Revolution Medicines, Inc. (RVMD)

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

You should read the following discussion and analysis of our financial condition and results of operations in conjunction with the unaudited condensed consolidated financial statements and the related notes included elsewhere in this Quarterly Report on Form 10-Q. In addition to historical financial information, this discussion contains forward-looking statements based upon current expectations that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report on Form 10-Q, our actual results could differ materially from the results described or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. We possess 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. Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens. Our research and development pipeline comprises inhibitors that bind directly to RAS variants (RAS(ON) Inhibitors) that are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or other therapeutic agents.

RAS(ON) Inhibitors

We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib (RMC-6236), our multi-selective inhibitor, zoldonrasib (RMC-9805), our G12D-selective inhibitor, elironrasib (RMC-6291), our G12C-selective inhibitor, and RMC-5127, our G12V-selective inhibitor. We also have other preclinical-stage RAS(ON) Inhibitor clinical development opportunities, including the RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C) and additional novel targeted approaches for patients with RAS-addicted cancers.

Daraxonrasib

Daraxonrasib, our RAS(ON) multi-selective inhibitor, is designed as an oral, tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at all three of the major RAS mutation hotspot positions, G12, G13, and Q61. Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins. Daraxonrasib has been granted a non-transferable voucher for daraxonrasib in pancreatic adenocarcinoma (PDAC) under the Commissioner’s National Priority Voucher (CNPV) pilot program, Orphan Drug Designation (ODD) by the FDA and European Medicines Agency (EMA) for the treatment of pancreatic cancer, and Breakthrough Therapy Designation from the FDA for patients with previously treated metastatic PDAC with KRAS G12 mutations and patients with NSCLC with KRAS mutations other than G12C who have received prior platinum-based chemotherapy and anti-PD-(L)1 therapy.

Zoldonrasib

Zoldonrasib is designed as an oral RAS(ON) G12D-selective tri-complex inhibitor. It is designed to exhibit low nanomolar potency for suppressing RAS pathway signaling and growth of RAS G12D-bearing cancer cells and is engineered to covalently inactivate RAS G12D irreversibly. Zoldonrasib has received Breakthrough Therapy Designation from the FDA 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.

Elironrasib

Elironrasib is designed as an oral RAS(ON) G12C-selective tri-complex inhibitor. It is designed to exhibit subnanomolar potency for suppressing RAS pathway signaling and growth of RAS G12C-bearing cancer cells and is engineered to be highly selective for RAS G12C over wild-type RAS and other cellular targets. Elironrasib is designed to be differentiated from first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its mechanism of directly inhibiting the RAS(ON) G12C form. Elironrasib has received Breakthrough Therapy Designation from the FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor.

RMC-5127

RMC-5127 is designed as an oral RAS(ON) G12V-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions. A first-in-human dose escalation clinical trial of RMC-5127 is

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ongoing. We currently expect to identify a recommended Phase 2 dose for RMC-5127 during the second half of 2026 and to share initial clinical data in 2027.

New Class of RAS(ON) Inhibitors

We have designed a new class of tri-complex RAS(ON) Inhibitors in order to overcome RAS-driven drug resistance and thereby extend the clinical benefit of RAS(ON) Inhibitors. We currently expect to initiate a first-in-human clinical trial from this class of RAS(ON) Inhibitors in the fourth quarter of 2026.

Other Development Opportunities

RMC-0708

RMC-0708 is designed as an oral RAS(ON) Q61H-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions. Clinical development of RMC-0708 is subject to our continuing assessment of portfolio priorities.

RMC-8839

RMC-8839 is designed as an oral RAS(ON) G13C-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition. Clinical development of RMC-8839 is subject to our continuing assessment of portfolio priorities.

Clinical Development

RAS Mutant Epidemiology in the United States

Variants in RAS proteins are among the most common oncogenic drivers of cancer. Based on tumor mutation frequencies from Foundation Medicine data, scaled to estimated patient numbers using cancer incidence from the American Cancer Society Cancer Facts and Figures, there are an estimated more than 190,000 new RAS mutant cancer diagnoses each year in the U.S. These include approximately 60,000 patients with NSCLC, representing approximately 30% of NSCLC diagnoses, approximately 75,000 patients with colorectal cancer (CRC), representing approximately 50% of CRC diagnoses, and approximately 56,000 patients with PDAC, representing more than 90% of PDAC diagnoses.

Pancreatic Cancer

Pancreatic cancer is one of the most common and difficult-to-treat cancers and patients have historically had limited treatment options. Because of this unmet need and the prevalence of RAS as a driver of PDAC, we believe that pancreatic cancer represents a particularly compelling opportunity for RAS-targeted therapies.

