40.8,NR) EPA not reached Five-year OS: placebo 45.1% (33.7,55.9) vs EPA 62.0% (52.7,70.0) Analysis population | Hazard Ratio (95% CI) | P-value Intention to treat | 0.68 (0.48, 0.96) | 0.0303 Per protocol | 0.60 (0.36, 0.99) | 0.0466 Number at risk rows: [illegible] Mark Hull Omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) versus placebo after resection of colorectal cancer liver metastases (EMT2): A multicentre, double-blind, randomised phase 3 trial ALMERIA AUDITORIUM - HALL 9 [Slide 2] Safety and tolerability Adverse Event reporting | Placebo (n=207) | EPA (n=204) Any AE | 124 (60%) | 111 (54%) AE before surgery | 37 (18%) | 31 (15%) AE after surgery | 113 (55%) | 102 (50%) Any gastrointestinal AE | 90 (44%) | 74 (36%) number of gastrointestinal AEs | 244 | 248 Serious AE | 67 (32%) | 60 (29%) number of serious AEs | 107 | 95 Episodes of AF (intra-/post-operative [≤30d]) | 6 (5) | 4 (2) Bleeding events (intra-/post-operative) | 26 (16) | 6 (3) VTE events (intra-/post-operative) | 8 (4) | 5 (2) In the ITT population, there were 6 non-CRC primary malignancies diagnosed in the placebo group and 5 non-CRC primary malignancies reported in the EPA group Mark Hull Omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) versus placebo after resection of colorectal cancer liver metastases (EMT2): A multicentre, double-blind, randomised phase 3 trial

1° endpoint - progression-free survival median (95% CI) PFS (months) placebo 12.9 (10.4,16.3) EPA 13.5 (11.8,17.9) Location of CRC recurrence similar Five-year PFS: placebo 24.5% (17.9,31.7) vs EPA 23.6% (16.4,31.5) Analysis population | Hazard Ratio (95% CI) | P-value Intention to treat | 0.89 (0.70, 1.13) | 0.3286 Per protocol | 0.97 (0.71, 1.32) | 0.8572 Favours EPA | Favours Placebo key 2° endpoint - overall survival CRC 51/57 deaths CRC 63/73 deaths median (95% CI) OS (months) placebo 59.0 (40.8,NR) EPA not reached Five-year OS: placebo 45.1% (33.7,55.9) vs EPA 62.0% (52.7,70.0) Analysis population | Hazard Ratio (95% CI) | P-value Intention to treat | 0.68 (0.48, 0.96) | 0.0303 Per protocol | 0.60 (0.36, 0.99) | 0.0466 Favours EPA | Favours Placebo Number at risk (number censored): Placebo 209 / EPA 209 at time 0 (remaining small-print at-risk values not transcribed; see notes) Survival table Endpoint: PFS (primary) and OS (key secondary) Arm | N | Median | Median CI Placebo | 209 | PFS 12.9 mo; OS 59.0 mo | PFS 10.4,16.3; OS 40.8,NR EPA | 209 | PFS 13.5 mo; OS not reached | PFS 11.8,17.9 HR: PFS ITT 0.89; OS ITT 0.68 HR CI: PFS 0.70, 1.13; OS 0.48, 0.96 P: PFS 0.3286; OS 0.0303 Landmark rates: 5 years PFS: Placebo 24.5% (CI 17.9,31.7) | EPA 23.6% (CI 16.4,31.5) 5 years OS: Placebo 45.1% (CI 33.7,55.9) | EPA 62.0% (CI 52.7,70.0)

Introduction of Ivonescimab • Ivonescimab is a first in class bispecific antibody that cooperatively targets both programmed cell death protein-1 (PD-1) and vascular endothelial growth factor (VEGF) • The HARMONi series of clinical studies evaluating ivonescimab have been conducted globally across multiple indications [Diagram: Anti-VEGF; Engineered Fc-Null Region; Anti-PD-1] Akesobio — China Phase 3 EGFR-TKI progressed NSCLC: Approvedby NMPA — HARMONi-A 1L PD-L1+ NSCLC: Approved by NMPA — HARMONi-2 1L squamous NSCLC: Approved by NMPA — HARMONi-6 1L BTC: Priority Review designation — HARMONi-GI1 1L Pancreatic: Ongoing — HARMONi-GI2 1L Colorectal: Ongoing — HARMONi-GI6 1L TNBC: Ongoing — HARMONi-BC1 1L HNSCC: Ongoing — HARMONi-HN1 IO-R NSCLC: Ongoing — HARMONi-8A SCLC: Ongoing — HARMONi-9 Summit therapeutics — Global Phase 3 EGFR-TKI progressed NSCLC: submitted — HARMONi 1L PD-L1-high NSCLC: Ongoing — HARMONi-7 1L NSCLC all comers: Ongoing — HARMONi-3 1L CRC: Ongoing — HARMONi-GI3 1L UC: Ongoing — HARMONi-GU1 1L PD-L1 CPS+ HNSCC: Ongoing — ILLUMINE[1] 1L BTC: initiating — EA2251[2] [1] [2] ILLUMINE study is conducted in collaboration with GORTEC in France, and EA2251 study in collaboration with ECOG-ACRIN in the United States. Jian Zhou, MD, PhD

This progress has been a long scientific journey CLDN18.2: From discovery to first approval: 23 years 2001 | Molecular and Cellular Biology | Tomoaki Niimi et al. | Identification of CLDN18.2 as a stomach-specific isoform 2008 | Clinical Cancer Research | Uğur Şahin, Özlem Türeci et al. | Identification of CLDN18.2 as pan-tumor therapeutic target 2016 | ASCO Annual Meeting | Salah-Eddin Al-Batran | FAST: First clinical proof of concept for targeting CLDN18.2 (IMAB362) 2023 | ASCO GI | Kohei Shitara | SPOTLIGHT: First positive phase III trial on this CLDN18.2 antibody (zolbetuximab) 2024 | First regulatory approval of a CLDN18.2-targeted therapy: zolbetuximab in Japan 2026 | ESMO Congress | Rui-Hua Xu and Kohei Shitara | CLARITY-Gastric 01 and G-HOPE-001: First Phase III results with the CLDN18.2-targeted ADCs (sonesitatug vedotin and Arcotatug tavatecan) [Thumbnail figures: histology image; expression bar charts; FAST OS curve (mOS 8.4 vs. 13.2 mo, HR 0.51, P<0.001 - small, partially legible); SPOTLIGHT KM; CLARITY-Gastric01 and G-HOPE-001 KM curves - [illegible]] Salah-Eddin Al-Batran

MAJOR STUDIES TO WATCH CANCER VACCINES INTerpath-001 Can individualised mRNA neoantigens help prevent melanoma relapse? KRAS DIRECTED KRASCENDO-1 Will a head-to-head trial raise the standard for KRAS G12C NSCLC? DRUG RESISTANCE SAFFRON Can EGFR/MET biomarker selection overcome acquired resistance? BILIARY TRACT CANCER HARMONi-GI1 Can a PD-1/VEGF bispecific improve first-line BTC care? ANTIBODY–DRUG CONJUGATES TroFuse-005 What role will novel ADCs have in recurrent endometrial cancer? PERIOPERATIVE THERAPY VOLGA Can an ADC–immunotherapy strategy improve bladder cancer care? GASTROESOPHAGEAL CANCER CLARITY-Gastric 01 How far can CLDN18.2-directed treatment extend?

[Slide 1] Targeting RAS in PDAC KRAS has historically been considered undruggable, but now we have >90 RAS-directed agents in clinical development and 3 FDA-approved direct RAS inhibitors RAS·GDP OFF · inactive GEF (e.g. SOS1) GDP → GTP exchange · activation RAS·GTP ON · active GAP (e.g. NF1) GTP hydrolysis → GDP + Pi · inactivation Simanshu DK et al. Cell. 2017; Punekar SR et al. Nat Rev Clin Oncol. 2022; Holderfield M, et al. Nature. 2024; rasinhibitors.com (accessed Oct 2026). GDP, guanosine diphosphate; GTP, guanosine triphosphate; GEF, guanine nucleotide exchange factor (e.g. SOS1); GAP, GTPase-activating protein (e.g. NF1); Pi, inorganic phosphate; RAF–MEK-ERK and PI3K–AKT, downstream signaling pathways; PDAC: pancreatic ductal adenocarcinoma. Monica Niger [Slide 2] Why a G12D-selective inhibitor, now? Selectivity for G12D spares wild-type RAS Wider therapeutic window less on-target toxicity Potential for safer combinations in earlier lines LBA85: HRS-4642 Plus Chemotherapy ± Adebrelimab as Perioperative Therapy in KRAS G12D-Mutant Pancreatic Cancer: Preliminary Results of a Phase 2 Study Can a G12D inhibitor be safely integrated into perioperative treatment? 3137RO: Safety and Efficacy of INCB161734, a Novel Oral KRAS G12D Inhibitor, in Combination with Chemotherapy in Patients (pts) with Advanced/Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Can we have a full-dose combination of chemotherapy and a G12D inhibitor? KRAS, Kirsten rat sarcoma viral oncogene homologue; PDAC, pancreatic ductal adenocarcinoma; pts, patients; RAS, rat sarcoma. Monica Niger [Slide 3] Take-home messages LBA85: HRS-4642 + chemotherapy ± adebrelimab, resectable disease Can a G12D inhibitor be safely integrated into perioperative treatment? • First perioperative experience with a G12D-selective inhibitor ± checkpoint inhibitors in PDAC • Promising activity and surgical safety • Caveats: small single-arm studies, uncertainty of activity endpoints and their surrogacy, immature survival • Next step: These data combined with the evidence in advanced disease support a randomized neoadjuvant trial • Open question: any role of adebrelimab? 3137RO: INCB161734 + chemotherapy, advanced disease Can we have a full-dose combination of chemotherapy and a G12D inhibitor? • Feasibility + good delivery of INCB161734 with both backbones may be a plus compared to daraxonrasib. • Promising activity and PFS at 6 months with both backbones • Caveats: immature follow-up and survival data • Chemotherapy RDI around 50%: dose, schedule and prophylaxis to optimize; the DAWN-303 Phase III randomized trial will directly compare safety and efficacy with chemotherapy alone • Next step: strong rationale for the neoadjuvant space PFS, progression-free survival; RDI, relative dose intensity. Monica Niger [Slide 4] What is next for KRAS G12D-mutant PDAC across earlier settings? Neoadjuvant / perioperative | Surgery | Adjuvant | Metastatic · first line NCT07240766 Ph II · N = 40 BR, KRAS G12D HRS-4642 + GnP + nimotuzumab, perioperative (single arm) NCT07691593 ¶ Ph II · N = 60 Non-metastatic HRS-4642 + NALIRIFOX ± adebrelimab, neoadjuvant R0 / R1 resection RASolute 304 NCT07252232 Ph III · N = 500 Resected after periop chemo; any RAS Daraxonrasib vs observation DAWN-303 NCT07522073 Ph III · N = 588 INCB161734 + investigator's chemo vs placebo + chemo NCT07232875 Ph III · N = 588 HRS-4642 + GnP vs placebo + GnP RASolute 305 NCT07621718 Ph III · N = 670 Zoldonrasib + mFOLFIRINOX or GnP vs placebo + chemo NCT07409272 Ph III · N = 614 Setidegrasib + mFOLFIRINOX or NALIRIFOX vs placebo + chemo NCT07656376 ¶ Ph II/III · N = 465 DN022150 + GnP vs placebo + GnP RASolute 309 NCT07805954 Ph III · N = 400 Zoldonrasib + daraxonrasib vs GnP (chemo-free option) RASolute 303 NCT07491445 Ph III · N = 900 Daraxonrasib ± GnP vs GnP · any RAS (chemo-free option) VS-7375 Ph III · planned 2026 VS-7375 + anti-EGFR vs VS-7375 + GnP vs SoC chemotherapy (chemo-free option) KRAS G12D-selective inhibitor / degrader Pan-RAS(ON) inhibitor ¶ Not yet recruiting. BR = borderline resectable; GnP = gemcitabine + nab-paclitaxel; SoC: Standard of Care N = planned enrollment. Sources: ClinicalTrials.gov; Verastem press release, 14 Oct 2026. Accessed 24 Oct 2026. Monica Niger

[Slide 1] Discussion 1678RO & 1680RO From combining therapies… …to engineering immunity. Phase 3 LEAP-012 Study of Lenvatinib Plus Pembrolizumab Versus Dual Placebo With Transarterial Chemoembolization for Unresectable Nonmetastatic Hepatocellular Carcinoma: Long-Term Overall Survival Results Josep M. Llovet1; Richard S. Finn2; Zhenggang Ren3; Yabing Guo4; Guohong Han5; Hailan Lin6; Sadahisa Ogasawara7; Ji Hoon Kim8; Haitao Zhao9; Chuan Li10; David C. Madoff11; R. Mark Ghobrial12; Anthony B. El-Khoueiry13; Arndt Vogel14; Xiang Peng15; Kalgi Mody16; Leonid Dubrovsky15; David Adelberg15,*; Masatoshi Kudo17 1680RO Phase I study of C-CAR031 (AZD7003), a GPC3-targeted TGFβRIIDN armoured autologous CAR-T, in advanced hepatocellular carcinoma: Updated results Qi Zhang1,2, Qihan Fu1,2, Wanyue Cao1,2, Jiaqi Huang3, Andy Zou4, Yihong Yao5, Yixin Hao4, Qijie Jian4, Jack Ashton6, Joana Hauser7, Xiao Qu8, Serena De Vita9, Tingbo Liang1,2 Anna Saborowski [Slide 2] Conclusions presented Conclusions • LEAP-012 met its primary end point of PFS but did not show OS benefit at IA3 • A median OS of approximately 40 months sets a new benchmark for trial design in unresectable, nonmetastatic HCC • The safety profile of lenvatinib plus pembrolizumab remains consistent with previous reports and earlier analysis of LEAP-012 Personal conclusions LEAP-012 was an important trial and adds relevant information regarding combination therapies in TACE-able HCC Lenvatinib plus pembrolizumab and TACE - will not become standard of care in intermediate HCC - high ORR observed across all combination trials may facilitate conversion to curative treatment in selected patients, but needs to be shown prospectively • increased toxicity must be carefully weighed against potential benefits on an individual patient level • great to see that mOS of 40 months is feasible in early/intermediate HCC, depending on baseline characteristics Anna Saborowski [Slide 3] Secondary Endpoints Impressive ORR: 44.4% and DCR >90 …but DOR disappoints: 4.4 mo (CI: 2.9-7.4) Qi Zhang, 1680RO, ESMO 2026 High ORR does not translate into extended DOR „Horizon of expectations“ for alternative approaches: Agent / trial | Strategy / treatment | Population / sample size | ORR | Median DOR IL-15-armoured CAR-T1 | GPC3-targeted CAR-T cells | n=12 | 33% | Not provided BGB-B20332 | GPC3 × 4-1BB bispecific antibody | n=94 overall ORR | 22-36% | 6 mo DOR (N=27): 79.2 MRG006A3 | GPC3-targeted ADC | n=12 High-GPC3 subgroup | 33.3% | 4.2 months TKIs/ICI in further line Phase 3 RESORCE4 | Regorafenib vs placebo | 2L after sorafenib n=379 vs 194 | 6.6% vs 2.6% | 5.9 vs 5.6 months CELESTIAL5 | Cabozantinib vs placebo | 2L or 3L after sorafenib n=470 vs 237 | 4.0% vs 0.4% | Not reported IMbrave2516 | Atezolizumab + TKI vs TKI alone | 2L after atezo + bev n=279 vs 278 | 7.5% vs 5.8% | 10.2 vs 6.9 months Anna Saborowski 1: Steffin et al., Nature, Vol 637, 2025; 2: Hong Jae Chon @ ESMO2026; 3: Hong Zhao, J Clin Oncol 44, 3028 (ASCO 2026); 4: Bruix et al, Lancet. 2017;389(10064):56–66; 5: Abou-Alfa et al, N Engl J Med. 2018;379(1):54–63.; 6: Vogel et al, J Clin Oncol. 2026;44(16_suppl):4002.

Overall Survival in Third-Line and Later Setting Median overall survival (months) | Control arm | Experimental arm Apatinib 2016 | 4.7 | 6.5 ATTRACTION-2 2017 | 4.1 | 5.3 JAVELIN Gastric 300 2018 | 5.0 | 4.6 TAGS 2018 | 3.6 | 5.7 INTEGRATE IIa 2024 | 4.0 | 4.5 CLARITY-Gastric01 2026 | 5.0 | 10.0 CLARITY-Gastric01 is a real step forward for our patients Randomized Trials ordered by year of primary report Li J, et al. J Clin Oncol, 2016; Kang YK, et al. Lancet, 2017; Bang YJ, et al. Ann Oncol, 2018; Shitara K, et al. Lancet Oncol, 2018; Pavlakis N, et al. J Clin Oncol, 2025; Xu RH, et al. ESMO Congress, 2026; LBA7 Salah-Eddin Al-Batran

Proportion of patients (%) ; Months 0-108 Single curve flat at 100% with censoring marks from ~40 to ~103 months Number at risk (censored) 0: 111 (0) | 12: 111 (0) | 24: 111 (0) | 36: 111 (0) | 48: 96 (16) | 60: 51 (60) | 72: 29 (82) | 84: 16 (95) | 96: 4 (107) | 108: 0 (111) Survival table Endpoint: Not printed on image (caption describes zero events; endpoint label absent) Neoadjuvant ipilimumab + nivolumab (single arm) | 111

1975P HCB301-101: Early Safety and Disease Control From a Phase 1 Study of a Tri-Functional SIRPα/PD-L1/TGF-β Biologic in Advanced Solid Tumors Ji Zhu, William Jeffrey Edenfield, Xigang Hu, Li Sun, Shuaishuai Zhang, Langtian Abigail Yu, Wei Ji, Chih-Yi Hsieh, Alvin Luk 1 Zhejiang Cancer Hospital; 2 Greenville Hospital System University Medical Center; 3 Zhujiang Hospital of Southern Medical University; 4 Xuzhou Central Hospital; 5 HanchorBio Inc.; 6 Hanchor Biopharma Inc. BACKGROUND The Challenge: Interdependent Immune Suppression in IO-Refractory Tumors Innate Checkpoint SIRPα-CD47: Inhibits macrophage phagocytosis; Reduce antigen presentation Adaptive Checkpoint PD-1/PD-L1: Induces T-cell exhaustion; Impairs effector function Stromal Exclusion TGF-β: Restricts T cell infiltration; Dampens macrophage and T cell activation Multicompartment Immune Resistance Requires Coordinated Checkpoint Blockade HCB301: A tri-specific SIRPα-PD-L1-TGF-β fusion protein designed for integrated innate, adaptive, and stromal immune modulation METHODS Phase 1 Dose-Escalation Study of HCB301 (NCT06487624) Open-label, multi-regional first-in-human study with BOIN-guided dose escalation BOIN Design: Target toxicity rate ϕ=0.25 Dose levels: 0.3, 0.6, 0.9, 1.2, 2.4, 4.8, 9.6, 15 mg/kg (0.3 mg/kg lead-in) All cohorts utilized 0.3 mg/kg step-up dosing prior to target dose administration. * Protocol amended to include an intermediate 0.9 mg/kg cohort. Treatment: Cycle 0 Day1: Step-up Dosing (0.3 mg/kg). Cycle 1 Day1 (7 days later): Target Dose weekly Population: Advanced solid tumors; Relapsed/refractory classical Hodgkin lymphoma (cHL) Primary Objectives: Evaluate safety & tolerability; Determine the MTD and RP2D Secondary/Exploratory Objectives: Preliminary antitumor activity (ORR, DCR, DOR, PFS, OS); Pharmacokinetics following single and repeat dosing; CD47 Receptor Occupancy (RO); Immunogenicity (ADA); Pharmacodynamic and predictive biomarkers RESULTS (as of July 2026) Baseline • 29 patients enrolled: 0.3 mg/kg: N=5; 0.6 mg/kg: N=13; 1.2 mg/kg: N=6; 0.9 mg/kg: N=5 • Median Age: 57.5 years • Median prior lines of systemic therapy: 4 Antitumor Activity (n= 21 efficacy evaluable) • Stable disease: 8/21 (38.1%) • Disease stabilization across multiple solid tumor types, including: > 0.6 mg/kg: HCC, CRC, hypopharyngeal carcinoma > 0.9 mg/kg: Cholangiocarcinoma, CRC > 1.2 mg/kg: CRC, pelvic malignancy, sarcoma. • Longest SD duration: Approximately 4 months. Figure 1. Patients Achieving Stable Disease by HCB301 Dose Level: 0.6 mg/kg 3; 0.9 mg/kg 2; 1.2 mg/kg 3 Safety • Grade 1-2 TEAEs: 86.0%; TRAEs Grade 1-2: 85.6% • Two DLTs: Grade 4 thrombocytopenia (1.2 mg/kg) • Thrombocytopenia: 25 patients; 85 events • Anemia: 17 patients; 30 events • Lymphopenia: 11 patients; 41 events • Infusion-related reactions: 14 patients; 33 events Note: Cytopenias were predominantly low-grade. No cumulative anemia signal was observed. Platelet declines were often rapid and transient, warranting close monitoring. Safety findings informed enhanced monitoring, step-up dosing, and evaluation at intermediate doses. Table 1. Treatment-Emergent Adverse Events of Interest (n=29) AE Term | Incidence n (%) | Grade 1-2 events n (%) | Total events (n) Thrombocytopenia | 17 (58.6%) | 41 (62.1%) | 66 Anemia | 13 (44.8%) | 32 (91.4%) | 35 Lymphopenia | 8 (27.6%) | 20 (66.7%) | 30 Infusion Related Reaction | 8 (27.6%) | 23 (95.8%) | 24 CONCLUSION • Early feasibility was demonstrated for HCB301, a tri-specific SIRPα–PD-L1–TGFβ immunotherapy targeting innate, adaptive, and stromal immune suppression. • Preliminary disease control was observed in heavily pretreated patients (8/21; 38.1%). • Predominantly low-grade cytopenias, with Grade 4 thrombocytopenia emerging as the key dose-limiting toxicity. • Further safety evaluation and dose optimization are needed to define the therapeutic window and guide future development. Study Sponsor: HanchorBio

Pre-specified DFS Analysis: ctDNA Positive vs ctDNA Negative Camupepimut treatment effect was consistent in ctDNA+ and ctDNA- n=119 | Prespecified: ctDNA Positive vs Negative ctDNA: Negative — Camupepimut (–) vs Observation (–): HR: 0.51 (0.25-1.02); P=0.0280 ctDNA: Positive — Camupepimut (+) vs Observation (+): HR: 0.57 (0.22-1.48); P=0.0489 Curve labels: Camupepimut, ctDNA- Median: Not Reached Observation, ctDNA- Median: 21.2 months Camupepimut, ctDNA+ Median: 4.3 months Observation, ctDNA+, Median: 1.9 months Y-axis: Disease-free Survival (%); X-axis: Months (0–30) At risk (months 0, 3, 6, 9, 12, 15, 18, 21, 24, 27) Camupepimut ctDNA –: 62, 57, 50, 42, 37, 35, 21, 14, 5, 0 Observation ctDNA –: 31, 24, 20, 19, 17, 16, 12, 8, 3, 0 Camupepimut ctDNA +: 20, 13, 7, 1, 1, 1, 1, 0, 0, 0 Observation ctDNA +: 6, 2, 1, 1, 0, 0, 0, 0, 0, 0 Eileen M. O'Reilly, MD, FASCO Survival table Endpoint: Disease-free survival by ctDNA status (pre-specified) Camupepimut, ctDNA- | 62 | Not Reached Observation, ctDNA- | 31 | 21.2 months Camupepimut, ctDNA+ | 20 | 4.3 months Observation, ctDNA+ | 6 | 1.9 months HR: ctDNA-: 0.51; ctDNA+: 0.57 HR CI: ctDNA-: 0.25-1.02; ctDNA+: 0.22-1.48 P: ctDNA-: P=0.0280; ctDNA+: P=0.0489

[Slide 1] Diagnosis & ABC staging | 1 Surgery or chemo first? | 2 Which regimen? | 3 Restaging: resect? Patient 1: Who benefits from neoadjuvant therapy? UNPUBLISHED Pooled PREOPANC trials, NCCN-resectable PDAC A | OS for NAT versus US NAT vs US: HR, 0.66 (0.53 to 0.83) Time after randomization (months) No. at risk (cumulative no. censored) 410 (0) 292 (0) 190 (1) 109 (32) 51 (73) 12 (104) 107 (0) 65 (0) 37 (0) 20 (0) 12 (0) 7 (3) B | Difference in 3-year OS P interaction = 0.024 NAT superior / US superior 64 to 80 years Age at randomization (years) Benefit of neoadjuvant therapy grows with age Significant from 64 to 80 years Interaction P = 0.024 Patient 1, 70 years: within the range of benefit MY VIEW For patient 1: neoadjuvant chemotherapy NAT, neoadjuvant therapy; US, upfront surgery. NCCN resectable, n = 517: neoadjuvant arms combined (410) vs upfront surgery (107, PREOPANC), partly non-randomised, PREOPANC-2 had no upfront-surgery arm. Verkolf EMM et al., under review Survival table Endpoint: OS, neoadjuvant therapy (NAT) vs upfront surgery (US), pooled PREOPANC trials, NCCN-resectable PDAC NAT (neoadjuvant arms combined) | 410 Upfront surgery | 107 HR: 0.66 HR CI: 0.53 to 0.83 [Slide 2] Diagnosis & ABC staging | 1 Surgery or chemo first? | 2 Which regimen? | 3 Restaging: resect? Patient 3: Resection or ablative radiation? Ablative radiotherapy vs patient 3's predicted survival | MSKCC ablative RT (n = 119, from start of RT) | Patient 3: surgery (TAPS model, from restaging) Median OS | 18 mo | 23 mo 2-year OS | 38% | 49% 3-year OS | NR | 33% MY VIEW: For patient 3: resection or ablative radiotherapy PREOPANC-4, phase III RCT, started September 2026 Locally advanced PDAC, favourable response ≥ 3 months induction chemotherapy, no RECIST progression, ECOG 0–1 R Surgical exploration - intent to resect MR-guided SABR - 5 × 10 Gy Primary endpoint: overall survival, n = 230 NR, not reported. Reyngold M et al. JAMA Oncol 2021;7:735-8 (MSKCC; 75 Gy/25 fx or 67.5 Gy/15 fx); PREOPANC-4: Dutch Pancreatic Cancer Group [Slide 3] 4 How to drain? | 5 Resect: worth the risk? | 6 Surgery, systemic first or locoregional? Patient 4, GBC: How to drain hilar obstruction? TESLA: randomised phase III trial, 5 Dutch centres, n = 148 P: Unresectable hilar obstruction I: Primary percutaneous stenting C: Endoscopic biliary drainage O: Major complication within 90 days, death included | Percutaneous stenting | Endoscopic drainage | P Major complication | 40% | 66% | P=0.002 Cholangitis | 3% | 32% | P<0.001 Reintervention | 14% | 49% | P<0.001 Papilla not crossed, no external drain UNPUBLISHED - For patient 4: primary percutaneous stenting, then systemic therapy GUIDELINE - ESGE 2026: endoscopic drainage preferred 51% perihilar CCA, 29% iCCA, 8% gallbladder cancer, 21% ≥ 80 years. Intention to treat. NCT06671418 UEG Week 2026, LB03. Pilot: Franssen S et al. JHEP Rep 2025;7:101541 [Slide 4] 4 How to drain? | 5 Resect: worth the risk? | 6 Surgery, systemic first or locoregional? Locoregional treatments for BTC Systemic therapy GUIDELINE Systemic backbone Gem-cis + durva or pembro 15% 3-year overall survival TOPAZ-1 HR 0.74, 3-y 14.6% vs 6.9% KEYNOTE-966 HR 0.83, 3-y 13% Additional locoregional treatments Small lesion: MWA - 1% Small lesion in hilum: SBRT - 10% Large solitary lesion: SIRT - 20% Multifocal disease: HAIP chemo - 70% MY VIEW - Share of patients with each tumour pattern HAIP chemo for liver-confined iCCA: 3-year OS 28%, 5-year OS 15% in 4 phase II trials Liver transplantation Perihilar CCA < 5% eligible 5-year OS 51% Depending on national protocol Intrahepatic CCA < 5% eligible 5-year OS 57% Only in trials: TRIATHLON RCT MY VIEW - For patient 6: systemic therapy, consider locoregional treatment Figure: Méndez Romero A, J Hepatol 2026; Oh DY, J Hepatol 2025; Kelley RK, Lancet 2023; pump: Rousian M, Alessandris R, J Hepatol 2026 Transplant: Mayo protocol, intention to treat, n = 211 (Tan EK, J Gastrointest Surg 2020); Methodist-MD Anderson, n = 18 (McMillan RR, Am J Transplant 2022)

[Slide 1] Background • BGB-B2033 is a novel, rationally designed IgG-based GPC3 x 4-1BB bispecific antibody that binds a unique epitope of 4-1BB – GPC3: tumor-associated antigen highly expressed in multiple tumors, including in ~90% of HCC with any staining(1) – Activates 4-1BB on CD8+ T-cells only in the presence of GPC3-expressing tumor cells, enabling targeted tumor activity – Has an engineered Fc region designed to extend PK exposure while maintaining localized immune activation(2) – Demonstrated ~linear PK and prominent PD effect of soluble 4-1BB increase at dose levels ≥300 mg(3) [Diagram] Activated T cell | Signal 1 | Signal 2 | Cytokines (e.g., IFN-γ, IL2) | TCR/CD3 complex | MHC I | 4-1BB clustering | GPC3 | Tumor cell | GPC3x41BB bsAb Unique 4-1BB binder: specifically designed epitope for efficient receptor clustering and T cell co-stimulation Silenced Fc: mitigate FcγRs-mediated liver toxicity; YTE mutation extends half-life and prolongs exposure Potent GPC3 anchor: strong affinity provides tumor specific 4-1BB activation 1. Ishiguro et al, Sci. Transl. Med. 2017,9, eaal4291. 2. Li et al. Poster #6009 AACR 2025. 3. Chon et al. J Clin Oncol 2026,44:3016. bsAb, bispecific antibody; GPC3, glypican-3; HCC, hepatocellular carcinoma; PD, pharmacodynamics; PK, pharmacokinetics; YTE, M252Y/S254T/T256E. Presenter: Hong Jae Chon, MD, PhD [Slide 2] Study Design (NCT06427941) Phase 1/2 study of BGB-B2033 alone or in combination with tislelizumab with or without bevacizumab in patients with advanced solid tumors Key Eligibility Criteria • Patients with aHCC who received at least 1 line of systemic therapy • Child Pugh A • BCLC C or BCLC B that is not amenable to or progressed after locoregional therapy and not amenable to curative treatment • ECOG PS 0-1 • At least 1 measurable lesion by RECIST 1.1 • Archival tissue or fresh biopsy for GPC3 testing Monotherapy Dose Escalation and Dose Optimization BGB-B2033 Q3W in Patients with aHCC This pooled analysis Dose Escalation: 1000 mg Q3W n=10 | 600 mg Q3W n=14 | 300 mg Q3W n=15 Dose Optimization (R): 900 mg Q3W n=28 | 450 mg Q3W n=27 Total Enrollment = 94 1-100 mg Q3W n=21 Last patient enrolled: 25 August 2026 | DCO: 22 September 2026 | Median study follow-up was 5.5 (range, 0.3-16.7) months IV infusion Q3W | Infusion duration Cycle 1/2: 60 ± 5 min; Cycle ≥3: 30 ± 5 min Endpoints Primary: • Safety • Recommended dose for expansion • MTD Secondary: • Objective response rate by investigator per RECISTv1.1 • Pharmacokinetics/pharmacodynamics • Immunogenicity aHCC, advanced hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; DCO, data cut-off; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GPC3, Glypican-3; MTD, maximum tolerate dose; Q3W, every 3 weeks; R, randomized; RECIST, Response Evaluation Criteria in Solid Tumors Presenter: Hong Jae Chon, MD, PhD [Slide 3] Consistent Antitumor Activity with BGB-B2033 was Observed Across Dose Escalation and Optimization Cohorts 300 mg Q3W n=14a Escalation cORR: 28.6% 450 mg Q3W n=25a Optimization cORR: 36.0% 600 mg Q3W n=14a Escalation cORR: 35.7% 900 mg Q3W n=27a Optimization cORR: 22.2% 1000 mg Q3W n=10a Escalation cORR: 30.0% Y-axis: Best Change From Baseline (%); legend: Progressive Disease | Stable Disease | Partial Response | Complete Response • 450 mg RP2D was selected based on linear PK, exposure-efficacy, PD plateau, and a flat exposure-safety relationship Data cut-off: 22 September 2026 a Investigator assessed and efficacy-evaluable patients cORR, confirmed objective response rate; PD, pharmacodynamic; PK, pharmacokinetic; RP2D, recommended phase 2 dose. ☆ The patient has an unconfirmed partial response, remains on treatment and is awaiting confirmation Presenter: Hong Jae Chon, MD, PhD [Slide 4] BGB-B2033 Was Well Tolerated, With Limited Grade ≥3 TRAEs Parameter, n (%) | Dose escalation 300 mg n=15 | 600 mg n=14 | 1000 mg n=10 | Dose optimization 450 mg n=27 | 900 mg n=28 | Total (N=94) Any TEAEs | 11 (73.3) | 9 (64.3) | 10 (100) | 26 (96.3) | 22 (78.6) | 78 (83.0) Leading to Discontinuation | 0 | 0 | 2 (20.0) | 1 (3.7) | 0 | 3 (3.2) Grade ≥3 TEAEs | 5 (33.3) | 1 (7.1) | 6 (60.0) | 5 (18.5) | 4 (14.3) | 21 (22.3) Any Serious TEAEs | 0 | 2 (14.3) | 4 (40.0) | 5 (18.5) | 4 (14.3) | 15 (16.0) Any TRAEs | 9 (60.0) | 7 (50.0) | 5 (50.0) | 18 (66.7) | 15 (53.6) | 54 (57.4) Leading to Discontinuation | 0 | 0 | 1 (10.0)a | 1 (3.7)b | 0 | 2 (2.1) Grade ≥3 TRAEs | 2 (13.3) | 0 | 1 (10.0) | 1 (3.7) | 1 (3.6) | 5 (5.3) IMAEs | 2 (13.3)c | 1 (7.1)d | 0 | 5 (18.5)e | 4 (14.3)f | 12 (12.8) TRAEs Occurring in >5% Patients (Grade 1-2 | Grade ≥3): AST increased 18.1% | 2.1% ALT increased 11.7% | 1.1% IRR 8.5% Platelet decreased 7.4% Bilirubin increased 6.4% Pyrexia 6.4% Hypothyroidism 5.3% Data cut-off: 22 September 2026 a Drug eruption (grade 3). b IRR (grade 2). c Hypothyroidism (n=2). d Rash (n=1). e Hypothyroidism (n=2), maculo-papular rash (n=1), rash (n=2). f Hypothyroidism (n=1), immune-mediated hepatitis (n=1), pancreatitis (n=1; grade 3), rash (n=1). AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; IMAE, immune-mediated adverse events; IRR, infusion-related reaction; TEAE, treatment emergent adverse event; TRAE, treatment-emergent treatment-related adverse event. Presenter: Hong Jae Chon, MD, PhD

3530O - Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (LARC): The phase 3 UNION trial Speakers Zhen Yu Lin (Wuhan, China) Lecture Time 11:10 - 11:20 Abstract Background Despite the use of neoadjuvant chemoradiotherapy, recurrence and distant metastasis remain common in LARC. Effective immunotherapy-based strategies for the predominantly proficient mismatch repair/microsatellite-stable population remain limited. UNION is the first phase 3 trial to evaluate a neoadjuvant strategy incorporating radiotherapy, immunotherapy, and chemotherapy in LARC. Here we present the prespecified event-free survival (EFS) analysis. Methods Patients with cT3-4 or N+ rectal adenocarcinoma (tumor located ≤10 cm from the anal verge) were randomly assigned (1:1) to receive short-course radiotherapy (SCRT; 25 Gy/5f; experimental group) or long-course chemoradiotherapy (50.4 Gy/28f with concurrent capecitabine 825 mg/m2 twice daily; standard of care group) followed by 2 neoadjuvant cycles and 6 adjuvant cycles of capecitabine and oxaliplatin (CAPOX). The experimental group additionally received neoadjuvant and adjuvant camrelizumab (200 mg, day 1) since CAPOX treatment for up to 17 cycles. The primary endpoint was blinded independent review committee (BIRC)-assessed pathological complete response rate. Key secondary endpoints with prespecified α allocation were investigator-assessed EFS and overall survival. Results Between July 2021 and March 2023, 231 patients were randomized to the experimental group (n=113) and standard of care group (n=118). As of October 1, 2025, the median follow-up duration was 36.8 months (95% CI, 34.8-37.8) and 35.6 months (95% CI, 34.3-36.9), respectively. The 3-year EFS rate was significantly higher in the experimental group compared with standard of care (91.3% [95% CI, 83.9-95.4] vs 77.4% [95% CI, 67.9-84.4], hazard ratio=0.33 [95% CI, 0.15-0.71], P=0.0029). BIRC-assessed EFS consistently favored the experimental group. During the whole treatment period, the incidence of grade ≥3 treatment-related adverse events was 51.3% (59/115) and 48.2% (54/112), respectively. Conclusions UNION is the first phase 3 trial to demonstrate a significant improvement in EFS with an immunotherapy-based regimen in LARC. This neoadjuvant strategy represents a new standard of care.

