Revolution Medicines (NASDAQ:RVMD) used its fourth-quarter and full-year 2025 earnings call to highlight progress across its RAS(ON) inhibitor pipeline, with management emphasizing multiple ongoing and planned registrational studies in pancreatic cancer and expanding late-stage ambitions in non-small cell lung cancer (NSCLC). The company also outlined growing commercialization preparations and provided 2026 expense guidance as clinical programs broaden.
Pipeline focus: four RAS(ON) programs and expanding registrational plans
Chief Executive Officer Mark Goldsmith said the company advanced a pipeline of four investigational drugs targeting major oncogenic RAS drivers: daraxonrasib (a multi-selective RAS(ON) inhibitor), elironrasib (a G12C-selective inhibitor), zoldonrasib (a G12D-selective inhibitor), and RMC-5127 (a G12V-selective inhibitor). Goldsmith said the company has “8 ongoing or planned phase III registrational trials” and that more than 2,500 patients have received one or more of its RAS(ON) inhibitors in aggregate.
Pancreatic cancer: daraxonrasib registrational readout expected in 1H 2026
Management described pancreatic cancer as its most advanced clinical focus and noted that more than 90% of pancreatic cancers are RAS-driven. Goldsmith said daraxonrasib received Breakthrough Therapy Designation from the FDA and was awarded one of the agency’s first Commissioner’s National Priority Voucher (CNPV) based on its potential to address unmet need in pancreatic cancer.
The company is evaluating daraxonrasib in three randomized registrational studies in pancreatic cancer:
- RASolute 302: daraxonrasib monotherapy in second-line metastatic pancreatic ductal adenocarcinoma (PDAC). Management said global enrollment is complete and a readout is expected in the first half of 2026. Goldsmith noted the study is overall survival (OS) event-driven and powered for OS, with an interim read on progression-free survival (PFS) anticipated.
- RASolute 303: initiated in first-line metastatic disease, evaluating daraxonrasib monotherapy and daraxonrasib plus chemotherapy.
- RASolute 304: initiated in the adjuvant setting for resectable disease after surgery and perioperative chemotherapy.
During Q&A, Goldsmith said treatment beyond progression is not permitted in RASolute 302 because the study was too far underway to modify, but the company has encouraged investigators to evaluate treatment beyond progression in newer studies “where it makes sense,” particularly in earlier-line settings. He described anecdotal reports from investigators continuing daraxonrasib despite radiographic progression when patients continued to benefit clinically, adding that the company wants to collect more data to understand any incremental benefit.
Goldsmith also addressed questions about potential crossover effects on OS in first-line trials if daraxonrasib were to become available in later-line settings, citing timing and global enrollment—particularly outside the U.S.—as potential buffers against that concern.
Zoldonrasib: initial PDAC combination data and new registrational trial initiation
Goldsmith highlighted initial data combining zoldonrasib with FOLFIRINOX in first-line metastatic pancreatic cancer. He said the initial safety and tolerability profile appeared largely consistent with modified FOLFIRINOX alone, with high zoldonrasib dose intensity maintained. As of the data cutoff, 63% of patients achieved a partial response (confirmed or pending confirmation), and the disease control rate was 95%, with “the vast majority” of patients remaining on treatment.
Based on these findings, the company said it plans to advance two first-line registrational combination studies. Management announced initiation of RASolute-305, a randomized, double-blind, placebo-controlled trial evaluating zoldonrasib plus investigator’s choice of gemcitabine/nab-paclitaxel or modified FOLFIRINOX versus chemotherapy plus placebo. Revolution Medicines also described RASolute-309, which will evaluate the doublet of zoldonrasib plus daraxonrasib, with initiation planned for the second half of 2026. The company said it plans to share clinical data from initial studies of zoldonrasib plus gemcitabine/nab-paclitaxel and the zoldonrasib plus daraxonrasib doublet in PDAC at one or more medical meetings this year.
Goldsmith confirmed on the call that the company expects to use the Commissioner’s National Priority Voucher for second-line PDAC.
