Revolution Medicines (RVMD) Q2 2026 earnings call transcript

Thank you, and welcome everyone to the second quarter 2026 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer, Dr. Alan Sandler, our Chief Development Officer, and Jack Anders, our Chief Financial Officer. Dr. Wei Lin, our Chief Medical Officer, and Anthony Mancini, our Chief Global Commercialization Officer, will join us for the Q&A portion of today's call.

We would like to inform you that certain statements we make during this call will be forward-looking because such statements deal with future events and are subject to many risks and uncertainties. Actual results may differ materially from those in the forward-looking statements. For 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 released financial results for the quarter ended June 30, 2026, and recent corporate updates. The press release and updated corporate presentation are available on the Investors section of our website at revmed. com.

With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer. Mark?

Thank you, Ryan, and thanks to everyone for joining us this afternoon. I'll begin today's call with initial remarks focused primarily on pancreatic cancer, and then Dr. Sandler will provide highlights of recent results and plans in non-small cell lung cancer. Jack Anders will then summarize our second quarter financial results before I share some closing comments and open the call to questions and answers.

2026 is proving to be a transformational year for Revolution Medicines, with substantial progress in many dimensions, supporting our mission to revolutionize treatment for patients with RAS-addicted cancers globally through the discovery, development, and delivery of innovative targeted medicines. We've continued to build on strong momentum in pancreatic cancer, reinforced by compelling results from Resolute 302, our recently completed global Phase III study in patients with previously treated metastatic disease. Catalyzed by the unprecedented clinical results, we quickly expanded availability to patients through our FDA-cleared expanded access program, advanced regulatory activities in support of potential approvals, strengthened our commercial readiness globally, and continued to expand our broad, pioneering R&D pipeline targeting RAS-driven cancers.

I'd like to spend a few more minutes reviewing some of these activities in more detail. First, at the American Society of Clinical Oncology, or ASCO, Dr. Brian Wolpin presented the full results from Resolute 302, which were also published simultaneously in the New England Journal of Medicine. The data demonstrated paradigm-changing clinical outcomes with diraxon racid monotherapy in patients with previously treated metastatic pancreatic cancer, including statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and patient-reported quality-of-life indicators compared to chemotherapy, along with a manageable safety and tolerability profile.

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

Our teams continue working closely with investigators, healthcare providers, patient advocacy organizations, and regulators to make this possible, and we're proud of the progress so far on behalf of patients. I'm also very pleased to note that our new drug application for DRAXON RACIB in pancreatic cancer has been accepted for review by the U. S. Food and Drug Administration.

We continue to engage constructively with the FDA as they review this application. We're also making progress with additional regulatory authorities around the world. The European Medicines Agency, or EMA, recently announced that it had designated Draxon RASIB as a high priority under EMA's Cancer Medicines Pathfinder project based on its potential to address a high unmet medical need, and that it has started a phased review of Draxon RASIB with the goal of accelerating assessment by evaluating the data as they become available ahead of the submission of a full marketing authorization application. We look forward to continuing collaborative interactions with the EMA and other health authorities around the world as we work to bring Draxon RACIB to patients as quickly as possible.

Third, we continue preparing for successful launch. In the U. S. , our medical affairs organization has been in the field for over a year and continues to actively engage the oncology community through scientific exchange. We have also built the commercial infrastructure needed to support launch. Our sales organization is in place, our field access team is operational, and our on-path patient services program, commercial supply, and distribution network are ready. We are well positioned to serve patients with pancreatic cancer from day one. Internationally, we continue to build our launch capabilities at an accelerating pace, positioning us to support future commercialization across key markets.

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

With Dirac's on RAS-ib, enrollment continues in the Resolute 303 and 304 Phase III programs in the first-line metastatic and adjuvant settings, respectively. With Zoldan RASIB, our RASON G12-D-selective covalent inhibitor, the Resolute 305 phase 3 trial in first-line metastatic pancreatic cancer is also enrolling in treating patients.