Figure 2: Change in ctDNA (%) from baseline to Week 2 for each of the 28 patients with evaluable data Median decrease: -86% Values: -100% | -99% | -99% | -97% | -97% | -96% | -94% | -93% | -92% | -90% | -90% | -89% | -88% | -87% | -85% | -82% | -79% | -78% | -74% | -73% | -72% | -70% | -69% | -64% | -54% | -39% | -34% | -26% LRM 350 mg | LRM 700 mg Anti-CCR5 (Leronlimab) Figure 3: change in ctDNA levels (measured in MTM/mL) from baseline to Week 4 observed in CLOVER study compared to control data from real world database* TAS-102 (n = 30) vs TAS-102 + Bev (n = 75): p = 0.01 (as bracketed) TAS-102 + Bev (n = 75) vs TAS-102 + Bev + LRM (n = 12): p = 0.0005 * Y-axis is truncated at 269.5% (tallest whisker); 11 points from TAS-102+BEV group above above the Y-axis limit not shown. CLOVER Trial

EFS PER BIRC ASSESSMENT AND OS ◆ Per BIRC assessment, the 3-year EFS rate was 87.2% (95% CI 78.2-92.7) in the experimental group versus 73.7% (95% CI 63.6-81.4) in the standard-of-care group (HR 0.41 [95% CI 0.21-0.81]). Concordance between the BIRC and investigator assessments strengthens the robustness of the findings. ◆ OS was reported descriptively without formal hypothesis testing, as the data maturity was expected to be ≤10% at this stage. The 3-year OS rate was 96.3% (95% CI 90.4–98.6) in the experimental group versus 89.8% (95% CI 81.7–94.4) in the standard-of-care group (HR 0.35 [95% CI 0.11–1.10]). Secondary endpoint: BIRC-assessed EFS Number of events/patients | 3-year rate (95% CI) Experimental group 12/113 | 87.2% (78.2–92.7) Standard of care group 28/118 | 73.7% (63.6–81.4) Stratified HR 0.41 (95% CI 0.21–0.81) Number at risk (Number censored) Experimental group 113 (0) 108 (4) 104 (7) 96 (11) 95 (12) 92 (14) 88 (16) 88 (16) 82 (20) 75 (27) 64 (38) 54 (48) 35 (66) 21 (80) 13 (88) 6 (95) 2 (99) 0 (101) Standard of care group 118 (0) 112 (6) 99 (12) 96 (14) 89 (17) 83 (18) 77 (19) 75 (20) 73 (21) 68 (26) 57 (36) 47 (45) 33 (59) 23 (69) 13 (77) 5 (85) 1 (89) 0 (90) Key secondary endpoint: OS Number of events/patients | 3-year rate (95% CI) Experimental group 4/113 | 96.3% (90.4–98.6) Standard of care group 11/118 | 89.8% (81.7–94.4) Stratified HR 0.35 (95% CI 0.11–1.10) Number at risk (Number censored) Experimental group 113 (0) 111 (1) 111 (1) 110 (1) 110 (1) 110 (1) 110 (1) 110 (1) 110 (1) 109 (1) 98 (12) 83 (26) 58 (51) 37 (72) 20 (89) 9 (100) 1 (108) 0 (109) Standard of care group 118 (0) 116 (2) 115 (2) 115 (2) 114 (3) 113 (4) 111 (4) 108 (6) 106 (7) 105 (8) 98 (14) 73 (35) 51 (57) 31 (77) 17 (90) 6 (101) 2 (1)[sic] 0 (107) BIRC, blinded independent review committee; EFS, event-free survival; OS, overall survival; CI, confidence interval; HR, hazard ratio. Presenter: Zhenyu Lin Survival table Endpoint: BIRC-assessed EFS and OS (descriptive) Experimental group | 113 Standard of care group | 118 HR: EFS (BIRC) 0.41; OS 0.35 HR CI: EFS 0.21–0.81; OS 0.11–1.10 Landmark rates: 3 years EFS (BIRC): Experimental group 87.2% (CI 78.2–92.7) | Standard of care group 73.7% (CI 63.6–81.4) 3 years OS: Experimental group 96.3% (CI 90.4–98.6) | Standard of care group 89.8% (CI 81.7–94.4)

[Slide 1] [Stage photo of presented slide] Concomitant somatostatin analog use in second-line therapy of gastroenteropancreatic neuroendocrine tumors: Survival results from the retrospective retroSAUNA study Dr Siddharth Chhajlani et al. Study Design • Retrospective study (471 pts) • In 22 NET expert centers • Between 2010 and 2025 (15 years) • Endpoints: PFS and OS Patients with non-functional GEP NET grade 1-2 with progression on 1L SSA → PRRT-substudy: 2L PRRT (n=292) → with 2L SSA (n=167) / w/o 2L SSA (n=125) → TT-substudy: 2L TT (*) (n=179) → with 2L SSA (n=126) / w/o 2L SSA (n=53) (*) with everolimus or sunitinib [Highlighted box] • Reason to continue the SSA ? • Change during the study period? Study Population | PRRT substudy (n=292): PRRT w/o SSA (n=125) | PRRT with SSA (n=167) | TT substudy (n=179): TT w/o SSA (n=53) | TT with SSA (n=126) Median age at start 2L (years, IQR) | 67 (59-73) | 66 (59-73) | 66 (58-72) | 65 (57-73) Sex (n, %) Female | 56 (45%) | 80 (48%) | 23 (43%) | 57 (45%) Sex Male | 69 (55%) | 87 (52%) | 30 (57%) | 69 (55%) NET grade (n, %) NET G1 | 34 (27%) | 58 (35%) | 14 (26%) | 34 (27%) NET G2 | 91 (73%) | 109 (65%) | 39 (74%) | 92 (73%) Location primary (n, %) pancreas | 51 (41%) | 45 (27%) | 42 (79%) | 66 (52%) small intestine | 50 (40%) | 88 (53%) | 3 (6%) | 36 (29%) other GI | 24 (19%) | 34 (20%) | 8 (15%) | 24 (19%) [Slide 4] [Wide stage photo of presented slide] High antitumor activity was seen across DLL3 subgroups, with a trend toward deeper and more durable benefit in the DLL3high subgroup [Waterfall: Best % change from baseline in sum of diameters; DLL3high / DLL3low / ◆ Ongoing] | All (N=44) | DLL3high (n=24) | DLL3low (n=20) ORR, % (95% CI) | 77.3 (63.0–87.2) | 87.5 (69.0–95.7) | 65.0 (43.3–81.9) PR, n (%) | 34 (77.3) | 21 (87.5) | 13 (65.0) DCR, % (95% CI) | 90.9 (78.8–96.4) | 95.8 (79.8–99.3) | 85.0 (64.0–94.8) SD, n (%) | 6 (13.6) | 2 (8.3) | 4 (20.0) PD, n (%) | 4 (9.1) | 1 (4.2) | 3 (15.0) Median DoR, months (95% CI)* | 12.5 (5.5–NC) | NC (5.1–NC) | 7.0 (5.5–NC) 12-month DoR rate, % (95% CI)† | 51 (29–73) | 54 (24–85) | 46 (13–79) Median PFS, months (95% CI)* | 7.7 (6.0–14.5) | 9.5 (6.0–NC) | 7.6 (4.6–9.0) 12-month PFS rate, % (95% CI)† | 35 (17–54) | 47 (18–75) | 27 (5–49) At data cut-off (February 3, 2026), 22 patients remained on obrixtamig treatment (DLL3high: n=15; DLL3low: n=7) *Median duration of follow up in the overall population: DoR, 7.1 months (95% CI: 4.9–11.0); PFS, 11.6 months (95% CI: 5.8–14.3); †Kaplan–Meier estimates CI, confidence interval; DLL3, delta-like ligand 3; DCR, disease control rate; DoR, duration of response; NC, not calculable; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease Jaume Capdevila

1998P : Germline IL7 variant confers organ-specific susceptibility to thyroid and joint immune-related adverse events independent of cancer type and treatment regimen Mustafa Saleh, Amin Nassar, Zeyun Lu, Elias Bou Farhat, Sarah Abou Alaiwi, Marc Machaalani, Michel AlChoueiri, Alexander Gusev, Toni K. Choueiri Results 1. Interaction testing across irAE categories and terms revealed a significant interaction with irAE term at G1+ (p=0.030), identifying thyroid autoimmunity and inflammatory arthritis as the phenotypes driving the IL7 association. 2. Fine-Gray analyses confirmed robustness with thyroid disorder sHR 2.51, p=0.013, arthralgia/arthritis sHR 3.02, p=0.005). Stepwise phenotype selection identified pancreatitis as an additional component of the IL7-associated cluster, jointly reaching p=9.12×10[illegible] (N=142 events). 3. No interaction with age, sex, tumor mutational burden (TMB), ICI regimen, or cancer type was significant, placing this germline effect outside conventional clinical risk factors. 4. IL7 risk allele did not associate with maximum irAE grade, establishing a grade-agnostic immune toxicity. In pts with high TMB, association was markedly amplified: thyroid disorder and arthralgia/arthritis HR 5.13, p=5.82×10[illegible], with pancreatitis added HR 5.66, p=8.05×10[illegible]. Methods [illegible]aracterized the IL7 germline association across 1,619 ICI-treated patients [illegible] DFCI receiving anti-PD(L)1 monotherapy (N=1,360), anti-CTLA4 (N=15), [illegible]ation ICI (N=244) spanning 16 cancer types. @Mustafajsalehmd @DrChoueiri @SashaGusevPosts Email: Mustafa_jamalsaleh@dfci.harvard.edu

Established ADCs in GI cancers HER2 is so far the only validated ADC target in GI oncology Agent | Target / payload | Setting | Trial | Key outcome | Ref Trastuzumab deruxtecan | HER2 / DXd | HER2+ gastric/GEJ, ≥3L | DESTINY-Gastric01 (rand. ph 2) | ORR 51% vs 14%; mOS 12.5 vs 8.4 mo | [8] Trastuzumab deruxtecan | HER2 / DXd | HER2+ gastric/GEJ, 2L | DESTINY-Gastric04 (ph 3) | mOS 14.7 vs 11.4 mo (HR 0.70); ILD 14% | [9,24] Disitamab vedotin | HER2 / MMAE | HER2 IHC 2+/3+ gastric, ≥3L (China, 2021) | RC48-C008 (ph 2) | ORR 24.8%; mPFS 4.1 mo; mOS 7.9 mo | [10,24] Trastuzumab deruxtecan | HER2 / DXd | HER2+ biliary tract | HERB (ph 2) | ORR 36.4% | [11] Trastuzumab deruxtecan | HER2 / DXd | HER2 IHC 3+ solid tumours (tumour-agnostic) | PanTumor02, Lung01, CRC02 (n = 192) | ORR 46.9–52.9%; FDA approval | [12,24] Trastuzumab deruxtecan | HER2 / DXd | HER2+ mCRC, ≥3L | DESTINY-CRC02 (rand. ph 2) | ORR 37.8% (5.4 mg/kg); mPFS 5.8 mo | [15,23] [8] Shitara K, et al. N Engl J Med 2020;382:2419–30. [9] Shitara K, et al. N Engl J Med 2025;393:336–48. [10] Peng Z, et al. Cancer Commun 2021;41:1173–82. [11] Ohba A, et al. J Clin Oncol 2024 (HERB; PMID 39102634). [12] Meric-Bernstam F, et al. J Clin Oncol 2024;42:47–58. [15] Raghav K, et al. Lancet Oncol 2024;25:1147–62. [23] Bartolini M, et al. ESMO Open 2026;11:108304. [24] Khan U, Shah MA. Cancer 2026;e70419 J.M.L. Roodhart

[Slide 1] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ IKF-AIO RAMIRIS Phase III Study design Key eligibility criteria - Advanced/ metastatic esophagogastric adenocarcinoma - Progression during/ after first-line platinum + fluoropyrimidine therapy - Prior taxane treatment R 1:1 Stratification: - Progression ≤3 vs >3 months after end of first-line therapy - ECOG performance status 0 vs. 1 Arm A: Ramucirumab 8 mg/ kg i.v., d1+15, q28 + FOLFIRI* i.v., d1+15, q28 Arm B: Ramucirumab 8 mg/kg i.v., d1+15, q28 + Paclitaxel 80 mg/m² i.v., d1, 8, 15, q28 Study endpoints Co-primary: Overall survival (OS); Objective overall response rate (ORR) Secondary: Progression-free survival (PFS); Disease control rate (DCR); Safety; Quality of life Study assumptions OS: Aim: 6.0 -> 8.6 months; target HR = 0.70; one-sided α = 0.020; 80% power; n= 318 required ORR: Aim: 10% -> 25%; one-sided α = 0.005; 80% power, n = 298 required -> Final sample size: n = 318 Study cohort n = 319 randomized n = 317 in ITT population (2 patients excluded) n = 304 in PP population Randomized multicenter phase III trial in 47 sites in Germany, Austria and Italy from Oct 2019 until Oct 2024 * FOLFIRI: irinotecan 180 mg/m²; 5-FU bolus 400 mg/m²; leucovorin 400 mg/m²; 5-FU 2400 mg/m² over 46 h Magdalena Scheck Magdalena Scheck FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for taxane-pretreated patients with advanced or metastatic gastroesophageal adenocarcinoma-Final results of the phase III IKFs602/AIO RAMIRIS Study ALMERIA AUDITORIUM - HALL 9 [Slide 2] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ Co-Primary endpoints OS and ORR (ITT population) [KM curve: Survival Probability vs Survival time (months)] | Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 Median OS (95% CI) | 8.7 [7.6, 10.6] | 7.5 [6.2, 9.3] HR (95.8% CI) P-value | 0.95 [0.74, 1.22] 0.33 Events n (%) | 139 (88%) | 137 (86%) Median follow-up (mo) | 8.2 | 6.6 No. at risk Arm A: 158 101 46 30 12 7 5 3 2 1 1 Arm B: 159 91 45 26 16 8 4 3 2 1 0 | Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 | P-value ORR | 40 (25%) | 36 (23%) | 0.29 CR | 4 (3%) | 0 (0%) PR | 36 (23%) | 36 (23%) SD | 61 (39%) | 61 (38%) PD | 33 (21%) | 46 (29%) Missing | 24 (15%) | 16 (10%) OS: HR from unstratified Cox proportional hazards model; p-value from unstratified log-rank test (one-sided). + Censored. The results for OSS and OR for ITT population are consistent with those for PP population. Magdalena Scheck Magdalena Scheck FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for taxane-pretreated patients with advanced or metastatic gastroesophageal adenocarcinoma-Final results of the phase III IKFs602/AIO RAMIRIS Study ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: OS (co-primary), ITT Arm | N | Median | Median CI Arm A Ram + FOLFIRI | 158 | 8.7 | 7.6, 10.6 Arm B Ram + Pacli | 159 | 7.5 | 6.2, 9.3 HR: 0.95 HR CI: 95.8% CI 0.74, 1.22 P: 0.33 (one-sided log-rank) [Slide 3] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ Progression-free survival ITT Population | Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 Median PFS (95% CI) | 5.5 [4.0, 6.3] | 3.7 [2.9, 4.2] HR (95.8% CI) P-value | 0.71 [0.56, 0.90] 0.002 Events n (%) | 142 (90%) | 149 (94%) No. at risk (partly illegible): Arm A 158 63 20 5 4 1 1 1 0; Arm B 159 43 7 3 1 0 PP Population | Arm A Ram + FOLFIRI n = 150 | Arm B Ram + Pacli n = 154 Median PFS (95% CI) | 5.6 [4.1, 6.4] | 3.7 [2.9, 4.3] HR (95.8% CI) P-value | 0.69 [0.55, 0.88] 0.001 Events n (%) | 138 (92%) | 148 (96%) No. at risk (partly illegible): Arm A 150 63 20 5 4 1 1 1 0; Arm B 154 43 7 3 1 0 Ram plus FOLFIRI resulted in a numerical improvement in PFS vs. SOC HR from unstratified Cox proportional hazards model; p-value from unstratified log-rank test (one-sided). + Censored. SOC standard of care Magdalena Scheck Magdalena Scheck FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for taxane-pretreated patients with advanced or metastatic gastroesophageal adenocarcinoma-Final results of the phase III IKFs602/AIO RAMIRIS Study ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: PFS (secondary), ITT and PP Arm | N | Median | Median CI ITT Arm A Ram + FOLFIRI | 158 | 5.5 | 4.0, 6.3 ITT Arm B Ram + Pacli | 159 | 3.7 | 2.9, 4.2 PP Arm A Ram + FOLFIRI | 150 | 5.6 | 4.1, 6.4 PP Arm B Ram + Pacli | 154 | 3.7 | 2.9, 4.3 HR: ITT 0.71; PP 0.69 HR CI: 95.8% CI ITT 0.56, 0.90; PP 0.55, 0.88 P: ITT 0.002; PP 0.001 (one-sided) [Slide 4] 16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ Safety TRAEs occurring in ≥10% of patients in either arm Ram + FOLFIRI (Grade ≥3 | Grade ≤2) vs Ram + Paclitaxel (Grade ≤2 | Grade ≥3), incidence in % Fatigue: 4 | 34 vs 21 | 3 Nausea: 4 | 31 vs 15 | 1 Diarrhea: 3 | 31 vs 11 | 1 Neutrophil count decreased: 15 | 9 vs 7 | 12 Mucositis: 3 | 19 vs 5 Vomiting: 2 | 15 vs 5 Hypertension: 9 | 4 vs 6 | 7 Platelet count decreased: 2 | 11 vs 2 | 1 Anorexia: 11 vs 4 | 1 Peripheral sensory neuropathy: 1 | 8 vs 20 | 1 Proteinuria: 6 vs 12 | 1 Legend: TRAE Grade ≤ 2; TRAE Grade ≥3 Safety population consists of all randomized patients who received at least one dose of study medication. Magdalena Scheck Magdalena Scheck FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for taxane-pretreated patients with advanced or metastatic gastroesophageal adenocarcinoma-Final results of the phase III IKFs602/AIO RAMIRIS Study ALMERIA AUDITORIUM - HALL 9

[Slide 1] 4303 P Cell-free chromatin epigenomic profiling enables non-invasive subtyping of pancreatic cancer Marc Eid*, Karl Semaan*, Damien Vasseur, Gunsagar Gulati, Ji-Heui Seo, Alexander Jordan, Leigh Culnane, Antoine Hollebecque, Antoine Italiano, Toni Choueiri, Kimberly Perez, Jonathan Nowak, Andrew Aguirre#, Brian Wolpin#, Sylvan Baca#, Matthew Freedman#, Harshabad Singh# *co-first authors #co-senior authors Background • Classical (C) and basal [obscured] subtypes are key prognostic biomarkers of pancrea[obscured] (PDAC) and may predict response to treatmen[obscured] • Current subtyping m[obscured] • Here, we report a n[obscured] PDAC subtyping based on profiling circulati[obscured] Methods • PDAC PDX model sub[obscured] bulk RNA-seq and the PurIST algorithm. • ChIP-seq for the pos[obscured] H3K27ac and H3K4me3, MeDIP-se[obscured] PDAC PDX. [remaining methods obscured by presenter] Widespread epigenomic differences between classical and basal-like PDAC A PDX (epi-)genomic datasets: RNA-seq (N=28), ATAC (N=27), H3K27ac (N=28), H3K4me3 (N=27), MeDIP (N=28); Subtype: Basal-like, Classical; Source: DFCI, MDACC B [genome tracks: CLDN18, GATA6, HNF1A, KRT6A, PTGES, GNAI2] C [volcano plots: H3K27ac, H3K4me3, ATAC-seq, MeDIP-seq; up in basal-like / up in classical] Validation of the epigenomic signature in an independent PDAC PDX cohort A [heatmaps H3K27ac, ATAC, H3K4me3; PDAC subtype Basal-like / Classical] B C:B ratio, Classical vs Basal-like: H3K27ac p= 0.0036; H3K4me3 p= 0.0036; MeDIP-seq p= 0.039 PIES enables accurate subtyping of PDAC from patient plasma A 1 mL of plasma; Cohorts: DFCI (N=26); Clinical trials: NCT03520790 (N=29), MOSCATO-02 (N=27) B ctDNA fraction, Classical vs Basal-like, p= 0.32 C AUPRC Classical vs. basal-like: All samples (AUPRC = 0.88); ≥3% ctDNA (AUPRC = 0.91); <3% ctDNA (AUPRC = 0.86) Patients with low PIES (basal-like) have worse outcomes A Progression-free survival multivariable Cox model (Adjusted Hazard Ratio, log scale) PIES: Low vs High 2.99 (1.30-6.90); p=0.01 ctDNA (%) 7.68 (0.73-81.00); p=0.09 Liver met: Yes vs. No 1.54 (0.69-3.42); p=0.29 ECOG: 1-2 vs. 0 1.49 (0.75-2.97); p=0.26 CA 19-9 (U/mL) 1.00 (1.00-1.00); p=0.44 Arm: GnP vs FFX 0.57 (0.26-1.28); p=0.17 B Circulating epigenome – All patients: High PIES vs Low PIES; Log-rank p= 0.046 Number at risk: High PIES 34 24 18 10 5 2; Low PIES 16 10 5 1 1 0 C Circulating epigenome – FFX arm: High PIES vs Low PIES; Log-rank p= 0.00014 Number at risk: High PIES 13 12 8 3 1 0; Low PIES 4 1 0 0 0 0 D Low PIES per circulating epigenome: FFX vs GnP; Log-rank p= 0.0097 Number at risk: FFX 4 1 0 0 0; GnP 12 9 5 1 1 Conclusion • In a multi-institutional cohort, PIES distinguished C and B PDAC subtypes with an AUPRC of 0.88 across all plasma samples, irrespective of ctDNA fraction, increasing to 0.91 in samples with ≥3% ctDNA. • PIES provides a non-invasive approach for determining PDAC transcriptional subtypes, with the potential to facilitate broader implementation of molecular subtyping and inform treatment selection. @marc_eid @KarlSemaan @SylvanBacaLab Presented at ESMO 2026 | Madrid, Spain [Slide 2] 4303 P Cell-free chromatin epigenomic profiling enables non-invasive subtyping of pancreatic cancer Marc Eid*, Karl Semaan*, Damien Vasseur, Gunsagar Gulati, Ji-Heui Seo, Alexander Jordan, Leigh Culnane, Antoine Hollebecque, Antoine Italiano, Toni Choueiri, Kimberly Perez, Jonathan Nowak, Andrew Aguirre#, Brian Wolpin#, Sylvan Baca#, Matthew Freedman#, Harshabad Singh# Background • Classical (C) and basal (B) transcriptional subtypes are key prognostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) and may predict response to treatment1-3. • Current subtyping methods rely on tissue biopsies. • Here, we report a novel non-invasive approach for PDAC subtyping based on profiling circulating tumor chromatin. Methods • PDAC PDX model su[obscured] identified using bulk RNA-seq and the PurIST algorithm. • ChIP-seq for the post-translational modifications H3K27ac and H3K4me3, MeDIP-seq, and ATAC-seq, were performed on PDAC PDX. • Differentially marked regions between C and B subtypes were identified using DESeq2 and were validated in an independent cohort of PDAC PDX models4. • cfChIP-seq for H3K27ac and H3K4me3, cfMeDIP-seq, and low-pass whole-genome sequencing (LPWGS) were performed on 1 mL of plasma from patients with metastatic pancreatic cancer. • ctDNA fraction was estimated from LPWGS data using ichorCNA. • A C/B score was derived for each epigenetic feature in individual patients' plasma samples by calculating the ratio of aggregate signal at classical:basal regions. • For each plasma sample, we combined the different epigenetic features to develop the Pancreatic Integrated Epigenomic Score (PIES). • Performance was evaluated using area under the precision-recall curve (AUPRC). • Progression-free survival (PFS) was compared between patients with Low and High PIES using multivariable Cox regression adjusted for ctDNA fraction, liver metastasis, ECOG, CA19-9, and treatment regimen. References 1. Singh H, et al. Clin Cancer Res. 2024;30:4932–4942. 2. Wenric S, et al. JCO Precis Oncol. 2025;9. 3. Dilly J, et al. Cancer Discov. 2024;14:2135–2161. 4. Lomberk G, et al. Nat Commun. 2018;9:1978. Dana-Farber Cancer Institute | Harvard Medical School | Gustave Roussy | MD Anderson Cancer Center [Right-hand results panels obscured by viewers; same poster as s1]

[Slide 1] TRIDENTE: study design Multicenter, single-arm phase II study RAS wild-type/BRAF V600E-mutant mCRC -> EC-based therapy -> PD -> ≥1 of SoC -> PD -> ENCO + BINI + CET (N = 21) • Encorafenib 300 mg QD • Binimetinib 45 mg BID • Cetuximab initially 400 mg/m2 and subsequently 250 mg/m2 QW • CR or PR by RECIST v1.1 • PD within 4 weeks after the last ENCO administration ≥ 4 months Key eligibility criteria • ≥ 20 years of age • ECOG PS 0-1 • Refractory or intolerant to fluoropyrimidine-based chemotherapy including oxaliplatin or irinotecan • Measurable disease per RECIST v1.1 • Primary endpoint: Investigator-assessed objective response rate (ORR)* • Secondary endpoints: Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety • Exploratory biomarker analysis: circulating tumor DNA at baseline and disease progression * Statistics: Threshold 3%, expected 20%, α = 0.05 (one-sided), power 80% ctDNA analysis using Guardant360® Daisuke Kotani, MD, PhD Clinical trial information: jRCTs031210511 [Slide 3] Progression-free survival and overall survival Progression-free survival Median PFS 2.8 months (95% CI, 2.4 – 3.9 months) PFS probability; Months after registration 0 3 6 9 12 Number at risk 21 8 1 1 0 Overall survival Median OS 9.6 months (95% CI, 4.9 – 17.0 months) OS probability; Months after registration 0 3 6 9 12 15 18 21 24 Number at risk 21 19 15 11 7 6 4 2 0 Median follow-up: 9.5 months (range, 1.6 – 23.5 months) Daisuke Kotani, MD, PhD Survival table Endpoint: PFS and OS (single arm, ENCO + BINI + CET) Arm | N | Median | Median CI ENCO + BINI + CET - PFS | 21 | 2.8 months | 95% CI, 2.4 – 3.9 months ENCO + BINI + CET - OS | 21 | 9.6 months | 95% CI, 4.9 – 17.0 months [Slide 4] ORR by baseline ctDNA status ORR (%) Detectable baseline plasma BRAF V600E and no resistance alterations* | 30.0% (3/10) | 95% CI, 6.7 - 65.2% Undetectable baseline plasma BRAF V600E or any resistance alterations* | 10.0% (1/10) | 95% CI, 0.3 - 44.5% Baseline ctDNA analysis was available in 20 patients (95.2%). There was no statistically significant difference between the groups (p = 0.284). When baseline BRAF V600E detection status was not considered, the ORR was 25.0% in patients without resistance alterations and 12.5% in those with resistance alterations. * Resistance alterations were defined as mutations in KRAS, NRAS, MAP2K1, or EGFR, or amplifications in MET, BRAF, or KRAS. Daisuke Kotani, MD, PhD

16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ FORTITUDE-102: Overall Survival by FGFR2 Amplification Status FGFR2 Amplified (Placebo vs Bema) Median OS, months (95% CI): Bema 16.6 (11.8–NE); Placebo 8.0 (5.4–18.8) OS HR (95% CI): 0.67 (0.34–1.32) P = 0.24 Number at Risk (0, 6, 12, 18, 24, 30 months) Placebo 22 14 8 5 0 0 Bema 25 21 14 6 1 0 FGFR2 Non-amplified (Placebo vs Bema) Median OS, months (95% CI): Bema 17.3 (13.7–19.8); Placebo 14.5 (13.0–16.0) OS HR (95% CI): 0.84 (0.61–1.15) P = 0.27 Number at Risk (0, 6, 12, 18, 24, 30 months) Placebo 128 113 69 26 8 0 Bema 121 99 74 33 8 1 Key findings: • In FORTITUDE-102, adding bemarituzumab to mFOLFOX6/CAPOX + nivolumab yielded a numerically greater treatment effect in FGFR2-amplified vs non-amplified patients (OS HR 0.67 [95% CI 0.34–1.32] vs 0.84 [0.61–1.15]; PFS HR 0.77 [95% CI 0.40–1.49] vs 0.87 [0.65–1.17]) • Results from the placebo arm suggest FGFR2 amplification may confer poor prognosis FGFR2 amplification identified by tissue and/or ctDNA NGS. Presented by: Zev Wainberg, MD [Speaker panel: Zev Wainberg — Efficacy of bemarituzumab in patients with advanced gastric and gastroesophageal junction cancer (GC/GEJ) by FGFR2 amplification status: Exploratory biomarker analysis from FORTITUDE-101 (F101) and FORTITUDE-102 (F102)] ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: OS by FGFR2 amplification status (exploratory) Arm | N | Median | Median CI FGFR2 amplified: Bema + mFOLFOX6/CAPOX + nivolumab | 25 | 16.6 mo | 11.8–NE FGFR2 amplified: Placebo + mFOLFOX6/CAPOX + nivolumab | 22 | 8.0 mo | 5.4–18.8 FGFR2 non-amplified: Bema + mFOLFOX6/CAPOX + nivolumab | 121 | 17.3 mo | 13.7–19.8 FGFR2 non-amplified: Placebo + mFOLFOX6/CAPOX + nivolumab | 128 | 14.5 mo | 13.0–16.0 HR: 0.67 (amplified); 0.84 (non-amplified) HR CI: 0.34–1.32 (amplified); 0.61–1.15 (non-amplified) P: 0.24 (amplified); 0.27 (non-amplified)

[Slide 1] DFS and OS in the mITT and PP Population Median follow-up: 52.8 months Disease-free survival — mITT population Modified intention-to-treat: 4-month vs 6-month groups · Center-stratified Cox model · N=1023 HR, 1.01 (95% CI, 0.82–1.25) One-sided P = 0.006 · NI met · margin HR 1.33 Legend: 6 months / 4 months No. at risk (months 0/12/24/36/48/60/72/84/96) 6 months: 512 / 450 / 394 / 358 / 209 / 95 / 40 / 13 / 5 4 months: 511 / 462 / 397 / 352 / 210 / 106 / 44 / 15 / 6 Disease-free survival — PP population Per protocol: 4-month group completing 5–6 cycles vs 6-month group completing 8 cycles · Center-stratified Cox model · N=736 HR, 0.96 (95% CI, 0.75–1.25) One-sided P = 0.007 · NI met · margin HR 1.33 No. at risk 6 months: 309 / 271 / 238 / 219 / 126 / 57 / 24 / 7 / 2 4 months: 427 / 388 / 332 / 296 / 175 / 86 / 33 / 12 / 5 Overall survival — mITT population Modified intention-to-treat: 4-month vs 6-month groups · Center-stratified Cox model · N=1023 HR, 1.06 (95% CI, 0.84–1.34) No. at risk 6 months: 512 / 489 / 439 / 401 / 229 / 107 / 48 / 14 / 5 4 months: 511 / 496 / 450 / 392 / 230 / 113 / 44 / 15 / 6 Overall survival — PP population Per protocol: 4-month group completing 5–6 cycles vs 6-month group completing 8 cycles · Center-stratified Cox model · N=736 HR, 0.95 (95% CI, 0.71–1.27) No. at risk 6 months: 309 / 295 / 264 / 240 / 137 / 66 / 26 / 8 / 2 4 months: 427 / 418 / 380 / 333 / 194 / 92 / 33 / 12 / 5 Dazhi Xu Survival table Endpoint: DFS (mITT, primary NI analysis); also DFS PP, OS mITT, OS PP 6 months XELOX (mITT) | 512 4 months XELOX (mITT) | 511 HR: 1.01 HR CI: 0.82-1.25 P: One-sided P = 0.006 (NI met, margin HR 1.33) [Slide 2] Conclusion • Four-month adjuvant XELOX: noninferior to the standard 6-month regimen for 3-year DFS with fewer high-grade adverse events and higher treatment completion rates • These data support 4-month XELOX as an evidence-based option for selected patients with stage II-IIIB gastric cancer after R0 D2 gastrectomy [Slide 3] What does LOMAC tell us? Adjuvant XELOX in GEA: 4 months is non-inferior to 6 months in terms of 3-year DFS and is associated with less neuropathy. DFS: ITT population Disease-free survival — mITT population Modified intention-to-treat: 4-month vs 6-month groups · Center-stratified Cox model · N=1023 Primary endpoint: 3-year DFS rate 6 months: 70.8% 4 months: 69.2% (-1.6%) HR, 1.01 (95% CI, 0.82–1.25) One-sided P = 0.006 · NI met · margin HR 1.33 No. at risk (months 0/12/24/36/48/60/72/84/96) 6 months: 512 / 450 / 394 / 358 / 209 / 95 / 40 / 13 / 5 4 months: 511 / 462 / 397 / 352 / 210 / 106 / 44 / 15 / 6 Toxicities: fewer TRAEs in 4 mos group Endpoint | 4 months | 6 months Grade ≥ 3 AEs | 8.4% | 15.0% Grade ≥ 3 sensory neuropathy | 0.4% | 5.9% Grade ≥ 3 fatigue | 0% | 1.4% Feng Wang 15 Survival table Endpoint: DFS (mITT); primary endpoint 3-year DFS rate 6 months XELOX | 512 4 months XELOX | 511 HR: 1.01 HR CI: 0.82-1.25 P: One-sided P = 0.006 (NI met, margin HR 1.33) Landmark rates: 3 years: 6 months XELOX 70.8% | 4 months XELOX 69.2%

[Slide 1] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Combination of Bezuclastinib + Sunitinib Inhibits the Broad Spectrum of Primary and Secondary KIT Mutations Bezuclastinib: Next-generation oral KIT inhibitor1-5 • In combination with sunitinib, covers the broad spectrum of KIT mutations1-4 • High selectivity & lack of off-target effects allow for combination2,3 Pivotal results from Peak trial assessing safety & efficacy of 2nd line bezuclastinib + sunitinib vs sunitinib in patients with GIST5: • Significantly superior efficacy, including mPFS of 16.5 months (vs 9.2 months for sunitinib monotherapy) & 46% ORR —PFS2 median not reached with combination vs 21.0 months with sunitinib alone • No new safety risks identified with the combination Exon* | Imatinib | Sunitinib | Regorafenib | Ripretinib | Bezuclastinib + Sunitinib [inhibition table for exons 9, 11, 13, 14, 17, 18 shown as colour shading: None / Moderate / Strong] Here, we present results from part 2 of the Peak clinical trial evaluating the efficacy & safety following crossover to bezuclastinib + sunitinib combination in patients with advanced GIST who progressed on sunitinib monotherapy GIST, gastrointestinal stromal tumor; KIT, proto-oncogene c-kit; mPFS, median progression-free survival; ORR, objective response rate; PFS2, progression-free survival 2. 1. Wagner AJ, et al. CTOS Annual Meeting; November 16–19, 2022; Vancouver, Canada. 2. Wagner AJ, et al. JAMA Oncol. 2021;7(9):1343-1350. 3. Guarnieri A, et al. AACR Annual Meeting; April 8–13, 2022; New Orleans, LA. 4. Wagner A, et al. ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. 5. Wagner A, et al. ASCO Annual Meeting; May 31-June 4, 2024; Chicago, IL. *This table of inhibitors is based on preclinical data Robin Jones Phase 3 peak crossover: Bezuclastinib + sunitinib combination following sunitinib monotherapy in patients with GIST MALAGA AUDITORIUM - HALL 3 [Slide 2] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Peak (NCT05208047) Is a Global, Randomized, Open-Label, Phase 3 Trial This analysis evaluated patients in Peak who crossed over to receive bezuclastinib + sunitinib combination after progressing on sunitinib monotherapy Patients 1:1 Randomized Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n=204) Sunitinib 37.5 mg QD (n = 209) EOT/BICR confirmed PD Crossover Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 128) EoT/BICR confirmed PD Crossover evaluation PFS ORR Safety 30-Day Safety and Post-Treatment Follow-up BICR, Blinded Independent Central Review; EoT, end of treatment; ORR, objective response rate, PD, disease progression; PFS, progression-free survival; QD, once daily Data cutoff: Sep 30, 2025 Robin Jones Phase 3 peak crossover: Bezuclastinib + sunitinib combination following sunitinib monotherapy in patients with GIST MALAGA AUDITORIUM - HALL 3 [Slide 3] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Patients Had Improved Disease Control With Crossover Therapy Compared With Sunitinib Monotherapy Progression-free Survival (%) Time (months) mPFS in 128 Crossover Patients Following Crossover to Combination 7.4 months 95% CI (5.6-11.0) • In patients who crossed over to combination therapy: • mPFS with 2nd-line sunitinib was 5.7 months (95% CI: 3.8-7.3 months) • mPFS with subsequent combination therapy was 7.4 months (95% CI: 5.6-11.0 months) CI, confidence interval; mPFS, median progression-free survival. Data cutoff: Sep 30, 2025 Robin Jones Phase 3 peak crossover: Bezuclastinib + sunitinib combination following sunitinib monotherapy in patients with GIST MALAGA AUDITORIUM - HALL 3 Survival table Endpoint: Progression-free survival after crossover (single arm) Arm | N | Median | Median CI Crossover to bezuclastinib + sunitinib | 128 | 7.4 mo | 5.6-11.0 Same patients on prior 2nd-line sunitinib (reference) | 128 | 5.7 mo | 3.8-7.3 [Slide 4] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Patients Had Improved Response Rate With Crossover Therapy Compared With Sunitinib Monotherapy • In patients who crossed over to combination therapy: • ORR to 2nd-line sunitinib was 20.3% (95% CI: 13.7%-28.3%) (n=26) • ORR to subsequent combination therapy was 29.7% (95% CI: 21.9%-38.4%) (n=38) • 80% (n=102) of patients entering the crossover had not achieved an objective response on sunitinib monotherapy (best response of SD or PD) • In patients with best response of disease progression on sunitinib, ORR was 56% with combination • 2 patients with PD on monotherapy achieved a CR on combination Sunitinib 37.5 mg QD (n = 209) Crossover Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 128) CR, complete response; ORR, objective response rate; PD, progressive disease; QD, once daily; SD, stable disease. Data cutoff: Sep 30, 2025 Robin Jones Phase 3 peak crossover: Bezuclastinib + sunitinib combination following sunitinib monotherapy in patients with GIST MALAGA AUDITORIUM - HALL 3

