DB-1323

DB-1323 is a next-generation antibody-drug conjugate (ADC) targeting mesothelin (MSLN), a cell-surface glycoprotein overexpressed in various solid tumors, including pancreatic and ovarian cancers. Developed by Duality Biologics, DB-1323 comprises a novel, fully human anti-MSLN immunoglobulin G1 (IgG1) monoclonal antibody conjugated to a proprietary DNA topoisomerase I inhibitor payload via a maleimide-tetrapeptide cleavable linker. A key differentiator of DB-1323 is its unique rapid-on/off binding kinetics, which allow the molecule to effectively evade soluble MSLN sinks while maintaining high avidity for membrane-bound MSLN on tumor cells. This design facilitates efficient internalization and subsequent release of the cytotoxic payload, leading to potent anti-tumor activity. Preclinical data have demonstrated superior efficacy compared to first-generation MSLN ADCs and a favorable safety profile in non-human primates, with a highest non-severely toxic dose (HNSTD) of 60 mg/kg.