Q2 2026 Revolution Medicines Inc Earnings Call

August 5, 2026

Operator: Good day, and thank you for standing by. Welcome to the Revolution Medicines Q2 2026 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan Asay, Senior Vice President, Corporate Affairs. Please go ahead.

Speaker #1: Good day, and thank you for standing by. Welcome to the Revolution Medicines Q2, 2026 earnings conference call. At this time, all participants are in a listen-only mode.

Speaker #1: there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. question, please press star 11 again.

Speaker #1: raised. To withdraw your today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan Asay, Senior Vice President, Corporate Affairs.

Speaker #1: ahead.

Speaker #2: Thank you, and welcome everyone to the second quarter of 2026

Ryan Asay: Thank you, and welcome everyone to the Q2 2026 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer, Dr. Alan Sandler, our Chief Development Officer, and Jack Anders, our Chief Financial Officer. Dr. Wei Lin, our Chief Medical Officer, and Anthony Mancini, our Chief Global Commercialization Officer, will join us for the Q&A portion of today's call. We would like to inform you that certain statements we make during this call will be forward-looking, because such statements deal with future events and are subject to many risks and uncertainties. Actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the US Securities and Exchange Commission.

Speaker #2: Earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer; Dr. Alan Sandler, our Chief Development Officer; and Jack Anders, our Chief Financial Officer.

Speaker #2: Dr. Wei Lin, our Chief Medical Please go Officer, and Anthony Mancini, our Chief Global Commercialization Officer, will join us for the Q&A portion of today's call.

Speaker #2: We would like to inform you that certain statements we make during this call will be forward-looking because such statements deal with future events and are subject to many risks and uncertainties.

Speaker #2: Actual results may differ materially from those in the forward-looking statements. For full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly report on Form 10-Q that are filed with the U.S.

Speaker #2: Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended June 30, 2026, and recent corporate updates. The press release and updated corporate presentation are available in the Investors section of our website at revmed.com.

Ryan Asay: This afternoon, we released financial results for the quarter ended June 30, 2026, and recent corporate updates. The press release and updated corporate presentation are available on the investors section of our website at revmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer. Mark?

Speaker #2: With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer. Mark,

Speaker #3: Thank you, Ryan, and thanks to everyone for joining us this afternoon. I'll begin today's call with initial remarks focused primarily on pancreatic cancer, and then Dr. Sandler will provide highlights of recent results and plans in non-small cell lung cancer.

Mark Goldsmith: Thank you, Ryan, and thanks to everyone for joining us this afternoon. I'll begin today's call with initial remarks focused primarily on pancreatic cancer, and then Dr. Sandler will provide highlights of recent results and plans in non-small cell lung cancer. Jack Anders will then summarize our Q2 financial results before I share some closing comments and open the call to questions and answers. 2026 is proving to be a transformational year for Revolution Medicines, with substantial progress in many dimensions, supporting our mission to revolutionize treatment for patients with RAS-addicted cancers globally through the discovery, development, and delivery of innovative targeted medicines. We've continued to build on strong momentum in pancreatic cancer, reinforced by compelling results from RASolute 302, our recently completed global Phase III study in patients with previously treated metastatic disease.

Speaker #3: Jack Anders will then summarize our second quarter financial results before I share some closing comments and open the call to questions and answers. 2026 is proving to be a transformational year for Revolution Medicines.

Speaker #3: With substantial progress in many dimensions, supporting our mission to revolutionize treatment for patients with RAS-addicted cancers globally through the discovery, development, and delivery of innovative targeted medicines.

Speaker #3: We've continued to build on strong momentum in pancreatic cancer, reinforced by compelling results from Resolute 302, our recently completed global Phase III study in patients with previously treated metastatic disease.

Speaker #3: Catalyzed by the unprecedented clinical results, we quickly expanded availability to patients through our FDA-cleared expanded access program, advanced regulatory activities in support of potential approvals, strengthened our commercial readiness globally, and continued to expand our broad pioneering R&D pipeline targeting RAS-driven cancers.

Mark Goldsmith: Catalyzed by the unprecedented clinical results, we quickly expanded availability to patients through our FDA-cleared expanded access program, advanced regulatory activities in support of potential approvals, strengthened our commercial readiness globally, and continued to expand our broad pioneering R&D pipeline targeting RAS-driven cancers. I'd like to spend a few more minutes reviewing some of these activities in more detail. First, at the American Society of Clinical Oncology, or ASCO, Dr. Brian Wolpin presented the full results from RASolute 302, which were also published simultaneously in "The New England Journal of Medicine." The data demonstrated paradigm-changing clinical outcomes with daraxonrasib monotherapy in patients with previously treated metastatic pancreatic cancer, including statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and patient-reported quality of life indicators compared to chemotherapy, along with a manageable safety and tolerability profile.

Speaker #3: I'd like to spend a few more minutes reviewing some of these activities in more detail. First set the American Society of Clinical Oncology, or ASCO, Dr. Brian Wolpen presented the full results from Resolute 302, which were also published simultaneously in the New England Journal of Medicine.

Speaker #3: The data demonstrated paradigm-changing clinical outcomes with Durexon-RASID monotherapy in patients with previously treated metastatic pancreatic cancer, including statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and patient-reported quality of life indicators compared to chemotherapy along with a manageable safety and tolerability profile.

Speaker #3: Second, based on these and earlier results, we believe Durexon-RASID represents a major advance for patients facing one of the most difficult-to-treat cancers and we are moving with urgency to make this potential new treatment available to eligible patients as quickly as possible.

Mark Goldsmith: Second, based on these and earlier results, we believe daraxonrasib represents a major advance for patients facing one of the most difficult to treat cancers, and we are moving with urgency to make this potential new treatment available to eligible patients as quickly as possible. In particular, since announcing our expanded access program shortly after disclosing top-line results from RASolute 302, we've made significant progress establishing access through healthcare providers across the United States. It has been deeply gratifying to activate sites participating in the program in almost all 50 US states and Puerto Rico, including both academic cancer centers and community oncology practices, with many additional sites still coming online to begin treating patients through the program. To date, our team has approved greater than 90% of reviewed requests and has provided daraxonrasib on behalf of more than 2,000 eligible patients.

Speaker #3: In particular, since announcing our expanded access program shortly after disclosing top-line results from Resolute 302, we've made significant progress establishing access through healthcare providers across the United States.

Speaker #3: It has been deeply gratifying to activate sites participating in the program in almost all 50 U.S. states and Puerto Rico, including both academic cancer centers and community oncology practices, with many additional sites still coming online to begin treating patients through the program.

Speaker #3: To date, our team has approved greater than 90% of reviewed requests and has provided Durexon-RASID on behalf of more than 2,000 eligible patients. Our teams continue working closely with investigators, healthcare providers, patient advocacy organizations, and regulators to make this possible and we're proud of the progress so far on behalf of patients.

Mark Goldsmith: Our teams continue working closely with investigators, healthcare providers, patient advocacy organizations, and regulators to make this possible. We're proud of the progress so far on behalf of patients. I'm also very pleased to note that our new drug application for daraxonrasib in pancreatic cancer has been accepted for review by the U.S. Food and Drug Administration. We continue to engage constructively with the FDA as they review this application. We're also making progress with additional regulatory authorities around the world. The European Medicines Agency, or EMA, recently announced that it had designated daraxonrasib as a high priority under EMA's Cancer Medicines Pathfinder Project based on its potential to address a high unmet medical need, and that it has started a phased review of daraxonrasib with the goal of accelerating assessment by evaluating the data as they become available ahead of the submission of a full marketing authorization application.

Speaker #3: I'm also very pleased to note that our new drug application for Durexon-RASID in pancreatic cancer has been accepted for review by the U.S. Food and Drug Administration.

Speaker #3: We continue to engage constructively with the FDA as they review this application. We're also making progress with additional regulatory authorities around the world. The European Medicines Agency, or EMA, recently announced that it had designated Durexon-RASID as a high priority under EMA's Cancer Medicines Pathfinder Project, based on its potential to address a high unmet medical need, and that it has started a phased review of Durexon-RASID with the goal of accelerating assessment by evaluating the data as they become available, ahead of the submission of a full marketing authorization application.

Speaker #3: We look forward to continuing collaborative interactions with the EMA and other health authorities around the world as we work to bring Durexon-RASID to patients as quickly as possible.

Mark Goldsmith: We look forward to continuing collaborative interactions with the EMA and other health authorities around the world as we work to bring daraxonrasib to patients as quickly as possible. Third, we continue preparing for a successful launch. In the US, our medical affairs organization has been in the field for over a year and continues to actively engage the oncology community through scientific exchange. We have also built the commercial infrastructure needed to support launch. Our sales organization is in place, our field access team is operational, and our OnPath patient services program, commercial supply, and distribution network are ready. We are well positioned to serve patients with pancreatic cancer from day one. Internationally, we continue to build our launch capabilities at an accelerating pace, positioning us to support future commercialization across key markets.

Speaker #3: Third, we continue preparing for successful launch. In the U.S., our medical affairs organization has been in the field for over a year, and continues to actively engage the oncology community through scientific exchange.

Speaker #3: We have also built the commercial infrastructure needed to support launch. Our sales organization is in place, our field access team is operational, and our OnPath patient services program, commercial supply, and distribution network are ready.

Speaker #3: We are well positioned to serve patients with pancreatic cancer from day one. Internationally, we continue to build our launch capabilities at an accelerating pace, positioning us to support future commercialization across key markets.

Speaker #3: Subject to regulatory approvals, we believe we are well-positioned to execute a strong launch, and deliver Durexon-RASID to patients quickly and broadly. Fourth, with our commitment to pancreatic cancer extending well beyond previously treated disease, we continue prosecuting a comprehensive development strategy involving multiple RASID inhibitors across lines of treatment.

Mark Goldsmith: Subject to regulatory approvals, we believe we are well positioned to execute a strong launch and deliver daraxonrasib to patients quickly and broadly. Fourth, with our commitment to pancreatic cancer extending well beyond previously treated disease, we continue prosecuting a comprehensive development strategy involving multiple RAS(ON) inhibitors across lines of treatment. With daraxonrasib, enrollment continues in the RASolute 303 and 304 phase III programs in the first-line metastatic and adjuvant settings respectively. With zoldonrasib, our RAS(ON) G12D selective covalent inhibitor, the RASolute 305 phase III trial in first-line metastatic pancreatic cancer is also enrolling and treating patients. Further, we recently initiated RASolute 309, evaluating the novel RAS(ON) inhibitor doublet of daraxonrasib plus zoldonrasib in the first-line treatment setting.

Speaker #3: With Durexon-RASID enrollment continues in the Resolute 303 and 304 phase III programs, in the first-line metastatic and adjuvant settings, respectively, with Zoldon-RASID, our RASID G12D selective covalent inhibitor, the Resolute 305 phase III trial in first-line metastatic pancreatic cancer, is also enrolling in treating patients.

