Core Insights - Revolution Medicines, Inc. is set to present nine oral and poster presentations at the AACR Annual Meeting, showcasing advancements in its RAS(ON) inhibitor pipeline for RAS-addicted cancers [1][4] Presentation Highlights - New Phase 1 data for zoldonrasib, a RAS(ON) G12D-selective inhibitor, will be featured in a plenary session, focusing on patients with previously treated KRAS G12D mutant non-small cell lung cancer [2] - Two Phase 1/2 datasets evaluating daraxonrasib, a RAS(ON) multi-selective inhibitor, will be presented, including monotherapy and combination therapy data with chemotherapy for first-line metastatic pancreatic ductal adenocarcinoma [3] - Additional presentations will cover preclinical research on a new class of mutant-targeted catalytic RAS(ON) inhibitors, aimed at maintaining antitumor activity despite resistance [4] Presentation Details - An invited presentation titled "Targeting the Oncogenic State of RAS: Lessons from Tri-Complex Inhibitors" will be given by Dr. Mallika Singh on April 18 [6] - An oral presentation on the preliminary safety and clinical activity of zoldonrasib will be presented by Dr. Jonathan Reiss on April 19 [7] - A mini-symposium will feature daraxonrasib plus chemotherapy as a first-line treatment for metastatic pancreatic adenocarcinoma, presented by Dr. Brian Wolpin on April 21 [8] - Additional poster presentations will cover various aspects of RAS(ON) inhibitors and their effects on cancer and immune cells [10] Company Overview - Revolution Medicines is a late-stage clinical oncology company focused on developing targeted therapies for RAS-addicted cancers, with a pipeline that includes multiple RAS(ON) inhibitors currently in clinical development [12]

Core Insights - Revolution Medicines, Inc. (NASDAQ:RVMD) is recognized as a promising investment in the cancer sector, particularly due to its advancements in RAS(ON) inhibitors [1][5] Financial Performance - The company reported a net loss of $364.9 million in Q4 2025, nearly doubling from $194.6 million in the same quarter of the previous year [4] - The full-year net loss for 2025 reached $1.1 billion, compared to $600.1 million in 2024 [4] - Research and development expenses surged to $294.9 million in Q4 2025 from $188.1 million in Q4 2024, with total R&D expenses for the year amounting to $987.3 million, up from $592.2 million in 2024 [4] Clinical Developments - The company is currently enrolling patients in the US for a Phase 3 trial of daraxonrasib in Non-Small Cell Lung Cancer (NSCLC) [2] - A pivotal readout from the RASolute 302 trial for daraxonrasib in pancreatic cancer is expected in the first half of 2026, marking a significant milestone for the company's RAS(ON)-targeting strategy [3] - Zoldonrasib has demonstrated a highly differentiated safety and tolerability profile as a G12D-selective covalent inhibitor [2] Market Position - Revolution Medicines focuses on targeted therapies for RAS-addicted cancers, which account for approximately 30% of new cancer diagnoses [5]

Core Insights - Revolution Medicines (RVMD) reported a Q4 2025 loss of $1.86 per share, which is wider than the Zacks Consensus Estimate of a loss of $1.56, and a significant increase from a loss of $1.12 in the same quarter last year [1][7] - The company has no approved products and did not generate any revenues in 2025 [5][8] - RVMD's stock fell 5% in after-market trading following the earnings report, despite a year-to-date increase of 30%, outperforming the industry growth of 10% [1][2] Financial Performance - Research and development expenses for Q4 2025 were $294.9 million, reflecting a nearly 57% year-over-year increase, driven by higher costs for clinical studies and manufacturing [3] - General and administrative expenses reached $66.7 million, up more than 136% year-over-year, primarily due to increased commercial preparation activities and employee-related expenses [3] - For the full year 2025, the company reported a loss of $5.95 per share, wider than the $3.58 loss from the previous year [8] Cash Position - As of December 31, 2025, Revolution Medicines had cash and cash equivalents of $2 billion, an increase from $1.9 billion as of September 30, 2025 [4] 2026 Guidance - RVMD expects operating expenses for 2026 to be between $1.6 billion and $1.7 billion, which includes non-cash stock-based compensation expenses of $180-$200 million [9] Pipeline Developments - The company is advancing daraxonrasib, an investigational oral RAS(ON) multi-selective inhibitor, into multiple late-stage studies for pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) [10][12] - The RASolute 302 study is assessing daraxonrasib in second-line metastatic PDAC, while the RASolute 303 study is evaluating its efficacy in the first-line setting [11] - RVMD has initiated the phase III RASolute 305 study to evaluate the combination of zoldonrasib with chemotherapy in first-line PDAC patients [14] Strategic Collaborations - To enhance its pipeline, Revolution Medicines has entered into collaborations with companies like Summit Therapeutics and Tango Therapeutics to evaluate combinations of its RAS(ON) inhibitors with their drugs [15] - A recent collaboration with Bristol Myers Squibb aims to evaluate daraxonrasib in combination with navlimetostat for certain pancreatic cancer patients [16]