[Slide 1] LBA48 – EMERALD-3 PHASE 3 STUDY Study Design and Endpoints [Embedded study schema, small text:] Study population: Confirmed HCC not amenable to curative treatment, but eligible for embolisation; Child-Pugh class A; ECOG PS 0 or 1; No extrahepatic disease; Excludes Vp3 and Vp4; No prior systemic therapy Stratification factors: Geographical region (Japan vs Asia [excluding Japan] vs rest of the world); Prior palliative locoregional therapy (1 >6 months vs 1 ≤6 months vs none); Baseline tumour burden (>Up-to-7 vs ≤Up-to-7) R, N=760 Arm A: STRIDE + L + TACE (n=293) Arm B: STRIDE + TACE (n=175) Arm C: TACE (n=292) *Participants were randomised 1:1:1 to Arms A, B and C until each arm reached 175 participants; following this, randomisation continued 1:1 to Arms A and C until reaching ~275 participants per arm Primary endpoint: PFS for Arm A vs C per RECIST v1.1 by BICR Key secondary endpoints: OS for Arm A vs C; PFS for Arm B vs C per RECIST v1.1 by BICR; OS for Arm B vs C Other secondary endpoints included: PFS2, PROs, safety Post-hoc exploratory assessments: TTNT; Mean ALBI and Child-Pugh scores over the treatment period ➢ Positive phase 3 study ➢ Primary endpoint PFS ➢ Post-hoc exploratory analyses ➢ Liver function trajectory, efficacy, post-progression outcomes and safety by baseline liver function ➢ Liver function is a key factor for HCC management ➢ Liver function may be worsened by repeated TACE ➢ Liver decompensation is a competing risk of death across stages ➢ Post-progression treatment options and outcomes are challenging Pinato DJ. ESMO 2025; Celsa C et al. Hepatology 2024; Cabibbo G et al. Clin Cancer Res 2024 Lorenza Rimassa, MD [Slide 2] LBA48 – EMERALD-3 PHASE 3 STUDY Conclusions > Liver function remained stable over the treatment period with STRIDE ± L + TACE, with consistent patterns for subsequent anti-cancer therapy use, irrespective of baseline liver function > I agree > STRIDE ± L + TACE showed clinically meaningful improvements in post-progression outcomes (TTNT and PFS2), with favorable OS vs TACE, regardless of baseline ALBI grade > I agree, but OS data are not mature > Safety outcomes were broadly consistent with the overall study population, regardless of baseline ALBI grade > I agree, but shorter duration of systemic therapy and lower number of TACE in ALBI grade 2 group > These results support a STRIDE-based regimen in combination with TACE as a potential new treatment option for eeHCC > I agree, but we have to wait for OS for STRIDE+L+TACE; or how can/should we consider the available OS for STRIDE+TACE? Lorenza Rimassa, MD [Slide 3] 1679O – PHASE 1 STUDY OF BGB-B2033 BISPECIFIC AB Study Design and Baseline Characteristics [Embedded study design schematic: Monotherapy Dose Escalation and Dose Optimization, BGB-B2033 Q3W in Patients with aHCC; Key Eligibility Criteria; Endpoints (Primary: Safety, MTD...; Secondary: Objective response rate by investigator per RECIST v1.1, Pharmacokinetics/pharmacodynamics, Immunogenicity); Total Enrollment = 94; dose optimization 300 mg Q3W N=28 [?], 450 mg Q3W N=27 [?]; embedded baseline characteristics table - small text largely illegible] > 94 heavily pretreated patients > 39 dose escalation, 55 dose optimization > Median age 56.5, male 84%, Asian 87.2% > HBV-related HCC 87.2% > Median n. of prior treatment lines 2 (1-8) > ≥3 prior treatment lines 24.5% > Previous systemic therapies > Anti-PD-(L)1 93.6% > TKI 68.1% > Anti-PD-(L)1 and TKI 61.7% > Median follow-up 5.5 (0.3-16.7) months Lorenza Rimassa, MD [Slide 4] 1679O – PHASE 1 STUDY OF BGB-B2033 BISPECIFIC AB Conclusions > BGB-B2033, a first-in-class GPC3 x 4-1BB bispecific antibody, continues to demonstrate compelling antitumor activity in patients with heavily pretreated aHCC > I agree, although DCR, PFS, and OS data are not yet available and a longer follow up is needed > At the RP2D (450 mg Q3W), cORR was 36% and the 6-month DOR was 74% > The favorable tolerability profile is notable as patients with heavily pretreated aHCC… > I agree > Given the compelling antitumor activity and favorable safety profile, global registrational studies are planned to be initiated by the end of the year > Phase 3 study of BGB-B2033 vs investigator's choice of sorafenib or lenvatinib in patients with HCC who progressed on prior systemic treatment > I agree; high unmet medical need: immunotherapy combinations are available as first-line systemic treatment options, but no level 1 evidence therapies are available for previously treated patients Lorenza Rimassa, MD

OS BY BASELINE ALBI GRADE: STRIDE + TACE vs TACE* ALBI Grade 1 | STRIDE + TACE (n=105) | TACE* (n=111) Total OS events, n (%) | 30 (28.6) | 51 (45.9) Median OS, months (95% CI) | NC (37.8–NC) | 39.2 (28.0–NC) HR (95% CI) | 0.57 (0.36–0.90) OS maturity: 37.5% ALBI Grade 2 | STRIDE + TACE (n=70) | TACE* (n=64) Total OS events, n (%) | 39 (55.7) | 39 (60.9) Median OS, months (95% CI) | 27.9 (17.8–NC) | 20.4 (16.6–30.1) HR (95% CI) | 0.81 (0.52–1.26) OS maturity: 58.2% Proportion of participants alive (%) vs Time from randomisation (months) 0-45 Number of participants at risk (ALBI Grade 1) | 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 | 30 | 33 | 36 | 39 | 42 | 45 STRIDE + TACE | 105 | 100 | 98 | 97 | 94 | 87 | 85 | 80 | 77 | 73 | 60 | 37 | 18 | 10 | 4 | 0 TACE | 111 | 109 | 106 | 98 | 92 | 88 | 79 | 76 | 70 | 65 | 53 | 31 | 16 | 10 | 5 | 0 Number of participants at risk (ALBI Grade 2) | 0 | 3 | 6 | 9 | 12 | 15 | 18 | 21 | 24 | 27 | 30 | 33 | 36 | 39 | 42 | 45 STRIDE + TACE | 70 | 65 | 63 | 58 | 53 | 49 | 43 | 39 | 37 | 35 | 31 | 23 | 6 | 1 | 0 | 0 TACE | 64 | 57 | 50 | 50 | 46 | 43 | 35 | 30 | 27 | 27 | 22 | 11 | 4 | 2 | 1 | 0 DCO2: 23 Feb 2026. *Out of the first 175 participants randomised to this treatment arm. Circles represent censored observations. For participants with baseline ALBI grade 1, median (range) follow-up duration for OS was 31.0 (0.7–43.2) months for STRIDE+TACE and 29.4 (2.8–43.9) months for TACE; for participants with baseline ALBI grade 2, median (range) follow-up duration was 27.4 (0.5–39.6) months and 19.7 (0.5–44.0) months, respectively. Masatoshi Kudo, MD, PhD Survival table Endpoint: Overall survival by baseline ALBI grade (STRIDE + TACE vs TACE) Arm | N | Median | Median CI ALBI Grade 1 - STRIDE + TACE | 105 | NC | 37.8–NC ALBI Grade 1 - TACE | 111 | 39.2 | 28.0–NC ALBI Grade 2 - STRIDE + TACE | 70 | 27.9 | 17.8–NC ALBI Grade 2 - TACE | 64 | 20.4 | 16.6–30.1 HR: ALBI 1: 0.57; ALBI 2: 0.81 HR CI: ALBI 1: 0.36–0.90; ALBI 2: 0.52–1.26

[Slide 3] Among Patients With a Confirmed Responsea to BGB-B2033, Tumor Reductions Were Sustained Over Time Across Cohorts DOR (95% CI), % | 450 mg Q3W (n=9)a | All Patients (N=27)a 3-month | 88.9 (43.3-98.4) | 92.4 (73.0-98.1) 6-month | 74.1 (28.9-93.0) | 79.2 (56.9-90.8) Y-axis: Target Lesion Percent Change from Baseline (%); X-axis: Time from First Treatment (Months) Status: Ongoing (solid) | Discontinued (dashed) Data cut-off: 22 September 2026 aInvestigator-assessed confirmed responders. Presenter: Hong Jae Chon, MD, PhD [Slide 4] Conclusion 1 With longer follow up, BGB-B2033, a first-in-class GPC3 x 4-1BB bispecific antibody, continues to demonstrate compelling antitumor activity in patients with heavily pretreated aHCC 2 At the RP2D (450 mg Q3W), cORR was 36% and the 6-month DOR was 74% 3 The favorable tolerability profile is notable as patients with heavily pretreated aHCC often have underlying liver disease that limits therapeutic options 4 Given the compelling antitumor activity and favorable safety profile, global registrational studies are planned to be initiated by the end of the year aHCC, advanced hepatocellular carcinoma; cORR, confirmed objective response rate; DOR, duration of response; GPC3, glypican-3; ORR, objective response rate; RP2D, recommended phase 2 dose; Q3W, every 3 weeks Presenter: Hong Jae Chon, MD, PhD

16:15 - 17:45 Rapid oral 1: Gastrointestinal tumour, upper digestive CHAIRS: MARIA IGNEZ BRAGHIROLI, FENG WANG, LUCJAN WYRWICZ DFS and OS in the mITT and PP Population Median follow-up: 52.8 months Disease-free survival - mITT population Modified intention-to-treat: 4-month vs 6-month groups · Center-stratified Cox model · N=1023 HR, 1.01 (95% CI, 0.82-1.25) One-sided P = 0.006 · NI met · margin HR 1.33 No. at risk: 6 months 512 450 394 358 209 95 40 13 5; 4 months 511 462 397 352 210 106 44 15 6 Disease-free survival - PP population Per protocol: 4-month group completing 5-6 cycles vs 6-month group completing 8 cycles · Center-stratified Cox model · N=736 HR, 0.96 (95% CI, 0.75-1.25) One-sided P = 0.007 · NI met · margin HR 1.33 No. at risk: 6 months 309 271 238 219 126 57 24 7 2; 4 months 427 388 332 296 175 86 33 12 5 Overall survival - mITT population HR, 1.06 (95% CI, 0.84-1.34) No. at risk: 6 months 512 489 439 401 229 107 46 14 5; 4 months 511 496 450 392 230 113 44 15 6 Overall survival - PP population HR, 0.95 (95% CI, 0.71-1.27) No. at risk: 6 months 309 295 264 240 137 66 26 8 2; 4 months 427 418 380 333 194 92 33 12 5 Months since randomization (0-96) Dazhi Xu Dazhi Xu Four months of adjuvant XELOX versus six months in stage II-IIIB gastric cancer: The LOMAC randomized trial ALMERIA AUDITORIUM - HALL 9 Survival table Endpoint: DFS (primary, non-inferiority) and OS, mITT and PP 6 months XELOX (mITT) | 512 4 months XELOX (mITT) | 511 6 months XELOX (PP) | 309 4 months XELOX (PP) | 427 HR: DFS mITT 1.01; DFS PP 0.96; OS mITT 1.06; OS PP 0.95 HR CI: DFS mITT 0.82-1.25; DFS PP 0.75-1.25; OS mITT 0.84-1.34; OS PP 0.71-1.27 P: DFS mITT one-sided P=0.006 (NI met, margin HR 1.33); DFS PP one-sided P=0.007

GroundBBreaker 301 Study (NCT07836530) Phase 3 study of BGB-B2033 vs investigator's choice of sorafenib or lenvatinib in patients with HCC who progressed on prior systemic treatment Key Eligibility Criteria • Adults (≥18 years) with histologically confirmed HCC not amenable to curative surgical or locoregional therapies • GPC3 expression level for stratification • Previously treated with up to 2 systemic regimens, including PD-(L)1 inhibitors • Measurable disease per RECIST v1.1 • ECOG PS 0 or 1 • Adequate organ function N=492 R 1:1 BGB-B2033 • 450mg Q3W intravenous administration • Until disease progression, unacceptable toxicity, or other discontinuation criteria Investigator's choice • Sorafenib BID or lenvatinib QD • Until disease progression, unacceptable toxicity, or other discontinuation criteria Primary endpoint: OS Secondary endpoints: ORR, PFS, and DOR per BICR and investigator assessment | Safety | PROs BICR, blinded independent central review; BID, twice daily; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; GPC3, glypican-3; HCC, hepatocellular carcinoma; ORR, objective response rate; OS, overall survival; PD-(L)1, programmed cell death protein (ligand) 1; PFS, progression-free survival; PRO, patient-reported outcome; Q3W, every 3 weeks; QD, daily; RECIST, Response Evaluation Criteria in Solid Tumors. Presenter: Hong Jae Chon, MD, PhD

2879RO - Durvalumab plus definitive chemoradiotherapy versus definitive chemoradiotherapy in patients with locally advanced esophagus carcinoma: ARION PRODIGE 67 randomized phase 2 trial Speakers Marie-Anouchka Modesto (Toulouse, France) Lecture Time 17:09 - 17:14 Abstract Background In locally advanced or unresectable esophageal cancer, definitive chemoradiotherapy (CRT) is the standard of care (SoC) combining radiotherapy with platinum-based chemotherapy, resulting in a 2-year disease-free survival of 25%, which remains an unmet medical need. As immune checkpoint inhibitors increase survival in the metastatic setting, a multicentric, this open-label, comparative phase II ARION trial was designed to assess efficacy and safety of PD1/PDL1 blockade by durvalumab (D) added to SoC. Methods Patients (pts) ≥18 years old, WHO performance status ≤1, non-metastatic, locally advanced squamous cell carcinoma (SCC) or unresectable adenocarcinoma (ADK), (stratified by tumor stage, histology, centers) were randomized between arm A with 12 monthly 1500 mg (D) infusions added to SoC (IMRT 50 Gy/25 daily fractions over 5 weeks) and 6 cycles of FOLFOX regimen: oxaliplatin 85 mg/m2, Leucovorin 200 mg/m2, 5-FU 400 mg/m2 bolus then continuous 2400 mg/m2 over 46 h) or arm B (SoC). Primary endpoint was centrally reviewed progression-free survival (cPFS). Overall survival (OS), PFS and safety were secondary endpoints. 74 cPFS events were required to detect a hazard ratio (HR) of 0.55 with 90% power (10% one-sided alpha). Results Between May 2019 and May 2024, 112 pts were randomized (Arm A: SoC + D, n=58 / Arm B: SoC, n=54) in 13 French sites. Analysis was performed after a 24-month follow-up. Median age was 67 years, 68% were male, 77% were SCC, 70% had nodal extension. There was no significant difference between arms for cPFS, PFS and OS (table). Treatment-related adverse events (AE) were higher in arm A. Grade ≥ 3 AE rates were similar in both arms. Table: 2879RO | | Arm A (exp) 12-month rate [95%CI] | Arm B (SoC) 12-month rate [95%CI] | Adjusted HR* [95%CI] [80%CI] | 1-sided p-value | | cPFS | 48.6% [34.6; 61.3] | 48.9% [34.7; 61.7] | 0.91 [0.55; 1.49] [0.66; 1.25] | 0.351 | | PFS | 50.1% [36.2; 62.5] | 48.1% [33.7; 61.2] | 0.92 [0.56; 1.50] [0.67; 1.27] | 0.369 | | OS | 75.1% [61.6; 84.4] | 67.9% [53.6; 78.7] | 0.99 [0.59; 1.68] [0.70; 1.40] | 0.489 | *for Histological subtype, Stage Conclusions In this indication, Durvalumab with CRT compared to SoC did not improve PFS. There was no new safety signal. Longer survival, follow-up and predictive factors for treatment efficacy will be presented.

[Slide 1] 2423P - Systemic Therapy in Advanced Gastric Neuroendocrine Neoplasms (G-NENs): Real-World Evidence from the R-GETNE National Registry (G-NENCARE) María San-Román-Gil1*, Paula Jiménez-Fonseca2, Alejandro García-Álvarez3, Carlos González-Merino4, Guillermo Crespo-Herrero5, Alberto Carmona-Bayonas6, Marta Benavent-Viñuales7, Carlos López-López8, Vicente Alonso-Orduña9, Ángel Segura-Huerta10, Nieves Martínez-Lago11, Javier Gallego-Plazas12, Marta Llanos-Muñoz13, Laura Nosti-Martínez2, Sergio Pérez-Fernández3, Rocío García-Carbonero1,14 GETNE Grupo Español de Tumores Neuroendocrinos y Endocrinos | Hospital Universitario 12 de Octubre | i+12 Instituto de Investigación Hospital 12 de Octubre INTRODUCTION • Most gastric NENs are indolent type 1 NETs diagnosed at an early stage, so advanced cases are uncommon. • Advanced G-NENs are underrepresented in clinical trials, which limits the evidence available for clinical practice. • We analysed the efficacy of systemic therapy and prognostic factors in advanced G-NENs from the Spanish national registry R-GETNE. METHODS • 191 of 711 (26.9%) G-NENs patients presented with or developed advanced disease registered in R-GETNE by 37 participating Spanish centres (1998–2024) • Overall survival was assessed from metastatic onset (mOS), defined as the start of 1st-line systemic therapy, using the Kaplan–Meier method and compared with the log-rank test; hazard ratios were estimated with Cox regression models. RESULTS Baseline characteristics are summarized in Table 1. 191 patients: 61 NETs (32%), 107 NECs (56%) and 23 (12%) with unknown differentiation. NETs vs NECs: mOS 50m vs 9m (HR 3.39; p<0.001). NETs: Ki-67 was the main prognostic factor - mOS: 66m in G1, 64m in G2-low (3–10%), 34m in G2-high (11–20%), and 10m in G3 tumors (HR 1.76; p=0.021) – FIGURE 1. NECs: numerically longer mOS with Ki-67 <50% (17m vs 9m; HR 1.34; p=0.32) – FIGURE 2; lung metastases vs none predicted worse mOS: 4m vs 10m (HR 2.07; p=0.04). Treatment: SSA predominated in NETs and platinum-CT in NECs (Table 2; FIGURES 3–4). Table 1. Clinicopathological characteristics: G-NETs vs G-NECs Characteristic | NET (n=61) | NEC (n=107) | p | Total (n=191) (^) Age, median (range), years | 62 (21–85) | 70 (38–96) | 0.012 | 67 (21–96) Male / Female, % | 62.3 / 37.7 | 69.2 / 30.8 | 0.40 | 69.1 / 30.9 ECOG PS 0 / 1 / 2 / ≥3, % | 48.9 / 39.5 / 9.3 / 2.3 | 10.5 / 54.6 / 25.6 / 9.3 | <0.001 | 23.7 / 49.6 / 19.3 / 7.4 Stage (at diagnosis) I / II / III / IV, % | 5.1 / 8.5 / 10.1 / 76.3 | 0 / 1.9 / 14.0 / 84.1 | 0.018 | 1.6 / 4.3 / 13.4 / 80.7 Ki-67 NET: <3% / 3–10% / 11–20% / >20%, % | 27.6 / 43.1 / 22.4 / 6.9 | – | | Ki-67 NEC: 21–50% / >50%, % | – | 21.2 / 78.8 | | Metastases: liver / non-regional LN / peritoneum / lung / bone, % (*) | 81.4 / 27.9 / 25.6 / 7.0 / 7.0 | 79.1 / 36.3 / 23.1 / 14.3 / 13.2 | >0.05 | 81.2 / 32.2 / 23.5 / 11.4 / 10.1 1st-line systemic treatment, % | 78.7 | 76.6 | 0.85 | 76.4 ECOG PS: Eastern Cooperative Oncology Group performance status; LN: lymph nodes. ^Total column includes 23 patients with unknown differentiation. *Patients may have more than one metastatic site. Figures 1–4: Overall survival from metastatic disease (G-NETs by Ki-67; G-NECs by Ki-67; 1st-line treatment – G-NETs; 1st-line treatment – G-NECs) [curve legends and in-figure HR boxes too small to read reliably] Table 2. mOS according to 1st-line treatment and Ki-67^ Ki-67 (n) | SSA | TT | Non-plat CT | Plat-CT | mOS G-NET · mOS by treatment | 66m | 34m | 7m | 10m | FIGURE 3 <3% (11) | 9 (82) | 1 (9) | 1 (9) | 0 | 66m 3–10% (21) | 13 (62) | 2 (10) | 2 (10) | 4 (19) | 64m 11–20% (11) | 6 (55) | 1 (9) | 0 | 4 (36) | 34m >20% (3) | 0 | 0 | 2 (67) | 1 (33) | 10m Total treated (46)^ | 28 (61) | 4 (9) | 5 (11) | 9 (20) | 48m G-NEC · mOS by treatment | – | – | 11m | 9m | FIGURE 4 21–50% (19) | 1 (5) | 1 (5) | 3 (16) | 14 (74) | 17m >50% (60) | 0 | 0 | 7 (12) | 53 (88) | 9m Total treated (79)^ | 1 (1) | 1 (1) | 10 (13) | 67 (85) | 9m ^Includes treated patients with known Ki-67 and type of 1st-line treatment. SSA: somatostatin analogues; TT: targeted therapy; Plat: Platinum; CT: chemotherapy; mOS: median overall survival from start of 1st-line therapy; m: months. CONCLUSIONS • This is one of the largest real-world studies describing treatment patterns and outcomes in advanced Gastric-NENs. • Advanced G-NENs show marked prognostic heterogeneity: Ki-67 drives prognosis and treatment choice in NETs, whereas disease-related factors predominate in NECs. • These findings provide valuable insights for clinical practice of a heterogeneous population underrepresented in clinical trials. Funding: Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE), RGETNE 2024 grant. // Acknowledgement: the participating centres, and the patients and their families. // Conflicts of interest: The presenting author has no conflict of interest regarding this communication. [Slide 2] 2423P - Systemic Therapy in Advanced Gastric Neuroendocrine Neoplasms (G-NENs): Real-World Evidence from the R-GETNE National Registry (G-NENCARE) INTRODUCTION • Most gastric NENs are indolent type 1 NETs diagnosed at an early stage, so advanced cases are uncommon. • Advanced G-NENs are underrepresented in clinical trials, which limits the evidence available for clinical practice. • We analysed the efficacy of systemic therapy and prognostic factors in advanced G-NENs from the Spanish national registry R-GETNE. METHODS • 191 of 711 (26.9%) G-NENs patients presented with or developed advanced disease registered in R-GETNE by 37 participating Spanish centres (1998–2024) • Overall survival was assessed from metastatic onset (mOS), defined as the start of 1st-line systemic therapy, using the Kaplan–Meier method and compared with the log-rank test; hazard ratios were estimated with Cox regression models. RESULTS Baseline characteristics are summarized in Table 1. 191 patients: 61 NETs (32%), 107 NECs (56%) and 23 (12%) with unknown differentiation. NETs vs NECs: mOS 50m vs 9m (HR 3.39; p<0.001). NETs: Ki-67 was the main prognostic factor - mOS: 66m in G1, 64m in G2-low (3–10%), 34m in G2-high (11–20%), and 10m in G3 tumors (HR 1.76; p=0.021) – FIGURE 1. NECs: numerically longer mOS with Ki-67 <50% (17m vs 9m; HR 1.34; p=0.32) – FIGURE 2; lung metastases vs none predicted worse mOS: 4m vs 10m (HR 2.07; p=0.04). Treatment: SSA predominated in NETs and platinum-CT in NECs (Table 2; FIGURES 3–4). [Table 1, Table 2, figures and conclusions too small/washed out in this photo; see companion image 2114682086393028852_s1]

ESMO Open - ORIGINAL ARTICLE Liquid biopsy-guided molecular hyperselection for anti-EGFR rechallenge therapy in refractory metastatic colorectal cancer: a pooled analysis of four trials D. Ciardiello, L. Boscolo-Bielo, C. M. Parseghian, A. Sartore-Bianchi, F. Pietrantonio, G. Martini, G. Mauri, G. Vetere, A. Avallone, A. De Stefano, S. Pisconti, G. Tortora, M. Messina, A. Fumagalli, A. Zaniboni, C. Pinto, G. Santabarbara, M. G. Zampino, R. Berardi, C. Lotesoriere, A. Cogoni, T. P. Latiano, E. Maiello, V. De Falco, L. Antonuzzo, A. Chiaramonte, A. Russo, F. Tosi, F. Villa, C. Cardone, N. Normanno, L. Altucci, R. Bordonaro, F. De Vita, G. Pellizzari, G. Curigliano, N. Fazio, E. Martinelli, T. Troiani, S. Siena, S. Kopetz, F. Ciardiello & S. Napolitano A: Disease-control rate (bar chart) Neg. hyp. vs Pos. hyp. B: Overall response rate (bar chart) Neg. hyp. vs Pos. hyp. C: Median Progression-free survival (95%CI) Pos. hyp.: 3.61 months (3.19-4.1) Neg. hyp.: 4.70 months (4.20-5.7) Hazard ratio: 1.50 (95%CI 1.14-1.96) P=0.00337 At risk (0, 3, 6, 9, 12 months): Pos. 90 | 57 | 16 | 5 | 3; Neg. 156 | 110 | 51 | 22 | 10 D: Median Overall survival (95%CI) Pos. hyp.: 11.4 months (10.3-14.2) Neg. hyp.: 15.0 months (12.6-16.8) Hazard ratio: 1.55 (95%CI 1.15-2.08) P=0.00432 At risk (0, 6, 12, 18, 24 months): Pos. 90 | 73 | 41 | 18 | 5; Neg. 156 | 134 | 76 | 34 | 14 Survival table Endpoint: PFS (panel C) and OS (panel D), hyperselection-negative vs -positive Arm | N | Median | Median CI Neg. hyp. (PFS) | 156 | 4.70 months | 4.20-5.7 Pos. hyp. (PFS) | 90 | 3.61 months | 3.19-4.1 Neg. hyp. (OS) | 156 | 15.0 months | 12.6-16.8 Pos. hyp. (OS) | 90 | 11.4 months | 10.3-14.2 HR: PFS 1.50; OS 1.55 HR CI: PFS 1.14-1.96; OS 1.15-2.08 P: PFS P=0.00337; OS P=0.00432

[Slide 2] Study Design A Phase 1/2 study (NCT06741644) is ongoing to evaluate CS2009 as monotherapy or in combination with chemotherapy (XELOX or FOLFOX) in patients with metastatic colorectal cancer (mCRC) across later-line and first-line settings. Key Eligibility Criteria • Patients with mCRC who are previously untreated and ineligible for radical surgery or local therapy, without known MSI-H/dMMR, or those in the later-line setting with progression/intolerance to standard of care • ECOG PS 0-1 • At least one measurable lesion Endpoints: Safety, ORR per RECIST v1.1 Safety was assessed in all treated patients. Efficacy was assessed in patients with at least one post-baseline tumor assessment per RECIST v1.1. Group 1 (≥2L mCRC monotherapy) Pre-treated mCRC → CS2009 monotherapy 30 mg/kg IV Q3W Group 2 (1L mCRC combination) Treatment-naïve mCRC → CS2009 30 mg/kg IV Q3W + XELOX up to 8 cycles, followed by CS2009 + capecitabine maintenance Group 3 (1L mCRC combination) Treatment-naïve mCRC → CS2009 20 mg/kg IV Q2W + FOLFOX up to 12 cycles, followed by CS2009 + leucovorin and 5-FU maintenance Treatment continued until progressive disease, unacceptable toxicity, consent withdrawal, or death Note: Data from Group 1 and Group 2 are presented. Group 3 data remain immature due to short follow-up and are not presented. ECOG PS: Eastern Cooperative Oncology Group performance status; IV: intravenous; L: line; FOLFOX: oxaliplatin + leucovorin + 5-FU; mCRC: metastatic colorectal cancer; MSI-H/dMMR: microsatellite instability-high/deficient mismatch repair; ORR: objective response rate; Q2W: once every 2 weeks; Q3W: once every 3 weeks; RECIST: Response Evaluation Criteria in Solid Tumors; XELOX: capecitabine + oxaliplatin. Dr. Feng Wang [Slide 3] Safety CS2009 monotherapy and in combination with chemotherapy demonstrated a favorable safety profile in mCRC n (%) | Group 1: Later-line mCRC CS2009 Monotherapy (N=23) Any-grade* | Grade ≥3 | Group 2: First-line mCRC CS2009 + XELOX (N=23) Any-grade* | Grade ≥3 Immune-related adverse event (irAE) Total | 6 (26.1) | 3 (13.0) | 9 (39.1) | 5 (21.7) Adrenal insufficiency | 2 (8.7) | 0 | 0 | 0 Alanine aminotransferase increased | 1 (4.3) | 1 (4.3) | 3 (13.0) | 1 (4.3) Amylase increased | 1 (4.3) | 1 (4.3) | 3 (13.0) | 0 Aspartate aminotransferase increased | 1 (4.3) | 1 (4.3) | 3 (13.0) | 1 (4.3) Hyperthyroidism | 1 (4.3) | 1 (4.3) | 2 (8.7) | 0 Hypothyroidism | 1 (4.3) | 0 | 2 (8.7) | 0 Lipase increased | 0 | 0 | 4 (17.4) | 1 (4.3) Possible anti-VEGF-related TRAE Total | 7 (30.4) | 2 (8.7) | 4 (17.4) | 1 (4.3) Proteinuria | 4 (17.4) | 0 | 2 (8.7) | 1 (4.3) Epistaxis | 2 (8.7) | 0 | 0 | 0 Urinary occult blood positive | 2 (8.7) | 0 | 1 (4.3) | 0 *Any-grade irAEs and possible anti-VEGF-related TRAEs reported in ≥2 patients. irAE: immune-related adverse event; mCRC: metastatic colorectal cancer; TRAE: treatment-related adverse event; VEGF: vascular endothelial growth factor; XELOX: capecitabine + oxaliplatin. Dr. Feng Wang [Slide 4] Efficacy: Group 1 (Later-line mCRC, monotherapy) Preliminary data demonstrated promising clinical efficacy for CS2009 monotherapy in later-line mCRC ORR 20.0% (3/15), DCR 93.3% (14/15) [Waterfall plot: Best change from baseline, %; legend ■ 30 mg/kg ▲ Prior Anti-angiogenic; bars labelled PD, SD, SD, SD, SD, SD, SD, SD, SD, SD, SD, SD, PR, PR, PR] BRAF Mut.: N UK UK N UK N UK UK N N N UK UK Y UK KRAS Mut.: Y UK Y Y UK N UK UK N N Y UK UK N UK Liver Met.: Y Y Y Y Y N Y N Y Y N Y N N N Location: R Rect. Rect. Rect. Rect. Rect. Rect. Rect. L Rect. L Rect. L R Rect. Prior lines of therapy for patients achieving PR: Patient 1: XELOX → bevacizumab + irinotecan + capecitabine Patient 2: FOLFOX → bevacizumab + FOLFIRI → encorafenib + cetuximab Patient 3: trilaciclib/placebo + bevacizumab + FOLFOXIRI → capecitabine + bevacizumab → trifluridine + bevacizumab [Spider plot: Change from baseline, % vs Months; legend — 30 mg/kg; ★ First New Lesion; ▸ Treatment ongoing] DCR: disease control rate; L: left colon; mCRC: metastatic colorectal cancer; Met.: metastasis; Mut.: mutation; N: no; ORR: objective response rate; PD: progressive disease; PR: partial response; R: right colon; Rect.: rectum; SD: stable disease; UK: unknown; Y: yes. Dr. Feng Wang

[Slide 1] FOG-001-101 Study Cohorts for Patients with Desmoid Tumors Dose Escalation (N=31)* Dose Level 2 150 mg QW N=1 Dose Level 3 300 mg QW N=12 Dose Level 4 450 mg QW N=16 Dose Level 6 900 mg QW N=2 Dose Optimization (N=45) Dose Level 4 (450 mg) QW x 2 cycles -> Dose Level 4 Q2W | N=15 Dose Level 4 (450 mg) QW x 4 cycles -> Dose Level 2 QW | N=15 Dose Level 2 (150 mg) QW x 4 cycles -> Dose Level 2 Q2W | N=15 Induction Phase | Maintenance Phase * IV weekly in 28-day cycles Dose optimization arms designed to evaluate Phase 3 Induction and Maintenance dose and schedule, and to satisfy Project Optimus requirement • Induction: Achieve rapid tumor reduction • Maintenance: Sustain antitumor benefit and optimize tolerability for chronic administration Mrinal Gounder, MD [Screen: 14:45 - 16:15 Proffered paper: Sarcoma; Chairs: Sebastian Bauer, Joanna Szkandera; Mrinal Gounder - A phase 1/2 trial of zolucatetide, a first-in-class direct β-catenin:TCF inhibitor: Updated safety and efficacy in patients with desmoid tumors; MALAGA AUDITORIUM - HALL 3] [Slide 2] Safety Summary TRAEs in ≥20% of Study Patients TRAEs, n (%) | 150 mg (n=16) All Grade | Grade ≥3 | 300 mg (n=12) All Grade | Grade ≥3 | 450 mg (n=46) All Grade | Grade ≥3 | 900 mg (n=2) All Grade | Grade ≥3 | All patients (N=76) All Grade | Grade ≥3 Any TRAE | 15 (93.8) | 1 (6.3) | 8 (66.7) | 0 | 44 (95.7) | 6 (13.0) | 2 (100) | 2 (100) | 69 (90.8) | 9 (11.8) TRAEs (any grade) in ≥20% of pts Fatigue | 7 (43.8) | 0 | 4 (33.3) | 0 | 27 (58.7) | 1 (2.2) | 2 (100) | 0 | 40 (52.6) | 1 (1.3) Alopecia | 5 (31.3) | 0 | 1 (8.3) | 0 | 21 (45.7) | 0 | 2 (100) | 0 | 29 (38.2) | 0 Nausea | 4 (25.0) | 0 | 3 (25.0) | 0 | 21 (45.7) | 0 | 1 (50.0) | 0 | 29 (38.2) | 0 Epistaxis | 4 (25.0) | 0 | 1 (8.3) | 0 | 16 (34.8) | 0 | 0 | 0 | 21 (27.6) | 0 AST increased | 1 (6.3) | 0 | 0 | 0 | 17 (37.0) | 1 (2.2) | 2 (100) | 1 (50.0) | 20 (26.3) | 2 (2.6) Blood bilirubin increased | 1 (6.3) | 0 | 0 | 0 | 15 (32.6) | 1 (2.2) | 2 (100) | 1 (50.0) | 18 (23.7) | 2 (2.6) Myalgia | 3 (18.8) | 0 | 0 | 0 | 15 (32.6) | 0 | 0 | 0 | 18 (23.7) | 0 Any serious TRAE | 2 (2.6)^1 TRAE leading to discontinuation of treatment | 0 TRAEs leading to death (Grade 5) | 0 ^1Events were one each of grade 1 fever and grade 2 peripheral sensory neuropathy • Most commonly reported TRAEs are low-grade, reversible, and manageable with monitoring and supportive care • No TRAEs resulting in treatment discontinuation or death • No high-grade gastrointestinal or skin toxicities • Not associated with ovarian toxicity • Bilirubin elevations were attributable to OATP transporter inhibition and not to hepatocellular injury or cholestasis Mrinal Gounder, MD Data cutoff: 22-Jun-2026 AST – Aspartate aminotransferase; TRAE – Treatment-related adverse event [Slide 3] Zolucatetide Depth of Response and Duration of Exposure at ≥450 mg Starting Dose Best Percent Change by RECIST 1.1 in Patients (N=46) Receiving ≥ 450 mg Starting 15 PRs | CR SD | PR | CR + Prior GSI Treatment - GSI-Naïve Duration of Exposure in Patients (N=48*) Receiving ≥ 450 mg Starting Dose On Treatment Time on treatment, median (range): 4.7 (0.5-22.3) months* Weeks on Treatment Arrows indicate timing of landmark analyses 46 patients with a starting dose ≥ 450 mg are RECIST-evaluable (≥1 post-baseline scan) • Disease control rate (SD+PR+CR) 100% • No patients have discontinued treatment due to PD • Responses seen irrespective of prior GSI exposure or CTNNB1/APC mutation type * One patient is not efficacy evaluable due to early resection of their desmoid tumor prior to completing a post-baseline scan, without subsequent dosing. A second patient has not had a first, 8-week scan. Mrinal Gounder, MD Data cutoff: 22-Jun-2026 CR – complete response, DL - dose level, PD – progressive disease, PR – partial response, SD – stable disease; RECIST – Response Evaluation Criteria in Solid Tumors [Slide 4] Conclusions – Zolucatetide (FOG-001) in Desmoid Tumors • Zolucatetide is a Helicon™ peptide that directly and selectively inhibits the β-catenin:TCF interaction As of the data cut-off of June 22, 2026: • Encouraging anti-tumor activity that deepens over time – Responses seen in 72% and 62% of patients at 32 and 24 week landmarks, respectively, among patients treated at ≥450 mg starting dose – Disease control rate of 100% – Irrespective of prior exposure to gamma secretase inhibitors or mutations in CTNNB1 or APC – No patients have discontinued treatment due to progressive disease • Favorable safety profile, consisting mainly of low-grade and reversible AEs – No treatment discontinuations due to AEs • A Phase 3 registrational study of zolucatetide in desmoid tumors is planned – 450 mg QW for 4 cycles (induction phase) followed by 300 mg Q2W (maintenance phase) selected as the recommended Phase 3 regimen Enrollment in desmoid tumor-specific cohorts is ongoing (NCT05919264) Mrinal Gounder, MD

[Slide 1] Method NB003-01 was a global, open-label clinical trial conducted in Asia (China, South Korean), North America (United States), and Europe (France, Spain, United Kingdom). Part 1 Dose Escalation (28-day cycle) (n=42) Advanced GIST after disease progression (PD) on at least imatinib Part 2 Dose Expansion (28-day cycle) (N=148) Cohort 1 (n=56): ≥5th Line GIST, PD on at least imatinib, sunitinib, regorafenib and ripretinib Cohort 2a (n=29): 3rd Line GIST, PD on both imatinib and sunitinib Cohort 2b (n=35): 4th Line GIST, PD on imatinib, sunitinib and regorafenib Cohort 3 (n=28): 2nd Line GIST, PD on imatinib Key Objectives Part 1: Assess safety and tolerability; determine the maximum tolerated dose (MTD) and the optimal dose of NB003. Part 2: Assess safety and tolerability; explore efficacy across different disease stages. The data presented are based on analysis of patients with KIT-mutant GIST in both the dose escalation and dose expansion cohorts (N=158). Ping Chi, MD, PhD [Slide 2] KIT Mutations (baseline ctDNA) vs. Responses 3rd line Max Reduction from Baseline in SoD (%) Dose Level: 15mg 20mg ctDNA (per patient, left to right): A502/D820; D579/W557/Y578/K642/V654/D677/K685/T670/Y823; W557; V560/V654/Y823; N567/N822; V559; W557/N822; W557/S821/Y823; N655/N822; V654; G565/V654/D820/N822; V560/V654; A502/N822; V559/D820/N822; V654; K558/D820/N822 KIT: Exon9 Exon11 Exon13 Exon14 Exon17 Responses were observed across diverse acquired KIT resistance mutations, including ATP-binding pocket (exons 13/14) and activation loop (exons 17/18) mutations. Ping Chi, MD, PhD ctDNA: circulating tumor DNA. [Slide 3] Conclusion In KIT-mutant GIST, NB003 demonstrated encouraging antitumor effects against a broad spectrum of TKI-resistant KIT mutations and meaningful clinical benefits across later-line treatment settings. NB003 demonstrated a manageable safety profile. Based on the overall safety, efficacy, and pharmacokinetic data, the recommended optimal regimen of NB003 is 15 mg twice daily. A multicenter, randomized Phase 3 trial comparing NB003 with regorafenib as third-line therapy for GIST (NB003-04, NCT07379047) is ongoing. Ping Chi, MD, PhD

