ILUSTRO Trial

[Slide 1] ASCO Gastrointestinal Cancers Symposium January 8-10, 2026 Moscone West San Francisco, CA & Online #GI26 gi.asco.org

[Slide 1] ILUSTRO Cohort 4 Study Design Cohort 4A: Safety Lead-In Phaseᶜ (n = 12) Key Eligibility Criteria Cycles 1-4 (~5.5 months): Cycles 5+: Previously untreated LA Zolbetuximab© nivolumab Zolbetuximab 400 mg/m2 + unresectable or mG/GEJ 600/400 mg/m2 + 240 mg + nivolumab 240 mg + adenocarcinoma OR mFOLFOX6 5-FU/FA® Q2W CLDN18.2+ (moderate-to- 800/400 mg/m2 Q2W strong CLDN18 staining in > 50% of tumor cells)a - Intermediate expression: ≥ 50 - < 75% of cells Cohort 4B: Expansion Phase (n = ~65) - High: ≥ 75% of cells Cycles 1-4 (~5.5 months): Cycles 5+: HER2-b Zolbetuximab 800/400d mg/m2 + Zolbetuximab 400 mg/m2 + ECOG PS 0-1 nivolumab 240 mg + mFOLFOX6 nivolumab 240 mg + Q2W 5-FU/FA® Q2W Endpoints and Analyses PFS, ORR, DCR, DOR, OS, safety and tolerability Preplanned analyses by CLDN18.2 and ad-hoc analyses by PD-L1 CPS' Cycle length was 42 days Sample sizos shown are approximations based on the expectation to provide safety information and determine tolerability of the dose level of interest (cohort 4A) and the expected number of 50 patients whose tumors had high CLDN18 2 expression, assuming an accrual period of 12 months and a follow up period of 3-6 months with 20-25 PFS events (cohort 48) By central IHC *By central or local HER2 testing The tolerability and safety of zolbetuximab nivolumab mFOLFOX6 was evaluated during a 2 week DLT assessment period cycle 1 day 1 doses of zolbetuximab in Cohort 4A were 600 mg/m2 (n 6) or 800 mg/m2 in 6), both followed by subsequent doses of 400 mg/m2 800 mg/m2 at cycle 1 day 1 followed by subsequent doses of 400 mg/m², *At the discretion of the investigator; By the Dako PD-L1 IHC 28-8 pharmDx assay ASCO Gastrointestinal Cancers Symposium #GI26 PRESENTED BY: Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN ADDRESS CUNICAL DNCOLOGY Presentation . property author and ASCO Permission required for - cr permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] PFS Stratified by CLDN18.2 Expression in Cohort 4B Median PFS was 18.0 months in the CLDN18.2-high population CLDN18.2 Median PFS, Events/n (%) months (95% CI) High 23/59 (39.0) 18.0 (11.1-NE) 1.0 Intermediate 7/11 (63.6) 6.7 (3.0-NE) 0.8 76.2% # 64.2% Probability of PFS # 0.6 # 0.4 61.4% 36.8% 0.2 CLDN18.2- high CLDN18.2- - intermediate 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months Number at risk: — 59 51 42 36 31 26 18 13 10 9 8 2 0 — 11 11 7 5 3 3 2 2 2 2 1 0 0 Date are shown for the safety analysis set One patient had no evaluable CLDN18 2 status PFS was assessed by investigators per RECIST v1 1. Median (95% CI) follow up times in Cohort 4B were 11.5 (9.4-15.6) months and 11.3 (3.9-NE) months for the high CLDN18 2 expression and intermediate CLDN182 expression subgroups, respectively ASCO Gastrointestinal #GI26 PRESENTED BY: Dr Kohei Shitara, Phase 2 LUSTRO trial ASCO AMERICAN SOCIETY CUPICAL ONCOLOGY Cancers Symposium Presentation . property author and ASCO Permasion request for - contact permissions@asco.org KNOWL EDGE CONQUERS CANCER --- [Slide 3] Key Takeaway Points Triplet therapy with zolbetuximab in combination with mFOLFOX6 and nivolumab: 1 2 3 Represents a promising Led to encouraging treatment strategy for PFS in Cohort 4B Showed an acceptable patients with HER2-, LA across patient and safety and tolerability unresectable or mG/GEJ biomarker subgroups profile adenocarcinoma whose tumors are CDLN18.2+ with PD-L1 CPS of â¥1 Median PFS was 14.8 months overall, 