Revolution Medicines (RVMD) Q3 2026 earnings call transcript

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

I'd like to inform you that certain statements we make during this call will be forward-looking because such statements deal with future events and are subject to many risks and uncertainties. Actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our recent periodic report that has been filed with the U. S. Securities and Exchange Commission.

This afternoon, we released financial results for the quarter ended September 30th, 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 our Chief Executive Officer, Dr. Mark Goldsmith. Mark?

Thank you, Ryan, and good afternoon, everyone. I'll begin today with several remarks focused on our progress in pancreatic cancer and across our broader RASOM portfolio. Anthony will then provide an update on the initial launch of RAS on Q. Alan will discuss progress across our clinical development programs, and Jack will review our third quarter financial results before our return with brief concluding remarks. The third quarter marked a transformational period for Revolution Medicines. On August 26, less than two years after enrollment began in the global randomized RASOLUTE 302 clinical trial, the FDA approved RAS-ONQ for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multi-agent systemic therapy, and we immediately began making it available by prescription in the United States.

The approval provided an important regulatory proof point for our RAS on approach and mark the beginning of a new chapter for our company. More importantly, eligible patients and their physicians now have an approved oral targeted medicine designed to directly and broadly inhibit RAS, the main cause of pancreatic cancer in a disease with a profound need for a therapeutic breakthrough. This milestone reflects years of scientific conviction, disciplined development, and focused execution by our team and collaborators.

It also formally opens the delivery phase of responsibility for Revolution Medicines. We are working tirelessly to execute the U. S. launch with urgency, help eligible patients access RAS on Q promptly, and support a positive treatment experience, and rigorously prepare to expand the launch internationally. With the U. S. approval in hand and our execution plans operational, the foundation in pancreatic cancer is being further reinforced by guideline recognition.

The NCCN guidelines are more expansive than the approved label and now include RAS-ON-Q as a Category 1 preferred subsequent therapy option for appropriate patients with locally advanced metastatic pancreatic cancer as well as recurrent disease following prior systemic therapy. In metastatic pancreatic cancer, we believe this guideline placement highlights the strength and relevance to medical practice of RAS-on-Q and supports the use of RAS-on-Q in the FDA-approved settings. Importantly, NCCN's recommendation for treatment in locally advanced disease extends its recommendation beyond the FDA-approved metastatic disease setting, while its first-line metastatic listing recognizes RAS-on-Q as a useful-in-certain-circumstances option with the applicable category linked to prescribers' assessments of performance status.

While these NCCN placements do not change the FDA-approved indication, they reflect NCCN's independent evaluation of the clinical data for RAS-ONQ in the context of significant unmet needs among patients with advanced pancreatic cancer. Based on the totality of clinical evidence, we believe RAS-ON-Q is well-positioned to become a new global standard of care option for appropriate patients with advanced pancreatic cancer.

This progress indicates significant momentum in our pursuit of bold ambitions in pancreatic cancer through a multi-asset strategy designed to extend RAS-ON inhibition as the core of treatment in earlier lines of therapy and additional disease settings in which RAS is a key cancer driver. Recent regulatory designations further underscore the momentum. The FDA granted breakthrough therapy designation for the investigational combination of RAS-on-Q with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer. In addition, the FDA granted orphan drug designation to Zoldan RASIB for the treatment of pancreatic cancer.

We are conducting four additional global phase 3 studies across first-line metastatic and adjuvant pancreatic cancer, including programs evaluating two distinct regimens in first-line RAS G12D pancreatic cancer, Zoldan RASIB plus chemotherapy, and the novel RASON inhibitor doublet of RASONQ plus Zoldan RASIB. While each of these regimens remains investigational, together they reflect our determination to develop multiple potential best-in-class options for patients across the pancreatic cancer continuum.

The growing body of evidence is also beginning to drive impact beyond pancreatic cancer. During the quarter, based on promising Phase I-II clinical evidence for RAS on Q and previously treated RAS mutant non-small cell lung cancer, the NCC guidelines recommended RAS on Q as a Category 2A available targeted agent for patients with metastatic non-small cell lung cancer harboring KRAS G12, G13, or Q61 mutations. While RAS on Q remains investigational and non-small cell lung cancer, this is an important treatment recommendation in RAS mutant non-small cell lung cancer where substantial unmet need remains. Later, Alan will provide an update on RASOL 301, a phase three study of RAS on Q and RAS mutant non-small cell lung cancer, and our broader development strategy in non-small cell lung cancer.

