IN30705 is an ADC formed by a new humanized anti-FAP mAb that has been conjugated to a novel cytolysin, TAM470, a synthetic microtubule inhibitor from the tubulysin family. IN30705 is designed to target FAP-expressing Cancer Associated Fibroblasts (CAFs) in tumor microenvironment.
The FAP protein is used as a docking for IN30705 so that, upon FAP binding onto the CAF cell membrane, the agent is internalized and transported to intracellular late endosome where the cytotoxic moiety is released. The targeting of CAFs and the associated stroma modulation would then delay disease progression, increase drug penetration, and reestablish the tumor immune response to anti-PD-1 therapy.
IN30705 is intended for the treatment of patients with advanced solid tumors known to have FAP-expressing CAFs: PDAC, GC, HNSCC, EC, NSCLC, HGSOC, BC,CRC, and leiomyosarcoma.
The Target: FAP
FAPa is a dimeric type II serine protease of 170 kDa which is overexpressed in more than 90% of carcinomas. Its highly focal expression in CAFs surrounding the tumor microvasculature, together with its fast and efficient internalization. FAP-expressing CAFs are a nonredundant, immunosuppressive component of the tumor microenvironment. The restriction of FAP expression to CAFs makes it an attractive cancer target with an a priori wide risk benefit balance.