PBS293-exatecan

PBS293-exatecan is a first-in-class, logic-gated, cis-bispecific antibody-drug conjugate (ADC) developed by Promatix Biosciences. It consists of a full IgG1 bispecific antibody (PBS293) targeting both epidermal growth factor receptor (EGFR) and ephrin type-A receptor 2 (EphA2), conjugated to an exatecan payload (a topoisomerase I inhibitor). Designed using Promatix's TxPro proteomics-based platform, PBS293-exatecan utilizes a hybrid avidity-gated 'AND-gate' mechanism. This design ensures that strong binding, internalization, and payload delivery occur selectively in tumor cells co-expressing both EGFR and EphA2, thereby sparing healthy tissues (such as skin keratinocytes and endothelial cells) that express only one of the targets. The program is in preclinical development for advanced colorectal cancer (CRC), with potential expansion into other solid tumors such as non-small cell lung cancer (NSCLC) and esophageal cancer.