Thank you and welcome everyone to the first quarter twenty twenty five earnings call. Joining me on today's call are Doctor. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer Steve Kelsey, our President of R and D Doctor. Wei Lin, our Chief Medical Officer, and Jack Anders, our Chief Financial Officer. I'd like to inform you that certain statements we made during this call will be forward looking Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10 ks and our quarterly reports on Form 10 that are filed with the U. S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended 03/31/2025 and recent corporate updates. The press release is available on the Investors section of our website at revmed.com along with an updated investor presentation, we will be referencing during today's call. With that, I'll turn the call over to Doctor. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer Mark? Thanks, Ryan. It's good to be with you this afternoon.

Today, I'll highlight some of the progress we've made this quarter against the strategic priorities we outlined earlier this year. I'll then pass the call over to Doctor. Steve Kelsey, who will walk through a strategic framework for our developing plans in non small cell lung cancer. Doctor. Wei Lin will then highlight updated data from several of our ongoing non small cell lung cancer cohorts that provide support for our plans in lung cancer. Jack Anders will then provide a summary of our first quarter financial results, before I share closing remarks. And open the call to Q and A. At Revolution Medicines, we remain committed to revolutionizing treatment for patients with RAS addicted cancers through the discovery development and delivery of innovative targeted medicines. We continue to make important strides in pursuit of this mission as we execute, advance, and extend our understanding of our novel RasOn inhibitors. We believe and have increasingly been able to demonstrate that our compounds have the potential to become important therapeutic options for patients living with RAS addictive cancers. Our first three clinical stage RAS on inhibitors with highly differentiated and promising clinical profiles, include doraxonrasib, a groundbreaking RasOn multiselective inhibitor, eleeronRASB, a distinguished G12C selective covalent inhibitor, [indiscernible] a highly innovative G12D selective covalent inhibitor.

We continue to make substantial progress advancing these programs with a vision to maximize the clinical impact across tumor types, and lines of therapy through a mix of single agent and combination strategies. Pancreatic cancer is an important priority, and our strategy involves executing on the ongoing Phase III RAASOLUTE-three zero two trial of daraxonrasib in patients with previously treated disease, while moving aggressively into earlier lines of therapy. We're working quickly to prepare for the initiation of two additional Phase III studies with diraxonrasib in pancreatic cancer, in the second half of twenty twenty five. One of these trials will be in patients with first line metastatic disease, and is expected to compare a reference arm of patients treated with chemotherapy to two investigational arms, one with patients treated with diraxonrasib monotherapy, and one with patients treated with diraxonrasib plus chemotherapy. The other early line trial will be as adjuvant treatment for patients with resectable pancreatic cancer who have undergone surgery and perioperative therapy, typically including chemotherapy. In addition to this robust plan for draxonrasib, to play an important role in the treatment of pancreatic cancer, across lines of therapy, we have similar ambitions for broad development in RAS mutant non small cell lung cancer.

The principal focus of today's call is to provide further color and support for our non small cell lung cancer strategy, And I'd like to invite Doctor. Steve Kelsey to walk you through our current conceptual framework. Steve?

Thanks, Mark. Improving treatment options for patients with RAS mutant lung cancer is an important priority for Revolution medicines. The majority of patients with non small cell lung are either diagnosed with or later develop metastatic disease. Treatment objectives for these patients include symptom improvement by reducing tumor burden, delaying disease progression, prolonging survival and improving quality of life. Thirty percent of patients with non small cell lung cancer harbor a RAS mutation There are still no full regulatory approvals for RAS inhibitors in any RAS mutant lung cancer. Nevertheless, due to the commercial availability of KRAS G12C off inhibitors, by accelerated and conditional approval mechanisms Ras mutant non small cell lung cancer has effectively evolved into two diseases and treatment paradigms. GTOC mutant disease, which represents around twelve percent of non small cell lung cancer and other RAS mutant non small cell lung cancer which we are referring to as non G12C RAS mutant non small cell lung cancer. The second group accounts for around eighteen percent of non small cell lung cancer. We expect segmentation of the rest mutant non small cell lung cancer space to continue into mutational groups as other mutant selective inhibitors advance through clinical development and receive regulatory approvals.