Market Overview - U.S. equity markets reached new all-time highs in Q4 2025, with the S&P 500 Index rising 2.66% and the Bloomberg U.S. Aggregate Bond Index increasing by 1.10% [1] - The U.S. economy showed resilience, although consumer confidence deteriorated toward year-end, raising concerns about future spending and the labor market [1] Fund Performance - The Aristotle Growth Equity Fund (Class I-2) returned 0.95%, underperforming the Russell 1000 Growth Index's 1.12% [1] - Poor security selection in the information technology and consumer discretionary sectors detracted from performance, while positive contributions from healthcare and industrials improved relative performance [1] Company Highlight: Revolution Medicines, Inc. - Revolution Medicines, Inc. (NASDAQ:RVMD) is a clinical-stage precision oncology company focused on developing therapies for RAS-addicted cancers [2][3] - As of February 25, 2026, Revolution Medicines, Inc. stock closed at $103.24 per share, with a one-month return of 5.13% and a 52-week gain of 164.18% [2] - The company has a market capitalization of $19.958 billion [2] - Revolution Medicines is developing RAS(ON) inhibitors to block growth signals from RAS proteins, with main drugs including Daraxonrasib, Elironrasib, and Zoldonrasib already in clinical trials [3] - The company is also working on bringing a new drug, RMC-5127, into trials soon and developing targeted treatments for other types of RAS mutations [3]

Financial Data and Key Metrics Changes - The company ended Q4 2025 with $2.03 billion in cash and investments, having entered a strategic partnership with Royalty Pharma that provided access to up to $2 billion in committed capital [21] - R&D expenses for Q4 2025 were $294.9 million, up from $188.1 million in Q4 2024, primarily due to increased clinical trial and manufacturing expenses [21][22] - G&A expenses for Q4 2025 were $66.7 million, compared to $28.2 million in Q4 2024, driven by commercial preparation activities and increased personnel-related expenses [22] - The net loss for Q4 2025 was $364.9 million, compared to $194.6 million in Q4 2024, attributed to higher operating expenses [22][23] - Full year 2026 GAAP operating expenses are expected to be between $1.6 billion and $1.7 billion, reflecting the expansion of clinical development programs [24] Business Line Data and Key Metrics Changes - The company has advanced its pipeline with four novel investigational drugs targeting major oncogenic RAS drivers, including daraxonrasib, elironrasib, zoldonrasib, and RMC-5127 [8][9] - There are currently eight ongoing or planned phase 3 registrational trials, with over 2,500 patients having received one or more RAS(ON) inhibitors [8] Market Data and Key Metrics Changes - The company is focusing on pancreatic cancer, where over 90% of cases are RAS-driven, and has multiple registrational trials underway or planned for 2026 [9][10] - The FDA has granted daraxonrasib Breakthrough Therapy Designation, highlighting its potential to address significant unmet needs in pancreatic cancer [10] Company Strategy and Development Direction - The company aims to revolutionize treatments for RAS-addicted cancers through innovative targeted medicines and has established a strong operational foundation for a successful commercial launch [7][20] - The company is committed to advancing its RAS(ON) inhibitor pipeline and exploring novel approaches to overcome RAS-driven drug resistance [18][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their pipeline to transform treatment standards for difficult-to-treat cancers, with key milestones expected in 2026 [26] - The company is preparing for its first commercial launch, initially focused on the U.S. market, and has made strategic hires to support this effort [20] Other Important Information - The company is exploring collaborations with other firms to evaluate RAS(ON) inhibitors in combination with new targeted therapies [16][17] - The company has initiated a clinical collaboration with Bristol Myers Squibb to evaluate daraxonrasib in combination with navlimetostat in pancreatic cancer patients [17] Q&A Session Summary Question: Plans to advance daraxonrasib combination in first-line non-small cell lung cancer - Management confirmed a high commitment to continue developing daraxonrasib in lung cancer, particularly in the first line, with ongoing dose optimization and efficacy testing [30][31] Question: Efficacy measure for the second-line PDAC trial - Management indicated that the study is powered for overall survival (OS) and progression-free survival (PFS), but no specific expectations could be provided at this time [36] Question: Impact of daraxonrasib use in first-line studies on OS outcomes - Management acknowledged potential complications with crossover from the control arm but emphasized that they expect to establish significant momentum before FDA review [41][42] Question: Ongoing partnered collaborations and decision-making for late-stage trials - Management explained that decisions about advancing into late-stage trials will be data-driven, considering the emerging combination data and the broader landscape of ongoing trials [48] Question: Treatment beyond progression in PDAC - Management noted that while treatment beyond progression is not permitted in the RASolute 302 study, they encourage evaluation of this possibility in other studies [78]

