Good day, and thank you for standing by. Welcome to Revolution Medicines' conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you would need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. In the interest of time, we ask to please limit yourselves to one question and one follow-up. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker, Ryan Asay, Senior Vice President of Corporate Affairs. Please go ahead. Thank you. Welcome everyone to this evening's webcast. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer, and Dr. Wei Lin, our Chief Medical Officer, Dr. Steve Kelsey, our President of R&D, Dr. Alan Sandler, our Chief Development Officer, Anthony Mancini, our Chief Global Commercialization Officer, and Jack Anders, our Chief Financial Officer will join us for the Q&A portion of today's call. As we begin our presentation, I would ask that you review our legal disclaimer on slide two. With that, I'll turn the call over to Dr. Mark Goldsmith, our Chairman and Chief Executive Officer. Mark? Thank you, Ryan, and thank you everyone for joining us. Today marks an important landmark for patients living with metastatic pancreatic cancer and a major milestone for Revolution Medicines. This afternoon in the ASCO plenary session, Dr. Brian Wolpin from the Dana-Farber Cancer Institute and the study's lead investigator presented results from RASolute 302, the first phase III study of daraxonrasib, demonstrating an unprecedented survival benefit in patients with previously treated metastatic pancreatic cancer. These results represent a potential turning point in treatment for a disease that has seen limited therapeutic progress until now. These findings also reinforce our conviction that RAS(ON) inhibition can fundamentally change treatment paradigms across multiple cancers that are driven by RAS. Based on these data, we are working with great intensity to prepare a new drug application for the U.S. FDA as the first step toward bringing daraxonrasib to patients globally. At the same time, we are executing or preparing to conduct multiple registration studies across tumor types, treatment settings, and combination approaches. We have significant momentum with a robust pipeline and aim to build the leading targeted oncology company serving patients with RAS-addicted cancers, supported by a differentiated discovery platform, multiple pioneering investigational medicines, and a broad pipeline designed for long-term impact. Powered by a highly productive innovation engine, deep sustainable asset portfolio, including groundbreaking investigational medicines, and a strong patient focus and science-driven organization, we're well-positioned to achieve our ambitions. We are not pursuing RAS opportunistically. We are systematically building coverage across the RAS landscape through our clinically validated discovery platform, spanning oncogenic mutations, tumor types, and treatment settings. Our strategy is designed to create long-term value through differentiated medicines, rational combinations, and a sustainable multi-product oncology franchise built on continuous innovation. Our mission is bold, to revolutionize treatment globally for patients living with RAS-addicted cancers through the discovery, development, and delivery of innovative targeted medicines. As pioneers in the RAS targeting field, we operate as a late-stage clinical oncology company, pushing the boundaries in three of the most common and difficult-to-treat segments in oncology, pancreatic, non-small cell lung, and colorectal cancer, both targeting areas of clinical unmet need today and creating a significant long-term opportunity. We have eight completed, ongoing, or announced registrational phase III studies, and extensive aggregate clinical experience to date, with more than 2,500 patients having received one or more of our RAS(ON) inhibitors. These include four RAS(ON) inhibitors in the clinic and a deep pipeline behind them, including a fifth on track to initiate clinical study this year and a rich set of innovative preclinical and discovery stage programs. Allow me now to briefly frame the RASolute 302 study, and then Dr. Wei Lin will walk you through the RASolute 302 results. Pancreatic ductal adenocarcinoma, or PDAC, remains one of the most aggressive and lethal cancers. Most patients are diagnosed with advanced disease, and current outcomes in the metastatic setting call for significant improvement. For patients whose disease has progressed following initial treatment, current chemotherapy options provide limited benefit, with median overall survival generally measured in months. Mechanistically, pancreatic cancer is driven by and highly dependent on RAS signaling within the tumor. More than 90% of PDAC tumors harbor oncogenic RAS mutations, and tumors without an identified RAS mutation often harbor an undetected RAS mutation and/or are dependent on RAS pathway signaling even in the absence of a mutation. Pancreatic cancers calls for RAS-targeted medicines. There are currently no approved RAS-targeted drugs for pancreatic cancer, representing one of the most significant unmet needs in oncology. Daraxonrasib is an oral, once daily RAS(ON) multi-selective inhibitor designed to target the active GTP-bound or RAS(ON) form of both mutant and wild-type RAS. Mechanistically, daraxonrasib acts as a synthetic molecular glue, binding to intracellular cyclophilin A to form a binary complex that selectively engages RAS(ON) proteins and suppresses signaling by sterically blocking engagement of downstream RAS effectors. This results in broad inhibition of RAS-driven tumor growth. Importantly, data from a prior phase I/II study recently published in the "New England Journal of Medicine," demonstrated encouraging clinical activity together with a manageable safety profile in previously treated advanced pancreatic cancer. RASolute 302 was designed to rigorously evaluate whether these early signals would translate into a clinically meaningful survival benefit in a global randomized phase III study. Wei, please take it from