Speaker #3: Further, we recently initiated Resolute 309, evaluating the novel RASID inhibitor doublet of Durexon-RASID plus Zoldon-RASID in the first-line treatment setting. These trials are supported by strong clinical data and continue to generate significant interest from investigators and patients around the world who recognize both the unmet needs and the underlying scientific rationale for these treatment strategies.

Mark Goldsmith: These trials are supported by strong clinical data and continue to generate significant interest from investigators and patients around the world who recognize both the unmet needs and the underlying scientific rationale for these treatment strategies. At last month's European Society for Medical Oncology's Gastrointestinal Cancers Congress, or ESMO GI, we presented new pancreatic cancer data for zoldonrasib that reinforced its compelling profile and the breadth of our development strategy in pancreatic cancer specifically, including the differentiated first-line treatment approaches underlying the RASolute 305 and 309 trials. In one study reported at ESMO GI, zoldonrasib, combined with standard of care chemotherapy, showed compelling preliminary antitumor activity in first-line treatment of patients with RAS G12D pancreatic cancer, including objective response rates of 82% and 61%, and disease control rates of 96% and 90%, in combination with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel, respectively.

Speaker #3: At last month's European Society for Medical Oncology's Gastrointestinal Cancers Congress, or ISMOGI, we presented new pancreatic cancer data for Zoldon-RASID that reinforced its compelling profile and the breadth of our development strategy in pancreatic cancer specifically, including the differentiated first-line treatment approaches underlying the Resolute 305 and 309 trials.

Speaker #3: In one study reported at ISMOGI, Zoldon-RASID combined with standard-of-care chemotherapy showed compelling preliminary anti-tumor activity in first-line treatment of patients with RASID G12D pancreatic cancer.

Speaker #3: Including objective response rates of 82% and 61%, and disease control rates of 96% and 90% in combination with modified FOLFIRINOX or gemcitabine plus NABPAC/LYTAXEL, respectively.

Speaker #3: Longer follow-up will further establish the durability profiles for these regimens. These combinations also demonstrated favorable safety and tolerability profiles with treatment-related adverse events broadly consistent with the established profiles of each respective chemotherapy component.

Mark Goldsmith: Longer follow-up will further establish the durability profiles for these regimens. These combinations also demonstrated favorable safety and tolerability profiles, with treatment-related adverse events broadly consistent with the established profiles of each respective chemotherapy component. These encouraging findings strongly support the global pivotal phase III RASolute 305 study of zoldonrasib plus chemotherapy in first-line treatment of patients with RAS G12D pancreatic cancer. In a second study reported at ESMO GI, the RAS(ON) inhibitor doublet of daraxonrasib plus zoldonrasib demonstrated compelling preliminary clinical activity in second and third-line or later treatment of patients with RAS G12D pancreatic cancer, including objective response rates of 50% and 47%, and disease control rates of 97% and 90%, respectively, observations that are consistent with earlier preclinical studies.

Speaker #3: These encouraging findings strongly support the global pivotal Phase III RESOLUTE-305 study of Zolad-RASID plus chemotherapy in first-line treatment of patients with RASID G12D pancreatic cancer.

Speaker #3: In a second study reported at ISMOGI, the RASID inhibitor doublet of Durexon-RASID plus Zoldon-RASID demonstrated compelling preliminary clinical activity in second and third-line or later treatment of patients with RASID G12D pancreatic cancer, including objective response rates of 50% and 47%, and disease control rates of 97% and 90%, respectively, observations that are consistent with earlier preclinical studies.

Speaker #3: Earlier indicators of durability for this combination are also compelling showing median progression-free survival of 9.6 months and 7.6 months in patients in second and third-line treatment or later, respectively.

Mark Goldsmith: Earlier indicators of durability for this combination are also compelling, showing median progression free survival of 9.6 months and 7.6 months in patients in second and third-line treatment or later, respectively. Median overall survival in the second-line setting was not yet reached, while the median overall survival in the third-line or later setting was 10.5 months. The combination also showed a favorable safety and tolerability profile. Treatment-related adverse events were broadly consistent with the established profile of daraxonrasib monotherapy. These encouraging preliminary results support the planned global pivotal phase III RASolute 309 study evaluating the combination of daraxonrasib plus zoldonrasib as first-line treatment in patients with RAS G12D pancreatic cancer. Our RAS(ON) inhibitors are also being evaluated in combination with other investigational approaches, including with MTA-cooperative PRMT5 inhibitors through clinical collaborations with Tango Therapeutics and Bristol-Myers Squibb.

Speaker #3: Median overall survival in the second-line setting was not yet reached, while the median overall survival in the third-line or later setting was 10.5 months.

Speaker #3: The combination also showed a favorable safety and tolerability profile. Treatment-related adverse events were broadly consistent with the established profile of Durexon-RASID monotherapy. These encouraging preliminary results support the planned global pivotal phase III Resolute 309 study evaluating the combination of Durexon-RASID plus Zoldon-RASID as first-line treatment in patients with RASID G12D pancreatic cancer.

Speaker #3: Our RASID inhibitors are also being evaluated in combination with other investigational approaches, including with MTA cooperative PRMT5 inhibitors through clinical collaborations with Tango Therapeutics and Bristol-Myers Squibb.

Speaker #3: I'd also like to note that RMC-5127, our RASID G12D-selective inhibitor, continues in the ongoing first-in-human study. To date, RMC-5127 has been well tolerated at all dose levels evaluated, with no dose-limiting toxicities reported so far.

Mark Goldsmith: I'd also like to note that RMC-5127, our RAS(ON) G12V selective inhibitor, continues in the ongoing first-in-human study. To date, RMC-5127 has been well tolerated at all dose levels evaluated, with no dose-limiting toxicities reported so far. Encouraging early signs of antitumor activity have been seen across multiple tumor types, including objective responses starting at the first dose level. Overall, we are increasingly confident in our ability to help redefine the standard of care for patients with pancreatic cancer across the continuum of disease, from early-stage settings to advanced metastatic disease, and across RAS tumor genotypes. With these opportunities comes a profound responsibility for Revolution Medicines that we take very seriously. Recognizing that every patient's disease and treatment journey is unique, and treatment optionality may best serve the collective unmet needs, we remain committed to developing a broad portfolio of potential treatment options as quickly as possible.

Speaker #3: Encouraging early signs of anti-tumor activity have been seen across multiple tumor types including objective responses starting at the first dose level. Overall, we are increasingly confident in our ability to help redefine the standard of care for patients with pancreatic cancer across the continuum of disease, from early-stage settings to advanced metastatic disease and across RASID tumor genotypes.

Speaker #3: With these opportunities comes a profound responsibility for revolution medicines that we take very seriously. Recognizing that every patient's disease and treatment journey is unique, and treatment optionality may best serve the collective unmet needs, we remain committed to developing a broad portfolio of potential treatment options as quickly as possible.

Speaker #3: I'll now turn the call over to Alan to discuss our progress and expanding efforts in non-small cell lung cancer along with other pipeline updates.

Mark Goldsmith: I'll now turn the call over to Alan to discuss our progress and expanding efforts in non-small cell lung cancer, along with other pipeline updates. Alan?

Speaker #3: Alan?

Speaker #2: Thank you, Mark. While pancreatic cancer remains an important and immediate opportunity for revolution medicines, non-small cell lung cancer represents another major malignancy where, despite meaningful advances in treatment, significant unmet needs remain.

Alan Sandler: Thank you, Mark. While pancreatic cancer remains an important and immediate opportunity for Revolution Medicines, non-small cell lung cancer represents another major malignancy where, despite meaningful advances in treatment, significant unmet needs remain. There is growing evidence that our RAS(ON) inhibitor portfolio has the potential to significantly improve outcomes for patients with RAS-driven non-small cell lung cancer. We believe daraxonrasib has the potential to become an important treatment option for patients with non-small cell lung cancer. Based on encouraging previously reported non-small cell lung cancer results in patients with tumors carrying diverse RAS mutations other than RAS G12C, the US FDA granted breakthrough therapy designation to daraxonrasib for previously treated metastatic non-small cell lung cancer with KRAS mutations other than G12C who have received prior platinum-based chemotherapy and anti-PD-L1 or PD-1 antibody therapy.

Speaker #2: There is growing evidence that our RASID inhibitor portfolio has the potential to significantly improve outcomes for patients with RASID-driven non-small cell lung cancer. We believe Durexon-RASID has the potential to become an important treatment option for patients with non-small cell lung cancer.

Speaker #2: Based on encouraging previously reported non-small cell lung cancer results in patients with tumors carrying diverse RASID mutations other than RASID G12C, the USFDA granted breakthrough therapy designation to Durexon-RASID for previously treated metastatic non-small cell lung cancer with KRAS mutations other than G12C, who have received prior platinum-based chemotherapy and anti-PD-L1 or PD-1 antibody therapy.

Speaker #2: Building on these encouraging phase I, II results, Resolve 301, our ongoing global phase III registrational study in patients with previously treated RASID mutant non-small cell lung cancer continues to see high demand and is enrolling well.

Alan Sandler: Building on these encouraging phase I/II results, RASolve 301, our ongoing global phase III registrational study in patients with previously treated RAS mutant non-small cell lung cancer continues to see high demand and is enrolling well. We also believe that combining targeted RAS(ON) inhibition with innovative bispecific antibodies targeting both the PD-1, PD-L1, and VEGF axes has the potential to improve outcomes for patients with previously untreated metastatic non-small cell lung cancer. In particular, through our ongoing clinical collaboration with Summit Therapeutics, we are evaluating daraxonrasib in combination with ivonescimab, Summit's PD-1, VEGF bispecific antibody, and platinum doublet therapy in first-line non-small cell lung cancer. With impactful targeted therapies available now for patients with non-small cell lung cancer with tumors harboring EGFR, ALK, ROS1, RET, KRAS G12C, or other genetic alterations, we recognize that practitioners increasingly view treatment of lung cancer through a biomarker-directed lens.

Speaker #2: We also believe that combining targeted RASID inhibition with innovative bispecific antibodies targeting both the PD-1, PD-L1, and VEGF axes has the potential to improve outcomes for patients with previously untreated metastatic non-small cell lung cancer.

Speaker #2: In particular, through our ongoing clinical collaboration with Summit Therapeutics, we are evaluating Durexon-RASID in combination with Avon Nesemab, Summit's PD-1/VEGF bispecific antibody, and platinum doublet therapy in first-line non-small cell lung cancer.

Speaker #2: With impactful targeted therapies available now for patients with non-small cell lung cancer, with tumors harboring EGFR, ALK, ROS1, RET, KRAS G12C, or other genetic alterations, we recognize that practitioners increasingly view treatment of lung cancer through a biomarker-directed lens.

Speaker #2: In the context of RASID-driven disease, significant unmet needs remain across patients with non-small cell lung cancer carrying diverse RASID mutations for which no approved targeted therapies have been approved.

