Financial Data and Key Metrics Changes - The company ended Q3 2025 with $1.93 billion in cash and investments, including a $250 million royalty monetization tranche received in June 2025, with an additional $1.75 billion in future committed capital under this arrangement [21] - R&D expenses for Q3 2025 were $262.5 million, up from $151.8 million in Q3 2024, primarily due to increased clinical trial-related and manufacturing expenses [21] - G&A expenses for Q3 2025 were $52.8 million, compared to $24.0 million in Q3 2024, driven by personnel-related expenses and increased commercial preparation activities [21] - The net loss for Q3 2025 was $305.2 million, compared to $156.3 million in Q3 2024, primarily due to higher operating expenses [22] - The company reiterated its 2025 financial guidance, expecting a full-year GAAP net loss between $1.03 billion and $1.09 billion [22] Business Line Data and Key Metrics Changes - Diraxonrasib has received three special designations from the FDA for its potential role in treating pancreatic cancer, including breakthrough therapy status and Orphan Drug designation [5][6] - The phase 3 trial, Resolute 302, for Diraxonrasib in second-line metastatic pancreatic cancer is nearing completion of enrollment, with data readout expected in 2026 [8] - Initial results for Diraxonrasib in first-line metastatic pancreatic cancer showed an objective response rate of 47% and a disease control rate of 89% [9] - The combination of Diraxonrasib with standard chemotherapy (GMP) demonstrated an objective response rate of 55% and a disease control rate of 90% [10] Market Data and Key Metrics Changes - The company is expanding its clinical programs in non-small cell lung cancer (NSCLC) and plans to initiate a registration trial in the first-line metastatic setting in 2026 [15] - Allieronrasib, a RAS-on G12C inhibitor, showed a confirmed objective response rate of 42% in heavily pretreated patients with G12C NSCLC [16] - The company is evaluating Zoledronrasib in a phase 1 monotherapy expansion cohort for previously treated NSCLC patients [17] Company Strategy and Development Direction - The company aims to build a leading global RAS-targeted medicines franchise, focusing on pancreatic, lung, and colorectal cancers [5] - The company is advancing its pipeline with multiple clinical trials, including the Resolute 303 trial for Diraxonrasib in first-line metastatic pancreatic cancer [10] - The company is exploring diverse combinations of RAS-on inhibitors with novel disease target inhibitors through collaborations [19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their RAS-on inhibitor portfolio to change standards of care across multiple cancer types [18] - The company is committed to understanding patient experiences with RAS-driven cancers and is expanding partnerships with advocacy organizations [24] - Management highlighted the importance of their strong financial position and expansive development plans to establish new global standards of care [23] Other Important Information - The company has made key appointments to strengthen its R&D and commercialization capabilities, including a new Chief Development Officer and regional leaders for the U.S. and European markets [19][20] Q&A Session Summary Question: Impact of FDA Commissioner's National Priority Voucher on Diraxonrasib timelines - Management indicated that the voucher could potentially shorten review timelines by one to two months and they are preparing for data readout and NDA submission [26] Question: Rationale for randomizing against observation in Resolute 304 trial - Management explained that requiring four months of standard care chemotherapy is to ensure uniformity in the patient population and to build upon the modest success seen with chemotherapy [32] Question: Expectations for phase 2 study results translating to phase 3 study - Management reassured that the patient populations in phase 1 and phase 3 studies are comparable, and they expect similar performance in the control arm [39] Question: Commercial readiness for Diraxonrasib - Management expressed confidence in their manufacturing capabilities and ongoing preparations for commercial launch readiness, including building a strong commercialization team [41] Question: Efficacy of combination treatment versus monotherapy - Management noted that both treatment strategies are being tested to evaluate their respective benefits, with updates expected in the first half of 2026 [46] Question: Commercial opportunity in the European Union - Management highlighted the significant patient population in Europe and their commitment to bringing Diraxonrasib to key markets [65] Question: Rationale for starting the adjuvant study before the first-line study - Management clarified that the adjuvant study is simpler and could be initiated earlier, without significant differences in overall conduct [70] Question: Resistance mechanisms in non-small cell lung cancer - Management indicated that data on resistance mechanisms in NSCLC is not yet