Core Insights - Revolution Medicines, Inc. has published a peer-reviewed research paper in Science detailing the discovery and development of zoldonrasib (RMC-9805), a selective covalent inhibitor targeting RAS(ON) G12D mutations in cancers [1][3] Group 1: Drug Development and Mechanism - Zoldonrasib targets RAS G12D mutations, which are prevalent in various cancers, including 92% of pancreatic ductal adenocarcinoma, 50% of colorectal cancer, and 30% of non-small cell lung cancer [2] - The drug employs a novel mechanism as a tri-complex inhibitor, successfully forming covalent bonds with RAS(ON) G12D proteins by utilizing a unique protein-protein interface [2][3] - Preclinical data indicate that zoldonrasib can drive significant tumor regressions in models with KRAS G12D mutations, showcasing its therapeutic potential [2][3] Group 2: Clinical Trials and Future Prospects - Zoldonrasib is currently in clinical trials, including a Phase 1 study (RMC-9805-001) evaluating its efficacy in patients with advanced solid tumors harboring KRAS G12D mutations [4] - Results from the NSCLC and PDAC studies have been presented at notable cancer research meetings, indicating ongoing evaluation and interest in the drug's performance [4] - The company is also developing additional RAS(ON) inhibitors, including daraxonrasib (RMC-6236) and elironrasib (RMC-6291), with plans for RMC-5127 (G12V-selective) to enter clinical development next [5]

Core Insights - Revolution Medicines and Iambic Therapeutics have entered a multi-year technology and research collaboration to develop novel drug candidates using Iambic's AI-driven discovery platform [1][2][4] - Iambic will utilize structures and molecular libraries from Revolution Medicines to train custom versions of its NeuralPLexer model for protein-ligand structure prediction [2][7] - The collaboration includes a financial component where Iambic could receive up to $25 million in upfront and milestone payments, along with ongoing R&D reimbursements [4][7] Company Overview - Revolution Medicines is focused on developing targeted therapies for RAS-addicted cancers, with a pipeline that includes RAS(ON) inhibitors currently in clinical development [8] - Iambic Therapeutics, founded in 2020, leverages AI technology to address complex drug discovery challenges and has a pipeline of clinical assets targeting unmet patient needs [6][8] Technology and Collaboration Details - The collaboration aims to enhance drug discovery capabilities by integrating Iambic's AI models with Revolution Medicines' proprietary data, allowing for rapid exploration of challenging oncology targets [3][5] - Iambic's AI-driven platform, including the NeuralPLexer and PropANE models, is designed to optimize lead selection and drug properties through advanced molecular predictions [5][6]

Pipeline and Drug Candidates - Revolution Medicines has a deep science-driven pipeline of targeted therapies for RAS-addicted cancers, with drug candidates expected to enter the clinic in 2022 [13, 14] - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with broad potential against RAS-addicted cancers [22] - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers [44] - RMC-9805 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12D cancers [62] - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers [74] Clinical Priorities and Activities - Revolution Medicines plans to submit INDs for RMC-6236 and RMC-6291 in the first half of 2022 and initiate single-agent dose escalation studies [42, 60] - The company aims to complete enrollment in RMC-4630-03 and provide preliminary evaluation in the second half of 2022 [98] - Revolution Medicines anticipates submitting INDs for RMC-9805 in the first half of 2023 and RMC-8839 in the second half of 2023 [118] RAS-Addicted Cancers and Patient Numbers - RAS proteins drive 30% of human cancers [7, 122] - There are an estimated 137,000 new KRASG12X patients per year in the U S [23] - There are approximately 29,000 new KRASG12C patients per year in the U S [45] - There are approximately 55,000 new KRASG12D patients per year in the U S [63] - There are approximately 3,000 new KRASG13C patients per year in the U S [75] Financial Position - Revolution Medicines had $577.1 million in cash, cash equivalents, and marketable securities as of December 31, 2021 [120]

