MT-5111

MT-5111 is an engineered toxin body (ETB) designed to target HER2-positive solid tumors. It consists of a single chain variable fragment (scFv) with affinity for the human epidermal growth factor receptor 2 (HER2), fused to an enzymatically active, de-immunized Shiga-like toxin A subunit. MT-5111 binds to a unique epitope on HER2 that is distinct from those targeted by trastuzumab and pertuzumab, allowing it to potentially overcome resistance mechanisms associated with other HER2-targeted therapies and enabling combination strategies. Its mechanism of action involves direct cell killing through enzymatic inactivation and permanent destruction of ribosomes, leading to apoptosis in HER2-expressing tumor cells. Unlike antibody-drug conjugates or tyrosine kinase inhibitors, its activity does not depend on kinase inhibition or immune-mediated cytotoxicity, making it effective even in resistant disease settings. The drug was developed by Molecular Templates for the treatment of advanced HER2-positive solid tumors such as breast cancer and gastric/gastroesophageal adenocarcinoma but has been discontinued after phase 1 clinical trials[3][4][5][6][7].