ALK208

ALK208 is a first-in-class trispecific antibody-drug conjugate (ADC) designed to target Programmed Death-Ligand 1 (PD-L1), B7-H3 (CD276), and Vascular Endothelial Growth Factor (VEGF). Developed by Akeso, the molecule is conjugated to a topoisomerase I inhibitor payload. It is engineered to provide a triple-action therapeutic approach: direct cytotoxic killing of tumor cells via the topoisomerase I inhibitor, restoration of antitumor immunity through PD-1/PD-L1 checkpoint blockade, and inhibition of tumor angiogenesis by neutralizing VEGF. Preclinical studies indicate that the concurrent binding of B7-H3 and PD-L1 enhances cellular internalization in double-positive tumor cells, while VEGF-mediated crosslinking further strengthens its cell-killing activity. ALK208 has demonstrated superior efficacy in xenograft models compared to monospecific and bispecific ADCs, with a safety profile that supports higher dosing levels for maximal target inhibition.

Other names

PD-L1/B7-H3/VEGF tri-specific ADC