[Slide 1] Study design retrosauna Study design - International retrospective study across 22 NET expert centers to evaluate the impact of continued SSA use alongside 2L therapy - Endpoints: progression-free survival (PFS) and overall survival (OS) after start of respectively PRRT or TT [Schema: Eligible patients -> PRRT-substudy = 2L PRRT -> PRRT with 2L SSA / PRRT w/o 2L SSA; TT-substudy = 2L TT (*) -> TT with 2L SSA / TT w/o 2L SSA; (*) with everolimus or sunitinib] Eligibility criteria Inclusion criteria - Age >=18 years at time of diagnosis - Histologically-proven diagnosis of advanced or metastatic, non-functional, well-differentiated GEP NET grade 1-2 - Radiological progression during 1L SSA - PRRT-substudy: started 2L treatment with PRRT (177Lu-DOTATATE or 177Lu-DOTATOC) with/without 2L SSA between 2010-2024 - TT-substudy: started either 2L treatment with TT (sunitinib or everolimus) with/without 2L SSA between 2010-2014 Exclusion criteria - Presence of high-grade NEN (NET grade 3 or neuroendocrine carcinoma) - Prior treatment with everolimus, sunitinib or PRRT - Presence of functional syndrome - Prior or concomitant palliative, systemic oncological treatment for other malignancy than GEP NET - 2L treatment of GEP NET with chemotherapy Siddharth Chhajlani, MD [Slide 2] Demographics retrosauna Flowchart: Patients with non-functional GEP NET grade 1-2 with progression on 1L SSA PRRT-substudy: 2L PRRT (n=292) -> with 2L SSA (n=167); w/o 2L SSA (n=125) TT-substudy: 2L TT (*) (n=179) -> with 2L SSA (n=126); w/o 2L SSA (n=53) (*) with everolimus or sunitinib Demographics table: Columns: TT substudy (n=179): TT w/o SSA (n=53) | TT with SSA (n=126) || PRRT substudy (n=292): PRRT w/o SSA (n=125) | PRRT with SSA (n=167) Median age at start 2L (years, IQR): 66 (58-72) | 65 (57-73) || 67 (59-73) | 66 (59-73) Sex (n, %) Female: 23 (43%) | 57 (45%) || 56 (45%) | 80 (48%) Sex (n, %) Male: 30 (57%) | 69 (55%) || 69 (55%) | 87 (52%) NET grade (n, %) NET G1: 14 (26%) | 34 (27%) || 34 (27%) | 58 (35%) NET grade (n, %) NET G2: 39 (74%) | 92 (73%) || 91 (73%) | 109 (65%) Location primary (n, %) pancreas: 42 (79%) | 66 (52%) || 51 (41%) | 45 (27%) Location primary small intestine: 3 (6%) | 36 (29%) || 50 (40%) | 88 (53%) Location primary other GI: 8 (15%) | 24 (19%) || 24 (19%) | 34 (20%) Siddharth Chhajlani, MD [Slide 3] TT substudy: Progression-free Survival Results retrosauna [KM curve legend: TT with SSA; TT without SSA; y-axis Probability of progression-free survival 0-1.0; x-axis Time (in months) 0-90] log-rank p=0.022 unadjusted HR (0.67, 95% CI 0.47-0.95; p=0.023) Table: TT w/o SSA | TT with SSA n group (events): n=53 (47 events) | n=126 (109 events) mPFS (95% CI): 9.7m (7.1-14.0) | 13.5m (10.4-20.9) log rank p=0.022 - In univariable Cox regression analysis, SSA therapy was associated with improved PFS (HR 0.67, 95% CI 0.47-0.95; p=0.023). - In multivariable Cox regression analysis (*), SSA therapy remained significantly associated with improved PFS (aHR 0.63, 95% CI 0.45-0.90; p=0.010). (*) after adjustment for sex, NET subtype, primary tumor location, and age Number at risk (censored) TT with SSA: 126 (0), 55 (5), 34 (2), 14 (4), 11 (1), 7 (2), 4 (1) TT without SSA: 53 (0), 15 (3), 5 (2), 3 (1), 2 (1), 0 (0), 0 (0) Siddharth Chhajlani, MD Survival table Endpoint: PFS (TT substudy) Arm | N | Median | Median CI TT with SSA | 126 | 13.5 mo | 10.4-20.9 TT w/o SSA | 53 | 9.7 mo | 7.1-14.0 HR: 0.67 (unadjusted); aHR 0.63 HR CI: 0.47-0.95 (unadjusted); 0.45-0.90 (adjusted) P: log-rank p=0.022; Cox p=0.023 (unadjusted), p=0.010 (adjusted) [Slide 4] PRRT substudy: Progression-free Survival Results retrosauna [KM curve legend: PRRT with SSA; PRRT without SSA; y-axis Probability of progression-free survival 0-1.0; x-axis Time (in months) 0-90] log-rank p=0.0013 unadjusted HR 0.63 (95% CI 0.48-0.84; p=0.001) Table: PRRT w/o SSA | PRRT with SSA n group (events): n=125 (94 events) | n=167 (112 events) mPFS (95% CI): 27.0m (23.2-31.5) | 33.3m (28.6-42.8) log rank p=0.0013 - In univariable Cox regression analysis, SSA therapy was associated with improved PFS (HR 0.63, 95% CI 0.48-0.84; p=0.001). - In multivariable Cox regression analysis (*), SSA therapy remained significantly associated with improved PFS (aHR 0.63, 95% CI 0.48-0.83; p=0.001). (*) after adjustment for sex, NET subtype, primary tumor location, and age Number at risk (censored) PRRT with SSA: 167 (0), 128 (8), 73 (19), 35 (19), 18 (3), 10 (2), 6 (1) PRRT without SSA: 125 (0), 86 (8), 38 (15), 14 (6), 4 (2), 2 (0), 1 (0) Siddharth Chhajlani, MD Survival table Endpoint: PFS (PRRT substudy) Arm | N | Median | Median CI PRRT with SSA | 167 | 33.3 mo | 28.6-42.8 PRRT w/o SSA | 125 | 27.0 mo | 23.2-31.5 HR: 0.63 (unadjusted); aHR 0.63 HR CI: 0.48-0.84 (unadjusted); 0.48-0.83 (adjusted) P: log-rank p=0.0013; Cox p=0.001 (unadjusted and adjusted)

[Slide 1] Efficacy Objective Responses in Cohort 2 (33%) and Cohort 3 (40%*), with disease control in ≥89% of patients in each cohort Best overall response by cohort | Cohort 1 N=2 (%) | Cohort 2 N=46 (%) | Cohort 3 N=20 (%) Disease control | 2 (100) | 41 (89.1) | 19 (95.0) ORR | 0 | 15 (32.6) | 8 (40.0) Confirmed PR | 0 | 14 (30.4) | 5 (25.0) Unconfirmed PR | 0 | 1 (2.2) | 3 (15.0)* Stable disease | 2 (100) | 26 (56.5) | 11 (55.0) Progressive disease | 0 | 5 (10.9) | 1 (5.0) ORR GEP-NET SSTR2+ | 0/2 (0.0) | 14/38 (36.8) | 6/17 (35.3) Disease control = CR/PR/SD. *Two additional uPRs reported as of 10 Sep 2026, for a total of 5 uPRs and an ORR of 50% (25% confirmed) for Cohort 3 [Waterfall plot: Percent Change from Baseline, y-axis 50 to -75; legend Dose Level: Cohort 1 / Cohort 2 / Cohort 3; ■ Additional unconfirmed PR as of 10 Sep 2026] All treated patients; Investigator-assessed RECIST v1.1; ORR = confirmed or unconfirmed CR/PR. Waterfall: 67 patients with a post-baseline measurement. CR, complete response; DCO, data cutoff; GEP-NET, gastroenteropancreatic neuroendocrine tumor; ORR, objective response rate; PR, partial response; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease; SSTR2+, somatostatin receptor subtype 2–positive; uPR, unconfirmed partial response for Cohort 3. [Slide 2] PFS Across ITT population, 72% of patients remained progression-free at 18 months Kaplan-Meier estimate of PFS Legend: Cohort 1 (N=2); Cohort 2 (N=46); Cohort 3 (N=20) Number at risk (months 0 / 5 / 10 / 15 / 20): Cohort 1: 2 / 2 / 2 / 2 / 2 Cohort 2: 46 / 40 / 33 / 23 / 6 Cohort 3: 20 / 16 / 7 / 0 X-axis: Time from Treatment Start (Months); Y-axis: Survival Probability Curves are truncated at 20 months, where few patients remain at risk (Cohort 1, n=2; Cohort 2, n=6). One Cohort 2 PFS event occurred after 20 months. Landmark PFS rate, % (95% CI) | Cohort 1 (N=2) | Cohort 2 (N=46) | Cohort 3 (N=20) | Cohorts 1-3 (N=68) 6 months | 100 | 82.6 (68.2–90.9) | 89.1 (62.7–97.2) | 85.7 (74.9–92.0) 12 months | 100 | 71.2 (55.7–82.2) | 76.3 (38.2–92.7)‡ | 74.2 (61.1–83.5) 18 months | 100 | 68.9 (53.1–80.3) | NE | 71.9 (58.3–81.8) At risk, 6 / 12 / 18 mo | 2 / 2 / 2 | 38 / 30 / 13 | 12 / 1 / 0 | 52 / 33 / 15 PFS events, n (%) | 0 | 15 (32.6) | 3 (15.0) | 18 (26.5) ‡1 patient at risk at 12 months. NE, not estimable (no patient at risk). Investigator-assessed RECIST v1.1; Kaplan-Meier estimates with log-log 95% CI. Cohort 3 is preliminary dose-exploration data and is shown separately in the landmark table. CI, confidence interval; ITT, intention-to-treat; mo, months; NE, not estimable; PFS, progression-free survival; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1. Survival table Endpoint: PFS (investigator-assessed RECIST v1.1) Cohort 1 | 2 Cohort 2 | 46 Cohort 3 | 20 Cohorts 1-3 | 68 Landmark rates: 6 months: Cohort 1 100 | Cohort 2 82.6 (CI 68.2–90.9) | Cohort 3 89.1 (CI 62.7–97.2) | Cohorts 1-3 85.7 (CI 74.9–92.0) 12 months: Cohort 1 100 | Cohort 2 71.2 (CI 55.7–82.2) | Cohort 3 76.3 (CI 38.2–92.7) | Cohorts 1-3 74.2 (CI 61.1–83.5) 18 months: Cohort 1 100 | Cohort 2 68.9 (CI 53.1–80.3) | Cohort 3 NE | Cohorts 1-3 71.9 (CI 58.3–81.8)

Concomitant somatostatin analog use in second-line therapy of gastroenteropancreatic neuroendocrine tumors: Survival results from the retrospective retroSAUNA study Dr Siddharth Chhajlani et al, Study Interpretation • Real-world study showing that SSA continuation is done in current practice. • The main biais is the reason to continue SSA beyond progression: driven per "centers' habits versus driven by prognostic factors? • Prospective randomized studies are ongoing: • STOPNET (NCT06345079) : stop SSA or not under PRRT (PEP = PFS rate at 20 months) • SAUNA (NCT05701241) : stop SSA or not, under PRRT or targeted therapy (PEP = PFS) • What is the quality of life of pursuing injections of SSA vs no ? • What is the cost-effectiveness of pursuing SSA ? • Outside of functioning NET requiring SSA or in selected cases, I will wait the results of prospective studies before pursuing SSA [struck through:] (SSA one day, SSA for the life in metastatic non-functioning NETs !)

906eP Clinical outcomes and prognostic factors with trifluridine/tipiracil plus bevacizumab in RAS/BRAF wild-type metastatic colorectal cancer: real-world evidence from the BeTAS study Nieves Martínez-Lago1, Iria Parajo Vazquez2, Belen de Frutos Gonzalez3, María Carmen Riesco Martinez4, Sandra López Peraita5, Borja González Gomez6, Carla Antonilli Perezz7, Ana López Alfonso8, Ana Fernández Montes9, Ismael Ghanem10, Martín Pérez Martelo1, Sara Agraso Busto2, Marcos Melian Sosa11, Elena Gallardo Martin12, Ana María Jiménez Gordo13, Luis Cabezón-Gutierrez14, Antía Cousillas Castiñeiras15, Marta Llanos Muñoz16, Maria Pilar Ochoa Rivas17, Margarita Reboredo Lopez2. 1 University Hospital & Health Research Institute (IDIS), Translational Medical Oncology Group (ONCOMET), Santiago de Compostela, Spain; 2 A Coruña University Hospital, A Coruña, Spain; 3 Ramón y Cajal University Hospital, Madrid, Spain; 4 Hospital Universitario 12 de Octubre, Madrid, Spain; 5 Hospital Universitario de Burgos, Burgos, Spain; 6 Hospital Universitario Lucus Augusti, Lugo, Spain; 7 Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain; 8 Hospital Universitario Infanta Leonor, Madrid, Spain; 9 Complejo Hospitalario Universitario de Ourense, Orense, Spain; 10 La Paz University Hospital, Madrid, Spain; 11 Instituto Valenciano de Oncología (IVO), Valencia, Spain; 12 Hospital Universitario Alvaro Cunqueiro, Vigo, Spain; 13 Hospital Universitario Infanta Sofía, Madrid, Spain; 14 Hospital Universitario De Torrejón, Madrid, Spain; Facultad de Medicina, Universidad Francisco Vitoria, Pozuelo de Alarcón, Madrid, Spain; 15 Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain; 16 Hospital Universitario de Canarias, San Cristóbal de La Laguna, Spain; 17 Hospital Central de la Defensa Gómez Ulla, Madrid, Spain. KEY FINDINGS RAS/BRAF wt N = 222 Study population | 3L treatment 50.0% FTD/TPI + BEV | Prior anti-EGFR 98.3% Rechallenge 17.2% | mPFS 4.3 mo 95% CI 3.4–5.2 | mOS 10.7 mo 95% CI 8.8–12.6 | Response ORR 8.5% DCR 51.2% RECIST-evaluable n=201 BACKGROUND ▸ FTD/TPI + BEV is an established later-line treatment option in mCRC following the phase III SUNLIGHT trial. ▸ In RAS/BRAF wild-type mCRC, multiple later-line strategies may be considered, while real-world evidence specifically characterizing outcomes with FTD/TPI + BEV in this molecular subgroup remains limited. OBJECTIVE To evaluate real-world effectiveness and prognostic factors in patients with RAS/BRAF wild-type mCRC treated with FTD/TPI + BEV. METHODS Multicenter real-world BeTAS study evaluating FTD/TPI + BEV in previously treated mCRC. Eligible patients had failure or intolerance to ≥2 prior systemic regimens. Among 593 patients with known RAS/BRAF status, 222 RAS/BRAF wild-type patients, defined according to baseline tumor tissue testing, were included in this analysis. Efficacy endpoints were OS, PFS, ORR and DCR. Prognostic factors were explored using Kaplan–Meier estimates and Cox proportional hazards models. PATIENT PROFILE – RAS/BRAF wt (N=222) 66.5 y Median age | 90.1% ECOG PS 0–1 | 80.6% Time from metastatic diagnosis ≥18 months | 70.7% <3 metastatic sites 69.8% Liver metastases | 50.0% Treated in 3L | 98.3% Anti-EGFR | 17.2% Rechallenge Tabernero classification: BPC 18.0% | GPC 37.8% | PPC 44.2% BPC: best prognostic category - GPC: good prognostic category - PPC: poor prognostic category RESPONSE RATE – RECIST-EVALUABLE (n=201) ORR 8.5% DCR 51.2% CR 0.5% | PR 8.0% | SD 42.8% | PD 48.8% EFFECTIVENESS Median follow-up: 30.6 months Progression-free survival [KM curve] mPFS 4.3 mo 95% CI 3.4–5.2 Overall survival [KM curve] mOS 10.7 mo 95% CI 8.8–12.6 EXPLORATORY MULTIVARIABLE PROGNOSTIC ANALYSIS Independent associations with OS and PFS were explored using multivariable Cox proportional hazards models. Variable | HR (95% CI) OS | P value | HR (95% CI) PFS | P value ECOG PS 0–1 vs. 2 | 0.61 (0.28–1.34) | 0.218 | 0.59 (0.29–1.21) | 0.158 Tabernero classification BPC vs. GPC | 0.64 (0.43–0.96) | 0.032 | 0.68 (0.47–0.99) | 0.050 Tabernero classification BPC vs. GPC | 0.41 (0.22–0.77) | 0.006 | 0.59 (0.35–0.99) | 0.044 Prior anti-VEGF No vs. yes | 0.60 (0.36–1.02) | 0.058 | 0.69 (0.44–1.09) | 0.115 Primary prophylactic G-CSF No vs. yes | 1.44 (0.92–2.25) | 0.115 | 1.45 (0.97–2.18) | 0.070 Grade 3–4 neutropenia No vs. yes | 1.83 (1.16–2.88) | 0.009 | 1.86 (1.24–2.89) | 0.003 HRs are adjusted estimates from multivariable Cox models. CONCLUSIONS 1 Clinically meaningful effectiveness in RAS/BRAF wt mCRC — FTD/TPI + BEV showed clinically meaningful real-world effectiveness in this molecular subgroup. 2 Supported by randomized phase III evidence — The role of FTD/TPI + BEV in later-line mCRC is supported by prospective randomized phase III evidence. 3 A robust evidence-based later-line option — These real-world findings reinforce FTD/TPI + BEV as an evidence-based option for RAS/BRAF wild-type mCRC. In RAS/BRAF wild-type mCRC, FTD/TPI + BEV shows clinically meaningful real-world effectiveness and remains a later-line strategy supported by randomized phase III evidence. CONTACT Nieves Martinez-Lago Nieves.Purificacion.Martinez.Lago@sergas.es X: @DraMartinezLago ACKNOWLEDGEMENTS To the patients and their families and the BeTAS investigators.

[Slide 2] Co-Primary endpoints OS and ORR (ITT population) Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 Median OS (95% CI): 8.7 [7.6, 10.6] | 7.5 [6.2, 9.3] HR (95.8% CI): 0.95 [0.74, 1.22]; P-value: 0.33 Events n (%): 139 (88%) | 137 (86%) Median follow-up (mo): 8.2 | 6.6 Y-axis: Survival Probability; X-axis: Survival time (months) No. at risk (0,6,12,...,60 mo): Arm A: 158 101 46 30 12 7 5 3 2 1 1 Arm B: 159 91 45 28 16 8 4 3 2 1 0 ORR table: Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 | P-value ORR: 40 (25%) | 36 (23%) | 0.29 CR: 4 (3%) | 0 (0%) PR: 36 (23%) | 36 (23%) SD: 61 (39%) | 61 (38%) PD: 33 (21%) | 46 (29%) Missing: 24 (15%) | 16 (10%) OS: HR from unstratified Cox proportional hazards model; p-value from unstratified log-rank test (one-sided). + Censored. The results for OSS and OR for ITT population are consistent with those for PP population. Magdalena Scheck Survival table Endpoint: OS (ITT) Arm | N | Median | Median CI Arm A Ram + FOLFIRI | 158 | 8.7 mo | 7.6–10.6 Arm B Ram + Pacli | 159 | 7.5 mo | 6.2–9.3 HR: 0.95 HR CI: 0.74–1.22 (95.8% CI) P: 0.33 (one-sided log-rank) [Slide 3] Progression-free survival ITT Population: Arm A Ram + FOLFIRI n = 158 | Arm B Ram + Pacli n = 159 Median PFS (95% CI): 5.5 [4.0, 6.3] | 3.7 [2.9, 4.2] HR (95.8% CI): 0.71 [0.56, 0.90]; P-value: 0.002 Events n (%): 142 (90%) | 149 (94%) No. at risk (0,6,12,...,48 mo): Arm A: 158 63 20 5 4 1 1 1 0; Arm B: 159 43 7 3 1 0 PP Population: Arm A Ram + FOLFIRI n = 150 | Arm B Ram + Pacli n = 154 Median PFS (95% CI): 5.6 [4.1, 6.4] | 3.7 [2.9, 4.3] HR (95.8% CI): 0.69 [0.55, 0.88]; P-value: 0.001 Events n (%): 138 (92%) | 148 (96%) No. at risk: Arm A: 150 63 20 5 4 1 1 1 0; Arm B: 154 43 7 3 1 0 Y-axis: Probability of Progression-free Survival; X-axis: Time to progression or death (months) Ram plus FOLFIRI resulted in a numerical improvement in PFS vs. SOC HR from unstratified Cox proportional hazards model; p-value from unstratified log-rank test (one-sided). + Censored. SOC standard of care Magdalena Scheck Survival table Endpoint: PFS (secondary; ITT) Arm | N | Median | Median CI Arm A Ram + FOLFIRI | 158 | 5.5 mo | 4.0–6.3 Arm B Ram + Pacli | 159 | 3.7 mo | 2.9–4.2 HR: 0.71 HR CI: 0.56–0.90 (95.8% CI) P: 0.002 (one-sided log-rank) [Slide 4] Conclusion ➢ Ram plus FOLFIRI did not achieve the primary endpoints of OS or ORR in taxane-pretreated pts. ➢ OS and ORR were numerically higher in Ram plus FOLFIRI compared to Ram plus paclitaxel. ➢ PFS was clearly improved with Ram plus FOLFIRI. ➢ No new safety signals were observed. Ram plus FOLFIRI showed increased rates of all-grade gastrointestinal toxicity, but reduced rates of peripheral neuropathy. ➢ Ram plus FOLFIRI might offer a potential treatment option for patients who had received one line of prior therapy and progressed upon taxane therapy and/ or with pre-existing neuropathy. Magdalena Scheck

[Slide 1] regarding the use of daraxonrasib, when available, in patients with RAS-wt, RASG13-mutated or RASG61-mutated tumours. The RASolute 302 trial was not powered or stratified to answer this question.8 Unexplained discrepancies appeared in this small subgroup between a clearly significant OS benefit and a potentially detrimental effect on PFS.8 Despite being eligible, efficacy and toxicity results in these patients were not analysed in the previous studies.7,8 Further data and analyses are needed to fully inform on the tolerability and magnitude of benefit across rare subsets as well as tolerability in patients with ECOG PS 2. Currently, the greatest strength of evidence for the use of daraxonrasib is in patients with RASG12-mutated tumours with ECOG PS 0-1. An algorithm for the management of metastatic PDAC is shown in Figure 1. [Slide 2] T. Conroy & M. Ducreux - Annals of Oncology Metastatic PC Previous (neo)adjuvant ChT and metastases <6 months after last ChT dose? No: - ECOG PS 0-1, bilirubin <1.5x ULN and no major comorbidities -> FOLFIRINOX [I, A; MCBS 5]b; NALIRIFOX [I, A; MCBS 2]b; or GN [I, B; MCBS 3]b - ECOG PS 2 with KPS ≥70 and bilirubin ≤1.5x ULN -> GN [II, A; MCBS 3]b - ECOG PS 2 with KPS <70 and/or bilirubin >1.5x ULN -> Gemcitabine [I, A] - ECOG PS 3-4 -> Symptom-directed care [IV, A] Second line after FOLFIRINOX/NALIRIFOX: - ECOG PS 0-1 and RASG12 mutation [ESCAT I-A]a -> Daraxonrasib [I, A; MCBS 5]b,c - ECOG PS 2 or no RASG12 mutation -> If FOLFIRINOX in first line:d Preferred: GP [I, B]; Alternatives: Gemcitabine [III, C]; GNe [III, C]. If NALIRIFOX in first line:f Gemcitabine-based regimen [V, C] Second line after gemcitabine-based: - ECOG PS 0-1 and RASG12 mutation [ESCAT I-A]a -> Daraxonrasib [I, A; MCBS 5]b,c - ECOG PS 2 or no RASG12 mutation -> Preferred: Nanoliposomal irinotecan-5-FU-LV [I, B; MCBS 3]b,g; Alternatives: mFOLFOX6 [II, C]h; OFF [II, C]h Yes: - ECOG PS 0-1 and RASG12 mutation [ESCAT I-A]a -> Daraxonrasib [I, A; MCBS 5]b,c - ECOG PS 2 or no RASG12 mutation -> Switch to another ChT regimen Figure 1. Systemic treatment of metastatic pancreatic cancer. Purple: algorithm title; blue: systemic anticancer therapy or their combination; white: other aspects of management and nontreatment aspects. 5-FU, 5-fluorouracil; ChT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; FDA, Food and Drug Administration; FOLFIRINOX, LV-5-FU-irinotecan-oxaliplatin; GN, gemcitabine-nab-paclitaxel; GP, gemcitabine-paclitaxel; KPS, Karnofsky performance status; LV, leucovorin; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mFOLFOX6, modified LV-5-FU-oxaliplatin; NALIRIFOX, liposomal irinotecan-5-FU-LV-oxaliplatin; OFF, oxaliplatin-5-FU-LV; PC, pancreatic cancer; ULN, upper limit of normal. aESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the ESMO Precision Oncology and Taxonomy Committee.9 bESMO-MCBS v2.010 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). cFDA approved, not EMA approved. dAfter FOLFIRINOX treatment, GP can be offered to patients without a RASG12-mut or with ECOG PS 2 and a favourable comorbidity profile [I, B]. Other options are gemcitabine alone [III, C] or GN [III, C; EMA and FDA approved in metastatic PC only (not advanced PC) and not approved as second-line therapy]. eEMA and FDA approved in metastatic PC only (not advanced PC). fAfter NALIRIFOX treatment, a gemcitabine-based regimen may be offered to patients without a RASG12-mut or with ECOG PS 2 and a favourable comorbidity profile [V, C]. gOnly in patients with, or who have recovered to, ECOG PS 0-1. hIf not given previously.

[Photo of two people standing in front of a poster at the ESMO 2026 poster hall; poster board numbers 4351P (left) and 4350P] [ESMO Congress Madrid 2026 logo] 4350P: Genetic Determinants of Cachexia-Related Phenotypes in Metastatic Pancreatic Cancer: PANTHEIA-SEOM Translational Study Vilma Pacheco-Barcia1, Andrea Ochaita Aguado2, Andrés J. Muñoz Martín3, Cristina Fernández Díaz2, Axel Mariño-Méndez4, María Ángeles Vicente Conesa5, Paula Cerdà Serdà6, María de Toro Carmena7, Jorge Hernando8, Jorge Adeva9, Silvia Cruz Gil2, Marta Gómez de Cedrón2, Alberto Carmona-Bayonas5, Ricardo Ramos Ruiz2, Paula Jiménez-Fonseca10, Lara Fernández2, Enrique Grande11, Ana Ramírez de Molina2. 1Hospital Universitario La Luz, Madrid, Spain. 2IMDEA Nutrition Institute, Madrid, Spain. 3Hospital General Universitario Gregorio Marañón, Madrid, Spain. 4Hospital Clínic de Barcelona, Barcelona, Spain. 5Hospital Universitario Morales Meseguer, Murcia, Spain. 6Hospital Universitario de la Santa Creu i Sant Pau. 7Hospital Universitario La Princesa, Madrid, Spain. 8Hospital Universitario de Vall d'Hebron, Barcelona, Spain. 9Hospital Universitario 12 de Octubre, Madrid, Spain. 10Hospital U. Central de Asturias, Oviedo, Spain. 11Hospital U. Quirónsalud Pozuelo. BACKGROUND [partially obscured by people] ...ancer cachexia affects most patients with metastatic pancreatic ...ancer and drives functional decline and mortality, yet its inherited determ[illegible] unknown. We explored whether germli[illegible] related to cachexia, ...arcopenia, [illegible] ...diture are associated with weigh[illegible] MET[HODS] [obscured] RESULTS [Figure: A. Weight loss by genotype (GG n=9, GT n=22, TT n=8; genotype, variant near KLF5); B. Association of the T allele across phenotypes - cachexia/weight-loss phenotypes vs body weight/mass; small text illegible] Figure 2. (A) Percentage weight loss from usual weight to the start of chemotherapy by genotype of the variant near KLF5. (B) Standardized effect of each T allele (95% CI) across phenotypes, ordered from cachexia/weight-loss phenotypes (purple) to body [w]eight/mass (blue). Regression adjusted for sex and age; * significant after Bonferroni correction. [Figure 3: Manhattan-style plot of associations across cachexia/weight-loss related phenotypes and body weight/mass; labels KLF5 (near), TRIB2, ACVR1B, MTHFR, BMP4; small text illegible] [...]ciations of the 26 variants (one colour per gene) with 16 phenotypes, ordered from cachexia/weight-loss related [p]urple background) to body weight/mass (blue background). Each dot is the −log10 P of an additive model adjusted [...]; dashed line, Bonferroni threshold (P = 0.05/26); dotted line, P = 0.05. Clinician-reported cachexia (yes/no; 4 [...]ed with Firth logistic regression. Weight loss • Each T allele of the variant near KLF5 was associated with 5.0 percentage points less weight loss (95% CI −7.6 to −2.4; P = 0.0004; Bonferroni P = 0.010), the only association surviving correction for multiple testing. • Median weight loss was 9.8% in GG, 7.9% in GT and 4.1% in TT carriers; cachexia† was present in 8/9 (89%), 16/22 (73%) and 1/8 (13%), respectively (OR per T allele 0.09; 95% CI 0.02–0.47; P = 0.004). Clinician-reported cachexia (4 cases) showed the same direction (OR 0.12; 95% CI 0.01–0.73; P = 0.019; Firth regression). • The effect was robust to clinical adjustment, centre, exclusion of non-European patients, permutation (family-wise P = 0.007) and bootstrap resampling (variant selected in 89% of resamples; effect range −4.7 to −6.3 points). • The association was specific to weight loss: there was no association with usual (pre-illness) body weight or BMI (P = 0.40 and P = 0.74; Figure 2B). • A variant in MTHFR was associated with higher pre-chemotherapy BMI (+3.8 kg/m² per G allele; Bonferroni P = 0.028), largely reflecting higher usual BMI rather than less weight loss. • Across all 416 tests (26 variants × 16 phenotypes), 25 were nominally significant (20.8 expected by chance); only the KLF5-near variant association with weight loss and the MTHFR associations with pre-chemotherapy weight and BMI passed Bonferroni correction (Figure 3). CONCLUSIONS • The T allele of a variant near KLF5, previously linked to lean mass, is associated with less pre-treatment weight loss and less cachexia in metastatic pancreatic cancer, independently of prior body size. • These preliminary findings require replication in a larger, independent cohort. Acknowledgments: Gratitude to the PANTHEIA study researchers, SEOM's Clinical Practice and Outcome Evaluation Section and PANDORA-SEOM. Author COIs: [small text, partially legible: speaker honoraria from Pierre Fabre, Nutricia, Servier, Pfizer, AstraZeneca, Leo Pharma; consultancy or advisory board from Advanced Accelerator Applications, a Novartis company, Pfizer, Nutricia, Servier; travel support from Amgen, Servier, Pfizer, Nutricia, Merck.] Funding: [small text, partially legible: Regional Government of the Community of Madrid, Government of Spain, European Council of Innovation; SEOM Grant 2024. Pfizer grant 2022. Nutricia and Servier research funding without restrictions.] Author contact: [email address, small text] [Badge on presenter: Vilma Pacheco-Barcia, ESMO Member, ESMO Officer, Invited Speaker]

[Slide 1] Peak (NCT05208047) Is a Global, Randomized, Open-Label, Phase 3 Trial This analysis evaluated patients in Peak who crossed over to receive bezuclastinib + sunitinib combination after progressing on sunitinib monotherapy Patients 1:1 Randomized Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n=204) Sunitinib 37.5 mg QD (n = 209) EOT/BICR confirmed PD Crossover Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 128) EoT/BICR confirmed PD Crossover evaluation PFS ORR Safety 30-Day Safety and Post-Treatment Follow-up BICR, Blinded Independent Central Review; EoT, end of treatment; ORR, objective response rate; PD, disease progression; PFS, progression-free survival; QD, once daily Data cutoff: Sep 30, 2025 [Slide 2] Patients Had Improved Response Rate With Crossover Therapy Compared With Sunitinib Monotherapy In patients who crossed over to combination therapy: ORR to 2nd-line sunitinib was 20.3% (95% CI: 13.7%-28.3%) (n=26) ORR to subsequent combination therapy was 29.7% (95% CI: 21.9%-38.4%) (n=38) 80% (n=102) of patients entering the crossover had not achieved an objective response on sunitinib monotherapy (best response of SD or PD) In patients with best response of disease progression on sunitinib, ORR was 56% with combination 2 patients with PD on monotherapy achieved a CR on combination Sunitinib 37.5 mg QD (n = 209) Crossover Bezuclastinib 600 mg QD + Sunitinib 37.5 mg QD (n = 128) CR, complete response; ORR, objective response rate; PD, progressive disease; QD, once daily; SD, stable disease. Data cutoff: Sep 30, 2025 [Slide 3] Safety During Crossover Was Consistent With the Pivotal Peak Trial | Bezuclastinib + Sunitinib (n=204) | Sunitinib (n=208)a | Sunitinib → Combination Crossover (n=128) Median treatment duration, weeks (range) | 61.4 (1.4-150.0) | 42.4 (2.0-152.0) | 23.9 (1.0-114.7) TEAEs, n (%) | 204 (100) | 207 (99.5) | 125 (97.7) TRAEs, n (%) | 202 (99.0) | 204 (98.1) | 121 (94.5) Gr3+ TRAEs, n (%) | 146 (71.6) | 109 (52.4) | 50 (39.1) Bezuclastinib related Gr3+ | 126 (61.8) | N/A | 46 (35.9) Sunitinib related Gr3+ | 141 (69.1) | 109 (52.4) | 45 (35.2) SARs, n (%) | 34 (16.7) | 24 (11.5) | 15 (11.7) Bezuclastinib related SAEs | 25 (12.3) | N/A | 10 (7.8) Sunitinib related SAEs | 31 (15.2) | 24 (11.5) | 14 (10.9) TRAEs leading to death, n (%) | 0 | 1 (0.5) | 0 Reductions of either drug due to TRAEs, n (%) | 114 (55.9) | 92 (44.2) | 33 (25.8) DC of study treatment due to TRAEs, n (%) | 15 (7.4) | 8 (3.8) | 3 (2.3) The incidence of TEAEs & TRAEs was similar between bezuclastinib + sunitinib combination & combination crossover No TRAEs leading to death in patients on bezuclastinib + sunitinib combination & combination crossover The only TRAEs leading to discontinuation in >1 patient were neutropenia (2.9%), increased ALT/AST (1.5%), & diarrhea (1.0%) in the combination arm,& diarrhea (1.6%) in the combination crossover arm aOne patient randomized to sunitinib but never dosed. ALT, alanine aminotransferase; AST, aspartate aminotransferase; DC, discontinuation; Gr, grade; N/A, not applicable; SAE, serious adverse event; SAR, serious adverse reaction; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event. Data cutoff: Sep 30, 2025 [Slide 4] Conclusion: Following Imatinib Treatment, the Majority of Patients Would Derive Improved Disease Control With Earlier Combination Therapy 2nd-line combination treatment resulted in mPFS of 16.5 months (vs 9.2 months with 2nd line sunitinib) – Durability of benefit from early combination treatment was also observed with PFS2 results: median was not reached with combination vs median of 21.0 months with sunitinib alone (HR=0.57) 71% (148/209) of patients had disease progression on 2nd line sunitinib as of data cut. 128 patients crossed over from 2nd line sunitinib to combination. Disease control & response rate were both improved with crossover therapy vs. sunitinib monotherapy; results were also favorable in comparison to 3rd line approved agents – mPFS was 5.7 months with 2nd line sunitinib & 7.4 months with subsequent combination therapy – ORR was 20.3% with 2nd line sunitinib & 29.7% with subsequent combination therapy – In patients with best response of disease progression on sunitinib, ORR was 56% with subsequent combination therapy Safety observations in combination crossover patients were consistent with bezuclastinib + sunitinib combination in the pivotal portion of the trial HR, hazard ratio; mPFS, median progression-free survival; ORR, objective response rate; PFS2, progression-free survival 2. Data cutoff: Sep 30, 2025

[Slide 1] 4212RO Biomarker Phase II Study of Cabozantinib in Advanced Radioiodine-Refractory Differentiated Thyroid Cancer: The GETNE-T2216 / CABOTHYROID Trial Jorge Hernando*, Francheska Cadacio, Guillermo Villacampa, José María Herranz, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Paula Jiménez-Fonseca, German Iglesias Álvarez, Miguel Navarro Martín, Neus Baste, Alberto Carmona-Bayonas, Lara Iglesias, María Quindós-Varela, Gloria Marquina, Tian Tian, Jaume Capdevila *Department of Medical Oncology, Gastrointestinal and Endocrine Tumor Unit & Neuroendocrine and Endocrine Tumor Translational Research Program (NET-VHIO), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain [GETNE — Grupo Español de Tumores Neuroendocrinos y Endocrinos logo] [Slide 2] GETNE-T2216 / CABOTHYROID Trial BIOMARKER ANALYSIS Comparison of methylation patterns between responders and non-responders [Volcano plot: -log10(q-value) vs Methylation Difference (%); legend: Hyper (Resp > Non), Hypo (Resp < Non)] [Pie chart] Promoter (≤1kb) (12.7%); Promoter (2-3kb) (1.4%); 1st Exon (15.5%); Other Exon (1.4%); 1st Intron (21.1%); Other Intron (35.2%); Distal Intergenic (12.7%) Genes identified with higher importance in response to cabozantinib prediction Symbol | Gene name | Chromosome | Annotation ANKRD26P1 | ankyrin repeat domain 26 pseudogene 1 | chr16 | Distal Intergenic CDH20 | cadherin 20 | chr18 | Intron LINC00273 | long intergenic non-protein coding RNA 273 | chr16 | Distal Intergenic FRG1 | FSHD region gene 1 | chr4 | Intron ZNF733P | zinc finger protein 733, pseudogene | chr7 | Distal Intergenic → EM-seq analysis showed differences in methylation patterns between responders vs. non responders. → ML analysis identified ANKRD26P1, LINC00273, and ZNF733P as the genes with higher importance in response prediction. [Slide 3] GETNE-T2216 / CABOTHYROID Trial EFFICACY - FULL ANALYSIS SET [Waterfall plot: Maximum reduction from baseline (%)] Confirmed BoR n=39 CR 0 (0.0%) PR 10 (24.4%) SD 27 (65.9%) PD 2 (4.9%) DCR = 89.7% (95% CI: 70.8-94.4) ORR = 24% Median DoR = 18.4 months (95% CI: 14.0-NR) Median TTR = 2.7 months (95% CI: 2.5-2.8) [PFS curve] Median PFS = 16.1 months (95% CI: 13.8-NR) Number at risk (censored): 41 (0), 31 (1), 22 (5), 9 (11), 1 (16), 0 (17) [0, 6, 12, 18, 24, 30 months] [OS curve] Number at risk (censored): 41 (0), 38 (0), 34 (1), 15 (17), 3 (29), 0 (32) Cabozantinib provides a fast response in in patients with DTC, even after progression to up to two MKIs. [Slide 4] GETNE-T2216 / CABOTHYROID Trial EFFICACY - UNIVARIATE ANALYSIS Symbol | Gene name ANKRD26P1 | ankyrin repeat domain 26 pseudogene 1 LINC00273 | long intergenic non-protein coding RNA 273 ZNF733P | zinc finger protein 733, pseudogene Forest plot of PFS Cox model (Events | Events Ref | HR (95% CI) p-val) Age (y) at inclusion | 24/41 | | 0.98 (0.94 - 1.02, p=0.368) Sex: Male (Ref: female) | 13/23 | 11/18 | 1.02 (0.46 - 2.29, p=0.953) Histology: PTC (Ref: FTC) | 16/25 | 8/16 | 1.38 (0.59 - 3.23, p=0.462) Previous treatments: Lenv+Sor (Ref: Lenv) | 12/17 | 8/13 | 1.07 (0.43 - 2.70, p=0.879) Sor (Ref: Lenv) | 4/11 | 8/13 | 0.29 (0.09 - 1.00, p=0.049) [highlighted] Presence of bone metastasis: Yes (Ref: No) | 12/18 | 12/23 | 1.75 (0.77 - 3.98, p=0.184) ECOG 1-2 (Ref: 0) | 10/20 | 14/21 | 0.67 (0.30 - 1.52, p=0.342) ANKRD26P1 Methylation High (Ref: Low) | 8/15 | 8/15 | 0.73 (0.27 - 1.96, p=0.527) LINC00273 Methylation High (Ref: Low) | 8/15 | 8/15 | 0.87 (0.32 - 2.33, p=0.783) ZNF733P Methylation High (Ref: Low) | 8/15 | 8/15 | 0.78 (0.29 - 2.09, p=0.617) Forest plot of OS Cox model (Events | Events Ref | HR (95% CI) p-val) Age (y) at inclusion | 9/41 | | 0.97 (0.91 - 1.03, p=0.289) Sex: Male (Ref: female) | 3/23 | 6/18 | 0.42 (0.10 - 1.67, p=0.217) Histology: PTC (Ref: FTC) | 4/25 | 5/16 | 0.52 (0.14 - 1.93, p=0.326) Previous treatments: Lenv+Sor (Ref: Lenv) | 4/17 | 5/13 | 0.53 (0.14 - 1.97, p=0.341) Sor (Ref: Lenv) | 0/11 | 5/13 | NE (NE, NE) Presence of bone metastasis: Yes (Ref: No) | 4/18 | 5/23 | 1.06 (0.28 - 3.95, p=0.931) ECOG 1-2 (Ref: 0) | 7/20 | 2/21 | 4.01 (0.83 - 19.3, p=0.083) ANKRD26P1 Methylation High (Ref: Low) | 3/15 | 3/15 | 0.92 (0.18 - 4.58, p=0.918) LINC00273 Methylation High (Ref: Low) | 2/15 | 4/15 | 0.46 (0.08 - 2.51, p=0.368) ZNF733P Methylation High (Ref: Low) | 3/15 | 3/15 | 0.92 (0.18 - 4.58, p=0.918) • Cabozantinib offer a greater disease control benefit in patients who previously received only sorafenib. • Each gene of importance was not prognostic of longer survival individually.

