FDA Clears Zymeworks' IND for ZW191, a Novel Folate Receptor-⍺ Targeted ADC

On July 22, 2024, Zymeworks Inc. (Nasdaq: ZYME), a biotechnology company in the clinical stage of development, reported that the United States Food and Drug Administration (FDA) has approved their investigational new drug (IND) application for ZW191. ZW191 is a novel folate receptor-⍺ (FR⍺) targeted topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate (ADC).

Paul Moore, the Chief Scientific Officer of Zymeworks, highlighted ZW191 as a key product in their pipeline. Designed to target FR⍺, which is found in various challenging cancers, ZW191 uses a unique antibody and drug-linker combination. This innovation provides a blend of stability and potency, potentially enhancing efficacy and enabling the targeting of lower FR⍺ levels compared to earlier drug candidates. This development milestone comes shortly after the FDA's clearance of ZW171 in June, with plans to start clinical trials for both ZW191 and ZW171 in 2024.

ZW191 leverages Zymeworks' drug conjugate platforms, incorporating the TOPO1i-based payload technology, ZD06519, to target FR⍺-expressing tumors such as ovarian and other gynecological cancers, as well as non-small cell lung cancer (NSCLC). The drug-antibody ratio (DAR) of eight was chosen to balance efficacy and tolerability. The FR⍺ monoclonal antibody used in ZW191 was developed in-house, selected for its enhanced internalization capabilities, allowing it to target varying levels of FR⍺ expression. FR⍺ is present in approximately 75% of ovarian carcinomas and 70% of NSCLC. Preclinical models have shown that ZW191 has strong anti-tumor activity and a robust safety profile.

The company plans to file for regulatory authorizations to begin clinical trials for ZW191 outside the US in the latter half of 2024. ZW191 is the first among three ADC molecules that include the ZD06519 payload planned for clinical development. Plans for IND filings for ZW220 (NaPi2b ADC) and ZW251 (GPC3 ADC) are slated for 2025.

Zymeworks is a global clinical-stage biotech firm focused on discovering, developing, and commercializing innovative biotherapeutics. Their mission is to significantly impact the lives of individuals affected by difficult-to-treat cancers and other diseases. The company's platforms and integrated drug development engines allow for the precise engineering and development of highly differentiated antibody-based therapeutics. Among their innovations is zanidatamab, a HER2-targeted bispecific antibody developed using their proprietary Azymetric™ technology. Zymeworks has partnered with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting them exclusive rights to develop and commercialize zanidatamab in different regions. Zanidatamab is currently undergoing multiple clinical trials globally as a potential leading treatment for HER2-expressing cancers.

A Biologics License Application (BLA) has been submitted to the FDA for zanidatamab, seeking accelerated approval as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) and has received Priority Review. Additionally, a BLA has been accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. If approved, zanidatamab would be the first HER2-targeted treatment specifically for BTC in both the U.S. and China. Zymeworks continues to advance a broad pipeline of candidates using its expertise in antibody-drug conjugates and multispecific antibody therapeutics targeting several novel areas of unmet medical need. Their therapeutic platforms are further enhanced through strategic partnerships with global biopharmaceutical companies.