We are highly encouraged that the EMA's Committee for Medicinal Products for Human Use, or CHMP, has also moved rapidly to adopt a positive opinion for Diracxon RACIB as a monotherapy indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy. For eligible patients in the European Union living with metastatic pancreatic cancer, a disease where profound unmet need persists, this opinion is a major step toward the potential availability of a new target of medicine. The unprecedented clinical benefit shown in Resolute 302 provides the foundation for this milestone, with superior efficacy versus chemotherapy, along with a manageable safety profile and favorable patient-reported outcomes.

Together with the U. S. approval, the CHMP opinion advances our broader ambition to bring the potential benefits of RAS on inhibition to patients around the world. The European Commission decision remains pending.

Anthony will discuss the work underway to prepare for country-level access following a potential approval. With that, I'll turn the call over to Anthony for an update on the initial launch of RAS on Q and our commercial readiness outside the U. S. Anthony?

Thank you, Mark. The U. S. launch of RAS on Q is off to a strong start. At approval, we outlined three priorities, enabling healthcare providers and eligible patients to achieve a positive treatment experience, ensuring broad coverage and seamless patient access with coordinated support, and establishing RAS on Q as a new standard of care for eligible patients with metastatic pancreatic cancer.

Early in the launch, we're encouraged by the progress we're seeing against each of these priorities. Razon Q generated net product revenue of $198 million for the quarter, reflecting more than 5,000 unique patients treated on a commercial basis. As a reminder, FDA approval occurred on August 26, so these results reflect approximately five weeks of commercialization activity. Demand in the quarter reflected three components.

First, demand included the transition of patients from our U. S. Expanded Access Program to commercial supply. That transition is now complete for U. S. patients continuing treatment. We prioritized continuity of care and successfully supported patients in obtaining their medication through the transition.

Second, separate from the expanded access program transition, early commercial demand included a sizable cohort of patients who had exhausted available treatment options at the time of approval and were waiting for a new treatment option, including patients later in their treatment journey. And third, following approval, we began serving new eligible patients, initiating RAS on Q. We're encouraged by the speed with which we were able to begin serving patients following approval, which reflects the significant unmet need in metastatic pancreatic cancer, the strength of Razon-Q's clinical profile and label, the strong launch readiness and initial execution across functions, as well as payer engagement and patient support in line with our expectations. These early results are highly encouraging. At the same time, with only five weeks of commercialization activity, it's too early to draw conclusions about the normalized trajectory of the launch.

The expanded access program transition and the initial cohort of patients awaiting commercial availability are finite early launch dynamics. As our launch matures, revenue will increasingly reflect ongoing treatment for newly eligible patients and ongoing treatment duration. We are also pleased by the breadth of early physician engagement with activation across both academic and community oncology settings, and healthcare providers have responded positively to the RAS on Q data, the approved label, and the recent NCCN guideline inclusion. Early payer access has been encouraging. We have strong functional access with Razon Q claims reimbursed across health plans collectively representing greater than 90% of US PDAC covered lives. Formal coverage policies are still developing for most plans as would be expected this early in the launch.

Our field access and on-path patient services teams are fully operational, supporting benefits verifications, coverage navigation, financial assistance, and patient support needs. Their work is central to our goal of helping eligible patients start and remain on treatment as seamlessly as possible. Overall, we're very encouraged by the early launch experience and by the progress we're seeing across key launch priorities. We remain focused on supporting healthcare providers and eligible patients, ensuring seamless access and coordinated support, and establishing RAS on Q as the new standard of care in metastatic pancreatic cancer. Following the October 15th positive opinion from the Committee for Medicinal Products for Human Use, or CHMP, we are advancing European launch preparations and country-level reimbursement activities in parallel while awaiting the European Commission decision.

The Resolute 302 study provides a strong clinical foundation for our European access plans, including work to support the Joint Clinical Assessment, or JCA, and national health technology assessment, pricing, and reimbursement processes. Launch timelines will depend on regulatory approval and country-specific access requirements. We expect to be ready to launch as these are met.

Subject to regulatory approval, we are also advancing launch readiness work in Japan. With that, Jack will provide additional financial information for the quarter later in the call. I'll now turn the call over to Dr. Alan Sandler.