Our aim at Revolution medicines is to establish our portfolio of Ras on inhibitors as the leading therapies for patients with RAS mutant non small cell lung cancer across all RAS mutations and lines of therapy. We strive to develop first and or best in class Rasol inhibitors and combinations Our strategy for metastatic disease depends on a number of variables. First, which RAS mutation the tumor harbors and whether a mutant selective RAS inhibitor has achieved proof of concept. Second, the line of therapy for metastatic disease. As the expectations and standards of care are different between initial therapy and salvage therapy. Directs on Rasib has shown encouraging anti tumor activity in patients with tumors harboring a wide range of RAS mutations. Nonetheless, in the face of RAS addiction by such tumors, we expect that mutant selective inhibitors should also have a role in treating tumors and corresponding RAS driver mutations. Combining these mutant selective inhibitors with a RasR multi select inhibitor may play an important role by delivering deeper target inhibition and overcoming resistance mechanisms in a way that neither approach can achieve on its own. Our previously published data show that doraxone rat, it active against a broad range of RAS mutations that have been frequently identified as mechanisms of escape from mutant selective KRAS inhibitors.

Consistent with this, and as we recently presented at AACR, new RAS point mutations are an infrequent cause of escape from diracson rasib in pancreatic cancer. A Ras on inhibitor doublet combination has the goal of improving outcomes and potentially providing a chemotherapy sparing option for patients with RAS mutant non small cell lung cancer. In the previously treated metastatic setting, use of a single agent rat inhibitor may be sufficient to improve outcomes over the current chemotherapy standard of care. This is the approach we're taking with doraxonrasib in patients with previously treated RAS mutant non small cell lung cancer in the RESOLVE three zero one study. For first line treatment of static disease, the dominant standard of care includes immune checkpoint inhibitors. Primarily pembrolizumab. Demonstrating safety and tolerability with pembrolizumab is critical as a means of enabling first line therapy and maximizing the durability of any clinical benefit. These concepts have currently been reduced to practice by Revolution Med Single agent thoraxon rasid provides a foundation for the investigation of Ras on inhibitors in all RAS mutant non small cell lung cancer in the second line and beyond setting. As recently presented at AACR, Zolgensma Rasen has encouraging activity as a single agent in second line plus RAT G12D mutant non small cell lung cancer.

In the first line, RAS G12C non small cell lung cancer setting we aspire to develop chemotherapy sparing RAS on inhibitor doublet of diraxonrastib plus eleron rastib with pembrolizumab. And thereby reserve platinum based chemotherapy for second line treatment. Doing. So has the potential to contribute to an improvement in overall survival. In first line, RASP non G12C non small cell lung cancer, we plan to develop doraxone rasib in combination with standard of care Eventually, Zoltanrasib with its encouraging monotherapy profile may offer a path to another chemotherapy sparing RACEP inhibitor doublet for patients with RAS G12D tumors. And similar doublet approaches may be possible with other rats mutant selected inhibitors, such as RMC five thousand one twenty seven targeting RAS G12V. I will now turn the call over to Doctor. Wei Lin, to provide an update across our non small cell lung cancer clinical programs. [indiscernible] Thank you, Steve.

I'll start by providing monotherapy updates across our portfolio. Beginning with duraxaneracid, our most advanced RAS on inhibitor, This multi selective inhibitor has demonstrated compelling results across multiple tumors including lung cancer. And is currently being evaluated in a phase three registrational study for patients with previously treated non small cell lung cancer.