Further, we recently initiated Resolute 309, evaluating the novel RASON inhibitor doublet of Diraxon RASIB plus Zoldan RASIB in the first-line treatment setting. These trials are supported by strong clinical data and continue to generate significant interest from investigators and patients around the world who recognize both the unmet needs and the underlying scientific rationale for these treatment strategies. At last month's European Society for Medical Oncology's Gastrointestinal Cancers Congress, or ESMOGI, we presented new pancreatic cancer data for Zoldan RASIB that reinforced its compelling profile and the breadth of our development strategy in pancreatic cancer specifically, including the differentiated first-line treatment approaches underlying the RASLUTE 305 and 309 trials. In one study reported at ESMO GI, Zoldan RASIB combined with standard of care chemotherapy showed compelling preliminary antitumor activity in first-line treatment of patients with RAS G12D pancreatic cancer, including objective response rates of 82% and 61% and disease control rates of 96% and 90% in combination with modified fulthirinox or gemperinone.

Cytobine plus NAB-PAClitaxel, respectively. Longer follow-up will further establish the durability profiles for these regimens. These combinations also demonstrated favorable safety and tolerability profiles, with treatment-related adverse events broadly consistent with the established profiles of each respective chemotherapy component. These encouraging findings strongly support the global pivotal Phase III Resolute 305 study of the Zoldan RASIB plus chemotherapy in first-line treatment of patients with RAS G12D pancreatic cancer. In a second study reported at ESMOGI, the RAS-on inhibitor doublet of diraxon RAS-ib plus zoldon RAS-ib demonstrated compelling preliminary clinical activity in second and third line or later treatment of patients with RAS-G12D pancreatic cancer, including objective response rates of 50% and 47% and disease control rates of 97% and 90% respectively.

observations that are consistent with earlier preclinical studies. Earlier indicators of durability for this combination are also compelling, showing median progression-free survival of 9.6 months and 7.6 months in patients in second- and third-line treatment or later, respectively. Median overall survival in the second-line setting was not yet reached, while the median overall survival in the third-line or later setting was 10.5 months.

The combination also showed a favorable safety and tolerability profile. Treatment-related adverse events were broadly consistent with the established profile of giraxone-racid monotherapy. These encouraging preliminary results support the planned global pivotal phase 3 Resolute 309 study evaluating the combination of giraxon RAS-Hib plus oldon RAS-Hib as first-line treatment in patients with RAS G12D pancreatic cancer. Our Rasson inhibitors are also being evaluated in combination with other investigational approaches, including with MTA-cooperative PRMT5 inhibitors through clinical collaborations with Tango Therapeutics and Bristol-Myers Squibb.

I'd also like to note that RMC5127, our Rasson G12V selective inhibitor, continues in the ongoing First in Human study. Today, RMC 5127 has been well-tolerated at all dose levels evaluated, with no dose-limiting toxicities reported so far.

Encouraging early signs of anti-tumor activity have been seen across multiple tumor types, including objective responses starting at the first dose level. Overall, we are increasingly confident in our ability to help redefine the standard of care for patients with pancreatic cancer across the continuum of disease, from early-stage settings to advanced metastatic disease and across vast tumor genotypes. With these opportunities comes a profound responsibility for Revolution Medicines that we take very seriously. Recognizing that every patient's disease and treatment journey is unique and treatment optionality may best serve the collective unmet needs, we remain committed to developing a broad portfolio of potential treatment options as quickly as possible. I will now turn the call over to Alan to discuss our progress and expanding efforts in non-small cell lung cancer, along with other pipeline updates.

Alan?