In May 2026, we presented results from our randomized Phase 3 registration study RASolute 302 comparing daraxonrasib against chemotherapy in patients with second line (2L) PDAC. In this study, daraxonrasib taken orally once daily demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared to standard of care cytotoxic chemotherapy delivered intravenously. In the overall (intent-to-treat) study population, daraxonrasib demonstrated a median OS of 13.2 months versus 6.7 months for chemotherapy, with a hazard ratio of 0.40 (p 0.0001). Daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals. Based on the results from this first interim analysis, all PFS and OS endpoint results are considered final. The FDA has accepted for review our New Drug Application (NDA) for daraxonrasib for previously treated metastatic pancreatic cancer and the EMA initiated a phased review of daraxonrasib under its Cancer Medicines Pathfinder project.

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Based on encouraging early-stage clinical results, we are evaluating daraxonrasib and zoldonrasib in the following global, randomized Phase 3 registrational studies in PDAC:

•
RASolute 303: comparing daraxonrasib with and without chemotherapy against chemotherapy in patients with first-line (1L) metastatic PDAC;

•
RASolute 304: evaluating daraxonrasib as an adjuvant therapy in patients with resectable PDAC who have received surgery and chemotherapy;

•
RASolute 305: evaluating zoldonrasib in combination with the investigator’s choice of chemotherapies in patients with 1L metastatic PDAC in a placebo-controlled study; and

•
RASolute 309: comparing daraxonrasib with zoldonrasib against chemotherapy in 1L patients with RAS G12D PDAC.

In April 2026, we presented updated Phase 1 clinical data for daraxonrasib in patients with 1L PDAC across monotherapy and combination cohorts at the American Association for Cancer Research (AACR) Annual Meeting.

In July 2026 at the European Society for Medical Oncology’s Gastrointestinal Cancers Congress, we presented data for (i) zoldonrasib in combination with chemotherapy in patients with 1L RAS G12D PDAC; and (ii) zoldonrasib in combination with daraxonrasib in patients with previously treated RAS G12D PDAC. We believe these data showed that zoldonrasib in combination with chemotherapy and zoldonrasib in combination with daraxonrasib were generally well tolerated and demonstrated encouraging antitumor activity that supported our initiation of RASolute 305 and RASolute 309, respectively.

Non-Small Cell Lung Cancer

NSCLC is another major cancer type in which RAS mutations are common. While advances in immunotherapy and chemotherapy have improved outcomes for some individuals, many patients with RAS mutant NSCLC continue to experience disease progression, highlighting the need for new targeted approaches. Importantly, RAS mutations in NSCLC extend beyond a single subtype, leaving a significant portion of patients without broadly effective targeted treatment options.

Based on encouraging early-stage clinical results, we are evaluating daraxonrasib and zoldonrasib in the following global, randomized Phase 3 registrational studies in NSCLC:

•
RASolve 301: comparing daraxonrasib against docetaxel in patients with locally advanced or metastatic RAS mutant NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. We currently expect to complete enrollment in RASolve 301 in 2026, to enable an expected clinical readout in 2027; and

•
RASolve 308: evaluating zoldonrasib in combination with standard of care in patients with 1L metastatic RAS G12D NSCLC in a placebo-controlled study.

Based on our evaluation of the treatment landscape for NSCLC, we are prioritizing a mutant-selective approach for development in

1L NSCLC; we expect to initiate RASolve 307, a global, randomized Phase 3 registrational trial evaluating elironrasib in combination with standard of care in 1L RAS G12C NSCLC in the fourth quarter of 2026 and plan to continue evaluating daraxonrasib in NSCLC in combination with bispecific antibodies targeting both the PD-1/PD-L1 and VEGF axes.

In August 2026, we reported initial Phase 1 clinical data for (i) zoldonrasib in combination with pembrolizumab and chemotherapy in patients with 1L RAS G12D NSCLC and (ii) elironrasib in combination with pembrolizumab and chemotherapy in patients with 1L RAS G12C NSCLC. We believe these data showed that zoldonrasib and elironrasib were generally well tolerated and demonstrated encouraging an

[Excerpt truncated for page length; source filing is linked above.]

Overview

We are a clinical-stage precision oncology company developing novel targeted therapies for RAS-addicted cancers. We possess 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. Guided by our understanding of genetic drivers and adaptive resistance mechanisms in cancer, we deploy precision medicine approaches to inform innovative monotherapy and combination regimens. Our research and development pipeline comprises inhibitors that bind directly to RAS variants (RAS(ON) Inhibitors) that are designed to be used as monotherapy, in combination with other RAS(ON) Inhibitors and/or other therapeutic agents.

