GENA-104 ADC

GENA-104 ADC is an antibody-drug conjugate (ADC) developed by Genome & Company that targets Contactin 4 (CNTN4), a novel immune checkpoint molecule overexpressed in various solid tumors. The ADC consists of a humanized IgG1 anti-CNTN4 antibody (GENA-104A16.hIgG1) with reduced effector function, conjugated via a cysteine-based hydrophilic, cleavable linker (Linker E) to the topoisomerase I inhibitor exatecan. GENA-104 ADC exerts its anti-tumor activity through multiple mechanisms: direct cytotoxicity following internalization and lysosomal release of the payload, a bystander effect on neighboring cells, and the induction of immunogenic cell death. Furthermore, by targeting CNTN4, it blocks the interaction with amyloid precursor protein (APP) on T cells, thereby reversing T cell suppression. Preclinical studies have demonstrated robust efficacy in xenograft models of fibrosarcoma and hepatocellular carcinoma, as well as high expression in patient-derived xenograft (PDX) models of gastric, hepatic, and prostate cancers.