Zymeworks Inc. · NASDAQ:ZYME
Zymeworks — Technical Presentation (January 2026)
20 slides from Zymeworks's technical presentation, Jan 5, 2026
Slide 1: Zanidatamab + chemotherapy ± tislelizumab for first-line HER2-positive gastroesophageal adenocarcinoma
Zanidatamab + chemotherapy ± tislelizumab for first-line HER2-positive locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma: Primary analysis from HERIZON-GEA-01 Elena Elimova1, Sun Young Rha2, Kohei Shitara3, Tianshu Liu4, Josep Tabernero5, Keun-Wook Lee6, Michael Schenker7
Slide 2: Key Takeaway Points
Key Takeaway Points HERIZON-GEA-01 supports zanidatamab as a new standard in HER2-targeting agents, potentially replacing trastuzumab, as well as the use of tislelizumab in 1L HER2+ mGEA Progression-Free Survival and Overall Survival • Statistically significant ~35% reduction in the risk of disease
Slide 3: Background
Background • Outcomes with current SoC for 1L HER2+ mGEA remain modest, with an mPFS of <1 year EC D2 4 and mOS of <2 years1-7 D Fa EC b Fv sc • Zanidatamab is a dual HER2-targeted bispecific IgG1-like antibody that binds to extracellular domains 2 and 4 on HER2 in a trans configuration8 § This bipa
Slide 4: HERIZON-GEA-01 Study Design
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 chemotherapya • Unresectable, locally advanced, Dual Primary Endp
Slide 5: Statistical Design
Statistical Design • Dual primary endpoints (PFS and OS): Analyzed in the intent-to-treat population using log-rank tests with a 2-sided α = 0.05 § Primary PFS analysis: After target event count was reached and patients had ≥7 months of follow-up § First interim OS analysis: Performed at the time of
Slide 6: Patient Disposition
Patient Disposition A total of 914 patients were randomized, and median follow-up was >2 years Randomized N = 914 Zanidatamab + tislelizumab + CT Zanidatamab + CT Trastuzumab + CT n = 302; 299 patients treateda n = 304; 300 patients treateda n = 308; 302 patients treated Ongoing treatment, n = 88 (2
Slide 7: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Demographics and clinical characteristics were balanced across all 3 treatment arms Zanidatamab + Zanidatamab + tislelizumab + CT Zanidatamab + CT Trastuzumab + CT tislelizumab + CT Zanidatamab + CT Trastuzumab + CT (n = 302) (n = 304) (n = 308) (n =
Slide 8: Primary Endpoint: PFS per BICR
Primary Endpoint: PFS per BICR Statistically significant and clinically meaningful improvement in PFS with zanidatamab + tislelizumab + CT vs trastuzumab + CT (>4-month prolongation in median PFS) 100 Zanidatamab + tislelizumab + CT Trastuzumab + CT Progression-free survival (%) Zanidatamab + tislel
Slide 9: Primary Endpoint: PFS per BICR
Primary Endpoint: PFS per BICR Statistically significant and clinically meaningful improvement in PFS with zanidatamab + CT vs trastuzumab + CT (>4-month prolongation in median PFS) 100 Zanidatamab + CT Trastuzumab + CT Progression-free survival (%) Zanidatamab + CT Median PFS (95% CI), mo 12.4 (9.8
Slide 10: PFS in Key Prespecified Subgroups
PFS in Key Prespecified Subgroups Improvements in PFS were generally consistent across major prespecified subgroups Events/patients Zanidatamab + Zanidatamab + Trastuzumab + Zani + TIS + CT PFS HRa Zani + CT PFS HRa Subgroup Category tislelizumab + CT CT CT vs Tras + CT (95% CI) vs Tras + CT (95% CI
Slide 11: Primary Endpoint: Overall Survival
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 Zanidatamab + 100 tislelizumab + CT Trastuzumab + CT Median OS (95% CI), mo 26.4 (21.5–30.3) 1
Slide 12: OS in Key Prespecified Subgroups
OS in Key Prespecified Subgroups Improvements in OS occurred across major prespecified subgroups, including regions and PD-L1 TAP scores Events/patients Zanidatamab + Zani + TIS + CT OS HRa Subgroup Category tislelizumab + CT Trastuzumab + CT vs Tras + CT (95% CI) All patients 134/302 170/308 0.72 (
Slide 13: Primary Endpoint: Overall Survival
Primary Endpoint: Overall Survival At this interim analysis, there was a strong trend toward significance for OS favoring zanidatamab + CT vs trastuzumab + CT (5-month improvement in median OS) 100 Zanidatamab + CT Trastuzumab + CT Median OS Zanidatamab + CT (95% CI), mo 24.4 (20.4–30.0) 19.2 (16.8–
Slide 14: Key Secondary Endpoint: Antitumor Activity
Key Secondary Endpoint: Antitumor Activity Responses were deeper and more durable in the zanidatamab-containing arms vs the trastuzumab + CT arm 100 Confirmed ORR in patients with measurable disease 80 70.7% 69.6% 95% CI (65.0–76.0) 95% CI (63.9–75.0) 65.7% 95% CI (59.9–71.2) CR CR CR cORR (%) 60 19
Slide 15: Safety Summary
Safety Summary The safety profile was generally manageable, and no unexpected safety signals were identified Zanidatamab + tislelizumab + CT Zanidatamab + CT Trastuzumab + CT (n = 294)a (n = 305)a (n = 302) Duration of treatment, median (IQR), weeks 43.1 (56.7) 31.0 (53.8) 30.0 (32.2) Any-grade TEAE
Slide 16: Common TRAEs (≥20% of Patients in Any Arm)
Common TRAEs (≥20% of Patients in Any Arm) Diarrhea was the most common TRAE in all treatment arms 100 90 Zani + TIS + CT Zani + CT Tras + CT 82% (n = 294)a (n = 305)a (n = 302) 80 76% Grade 1–2 ¢ ¢ ¢ 70 Grade ≥3 ¢ ¢ ¢ Patients (%) 60 51% 50% 50 48% 42% 40% 40 38% 39% 38% 37% 36% 35% 31% 32% 30% 30
Slide 17: Treatment-Emergent Diarrhea
Treatment-Emergent Diarrhea Treatment-emergent diarrhea generally occurred early in treatment and resolved within 3 weeks, and few patients discontinued zanidatamab due to diarrhea Zanidatamab + tislelizumab + CT Zanidatamab + CT Trastuzumab + CT (n = 294)a (n = 305)a (n = 302) Treatment-related dia
Slide 18: Discussion
Discussion • HERIZON-GEA-01 is the first phase 3 study in mGEA to demonstrate a median PFS >1 year and a median OS >2 years • These findings support zanidatamab as a promising new standard in HER2-targeting agents, with potential to replace trastuzumab in first-line treatments for HER2+ mGEA • The c
Slide 19: Acknowledgments
Acknowledgments The authors would like to thank all the patients and their families as well as all the investigators, clinical trial researchers, personnel, and staff who contributed to or participated in the trial • Clinical research was funded by Jazz Pharmaceuticals in collaboration with BeOne Me
Slide 20: Lay Summary
Lay Summary Why did we perform this research? • Current treatments for people with locally advanced or metastatic gastroesophageal adenocarcinoma (or mGEA) only provide modest benefit • Some of these tumors have too much of a protein called human epidermal growth factor receptor 2 (or HER2) on the c