here. RASolute 302 is a global randomized, open-label, phase III study that enrolled patients with previously treated metastatic PDAC. Patients were randomized one-to-one to receive either daraxonrasib 300 mg orally once daily, or investigator's choice of standard care chemotherapy. The primary analysis population included patients with RAS G12 mutant tumors. The broader overall population included patients both with and without identified RAS mutations. Dual primary endpoints were overall survival and progression-free survival, measured by blinded independent central review in patients with RAS G12 mutant tumors. Key secondary endpoints included overall survival and progression-free survival in the overall population, objective response rate, and patient-reported outcomes. The study design included two planned interim analyses for overall survival. The results we are presenting today are from the first interim analysis. Importantly, this pre-specified analysis crossed the protocol-defined boundaries for statistical significance, and therefore constitute the final analysis for all outcomes. A total of 500 patients were randomized. 248 patients were assigned to daraxonrasib and 252 to chemotherapy. Notably, substantially more patients remained on treatment with daraxonrasib at data cutoff compared with chemotherapy. In addition, fewer daraxonrasib patients discontinued treatment due to toxicity or symptomatic deterioration. These observations are consistent with both meaningful clinical benefit and a manageable tolerability profile. Baseline characteristics were well-balanced across treatment arms and representative of patients typically seen with previously treated metastatic pancreatic cancer. Importantly, the study population reflected the expected distribution in pancreatic cancer, with the majority of tumors harboring RAS G12D or G12V mutations. Turning to efficacy. The dual primary endpoint of overall survival in the RAS G12 population was met. Daraxonrasib reduced the risk of death by 60% compared with chemotherapy. At a median follow-up time of 8.5 months, median overall survival was 13.2 months with daraxonrasib versus 6.6 months with chemotherapy, with hazard ratio of 0.40 and a highly statistically significant P value. To our knowledge, no prior phase III study in metastatic pancreatic cancer has demonstrated median overall survival exceeding one year in any line of therapy. These are unprecedented outcomes for patients with a devastating disease. The overall survival benefit was nearly identical in the overall intent to treat population, which included both the RAS G12 population and patients carrying the tumors harboring other RAS mutations, as well as tumors without an identified RAS mutation. The risk of death was reduced by 60%. Median overall survival again reached 13.2 months with daraxonrasib, compared with 6.7 months for chemotherapy, with hazard ratio of 0.40. These clinical findings firmly establish the biological relevance of RAS pathway inhibition in pancreatic cancer broadly, and the survival benefit of targeting RAS in patients living with pancreatic cancer, with or without an identified RAS mutation. Collectively, we believe these results establish a new benchmark for survival outcomes in previously treated metastatic pancreatic cancer. The observed overall survival benefit of daraxonrasib versus chemotherapy was consistent across pre-specified subgroups, including tumor RAS mutational status. These findings support the robustness and consistency of the survival benefit observed with daraxonrasib. The second dual primary endpoint, progression-free survival, was also met. Daraxonrasib reduced the risk of progression or death by 55% versus chemotherapy in the RAS G12 population. Median progression-free survival was 7.3 months compared with 3.5 months for chemotherapy. Results were consistent in the overall population. Taken together, the PFS findings complement the overall survival benefit and further demonstrate meaningful disease control observed with daraxonrasib treatment. Objective response rates were also substantially improved, with ORR in the daraxonrasib arm approximately 3x higher than in the chemotherapy arm. In the overall population, the objective response rate was 31.6% with daraxonrasib, compared with 11.2% for chemotherapy. These response data further support the broad antitumor activity of daraxonrasib in metastatic pancreatic cancer. Turning to safety, daraxonrasib showed a manageable safety profile with no unexpected safety findings. Importantly, treatment discontinuation due to treatment-related adverse events were very rare at 1.2%. Grade 3 or higher treatment-related adverse events were also less frequent with daraxonrasib compared with chemotherapy. One patient in the daraxonrasib arm experienced grade 5 pneumonitis, which was considered possibly related by the investigator. Median dose intensity for daraxonrasib remained high at over 93%, supporting the feasibility of sustained treatment delivery. Overall, we believe daraxonrasib's tolerability profile is particularly notable in the context of the substantial efficacy benefit observed. The most common treatment-related adverse events with daraxonrasib were primarily low-grade dermatologic and gastrointestinal events. Importantly, severe events were infrequent and generally manageable through supportive care and dose modifications. Chemotherapy demonstrated the expected pattern of hematologic toxicity and peripheral neuropathy that are associated with these agents. We also observed meaningful improvements in patient-reported outcomes for patients receiving daraxonrasib. In particular, daraxonrasib significantly delayed deterioration both in pain symptoms and in overall quality of life compared with chemotherapy. Median time to worsening of pain was more than doubled on daraxonrasib versus chemotherapy, and patients receiving daraxonrasib experienced longer preservation of global health status and quality of life. These findings are especially important in pancreatic cancer, where symptom