Alan Sandler: In the context of RAS-driven disease, significant unmet needs remain across patients with non-small cell lung cancer carrying diverse RAS mutations for which no approved targeted therapies have been approved. Revolution Medicines is uniquely positioned to address these needs through our broad and differentiated pipeline of targeted inhibitors. Approximately 30% of patients with non-small cell lung cancer have tumors harboring a RAS mutation, and our RAS(ON) mutant-selective inhibitors, elironrasib, zoldonrasib, and RMC-5127, targeting RAS G12C, G12D, and G12V respectively, have the potential to address over 70% of RAS-driven mutations in this disease. In the first-line setting, we're actively evaluating elironrasib and zoldonrasib in combination with the current standard of care regimen of pembrolizumab plus platinum doublet chemotherapy. We've previously reported phase I data for zoldonrasib and elironrasib monotherapy in previously treated RAS G12D or G12C non-small cell lung cancer respectively, each exhibiting highly encouraging monotherapy efficacy and safety profiles.

Speaker #2: Revolution Medicines is uniquely positioned to address these needs through our broad and differentiated pipeline of targeted inhibitors. Approximately 30% of patients with non-small cell lung cancer have tumors harboring a RAS-identified mutation.

Speaker #2: And our RAS(ON) mutant-selective inhibitors—Eleron-RAS(ON), Zoldon-RAS(ON), and RMC-5127—targeting RAS(ON) G12C, G12D, and G12B, respectively, have the potential to address over 70% of RAS(ON)-driven mutations in this disease.

Speaker #2: In the first-line setting, we're actively evaluating Eleron-RASID and Zoldon-RASID in combination with the current standard of care regimen of pembrolizumab plus platinum doublet chemotherapy.

Speaker #2: We've previously reported phase I data for Zoldon-RASID and Eleron-RASID monotherapy in previously treated RASID G12D or G12C non-small cell lung cancer, respectively. Each exhibiting highly encouraging monotherapy efficacy and safety profiles.

Speaker #2: Today, I'm pleased to share new observations for each of these compounds in combination with pembrolizumab and chemotherapy in patients with previously untreated non-small cell lung cancer.

Alan Sandler: Today, I'm pleased to share new observations for each of these compounds in combination with pembrolizumab and chemotherapy in patients with previously untreated non-small cell lung cancer, data which we believe demonstrate the differentiated and compelling potential of our RAS(ON) mutant-selective inhibitors in this treatment context. I'll begin with zoldonrasib, our RAS(ON) G12D selective inhibitor. The baseline characteristics of patients enrolled in this cohort are representative of the KEYNOTE-189 study population, which evaluated pembrolizumab plus platinum doublet chemotherapy. The principal difference is a somewhat lower proportion of patients with high PD-L1 expression, while other key demographic and disease characteristics are broadly consistent with expectations for patients with previously untreated metastatic non-small cell lung cancer. Taken together, these baseline characteristics provide an appropriate context for interpreting the safety and efficacy observations I'll discuss next. The safety profile of zoldonrasib was highly encouraging.

Speaker #2: Data which we believe demonstrate the differentiated and compelling potential of our RASID mutant selective inhibitors in this treatment context. I'll begin with Zoldon-RASID, our RASID G12D selective inhibitor.

Speaker #2: The baseline characteristics of patients enrolled in this cohort are representative of the KEYNOTE-189 study population, which evaluated pembrolizumab plus platinum doublet chemotherapy. The principal difference is a somewhat lower proportion of patients with high PD-L1 expression.

Speaker #2: While other key demographic and disease characteristics are broadly consistent with expectations for patients with previously untreated metastatic non-small cell lung cancer, taken together, these baseline characteristics provide an appropriate context for interpreting the safety and efficacy observations I'll discuss next.

Speaker #2: The safety profile of Zoldon-RASID was highly encouraging. Treatment-related adverse events were, again, broadly consistent with the established profile of pembrolizumab plus chemotherapy. With no new or unexpected safety signals observed.

Alan Sandler: Treatment-related adverse events were again broadly consistent with the established profile of pembrolizumab plus chemotherapy, with no new or unexpected safety signals observed. With a data cutoff of 11 May 2026, the majority of adverse events were Grade 1 or Grade 2. No Grade 5 treatment-related adverse events were reported, and there was a low incidence of liver enzyme elevations, which were manageable with standard dose modifications. The combination of zoldonrasib with pembrolizumab and platinum-based chemotherapy demonstrated encouraging antitumor activity in patients with previously untreated KRAS G12D non-small cell lung cancer. With a data cutoff of 11 May 2026, and median follow-up of 3.4 months, the objective response rate was 82%, with disease control achieved in all evaluable patients. Importantly, responses were observed across PD-L1 expression subgroups, including patients with low PD-L1 expression, supporting the broad activity of this combination. Although follow-up remains early, these findings provide encouraging evidence supporting this differentiated treatment strategy. Overall, these findings support the continued development of zoldonrasib in combination with standard of care.

Speaker #2: With the data cutoff of May 11, 2026, the majority of adverse events were grade I or grade II. No grade V treatment-related adverse events were reported, and there was a low incidence of liver enzyme elevations, which were manageable, with standard dose modifications.

Speaker #2: The combination of Zoldon-RASID with pembrolizumab and platinum-based chemotherapy demonstrated encouraging anti-tumor activity in patients with previously untreated KRAS G12D non-small cell lung cancer. With the data cutoff of May 11, 2026, and median follow-up of 3.4 months, the objective response rate was 82%, with disease control achieved in all valuable patients.

Alan Sandler: With a data cutoff of 11 May 2026, and median follow-up of 3.4 months, the objective response rate was 82%, with disease control achieved in all evaluable patients. Importantly, responses were observed across PD-L1 expression subgroups, including patients with low PD-L1 expression, supporting the broad activity of this combination. Although follow-up remains early, these findings provide encouraging evidence supporting this differentiated treatment strategy. Overall, these findings support the continued development of zoldonrasib in combination with standard of care.

Speaker #2: Importantly, responses were observed across PD-L1 expression subgroups, including patients with low PD-L1 expression, supporting the broad activity of this combination. And although follow-up remains early, these findings provide encouraging evidence supporting this differentiated treatment strategy.

Alan Sandler: Turning now to elironrasib, our RAS(ON) G12C selective inhibitor. As with the zoldonrasib cohort, the baseline characteristics of patients enrolled in this study are generally representative of the population treated in pembrolizumab plus platinum doublet chemotherapy. The primary difference being a somewhat lower proportion of patients with PD-L1 negative subgroup, and a higher proportion of patients with PD-L1 expression in the 1% to 49% subgroup. Overall, these baseline characteristics establish an appropriate context for interpreting the efficacy and safety observations I'll review next. Elironrasib continues to demonstrate a manageable safety and tolerability profile in combination with pembrolizumab and chemotherapy.

Speaker #2: Overall, these findings support the continued development of Zoldon-RASID in combination with standard of care. Turning now to Eleron-RASID, our RASID G12C selective inhibitor. As with the Zoldon-RASID cohort, the baseline characteristics of patients enrolled in this study are generally representative of the population treated in pembrolizumab plus platinum doublet chemotherapy.

Speaker #2: The primary difference being a somewhat lower proportion of patients in the PD-L1 negative subgroup, and a higher proportion of patients with PD-L1 expression in the 1–49% subgroup.

Speaker #2: Overall, these baseline characteristics establish an appropriate context for interpreting the efficacy and safety observations I'll review next. Eleron-RASID continues to demonstrate a manageable safety and tolerability profile in combination with pembrolizumab and chemotherapy.

Speaker #2: Treatment-related adverse events were consistent with the established safety profile of pembrolizumab-based chemotherapy, with minimal evidence of additive toxicity attributable to Eleron-RASID. We were particularly encouraged by the favorable liver safety profile with relatively few grade III or higher transaminase elevations and no unexpected safety findings.

Alan Sandler: Treatment-related adverse events were consistent with the established safety profile of pembrolizumab-based chemotherapy, with minimal evidence of additive toxicity attributable to elironrasib. We were particularly encouraged by the favorable liver safety profile, with relatively few grade 3 or higher transaminase elevations and no unexpected safety findings. Turning now to efficacy of elironrasib in combination with pembrolizumab and chemotherapy. Similar to what we observed with zoldonrasib, we have observed highly encouraging antitumor activity with elironrasib in combination with pembrolizumab and platinum-based chemotherapy in patients with previously untreated RAS G12C non-small cell lung cancer. Across the treated population, with a data cutoff of 11 May 2026, and 8.7 months of median follow-up, the confirmed objective response rate was 85%, with a disease control rate of 97%.

Speaker #2: Turning now to efficacy of Eleron-RASID in combination with pembrolizumab and chemotherapy. Similar to what we observed with Zoldon-RASID, we have observed highly encouraging anti-tumor activity with Eleron-RASID in combination with pembrolizumab and platinum-based chemotherapy in patients with previously untreated RASID G12C non-small cell lung cancer.

Speaker #2: Across the treated population, with the data cutoff of May 11, 2026, and 8.7 months of median follow-up, the confirmed objective response rate was 85%, with a disease control rate of 97%.

Speaker #2: Responses were observed across PD-L1 expression subgroups, and, like Zoldon-RASID, the Eleron-RASID combination regimen appears to be highly competitive with the current standard of care, the Keynote-189 regimen.

Alan Sandler: Responses were observed across PD-L1 expression subgroups. Like zoldonrasib, the elironrasib combination regimen appears to be highly competitive with the current standard of care of KEYNOTE-189 regimen. The early observations of durability were also encouraging with a progression-free survival rate at 6 months of 95%. We believe these early findings suggest that the responses observed are not only frequent, but also have the potential to be durable. We believe these results reinforce the significant potential for targeted RAS(ON) inhibition to further improve outcomes when combined with current standard of care. Taken together, we believe these observations support continued development of elironrasib in combination with standard of care pembrolizumab and platinum-based chemotherapy.

Speaker #2: The early observations of durability were also encouraging, with a progression-free survival rate at six months of 95%. We believe these early findings suggest that the responses observed are not only frequent, but also have the potential to be durable.

Speaker #2: We believe these results reinforce the significant potential for targeted RASID inhibition to further improve outcomes when combined with current standard of care. Taken together, we believe these observations support continued development of Eleron-RASID in combination with standard of care pembrolizumab and platinum-based chemotherapy.

Speaker #2: As a whole, and consistent with the impact seen in pancreatic cancer, these emerging data showing a well-tolerated and highly encouraging anti-tumor profile provide evidence that our RASID mutant selective inhibitors have the potential to become important first-line treatment options for patients with metastatic non-small cell lung cancer.

