Zymeworks (ZYME) Reports First Patient Dosed in Phase 1b/2 Trial of ZW25 in First-Line HER2-Positive Breast Cancer

Zymeworks Inc. (NYSE: ZYME) today announced that its partner, BeiGene, Ltd., has dosed the first patient in a two-arm Phase 1b/2 trial evaluating Zymeworks’ HER2-targeted bispecific antibody ZW25 in combination with chemotherapy as a first-line treatment for patients with metastatic HER2-positive breast cancer and in combination with chemotherapy and BeiGene’s PD-1-targeted antibody tislelizumab as a first-line treatment for patients with metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). Zymeworks will receive a payment under its collaboration with BeiGene as a result of the achievement of this development milestone.

“To date, ZW25 has demonstrated promising activity in late-stage, treatment-refractory HER2‑expressing tumors. This new clinical trial provides a unique opportunity to evaluate the additional potential benefit of ZW25 in first-line metastatic breast tumors which have not developed resistance to multiple HER2-targeted therapeutics,” said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. “In addition, the GEA arm of this trial complements our ongoing Phase 2 trial of ZW25 plus chemotherapy in first-line GEA, and we are excited to examine possible synergies between ZW25 and BeiGene’s PD-1 inhibitor tislelizumab. We look forward to the results of these trials, which have the potential to further expand the population of patients who may benefit from ZW25.”

“Through this collaboration with Zymeworks, our broad development program for tislelizumab is expanding into HER2-expressing tumors as a potential first-line treatment,” said Lai Wang, Ph.D., Senior Vice President, Head of Global Research and APAC Clinical Development at BeiGene. “ZW25 has demonstrated appealing clinical activity against HER2-positive tumors, and we are excited to gain additional understanding of its use as a monotherapy and in combinations as well.”

This Phase 1b/2 clinical trial is a multicenter, open-label, two-arm study (NCT04276493). Arm one of the trial will evaluate the safety, tolerability, and preliminary antitumor activity of ZW25 in combination with docetaxel in patients with metastatic HER2‑positive breast cancer. The second arm of the trial will evaluate the safety, tolerability, and preliminary antitumor activity of ZW25 in combination with tislelizumab and chemotherapy in patients with HER2-positive GEA, including gastric and gastroesophageal junction (GEJ) adenocarcinomas.

An ongoing Phase 1 trial is evaluating the safety and antitumor activity of ZW25 as a single agent and in combination with chemotherapy in HER2‑expressing cancers that have progressed after prior standard of care treatments, including HER2-targeted agents (Phase 1: NCT02892123). ZW25 is also being evaluated in a Phase 2 trial in first-line HER2-positive GEA in combination with standard of care chemotherapy (Phase 2: NCT03929666) as well as in combination with the oral CDK4/6 inhibitor palbociclib (Ibrance®, Pfizer) and fulvestrant in advanced HER2‑positive, HR‑positive breast cancer (Phase 2: NCT04224272). Zymeworks, in collaboration with BeiGene, also plans to initiate registration-enabling studies of ZW25 in patients with previously treated HER2-positive biliary tract cancer and develop ZW25 as a potential first-line treatment for patients with HER2-positive GEA.

About ZW25

ZW25 is being evaluated in multiple Phase 1 and Phase 2 clinical trials globally. It is a bispecific antibody, based on Zymeworks’ Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing ZW25 as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted two Fast Track Designations to ZW25, one as a single agent for refractory biliary tract cancer and one in combination with standard of care chemotherapy, for first-line GEA. ZW25 has also received Orphan Drug Designations for the treatment of biliary tract, gastric, and ovarian cancers.

About the Zymeworks-BeiGene Collaboration

In November 2018, Zymeworks and BeiGene entered into license and collaboration agreement in which BeiGene was granted an exclusive license for the research, development and commercialization of ZW25 and ZW49 in Asia (excluding Japan), Australia, and New Zealand. The companies are collaborating on joint global development for selected indications, with the goal of developing ZW25 and ZW49 worldwide across multiple HER2‑expressing cancers and lines of therapy.

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