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

Building on these encouraging phase 1-2 results, Resolve 301, our ongoing global phase 3 registrational study in patients with previously treated RAS mutant non-small cell lung cancer, continues to see high demand and is enrolling well. We also believe that combining targeted RAS-on inhibition with innovative bispecific antibodies targeting both the PD-1, PD-L1, and VEGF accesses has the potential to improve outcomes for patients with previously untreated metastatic non-small cell lung cancer. In particular through our ongoing clinical collaboration with Summit Therapeutics we are evaluating Diraxxon Rasheb in combination with Ivan Nesimab Summit PD VEGF bispecific antibody and Platinum doublet therapy in first non cell lung cancer With impactful targeted therapies available now for patients with non-small cell lung cancer with tumors harboring EGFR, ALK, ROS1, RET, KRAS G12C, or other genetic alterations, we recognize that practitioners increasingly view treatment of lung cancer through a biomarker-directed lens.

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

Revolution Medicines is uniquely positioned to address these needs through our broad and differentiated pipeline of targeted inhibitors. Approximately 30% of patients with non-small cell lung cancer have tumors harboring a RAS mutation, and our RAS on mutant selective inhibitors, Elleron Rassib, Zoldan Rassib, and RMC5127 targeting RAS G12C, G12D, and G12D, respectively, have the potential to address over 70% of RAS-driven mutations in this disease. In the first-line setting, we're actively evaluating Eleron Rasib and Zoldan Rasib in combination with the current standard of care regimen of pembrolizumab plus platinum doublet chemotherapy. Monotherapy. We've previously reported Phase I data for Zoldan RASIB and Euleron RASIB monotherapy in previously treated RAS G12D or G12C non-small cell lung cancer, respectively, each exhibiting highly encouraging monotherapy efficacy and safety profiles.

Today, I'm pleased to share new observations for each of these compounds in combination with pembrolizumab and chemotherapy in patients with previously untreated non-small cell lung cancer. Data which we believe demonstrate the differentiated and compelling potential of our Rasson mutant selective inhibitors in this treatment context. I'll begin with Zoldan RASIB, a RASON G12D selective inhibitor. The baseline characteristics of patients enrolled in this cohort are representative of the Keynote 189 study population, which evaluated pembrolizumab plus platinum doublet chemotherapy. The principal difference is a somewhat lower proportion of patients with high PD-L1 expression, while other key demographic and disease characteristics are broadly consistent with expectations for patients with previously untreated metastatic non-small cell lung cancer.

Taken together, these baseline characteristics provide an appropriate context for interpreting the safety and efficacy observations I'll discuss next. The safety profile of Zoldan Rassib was highly encouraging. Treatment-related adverse events were again broadly consistent with the established profile of Pembrolizumab plus chemotherapy, with no new or unexpected safety signals observed. With a data cutoff of May 11, 2026, the majority of adverse events were grade one or grade two. No grade five treatment-related adverse events were reported, and there was a low incidence of liver enzyme elevations, which were manageable with standard dose modifications. The combination of Zoldan Rassib with Pembrolizumab and platinum-based chemotherapy demonstrated encouraging anti-tumor activity in patients with previously untreated KRAS G12D non-small cell lung cancer.

With a data cutoff of May 11, 2026, and median follow-up of 3.4 months, the objective response rate was 82%, with disease control achieved in all evaluable patients.

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

Overall, these findings support the continued development of Zoldan RASIB in combination with standard of care. Turning now to Eloran RASIB, a RASON G12C selective inhibitor. As with the Zoldan-Rasiv cohort, the baseline characteristics of patients enrolled in this study are generally representative of the population treated in Pembrolizumab plus platinum doublet chemotherapy. The primary difference being a somewhat lower proportion of patients with PD-L1 negative subgroup and a higher proportion of patients with PD-L1 expression in the 1 to 49% subgroup. Overall, these baseline characteristics establish an appropriate context for interpreting the efficacy and safety observations I'll review next.