Core Insights - Revolution Medicines, Inc. reported significant clinical advancements in its RAS(ON) inhibitors portfolio, particularly focusing on daraxonrasib and zoldonrasib for RAS-addicted cancers, with pivotal data expected in 2026 [2][5][6] Clinical Progress - The company is advancing daraxonrasib in three Phase 3 studies for pancreatic ductal adenocarcinoma (PDAC) and has shown promising results in combination therapies [3][4] - Zoldonrasib has demonstrated a favorable safety profile and is being evaluated in various combinations, with initial data showing a 63% partial response rate in patients with metastatic PDAC [4][5] - The company plans to initiate multiple Phase 3 trials in 2026, including RASolve 308 for zoldonrasib in NSCLC [9][10] Financial Performance - As of December 31, 2025, the company reported cash and marketable securities of $2.0 billion, including a $250 million royalty monetization tranche [19] - Research and development expenses for Q4 2025 were $294.9 million, up from $188.1 million in Q4 2024, primarily due to increased clinical trial costs [20] - The net loss for the full year 2025 was $1.1 billion, compared to a net loss of $600.1 million in 2024, reflecting higher operational costs [25] Future Guidance - The company anticipates full-year 2026 GAAP operating expenses to be between $1.6 billion and $1.7 billion, including estimated non-cash stock-based compensation of $180 to $200 million [26]

Financial Data and Key Metrics Changes - The company ended 2025 with a strong cash position of approximately $713.4 million, with no debt [30] - Total GAAP operating expenses for Q4 2025 were $225 million, a decrease from $234.2 million in Q3 2025, primarily due to lower stock-based compensation expenses [30][31] - Non-GAAP operating expenses for Q4 2025 were $113.3 million, an increase from $103.4 million in Q3 2025, mainly driven by increased R&D expenses related to clinical trials [31] Business Line Data and Key Metrics Changes - The HARMONi-3 phase III trial for Ivonescimab has completed screening for the squamous cohort, with the last patient expected to be randomized shortly [8][10] - The company has announced a new phase III study, ILLUMINE, evaluating Ivonescimab in head and neck cancer, with initial enrollment expected to begin early next quarter [11][12] Market Data and Key Metrics Changes - Over 60,000 patients in China have received Ivonescimab based on two approved indications, with a third indication currently under review [16] - The total addressable market for Ivonescimab is estimated to exceed $100 billion globally, with potential improvements over current standards of care [27] Company Strategy and Development Direction - The company is focused on expanding its clinical development plan and preparing for commercialization, anticipating a decision from the FDA on its BLA by the end of the year [7][19] - The strategy includes accelerating enrollment in clinical trials and enhancing commercial readiness for potential launches [30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the interim PFS analysis for HARMONi-3, which is expected in Q2 2026, and emphasized the importance of the positive data from previous trials [29][38] - The company is confident that the PFS benefits observed in trials will translate into overall survival benefits in the frontline population [74][77] Other Important Information - The company has initiated collaborations with Revolution Medicines and GSK to evaluate Ivonescimab in combination with novel therapies [14][23] - A total of 15 phase III trials are currently ongoing or have been announced, with a significant number of patients enrolled across various studies [15][17] Q&A Session Summary Question: What drove the decision to include the interim PFS analysis for HARMONi-3? - The decision was based on positive data from HARMONi-2 and HARMONi-6, allowing for earlier discussions with regulatory agencies [36][37] Question: Was there anything specific in HARMONi-3 that increased confidence for the interim analysis? - The decision was data-backed, influenced by the positive results from HARMONi-2 and HARMONi-6, rather than new information from HARMONi-3 [42][43] Question: What gives confidence that positive PFS data will translate to OS benefits? - The company highlighted the consistency of results across multiple trials and the importance of PFS in delaying the next line of therapy, which should translate to OS benefits [74][77]