Thank you, Anthony. RazOnQ's approval provides an important foundation for our deep commitment in pancreatic cancer. At the European Society for Medical Oncology Congress, we presented additional RazOnQ 302 analyses showing that the overall survival benefit with RazOnQ versus chemotherapy was observed consistently across key patient subgroups, including RAS genotype subgroups, prior treatment settings, and preselected chemotherapy regimens. Overall survival is the most clinically meaningful endpoint in metastatic pancreatic cancer, and these findings reinforce the broad clinical relevance of RAS on Q in the previously treated setting Our strategy in pancreatic cancer extends well beyond the current approved setting and we are advancing a broad pancreatic cancer development program across first metastatic and resectable disease. Let's begin with Razolute 303, our global phase 3 study of RAS on Q monotherapy and in combination with chemotherapy in first-line metastatic pancreatic cancer.

I'm pleased to report that U. S. enrollment is now complete, and we expect to complete global enrollment in the first half of 2027. We are also pleased to have begun dosing patients in Razolute 309, our global Phase III study of the novel Razon inhibitor doublet of RazonQ plus Zoldan RASib in first-line RAS G12D pancreatic cancer. Taken together with the ongoing Resolute 304 study in the adjuvant setting and Resolute 305 evaluating Zoldan RASib plus chemotherapy in the first-line setting, these active studies reflect the breadth and pace of our multi-asset pancreatic cancer Phase III development strategy.

At the EORTC-NCI AACR Symposium on Molecular Targets and Cancer Therapeutics later this month, we will present longer-term follow-up from the Phase I study of the combination of RAS-ON-Q with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer, building on encouraging data previously reported and further characterizing the regimen's clinical activity and safety profile. As Mark noted, the FDA's breakthrough therapy designation for the combination of RAS-on-Q with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer is an important regulatory milestone for that program.

Turning to non-small cell lung cancer, we continue to execute a broad strategy designed to address substantial unmet needs across RAS-driven disease.

In Resolve 301, our global phase 3 study of RAS-on-Q monotherapy in patients with previously treated RAS mutant non-small cell lung cancer, We are winding down global enrollment and expect all sites to close enrollment by the end of the month, positioning us for the planned initial Phase III readout in 2027.

During the quarter, Phase I-II data for RAS on Q in previously treated RAS mutant non-small cell lung cancer were published in the New England Journal of Medicine, providing peer-reviewed support for the program. As Mark noted, the NCCN guidelines also now include RAS on Q as a Category 2A available targeted agent in the emerging biomarkers table for metastatic non-small cell lung cancer with KRAS G12, G13, or Q61 mutations. RAS-ONQ remains investigational in non-small cell lung cancer, and we will continue to advance its development through the RAS-ALV-301 study.

We are also advancing our broader first-line non-small cell lung cancer strategy with our mutant-selective RAS-ON inhibitors. We have begun dosing patients in Rasolv 308, evaluating Zoldan Rasib in combination with Pembrolizumab and Platinum Doublet chemotherapy in first-line Ras G12D non-small cell lung cancer. We have also initiated Resolve 307, evaluating Eleron Rasib in combination with Pembrolizumab and Platinum Doublet chemotherapy in first-line Ras G12C non-small cell lung cancer. In colorectal cancer, we are encouraged by the strong clinical activity we've seen in a cohort of patients with RAS G12D colorectal cancer receiving first-line treatment with a combination of Zoldanrasib, Cetuximab, and Folfax. We've observed encouraging objective response rates and disease control rates along with an acceptable safety, and tolerability profile that is generally consistent with what would be expected for cetuximab and Folfox.

We'll need longer follow-up to assess durability. Nevertheless, we believe the initial clinical profile in this very challenging disease merits a global randomized phase three trial, Razinate 312, comparing the combination of Zoldan-Racib, cetuximab, and investigator's choice of full FOX or full theory with standard of care. We expect to provide a clinical data update from our earlier phase colorectal cancer studies, along with the RASIN-8 312 trial design in the first half of 2027.

The RASIN-8 312 trial is being initiated. Under the agreement we announced earlier this year, B-1 is funding and conducting this global registrational Phase 3 study on our behalf using its global development superhighway. We are steadfast in our commitment to address this important RAS-driven cancer and the needs of this underserved patient population.

In our earlier stage pipeline, RMC5127, our RAS-ON G12V selective inhibitor, continues in its first in human study. We are in the late stages of identifying a candidate-recommended Phase II dose, and we expect to share initial clinical monotherapy data in 2027.

