HERIZON-GEA-01 Trial

HERIZON-GEA-01 — Health-Related Quality of Life (HRQoL), ESMO GI 2026 (Abstract 494O), presented by Kohei Shitara. Key findings reported from these slides (source: OncoDaily ESMO GI 2026 congress coverage and presenter-shared slides): - EORTC QLQ-C30 questionnaire completion exceeded 95% through cycle 34 day 1 across all arms. - Physical functioning: mean baseline scores 81.5-83.5 across arms; at cycle 2, reductions were slightly larger with zanidatamab-containing regimens vs trastuzumab but differences remained small; most patients maintained or improved physical functioning from baseline between cycles 2 and 8. - Global Health Status/QoL: changes from baseline were numerically similar across the three arms, with no substantive changes over time. - Symptom scales: diarrhea (the most common treatment-related AE in the zanidatamab arms) showed the greatest worsening from baseline at cycle 8 day 1, consistent with the trial's established safety profile. Note: this ESMO GI 2026 HRQoL analysis is descriptive/supportive; efficacy figures (PFS 12.4 vs 8.1 mo; OS 26.4 vs 19.2 mo) are from the ASCO GI 2026 primary readout (DCO 1-Oct-2025). These regimens remain investigational and are not FDA approved in 1L GEA.

[Slide 1] HERIZON-GEA-01: Overall Survival (interim) Zanidatamab + Tislelizumab + CT: Putting into the context of current standard. 2 100 CT Transfurnad HERIZON-GEA-01 KEYNOTE-811 Median 05 (95%C), no 26.4(21.5-30.3) 19.2(16.8-21.8) Zanidatamab Entellaumab CT (n=914) (n=698) 75 HR (95% C) 0.72(0.57-0.90) P = 0,0043 Treatment Zani + TIS + CT Zani + CT vs Tras + Pembro + CT vs CT 54.3% Overat I & vs Tras + CT Tras + CT Tras + CT per.o. 47.5-415 41.8% 50 INC Population Overall Overall PD-L1 CPS >1 38.8% 113454 25 os (mo) 26.4 vs 19.2 30.2% 24.4 vs 19.2 20.0 vs 16.8 20.1 vs 15.7 BES-C) DAME HR 0.72 0.80 0.80 0.79 0 Censored PFS (mo) 12.4 VS 8.1 12.4 VS 8.1 10.0 VS 8.1 10.9 VS 7.3 0 3 $ , 12 15 18 21 24 27 30 R 36 39 42 45 48 Months from randomization HR 0.63 0.65 0.73 0.72 Date à - 267 24) 22 - 157 125 * 12 - 4) * 27 # 4 2 0 If b 308 254 21 29 18 NO 105 IT . . # # If 1 2 1 0 Notable OS improvement with Trastuzumab + CT VS historical benchmarks Multidisciplinary care? Subsequent therapies? Regional differences? Uanigian et at Ann Oncol 2024 35(Suppl): 5877- S878 ASCO Gastrointestinal #GI26 = Daniel Lin, MD, MSc ASCO - - - Cancers Symposium Presentation - the - - ABCO Permission required for - - - KNOWLEDGE COMQUERS CARCER ASCO Gastrointestinal Cancers Symposium

[Slide 1] HER2+ Gastric Cancer breaks the OS barrier @DrRishabhOnco HERIZON-GEA-01 I Phase III I # GI26 First clear frontline OS win in a decade Who & What Phase III, n=914 1L HER2+ metastatic GEA Global trial Treatment arms Trastuzumab Zanidatamab Zanidatamab + + chemo + chemo chemo + tislelizumab PFS 8.1 12.4 months ~35% lower progression risk 26.4 Median OS 26.4 months ~28% lower risk of death Benefit across MO regions ~54% alive at 2 years Independent of PD-L1 ! Safety Higher toxicity with triplet Clinical takeaway: No new safety signals Dual HER2 targeting + PD-1 is poised to replace trastuzumab Save for clinic as 1L standard in HER2+ mGEA

