8-K: Zymeworks Secures China NMPA Approval for Zanidatamab in HER2-Positive Biliary Tract Cancer, Triggering $20 Million Milestone Payment

Zymeworks Inc. announced that China's National Medical Products Administration (NMPA) has granted conditional approval for zanidatamab, its dual HER2-targeted bispecific antibody, for the treatment of previously treated, unresectable or metastatic HER2-positive biliary tract cancer, marking a significant regulatory and financial milestone.

Summary

• Zymeworks Inc. received conditional approval from China's National Medical Products Administration (NMPA) for zanidatamab for the treatment of previously treated, unresectable or metastatic HER2-positive (HER2+) biliary tract cancer (BTC).
• This approval makes zanidatamab the first and only dual HER2-targeted bispecific antibody approved for HER2-high expression (IHC3+) BTC in China.
• The conditional approval is based on positive results from the HERIZON-BTC-01 clinical study, which demonstrated overall survival benefit for patients.
• Continued approval is contingent on verification of clinical benefit through ongoing confirmatory trials.
• Zymeworks is entitled to receive a $20 million milestone payment from its collaboration partner, BeOne Medicines Ltd., in connection with this NMPA approval.
• The company has already received $61 million in upfront and milestone payments from BeOne Medicines and is eligible for up to an additional $144 million in development and commercial milestones.
• Zymeworks is also eligible to receive tiered royalties of up to 19.5% of net sales in BeOne Medicines' territories, potentially increasing to up to 20% under certain conditions.
• Zanidatamab previously received accelerated approval from the U.S. FDA in November 2024 for the same indication and a positive opinion from the European Medicines Agency (EMA) CHMP in April 2025.

Sentiment

Score: 9

Explanation: The document conveys a highly positive sentiment due to a significant regulatory approval in a major market (China), which triggers a substantial milestone payment and opens up significant future revenue potential through additional milestones and royalties. The 'first and only' status for this indication further enhances the positive outlook, despite the conditional nature of the approval.

Positives

• NMPA conditional approval of zanidatamab for HER2+ BTC in China, expanding its global market reach.
• Zanidatamab is the first and only dual HER2-targeted bispecific antibody approved for HER2+ BTC in China, establishing a strong market position.
• Receipt of a $20 million milestone payment from BeOne Medicines, adding to the $61 million already received.
• Eligibility for up to an additional $144 million in future development and commercial milestones.
• Potential for tiered royalties of up to 19.5% (and potentially 20%) on net sales in BeOne Medicines' territories.
• The approval is based on demonstrated overall survival benefit in the HERIZON-BTC-01 clinical study.
• Prior approvals/positive opinions from the U.S. FDA and EMA indicate broad international recognition of zanidatamab's efficacy.

Risks

• Continued approval of zanidatamab in China depends on the verification of clinical benefit in the patient population through ongoing confirmatory trials.
• Clinical trials, including required confirmatory trials, may not demonstrate sufficient safety and efficacy of zanidatamab or other product candidates.
• Product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable.
• Conditional regulatory approval may be withdrawn or revoked if product candidates fail to satisfy the requirements.
• Regulatory agencies may impose additional requirements or delay the initiation of clinical trials.
• The company's ability to receive future milestone payments and royalties is not guaranteed and depends on successful development and commercialization.
• Potential negative impacts from new or changing laws and regulations, market conditions, and tariffs.
• Potential negative impacts of FDA regulatory delays, new policies, budget cuts, and changes in drug pricing controls.
• Impact of pandemics and other health crises on business, research, clinical development plans, timelines, and results of operations.
• Inability to maintain or enter into new partnerships or strategic collaborations.

Future Outlook

Zymeworks anticipates continued verification of zanidatamab's clinical benefit through ongoing confirmatory trials for its conditional approval in China. The company remains committed to realizing zanidatamab's potential to transform the standard of care across HER2-expressing cancers globally, with ongoing regulatory reviews in the EU and multiple global clinical trials. Zymeworks is also rapidly advancing its wholly-owned pipeline, with Phase 1 studies for ZW171 and ZW191 actively recruiting and an Investigational New Drug (IND) application for ZW251 planned for mid-2025.