833P Outcomes with trifluridine/tipiracil plus bevacizumab across age groups in metastatic colorectal cancer: real-world evidence from the BeTAS study Nieves Martínez-Lago(1), Iria Parajo Vazquez(2), Belen de Frutos Gonzalez(3), María Carmen Riesco Martinez(4), Sandra López Peraita(5), Borja González Gómez(6), Carla Antonilli Perez(7), Ana López Alfonso(8), Ana Fernández Montes(9), Ismael Ghanem(10), Martín Pérez Martelo(1), Sara Agraso Busto(2), Marcos Melian Sosa(11), Elena Gallardo Martin(12), Ana María Jiménez Gordo(13), Luis Cabezón-Gutiérrez(14), Antía Cousillas Castiñeiras(15), Marta Llanos Muñoz(16), Maria Pilar Ochoa Rivas(17), Margarita Reboredo Lopez(2). [Affiliations: Spanish hospitals - small print, partially legible] KEY FINDINGS Study population N = 593 Previously treated mCRC >75 years 156 (26.3%) mPFS 3.7 | 4.2 | 5.1 mo (<50 | 50-75 | >75) p=0.113 mOS 11.5 | 9.9 | 11.2 mo (<50 | 50-75 | >75) p=0.944 Response ORR 2.4 | 7.3 | 16.3; DCR 52.4 | 48.2 | 58.9 (<50 | 50-75 | >75) G3-4 neutropenia 31.8 | 32.8 | 37.8% (<50 | 50-75 | >75) p=0.458 BACKGROUND + OBJECTIVE BACKGROUND - FTD/TPI + BEV is an established later-line treatment option in mCRC following the phase III SUNLIGHT trial. - Older patients remain underrepresented in randomized trials, and real-world evidence on outcomes across age groups remains limited. OBJECTIVE To evaluate effectiveness, safety, and prognostic factors across age subgroups (<50, 50-75, and >75 years) in patients with mCRC treated with FTD/TPI + BEV in routine clinical practice. PATIENT PROFILE - AGE DISTRIBUTION <50 years n=44 7.4% | 50-75 years n=393 66.3% | >75 years n=156 26.3% Clinicopathological characteristics, % | <50 (n) | 50-75 (n) | >75 (n) ECOG PS 2 | 2.3 | 8.9 | 14.7 <18 months from metastatic diagnosis | 45.4 | 27.2 | 35.3 Liver metastases | 59.1 | 67.4 | 71.1 >=3 metastatic sites | 43.2 | 31.3 | 23.1 Tabernero classification, % Best (BPC) | 13.6 | 19.3 | 15.4 Good (GPC) | 20.5 | 30.5 | 32.7 Poor (PPC) | 65.9 | 50.2 | 51.9 EFFECTIVENESS Median follow-up: 30.6 months PFS / OS Kaplan-Meier by age subgroup (<50, 50-75, >75) mPFS 4.3 mo 95% CI 3.8-4.8 mOS 10.7 mo 95% CI 9.7-11.6 SAFETY No significant differences in grade 3-4 TRAEs across age groups. Grade 3-4 TRAEs, % | <50 (n) | 50-75 (n) | >75 (n) | p value Neutropenia | 31.8 | 32.8 | 37.8 | 0.458 Anemia | 4.5 | 4.6 | 3.2 | 0.740 Asthenia | 2.3 | 4.3 | 4.5 | 0.531 Diarrhea | 0.0 | 3.6 | 0.6 | 0.286 Thrombocytopenia | 2.3 | 1.5 | 1.3 | 0.069 Bleeding | 0.0 | 1.8 | 1.3 | 0.203 Hepatic toxicity (AST/ALT increase) | 0.0 | 1.8 | 1.3 | 0.800 Hypertension | 0.0 | 0.8 | 1.3 | 0.888 Mucositis | 0.0 | 0.5 | 0.6 | 0.598 METHODS Multicenter real-world BeTAS study evaluating FTD/TPI + BEV in previously treated mCRC. Eligible patients had failure or intolerance to >=2 prior systemic regimens. A total of 593 patients treated between July 2019 and February 2026 were included into three age groups: <50 years (n=44), 50-75 years (n=393), and >75 years (n=156). Efficacy endpoints were OS, PFS, ORR and DCR; safety was assessed through grade 3-4 treatment-related adverse events (TRAEs). Outcomes across age groups were evaluated using Kaplan-Meier estimates, log-rank tests and multivariable Cox proportional hazards models. RESPONSE RATE - RECIST-EVALUABLE PATIENTS RECIST-evaluable: <50 n=42; 50-75 n=359; >75 n=141 <50 (n=42) | CR 0.0 | PR 2.4 | SD 50.0 | PD 47.6 50-75 (n=359) | CR 0.6 | PR 6.7 | SD 40.9 | PD 51.8 >75 (n=141) | CR 0.7 | PR 15.6 | SD 42.6 | PD 41.1 | ORR, % | DCR, % <50 | 2.4 | 52.4 50-75 | 7.3 | 48.2 >75 | 16.3 | 58.9 EXPLORATORY MULTIVARIABLE PROGNOSTIC ANALYSIS Age was not independently associated with OS or PFS. Variable | OS HR (95% CI) | p value | PFS HR (95% CI) | p value Age >50 vs >75 | 1.03 (0.62-1.69) | 0.857 | 1.24 (0.82-1.83) | 0.302 Age 50-75 vs >75 | 0.92 (0.62-1.39) | 0.697 | 1.01 (0.74-1.53) | 0.982 ECOG PS 2 vs 0 | 1.69 (1.02-2.40) | 0.003 | 0.89 (1.03-1.69) | 0.049 Tabernero BPC vs GPC | 0.62 (0.32-0.91) | 0.001 | 0.71 (0.58-0.69) | 0.046 Tabernero BPC vs PPC | 0.41 (0.24-0.69) | <0.001 | 0.33 (0.24-0.45) | <0.001 Prior anti-VEGF vs others | 0.84 (0.62-1.14) | 0.269 | 1.05 (0.78-1.40) | 0.681 Primary prophylactic GCSF vs ches | 0.90 (0.72-1.14) | 0.401 | 0.81 (0.67-0.99) | 0.042 >=3 metastatic sites vs <3 sites | 1.72 (1.33-2.24) | <0.001 | 1.79 (1.36-2.32) | <0.001 CONCLUSIONS 1 Effectiveness across age groups: No significant differences in PFS or OS were observed across age groups in this real-world patient population. 2 Consistent safety profile: No significant differences in grade 3-4 treatment-related adverse events were observed across age groups. 3 Age was not independently prognostic: Despite a higher prevalence of ECOG PS 2 in older patients, age was not independently associated with OS or PFS. CONTACT Nieves Martinez Lago Nieves.Purificacion.MartinezLago@sergas.es ACKNOWLEDGEMENTS We thank all patients, their families, and the BeTAS investigators. FTD/TPI + BEV in metastatic colorectal cancer: real-world evidence from the BeTAS study | 833P | ESMO Congress 2026 | Madrid, Spain (23-27 October 2026)

[Slide 1] Clinical validity of the ctDNA response evaluation criteria (ctDNA-RECIST) in patients with advanced biliary tract cancer Karen-Lise G. Spindler1,2, Louise B. Callesen1,2, Julia S. Johansen3, Alice Markussen3, Rikke F. Andersen4, Troels D. Christensen3 Circulating tumour DNA – ctDNA-RECIST Response Evaluation Criteria in Solid Tumours INTRODUCTION • Imaging can be complex in biliary tract cancers (BTC) and RECIST 1.1 response is a suboptimal surrogate marker for overall survival (OS) • Circulating tumor DNA (ctDNA) measurement is known to hold a strong correlation to response and survival endpoints • We have presented criteria for early ctDNA response evaluations (ctDNA-RECIST) based on digital droplet PCR (ddPCR) analysis of ctDNA • The tumor agnostic ctDNA aberrant methylation (AM) marker is a feasible pragmatic ctDNA approach for clinical implementation AIMS To demonstrate the clinical validity of the ctDNA HOXA 9 analysis in patients with advanced biliary tract cancer (BTC) To validate the ctDNA-RECIST criteria for future prospective studies METHODS • Participants: This study included 238 patients with advanced BTC from 4 clinical studies: NCT 01247337, NCT 05184400, EudraCT 2013-001559-11, 2013-004854-46 previously published. • Blood samples were drawn in EDTA tubes prior to the first cycle (baseline), prior to the second cycle and at the first imaging evaluation (Figure 1). • ctDNA analysis: Four mL plasma was analyzed for aberrant methylation of HOXA9 by ddPCR, and 5 droplets defined positivity (Figure 1). • ctDNA response classification was done according to ctDNA-RECIST (Table 1, Figure 2). (DC=PR+SD) • Statistical analysis included descriptive analysis and Kaplan-Meier statistics with log rank tests. RESULTS: BASELINE [partly obscured by rosette] Overall median OS was 12 months Baseline ctDNA detection rate - 85% Figure 4. Baseline ctDNA levels were significantly associated with location of the primary tumor, disease stage, liver involvement, and poor ECOG PS. Figure 5. Kaplan-Meier estimates of OS according to baseline ctDNA detection. Baseline ctDNA detection was associated with shorter OS (18.6 months versus 11.0 months (HR 1.79 95% CI 1.24-2.61 ). RESULTS: ctDNA-RECIST OUTCOMEs Early ctDNA evaluation classified ctDNA[obscured] ctDNA-DC (122/134-91.0%), and ctDNA[obscured] CONCLUSION This study confirms the clinical validity of ctDNA aberrant m[obscured] ctDNA-RECIST criteria in patients with metastatic BTC[obscured] BEST POSTER 460P [Slide 2] Clinical validity of the ctDNA response evaluation criteria (ctDNA-RECIST) in patients with advanced biliary tract cancer Karen-Lise G. Spindler1,2, Louise B. Callesen1,2, Julia S. Johansen3, Alice Markussen3, Rikke F. Andersen4, Troels D. Christensen3 Circulating tumour DNA – ctDNA-RECIST Response Evaluation Criteria in Solid Tumours INTRODUCTION • Imaging can be complex in biliary tract cancers (BTC) and RECIST 1.1 response is a suboptimal surrogate marker for overall survival (OS) • Circulating tumor DNA (ctDNA) measurement is known to hold a strong correlation to response and survival endpoints • We have presented criteria for early ctDNA response evaluations (ctDNA-RECIST) based on digital droplet PCR (ddPCR) analysis of ctDNA • The tumor agnostic ctDNA aberrant methylation (AM) marker is a feasible pragmatic ctDNA approach for clinical implementation AIMS To demonstrate the clinical validity of the ctDNA HOXA 9 analysis in patients with advanced biliary tract cancer (BTC) To validate the ctDNA-RECIST criteria for future prospective studies METHODS • Participants: This study included 238 patients with advanced BTC from 4 clinical studies: NCT 01247337, NCT 05184400, EudraCT 2013-001559-11, 2013-004854-46 previously published. • Blood samples were drawn in EDTA tubes prior to the first cycle (baseline), prior to the second cycle and at the first imaging evaluation (Figure 1). • ctDNA analysis: Four mL plasma was analyzed for aberrant methylation of HOXA9 by ddPCR, and 5 droplets defined positivity (Figure 1). • ctDNA response classification was done according to ctDNA-RECIST (Table 1, Figure 2). (DC=PR+SD) • Statistical analysis included descriptive analysis and Kaplan-Meier statistics with log rank tests. Table 1 * ctDNA-RECIST definitions ctDNA PD: progressive disease. ctDNA increase above the previous/lowest value with no overlap of CI's | ctDNA PD ctDNA PR: partial response. ctDNA decrease below the previous value with no overlap of the two CI's but the lower CI does not overlap 0 | ctDNA DC: disease control. Partial response and stable disease can be combined and classified as disease control ctDNA SD: stable disease. ctDNA value with a CI overlapping the CI of the previous value. ctDNA NCR: near complete response. ctDNA decrease below the previous value with no overlap of the two CI's and with the lower CI overlapping 0. | ctDNA MR: maximal response. Complete and near complete response can be combined and classified as maximal responders CR: complete response. ctDNA decrease to an undetectable level. RESULTS: BASELINE FINDINGS Overall median OS was 12 months Baseline ctDNA detection rate - 85% Figure 4. Baseline ctDNA levels were significantly associated with location of the primary tumor, disease stage, liver involvement, and poor ECOG PS. Figure 5. Kaplan–Meier estimates of OS according to baseline ctDNA detection. Baseline ctDNA detection was associated with shorter OS (18.6 months versus 11.0 months (HR 1.79 95% CI 1.24-2.61 ). RESULTS: ctDNA-RECIST OUTCOMEs Early ctDNA evaluation classified ctDNA-PD (N=1/134-0.7%), ctDNA-DC (122/134-91.0%), and ctDNA-MR (11/134-8.2%). Figure 8. Kaplan–Meier estimates of OS according to ctDNA response: Patients with early ctDNA-MR had longer median OS (15.9 mo), compared to patients with ctDNA-DC (8.9 mo, HR 2.1 95%CI 1.07-4.20, p=0.031). The same applied for PFS (10.0 and 5.9 mo, HR 1.58 95% CI 0.83-3.03, p = 0.16). CONCLUSION This study confirms the clinical validity of ctDNA aberrant methylation of HOXA9 and the potential utility of our ctDNA-RECIST criteria in patients with metastatic BTC, which could be used in prospective studies. Funding: This work has been supported by grants from Danish Cancer Society, Novo Nordisk Foundation, Health Research Foundation of Central Denmark Region and Kirsten and Freddy Johansen Foundation FPN: 460P ESMO 2026

Early postoperative recurrence identifies a biologically aggressive KRAS/MAPK-enriched phenotype in cholangiocarcinoma Natalia S. Tissera 1,2, Andrea Casadei-Gardini 3, Virginia Genovesi 4,5, Anthony Turpin 6, Caterina Vivaldi 4,5, Cristina Dopazo 7, Maria Teresa Salcedo 8, Francesca Ratti 9, Silvia Buonanno 9, Remo Alessandris 9,10, Viviane Gnemmi 11, Emmanuel Boleslawski 12, Sharela Vega 1, Sergio Pérez-Fernandez 1, Ana Vivancos 13, Alejandro García 1, Jorge Hernando 1, Jaume Capdevila 1, Tian Tian 14,15, Teresa Macarulla 14,15 ESMO 2026 478P BACKGROUND Early recurrence (ER) after curative-intent resection for cholangiocarcinoma (CCA) is frequent and associated with poor prognosis; however, its molecular determinants remain unclear. Objective: To evaluate clinicopathologic and molecular features of ER. METHODS Multicenter and retrospective study (2001–2025) 4 European centers • Curative-intent CCA resections • Excluded metastatic disease, neoadjuvant treatment, mixed HCC-CCA and 90-day mortality • Recurrence groups: <12, 12–<36 and ≥36 months/no recurrence • Analyses used Kaplan-Meier and Cox models. RECURRENCE GROUPS ANALYTIC COHORT: 289 PATIENTS G1 <12 months 162 (56.1%) G2 12–<36 months 79 (27.3%) G3* Late recurrence ≥36 mo / no recurrence with ≥36 mo f-up 48 (16.6%) SURVIVAL OUTCOMES Median follow-up: 61.8 months (95% CI 48.6–85.0) Disease-free survival Median 10.8 months (95% CI 9.5–12.0) Overall survival Median 36.5 months (95% CI 30.9–42.0) OVERALL SURVIVAL BY RECURRENCE GROUP 12-month landmark sensitivity analysis: Recurrence ≤12 months was associated with subsequent mortality: adjusted HR 2.50 (95% CI 1.66–3.78), p<0.001. Median OS: G1 24.2, G2 38.8, G3 119.5 months Log-rank p<0.001 FIRST RECURRENCE ANATOMY Evaluable distant-component recurrences (n=161) Liver only / Lung only G1 40/94 (43%) | 4/94 (4%) G2 19/49 (39%) | 4/49 (8%) G3a 5/18 (28%) | 4/18 (22%) CONCLUSION ER identifies a clinically and biologically aggressive CCA phenotype with nominal KRAS/MAPK enrichment, [obscured]

Taking the leadership of the Immunology Institute and breaking medical siloes ○ Medical training is based on organs ○ Immune system is the same across organs ○ Pathophysiology likely shared by many organs ○ Macrophages respond to injuries cues (many shared across diseases) ○ Focus on mechanism-based pathophysiology rather than organ-specific approaches [Image: silos labelled Cancer, Skin, Heart, Brain, Gut, Joints — BREAKING MEDICAL SILOS] Mapping Immune programs across diseases Accelerate knowledge Cardiology | Rheumatology | Oncology | Dermatology | Gastroenterology | Neurology

[Slide 1] A Survival Function Censored Survival probability (%) OS (Months) Number at risk All patients 45 27 20 13 6 2 1 B PFS (Months) Number at risk All patients 45 12 8 6 3 1 1 Fig. 1 Kaplan–Meier survival estimates in the overall cohort. (A) Overall survival (OS), defined as the time from nivolumab initiation to death from any cause. (B) Progression-free survival (PFS), defined as the time from nivolumab initiation to disease progression or death, whichever occurred first. Vertical tick marks indicate censored observations. Survival table Endpoint: OS and PFS (overall cohort) All patients | 45 [Slide 2] GIPI Score Good Intermediate Poor Good-censored Intermediate-censored Poor-censored Survival probability (%) OS (Months) Number at risk Good (0) 19 15 12 8 3 2 1 Intermediate (1) 17 8 5 2 1 0 0 Poor (2) 7 3 2 2 2 0 0 Fig. 2 Kaplan–Meier curves for OS according to GIPI risk category. Patients were classified as good-risk, intermediate-risk, or poor-risk according to the Gastrointestinal Immune Prognostic Index. The number of patients included in each subgroup is reported in Table 5. Given the small size of the poor-risk subgroup, estimates should be interpreted cautiously. The intermediate- and poor-risk curves crossed during late follow-up, when few patients remained at risk. Survival distributions were estimated using the Kaplan–Meier method and compared using the log-rank test. GIPI, Gastrointestinal Immune Prognostic Index; OS, overall survival. Survival table Endpoint: OS by GIPI score Good (0) | 19 Intermediate (1) | 17 Poor (2) | 7 [Slide 3] GRIm Score Low Risk High Risk Low Risk-censored High Risk-censored Survival probability (%) OS (Months) Number at risk Low risk (0) 39 26 19 12 6 2 1 High risk (1) 4 0 0 0 0 0 0 Fig. 3 Kaplan–Meier curves for OS according to GRIm score. Patients were classified as low-risk or high-risk according to the Gustave Roussy Immune Score. The number of patients included in each subgroup is reported in Table 5. Given the small size of the high-risk subgroup, estimates should be interpreted cautiously. Survival distributions were estimated using the Kaplan–Meier method and compared using the log-rank test. GRIm, Gustave Roussy Immune Score; OS, overall survival. Survival table Endpoint: OS by GRIm score Low risk (0) | 39 High risk (1) | 4

[Slide 1] Design of ARION UCGI 33/PRODIGE 67 Randomized phase 2 trial (NCT03777813) ✓ Eligible patients : ✓ LA non-metastatic biopsy-proven squamous cell carcinoma or adenocarcinoma of the esophagus ✓ ≥18 years old, ✓ WHO performance status ≤1, ✓ Treatment Arms : ✓ Standard Arm : SoC = Chemoradiotherapy (CRT) : RT 50 Gy + 6 FOLFOX q2w ✓ Experimental Arm: SoC + PD-L1 blocker Durvalumab 1500 mg q4w up to 12 months ✓ Objectives : ✓ The primary end point : efficacy of durvalumab added to SoC, in terms of centrally reviewed Progression Free Survival (cPFS). ✓ Secondary end points: PFS OS Safety QoL EXPERIMENTAL ARM CRT+ Durvalumab (N=60) Durvalumab 1500 mg q4w during Year 1 RT 50 Gy + FOLFOX q2w Screening Endoscopy Biopsy FDG-PET/CT QoL R 1:1 M6 CT scan QoL | M9 CT scan QoL | Year 1 CT scan QoL | M18 CT scan QoL | Year 2 CT scan QoL STANDARD of CARE ARM (N=60) RT 50 Gy + FOLFOX q2w Stratification factors: • Center • Histological Type: Adenocarcinoma vs Squamous cell carcinoma • Stage: I/II vs III/IV vs unknown Primary endpoint: Centrally Reviewed PFS Secondary endpoints: Safety, OS, QoL Ancillary studies: - Biomarkers CPS score + TIL (CD3 CD8 CD 68) - Gut microbiota - Plasmatic biomarkers of response to IO and / or CRT Assessed for eligibility N= 188 Randomized patients N =112 Arm A: CRT + DURVA N = 58 Received allocated intervention N =57 Did not receive allocated treatment N = 1 Arm B: CRT N = 54 Received allocated intervention N =53 Did not receive allocated treatment N =1 Intent To Treat population N = 58 Safety population N = 57 Intent To Treat population N =54 Safety population N = 53 From May 2019 to May 2024 Modesto A, Tougeron D, Tremolières P, Ronchin P, Jouve AD, Leignel DA, et al. Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol. BMC Cancer. 2023 Oct 12;23(1):966 Anouchka MODESTO M.D Ph.D. [Slide 2] Survival Primary endpoint : Centrally reviewed PF Survival One year 50,5% vs 48.9 % adj HR* = 0.86, 95%CI [0.52; 1.41] ; 80%CI [0.62; 1.19] 1-sided p = 0.273 *Adjusted for Stratification factors Y-axis: centralized Progression-free survival; X-axis: Months (0-27) Number at risk (months 0/3/6/9/12/15/18/21/24/27) Arm A: 58 53 42 33 25 20 18 18 9 0 Arm B: 54 46 33 28 24 21 20 18 5 0 Legend: Arm A / Arm B No impact of CPS score One year OS < 65 years 90.5% vs 55.6% (p=0.072) Secondary end point : Overall Survival One year 75.1% vs 67,9 % adj HR* = 0.97, 95%CI [0.57; 1.64] ; 80%CI [0.69; 1.37], 1-sided p = 0.451 *Adjusted for Stratification factors Y-axis: Overall survival; X-axis: Months (0-27) Number at risk Arm A: 58 56 54 50 42 40 35 30 20 0 Arm B: 54 48 43 39 36 35 30 29 13 0 Legend: Arm A / Arm B Anouchka MODESTO M.D Ph.D. Survival table Endpoint: Centrally reviewed PFS (primary); OS (secondary) Arm A: CRT + durvalumab | 58 Arm B: CRT | 54 HR: 0.86 (adjusted, cPFS) HR CI: 95% CI 0.52-1.41; 80% CI 0.62-1.19 P: 1-sided p = 0.273 Landmark rates: 1 year: Arm A: CRT + durvalumab 50.5% (cPFS) | Arm B: CRT 48.9% (cPFS) | Arm A: CRT + durvalumab 75.1% (OS) | Arm B: CRT 67.9% (OS) [Slide 3] Tolerance and Quality of life ➢ Radiation Therapy completion (50 Gy) : 97% ➢ FOLFOX completion: 70% ➢ Median delivered Durva (Exp arm) : 9 courses ➢ Grade 3-5 TRAE 75,4% vs 75,5% ➢ No safety signal QLQ-C30 : Global health status [line chart, Global health status (mean) by Baseline, M3, M6, M9, M12, M18, M24; Arm A / Arm B] QLQ-OES18 : Dysphagia [line chart, Dysphagia (mean) by Baseline, M3, M6, M9, M12, M18, M24; Arm A / Arm B] Anouchka MODESTO M.D Ph.D. [Slide 4] Conclusion ✓ Anti PDL-1 Durvalumab + CRT was not associated with improved centrally reviewed PFS ✓ Trend to improve OS if < 65 years : one year OS 90% vs 55,6% (p=0,07) ✓ No safety signal ✓ Pending questions: – Regional lymph nodes at risk of containing microscopic disease received large fields of prophylactic irradiation – Optimal timing of RT and IO : sequential > concurrent? – Patients selection and Biomarkers beyond CPS. [photo of Rodin's The Thinker sculpture] Anouchka MODESTO M.D Ph.D.

Cachexia shifted adipose CD8+ T cells toward exhausted states UMAP: Non-cachexia, Cachexia Tpex score | Tex-int score | Tex-term score (Module score) Tpex | Tex-int | Tex-term Percentage of CD8 T cells SAT | VAT Tpex: SAT ns; VAT * Tex-int: SAT *; VAT * Tex-term: SAT *; VAT ns Cachexia status: Non-cachexia, Cachexia Tpex – progenitor exhausted CD8 T cell Tex-int – intermediate exhausted CD8 T cell Tex-term – terminally exhausted CD8 T cell Joo Sung Shim, MD, MSc J.Han et al., Cell Discovery 2022

[Slide 1] STUDY DESIGN Randomised, open-label phase 3 trial (NCT04928807) Key Eligibility Criteria • Untreated histologically confirmed rectal adenocarcinoma, clinically staged as T3–4 or N+ • Patients who planned to undergo surgery following neoadjuvant treatment • ≤10 cm distance from the anal verge • Eastern Cooperative Oncology Group performance status of 0 or 1 (N=231) R 1:1 Experimental group: SCRT → Camrelizumab + CAPOX (Q3W, 2 cycles) → TME → Camrelizumab + CAPOX (Q3W, 6 cycles) → Camrelizumab (Q3W, up to 9 cycles) Standard of care group: LCCRT → CAPOX (Q3W, 2 cycles) → TME → CAPOX (Q3W, 6 cycles) Primary Endpoint: • BIRC-assessed pCR (ypT0N0) rate Key Secondary Endpoints: • Investigator-assessed EFS • OS Other Secondary Endpoints: • Completion rate of neoadjuvant therapy • R0 resection rate • Tumour regression grade • BIRC-assessed EFS • Investigator-assessed DFS • Quality of life • Safety Stratification factors • Clinical T stage (≤T3 vs T4) • Clinical N stage (N0 vs N+) SCRT: 25 Gy in 5 fractions. LCCRT: 50.4 Gy in 28 fractions with concurrent oral capecitabine 825 mg/m² twice daily. CAPOX: oral capecitabine 1000 mg/m² twice daily on days 1-14 and intravenous oxaliplatin 130 mg/m² on day 1. Camrelizumab: 200 mg intravenously on day 1. Consolidation therapy was administered one week after SCRT in the experimental group and two weeks after LCCRT in the standard-of-care group. TME was performed within 10 weeks after the completion of radiotherapy. SCRT, short-course radiotherapy; CAPOX, capecitabine plus oxaliplatin; TME, total mesorectal excision; LCCRT, long-course chemoradiotherapy; BIRC, blinded independent review committee; pCR, pathological complete response; EFS, event-free survival; OS, overall survival; DFS, disease-free survival. Presenter: Zhenyu Lin [Livestream frame: 10:15 - 11:45 Proffered paper: Gastrointestinal tumours, lower digestive; CHAIR: GUILLERMO ARGILES MARTINEZ; speaker card: Zhen Yu Lin — Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (LARC): The phase 3 UNION trial; ALMERIA AUDITORIUM - HALL 9] [Slide 2] KEY SECONDARY ENDPOINT: Investigator-assessed EFS ◆ Median duration of follow-up was 36.7 months (IQR 32.6-39.9) in the experimental group and 34.7 months (IQR 31.1-39.1) in the standard-of-care group. ◆ Per investigator assessment, the experimental regimen provided a statistically significant and clinically meaningful improvement in EFS compared with standard of care (3-year rate: 91.3% [95% CI 83.9-95.4] vs 77.4% [95% CI 67.9-84.4]; HR 0.33 [95% CI 0.15-0.71], p=0.0029; crossing the prespecified boundary of statistical significance [0.0102]). Legend: Experimental group; Standard of care group Number of events/patients | 3-year rate (95% CI) 9/113 | 91.3% (83.9–95.4) 25/118 | 77.4% (67.9–84.4) Stratified HR 0.33 (95% CI 0.15–0.71), two-sided log-rank p=0.0029 Event | Experimental group (N=113) | Standard of care group (N=118) EFS event | 9 (8.0) | 25 (21.2) Local recurrence only | 0 | 4 (3.4) Distant metastases only | 6 (5.3) | 17 (14.4) Local recurrence and distant metastases | 1 (0.9) | 2 (1.7) Death as the first event | 2 (1.8) | 2 (1.7) Number at risk (Number censored) Experimental group 113 (0) 108 (4) 104 (7) 98 (10) 98 (10) 95 (12) 92 (14) 92 (14) 86 (18) 78 (26) 64 (41) 51 (53) 29 (75) 15 (89) 7 (97) 2 (102) 0 (104) Standard of care group 118 (0) 111 (7) 100 (12) 95 (14) 87 (17) 84 (18) 80 (19) 78 (19) 74 (22) 69 (27) 56 (39) 42 (53) 25 (70) 14 (81) 8 (85) 2 (91) 1 (92) 0 (93) EFS, event-free survival; IQR, interquartile range; HR, hazard ratio; CI, confidence interval. Data cutoff date: October 1, 2025. Presenter: Zhenyu Lin [Livestream frame: Proffered paper: Gastrointestinal tumours, lower digestive; speaker card: Zhen Yu Lin — The phase 3 UNION trial] Survival table Endpoint: Investigator-assessed EFS Experimental group (SCRT + camrelizumab + CAPOX) | 113 Standard of care group | 118 HR: 0.33 HR CI: 0.15–0.71 P: two-sided log-rank p=0.0029 Landmark rates: 3 years: Experimental group 91.3% (CI 83.9–95.4) | Standard of care group 77.4% (CI 67.9–84.4)

[Slide 1] CRS • Non-specific immune response characterized by excessive and rapid activation of T-cells and other effector cells, leading to hypersecretion of proinflammatory cytokines such as IL-6, IL-10, IL-18, IFN-γ, and TNF-α • Often begins with fever, and can escalate to hypotension, disseminated intravascular coagulation, and acute respiratory distress syndrome with hypoxemia • Rarely severe (Grade 3 & 4: 1 – 7%) • Usually occurs within 48 hours after the first dose • Becomes more attenuated with subsequent treatment → It is recommended to use steroids, antihistamines and paracetamol in the first 2 cycles and discontinue if no CRS is experienced Christophe Le Tourneau, MD, PhD [Slide 2] ICANS • Immune effector Cell-Associated Neurotoxicity Syndrome • Often co-occurs with CRS • Disruption of the blood-brain barrier and transcient central cytokine leak due to cytokine-mediated endothelial dysfunction • Linked to IL-1-mediated neuroinflammation, blood-brain barrier breakdown, and disturbance of neuronal excitability • Early symptoms include tremor, dysgraphia, dysphasia (especially in naming objects), apraxia, and lethargy, with potential progression to seizures, encephalopathy, or coma • Remains rare (1 – 8%) Christophe Le Tourneau, MD, PhD [Slide 3] On-target off-tumor toxicity • Due to antigens expressed on normal tissues • Toxicities depend on the targets: - CEA → GI toxicity - EGFR → skin toxicity - EpCAM → liver toxicity, diarrhea - gp100 → skin toxicity - GPRC5D → skin & nail disorders, loss of sense of taste - BCMA → hypogammaglobulinemia, risk of infection Christophe Le Tourneau, MD, PhD [Slide 4] Infusion-related reactions (IRR) Neurologic and psychiatric: Dizziness, Headache, Weakness, Syncope, Seizure, Anxiety, Sense of impeding doom 40% Respiratory: Dyspnea, Nasal Congestion, Rhinitis, Sneezing, Oropharyngeal or laryngeal edema, Bronchospasm, Tachypnea, Cyanosis, Respiratory arrest 30% Cardiovascular: Tachycardia, Hypotension, Arrhythmia, Chest pain, Ischemia or infarction, Cardiac arrest 90% Cutaneous: Flushing, Erythema, Pruritus, Urticaria, Angioedema, Rash Gastrointestinal: Nausea, Vomiting, Cramping, Diarrhoea Other: Chills, Fever Figure 1. Signs and symptoms of infusion reactions. Christophe Le Tourneau, MD, PhD Barroso et al., ESMO Open 2024;9:1-18