Alan Sandler: As a whole, consistent with the impact seen in pancreatic cancer, these emerging data, showing a well-tolerated and highly encouraging antitumor profile, provide evidence that our RAS(ON) mutant-selective inhibitors have the potential to become important first-line treatment options for patients with metastatic non-small cell lung cancer. We are observing that practitioners increasingly view treatment of lung cancer through a biomarker-directed lens and recognize the significant unmet needs that remain across patients with RAS mutant non-small cell lung cancer. With our broad and differentiated portfolio of RAS(ON) mutant-selective inhibitors, we believe we are uniquely positioned to address these needs. Accordingly, in the next stage of our approach in non-small cell lung cancer, we are advancing both zoldonrasib and elironrasib into registrational development in combination with standard of care in first-line non-small cell lung cancer, with the goal of addressing the majority of patients with RAS mutant disease.

Speaker #2: We are observing that practitioners increasingly view the treatment of lung cancer through a biomarker-directed lens and recognize the significant unmet needs that remain across patients with RASID-mutant non-small cell lung cancer.

Speaker #2: With our broad and differentiated portfolio of RASID mutant-selective inhibitors, we believe we are uniquely positioned to address these needs. Accordingly, in the next stage of our approach in non-small cell lung cancer, we are advancing both Zoldon-RASID and Eleron-RASID into registrational development in combination with standard of care in first-line non-small cell lung cancer, with the goal of addressing the majority of patients with RASID mutant disease.

Speaker #2: We recently initiated RASID 308, a randomized placebo-controlled trial evaluating Zoldon-RASID with pembrolizumab plus doublet platinum chemotherapy in patients with RASID G12D non-small cell lung cancer.

Alan Sandler: We recently initiated RASolute 308, a randomized placebo-controlled trial evaluating zoldonrasib with pembrolizumab plus doublet platinum chemotherapy in patients with RAS G12D non-small cell lung cancer. We expect to initiate RASolute-307, a randomized placebo-controlled trial evaluating elironrasib with pembrolizumab plus doublet platinum chemotherapy in patients with RAS G12C non-small cell lung cancer. Further, with the encouraging initial observations mentioned earlier for RMC-5127 in patients with tumors harboring a G12V mutation, we anticipate studying RMC-5127 in the first-line non-small cell lung cancer setting as well. While we conduct registrational studies for mutant-selective inhibitors, we are also evaluating a broader set of first-line treatment strategies, including our multi-selective inhibitor daraxonrasib, as well as our mutant-selective inhibitors in combinations with emerging bispecific antibodies and chemotherapy. The additional information and insights we gain over time will inform decisions about potential future registrational plans.

Speaker #2: And we expect to initiate RASID 307, a randomized placebo-controlled trial evaluating Eleron-RASID with pembrolizumab plus doublet platinum chemotherapy in patients with RASID G12C non-small cell lung cancer.

Speaker #2: Further, with the encouraging initial observations mentioned earlier for RMC 5127 in patients with tumors harboring a G12V mutation, we anticipate studying RMC 5127 in the first-line non-small cell lung cancer setting as well.

Speaker #2: While we conduct registrational studies for mutant selective inhibitors, we are also evaluating a broader set of first-line treatment strategies including our multi-selective inhibitor Durexon-RASID, as well as our mutant selective inhibitors in combinations with emerging bispecific antibodies and chemotherapy.

Speaker #2: The additional information and insights we gain over time will inform decisions about potential future registrational plans. This layered portfolio strategy reflects our deep commitment to developing multiple targeted treatments across the spectrum of RASID mutant non-small cell lung cancer.

Alan Sandler: The additional information and insights we gain over time will inform decisions about potential future registrational plans. This layered portfolio strategy reflects our deep commitment to developing multiple targeted treatments across the spectrum of RAS mutant non-small cell lung cancer. As we have done in pancreatic cancer, we are advancing multiple potential solutions on behalf of patients with the goal of providing multiple first-line treatment options for patients with RAS mutant non-small cell lung cancer. I'll now hand the call over to Jack.

Alan Sandler: This layered portfolio strategy reflects our deep commitment to developing multiple targeted treatments across the spectrum of RAS mutant non-small cell lung cancer.

Speaker #2: As we have done in pancreatic cancer, we are advancing multiple potential solutions on behalf of patients, with the goal of providing multiple first-line treatment options for patients with RASID mutant non-small cell lung cancer.

Mark Goldsmith: As we have done in pancreatic cancer, we are advancing multiple potential solutions on behalf of patients with the goal of providing multiple first-line treatment options for patients with RAS mutant non-small cell lung cancer. I'll now hand the call over to Jack.

Speaker #2: I'll now hand the call over to Jack.

Speaker #1: Thanks, Alan. Our financial position remains exceptionally strong and continues to provide the flexibility needed to support the rapid advancement of our portfolio and our commercial preparations.

Jack Anders: Thanks, Alan. Our financial position remains exceptionally strong and continues to provide the flexibility needed to support the rapid advancement of our portfolio and our commercial preparations. We ended Q2 2026 with $3.9 billion in cash and investments. This balance includes the proceeds from our concurrent public offerings of common stock and convertible notes in April of this year, resulting in $2.2 billion in gross proceeds before deducting underwriting discounts, commissions, and offering expenses. The ending Q2 balance also includes the receipt of the second royalty tranche of $250 million from our funding arrangement with Royalty Pharma. There remains up to an additional $1.5 billion in committed flexible capital under this funding arrangement, subject to the achievement of specific milestones. Moving to expenses. R&D expenses for Q2 2026 were $395 million, compared to $224 million for Q2 2025.

Speaker #1: We ended the second quarter of 2026 with $3.9 billion in cash and investments. This balance includes the proceeds from our concurrent public offerings of common stock and convertible notes in April of this year.

Speaker #1: Resulting in $2.2 billion in gross proceeds before deducting underwriting discounts commissions and offering expenses. The ending second quarter balance also includes the receipt of the second royalty tranche of $250 million from our funding arrangement with royalty pharma.

Speaker #1: There remains up to an additional $1.5 billion in committed flexible capital under this funding arrangement, subject to the achievement of specific milestones. Moving to expenses, R&D expenses for the second quarter of 2026 were $395 million compared to $224 million for the second quarter of 2025.

Speaker #1: The increase in 2026 was primarily due to increased clinical trial and manufacturing expenses for Durexon-RASID and Zoldon-RASID. Increased personnel-related costs, due to additional headcount, and higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026, previously described on our Q1 2026 earnings call.

Jack Anders: The increase in 2026 was primarily due to increased clinical trial and manufacturing expenses for daraxonrasib and zoldonrasib, increased personnel-related costs due to additional headcount, and higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026, previously described on our Q1 2026 earnings call. G&A expenses for Q2 2026 were $110 million, compared to $41 million for Q2 2025. The increase in G&A expenses in 2026 was primarily due to higher personnel-related costs associated with additional headcount, higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026, increased commercialization preparation activities, and higher administrative costs. Net loss for Q2 2026 was $644 million, compared to $248 million for Q2 2025.

Speaker #1: G&A expenses for the second quarter of 2026 were $110 million compared to $41 million for the second quarter of 2025. The increase in G&A expenses in 2026 was primarily due to higher personnel-related costs associated with higher with additional headcount.

Speaker #1: Higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026. Increased commercialization preparation activities and higher administrative costs. Net loss for the second quarter of 2026 was $644 million, compared to $248 million for the second quarter of 2025.

Speaker #1: Net loss for the quarter ended June 30, 2026, included a non-cash charge of $151 million related to a change in the fair value of warrants we assumed as part of the company's acquisition of EQRx.

Jack Anders: Net loss for the quarter ended 30 June 2026 included a non-cash charge of $151 million related to a change in the fair value of warrants we assumed as part of the company's acquisition of EQRx. This change in the fair value of warrants is due to the increase in our stock price. The additional increase in net loss in 2026 was due to higher operating expenses. Turning to financial guidance. The company is updating its projected 2026 GAAP operating expense expectations and now expects full year 2026 GAAP operating expenses to be between $2.1 billion and $2.2 billion. This includes expected non-cash stock-based compensation expense of between $270 million and $290 million. Today's updated guidance reflects our growing confidence in the breadth of our clinical pipeline and the magnitude of the opportunities ahead.

Speaker #1: This change in the fair value of warrants is due to the increase in our stock price. The additional increase in net loss in 2026 was due to higher operating expenses.

Speaker #1: Turning to financial guidance, the company's updating its projected 2026 gap operating expense expectations and now expects full-year 2026 gap operating expenses to be between $2.1 billion and $2.2 billion, this includes expected non-cash stock-based compensation expense of between $270 and $290 million.

Speaker #1: Today's updated guidance reflects our growing confidence in the breadth of our clinical pipeline and the magnitude of the opportunities ahead. As a result, we plan to increase our investment and spending in 2026, driven largely by three main factors.

Jack Anders: We plan to increase our investment and spend in 2026, driven largely by three main factors. First, we are accelerating and increasing manufacturing for both commercial and clinical supply of daraxonrasib and zoldonrasib to ensure we have sufficient supply to meet a range of potential demand scenarios. Second, we anticipate higher clinical development expenses as we continue to execute on our aggressive development strategy across multiple programs within our portfolio with increased confidence. Third, we are accelerating and increasing investments in our commercial readiness efforts to support our preparedness for potential US launches, while also expanding our international infrastructure to support potential future launches outside the US. These additional investments in 2026 position us to execute on our bold ambitions for our portfolio. That concludes the financial update. I'll now turn the call back over to Mark.

Speaker #1: First, we are accelerating and increasing manufacturing for both commercial and clinical supply of Durexon-RASID and Zoldon-RASID to ensure we have sufficient supply to meet a range of potential demand scenarios.

Speaker #1: Second, we anticipate higher clinical development expenses as we continue to execute on our aggressive development strategy across multiple programs within our portfolio, with increased confidence.

Speaker #1: And third, we are accelerating and increasing investments in our commercial readiness efforts to support our preparedness for potential U.S. launches, while also expanding our international infrastructure to support potential future launches outside the U.S.

Speaker #1: additional investments in 2026 position us to execute on our bold ambitions for our portfolio. That concludes the financial update on now turning the call back over to Mark.

Speaker #2: Thank you, Jack. Before we open the call for questions, I'd like to briefly highlight our key upcoming priorities. Overall, we've begun the second half of 2026 with strong momentum, and a compelling set of priorities.

Mark Goldsmith: Thank you, Jack. Before we open the call for questions, I'd like to briefly highlight our key upcoming priorities. Overall, we've begun the H2 2026 with strong momentum and a compelling set of priorities. In pancreatic cancer, following the unprecedented results from RASolute 302, the U.S. FDA has accepted our full NDA submission for review. The EMA has initiated its phased review of daraxonrasib, and we are well prepared to execute a successful launch subject to regulatory approvals. In addition, the global RASolute 303, 304, and 305 studies are actively enrolling, and we have initiated RASolute 309.

