Abstract:
CDH3 has been identified as a widely overexpressed antigen across various cancers. Utilizing RenLite CDH3 knockout mice, we identified Ab.20, a monoclonal antibody specifically targeting CDH3. Ab.20 effectively binds to multiple tumor cell lines and demonstrates strong internalization activity. In proof-of-concept studies, the Ab.20-vcMMAE conjugate showed superior efficacy compared to the benchmark Ab-vcMMAE in patient-derived xenograft (PDX) models. Subsequently, Ab.20 was conjugated with BLD1102, a novel topoisomerase I inhibitor payload, resulting in BCG014, which demonstrated potent efficacy in a PDX model. Ongoing studies are focused on further evaluating the efficacy, pharmacokinetics (PK), and toxicity of BCG014.