Finally, RM055, our first mutant-targeted catalytic RASON inhibitor, remains on track for initiation of its first in-human clinical study in the fourth quarter. Taken together, the progress across our pipeline reinforces the breadth of our RAS-On platform and our opportunity to build multiple important medicines for patients with RAS-driven cancers.

Beyond the programs we sponsor directly, we are collaborating with leading academic institutions and investigators to advance a robust, externally sponsored research program. Studies that Revolution Medicines supports through this program enable independent investigators to explore our RAS-on inhibitors in additional scientifically compelling settings and populations with significant unmet medical needs, including but not limited to pancreatic and other gastroenterology microintestinal cancers. This program provides another avenue to build evidence across RAS-driven cancers and underscores the breadth of interest in our pipeline.

With that, I'll now turn the call over to Jack.

Thanks, Alan. The third quarter of 2026 represented our first quarter as a commercial stage company following the U. S. approval of RAS on Q. RAS on Q generated net product revenue of $197.6 million during the quarter. This reflects a partial quarter and also includes initial stocking of inventory into the channel. We ended the quarter with less than two weeks of inventory in the channel, and in the long run, expect to manage channel inventory at approximately two weeks. The gross-to-net discount for the quarter came in at the lower end of our anticipated 20 to 30 percent range. We are early in the U. S. launch, and as pair mix and discounts evolve and mature, we expect the gross-to-net discount to increase within that anticipated range.

Cost of sales for the quarter was $0.3 million. This amount should not be viewed as representative of normalized cost of sales as products sold during the quarter includes product manufactured before FDA approval, which was previously expensed to R&D.

Turning to our capital position, we ended the third quarter with $3.7 billion in cash, cash equivalents, and marketable securities. This balance does not include an additional $250 million in proceeds received after the quarter relating to the first debt tranche under our funding arrangement with Royalty Pharma. The approval of Razon Q triggered two separate financing tranches under the agreement, a mandatory first debt tranche, which we received in October, and an optional third royalty tranche. We elected not to draw the optional third royalty tranche given our strong cash position, as taking the optional tranche would have committed us to pay incremental future royalties under the funding arrangement. There remains up to an additional $1 billion in committed capital under the funding arrangement, subject to the achievement of specified milestones, all of which is optional and at our election to draw.

Our financial position continues to provide the flexibility to support the U. S. launch of RASONQ, our continued global commercialization buildout, and the broad advancement of our RASON inhibitor portfolio.

Moving to expenses, R&D expenses for the third quarter of 2026 were $417.1 million compared to $262.5 million for the third quarter of 2026. The increase in R&D expenses was primarily driven by higher clinical trial and manufacturing expenses for Razon-Q, Zoldan-Rasib, and RMC 5127, increased personnel-related costs due to additional headcount, and higher stock-based compensation expense. SG&A expenses for the third quarter of 2026 were $153.3 million compared to $52.8 million for the third quarter of 2025.

The increase in SG&A expenses was primarily driven by higher personnel-related costs associated with additional headcount, higher commercial expenses associated with the RAS on Q commercial launch, and higher stock-based compensation expense. Net loss for the third quarter of 2026 was $407.5 million compared to $305.2 million for the third quarter of 2025. Net loss for the third quarter of 2026 included a non-cash charge of $40.7 million related to a change in the fair value of warrants we assumed as part of our EQRX acquisition.

This charge related to an increase in our stock price during the quarter. Turn into financial guidance. We are reiterating our guidance for full year 2026 GAAP operating expenses of $2.1 billion to $2.2 billion. This includes expected non-cash stock-based compensation expense of $270 million to $290 million. As we turn to 2027, we expect to increase our investments in advancing our broad RAS on inhibitor portfolio and also expect to increase our commercialization efforts, including expanding our global commercialization infrastructure.

While we are not providing a specific range at this time, we do expect full-year 2027 GAAP operating expenses to increase from our current GAAP operating expense run rate.

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

Thank you, Jack. Before we open the call for questions, I'd like to briefly highlight two collaborations that further support our long-term strategy. During the quarter, we announced a multi-part collaboration with B1 Medicines that expands both our combination development capabilities and our regional commercial reach. The clinical development component will evaluate novel combination approaches involving select B1 oncology assets and assets from among our four clinical stage RAS-on inhibitors, including RAS-on-Q.