18.0 months in patients with Safety and tolerability were Provides a strong rationale for the CLDN18.2 high tumors, and 23.6 consistent with prior studies ongoing randomized phase 3 months in patients with high of zolbetuximab or nivolumab LUCERNA trial in CLDN18.2+ and CLDN18.2 and PD-L1 CPS ≥ 1 plus mFOLFOX6 PD-L1+ mG/GEJ adenocarcinoma ASCO Gastrointestinal #GI26 PRESENTED - Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO - I I Cancers Symposium I I . and Permission required KNOWLEDGE COMOLERS CANCER --- [Slide 4] Conclusions Triplet therapy with zolbetuximab plus mFOLFOX6 and nivolumab led to encouraging PFS in Cohort 4B of ILUSTRO Median PFS of 14.8 months in Cohort 4B PFS favored patients with high CLDN18.2 (ie, ≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining as determined by central IHC): - high CLDN18.2 (median PFS 18.0 months) versus intermediate (6.7 months) - high CLDN18.2 and PD-L1 CPS ≥ 1 (median PFS 23.6 months) versus CPS <1 (12.1 months) ORR was 62.1% in patients with measurable disease and 68.1% in patients with high CLDN18.2 Zolbetuximab plus mFOLFOX6 and nivolumab demonstrated acceptable safety and tolerability The safety profile was consistent with prior studies of zolbetuximab or nivolumab plus mFOLFOX6 Nausea and decreased appetite were the most frequent TEAEs A triplet therapy approach may represent a promising strategy for patients with CLDN18.2+, HER2-, LA unresectable or mG/GEJ adenocarcinoma with PD-L1 CPS ≥ 1 Results have informed the design of the phase 3 LUCERNA study (NCT06901531, poster K4): - Zolbetuximab + pembrolizumab and chemotherapy as first-line treatment for patients with CLDN18.2-positive, HER2-negative, PD-L1-positive locally advanced unresectable or metastatic G/GEJ adenocarcinoma: Phase 3, double-blind, randomized trial (LUCERNA) ASCO Gastrointestinal Cancers Symposium #GI26 Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN SOCIETY PRESENTED BY. CURICAL ONCOLOGY Presentation property author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

[Slide 1] Phase 3 LUCERNA (NCT06901531) Study Design Key inclusion criteria Planned Zolbetuximab IV Zolbetuximab IV (N = 500) 800 mg/m2 Cycle 1 Day 1 400 mg/m2 Q2W or 600 mg/m2 Q3W Adult* patients with LA unresectable or 400 mg/m2 Q2W or 600 mg/m2 Q3W mG/GEJ adenocarcinoma Pembrolizumab IV Pembrolizumab IV HER2-5 200 mg Q3W or 400 mg Q6W 200 mg Q3W or 400 mg Q6W CLDN18.2+ CAPOX' / mFOLFOX6® Capecitabine' / folinic acid + fluorouracil' PD-L1+ (CPS 2 1) ECOG PS 0-1 R Cycles 1-4 (42 days/cycle) Cycles 5+ (42 days/cycle) 1:1 Key exclusion criteria Placebo IV Q2W or Q3W Placebo IV Q2W or Q3W Receipt of prior systemic chemotherapy Pembrolizumab IV Pembrolizumab IV and/or immunotherapy 200 mg Q3W or 400 mg Q6W 200 mg Q3W or 400 mg Q6W Receipt of prior CLDN18.2-targeted therapy CAPOX I mFOLFOX6® Capecitabine' I folinic acid + fluorouracil' Cycles 1-4 (42 days/cycle) Cycles 5+ (42 days/cycle) Stratification factors Region (Asia vs non-Asia) PD-L1 CPS (a 1 to < 10 vs 2 10) Primary endpoint Secondary endpoints Exploratory endpoints OS PFS ORR HRQoL Biomarkers DOR PK PFS2 Safety Immunogenicity *2 18 years of age; HER2 IHC score of 0+/1+, or HER2 IHC score of 2+ if ISH-, per local or central testing: 2 75% of tumor cells demonstrating moderate-to-strong membranous CLND18 staining using the VENTANA CLDN18 (43-14A) RxDx Assay per central testing; Using the Aglient PD-L1 IHC 22C3 pharmDx assay per central testing: *1 prior dose of CAPOX or mFOLFOX6, with or without pembrolizumab, is allowed; Oral capecitabine 1000 mg/m2 twice daily on Days 1-14 and 22-35, and IV oxaliplatin 130 mg/m2 Q3W; Folinic acid 400 mg/m², fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2, and oxaliplatin 65 mg/m2, IV Q2W; Up to 24 months; Per investigator discretion; Per RECIST version 1.1 by investigator assessment ASCO Gastrointestinal #GI26 PRESENTED BY Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN SOCIETY X CURICAL ONCOLOGY Cancers Symposium Presentation . property of the author and ASCO Permission required or - permissons@asca.org KNOWLEDGE CONQUERS CANCER

