Financial Data and Key Metrics Changes - The company ended Q2 2025 with $2.1 billion in cash and investments, including $250 million from the Royalty Pharma partnership [22] - R&D expenses for 2025 were $224.1 million, up from $134.9 million in 2024, primarily due to clinical trial and manufacturing expenses [23] - G&A expenses increased to $40.6 million in 2025 from $21.7 million in 2024, driven by personnel-related expenses and stock-based compensation [24] - The net loss for 2025 was $247.8 million, compared to $133.2 million in 2024, mainly due to higher operating expenses [24] - The projected full-year 2025 GAAP net loss is estimated to be between $1.03 billion and $1.09 billion [25] Business Line Data and Key Metrics Changes - The company has three clinical stage RasOn inhibitors: TiraxonRasib, Oleeronrasib, and Zoldonrasib, with ongoing trials and promising data [8][10] - Diraxonrasib received breakthrough therapy designation for previously treated metastatic pancreatic cancer with KRAS G12 mutations, indicating significant unmet medical needs [9] - The ongoing global Phase 3 trial RESLU-302 for diraxonrasib is progressing well, with expectations to complete enrollment this year [9][10] Market Data and Key Metrics Changes - The company is focusing on pancreatic cancer and non-small cell lung cancer (NSCLC) as key markets, with multiple ongoing trials in these areas [10][12] - The company is expanding its clinical trials to include international sites, particularly in Europe and Japan, for NSCLC [11] Company Strategy and Development Direction - The company aims to establish a leading global RAS-targeted franchise, focusing on innovative targeted therapies for RAS addicted cancers [19][26] - A significant partnership with Royalty Pharma provides $2 billion in committed capital, enhancing the company's financial strength and strategic agility [19][20] - The company is investing in next-generation assets and collaborations to enhance its drug discovery capabilities [18][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress of clinical trials and the potential of their pipeline to transform treatment for patients with RAS-driven cancers [8][19] - The company is committed to independent global development and commercialization strategies for its RAS-targeted portfolio [19][25] Other Important Information - The company is preparing to enter clinical development for RMC-5127, a RasOn G12V selective inhibitor, expected to initiate a Phase 1 trial in 2026 [17] - The collaboration with Summit Therapeutics aims to evaluate combinations of their PD-1 VEGF bispecific antibody with the company's RasOn inhibitors [16][18] Q&A Session Summary Question: Enrollment progress for RESLU-302 and chemotherapy combinations - Management confirmed good progress in enrollment for RESLU-302 and emphasized the importance of safety and tolerability in chemotherapy combinations [30][32][35] Question: Chemotherapy regimens and data readout timelines - Management indicated that the chemotherapy regimens are within standard practice and that the first analysis of data is expected in 2026, but specifics on interim analyses were not provided [39][42][44] Question: Data updates for doraxonerasib and considerations for frontline studies - Management stated that sufficient data will guide decisions for moving forward with studies and emphasized the importance of safety and dose intensity [48][51][52] Question: RAF upregulation and combination therapies - Management acknowledged RAS amplification as a challenge but expressed confidence in their inhibitors' effectiveness and the potential benefits of combination therapies [59][62] Question: Commercialization readiness and market engagement - The commercialization team is actively engaged in market shaping activities and building operational capabilities for future product launches [73][74] Question: Summit partnership and prioritization of combinations - Management noted that while they cannot provide specific prioritization details, they are excited about the collaboration and its potential across various solid tumors [78][80]

