Revolution Medicines Announces FDA Breakthrough Therapy Designation for Zoldonrasib

Rhea-AI Summary

Revolution Medicines (Nasdaq: RVMD) announced that the U.S. FDA granted Breakthrough Therapy Designation to zoldonrasib for adults with KRAS G12D-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) previously treated with anti-PD-1/PD-L1 therapy and platinum chemotherapy. The designation is based on data from the monotherapy cohort of the Phase 1 RMC-9805-001 trial, which demonstrated encouraging antitumor activity and acceptable safety and tolerability. Zoldonrasib is a tri-complex RAS(ON) G12D-selective covalent inhibitor that binds cyclophilin A. This is the first Breakthrough Therapy Designation for an investigational drug specifically targeting RAS G12D in NSCLC and follows prior designations for the company's daraxonrasib and elironrasib.

Positive

• First Breakthrough Therapy Designation for a RAS G12D-specific investigational drug
• Designation based on Phase 1 monotherapy cohort showing encouraging antitumor activity
• Zoldonrasib is a tri-complex RAS(ON) G12D-selective covalent inhibitor
• Adds to prior designations for daraxonrasib and elironrasib, reinforcing RAS(ON) program

Negative

• Designation relies on preliminary Phase 1 monotherapy data, not on confirmatory trials
• Indication limited to patients previously treated with anti-PD-1/PD-L1 and platinum chemotherapy

Key Figures

Breakthrough designations (RAS(ON)) 3 inhibitors Third RAS(ON) inhibitor from Revolution Medicines to receive Breakthrough Therapy Designation

First NSCLC G12D BTD 1st designation First Breakthrough Therapy Designation for an investigational drug targeting KRAS G12D in NSCLC

Trial phase Phase 1 RMC-9805-001 monotherapy cohort supporting zoldonrasib Breakthrough Therapy Designation

Cash & securities $1.93B Cash and marketable securities at Sept 30, 2025

Q3 2025 R&D $262.5M Research and development expense in Q3 2025

Q3 2025 G&A $52.8M General and administrative expense in Q3 2025

Q3 2025 net loss $305.2M Net loss reported for Q3 2025

FY2025 net loss guidance $1.03B–$1.09B GAAP net loss guidance range reiterated for full-year 2025

Market Reality Check

$107.47 Last Close

Volume Volume 13,666,680 is 4.58x the 20-day average of 2,982,219, signaling outsized interest pre-news. high

Technical Price 102.71 trades above 200-day MA at 48.25 and is near the 52-week high of 105.

Peers on Argus

RVMD shows a large move with price change of 28.63%, while key biotech peers like BPMC, VRNA, MDGL, and ROIV show marginal gains (≤0.69%) and MRNA up 4.03%, indicating today’s action is stock-specific rather than a broad sector rotation.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Jan 05	Conference presentation	Neutral	+1.9%	J.P. Morgan Healthcare Conference presentation and webcast logistics.
Dec 18	Clinical trial progress	Positive	-1.0%	First patient randomized in Phase 3 RASolute 304 trial for daraxonrasib.
Nov 05	Earnings and pipeline	Neutral	+1.3%	Q3 2025 financials and RAS(ON) clinical updates including multiple Phase 3 plans.
Nov 04	Investor conferences	Neutral	-1.3%	Participation in November 2025 investor conference fireside chats.
Oct 29	Earnings scheduling	Neutral	+1.5%	Announcement of timing and webcast details for Q3 2025 results.

Pattern Detected

Recent RVMD news over the last few months led to modest single-digit price moves; today’s double-digit reaction to the FDA designation is much larger than prior responses.

Recent Company History

This announcement adds another regulatory milestone to Revolution Medicines’ recent trajectory. In Q3 2025, the company highlighted multiple RAS(ON) programs and existing FDA Breakthrough and Orphan Drug designations for daraxonrasib, alongside cash and securities of $1.93B. Subsequent news involved conference presentations and initiation of the Phase 3 RASolute 304 trial for daraxonrasib with a planned enrollment of about 500 PDAC patients. Those items produced relatively small price reactions, whereas today’s Breakthrough Therapy Designation for zoldonrasib represents a more material clinical and regulatory development within the RAS(ON) portfolio.

