IMD2146

IMD2146 is a novel dual-payload antibody-drug conjugate (ADC) designed to target tumors expressing EGFR and TROP2 while delivering two synergistic payloads: a pan-RAS inhibitor (QHL-P1711) and a Topoisomerase 1 inhibitor (DXd). Developed by Affinity Biopharmaceutical, the agent utilizes a bispecific antibody backbone and a proprietary tumor microenvironment (TME)-activated linker (TMEAlinker) that is selectively cleaved by legumain, a protease overexpressed in the TME. This design aims to expand the therapeutic window of pan-RAS inhibition by avoiding systemic toxicities, such as skin rash, and to overcome resistance to Topoisomerase 1 inhibitors. Preclinical studies have demonstrated superior efficacy in various RAS-mutant and Topo1i-resistant tumor models, along with favorable stability and safety profiles in non-human primates.