Revolution Medicines Announces Publication on the Discovery of and Translational Research for RMC-6236, an Investigational RAS(ON) Multi-Selective Tri-Complex Inhibitor Designed to Block Full Spectrum of Oncogenic RAS(ON) Proteins

Simultaneous publication and presentation of RMC-6236 chemical structure, preclinical data and case studies during the “KRAS: Broadening the Attack Beyond G12C with Small Molecules and Immuno-Oncology" Session at AACR 2024 in San Diego

REDWOOD CITY, Calif., April 09, 2024 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced the publication of a peer-reviewed research paper in Cancer Discovery. The scientific paper details the discovery and preclinical to clinical translation for RMC-6236, an investigational RAS(ON) multi-selective inhibitor, and includes exemplary case studies from the current Phase 1/1b clinical trial demonstrating the initial anti-tumor activity of RMC-6236. This original research was led by scientists at Revolution Medicines and conducted in collaboration with researchers from across the U.S. and Europe.

Oncogenic RAS proteins drive up to 30 percent of all human cancers, most notably non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). RAS G12 mutations, such as G12D, G12V and G12C, predominate in human cancers. Currently approved KRAS-targeted cancer therapies target one particular KRAS mutation, KRAS G12C, in the GDP-bound (OFF) state. The paper describes the discovery of RMC-6236, an oral, multi-selective inhibitor of the active GTP-bound (ON) state of both mutant and wild-type RAS. In preclinical studies, RMC-6236 was effective in inhibiting the growth of RAS-dependent tumor cells, while sparing normal tissues. RMC-6236 was found to be well-tolerated and drove deep and durable tumor regressions across multiple cancer types including NSCLC, PDAC, CRC, gastric and gynecologic cancers, with tumor models dependent on KRAS G12 mutations being particularly sensitive. This benefit was found to extend to models with K/N/HRAS hotspot mutations at G13 and Q61 as well.

The paper also highlights translational pharmacokinetics (PK)/efficacy and PK/pharmacodynamics modeling, which predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, case studies from the Phase 1/1b RMC-6236 monotherapy clinical trial are featured, describing two patients with advanced KRAS-G12V NSCLC and KRAS-G12D PDAC, respectively, who were treated with 300 mg of RMC-6236 daily. Each of these two patients achieved a complete response as best response demonstrating the potential anti-tumor activity of RMC-6236.