burden is typically profound and sustained. Importantly, improvements in patient-reported quality of life with daraxonrasib were consistent with the meaningful overall survival and progression-free survival benefits observed in the study. In summary, daraxonrasib demonstrated unprecedented statistically significant and clinically meaningful improvements across every major efficacy endpoint evaluated in RASolute 302. The study showed a 60% reduction in the risk of death and approximately doubling of median overall survival to greater than one year, doubling of progression-free survival and near tripling of response rate, superior patient-reported outcomes, and a manageable safety and tolerability profile along sustained treatment. We believe these results redefine treatment expectations in patients with previously treated metastatic pancreatic cancer, support daraxonrasib as a potential new standard of care, and firmly validate the clinical benefit of RAS(ON) inhibition in pancreatic cancer. These patient outcomes increase our confidence in the work we're doing to extend targeted therapy to other RAS-addicted cancers. With that, I'll hand the call back to Mark. Thank you, Wei. The implications of RASolute 302 extend well beyond this important individual study. These results establish the first targeted therapy to demonstrate a transformative survival benefit in patients with metastatic pancreatic cancer, offering a compelling basis for becoming the new standard of care in a disease clinically proven to be primarily driven by RAS. These results also clinically validate our broader RAS(ON) inhibition strategy in pancreatic cancer and increase confidence in the studies we are conducting related to expansion into earlier lines of therapy, rational combination regimens, and additional tumor types. Finally, these results reinforce the value of the scientific and strategic foundation we've built at Revolution Medicines. What began as a differentiated discovery platform has evolved into what we believe can become a global franchise in targeted oncology medicines with what we believe is a significant opportunity to reshape treatment paradigms across RAS-addicted cancers. Given the compelling and consistent benefit for patients observed in RASolute 302, we at RevMed feel a deep sense of responsibility to deliver this benefit more broadly to patients and are moving with urgency to enable potential commercialization. We are offering treatment crossover to patients in the chemotherapy arm of the RASolute 302 study and have operationalized an FDA-authorized early access program in the United States. Many U.S. prescribers and institutions are now registered in the expanded access program, and drug is being shipped on behalf of their approved patients. We are also actively preparing regulatory submissions globally, focused initially on a planned U.S. FDA submission under a Breakthrough Therapy Designation and a Commissioner's National Priority Voucher. Multiple components of the NDA are advancing through a rolling submission process, and the clinical data and analyses will be incorporated as soon as possible. Recognizing the need for improved options globally, sequential filings are also planned across international regulatory authorities. Operationally, we are well prepared to provide broader access. Over the past several years, we have built a strong commercialization organization with highly experienced leaders and staff with valuable collective oncology launch expertise. We have established core U.S. market infrastructure, and our U.S. field teams are in place, including having onboarded an experienced U.S. account manager team. We also continue to grow our international teams. Taken together, we believe we are positioned to execute a successful global launch pending regulatory approvals. Before concluding, I want to briefly step back and frame what we believe investors should take away from today. RASolute 302 is not simply a compelling positive phase III study in previously treated pancreatic cancer. We believe it represents validation of our productive, bold, and differentiated scientific platform, proof that RAS(ON) inhibition can deliver transformational outcomes for patients with RAS-addicted cancers, and a catalytic step for creating an industry-leading global targeted medicines franchise for patients with RAS-addicted cancers. We have a broad and innovative clinical stage pipeline focused on RAS(ON) inhibitors, including four groundbreaking and differentiated clinical programs. Daraxonrasib, a RAS(ON) multi-selective inhibitor, zoldonrasib, a RAS(ON) G12D selective inhibitor, elironrasib, a RAS(ON) G12C selective inhibitor, RMC-5127, a RAS(ON) G12V selective inhibitor, and a fifth compound, a true catalytic RAS(ON) inhibitor poised for initiating clinical study. Our development strategy for these assets is deliberately broad to maximize the clinical impact across tumor types and lines of therapy through both monotherapy and combination approaches. Importantly, this strategy creates rich opportunities for continuing value creation over time while reinforcing our leadership position in RAS-targeted oncology. Our capabilities extend beyond individual molecules. We have built an integrated organization that connects discovery, science, translational medicine, clinical development, and commercial execution. Insights generated from each stage continuously strengthen the next and fuel a virtuous cycle of innovation capable of producing differentiated medicines over many years. I'll conclude with our core purpose. Everything we do at Revolution Medicines is centered around patients, and our impact is measured by patients' experience. RAS-addicted cancers, including but not limited to pancreatic cancer, remain among the most devastating diseases in oncology. For many patients, treatment options remain limited, and outcomes remain poor. We believe the work we are doing has the potential to fundamentally improve those outcomes. Today's RASolute 302 results represent an important step toward realizing