October 14, 2025
- FMC-242 is a potentially best-in-class covalent allosteric inhibitor that breaks the interaction between PI3Kα and RAS, targeting the largest genetic drivers of cancer –
- Potential as a monotherapy and as a foundational treatment when used in combination –
- Preclinical and combination data to be presented at the AACR-NCI-EORTC International Conference on October 25, 2025 –
BOSTON and SOUTH SAN FRANCISCO, Calif. (October 14, 2025) – Frontier Medicines Corporation, a clinical-stage precision medicines company unlocking the proteome to develop small molecule, precision oncology and immunology drugs against previously undruggable disease-causing targets, today announced its latest development candidate. FMC-242 is a covalent allosteric inhibitor that breaks the interaction between PI3Ka and RAS proteins to inhibit downstream effector signaling in tumors without impacting normal PI3Ka functions, such as glycemic regulation.
“By selectively breaking the PI3Kα/RAS interaction, we inhibit oncogenic AKT signaling without the metabolic side effects observed with kinase inhibitors. This approach has the potential to benefit patients with activating mutations or amplification of receptor tyrosine kinases, RAS, and PI3Ka, and may overcome resistance to commonly used targeted therapies, including HER2, EGFR, and RAS inhibitors,” said Kevin Webster, Ph.D., chief scientific officer of Frontier Medicines. “Early data suggest that FMC-242 has potential as a monotherapy and in combination within our pipeline, and we look forward to sharing additional details at the AACR-NCI-EORTC Symposium later this month.”
“FMC-242 illustrates the strength, productivity, and efficiency of the Frontier™ Platform and its ability to unlock the proteome to develop differentiated medicines against traditionally undruggable targets,” said Chris Varma, Ph.D., co-founder, chair, and chief executive officer of Frontier Medicines. “Like our other pipeline programs, FMC-242 was discovered in just two years by our crackerjack team of scientists applying our industry-leading covalent drug platform powered by chemoproteomics and AI. We anticipate an IND filing for FMC-242 in 2026. Also, keeping with our practice of producing one new drug candidate per year, we look forward to providing additional details on our covalent KRAS G12D program in 2026, which is currently in lead optimization.”
About FMC-242 and PI3Kα/RAS
PI3Ka is the second most commonly mutated oncogene and plays an essential role in both KRAS- and RTK-driven cancers, such as colorectal, lung, and breast cancers, among others. Traditionally, PI3K inhibitors aim to block the PI3K/AKT/mTOR pathway, which can slow or stop cancer cell growth. FMC-242 is a covalent allosteric inhibitor that breaks the interaction between PI3Ka and RAS to inhibit downstream effector signaling in tumors without impacting normal functions. The mechanism of action inhibits PI3Kα/AKT effector signaling in tumors while minimizing the toxicities commonly associated with the broader class of inhibitors.
About Frontier Medicines
Frontier Medicines is a clinical-stage precision medicine company pioneering groundbreaking medicines to transform treatment for genetically defined patient populations, starting with oncology and immunology. Our proprietary chemoproteomics-powered drug discovery engine, the Frontier™ Platform, leverages covalent chemistry and machine learning to unlock difficult-to-drug, disease-causing proteins for drug development. Today, we are advancing a diversified pipeline of wholly owned precision medicines against the most critical drivers of cancer and high-value immunology programs. For more information, please visit www.frontiermeds.com. Follow Frontier on LinkedIn.
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