Financial Data and Key Metrics Changes - The company ended Q2 2025 with $2.1 billion in cash and investments, including $250 million from the Royalty Pharma partnership [19] - R&D expenses increased to $224.1 million in 2025 from $134.9 million in 2024, primarily due to clinical trial and manufacturing expenses [20] - G&A expenses rose to $40.6 million in 2025 from $21.7 million in 2024, driven by personnel-related expenses and stock-based compensation [21] - The net loss for 2025 was $247.8 million, compared to $133.2 million in 2024, attributed to higher operating expenses [22] - The projected full-year 2025 GAAP net loss is estimated to be between $1.03 billion and $1.09 billion [23] Business Line Data and Key Metrics Changes - The company has three clinical-stage RasOn inhibitors: TiraxonRasib, Oleuronrasib, and Zoldonrasib, with ongoing trials in pancreatic cancer and non-small cell lung cancer [6][10] - Diraxonrasib received breakthrough therapy designation from the FDA for previously treated metastatic pancreatic cancer with KRAS G12 mutations [7] - Oleuronrasib was granted breakthrough therapy designation for locally advanced or metastatic KRAS G12C non-small cell lung cancer [12] Market Data and Key Metrics Changes - Enrollment for the RESLU-302 Phase 3 trial in pancreatic cancer is progressing well, with expectations to complete enrollment this year [8] - The company is also initiating a first-line metastatic pancreatic cancer registrational trial, with plans to share trial design later this year [9] Company Strategy and Development Direction - The company aims to establish a leading global RAS-targeted franchise for treating RAS addicted cancers, focusing on innovative targeted therapies [17] - A partnership with Royalty Pharma provides $2 billion in committed capital to support clinical development and commercialization plans [18] - The company is preparing to enter clinical development for RMC-5127, a RasOn G12V selective inhibitor, expected to initiate a Phase 1 trial in 2026 [15] Management's Comments on Operating Environment and Future Outlook - Management emphasized the urgency of advancing development for patients with pancreatic cancer due to significant unmet medical needs [7] - The company is confident in its ability to establish new global standards of care for patients with RAS addicted cancers [24] - Management highlighted the importance of safety and tolerability in ongoing assessments to inform study designs for future trials [32] Other Important Information - The company is collaborating with Summit Therapeutics to evaluate combinations of their bispecific antibody with RasOn inhibitors [14] - The collaboration with Iambic aims to enhance drug discovery through AI capabilities, potentially improving lead discovery and optimization processes [16] Q&A Session Summary Question: Enrollment progress for RESLU-302 and chemotherapy combinations - Management indicated that enrollment is progressing well, with a solid position to share data in 2026. Efficacy assessments will inform study design, but safety and tolerability remain primary concerns [29][32] Question: Chemotherapy regimens and data readout in 2026 - Management confirmed that the chemotherapy regimens are within standard practice and that the 2026 data readout refers to the first analysis, which may be interim or final [40][42] Question: Data update for frontline pancreatic cancer trial - Management stated that they are building a sufficient data set to guide decision-making and will share more information as it becomes available [46] Question: RAF upregulation and combination therapies - Management acknowledged RAS amplification as a challenge but emphasized that therapeutic strategies are in place to address it. They also noted that there is no evidence that degraders are superior to inhibitors [60][62] Question: Commercialization readiness and field team build-out - Management confirmed that the US field team is being built out, with a focus on market shaping activities and engagement with oncologists [70][71]