Eliron-Rasib continues to demonstrate a manageable safety and tolerability profile in combination with pembrolizumab and chemotherapy. The Revolution Medicines, Inc. Turning now to efficacy of L-Ran RASIB in combination with pembrolizumab and chemotherapy. Similar to what we observed with Zoldan RASIB, we have observed highly encouraging anti-tumor activity with L-Ran RASIB in combination with pembrolizumab and platinum-based chemotherapy in patients with previously untreated RAS G12C non-small cell lung cancer. Across the treated population, with the data cut off of May 11, 2026, and 8.7 months of median follow-up, the confirmed objective response rate was 85%, with a disease control rate of 97%. Responses were observed across PD-L1 expression subgroups, and like Zoldan-Rasib, the Eleron-Rasib combination regimen appears to be highly competitive with the current standard of care of Keynote 189 regimen.

The early observations of durability were also encouraging with a progression-free survival rate at six months of 95%. We believe these early findings suggest that the responses observed are not only frequent, but also have the potential to be durable. We believe these results reinforce the significant potential for targeted RAS on inhibition to further improve outcomes when combined with current standard of care. Taken together, we believe these observations support continued development of L-iron-Rasib in combination with standard of care, pembrolizumab, and platen-based chemotherapy. As a whole, and consistent with the impact seen in pancreatic cancer, these emerging data showing a well-tolerated and highly encouraging anti-tumor profile provide evidence that our RAS-on mutant selective inhibitors have the potential to become important first-line treatment options for patients with metastatic non-small-shell lung cancer.

We are observing that practitioners increasingly view treatment of lung cancer through a biomarker-directed lens and recognize the significant unmet needs that remain across patients with RAS-Mutant non-small cell lung cancer. With our broad and differentiated portfolio of RAS-On mutant selective inhibitors, we believe we are uniquely positioned to address these needs. Accordingly, in the next stage of our approach in non-small cell lung cancer, we are advancing both Zoldan RASIV and Eleron RASIV into registrational development in combination with standard of care in first-line non-small cell lung cancer with the goal of addressing the majority of patients with RAS mutant disease. We recently initiated RASOLV308, a randomized placebo-controlled trial evaluating Zoldan RASIB with pembrolizumab plus doublet platinum chemotherapy in patients with RASG12D non-small cell lung cancer.

And we expect to initiate Resolve 307, a randomized placebo-controlled trial evaluating Eleron RASIB with pembrolizumab plus doublet platinum chemotherapy in patients with RAS G12C non-small cell lung cancer. Further, with the encouraging initial observations mentioned earlier for RMC5127 in patients with tumors harboring a G12V mutation, we anticipate studying RMC5127 in the first-line non-small cell lung cancer setting as well. While we conduct registrational studies for mutant selective inhibitors, we are also evaluating a broader set of first-line treatment strategies, including our multi-selective inhibitor, Duraxon Rassib, as well as our mutant selective inhibitors in combinations with emerging bispecific antibodies and chemotherapy. The additional information and insights we gain over time will inform decisions about potential future registrational plans.

This layered portfolio strategy reflects our deep commitment to developing multiple targeted treatments across the spectrum of RAS mutant non-small cell lung cancer. As we have done in pancreatic cancer, we are advancing multiple potential solutions on behalf of patients with the goal of providing multiple first-line treatment options for patients with RAS mutant non-small cell lung cancer.

I'll now hand the call over to Jack.

Thanks, Alan. Our financial position remains exceptionally strong and continues to provide the flexibility needed to support the rapid advancement of our portfolio and our commercial preparations. We ended the second quarter of 2026 with $3.9 billion in cash and investments. This balance includes the proceeds from our concurrent public offerings of common stock and convertible notes in April of this year, Resulting in $2.2 billion in gross proceeds before deducting underwriting discounts, commissions, and offering expenses.

The ending second quarter balance also includes the receipt of the second royalty tranche of $250 million from our funding arrangement with Royalty Pharma. There remains up to an additional $1.5 billion in committed flexible capital under this funding arrangement, subject to the achievement of specific milestones.