Market Pulse Summary

This announcement highlights a major regulatory step for Revolution Medicines, as zoldonrasib receives FDA Breakthrough Therapy Designation based on Phase 1 data in KRAS G12D-mutated NSCLC. It complements earlier designations for daraxonrasib and strengthens the company’s RAS(ON) franchise. Investors may track upcoming clinical readouts, regulatory interactions, and how the company deploys its $1.93B cash and securities against guided net losses of $1.03B–$1.09B when assessing future risk and opportunity.

Key Terms

breakthrough therapy designation regulatory

"Breakthrough Therapy Designation granted to zoldonrasib for the treatment of adult patients..."

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

kras g12d medical

"adult patients with KRAS G12D-mutated locally advanced or metastatic non-small cell lung cancer..."

KRAS G12D is a specific change in the KRAS gene where one building block in the cell’s instruction manual is swapped, causing the KRAS protein to get stuck in an “on” position and drive uncontrolled cell growth. Investors care because this switch is a common cause of certain cancers and creates a clear target for tests and treatments; successful drugs or diagnostics aimed at KRAS G12D can affect drug sales, trial outcomes, and regulatory approvals.

non-small cell lung cancer medical

"locally advanced or metastatic non-small cell lung cancer (NSCLC)..."

A broad category of lung tumors that grow from the cells lining the airways and make up the majority of lung cancer cases; it includes several subtypes that behave and respond to treatment differently, like different models of the same car family. It matters to investors because its large patient population and variety of treatment options — surgery, traditional chemo, targeted drugs and immunotherapies — create major markets where clinical trial results, drug approvals or changing treatment guidelines can quickly affect a company’s revenue and stock value.

nsclc medical

"metastatic non-small cell lung cancer (NSCLC) who have been previously treated..."

NSCLC stands for non-small cell lung cancer, which is the most common type of lung cancer. It develops in the lungs and can spread to other parts of the body, making it serious but often treatable if caught early. Understanding NSCLC helps people recognize the importance of lung health and early detection.

anti-pd-1/pd-l1 therapy medical

"previously treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy..."

Drugs that block the PD-1 or PD-L1 pathway, which normally acts like a brake on the immune system, letting immune cells spot and attack cancer cells more effectively; they are commonly called immune checkpoint inhibitors. Investors watch these therapies because clinical trial outcomes, regulatory approvals, pricing, and combination use can rapidly change a drugmaker’s revenue potential and valuation — similar to a company gaining access to a much larger market after removing a key barrier.

ras(on) medical

"Revolution Medicines’ third RAS(ON) inhibitor to receive this designation..."

A RAS (oncogene) is a family of genes that act like a cell’s growth switch; when they work normally they help cells respond to signals, but certain mutations can make the switch stuck in the ‘on’ position and drive uncontrolled cell growth. Investors watch RAS closely because mutations are common drivers of many cancers, and drugs that can safely target or correct RAS-driven growth can become major commercial opportunities or affect the value of companies developing such therapies.

phase 1 medical

"data from the monotherapy cohort of the Phase 1 RMC-9805-001 clinical trial..."

Phase 1 is the first stage of testing a new drug or medical treatment in people, focused primarily on safety, how the body handles the product, and finding a tolerated dose. Think of it as a short, tightly controlled experiment with a small group to check for dangerous side effects before wider testing; for investors it is an early milestone that reduces some uncertainty but still carries high risk and potential for both big value changes and setbacks.

oncogenic medical

"selectively recognizes and inhibits the active, oncogenic RAS G12D(ON) mutant."

Oncogenic describes anything—such as a gene change, virus, or chemical—that can cause normal cells to become cancerous and form tumors. Investors should care because oncogenic findings can shape a drug or product’s safety profile, regulatory approval, liability risk and marketability; think of an oncogenic factor like a stray spark that can start a costly, hard-to-control fire in a product or clinical program.

AI-generated analysis. Not financial advice.

• Breakthrough Therapy Designation granted to zoldonrasib for the treatment of adult patients with KRAS G12D-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have been previously treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy
• First Breakthrough Therapy Designation for an investigational drug specifically targeting KRAS G12D mutation in NSCLC
• Revolution Medicines’ third RAS(ON) inhibitor to receive this designation

REDWOOD CITY, Calif., Jan. 08, 2026 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to zoldonrasib, a RAS(ON) G12D-selective inhibitor, for the treatment of adult patients with KRAS G12D-mutated locally advanced or metastatic NSCLC who have been previously treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy.

