BT7480

BT7480 is a novel, fully synthetic, first-in-class Bicycle tumor-targeted immune cell agonist (Bicycle TICA) designed to co-ligate Nectin-4 on tumor cells and CD137 (4-1BB; TNFRSF9) on immune cells. It consists of three bicyclic peptides—one targeting Nectin-4 and two targeting CD137—conjugated via a branched trimeric polyethylene glycol linker. By bringing together Nectin-4-expressing tumor cells and CD137-expressing immune cells, BT7480 induces oligomerization and activation of CD137, resulting in localized costimulatory signaling that enhances antitumor immunity. Preclinical studies demonstrated potent antitumor activity with complete regressions in syngeneic mouse models, robust immunomodulation including myeloid cell activation followed by T-cell infiltration, and resistance to tumor re-challenge. The drug is well tolerated in preclinical species without the hepatic toxicity seen with non-targeted CD137 agonists. Clinically, it is being evaluated for advanced solid tumors associated with high Nectin-4 expression such as urothelial carcinoma, pancreatic cancer, breast cancer, ovarian cancer, esophageal cancer, head and neck squamous cell carcinoma, gastric cancer, lung cancers (including non-small cell), among others[1][2][6][7][8][9].