Core Insights - Revolution Medicines has initiated its first-in-human clinical trial for RMC-5127, a selective inhibitor targeting the RAS G12V mutation, which is prevalent in various cancers [1][2][3] Company Overview - Revolution Medicines is a late-stage clinical oncology company focused on developing targeted therapies for RAS-addicted cancers [4] - The company's R&D pipeline includes multiple RAS(ON) inhibitors, with RMC-5127 being the fifth disclosed mutant-selective inhibitor and the fourth in clinical development [3][4] Clinical Trial Details - The trial, named RMC-5127-001, is an open-label study assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-5127 as both a monotherapy and in combination settings [2] - It will enroll patients with RAS G12V–mutated solid tumors, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non–small cell lung cancer (NSCLC), who have either progressed on or are intolerant to prior standard therapies [2] Market Opportunity - RAS G12V is the second most common RAS mutation, with approximately 48,000 new cases diagnosed annually in the U.S., primarily among patients with PDAC, CRC, or NSCLC [3]

Summary of Revolution Medicines FY Conference Call Company Overview - **Company**: Revolution Medicines (NasdaqGS:RVMD) - **Industry**: Biotechnology, specifically focused on oncology and RAS-addicted cancers - **Mission**: To revolutionize treatment for patients with RAS-addicted cancers through innovative targeted medicines [2][3] Core Points and Arguments Clinical Development and Pipeline - Revolution Medicines is advancing in three major RAS-addicted cancers: pancreatic, non-small cell lung, and colorectal cancer [3] - The company has four RAS(ON) inhibitors in clinical trials and a deep pipeline, with eight ongoing or announced registrational phase 3 trials [3] - **Key Investigational Drugs**: - **RMC-6236**: A multi-selective RAS(ON) inhibitor with promising clinical profiles [3][6] - **RMC-6291**: A selective inhibitor for RAS G12C mutations [3] - **RMC-9805**: A selective inhibitor for RAS G12D mutations [3] - **RMC-5127**: A selective inhibitor for RAS G12V mutations [3] Market Need and Unmet Needs - Over 90% of pancreatic ductal adenocarcinoma tumors harbor an oncogenic RAS mutation, indicating a significant need for targeted therapies [4] - Approximately 30% of non-small cell lung cancers and over 50% of colorectal cancers also carry oncogenic RAS mutations, highlighting the unmet need for effective treatments [5] Clinical Trial Highlights - **Pancreatic Cancer**: - RMC-6236 has shown promising clinical durability in second-line treatment settings compared to standard cytotoxic chemotherapy [6][10] - Ongoing trials include RASolute 302, 303, and 304, focusing on various treatment regimens [8][10] - **Non-Small Cell Lung Cancer**: - RMC-6236 is being evaluated in RASolute 301, with encouraging early data from combination therapies [12][13] - RMC-9805 and RMC-6291 are also being explored for their roles in treating specific RAS mutations [13][15] - **Colorectal Cancer**: - The company is pursuing combination studies to maximize clinical impact due to the heterogeneous nature of these cancers [15][16] Innovation and Future Directions - Introduction of a new class of RAS(ON) inhibitors designed to overcome drug resistance, with plans to advance the first compound into clinical trials [19][21] - Continuous investment in research and development to maintain leadership in targeted therapeutics for RAS-addicted cancers [17][22] Financial Position - As of Q3 2025, Revolution Medicines reported a strong financial position with $1.9 billion in cash and an additional $1.75 billion in committed capital from Royalty Pharma [23] - The company is well-positioned for broad execution across its clinical programs and operational capabilities [23] Upcoming Milestones - Key data disclosures for RMC-6236 and RMC-9805 are expected in the first half of 2026, including results from ongoing trials [24][25] - Plans to initiate new registrational trials for both pancreatic and non-small cell lung cancers in 2026 [24][25] Other Important Content - The company emphasizes the importance of data maturity before disclosure, aiming to provide relevant information to support clinical programs [28][30] - Concerns regarding external factors affecting trial outcomes and regulatory processes were acknowledged, highlighting the unpredictability of clinical research [34][36] - The differentiation of ZOLD on RASIB was discussed, noting its favorable tolerability profile and potential as a class-leading compound [39][40] This summary encapsulates the key points from the Revolution Medicines FY Conference Call, focusing on the company's strategic direction, clinical advancements, market needs, and financial health.

On Target to Outsmart Cancer 44th Annual JP Morgan Healthcare Conference January 12, 2026 © 2026 Revolution Medicines, Inc. 2 Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, availability of funding, abil ...