[Slide 1] PFS Stratified by CLDN18.2 Expression in Cohort 4B Median PFS was 18.0 months in the CLDN18.2-high population Median PFS, CLDN18.2 Events/n (%) months (95% CI) High 23/59 (39.0) 18.0 (11.1-NE) 1.0 Intermediate 7/11 (63.6) 6.7 (3.0-NE) 0.8 76.2% 64.2% Probability of PFS + 0.6 # 0.4 61.4% 36.8% 0.2 CLDN18.2 high CLDN18.2 - intermediate 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months Number at risk: - 59 51 42 36 31 26 18 13 10 9 8 2 0 — 11 11 7 5 3 3 2 2 2 2 1 0 0 Data are shown for the safety analysis set One patient had no evaluable DN18 2 status PFS was assessed by investigators per RECIST it 1. Median (56% CI) follow up times in Cohort 48 were 11.5 9.4-15 months and 11.3 (3.9-NE) months for the high CLDN18 2 expression and intermediate CLDN18 2 expression subgroups, respectively ASCO Gastrointestinal #GI26 Dr Kohei Shitara Phase 2 ILUSTRO trial ASCO AMERICAN - - Cancers Symposium Presentation . imperty - - ASCO Permason - contact KNOWLEDGE CONQUERS CANCER --- [Slide 2] PFS by PD-L1 CPS in the CLDN18.2-High Population in Cohort 4B Median PFS was 23.6 months in patients with PD-L1 CPS > 1 Median PFS PD-L1 status Events/n (%) 1.0 (months) 85.0% CPS ≥ 1 13/36 (36.1) 23.6 0.8 69.4% CPS <1 9/21 (42.9) 12.1 Probability of PFS + 0.6 73.3% 0.4 59.5% 0.2 CPS a1 CPS <1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months Number at risk: - 36 32 23 21 19 17 13 9 8 7 6 2 0 - 21 19 19 15 12 9 5 4 2 2 2 0 0 Data are shown for the safety analysis set PFS was assessed by investigators per REGIST v1 1. Median (95% (2)follow up times n Cohort 48 were 23.6(129-NE) months and 12.1 (7. 2-NE) months for CPS 1 and CPS 1, respectively ASCO Gastrointestinal #GI26 PRESENTED BY Dr Kohei Shitara Phase 2 ILUSTRO trial ASCO AMERICAN SOCIETY - - Cancers Symposium I I I I I KNOWLEDGE CONQUERS CANCER --- [Slide 3] Tumor Responses in Patients in Cohort 4B ORR was 68.1% in patients in the CLDN18.2-high group 100 Cohort 4B 80 ORR CLDN18.2 CLDN18.2 Overall high intermediate 60 (n = 58)* (n = 47) (n = 10) 40 n (%) 36 (62.1) 32 (68.1) 4 (40.0) Best change from baseline (%) 95% CI 48.4-74.5 52.9-80.9 12.2-73.8 20 so 0 PD PD PD so PD* -20 -40 -60 CLDN18 2 high/CPS 2 1 CLDN18 2 high/CPS < 1 -80 CLDN18.2 intermediate/CPS 2 1 -100 CLDN18.2 intermediate/CPS < 1 Data are shown for the full analysis set ORR data include patients with measurable disease Waterfall part (n 57) includes all patients with baseline and posibaseline measurements, and does not include patients classified in non- CRinon-PD *One patient had no evaluable CLDN18 2 status This patient had no evaluable CPS status ASCO Gastrointestinal PRESENTED BY Dr Kohei Shitara Phase 2 ILUSTRO trial #GI26 ASCO - - Cancers Symposium I I KNOWLEDGE CONQUERS CANCER --- [Slide 4] Phase 3 LUCERNA (NCT06901531) Study Design Key inclusion criteria Planned Zolbetuximab IV Zolbetuximab IV (N 500) 800 mg/m2 Cycle 1 Day 1 400 mg/m2 Q2W or 600 mg/m2 Q3W Adult* patients with LA unresectable or 400 mg/m2 Q2W or 600 mg/m2 Q3W mG/GEJ adenocarcinoma Pembrolizumab IV Pembrolizumab