Q1 2026 Revolution Medicines Inc Earnings Call

May 6, 2026

Operator: Good day, and thank you for standing by. Welcome to the Revolution Medicines Q1 2026 earnings call. At this time, participants are in a listen-only mode. After the speaker's 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 then hear an automated message advising you 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 it over to Ryan Asay, Senior VP of Corporate Affairs. Ryan, you have the floor.

Operator: Good day, and thank you for standing by. Welcome to the Revolution Medicines Q1 2026 Earnings Call. At this time, participants are in a listen-only mode. After the speaker's 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 then hear an automated message advising you 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 it over to Ryan Asay, Senior VP of Corporate Affairs. Ryan, you have the floor.

Speaker #1: Good day, and thank you for standing by. Welcome to the Revolution Medicines Q1 2026 earnings call. At this time, participants are in a listen-only mode.

Speaker #1: After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 1-1 on your telephone.

Speaker #1: You will then hear an automated message advising you your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded.

Speaker #1: I would now like to hand it over to Ryan Asay, Senior VP of Corporate Affairs. Ryan, you have the floor.

Speaker #2: Thank you, Operator, and welcome, everyone, to the first quarter 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.

Ryan Asay: Thank you, operator, welcome everyone to the Q1 2026 Earnings Call. Joining me on today's call are Dr. Mark A. Goldsmith, Revolution Medicines Chairman and Chief Executive Officer, Dr. Alan Sandler, our Chief Development Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of R&D, 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 forward-looking statements.

Speaker #2: Dr. Steve Kelsey, our President of R&D; 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.

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, actual results may differ materially from those in forward-looking statements.

Speaker #2: For a 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 at the U.S.

Ryan Asay: 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 U.S. Securities and Exchange Commission. This afternoon, we release financial results for the quarter ended 31 March 2026, and recent corporate updates. The press release and updated corporate presentation are available on the investor 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: Securities and Exchange Commission. This afternoon, we release financial results for the quarter ended March 31, 2026, and recent corporate updates. The press release and updated corporate presentation are available on the Investors section of our website, at revmed.com.

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

Speaker #3: Thanks, Ryan. It's good to be with you this afternoon to discuss the tremendous progress we've made in 2026. This is a pivotal moment for our organization, and for patients worldwide, living with pancreatic cancer who are in need of new therapeutic options.

Mark A. Goldsmith: Thanks, Ryan. It's good to be with you this afternoon to discuss the tremendous progress we've made in 2026. This is a pivotal moment for our organization and for patients worldwide living with pancreatic cancer who are in need of new therapeutic options. It is anchored by the top-line readout for RASolute 302 last month, in which daraxonrasib monotherapy demonstrated an unprecedented improvement in overall survival compared with chemotherapy in patients with previously treated metastatic pancreatic cancer. The RASolute 302 results represent a transformative advance for patients. They also firmly validate our pioneering RAS inhibitor strategy and reinforce its potential to improve outcomes in RAS-driven cancers.

Mark Goldsmith: Thanks, Ryan. It's good to be with you this afternoon to discuss the tremendous progress we've made in 2026. This is a pivotal moment for our organization and for patients worldwide living with pancreatic cancer who are in need of new therapeutic options. It is anchored by the top-line readout for RASolute 302 last month, in which daraxonrasib monotherapy demonstrated an unprecedented improvement in overall survival compared with chemotherapy in patients with previously treated metastatic pancreatic cancer. The RASolute 302 results represent a transformative advance for patients. They also firmly validate our pioneering RAS inhibitor strategy and reinforce its potential to improve outcomes in RAS-driven cancers.

Speaker #3: It is anchored by the top-line readout for Resolute302 last month, in which direct-on-racid monotherapy demonstrated an unprecedented improvement in overall survival compared with chemotherapy in patients with previously treated metastatic pancreatic cancer.

Speaker #3: The Resolute302 results represent a transformative advance for patients. They also firmly validate our pioneering RAS1 inhibitor strategy, and reinforce its potential to improve outcomes in RAS-driven cancers.

Speaker #3: Our investor conviction enabled an historic $2 billion dual-tranche capital raise that will allow us to continue our important work broadly: advancing our current portfolio of four groundbreaking clinical-stage oral RAS(1) inhibitors and bringing forward the next wave of innovation targeting RAS-addicted cancers, including our new class of catalytic RAS(1) inhibitors.

Mark A. Goldsmith: High investor conviction enabled an historic $2 billion dual tranche capital raise that will allow us to continue our important work broadly, advancing our current portfolio of 4 groundbreaking clinical-stage oral RAS inhibitors, and bringing forward the next wave of innovation targeting RAS-addicted cancers, including our new class of catalytic RAS inhibitors. On today's call, following my remarks, I'll pass the call over to Dr. Alan Sandler, who will provide an overview on the recent clinical progress we've made across our portfolio, including the most recent data presented at the American Association for Cancer Research annual meeting. Jack Anders will summarize our Q1 financial results before we open the call to Q&A. Let me first spend a few moments talking about RASolute 302, the global Phase 3 trial evaluating daraxonrasib monotherapy in patients with previously treated pancreatic cancer.

Mark Goldsmith: High investor conviction enabled an historic $2 billion dual tranche capital raise that will allow us to continue our important work broadly, advancing our current portfolio of 4 groundbreaking clinical-stage oral RAS inhibitors, and bringing forward the next wave of innovation targeting RAS-addicted cancers, including our new class of catalytic RAS inhibitors. On today's call, following my remarks, I'll pass the call over to Dr. Alan Sandler, who will provide an overview on the recent clinical progress we've made across our portfolio, including the most recent data presented at the American Association for Cancer Research annual meeting. Jack Anders will summarize our Q1 financial results before we open the call to Q&A. Let me first spend a few moments talking about RASolute 302, the global Phase 3 trial evaluating daraxonrasib monotherapy in patients with previously treated pancreatic cancer.

Speaker #3: On today's call, following my remarks, I'll pass the call over to Dr. Alan Sandler, who will provide an overview of the recent clinical progress we've made across our portfolio.

Speaker #3: Including the most recent data presented at the American Association for Cancer Research annual meeting. Jack Anders will then summarize our first quarter financial results, before we open the call to Q&A.

Speaker #3: Let me first spend a few moments talking about Resolute302, the global Phase 3 trial evaluating direct-on-racid monotherapy in patients with previously treated pancreatic cancer.

Speaker #3: The top-line readout for direct-on-racid marked a major milestone in this disease, significantly raising the bar in the development of new treatments for patients living with pancreatic cancer, the most RAS-addicted of all human cancers.

Mark A. Goldsmith: The top-line readout for daraxonrasib marked a major milestone in this disease, significantly raising the bar in the development of new treatments for patients living with pancreatic cancer, the most RAS-addicted of all human cancers. In RASolute 302, daraxonrasib demonstrated unprecedented impact, meeting its primary and key secondary endpoints and showing statistically significant and clinically meaningful improvement in progression-free survival and overall survival compared to standard of care chemotherapy. In the overall intent-to-treat study population, which includes patients carrying tumors with or without an identified RAS mutation, daraxonrasib drove a 60% reduction in risk of death compared with chemotherapy and with a median overall survival exceeding 1 year. Daraxonrasib was generally well-tolerated, and no new safety signals were observed. These are dramatic practice-changing results, and our focus now is on moving with urgency to bring this potential new option to patients.

Mark Goldsmith: The top-line readout for daraxonrasib marked a major milestone in this disease, significantly raising the bar in the development of new treatments for patients living with pancreatic cancer, the most RAS-addicted of all human cancers. In RASolute 302, daraxonrasib demonstrated unprecedented impact, meeting its primary and key secondary endpoints and showing statistically significant and clinically meaningful improvement in progression-free survival and overall survival compared to standard of care chemotherapy. In the overall intent-to-treat study population, which includes patients carrying tumors with or without an identified RAS mutation, daraxonrasib drove a 60% reduction in risk of death compared with chemotherapy and with a median overall survival exceeding 1 year. Daraxonrasib was generally well-tolerated, and no new safety signals were observed. These are dramatic practice-changing results, and our focus now is on moving with urgency to bring this potential new option to patients.

Speaker #3: In Resolute302, direct-on-racid demonstrated unprecedented impact, meeting its primary and key secondary endpoints, and showing statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared to standard-of-care chemotherapy.

Speaker #3: In the overall intent-to-treat study population, which includes patients carrying tumors with or without an identified RAS mutation, direct-on-racid drove a 60% reduction in the risk of death compared with chemotherapy, and with a median overall survival exceeding one year.

Speaker #3: Direct-on-racid was generally well tolerated, and no new safety signals were observed. These are dramatic practice-changing results, and our focus now is on moving with urgency to bring this potential new option to patients.

Speaker #3: We intend to submit a new drug application to the U.S. Food and Drug Administration, under the FDA Commissioner's National Priority Voucher Program. And we'll also execute our plan to file with other global regulatory authorities.

Mark A. Goldsmith: We intend to submit a New Drug Application to the U.S. Food and Drug Administration under the FDA Commissioner's National Priority Voucher Program and will also execute our plan to file with other global regulatory authorities. Last week, we reported that the FDA issued a safe to proceed letter allowing us to initiate an expanded access treatment protocol for daraxonrasib in patients with previously treated metastatic pancreatic cancer. This will allow us to move as quickly as possible to ensure safe and equitable access to daraxonrasib for eligible patients in the US. We were also pleased to announce recently that RASolute 302 will be featured in the plenary session of this year's American Society of Clinical Oncology, or ASCO, annual meeting in Chicago. We and the investigators look forward to sharing detailed results with the scientific community at that time.

Mark Goldsmith: We intend to submit a New Drug Application to the U.S. Food and Drug Administration under the FDA Commissioner's National Priority Voucher Program and will also execute our plan to file with other global regulatory authorities. Last week, we reported that the FDA issued a safe to proceed letter allowing us to initiate an expanded access treatment protocol for daraxonrasib in patients with previously treated metastatic pancreatic cancer. This will allow us to move as quickly as possible to ensure safe and equitable access to daraxonrasib for eligible patients in the US. We were also pleased to announce recently that RASolute 302 will be featured in the plenary session of this year's American Society of Clinical Oncology, or ASCO, annual meeting in Chicago. We and the investigators look forward to sharing detailed results with the scientific community at that time.

Speaker #3: And last week, we reported that the FDA issued a safe-to-proceed letter allowing us to initiate an expanded access treatment protocol for direct-on-racid in patients with previously treated metastatic pancreatic cancer.

Speaker #3: This will allow us to move as quickly as possible to ensure safe and equitable access to direct-on-racid for eligible patients in the U.S. We were also pleased to announce recently that Resolute302 will be featured in the plenary session of this year's American Society of Clinical Oncology, or ASCO, annual meeting in Chicago.

Speaker #3: We and the investigators look forward to sharing detailed results with the scientific community. At that time. I'll now pass the call over to Alan to walk through some recent clinical program updates.

Mark A. Goldsmith: I'll now pass the call over to Alan to walk through some recent clinical program updates. Alan.

Mark Goldsmith: I'll now pass the call over to Alan to walk through some recent clinical program updates. Alan.

Speaker #3: Alan?

Speaker #2: Thanks, Mark. The extraordinary results from RESOLUTE-302 validate our tri-complex inhibitor platform, and give us increased confidence in direct-on-RAScid's potential in earlier treatment lines in pancreatic cancer.

Alan Sandler: Thanks, Mark. The extraordinary results from RASolute 302 validate our tri-complex inhibitor platform and give us increased confidence in daraxonrasib's potential in earlier treatment lines in pancreatic cancer. This confidence was reinforced at AACR, where we shared updated clinical data from the phase 1/2 studies for daraxonrasib monotherapy and in combination with chemotherapy in first-line metastatic pancreatic cancer. Both the monotherapy and combination cohorts demonstrated encouraging preliminary durability data. In the monotherapy study, while median progression-free survival and median overall survival were not mature as of the data cutoff, the Kaplan-Meier estimates at 6 months were 71% and 83%, respectively. In the combination of daraxonrasib with gemcitabine and nab-paclitaxel, the Kaplan-Meier estimates at 6 months for progression-free survival and overall survival were 84% and 90%, respectively.

Speaker #2: This confidence was reinforced at AACR, where we shared updated clinical data from the Phase 1/2 studies for direct-on-racid monotherapy, and in combination with chemotherapy, in first-line metastatic pancreatic cancer.

Speaker #2: Both the monotherapy and combination cohorts demonstrated encouraging preliminary durability data. In the monotherapy study, while median progression-free survival and median overall survival were not mature as of the data cutoff, the Kaplan-Meier estimates at six months were 71% and 83%, respectively.

