Revolution Medicines Announces Publications on the Discovery and Preclinical Profile of Representative of a New Class of RAS(ON) Multi-Selective Inhibitors Designed to Block Full Spectrum of Oncogenic RAS(ON) Proteins - Seite 2

The second report describes research into the pharmacology and anti-tumor activity of the tool compound, RMC-7977, which was evaluated across a diverse range of preclinical PDAC models. Broad and pronounced anti-tumor activity was observed across various preclinical models following direct RAS inhibition by RMC-7977 at exposures that were well tolerated in vivo, providing a strong preclinical rationale for evaluating broad-spectrum RAS inhibition in the clinical PDAC setting. Furthermore, careful analysis of recognized clinical resistance mechanisms in a sophisticated model of PDAC treated with RMC-7977 revealed a promising combination treatment regimen that may be capable of countering monotherapy drug resistance.

“This innovative research extends the impact of our tri-complex inhibitor platform to a wide range of common, oncogenic RAS mutants for which no targeted drugs are available, and supported the discovery of RMC-6236, our clinical-stage RAS(ON) multi-selective inhibitor. The findings reverse long-standing scientific dogma by showing that it is possible to obtain meaningful anti-tumor activity by broadly targeting the RAS class of proteins without unacceptable effects in normal tissues,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “The preclinical findings reported in these scientific papers, combined with initial data we have disclosed from an ongoing clinical study of RMC-6236, support further evaluation of RMC-6236 in patients living with RAS-addicted cancers, for whom there remain large unmet medical needs.”

The investigational oral drug candidate RMC-6236 is a RAS(ON) multi-selective inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Revolution Medicines is currently evaluating RMC-6236 as monotherapy in a first-in-human trial in patients with advanced solid tumors harboring G12X, G13X, and Q61X mutations (NCT05379985). Based on promising preliminary data in this trial, planning is underway to initiate pivotal studies of RMC-6236 as monotherapy in NSCLC and PDAC. RMC-6236 is also being evaluated in combination with pembrolizumab with or without chemotherapy in patients with advanced RAS-mutated solid tumors (NCT06162221) and in combination with RMC-6291, the company’s investigational RAS(ON) G12C-selective inhibitor, for patients with advanced KRAS G12C-mutated solid tumors (NCT06128551).