Ziihera® (zanidatamab-hrii) Combinations Achieve Unprecedented Results in First-Line HER2+ Locally Advanced or Metastatic GEA including more than Two Years Median Overall Survival Benefit

• Positive results from Phase 3 HERIZON-GEA-01 results support Ziihera as the HER2-targeted agent-of-choice in HER2+ first-line metastatic GEA and Ziihera plus chemotherapy to replace trastuzumab as the new standard of care, with or without tislelizumab regardless of PD-L1 status
• Late-breaking results to be presented at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI) on January 8, 2026
• Ziihera engineered and initially developed by Zymeworks using our proprietary Azymetric™ technology platform
• Zymeworks is eligible to receive up to $440.0 million in milestone payments to be earned related to regulatory approvals of Ziihera in GEA in the United States, Europe, Japan, and China

VANCOUVER, British Columbia, Jan. 06, 2026 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a biotechnology company managing a portfolio of licensed healthcare assets, while developing a diverse pipeline of novel, multifunctional biotherapeutics, today announced positive efficacy and safety results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera® (zanidatamab-hrii) in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra® (tislelizumab), as first-line treatment for adults with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus.

The data will be presented as a late-breaking oral presentation at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco on January 8, 2026 from 8:57- 9:07 am PST (abstract number: LBA285).

“These results underscore the promise of zanidatamab to meaningfully advance care for patients with HER2-positive disease. They also reflect the power of our Azymetric™ platform to generate highly differentiated, multifunctional biologics and validate our partnership-driven approach with Jazz and BeOne to efficiently deliver innovative therapies on a global scale,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “Importantly, the HERIZON-GEA-01 data further establish Ziihera as the new HER2-targeted agent-of-choice in first-line locally advanced or metastatic HER2-positive GEA with the potential to redefine first-line treatment for patients in this setting. Alongside continued progress across Jazz and BeOne’s broader development efforts, these data reinforce our belief in Ziihera’s potential across a range of HER2-expressing solid tumors. We look forward to Jazz and BeOne moving rapidly towards global regulatory submissions based on the HERIZON-GEA-01 data.”

The study found:

• Both investigational arms, Ziihera plus tislelizumab and chemotherapy and Ziihera plus chemotherapy, led to a statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with approximately 35% reduction in the risk of disease progression or death versus trastuzumab plus chemotherapy. This resulted in a median PFS of more than one year, representing a greater than four month improvement compared to the control arm.
• Ziihera plus tislelizumab and chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit with a median OS of more than two years (26.4 months), the longest reported in a Phase 3 trial in GEA, representing a greater than seven-month improvement in median OS and a 28% reduction in the risk of death versus trastuzumab plus chemotherapy.
• At this first interim analysis, Ziihera plus chemotherapy showed a median OS of more than two years, with a strong trend toward statistical significance, favoring Ziihera plus chemotherapy versus trastuzumab plus chemotherapy. An additional planned OS interim analysis for Ziihera plus chemotherapy is currently expected in mid-2026.
• The OS and PFS benefits were generally consistent across major prespecified subgroups including geographic region and PD-L1 status for both investigational arms.

Efficacy Summary from HERIZON-GEA-01

* Did not reach statistical significance at the first interim OS analysis.

The safety profile of Ziihera in combination with chemotherapy, with or without tislelizumab, was consistent with the known effects of HER2-directed therapy and immunotherapy, and no new safety signals were identified. Duration of treatment was longest on the Ziihera plus tislelizumab and chemotherapy arm. Rates of Grade ≥3 treatment-related adverse events (TRAEs) were 71.8% with Ziihera plus tislelizumab and chemotherapy, 59.0% with Ziihera plus chemotherapy, and 59.6% with trastuzumab plus chemotherapy. Discontinuations due to Ziihera- or trastuzumab-related and treatment discontinuations due to adverse events were 11.9% with Ziihera plus tislelizumab and chemotherapy, 8.5% with Ziihera plus chemotherapy, and 2.3% in the trastuzumab plus chemotherapy arm. The most common Grade ≥3 TRAE was diarrhea (24.5% of patients with Ziihera plus tislelizumab and chemotherapy; 20.0% with Ziihera plus chemotherapy; and 12.9% of patients in the trastuzumab plus chemotherapy arm). Importantly, discontinuation of either Ziihera or trastuzumab due to treatment-related diarrhea was uncommon (4.1% of patients with Ziihera plus tislelizumab and chemotherapy, 1.3% with Ziihera plus chemotherapy, and 0% of patients in the trastuzumab plus chemotherapy arm). Treatment-emergent diarrhea generally occurred early in treatment and resolved within three weeks. The manageable safety profile supports the feasibility of these combinations in the first-line metastatic setting.

Under the Company’s existing arrangements with Jazz and BeOne Medicines, Zymeworks is eligible to receive substantial near-term milestone payments related to future regulatory approvals in GEA totaling $440.0 million, as follows: United States - $250.0 million; Europe - $100.0 million; Japan - $75.0 million; China - $15.0 million. The Company also expects that royalty revenue from Ziihera sales will increase as potential regulatory approvals are obtained in global markets for GEA. In addition, Zymeworks could be eligible to receive future milestones and increased royalties from the development, regulatory approval, and commercialization of any additional indications for Ziihera by Jazz and BeOne, including breast cancer.

The full U.S. Prescribing Information for Ziihera, including BOXED Warning, is available at: https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf

About the HERIZON-GEA-01 Phase 3 Trial
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly by Jazz and BeOne Medicines, to evaluate and compare the efficacy and safety of Ziihera plus chemotherapy, with or without tislelizumab, to trastuzumab plus chemotherapy as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Appropriate patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: Ziihera in combination with chemotherapy and tislelizumab; Ziihera in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.

About Gastroesophageal Adenocarcinoma
GEA, including cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide, and approximately 20% of patients have HER2+ disease.1,2,3 HER2+ GEA has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 30% for gastric cancer and about 19% for GEA.4

About Zymeworks Inc.
Zymeworks is a global biotechnology company managing a portfolio of licensed healthcare assets and developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, including cancer, inflammation, and autoimmune disease. The Company’s asset and royalty aggregation strategy focuses on optimizing positive future cash flows from an emerging portfolio of licensed products such as Ziihera® (zanidatamab-hrii) and other licensed products and product candidates, such as pasritamig. In addition, Zymeworks is also building a portfolio of healthcare assets that can generate strong cash flows, while supporting the early-stage development of innovative medicines. Zymeworks engineered and developed Ziihera, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology, and has entered into separate agreements with BeOne Medicines Ltd. (formerly BeiGene, Ltd.) and Jazz Pharmaceuticals Ireland Limited granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zymeworks is rapidly advancing a robust pipeline of product candidates, leveraging its expertise in both antibody drug conjugates and multispecific antibody therapeutics targeting novel pathways in areas of significant unmet medical need. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutics. These capabilities have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X.