Moving to expenses, R&D expenses for the second quarter of 2026 were $395 million compared to $224 million for the second quarter of 2025. The increase in 2026 was primarily due to increased clinical trial and manufacturing expenses for Diracxon RASIB and Zoldan RASIB, increased personnel-related costs due to additional headcount, and higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026, previously described on our Q1-2026 earnings call. GNA expenses for the second quarter of 2026 were $110 million compared to $41 million for the second quarter of 2025. The increase in GNA expenses in 2026 was primarily due to higher personnel-related costs associated with additional headcount, higher stock-based compensation expense related to increased headcount and changes in retirement provisions in 2026, Increased commercialization preparation activities and higher administrative costs.

Net loss for the second quarter of 2026 was $644 million compared to $248 million for the second quarter of 2025. Net loss for the quarter ended June 30, 2026 included a non-cash charge of $151 million related to a change This change in the fair value of warrants we assumed as part of the company's acquisition of EQRX. This change in the fair value of warrants is due to the increase in our stock price. The additional increase in net loss in 2026 was due to higher operating expenses.

Turning to financial guidance, the company is updating its projected 2026 GAAP operating expense expectations It now expects full year 2026 GAAP operating expenses to be between $2.1 billion and $2.2 billion. This includes expected non-cash stock-based compensation expense of between $270 and $290 million.

Today's updated guidance reflects our growing confidence in the breadth of our clinical pipeline and the magnitude of the opportunities ahead As a result we plan to increase our investment and spend in 2026 driven largely by three main factors First, we are accelerating and increasing manufacturing for both commercial and clinical supply of diraxon RASIB and Zoldan RASIB to ensure we have sufficient supply to meet a range of potential demand scenarios.

Second, we anticipate higher clinical development expenses as we continue to execute on our aggressive development strategy across multiple programs within our portfolio with increased confidence. And third, we are accelerating and increasing investments in our commercial readiness efforts to support our preparedness for potential U. S. launches, while also expanding our international infrastructure to support potential future launches outside the U. S. These additional investments in 2026 position us to execute on our bold ambitions for our portfolio. That concludes the financial update. I'm now turning the call back over to Mark.

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

In lung cancer, we expect to complete enrollment in Resolve 301 this year, supporting an initial readout in 2027. We also continue following patients in the Zoldan RACID monotherapy expansion cohort in previously treated RAS G12D non-small cell lung cancer and have initiated RESOLV308, evaluating Zoldan RACID in combination with standard of care in first-line RAS G12D non-small cell lung cancer. We are also preparing to initiate Resol 307, evaluating Eliron RACID in combination with standard of care in first-line RASP G12C non-small cell lung cancer in the fourth quarter of 2026.

In colorectal cancer, we look forward to providing a data update and visibility into our development plans during the fourth quarter of this year. With our earlier stage pipeline, we expect to identify the recommended Phase II dose for RMC5127 in the second half of this year and share initial clinical data in 2027. We also remain on track to initiate the first in human study of RM055, our first inhibitor from our innovative new class of mutant-targeted catalytic Rasson inhibitors in the fourth quarter. Taken together, these milestones reflect the breadth, pace, and ambition of Revolution Medicines today.

We are preparing for a potential first commercial launch, conducting multiple registration programs, and leading with further RAS innovation, all with intensity and continued excellence in execution. The progress we've made is the result of years of growing scientific conviction, disciplined investment, and relentless effort by our team and collaborators.

We believe we are now in a strong position to redefine what is possible for patients with RAS-driven cancers, beginning with pancreatic cancer and lung cancer and colorectal cancer coming soon as well. With our differentiated know-how, organizational depth, and financial strength, we intend to continue operating against our aggressive plan with the urgency patients deserve. I'd like to thank patients and their families, our investigators and healthcare partners, our employees, and our shareholders for their continued support and confidence. The ongoing support of all of our partners and constituencies is needed to deliver revolutionary advances on behalf of patients.