that vision. At the same time, we are investing at scale to build a durable, industry-leading global oncology company aiming to provide exceptional long-term value for patients, physicians, caregivers, employees, and shareholders. With that, I'll now turn the call over to the operator for the Q&A portion of the call. Thank you, sir. As a reminder, to ask a question, you will need to press star one one on your telephone. To withdraw your question, please press star one one again. Please limit yourself to one question and one follow-up, and if time permits, we'll be able to take more questions at that time. Please stand by while we compile the Q&A roster. I show our first question comes from the line of Marc Frahm from TD Cowen. Please go ahead. Hi, this is Eleanor on for Mark. Thanks for taking our question, and congratulations on the fantastic data. That was a really powerful plenary. We noticed that 57% of the patients in the control arm were treated with gemcitabine/ABRAXANE. Have you compared daraxonrasib to this subgroup specifically, and is there any reason to expect that the hazard ratio might differ in the patients treated with gemcitabine/ABRAXANE versus other regimens? It's almost like daraxonrasib has already beaten gemcitabine/ABRAXANE in a second-line trial, this just kind of would further support potential success in the front-line. Thanks very much for your question. I think Dr. Lin can answer those comments about whether or not there's any more information relative to alternatives there. Yeah. As you pointed out, about 6% of patients received gemcitabine/ABRAXANE, and a further [audio distortion] received [audio distortion]. The remaining 10% were on a carboplatin-based therapy, including FOLFIRI. Clearly representative of the global usage in second-line. I think the trial, certainly the cohorts are representative. With regard to specific chemo regimens, and certainly given the high proportion receiving [audio distortion], the gemcitabine/ABRAXANE efficacy comparison is very good overall. A detailed sub analysis would be required [audio distortion] and would be valuable. Thank you. That's helpful. Congrats again. Thank you very much. Thank you. I show our next question in the queue comes from the line of Charles Zhu from LifeSci Capital. Please go ahead. Hi, this is Sue on for Charles. Thanks for taking our questions and congrats on the data. Obviously, this is the first innovative drug in pancreatic cancer in a really long time. How well do you think prophylactic measures on rash worked for 302? Do you think rash events, either any grade or grade 3, could be further optimized beyond what is presented today as physicians get more used to using daraxonrasib? Can you talk about your plans regarding physician and patient education on implementing preventative measures? Thanks. Yeah. Hi, Sue. Thanks for your questions. I think back to Wei, who can comment on measures that we can take to help physicians and also their own experience and how that changes over time. Right. Yeah. Certainly, it was recommended the rash prophylaxis that are typical for EGFR inhibitors such as oral antibiotics, sunblock, as well as skin lotions. Those were recommended. They were applied throughout the trial. I think as we try to launch a product and making it hopefully available, those recommendations will probably be put into clinical practice. I think we're certainly doing studies and generating data demonstrating the effectiveness of these prophylaxis, and there's a wealth of experience within the GI community, especially with EGFR antibodies, with effectiveness of these prophylaxis for patients. I think we hope this become a common use for patients using daraxonrasib as well. Yeah. Hi, this is Alan Sandler. I just want to add to exactly what Wei had said and just emphasize that the point that you had made, that the more experienced physicians have with daraxonrasib, the better they are in terms of anticipating and treating the rash. In addition, our medical affairs groups will be coming up with standardized approaches for the prophylaxis for folks, particularly for those doctors who may be utilizing daraxonrasib for the first time. I think all of this will be an effort to ensure that patients are treated appropriately. I might add one more thing to Alan's comment, which is that, remember, most of these investigators were not part of the phase I/ II experience, their first few patients on trial would be their learning experience. That comes from expanding to 59 sites across six countries. That reinforces the point that Alan just made. Thank you. Congrats again. Thank you. Thank you. I show our next question comes from the line of Faisal Khurshid from Jefferies. Please go ahead. Hello, this is [Anan Shan] for Faisal. Do you think you can get the first-line therapy on the label along with the initial approval on second-line, maybe leveraging the phase I data without having to wait for the phase IIIs to read out? Maybe even something innovative where they give you a full approval on second-line and accelerated approval for first-line with the ongoing phase III serving as confirmatory evidence. Just wondering about the possibility of that. Thanks. Yeah. We appreciate the point that you're raising here. Given that RAS biology underlies first-line disease just as it does second-line and later lines, there's some logic to that. The fact that in the 302 study, the second-line patients' outcomes outperformed, at least numerically outperformed, the historical experience in first-line, and then, of course, as you point out also, the preliminary data we've shown in first-line in single arm studies, that all adds up to a picture. It's really up to the FDA. Our primary objective right now has to be to make sure that we get the 302 study to them in a way that's clear and supportive of a robust label. We understand the point that you're raising, and let's just let this all play out. In the meantime, we are running, of course, a first-line trial, as you know, a three-arm trial, and we'll continue to have