CPL976-MMAE

CPL976-MMAE is a novel, potentially first-in-class bispecific antibody-drug conjugate (ADC) targeting both AXL and programmed death-ligand 1 (PD-L1). Developed by Celon Pharma, the drug consists of a bispecific antibody (CPL976 or CPBT0976) in a VHH-Fc-VHH format, with two VHH domains targeting PD-L1 and two targeting AXL. This bispecific antibody is conjugated to the cytotoxic payload monomethyl auristatin E (MMAE), a potent tubulin inhibitor, using site-specific conjugation technology via Fc glycan remodeling and click chemistry. By simultaneously targeting AXL and PD-L1, CPL976-MMAE enhances tumor specificity, promotes rapid receptor internalization and degradation, and delivers the cytotoxic payload directly to solid tumor cells, thereby minimizing off-target toxicities. It is currently in preclinical development for the treatment of solid tumors, including breast cancer.