FMC-242 / Frontier Medicines - LARVOL DELTA

Combination of FMC-242, a first-in-class, covalent allosteric breaker of the PI3Kα-RAS interaction, with KRAS inhibitors drives enhanced anti-tumor activity including regression in CDX/PDX models harboring KRAS mutations (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Oncology • KRAS • PIK3CA

FMC-242, a highly potent and selective covalent inhibitor of the PI3Kα -RAS interaction, demonstrates robust anti-tumor activity as monotherapy and in combination with targeted therapies (AACR 2026) - "Combination of FMC-242 with targeted therapies including EGFR inhibitors, KRASG12C inhibitors such as FMC-376, divarasib, olomorasib, or pan-RAS/KRAS agents results in enhanced efficacy and tumor regressions in vivo. Together, these data demonstrate the potential of FMC-242, a selective covalent inhibitor of PI3Kα -RAS interaction, to deliver improved outcomes for patients as monotherapy and in combination with targeted therapies in the clinic."

Combination therapy • Monotherapy • Oncology • HER-2 • KRAS • PIK3CA

Frontier Medicines to Present Findings on PI3Kα-RAS Breaker FMC-242 and AI-Powered Frontier Platform at AACR Annual Meeting 2026 (Businesswire) - "FMC-242 is Frontier’s first-in-class allosteric breaker of the PI3Kα-RAS interaction that is in preclinical development for the treatment of solid tumors driven by RTK activation, RAS mutations and PI3Kα mutations, as both a single agent and in combination with other therapies including KRAS inhibitors....Application of the Frontier Platform, which integrates chemoproteomics, covalent chemistry, and machine learning, has enabled identification of selective covalent small-molecule leads across high-value cancer targets, including historically difficult drivers such as KEAP1, ADAR, DHX9, PTPN11, and MYC."

Preclinical • Solid Tumor

FMC-242, a highly potent and selective covalent inhibitor of the PI3Ka-RAS interaction that demonstrates improved efficacy and tolerability as monotherapy and in combination with targeted therapies in preclinical models (AACR-NCI-EORTC 2025) - "Inhibition of the PI3Ka-RAS interaction does not affect insulin signaling or blood glucose levels and is well tolerated in vivo. Together, these data demonstrate the promise of FMC-242 as a selective covalent inhibitor of PI3Ka-RAS interaction, with the potential to deliver improved outcomes for patients as a monotherapy and in combination with targeted therapies such as KRAS or RTK inhibitors in the clinic."

Combination therapy • Late-breaking abstract • Monotherapy • Preclinical • Oncology • HER-2 • KRAS