We're currently activating study sites for RESOLVE-three zero one. The study randomized approximately four twenty patients to either grafaniracid monotherapy or docetaxel. These patients must have received either one or two prior lines of therapy including immunotherapy and platinum based chemotherapy. Given either concurrently or sequentially. Resolve-three zero one incorporates a nested design but the primary analysis being performed in the core population of non small cell lung cancer patients with RAS G12X mutations excluding G12C.

The extended population will incorporate all patients with RAS mutant non small cell lung cancer. Including those with tumors harboring G12C, G13, or Q61 mutations. The study has dual primary endpoints of progression free survival and overall survival. Moving to T12D, small cell lung cancer, we've previously shown promising activity by thoraxon rasib in patients with these tumors. And the ongoing RESOLUTE-three zero one recreational study includes such patients. Last month, at AACR, initial clinical results presented for zodonatinib, our Rasgon G12D selective covalent inhibitor from the non small cell lung cancer cohort. I'll walk you through these data Nodon RACIP was well tolerated with manageable and predominantly low grade treatment related adverse events. As shown on the safety table. As of the December second, 2024 data cut off, At the twelve hundred milligram once daily dose, two grade three adverse events were reported among ninety patients with only two dose interruptions [indiscernible] no dose reductions. Soronrasib achieved a favorable mean dose intensity of 98%.

Odoramafib monotherapy has the twelve hundred milligram daily dose demonstrated encouraging antitumor activity. The waterfall plot shows the best percentage change in tumor size for patients with non small cell lung cancer who received their first dose of zodonrapid at least eight weeks prior the data cutoff date.

The objective response rate was sixty one percent, including patients, with a confirmed response or a response that was pending confirmation. The disease control rate was eighty nine percent. We'll continue following these patients to define durability.

Now I'll move to our RAS on g twelve c mutant selective covalent inhibitor gileron rasib. In non small cell lung cancer.

We reported the first clinical data on the veteran rapid in non small cell lung cancer at the triple meeting in 2023. And today, I'll share updated elamiracid monotherapy data. That includes more patients and longer follow-up as a foundation for combination strategies to move into first line metastatic and eventually earlier lines of non small cell lung cancer. As of the April 7, 2025 data cutoff, thirty six patients who had received prior treatment with standard care were treated with veironrapid monotherapy at two hundred milligrams twice daily.

With leroniracib, generally well tolerated with treatment related adverse events consistent with previously reported data. The most frequently observed treatment related adverse events were gastrointestinal and asymptomatic QPC prolongation. [indiscernible] a favorable mean dose intensity of ninety four percent.

There we show the clinical activity in the same thirty six patients treated with varenrafib monotherapy the dose of two hundred milligram twice daily The objective response rate in these patients was fifty six percent, The disease control rate was ninety four percent. The estimated median progression free survival in these patients was nine point nine months.

I'll now cover our combination clinical development to enable our goal of improving treatment outcomes for patients with RAS mutant non small cell lung cancer the first line metastatic setting. The need for improved treatment options for patients with metastatic non small cell lung cancer remains high. In the first line setting, two regimens are widely used globally. Embolizumab plus chemotherapy is the most commonly used treatment for all patients regardless of their tumor PD L1 expression status. As measured by tumor proportion score. Or TPS. And pembrolizumab monotherapy is the preferred regimen in patients with TPS greater than or equal to fifty percent which accounts for about one third of patients with non small cell lung cancer. While the introduction of immunotherapy, has been transformative for patients with non small cell lung cancer, especially those with high PD L1 expression. [indiscernible] indicate non small cell lung cancer remains a disease with high unmet need. Because among the approximately two thirds of patients, who have tumors with lower or no PD L1 expression even the best available standard care has not resulted in reported response rates. Above forty percent.

In RAS mutant non small cell lung cancer in the second line, and beyond. Treatment is generally either the chemotherapy docetaxel or a KRAS G12C Op inhibitor.