dialogue with the FDA. Thanks so much. Appreciate it. Thank you. I show our next question comes from the line of Laura Prendergast from Stifel. Please go ahead. Hey, guys. Congrats on the very exciting data today. Can you speak to the inclusion of some first-line patients in RASolute 302, who didn't seem to do well in their adjuvant setting therapy? Their disposition at baseline, how they performed versus the second-line patients enrolled, and to follow up on the last question, any implications this could have for an FDA label? Wei, you want to come in? Yeah. The patient referring to are patients who have received adjuvant therapy and then have progressed within six months, and therefore, they're considered to be second-line patients. Those patients' interim prognosis are actually exactly the same. The patients who are newly diagnosed with metastatic disease who received their treatment. There is, well, we haven't done detailed analysis in terms of prior experiences. Those patients are always treated as the same, and their prognostics are about the same. We don't think it represents much of an issue, and it's a relatively small number of patients as well. Just to add again, that those patients who received the neoadjuvant or adjuvant setting and then failed to be able to go on study, they had to do that within a time period of less than six months. Again, which sort of mirrors what the first-line chemotherapy would have been. Thank you. Thank you. Thank you. I show our next question comes from the line of Cory Kasimov from Evercore ISI. Please go ahead. Hi, guys. This is Noah. I'm for Cory. Congrats on the fantastic data. Just a bigger picture question for us. Given the discussing commentary on the call to action and to use RASolute 302 as a starting point for ongoing development in pancreatic cancer, I guess, just how public can you guys be about your future development plans for both daraxonrasib and the broader pipeline to stay ahead of the growing competitive field? Thanks for your question. We have a pretty expansive registrational program around daraxonrasib, both in pancreatic cancer and outside pancreatic cancer. We're covering most lines of therapy, and we're covering them in multiple ways, in some cases, including in first-line daraxonrasib alone, daraxonrasib with zoldonrasib. I think we have quite an extensive program, and we'll continue to do that. I found the comment to be supportive of exactly what we're doing. I didn't think that there was much that we're leaving on the table, but we're of course scrubbing that every day and looking for other opportunities to expand even further. With the pipeline behind it, zoldonrasib, our RMC-5127, our G12V selective inhibitor, we have opportunities to move and are moving the mutant selective inhibitors into pancreatic cancer studies as well. Of course, outside of pancreatic cancer, lung cancer and colorectal cancer. I think we have a pretty extensive program, and the pipeline chart outlines some of that. In some cases, the chart's so full that we had to compress a number of different things into a single line. That information's all available on clinicaltrials.gov, and it shows the many different things that we're doing, either pre-registrational or as part of a registrational strategy. Got it. Thanks, guys. Thank you. I show our next question comes from the line of Michael Schmidt from Guggenheim Securities. Please go ahead. Hi, this is Sarah on for Michael. Thanks so much for taking my question, and congrats on today's data. Continuing on the theme of potential expansion opportunities for daraxonrasib, I guess, wanted to ask if you had any updated comments on plans in front-line lung. We saw some data this weekend on G12Cs in the front-line setting, so I guess how does the evolving front-line landscape sort of impact how you're thinking about the opportunity for daraxonrasib? Thank you. Yeah. Thanks, Sarah, for the question. I'll just make a high-level comment. I don't know if anybody would want to add something to it here, which is that lung cancer is really the tumor type in which mutant identification of specific forms of RAS have already caused a stratification of disease types. There is a G12C lung cancer is a thing now, and G12D lung cancer will become a thing pretty quickly, and G12V and probably beyond that as well. We are definitely paying attention to that. We want to be both drivers of it and also be compatible with how physicians think about things. Stay tuned as we continue to update our first-line strategy, but clearly it's a high priority for us in non-small cell lung cancer, just as it is in pancreatic cancer, and indeed in colorectal cancer as well. We'll continue to take that into account and clarify things over time. Got it. Thank you. Thank you. I show our next question comes from the line of Brian Cheng from JP Morgan. Please go ahead. Thanks for taking our question. This is Sarah on for Brian. Could you provide some color on the demand coming from the compassionate use program? How many centers are now offering daraxonrasib in this program, and how should we think about the number of patients that can be in this program by the time that you get the approval? Thanks. Yeah. Thanks for your question, Sarah. We can't quantitate it for you at the moment, as it is constantly moving, but the demand has been very, very high. Our call center and our med info line receive a very large volume of inquiries, both from within the U.S. and outside the U.S. Those inquiries come from individual patients, they come from doctors, they come from institutions. We have fielded those. We're very much on top of it. It's a fully operational program now. There are many registered institutions and physicians within those institutions within our Expanded Access Program. We're now shipping daraxonrasib to the individual doctors who have approved patients and who are coming from an approved certified institution. We're well on our way to serve patients. In terms of what the scope will end up being, that's hard to say. It's really hard to