[Slide 1] STUDY DESIGN EMERALD-3 is a global, randomised, open-label, sponsor-blinded, multicentre, Phase 3 study(1) Study population(1): • Confirmed HCC not amenable to curative treatment, but eligible for embolisation • Child-Pugh class A • ECOG PS 0 or 1 • No extrahepatic disease • Excludes Vp3 and Vp4 • No prior systemic therapy Stratification factors(1): • Geographical region (Japan vs Asia [excluding Japan] vs rest of the world) • Prior palliative locoregional therapy (1 >6 months vs 1 ≤6 months vs none) • Baseline tumour burden (>Up-to-7 vs ≤Up-to-7) R* N=760 Arm A: STRIDE + L + TACE† (n=293) Arm B: STRIDE + TACE† (n=175) Arm C: TACE† (n=292) *Participants were randomised 1:1:1 to Arms A, B and C until each arm reached 175 participants; following this, randomisation continued 1:1 to Arms A and C until reaching ~275 participants per arm Primary endpoint‡: • PFS for Arm A vs C per RECIST v1.1 by BICR Key secondary endpoints‡: • OS for Arm A vs C • PFS for Arm B vs C per RECIST v1.1 by BICR • OS for Arm B vs C Other secondary endpoints included‡: • PFS2, PROs, safety Post-hoc exploratory assessments: • TTNT • Mean ALBI and Child-Pugh scores over the treatment period EMERALD-3: NCT05301842. In this post-hoc exploratory analysis, underlined variables are reported by baseline liver function. †DEB-TACE or conventional TACE. TACE starts ≥7 days after tremelimumab + durvalumab ± lenvatinib for Arms A and B or within 7 days of randomisation for Arm C, followed by additional procedures at the investigator's discretion. Treatment will continue for up to a maximum of 36 months. ‡Under a multiple testing procedure, the primary endpoint and key secondary endpoints are assessed sequentially in hierarchical order. BICR, blinded independent central review; DEB-TACE, drug-eluting bead transarterial chemoembolisation; ECOG PS, Eastern Cooperative Oncology Group performance status; PFS2, time from randomisation to earliest progression following first objective progression after the first subsequent therapy or death; PRO, patient-reported outcome; R, randomised; RECIST, Response Evaluation Criteria in Solid Tumors; TTNT, time from randomisation to first subsequent therapy or death; Vp3, thrombosis in the right or left portal vein; Vp4, thrombosis in the main truck of the portal vein. 1. Kudo M, et al. Lancet Oncol 2026;27:1077–1093. Masatoshi Kudo, MD, PhD [Slide 2] BASELINE CHARACTERISTICS BY ALBI GRADE n (%) unless otherwise indicated | ALBI Grade 1: STRIDE + L + TACE (n=188) | STRIDE + TACE (n=105) | TACE (n=183) | ALBI Grade 2*: STRIDE + L + TACE (n=105) | STRIDE + TACE (n=70) | TACE (n=109) Age, years, median (range) | 66 (25–86) | 66 (33–83) | 64 (34–83) | 67 (33–86) | 63 (32–85) | 67 (43–85) Geographical region: Japan | 15 (8.0) | 7 (6.7) | 10 (5.5) | 7 (6.7) | 4 (5.7) | 12 (11.0) Asia (excluding Japan) | 119 (63.3) | 82 (78.1) | 119 (65.0) | 53 (50.5) | 55 (78.6) | 54 (49.5) Rest of world | 54 (28.7) | 16 (15.2) | 54 (29.5) | 45 (42.9) | 11 (15.7) | 43 (39.4) ECOG PS 0 | 154 (81.9) | 94 (89.5) | 156 (85.2) | 82 (78.1) | 51 (72.9) | 83 (76.1) Aetiology: Hepatitis B virus | 94 (50.0) | 61 (58.1) | 98 (53.6) | 37 (35.2) | 38 (54.3) | 40 (36.7) Hepatitis C virus | 23 (12.2) | 11 (10.5) | 24 (13.1) | 16 (15.2) | 8 (11.4) | 13 (11.9) None / neither | 68 (36.2) | 33 (31.4) | 57 (31.1) | 52 (49.5) | 23 (32.9) | 52 (47.7) Child-Pugh: Class A – score of 5 | 176 (93.6) | 100 (95.2) | 172 (94.0) | 70 (66.7) | 44 (62.9) | 73 (67.0) Class A – score of 6 | 12 (6.4) | 5 (4.8) | 11 (6.0) | 32 (30.5) | 26 (37.1) | 34 (31.2) BCLC stage A | 33 (17.6) | 20 (19.0) | 42 (23.0) | 18 (17.1) | 13 (18.6) | 27 (24.8) B | 123 (65.4) | 69 (65.7) | 112 (61.2) | 64 (61.0) | 45 (64.3) | 59 (54.1) C | 32 (17.0) | 16 (15.2) | 28 (15.3) | 23 (21.9) | 12 (17.1) | 22 (20.2) Tumour burden (Up-to-7 criteria†) ≤7 | 82 (43.6) | 38 (36.2) | 72 (39.3) | 33 (31.4) | 22 (31.4) | 43 (39.4) >7 | 106 (56.4) | 67 (63.8) | 111 (60.7) | 72 (68.6) | 48 (68.6) | 66 (60.6) Portal vein invasion Vp1 or Vp2 | 17 (9.0) | 12 (11.4) | 19 (10.4) | 12 (11.4) | 7 (10.0) | 9 (8.3) Prior palliative embolisation before randomisation‡ | 29 (15.4) | 22 (21.0) | 37 (20.2) | 22 (21.0) | 7 (10.0) | 13 (11.9) DCO1: 2 Sep 2025. Tumour burden and prior palliative embolisation before randomisation are from Interactive Response Technology data. *Includes 1 participant with ALBI grade 3 in the STRIDE + lenvatinib + TACE arm; †Within Up-to-7 criteria: sum of size of largest tumour (in cm) and number of tumours of ≤7; beyond Up-to-7 criteria: sum of size (in cm) and number of tumours >7. ‡Includes participants who received one embolisation procedure at >6 months and those who received one embolisation procedure at ≤6 months. BCLC, Barcelona Clinic Liver Cancer; DCO, data cut-off; Vp1, thrombus beyond second order branches; Vp2, thrombus in second order branches. Masatoshi Kudo, MD, PhD [Slide 3] MEAN ALBI SCORE OVER TREATMENT PERIOD BY BASELINE ALBI GRADE Left panel: ALBI Grade 1 | Right panel: ALBI Grade 2* Legend: STRIDE + L + TACE | STRIDE + TACE | TACE Y-axis: Mean ALBI score (0 to -4); X-axis: Analysis visit number (1, 5, 6, 8 ... 42) Reference bands: ALBI Grade 3: > -1.39 | ALBI Grade 2: >-2.60 to ≤ -1.39 | ALBI Grade 1: ≤ -2.60 Number of participants (ALBI Grade 1): STRIDE + L + TACE 185 158 155 135 141 139 137 127 128 123 117 110 104 98 90 90 84 77 74 73 70 69 65 63 58 55 52 47 44 40 38 33 28 26 26 21 20 19 8 STRIDE + TACE 105 36 86 28 83 84 75 74 68 65 63 59 55 57 55 52 48 50 46 44 44 43 39 37 35 35 35 34 33 34 32 28 29 23 20 17 12 TACE 181 53 109 33 86 88 67 50 34 30 24 19 15 12 11 10 10 9 8 7 7 5 5 5 5 Number of participants (ALBI Grade 2*): STRIDE + L + TACE 102 90 87 78 81 75 71 68 64 59 57 54 51 44 47 44 41 36 36 34 30 31 25 20 19 18 16 14 14 12 10 7 8 7 7 7 6 7 STRIDE + TACE 70 23 62 20 53 52 47 43 38 32 32 32 32 31 29 29 28 23 22 23 21 20 19 18 17 17 16 13 15 16 16 13 15 15 11 12 12 7 TACE 109 34 51 20 38 38 28 19 12 9 8 8 5 5 5 DCO2: 23 Feb 2026. Visits with <5 participants were excluded to avoid overinterpretation of changes in mean values due to small sample sizes. *Includes 1 participant with ALBI grade 3 in the STRIDE + lenvatinib + TACE arm. ALBI scores were derived from albumin and bilirubin separately assessed every 14 days from baseline up to Cycle 3, then every 28 days thereafter until treatment discontinuation or up to Cycle 37 Day 1 (analysis visit 42). For participants with baseline ALBI grade 1, median (range) follow-up duration for ALBI assessment was 11.9 (0–35.2) months for STRIDE+L+TACE, 11.8 (0–34.9) months for STRIDE+TACE, and 2.0 (0–24.1) months for TACE; for participants with baseline ALBI grade 2*, median (range) follow-up duration was 9.3 (0–35.1) months, 5.8 (0–34.3) months, and 0.9 (0–28.4) months, respectively. Duration of follow-up was calculated between final visit and start of treatment. Where the final visit was baseline and occurred prior to start of treatment, duration was set to 0. All visits, including those with fewer than 5 participants, were included in the duration of follow-up calculation. Masatoshi Kudo, MD, PhD [Slide 4] MEAN CHILD-PUGH SCORE OVER TREATMENT PERIOD BY BASELINE SCORE Left panel: Child-Pugh Class A – score of 5 | Right panel: Child-Pugh Class A – score of 6 Legend: STRIDE + L + TACE | STRIDE + TACE | TACE Y-axis: Mean Child-Pugh score; X-axis: Analysis visit number; band label: Child-Pugh Class A Number of participants (score of 5): STRIDE + L + TACE 242 181 171 164 165 157 158 150 143 135 127 122 116 116 105 99 99 93 88 83 80 72 71 66 63 58 54 50 46 37 31 30 28 23 23 21 11 STRIDE + TACE 144 111 107 113 99 94 88 85 82 79 73 74 71 68 65 63 57 56 56 53 50 47 46 44 42 41 40 39 34 35 28 27 24 15 6 TACE 242 158 130 106 83 62 38 31 26 23 17 15 14 13 12 11 10 8 9 6 6 6 5 5 Number of participants (score of 6): STRIDE + L + TACE 43 32 27 30 28 27 22 21 22 20 19 14 14 13 11 8 8 7 7 7 7 5 5 STRIDE + TACE 31 23 18 18 19 18 14 12 9 11 12 13 10 11 12 9 11 12 9 8 9 8 8 9 6 9 8 5 8 8 8 6 6 6 TACE 46 26 19 15 9 7 5 DCO2: 23 Feb 2026. Visits with <5 participants were excluded to avoid overinterpretation of changes in mean values due to small sample sizes. Child-Pugh score for class A-C ranges from 5–15, derived from clinical laboratory assessments collected at baseline then every 28 days until treatment discontinuation or up to Cycle 37 Day 1 (analysis visit 42). For participants with baseline Child-Pugh Class A (score of 5), median (range) follow-up duration for Child-Pugh assessment was 11.9 (0–35.1) months for STRIDE+L+TACE, 11.2 (0–34.9) months for STRIDE+TACE, and 1.8 (0–28.4) months for TACE; for participants [partly obscured] Class A (score of 6), median (range) follow-up duration was 7.8 (0–35.2) months, 5.6 (0–33.2) months and 0.9 (0–17.3) months, respectively. Duration of follow-up was calculated between final visit and start of treatment. Where the final visit was baseline and occurred [obscured] duration was set to 0. All visits, including those with fewer than 5 participants, were included in the duration of follow-up calculation. Masatoshi Kudo, MD, PhD

[Slide 1] Age does NOT impact checkpoint inhibitor efficacy Overall survival benefit of immunotherapy by age group Re-expression of Table 1 (OS subgroup analysis) Subgroup | No. of studies | Age <65 years HR (95% CI) | Age ≥65 years HR (95% CI) | P value for subgroup difference All | 26 | 0.77 (0.70-0.85) | 0.77 (0.70-0.85) | 0.99 Primary disease site NSCLC | 10 | 0.71 (0.61-0.84) | 0.78 (0.68-0.90) | 0.39 Melanoma | 6 | 0.76 (0.63-0.92) | 0.72 (0.60-0.87) | 0.68 Other tumors | 10 | 0.83 (0.72-0.97) | 0.78 (0.65-0.94) | 0.61 Type of immunotherapy Anti-PD-1/PD-L1 antibody | 18 | 0.77 (0.68-0.87) | 0.71 (0.64-0.79) | 0.36 Anti-CTLA-4 antibody | 7 | 0.82 (0.71-0.94) | 0.93 (0.80-1.07) | 0.23 Line of treatment 1st line | 11 | 0.74 (0.62-0.89) | 0.81 (0.69-0.95) | 0.49 ≥2nd line | 15 | 0.79 (0.71-0.87) | 0.74 (0.66-0.83) | 0.45 Hazard ratio for overall survival (0.5-1.2); Favors immunotherapy / No benefit; legend: Age <65 years, Age ≥65 years Kim et al, ESMO Open 2022 [Slide 2] Tolerability of peri-operative treatment in older patients: CRITICS CRITICS cohort composition ≥70 years (n=172) | <70 years (n=616) Age group: ≥70 years 172 (22%); <70 years 616 (78%); Median age: 59 vs 73 years Sex: Male 121 (70%) [≥70] vs 408 (66%) [<70]; Female 51 (30%) vs 208 (34%) WHO performance status: WHO PS 0 104 (60%) vs 430 (70%); WHO PS 1 54 (31%) vs 155 (25%); Not performed 14 (8%) vs 28 (5%) Patients (%) Based on Table 1 from Slagter et al. Older versus younger adults with gastric cancer receiving perioperative treatment: Results from the CRITICS trial. WHO performance status had 3 missing values overall. Based on Slagter et al, EJC 2020 [Slide 3] Tolerability of peri-operative FLOT in older patients RealFLOT cohort composition (n=206) Selected real-world cohort of resectable gastric or gastro-oesophageal junction adenocarcinoma Sex: Male 141 (68%); Female 65 (32%) Age group: <65 years 117 (57%); ≥65 years 89 (43%) ECOG performance status: 0 189 (92%); 1 17 (8%) Patients (%) [0-100] Based on Table 1. Median age 63 years (range 36-77); 43% were aged ≥65 years; all patients had ECOG PS 0-1. Based on Giommoni et al, BMC Cancer 2021 [Slide 4] Age and microbiome The age-related microbiome shift is strongest in healthier older adults MrOS cohort Discovery Cohort (N=599): Walk Speed High n=200 ***; Walk Speed Low n=399; Excellent n=205 *; <Excellent n=394; Low Med n=292 *; High Med n=307; LSC High n=205 *; LSC Low n=394; Composite Healthy n=133 **; Rest of cohort n=466 Validation Cohort (N=308): Walk Speed High n=106; Walk Speed Low n=202; Excellent n=106; <Excellent n=202; Low Med n=141 *; High Med n=167; LSC High n=111; LSC Low n=197; Composite Healthy n=61 *; Rest of cohort n=247 [Forest plots: Spearman Rho (-0.10 to 0.3) and Adj. β-Coef. (-0.01 to 0.01); significance markers ***, **, *, # on adj. β-coef. panel] Osteoporotic Fractures in Men study Based on Wilmanski et al, Nature Metabolism

[Slide 2] Interactive prognostic model of overall survival in advanced gastric adenocarcinoma in the immunotherapy era: the AGAMENON-SEOM registry FPN: 8949 ESMO Congress 2026 · Madrid, 23-27 October G. Marín, R. Hernández San Gil, B. García Porlan, I. Gardeazabal, A. Custodio, A. Fernández Montes, E. Terán Brage, A. Francisco Fernández, M. Ruiz Martín, T. Sauri, A. Calvo, F. Longo Muñoz, P. Ribera Fernández, L. Visa, C. Hierro, L. Gutiérrez, A. Martín Carnicero, P. Jimenez-Fonseca, J. Gallego, A. Carmona Bayonas BACKGROUND • Adding immune checkpoint inhibitors (ICI) to first-line chemotherapy changed the treatment of advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma. • Access to ICI depends on PD-L1 CPS, a continuous variable dichotomised at trial-specific cut-offs (CPS ≥1, ≥5, ≥10). • No validated prognostic model integrates continuous PD-L1 with routine clinical and laboratory variables. Aims: (1) build an individualised OS model and interactive calculator; (2) validate it; (3) explore long-term (3-year) survival and a "cured" fraction by CPS. METHODS • Design: observational, multicentre AGAMENON-SEOM registry (41 hospitals). • Population: advanced HER2-negative non-squamous gastric/GEJ adenocarcinoma; first-line CT ± anti-PD-1 from 2021. Registry 5,814 → first line since 2021, 1,581 → HER2-negative, 1,229 → 1,178 with evaluable follow-up. • Endpoint: OS from start of first line. • Analysis: Kaplan-Meier, log-rank; multivariable Cox with a-priori covariates; restricted cubic splines for CPS, neutrophil-to-lymphocyte ratio (NLR) and age; ICI × spline(log-CPS) interaction; multiple imputation. • Performance: C-index (apparent, bootstrap, external), calibration at 1–3 years; temporal validation in later patients. Mixture cure models with four latency distributions. PATIENT CHARACTERISTICS | Total | CT alone | CT + anti-PD-1 Patients, n | 1,178 | 688 | 490 Age, median [IQR] | 66 [57–74] | 66 [56–74] | 66 [58–74] Male | 67% | 66% | 68% ECOG ≥2 | 12% | 15% | 9% Lauren diffuse | 59% | 64% | 52% Peritoneal metastases | 48% | 53% | 42% CPS, median [IQR] | 6 [1–15] | 1 [0–4] | 12 [6–23] CPS ≥10 (of tested) | 38% | 11% | 62% Oxaliplatin regimen | 91% | 85% | 98% Deaths | 65% | 70% | 57% Percentages of known values. CPS tested in 74% (60% CT alone; 93% CT + anti-PD-1). RESULTS 12.4 vs 10.1 mo — Median OS, CT + anti-PD-1 vs CT (n = 1,178; 762 deaths) HR 0.75 — 95% CI 0.65–0.87; unadjusted; log-rank p <0.001 19% vs 11% — Alive at 3 years (1-/2-year: 52/29% vs 45/19%) ICI benefit grows continuously with PD-L1 CPS Multivariable Cox, ICI × spline(log-CPS), n = 1,178: interaction p = 0.013; non-linear component p = 0.008. CPS <5: few patients treated with ICI HR at CPS 1: 0.71; CPS 5: 0.99; CPS 10: 0.90; CPS 20: 0.72; CPS 50: 0.50; CPS 100: 0.37 HR, CT + anti-PD-1 vs CT PD-L1 CPS (log scale) Continuous spline estimate with 95% CI (shaded); labels show HR at selected CPS values. Adjusted for regimen, ECOG, NLR, age, sex, ascites, Lauren, bone metastases, number of sites and albumin. No single cut-off captures the gradient. Calculator model: multivariable Cox (n = 999; 652 events) Variable | HR (95% CI) | p Oxaliplatin regimen (vs other) | 0.67 (0.52–0.86) | 0.002 ECOG 0 (vs ≥2) | 0.57 (0.43–0.76) | <0.001 ECOG 1 (vs ≥2) | 0.70 (0.55–0.89) | 0.003 Female sex | 0.82 (0.69–0.98) | 0.032 Mild ascites (vs none) | 1.11 (0.89–1.40) | 0.35 Moderate ascites | 1.36 (0.96–1.91) | 0.081 Severe ascites | 1.99 (1.21–3.29) | 0.007 Intestinal histology (vs diffuse) | 0.70 (0.57–0.87) | 0.001 Bone metastases | 1.34 (1.06–1.70) | 0.014 ≥3 metastatic sites | 1.42 (1.16–1.74) | <0.001 Albumin 2.5–3.5 g/dL (vs normal) | 1.21 (0.95–1.53) | 0.12 Albumin <2.5 g/dL | 1.49 (1.12–1.98) | 0.006 Also: NLR (spline, p <0.001), age (spline, p = 0.001) and ICI × log-CPS (spline; interaction p = 0.055, non-linear p = 0.025). Green: lower risk; red: higher risk. 0.685 / 0.673 — Derivation C-index, apparent / optimism-corrected; calibration slope 1.03 (0.90–1.16) 0.67 (0.61–0.74) — Temporal validation C-index, n = 171 later patients (91 deaths); slope 0.82 (0.48–1.16) INTERACTIVE CALCULATOR: AGAMENON-SEOM App screenshot (Spanish interface). Reference profile: 66-year-old man, ECOG 1, NLR 3.5, Lauren intestinal, no ascites or bone metastases, 1–2 metastatic sites, normal albumin, oxaliplatin regimen. Same patient, CPS | CT alone | CT + anti-PD-1 5 | 14.9 m (21%) | 15.8 m (23%) 20 | 13.5 m (18%) | 17.4 m (27%) 50 | 12.6 m (15%) | 20.4 m (33%) Predicted median OS (probability alive at 3 years). agamenon.shinyapps.io/immunotherapy Free access. Research tool; does not replace clinical judgement. Long-term survival and "cure" • CPS ≥10: alive at 2/3 years 31%/20% with CT + anti-PD-1 vs 14%/11% with CT alone (Kaplan-Meier). • Predicted 3-year OS falls with CPS on CT alone and rises from CPS 10 with anti-PD-1 (≈30% at CPS 100). • Cured fraction with anti-PD-1 depends on the assumed distribution (15%, 12%, 7% or 0%); the best-fitting model has no cure fraction. No plateau yet (max follow-up 46 months). CONCLUSIONS • ICI benefit is not a threshold effect: it grows continuously and non-linearly with CPS (interaction p = 0.013). • First AGAMENON-SEOM prognostic model for the immunotherapy era: continuous CPS, treatment and ten clinical-laboratory variables in a free online calculator, validated in independent patients (C-index 0.67). • 3-year survival depends on CPS and treatment; a cured fraction is not yet identifiable and needs longer follow-up. Disclosure (first and presenting author, G. Marín)

[Slide 1] a Pre-ICB combination ~ 6 months pre-invika treatment b Baseline (for invika) disease progression post ICB combination c Invika monotherap 9+ months post-treatment [CT chest images, red arrows marking lesions in a and b] [Slide 2] b OBD HPV+ | OBD including TMB-H or MSI-H or immunogenic Best percentage change from baseline in target lesions Tumor types (left to right): Anal, HNSCC, Cervical, Anal, HNSCC | MSS CRC, MSS CRC, NSCLC, Uveal melanoma, TNBC, MSS CRC, DDA, NSCLC, MSS CRC, Esophageal, MSS CRC, MSS CRC, Ovarian, Oropharyngeal, MSS CRC, Pancreatic, Cervical, MSI CRC, Melanoma*, MSS CRC, MSS CRC, NSCLC

[Slide 2] 2423P - Systemic Therapy in Advanced Gastric Neuroendocrine Neoplasms (G-NENs): Real-World Evidence from the R-GETNE National Registry (G-NENCARE) María San-Román-Gil, Paula Jiménez-Fonseca, Alejandro García-Álvarez, Carlos González-Merino, Guillermo Crespo-Herrero, Alberto Carmona-Bayonas, Marta Benavent-Viñuales, Carlos López-López, Vicente Alonso-Orduña, Ángel Segura-Huerta, Nieves Martínez-Lago, Javier Gallego-Plazas, Marta Llanos-Muñoz, Laura Nosti-Martínez, Sergio Pérez-Fernández, Rocío García-Carbonero Table 1. Clinicopathological characteristics: G-NETs vs G-NECs Characteristic | NET (n=61) | NEC (n=107) | p | Total (n=191) (^) Age, median (range), years | 62 (21–85) | 70 (38–96) | 0.012 | 67 (21–96) Male / Female, % | 62.3 / 37.7 | 69.2 / 30.8 | 0.40 | 69.1 / 30.9 ECOG PS 0 / 1 / 2 / ≥3, % | 48.9 / 39.5 / 9.3 / 2.3 | 10.5 / 54.6 / 25.6 / 9.3 | | Stage (at diagnosis) I / II / III / IV, % | 5.1 / 8.5 / 10.1 / 76.3 | 0 / 1.9 / 14.0 / 84.1 | <0.001 | 23.7 / 49.6 / 19.3 / 7.4 Ki-67 NET: <3% / 3–10% / 11–20% / >20%, % | 27.6 / 43.1 / 22.4 / 6.9 | – | 0.018 | 1.6 / 4.3 / 13.4 / 80.7 Ki-67 NEC: 21–50% / >50%, % | – | 21.2 / 78.8 | | Metastases: liver / non-regional LN / peritoneum / lung / bone, % (*) | 81.4 / 27.9 / 25.6 / 7.0 / 7.0 | 79.1 / 36.3 / 23.1 / 14.3 / 13.2 | >0.05 | 81.2 / 32.2 / 23.5 / 11.4 / 10.1 1st-line systemic treatment, % | 78.7 | 76.6 | 0.85 | 76.4 Figure 1 / Figure 2 / Figure 3 / Figure 4: Overall survival from metastatic disease Table 2. mOS according to 1st-line treatment and Ki-67^ Ki-67 (n) | SSA | TT | Non-plat CT | Plat-CT | mOS G-NET · mOS by treatment | 66m | 34m | 7m | 10m | FIGURE 3 <3% (11) | 9 (82) | 1 (9) | 1 (9) | 0 | 66m 3–10% (21) | 13 (62) | 2 (10) | 2 (10) | 4 (19) | 64m 11–20% (11) | 6 (55) | 1 (9) | 0 | 4 (36) | 34m >20% (3) | 0 | 0 | 2 (67) | 1 (33) | 10m Total treated (46)^ | 28 (61) | 4 (9) | 5 (11) | 9 (20) | 48m G-NEC · mOS by treatment | – | – | 11m | 9m | FIGURE 4 21–50% (19) | 1 (5) | 1 (5) | 3 (16) | 14 (74) | 17m >50% (60) | 0 | 0 | 7 (12) | 53 (88) | 9m Total treated (79)^ | 1 (1) | 1 (1) | 10 (13) | 67 (85) | 9m CONCLUSIONS • This is one of the largest real-world studies describing treatment patterns and outcomes in advanced Gastric-NENs. • Advanced G-NENs show marked prognostic heterogeneity: Ki-67 drives prognosis and treatment choice in NETs, whereas disease-related factors predominate in NECs. • These findings provide valuable insights for clinical practice of a heterogeneous population underrepresented in clinical trials.

485P FFPN-485P Adjuvant Chemotherapy for Operated Ampullary Adenocarcinomas Based on Histology and Intensification - Results from the Pancreatobiliary Cohort APACHI STUDY Anant Ramaswamy, Venkatesh Darshan, Prabhat G. Bhargava, Vikram A. Chaudhari, Manish Bhandare, Anuradha Mehta, George John, Subhash Yadav, Rajiv K. Kaushal, Munita Bal, Reena Engineer, Rahul Krishnatry, Shivakumar Gudi, Sadhana Kannan, Poonam Jadhav, Sharon F. Sunn, Shailesh Shrikhande, Vikas S. Ostwal Tata Memorial Centre, Mumbai, India BACKGROUND The mainstay of management for resectable ampullary adenocarcinoma (AC) is resection. The role of adjuvant therapy in resected AC is debatable. Most guidelines suggest a histology based approach (intestinal vs pancreatobiliary subtyping) to adjuvant therapy, but there is limited prospective data for the same. AC are relatively common in India in comparison to pancreatic cancers. AIMS & OBJECTIVES PRIMARY ENDPOINT: 2-year Recurrence Free Survival (RFS) SECONDARY ENDPOINTS: 2-year Overall Survival (OS) Adverse events Proportion of patients completing planned treatment Serious adverse events (SAEs) ELIGIBILITY Key Inclusion Criteria: Age: 18-75 years Diagnosis: Histologically confirmed Stage II-III adenocarcinoma of the ampulla post R0/R1 resection (as per AJCC 8th edition) Performance Status: ECOG PS 0-1 Organ Function: Adequate end-organ function Histological Subtype: Intestinal (IT) or pancreatobiliary (PB) Informed Consent: Ability to provide written informed consent TRIAL DESIGN & SAMPLE SIZE ESTIMATION Study Design: APACHI is designed as a two arm, non-randomized, open-label, prospective, parallel, adaptive design Phase II clinical trial. Sample Size Estimation: Available evidence with the use of gemcitabine as adjuvant therapy in operated AC shows a differential RFS with respect to AC and PB subtypes. The study is conducted as two parallel, single-stage Phase II clinical trials. Statistical analyses will be performed within each treatment arm with no formal statistical comparisons between the treatment arms. The 2 year RFS post surgery and adjuvant gemcitabine for AC-PB subtype is approximately 60%. For the AC-PB cohort, assuming expected 2 year RFS with gemcitabine chemotherapy (historical cohort) is 60%, a study with a power of 80% and two-sided alpha of 10% will require 67 patients to show an improvement in 2 year RFS to 75% with mFOLFIRINOX. (inclusive of an attrition rate of 10%). METHOD Phase II non - randomized open label prospective parallel adaptive design Operated periampullary (Stage II or stage III) R0/R1 resection N = 193 PB Cohort Reported & Complete Pancreatobiliary subtype -> Modified FOLFIRINOX biweekly x 6 Intestinal subtype -> CAPOX x 4 every 3 weeks Primary endpoint: RFS Secondary endpoints: OS, QOL, Tolerance, Toxicity, Recurrence IT & PB subtypes will be classified based on morphology and IHC CHARACTERISTICS of STUDY COHORT Characteristic | Number (Percentage) (N=66) Age (Range) | 50 (23-72) Stage II | 16 (24) Stage III | 50 (76) Median Nodal retrieval (range) | 23 (3-54) R0 resection | 64 (97%) Presence of PNI | 25 (38) Presence of LVI | 23 (35) Completed planned chemotherapy | 52 (81) Number of recurrences | 29 (44) CONCLUSION - Adjuvant mFOLFIRINOX for 3 months was feasible in patients with resected stage II-III ampullary cancers (pancreato-biliary subtype) with high treatment completion rates, but did not achieve statistical significance in improving 2-year RFS compared to historical controls treated with gemcitabine. - Further trials and genomic data might provide further information on the management of these relatively rare subset of Gastrointestinal cancers. DISCLOSURES & CONTACT - Funding and Drug Support: The study received grants from Reliance Life Sciences and TRAC, along with an honorarium from Cadila. - Correspondence: Dr Anant Ramaswamy (anantr13@gmail.com). RESULTS Survival plots and key findings: - Recurrence Free Survival - Pancreatobiliary Cohort (Primary Endpoint) - Overall Survival - Pancreatobiliary Cohort - Recurrence Free Survival - Stage Wise

[Slide 1] EOCRC and LOCRC are driven by distinct genetic HLA Class I signatures Distinct HLA class I allele background suggests a potential divergent neoepitope presentation profiles between groups that might constrain the breadth and efficacy of the CD8 responses in EOCRC versus LOCRC HLA Allele Combinations | EOCRC n=58 n(%PF) | LOCRC n=31 n(%PF) | Healthy Controls n=275 n(%PF) | EOCRC vs LOCRC (p FDR) | EOCRC vs controls (p FDR) | LOCRC vs controls (p FDR) B*15, B*57 | 19 (32.8) | 4 (12.9) | 29 (10.5) | 0.075596 | 0.001399 | 0.891574 B*15, B*57, B*51, B*52, B*53 | 30 (51.7) | 5 (16.1) | 73 (26.5) | 0.017706 | 0.005756 | 0.44255 B*15, B*57, B*18 | 24 (41.4) | 7 (22.6) | 65 (23.6) | 0.147248 | 0.029532 | 1 B*15, B*57, B*18, B*51, B*52, B*53 | 34 (58.6) | 8 (25.8) | 105 (38.2) | 0.027786 | 0.029532 | 0.44255 B*15, B*57, B*49, B*50, B*51, B*52, B*53 | 34 (58.6) | 7 (22.6) | 120 (43.6) | 0.019454 | 0.12608 | 0.210468 B*15, B*57, B*49, B*50, B*18, B*51, B*52, B*53 | 35 (60.3) | 10 (32.3) | 146 (53.1) | 0.065667 | 0.494016 | 0.210468 B*08, B*35 | 13 (22.4) | 18 (58.1) | 57 (20.7) | 0.017706 | 0.741413 | 0.000938 PF = phenotypic frequency [Slide 2] Conclusions Divergent Immune Profiles • EOCRC: Systemic hyper-inflammation (higher Th17, IL-1β, TNF-α), immune exhaustion, and suppressive regulatory cells (higher Tc9, Th2) favor tumor evasion. • LOCRC: Chronic adaptive exhaustion driven by aging (higher CTLA-4). Bacterial Translocation and Activation • LOCRC: Higher systemic microbial-driven profile (higher LPS, LBP, MCP-4) due to increased gut barrier vulnerability. • EOCRC: Higher systemic levels of epithelial antimicrobial defense (higher HBD2/HBD3) Genetic Background • Distinct HLA class I allele combinations (B*15/B*57 in EOCRC; B*08/B*35 in LOCRC) suggest a potential differential capacity to present and detect tumor antigens in EO and LOCRC, requiring further exploration EOCRC and LOCRC are biologically distinct diseases that can be differentiated by blood biomarkers, indicating that clinical and therapeutic strategies cannot rely on a universal biomarker

Efficacy Across the Three Abstracts and Chemotherapy Benchmarks Measure | LBA57 Opamtistomig | 2392O Opamtistomig + EP/EC | TOPIC-NEC EP | 2393O Pumitamig + FOLFIRI | BEVANEC FOLFIRI Setting | 3L+ EP-NEC | 1L EP-NEC | 1L digestive NEC | 2L NEN after platinum | 2L GEP-NEC or unknown N | 96 | 69 FAS; 65 efficacy | 84 assigned; 77 measurable | 31 treated; 30 evaluable | 67 treated ORR | 26.0% | 60.0% confirmed (39/65) | 54.5% | 40.0% confirmed | 18% (11/61) DCR | 35.4% | 90.8% | Not reported | 86.7% | 57% Median DOR | 9.8 mo | 10.2 mo | Not reported | 5.9 mo | 5.8 mo Median PFS | 1.4 mo | 5.7 mo | 5.6 mo | 5.5 mo | 3.5 mo OS | 8.7 mo; 12-mo 39.4% | NR; 18-mo 55.7% | 12.5 mo; 12-mo 52.1% | 12.8 mo; 12-mo 51.1% | 8.9 mo; 6-mo 60% Evidence role | Single-arm drug-specific activity | Single-arm first-line signal | Phase III (EP vs IP) | Single-arm second-line signal | Non-comparative randomized phase II Lu et al., ESMO 2026, LBA57; Zhang et al., ESMO 2026, 2392O; Xu et al., ESMO 2026, 2393O; Morizane et al., JAMA Oncol. 2022 Walter et al., Lancet Oncol. 2023 Jaydira Del Rivero

[Slide 1] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Secondary KIT mutations (exons 13/14/17/18) drive resistance; no single approved TKI covers them all, and 3L + benefit is modest (regorafenib mPFS 4.8 mo, avapritinib 4.2 mo) Abstract | Strategy | Design / population | Headline result 3717RO Bezuclastinib + sunitinib | Combine complementary TKIs | Peak part 2: crossover after progression on 2L sunitinib (n=128) | mPFS 7.4 mo, ORR 29.7% (vs 5.7 mo, 20.3% on sunitinib) 3718RO Velzatinib ctDNA | Broad-spectrum KIT inhibitor + biomarker | StrateGIST 1 phase 1/1b; exploratory ctDNA analysis, all lines | mKIT clearance by wk 8 (~50% of pts): HR 0.57 for progression/death (0.51–0.65 across wk 2–8) 3719RO NB003 | Broad-spectrum KIT inhibitor | Phase I (n=158 KIT-mutant), median 3 prior TKIs | 3L: ORR 46.7%, mPFS 13.8 mo; 4L: ORR 45.7%, mPFS 11.0 mo; ≥5L: ORR 12.5%, mPFS 3.9 mo Dr Palma Dileo Palma Dileo Invited Discussant 3717RO, 3718RO and 3719RO MALAGA AUDITORIUM - HALL 3 [Slide 2] 08:30 - 10:00 Rapid oral: Sarcoma CHAIRS: MARK DICKSON, PALMA DILEO, CESAR SERRANO Putting it together: where might each approach fit? Regimen / setting | mPFS (mo) | ORR (%) Regorafenib (3L, reference) | 4.8 | – Avapritinib (3L, reference) | 4.2 | – Bezuclastinib + sunitinib after sunitinib (crossover) | 7.4 | 29.7 NB003, 3L | 13.8 | 46.7 NB003, 4L | 11.0 | 45.7 Bezuclastinib + sunitinib, 2L (Peak main) | 16.5 | 46 Messages for practice and trial design • Treating earlier is likely better: benefit of combination falls from 16.5 to 7.4 mo after sunitinib failure • Broad-spectrum single agents (NB003, velzatinib) show activity in heavily pretreated pts; randomized 3L data are awaited • Combination vs single broad-spectrum agent: unresolved, and the toxicity trade-off differs • ctDNA could serve all three: early efficacy readout, response-adapted strategies and enrichment, but needs prospective validation Non-randomized and cross-trial data – not for direct comparison Dr Palma Dileo Palma Dileo Invited Discussant 3717RO, 3718RO and 3719RO MALAGA AUDITORIUM - HALL 3

[Slide 2] 3717RO – Crossover to bezuclastinib + sunitinib after progression on sunitinib mPFS (months) Sunitinib 2L (same pts) 5,7 Combination after crossover 7,4 Combination 2L (Peak main) 16,5 Third bar is a different (randomized, first-line-of-combination) population – shown for context only 29.7% ORR on combination (vs 20.3%) 56% ORR if best response to sunitinib was PD 39% Gr≥3 TRAEs (vs 72% upfront) Encouraging • Activity after sunitinib failure; 2 CRs in pts with PD on monotherapy • No new safety signals; low discontinuation (2.3%) • Supports the biological rationale of covering secondary mutations Interpret with caution • Non-randomized part, within-patient sequence, not a head-to-head; 95% CIs overlap (7.4 [5.6–11.0] vs 5.7 [3.8–7.3]) • Selected pts (sunitinib mPFS 5.7 mo here vs 9.2 mo in whole arm); shorter exposure (24 vs 61 wk) may explain lower Gr3+ AEs • Message is for earlier use: 7.4 mo at crossover vs 16.5 mo upfront Dr Palma Dileo [Slide 3] 3718RO – Velzatinib: ctDNA clearance as an early biomarker of benefit mPFS (months) by mKIT ctDNA clearance (>99% drop in maxVAF) Cleared | Not cleared Week 2: 11,0 | 5,0 Week 4: 9,5 | 5,5 Week 8: 11,0 | 5,5 Week 32: 13,7 | 10,4 HR 0.39 Baseline ctDNA detected vs not (PFS 7.3 vs 16.6 mo) HR 0.51–0.65 Clearance, wk 2 / 4 / 8: HR 0.51 / 0.65 / 0.57 (all P<0.05) HR 0.55 Week 32; P=0.068 (57% cleared) Strengths • Serial sampling; prognostic at baseline and dynamic on treatment • Mutation-agnostic: maxVAF (KIT/PDGFRA) outperformed mean VAF and G360 score (HR 0.50 vs 0.81 / 0.69; n=73) • Clearance across exons (67–82%) Open questions • Exploratory, ongoing, samples not all analysed; timepoint cohorts differ • Landmark analysis: later PFS in cleared pts partly reflects survival to sampling • Not independent of imaging; no adjustment for line or burden shown; maxVAF picked in 73-pt subset (HR 0.50 vs 0.57 in all pts at wk 8) • Would a clearing-based decision change outcome? Dr Palma Dileo [Slide 4] Take-home messages 1 Resistance in GIST is a mosaic of secondary KIT mutations: broader KIT coverage is the shared goal of all three abstracts. 2 Bezuclastinib + sunitinib rescues some pts after sunitinib failure, but its value is greatest when used earlier. 3 NB003 shows striking 3L/4L activity in a phase I; the randomized phase 3 against regorafenib will be the test. 4 Early mKIT ctDNA clearance on velzatinib tracks with PFS; it is hypothesis-generating and needs validation before guiding treatment. Dr Palma Dileo

[Slide 2] Diagnosis & ABC staging | 1 Surgery or chemo first? | 2 Which regimen? | 3 Restaging: resect? Patient 1: Surgery first or chemotherapy first? Meta-analysis of RCTs (OS) HR for death (95% CI) Borderline resectable meta-analysis, n = 677 Resectable meta-analysis, n = 517 CISPD-1 resectable, n = 324 PREOPANC-3 resectable; perioperative vs adjuvant mFOLFIRINOX - Results 2027 Alliance A021806 resectable; perioperative vs adjuvant mFOLFIRINOX - Results 2027 0.60 (0.38–0.96) 0.90 (0.63–1.28) 0.73 (0.53–1.00) ← Favours neoadjuvant | Favours upfront surgery → GUIDELINE Borderline resectable: chemotherapy first. Resectable: surgery first Diamonds: meta-analysis (MA) of 9 RCTs incl. PREOPANC-1, PREP-02/JSAP-05, ESPAC-5, NEONAX, NORPACT-1. Square: CISPD-1, after the MA; single centre (China), EFS primary. Dickerson LD et al. BJS Open 2025; van Dam JL et al. Eur J Cancer 2022 ★; Labori KJ et al. Lancet Gastroenterol Hepatol 2024; Bai X et al. Cancer Cell 2025;43:2259–67 [Slide 3] Diagnosis & ABC staging | 1 Surgery or chemo first? | 2 Which regimen? | 3 Restaging: resect? Patient 2: Which neoadjuvant regimen? RCTs comparing FOLFIRINOX with gemcitabine-based regimens HR for death (95% CI) Metastatic and adjuvant PRODIGE 4 metastatic 0.57 (0.45–0.73) PRODIGE 24 adjuvant 0.64 (0.48–0.86) Neoadjuvant and induction SWOG S1505 † R; vs gem/nab-P 0.96 (0.58–1.59) PREOPANC-2 R + BR; vs gem-CRT 0.88 (0.69–1.13) NEOPAN LA; vs gemcitabine 1.02 (0.73–1.43) ← Favours FOLFIRINOX | Favours gemcitabine-based → CASSANDRA (R + BR) PAXG vs mFOLFIRINOX EFS HR 0.63 (0.47–0.84) OS not yet reported MY VIEW For patient 2: FOLFIRINOX or gemcitabine-based regimen † HR reconstructed from published KM curves (Guyot; 32 vs 28 deaths). R/BR/LA, resectable/borderline/locally advanced; gem-CRT, gemcitabine-based chemoradiotherapy Conroy T et al. N Engl J Med 2011; 2018; Janssen QP et al. Lancet Oncol 2025 ★; Ducreux M et al. J Clin Oncol 2025; Sohal DPS et al. JAMA Oncol 2021; Reni M et al. Lancet 2026

