FDA Clears IND Application for Zymeworks' Novel FRα-Targeted ADC, ZW191
核心洞察
Zymeworks' ZW191, a novel folate receptor-α (FRα (搜索)) targeted topoisomerase I inhibitor antibody-drug conjugate (ADC), receives FDA clearance for its Investigational New Drug (IND) application.
ZW191 incorporates a novel antibody and drug-linker designed for enhanced stability, payload potency, and strong bystander activity, potentially improving efficacy in FRα (搜索)-expressing tumors.
Clinical development of ZW191 is set to begin in 2024, with plans to file for regulatory authorization in non-US jurisdictions in the second half of the year.
Zymeworks Inc. has announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for ZW191, a novel folate receptor-α (FRα (搜索)) targeted topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate (ADC). The company plans to initiate clinical development of ZW191 during 2024.
ZW191 is designed to target FRα (搜索), which is expressed in several difficult-to-treat cancers. The ADC incorporates a novel antibody and drug-linker that provide a unique combination of antibody-linker stability and payload potency, together with strong bystander activity. This design could result in improved efficacy and enable targeting lower levels of FRα compared to previously developed drug candidates.
Differentiated Design for Enhanced Efficacy
According to Paul Moore, Chief Scientific Officer of Zymeworks, ZW191 reflects the company's strength in developing best-in-class ADCs. The drug was developed using Zymeworks’ drug conjugate platforms, including the novel TOPO1i-based payload technology, ZD06519. A drug-antibody-ratio (DAR) of eight was selected to balance tolerability and efficacy. The FRα (搜索) monoclonal antibody incorporated in ZW191 was generated in-house and selected based on enhanced internalization characteristics to enable targeting of high, mid, and low levels of FRα expression.
Targeting FRα-Expressing Tumors
FRα (搜索) is a clinically validated target expressed in approximately 75% of ovarian carcinomas (搜索) and 70% of NSCLC. Preclinical models have demonstrated that ZW191 has robust anti-tumor activity and a strong safety profile.
Clinical Development Plans
The company expects to file applications seeking regulatory authorization to initiate clinical studies for ZW191 in non-US jurisdictions in the second half of 2024. ZW191 is the first of three ADC molecules incorporating the company’s proprietary ZD06519 payload designated for clinical development, with IND filings for ZW220 (NaPi2b ADC) and ZW251 (GPC3 ADC) on schedule for 2025.