NSCLC and CRC: registrational build-out and combination strategy
In NSCLC, Goldsmith said the company continues enrolling patients in RASolve 301, a global randomized trial evaluating daraxonrasib monotherapy in previously treated patients, with plans to “substantially” complete enrollment in 2026. Management said it expects to disclose plans for advancing daraxonrasib combination therapy in first-line NSCLC this year, while continuing dose optimization and proof-of-concept work in combinations.
For zoldonrasib in lung cancer, management noted that the monotherapy expansion cohort is fully enrolled and that zoldonrasib received Breakthrough Therapy Designation, described as the company’s third RAS(ON) inhibitor to receive the distinction. The company said it is preparing to initiate RASolve 308, a first randomized registrational trial of zoldonrasib plus standard of care in first-line metastatic RAS G12D NSCLC.
For elironrasib, management said it continues to evaluate the G12C-selective inhibitor in G12C inhibitor-naïve and inhibitor-experienced patients and has reported encouraging results in monotherapy and combinations (including with pembrolizumab and as a doublet with daraxonrasib). The company said it plans to share an update on a registrational strategy for elironrasib this year.
In colorectal cancer, executives reiterated that the opportunity remains important, but emphasized biological complexity. President of R&D Steve Kelsey said colorectal cancer tends to require combination approaches and that response rates are generally lower than in other RAS-driven tumors, complicating rapid early-stage decision-making. Management said it plans to provide visibility into combination data in colorectal cancer this year as it prioritizes registrational opportunities.
Collaborations and commercialization build
Revolution Medicines discussed multiple clinical collaborations aimed at expanding combination options, including studies with Tango Therapeutics (vopimetostat, an MTA-cooperative PRMT5 inhibitor), a new collaboration with Bristol Myers Squibb (navlimetostat, another MTA-cooperative PRMT5 inhibitor) in MTAP-deleted pancreatic cancer, and a collaboration with Summit Therapeutics evaluating the company’s RAS(ON) inhibitors with Summit’s PD-1/VEGF bispecific antibody, ivonesimab. Management said the first patient in the ivonesimab collaboration trial has been dosed. Chief Medical Officer Wei Lin said the APEX study includes dose escalation across solid tumors for ivonesimab in combination with daraxonrasib, zoldonrasib, and elironrasib, followed by expansion cohorts focused on pancreatic cancer, NSCLC, and colorectal cancer.
On commercialization, management said the company is building U.S. launch capabilities and has onboarded regional field sales leadership, with recruitment for its first field sales team underway. Chief Global Commercialization Officer Anthony Mancini said the company is also pursuing readiness in Europe and Japan.
Financially, Chief Financial Officer Jack Anders said Revolution Medicines ended Q4 2025 with $2.03 billion in cash and investments. He also noted the company’s 2025 strategic partnership with Royalty Pharma, which provides access to up to $2 billion in committed capital; the company received a first tranche of $250 million in June 2025, with $1.75 billion remaining under the arrangement.
For Q4 2025, the company reported R&D expenses of $294.9 million (up from $188.1 million a year earlier) and G&A expenses of $66.7 million (up from $28.2 million), driven by clinical, manufacturing, hiring, and commercialization preparation costs, as well as stock-based compensation. Net loss for Q4 2025 was $364.9 million, compared to $194.6 million in Q4 2024, with Anders citing higher operating expenses and several non-cash items.
Looking ahead, Anders said the company is shifting guidance from GAAP net loss to GAAP operating expenses for 2026 and expects $1.6 billion to $1.7 billion in GAAP operating expenses, including an estimated $180 million to $200 million in non-cash stock-based compensation.
About Revolution Medicines (NASDAQ:RVMD)
Revolution Medicines is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapies to treat RAS-dependent cancers and other diseases driven by the RAS/MAPK pathway. The company’s research efforts target historically “undruggable” proteins, aiming to inhibit critical nodes in cell signaling that promote tumor growth and therapeutic resistance.
The lead pipeline includes RMC-4630, a SHP2 inhibitor; RMC-6291, a selective KRAS G12C inhibitor; and RMC-6236, a pan-RAS inhibitor designed to address multiple RAS mutations.