[Slide 1] Surgery alone is not enough Landmark trials that shaped the current SoC [survival curves by pathologic stage: Present p Stage 0, I, IIA, IIB, III, IIIA?, IV, IVA, IVB; Survival (%) vs Years 0–10] 2001: Intergroup 0116 - Adjuvant bolus FL + RT - 20% GEJ 2002: OE02 - Neoadjuvant CF - Oesophageal only 2006: MAGIC - Perioperative ECF 2011: ACTS-GC - Adjuvant S-1; FFCD / FNCLC - Perioperative CF 2012: CROSS - Neoadjuvant carboplatin and paclitaxel + RT - Oesophageal and GEJ only; CLASSIC - Adjuvant CAPOX 2019: FLOT4 / AIO - Perioperative FLOT 2021: RESOLVE - Perioperative or adjuvant SOX; PRODIGY - Neoadjuvant D-Ox-S-1 TOPGEAR - Perioperative chemotherapy ± neoadjuvant CRT Daniela Molena, MD [Slide 2] FLOT 4: Establishing the Benchmark for the Next Generation of Trials OS in ITT population (%) FLOT ECF / ECX HR, 0.77 (95% CI, 0.63–0.94); p=0.012 Time (months) No. at risk FLOT 356 297 231 140 87 39 5 ECF / ECX 360 287 202 126 83 33 9 Primary endpoint results in ITT population: mOS, 50 vs 35 months (HR, 0.77) 5-year OS, 45% vs 36% Safety profile: Toxic deaths, <1% for each group Treatment-related SAEs, 27% vs 27% 1. Demonstrated an overall survival advantage 2. Improved pathological and surgical outcomes 3. Established a reproducible perioperative backbone 4. Became the standard of care for fit patients 5. Provided the foundation for immunotherapy trials Daniela Molena, MD Al-Batran SE, et al., Lancet 2019 Survival table Endpoint: OS (ITT) FLOT | 356 | 50 months ECF / ECX | 360 | 35 months HR: 0.77 HR CI: 0.63–0.94 P: 0.012 Landmark rates: 5-year: FLOT 45% | ECF / ECX 36% [Slide 3] MATTERHORN: A New Standard Is Born 0.71 EFS hazard ratio 67.4% 2-year EFS with durvalumab 19.2% Pathological complete response 2-year EFS Durvalumab + FLOT 67.4% FLOT alone 58.5% pCR Durvalumab + FLOT 19.2% FLOT alone 7.2% Durvalumab + FLOT | FLOT alone | Durvalumab + FLOT (n=474) | Placebo + FLOT (n=474) Median EFS, months (95% CI) | NR (40.7–NR) | 32.8 (27.9–NR) HR (95% CI) | 0.71 (0.58–0.86) Stratified log-rank p-value | <0.001 Daniela Molena, MD Janjigian YY, et al. N Engl J Med 2025 [Slide 4] Better Systemic Therapy, but Surgery Remains Central 18-mo OS Δ: 4.0 81.1% 77.1% 24-mo OS Δ: 5.1 75.5% 70.4% 36-mo OS Δ: 6.7 68.6% 61.9% +34.5% 41% Durvalumab + FLOT Placebo + FLOT FLOT (FLOT4 Trial) ECF/ECX (FLOT4 Trial) Surgery alone (Magic) Median (range) duration of follow-up, mo Durvalumab + FLOT: 43.0 (3.4–57.0) Placebo + FLOT: 42.9 (0.0–56.5) Time since randomization (mo) No. of participants at risk | Total no. of events Durvalumab + FLOT 474 464 438 422 403 389 377 367 351 338 334 323 316 255 182 112 71 29 6 1 0 | 160 Placebo + FLOT 474 457 439 414 395 374 355 338 324 310 298 293 278 221 167 99 61 23 7 0 0 | 192 Daniela Molena, MD Survival table Endpoint: OS (MATTERHORN, with FLOT4/MAGIC historical overlays) Durvalumab + FLOT | 474 Placebo + FLOT | 474 Landmark rates: 18-mo: Durvalumab + FLOT 81.1% | Placebo + FLOT 77.1% 24-mo: Durvalumab + FLOT 75.5% | Placebo + FLOT 70.4% 36-mo: Durvalumab + FLOT 68.6% | Placebo + FLOT 61.9%

[Slide 1] Perioperative Therapy in 2026: What Have We Learned? 1. Chemoimmunotherapy is changing the standard of care. MATTERHORN demonstrates improved survival with durvalumab + FLOT in resectable gastric/GEJ cancer 2. Surgery remains central to curative-intent treatment. Modern perioperative strategies improve outcomes while preserving surgical delivery 3. Response is important, but not synonymous with cure. pCR is prognostic; cCR cannot yet reliably exclude residual disease or justify routine omission of surgery 4. The future is biomarker-driven personalization. MSI-H/dMMR opens opportunities for de-escalation; ctDNA may help guide future treatment decisions Daniela Molena, MD [Slide 2] Perioperative Therapy in 2026: What Have We Learned? 1. Chemoimmunotherapy is changing the standard of care. MATTERHORN demonstrates improved survival with durvalumab + FLOT in resectable gastric/GEJ cancer 2. Surgery remains central to curative-intent treatment. Modern perioperative strategies improve outcomes while preserving surgical delivery Daniela Molena, MD [Slide 3] The Future: Escalate, Maintain, or De-escalate? Personalizing Perioperative Therapy: The Next Frontier ESCALATE - Persistent molecular disease or high-risk biology - Investigate intensified systemic therapy MAINTAIN - Most patients with resectable disease - Evidence-based perioperative therapy + high-quality surgery DE-ESCALATE - MSI-H/dMMR and exceptional responders - Chemotherapy-free strategies; organ preservation in clinical trials The future is not more treatment for everyone, but the right treatment for each patient. Daniela Molena, MD [Slide 4] ctDNA: Detecting Residual Risk, Not Proving Cure Beyond Clinical Response: Can ctDNA Close the Gap? After neoadjuvant therapy Endoscopy + imaging + biopsies + molecular assessment ctDNA undetectable - Associated with lower recurrence risk in some cohorts - Does not exclude residual local or nodal disease ctDNA detectable - May identify molecular residual disease and increased recurrence risk - Whether treatment escalation improves survival remains under investigation Can molecular response guide treatment escalation or de-escalation? ctDNA complements clinical assessment; it does not yet establish pathological complete response. Daniela Molena, MD

[Slide 2] ASTRA System Overview ASTAR: Agentic System for Tumor Resectability Assessment INPUT Multimodal patient data Specialized agents • Data Aggregator Consolidates multimodal clinical data • Radiology Report Interpreter Converts free-text MR reports into structured reports • Surgical Candidacy Assessor Assesses radiologic unresectability • Multidisciplinary Consensus Simulator Integrates clinical evidence to assess clinical unresectability OUTPUT • Structured MR report • Unresectability 1 Input (Task, context) PACS EHR Curated guidelines 2 Observations (Reasoning, Planning) pCCA? Tool calls 3 Agentic Workflow (Human in the loop, RAG) Guidelines search Human interaction 4 Output (Structured report, Resectability) Data Aggregator Agent: PACS EHR → MR report, Blood test, Medical record, Image report Radiology Report Interpreter Agent: Free-text MR report → Structured MR report → Signed structured report Surgical Candidacy Assessor Agent: Structured MR report → Radiologic Unresectability Yes / NO Multidisciplinary Consensus Simulator Agent: Medical records, Image report, Test report → Clinical Unresectability Yes / NO [Slide 3] Study Design Retrospective Evaluation → Reader study → Prospective validation → Silent trial n =518 — Foundation model selection benchmark n =104 — Unaided vs ASTRA-assisted n =53 — Blinded vs expert MDT consensus n =29 n =29 — Clinical co-pilot Outcomes assessed • Resectability assessment accuracy • Report structuring accuracy • Inter-rater agreement • Pre-MDT report quality • Pre-MDT briefing time [Slide 4] 172RO (Huang et al) 1 Input (Task, context) PACS EHR Curated guidelines 2 Observations (Reasoning, Planning) pCCA? Tool calls 3 Agentic Workflow (Human in the loop, RAG) Guidelines search Human interaction 4 Output (Structured report, Resectability) Data Aggregator Agent / Radiology Report Interpreter Agent / Surgical Candidacy Assessor Agent / Multidisciplinary Consensus Simulator Agent Prospective validation March 2025 - April 2026 External Validation Surgeons only n =29 ← Real-world Deployment → Surgeons + ASTRA n =29 ASTRA performance: Accuracy/Recall/Precision/F1; Report quality score (Completeness, Correctness, Necessity, Safety) Primary outcomes: Decision accuracy; Decision efficiency Secondary outcomes: Report quality score (Completeness, Correctness, Necessity, Safety); User acceptance survey ASTRA performance: Report structuring performance; Radiologist modification rate; Adoption rate E Radiologic Unresectability Control group (Ground Truth rows Yes/No; predicted No/Yes): Yes: 10.00% n=1 | 90.00% n=9; No: 78.95% n=15 | 21.05% n=4 Intervention group: Yes: 9.09% n=1 | 90.91% n=10; No: 100.00% n=18 | 0.00% n=0 Clinical Unresectability Control group: Yes: 22.73% n=5 | 77.27% n=17; No: 57.14% n=4 | 42.86% n=3 Intervention group: Yes: 13.64% n=3 | 86.36% n=19; No: 100.00% n=7 | 0.00% n=0 F Time(s): 518 vs 255 *** G Completeness: Control 5.2 / 48.3 / 32.8 / 13.8; Intervention 43.1 / 56.9 Correctness: Control 32.8 / 29.3 / 15.5 / 22.4; Intervention 27.6 / 55.2 / 10.3 / 6.9 Necessity: Control 3.4 / 39.7 / 34.5 / 22.4; Intervention 55.2 / 34.5 / 10.3 Safety: Control 1.7 / 34.5 / 27.6 / 10.3 / 25.9; Intervention 36.2 / 50 / 5.2 / 8.6 Score scale 5 4 3 2 1 Control Group Intervention Group Marco Lorenzi - Agentic AI for cancer decision-making (172RO and 280RO)

Characterising long-term non-progressors receiving Atezolizumab and Bevacizumab for advanced hepatocellular carcinoma (HCC) Dr Sam Rozewicz¹; Dr Andrea Martirena²; Menon Shanthakumar¹; Dr Robert Goldstein¹; Prof Timothy Meyer¹; Dr Alexa Childs¹ ¹Royal Free Hospital, London, UK. ²Fundación Jiménez Díaz University Hospital, Madrid, Spain NHS Royal Free London NHS Foundation Trust Introduction: • Atezolizumab and bevacizumab (AB) is an established first line treatment for advanced HCC. Despite an objective response rate (ORR) of 30% and improved median overall survival (mOS) compared with sorafenib, over 60% of patients receiving AB will progress within 12 months of starting treatment. • In this study we aimed to characterise long-term non-progressors (LTNP) and assess clinicopathological factors associated with sustained benefit from AB in a real-world cohort. Methods: • Patients treated with AB at The Royal Free Hospital (London) between July 2020 and December 2024 were identified from MDT records and clinicopathological characteristics and survival outcomes retrospectively reviewed. Radiological response was assessed every 9-12 weeks using RECIST v1.1. • We compared LTNP, defined as patients with progression-free survival of ≧12 months from treatment initiation with short-term progressors (STP), those who progressed <12 months. Results: Figure 1. Proportion of LTNP vs STP — Total 166 patients; LTNP (n=54) 32%; STP (n=112) 68% Figure 2. Kaplan Meier Estimates of Overall Survival — mOS LTNP 29.2mths vs STP 7.7 mths HR 0.19 (95% CI 0.13-0.3) • At 18 mths, 63% of LTNP had not progressed. • Median treatment duration was 15 mths in LTNP v 2.8 mths in STP (p<0.01). • 26.4% of LTNP discontinued B before A due to AE v 7.1% STP (p<0.01). • For LTNP that did stop B, median time on treatment with both agents was 12.5 mths. Table 1. Patient Characteristics Patient characteristics | Overall, n=166 (%) | LTNP, n=54 (%) | STP, n=112 (%) | p value Age, years, median | 70 | 71 | 69 | 0.625 Male gender | 143 (86.1) | 51 (94.4) | 92 (82.1) | 0.032 ECOG 0 | 78 (47) | 32 (59.3) | 46 (41.1) | 0.143 ECOG 1 | 82 (49.4) | 21 (38.9) | 61 (54.5) | ECOG 2+ | 6 (3.6) | 1 (1.9) | 5 (4.5) | Cirrhosis present | 117 (70.5) | 39 (72.2) | 78 (69.9) | 0.733 Aetiology of CLD — MASLD | 38 (22.9) | 13 (24.1) | 25 (22.3) | 0.833 ArLD | 30 (18.1) | 10 (18.5) | 20 (17.9) | Viral hepatitis | 54 (32.5) | 18 (33.3) | 36 (32.1) | Other | 18 (10.8) | 7 (13.0) | 11 (9.8) | Portal vein thrombus | 72 (43.4) | 20 (37.0) | 52 (46.4) | 0.253 Extra-hepatic spread present | 29 (17.6) | 5 (9.3) | 24 (21.6) | 0.05 AFP ng/ml, median | 30.1 | 10.6 | 56.2 | 0.411 ALBI Grade 1 | 113 (68.1) | 39 (72.2) | 74 (66.1) | 0.436 ALBI Grade 2 | 53 (31.9) | 15 (27.8) | 38 (33.9) | • LTNP were more likely to be male (94.4% v 82.1%, p=0.03) and less likely to have extra-hepatic disease (9.3% v 21.6%, p=0.05). • There were no significant differences in other baseline characteristics: portal vein involvement, baseline AFP, ALBI grade, prior HCC therapy, ECOG PS, presence of cirrhosis and aetiology of liver disease. • LTNP discontinued therapy due to PD (n=19), AE (9), liver decompensation (7) and death (4). Figure 3. Radiological response per RECIST 1.1 in LTNP vs STP Objective Response Rate (ORR) (CR + PR): LTNP (n=54) 58.5% | STP (n=112) 11.5% | p < 0.01 Stable Disease (SD): LTNP 41.5% | STP 29.2% | p < 0.01 • LTNP experienced higher ORR compared to STP Figure 4. Frequency and management of ImAE in LTNP vs STP Patients experiencing ImAE (% of patients): LTNP 37.7% | STP 23.0% | p=[illegible] Stopped treatment due to ImAE (% of those with ImAE): LTNP 25.0% | STP 46.2% | p=[illegible] Conclusion: In this single centre, real world cohort, we demonstrate that 32% patients treated with first-line AB are LTNP which in turn is associated with improved survival. Objective radiological response is the strongest predictor of LTNP but 41.5 % of those with SD will also achieve LTNP. FPN: 1722eP Contact: Dr Sam Rozewicz Email: samuel.Rozewicz@nhs.net Disclosure statement: No conflicts of interest to declare

[Slide 1] Higher pCR Does Not Necessarily Mean Better Survival Event-free survival CRT vs Chemo ± IO CRT Chemo ± IO HR = 0.59; P = 0.012 Years since Surgery At Risk / Events rows [illegible] • 650 (80%) CRT; 161 (20%) Chemo ± IO • Median follow-up 29.9 months • pCR higher in CRT (23% vs 14%) • pN0 higher in CRT (61% vs 46%; both P < .001) • R0 resection 96% in both groups • 2-year EFS greater in Chemo ± IO (66% vs 53%; adjusted hazard ratio, 0.53; P = .007) • 2-years OS not statistically different between groups Daniela Molena, MD Alkaali A, et al. JTCVS 2026 Survival table Endpoint: Event-free survival CRT | 650 Chemo ± IO | 161 HR: 0.59 P: 0.012 Landmark rates: 2-year: Chemo ± IO 66% | CRT 53% [Slide 2] pCR Is Prognostic, but Does Treatment Modality Matter? Patients WITH pCR n = 174 log-rank p = 0.024 HR not estimable (0 events in CT ± IO) Patients WITHOUT pCR n = 637 log-rank p < 0.001 HR 0.54 (95% CI 0.39–0.73) Event-free survival (%) Months from surgery No. at risk WITH pCR: CRT 151 113 91 67; CT ±IO 23 16 8 1 WITHOUT pCR: CRT 499 254 176 122; CT ±IO 138 85 37 10 — CRT — CT ± IO • 650 (80%) CRT; 161 (20%) Chemo ± IO • Median follow-up 29.9 months • CRT achieves more regression • Poor response (CAP 3) is 2.5× more common with CT ± IO (38% vs 15%) • pCR after Chemo ± IO reflects local and systemic control Daniela Molena, MD Molena D., et al. ISDE oral presentation 2026 Survival table Endpoint: Event-free survival by pCR status WITH pCR (CRT 151 / CT±IO 23) | 174 WITHOUT pCR (CRT 499 / CT±IO 138) | 637 HR: 0.54 (without-pCR subgroup) HR CI: 0.39–0.73 P: <0.001 (without pCR); 0.024 (with pCR) [Slide 3] FROM RESPONSE TO TREATMENT DECISIONS Can Clinical Complete Response Safely Replace Pathological Confirmation? pCR - Confirmed in resected tissue cCR - Estimated by clinical testing Cure - Demonstrated by durable outcomes These are related, but not interchangeable endpoints. Daniela Molena, MD [Slide 4] Clinical Complete Response: Can We Trust What We Cannot See? What we can assess • Endoscopy and biopsies • EUS ± FNA • CT and PET imaging • Clinical examination What we may miss • Microscopic residual tumor • Submucosal or deeper viable disease • Residual nodal metastases • Occult distant disease cCR ≠ pCR ≠ Cure Negative clinical assessments reduce suspicion of residual disease; they do not establish its absence. Daniela Molena, MD

[Slide 1] ppmSeq reads both strands of each cfDNA molecule PCR-free, error-corrected whole-genome sequencing (Ultima Genomics) Standard WGS Error or mutation? PCR and sequencing errors contribute to sequencing noise ppmSeq Both strands: consensus call | One strand: likely error Errors are removed using information from both strands Tumour-informed MRD Tumour (FFPE/FF) → Tumour WGS (CRAM); Normal (buffy coat) → Normal WGS (CRAM) → Somatic variant calling → Somatic variants (VCF) cfDNA (plasma) [illegible] → Plasma WGS (CRAM) → Personalised variant query → ctDNA fraction (ppm); MRD status (landmark) Schematic adapted from Ultima Genomics [Slide 3] ctDNA Positivity and Tumor Fraction across Timepoints Distribution of tumor fraction Tumour fraction (ppm) • Detected ○ Not detected ultrasensitive level (< 100 ppm) Baseline n = 233 | 100% positive Post-1M n = 240 | 21.2% positive Post-3M n = 218 | 14.7% positive Post-6M n = 180 | 8.9% positive Post-9M n = 125 | 12.8% positive Post-12M n = 83 | 7.2% positive Proportion of ultrasensitive detection Baseline 9.4% Post-1M 52.9% Post-3M 50.0% Post-6M 50.0% Post-9M 50.0% Post-12M 16.7% Detection rate (%) — Detected ≥ 100 ppm / Detected < 100 ppm / Not detected • ctDNA was detected in 100% of baseline samples (233/233). [Slide 4] Tumor Fraction by Recurrence Sites Tumor fraction at first detection by the site of subsequent recurrence Site of recurrence | n | Median tumor fraction at first detection | First detection < 100 ppm Lung only | 5 | 29 ppm | 3/5 Peritoneum only | 2 | 943 ppm | 1/2 Other/multiple | 5 | 1,192 ppm | 0/5 Liver only | 11 | 1,455 ppm | 4/11

[Slide 1] Which is optimal treatment; neoCRT or neoCTx? ➢ Better local tumor response with neoCRT than with chemotherapy alone: • CROSS: pCR 49% in the OSCC subgroup • JCOG1109: pCR 36.7% with neoCRT, 18.6% with triplet CTx • NeoRes: pCR 28% with neoCRT, 9% with doublet CTx P van Hagen et al, N Engl J Med 366:2074-84, 2012 Kato K, et al Lancet 2024. 404(10447):55-66. Klevebro et al, Ann Oncol 27:660-667, 2016 ➢ Different pattern of recurrence following neoCRT vs. neoCTx: • CROSS: 5-year distant-only recurrence 27% with neoCRT and 28% with surgery alone • JCOG1109: 5-year distant-only recurrence 18.5% with neoCRT and 12.5% with triplet CTx ➢ Tendency of higher non-cancer mortality following neoCRT: • CROSS: 5-year non-cancer death 15% with neoCRT and 11% with surgery alone • JCOG1109: 5-year non-cancer death 13.7% with neoCRT and 4.5% with triplet CTx • NeoRes: 5-year non-cancer death 12.2% with neoCRT and 8.8% with doublet CTx Eyck BE et al, J Clin Oncol; 20;39(18):1995-2004. 2021 Kato K, et al. J Clin Oncol 42(16_suppl): 4082, 2024 Von Dobeln GA, et al. Dis Esophagus 32(2): 1-11, 2019 Ken Kato, MD, PhD [Slide 2] JCOG1109 "NExT Trial" Thoracic ESCC cStage II/III (UICC-TNM 7th) PS 0-1, 20-75 y.o. Primary endpoint: Overall survival Secondary endpoint: PFS, pCR, Safety R → Neo-Doublet Chemotherapy : 5-FU+CDDP x2 / Neo-Triplet Chemotherapy: 5-FU+CDDP+Docetaxel x3 / Neo Doublet Chemoradiotherapy: 5-FU+CDDPx2 +RT 41.4Gy → Esophagectomy With D2-3 LN dissection Overall survival : Neo CF vs Neo DCF 3 years: 72.1% | 62.6% HR = 0.68(0.50-0.92) p = 0.006 (< 0.025) No. of patients | Median (95% CI): Doublet chemotherapy 199 | 5.6y (3.9y-NE); Triplet chemotherapy 202 | NR (6.7y-NE) Hazard ratio (95% CI) 0.68 (0.50-0.92), stratified log-rank test one-sided p = 0.006 No. at Risk: [Doublet] chemotherapy 199 178 143 123 98 66 38 19 4 0; [Triplet] chemotherapy 202 182 156 143 113 82 56 26 8 0 Overall survival : Neo CF vs Neo CF+RT 3 years: 68.3% | 62.6% HR = 0.84(0.63-1.12) p = 0.12 No. of patients | Median (95% CI): Doublet-chemotherapy 199 | 5.6 y (3.9y-NE); Doublet-chemotherapy plus radiotherapy 200 | 7.0 y (5.2y-NE) Hazard ratio (95% CI) 0.84 (0.63-1.12), stratified log-rank test one-sided p = 0.12 No. at Risk: Doublet-chemotherapy 199 178 143 123 98 66 38 19 4 0; Doublet-chemotherapy plus radiotherapy 200 182 151 133 111 79 47 19 4 0 Years after randomization Ken Kato, MD, PhD Kato K, et al Lancet 404(10447):55-66, 2024 Survival table Endpoint: Overall survival (JCOG1109) Arm | N | Median | Median CI Neo-doublet CF | 199 | 5.6 y | 3.9y-NE Neo-triplet DCF | 202 | NR | 6.7y-NE Neo CF+RT | 200 | 7.0 y | 5.2y-NE HR: DCF vs CF 0.68; CF+RT vs CF 0.84 HR CI: 0.50-0.92; 0.63-1.12 P: 0.006 (one-sided, <0.025); 0.12 Landmark rates: 3 years: Neo-triplet DCF 72.1% | Neo-doublet CF 62.6% | Neo CF+RT 68.3% [Slide 3] JCOG9907 Resectable, SCC (100%) cStage II/III Age 20-75 y.o PS0-1, No prior TX Primary endpoint : PFS; Secondary endpoint : OS R → Esophagectomy+ D-2or3 LN dissection → Adjuvant Chemotherapy : CDDP/5-FUx2course (expect pN0) R → Neoadjuvant Chemotherapy : CDDP/5-FUx2 course → Esophagectomy+ D-2or3 LN dissection Progression Free Survival: Pre group (n = 164); Post group (n = 166) Hazard Ratio0.84 (95% CI 0.63–1.11) Number at risk: Post 166 110 80 66 49 35 24 17 14; Pre 164 115 93 80 59 42 25 18 7 Overall Survival: Pre group (n = 164); Post group (n = 166) Hazard Ratio0.73 (95% CI 0.54–0.99, P=0.04) Number at risk: Post 166 138 112 84 55 38 24 17 14; Pre 164 147 119 102 76 53 30 22 11 Years Ken Kato, MD, PhD Ando et al.; Ann Surg Oncol.;19(1):68-74, 2012 Survival table Endpoint: PFS (primary) and OS, JCOG9907 Pre group (neoadjuvant CF) | 164 Post group (adjuvant CF) | 166 HR: PFS 0.84; OS 0.73 HR CI: PFS 0.63–1.11; OS 0.54–0.99 P: OS 0.04 [Slide 4] NEOCRTEC5010 ESCC T1-4N1M0/T4N0M0 18-70yo PS0-1 Primary endpoint : Overall survival R → Surgery (n=227) / NeoCRT (40.0Gy)+Surgery(n=224) (Vinorelbine+CDDP) Overall survival: Group CRT / Group S HR, 0.71 (95% CI, 0.53 to 0.96); P = .025 Disease free survival: Group CRT / Group S HR, 0.58 (95% CI, 0.43 to 0.78); P = .000 Follow-up (months) Ken Kato, MD, PhD Yang H et al, J Clin Oncol 36:2796-2803, 2018 Survival table Endpoint: OS (primary) and DFS, NEOCRTEC5010 NeoCRT + Surgery (Group CRT) | 224 Surgery (Group S) | 227 HR: OS 0.71; DFS 0.58 HR CI: OS 0.53 to 0.96; DFS 0.43 to 0.78 P: OS .025; DFS .000 (as printed)

[Slide 1] Lesion size and total burden both associate with response T-VEC Response probability by lesion size, n = 27 [Curve: Probability of response, % vs Maximum lesion diameter, mm (0-60)] 50% at 1.5 cm, under 10% above 3 cm RP1 + nivolumab ORR by total target-lesion size, n = 140 20 mm or less | 63% 21 to 50 | 39% 51 to 100 | 35% 101 to 150 | 15% more than 150 | 12% 63% at 20 mm or less, 12% above 150 mm Masoud SJ et al. Ann Surg Oncol 2019;26:4633. Yamada MM et al. JITC 2025;13:e013564. FDA CTGTAC briefing document, 30 July 2026. [Slide 2] Surgical principles of TIL procurement Choose the site for the product and the patient Lymph node and subcutaneous metastases first; manufacture failure 2.8% from nodes, 19.4% from subcutaneous tissue Minimize morbidity, preserve fitness for lymphodepletion Complications in 17% of 93 procurements, almost all Clavien-Dindo I to II; recovery about 21 days The hybrid patient Can harvest and palliation be one operation? Site selection Tumor Size | 1.5 cm or greater Tumor Location | Risk of contamination: avoid intraluminal sites Extent of Surgery | Complete resection often easier but not necessary; Low threshold for drain to avoid infected seroma during subsequent therapy Pathologic features | Reduce adiposity and necrotic tissue; Tumor periphery may be enriched for TIL Prior Therapy | Assessment of radiographic response to prior therapies, areas of progression; Caution in sites in prior radiation fields or previous infections. In general, harvest from prior radiated area only when there is progression after radiation Tas L et al. Br J Surg 2025;112:znaf090. Kirane and Ariyan, J Cell Ther 2024. Table from prior lecture. [Slide 3] Case 2. Procurement and palliation in one operation Progression on anti-PD-1 → Referred for TIL: post-RT axillary tumor, deemed unresectable → Open wound into tumor: Superinfection and sepsis → One operation: TIL procured from a separate site; axillary resection with latissimus advancement flap → Lymphodepletion and infusion → Complete response to TIL Axillary tumor and wound: Bulky axillary tumor; Open wound into tumor; Recurrent infection and sepsis Resection and flap: Palliative resection + latissimus flap; Posterior donor site; TIL procurement from a separate site After TIL: Systemic response — Before TIL / After TIL; H&N nodes; Pancreatic mass; Peritoneal nodules; PET schematic; Recovered for lymphodepletion and TIL; Resolution of previously avid disease Schematic depiction of the clinical course. PET findings illustrated from the case description, not actual patient scans.

What makes arcotatug tavatecan different? A CLDN18.2-targeted "delivery vehicle", rather than an immune-effector antibody Arcotatug tavatecan DAR 4:1 [Antibody-drug conjugate schematic with labels:] Anti-CLDN18.2-antibody; Exatecan payload TOPO I inhibitor; Glycan-based conjugated cleavable linker; Fc-silenced to mitigate side effects Selectively delivers cytotoxin into CLDN18.2+ tumours ➢ CLDN18.2 ADC: internalization releases exatecan, a potent TOP1 inhibitor with bystander killing; myelosuppression is the main toxicity. ➢ Fc-silenced design minimizes ADCC/CDC, distinguishing it from zolbetuximab and potentially reducing on-target/off-tumor gastric mucosal toxicity. ➢ CLDN18.2 expression levels and heterogeneity may be particularly relevant for effective payload delivery. Filippo Pietrantonio, MD Liu J et al, Nat Med 2025; Shitara et al, ESMO 2026

[Slide 1] BTC: Delayed Diagnosis an Ongoing Issue1 - 35 patients: iCCA (42.9%), dCCA (17.1%), gallbladder (14.3%), ampullary (14.3%) and pCCA (11.4%) - The majority of patients (60%) had metastases at diagnosis. Only 37.1% underwent surgery and 17.1% received no treatment 1 Treatment options [pie]: Surgery 37.1% | No treatment 17.1% | First-line treatment 45.8% Conclusion - Biliary tumors are often diagnosed at advanced stages due to significant diagnostic delays caused by non-specific symptoms. - These delays limit curative treatment options and worsen prognosis. - Improved early detection strategies and awareness are crucial to enhancing outcomes and survival rates. BTC, biliary tract cancer; dCCA, distal cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; pCCA, perihilar cholangiocarcinoma. 1. Martirena A et al. Presented at CCF 2025. [Slide 2] BTC: Precision Medicine is Real1 Advanced BTC [pie]: GBC (35%) | eCCA (30%) | iCCA (25%) | AMP (5%) Distribution of targetable alterations in advanced BTC [stacked bars for iCCA, eCCA, GBC] Categories: FGFR2 fusions; FGFR2 mutations; IDH1 mutation; IDH2 mutation; HER2 overexpression; HER2 mutation; BRAF V600E; MSI-H/dMMR; TMB-high; RET fusion; NTRK fusion; NRG1 fusion; RAS mutations; MTAP deletion; MDM2 amplification; MET amplification; Others Approved therapies [legend] Overview of the main potentially targetable alterations identified in advanced BTC (aBTC). It is expected that half of patients diagnosed with aBTC will have a diagnosis of eCCA, followed by iCCA (one quarter) and GBC (one quarter). Within the targetable alterations, FGFR2 fusions and IDH1 mutations are most frequent in iCCA, while HER-2 amplifications are mainly seen in eCCA and GBC. Other alterations seem to have a similar distribution within BTC subgroups. Green bars highlight the targets with approved therapies; many others are currently in development. aBTC, advanced biliary tract cancer; AMP, ampullary tumor; BRAF, B-Raf proto-oncogene; BTC, biliary tract cancer; dMMR, deficient mismatch repair; eCCA, extrahepatic cholangiocarcinoma; FGFR2, fibroblast growth factor receptor 2; GBC, gallbladder cancer; HER2, human epidermal growth factor receptor 2; iCCA, intrahepatic cholangiocarcinoma; IDH1/2, isocitrate dehydrogenase 1/2; MDM2, mouse double minute 2 homolog; MET, mesenchymal-epithelial transition factor; MSI-H, microsatellite instability-high; MTAP, methylthioadenosine phosphorylase; NRG1, neuregulin 1; NTRK, neurotrophic tyrosine receptor kinase; RAS, rat sarcoma virus; RET, rearranged during transfection; TMB, tumor mutational burden. 1. Lamarca A et al. J Hepatol. 2026; 85:794-807.

[Slide 1] Neoadjuvant immunotherapy in dMMR/MSI-H GEA Around 60% cCR rate of ICI (3-6 months) in peri-operative dMMR/MSI-H gastric cancer Study | Regimen/Intent | Duration | Result NEONIPIGA | Nivo*6 + Ipi*2 → surgery → nivo*9 cycles | Pre-O 3months Post-O 9 months | 29 operated pCR 59% MPR 79% INFINITY | Durva*3 + Treme*1 → surgery or W &W | Pre-O 3 months | pCR 60% in 15 resected pts cCR 76% in 17 W&W pts Pan-cancer (GEA) | Dostarlimab*9 | Pre-O 6 months | pCR 52.9% in 17 pts IMHOTEP (GEA) | Pembro* 1–2 → surgery → Pembro*9 | Pre-O 1.5-3 months Post-O 9 months | pCR 19.4% in 29 pts Can response-guided immunotherapy modification enable organ preservation in GEA? 1. André T et al., J Clin Oncol. 2023 2. Raimondi A et al., Ann Oncol. 2025 3. Fouchardiere C et al., Ann Oncol. 2024 4. Cercek A et al., N Engl J Med. 2025 Feng Wang 5 [Slide 2] How to define cCR in GEA? Clinical complete response (cCR) at 1 year, defined as at 1 year after the start of treatment with dostarlimab, are: - alive - without tumor resection - free of disease progression with a CT of the thorax/abdomen/pelvis normal - with complete or near complete endoscopy (Grade 3 or 4) - with negative biopsies cCR under endoscopy [endoscopy image] Residual disease under EUS [EUS image with arrow] 1 year evaluation was not enough. Submucosal residual disease may be missed under endoscopy. Feng Wang 7 [Livestream side panel: video of speaker at podium] Feng Wang — Invited Discussant 2877RO, 2878RO and LBA81 [Slide 3] Operation related complications vs serious irAE High incidences of surgical complications [Pie chart] Non-Fistulas (n = 5) | Fistulas (n = 4) 1 postoperative death due to a fistula complication The operation-related complication rate was higher than the 2-6% reported for D2 surgery in East Asia. dMMR/MSI-H GEA cohort receiving radical resection without ICI in SYSUCC [KM curve] 5-year RFS rate: 64% [KM curve] 5-year OS rate: 77% Grade 3-4 dostarlimab-related AEs: 21% Treatment interruption for SAE (n=5) What is the incidence of long term irAE? Feng Wang 8 Unpublished Data [Slide 4] Mono PD-1 Blockade in GEA: is it sufficient, and for how long? Short-course dual ICI significantly increased pCR rates in dMMR colon cancer Inclusion criteria • Previously untreated colon cancer • MSI-H or dMMR • Radiologically assessed stage IIB-III (cT4 or N+) • ECOG PS 0 or 1 R 1:1 → Sintilimab 200 mg Q3W*2 + IBI310 1 mg/kg Q6W*1 | Sintilimab 200 mg Q3W*2 → Surgery Primary endpoint: pCR rate Secondary endpoint: EFS, OS, RVT, R0 resection rate [Waterfall: Pathologic tumor regression (%); legend anti-PD1+anti-CTLA4, anti-PD1] Inter-group difference: 28.3% (95% CI: 10.8 - 45.7) p = 0.0015 pCR rate: anti-PD1 46.7% | anti-PD1+ anti-CTLA4 78.4% A longer course of neoadjuvant ICI was associated with higher CR rates in locally advanced dMMR CRC [Bubble plot: Complete Response (%) vs Median Duration of Treatment (mo); labelled studies include Cercek et al., 2024 (anti-PD-1); Kothari et al., 2022 (anti-PD-1); Pei et al., 2023 (anti-PD-1); Xie et al., 2023 (anti-PD-1); Ludford et al., 2023 (anti-PD-1); J. Li et al., 2024 (PICC); Zhang et al., 2022 (anti-PD-1); Chen et al., 2023 (anti-PD-1); de la Fouchardiere et al., 2024 (IMHOTEP) (anti-PD-1); Y. Li et al., 2024 (anti-PD-L1); Shiu et al., 2024 (NEOPRISM-CRC) (anti-PD-1); Xu et al., 2024 (NEOSHOT) (anti-PD-1); Avallone et al., 2020 (NICOLE) (anti-PD-1); Type of Cancer: Colorectal, Colon, Rectal; No. of Patients 5/10/25/50/75] Probit treatment-duration coefficient, 0.36 (95% CI, 0.26–0.47) P<0.001 for treatment-duration coefficient P=0.08 for testing for goodness of fit 1. Wang F et al., Cancer Cell 2025 2. Rousseau B et al., NEJM 2025 Feng Wang 9

[Slide 1] Adjuvant therapy in resected BTC • Capecitabine • S-1 Panel C: RFS (proportion) vs Time (months) 0-144; Treatment: Observation / Capecitabine; HR 0.81 (0.65 to 1.01) No. at risk: Observation At risk | 224 | 124 | 93 | 76 | 71 | 66 | 55 | 49 | 35 | 24 | 16 | 8 | 2 Censored | 0 | 1 | 2 | 5 | 5 | 5 | 14 | 20 | 33 | 43 | 49 | 57 | 63 Events | 0 | 99 | 129 | 143 | 148 | 153 | 155 | 155 | 156 | 157 | 159 | 159 | 159 Capecitabine At risk | 223 | 149 | 109 | 88 | 84 | 71 | 59 | 51 | 39 | 25 | 15 | 7 | 4 Censored | 0 | 6 | 6 | 9 | 9 | 9 | 19 | 27 | 38 | 51 | 61 | 69 | 72 Events | 0 | 68 | 108 | 126 | 130 | 143 | 145 | 145 | 146 | 147 | 147 | 147 | 147 Panel D: RFS (proportion) vs Time (months) 0-144; Treatment: Observation / Capecitabine; HR 0.77 (0.61 to 0.97) No. at risk: Observation At risk | 220 | 121 | 90 | 74 | 69 | 64 | 53 | 47 | 33 | 23 | 16 | 8 | 2 Censored | 0 | 1 | 2 | 5 | 5 | 5 | 14 | 20 | 33 | 42 | 48 | 56 | 62 Events | 0 | 98 | 128 | 141 | 146 | 151 | 153 | 153 | 154 | 155 | 156 | 156 | 156 Capecitabine At risk | 210 | 146 | 108 | 88 | 84 | 71 | 59 | 51 | 39 | 25 | 15 | 7 | 4 Censored | 0 | 2 | 2 | 5 | 5 | 5 | 15 | 23 | 34 | 47 | 57 | 65 | 68 Events | 0 | 62 | 100 | 117 | 121 | 134 | 136 | 136 | 137 | 138 | 138 | 138 | 138 5-year RFS benefit 3% ITT OS HR 0.79 (0.63 - 1.00) Multiple studies with negative results - GEMOX (PRODIGE 12) - BCAT Meta-analysis of 4 phase III RCTs (n=1,308): benefit with 5-FU–based therapy (OS HR 0.78), no benefit with gemcitabine-based therapy (OS HR 1.03) • Bridgewater J et al. Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study. J Clin Oncol. 2022 Jun 20;40(18):2048-2057 • Akkus E et al. Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials. Eur J Cancer. 2025 May 2:220:115342 Sebastián Mondaca, MD, MBA Survival table Endpoint: RFS (BILCAP long-term; panels C and D, populations not labeled on slide) Observation (panel C) | 224 Capecitabine (panel C) | 223 Observation (panel D) | 220 Capecitabine (panel D) | 210 HR: C: 0.81; D: 0.77 HR CI: C: 0.65 to 1.01; D: 0.61 to 0.97 Landmark rates: 5 years: Capecitabine vs observation (ITT) RFS benefit 3% [Slide 2] Study design Key inclusion criteria • Age 18 years or older • Histologically confirmed CCA or muscle-invasive gallbladder cancer • Macroscopically complete resection with curative intent (R0 and R1) • ECOG 0 or 1 • Adequate renal, haematological, and liver function • Start of adjuvant treatment within 6 to 16 weeks after definitive surgery R 1:1 Group A CisGem (ABC 02): 8 cycles cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and 8 of a 21 day cycle CT or MRI q 3 months for 2 years, imaging q 6 months for 3 additional years Group B Capecitabine (BILCAP): 8 cycles capecitabine 1.250 mg/m2 BID on days 1 through 14 of a 21 day cycle Primary endpoint • Disease-free survival (DFS), i.e. recurrence or death due to any cause Secondary endpoints • Overall survival (OS) • Cumulative Recurrence • Safety (CTCAE version 4.03) • Quality of life (QoL) monitored with EORTC QLQ-C30 and BIL 21 We expect and improvement in DFS from 50.9% with capecitabine to 60.2% with CisGem, resulting in a hazard ratio (HR) of 0.75. Our statistical analysis plan (SAP) pre-defined the difference in restricted mean survival time (RMST) over 3 years to quantify the treatment effect in case of violation of the proportional hazard assumption. Sebastián Mondaca, MD, MBA [Slide 3] Primary outcome: DFS Group A CisGem | Group B Capecitabine RMST (3 years) Δ 2.6 months, p=0.011 Disease-free survival probability ; Time since randomization (years) 0-5 Group A | 297 | 191 | 140 | 110 | 75 | 35 Group B | 294 | 169 | 122 | 101 | 72 | 30 RMST has several advantages: - No PH assumption - Clinically intuitive - Absolute measure ...but it is blind to what happens after the truncation time Tail of the curve Truncation time was prespecified Sebastián Mondaca, MD, MBA Survival table Endpoint: DFS Group A CisGem | 297 Group B Capecitabine | 294 P: 0.011 (RMST difference at 3 years) [Slide 4] The non-inferiority mindset At least, Gem-Cis does not seem to be worse than capecitabine (DFS HR 0.82; 95% CI 0.67 - 1.01) 1- An alternative should be preferred if there is a benefit in QoL or in another area 2-When the benefit of the SOC is limited, you have to be careful when adopting an alternative without proven benefit [Chart] QLQ-C30 global health status (+/- SD) vs Time since randomization (months) 3 6 9 12 15 18 21 24 Group A CisGem | Group B Capecitabine Sebastián Mondaca, MD, MBA