Pipeline and Drug Candidates - Revolution Medicines is developing a deep pipeline of targeted therapies for RAS-addicted cancers, with the first two drug candidates expected to enter the clinic in 2022 [13] - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with potential against various RAS-addicted cancers, targeting approximately 137,000 new KRASG12X patients per year in the U S [19, 20] - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers, addressing approximately 29,000 new KRASG12C patients per year in the U S [38, 39] - RMC-9805 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG12D cancers, targeting approximately 55,000 new KRASG12D patients per year in the U S [59, 60] - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers, addressing approximately 3,000 new KRASG13C patients per year in the U S [69, 70] Preclinical Data and Activity - RMC-6236 demonstrated robust anti-tumor activity in cancer models, with 44% ORR (8/18) in NSCLC, 53% ORR (8/15) in PDAC, and 61% ORR (11/18) in CRC [24] - RMC-6291 showed superior outcomes in a mouse clinical trial with KRASG12C NSCLC models, achieving 72% ORR (18/25) and 92% DCR (23/25) [43] - Preclinical research indicates that RMC-6236 and RMC-6291 exhibit anti-tumor immunity in vivo and strong additivity with checkpoint inhibitors [29, 52] Clinical Development and Strategy - Revolution Medicines plans to initiate single-agent dose escalation for RMC-6236 in patients with cancers harboring KRASG12X mutations, focusing on NSCLC, pancreatic cancer, and CRC [36] - The company also intends to start single-agent dose escalation for RMC-6291 in KRASG12C tumors, including expansion cohorts in select populations like NSCLC [58] - RMC-4630, a RAS companion inhibitor, is undergoing clinical combination studies, including with sotorasib and adagrasib, to address resistance mechanisms in KRASG12C tumors [91, 93] Financial Status - As of March 31, 2022, Revolution Medicines had approximately $518 8 million in cash, cash equivalents, and marketable securities [125] - The company anticipates a GAAP net loss of $260 million to $290 million for 2022, including $35 million to $40 million in non-cash stock-based compensation expense [125, 126]

Overview - Revolution Medicines is targeting RAS-addicted cancers, which are driven by RAS proteins and affect approximately 30% of human cancers[6, 8, 119] - The company is developing RAS(ON) inhibitors and RAS companion inhibitors to address this high unmet need[6, 11] RMC-6236 (RASMULTI Inhibitor) - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with potential against various RAS-addicted cancers, targeting approximately 137,000 new KRASG12X patients per year in the U S [17, 18] - Preclinical data shows robust anti-tumor activity in cancer models with common RAS variants, including KRASG12D, KRASG12V, KRASG12R, and KRASG12C[20] - In preclinical studies, RMC-6236 demonstrated a 44% Objective Response Rate (ORR) and 56% Disease Control Rate (DCR) in NSCLC models, 61% ORR and 89% DCR in PDAC models, and 53% ORR and 100% DCR in CRC models[24] RMC-6291 (KRASG12C Inhibitor) - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers, addressing approximately 29,000 new patients per year in the U S [33, 34] - Preclinical studies in KRASG12C NSCLC models showed a 72% ORR and 92% DCR with RMC-6291, compared to 52% ORR and 72% DCR with Adagrasib[39] - RMC-6291 also demonstrated anti-tumor immunity in vivo and strong additivity with checkpoint inhibitors[48] RMC-9805 (KRASG12D Inhibitor) - RMC-9805 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG12D cancers, targeting approximately 55,000 new patients per year in the U S [51, 52] - Preclinical data shows rapid, deep, and sustained regressions in KRASG12D lung, pancreatic, and colorectal cancers[53] - In preclinical studies, RMC-9805 demonstrated a 64% ORR and 68% DCR across various KRASG12D cancer models[61] RMC-8839 (KRASG13C Inhibitor) - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers, addressing approximately 3,000 new patients per year in the U S [64, 65] - Preclinical data shows rapid, deep, and sustained regressions in KRASG13C lung cancers[66] Financial Status - As of September 30, 2022, Revolution Medicines had $655 million in cash, cash equivalents, and marketable securities, projecting funding for planned operations through 2024[116] - The company anticipates a 2022 GAAP net loss of $260 million to $280 million, including approximately $30 million to $35 million in non-cash stock-based compensation expense[116]

On Target to Outsmart Cancer November 6, 2024 © 2024 Revolution Medicines, Inc. 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, ability to manage existing collaborations and esta ...

Core Insights - Revolution Medicines and Summit Therapeutics have entered a clinical collaboration to evaluate the safety and efficacy of RAS(ON) inhibitors in combination with Summit's ivonescimab across multiple solid tumor types [1][2][3] 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 daraxonrasib (RMC-6236), elironrasib (RMC-6291), and zoldonrasib (RMC-9805) [4] - Summit Therapeutics is a biopharmaceutical oncology company dedicated to developing patient-friendly therapies aimed at improving quality of life and addressing unmet medical needs [5][6] Clinical Collaboration Details - The collaboration will assess combinations of RAS(ON) inhibitors with ivonescimab in three priority tumor types: RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) [2] - Under the agreement, Summit will provide ivonescimab for clinical research, while Revolution Medicines will act as the study sponsor, with both companies retaining commercial rights to their respective compounds [2] Drug Development Insights - Initial evidence suggests that daraxonrasib and elironrasib can provide additive antitumor activity when combined with a PD-1 antibody in first-line treatment for RAS mutant non-small cell lung cancer [2] - The collaboration aims to explore the therapeutic potential of combining investigational drugs from Revolution's RAS(ON) inhibitor portfolio with Summit's advanced PD-1 / VEGF bispecific inhibitor [3]

