ASP8951

ASP8951 is an investigational antibody-drug conjugate (ADC) developed by Astellas Pharma that targets Claudin 18.2 (CLDN18.2), a protein frequently overexpressed in gastric and gastroesophageal junction (GEJ) adenocarcinomas. The drug consists of a humanized monoclonal antibody specific for CLDN18.2 conjugated to a potent topoisomerase I inhibitor payload (an exatecan derivative) via a protease-cleavable linker. Upon binding to CLDN18.2 on the tumor cell surface, the ADC is internalized, and the payload is released within the lysosome, leading to DNA damage, inhibition of replication, and subsequent apoptosis. This targeted approach aims to maximize anti-tumor activity while minimizing systemic toxicity. ASP8951 is currently undergoing Phase 1 clinical evaluation for patients with advanced solid tumors that express CLDN18.2, including gastric and GEJ cancers.