Press Release

Revolution Medicines Reports Preclinical Tumor Regressions Induced by First-in-Class KRAS-G12D(ON) Inhibitors

September 16, 2020

Presentation at 2nd Annual RAS-Targeted Drug Development Conference Highlights First Publicly Reported Data for Inhibitors of Notorious Cancer Protein KRASG12D(ON)

REDWOOD CITY, Calif., Sept. 16, 2020 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company focused on developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, today reported data demonstrating that its first-in-class KRASG12D(ON) inhibitors induced tumor regressions in a preclinical model of human pancreatic cancer carrying an oncogenic KRASG12D mutation. This first public disclosure of results showing anti-tumor activity for potent inhibitors of the notorious KRASG12D(ON) cancer protein was made by Steve Kelsey, M.D., president of research and development, in a presentation entitled “Approaches to Inhibiting RAS Driven Tumors Beyond KRASG12C” at the 2nd Annual RAS-Targeted Drug Development Conference. 

Revolution Medicines uses its proprietary tri-complex technology platform to create innovative compounds designed to inhibit the active, GTP-bound form of RAS, or RAS(ON), proteins. The company previously reported representative preclinical profiles of its potent inhibitors of another common cancer driver, KRASG12C(ON). The newly presented data demonstrated that its KRASG12D(ON) inhibitors induced significant decreases in tumor volume in a xenograft model of human pancreatic cancer driven by a KRASG12D mutation. This anti-tumor activity was observed across multiple dose levels, and all dose levels were well tolerated. The KRASG12D(ON) program is currently in lead optimization.

The KRASG12D genotype is of particularly high clinical interest as there are currently no approved targeted therapies for the treatment of cancers driven by this mutation, which is found in approximately 35 percent of pancreatic cancer cases and 15 percent of colorectal cancers in the U.S. The company continues its efforts to discover and develop inhibitors of multiple oncogenic mutants of RAS proteins, which in aggregate are believed to drive approximately 30% of all human cancers in the U.S. Earlier in 2020 the company named KRASG12C, KRASG12D, KRASG13C and NRASG12C as its four initial priority RAS(ON) targets.

“It is gratifying for our R&D organization to present this exciting demonstration of preclinical anti-cancer activity of compounds targeting the oncogenic KRASG12D(ON) protein. Advancement of our KRASG12D(ON) inhibitor program into the lead optimization stage represents an important corporate milestone, and highlights the substantial progress that we continue to make across our broad-based mutant RAS(ON) inhibitor effort,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “We believe that targeted inhibitors directed to mutant forms of RAS that drive various cancers, and in particular the RAS(ON) form of these proteins, represent a potential therapeutic strategy for serving important unmet needs on behalf of patients battling RAS-driven cancers.”  

About Revolution Medicines, Inc.

Revolution Medicines is a clinical-stage precision oncology company focused on developing novel targeted therapies to inhibit high-value frontier targets in RAS-addicted cancers. The company possesses sophisticated structure-based drug discovery capabilities built upon deep chemical biology and cancer pharmacology know-how and innovative, proprietary technologies that enable the creation of small molecules tailored to unconventional binding sites. 

The company’s R&D pipeline includes RMC-4630, a clinical-stage investigational drug that is designed to selectively inhibit the activity of SHP2, an upstream node in RAS signaling. Preclinical programs include inhibitors of multiple mutant RAS proteins and SOS1.  RMC-5552, currently in IND-enabling development, is designed for use against tumors featuring mTORC1 activation, including certain RAS-addicted cancers.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding the potential anti-tumor activity of RAS(ON) inhibitors in KRASG12D or other mutant RAS(ON) driven tumors, Revolution Medicines’ efforts to discover and develop inhibitors of multiple oncogenic mutants of RAS proteins and the potential benefits of, and markets for, Revolution Medicines’ potential product candidates. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including Revolution Medicines’ programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Revolution Medicines’ ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of Revolution Medicines’ capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape and the effects on our business of the worldwide COVID-19 pandemic. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 10, 2020, and its future periodic reports to be filed with the Securities and Exchange Commission. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.

Contacts: For Investors: Vida Strategic Partners Stephanie Diaz 415-675-7401 For Media: Vida Strategic Partners Tim Brons 415-675-7402