Speaker #2: In pancreatic cancer following the

Speaker #2: submission for review, the EMA has initiated its phased review of Durexon-RASID, and we are well prepared to execute a successful launch subject to regulatory approvals.

Speaker #2: In addition, the global Resolute These 303, 304, and 305 studies are actively enrolling and we have initiated Resolute 309. In lung cancer, we expect to complete enrollment in Resolve 301 this year, supporting an initial readout in 2027.

Mark Goldsmith: In lung cancer, we expect to complete enrollment in RASolve 301 this year, supporting an initial readout in 2027. We also continue following patients in the zoldonrasib monotherapy expansion cohort in previously treated RAS G12D non-small cell lung cancer and have initiated RASolute 308, evaluating zoldonrasib in combination with standard of care in first-line RAS G12D non-small cell lung cancer. We are also preparing to initiate RASolute-307, evaluating elironrasib in combination with standard of care in first-line RAS G12C non-small cell lung cancer in the Q4 2026. In colorectal cancer, we look forward to providing a data update and visibility into our development plans during the Q4 this year. With our earlier stage pipeline, we expect to identify the recommended phase II dose for RMC-5127 in the H2 this year and share initial clinical data in 2027.

Speaker #2: We also continue following patients in the Zoldon-RASID monotherapy expansion cohort and previously treated RAS G12D non-small cell lung cancer, and have initiated Resolve 308, evaluating Zoldon-RASID in combination with standard of care in first-line RAS G12D non-small cell lung cancer.

Speaker #2: We are also preparing to initiate Resolve 307, evaluating Eliron-RASID in combination with standard of care in first-line RAS G12C non-small cell lung cancer, in the fourth quarter of 2026.

Speaker #2: In colorectal cancer, we look forward to providing a data update and visibility into our development plans during the fourth quarter of this year. With our earlier stage pipeline, we expect to identify the recommended phase two dose for RMC 5127 in the second half of this year and share initial clinical data in 2027.

Speaker #2: We also remain on track to initiate the first in-human study of RM055, our first inhibitor from our innovative new class of mutant-targeted catalytic RASON inhibitors in the fourth quarter.

Mark Goldsmith: We also remain on track to initiate the first in-human study of RM055, our first inhibitor from our innovative new class of mutant-targeted catalytic RAS(ON) inhibitors in the Q4. Taken together, these milestones reflect the breadth, pace, and ambition of Revolution Medicines today. We are preparing for a potential first commercial launch, conducting multiple registration programs, and leading with further RAS innovation, all with intensity and continued excellence in execution. The progress we've made is the result of years of growing scientific conviction, disciplined investment, and relentless effort by our team and collaborators. We believe we are now in a strong position to redefine what is possible for patients with RAS-driven cancers, beginning with pancreatic cancer and lung cancer, and colorectal cancer coming soon as well. With our differentiated knowhow, organizational depth, and financial strength, we intend to continue operating against our aggressive plan with the urgency patients deserve.

Speaker #2: Taken together, these milestones reflect the breadth, pace, and ambition of Revolution Medicines today. We are preparing for a potential first commercial launch, conducting multiple registration programs and leading with further RAS innovation, all with intensity and continued excellence in execution.

Speaker #2: The progress we've made is the result of years of growing scientific conviction, disciplined investment, and relentless effort by our team and collaborators. We believe we are now in a strong position to redefine what is possible for patients with RAS-driven cancers, beginning with pancreatic cancer and lung cancer, with colorectal cancer coming soon as well.

Speaker #2: With our differentiated know-how, organizational depth, and financial strength, we intend to continue operating against our aggressive plan with the urgency patients deserve. I'd like to thank patients and their families, our investigators and healthcare partners, our employees, and our shareholders for their continued support and confidence.

Mark Goldsmith: I'd like to thank patients and their families, our investigators and healthcare partners, our employees, and our shareholders for their continued support and confidence. The ongoing support of all of our partners and constituencies is needed to deliver revolutionary advances on behalf of patients. With that, I'll turn the call over to the operator for the Q&A portion of the call.

Speaker #2: The ongoing support of all of our partners and constituencies is needed to deliver revolutionary advances on behalf of patients. With that, I'll turn the call over to the operator for the Q&A portion of the call.

Speaker #3: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced.

Operator: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please limit to one question and one follow-up question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Marc Frahm with TD Cowen. Your line is now open.

Speaker #3: To withdraw your question, please press star-one-one again. Please limit to one question and one follow-up question. Please stand by while we compile the Q&A roster.

Speaker #3: Our first question comes from the line of Mark Fromm with TD Cohen. Your line is now open.

Speaker #4: Hi, thanks for taking my questions. I know the progress, and congrats on all the progress you've made so far. Maybe on CRC, since we're going to be getting that, just what's your latest thoughts on what proof of concept looks like in that indication?

Marc Frahm: Hi. Thanks for taking all my questions and all the progress, and congrats on all the progress you've made so far. Maybe on CRC, since we're going to be getting that, just what's your latest thoughts on what proof of concept looks like in that indication, particularly after we've seen adagrasib's confirmatory trial in the second-line setting kind of failed to demonstrate PFS or OS benefit despite what appeared to be pretty exciting response rate data? Just on the lung cancer side, can you just walk through the confidence that on the G12C, not just that you can beat current standard of care, but there's also second-gen G12C trials running right now in the first line. Why do you think you're going to be better than those that will presumably have data faster than your trials?

Speaker #4: Particularly after we've seen at a RASID confirmatory trial in the second-line setting, kind of failed to demonstrate PFS or OS benefit, despite what appeared to be pretty exciting response rate data.

Speaker #4: And then just on the lung cancer side, can you just walk through the confidence that on the G12C, not just that you can beat current standard of care, but there's also a second-line trials or second-gen G12C trials running right now in the first line.

Speaker #4: Why do you think you're going to be better than those that will presumably have data faster than your trials?

Speaker #5: Hi, Mark. Thanks for your question. On the CRC question, I think that's best addressed when we are able to frame our plans and provide some data.

Mark Goldsmith: Hi, Mark. Thanks for your questions. On the CRC question, I think that's best addressed when we are able to frame our plans and provide some data. I'm just going to ask that we defer that to a later time when I can be more concrete. On the non-small cell lung cancer question, with regard to elironrasib, maybe Alan Sandler can make a comment on that.

Speaker #5: So I'm just going to ask that we defer that to a later time when I can be more concrete. On the non-small cell lung cancer question, with regard to Eliron-RASID, maybe Alan Sandler can make a comment on that.

Alan Sandler: Sure. Thanks, and thanks for the question. An important question. We believe that elironrasib has a very good profile, both safety and efficacy, and we're always data-driven in terms of our decision-making. We felt that it was important to have a robust data set available in order to make this important decision. Given that, and given the data that we've shown you today, we believe that elironrasib has a highly competitive profile, both again in monotherapy, potentially in subsequent lines of therapy, and also in that first-line line of therapy in combination with pembrolizumab and doublet chemotherapy. In addition, what I would add is, with our suite of mutant-selective agents, we have a very compelling position in that setting as we will be able to target over 70% of the patients with RAS mutant non-small cell lung cancer.

Speaker #6: Sure. Thanks. And thanks for the question. So an important question. We believe that Eliron-RASID has a very good profile, both safety and efficacy. And we're always data-driven in terms of our decision-making.

Speaker #6: And we felt that it was important to have a robust data set available in order to make this important decision. Given that and given the data that we've shown you today, we believe that Eliron-RASID has a highly competitive profile both, again, in monotherapy, potentially in subsequent lines of therapy, and also in that first-line line of therapy in combination with pembrolizumab and doublet chemotherapy.

Speaker #6: And in addition, what I would add is with our suite of mutant-selective agents, we have a very compelling position in that setting as we will be able to target over 70% of the patients with RAS mutant non-small cell lung cancer.

Speaker #4: Okay. Thank you, and congrats on all the progress.

Marc Frahm: Okay. Thank you, and congrats on all the progress.

Speaker #3: Thank you. Our next question comes from the line of Charles Zhu with Lifesci Capital. Your line is now open.

Operator: Thank you. Our next question comes from the line of Charles Zhu with LifeSci Capital. Your line is now open.

Speaker #7: Hey, everyone. Thanks for taking the questions and congrats on all the broad progress across the board. Maybe one from me regarding front-line non-small cell lung cancer.

Charles Zhu: Hey, everyone. Thanks for taking the questions and congrats on all the broad progress across the board. Maybe one from me regarding frontline non-small cell lung cancer. Great to see the current or ongoing plans with various mutant-selective inhibitors in combination with standard of care. I think you had also mentioned evaluating further opportunities, not only with novel bispecifics, which makes sense, but also with the multi-selective RAS inhibitors. Curious as to your thoughts around, given the multiple mutant-selective you have covering a lot of those patients, how might you position a RAS multi-selective in that frontline setting? Did that terminology refer to the daraxonrasib or possibly RM-055 as well? Thank you.

Speaker #7: So great to see either current or ongoing plans with various mutant-selective inhibitors in combination with standard of care. I think you had also mentioned evaluating further opportunities, not only with novel bispecifics, which makes sense, but also with a multiselective RAS inhibitors.

Speaker #7: Curious as to your thoughts around, given the multiple mutant-selectives we have covering a lot of those patients, how might you position a RAS multiselective in that front-line setting?

Charles Zhu: Curious as to your thoughts around, given the multiple mutant-selective you have covering a lot of those patients, how might you position a RAS multi-selective in that frontline setting? Did that terminology refer to the daraxonrasib or possibly RM-055 as well? Thank you.

Speaker #7: And did that terminology refer to the RAS on RASID or possibly RMO55 as well? Thank you.

Speaker #5: Yeah. Thank you, Charles. Appreciate the question. I think all possibilities are still on the table. We've intentionally pursued both the multiselective as well as the mutant-selective inhibitors.

Mark Goldsmith: Thank you, Charles. Appreciate the question. I think all possibilities are still on the table. We've intentionally pursued both the multi-selective as well as the mutant-selective inhibitors to create the most optionality for us and then ultimately, for patients. I think all of this will play out over time if we still think it's premature to make any exclusive commitments down any particular treatment regimen. As long as there remains the possibility that more than one regimen might be complementary and provide options for various patients, we'll pursue them. This will continue to play out. You're now seeing our moving pretty aggressively with two mutant-selective inhibitors and the third to come behind it. By no means are we deprioritizing either daraxonrasib or RM-055 that's coming up, or things that might come behind that as well.

Speaker #5: To create the most optionality for us and then ultimately for patients. And I think all of this will play out over time. If we still think it's premature to make any exclusive commitments down any particular treatment regimen, and as long as there remains the possibility that more than one regimen might be complementary and provide options for various patients, we'll pursue them.

Speaker #5: So this will continue to play out. You're now seeing our moving pretty aggressively with two mutant-selective inhibitors, and a third to come behind it.

Speaker #5: But by no means are we deprioritizing either JAX on RASID or RMO55 that's coming up, or things that might come behind that as well.