mature for public disclosure, and the selection of pembrolizumab is based on its established role in standard care [76]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with $1.93 billion in cash and investments, including a $250 million royalty monetization tranche received in June 2025, with an additional $1.75 billion in future committed capital [21] - R&D expenses for Q3 2025 were $262.5 million, up from $151.8 million in Q3 2024, primarily due to increased clinical trial-related and manufacturing expenses [21][22] - G&A expenses rose to $52.8 million in Q3 2025 from $24.0 million in Q3 2024, driven by personnel-related expenses and increased commercial preparation activities [22] - The net loss for Q3 2025 was $305.2 million, compared to $156.3 million in Q3 2024, attributed to higher operating expenses [22] Business Line Data and Key Metrics Changes - Diraxonrasib, a key product, received three special designations from the FDA, including breakthrough therapy status and Orphan Drug designation, highlighting its potential in treating pancreatic cancer [5][6] - The Phase III trial, Resolute 302, for Diraxonrasib in second-line metastatic pancreatic cancer is nearing completion of enrollment, with data readout expected in 2026 [8][10] - Initial results for Diraxonrasib in first-line metastatic pancreatic cancer showed an objective response rate of 47% and a disease control rate of 89% [8][9] Market Data and Key Metrics Changes - The company is expanding its clinical programs in non-small cell lung cancer (NSCLC) with ongoing trials for Diraxonrasib and Allieronrasib, targeting both previously treated and first-line settings [15][16] - The Resolve 301 registration trial for Diraxonrasib in NSCLC continues to enroll patients in the U.S., Europe, and Japan [15] Company Strategy and Development Direction - The company aims to build a leading global franchise for RAS-targeted medicines, focusing on pancreatic, lung, and colorectal cancers [5][23] - Plans to initiate a registration trial for Zoledronrasib in combination with Diraxonrasib in first-line metastatic pancreatic cancer are set for the first half of 2026 [14] - The company is enhancing its commercialization capabilities with new key appointments in the U.S. and European regions [19][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their RAS-on inhibitor portfolio to change standards of care across multiple cancer types [18] - The company is committed to understanding patient experiences with RAS-driven cancers and is expanding partnerships with advocacy organizations [23] Other Important Information - The company reiterated its 2025 financial guidance, expecting a full-year GAAP net loss between $1.03 billion and $1.09 billion [22] - The company is on track to initiate the first-in-human trial for RMC 5127, an oral tri-complex RAS-on G12V selective inhibitor, in Q1 2026 [18] Q&A Session Summary Question: Impact of FDA Commissioner's National Priority Voucher on Diraxonrasib timelines - Management noted that the voucher could potentially shorten review timelines by one to two months and they are preparing for an NDA submission [26] Question: Rationale for randomizing against observation in Resolute 304 - Management explained that requiring four months of standard care chemotherapy is to ensure uniformity in the patient population and to build upon the modest success seen with chemotherapy [29][32] Question: Differences in patient characteristics between Phase II and Phase III studies - Management reassured that the patient populations in Phase I and Phase III studies are comparable, with historical data supporting this [36][39] Question: Commercial readiness for Diraxonrasib - Management highlighted strong manufacturing capabilities and ongoing efforts to build a talented commercialization team to ensure launch readiness [40][41] Question: Efficacy expectations for combination treatment versus monotherapy - Management indicated that both treatment strategies are being tested to evaluate their respective benefits, with updates expected in the first half of 2026 [44][46] Question: Commercial opportunity in the European Union - Management emphasized the significant patient population in Europe and the compelling value proposition for Diraxonrasib in the second-line pancreatic cancer indication [63][65] Question: Rationale for starting the adjuvant study before the first-line study - Management clarified that the adjuvant study is simpler and could be initiated earlier, without significant implications for overall conduct [68][70] Question: Resistance mechanisms in non-small cell lung cancer - Management stated that data on resistance mechanisms in NSCLC is not yet mature enough for public disclosure, and the selection of pembrolizumab is based on its established role in standard care [73][76]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with $1.93 billion in cash and investments, including a $250 million royalty monetization tranche received in June 2025, with an additional $1.75 billion in future