Under a separate regional rights agreement, B1 holds exclusive development and commercialization rights to these four assets in select Asian markets. Importantly, as referenced earlier by Alan, B1 is also funding and conducting on our behalf a global registrational phase 3 study of Zoldan RASN, RASN8 312, and first-line RASG12D colorectal cancer. This brings significant additional development capability into play as we continue to execute our broad global portfolio strategy. In October, we also entered into clinical collaborations with Bristol-Myers Squibb to evaluate Pemitamig, an investigational PD-L1 VEGF bispecific antibody, in four planned early-stage combination study cohorts across our portfolio of Rasson inhibitors.

Pimitamig is an investigational PD-L1 VEGF bispecific immunomodulator jointly developed by BioNTech and Bristol-Myers Squibb. The planned cohorts include Razon-Q in non-small-cell lung cancer and pancreatic cancer, Aliron-Rasib in non-small-cell lung cancer, and Zold-On-Rasib in colorectal cancer. We will provide additional details as the cohorts are initiated. Our collaboration with Summit on Ivanesimab the first member of this class of bispecific inhibitors to enter clinical development remains fully active and productive Together, these collaborations are components of our larger, deliberate strategy to build development capacity, expand the reach of our medicines, and evaluate rational combinations that may further improve outcomes for patients with RAS-addicted cancers. stepping back we are proud of the robust activities and broad progress spanning all aspects of our discover develop and deliver model on behalf of patients that includes an encouraging initial phase of the u. s commercial launch of raz on q with its compelling product profile addressing serious unmet needs with strong progress toward entering international markets A broad portfolio of pivotal trials with our first three clinical RAS-on inhibitors in three major RAS-driven tumor types, the Resolute Phase III series in pancreatic cancer, the Resolve Phase III series in non-small cell lung cancer, and the Razinate Phase III series in colorectal cancer.

Exciting clinical collaborations exploring additional combination strategies as well as external research pushing the boundaries. building clinical momentum with our fourth RAS-on inhibitor, and a pending first-in-human study of our fifth that represents a new class of inhibitors, and a maturing collection of innovative preclinical programs and assets that are continuously informed by our vast scientific and clinical experience in RAS-driven cancers.

Looking ahead, our priorities are clear. Deliver RAS on Q with urgency to eligible U. S. patients with metastatic pancreatic cancer and prepare for potential commercial availability in Europe and Japan. Advance our multi-asset clinical development strategy across pancreatic cancer, non-spell cell lung cancer, colorectal cancer, and other RAS-driven cancers. deliver the next wave of clinical milestones, including an update on our colorectal cancer program while continuing to advance our earlier stage RAS on pipeline.

RAS on Q's approval and launch mark a monumental step forward for patients living with RAS-dependent cancers and open an important new chapter for Revolution Medicines. With this momentum, we continue our deep commitment to discovering, developing, and delivering innovative, targeted medicines with the urgency patients deserve.

With that, I'll turn the call over to the operator for questions.

Thanks a lot, Charles. Anthony?

Yeah, thanks for the question, Charles. I think as I described in my prepared remarks, there are really three cohorts of patients described in the demand in this early phase. The EAP patients, a good percentage of those EAP patients will have received several months of therapy before transitioning to commercial product. The patients who had exhausted available treatment options who are really awaiting an approved treatment. Those two treatment cohorts are finite, as we outlined. We're not providing a detailed breakdown of those, but what we can say is that a meaningful portion of those initial patients are later stage patients that are lower performance status and as a result may have shorter treatment durations. The third cohort, though, that we described really would represent kind of more of a normal demand trajectory.

So, they're really newly eligible patients on RAS on Q following approval, and we expect to see duration of therapy follow a duration that's more in line with our expectations in the clinical trial. I think I'll leave it there. Charles, thanks for the question.

Thanks for the question, Tyler. We said in the prepared remarks that channel inventory, which is the stocking, we ended the quarter with less than two weeks of inventory in the channel. And on a go-forward basis, more long-term, we'd expect to manage that level at around two weeks.

Yeah, thanks. Thanks, Michael. I think that the scope of our CRC program will evolve over time. We're very committed to colorectal cancer. And so the 312 study is really just the first. We certainly don't expect it to be the last of the late stage development programs. All of those decisions will be data-driven, as the 312 study was as well. So I just say stay tuned. This is an area that will require significant investment over time. We'll continue to generate data across various combination strategies. with regard to mutations beyond G12D. We're certainly of high interest, even though G12D is the most common mutation in colorectal cancer. G12D is the second most common.

