Revolution Medicines, Inc. Q4 FY2024 earnings call

• Mission: To revolutionize treatment for patients with RAS - addicted cancers through discovery, development, and delivery of innovative targeted medicines, anchored in discovery, development, and delivery pillars. - Pipeline progress: In 2024, made progress in advancing RAS - focused investigational drugs, reported clinical data for daraxonrasib, elironrasib, zoldonrasib, and initial evidence of combination strategies. - 2025 priorities: 1. Execute pivotal trials with daraxonrasib monotherapy in previously treated metastatic pancreatic cancer and non - small cell lung cancer. 2. Advance daraxonrasib into earlier line randomized pivotal trials in pancreatic cancer, including first - line metastatic and adjuvant settings. 3. Generate data to inform development priorities for mutant selective inhibitors and prepare to initiate pivotal trials. 4. Progress earlier - stage pipeline, including advancing RMC - 5127 to clinic - ready stage. 5. Grow commercial and operational capabilities in support of potential launch.

No specific product segment financial performance with revenue contribution % provided as the focus is on the RAS(ON) inhibitor pipeline and overall company progress. The company has a pipeline of RAS(ON) inhibitors including daraxonrasib, elironrasib, zoldonrasib, etc., and has made progress in advancing these in clinical trials.

• Full year 2025 GAAP net loss is expected to be between $840 million and $900 million, including estimated non - cash stock - based compensation expense of $115 million to $130 million. The increase is due to increased expenses from progression and expansion of clinical development programs and increased commercial preparation efforts.

• Forward - looking statements are subject to many risks and uncertainties, and actual results may differ materially from forward - looking statements. Risks and uncertainties are detailed in the annual report on Form 10 - K and quarterly reports on Form 10 - Q filed with the U.S. Securities and Exchange Commission.

Q: Walk us through the decision to move forward with the 2 Phase III studies in the earlier line PDAC and specifically what gives conviction on the Phase III in the adjuvant setting and the role of RAS in the earlier line setting A: Mark Goldsmith said based on the data reported in pancreatic cancer, they have conviction to try to own the entire PDAC space. For the adjuvant setting, the proof - of - concept from monotherapy data in previously treated patients supports pursuing it. And there's no evidence that resectable PDAC patients have different RAS driver representation than other pancreatic cancer patients Q: Proposed pivotal study in the adjuvant setting, about resectable PDAC proportion and regulatory bar for registration A: Wei Lin commented that in the short term, the proportion of resectable PDAC is not expected to change as there's no screening like in other cancers. Mark Goldsmith said they can't comment on the regulatory bar details like PFS OS at present Q: Follow - up on the questions about adjuvant design, including borderline resectable disease and how to balance moving quickly versus redundant trials A: Wei Lin said they want to offer daraxonrasib to the broadest patient population possible in the adjuvant setting. Mark Goldsmith said they grapple with moving swiftly to serve patients, and they'd rather be first to the table to create the bar rather than chasing others Q: First - line metastatic pancreatic cancer strategy, work needed with chemotherapy combination and thoughts on zoldonrasib in pancreatic cancer registration strategy A: Mark Goldsmith said they are evaluating chemotherapy combination to support the third arm in the trial, focusing on safety. Wei Lin commented that zoldonrasib has a high prevalence in pancreatic cancer and they are evaluating it as a separate registration trial or in combination with daraxonrasib Q: Colorectal cancer data disclosure cadence and guidance on registrational path for colorectal cancer and beyond big three KRAS - driven tumors A: Mark Goldsmith said they don't have guidance on next disclosures about colorectal cancer, they continue to study it, and they'll share information when it starts to point to future strategies Q: Phase I study in PDAC, plans to update overall survival data A: Mark Goldsmith said the OS data continues to mature and they don't have a specific plan to share it right now but will share it at some point Q: First - line lung opportunity, potential for non - G12C frontline indication and triplet data update A: Steve Kelsey commented that they divide RAS - mutant lung cancer into distinct sets, they are aggressively enrolling combinations and waiting for durability data to mature to report on it Q: Study of daraxonrasib in the adjuvant setting for resectable PDAC, dosing duration and thoughts on non - small cell lung cancer earlier lines A: Mark Goldsmith said it's early to get into trial design details. He said they are interested in non - small cell lung cancer earlier lines but it's too early to share specific strategy details Q: Study of daraxonrasib in front - line PDAC, dosing duration of chemo combo A: Wei Lin said they are evaluating combinations and it's too early to share specific details. Mark Goldsmith added that they want patients to get through initial treatment periods to benefit from daraxonrasib Q: Entertaining potential collaboration opportunities with daraxonrasib or other assets A: Mark Goldsmith said they are both entertaining and engaged in collaborations, including clinical collaborations like with Tango Therapeutics Q: Additional data needed for zoldonrasib to initiate pivotal combination trials and updates on other indications A: Mark Goldsmith said they are evaluating zoldonrasib in combination with other agents and expect to share additional clinical data on zoldonrasib mid - year, but couldn't provide details on data from other indications like gastric and CRC at present Q: Completion of second - line PDAC study, potential approval and impact on first - line trial A: Mark Goldsmith said they are highly confident to complete enrollment of the second - line PDAC study in 2025, and it puts pressure on the first - line trial. He also commented on accelerated approval being a question best addressed to regulators