ZW251

ZW251 is a novel antibody-drug conjugate (ADC) developed by Zymeworks for the treatment of hepatocellular carcinoma (HCC). It consists of a humanized monoclonal antibody that targets glypican-3 (GPC3), a cell surface oncofetal antigen highly expressed in most HCC tumors but minimally present in normal adult tissues. The antibody is conjugated to a topoisomerase 1 inhibitor payload (ZD06519), which is released upon internalization into GPC3-expressing cells, leading to DNA damage and cell death. Preclinical studies have demonstrated robust anti-tumor activity across multiple HCC models with varying levels of GPC3 expression and favorable tolerability in non-human primates. The drug employs an optimized drug-antibody ratio and proprietary linker technology to balance efficacy and safety[1][3][5].