IV HER2- 200 mg Q3W or 400 mg Q6W 200 mg Q3W or 400 mg Q6W CLDN18.2+ CAPOX' / mFOLFOX6® Capecitabine / folinic acid + fluorouraci PD-L1+ (CPS 2 1) ECOG PS 0-1 R Cycles 1-4 (42 days/cycle) Cycles 5+ (42 days/cycle) 1:1 Key exclusion criteria Placebo IV Q2W or Q3W Placebo IV Q2W or Q3W Receipt of prior systemic chemotherapy Pembrolizumab IV Pembrolizumab IV and/or immunotherapy 200 mg Q3W or 400 mg Q6W 200 mg Q3W or 400 mg Q6W Receipt of prior CLDN18.2-targeted therapy CAPOX / mFOLFOX6 Capecitabine / folinic acid + fluorouraci Cycles 1-4 (42 days/cycle) Cycles 5+ (42 days/cycle) Stratification factors Region (Asia vs non-Asia) PD-L1 CPS (a 1 to < 10 vs 2 10) Primary endpoint Secondary endpoints Exploratory endpoints os PFS ORR HRQoL Biomarkers DOR PK PFS2 Safety Immunogenicity % 18 years of age: PHER2 IHC score of 0+/1+, or HER2 IHC score of 2+ TISH- per local or central testing . 75% of numer cells demonstrating moderate-to-strong membranous CLND18 staining using the VENTANA CLDN18 (43-14A) RxDx Assay per central testing Using the Agilent PD-L1 IHC 2203 pharmOx assay per central testing "1 prior dose of CAPOX or mFOLFOX6 with or without pembrolizumab. is allowed; Oral capecitabine 1000 mg/m2 twice daily on Days 1-14 and 22-35. and IV oxaliplatin 130 mg/m2 Q3W: Folinic acid 400 mg/m2, fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2, and oxaliplatin 85 mg/m2, IV Q2W: "Up to 24 months Per investigator discretion Per RECIST version 1.1 by investigator assessment ASCO Gastrointestinal #GI26 Dr Kohei Shitara Phase 2 ILUSTRO trial ASCO - I Cancers Symposium I - ASCO Permason I KNOWLEDGE CONQUERS CANCER

[Slide 1] Phase 2 ILUSTRO trial of 1L zolbetuximab plus mFOLFOX6 and nivolumab in patients with CLDN18.2+ locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma Kohei Shitara, Hirokazu Shoji, Nicola Fazio, Sara Lonardi, Keun-Wook Lee, Li-Yuan Bai, Kensei Yamaguchi, Jean-Philippe Metges, Gianluca Masi, Denis Smith, Tae-Yong Kim, Maria Matsangou, Archita Shrivastava, Miaomai Zhou, Aziz Zaanan, Samuel J. Klempner Presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI); January 8-10, 2026 In Person: San Francisco, CA, USA Virtual: Oral Abstract Session A: Cancers of the Esophagus and Stomach Abstract: LBA284 ASCO Gastrointestinal #GI26 PRESENTED BY Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN SOCETY OF CUNICAL ENCOLOGY Cancers Symposium Presentation property author and ASCO Permission required or ISSUE contact permissions@asco.org KNOWLEDGE CONQUERS CANCER ASCO Gastrointestinal Cancers Symposium --- [Slide 2] ILUSTRO Cohort 4 Study Design Cohort 4A: Safety Lead-In Phasec (n = 12) Key Eligibility Criteria Cycles 1-4 (~5.5 months): Cycles 5+: Previously untreated LA Zolbetuximab© nivolumab Zolbetuximab 400 mg/m2 + unresectable or mG/GEJ 600/400 mg/m2 + 240 mg + nivolumab 240 mg + adenocarcinoma OR mFOLFOX6 5-FU/FA® Q2W CLDN18.2+ (moderate-to- 800/400 mg/m2 Q2W strong CLDN18 staining in > 50% of tumor cells)a - Intermediate expression: 2 50 < 75% of cells Cohort 4B: Expansion Phase (n = ~65) - High: > 75% of cells Cycles 1-4 (~5.5 months): Cycles 5+: HER2-b Zolbetuximab 800/400 mg/m2 + Zolbetuximab 400 mg/m2 + ECOG PS 0-1 nivolumab 240 mg + mFOLFOX6 nivolumab 240 mg + Q2W 5-FU/FA Q2W Endpoints and Analyses PFS, ORR, DCR, DOR, OS, safety and tolerability Preplanned analyses by CLDN18.2 and ad-hoc analyses by PD-L1 CPS' Cycle length was 42 days Sample 54205 shown are approximations based on the expectation to provide safety information and determine tolerability of the dose level of interest (cohort 4A) and