predict exactly. As to the timing, well, that's hard to predict, too. That depends also on when the FDA receives and then reviews and makes a decision about approval, because that will have impact also. If you're asking about whether there's sort of a cap on the number of people being served, there is not. There is not ranking of individuals. Anybody who is eligible and who is supported by an application from a U.S. licensed physician, that has to be eligible themselves through their institution, they'll be served by our Expanded Access Program. I think that's clearly ramping up. Here we are. We're still in the month of May. This program was just cleared by the FDA earlier in this month, and we're already operational and delivering drug on behalf of patients. Great. Thank you. Thank you. Our next question comes from the line of Michael Yee from UBS. Please go ahead. Hi, this is Madeline on for Michael. Thanks for taking our question and congratulations on the data today. Wanted to ask quickly about the duration of treatment, 6.2 months. Comparing that to the PFS number and just sort of thinking about that in the real world, could the difference between PFS and the duration of treatment be related to scan frequency? How do you think about the limiting factor in terms of 8.5 months median follow-up, as well as, what are you hearing from physicians in terms of treating past progression in the real world? Thank you. Madeline, thanks for your question. Those are two very important questions, and be happy to comment on it. Wei? Yeah, sure. The treatment duration and the measurment of survival are analyzed by different statistical methodologies. They don't always correlate perfectly. The progression is actually assessed by a true progression, radiographic progression, versus the treatment is really how long a patient is on the treatment drug. Sometimes patient may discontinue for reasons such as adverse event or other decisions. Therefore, the treatment duration may be actually a different number than progression-free survival. We just had a train go by us, so we'll pick up from there. Yeah. I think that largely kind of explains the difference between the two numbers. There certainly are differences in duration of follow-up in this study compared to our earlier study, if you're wondering about the median PFS values and how they may be a little bit different. There are differences as well in the frequency of scanning under this protocol versus the other, at least after a certain amount of time. There are a variety of factors that go into that. This was statistically significant. It's the final read, but it doesn't mean it's the final ever looked at. It is the one that's provided to the FDA. We don't know today that it's actually representative of the true duration of treatment, which I'm sure you're trying to use to project things. As to treatment beyond progression, Alan, you want to comment on that? Yes. There, I think a couple of important points. The treatment beyond progression was not part of the protocol for 302. However, it is formally allowed in all of our subsequent protocols. In terms of physicians and what they're thinking, there is certainly interest in the concept of doing that, and we have anecdotal evidence of patients who seem to derive some benefit for it, which is why we're looking at it in a prospective manner in our clinical trials. It'll be interesting to see what happens after the daraxonrasib is approved and how physicians will do that. It's certainly not unprecedented with other forms of therapy in oncology. We'll see how that particularly plays out. This evidence that we have prospectively may provide further evidence in order to support that use. If I may just add to that, back to the biology, I think I said it earlier, RAS is the cancer driver in pancreatic cancer, whether you're in first line, second line, or third line of treatment, and whether or not you've progressed on a RAS inhibitor, in all likelihood, you've progressed because the tumor has increased its RAS signaling. Taking your foot off the brake seems like exactly the wrong thing to do from a biological perspective. I'm not speaking to the clinical outcomes yet, because we don't really have that rigorously assessed. From a biological perspective, it really doesn't make sense to try to defeat a cancer that's hungry for RAS and to withdraw the RAS treatment. That has to be established through collection of data. Great. Thank you so much. Huge congratulations. Thank you. Thank you. I show our next question comes from the line of Jay Olson from Oppenheimer. Please go ahead. Oh, hey, guys. Congratulations on this major accomplishment for cancer patients, and thanks for providing this update on a super busy day. The discussant spoke about the opportunity to expand the use of daraxonrasib into combinations and earlier lines of PDAC therapy, including adjuvant, neoadjuvant, and she shared a list of all the studies you're running. Can you just talk about the read-across from 302 study results to your other PDAC studies? I think she suggested that your mutant-specific RAS inhibitors could offer improved tolerability. Is that something that you'll be looking for? If you could talk about the timeline of when you would anticipate having the G12 mutant level subgroup analyses, such as G12V and wild type subgroups from RAS 302 that was discussed, I think someone said it could be shared later this year. Is that correct? Thank you. Let's come back to that second point, but Steve Kelsey can comment on the first point, the main part of your question. Well, I think there were two parts, two questions. The first was how confident are we, if I can paraphrase, how confident are we in the other studies we're running with daraxonrasib based on the readout from the 302 study? We generated a fairly substantial body of phase I/II data before we started most of our phase III studies, with the possible exception of the 304 study, which we inferred from the phase I/II data that we already had in both second-line plus and first-line