RAS(ON) Inhibitors

We are advancing a deep pipeline of RAS(ON) Inhibitors, including daraxonrasib (RMC-6236), our multi-selective inhibitor, zoldonrasib (RMC-9805), our G12D-selective inhibitor, elironrasib (RMC-6291), our G12C-selective inhibitor, and RMC-5127, our G12V-selective inhibitor. We also have other preclinical-stage RAS(ON) Inhibitor clinical development opportunities, including the RAS(ON) mutant-selective inhibitors RMC-0708 (Q61H) and RMC-8839 (G13C) and additional novel targeted approaches for patients with RAS-addicted cancers.

Daraxonrasib

Daraxonrasib, our RAS(ON) multi-selective inhibitor, is designed as an oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at all three of the major RAS mutation hotspot positions, G12, G13, and Q61. Daraxonrasib inhibits all three major RAS isoforms, suppressing the mutant cancer driver and cooperating wild-type RAS proteins. In October 2025, the U.S. Food and Drug Administration (FDA) granted us a non-transferable voucher for daraxonrasib in pancreatic ductal adenocarcinoma (PDAC) under the Commissioner’s National Priority Voucher (CNPV) pilot program. Also in October 2025, daraxonrasib was granted Orphan Drug Designation by the FDA for the treatment of pancreatic cancer. In June 2025, daraxonrasib received Breakthrough Therapy Designation from the FDA for previously treated metastatic PDAC in patients with KRAS G12 mutations.

Zoldonrasib

Zoldonrasib is designed as a RAS(ON) oral G12D-selective tri-complex inhibitor. It is designed to exhibit low nanomolar potency for suppressing RAS pathway signaling and growth of RAS G12D-bearing cancer cells and is engineered to covalently inactivate RAS G12D irreversibly. In December 2025, zoldonrasib received Breakthrough Therapy Designation from the FDA 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.

Elironrasib

Elironrasib is designed as a RAS(ON) oral G12C-selective tri-complex inhibitor. It is designed to exhibit subnanomolar potency for suppressing RAS pathway signaling and growth of RAS G12C-bearing cancer cells and is engineered to be highly selective for RAS G12C over wild-type RAS and other cellular targets. Elironrasib is designed to be differentiated from first-generation KRAS(OFF) G12C inhibitors, which sequester the KRAS(OFF) G12C form, by its mechanism of directly inhibiting the RAS(ON) G12C form. In July 2025, elironrasib received Breakthrough Therapy Designation from the FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor.

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RMC-5127

RMC-5127 is designed as a RAS(ON) oral G12V-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS G12V-bearing cancer cells and is engineered for selective inhibition of RAS G12V over other RAS isoforms via non-covalent binding interactions. A first-in-human dose escalation clinical trial of RMC-5127 is ongoing.

New Class of RAS(ON) Inhibitors

We have designed a new class of RAS(ON) Inhibitors in order to overcome RAS-driven drug resistance and thereby extend the clinical benefit of RAS(ON) Inhibitors. We currently expect to initiate a first-in-human clinical trial from this class of RAS(ON) Inhibitors in the fourth quarter of 2026.

Other Development Opportunities

RMC-0708

RMC-0708 is designed as a RAS(ON) oral Q61H-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions. Clinical development of RMC-0708 is subject to our continuing assessment of portfolio priorities.

RMC-8839

RMC-8839 is designed as a RAS(ON) oral G13C-selective tri-complex inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of KRAS G13C-bearing cancer cells and is engineered to covalently inactivate KRAS G13C for irreversible inhibition. Clinical development of RMC-8839 is subject to our continuing assessment of portfolio priorities.

Clinical Development

RAS Mutant Epidemiology in the United States

Variants in RAS proteins are among the most common oncogenic drivers of cancer. Based on tumor mutation frequencies from Foundation Medicine data, scaled to estimated patient numbers using cancer incidence from the American Cancer Society Cancer Facts and Figures, there are an estimated more than 190,000 new RAS mutant cancer diagnoses each year in the U.S. These include approximately 60,000 patients with NSCLC, representing approximately 30% of NSCLC diagnoses, approximately 75,000 patients with colorectal cancer (CRC), representing approximately 50% of CRC diagnoses, and approximately 56,000 patients with PDAC, representing more than 90% of PDAC diagnoses.

Pancreatic Cancer

Pancreatic cancer is one of the most common and difficult-to-treat cancers and patients have historically had limited treatment options. Because of this unmet need and the prevalence of RAS as a driver of PDAC, we believe that pancreatic cancer represents a particularly compelling opportunity for RAS-targeted therapies.

