CPL-976

CPL-976 (also known as CPBT-0976) is a preclinical, first-in-class bispecific antibody developed by Celon Pharma. It is designed in a VHH-Fc-VHH nanobody format, featuring humanized llama-derived heavy chain variable domains (VHH) fused to a human IgG1 Fc fragment. CPL-976 simultaneously targets the immune checkpoint programmed death-ligand 1 (PD-L1) and the receptor tyrosine kinase AXL. Its mechanism of action involves the simultaneous internalization and degradation of both targets, thereby disrupting the PD-1/PD-L1 and AXL/GAS6 signaling axes. This dual targeting is intended to enhance the anti-tumor immune response and overcome resistance to standard PD-1/PD-L1 therapies. Preclinical studies have demonstrated efficacy in breast, lung, and melanoma cancer cell lines, as well as syngeneic mouse tumor models.