Speaker #2: In the combination of direct-on-racid with gemcitabine and navpaclitaxol, the Kaplan-Meier estimates at six months for progression-free survival and overall survival were 84% and 90%, respectively.

Speaker #2: Across both studies, direct-on-racid safety and tolerability profile remained consistent with earlier findings in this patient population, with no new safety signals observed. These compelling results strongly support our decision to rapidly advance Resolute303, our Phase 3 study evaluating both direct-on-racid monotherapy and direct-on-racid in combination with chemotherapy, in first-line metastatic disease.

Alan Sandler: Across both studies, daraxonrasib's safety and tolerability profile remained consistent with earlier findings in this patient population, with no new safety signals observed. These compelling results strongly support our decision to rapidly advance RASolute 303, our phase 3 study evaluating both daraxonrasib monotherapy and daraxonrasib in combination with chemotherapy in first-line metastatic disease. The trial is enrolling globally. In addition to our first and second-line daraxonrasib registrational studies in pancreatic cancer, patient enrollment is ongoing in RASolute-304, our registrational trial of daraxonrasib monotherapy in the adjuvant setting in patients with resectable disease following conventional surgery and perioperative chemotherapy. We are also making progress in two registrational studies for zoldonrasib, our covalent RAS(ON) G12D selective inhibitor in first-line pancreatic cancer.

Speaker #2: The trial is enrolling globally. In addition to our first and second-line direct-on-racid registrational studies in pancreatic cancer, patient enrollment is ongoing in Resolute304, our registrational trial of direct-on-racid monotherapy in the adjuvant setting, in patients with resectable disease following conventional surgery and perioperative chemotherapy.

Speaker #2: We're also making progress in two registrational studies for zoledonracid, our covalent RAFON G12D selective inhibitor in first-line pancreatic cancer. We have initiated Resolute305, a randomized double-blind placebo-controlled registrational trial evaluating zoledonracid choice of chemotherapy, either gemcitabine and navpaclitaxol, or modified FOLFIRINOX compared with placebo plus chemotherapy.

Alan Sandler: We have initiated RASolute-305, a randomized, double-blind, placebo-controlled registrational trial evaluating zoldonrasib in combination with investigator's choice of chemotherapy, either gemcitabine and nab-paclitaxel or modified FOLFIRINOX, compared with placebo plus chemotherapy. We remain on track to initiate RASolute-309, our first registrational study to evaluate the RAS(ON) inhibitor doublet combination of zoldonrasib with daraxonrasib in the H2 of the year. Moving to non-small cell lung cancer, another focus of development for RAS(ON) inhibitors. With approximately 30% of non-small cell lung cancers harboring a RAS mutation, including 18% with non-G12C mutations, unmet needs in non-small cell lung cancer remain a priority that we aim to address through several ongoing and planned registrational studies. Beginning with daraxonrasib, we continue to enroll patients globally in RASolve-301, our global randomized trial evaluating daraxonrasib monotherapy in previously treated patients.

Speaker #2: And we remain on track to initiate Resolute-309, our first registrational study to evaluate the RAF:ON inhibitor doublet combination of zoledronracid with direct-on-racid in the second half of the year.

Speaker #2: Moving to non-small cell lung cancer, another focus of development for RAFON inhibitors. With approximately 30% of non-small cell lung cancers harboring a RAS mutation, including 18% with non-G12C mutations, unmet needs in non-small cell lung cancer remain a priority that we aim to address through several ongoing and planned registrational studies.

Speaker #2: Beginning with direct-on-racid, we continue to enroll patients globally in Resolve301, our global randomized trial evaluating direct-on-racid monotherapy in previously treated patients. Based on the strengths of the Phase 1 results for direct-on-racid monotherapy in non-small cell lung cancer, as well as additional confidence from the recent positive Resolute302 results, we are expanding the Resolve301 study to increase the statistical power of the overall survival component of the dual primary endpoint.

Alan Sandler: Based on the strength of the phase 1 results for daraxonrasib monotherapy in non-small cell lung cancer, as well as additional confidence from the recent positive RASolute 302 results, we are expanding the RASolve-301 study to increase the statistical power of the overall survival component of the dual primary endpoint. Enrollment is going well, and we anticipate substantially completing enrollment in the expanded study this year. We also expect to disclose our plans regarding daraxonrasib combination therapy in first-line non-small cell lung cancer this year. Turning to G12D non-small cell lung cancer. At AACR, we presented updated clinical data for zoldonrasib monotherapy in a subset of patients who had previously been treated with immune checkpoint inhibitors and platinum chemotherapy. Zoldonrasib was generally well-tolerated and demonstrated a safety profile consistent with previously reported findings.

Speaker #2: Enrollment is going well, and we anticipate substantially completing enrollment in the expanded study this year. We also expect to disclose our plans regarding direct-on-racid combination therapy in first-line non-small cell lung cancer this year.

Speaker #2: Turning to G12D non-small cell lung cancer, at AACR, we presented updated clinical data for zoledonracid monotherapy in a subset of patients who had previously been treated with immune checkpoint inhibitors and platinum chemotherapy.

Speaker #2: Zoledonracid was generally well tolerated and demonstrated a safety profile consistent with previously reported findings. Zoledonracid demonstrated encouraging clinical activity with a confirmed objective response rate of 52%.

Alan Sandler: Zoldonrasib demonstrated encouraging clinical activity with a confirmed objective response rate of 52%, disease control rate of 93%, and a median progression-free survival of 11.1 months. Overall survival data were immature at the time of analysis. The estimated survival rate at 12 months was 73%, while the median had not yet been reached, which is encouraging data at this early look. We continue to believe deeply in the potential of zoldonrasib given its compelling safety and tolerability profile and encouraging clinical activity, which strongly support our plans to advance zoldonrasib across monotherapy and combination setting in lung cancer and other RAS G12D-driven cancers.

Speaker #2: Disease control rate of 93%. And a median progression-free survival of 11.1 months. Overall survival data were immature at the time of analysis. The estimated survival rate at 12 months was 73%, while the median had not yet been reached, which is encouraging data at this early look.

Speaker #2: We continue to believe deeply in the potential of zoledonracid given its compelling safety and tolerability profile and encouraging clinical activity, which strongly support our plans to advance zoledonracid across monotherapy and combination setting in lung cancer and other RAS G12D-driven cancers.

Speaker #2: Building on the strength of our monotherapy data, we are preparing to initiate, in the first half of this year, Resolve308, a global double-blind placebo-controlled registrational trial evaluating zoledonracid in combination with the keynote 189 regimen which is the standard of care in first-line treatment for metastatic non-small cell lung cancer.

Alan Sandler: Building on the strength of our monotherapy data, we are preparing to initiate in the H1 of this year RASolve-308, a global, double-blind, placebo-controlled registrational trial evaluating zoldonrasib in combination with the KEYNOTE-189 regimen, which is the standard of care in first-line treatment for metastatic non-small cell lung cancer, compared to the KEYNOTE-189 regimen with placebo. For patients with G12C non-small cell lung cancer, elironrasib, a RAS(ON) mutant selective inhibitor, has demonstrated a differentiated and compelling clinical profile in both G12C inhibitor-naïve and G12C inhibitor-experienced lung cancer patients. We remain on track to share an update on our elironrasib registrational strategy this year. Our third RAS-addicted cancer focus is colorectal cancer, which remains an area of high unmet need and interest for the company.

Speaker #2: Compared to the keynote 189 regimen, with placebo. For patients with G12C non-small cell lung cancer, Elleronracid, our RAFON mutant selective inhibitor, has demonstrated a differentiated and compelling clinical profile in both G12C inhibitor naive and G12C inhibitor experienced lung cancer patients.

Speaker #2: We remain on track to share an update on our Elleronracid registrational strategy this year. Our third RAS-addicted cancer focus is colorectal cancer. Which remains an area of high unmet need and interest for the company.

Speaker #2: We have a range of combination studies underway designed to better understand this genetically complex and heterogeneous disease. Including studies to evaluate RAFON inhibitor doublet combination and RAFON inhibitors in combination with current standards of care and with other targeted drugs.

Alan Sandler: We have a range of combination studies underway designed to better understand this genetically complex and heterogeneous disease, including studies to evaluate RAS(ON) inhibitor doublet combinations and RAS(ON) inhibitors in combination with current standards of care and with other targeted drugs. We remain on track to share combination data this year as we work to prioritize registrational opportunities. I'll conclude with brief highlights on two of our early-stage programs. We continue enrolling patients in the first-in-human trial of RMC-5127, our fourth RAS(ON) inhibitor. RMC-5127 is selective for RAS G12V, the second most common RAS variant in solid tumors. We expect to identify a recommended monotherapy phase 2 dose for this compound in H2 2026. Finally, AACR brought with it the opportunity to showcase our new class of innovative mutant targeted catalytic RAS(ON) inhibitors.

Speaker #2: We remain on track to share combination data this year as we work to prioritize registrational opportunities. I'll conclude with brief highlights on two of our early-stage programs.

Speaker #2: We continue enrolling patients in the first-in-human trial of RMC-5127, our fourth RAFON inhibitor. RMC-5127 is selective for RAS G12V, the second most common RAS variant in solid tumors.

Speaker #2: We expect to identify a recommended monotherapy Phase 2 dose for this compound in the second half of 2026. Finally, AACR brought with it the opportunity to showcase our new class of innovative mutant-targeted catalytic RAFON inhibitors.

Speaker #2: These inhibitors are designed to promote the conversion of mutant RAS in its active GTP-bound RAFON state back to the inactive GDP-bound RAS off-state. Thereby mimicking the normal physiologic regulation of wild-type RAS.

Alan Sandler: These inhibitors are designed to promote the conversion of mutant RAS in its active GTP-bound RAS(ON) state back to the inactive GDP-bound RAS off state, thereby mimicking the normal physiologic regulation of wild-type RAS. These preclinical data demonstrated that at well-tolerated doses, RM 055 achieved robust and durable antitumor activity across KRAS G12 mutant xenograft models of pancreatic cancer, non-small cell lung cancer, and colorectal cancer. Notably, tumors that had escaped prior RAS inhibitor treatment were sensitive to RM 055, which drove deep and durable regression. Its compelling differentiated profile warrants clinical investigation of its potential to counter emergent drug resistance and to extend clinical benefit, and we remain on track to initiate a first-in-human clinical trial in Q4. With that, I'd like to pass the call back over to Mark. Mark?

Speaker #2: These preclinical data demonstrated that at well-tolerated doses, RM055 achieved robust and durable anti-tumor activity across KRAS G12 mutant xenograft models of pancreatic cancer, non-small cell lung cancer, and colorectal cancer.

Speaker #2: Notably, tumors that had escaped prior RAS inhibitor treatment were sensitive to RM055, which drove deep and durable regressions. Its compelling, differentiated profile warrants clinical investigation of its potential to counter emergent drug resistance and to extend clinical benefits, and we remain on track to initiate a first-in-human clinical trial in the fourth quarter.

Speaker #2: With that, I'd like to pass the call back over to Mark. Mark?

Speaker #1: Thanks, Alan. In addition to the substantial R&D progress we've made across our pipeline, we continue to be very gratified by the build-out of our commercialization infrastructure and operational capabilities to support the company's global commercialization ambitions.

Mark A. Goldsmith: Thanks, Alan. In addition to the substantial R&D progress we've made across our pipeline, we continue to be very gratified by the build-out of our commercialization infrastructure and operational capabilities to support the company's global commercialization ambitions. We've established the operational wherewithal required to move with speed and agility, focused initially in the US and extending into priority international regions. We are resourcing our efforts to ensure that we have the best strategies, tactics, operational capabilities, and people to bring daraxonrasib with urgency to patients pending regulatory approvals. We expect to be launch-ready under best case approval timing scenarios. We have experienced and talented executives leading our commercialization team across medical affairs, market access, marketing, and sales. These groups are deeply engaged in market preparedness and assessment, planning, physician and advocacy engagement, sharpening operational capabilities, and conducting other launch readiness activities.

Mark Goldsmith: Thanks, Alan. In addition to the substantial R&D progress we've made across our pipeline, we continue to be very gratified by the build-out of our commercialization infrastructure and operational capabilities to support the company's global commercialization ambitions. We've established the operational wherewithal required to move with speed and agility, focused initially in the US and extending into priority international regions. We are resourcing our efforts to ensure that we have the best strategies, tactics, operational capabilities, and people to bring daraxonrasib with urgency to patients pending regulatory approvals. We expect to be launch-ready under best case approval timing scenarios. We have experienced and talented executives leading our commercialization team across medical affairs, market access, marketing, and sales. These groups are deeply engaged in market preparedness and assessment, planning, physician and advocacy engagement, sharpening operational capabilities, and conducting other launch readiness activities.

