ZW191

ZW191 is a novel antibody-drug conjugate (ADC) developed by Zymeworks for the treatment of advanced solid tumors expressing folate receptor alpha (FRα), including ovarian, endometrial, and non-small cell lung cancers. The ADC consists of a fully humanized IgG1 monoclonal antibody targeting FRα, covalently linked to a proprietary topoisomerase I inhibitor payload (ZD06519) via a maleimidocaproyl-GGFG-aminomethyl protease-cleavable linker. Upon binding to FRα on tumor cells and internalization, the cytotoxic payload is released intracellularly, inducing cell death in both FRα-positive and neighboring FRα-negative cells through bystander-mediated killing. Preclinical studies have demonstrated superior or comparable anti-tumor activity to mirvetuximab soravtansine across various levels of FRα expression in ovarian cancer as well as strong activity in NSCLC, endometrial cancer, and triple-negative breast cancer models. The drug has shown favorable safety and tolerability profiles in preclinical toxicology studies[1][3][4][6][9].