SPR2015

SPR2015 is a highly potent and selective small molecule inhibitor of the KRAS G12D (on) state. It utilizes a unique tri-complex mechanism of action, binding to the endogenous intracellular protein cyclophilin A (CypA) to form a high-affinity complex that subsequently forms a covalent bond with the KRAS G12D mutant protein. This interaction effectively inhibits KRAS signaling and downstream pathways. Developed by Sperogenix Therapeutics, SPR2015 has demonstrated significant anti-tumor efficacy in preclinical models of colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC). In head-to-head preclinical trials involving over 15 CRC xenograft models, SPR2015 achieved a 64.7% objective response rate (ORR) and a 94.1% disease control rate (DCR) as a monotherapy. The drug is currently in IND-enabling development, with Phase 1 clinical trials expected to commence by the end of 2026.