And, of course, RMC5127 is working its way through the dose escalation and RP2D evaluation. So stay tuned. We'll be working to cover as much of the colorectal cancer space as we can and to move, to keep working towards early lines of therapy in order to have the greatest impact on behalf of the patients.

Thank you, Andrea. Nice to have you back. Anthony?

Yeah, thanks for the question, Andrea. We're really encouraged by the breadth of interest and the early uptake across both the academic cancer centers and the community oncology practices. What I'll add is approximately 2,700 unique healthcare providers prescribed RAS on Q in the quarter.

And the utilization across the academic and community settings was representative of the overall patient volume. So it was about a 40% academic contribution and about a 60% community contribution. So we're really pleased with that. Our focus is to continue to educate healthcare providers, and particularly as we build familiarity in the community practice, our goal is to create a positive patient and customer experience, and that really is all about understanding the label, understanding the safety profile, and really being aware of all the resources available to help eligible patients start on RAS on Q and stay on RAS on Q. Great.

Thank you. I'll ask Anthony to deliver the disappointing news.

No, Corey, thanks for the question. I think we're five weeks into the launch, you know, in the quarter. One of the things that has happened in October is the EAP program has officially wound down. And so, you know, we know that all of our EAP transitions have been completed by the end of this month. I think adding additional color probably at this time without the full quarter probably isn't going to be a helpful exercise. So we'll leave it there.

Good comment on that. Yeah.

Thanks, Brian, for the question. Right now, what I can comment on is that the majority of patients that we're seeing are metastatic PDAC patients that are previously treated. At this point, given the small numbers, I mean, there likely are some locally advanced patients and some frontline patients, but it's the majority is certainly in the later stages at this point.

Yeah, Brian, with regard to CRC, I think your question related to the funding and conduct of the 312 trial and why B1. Well, we established a relationship with them earlier this year, a multi-part collaboration, and part of that collaboration included their commitment of the resources, the person power, the global footprint, to conduct one Phase III trial on our behalf and at their cost, which was essentially in exchange for certain commercial rights that they would obtain.

So this is simply part of a multilevel collaboration. It's an economic benefit to us, but it also takes advantage of very high-quality global development capability that complements ours. We have similarly been developing that capability, but this adds bandwidth and it frees up our internal resources to continue to conduct other studies and to open up new lines of investigation.

So it's a win for us and we're very pleased and actually quite excited that they're moving forward with it and they're initiating that study as we speak.

Yeah, thanks a lot. Well, I guess there's a two-part. Is that a question, is that an opportunity we could pursue or want to pursue, or are we pursuing it?

Alan?

Yes. Thanks for the question. So, I think there's a number of different ways to, again, look at drug development, and, of course, overall survival remains the most clinically meaningful endpoint, and most important, the overall benefit risk. And what I'd also like to say, And this was established, of course, in Resolute 302 with ResOnQ. Importantly, Resolute 303, 305, and 309 already include PFS and OS as dual primary endpoints. So these are also well underway in their conduct. With respect to ORR, it's certainly unclear that that is an endpoint that can stand on its own and typically historically has always been associated with an additional durability endpoint such as PFS and OS, which I just commented upon and stated that our studies have already incorporated that in.

So I think we have a very robust approach and we'll be in discussions with the FDA appropriately as data comes forward.

Yeah, thank you, Michael. Well, we certainly recognize the encouraging clinical data that were generated by Tango, as has the field, that essentially provides proof of concept for the field. And I think there's no doubt that there will be continued investigation of PRMT inhibition in combination with RAS multi-inhibitors or various other selective inhibitors. and we certainly share the goal of advancing promising regimens for patients as quickly as possible. As you point out, we're currently evaluating three PRMT5 inhibitors. We had four. One of those was from Amgen. That program was discontinued, but we now have three, Tango, of course, BMS, and B1, and each of those has a somewhat different profile. I don't think it would be meaningful for me today to try to highlight what those features are, because that will ultimately be proven out through extensive clinical evaluation in the combinations.

But they do have distinct pharmacologic features, and we'll see how all of that goes. We think it's very attractive and very serving of patients' interests to have those multiple studies underway for us to have an opportunity to see how they all perform relative to each other. As to whether or not we would bring in a PRMT5 inhibitor into our shop, well, I guess first, I probably wouldn't tell you if that's something we did want to do, and I wouldn't tell you if that's something we didn't want to do, so I just really can't answer that. You know, we do think that the community, the world is being served by the studies that are on their way now, but that would ultimately just be a business or strategic question for us to make at any given point in time.