Speaker #4: Got it. Thanks for taking the questions and congrats again.

Charles Zhu: Got it. Thanks for taking the questions, and congrats again.

Speaker #5: Thank you.

Mark Goldsmith: Thanks.

Speaker #3: Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is now open.

Operator: Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is now open.

Speaker #6: Oh, hey. Thanks for taking my question and congrats on all the progress and news today. I had a question on direct on RASID and just curious if you have any early feedback from the EAP program and how the products perhaps are performing relative to the clinical trial experience.

Michael Schmidt: Oh, hey. Thanks for taking my question and congrats on all the progress and news today. I had a question on daraxonrasib, and I'm just curious if you have any early feedback from the EAP program and how the product's perhaps performing relative to the clinical trial experience. Secondly, what could the regulatory timelines in Europe look like based on this phased review process that's underway there? Thanks so much.

Speaker #6: And secondly, what could the regulatory timelines in Europe look like based on this phased review process that's underway there? Thanks so much.

Speaker #5: Thank you, Michael. The EAP is quite robust now. We're serving a lot of patients. We don't have a mechanism to get explicit or quantitative feedback from those who are prescribing it since that this is a clinical access program.

Mark Goldsmith: Thank you, Michael. The EAP is quite robust now. We're serving a lot of patients. We don't have a mechanism to get explicit or quantitative feedback from those who are prescribing it, since this is a clinical access program, it's not a clinical trial. We really don't have quantitative information, and I'm not sure that we ultimately ever will. Sort of on a qualitative basis, we certainly have feedback from some institutions that they're very enthusiastic. Some of the larger institutions have enrolled quite large numbers of patients, and they're continuing to enroll new patients, so that suggests that their experience so far is encouraging. We also do get anecdotal information from patients or their families. That doesn't add up to a fair and broad-based representation. From that anecdotal evidence, patients and their families are quite encouraged by having received access.

Speaker #5: It's not a clinical trial. So we really don't have quantitative information and I'm not sure that we ultimately ever will. Certified on a qualitative basis, we certainly have feedback from some institutions that they're very enthusiastic some of the larger institutions have enrolled quite large numbers of patients.

Speaker #5: And they're continuing to enroll new patients, so that suggests that their experience so far is encouraging. We also do get anecdotal information from patients or their families, but that doesn't add up to a fair and broad-based representation.

Speaker #5: But from that anecdotal evidence, patients and their families are quite encouraged by having received access. So that's pretty much what we know from the EAP now.

Mark Goldsmith: That's pretty much what we know from the EAP now, and it, I'm sure, will continue to grow. With regard to the regulatory timelines in Europe, there's really not much we can provide on that. The EMA made it clear that the phased review is intended to be an expedited review process. What that actually ends up meaning really is a question for the EMA, and we'll just support it as well as we can.

Speaker #5: And I'm sure it will continue to grow. With regard to the regulatory timelines in Europe, there's really not much we can provide on that.

Speaker #5: The EMA made it clear that the phased review is intended to be an expedited review process. What that actually ends up meaning really is a question for the EMA and we'll just support it as well as we can.

Speaker #6: Thank you.

Michael Schmidt: Thank you.

Speaker #3: Thank you. Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is now open.

Operator: Thank you. Our next question comes from the line of Cory Kasimov with Evercore ISI. Your line is now open.

Speaker #7: Hey. Good afternoon, guys. Thank you for taking my questions. So I want to ask about your phase three front-line PDAC studies. For patients that end up in the control arm, how do you plan to assess those that drop out potentially even after receiving just a single dose of chemo?

Cory Kasimov: Hey, good afternoon, guys. Thank you for taking my questions. I want to ask about your phase III frontline PDAC studies. For patients that end up in a control arm, how do you plan to assess those that drop out, potentially even after receiving just a single dose of chemo and eventually go on to receive commercial daraxonrasib upon approval? How much of a risk might this dynamic pose to your frontline studies in terms of measuring OS and potentially even PFS? A follow-up, just a clarification question. With the EAP, do those patients convert to commercial patients upon approval of daraxonrasib? Thank you very much.

Speaker #7: And then eventually go on to receive commercial direct on RASID upon approval. How much of a risk might this dynamic pose to your front-line studies in terms of measuring OS and potentially even PFS?

Speaker #7: And then a follow-up, just a clarification question. With the EAP, do those patients convert to commercial patients upon approval of direct on RASID? Thank you very much.

Speaker #5: Thank you, Corey. Appreciate your questions. The first question is about first-line PDAC in the phase 3 trial. I think you're really raising the question of some form of crossover risk for patients moving on to direct on RASID.

Mark Goldsmith: Thank you, Cory. Appreciate your questions. The first question is about first-line PDAC in the phase III trial. I think you're really raising the question of some form of crossover risk for patients moving on to daraxonrasib. Maybe Wei Lin, our Chief Medical Officer, can comment on that, and then I'll come back to the EAP.

Speaker #5: Maybe Waylan, our chief medical officer, can comment on that, and then I'll come back to the EAP.

Speaker #6: Yeah. Thanks, Mark. Thanks for the question. Yeah. It is certainly a very important question that we have given a lot of thought and planning to because we want to ensure the success for 303 trial in front-line PDAC while we're trying to making sure patients globally have access to direct on RASID in the future.

Wei Lin: Yeah.

Wei Lin: Yeah. Thanks, Mark. Thanks for the question. Yeah. It is certainly a very important question that we have given a lot of thought and planning to because we want to ensure the success of the 303 trial in frontline PDAC, while we're trying to making sure patients globally have access to daraxonrasib in PDAC studies. I think currently, the phase III trial has a co-primary endpoint of PFS and overall survival, the drop-out in the control arm would not affect the PFS, obviously, but it could potentially affect the overall survival analysis.

Wei Lin: Thanks, Mark. Thanks for the question. Yeah. It is certainly a very important question that we have given a lot of thought and planning to because we want to ensure the success of the 303 trial in frontline PDAC, while we're trying to making sure patients globally have access to daraxonrasib in PDAC studies. I think currently, the phase III trial has a co-primary endpoint of PFS and overall survival, the drop-out in the control arm would not affect the PFS, obviously, but it could potentially affect the overall survival analysis. Right now, we're trying to be very thoughtful in the geographically, the sites that we're activating daraxonrasib

Speaker #6: I think currently, the Phase 3 trial has a co-primary endpoint of PFS and overall survival. And then the dropout in the control arm would not affect the PFS, obviously, but it could potentially affect the overall survival analysis.

Speaker #6: And so right now, we're trying to be very thoughtful in the geographically the sites that we're activating direct on RASID 303 trial in, knowing that the global approval as well as access will be graduated starting with the US and the rest of the world in a gradual fashion.

Wei Lin: Right now, we're trying to be very thoughtful in the geographically, the sites that we're activating daraxonrasib 303 trial in, knowing that the global approval as well as access will be graduated, starting with the US and then the rest of the world in a gradual fashion. That's certainly, I think, one area. The other's really working with investigators to making sure that the patients really understand their options before they come on trials. The trial being conducted in a rigorous fashion, the integrity of the center experiments maintained.

Wei Lin: 303 trial in, knowing that the global approval as well as access will be graduated, starting with the US and then the rest of the world in a gradual fashion. That's certainly, I think, one area. The other's really working with investigators to making sure that the patients really understand their options before they come on trials. The trial being conducted in a rigorous fashion, the integrity of the center experiments maintained.

Speaker #6: So that's certainly I think one area. And the other is really working with investigators to making sure that the patients really understand their options before they come on trials and then probably conduct it in a rigorous fashion so then the integrity of the center experiments maintain.

Speaker #7: So that's with regard to the front-line PDAC and crossover risk on the expanded access program. It's an important program, important pathway for eligible patients before potential approval.

Mark Goldsmith: That's with regard to the frontline PDAC and crossover risk on the expanded access program. It's an important program, important pathway for eligible patients before potential approval. Once an approval occurs, our patient support services team will work very closely with treating physicians, healthcare providers, and the intention here, of course, is to help minimize treatment interruptions, provide seamless transition of care over to commercial supply. That is a top priority for us. These patients will have access to our comprehensive patient support services, as we mentioned, the OnPath support, and that'll include coverage navigation, financial assistance, and adherence support. We expect most patients would transition within a few-month period.

Speaker #7: Once an approval occurs, are patients' support services team will work very closely with treating physicians to help care providers and the intention here, of course, is to help minimize treatment interruptions, provide seamless transition of care over to commercial supply.

Speaker #7: That is a top priority for us. These patients will have access to our comprehensive patient support services as we mentioned, the OnPath support. That'll include coverage navigation, financial assistance, and adherence support.

Speaker #7: We expect most patients would transition within a few months. That's helpful. Thank you guys very much.

Cory Kasimov: That's helpful. Thank you guys very much.

Speaker #3: Thank you. Our next question comes from the line of Brian Chang with JP Morgan. Your line is now open.

Operator: Thank you. Our next question comes from the line of Brian Chang with J.P. Morgan. Your line is now open.

Speaker #8: Hi, guys. Thanks for taking our question this afternoon. Just first, on the EAP, can you talk about whether these patients are being recruited in the sites that have had prior direct on RASID experience?

Brian Chang: Hey, guys. Thanks for taking our question this afternoon. Just first, on the EAP, can you talk about whether these patients are being recruited in the sites that have had prior daraxonrasib experience? You noted that more than 90% of the requests have been accepted. What is a common reason for patients who get rejected? Just one quick one on the 307 and 308 trial for frontline non-small cell trials. Are these studies setting any minimum or maximum threshold for the proportion of PD-L1 expression, depending on whether it's low or high that you're recruiting? Just curious if you can give us a sense of the trial design there. That would be great. Thank you.

Brian Cheng: Hey, guys. Thanks for taking our question this afternoon. Just first, on the EAP, can you talk about whether these patients are being recruited in the sites that have had prior daraxonrasib experience? You noted that more than 90% of the requests have been accepted. What is a common reason for patients who get rejected? Just one quick one on the 307 and 308 trial for frontline non-small cell trials. Are these studies setting any minimum or maximum threshold for the proportion of PD-L1 expression, depending on whether it's low or high that you're recruiting? Just curious if you can give us a sense of the trial design there. That would be great. Thank you.

Speaker #8: And you noted that more than 90% of the requests have been accepted. What is the common reason for patients to get rejected? And then just one quick one on the 307 and 308 trial for front-line non-small cell trials.

Speaker #8: Are these studies setting any minimum or maximum threshold for the proportion of PDL1 expressions? Depending on whether it's low or high, that you're recruiting just curious if you can give us a sense of the trial design there would be great.

Speaker #8: Thank you.

Speaker #5: Nicely done. I think you squeezed in three questions if not two questions. Well done. Maybe Alan can comment first on the 307, 308 PDL1 expression topic.