Speaker #1: We've established the operational wherewithal required to move the speed and US and extending into priority international regions. We are resourcing our efforts to ensure that we have the best strategies and tactics operational capabilities and people to bring Juraxonracid with urgency to patients pending regulatory approvals.

Speaker #1: We expect to be launch-ready under best-case approval timing scenarios. We have experienced and talented executives leading our commercialization team across medical affairs, market access, marketing, and sales. These groups are deeply engaged in market preparedness and assessment, planning, physician and advocacy engagement, sharpening operational capabilities, and conducting other launch readiness activities.

Speaker #1: We recently appointed several experienced leaders across the Asia-Pacific and European regions including Neil McGregor, as our Tetsuo Endo, as general manager for Japan, and Martin Volkel, as general manager for Germany.

Mark A. Goldsmith: We recently appointed several experienced leaders across the Asia Pacific and European regions, including Neil MacGregor as our General Manager for APAC, Tetsuo Endo as General Manager for Japan, and Martin Voelkl as General Manager for Germany. I'd now like to turn the call over to Jack Anders, our Chief Financial Officer, to summarize our Q1 financial results. Jack?

Mark Goldsmith: We recently appointed several experienced leaders across the Asia Pacific and European regions, including Neil MacGregor as our General Manager for APAC, Tetsuo Endo as General Manager for Japan, and Martin Voelkl as General Manager for Germany. I'd now like to turn the call over to Jack Anders, our Chief Financial Officer, to summarize our Q1 financial results. Jack?

Speaker #1: I'd now like to turn the call over to Jack Anders, our chief financial officer, to summarize our first quarter financial results. Jack?

Speaker #2: Thanks, Mark. We ended the first quarter of 2026 with 1.9 billion in cash and investments, and further strengthened our financial position after the quarter with 2.1 billion in net proceeds from our concurrent upsize offerings of common stock and convertible debt in April.

Jack Anders: Thanks, Mark. We ended Q1 2026 with $1.9 billion in cash and investments and further strengthened our financial position after the quarter with $2.1 billion in net proceeds from our concurrent upsized offerings of common stock and convertible debt in April. Before we dive into the income statement for the quarter, I'd like to highlight that our stock-based compensation expense for the quarter was higher than usual and explain the reason behind it. Stock-based compensation expense was $87.3 million for the quarter ended 31 March 2026, compared to $25.1 million for the quarter ended 31 March 2025. In Q1 2026, the company updated its equity compensation program to introduce competitive retirement benefits for employees who meet specific minimum age and service requirements.

Speaker #2: Before we dive into the income statement for the quarter, I'd like to highlight that our stock-based compensation expense for the quarter was higher than usual, and explain the reason behind it.

Speaker #2: Stock-based compensation expense was $87.3 million for the quarter-ended March 31, 2026, compared to $25.1 million for the quarter-ended March 31, 2025. In the first quarter of 2026, the company updated its equity compensation program to introduce competitive retirement benefits for employees who meet specific minimum age and service requirements.

Speaker #2: The modification of this program resulted in an incremental $44.6 million in stock-based compensation for the first quarter of 2026. This incremental expense was primarily due to the accelerated timing of recognition of stock-based compensation expense originally scheduled in future periods for outstanding eligible awards.

Jack Anders: The modification of this program resulted in an incremental $44.6 million in stock-based compensation for Q1 2026. This incremental expense was primarily due to the accelerated timing of recognition of stock-based compensation expense originally scheduled in future periods for outstanding eligible awards. As a result of this timing pull-in, we expect higher non-recurring lumpiness in stock-based compensation expense for H1 2026, with stock-based compensation expense decreasing and returning to a more normalized trajectory in H2 of the year. As a result of this change, the company is increasing its estimate of full year 2026 stock-based compensation expense by approximately $80 million and now expects full year 2026 stock-based compensation expense to be between $260 to 280 million.

Speaker #2: As a result of this timing pull-in, we expect higher non-recurring lumpiness in stock-based compensation expense for the first half of 2026, with stock-based compensation expense decreasing and returning to a more normalized trajectory in the second half of the year.

Speaker #2: As a result of this change, the company is increasing its estimate of full-year 2026 stock-based compensation expense by approximately $80 million. And now expects full-year 2026 stock-based compensation expense to be between $260 and $280 million.

Speaker #2: Additionally, the company is also updating its projected gap operating expense guidance to reflect this expected increase in stock-based compensation expense. And now expects full-year gap operating expenses to be between $1.7 billion and $1.8 billion.

Jack Anders: The company is also updating its projected GAAP operating expense guidance to reflect this expected increase in stock-based compensation expense and now expects full year GAAP operating expenses to be between $1.7 billion and $1.8 billion. Moving to expenses for the quarter. R&D expenses for Q1 2026 were $344.0 million, compared to $205.7 million for Q1 2025. This increase was primarily due to higher clinical trial and manufacturing expenses for daraxonrasib and zoldonrasib due to acceleration of the pace and expansion of these programs. R&D expenses were also higher as a result of increased headcount costs and higher stock-based compensation expense, as described earlier.

Speaker #2: Moving to expenses for the quarter, R&D expenses for the first quarter of 2026 were $344.0 million, compared to $205.7 million for the first quarter of 2025.

Speaker #2: This increase was primarily due to higher clinical trial and manufacturing expenses for Juraxonracid and Zoldanracid, due to acceleration of the pace and expansion of these programs.

Speaker #2: R&D expenses were also higher, as a result of increased headcount costs and higher stock-based compensation expense, as described earlier. G&A expenses for the first quarter of 2026 were $101.3 million, compared to $35.0 million for the first quarter of 2025.

Jack Anders: G&A expenses for the first quarter of 2026 were $101.3 million, compared to $35.0 million for the first quarter of 2025. The increase in G&A expenses was primarily due to higher stock-based compensation expense, as described earlier. Increased headcount costs, increased commercial preparation activities, and higher administrative costs. Net loss for the first quarter of 2026 was $453.8 million, compared to $213.4 million for the first quarter of 2025. The increase in net loss was due to higher operating expenses. That concludes the financial update. I'll now turn the call back over to Mark.

Speaker #2: The increase in G&A expenses was primarily due to higher stock-based compensation expense as described earlier. Increased headcount costs increased commercial preparation activities, and higher administrative costs.

Speaker #2: Net loss for the first quarter of 2026 was $453.8 million, compared to $213.4 million for the first quarter of 2025. The increase in net loss was due to higher operating expenses.

Speaker #2: That concludes the financial update. I'll now turn the call back over to Mark.

Speaker #1: Thank you, Jack. The remarkable start to 2026 is the results of years of unwavering dedication, relentless perseverance, and hard work by our team and collaborators standing on the shoulders of others.

Mark A. Goldsmith: Thank you, Jack. The remarkable start to 2026 is the result of years of unwavering dedication, relentless perseverance, and hard work by our team and collaborators standing on the shoulders of others. With the unprecedented performance of daraxonrasib monotherapy in the RASolute 302 study, we believe we are in the position to change the standard of care for patients living with pancreatic cancer, subject to regulatory review and approval. The global response to the RASolute 302 data has been overwhelming. The news brings with it hope and possibility for patients, physicians, and the advocacy community that have all been waiting too long for new, more effective treatment options. We are now an important step closer to fulfilling our mission of discovering, developing, and delivering innovative targeted medicines to patients living with cancer. We have an extraordinary opportunity, and we take very seriously the responsibility that goes with it.

Mark Goldsmith: Thank you, Jack. The remarkable start to 2026 is the result of years of unwavering dedication, relentless perseverance, and hard work by our team and collaborators standing on the shoulders of others. With the unprecedented performance of daraxonrasib monotherapy in the RASolute 302 study, we believe we are in the position to change the standard of care for patients living with pancreatic cancer, subject to regulatory review and approval. The global response to the RASolute 302 data has been overwhelming. The news brings with it hope and possibility for patients, physicians, and the advocacy community that have all been waiting too long for new, more effective treatment options. We are now an important step closer to fulfilling our mission of discovering, developing, and delivering innovative targeted medicines to patients living with cancer. We have an extraordinary opportunity, and we take very seriously the responsibility that goes with it.

Speaker #1: With the unprecedented performance of Juraxonracid monotherapy in the resolute 302 study, we believe we are in the position to change the standard of care for patients living with pancreatic cancer subject to regulatory review and approval.

Speaker #1: The global response to the resolute 302 data has been overwhelming, the news brings with it hope, and possibility for patients, physicians, and the advocacy community that have all been waiting too long for new, more effective treatment options.

Speaker #1: We are now an important step closer to fulfilling our mission of discovering, developing, and delivering innovative, targeted medicines to patients living with cancer. We have an extraordinary opportunity and we take very seriously the responsibility that goes with it.

Speaker #1: Before I close, I'd like to recognize our continuing partnerships with patients and caregivers, healthcare providers, and investors as well as the remarkable dedication and efforts of RevMed employees.

Mark A. Goldsmith: Before I close, I'd like to recognize our continuing partnerships with patients and caregivers, healthcare providers, and investors, as well as the remarkable dedication and efforts of RevMed employees. It requires the ongoing support of all of our partners and constituencies to do revolutionary work on behalf of patients. With that, I'll turn the call over to the operator for the question and answer portion of the call.

Mark Goldsmith: Before I close, I'd like to recognize our continuing partnerships with patients and caregivers, healthcare providers, and investors, as well as the remarkable dedication and efforts of RevMed employees. It requires the ongoing support of all of our partners and constituencies to do revolutionary work on behalf of patients. With that, I'll turn the call over to the operator for the question and answer portion of the call.

Speaker #1: It requires the ongoing support of all of our partners and constituencies to do revolutionary work on behalf of patients. With that, I'll turn the call over to the operator for the question-and-answer portion of the call.

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

Operator: Thank you. At this time, we will conduct a 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. We do ask that each person limit their question to 1 question and 1 follow-up. Our first question comes from the line of Cory Kasimov with Evercore ISI. Cory, go ahead with your question.

Speaker #3: To withdraw your question, please press *11 again. We do ask that each person limit their question to one question and one follow-up. Our first question comes from the line, "Of Corey Kazmov with Evercore ISI.

Speaker #3: Corey, go ahead with your question."

Speaker #1: Great. Good afternoon, guys. Thanks for taking the question and congrats on all the recent, very exciting progress. So I wanted to ask, you recently noted you could share data at a medical meeting that supports the rationale for resolute 309, the phase three frontline PDAC trial, looking at Zoldanracid plus Juraxonracid versus chemo.

Cory Kasimov: Great. Good afternoon, guys. Thanks for taking the question and congrats on all the recent very exciting progress. Wanted to ask, you recently noted you could share data at a medical meeting that supports the rationale for RASolute 309, the Phase 3 frontline PDAC trial looking at zoldonrasib plus daraxonrasib versus chemo. Would this include durability data or just response rate as we've seen with some of your initial disclosures? Maybe more importantly, how much additive efficacy would you be looking for here to say it's clinically meaningful to justify the combination over the, you know, the exciting monotherapy results we've seen with both of these agents? Thank you.

Speaker #1: Would this include durability data, or just response rate, as we've seen with some of your initial disclosures? And maybe more importantly, how much additive efficacy would you be looking for here to say it's clinically meaningful—to justify the combination over the exciting monotherapy results we've seen with both of these agents?

Speaker #1: Thank you.

Mark A. Goldsmith: Thanks, Cory. Appreciate your comments and question. It's probably too early for us to lay out what that presentation would look like. We typically don't forecast it. You know, we'll show what we have. We think it will justify our plans and we'll provide that in due course. The second question also probably, unfortunately, I can't be too helpful about what's the, you know, what's the threshold for added value that justifies doing that. I mean, of course, we look at the totality of the evidence, we look at the historical benchmarks, and ultimately, as you sort of implied in your question, durability is, you know, the most important parameter.

Speaker #4: Thanks, Corey. Appreciate your comments and question. It's probably too early for us to lay out what that presentation would look like. We typically don't forecast it.

Mark Goldsmith: Thanks, Cory. Appreciate your comments and question. It's probably too early for us to lay out what that presentation would look like. We typically don't forecast it. You know, we'll show what we have. We think it will justify our plans and we'll provide that in due course. The second question also probably, unfortunately, I can't be too helpful about what's the, you know, what's the threshold for added value that justifies doing that. I mean, of course, we look at the totality of the evidence, we look at the historical benchmarks, and ultimately, as you sort of implied in your question, durability is, you know, the most important parameter.