the expected number of 50 patients whose tumors had high CLDN18 expression, assuming an accrual period of 12 months and follow period of 3-6 months with 20-25 PFS events (cohort 4B) By contral IHC *By central or local HER2 testing The tolerability and safety of zolbetuximab nivolumab mFOLFOX6 was evaluated during wook DLT assessment period, cycle day doses of zolbetuximab in Cohort LA were 600 mg/m2 (n 6) 800 mg/m2 (n 6), both followed by subsequent doses of 400 mg/m²; 800 mg/m2 at cycle day followed by subsequent doses of 400 mg/m², *At the discretion of the investigator, By the Dako PD-L1 IHC 28-8 pharmDx assay ASCO Gastrointestinal #GI26 PRESENTED BY: Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN CUNICAL Cancers Symposium Presentation property the author and ASCO Permission required for reuse contact permisions@asco.org KNOWLEDGE CONQUERS CANCER ASCO Gastrointestinal Cancers Symposium --- [Slide 3] PFS Stratified by CLDN18.2 Expression in Cohort 4B Median PFS was 18.0 months in the CLDN18.2-high population Median PFS, CLDN18.2 Events/n (%) months (95% CI) High 23/59 (39.0) 18.0 (11.1-NE) 1.0 Intermediate 7/11 (63.6) 6.7 (3.0-NE) 0.8 76.2% + 64.2% Probability of PFS 0.6 + 0.4 61.4% 36.8% 0.2 CLDN18.2 high CLDN18. intermediate 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months Number at risk: 59 51 42 36 31 26 18 13 10 9 8 2 0 11 11 7 5 3 3 2 2 2 2 1 0 0 Data are shown for the safety analysis set One patient had no evaluable CLDN18 2 status PFS was assessed by investigators per RECIST v1 1. Median (95% CI) follow up times in Cohort 4B were 11.5 (9.4-15.6) months and 11.3 (3.9-NE) months for the high CLDN18 2 expression and intermediate CLDN182 expression subgroups, respectively ASCO Gastrointestinal #GI26 PRESENTED BY: Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN CURRCAL ONCOLOGY Cancers Symposium Presentation property author and ASCO Permission required for - contact permissions@asco.org KNOWL EDGE CONQUERS CANCER ASCO Gastrointestinal Cancers Symposium --- [Slide 4] Conclusions Triplet therapy with zolbetuximab plus mFOLFOX6 and nivolumab led to encouraging PFS in Cohort 4B of ILUSTRO Median PFS of 14.8 months in Cohort 4B PFS favored patients with high CLDN18.2 (ie, ≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining as determined by central IHC): - high CLDN18.2 (median PFS 18.0 months) versus intermediate (6.7 months) - high CLDN18.2 and PD-L1 CPS ≥ 1 (median PFS 23.6 months) versus CPS <1 (12.1 months) ORR was 62.1% in patients with measurable disease and 68.1% in patients with high CLDN18.2 Zolbetuximab plus mFOLFOX6 and nivolumab demonstrated acceptable safety and tolerability The safety profile was consistent with prior studies of zolbetuximab or nivolumab plus mFOLFOX6 Nausea and decreased appetite were the most frequent TEAEs A triplet therapy approach may represent a promising strategy for patients with CLDN18.2+, HER2-, LA unresectable or mG/GEJ adenocarcinoma with PD-L1 CPS ≥ 1 Results have informed the design of the phase 3 LUCERNA study (NCT06901531, poster K4): - Zolbetuximab + pembrolizumab and chemotherapy as first-line treatment for patients with CLDN18.2-positive, HER2-negative, PD-L1-positive locally advanced unresectable or metastatic G/GEJ adenocarcinoma: Phase 3, double-blind, randomized trial (LUCERNA) ASCO Gastrointestinal Cancers Symposium #GI26 PRESENTED BY Dr Kohei Shitara, Phase 2 ILUSTRO trial ASCO AMERICAN SOCIETY CLINICAL ONCOLOGY Presentation property author and ASCO Permission required for - contact permissions@weco.org CHOWLEDGE CONQUERS CANCER ASO