pancreatic cancer. I think the thing that's most gratifying is that the data that we made public maybe 18 months ago or so from the phase I/II cohort of patients with second-line pancreatic cancer was almost exactly reproduced in this randomized phase III study that we did. I think we can then infer that a lot of our earlier data may be reasonably predictive of what's going to happen in the other phase III studies. I think that at least reinforces the confidence that we had in those studies when we started them. These are long and very expensive studies, so you have to have a reasonable degree of confidence they're going to work before you start them off. I think that's been reinforced by the outcome from the 302 study. With regards to mutant-selective inhibitors, not all mutant-selective inhibitors are created equal. It's a conundrum to us why so many of the mutant-selective inhibitors of G12C seem to demonstrate gastrointestinal toxicity that is at least as bad, if not worse, than daraxonrasib, which is a RAS multi-inhibitor when they are supposedly absolutely selective for G12C. Having said that, our mutant-selective G12D inhibitor is extremely well-tolerated. We're currently exploring that both on its own with standard of care in pancreatic cancer, in first-line pancreatic cancer, but also in combination with daraxonrasib in first-line pancreatic cancer. I think the place of the mutant-selective inhibitors will fall out based on their own individual efficacy and tolerability profiles. We believe that the mutant-selective RAS(ON) inhibitors that we have, which now include elironrasib for G12C, zoldonrasib G12D, and RMC-5127 for G12V, are pretty good with regards to tolerability and gives us a lot of flexibility. With regards to subgroup analysis, I think Wei Lin commented earlier in the call that we do intend to do exploratory subgroup analyses of the data from 302. I wouldn't expect too much definitive to come out of that because probably the only two mutant subgroups that are going to be sufficiently large to tell anything determined are the G12D subgroup and the G12V subgroup. Those exploratory analyses will be performed now that the main analysis has been performed and made public. Great. Thank you. It's hard to add much to what Steve said. I'm still going to add something, which is pancreatic cancer is caused by RAS, first-line, second-line, third-line, whether it's locally resectable, or whether it's locally advanced, or whether it's metastatic. The underlying biology is the same there, and so I'll take an even more bullish position on it. Inhibiting RAS is going to make a difference across these. We just have to design trials and execute trials that will assess that formally, and that's what's being done now. Those trials are underway, and we'll learn the answers from them. Thanks. Congrats again. Thank you. Thank you. I show our next question comes from the line of Sean McCutcheon from Raymond James. Please go ahead. Hi, guys. Congrats again on the stellar data. Maybe could you speak to the rate of high-grade stomatitis, how stomatitis is managed on the study and expectation for real-world mitigation strategies? Thanks. Sure. Thanks for your question. Wei? Yeah. Stomatitis is actually also part of the RAS inhibition because in addition to RAS, the PI3K/MAP kinase pathway is also affected with RAS inhibition. This stomatitis is actually reminiscent of the mTOR inhibitors. On the study, we have implemented a management guideline very similar to the mTOR inhibitor, which involving oral mouthwash with a steroid, and that's been fairly effective. There's also, as Alan mentioned, along with the rash management, our medical care team will also be promoting additional management when it comes to stomatitis, which include not only management when the stomatitis is after onset, but also there's offering potential to prophylax because that's another opportunity for improving the safe intolerability of long-term use, is to use a steroid mouthwash to prevent the onset in addition to correctly managing the stomatitis. Thanks. Thank you. I show our next question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead. Hi, this is Yiwen on for Jonathan. Thanks for taking our questions, and congrats on the data. Just two small questions on the non-G12X population. Can you provide more color on why these patients seem to derive an overall survival benefit but not a PFS benefit from daraxonrasib? Also, can you provide more color on the resistance mechanisms to daraxonrasib in this study, and how might that inform strategies for next-generation inhibitors and combinations? Thank you. Thanks for your question. I'm going to take the second question, which is resistance from this study. We don't have any data on resistance from this study. We have data that we've reported now in several different venues, I think, on resistance mechanisms, and they typically involve the cell finding ways to increase RAS signaling that works around the inhibitor, either amplifying the underlying oncogene and expressing more protein that can signal more, that sort of thing. We think the main thing to do for RAS inhibitor resistance in pancreatic cancer is to increase your inhibition of RAS. We have several strategies for doing that, including combining a second RAS inhibitor. We also, of course, have our newest innovative class of compounds that is catalytic in its activity, represented by RM-055. There are various strategies for dealing with that, but we do not have any data today from the RASolute 302 non-G12X. Why did it appear to show a PFS that is not as compelling, yet the overall survival value is fine? Yeah. I think there's a number of potential questions and issues, I guess, that's opposed with this. Number one, of course, overall survival is the most definitive evaluation of treatment effect. The second would be the fact that they are, of course, small numbers. When you have small subgroups such as this, you can have treatment effects that vary, are certainly less precise because you just don't have