committed capital under this arrangement [21][22] - R&D expenses for Q3 2025 were $262.5 million, up from $151.8 million in Q3 2024, primarily due to increased clinical trial-related and manufacturing expenses [21][22] - G&A expenses for Q3 2025 were $52.8 million, compared to $24.0 million in Q3 2024, driven by personnel-related expenses and increased commercial preparation activities [21][22] - The net loss for Q3 2025 was $305.2 million, compared to $156.3 million in Q3 2024, attributed to higher operating expenses [21][22] - The company reiterated its 2025 financial guidance, expecting a full-year GAAP net loss between $1.03 billion and $1.09 billion [22] Business Line Data and Key Metrics Changes - Diraxonrasib, the company's lead product, has received three special designations from the FDA for its potential in treating pancreatic cancer, including breakthrough therapy status and orphan drug designation [4][5] - The phase 3 trial, Resolute 302, for Diraxonrasib in second-line metastatic pancreatic cancer is nearing completion of enrollment, with data readout expected in 2026 [7][9] - Initial results for Diraxonrasib in first-line metastatic pancreatic cancer showed an objective response rate of 47% and a disease control rate of 89% for monotherapy [8] - The combination of Diraxonrasib with standard chemotherapy (GMP) demonstrated an objective response rate of 55% and a disease control rate of 90% [8][9] Market Data and Key Metrics Changes - The company is expanding its clinical programs in non-small cell lung cancer (NSCLC) with ongoing trials for Diraxonrasib and Allieronrasib, targeting both previously treated and first-line metastatic settings [14][15] - The Resolve 301 registration trial for Diraxonrasib versus docetaxel in RAS mutant NSCLC continues to enroll patients in the U.S., Europe, and Japan [14] - The company is also evaluating Zoledronrasib in a phase 1 monotherapy expansion cohort for previously treated NSCLC [16] Company Strategy and Development Direction - The company aims to build a leading global franchise for RAS-targeted medicines, focusing on pancreatic, lung, and colorectal cancers [4][18] - There is a strong emphasis on advancing clinical trials and expanding partnerships to enhance treatment strategies for RAS-addicted cancers [18] - The company is committed to patient-friendly clinical protocols and educational initiatives, aligning with global awareness months for pancreatic and lung cancers [23] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of their RAS-on inhibitor portfolio to change standards of care across multiple cancer types [17] - The company is actively preparing for data readouts and NDA submissions, leveraging the FDA's National Priority Voucher to potentially accelerate review timelines [26][27] - Management highlighted the importance of ongoing collaborations to explore diverse treatment strategies and combinations [18] Other Important Information - The company has made key appointments to strengthen its R&D and commercialization capabilities, including a new Chief Development Officer and regional leaders for U.S. and European markets [18][19] - The company is exploring various combinations of RAS-on inhibitors with novel disease target inhibitors to expand treatment options [18] Q&A Session Summary Question: Impact of FDA Commissioner's National Priority Voucher on Diraxonrasib timelines - Management indicated that the voucher could potentially shorten review timelines by one to two months and they are preparing aggressively for data readout and NDA submission [26][27] Question: Rationale for randomizing against observation in Resolute 304 trial - Management explained that requiring four months of standard care chemotherapy is to ensure uniformity in the patient population and build upon the modest success seen with chemotherapy [30][32] Question: Expectations for phase 2 study results translating to phase 3 study - Management reassured that the patient populations in phase 1 and phase 3 studies are comparable, and they expect similar performance in the control arm based on historical data [39][40] Question: Commercial readiness and manufacturing capacity - Management confirmed strong organizational and supply chain capabilities to support product launch and emphasized ongoing preparations for commercialization readiness [41][42] Question: Efficacy of combination treatment versus monotherapy - Management highlighted that both treatment strategies are being tested to evaluate their potential benefits, with updates expected in the first half of 2026 [46][48] Question: Commercial opportunity in the European Union - Management expressed confidence in the market potential for Diraxonrasib in Europe, emphasizing the significant number of patients to treat and the compelling value proposition [68] Question: Rationale for starting the adjuvant study before the first-line study - Management clarified that the adjuvant study is simpler and could be initiated earlier, without significant implications for overall conduct [70]