anti-EGFR/anti-HER3 bispecific antibody-drug conjugate IBI3005

An antibody-drug conjugate (ADC) composed of a bispecific antibody directed against the tumor associated antigens (TAAs) human epidermal growth factor receptor (EGFR; HER1; ErbB1), and human epidermal growth factor receptor 3 (HER3; ErbB3) conjugated to a camptothecin derivative, with potential antineoplastic activity. Upon administration, anti-EGFR/anti-HER3 bispecific ADC IBI3005 targets and simultaneously binds to EGFR and HER3 expressed on tumor cells. This blocks EGFR activation by ligands and EGFR-mediated signaling. Upon binding and internalization, the camptothecin derivative is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis in EGFR- and HER3-expressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. HER3, a member of the EGFR family of receptor tyrosine kinases, is frequently overexpressed in tumors.