the number of patients to look at that. The confidence intervals as a result are quite wide, encompassing both effect and greater than one. I think that that's basically sort of the summary of it at this particular point. Numbers are quite small and variable, but let's not forget overall survival and the consistent benefit that we've seen across all of the subgroups throughout overall survival in this study. Understood. Thank you. Thank you. I show our next question comes from the line of Kalpit Patel from Wolfe Research. Please go ahead. Hey, this is Gugan on for Kalpit. Today's 33% ORR in 2L+, that's a benchmark. What ORR would you need to see in the MTAP deleted subgroup to feel confident vopimetostat and daraxonrasib are adding a signal over daraxonrasib monotherapy? To see a benefit of adding what to daraxonrasib? I couldn't quite hear that. Vopimetostat. Oh, vopimetostat. Oh, I see. Yeah. I'm not going to answer that question. I think the underlying question really here is to what degree is response rate predictive of durability, and we don't really have an answer to that question today. Certainly, we have some level of relationship between a higher response rate here in this study, as we saw in the phase I/II study, and durability. We don't know what that relationship really is, since we only have two points on a line. We have everything else, and we have daraxonrasib, and there's nothing in between or on either side of that. We don't know the answer. I get why you're asking it, but we can't help you answer that today. Sounds good. Thank you, and congrats again. Thank you very much. Thank you. I show our next question comes from the line of Kelsey Goodwin from Piper Sandler. Please go ahead. Good evening. This is Brittany Stopa on for Kelsey. Thank you for taking our question, and congratulations on the strength of the data and the powerful response from the audience during the plenary session. There is not much to poke at in the data, but just one small question from us. Given the median follow-up of 8.5 months at this analysis, do you have any thoughts on how PFS and overall survival benefit might evolve with more matured follow-up? Do you plan to provide additional analysis at any time in the future? Thank you. Thanks very much for your comments and for your question. Alan, you want to comment on follow-up? Could the survival parameters move? If so, where do you predict they would move to? Obviously, it's not possible to predict. However, what we would say is, with the results of the hazard ratio of 0.4 and that highly statistically significant finding, we anticipate that with additional follow-up, we'll continue to see the broad benefit that we have seen, particularly for the PFS, which is more mature than the overall survival. We do believe that both are strong enough, that will continue to be seen. Although this is the final analysis, as has been stated, we will be looking at subsequent follow-up, although not with more than a descriptive P-value approach, and not with an alpha spend. We look forward to doing that as well. I might add, though, we are now allowing crossover for patients who progressed in the chemotherapy group for those patients who are still on study. That could have some impact on looking at overall survival but shouldn't affect progression-free survival. Thanks for your question. Thank you. I show we have time for one more question. Our last question comes from the line from Ami Fadia from Needham. Please go ahead. Hi. Good evening. Thanks for taking my question. Firstly, congratulations for this really strong data and the achievement. My question was really around the expanded access. Can you elaborate on the expanded access and if there is potential for that outside the U.S.? Then within the U.S., do you think patients that are in third line could get access to daraxonrasib at this stage? Then just more broadly, given all the data that you've generated in PDAC and lung, can you give us some comments on how you're exploring colorectal cancer and what we might expect to see in the foreseeable future? Thank you. You've asked three of your permitted two questions. Yeah. We'll do what we can. With regard to the Expanded Access Program, right now it's an FDA-authorized U.S. program that operates through licensed U.S. physicians. That's who we're authorized. Outside of the U.S., we understand the urgency for patients elsewhere as well. There are local specific requirements in each country. We have people on the ground exploring that, exploring that with the right officials as well, and to understand that. The main thing we're doing outside the U.S. is expanding our clinical trial footprint. We've increased the size of that footprint by an order of magnitude. That will allow more opportunities for clinical trials as the nearest term thing that we can do. CRC, I'm just going to put off today. Do you want to comment on third line? Who's eligible at the EAP? Are third-line patients eligible? We would say that the answer is yes for third line. It mirrors the second line and beyond with the appropriate parameters that are seen in the 302 study, such as performance status. Performance status. Yeah. Thank you, Ami. Thanks. Thank you. Appreciate it. Bye. Thank you. This concludes our Q&A session. At this time, I'd like to turn the call back over to Dr. Mark Goldsmith, Chairman and CEO, for closing remarks. Thank you, operator, and thank you to everyone who joined us today. We are indebted to patients and their families who participated in RASolute 302 and other studies, to investigators and scientific collaborators, to investors who have financed the work, and, of course, to our remarkably dedicated employees. We are highly motivated by these significant results from the RASolute 302 trial, from the potential therapeutic impact for patients with pancreatic cancer or other RAS-addicted cancers, and the profound opportunity ahead for Revolution Medicines. We very much appreciate your continued interest and support. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.