With that, I'll turn the call over to the operator for the Q&A portion of the call.

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

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

Yeah, thank you, Charles. Appreciate the question. I think all possibilities are still on the table. Well, you know, we've intentionally pursued both the multi-selective as well as the mute-selective inhibitors to create the most optionality for us and then ultimately for patients. And I think all of this will play out over time if we still think it's premature to make any exclusive commitments down any particular treatment regimen. And as long as there remains the possibility that more than one regimen might be complementary and provide options for various patients, we'll pursue them. So this will continue to play out.

You're now seeing are moving pretty aggressively with two selective inhibitors and the third to come behind it. But by no means are we deprioritizing either Draxon Rassib or R055 that's coming up or things that might come behind that as well.

Thank you, Michael. So, you know, the EAP is quite robust now. We're serving a lot of patients. We don't have a mechanism to get explicit or quantitative feedback from those who are prescribing it, since this is a clinical access program. It's not a clinical trial. So we really don't have quantitative information, and I'm not sure that we ultimately ever will.

Sort of on a qualitative basis, we certainly have feedback from some institutions that they're very enthusiastic. Some of the larger institutions have enrolled quite large numbers of patients, and they're continuing to enroll new patients. So that suggests that their experience so far is encouraging. We also do get anecdotal information from patients or their families, but that doesn't add up to a fair and broad-based representation.

But from that anecdotal evidence, patients and their families are quite encouraged by having received access. So that's pretty much what we know from the EAP now, and I'm sure it will continue to grow. So, with regard to the regulatory timelines in Europe, there's really not much we can provide on that. The EMA made it clear that the phase review is intended to be an expedited review process. What that actually ends up meaning really is a question for, you know, the EMA, and we'll just support it as well as we can.

I think you're really raising the question of crossover, some form of crossover risk for patients moving on to Daraxon RASID. Maybe Wade Lynn, our Chief Medical Officer, can comment on that, and then I'll come back to the EAP.

Thanks, Mark. Thanks for the question. It is certainly a very important question that we have given a lot of thought and planning to, I think that's a good point, too, because we want to ensure the successful 303 trial in frontline PDAV while we're trying to make sure patients globally have access to the Revolution Medicines. I think, you know, currently the Phase 3 trial has a co-primary endpoint of PFS and oral survival, and then the dropout in the control would not affect the PFS, obviously, but it could potentially affect the oral survival analysis. And so right now we're trying to be very thoughtful in geographically the sites that we're activating the RECO-312 in, knowing that the global approval as well as access will be graduated, starting with the U. S. and the rest of the world in a gradual fashion.

So that's certainly, I think, one error. And the other is really working with investigators to making sure that the patients really understand their options before they come up to trials, and then probably are conducted in a rigorous fashion, so then the integrity of the center experiments may be.

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

Nicely done. I think you squeezed in three questions, if not two questions. Well done. Maybe Alan can comment first on the 307-308 PD-L1 expression topic.

Right. So, yeah, we are not putting guidelines in terms of requirements of the numbers that have. We'll let that play out in a large study, such as phase three study. There should be a natural number of patients that appear on well-representation of all three. What we will do, you know, we generally want to stratify to make sure that there is equal representation on both arms. And I think that's the most important aspect of that. It's more about balance than anything else. Yeah.

Thanks, Alan. And then on the EAP, there are participants in the program who have been investigators and have treated patients before, and there are participants who have not. And significant numbers of both, I don't know that I can quantitate that for you, but I think we're experiencing both kinds. We've certainly put a lot of effort into providing education and support to all of the prescribers. So the experience that the more experienced providers have obtained, we've learned from, we've all learned from, and we've developed protocols, approaches that we have invested heavily in developing and also conveying through education to anybody who might prescribe Durexone RACID. Right. As to the greater than 90% rate, actually a very high rate as to who might be disapproved, it's really not subjective.