Speaker #4: We'll show what we have. We think it will justify our plans and we'll provide that in due course. The second question also probably unfortunately can't be too helpful about what's the threshold for added value that justifies doing that.

Speaker #4: I mean, of course, we look at the totality of the evidence. We look at the historical benchmarks. And ultimately, as you sort of implied in your question, durability is the most important parameter.

Speaker #1: Got it. Thank you.

Cory Kasimov: Got it. Thank you.

Speaker #3: Our next question comes from Charles Zhu with LifePsy Capital. Charles, go ahead with your question.

Operator: Our next question comes from Charles Zhu with LifeSci Capital. Charles, go ahead with your question.

Charles Zhu: Good afternoon, everyone. Thank you for taking my questions, and congrats on everything. I've got a couple kind of at the opposite ends of the spectrum. One, how many patients do you think you can accommodate on your expanded access program for daraxonrasib and RASolute 302, and what are the potential implications as you start thinking about potentially converting-

Speaker #5: Good afternoon, everyone. Thank you for taking the questions and congrats on everything. I got a couple kind of at the opposite end of the spectrum.

Speaker #5: One, how many patients do you think can accommodate on your expanded access program for Juraxonracid and resolute 302? And what are the potential implications as you start thinking about potentially converting?

Speaker #4: HROs? Charles, we're not able to pick up what you're saying. Stacey, I don't know if there's anything you can do on your side to improve the audit quality.

Mark A. Goldsmith: Hey, Charles. Charles, we're not able to pick up what you're saying. Stacy, I don't know if there's anything you can do on your side to improve the audio quality.

Mark Goldsmith: Hey, Charles. Charles, we're not able to pick up what you're saying. Stacy, I don't know if there's anything you can do on your side to improve the audio quality.

Speaker #3: Charles, are you in a good position to speak with us?

Operator: Charles, are you in a good position to speak with us? We'll get Charles back.

Mark A. Goldsmith: Why don't we move on to the next call and come back to Charles?

Mark Goldsmith: Why don't we move on to the next call and come back to Charles?

Speaker #4: Why don't we move on to the next call and come back, Charles?

Operator: Yeah. We'll get Charles back queued up. Our next call comes from Michael Schmidt with Guggenheim Securities. Michael, go ahead with your question.

Speaker #3: Yeah, we'll get Charles back queued up. Our next call comes from Michael Schmidt with Guggenheim Securities. Michael, go ahead with your question.

Speaker #6: Yeah. Hey, guys. Thanks for taking my questions. And again, congrats on the resolute 302 data. Looking forward to the full data presentation at ASCO.

Michael Schmidt: Yeah. Hey, guys. Thanks for taking my questions. You know, again, congrats on RASolute 302 data. Looking forward to the full data presentation at ASCO. Yeah, a question on the EAP program. I know this was just announced a few days ago, but Mark, I don't know if you could comment what you're seeing so far in terms of demand for the EAP program, and what do you think how many patients could potentially benefit from this prior to officially receiving FDA approval? Then maybe just, if you could share your view of the size of the second-line pancreatic cancer opportunity based on your market research, how many patients in the US do you think would be treatment eligible for daraxonrasib based on the 302 study? Thanks so much.

Speaker #6: Yeah, a question on the EAP program. I know this was just announced a few days ago, but Mark, I don't know if you could comment on what you're seeing so far in terms of demand for the EAP program, and what you think—how many patients could potentially benefit from this prior to officially receiving FDA approval?

Speaker #6: And then maybe just if you could share your view of the size of the second-line pancreatic cancer opportunity based on your market research, how many patients in the US do you think would be treatment eligible for Juraxonracid based on the 302 study?

Speaker #6: Thanks so much.

Mark A. Goldsmith: Thanks, Michael. Nice to hear from you. You know, on the first question, of course, we're working hard to get in a position to be providing drugs to those who need it. The demand has been very clear from the moment that it was announced, and we don't expect that to slow down anytime soon. You know, we're putting all the resources that we can on it to help meet that need. I can't really give you a projection as to the number. I don't know how we could make that projection. We'll just have to play it out. I think there is clearly widespread knowledge of awareness of daraxonrasib and, you know, those calls started coming in within, you know, minutes after the announcement.

Speaker #4: Thanks, Michael. Nice to hear from you. On the first question, of course, we're working hard to get in a position to be providing drugs to those who need it.

Mark Goldsmith: Thanks, Michael. Nice to hear from you. You know, on the first question, of course, we're working hard to get in a position to be providing drugs to those who need it. The demand has been very clear from the moment that it was announced, and we don't expect that to slow down anytime soon. You know, we're putting all the resources that we can on it to help meet that need. I can't really give you a projection as to the number. I don't know how we could make that projection. We'll just have to play it out. I think there is clearly widespread knowledge of awareness of daraxonrasib and, you know, those calls started coming in within, you know, minutes after the announcement.

Speaker #4: The demand has been very clear from the moment that it was announced. And we don't expect that to slow down anytime soon. And we're putting all the resources that we can on it to help meet that need.

Speaker #4: I can't really give you a projection as to the number. I don't know how we can make that projection. We'll just have to play it out.

Speaker #4: I think there is clearly widespread knowledge of awareness of Juraxonracid and those calls started coming in within minutes after the announcement. The size of the second-line opportunity we might want to talk about this.

Mark A. Goldsmith: The size of the second-line opportunity, Wei might wanna talk about this. We can't characterize it for you in great depth, but, you know, we typically think about roughly 60,000 new cases in each year, then maybe Wei can comment on both what's historical attrition, and then also whether or not daraxonrasib might affect that.

Mark Goldsmith: The size of the second-line opportunity, Wei might wanna talk about this. We can't characterize it for you in great depth, but, you know, we typically think about roughly 60,000 new cases in each year, then maybe Wei can comment on both what's historical attrition, and then also whether or not daraxonrasib might affect that.

Speaker #4: We can't characterize it for you at great depth, but we typically think about roughly 60,000 new cases in each year, and then maybe we can comment on both what's historical attrition and then also whether or not Juraxonracid might affect that.

Speaker #5: Yeah. How do you do that? These are obviously just estimates based on clinical practice. It's more common about 60,000 Americans are newly diagnosed each year with pancreatic cancer.

Wei Lin: Yeah, happy to do that. These are obviously just estimates based on clinical practice. As Mark commented, about 60,000 Americans are newly diagnosed each year with pancreatic cancer. About 50% to 60% of those patients are diagnosed with metastatic disease. Those patients are eligible to receive first-line therapy for metastatic disease. Typically, because of both the aggressive nature of disease as well as the toxicity of chemotherapy, about half of the patients receive first-line metastatic treatment, receive subsequent second-line treatment. That gives you a sense of the overall attrition as well as the size.

Speaker #5: About 50 to 60 percent of those patients are diagnosed with metastatic disease. And so those patients are eligible to be seen first-line therapy for metastatic disease.

Speaker #5: And typically, because of both the aggressive nature of the disease as well as the toxicity of chemotherapy, about half of the patients receive first-line metastatic treatment, receive subsequent second-line treatment.

Speaker #5: So that gives you a sense of the overall attrition, as well as the size.

Mark A. Goldsmith: You know, just to add to that, you know, that could certainly change in the context of first-line treatment, but we don't have anything to address on that point today.

Mark Goldsmith: You know, just to add to that, you know, that could certainly change in the context of first-line treatment, but we don't have anything to address on that point today.

Speaker #1: And just to add to that, that could certainly change in the context of first-line treatment. But we don't have anything to address on that point today.

Speaker #3: Thank you. Our next question comes from Faisal Khashid with Jefferies. Faisal, go ahead with your question.

Michael Schmidt: Thank you.

Operator: Our next question comes from Faisal Khurshid with Jefferies. Faisal, go ahead with your question.

Speaker #7: Hey, guys. Thank you so much for taking the question. I just wanted to ask about the Resolve 301 upsizing. Could you clarify what exactly led to the upsizing?

Faisal Khurshid: Hey, guys. Thank you so much for taking the question. Just wanted to ask on the RASolve-301 upsizing. Could you clarify what exactly led to the upsizing? What were you powered for before, and what are you powered for now? Does this change the timeline from enrollment completion to readout? Thank you.

Speaker #7: What were you powered for before? And what are you powered for now? And does this change the timeline from enrollment completion to readout? Thank you.

Mark A. Goldsmith: Thanks a lot for your question. I'm gonna answer the second question, and then Alan Sandler's gonna talk about the first. We don't think it will change the timing of the readout given the high pace of enrollment and where we stand today. We don't expect to impact our projection that we'll complete or substantially complete enrollment this year. The more subtle question about the sizing of the trial, Alan can comment on.

Speaker #4: Thanks a lot for your question. I'm going to answer the second question and then Al and Taylor are just going to talk about the first.

Mark Goldsmith: Thanks a lot for your question. I'm gonna answer the second question, and then Alan Sandler's gonna talk about the first. We don't think it will change the timing of the readout given the high pace of enrollment and where we stand today. We don't expect to impact our projection that we'll complete or substantially complete enrollment this year. The more subtle question about the sizing of the trial, Alan can comment on.

Speaker #4: We don't think it will change the timing of the readout given the high pace of enrollment and where we stand today. So we don't expect to impact our projection that we'll complete or substantially complete enrollment this year.

Speaker #4: But the more subtle question about the sizing of the trial, Allen can comment on.

Speaker #6: Sure. Thanks. So an important point is we've realized the importance of overall survival. And given the results that we've seen in 302, and also the phase one monotherapy data, we have a very high conviction that on our ability to obtain overall survival benefit.

Alan Sandler: Sure. Thanks. An important point is, you know, we've realized the importance of overall survival. Given the results that we've seen in 302 and also the Phase 1 monotherapy data, we have a very high conviction that on our ability to obtain overall survival benefit. As a result of that, we're gonna further prioritize overall survival in 301 by expanding the enrollment, as you've noted, going from 420 to 590 patients. That'll increase the statistical power of that component of what is a dual primary endpoint.

Speaker #6: So as a result of that, we're going to further prioritize overall survival in 301 by expanding the enrollment, as you've noted, going from 420 to 590 patients.

Speaker #6: That will increase the statistical power of that component of what is a dual primary endpoint. And then again, as Mark has mentioned, we there's a great pace in terms of the patient enrollment and we think that we will substantially complete the enrollment even with the expanded study this year.

Alan Sandler: Again, as Mark has mentioned, we, there's a great pace in terms of the patient enrollment, and we think that we will substantially complete the enrollment even with the expanded study this year.

Speaker #7: Got it. Thank you.

Faisal Khurshid: Got it. Thank you.

Speaker #3: Our next question comes from the line of Brian Chang with JPMorgan. Brian, go ahead with your question.

Operator: Our next question comes from the line of Brian Chang with J.P. Morgan. Brian, go ahead with your question.

Speaker #8: Hey, guys. Thanks for taking our questions. This afternoon. Mark, during the call, you said the best-case timing scenario for DAREX launch across the globe—how should we think about the timing and the cadence then for the filing and launches, specifically across APAC and European regions?

Brian Chang: Hey, guys. Thanks for taking our questions this afternoon. Mark, during the call, you said the best-case timing scenario for darax at launch across the globe. How should we think about the timing and the cadence then for the filing and launches specifically across APAC and European regions? Just on the NDA application, towards the FDA, can you give us a little bit more color, a little bit more granularity in terms of the things that are left to complete? Thank you.

Brian Cheng: Hey, guys. Thanks for taking our questions this afternoon. Mark, during the call, you said the best-case timing scenario for darax at launch across the globe. How should we think about the timing and the cadence then for the filing and launches specifically across APAC and European regions? Just on the NDA application, towards the FDA, can you give us a little bit more color, a little bit more granularity in terms of the things that are left to complete? Thank you.

Speaker #8: And just on the NDA application towards the FDA, can you give us a little bit more color—a little bit more granularity—in terms of the things that are left to complete?

Speaker #8: Thank you.

Mark A. Goldsmith: Yeah. Thanks, Brian. Can't really give you any specific timing with regard to the filings outside the United States, but just generally speaking, we are starting with the US filing as the initial priority. There will be some sequential framework for filing in other countries, and we are already engaged with regulatory authorities outside of the United States in order to make sure that we can deliver what they need, and in as timely a manner as possible. For the NDA, your question was what's left to deliver? Is that how you put it?

Speaker #4: Yeah. Thanks, Brian. Can't really give you any specific timing with regard to the filings outside the United States. But just generally speaking, we are starting with the US filing as the initial priority.