Mark Goldsmith: Nicely done. I think you squeezed in three questions in two questions. Well done. Maybe Alan can comment first on the 307/308 PD-L1 expression topic.

Speaker #6: Right. So yeah, we are not putting guidelines in terms of requirements of the numbers that have we'll let that play out in a large study such as phase three study.

Alan Sandler: Right. Yeah, we're not putting guidelines in terms of requirements of the numbers that have. We'll let that play out in a large study such as phase III study. There should be a natural number of patients that appear on well representation of all three. What we will do, we generally want to stratify to make sure that there is equal representation on both arms. I think that's the most important aspect of that plan.

Speaker #6: There should be a natural separation or a natural number of patients that appear in well-represented groups of all three. What we generally do is stratify to make sure that there is equal representation in both arms.

Speaker #6: And I think that's the most important aspect of that question.

Mark Goldsmith: It's more about balance-

Speaker #5: It's more about balance. Than anything else. Yeah. Thanks, Alan. And then the on the EAP, there are participants in the program who have been investigators, and they've treated patients before, and they're participants who have not.

Alan Sandler: Balance

Mark Goldsmith: than anything else. Yeah. Thanks, Alan. On the EAP, there are participants in the program who have been investigators and have treated patients before, and there are participants who have not, and significant numbers of both. I don't know that I can quantitate that for you, but I think we're experiencing both kinds. We've certainly put a lot of effort into providing education and support to all of the prescribers. The experience that the more experienced providers have obtained, we've learned from, we've all learned from, and we've developed protocols, approaches that we have invested heavily in developing and also conveying through education to anybody who might prescribe daraxonrasib. As to the greater than 90% rate, actually a very high rate as to who might be disapproved, it's really not subjective. It comes down to the eligibility criteria that are established in the FDA-cleared protocol.

Speaker #5: And significant numbers of both. I don't know that I can quantitate that for you, but I think we're experiencing both kinds. We've certainly put a lot of effort into providing education and support to all of the prescribers.

Speaker #5: So the experience that the more experienced providers have obtained—we've learned from, we've all learned from—and we've developed protocols, approaches that we have invested heavily in developing and also conveying through education to anybody who might prescribe.

Speaker #5: Direct on RASID. As to the greater than 90% rate, actually a very high rate as to who might be disapproved, it's really not subjective.

Mark Goldsmith: As to the greater than 90% rate, actually a very high rate as to who might be disapproved, it's really not subjective. It comes down to the eligibility criteria that are established in the FDA-cleared protocol. It's very well-defined. There are very few edge cases where it requires some judgment. Most of it's really just making sure that somebody is actually eligible, and if they're eligible and the request comes through a US-licensed physician from a qualified institution that's met all the institutional requirements, then they will be approved.

Speaker #5: It comes down to the eligibility criteria that are established in the FDA cleared protocol. It's very well-defined. There are very few edge cases where it requires some judgment.

Mark Goldsmith: It's very well-defined. There are very few edge cases where it requires some judgment. Most of it's really just making sure that somebody is actually eligible, and if they're eligible and the request comes through a US-licensed physician from a qualified institution that's met all the institutional requirements, then they will be approved.

Speaker #5: Most of it's really just making sure that somebody is actually eligible. And if they're eligible, and the request comes through a US licensed physician from a qualified institution that's met all the institutional requirements, then they will be approved.

Speaker #3: Thank you. Our next question comes from the line of Faisal Khurshid with Jefferies. Your line is now open.

Operator: Thank you. Our next question comes from the line of Faisal Khurshid with Jefferies. Your line is now open.

Speaker #9: Hey, guys. Thank you so much for taking the question. There's been a lot of investor excitement about PRMT5 combination data, generated with your molecule, from your partner Tango.

Faisal Khurshid: Hey, guys. Thank you so much for taking the question. There has been a lot of investor excitement about PRMT5 combination data generated with your molecule from your partner, Tango. Just want to understand from your perspective, what is your latest thoughts on the potential of that combination, and do you feel like you need a PRMT5 within your own portfolio in order to kind of cover all of your bases? Thank you.

Speaker #9: Just want to understand from your perspective, what's your latest thoughts on the potential of that combination? And do you feel like you need a PRMT5 within your own portfolio in order to kind of cover all of your bases?

Speaker #9: Thank you.

Speaker #5: Thanks for your questions. Yeah, our position on PRMT5 inhibitors remains what it's been, which is that, biologically, it's intriguing. Pharmacologically, it's an intriguing hypothesis that's supported by preclinical work.

Mark Goldsmith: Thanks for your questions. Yeah, our position on PRMT5 inhibitors remains what it has been, which is that pharmacologically it is an intriguing hypothesis that is supported by preclinical work. Tango has now put forth some initial data that show high response rates. We think that body of evidence should be grown, we know that Tango is working to do that, grown both in terms of numbers of patients, exposure to different dose levels, so dose optimization and a longer follow-up, that will help us really establish a level of conviction about whether, and if so, how to go forward with it. Certainly a credible idea, we will just continue to learn more about it as we support Tango in their efforts. With regard to do we need a PRMT5 inhibitor in our portfolio? I do not think we need it.

Speaker #5: Tango's now put forth some initial data that show high response rates. We think that body of evidence should be grown. And we know that Tango is working to do that.

Speaker #5: Grown both in terms of numbers of patients, exposure to different dose levels, so dose optimization, and a longer follow-up. And that will help us really establish a level of conviction about whether and if so how to go forward with it.

Speaker #5: So, certainly a credible idea, and we'll just continue to learn more about it as we support Tango in their efforts. With regard to whether we need a PRMT5 inhibitor in our portfolio, I don't think we need it.

Speaker #5: We have plenty to do that's high priority within RevMed as we've described. Now, one looks at the pipeline if a pretty rich pipeline of work.

Mark Goldsmith: We have plenty to do that is high priority within RevMed, as we have described. Now, one looks at the pipeline. It is a pretty rich pipeline of work. The other thing to point out, of course, is that there are many PRMT5 inhibitors, growing number out there, each with a slightly different profile, some with more or less propensity to drug-drug interactions that would have to be managed, different levels of potency and so on. I think there is a lot of opportunity out there. I think at the end of the day, daraxonrasib should be the backbone of therapy, or zoldonrasib in the context of the right settings, G12D selective setting. We may add various things, whether it is PRMT5 inhibitors, immunologic agents, other RAS inhibitors, chemotherapy, et cetera. Wide variety of possibilities there.

Speaker #5: And the other thing to point out, of course, is that there are many PRMT5 inhibitors growing number out there, each with a slightly different profile.

Speaker #5: Some with more or less propensity to drug-drug interactions that would have to be managed. Different levels of potency and so on. So I think there's a lot of opportunity out there.

Speaker #5: I think at the end of the day, direct on RASID should be the backbone of therapy. Or Zold on RASID in the context of the right settings, G12D selective setting.

Speaker #5: And we may add various things whether it's PRMT5 inhibitors, immunologic agents, other RASID inhibitors, chemotherapy, etc., a wide variety of possibilities there.

Speaker #9: Great. Thank you.

Faisal Khurshid: Great. Thank you.

Speaker #3: Thank you. Our next question comes from the line of Michael Yee with UBS. Your line is now open.

Operator: Thank you. Our next question comes from the line of Michael Yee with UBS. Your line is now open.

[Analyst] (UBS): Hi, this is Madeline on for Michael. Just wanted to get any updated commentary around, obviously, there is some precedent in oncology to get accelerated approval in the first line based on similar data to what you have, along with the full approval that you're expecting for the second-line PDAC indication. Just wondering if you have any updated commentary around that now that your NDA has been accepted by the FDA.

Madeleine Lee: Hi, this is Madeline on for Michael. Just wanted to get any updated commentary around, obviously, there is some precedent in oncology to get accelerated approval in the first line based on similar data to what you have, along with the full approval that you're expecting for the second-line PDAC indication. Just wondering if you have any updated commentary around that now that your NDA has been accepted by the FDA.

Speaker #10: Hi, this is Madeline on for Michael. Just wanted to get your any updated commentary around—obviously, there is some precedent in oncology to get accelerated approval in the first line, based on similar data to what you have.

Speaker #10: Along with the full approval that you're expecting for the second line PDAC indications, I'm just wondering if you have any updated commentary around that now that you're NDA has been accepted by the FDA.

Mark Goldsmith: Not really much to add to that. We're certainly aware of the history here. The NDA is primarily driven by the 302 data set, which is randomized data in patients being treated in second line for metastatic pancreatic cancer. There are additional data outside of that study that, of course, many people have access to, including the FDA have access to it, how they want to deal with that, I think we'll just have to learn over time.

Speaker #5: Not really much to add to that. We're certainly aware of the history here. The NDA is primarily driven by the 302 dataset, which is randomized data in patients being treated for second line with in second line for metastatic pancreatic cancer.

Speaker #5: But there are additional data outside of that study that, of course, many people have access to, including the FDA have access to it. And so how they want to deal with that, I think we'll just have to learn over time.

Speaker #10: Thank you.

[Analyst] (UBS): Thank you.

Madeleine Lee: Thank you.

Speaker #3: Thank you. Our next question comes from the line of Alex Stranahan with Bank of America. Your line is now open.

Operator: Thank you. Our next question comes from the line of Alec Stranahan with Bank of America. Your line is now open.

Speaker #11: Hey, guys. Thanks for taking our questions. Two from us. First, on direct on RASID in the metastatic RAS, lung cancer setting, curious which data was shared with the FDA to support breakthrough therapy designation here?

Alec Stranahan: Hey, guys. Thanks for taking our questions, two from us. First, on daraxonrasib and the metastatic RAS mutant lung cancer setting, curious which data was shared with the FDA to support breakthrough therapy designation here, and if there's any read-through to be made to what we could see from RASolve 301. Appreciate you probably aren't talking at all about pricing at this point, but from a qualitative perspective, assuming initial approval is with the 300 mg dose, how would you think about relative price in combos that are investigating a lower daraxonrasib dose, like in the PRMT5 studies? If you have any thoughts here that you could share, that'd be great. Thank you.

Speaker #11: And if there's any read-through to be made to what we could see from Resolve 301. And appreciate you probably aren't talking at all about pricing at this point, but from a qualitative perspective, assuming initial approval is with the 300-mig dose, how would you think about relative price in combos that are investigating a lower direct on RASID dose, like in the PRMT5 studies?

Speaker #11: If you have any thoughts here that you could share, that'd be great. Thank you.

Speaker #5: So the first question was what data did we share with the FDA? Well, there's kind of a general rule of thumb. You have to share pretty much everything with the FDA.

Mark Goldsmith: The first question was, what data did we share with the FDA? Well, as kind of a general rule of thumb, you have to share pretty much everything with the FDA, so anything they want to look at, they look at. I don't think we can provide any more specificity around that, unfortunately. With regard to pricing, it's early for us to be talking about pricing. You're raising more of a kind of layered or nuanced question about pricing in combinations, and I guess I'd say the same thing. It's probably too early to be talking about that. We don't have a combination that's approaching commercialization today and nothing to address. I think you might have had another layer to it, but given that I didn't hit the first two layers, I'm not sure we'll make it to the third.

