Revolution Medicines and Summit Therapeutics Enter into Clinical Collaboration to Evaluate Combinations of Three RAS(ON) Inhibitors with Ivonescimab in RAS Mutant Tumors

Rhea-AI Summary

Revolution Medicines (Nasdaq: RVMD) and Summit Therapeutics (Nasdaq: SMMT) have announced a clinical collaboration to evaluate combinations of Revolution's RAS(ON) inhibitors with Summit's ivonescimab in RAS mutant tumors. The collaboration will focus on three key compounds from Revolution Medicines: daraxonrasib (RMC-6236), zoldonrasib (RMC-9805), and elironrasib (RMC-6291).

The study will evaluate these combinations across three priority tumor types: RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC). Under the agreement, Summit will supply ivonescimab while Revolution Medicines will sponsor the study. Both companies will maintain commercial rights to their respective compounds, and the agreement is mutually non-exclusive.

Initial evidence has shown that daraxonrasib and elironrasib can safely deliver additive antitumor activity when combined with a PD-1 antibody in first-line treatment of patients with RAS mutant non-small cell lung cancer.

Positive

• Promising initial evidence of additive antitumor activity with PD-1 antibody combinations
• Clinical collaboration covers three major cancer types (NSCLC, PDAC, CRC)
• Companies maintain their respective commercial rights
• Agreement is mutually non-exclusive, allowing flexibility for other partnerships

Negative

• None.

Insights

Oncology Researcher

Revolution Medicines partners with Summit to test promising RAS inhibitor/immunotherapy combinations against difficult-to-treat cancers with strong scientific rationale.

This clinical collaboration represents a scientifically compelling approach combining two distinct therapeutic modalities with complementary mechanisms of action. Revolution Medicines' RAS(ON) inhibitors directly target the active, GTP-bound form of RAS proteins that drive approximately 30% of all cancers. Their portfolio includes daraxonrasib (multi-selective), zoldonrasib (G12D-selective), and elironrasib (G12C-selective) - each targeting specific RAS mutations that have historically been extremely challenging to drug effectively.

Summit's ivonescimab is particularly interesting as a bispecific antibody that simultaneously blocks both PD-1 (unleashing T-cell anti-tumor activity) and VEGF (inhibiting tumor angiogenesis). This dual-targeting approach provides a mechanistic advantage over standard PD-1 inhibitors by addressing both immune evasion and the tumor microenvironment.

The scientific rationale is strengthened by Revolution's disclosure of promising early evidence showing their RAS inhibitors can safely deliver additive anti-tumor effects when combined with PD-1 antibodies in first-line NSCLC. The collaboration will evaluate these combinations across three aggressive RAS-driven cancers with high mortality rates: non-small cell lung cancer, pancreatic cancer, and colorectal cancer.

This multi-pronged approach targeting both the driver mutation (RAS) and immune evasion mechanisms (PD-1/VEGF) represents a rational strategy to overcome resistance pathways and potentially improve outcomes in these difficult-to-treat malignancies.

Biotech Investment Analyst

Strategic partnership expands both companies' cancer pipelines with minimal financial risk while retaining full commercial rights to their assets.

This collaboration significantly enhances both companies' clinical development strategies while maintaining favorable economics. The structure is strategically advantageous - Revolution Medicines will sponsor the studies while Summit provides ivonescimab, creating a capital-efficient arrangement for both parties. Critically, each company retains full commercial rights to their respective compounds, preserving long-term value.

The non-exclusive nature of the agreement is equally important, giving both companies flexibility to pursue additional partnerships. For Revolution Medicines, this represents the expansion of their RAS(ON) inhibitor development program beyond their existing clinical trials. They now gain access to a novel PD-1/VEGF bispecific with a differentiated profile without surrendering any economic interest in their compounds.

For Summit, this partnership accelerates their clinical development strategy for ivonescimab by testing it in combination with cutting-edge targeted therapies across multiple indications. The targeted patient populations - those with RAS mutations in NSCLC, PDAC, and CRC - represent substantial commercial opportunities with high unmet needs.

The collaboration strategically positions both companies in the competitive oncology landscape, where combination approaches are increasingly viewed as necessary to achieve meaningful clinical outcomes. By testing multiple combinations across three RAS(ON) inhibitors and three cancer types, the companies create multiple "shots on goal" while sharing development costs and expertise - increasing their chances of clinical and commercial success.

REDWOOD CITY, Calif. and MIAMI, June 30, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers and Summit Therapeutics, Inc. (Nasdaq: SMMT), a biopharmaceutical oncology company focused on patient-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs, today announced the companies have entered into a clinical collaboration in multiple solid tumor settings to evaluate the safety and efficacy of each of Revolution Medicines’ clinical-stage RAS(ON) inhibitors, including the multi-selective inhibitor daraxonrasib (RMC-6236), G12D-selective inhibitor zoldonrasib (RMC-9805) and G12C-selective inhibitor elironrasib (RMC-6291), in combination with Summit Therapeutics’ ivonescimab, a PD-1 / VEGF bispecific antibody.