It comes down to the eligibility criteria that are established in the FDA-cleared protocol. It's very well defined. There are very few edge cases where it requires some judgment. Most of it's really just making sure that somebody is actually eligible. And if they're eligible and the request comes through a U. S. licensed physician from a qualified institution that's met all the institutional requirements, then they will be approved.

Thanks for your questions. Yeah, our position on PRNC5 inhibitors remains what it's been, which is that biologically, it's intriguing.

Pharmacologically, it's an intriguing hypothesis that's supported by preclinical work. Tango's now put forth some initial data that show high response rates. We think that body of evidence should be grown, and we know that Tango's working to do that, Grown both in terms of numbers of patients, exposure to different dose levels, so dose optimization, and a longer follow-up, and that will help us really establish a level of conviction about whether, and if so, how to go forward with it. So certainly a credible idea, and we'll just continue to learn more about it as we support Tango in their efforts. With regard to, do we need a PRMT5 inhibitor in our portfolio? I don't think we need it.

We have plenty to do that's high priority within RevMed, as we've described now. One looks at the pipeline. It's a pretty rich pipeline of work. And the other thing to point out, of course, is that there are many PRMT5 inhibitors, growing number out there, each with a slightly different profile, some with more or less propensity to drug-drug interactions that would have to be managed, different levels of potency, and so on. So, I think there's a lot of opportunity out there. I think at the end of the day, Draxon RASIB should be the backbone of therapy, or Zoldan RASIB in the context of the right settings, G2LD selective setting. And we may add various things, whether it's PRMC5 inhibitors, immunologic agents, other RAS inhibitors, chemotherapy, et cetera, a wide variety of possibilities there.

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

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

Yeah, hi, Laura. Thanks for your questions. Visibility into our development strategy, we'll show some data, and we'll tell you what we plan to do with it. As to what investors will leave, you know, what impressions they'll leave with that, that's up to investors to decide. I don't think it serves us to get out in front of that. But that's our plan, and typically in the past when we've announced a development strategy, we've supported it by data that justify it. So I think that would be a reasonable expectation.

Yeah, regarding tumors outside of the big three, we're certainly interested in those. I mean, our expectation is that Diracxon RACIB and other compounds as well, the Diracxon RACIB, could serve a wide variety of tumors. Of course, there's smaller subsets of patients, and we have prioritized the big three, as you put them, which makes sense to do. But we do have data across other tumor types. We've shown some of that data publicly. We have other data that hasn't yet made it out into the public domain. We have external research collaborations as ways to explore this. So, yes, I think you should expect that Draxon Rassib will continue to make its way into other contexts, but the exact strategy by which we develop those may differ from indication to indication, context to context.

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

There's very, very high interest in it, and it continues to grow. So, with regard to the commercial question, maybe Anthony can come in.

Yeah, thanks for the question. We've been preparing for some time and are ready for a successful EDAC launch in the U. S. , and as we think about commercialization infrastructure, there are parts of that commercialization infrastructure that are broad and that can apply to our future indications, but as for our sales force, Which, as Mark alluded to in his prepared remarks, are fully trained and in place. We have a team of around 60 individuals that will fill the need for PDAC. But it's also important to note that there are many different stakeholders in the U. S. market, and we're prepared for those as well. So we have a fully operational field access team, field patient services team, MSL team, and FOT leader liaison team that are in place.

We're excited and ready to go. All systems go, but yes, we're ready for PDAC, and we will be ready should other indications come.

Thanks for your question. Do you want to comment? The question is whether if Diva RASIV is approved, I think is what he's asking, then would we be required to run a later on RASIV frontline study against that? Yeah, we'll be having, you know, all of our head discussions with the FDA. We basically, you really, the control arm is dictated by the current state of affairs at the time that the study is initiated, and that requires not necessarily a positive study, but that requires a full approval. And so since that's not the case at this time, we don't feel that that would be necessary.

Thank you, Operator, and thank you to everyone for participating today and for your continued support of Revolution Medicines.