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Frontier Medicines Selects KRAS G12C Inhibitor as Lead Development Candidate

NEW YORK – Frontier Medicines said on Thursday that it has selected FMC-376, a KRAS G12C inhibitor, as its lead development candidate and advanced two preclinical programs targeting E3 ligases.

Frontier plans to file an investigational new drug (IND) application for FMC-376 this year and has advanced the candidate into IND-enabling studies. FMC-376 inhibits both the active and inactive forms of KRAS G12C, which Frontier believes may overcome non-response and resistance seen in other KRAS G12C inhibitors that only target inactive KRAS.

Frontier also announced that it has moved the second and third programs under a drug discovery, development, and commercialization partnership with AbbVie into lead optimization. AbbVie partnered with Frontier in 2020 to use its drug discovery platform to identify small molecules for programs directed to novel E3 ligases.

Under the agreement with AbbVie, Frontier will conduct preclinical drug discovery and development for the E3 ligase programs, and AbbVie will reimburse the research and development costs. If the programs are successful, AbbVie will take over clinical development and commercialization. Frontier will also receive certain milestone and royalty payments on any drug commercialized. Frontier advanced the first, undisclosed program from this partnership into preclinical development last January.

"Our collaboration with Frontier is continuing to make progress against difficult-to-drug protein targets," Jonathon Sedgwick, global head of discovery research at AbbVie, said in a statement. "Two years into our partnership, Frontier's technology is showing important advances in the drugging of previously inaccessible biology, this time towards enabling binders for novel E3 ligases, with the potential to be applied to the discovery and development of new and better therapeutic options for patients."