[Slide 1] HERIZO CLASS Primary + tislelizumab Endpoint: + CT demonstrated Overall a statistically + CT Survival significant and clinically Zanidatamab meaningful CT + OS Trastuzumab benefit + with CT a >7-month Zanidatamab improvement in median OS VS trastuzumab tislelizumab Median os 26.4 (21.5-30.3) 19.2 (16.8-21.8) 100 (95% CI), mo Zanidatamab + tislelizumab + CT 0.72 (0.57-0.90) HR (95% CI) P 0.0043 75 54.3% Trastuzumab + CT (95% CI: 47.6-60.5) 43.8% Overall survival (%) (95% Cl: 36.5-50.9) 50 38.8% (95% CI: 32.2-45.4) 30.0% 25 (95% CI: 23.4-35.8) 0 + Censored 18 27 30 33 36 39 42 45 48 0 3 6 9 12 15 21 24 Months from randomization Patients t nisk 96 82 64 49 36 27 10 4 2 0 Zani ns 302 267 246 222 190 157 125 CT 106 77 61 50 33 22 17 8 2 2 0 Tras CT 308 284 261 219 178 140 CT, chemolhericy HR hazard ratio, 05. overall survivel TIS, isleizumab, Tras, trastuzumab; Zani, zanidatamab ASCO AMERICAN SOCIETY of ASCO Gastrointestinal #GI26 PRESENTED BY FC Elena Elimova, MD CURICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER Cancers Symposium Thousation property who and ASCO Perman required - contact permissers@asco.org using the ASCO Meetings mobile app or at.asco.org/gi-program --- [Slide 2] HERIZON CEA-301 Primary Endpoint: Overall Survival Zanidatamab + tislelizumab + CT demonstrated a statistically significant and clinically meaningful os benefit with a >7-month improvement in median os VS trastuzumab + CT 100 Zanidatamab + tislelizumab + CT Trastuzumab + CT Median os Zanidatamab + tislelizumab + CT (95% CI), mo 26.4 (21.5-30.3) 19.2 (16.8-21.8) 75 HR (95% CI) 0.72 (0.57-0.90) P= 0.0043 Overall survival (%) Trastuzumab + CT 54.3% (95% Cl: 47.6-60.5) 43.8% 50 (95% Cl: 36.5-50.9) 38.8% (95% Cl: 32.2-45.4) 25 30.0% (95% Cl: 23.4-36.8) 0 + Censored 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Months from randomization Patients at risk Zani + TIS 302 267 246 222 190 157 125 96 82 64 49 36 + CT 27 10 4 2 0 Tras + CT 308 284 261 219 178 140 106 77 61 50 33 22 17 8 2 2 0 CT, chemotherapy; HR, hazard ratio; OS, overall survival; TIS, tislelizumab; Tras, trastuzumab; Zani, zanidatamab ASCO Gastrointestinal #GI26 PRESENTED BY: Elena Elimova, MD ASCO AMERICAN SOCIETY OF Cancers Symposium CLINICAL ONCOLOGY Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

[Slide 1] HERIZON-GEA-01 Updated os and PFS Data Vs KEYNOTE 811: ASCO GI 2026 HERIZON-GEA-01 KEYNOTE 811 P3 (N=920) P3 (N=738) Trials Jazz Pharmaceuticals MERCK Status Active, not recruiting Active, not recruiting Completed Completed Treatments Zani + Tis + CT VS Tras + CT Zani + CT VS Tras + CT Tras + Pembro + CT vs Tras + CT Tras + Pembro + CT VS Tras + CT N 914 914 698 698 Population Overall Overall Overall PD-L1 CPS ≥1 OS HR 0.72 (0.57,0.90) 0.80 (0.64, 1.01) 0.79 0.73 mos 26.4 VS 19.2 24.4 VS 19.2 20.0 VS 16.3 21.0 VS 15.7 PFS HR 0.63 (0.51, 0.78) 0.65 (0.52, 0.81) 0.73 0.71 mPFS 12.4 VS 8.1 12.4 VS 8.1 11.0 VS 8.1 10.9 VS 7.3 Adapted from Daniel Lin (On X 2026) LARVOL

[Slide 1] HERIZON DEA-301 HERIZON-GEA-01 Study Design Global phase 3 trial of zanidatamab + chemotherapy ± tislelizumab VS trastuzumab + chemotherapy in previously untreated patients with HER2+ mGEA Key Eligibility Criteria Arm A: Trastuzumab + Age >18 years chemotherapy Unresectable, locally advanced, Dual Primary Endpoints recurrent or metastatic GEA PFS (per BICR) HER2 IHC 3+ or IHC 2+/ISH+ R Arm B: Zanidatamab OS per central testing 1:1:1 1800 mg (<70 kg)/2400 mg (270 kg) IV Q3W ECOG PS 0 or 1 + chemotherapy* CT/MRI Select Secondary Endpoints Q6W No prior treatment for locally advanced N = 914 cORR (per BICR) or metastatic disease Frequency and severity of AEs No prior HER2-targeted agents or Arm C: Zanidatamab immunotherapy in any setting 1800 mg (<70 kg)/2400 mg (270 kg) IV Q3W ClinicalTrials.gov: NCT05152147 + tislelizumabᵇ + chemotherapya Stratification Factors Prophylaxis to prevent IRR and diarrhea was Geographic region mandatory in the zanidatamab-containing arms HER2 status ECOG PS Treatment until disease progression/death/unacceptable toxicity Chemotherapy could be discontinued after 6 cycles Physician's choice of capecitabine plus oxaliplatin or 5 Sucrouracil plus cisplatin Chemotherapy was administered for at least 6 cycles or until disease progression, unacceptable toxicity, or another criterion for treatment discontinuation was met *Tislelizumab 200 mg was administered IV Q3W CT/MRI scans were performed every 6 weeks for the first 54 weeks, then every wooks AE, adverse event, BICR binded independent contral review, CORR, confirmed objective response rate, CT, computed tomography ECOG PS, Eastern Cooperative Oncology Group performance status, GEA, gastroesophageal adenocarcinoma, HER2, human epidermal growth factor receptor 2. IHC, immunohistochemistry, IRR, infusion related reaction; ISH, in situ hybridization, IV, intravenously, mGEA, advanced or metastatic GEA MRI, magnetic resonance imaging OS, overall survival PFS, progression free survival, Q3W, every 3 weeks, Q6W. every 6 weeks, R. randomization ASCO Gastrointestinal #GI26 PRESENTED BY Elena Elimova, MD ASCO - ENCOLOGY Cancers Symposium Presentation property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER