Revolution Medicines, Inc.

Revolution Medicines, Inc. is a clinical-stage precision oncology company developing novel targeted therapies for 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. Guided by an understanding of genetic drivers and adaptive resistance mechanisms in cancer, the company deploys precision medicine approaches to inform innovative monotherapy and combination regimens. The 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.

The company faces significant competition from major pharmaceutical and biotechnology companies, academic institutions, and research entities. Competitors include companies developing treatments for cancer such as small molecule drug products, biologics, cell-based therapies and traditional chemotherapy. Specific competitors named in the filing include Amgen, Eli Lilly, Roche/Genentech, AstraZeneca, Pfizer, and numerous others developing programs targeting KRAS G12C, KRAS G12D, KRAS G12V, and pan-RAS inhibitors. The company believes its RAS(ON) Inhibitors, which target the active GTP-bound form of RAS, offer a differentiated mechanism of action with potential improvements over first-generation RAS(OFF) inhibitors like sotorasib and adagrasib.

The company generates revenue through collaboration agreements, having recognized $11.580 million ¹ in collaboration revenue in 2023 under the Sanofi Agreement, which was terminated in June 2023. The company has never generated revenue from product sales and has no products approved for commercial sale. The company intends to retain significant development and commercialization rights to its product candidates and, if marketing approval is obtained, to commercialize its product candidates on its own in the U.S. and other regions, while considering focused business relationships for specific geographies.

The company is advancing a deep pipeline of RAS(ON) Inhibitors. Daraxonrasib (RMC-6236) is a multi-selective inhibitor designed as an oral, RAS-selective tri-complex inhibitor of multiple RAS(ON) variants containing cancer driver mutations at G12, G13, and Q61 hotspot positions. In October 2025, the FDA granted a non-transferable voucher for daraxonrasib in pancreatic ductal adenocarcinoma (PDAC) under the Commissioner's National Priority Voucher pilot program, and daraxonrasib was granted Orphan Drug Designation for the treatment of pancreatic cancer. In June 2025, daraxonrasib received Breakthrough Therapy Designation for previously treated metastatic PDAC in patients with KRAS G12 mutations. Zoldonrasib (RMC-9805) is a G12D-selective inhibitor designed to exhibit low nanomolar potency and engineered to covalently inactivate RAS G12D irreversibly. In December 2025, zoldonrasib received Breakthrough Therapy Designation 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 (RMC-6291) is a G12C-selective inhibitor designed to exhibit subnanomolar potency and engineered to be highly selective for RAS G12C over wild-type RAS. In July 2025, elironrasib received Breakthrough Therapy Designation 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 is a G12V-selective inhibitor designed to exhibit picomolar potency, with a first-in-human dose escalation clinical trial ongoing. Preclinical-stage opportunities include RMC-0708 (Q61H) and RMC-8839 (G13C). The company has designed a new class of RAS(ON) Inhibitors to overcome RAS-driven drug resistance and expects to initiate a first-in-human clinical trial in the fourth quarter of 2026.

Significant operational developments during the period include multiple clinical collaborations. In February 2026, the company entered into a clinical collaboration with Bristol Myers Squibb to evaluate navlimetostat in combination with daraxonrasib in patients with PDAC. In February 2025, the company entered into a clinical collaboration with Amgen to evaluate AMG 193 in combination with daraxonrasib in patients with 2L PDAC. In June 2025, the company entered into a clinical collaboration with Summit Therapeutics to evaluate ivonescimab in combination with daraxonrasib, elironrasib and zoldonrasib. In May 2025, the company entered into a collaboration with Iambic Therapeutics to use artificial intelligence capabilities to enhance lead discovery and optimization processes. In November 2024, the company entered into a clinical collaboration with Tango Therapeutics to evaluate vopimetostat in combination with daraxonrasib or zoldonrasib. In November 2024, the company entered into a collaboration with Break Through Cancer to assess biopsy samples from patients receiving daraxonrasib. In March 2024, the company entered into a collaboration agreement with Aethon Therapeutics for research related to bispecific antibodies. In June 2025, the company entered into the Royalty Purchase Agreement with Royalty Pharma, receiving an upfront payment of $250.0 million ² for the right to receive royalty payments on worldwide net product sales of RMC-6236 Products and RMC-9805 Products, with up to an additional $1.0 billion ³ in synthetic royalty funding divided into four additional tranches of up to $250.0 million ⁴ each. In June 2025, the company entered into a Loan Agreement providing for a term loan facility of up to $750.0 million ⁵. During the year ended December 31, 2025, the company sold an aggregate of 6,163,501 ⁶ shares of common stock under the 2024 ATM, resulting in gross proceeds of $353.4 million ⁷.

The company has incurred significant net losses since inception. Net losses were $1.1 billion ⁸, $600.1 million ⁹ and $436.4 million ¹⁰ for the years ended December 31, 2025, 2024 and 2023, respectively. As of December 31, 2025, the company had an accumulated deficit of $2.9 billion ¹¹. As of December 31, 2025, the company had cash, cash equivalents and marketable securities of $2.0 billion ¹². Research and development expenses increased by $395.1 million ¹³, or 67% ¹⁴, during the year ended December 31, 2025 compared to 2024, primarily due to higher clinical trial and manufacturing expenses. General and administrative expenses increased by $97.7 million ¹⁵, or 100% ¹⁶, during the year ended December 31, 2025 compared to 2024, primarily due to commercial preparation expenses and increased headcount.

A major growth vector is the advancement of daraxonrasib and zoldonrasib in global, randomized Phase 3 registrational studies in PDAC. These include RASolute 302 comparing daraxonrasib against chemotherapy in patients with 2L PDAC, with a clinical readout currently expected in the first half of 2026 ¹⁷; RASolute 303 comparing daraxonrasib with and without chemotherapy against chemotherapy in patients with 1L metastatic PDAC; RASolute 304 evaluating daraxonrasib as an adjuvant therapy in patients with resectable PDAC; and RASolute 305 comparing zoldonrasib in combination with chemotherapy against chemotherapy in patients with 1L metastatic PDAC. The company expects 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 ¹⁸. In NSCLC, the company is 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, and expects to substantially complete enrollment in 2026 ¹⁹. The company also expects 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 ²⁰.

Another growth vector is the combination strategy involving RAS(ON) inhibitor doublets, pairing the multi-selective inhibitor daraxonrasib with mutant-selective inhibitors such as elironrasib or zoldonrasib. The company believes these doublets may address potential resistance mechanisms and translate to more durable clinical benefit. The company is also pursuing combination strategies with standard of care therapies, including immunotherapies, and other novel therapies. In CRC, the company is pursuing a combination-focused strategy and expects to provide updated combination data in 2026 ²¹. The company also expects to provide an update on plans for advancing daraxonrasib combination therapy in 1L NSCLC in 2026 ²² and share an update on the registrational strategy for elironrasib in NSCLC in 2026 ²³.

The company expects research and development expenses to increase for the foreseeable future as it continues to invest in discovering and developing product candidates and advancing product candidates into later stages of development, which may include conducting larger clinical trials. General and administrative expenses are also expected to increase due to anticipated increases in operating and commercial preparation activities, which may result in increases in personnel-related costs associated with increased headcount, other administrative and professional services, and related overhead.

The company relies on and will continue to rely on contract development and manufacturing organizations (CDMOs) for all manufacturing activities. The company has entered into contracts with CDMOs for production of drug substance and drug product for clinical trials, IND-enabling development studies and commercial supply. The company plans to enter into additional contracts with these or other manufacturers for additional supply. As of December 31, 2025, the company had 883 ²⁴ full-time employees, including 673 ²⁵ employees engaged in research and development. The company expects to need additional managerial, research and development, operational, sales, marketing, financial and other personnel as development and commercialization plans develop.