Based on encouraging early-stage clinical results, we are evaluating daraxonrasib and zoldonrasib in the following global, randomized Phase 3 registrational studies in PDAC:

•
RASolute 302: comparing daraxonrasib against chemotherapy in patients with second line (2L) PDAC; a clinical readout for this study is currently expected in the first half of 2026;

•
RASolute 303: comparing daraxonrasib with and without chemotherapy against chemotherapy in patients with first line (1L) metastatic PDAC;

•
RASolute 304: evaluating daraxonrasib as an adjuvant therapy in patients with resectable PDAC; and

•
RASolute 305: comparing zoldonrasib in combination with the investigator’s choice of either gemcitabine nab-paclitaxel or modified FOLFIRINOX against the investigator’s choice of the chemotherapies in patients with 1L metastatic PDAC in a placebo-controlled study.

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In addition, we expect to initiate RASolute 309, a global, randomized Phase 3 registrational trial evaluating the combination of daraxonrasib with zoldonrasib in patients with 1L PDAC in the second half of 2026.

Non-Small Cell Lung Cancer

NSCLC is another major cancer type in which RAS mutations are common. While advances in immunotherapy and chemotherapy have improved outcomes for some individuals, many patients with RAS mutant NSCLC continue to experience disease progression, highlighting the need for new targeted approaches. Importantly, RAS mutations in NSCLC extend beyond a single subtype, leaving a significant portion of patients without broadly effective targeted treatment options.

Based on encouraging early-stage clinical results we are evaluating daraxonrasib in RASolve 301, a global, randomized Phase 3 registrational trial comparing daraxonrasib versus docetaxel in patients with locally advanced or metastatic RAS mutant NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. We currently expect to substantially complete enrollment in RASolve 301 in 2026.

We also currently expect to initiate RASolve 308, a global, randomized placebo-controlled Phase 3 registrational trial evaluating zoldonrasib in combination with standard of care in patients with 1L metastatic RAS G12D NSCLC in the first half of 2026.

We currently expect to provide an update on our plans for advancing daraxonrasib combination therapy in 1L NSCLC in 2026. We also currently expect to share an update on our registrational strategy for elironrasib in NSCLC in 2026.

Colorectal Cancer

Colorectal cancers are genetically complex and heterogeneous, and patients with RAS mutant disease typically have limited targeted treatment options, particularly after progression on standard therapies. As a result, outcomes remain poor for many patients, underscoring the need for new therapeutic approaches that more effectively address the underlying drivers of the disease.

To address this need, we are pursuing a combination-focused strategy designed to maximize clinical impact in this challenging setting. We believe that our early clinical experience supports continued exploration of these strategies. As data mature, we plan to prioritize registrational opportunities with the goal of improving outcomes and expanding treatment options for patients with RAS mutant colorectal cancer. We currently expect to provide updated combination data in CRC in 2026.

Collaborations

Bristol Myers Squibb Collaboration

In February 2026, we entered into a clinical collaboration with Bristol Myers Squibb (BMS) pursuant to which BMS plans to evaluate its compound navlimetostat, an MTA-cooperative PRMT5 inhibitor, in combination with daraxonrasib in patients with PDAC as part of a BMS-sponsored trial.

Amgen Collaboration

In February 2025, we entered into a clinical collaboration with Amgen Inc. (Amgen) pursuant to which Amgen is evaluating its compound AMG 193, an MTA-cooperative PRMT5 inhibitor, in combination with daraxonrasib in patients with 2L PDAC as part of an Amgen-sponsored trial.

Summit Collaboration

In June 2025, we entered into a clinical collaboration with Summit Therapeutics, Inc. (Summit) pursuant to which we are evaluating the safety and efficacy, in multiple solid tumor settings, of our clinical-stage RAS(ON) Inhibitors, including daraxonrasib, elironrasib and zoldonrasib, in combination with Summit’s ivonescimab, a PD-1/VEGF bispecific antibody. The first patient was recently dosed in this clinical trial.

Iambic Collaboration

In May 2025, we entered into a collaboration with Iambic Therapeutics (Iambic), pursuant to which Iambic uses its artificial intelligence capabilities to generate customized models through training with our proprietary data. Our aim in this collaboration is to enhance our lead discovery and optimization processes directed against both current and new drug targets to enable continued development of our pipeline.

Tango Collaboration

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In November 2024, we entered into a clinical collaboration with Tango Therapeutics, Inc. (Tango) pursuant to which Tango is evaluating its compound vopimetostat (TNG462), an MTA-cooperative PRMT5 inhibitor, in combination with daraxonrasib or zoldonrasib in patients with MTAP-depleted, RAS mutant PDAC or lung cancer as part of a Tango-sponsored trial.

Break Through Cancer Collaboration

In November 2024, we entered into a collaboration with Break Through Cancer. The collaboration is designed to assess biopsy samples taken from patients receiving daraxonrasib in the investigational setting, with the goal of identifying biomarkers that could predict tumor response and how cancer cells adapt to the therapy. We believe this ap

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