Mark Goldsmith: Yeah. Thanks, Brian. Can't really give you any specific timing with regard to the filings outside the United States, but just generally speaking, we are starting with the US filing as the initial priority. There will be some sequential framework for filing in other countries, and we are already engaged with regulatory authorities outside of the United States in order to make sure that we can deliver what they need, and in as timely a manner as possible. For the NDA, your question was what's left to deliver? Is that how you put it?

Speaker #4: There will be some sequential framework for filing in other countries. And we're already engaged with regulatory authorities outside of the United States in order to make sure that we can deliver what they need and in as timely a manner as possible.

Speaker #4: For the NDA, your question was what's left to deliver. Is that how you put it?

Speaker #7: Yeah. What are the things that are left to complete before you complete the NDA application?

Brian Chang: Yeah. What are the things that are left to complete before you complete the NDA application?

Brian Cheng: Yeah. What are the things that are left to complete before you complete the NDA application?

Speaker #4: Yeah. Well, we've been fully engaged with the FDA for a long time, as you know. And of course, with the CNPB and the breakthrough designation, we've had a higher level of engagement than you might otherwise have.

Mark A. Goldsmith: Yeah. Well, we've been fully engaged with the FDA for a long time, as you know, of course, with the CHMP and the breakthrough designation, we've had a higher level of engagement than you might otherwise have. We are providing them information as it becomes available and mature enough to provide to them. You know, ultimately, the clinical package is the thing that will be provided. I can't give you a specific timing on that. There's, you know, a full throttle effort to do it. We feel the urgency around it. Certainly, the question earlier about the EAP provides a pretty strong signal about how urgent that is, we'll continue to move this forward as fully as we possibly can.

Mark Goldsmith: Yeah. Well, we've been fully engaged with the FDA for a long time, as you know, of course, with the CHMP and the breakthrough designation, we've had a higher level of engagement than you might otherwise have. We are providing them information as it becomes available and mature enough to provide to them. You know, ultimately, the clinical package is the thing that will be provided. I can't give you a specific timing on that. There's, you know, a full throttle effort to do it. We feel the urgency around it. Certainly, the question earlier about the EAP provides a pretty strong signal about how urgent that is, we'll continue to move this forward as fully as we possibly can.

Speaker #4: And so we are providing them information as it becomes available. And sure enough, to provide to them. And ultimately, the clinical package is the thing that will be provided—I can't give you a specific timing on that.

Speaker #4: There's a full throttle effort to do it. We feel the urgency around it. Certainly, the question earlier about the EAP provides a pretty strong signal about how urgent that is.

Speaker #4: And we'll continue to move this forward as fully as we possibly can.

Speaker #7: Great. Thanks, Mark.

Brian Chang: Great. Thanks, Mark.

Brian Cheng: Great. Thanks, Mark.

Speaker #3: Our next question comes from Mark Framm with TD Cohen. Mark, go ahead with your question.

Operator: Our next question comes from Marc Frahm with TD Cowen. Marc, go ahead with your question.

Marc Frahm: Great. Thanks for taking my questions. Maybe following up a little bit on Cory's question earlier, just on the zoldonrasib plus daraxonrasib combo. Can you maybe speak to the 309 design, particularly in light of the 302 finding and, you know, the survival data, I mean, looking better than anything we've ever seen even in first-line? Just why is 309 comparing to chemo still the right design or should it really be switched over to consider daraxonrasib monotherapy as the comparator arm there, at a minimum? You know, one, to get the contribution of parts, but also just from a clinical execution perspective of, you know, where the ball is headed, seems to be headed in pancreatic cancer.

Speaker #7: All right. Thanks for taking my questions. Maybe following up a little bit on Corey's question earlier. Just on the Zoledemiracetab combo—can you maybe speak to the 309 design, particularly in light of the 302 finding and the survival data?

Speaker #7: I mean, looking better than anything we've ever seen, even in first line. Just why is 309 comparing to chemo still the right design? And or should it really be switched over to consider DAREX and RASIM monotherapy as the comparator arm there at a minimum?

Speaker #7: One, to get the contribution of parts, but also just from a clinical execution perspective of where the ball is headed seems to be headed in pancreatic cancer.

Mark A. Goldsmith: Yeah. Thanks, Mark. That's a good question. You know, it's a subtle one. You know, of course, today, standard care is chemotherapy, and until that's, you know, until there's a dataset that moves the FDA, you know, to approve a different treatment, and a different treatment at the level that people consider the new standard of care, then chemotherapy is the standard of care. You know, I think you're sort of inviting me to comment that, of course, we think daraxonrasib has a real potential in monotherapy, but also in combinations in first line. Among those combinations, chemotherapy is one that we've already provided some early stage data on and we're quite excited about. That combination is in the RASolute-303 trial.

Speaker #4: Yeah. Thanks, Mark. That's a good question. It's a subtle one. Of course, today, standard care is chemotherapy. And until that's until there's a data set that moves the FDA to approve a different treatment, and a different treatment at the level that people consider the new standard of care, then chemotherapy is the standard of care.

Mark Goldsmith: Yeah. Thanks, Mark. That's a good question. You know, it's a subtle one. You know, of course, today, standard care is chemotherapy, and until that's, you know, until there's a dataset that moves the FDA, you know, to approve a different treatment, and a different treatment at the level that people consider the new standard of care, then chemotherapy is the standard of care. You know, I think you're sort of inviting me to comment that, of course, we think daraxonrasib has a real potential in monotherapy, but also in combinations in first line. Among those combinations, chemotherapy is one that we've already provided some early stage data on and we're quite excited about. That combination is in the RASolute-303 trial.

Speaker #4: I think your sort of inviting me to comment that, of course, we think DAREX and RASIM has a real potential in monotherapy, but also in combinations in first line.

Speaker #4: And among those combinations, chemotherapy is one that we've already provided some early-stage data on, and we're quite excited about. And that combination is in the 303 trial.

Speaker #4: So we're already going into combinations and it's really just a question of when that bar moves. But we have high confidence that the combination can deliver something that is differentiated from chemotherapy, but also even from monotherapy.

Mark A. Goldsmith: We're already going into combinations, and it's really just a question of when that bar moves. We have high confidence that the combination can deliver something that is differentiated from chemotherapy, but also even from monotherapy. I think the other thing to keep in mind is we do a lot of things where there's overlap in the patient populations that we might be able to serve in different ways. We don't shy away from that. As you know, we've discussed that before. Because every patient has his or her own specific needs, and giving doctors options, even if the outcomes on paper may look fairly similar across broad populations, there still may be reasons why one particular patient would benefit or would be perceived to benefit from one particular combination or monotherapy approach versus another.

Mark Goldsmith: We're already going into combinations, and it's really just a question of when that bar moves. We have high confidence that the combination can deliver something that is differentiated from chemotherapy, but also even from monotherapy. I think the other thing to keep in mind is we do a lot of things where there's overlap in the patient populations that we might be able to serve in different ways. We don't shy away from that. As you know, we've discussed that before. Because every patient has his or her own specific needs, and giving doctors options, even if the outcomes on paper may look fairly similar across broad populations, there still may be reasons why one particular patient would benefit or would be perceived to benefit from one particular combination or monotherapy approach versus another.

Speaker #4: I think the other thing to keep in mind is, we do a lot of things where there's overlap in the patient populations that we might be able to serve in different ways.

Speaker #4: We don't shy away from that, as you know. We've discussed that before. Because every patient has his or her own specific needs. And giving doctors options even if the outcomes on paper may look fairly similar across broad populations, there still may be reasons why one particular patient would benefit or would be perceived to benefit from one particular combination or monotherapy approach versus another.

Speaker #4: So providing the most wholesome set that we can based on the science and then ultimately on the clinical data increases the chance that we're the ones who are delivering the best possible options for patients.

Mark A. Goldsmith: Providing the most fulsome set that we can based on the science and then ultimately on the clinical data, increases the chance that we're the ones who are delivering the best possible options for patients. That's the high level of comment.

Mark Goldsmith: Providing the most fulsome set that we can based on the science and then ultimately on the clinical data, increases the chance that we're the ones who are delivering the best possible options for patients. That's the high level of comment.

Speaker #4: So that's the high-level comment.

Operator: Stand by for our next question. Our next question comes from Jonathan Chang with Leerink Partners. Jonathan, go ahead with your question.

Speaker #3: Stand by for our next question. Our next question comes from Jonathan Chang with Leering Partners. Jonathan, go ahead with your question.

Speaker #8: Hi, guys. Thanks for taking my questions and congrats on the progress. Can you talk about your latest thinking on getting to a chemo-free option in frontline pancreatic cancer?

Jonathan Chang: Hi, guys. Thanks for taking my questions, and congrats on the progress. Can you talk about your latest thinking on getting to a chemo-free option in frontline pancreatic cancer? What gives you confidence in being able to achieve this, and what do you think is the best strategy for achieving this?

Speaker #8: What gives you confidence in being able to achieve this? And what do you think is the best strategy for achieving this?

Mark A. Goldsmith: Yeah. Thanks, Jonathan. Nice, nice to talk with you. Well, we just talked about one of those strategies for a chemo-free frontline, which is monotherapy daraxonrasib. I think the data, single arm data we've shown so far are compelling enough that it just very much justified incorporating that into the Phase 3 first line trial, and we'll see how that performs. We have every expectation that it could deliver a chemo-free regimen. The second option is also one we just talked about, which is combining immune selective inhibitor with daraxonrasib. That would be a chemo-free strategy. That specific combination of zoldonrasib plus daraxonrasib, of course, is for the 40% of pancreatic cancer cases that are carrying a RAS G12D mutation.

Speaker #4: Yeah. Thanks, Jonathan. Nice to talk with you. Well, we just talked about one of those strategies for a chemo-free frontline, which is monotherapy DAREX and RASIM.

Mark Goldsmith: Yeah. Thanks, Jonathan. Nice, nice to talk with you. Well, we just talked about one of those strategies for a chemo-free frontline, which is monotherapy daraxonrasib. I think the data, single arm data we've shown so far are compelling enough that it just very much justified incorporating that into the Phase 3 first line trial, and we'll see how that performs. We have every expectation that it could deliver a chemo-free regimen. The second option is also one we just talked about, which is combining immune selective inhibitor with daraxonrasib. That would be a chemo-free strategy. That specific combination of zoldonrasib plus daraxonrasib, of course, is for the 40% of pancreatic cancer cases that are carrying a RAS G12D mutation.

Speaker #4: And I think the data single-arm data that we've shown so far are compelling enough that it just very much justified incorporating that into the phase three first-line trial.

Speaker #4: And we'll see how that performs. But we have every expectation that it could deliver a chemo-free regimen and then the second option is also one we just talked about, which is combining immune selective inhibitor with DAREX and RASIM.

Speaker #4: That would be a chemo-free strategy. And that specific combination of Zoledem plus DAREX and, of course, is for the 40% of pancreatic cancer cases that are carrying a RAS G12D mutation.

Speaker #4: We have other immune selective inhibitors directed against additional mutations that are common in, or can be found in, breast cancer. So, we could and would likely fill out that collection of regimens—it just happens that Zoledem and RASIM plus DAREX is on the vanguard to work because of the maturity of the compound and the data that we have so far.

Mark A. Goldsmith: We have other multi-selective inhibitors directed against additional mutations that are common in, or can be found in RAS cancer. We could and would likely fill out that collection of regimens. It just happens that zoldonrasib plus daraxonrasib is on the vanguard of the work because of maturity of the, of the compound and the data that we have so far. I think those are two very compelling chemo-free regimens. There are others that one can consider. There are immunologic agents that could be combined. There are other targeted agents that could be combined. We're already exploring, as you know, PRMT5 combination, PRMT5 inhibitor combination, et cetera. I'm sure there will be other things to come over time.

Mark Goldsmith: We have other multi-selective inhibitors directed against additional mutations that are common in, or can be found in RAS cancer. We could and would likely fill out that collection of regimens. It just happens that zoldonrasib plus daraxonrasib is on the vanguard of the work because of maturity of the, of the compound and the data that we have so far. I think those are two very compelling chemo-free regimens. There are others that one can consider. There are immunologic agents that could be combined. There are other targeted agents that could be combined. We're already exploring, as you know, PRMT5 combination, PRMT5 inhibitor combination, et cetera. I'm sure there will be other things to come over time.

Speaker #4: So I think those are two very compelling chemo-free regimens. There are others that one can consider. There are immunologic agents that can be combined.

Speaker #4: There are other targeted agents that could be combined. We're already exploring, as you know, PRMT5 combination. PRMT5 inhibitor combination. Etc. I'm sure there will be other things to come over time.

Speaker #8: Understood. Thank you.

Jonathan Chang: Understood. Thank you.

Speaker #3: Our next question comes from Charles Zhu with LifeSci Capital. Charles, go ahead with your question.