As illustrated in the table reported response rates for docetaxel, have been less than fifteen percent even with the commercially available KRAS G12C Op inhibitors, of sotoracid and adagasib. Reported patient outcomes have been modest with response rates of approximately thirty percent. Combinations are likely to remain a foundation of first line metastatic treatment for non small cell lung cancer. Our main objective is to determine the best way to bring targeted RAS inhibitors into combination with immunotherapy for the first line treatment of RAS mutant non small cell lung cancer.

These figures from preclinical experiments illustrate two concepts that guide our clinical approaches. The first concept shown on the left is that two radsong inhibitors can be combined to increase antitumor activity.

In this experiment with a KRAS G12C non small cell lung cancer model, Either they're on RACF or duraxon Rasib alone. Significantly increased progression free survival compared to control. As measured by time to tumor doubling. Notably, the combination of eleroniracib plus duraxaneracib prolonged progression free survival even further. Indicating additive durability from the RasOn inhibitor doublet.

The second concept shown in experiment on the right, is that [indiscernible] with immunotherapy. In this experiment, we used an immune refractory KRAS G12C small cell lung cancer tumor. That was unresponsive to anti PD-one inhibitor alone. And only partially responsive to anti PD-one combined with either RAS ON inhibitor. Essentially, no progression was seen in this model during one hundred days of treatment with anti PD-one. Combined with a RADSON inhibitor doublet. Encouraged by preclinical results of this sort, I will now describe new clinical data from our evaluation of pairwise combinations of diraclon rasit plus pembrolizumab valeroneuracid plus pembrolizumab, and eleroniracib plus [indiscernible] That suggest these concepts. May translate in patients with KRAS Z12C non small cell lung cancer.

The first combination data set I'll review is duraxomiraciv plus templizumab with or without chemotherapy. Doraxone Rasib plus Pembrolizumab with or without chemotherapy has been generally well tolerated in patients with non small cell lung cancer. Previously, we showed acceptable tolerability for the combination of doroxonracib pembrolizumab in later line. Patients. And with further follow-up, the tolerability profile in those patients has remained stable. Today, focusing on patients with first line disease.

While the follow-up is shorter for patients in the first line setting, the tolerability profile of daratumumab plus pembrolizumab is consistent with what has been observed in the second line study. With or without the addition of chemotherapy. No new safety signals were seen, and the overall tolerability profile is consistent with that of directional RASF plus standard of care agents.

Rash, gastrointestinal toxicities, and stomatitis mucositis. Remain the most commonly observed adverse events for doroxoniraciv and neutropenia and thrombocytopenia emerged with addition of chemotherapy. The tolerability profile supports the further development of duroxomiracib plus pembrolizumab. With without chemotherapy.

Dose reductions and discontinuation of paroxysmal acid or pembrolizumab in this combination were modest. Dirucine Rastiv achieved a favorable mean dose intensity of ninety three percent, in combination with pembrolizumab. And ninety percent with additional chemotherapy. While only a limited number of first line patients have had sufficient follow-up to have had a tumor assessment. We're encouraged by the antitumor activity seen to date.

In the left figure, patients had tumors with TPS greater than or equal to fifty percent. And were treated with diruxanoracic plus pembrolizumab. Consistent with a population who would have received pembrolizumab monotherapy as standard of care. Of the seven efficacy evaluable patients, who had undergone at least one tumor assessment, eighty six percent of these TPS greater than or equal to fifty percent patients [indiscernible] a RECIST response. And all had achieved disease control. And remained on treatment. While the data set will continue to evolve, with addition of more patients and longer follow-up.

This is a very encouraging start. In the figure on the right, patients with TPS less than fifty percent were treated with dirastomerase plus pembrolizumab and chemotherapy. Consistent with the roughly two third of first line patients who would likely receive pembrolizumab plus chemotherapy as standard of care. Of the ten efficacy valuable patients, who had undergone at least one scan, sixty percent of these TPS less than thirty percent patients, had a RECIST response.

And ninety percent achieved disease control. These data support the continued development of Daraxon Racid plus standard of care in first line RASP mutant non small cell lung cancer.

I'll now touch on the Aviron RACID plus pembrolizumab combination.