Journal Pre-proof Probability of disease-free survival (%) Number of events, n (%) 3yr-event-free survival rate (95% CI) mFOLFIRINOX 146 (36.7) 65.6 (60.6-70.2) mFOLFOX6 138 (34.8) 66.3 (61.4-70.8) HR=1.07 (95% CI, 0.84-1.36) - stratified logrank p=0.61 Time (months) Patients at risk mFOLFIRINOX 398 324 266 227 166 102 0 mFOLFOX6 397 323 278 242 181 117 0 mFOLFIRINOX mFOLFOX6 Survival table Endpoint: Disease-free survival mFOLFIRINOX | 398 mFOLFOX6 | 397 HR: 1.07 HR CI: 0.84-1.36 P: 0.61 (stratified logrank) 3-yr rate (printed '3yr-event-free survival'): 65.6% (60.6-70.2) vs 66.3% (61.4-70.8)

[Slide 1] 13:30 - 15:00 Transforming oncology with generative AI and autonomous tools CHAIRS: EVANGELIA CHRISTODOULOU, JAKOB KATHER Context is the bridge across the AI chasm [image of two bridge spans labeled 'Publication & Pilot' and 'Implementation & Impact'] "...the so-called 'AI chasm', that is the gulf between developing a scientifically sound algorithm and its use in any meaningful real-world applications." P. Keane & E. Topol, npj Digital Medicine 2018 The chasm occurs where the development context and the deployment context diverge: 1 The question the model answers vs. the decision in front of us 2 The quality of training data vs. the data at the site of implementation 3 The people (patients, clinicians, staff), process and technology behind each Caroline Chung, MD, MSc [Speaker panel] Caroline Chung — Validating AI for oncology: Navigating the road to clinical implementation CADIZ AUDITORIUM - NCC [Slide 2] 13:30 - 15:00 Transforming oncology with generative AI and autonomous tools CHAIRS: EVANGELIA CHRISTODOULOU, JAKOB KATHER AI reaches patients as a system Model validation is only evaluating one part of the system System-level validation: the whole path, from patient data to outcome Model-level validation Patient data — Imaging, pathology, molecular, EHR → AI system — Models, retrieval, tools → Interface & workflow — What, when, to whom → Clinical decision quality: Clinician decides → Accept / Modify or override / Abstain or escalate → Action → patient outcome Monitor performance and context over time [feedback loop to Patient data] Each component of the system will influence the overall ability to achieve the set goal (i.e. purpose). Caroline Chung, MD, MSc [Speaker panel] Caroline Chung — Validating AI for oncology: Navigating the road to clinical implementation CADIZ AUDITORIUM - NCC [Slide 3] 13:30 - 15:00 Transforming oncology with generative AI and autonomous tools CHAIRS: EVANGELIA CHRISTODOULOU, JAKOB KATHER AI headlines often break down in the real world CLAIM | COUNTER-EVIDENCE | SOURCE AI takes a better history | Outside text-chat OSCEs, accuracy drops when vignettes become multi-turn patient conversations | Johri et al., Nat Med 2025 AI out-diagnoses physicians | Real ED notes: physicians 0.83 vs GPT-4-turbo ≤0.58 on admission; only 5% of 519 LLM studies used real data | Williams, Nat Commun 2024 · Bedi, JAMA 2025 Removing the human is free | Unassisted adenoma detection fell 28.4% → 22.4% after AI; wrong AI cut expert mammography accuracy to 45.5% | Budzyń, Lancet Gastro Hep 2025 · Dratsch, Radiology 2023 These are failures to define the purpose, not failures of algorithm design. Caroline Chung, MD, MSc [Speaker panel] Caroline Chung — Validating AI for oncology: Navigating the road to clinical implementation CADIZ AUDITORIUM - NCC [Slide 4] 13:30 - 15:00 Transforming oncology with generative AI and autonomous tools CHAIRS: EVANGELIA CHRISTODOULOU, JAKOB KATHER Three levels of validation Purpose sets the metric at every level · context is measured throughout Real-world implementation — Does it support the right decision here, for these patients? — Metric: clinical decision quality in the workflow Pressure testing — Raises confidence it will be robust across real-world data quality — Metric: breakdown threshold and how it fails Controlled environment — The foundation: can it do the intended task under known conditions? — Metric: discrimination and calibration of intended performance [arrow] Increasing complexity / Increasing robustness / Baseline level of model performance Caroline Chung, MD, MSc [Speaker panel] Caroline Chung — Validating AI for oncology: Navigating the road to clinical implementation CADIZ AUDITORIUM - NCC

Phase 3 Peak Crossover: Bezuclastinib + Sunitinib Combination Following Sunitinib Monotherapy in Patients With GIST Robin Jones,1 Neeta Somaiah,2 Andrew J. Wagner,3 Jonathan C. Trent,4 Sebastian Bauer,5 Margaret von Mehren,6 Michael C. Heinrich,7 Min-Hee Ryu,8 Breelyn A. Wilky,9 Albiruni R. A. Razak,10 Omar Farooq Khan,11 Silvia Gasperoni,12 Rashmi Chugh,13 Antoine Italiano,14 Amanda Pilla,15 Liangxing Zou,15 Celeste LaHaie,15 William D. Tap16 1. Royal Marsden Hospital, Sutton, UK; 2. MD Anderson Cancer Center, Houston, TX, USA; 3. Dana-Farber Cancer Institute, Boston, MA, USA; 4. University of Miami - Sylvester Cancer Center, Miami, FL, USA; 5. Universitaetsklinikum Essen, Essen-Stadtbezirke III, Germany; 6. Fox Chase Cancer Center, Philadelphia, PA, USA; 7. Oregon Health & Science University (OHSU), Portland, OR, USA; 8. Asan Medical Center, Seoul, South Korea; 9. University of Colorado, Denver, CO, USA; 10. Princess Margaret Hospital, Toronto, Canada; 11. Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 12. University Hospital of Careggi, Florence, Italy; 13. University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, MI, USA; 14. Institut Bergonie, Bordeaux, France; 15. Cogent Biosciences, Boulder, CO, USA; 16. David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY, USA. 23-27 October 2026

SBRT is an effective local therapy for large HCCs • 1 year LC 87% 102 HCC med 7.2cm (1.4 – 23.1cm) (Bujold), 30-54 Gy in 6 • 1 year LC 92% 16 HCC med 7.5 cm (5.1 – 9.7 cm) (Beaton) • 2 year LC 75% 156 HCC med 12.7 cm (5 - 25.7 cm) (Wong), 4Gy x 6-10 +/- TACE • 3 year LC 72% 34 HCC 4-10 cm (Kuo) • 3 year LC 82% 55 HCC >10 cm (Kuo) [Paper excerpts:] Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma — Alexis Bujold, Christine A. Massey, John J. Kim, James Brierley, Charles Cho, Rebecca K.S. Wong, Rob E. Dinniwell, Zahra Kassam, Jolie Ringash, Bernard Cummings, Jenna Sykes, Morris Sherman, Jennifer J. Knox, and Laura A. Dawson Radiation dose is associated with improved local control for large, but not small, hepatocellular c[arcinoma — obscured] — Uri Amit, Jahan J Mohiuddin, Shwetha Manjunath, Nikhil Grand[i — obscured] Long-Term Outcome of Stereotactically Designed Hypofractionated Image Guided Radiation Therapy in Large, Unresectable Hepatocellular Carcinoma — Natalie Sean Man Wong, MBBS, MRes(Med), FRCR; Francis Ann Shing Lee, MBChB, FRCR; Venus Wan Yan Lee, PhD; ... Multimodality Treatment with [obscured] Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas – A Single Institution Phase II Study — L. Beaton, E.M. Dunne, R. Yeung, T. Rackley, B. Weber, C. Mar, C.J. Yong-Hing, E.M. Yoshida, K. DeVries, R. Lee, C. Duzenli, S.K. Loewen, M. Liu, D. Schellenberg, R. Ma Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma — Hsing-Tao Kuo, Jenny Que, Li-Ching Lin, Ching-Chieh Yang, Lok-Beng Koay, Chia-Hui Lin [Callout box] • Local control high for large HCC • Lower survival and PFS as volume of HCC increases

[Slide 1] IM96: A GUCY2C-targeted CAR-T Global Disease Burden • 1.93 million new cases each year, 3rd most common cancer worldwide1 • 2nd leading cause of cancer death1 • 15% 5-year survival for mCRC2 The Efficacy Ceiling • ≈ 95% (pMMR/MSS) remains immunotherapy-refractory • Currently available 3rd-line drugs with 1.0%-1.6% ORR and 1.9-2.0 months mPFS Product | Regorafenib3,4 | Trifluridine/tipiracil5,6 ORR | 1.0% | 1.6% mPFS (Month) | 1.9 | 2.0 GUCY2C (Guanylate cyclase 2C) • Ectopically expressed in a variety of gastrointestinal malignancies • Overexpression in >80% of colorectal cancer patients • Intestinally-restricted expression in normal tissues IM96 CAR-T • Autologous CAR-T cell product with tuned tonic signaling [Diagram: Humanized scFv; Specific killing; GUCY2C; Gastrointestinal tumor cell; IM96 CAR-T; CD28; CD3ζ] IIT Data Published in ASCO and JCO • In patients with colorectal cancer who received ≥2 prior lines of therapy, safety was manageable; • The 12–20*10^8 dose cohort demonstrated an ORR of 38.5% and mPFS of 7 months (Qi C, et al . J Clin Oncol. 2026 ). • As of August 2026, one patient with target lesion CR achieved an OS of 38 months. Variable | DL3 and DL4 groups: All (N=13) | Liver metastasis (N=6) Objective response | 38.5% | 33.3% Disease control rate | 69.2% | 83.3% Median progression free survival-months | 7.0 | 7.0 6-month overall survival | 91.7% | 83.3% Chang Liu Reference: 1. CA Cancer J Clin. 2024; 74(3): 229-263.; 2. CA Cancer J Clin. 2026;e70043.; 3. Lancet. 2013, 381: 303-312; 4. Lancet Oncol. 2015, 16: 619-629; 5. N Engl J Med 2015;372:1909-1919; 6. J Clin Oncol. 2017, 36: 350-358 [Slide 2] Antitumor Activity Observed at All Dose Levels • The overall ORR was 39% (7/18), with 42% in the 20×10^8 cohort and 33% in the 12×10^8 cohort. • The overall DCR was 94% (17/18), with 100% in the 20×10^8 cohort and 83% in the 12×10^8 cohort. • Depth of response was superior in the 20×10^8 cohort versus the 12×10^8 cohort. [Swimmer plot: Pt01–Pt18; 20*10^8 (Pt07–Pt18), 12*10^8 (Pt01–Pt06); legend: PD, SD, PR, Ongoing, Withdraw, OS, Death; x-axis Month Post CAR-T Infusion 0–15] As of August 11, 2026 [Waterfall Plot: Best Change from Baseline (%) by Patient ID; Dose Group 12x10^8 cells, 20x10^8 cells] Best response labels left to right: PD, SD, SD, SD, SD, SD, SD, SD, SD, SD, SD, PR, PR, PR, PR, PR, PR, PR As of August 11, 2026 Chang Liu

Anti PD(L)-1 Positive phase 3 trials Immunotherapy PD(L)1 • CT + nivolumab • CT + pembrolizumab • CT + tislelizumab • CT + sintilimab • CT + sugemalimab Study | n | Arms | CT | mOS (m); HR CM649 | 1.581 | CT + Nivolumab / CT | Capox or Folfox | 14.4 (CPS ≥5) / 11.1; HR 0.71; p 0.0001 [box: CPS ≥1: 14.0 / 11.3] KN 859 | 1.579 | CT + Pembrolizumab / CT | Capox (86%) or Cisplatin + 5FU | 12.9 (ITT) / 11.5 / HR 0.78 [box: CPS ≥1: 13.0 / 11.4] RATIONALE 305 | 997 | CT + Tislelizumab / CT | Capox (93%) or Cisplatin + 5FU | 15.0 (ITT) / 12.9 / HR: 0.80; p 0.001 [box: TAP ≥5: 17.2 / 12.6 / HR: 0.74; P 0.006] ORIENT16 | 650 | CT + Sintilimab / CT | Capox | 15.2 (ITT) / 12.3 / HR: 0.77, p 0.009 [box: CPS ≥5: 18.4 / 12.9 / HR 0.66; 0.002] GEMSTONE 303 (antiPDL1) | 479 | CT + Sugemalimab / CT | Capox | 15.6 (CPS ≥5) / 12.6 / HR: 0.75; p 0.006 CM649: primary endpoint amendment: OS or PFS by blinded independent central review, in PD-L1 (CPS) ≥5 patients # CM649: Primary endpoint in PDL1 CPS ≥5; KN859: CPS ≥1; Rationale 305: All and TAP ≥5% Orient16: All. CPS ≥5: OS: 18.4 Gemstone 303: CPS ≥5 required for inclusion Anelisa K. Coutinho, MD Janjigian et al. Lancet ;398:27–40, 2021 | Rha et al. Lancet Oncol. 24:1181–1195, 2023 | Xu et al. JAMA. 330:2064–2074, 2023 | Qiu et al. BMJ. 385:e078876, 2024 | Zhang et al. JAMA. 333:1305–1314, 2025 | Janjigian et al. Ann Oncol 37:787–797, 2026 [Photo also shows stage with ESMO Congress Madrid 2026 backdrop and a seated panelist]

[Slide 3] 4355P Biomarker signals in MSS/pMMR metastatic colorectal cancer (mCRC) are predominantly prognostic, not predictive – lessons from the randomized phase-2 METIMMOX trial Benjamin P. Geisler1,2@, Megan Othus3, Sebastian Meltzer2, Paula A. Bousquet2, Emily A. Burger1,4, Eline Aas1,5, Anne H. Ree2,6 1Department of Health Management and Health Economics, University of Oslo, Oslo, Norway; 2Department of Oncology, Akershus University Hospital, Lørenskog, Norway; 3Fred Hutchinson Cancer Center, Seattle WA, United States; 4Center for Health Decision Science, Harvard T. H. Chan School of Public Health, Boston MA, United States; 5Division for Health Services, Norwegian Institute of Public Health, Oslo, Norway; 6Institute of Clinical Medicine, University of Oslo, Oslo, Norway Background [I]mmune checkpoint blockade is ineffective in unselected MSS/pMMR mCRC. [M]ETIMMOX (randomized phase 2; NCT03388190): alternating oxaliplatin-based chemotherapy (FLOX) + nivolumab vs FLOX alone; identical PFS. [P]ost hoc subgroup signals (TMB/BRAF, CRP, TLR) conflated prognostic and predictive effects; we separated them in one pre-specified interaction model per endpoint. Methods ○ 68 complete cases (59 deaths; 63 PFS events). ○ Biomarkers before nivolumab: TMB ≥9 mut/Mb or BRAF V600E; CRP <5 mg/L after 2 FLOX cycles common to both arms (by chance 47% vs 19% positive). ○ TLR ≥10% at the first on-treatment CT: analyzed as intermediate endpoint with a week-9 landmark. ○ Per endpoint (PFS, OS): one Firth-corrected Cox model with age, sex, treatment, biomarker main effects and treatment × biomarker interactions (Figure 1); profile-likelihood 95% CIs, PLRT. ○ Ridge-penalized Cox as co-primary stability estimator. [Figure 1: DAG - Age/Sex, TMB/BRAF, CRP → PFS/OS; partially obscured by presenter] Results Figure 2. Kaplan-Meier survival by biomarker status and treatment arm a) CRP <5 mg/L at week 4 (n = 68) b) TMB ≥9 mut/Mb or BRAF V600E (n = 68) c) TLR ≥10%, week-9 landmark (n = 65) [Overall survival panels a-c; Progression-free survival panels d-f; x-axis Weeks since randomization / Weeks since week-9 landmark] Legend: FLOX/nivolumab, biomarker-positive; FLOX/nivolumab, biomarker-negative; FLOX alone, biomarker-positive; FLOX alone, biomarker-negative ○ No marginal treatment effect: OS HR 0.96 (95% CI 0.58–1.61); PFS HR 0.77 (0.44–1.38). ○ Prognostic: CRP <5 mg/L and TMB/BRAF positivity were associated with longer PFS (HR 0.39 each) and, for CRP, longer OS (HR 0.49), regardless of treatment (Table 1, Figure 2). ○ Not predictive: no treatment × biomarker interaction reached significance (Figure 3). Largest signal: CRP × treatment for PFS, HR 0.26 (0.06–1.34), p = 0.10, but it shrinks toward 1 under ridge (HR 0.66) and is weaker for OS (HR 0.65). ○ TLR: strongly prognostic (landmark HR 0.35 OS, 0.21 PFS), but more frequent with FLOX alone (76% vs 53%), with inconsistent interactions (HR 2.47 OS, 0.88 PFS): a marker of chemotherapy-responsive disease, not of nivolumab benefit. Table 1. Hazard ratios (95% profile-likelihood CI) from Firth-corrected Cox regression Term | Model | OS HR (95% CI) | p | Ridge HR | PFS HR (95% CI) | p | Ridge HR Treatment (FLOX/nivolumab vs FLOX) | Univariable | 0.96 (0.58–1.61) | 0.87 | – | 0.77 (0.44–1.38) | 0.38 | – CRP <5 mg/L at week 4 | Univariable (prognostic) | 0.49 (0.27–0.84) | 0.009 | – | 0.39 (0.20–0.73) | 0.003 | – TMB ≥9 mut/Mb or BRAF V600E | Univariable (prognostic) | 0.68 (0.40–1.13) | 0.14 | – | 0.39 (0.21–0.73) | 0.003 | – TLR ≥10% (week-9 landmark)† | Univariable (prognostic) | 0.35 (0.21–0.61) | <0.001 | – | 0.21 (0.11–0.42) | <0.001 | – CRP × treatment | Unified interaction model | 0.65 (0.19–2.60) | 0.52 | 0.80 | 0.26 (0.06–1.34) | 0.10 | 0.66 TMB/BRAF × treatment | Unified interaction model | 0.95 (0.32–2.82) | 0.92 | 0.91 | 0.65 (0.18–2.41) | 0.52 | 0.74 TLR × treatment | Landmark responder model† | 2.47 (0.75–7.75) | 0.14 | 1.13 | 0.88 (0.21–3.38) | 0.85 | 0.63 [Table footnote: small print, partially illegible] Figure 3. Treatment × biomarker interactions [forest plot, small print illegible] Conclusion In this exploratory analysis, biomarker signals in MSS/pMMR mCRC were predominantly prognostic rather than predictive. The CRP × treatment interaction for PFS is hypothesis-generating, and evaluation in adequately powered prospective studies could be considered. @ b.p.geisler@medisin.uio.no Disclosure: B.P. Geisler has no potential conflicts of interest to declare. Funding: [small print, partially illegible] ...

[Slide 1] Among Three Methods Tested, Clearance of mKIT maxVAF Had the Strongest Correlation With PFSa Guardant G360 molecular response scoreb HR=0.69 P=0.182 Clearance / No clearance mPFS: 9.2m vs 5.5m Mean VAF (all variants)c HR=0.81 P=0.465 mPFS: 9.2m vs 5.6m maxVAF (KIT/PDGFRA only)d HR=0.5 P=0.0104 mPFS: 11m vs 5.5m PFS probability Progression-free survival (months) At Risk Clearance defined as >99% reduction in ctDNA as assessed by each modality. Each analysis included 73 common patients to determine the most accurate method to use. ctDNA, circulating tumor DNA; G360, Guardant Health 360; HR, hazard ratio; maxVAF, maximum variant allele frequency; mKIT, mutant KIT; mPFS, median progression-free survival; mRECIST, Modified Response Evaluation Criteria in Solid Tumors; VAF, variant allele frequency. actDNA clearance was defined as a >99% reduction of mKIT VAF (which includes KIT and PDGFRA) from baseline. In this analysis, clinical activity was assessed by mRECIST v1.1 and plasma samples were analyzed at baseline and weeks 2, 4, 8, and 32, using G360 (74-gene panel). Results presented here examine ctDNA clearance at week 8. Artificial Intelligence (AI) technology was used as an assistant for coding, but not for the generation of figures. bGuardant uses a proprietary algorithm to calculate molecular response based on mean VAF and clonal hematopoiesis variants filtering. cMean VAF is calculated using all somatic variants, without filtering variants associated with clonal hematopoiesis. dMaxVAF is the highest VAF of a single KIT/PDGFRA mutation and could differ between cycle 1 day 1 and an on-treatment timepoint. Sebastian Bauer Survival table Endpoint: PFS by week-8 ctDNA clearance (clearance vs no clearance), three methods G360 molecular response score: clearance vs no clearance | 9.2 mo vs 5.5 mo Mean VAF (all variants): clearance vs no clearance | 9.2 mo vs 5.6 mo maxVAF (KIT/PDGFRA only): clearance vs no clearance | 11 mo vs 5.5 mo HR: G360: 0.69; mean VAF: 0.81; maxVAF: 0.5 P: G360: 0.182; mean VAF: 0.465; maxVAF: 0.0104 [Slide 2] Conclusions In this exploratory analysis, mKIT ctDNA clearancea was associated with longer PFS – at week 8, there was a 40–50% reduction in risk of progression compared to those without clearance ctDNA clearance with velzatinib was rapid and increased over time (30% after 2 weeks and ~50% after 8 weeks) ctDNA clearance could be a useful predictive biomarker for KIT-directed treatments with broad mutational coverage; however, further analyses with a larger sample size and longer follow-up are needed Further research (that considers treatment line) in later phase trials (StrateGIST 3 and StrateGIST Frontline) will explore the role of ctDNA monitoring in optimizing outcomes for patients with advanced GIST ctDNA, circulating tumor DNA; GIST, gastrointestinal stromal tumor; mKIT, mutant KIT; PFS, progression-free survival. actDNA clearance was defined as a >99% reduction of mKIT/mPDGFRA VAF from baseline. Sebastian Bauer

Gastric Cancer -> Biomarker Testing (• HER2 • Claudin 18.2 • PD-L1 • MSI • Biomarker X) -> 1st-Line Targeted Therapy -> 2nd-Line Targeted Therapy -> Repeat Biopsy (Tissue +/- ctDNA) / ctDNA / Disease Progression (Liver Metastases) -> Biomarker Testing (• HER2 • Claudin18.2 • PD-L1 • MSI • Biomarker X) -> 2nd-Line Targeted Therapy -> Progression (Peritoneal Metastases) / Repeat Biopsy (Tissue +/- ctDNA) -> Biomarker Testing (• HER2 • Claudin18.2 • PD-L1 • MSI • Biomarker X) -> 3rd-Line Targeted Therapy Raghav Sundar MD PhD Made on Biorender Leo AI

8. Organoids for Running Virtual Trials KEY ISSUE Limitations of conventional clinical trials. Patient-derived organoids enable ex vivo testing of multiple treatment options, with potential integration into cancer digital twins and virtual trials. KEY INSIGHT Organoid-based virtual trials could improve treatment selection and accelerate drug development. ESMO COMMITMENT ESMO supports translational research and the evaluation of patient-derived organoids as predictive biomarkers for precision oncology. Patient-Derived Organoids Predict Treatment Response in Metastatic Colorectal Cancer Smabers LP et al., Clinical Cancer Research (2025)

Pancreatic cancer: From biology to emerging therapies CHAIRS: IRIT BEN-AHARON, MAEVE LOWERY MEK inhibitors in PDAC Atebimetinib is a novel allosteric small molecule inhibitor of MEK1/2 Atebimetinib (320 mg QD) + mGnP DCR: 82% [95 CI 69, 91] ORR: 36% [95 CI 23, 51] Participant Population: First-line (1L) metastatic Pancreatic Ductal Adenocarcinoma (PDAC) MAPKeeper 301 • First line (1L) PDAC • Metastatic setting • ECOG PS 0-1 R 1:1 N=255 Atebimetinib + mGnP1 N=255 Gem/nab-Pac 1L SoC Chemotherapy2 Primary Endpoints: OS Secondary Endpoints: PFS, DCR, ORR, QoL NCT07562152 Phase 2a | Atebimetinib (320 mg QD) + mGnP OS, N=55 — Ph2a IMRX (320 mg atebi + mGnP, N=55) IMRX - Phase 2a (N=55, atebi + mGnP) 17.3 mo OS Probability Months Censored Participant off study Censored Participant still on study At risk / Events / Censored Chung et al, presented at 2026 ASCO Meeting Survival table Endpoint: Overall survival, phase 2a single arm Atebimetinib 320 mg QD + mGnP (IMRX phase 2a) | 55 | 17.3 mo

T-cell engager trials in upper GI cancers Monotherapy | Combination | Randomised trials CLDN18.2 × CD3 IBI389 · phase I (1) Pretreated G/GEJ, CLDN18.2 ≥10%, n = 27 ORR 22%; mPFS 4.3 mo IBI389 · phase I (2) Pretreated pancreatic cancer, n = 27 ORR 30%; 39% if CLDN18.2 ≥40% ASP2138 · phase I/Ib (3) Pretreated G/GEJ · CLDN18.2 ≥1% ORR 9% (3/32) ASP2138 · phase Ib (3) 1L G/GEJ · + pembrolizumab + mFOLFOX6 Unconfirmed ORR 69% (62.5% at 2,000 μg) QLS31905 · phase Ib (4) 1L pancreatic · + gem/nab-paclitaxel · 800 μg/kg, n = 52 ORR 61.5% ASP2138 · phase III (5) 1L HER2– G/GEJ, n = 570 · vs chemo ± pembrolizumab Recruiting · NCT07673887 QLS31905 · phase III (6) 1L CLDN18.2+ pancreatic, n = 602 · vs placebo + chemo Recruiting · NCT07079228 Co-stimulation Tumour antigen × 4-1BB BGB-B2033 (GPC3 × 4-1BB) · phase I (7) Pretreated HCC, n = 61 cORR 20% Givastomig (CLDN18.2 × 4-1BB) · phase I (8) Pretreated G/GEJ ORR 16% Givastomig · phase Ib (9) 1L G/GEJ · + nivolumab + mFOLFOX6, n = 54 ORR 77% at 8 mg/kg; mPFS 16.9 mo GIVA-2 · randomised phase II (10) 1L G/GEJ · + nivolumab + chemo · n = 180 Recruiting · NCT07432295 Selected trials: [illegible]

[Slide 1] EFFICACY • 17/18 (94%) patients had a pathologic response: • 15/18 (83%) an MPR, meeting the primary endpoint; • 13/18 (72%) had a pCR; • Two patients had a partial response and one patient with 70% RVT was a non-responder. • In the patient with a synchronous colon and rectal tumor, the rectal tumor showed a complete endoscopic response and patient opted for rectal organ preservation, while surgery was performed for the colon tumor (partial response) • Radiographic assessment did not accurately predict pathologic response Pathologic Response n = 18 Legend: - ypN- ; + ypN+ Tumor Regression (%) | reference lines: Pathologic response; MPR Radiologic response legend: Complete Response | Partial Response | Stable Disease SURVIVAL After a median FU of 15 months (range 13,7 – 21,6): • All patients were alive; • One patient (partial responder; ypT4abN2), who received adjuvant chemotherapy, developed peritoneal metastases a year later; • One patient with an MPR experienced a solitary lymph node metastasis 6 months after surgery; • The patient with complete clinical response of the rectal tumor has no signs of regrowth at 7 months FU. Corresponding email address: m.chalabi@nki.nl [Slide 2] METHODS • Investigator-initiated, single center, phase II platform study • Patients with colorectal, non-metastatic, resectable, dMMR adenocarcinoma. MMR deficiency confirmed by IHC • Botensilimab 50 mg I.V. on D1 + balstilimab 450 mg I.V. on D1 and D22, followed by surgery within 8 weeks after start of treatment • PRIMARY ENDPOINT: Major pathologic response (MPR, ≤ 10% residual viable tumor, RVT, in primary tumor and lymph nodes); • Simon's two-stage design: 8 patients in stage 1, expanding to 18 if > 2 MPRs. Primary endpoint met if ≥ 7/18 MPRs. • SECONDARY ENDPOINTS: • Pathologic complete response (pCR, no RVT in both primary tumor and lymph nodes), partial pathologic response (10 – 50 % RVT), no pathologic response (> 50% RVT); • EFS, DFS, OS; • Translational analyses including WES, scRNAseq, and ctDNA. Baseline | D1 week 0: Cycle 1 bot 50 mg /bal 450 mg | D22 week 3: Cycle 2 bal 450 mg | +/- week 8: Surgery Screening Endoscopy (PET-)CT scan | +/- week 8 (PET-)CT scan

[Slide 2] Pancreatic Cancer In Young Population Is On The Rise • Median age at onset is 71y; PC is considered a disease of older population. • Yet, in the past decades the early-onset component is on the rise regardless of the general increase in incidence. Pancreas Cohort rate ratio There is a Birth Cohort Effect: The incidence rate is approximately two-to-three times higher in the 1990 birth cohort than in the 1955 birth cohort for pancreatic cancer in both male and female individuals ((2.61 [2.22–3.07]). Irit Ben-Aharon MD, PhD Sung et al., Lancet Pub Health 2024 [Slide 3] Early-Onset Pancreatic Cancer - Demographics A Aged ≥55 B Aged <55 C Aged 35-54 D Aged 15-34 Men Women Age-Adjusted Incidence Rate (per 100,000 population) Year Cancer cases (N = 283 817)a All ages Men 141 520 (49.8) Women 142 297 (50.1) Aged ≥55 y Men 123 156 (43.3) Women 128 204 (45.1) Aged <55 y Men 18 334 (6.5) Women 14 035 (4.9) Aged 35-54 y Men 17 692 (6.2) Women 13 139 (4.6) Aged 15-34 y Men 642 (0.2) Women 896 (0.3) Irit Ben-Aharon MD, PhD Gadaam et al. [illegible] Abboud et al, [illegible] [Slide 4] Early-Onset Pancreatic Cancer – Lessons from EOGI Cancer Exposome – a term that collectively describes the effect of lifestyle and environmental factors, and may be divided into 3 compartments: • Specific external exposome Diet, drugs, biological agents, screen use etc. • General external exposome Air pollution, traffic, noise etc. • Internal exposome (host factors) Microbiome, genetics, aging Irit Ben-Aharon MD, PhD

[Slide 2] RESULTS · PHASE 2 · PATIENT SUMMARY Patient summaries rated 9.0 / 10 by 15 Clinicians & AHPs 145 reviews · 15 MDT members, 6 roles · every case, ready or deferred All Clinicians & AHPs | 9.0 / 10 | 92% | 134 of 145 rated 8-10 Medical oncologists | 9.2 / 10 | 93% | 28 of 30 rated 8-10 Colorectal surgeons | 9.0 / 10 | 94% | 67 of 71 rated 8-10 Mean summary rating by role (1–10) Colorectal surgeon (7) | 8.98 Nurse & MDT coordinator (2) | 9.2 Medical oncologist (3) | 9.2 Pathologist (2) | 10 Shazad Ashraf [Slide 3] Conclusions THE PROBLEM In 14,180 MDT cases, 8.2% were deferred and trials were discussed in only 3.9%. PHASE 1 · ABSTRACT Across 15 synthetic cases, BEAGLE®-MDT scored 9.2-10.0 / 10 for summaries, management and trial matching. PHASE 2 · NEW SINCE ABSTRACT Across 15 MDT members, the new deferral gate matched clinicians in 83% of reviews; open trials identified for 92% of cases. WHAT COMES NEXT Improve trial identification and patient/referrer letters. Shadow-mode and prospective evaluation to demonstrate fewer deferrals, more trial access, and safety. BEAGLE®-MDT is designed to support, not replace, multidisciplinary clinical expertise.

Progress Towards Personalised Care in Advanced CCA: Impact of an Online Micro-Learning Educational Initiative on Clinician Knowledge, Competence, and Practice Readiness Ben Johnson1, Michael Beyer1, Rianna Hanif1, Jessica Massey1, Angela Lamarca2, Nicola Normanno3, Rachna Shroff4† 1PVI, PeerView Institute for Medical Education, London, UK; 2Fundacion Jimenez Diaz University Hospital, Madrid, Spain; 3IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" – IRST S.r.l., Meldola, Italy; 4University of Arizona Cancer Center (UACC), University of Arizona College of Medicine – Tucson, Tucson, Arizona, USA. † In memoriam: Dr. Shroff was instrumental in the development of this activity. We are grateful for her contributions to this activity and the field of medicine. Background & Methods The goal of precision oncology is to deliver the right treatment to the right patient, at the right dose and at the right time. In cholangiocarcinoma (CCA), key actionable alterations, including FGFR2 alterations, IDH1/2 mutations, BRAF V600E mutations, HER2 overexpression and alterations, NTRK fusions and MSI-H/dMMR status, now inform personalised treatment selection. As the therapeutic landscape evolves, clinicians require practical support to interpret molecular findings and integrate evidence-based targeted approaches into patient-centred care. Design: PeerView deployed a CME-certified, online video-based micro-learning activity that blended the clinical journey of a patient with advanced CCA with expert guidance and relevant clinical evidence on implementing targeted treatment approaches. Five assessment questions were administered to learners after the education and to a demographically matched group of non-participants to evaluate differences in knowledge and competence. Here, we report the findings 7 months after launching this initiative. Programme Reach 2,491 learners across 72 countries(a) 34,386 patients with advanced CCA potentially impacted per month(b) 1,309 supplementary material downloads, demonstrating active engagement beyond passive viewing Interprofessional audience comprising oncologists (42%), gastroenterologists (13%), pathologists (11%), nurses/NPs/PAs (9%) and other HCPs (25%) a Data cut-off: 7 months from launch (November 2025-June 2026). b Estimated from participant-reported monthly patient load. Impact on Knowledge & Competence The objective of this initiative was to improve the understanding and practical application of precision approaches in the management of advanced CCA. 40 percentage point (pp) mean difference across all assessed knowledge and competence domains [legend] Non-participants / Learners 57 pp difference — 35% → 92% — in understanding of the clinical landscape for the management of advanced CCA and the differences in available targeted therapies 38 pp difference — 45% → 83% — in the ability to formulate team-based, personalised CCA clinical care plans that align therapy with a patient's molecular profiling results and support treatment across the care continuum 8 pp difference — 75% → 83% — in the ability to integrate evidence-based molecular profiling tools and interpret results to inform therapeutic decision-making in advanced CCA ✓ Following participation, no learners selected 'I'm not sure' on any of the five assessed knowledge/competence questions. These findings suggest meaningfully increased confidence in applying the educational content. ★ Key finding: Understanding of evidence on emerging combination targeted therapy represented the largest knowledge gap between non-participants and learners. On a question assessing this area, 16% of non-participants and 92% of learners responded correctly—a 76-pp difference and the largest of any assessed question. This suggests that clinicians in the target audience may benefit from accessible updates as the therapeutic landscape evolves. Ongoing Unmet Needs Self-reported practice considerations among non-participants (n = 50) 84% reported opportunities for further support in applying updated treatment guidance in routine practice 68% described practical challenges in ensuring timely, comprehensive molecular profiling 72% identified a need for further support in recognising appropriate clinical trial referral opportunities Key Themes Identified for Future Education Open-ended requests for more information/future education among non-participants (n = 50) 1 Therapeutic sequencing after frontline chemoimmunotherapy — Uncertainty about optimal treatment decisions following progression on frontline regimens was the most frequently cited clinical challenge. 2 Targeted therapy safety in community settings — Targeted therapy toxicities were a particular area of uncertainty for non-specialist and community-based clinicians. Recognition and grading of toxicities and dose-modification protocols represent a distinct, actionable educational gap. 3 Keeping pace with the emerging evidence base — Rapidly evolving early-phase combination trial data represented the largest driver of knowledge gaps in this programme. Clinicians require accessible, evidence-based updates to translate emerging findings confidently into clinical decision-making. The corresponding author has no conflicts of interest to share. Corresponding author contact: ben.johnson@peerview.com Jointly accredited CME activity | PVI, PeerView Institute for Medical Education This activity is supported by an educational grant from Servier. [Back to search button]

Analysis of metabolic comorbidities in patients with pancreatic ductal adenocarcinoma and pathogenic germline variants Elizabeth A. Fung, Phoebe T.M. Cheng, Joanna M. Karasinska, Carol Cremin, Eugene Cheung, Steve E. Kalloger, James T. Topham, Lan Valerie Tao, Haley M. Beckmann, David F. Schaeffer, Kasmintan Schrader, Daniel J. Renouf PANCREAS CENTRE BC BC CANCER CONCLUSIONS • HRR PGV+ patients are more likely to present with BMI ≥25 compared to PGV- patients and other PGV+ subtypes. • PGV+ patients have a trend towards lower rates of diabetes and/or dyslipidemia compared to PGV- patients (p=0.08). • HRR PGV+ patients treated with FFX have significantly greater OS than patients treated with GA. No survival differences are observed within PGV- and cell cycle PGV+ patients.