“We’ve disclosed promising initial evidence that each of daraxonrasib and elironrasib can deliver additive antitumor activity safely when combined with a PD-1 antibody in first-line treatment of patients with RAS mutant non-small cell lung cancer,” said Mark A. Goldsmith, M.D., Ph.D., chairman and chief executive officer of Revolution Medicines. “Combinations with novel PD-1 bispecific inhibitors could unlock further therapeutic potential. We are eager to evaluate combinations of investigational drugs from our RAS(ON) inhibitor portfolio with ivonescimab, an advanced PD-1 / VEGF bispecific inhibitor with a differentiated profile, in a range of common RAS mutant cancers.”

The clinical collaboration aims to evaluate these combinations across three priority tumor types including RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Under the terms of the agreement, Summit Therapeutics will supply ivonescimab for clinical research and Revolution Medicines will be the study sponsor. Each company will retain commercial rights to their respective compounds, and the agreement is mutually non-exclusive.

“We’re thrilled to partner with Revolution Medicines to evaluate in a clinical setting how our highly promising ivonescimab combined with their compelling RAS(ON) inhibitors could potentially improve outcomes for patients with lung and gastrointestinal cancers,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer and Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “As we continue to rapidly advance the development of ivonescimab across non-small cell lung cancer and other solid tumors, we believe that it is critically important to combine ivonescimab with some of the most promising medicines and drug candidates as we seek to provide innovative therapy options to patients facing high unmet needs.”

About Revolution Medicines, Inc.
Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn.

About Summit Therapeutics, Inc.
Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs.

Summit was founded in 2003 and its shares are listed on the Nasdaq Global Market (symbol “SMMT”). It is headquartered in Miami, Florida, and has additional offices in Menlo Park, California, and Oxford, UK.

For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX.

Revolution Medicines Forward Looking Statements
This press release contains forward-looking statements regarding Revolution Medicines 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 progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; the ability of the company’s RAS(ON) inhibitors to deliver additive antitumor activity in combination with a PD-1 antibody or a PD-1 / VEGF bi-specific inhibitor and related therapeutic options; and the aims and plans of the clinical collaboration with Summit Therapeutics. 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 the company’s 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 the company’s programs’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company’s ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company’s capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company’s business of the global events, such as international conflicts or global pandemics. 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 (the “SEC”) on May 7, 2025, and its future periodic reports to be filed with the SEC. 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.

Summit Forward-looking Statements
Any statements in this press release about the Summit Therapeutics’ future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Summit Therapeutics’ product candidates, entry into and actions related to the Summit Therapeutics’ partnership with Akeso Inc., the Summit Therapeutics' anticipated spending and cash runway, the therapeutic potential of the Summit Therapeutics’ product candidates, the potential commercialization of the Summit Therapeutics’ product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Summit Therapeutics’ ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Summit Therapeutics’ pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Summit Therapeutics’ foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that the Summit Therapeutics makes with the Securities and Exchange Commission. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Summit Therapeutics’ views only as of the date of this release and should not be relied upon as representing the Summit Therapeutics’ views as of any subsequent date. The Summit Therapeutics specifically disclaims any obligation to update any forward-looking statements included in this press release.

Revolution Medicines Media & Investor Contact:
media@revmed.com
investors@revmed.com

Summit Therapeutics’ Media & Investor Contact:
Dave Gancarz
Chief Business & Strategy Officer

Nathan LiaBraaten
Senior Director, Investor Relations

investors@smmttx.com
media@smmttx.com

FAQ

What is the purpose of the Revolution Medicines and Summit Therapeutics collaboration?

The collaboration aims to evaluate the safety and efficacy of Revolution's RAS(ON) inhibitors (daraxonrasib, zoldonrasib, and elironrasib) in combination with Summit's ivonescimab for treating RAS mutant tumors.

Which cancer types will be studied in the Revolution Medicines (RVMD) clinical trials?

The clinical trials will focus on three priority tumor types: RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC).

What are the key terms of the RVMD-Summit Therapeutics partnership agreement?

Summit Therapeutics will supply ivonescimab, Revolution Medicines will be the study sponsor, both companies will retain commercial rights to their compounds, and the agreement is mutually non-exclusive.

What initial results have been shown for Revolution Medicines' RAS inhibitors?

Initial evidence shows that daraxonrasib and elironrasib can safely deliver additive antitumor activity when combined with a PD-1 antibody in first-line treatment of RAS mutant non-small cell lung cancer patients.

Which drug candidates from Revolution Medicines (RVMD) are included in the collaboration?

The collaboration includes three RAS(ON) inhibitors: daraxonrasib (RMC-6236), a multi-selective inhibitor; zoldonrasib (RMC-9805), a G12D-selective inhibitor; and elironrasib (RMC-6291), a G12C-selective inhibitor.