Operator: Our next question comes from Charles Zhu with LifeSci Capital. Charles, go ahead with your question.

Speaker #9: Hello. Thanks for giving me another stab at this. Can you hear me now?

Charles Zhu: Hello. Thanks for giving me another stab at this. Can you hear me now?

Speaker #10: Yes.

Operator: Yes.

Speaker #4: Yes.

Mark A. Goldsmith: Yes.

Mark Goldsmith: Yes.

Speaker #9: All righty. Perfect. I believe a bunch of clinical-type questions were taken. So I'll ask one a little bit earlier. But RM055, nice to see your presentation at AACR.

Charles Zhu: All righty. Perfect. I believe a bunch of clinical type questions were taken, so I'll ask one a little bit earlier. RM055, nice to see your presentation at AACR, as well as some of the work you helped support over at Piero Livio's lab that was just published yesterday. Can you comment a little bit perhaps on RM055's ability to potentially address daraxonrasib resistance mechanisms that go beyond that of a KRAS amplification? Can you also talk a little bit about perhaps how you might be achieving what appears to be, at least pre-clinically, a wider therapeutic window for RAS mutants over RAS wild types over that which daraxonrasib can achieve?

Speaker #9: As well as some of the work you helped support over at Piero LiLido's lab. That was just published yesterday. But can you comment a little bit, perhaps, on RM055's ability to potentially address DAREX and RASIM resistance mechanisms that go beyond that of a KRAS amplification?

Speaker #9: And can you also talk a little bit about perhaps how you might be achieving what appears to be at least preclinically a wider therapeutic window for RAS mutants over RAS wild types over that of which DAREX and RASIM can achieve?

Speaker #9: Any color as to how you're accomplishing that mechanistically and if you can also kind of see that in your preclinical models as you advance that into the clinic?

Charles Zhu: Any color as to how you're accomplishing that mechanistically, and if you can also kind of see that in your pre-clinical models as you advance that into the clinic. Thank you.

Speaker #9: Thank you.

Speaker #4: Thanks, Charles. Those were loud and clear. Yeah. Steve Kelsey, I think I'll comment on both of those important topics.

Mark A. Goldsmith: Thanks, Charles. Those were loud and clear. Yeah. Steve Kelsey, I think, will comment on both of those important topics.

Mark Goldsmith: Thanks, Charles. Those were loud and clear. Yeah. Steve Kelsey, I think, will comment on both of those important topics.

Steve Kelsey: Sure. Yeah, I think the RAS amplification can be perceived as, you know, a standalone mechanistic basis for escape from daraxonrasib, but it also acts as a surrogate for increasing flux through the RAS pathway generally. In most of the experiments that we've done, RM055 is a better inhibitor of increased flux through the RAS pathway generally, particularly when it's going down through a G12 mutation. I think there is a general principle of escape from daraxonrasib occurring through reactivation of RAS pathway signaling. It's not just amplification of the mutant allele that can do that, and I think there's every reason to believe that RM055 may be effective beyond just pure RAS mutation amplification.

Speaker #5: Sure. Yeah. I think the RAS amplification can be perceived as a standalone mechanistic basis for escaping DAREX and RASIM. But it also acts as a surrogate for increasing flux through the RAS pathway generally.

Speaker #5: And in most of the experiments that we've done, RM055 is a better inhibitor of flux through increased flux through the RAS pathway generally, particularly when it's going down through a G12 mutation.

Speaker #5: So I think there is a general principle of escape from DAREX and RASIM occurring through reactivation of RAS pathway signaling. It's not just amplification of the mutant allele that can do that.

Speaker #5: And I think there's every reason to believe that RM055 may be effective beyond just pure RAS mutant amplification. Your point about therapeutic index, it's all to do with the relative importance of hydrolysis of RAS on back to RAS off between cancer and normal tissue.

Steve Kelsey: your point about therapeutic index, it's all to do with the relative importance of hydrolysis of RAS on back to RAS off between cancer and normal tissue. Normal tissue, most of the RAS in normal tissue was already in the off state anyway, but it's being catalyzed back. The active RAS is being catalyzed back to RAS off by, very effectively by the naturally occurring GAPs. The whole point of RAS mutation cancer is that that just doesn't happen. The ability of the mutant RAS to withstand that catalytic hydrolysis back, that hydrolysis back to the RAS off state is very different, and it varies from mutation to mutation.

Speaker #5: Normal tissue most of the RAS in normal tissue was already in the off-state anyway. But it's being catalyzed back. The active RAS is being catalyzed back to RAS off by very effectively by the naturally occurring gaps.

Speaker #5: And the whole point of RAS mutation cancer is that that just doesn't happen. The ability of the mutant RAS to withstand that catalytic hydrolysis back, that hydrolysis back to the RAS off state is very different.

Speaker #5: And it varies from mutation to mutation. But what we've done is very selectively targeted the inability of particularly, as I said, G12 mutant RAS to be hydrolyzed back to RAS off by forcing it to be hydrolyzed back to RAS off.

Steve Kelsey: What we've done is very selectively targeted the inability of particularly, as I said, G12 mutant RAS to be hydrolyzed back to RAS off by forcing it to be hydrolyzed back to RAS off. This drug has almost negligible effect on normal tissue in that respect, and a very significant increased deactivation of mutant RAS in cancer cells.

Speaker #5: And it really has very this drug has almost negligible effect on normal tissue in that respect. And a very significant increased deactivation of mutant RAS in cancer cells.

Speaker #9: Got it. Thanks for taking the questions. And congrats again on everything.

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

Speaker #4: Thank you.

Steve Kelsey: Thank you.

Mark Goldsmith: Thank you.

Speaker #3: Our next question comes from the line of Michael Yee with UBS. Michael, go ahead with your question.

Operator: Our next question comes from the line of Michael Yee with UBS. Michael, go ahead with your question.

Speaker #5: Great. Thanks, guys. Congrats on the progress. Two quick ones. On colorectal cancer data coming up, can you help guide expectations on how to think about combination with EGFR given overlapping RAS and how to think about mitigation or how to interpret results given higher efficacy but also trying to mitigate RAS in that strategy?

Michael Yee: Great. Thanks, guys. Congrats on the progress. 2 quick ones. On the colorectal cancer data coming up, can you help guide expectations on how to think about combination with EGFR given overlapping rash and how to think about mitigation or how to interpret results given higher efficacy, but also trying to mitigate rash in that strategy? Also in the first-line pancreatic cancer study, which is enrolling, we definitely get huge feedback that it's gonna enroll super fast at a number of different sites. Is it safe to assume that there's probably an interim in that study as well eventually once you complete enrollment? Thanks.

Speaker #5: And then also in the first-line PANC study, which is enrolling we definitely get huge feedback that it's going to enroll super fast at a number of different sites.

Speaker #5: Is it safe to assume that there's probably an interim in that study as well eventually once you complete enrollment? Thanks.

Mark A. Goldsmith: Thanks, Michael. Nice to hear from you. Who wants to address the CRC? I mean, maybe I'll just make the comment that it is true that daraxonrasib itself has essentially overlap with the EGFR antagonists from the perspective of suppression of RAS signaling that drives, that drives, the skin side effects. That is a harder combination to contemplate. That really doesn't apply at all with the mutant selective inhibitors. And that's why the G12C selective inhibitors that, you know, launched the field, essentially, sotorasib and adagrasib and now others, can be combined pretty readily. It really fundamentally addresses the whole gap in the EGFR coverage that occurs in the RAS mutant tumors and the whole reason why EGF receptor antagonism is contraindicated typically in RAS mutant tumors.

Speaker #4: Thanks, Michael. Nice to hear from you. Wants to address the CRC I mean, maybe I'll just make the comment that it is true that DAREX and RAS of itself has essentially overlapped with the EGFR antagonists from the perspective of suppression of RAS signaling that drives the skin side effects.

Mark Goldsmith: Thanks, Michael. Nice to hear from you. Who wants to address the CRC? I mean, maybe I'll just make the comment that it is true that daraxonrasib itself has essentially overlap with the EGFR antagonists from the perspective of suppression of RAS signaling that drives, that drives, the skin side effects. That is a harder combination to contemplate. That really doesn't apply at all with the mutant selective inhibitors. And that's why the G12C selective inhibitors that, you know, launched the field, essentially, sotorasib and adagrasib and now others, can be combined pretty readily. It really fundamentally addresses the whole gap in the EGFR coverage that occurs in the RAS mutant tumors and the whole reason why EGF receptor antagonism is contraindicated typically in RAS mutant tumors.

Speaker #4: So that is a harder combination to contemplate. That really doesn't apply at all with the mutant selective inhibitors. And that's why the G12C selective inhibitors that launched the field essentially so DAREX and added RASIM and now others can be combined pretty readily.

Speaker #4: And it really fundamentally addresses the whole gap in the EGFR coverage that occurs in the RAS mutant. Tumors and the whole reason why EGF receptor antagonism is contraindicated typically in RAS mutant tumors.

Speaker #4: You really need the RAS inhibitor. So that combination is in principle something that can be pursued. Stay tuned. We'll talk about it when we're able to do so.

Mark A. Goldsmith: You really need the RAS inhibitor. That combination is, in principle, something that can be pursued. Stay tuned. We'll talk about it when we're able to do so. Question about the first line. I forgot the tail end of the actual question part of it. It was.

Mark Goldsmith: You really need the RAS inhibitor. That combination is, in principle, something that can be pursued. Stay tuned. We'll talk about it when we're able to do so. Question about the first line. I forgot the tail end of the actual question part of it. It was.

Speaker #4: The question about the first line I forgot the tail end of the actual question part of it. It was.

Speaker #5: Did it have an interim analysis built into it?

Michael Yee: Does it have an interim analysis still continued?

Mark A. Goldsmith: Oh, does it have an interim analysis? Wei, you wanna comment on that?

Mark Goldsmith: Oh, does it have an interim analysis? Wei, you wanna comment on that?

Speaker #4: Oh, does it have an interim analysis way you want to comment on that?

Wei Lin: Well, I guess, at this current state, we don't plan to disclose the analysis plan.

Speaker #5: I guess so. This current stage, we don't plan to disclose the analysis plan.

Speaker #4: Okay. So there, you've heard it from our chief medical officer.

Mark A. Goldsmith: Okay.

Mark Goldsmith: Okay.

Wei Lin: So.

Mark A. Goldsmith: There, you heard it from our Chief Medical Officer.

Mark Goldsmith: There, you heard it from our Chief Medical Officer.

Speaker #5: Thank you. Thank you. Thank you.

Michael Yee: Thank you. Thank you. Thank you.

Speaker #3: Our next question comes from Laura Pendergast with Stifel. Laura, go ahead with your question.

Operator: Our next question comes from Laura Prendergast with Stifel. Laura, go ahead with your question.

Speaker #10: Hey, guys. Thanks for the update. I was curious what are some of the top variables still under consideration for DAREX and RASIB in first-line lung cancer as far as strategy goes?

Laura Prendergast: Hey, guys. Thanks for the update. I was curious, you know, what are some of the top variables still under consideration for daraxonrasib in first-line lung cancer as far as strategy goes? On the back of RASolute 302, you know, showing such a, you know, unprecedented OS, you know, what kind of pricing power are you guys thinking, you know, this could unlock? Are there any benchmarks for pricing that you guys are most focused on?

Speaker #10: And then on the back of RAS flu 302, showing such a unprecedented OS, what kind of pricing power are you guys thinking this could unlock?

Speaker #10: And are there any benchmarks for pricing that you guys are most focused on?

Mark A. Goldsmith: Yeah. Hi, Laura. Nice to hear from you. Don't think we can really comment on the pricing. You know, of course, the OS impact is something everybody's interested in, starting with patients and their families and all the way up to insurers and payers in other geographies. You know, it will be relevant to their considerations, but that's about all we could say about pricing today. Then your question on first-line non-small cell lung cancer, which was what?

Speaker #4: Yeah. Hi, Laura. Nice to hear from you. I don't think we can really comment on the pricing. Of course, the OS impact is something everybody's interested in, starting with patients and their families and all the way up to insurers and payers and other geographies.

Mark Goldsmith: Yeah. Hi, Laura. Nice to hear from you. Don't think we can really comment on the pricing. You know, of course, the OS impact is something everybody's interested in, starting with patients and their families and all the way up to insurers and payers in other geographies. You know, it will be relevant to their considerations, but that's about all we could say about pricing today. Then your question on first-line non-small cell lung cancer, which was what?

Speaker #4: So it will be relevant to their considerations. But that's about all we could say about pricing today. And then your question on first-line non-small cell lung cancer, which was what?