Okay, thanks for those questions, Anthony.

Yeah, thanks, Astica, for the questions. So far, look, as we said, there have been reimbursed claims across health plans that collectively represent greater than 90% of USPDAC-covered lives. What that means is really we have strong functional access and patients are gaining access through established payer review processes, so medical exception, prior off, in advance of formal coverage policies.

Now, we have a full field-based reimbursement team that's assisting both the academic setting and the community setting with navigating those things. That's going really, really well. But in this period of time before formal coverage policies, you know, there are claims that are reimbursed that may not get reimbursed post-coverage policies. It's just a period of time that we're in right now.

But this is what we've expected, and we expect to continue to work on ensuring that the various payers have what they need at P&T that are coming up. But yeah, there's no big differences, and we're not seeing anything unexpected at this point, ASTAC.

Thank you. AJ, those are great questions. I think it's just too early to have any information that would be meaningful at this point. I think as we see more patients treated over time and for longer duration, I think those sorts of concepts will start to emerge.

Yeah, thanks, Greg. I'm not sure that we would necessarily see it that way. They're both pretty broad collaborations. There's high interest by both of those parties. These compounds are not identical, of course. One's focused on PD-1, on the PD-1 axis, and the other's a PD-L1 component on the PD-1 axis. Those may or may not have differences. I just think it's just far too early to tell. And we're excited to be, you know, we were the first to be combining RAS inhibitors with a bispecific. Now we're the second to be combining RAS inhibitors or RAS on inhibitors specifically with the bispecific. And, you know, this is part of a broad approach. We've got a very big footprint in the field, in the industry now.

And this is the best way for us to maximize assessment of the potential value of our compounds in various contexts in these very important diseases.

Yeah, thank you, Laura. Generally, we don't give that level of resolution of guidance about future disclosures. I think Alan already pointed out in his prepared remarks that the ENA presentation would kind of reinforce our understanding of the profile of that combination as to what exactly will be included. That's something that will be revealed when the presentation is made. And similarly with CRC, I think that our commitment has always been that we would provide the data supporting a decision to move forward, and sometimes we provide those data well ahead of initiating trials. Sometimes we provide it right at the time of launching a trial, and in this particular case we'll provide it a little bit after initiation of the trial.

But as to exactly what's the scope of that disclosure, unfortunately, you know, it's our practice not to, and as you know, we've had this conversation before, it's our practice not to re-preview that in advance.

Thanks. Yeah, so we did note that we expected to increase within that range as the pair mix and discounts kind of evolve and mature. I would say largely, you know, from an expectation perspective on a go-forward basis, you know, as we think about kind of channel discounts, those are the ones that we would probably expect a little bit more to affect the gross to net discounts. So we're talking 340B, some potential distribution fees that we may be paying within the channel.

So that's how we're thinking. It's still very, very early in the launch, and we'll get more information as we go along, but that's kind of how we're viewing it at this time.

Yeah, well, maybe I'll make a conceptual comment and then just a concrete point. The conceptual comment is that I think it's unclear, and we've had this position for several years now, whether an early chemo-free approach ultimately delivers the greatest long-term benefit or whether combining with chemo, you know, would deliver more value. We're very neutral on this point, and I think it's a debate that's been around in the oncology field for a long time, and it comes down to sort of just empirically evaluating it. There's no theoretical way to differentiate or to rank or prioritize those.

I think the second comment is I think we've got the first chemo-free first-line regimen and the second first-line chemo-free regimen already well underway. The 303 trial already has an arm. That's Draxon Rassiv alone.

And even though the FDA has already approved Draxon Rassiv for first-line use when it's at the discretionary positions based on candidacy for other treatments. So that's one. And then secondly, we've combined Draxon Rassiv with Zoldan Rassiv in our 309 trial, and that is moving forward as well. So we're evaluating that. We're evaluating in combination with chemo. We're evaluating diraxone-rasmine in combination with chemo, zolone-rasmine in combination with chemo. I think we've got a lot going on there, but it's still TBD, how those will all perform relative to each other.

Well, thank you, Operator, and thank you to everyone who joined us today and for your continued interest in Revolution Medicines. We appreciate the continued support of our shareholders, collaborators, investigators, and above all, the patients and families we serve. Operator, you may now conclude the call.