On March 17, 2026 Frontier Medicines Corporation, a clinical-stage precision medicines company unlocking the proteome to develop small molecule oncology and immunology drugs against previously undruggable disease-causing targets, reported that it will present preclinical data on its FMC-242 program, as well as advances from its AI-powered Frontier Platform, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026, taking place April 17-22, 2026, in San Diego. 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We look forward to presenting new preclinical data at AACR (Free AACR Whitepaper) demonstrating that FMC-242 drives robust anti-tumor activity both as a monotherapy and in combination with targeted agents, while maintaining a favorable tolerability profile," said Kevin Webster, Ph.D., Chief Scientific Officer of Frontier Medicines. "These findings highlight the potential of selectively disrupting the PI3Kα-RAS interaction to address tumors driven by RTK activation and RAS mutations. Together with new data showcasing our AI-powered Frontier Platform, this work underscores how systematically mapping the proteome for covalent binding sites enables us to expand the range of high-value cancer targets we can drug and advance precision medicines for patients."
Summary of the findings to be presented and poster presentation details are as follows:
Title: 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
Poster Number: 5762
Session Title: Multi-Axis Antineoplastic Agents
Session Date & Time: April 21, 2026, 2:00 – 5:00 p.m. PT
Location: Poster Section 14, San Diego Convention Center
Summary of Findings: FMC-242 is a first-in-class, potent, selective, orally bioavailable covalent allosteric breaker of the PI3Kα-RAS interaction. In cell line- and patient-derived xenograft models with HER2 amplification and/or KRAS mutations, FMC-242 demonstrated potent anti-tumor activity with favorable tolerability and no effect on insulin signaling or blood glucose. In combination with EGFR inhibitors, KRASG12C inhibitors (including FMC-376), and pan-RAS/KRAS agents, FMC-242 further enhanced anti-tumor activity, supporting its potential as a differentiated monotherapy and combination approach.
Title: Finding Goldilocks: How AI-powered covalent drug discovery removes the "un" from "undruggable"
Poster Number: 4183
Session Title: Integrative Computational Approaches 2
Session Date & Time: April 21, 2026, 9:00 a.m. – 12:00 p.m. PT
Location: Poster Section 4, San Diego Convention Center
Summary of Findings: 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. The platform maps covalent binding sites across the proteome and applies AI-guided predictive modeling and optimized covalent fragment libraries to accelerate compound design, expanding the range of tractable oncogenic targets previously considered undruggable.
About FMC-242
FMC-242 is a first-in-class allosteric breaker of the PI3Kα-RAS interaction that breaks the interaction between PI3Kα and RAS to inhibit downstream signaling in tumors without impacting normal functions such as glucose homeostasis. The mechanism of action inhibits RAS driven PI3Kα-AKT signaling in tumors while minimizing the off-target effects and toxicities commonly associated with the broader class of kinase inhibitors. In preclinical models, FMC-242 has shown potent anti-tumor activity demonstrating the potential to impact patients with lung, colorectal, breast and other cancers that are driven by RTK activation, RAS mutation and PI3Kα mutations either as a single agent or in combination with other therapies including KRAS inhibitors. PI3Kα 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.
(Press release, Frontier Medicines, MAR 17, 2026, View Source [SID1234663650])