Speaker #5: So anything they want to look at, they look at. I don't think we can provide any more specificity around that, unfortunately. With regard to pricing, it's early for us to be talking about pricing.

Speaker #5: You're raising more of a kind of layered or nuanced question about pricing in combinations. And I guess I'd say the same thing. It's probably too early to be talking about that.

Speaker #5: We don't have a combination that's approaching commercialization today. And nothing to address. I think you might have had another layer to it, but given that I didn't hit the first two layers, I'm not sure we'll make it to the third.

Speaker #11: That's fine. Yeah, thank you.

Alec Stranahan: That's fine. Yeah. Thank you.

Speaker #3: Thank you. Our next question comes from the line of Lara Prendergast with Stifel. Your line is now open.

Operator: Thank you. Our next question comes from the line of Laura Prendergast with Stifel. Your line is now open.

Speaker #10: Hey, guys. Congrats on all the progress. I was hoping you could clarify what you mean by visibility into CRC development strategy expected in the fourth quarter.

Laura Prendergast: Hey, guys. Congrats on all the progress. I was hoping you could clarify what you mean by visibility into CRC development strategy expected in Q4. I guess the real question here is should investors expect to leave this update, having conviction that you have a registrational path in CRC? Second question is, do you guys have any plans to make a registrational move outside the big three RAS indications? Kind of maybe bringing back that tumor agnostic approach question. Is this something that we could see down the road once you've read out pivotal data for your first two PDAC and lung indications?

Speaker #10: I guess the real question here is, should investors expect to that you have a registrational path in CRC? And then second question is, do you guys have any plans to make a registrational move outside the big three RAS indications?

Speaker #10: Kind of, maybe bringing back that tumor-agnostic approach question, is this something that we could see down the road once you’ve read out pivotal data for your first two—PDAC and lung—indications?

Speaker #5: Yeah. Hi, Laura. Thanks for your questions. Visibility for development strategy will show some data, and we'll tell you what we plan to do with it.

Mark Goldsmith: Yeah. Hi, Lara. Thanks for your questions. Visibility into our development strategy. We'll show some data, and we'll tell you what we plan to do with it. As to what investors will leave, what impression they'll leave with that's up to investors to decide. I don't think it serves us to get out in front of that. That's our plan, and typically in the past, when we've announced a development strategy, we've supported it by data that justify it. I think that would be a reasonable expectation. Yeah. Regarding tumors outside of the big three, we're certainly interested in those. I mean, our expectation is that daraxonrasib and other compounds as well, but daraxonrasib could serve a wide variety of tumors. Of course, they're smaller subsets of patients, and we have prioritized the big three, as you put them, which makes sense to do.

Speaker #5: As to what impression investors will leave with, that's up to investors to decide. I don't think it serves us to get out in front of that.

Speaker #5: But that's our plan. And typically in the past, when we've announced a development strategy, we've supported it by data that justify it. So I think that would be a reasonable expectation.

Speaker #5: Yeah, regarding tumors outside of the big three, we're certainly interested in those. I mean, our expectation is that direct on RASID and other compounds as well, the direct on RASID could serve a wide variety of tumors.

Speaker #5: Of course, there's smaller subsets of patients. And we have prioritized the big three as you put them which makes sense to do. But we do have data across other tumor types.

Mark Goldsmith: We do have data across other tumor types. We've shown some of that data publicly. We have other data that hasn't yet made it out into the public domain. We have external research collaborations as ways to explore this. Yes, I think you should expect that daraxonrasib will continue to make its way into other contexts, but the exact strategy by which we develop those may differ from indication to indication, context to context.

Speaker #5: We've shown some of that data publicly. We have other data that hasn't yet made it out into the public domain. We have external research collaborations as ways to explore this.

Speaker #5: So yes, I think you should expect the direct on RASID will continue to make its way into other contexts. But the exact strategy by which we develop those may differ from indication to indication context to context.

Laura Prendergast: Got it. Thanks very much.

Speaker #10: Got it. Thanks very much.

Speaker #3: Thank you. Our next question comes from the line of Leonid Timishev with RBC. Your line is now open.

Operator: Thank you. Our next question comes from the line of Leonid Timashev with RBC. Your line is now open.

Speaker #11: Hey, guys. Thanks for taking my question. Just wanted to ask on the commercial side. At least clinically, you guys have always been planning for success.

Leonid Timashev: Hey, guys. Thanks for taking my question. Just wanted to ask on the commercial side, at least clinically, you guys have always been planning for success. I guess, to what extent does that extend to the sales force sizing commercially? Are you planning a force that's commensurate with the second-line PDAC setting? Are you also going to size it for frontline and potentially non-small cell lung cancer right away, or is this going to expand later? Maybe just a quick follow-up as well, just on the EAP, are those 2,000 patient adds starting from May 1st-ish, when the FDA first made that announcement? I'm just trying to better understand sort of the cadence of how quickly patients came on. Thanks.

Speaker #11: I guess to what extent does that extend to the Salesforce sizing commercially? Are you planning a force that's commensurate with the second line PDAC setting?

Speaker #11: Are you also going to size it for front line and potentially non-small cell lung cancer right away? Or is this going to expand later?

Speaker #11: And then maybe just a quick follow-up as well, just on the EAP. Are those 2,000 patient adds starting from May—when the FDA first made that announcement, around May 1st?

Speaker #11: I'm just trying to better understand, sort of, the cadence of how quickly patients came on. Thanks.

Speaker #5: Well, I'll comment on the second one and then Anthony Mancini can comment on the commercial organization. The number that I gave was greater than 2,000.

Mark Goldsmith: Well, I'll comment on the second one, Anthony Mancini can comment on the commercial organization. The number that I gave was greater than 2,000, so it wasn't 2,000, greater than 2,000. That is a cumulative number. As you might recall, I think that once we filed the EAP request, it was approved within a couple of days, I think within three weeks, we were shipping the first drug on behalf of patients. It started out more as a trickle and then expanded, as you'd expect over time, as sites became part of the program, completed their process for entering the program. I don't know that you can quite get a rhythm out of it, other than to say qualitatively, it's a very robust program. There's very high interest in it, and it continues to grow.

Speaker #5: So, it wasn't 2,000, greater than 2,000. And that is a cumulative number. As you might recall, I think that once we filed the EAP requests, they were approved within a couple of days.

Speaker #5: And I think within three weeks, we were shipping the first drug on behalf of patients and it started out more as a trickle and then expanded as you'd expect over time as sites became part of the program, completed their process for entering the program.

Speaker #5: So I don't know that you can quite get a rhythm out of it other than to say qualitatively, it's a very robust program. There's very, very high interest in it, and it continues to grow.

Speaker #5: With regard to the commercial question, maybe Anthony can comment.

Mark Goldsmith: With regard to the commercial question, maybe Anthony can comment.

Speaker #2: Yeah, Leonid, thanks for the question. We've been preparing for some time and are ready for a successful PDAC launch in the US. As we think about commercialization infrastructure, there are parts of that infrastructure that are broad and can apply to our future indications.

Anthony Mancini: Yeah. Leonid, thanks for the question. We've been preparing for some time and are ready for a successful PDAC launch in the US. As we think about commercialization infrastructure, there are parts of that commercialization infrastructure that are broad and that can apply to our future indications. As for our sales force, which as Mark alluded to and has prepared, our fully trained and in place. We have a team of around 60 individuals that'll fill the need for PDAC. It's also important to note that there are many different stakeholders in the US market, and we're prepared for those as well. We have a fully operational field access team, field patient services team, MSL team, and thought leader liaison team that are in place. We're excited and ready to go.

Speaker #2: But as for our Salesforce, which as Mark alluded to and is prepared in Mark, are fully trained and in place, we have a team of around 60 individuals that'll fill the need for PDAC.

Speaker #2: But it's also important to note that there are many different stakeholders in the US market, and we're prepared for those as well. So we have a fully operational field access team, field patient services team, MSL team, and thought leader liaison team that are in place.

Speaker #2: We're excited and ready to go all systems go, but yes, we're ready for PDAC, and we will be ready should other indications come.

Anthony Mancini: All systems go. Yes, we're ready for PDAC, and we will be ready should other indications come.

Speaker #3: Thank you. Our next question comes from the line of Calpit Patel with Wolfe Research. Your line is now open.

Operator: Thank you. Our next question comes from the line of Kalpit Patel with Wolfe Research. Your line is now open.

Speaker #11: Hey, Googling on for Calpit. Just a quick one from us. Given Roche's head-to-head win against sotorasib and adagrasib in Crescendo-1, do you think you'd need to run a trial against Durasib?

[Analyst] (Wolfe Research): Hey, Gouganon for Kalpit. Just a quick one from us. Given Roche's head-to-head win against sotorasib and adagrasib in CRESCENDO-1, do you think you'd need to run a trial against divarasib?

Gugan Raghuraman: Hey, Gouganon for Kalpit. Just a quick one from us. Given Roche's head-to-head win against sotorasib and adagrasib in CRESCENDO-1, do you think you'd need to run a trial against divarasib?

Speaker #5: Thanks for your question. Do you want to comment? The question is whether, if Durasib is approved—I think is what he's asking—then would we be required to run another on RASID frontline study against that?

Mark Goldsmith: Thanks for your question. Do you want to comment? The question is whether if divarasib is approved, I think is what he's asking, then would we be required to run an niraparib frontline study against that?

Speaker #2: Yeah. We'll be having all of our head discussions with the FDA. We basically you're really the control arm is dictated by the current state of affairs at the time that the study is initiated.

Alan Sandler: Yeah. We'll be having all of our head discussions with the FDA. Really, the control arm is dictated by the current state of affairs at the time that the study is initiated. That requires not necessarily a positive study, but that requires a full approval. Since that's not the case at this time, we don't feel that that would be necessary.

Speaker #2: And that requires not necessarily a positive study, but that requires a full approval. And so, since that's not the case at this time, we don't feel that that would be necessary.

Speaker #11: Sounds good. Thank you.

[Analyst] (Wolfe Research): Sounds good. Thank you.

Gugan Raghuraman: Sounds good. Thank you.

Speaker #3: Thank you. This concludes the question and answer session. I would now like to turn it back to Dr. Mark Goldsmith for closing remarks.

Operator: Thank you. This concludes the question and answer session. I would now like to turn it back to Dr. Mark Goldsmith for closing remarks.

Speaker #5: Thank you, operator. And thank you to everyone for participating today and for your continued support of our patient medicines.

Mark Goldsmith: Thank you, operator. Thank you to everyone for participating today and for your continued support of Revolution Medicines.

Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Q2 2026 Revolution Medicines Inc Earnings Call

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