Management Comments

• Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks, stated: "Zanidatamabs conditional approval in China is a meaningful advancement for patients living with HER2-positive BTC, a population with historically high unmet need and poor prognoses."
• Galbraith added: "This milestone affirms the strength of zanidatamabs clinical potential and reflects our continued focus on translating innovation into real impact for patients around the globe."
• Galbraith expressed gratitude: "We are deeply grateful to our partners at BeOne Medicines, and to the patients, families, and clinical teams whose contributions have made this milestone a reality."
• Galbraith reiterated commitment: "As Zymeworks continues to advance our broader development programs and R&D pipeline, we remain committed to realizing zanidatamabs potential to transform the standard of care across HER2-expressing cancers."

Industry Context

The approval of zanidatamab in China for HER2-positive BTC addresses a significant unmet medical need in a cancer type often associated with poor prognosis and rising incidence, particularly in Asian countries. As the first and only dual HER2-targeted bispecific antibody approved for this indication in China, it positions Zymeworks and its partner BeOne Medicines as leaders in this specific therapeutic area. This follows similar regulatory successes in the U.S. and Europe, indicating a growing global recognition of HER2 as a validated target for antitumor therapy beyond traditional indications, and highlights the increasing importance of bispecific antibodies in oncology.

Comparison to Industry Standards

• Zanidatamab is highlighted as the 'first and only' dual HER2-targeted bispecific antibody approved by the NMPA for HER2-high expression biliary tract cancer (BTC) in China, setting a new benchmark for this specific indication.
• This approval follows the U.S. FDA's accelerated approval in November 2024 for the same indication, positioning zanidatamab as a leading therapy globally for HER2+ BTC.
• The positive opinion from the European Medicines Agency (EMA) CHMP in April 2025 further reinforces its standing against global benchmarks for advanced HER2+ BTC.
• The document does not list specific comparable companies or projects, but its 'first and only' status implies it has surpassed or is ahead of other potential HER2-targeting therapies in this specific BTC indication in China.

Related Party Transactions

• License and Collaboration Agreement with BeOne Medicines Ltd. (formerly BeiGene, Ltd.), granting BeOne an exclusive license for zanidatamab in Asia (excluding Japan), Australia, and New Zealand.

Stakeholder Impact

• **Shareholders**: Positive impact due to NMPA approval, triggering milestone payments, and opening up significant future revenue streams from royalties and additional milestones, potentially increasing share price.
• **Patients**: Provides a new, and currently unique, treatment option (zanidatamab) for previously treated, unresectable or metastatic HER2-positive biliary tract cancer patients in China, addressing a high unmet medical need.
• **Employees**: Positive impact through validation of R&D efforts and potential for continued growth and stability.
• **Partners (BeOne Medicines Ltd.)**: Enables BeOne Medicines to commercialize zanidatamab in its licensed territories, potentially generating significant sales and market share.
• **Regulatory Authorities**: The NMPA's conditional approval reflects a rigorous review process and contributes to the availability of innovative therapies in China.

Next Steps

• Conduct ongoing confirmatory trials to verify clinical benefit for continued NMPA approval of zanidatamab in HER2+ BTC.
• Advance regulatory review of zanidatamab in the EU for second-line BTC.
• Continue evaluating zanidatamab in multiple global clinical trials for other HER2-expressing cancers.
• Continue active recruitment for Phase 1 studies of wholly-owned product candidates ZW171 and ZW191.
• File an Investigational New Drug (IND) application for ZW251 by mid-2025.

Key Dates

Recommendation

Keywords

Zymeworks, zanidatamab, NMPA approval, HER2-positive, biliary tract cancer, BTC, bispecific antibody, biotechnology, oncology, cancer treatment, milestone payment, clinical study, HERIZON-BTC-01, BeOne Medicines, China, FDA approval, EMA positive opinion