Laura Prendergast: What are the variables we're thinking through?

Ryan Asay: What are the variables we're thinking through?

Speaker #5: What are the variables we're thinking through?

Speaker #4: Oh, I see. With regard to DAREX and RASIB in first-line. Well, we've alluded to it. We commented that there are a couple of things going on.

Mark A. Goldsmith: Oh, I see. With regard to daraxonrasib in first-line. Well, we've alluded to it. You know, we commented that there are a couple of things going on. Probably the one of the most important is that we're now dosing patients with imatinib, which may become, you know, we're all waiting to see how that progresses, but it points towards, you know, potentially becoming the new standard of care for first-line non-small cell lung cancer, in which case, that's something we need to take into account, which we hadn't really taken into account before we had the real relationship with Summit. That's now, you know, very much active and we're dosing patients. That's probably the main variable.

Mark Goldsmith: Oh, I see. With regard to daraxonrasib in first-line. Well, we've alluded to it. You know, we commented that there are a couple of things going on. Probably the one of the most important is that we're now dosing patients with imatinib, which may become, you know, we're all waiting to see how that progresses, but it points towards, you know, potentially becoming the new standard of care for first-line non-small cell lung cancer, in which case, that's something we need to take into account, which we hadn't really taken into account before we had the real relationship with Summit. That's now, you know, very much active and we're dosing patients. That's probably the main variable.

Speaker #4: Probably one of the most important is that we're now dosing patients with Ibanesumab, which may become we're all waiting to see how that progresses.

Speaker #4: But it points towards potentially becoming the new standard of care for front-line non-small cell lung cancer, in which case that's something we need to take into account, which we hadn't really taken into account before we had the real relationship with Summit that's now very much active and we're dosing patients.

Speaker #4: That's probably the main variable. I think the other thing just conceptually to comment on is the mutant selective inhibitors are already pretty well established simply because of the G12C inhibitors that launched the field.

Mark A. Goldsmith: I think the other thing just conceptually to comment on is the mutant selective inhibitors are already pretty well established simply because of the G12C inhibitors that launched the field. That's sort of a paradigm that lung cancer doctors are now used to thinking that G12C is its own disease, which means G12D will be its own disease and G12V will be its own disease. Pretty quickly, you've covered, you know, most of the mutations in RAS lung cancer. We happen to have a G12D selective inhibitor, which is performing, you know, particularly well. We happen to have a G12C selective inhibitor, which is quite differentiated and compelling. We have a G12V selective inhibitor that's in the clinic now, and we expect good things from that.

Mark Goldsmith: I think the other thing just conceptually to comment on is the mutant selective inhibitors are already pretty well established simply because of the G12C inhibitors that launched the field. That's sort of a paradigm that lung cancer doctors are now used to thinking that G12C is its own disease, which means G12D will be its own disease and G12V will be its own disease. Pretty quickly, you've covered, you know, most of the mutations in RAS lung cancer. We happen to have a G12D selective inhibitor, which is performing, you know, particularly well. We happen to have a G12C selective inhibitor, which is quite differentiated and compelling. We have a G12V selective inhibitor that's in the clinic now, and we expect good things from that.

Speaker #4: And that's sort of a paradigm that lung cancer doctors are now used to, thinking that G12C is its own disease, which means G12D will be its own disease, and G12B will be its own disease.

Speaker #4: And pretty quickly, you've covered most of the mutations in RAS lung cancer. We happen to have a G12D selective inhibitor, which is performing particularly well.

Speaker #4: We happen to have a G12C selective inhibitor, which is quite differentiated and compelling. We have a G12B selective inhibitor that's in the clinic now.

Speaker #4: And we expect good things from that. So, there are multiple ways to cover that. And in a field in which it's already broken down by genotype, that's one possible strategy.

Mark A. Goldsmith: There are multiple ways to cover that, and it is in a field in which it's already broken down by a genotype. That's one possible strategy. Those are kind of several of the major considerations.

Mark Goldsmith: There are multiple ways to cover that, and it is in a field in which it's already broken down by a genotype. That's one possible strategy. Those are kind of several of the major considerations.

Speaker #4: So those are kind of several of the major considerations.

Speaker #10: Understood. Thank you very much.

Laura Prendergast: Understood. Thank you very much.

Speaker #3: Our next question comes from Jay Olson with Oppenheimer. Jay, go ahead with your question.

Operator: Our next question comes from Jay Olson with Oppenheimer. Jay, go ahead with your question.

Speaker #11: Oh, hey. Congrats on all the progress. And thanks for providing this update. How would you like to set expectations for the upcoming ASCO plenary presentation in terms of where you'd like investors to focus their attention?

Jay Olson: Oh, hey. Congrats on all the progress, and thanks for providing this update. How would you like to set expectations for the upcoming ASCO plenary presentation in terms of where you'd like investors to focus their attention? Thank you.

Speaker #11: Thank you.

Mark A. Goldsmith: I think my main expectation is it's going to be crowded. I'm not sure really how to help you on that. I mean, we'll be providing, I think, through the investigators a full, you know, a full update on it. You know, the update will be consistent with what we've said so far, but provide, you know, significantly more information that the experts in the field need to see and evaluate in that, you know, in that setting.

Speaker #4: I think my main expectation is it's going to be crowded. I'm not sure really how to help you on that. I mean, we'll be providing a, I think, through the investigators a full update on it.

Mark Goldsmith: I think my main expectation is it's going to be crowded. I'm not sure really how to help you on that. I mean, we'll be providing, I think, through the investigators a full, you know, a full update on it. You know, the update will be consistent with what we've said so far, but provide, you know, significantly more information that the experts in the field need to see and evaluate in that, you know, in that setting.

Speaker #4: And the update will be consistent with what we've said so far, but provide significantly more information that the experts in the field need to see and evaluate in that setting.

Speaker #11: Great. Thank you.

Jay Olson: Great. Thank you.

Speaker #3: Our next question comes from Kelsey Goodwin with Piper Sandler. Kelsey, go ahead with your question.

Operator: Our next question comes from Kelsey Goodwin with Piper Sandler. Kelsey, go ahead with your question.

Kelsey Goodwin: Hey, thanks so much for taking my question. Congrats on all the progress recently. I think two quick ones from me. First, I guess any additional color that you're providing on the sales force. Secondly, I think building on one of your prior answers in this question and answer session, I guess as we start to think about that front line to second line attrition rate once daraxonrasib comes onto the market, I guess, do you have a sense what percent of that 50% of patients that don't proceed to second line are unfit for therapy altogether versus, you know, ineligible or unwilling to take another chemotherapy just as we, you know, start to model that out a bit more refined? Thanks so much.

Speaker #10: Hey. Thanks so much for taking my question. Congrats on all the progress recently. I think two quick ones for me. First, I guess any additional color that you're providing on the Salesforce and then secondly, I think building on one of your prior answers in this question and answer session, I guess as we start to think about that front-line to second-line attrition rate, once DAREX and RASIB comes onto the market, I guess do you have a sense what percent of that 50% of patients that don't proceed to second line are unfit for therapy altogether versus ineligible or unwilling to take another chemotherapy?

Speaker #10: Just as we start to model that out a bit more refined. Thanks so much.

Speaker #4: Yeah. Thanks, Kelsey. Anthony, you want to just comment on the sort of sales organization more broadly?

Mark A. Goldsmith: Yeah. Thanks. Thanks, Kelsey. Anthony, you wanna just comment on the sort of sales organization more broadly?

Mark Goldsmith: Yeah. Thanks. Thanks, Kelsey. Anthony, you wanna just comment on the sort of sales organization more broadly?

Anthony Mancini: Yeah, thanks for the question, Kelsey. I think for the US region, we're in the final stages of building out our field-based teams all across different functions in the field, med affairs, market access, and sales. We've had an MSL team and a thought leader liaison team in place for quite some time. We also have a market access account team that's been in place that's been engaging with payers and organized customers, you know, really around the unmet need in pancreatic cancer, around the pipeline and the early clinical data for daraxonrasib through pre-approval information exchanges. We're really pleased to say that we're in the final stages of onboarding our US sales force that we're pleased with the team.

Speaker #5: Yeah. So thanks for the question, Kelsey. I think for the US region, we're in the final stages of building out our field-based teams all across different functions in the field: med affairs, market access, and sales.

Speaker #5: We've had an MSL team and a thought leader liaison team in place for quite some time. We also have a market access account team that's been in place, that's been engaging with payers and organized customers really around the unmet need in pancreas cancer, around the pipeline in the early clinical data for DAREX and RASIB through pre-approval information exchanges.

Speaker #5: And we're really pleased to say that we're in the final stages of onboarding our US Salesforce that we're pleased with the team. They have deep expertise and solid tumors.

Anthony Mancini: They have deep expertise in solid tumors across GI malignancies and in oral oncology and they'll be fully trained and ready to go with HCP engagements if we were to receive an FDA approval.

Speaker #5: Across GI malignancies and in oral oncology and they'll be fully trained and ready to go. With HCP engagements, if we were to achieve an FDA approval.

Mark A. Goldsmith: Thanks Anthony. On the first line to second line, it's a good question. It's an important question. It's a little bit hard to get a detailed and clear understanding of because in reviewing records and so on, it's not always clear. In fact, it's surprisingly how common it is that it's not clear why somebody hasn't gone on to second line. You don't always identify an obvious performance status issue or concurrent illness or disease status that would prevent somebody from moving on. Therefore, they might have decided not to proceed because of intolerability, or they might have decided not to proceed because of perceived intolerability before they tried it, or because they wanna focus their life at this stage on family and not on chemo infusions. There's a wide variety of reasons.

Speaker #4: Thanks, Anthony. And on the first-line to second-line it's a good question. It's an important question. It's a little bit hard to get detailed and clear understanding of because in reviewing records and so on, it's not always clear.

Mark Goldsmith: Thanks Anthony. On the first line to second line, it's a good question. It's an important question. It's a little bit hard to get a detailed and clear understanding of because in reviewing records and so on, it's not always clear. In fact, it's surprisingly how common it is that it's not clear why somebody hasn't gone on to second line. You don't always identify an obvious performance status issue or concurrent illness or disease status that would prevent somebody from moving on. Therefore, they might have decided not to proceed because of intolerability, or they might have decided not to proceed because of perceived intolerability before they tried it, or because they wanna focus their life at this stage on family and not on chemo infusions. There's a wide variety of reasons.

Speaker #4: In fact, it's surprisingly how common it is that it's not clear why somebody hasn't gone on to second line. You don't always identify an obvious performance status issue or concurrent illness or disease status that would prevent somebody from moving on.

Speaker #4: And therefore, they might have decided not to proceed. Because of intolerability, or they might have decided not to proceed because of perceived intolerability before they tried it, or because they want to focus their life at this stage on family and not on chemo infusions.

Speaker #4: There are a wide variety of reasons. And then, sadly, it's also true that patients who start chemotherapy in first line sometimes don't survive to second line.

Mark A. Goldsmith: You know, sadly, it's also true that patients who start chemotherapy in first line sometimes don't survive to second line. You know, it's a pretty devastating illness as everybody knows. There are a lot of different reasons. Some of those could be addressed by a regimen that is more convenient, that is better tolerated. A once-a-day pill that really is generally well-tolerated and safety issues are manageable could for sure impact somebody's decision. We don't know whether or not it will. We'll only know that if we get to the finish line with an approval and then can see how patients do in that context.

Mark Goldsmith: You know, sadly, it's also true that patients who start chemotherapy in first line sometimes don't survive to second line. You know, it's a pretty devastating illness as everybody knows. There are a lot of different reasons. Some of those could be addressed by a regimen that is more convenient, that is better tolerated. A once-a-day pill that really is generally well-tolerated and safety issues are manageable could for sure impact somebody's decision. We don't know whether or not it will. We'll only know that if we get to the finish line with an approval and then can see how patients do in that context.

Speaker #4: So it's a pretty devastating illness as everybody knows. So there are a lot of different reasons. Some of those could be addressed by a regimen that is more convenient, that is better tolerated, a once-a-day pill that really is generally well tolerated and safety issues are manageable, could for sure impact somebody's decision.

Speaker #4: We don't know whether or not it will. We'll only know that if we get to the finish line with an approval, and then can see how patients do in that context.

Speaker #10: Perfect. Thank you so much.

Kelsey Goodwin: Perfect. Thank you so much.

Speaker #3: Our next question comes from Kalpit Patel of Wolf Research. Kalpit, go ahead with your question.

Operator: Our next question comes from Kalpit Patel of Wolfe Research. Kalpit, go ahead with your question.