The Breakthrough Therapy Designation is based on data from the monotherapy cohort of the Phase 1 RMC-9805-001 clinical trial evaluating zoldonrasib in patients with advanced KRAS G12D solid tumors. Results from the monotherapy cohort of the trial have demonstrated a robust clinical profile, including encouraging antitumor activity and acceptable safety and tolerability.

“The Breakthrough Therapy Designation for zoldonrasib, our RAS(ON) G12D-selective covalent inhibitor – the first ever granted for an investigational drug specifically targeting the RAS G12D mutation – underscores the significant unmet need for patients with KRAS G12D cancers, which currently lack any approved targeted therapies,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “This recognition expands upon prior designations for the RAS(ON) multi-selective inhibitor daraxonrasib and G12C-selective inhibitor elironrasib, further recognizing the promise of our first three clinical-stage RAS(ON) inhibitors as potentially transformative therapies for people living with RAS-addicted cancers.”

Zoldonrasib is an innovative tri-complex inhibitor that binds to cyclophilin A, creating a complex that selectively recognizes and inhibits the active, oncogenic RAS G12D(ON) mutant. Revolution Medicines is evaluating zoldonrasib as a monotherapy and combination treatment across multiple tumor types and lines of therapy.

Breakthrough Therapy Designation is intended to expedite the development and review of potential new medicines designed to treat serious conditions and address significant unmet medical needs. Pursuant to FDA guidelines, the medicine needs to have shown encouraging preliminary clinical evidence that demonstrates substantial improvement on a clinically significant endpoint over available medicines.

About Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all lung cancers, with more than 197,000 people diagnosed in the U.S. each year.^1,2,3 Despite treatment advancements, NSCLC remains a leading cause of cancer-related mortality worldwide, primarily due to its late-stage diagnosis and limited response to conventional therapies. G12D is the most common oncogenic driver of human cancers and represents 4% of NSCLC cases.⁴

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; zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor; and RMC-5127, a RAS(ON) G12V-selective inhibitor, are currently in 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.

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 therapeutic potential of zoldonrasib and the ability of the company’s product engine to generate potential treatment approaches. Forward-looking statements are typically, but not always, identified by the use of words such as “potentially,” "anticipate," 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 November 5, 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.

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

¹ American Cancer Society. What is Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed December 2025.
² National Cancer Institute. Non-Small Cell Lung Cancer Treatment. Available at: https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq. Accessed December 2025.
³ American Cancer Society. Key Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Accessed December 2025.
⁴ Ricciuti B, Alessi JV, Elkrief A, et al. Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRAS^G12D-mutated non-small-cell lung cancer. Ann Oncol. 2022;33(10): 1029-1040. doi:10.1016/j.annonc.2022.07.005

FAQ

What did Revolution Medicines (RVMD) announce on January 8, 2026 about zoldonrasib?

The company said the FDA granted Breakthrough Therapy Designation for zoldonrasib in KRAS G12D-mutated locally advanced or metastatic NSCLC previously treated with anti-PD-1/PD-L1 and platinum chemotherapy.

Why did the FDA grant Breakthrough Therapy Designation to zoldonrasib (RVMD)?

The designation was granted based on Phase 1 RMC-9805-001 monotherapy cohort data showing encouraging antitumor activity and acceptable safety and tolerability.

What is zoldonrasib and how does it work in KRAS G12D cancers?

Zoldonrasib is described as a tri-complex RAS(ON) G12D-selective covalent inhibitor that binds cyclophilin A to selectively inhibit the active RAS G12D(ON) mutant.

Does the Breakthrough Therapy Designation mean zoldonrasib is approved for NSCLC?

No; Breakthrough Therapy Designation expedites development and review but is not an approval and is based on preliminary clinical evidence.

How does this designation affect Revolution Medicines' RAS program (RVMD)?

The designation marks zoldonrasib as the first G12D-specific breakthrough and follows prior designations for daraxonrasib and elironrasib, highlighting progress across the company's RAS(ON) portfolio.