Frontier Medicines has received FDA allowance to proceed under an Investigational New Drug application for FMC-242, clearing the Boston and South San Francisco company to begin human testing in selected advanced solid tumors.
FMC-242 is an oral, covalent, allosteric molecule designed to break the physical interaction between PI3Kalpha and RAS. Frontier built it with CovalentAI, its platform for finding covalent binding sites across the proteome.
Why that protein pair
Only one oncogene in human cancer mutates more often than PI3Kalpha, and it features in tumors driven by either PI3Kalpha or RAS. Rather than inhibiting a single kinase, the molecule is meant to disrupt the partnership between the two proteins, a configuration Frontier argues has been hard to reach with conventional chemistry. CEO Chris Varma called the allowance an important step as the program enters clinical development.
What the trial looks like
In the trial, FMC-242 will be given alone and alongside other targeted agents to people whose disease is advanced or has spread. Preclinical work presented at AACR in April showed anti-tumor activity in models with HER2 amplification or KRAS mutations, with no observed effect on insulin signaling or blood glucose – a familiar liability for drugs that hit PI3Kalpha directly.
Combination data paired the molecule with EGFR inhibitors, KRAS G12C inhibitors and pan-RAS agents. Frontier has not disclosed a start date for enrollment.