The company expects to continue to spend substantial amounts to continue the preclinical and clinical development of current and future programs and to prepare for their potential commercialization. As of December 31, 2025, the company had cash, cash equivalents and marketable securities of $2.0 billion ²⁶. Through December 31, 2025, the company has raised $2.1 billion ²⁷ in underwritten public offerings, net of underwriting discounts and commissions and offering expenses, and has completed sales generating $599.9 million ²⁸ in gross proceeds pursuant to at-the-market equity offering programs. In June 2025, the company received $250.0 million ²⁹ of gross proceeds under the Royalty Purchase Agreement. The company believes that existing cash, cash equivalents and marketable securities will enable it to fund planned operations for at least 12 months following the date of the filing.

The company faces significant headwinds including the fact that it is a clinical-stage precision oncology company with a limited operating history and no products approved for commercial sale. The company has incurred significant losses since inception and expects to incur losses for at least the next several years and may never achieve or maintain profitability. The company will require substantial additional financing to achieve its goals, which may not be available on acceptable terms, or at all. The company's business is dependent on the successful development of its current and future product candidates, and preclinical development is uncertain with results of early-stage clinical trials potentially not predictive of future results. The company faces significant competition, and if competitors develop and market products that are more effective, safer or less expensive, commercial opportunities will be negatively impacted.

The company faces regulatory and macro headwinds including the Inflation Reduction Act of 2022, which requires manufacturers of certain drugs to engage in price negotiations with Medicare and imposes rebates to penalize price increases that outpace inflation. The One Big Beautiful Bill Act, enacted in July 2025, imposes significant reductions in the funding of the Medicaid program. The U.S. presidential administration has pursued a two-fold strategy to reduce drug costs, including threatening significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, and publishing proposed regulations in December 2025 referred to as Globe and Guard, which if finalized would implement mandatory payment models under which manufacturers would be required to pay rebates based on most favored nation pricing.

The company is a clinical-stage precision oncology company with no products approved for commercial sale and has incurred significant net losses since inception, with net losses of $1.1 billion ³⁰ for 2025 and an accumulated deficit of $2.9 billion ³¹ as of December 31, 2025. The company expects to incur losses for at least the next several years and may never achieve profitability. The company will require substantial additional financing to achieve its goals, and as of December 31, 2025, had cash, cash equivalents and marketable securities of $2.0 billion ³², but failure to obtain necessary capital when needed could force the company to delay, limit, reduce or terminate product development or commercialization efforts. The company's business is dependent on the successful development of its current and future product candidates, and the results of preclinical studies and early-stage clinical trials may not be predictive of future results. The company faces significant competition from companies developing or marketing treatments for cancer, including many major pharmaceutical and biotechnology companies, and if competitors develop and market products that are more effective, safer or less expensive, commercial opportunities will be negatively impacted. The company's ability to utilize net operating loss carryforwards has been limited by ownership changes under Sections 382 and 383 of the Internal Revenue Code, and could be further limited if additional ownership changes occur.

Management's message emphasizes the goal of revolutionizing treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines. The key strategic priorities emphasized are: executing on robust clinical development programs with the goal of maximizing impact for patients; expanding commercial and operational capabilities to enable delivery of successful commercial launches with the goal of changing global standards of care; and continuing to leverage the proprietary tri-complex discovery platform targeting RAS(ON). Management believes these goals are complementary and lead to a virtuous cycle of innovation driven by bench, bedside and commercial insights. The filing contains forward-looking statements regarding expectations for clinical trial readouts, including that a clinical readout for RASolute 302 is currently expected in the first half of 2026 ³³, that the company expects to substantially complete enrollment in RASolve 301 in 2026 ³⁴, and that the company expects to initiate a first-in-human clinical trial from a new class of RAS(ON) Inhibitors in the fourth quarter of 2026 ³⁵.