Speaker #5: Yeah, hey, thanks for taking our questions and congrats on the Trial Ahead movie. So, for RESOLUTE-303, how should we think about that study's enrollment graph versus the second-line study that you just completed, in terms of timing of enrollment completion?

Kalpit Patel: Yeah. Hey, thanks for taking our questions and congrats on the trial ahead with Mogi. So for RASolute 303, how should we think about that study's enrollment ramp versus the second line study that you just completed, in terms of timing of enrollment completion? Can you remind us if crossover is allowed in that RASolute 303 study? Separately, any comments on potentially starting a registrational trial with daraxonrasib and a PRMT5 inhibitor? Thank you.

Speaker #5: And then can you remind us if crossover is allowed in that Resolute 303 study? And separately, any comments on potentially starting a registrational trial with Direxon and a PRMD5 inhibitor?

Speaker #5: Thank you.

Mark A. Goldsmith: Thanks very much for your questions. The timing of completion, we can't comment on that now. We're just not at a stage where we can project a timeline with any confidence. Maybe the even more important point would be we know there's very, very high interest in this and, you know, sites that have activated are enrolling. There are plenty of sites that still are yet to be online, and there are patients, you know, lined up at many of these facilities. We're aware of that. We expect there to be very high demand for this for a variety of reasons, not the least of which is the disclosure of the RASolute 302, you know, key findings.

Speaker #4: Thanks very much for your questions. The timing of completion we can't comment on that now. We're just not at a stage where we can project a timeline with any confidence.

Mark Goldsmith: Thanks very much for your questions. The timing of completion, we can't comment on that now. We're just not at a stage where we can project a timeline with any confidence. Maybe the even more important point would be we know there's very, very high interest in this and, you know, sites that have activated are enrolling. There are plenty of sites that still are yet to be online, and there are patients, you know, lined up at many of these facilities. We're aware of that. We expect there to be very high demand for this for a variety of reasons, not the least of which is the disclosure of the RASolute 302, you know, key findings.

Speaker #4: But maybe an even more important point would be, we know there's very, very high interest in this. And sites that have activated are enrolling, but there are plenty of sites that still are yet to be online, and there are patients lined up at many of these facilities—we're aware of that.

Speaker #4: So we expect there to be very high demand for this. For a variety of reasons, not the least of which is the disclosure of the 302 key findings, which increases people's commitment to it.

Mark A. Goldsmith: Which

Mark Goldsmith: Which This is people's commitment to it. Crossover. Crossover is not allowed in the trial design. As you know, of course, it's up to any individual patient. They can cross over on their own if there is an approved therapy to cross over to. In terms of actual crossover design, we can't really provide it when OS is the standard, and that's the sort of conundrum of a Phase 3 trial for which overall survival is the endpoint. You know, we're currently kind of in the process of transitioning from equipoise to out of equipoise. Where we stand in that is sort of, is a matter of judgment, and it's really a question for the regulatory agency. They have to make that determination. As long as OS is required, it's very difficult to achieve that with a crossover design. Do you wanna add to those points? No?

Mark A. Goldsmith: This is people's commitment to it. Crossover. Crossover is not allowed in the trial design. As you know, of course, it's up to any individual patient. They can cross over on their own if there is an approved therapy to cross over to. In terms of actual crossover design, we can't really provide it when OS is the standard, and that's the sort of conundrum of a Phase 3 trial for which overall survival is the endpoint. You know, we're currently kind of in the process of transitioning from equipoise to out of equipoise. Where we stand in that is sort of, is a matter of judgment, and it's really a question for the regulatory agency. They have to make that determination.

Speaker #4: Crossover is not allowed in the trial design. As you know, of course, it's up to any individual patient. They can crossover on their own if there is an approved therapeutic crossover too.

Speaker #4: But in terms of actual crossover design, we can't really provide it when OS is the standard. And that's the sort of conundrum of a phase three trial for which overall survival is the endpoint.

Speaker #4: And where we're currently kind of in the process of transitioning from Equipois to out of Equipois, and where we stand in that is sort of a matter of judgment.

Speaker #4: And it's really a question for the regulatory agency. They have to make that determination. And as long as OS is required, it's very difficult to achieve that with a crossover design.

Mark A. Goldsmith: As long as OS is required, it's very difficult to achieve that with a crossover design. Do you wanna add to those points? No?

Speaker #4: Anything you want to add to those points? No?

Anthony Mancini: The only additional comments I would make, again, because of the concern for overall survival being a primary endpoint is we've established a broad geographic footprint in order to mitigate the potential for impact of second line therapy with daraxonrasib moving forward. Smaller US footprint, larger ex US moving forward.

Speaker #5: The only additional comment I would make again, because of the concern for overall survival being a primary endpoint, is we've established a broad geographic footprint in order to mitigate the potential for impact of second-line therapy with Direxon moving forward.

Speaker #5: So smaller US footprint, larger ex-US moving forward.

Speaker #4: Right. Good comment. And then the last thing was with regard to PRMD5. We don't have any update to provide on that today. We're enthusiastically engaged in the collaboration with several companies now who are evaluating PRMD5 inhibitors in combination with RAS inhibitors.

Mark A. Goldsmith: Right. Good comment. The last thing was with regard to PRMT5. We don't have any update to provide on that today. We're enthusiastically engaged in collaboration with several companies now who are evaluating PRMT5 inhibitors in combination with RAS inhibitors, and we're keenly interested in how that goes.

Mark Goldsmith: Right. Good comment. The last thing was with regard to PRMT5. We don't have any update to provide on that today. We're enthusiastically engaged in collaboration with several companies now who are evaluating PRMT5 inhibitors in combination with RAS inhibitors, and we're keenly interested in how that goes.

Speaker #4: And we're keenly interested in how that work goes.

Speaker #5: Thank you.

Kalpit Patel: Thank you.

Speaker #3: Our final question comes from the line of Alex Stranahan with Bank of America. Alex, go ahead with your question.

Operator: Our final question comes from the line of Alec Stranahan with Bank of America. Alec, go ahead with your question.

Speaker #6: Hey, guys. Thanks for taking my questions and for squeezing me in here at the end. I guess two from me. First, I would be interested to hear from your experience whether the initial ORR with Direxon RASIB was a good metric for predicting PFS and OS benefit in larger studies.

Alec Stranahan: Hey, guys. Thanks for taking my questions and for squeezing me in here at the end. I guess, two from me. First would be interested to hear from your experience whether the initial ORR with daraxonrasib was a good metric for predicting PFS and OS benefit in larger studies. Like, does a higher numerical ORR translate to better survival or if duration of response or time on therapy may be more telling for this? Just trying to think through some headline numbers we're seeing from others in the, in the space. Quickly, will you be allowing third line plus patients into the EAP as well? Thank you.

Speaker #6: Does the higher numerical ORR translate to better survival? Or is duration of response or time on therapy maybe more telling for this? Just trying to think through some headline numbers.

Speaker #6: We're seeing from others in the space. And quickly, will you be allowing third-line plus patients into the EAP as well? Thank you.

Speaker #4: Thanks, Alex. On the last question, yes, the eligible population includes previously treated. It goes beyond the pure second-line that are in the that were in the 302 trial.

Mark A. Goldsmith: Thanks, Alec. On the last question, yes, the eligible population includes previously treated and it goes beyond the pure second line that are in the 302 trial. Is ORR predictive of PFS or OS? Who wants to comment on that?

Mark Goldsmith: Thanks, Alec. On the last question, yes, the eligible population includes previously treated and it goes beyond the pure second line that are in the 302 trial. Is ORR predictive of PFS or OS? Who wants to comment on that?

Speaker #4: Is ORR predictive of PFS? Or OS? Who wants to comment on that?

Speaker #5: Well, we don't show analysis on that. It's broadly correlative with ORR is broadly correlates with PFS. It's not such a tight documentary relationship that you can actually say that if the ORR is 5%, it points higher that the PFS is going to be 5%, it points higher.

Steve Kelsey: Well, we've certainly done some analysis on that. It's broadly correlative with PFS. ORR is broadly correlative with PFS. It's not, it's not such a tight stocky metric relationship that you can actually say that if the ORR is 5 percentage points higher, that the PFS is going to be 5 percentage points higher. But the, it is broadly correlative. There are better ways of predicting PFS and which involve multiparametric analyses that include ORR, but are not restricted to ORR. We have not made those broadly available to other people because obviously it's a competitive advantage for us to know that and not share it with our competitors. But, definitely ORR is a component of that framework for sure.

Speaker #5: But the but it is broadly correlate. There are better ways of predicting PFS. And which involve multi-parametric analyses that include ORR but are not restricted to ORR.

Speaker #5: We have not made those broadly available to other people because obviously, it's a competitive advantage for us to know that and not share it with our competitors.

Speaker #5: But definitely, ORR is a component of that framework for sure. So I think as we're learning more and you're right, I mean, we're learning a lot more now that we have decent drugs for pancreatic cancer.

Steve Kelsey: I think as we're learning more, and you're right, you know, I mean, we're learning a lot more now that we have decent drugs for pancreatic cancer. We're learning a lot more about the relationship between all of these outcomes. I mean, in other diseases like lung cancer, breast cancer, and colorectal cancer, it took years to figure out these relationships, and they're still not totally clear. Yeah. I think that you will see relationships emerging, whether they're causal or otherwise. I wouldn't draw too many straight lines.

Speaker #5: We're learning a lot more about the relationship between all of these outcomes. But I mean, in other diseases, like lung cancer and breast cancer and colorectal cancer, it took years and years and years to figure out these relationships.

Speaker #5: And there's still not totally clear. So yeah. I think that you will see relationships emerging, whether they're causal or otherwise. But I wouldn't draw too many straight lines.

Speaker #4: Yeah. I'll pile on on that. There's obviously some relationship. But what you can do with that and how you should interpret ORR data and have vision for what that's going to translate into premature and.

Mark A. Goldsmith: Yeah. That's it. I'll pile on on that. There's obviously some relationship, but what you can do with that and how you should interpret ORR data.

Mark Goldsmith: Yeah. That's it. I'll pile on on that. There's obviously some relationship, but what you can do with that and how you should interpret ORR data. Have vision for what that's gonna translate into, premature.

Mark A. Goldsmith: Have vision for what that's gonna translate into, premature.

Steve Kelsey: Yeah. The other, the other thing is, of course, with RAS inhibitors, the numerical value of ORR at any point in time isn't very accurate anyway. You know, patients can take up to and sometimes beyond six months to fulfill the RECIST definition of response. At any given point in time, there may still be people who might become responders who have not yet become responders. The RECIST definition of response isn't a particularly robust endpoint in its own right. You know, there's a lot of wiggle room and uncertainty around all of these analyses. It's very tempting to believe that the overall response rate determined by RECIST is a pure and absolute and accurate measurement. I can tell you it absolutely is not.

Speaker #5: The other thing is, of course, with RAS inhibitors, the numerical value of ORR at any point in time isn't very accurate anyway. Patients can take up to and sometimes beyond six months to fulfill the RESIST definition of response.

Speaker #5: So at any given point in time, there may still be people who might become responders who have not yet become responders. And the RESIST definition of response isn't a particularly robust endpoint in its own right.

Speaker #5: So there's a lot of there's a lot of wiggle room and uncertainty around all of these analyses. It's very tempting to believe that overall, the overall response rate determined by RESIST is a pure and absolute and accurate measurement.

Speaker #5: But it absolute I can tell you it absolutely is not. If you look at those CT scans and try to compute the unidimensional measurements of the target lesions, then you'll realize just how fraught with uncertainty the whole thing is.

Steve Kelsey: If you look at those CT scans and try to compute the uni-dimensional measurements of the target lesions, then you'll realize just how fraught with uncertainty the whole thing is.

Mark A. Goldsmith: Alec, I'm glad you asked.

Mark Goldsmith: Alec, I'm glad you asked.

Speaker #4: Alex, I'm glad you asked.

Speaker #6: Very good. Thank you, guys.

Alec Stranahan: Very good. Thank you, guys.

Steve Kelsey: Sorry, Alec. It really is rather long.

Speaker #5: Sorry, Alex. We're just right along.

Operator: This does conclude the question and answer session. I would now like to turn it back to Mark Goldsmith for closing remarks.

Speaker #3: This does conclude the question and answer session. I'd now like to turn it back to Mark Goldsmith for closing remarks.

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

Speaker #4: Thank you, operator. And thank you, everyone, for participating today. And for your continued support of Revolution Medicines.

Mark Goldsmith: Thank you, operator, and thank you 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.

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Q1 2026 Revolution Medicines Inc Earnings Call

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Q1 2026 Revolution Medicines Inc Earnings Call

Wednesday, May 6th, 2026 at 8:30 PM

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