Pipeline and Clinical Development - Daraxonrasib, a multi-selective RAS(ON) inhibitor, is being evaluated in a Phase 3 trial for 2L metastatic PDAC and has planned Phase 3 initiations for 1L metastatic and adjuvant resectable PDAC [15] - Elironrasib, a G12C-selective inhibitor, shows promising antitumor activity in previously treated RAS G12C NSCLC, with an objective response rate (ORR) of 56% (20 out of 36 patients) and a disease control rate (DCR) of 94% (34 out of 36 patients) at 200 mg BID [40] - Zoldonrasib, a G12D-selective inhibitor, demonstrates initial activity in previously treated KRAS G12D NSCLC, with an ORR of 61% (11 out of 18 patients) and a DCR of 89% (16 out of 18 patients) at 1200 mg QD [72] Daraxonrasib Clinical Data - In 2L PDAC patients treated with daraxonrasib at 300 mg daily, the median PFS was 85 months in RAS mutant patients, and the OS rate at 6 months was 97% [24] - In 2L/3L RAS G12X NSCLC patients treated with daraxonrasib at 120-220 mg daily, the median PFS was 98 months and the median OS was 177 months [28] - Daraxonrasib combined with pembrolizumab +/- chemotherapy in 1L RAS mutant NSCLC showed an ORR of 60% and a DCR of 90% in patients with TPS < 50%, and an ORR of 86% and a DCR of 100% in patients with TPS ≥ 50% [32] Financial Position - The company has a strong financial position with $21 billion in cash, cash equivalents, and marketable securities as of June 30, 2025 [119] - The company anticipates a 2025 GAAP Net Loss of $103 - $109 Billion [119]

Pipeline and Focus - Revolution Medicines' pipeline is led by three clinical-stage RAS(ON) inhibitors: Daraxonrasib (MULTI), Elironrasib (G12C), and Zoldonrasib (G12D)[6, 15] - The company's strategy is to maximize the impact of its RAS(ON) inhibitor portfolio by commercializing daraxonrasib initially in late-stage disease and developing RAS(ON) inhibitors in earlier lines of therapy[18, 19] - Revolution Medicines is also innovating for patients by producing new, differentiated drug candidates, including RMC-5127 (G12V-selective inhibitor) and next-generation programs[19, 15] Daraxonrasib (MULTI) - In 2L patients with KRAS G12X PDAC treated with daraxonrasib at 300 mg daily, the median PFS was 8.8 months, and the OS rate at 6 months was 100%[24] - In 2L/3L patients with RAS G12X NSCLC treated with daraxonrasib at 120-220 mg daily, the median PFS was 9.8 months, and the median OS was 17.7 months[28] - In 1L RAS mutant NSCLC patients treated with Daraxonrasib 100-200 mg + Pembrolizumab + Chemotherapy, the ORR was 60% and the DCR was 90% in the TPS < 50% subgroup[32] - In 1L RAS mutant NSCLC patients treated with Daraxonrasib 200 mg + Pembrolizumab, the ORR was 86% and the DCR was 100% in the TPS ≥ 50% subgroup[32] Elironrasib (G12C) - In previously treated RAS G12C NSCLC patients, Elironrasib (200 mg BID) showed an ORR of 56% and a DCR of 94%[40] - In previously treated RAS G12C NSCLC patients, Elironrasib (200 mg BID) showed a median PFS of 9.9 months[40] - In 1L RAS G12C NSCLC patients with TPS ≥ 50%, Elironrasib 200 mg BID + Pembrolizumab showed an ORR of 100% and a DCR of 100%[45] - In CRC patients previously treated with KRAS(OFF) G12C inhibitor, Elironrasib + Daraxonrasib doublet showed an ORR of 25% and a DCR of 92%[51] - In 2L+ NSCLC patients following G12C(OFF) inhibitor, Elironrasib showed an ORR of 42% and a DCR of 79%[55] - In 2L+ NSCLC patients following G12C(OFF) inhibitor, Elironrasib + Daraxonrasib showed an ORR of 62% and a DCR of 92%[56] Zoldonrasib (G12D) - In previously treated patients with KRAS G12D PDAC treated with 1200 mg daily dose, the ORR was 30% and the DCR was 80%[67] - In previously treated patients with KRAS G12D NSCLC treated with 1200 mg QD, the ORR was 61% and the DCR was 89%[72] Financials - Revolution Medicines has $2.1 billion in cash, cash equivalents, and marketable securities as of June 30, 2025[119] - The company anticipates a 2025 GAAP Net Loss of $1.03 – $1.09 billion, including $115 million to $130 million in non-cash stock-based compensation expense[119] - Royalty Pharma partnership bolsters financial position by providing $2 billion in flexible committed capital[116]