Summary of Revolution Medicines Conference Call Company Overview - **Company**: Revolution Medicines - **Industry**: Biotechnology, specifically focused on targeted therapies for RAS addicted cancers Key Points and Arguments 1. **Partnership with Royalty Pharma**: Revolution Medicines announced a significant partnership with Royalty Pharma, which will provide up to $2 billion in committed capital to support the development of their late-stage pipeline of RAS inhibitors while allowing the company to retain full control of its assets [4][5][6] 2. **Financial Position**: As of March 30, 2025, Revolution Medicines reported $2.1 billion in cash and investments. The partnership with Royalty Pharma adds an additional $2 billion in capital, structured to avoid equity dilution for shareholders [5][6][30] 3. **Funding Structure**: The funding arrangement includes approximately two-thirds in the form of a synthetic royalty and the remainder as corporate debt. The synthetic royalty will provide $1.25 billion in exchange for tiered royalties on future sales of diraxonrasib, with specific milestones triggering access to funds [24][25][29] 4. **Clinical Development Plans**: The company is committed to advancing its pipeline, which includes diraxonrasib, a multi-selective RAS inhibitor, and other candidates targeting various RAS mutations. The focus remains on executing robust global Phase III clinical trials [10][18][19] 5. **Market Focus**: The U.S. market is a strategic priority for Revolution Medicines, with plans to establish a standalone U.S.-based commercial capability. The company also aims to expand into select international markets, including Europe and Japan, using a phased approach [20][21][22] 6. **Regulatory Designation**: Diraxonrasib has received breakthrough therapy designation from the FDA for previously treated metastatic pancreatic cancer with KRAS G12 mutations, indicating strong potential for market impact [33] 7. **Strategic Independence**: Revolution Medicines aims to maintain strategic and execution control over its global commercialization efforts, which is expected to enhance decision-making speed and align strategic priorities without the complications of partnerships [45][46] 8. **Clinical Pipeline**: The company is focused on developing a portfolio of RAS inhibitors, including diraxonrasib, elyronrasib, and zoldonrasib, targeting various cancer types such as pancreatic cancer, non-small cell lung cancer, and colorectal cancer [18][19][73] Additional Important Content 1. **Market Opportunity**: The company recognizes the significant unmet medical need in treating RAS addicted cancers, particularly pancreatic cancer, which has a high prevalence of RAS mutations [19] 2. **Financial Guidance**: Revolution Medicines has withdrawn its previous guidance on expected GAAP net loss for 2025 as it evaluates the accounting treatment of the new funding arrangement [31][94] 3. **Talent Acquisition**: The company is actively growing its organization to support its ambitious clinical and commercialization plans, attracting experienced professionals in the biotechnology field [10][96] 4. **Long-term Vision**: Revolution Medicines is committed to creating an industry-leading targeted medicines franchise for patients with RAS addicted cancers, emphasizing the importance of innovative drug mechanisms and clinical data [33][34] This summary encapsulates the critical insights and strategic direction of Revolution Medicines as discussed in the conference call, highlighting their financial strategies, clinical development plans, and market focus.

Core Insights - Revolution Medicines has partnered with Royalty Pharma to secure $2 billion in flexible funding aimed at supporting its global development and commercialization strategy for RAS-addicted cancers [1][2][5] - The funding agreement allows Revolution Medicines to maintain full control over the development and commercialization of its RAS(ON) inhibitor portfolio, which is crucial for establishing new standards of care [1][2][3] Funding Agreement Overview - The funding consists of up to $1.25 billion in synthetic royalty monetization on sales of daraxonrasib and up to $750 million in corporate debt [3][5] - The agreement provides significant flexibility, with $1.25 billion available at the company's discretion, contingent on achieving specific milestones [3][5] Synthetic Royalty Details - Royalty Pharma will provide up to $1.25 billion in exchange for tiered royalties over 15 years on worldwide annual net sales of daraxonrasib, with decreasing royalty rates based on sales volume [6][13] - The first two tranches of $250 million each are payable before FDA approval, with the first tranche already received [6][13] Debt Facility Details - The debt facility consists of up to $750 million in senior secured term loans, with the first tranche available after FDA approval of daraxonrasib for metastatic pancreatic ductal adenocarcinoma [13] - The interest rate for the debt is based on the 3-month Standard Overnight Financing Rate (SOFR) plus 5.75%, with a SOFR floor of 3.50% [13] Cash Runway Update - Following the funding agreement, the company has removed its cash runway end date guidance, indicating improved financial stability [9] Company Background - Revolution Medicines is 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 (NASDAQ: RVMD) has shown promising developments, particularly highlighted during the ASCO GI meeting in January [1] Company Analysis - The company is focused on the biotechnology sector, with a strong emphasis on clinical trials and scientific research [1] - The analyst has a PhD in biochemistry and extensive experience in analyzing biotech companies, indicating a deep understanding of the industry [1] Industry Context - The biotechnology industry is characterized by its complexities and the necessity for thorough due diligence to avoid investment pitfalls [1]