Zymeworks Presents New Data from Multiple Preclinical Development Programs at 2024

ZW191 is a FRα-targeting antibody-drug conjugate (ADC) differentiated by its novel antibody and novel topoisomerase I inhibitor payload. The compelling preclinical activity profile supports ZW191 development across multiple tumor types, including FRα-high/mid/low ovarian cancers and other FRα-expressing indications, including non-small cell lung cancer, endometrial cancer, and triple-negative breast cancer. An investigational new drug (IND) submission or foreign equivalent is planned for 2024.

 

Key Results:

 

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Superior internalization, payload delivery, and spheroid penetration to other FRα-targeted multi-specific antibodies.

Bystander active payload drives activity in settings with heterogeneous FRα expression.

Well-tolerated, with a highest non-severely toxic dose of 60 mg/kg in non-human primates.

Screening novel format antibodies to design bispecific ADCs that address target heterogeneity

Abstract: 2052

Session Category: Experimental and Molecular Therapeutics

Session Title: New Technologies

 

Inter-patient and intra-tumoral target expression heterogeneity is an obstacle in the design of ADCs that target a single tumor associated antigen (TAA). While bystander active payloads mitigate intra-tumoral target heterogeneity, bispecific ADCs that target two different TAAs independently provide an additional approach to overcome limitations associated with the expression profile of any single target antigen. Critical to this bispecific ADC approach however is identification of the optimal bispecific antibody format suited for payload delivery to two independent tumor antigens. To address this challenge a novel design and screening approach of bispecific ADCs was employed, using FRα and NaPi2b as an exemplary target pair, independently expressed across various cancer types.

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