Demonstrating the safety of this combination is important as we take a pairwise approach toward our goal of developing a chemotherapy sparing triplet combination [indiscernible] and pembrolizumab in patients with first line metastatic KRAS G12C non small cell lung cancer. We previously showed acceptable tolerability for the leonraspib plus tembrolizumab combination in the second line. Plus setting. With further of [indiscernible] we have not observed increase in additive toxicity. Today, we'll focus on initial results in patients with first line non small cell lung cancer.

As of the February 10, 2025 data cutoff. The combination of pevariraparib with pembrolizumab showed a well tolerated profile. With few grade three or higher treatment related adverse events. No new safety signals were observed. This tolerability profile translated to an acceptable dose modification rate in either the second line or first line setting. And eleroniracib maintained a favorable mean dose intensity of 85%. The combination of eleroniracid with pembrolizumab showed encouraging preliminary antitumor activity. Among five efficacy valuable patients, with first line non small cell lung cancer, [indiscernible] a TPS greater than or equal to fifty percent all achieved a recid response. Our development strategy in the first line RAS G12C mutant non small cell lung cancer, is replaced the standard care with the triplet regimen [indiscernible] As a chemo sparing regimen. I've just shown data supporting the combine ability and uncan tumor activity of doroxonraciclib plus pembrolizumab and if they are onrasib. Plus pembrolizumab. The third peer wise combination needed to support this triplet regimen is the rasong inhibitor doubloid. Of everon rasib plus dirastone rasit.

It's Rasan inhibitor doublet. Concept is supported by strong results in preclinical models. Including models that are refractory to monotherapy approaches.

In these preclinical models, EAP, and durable responses are seen in RAS on inhibitor doublets. In December 2024, we shared initial clinical data for the RADS1 inhibitor doublet of valerulmiracib plus duraxaneracib.

To establish the mechanistic proof of principle for this combination.

We evaluated a challenging population of colorectal cancer patients who had been previously treated with not only standard care chemotherapy, but also with KRAS C12C off inhibitors and anti EGFR antibodies. These early results demonstrated an acceptable tolerability profile along with encouraging anti tumor activity. In a very difficult to treat patient population. These results provided strong rationale for continued development of this RAS on inhibitor doublet approach. Across tumor types and lines of therapy. Today, I'll share initial dose finding data from this RadSon inhibitor doublet. In patients with non small cell lung cancer. The data in this table demonstrate the combinability of evironrasib with duraxaneracid. With a tolerability profile that is largely consistent with that of daratumumab itself. Even with longer follow-up, hepatotoxicity did not emerge as a safety signal in this larger cohort of lung cancer patients. QT prolongation of ECG was not symptomatic and is not calm with a grade three rate of only three percent. This tolerability profile translated to no treatment discontinuations a favorable mean dose intensity of ninety five percent for the oral acid and eighty five percent for diruxaniracid.

The combination of valoronaracid plus diruchan acid showed encouraging preliminary anti tumor activity in twenty six patients previously treated KRAS G12C non small cell lung cancer. Who had been previously treated with a KRAS C12C off inhibitor. Because dose augmentation of the RASP on inhibitor doublet is ongoing, We're sharing doroxon rancid at doses ranging from one hundred milligrams to two hundred milligrams.

On the left, we're showing the laramiracet monotherapy data in patients who were previously treated with a KRAS T12C off inhibitor.

Response rate and disease control rate for vemuracid monotherapy were forty two percent and seventy nine percent respectively. On the right, for the combination of evaporin acid and [indiscernible] The response rate was sixty two percent. And the disease control rate was ninety two percent. Well above the activity seen in this population with remorasib monotherapy. The majority of patients on the combination remained on treatment as of the 02/10/2025 data cut off date.

Taking a step back, and looking at our data driven lung cancer strategy, We believe we have a clear path to pursue our ambition to change the standard of care for patients with RAS mutant lung cancer. Both in first line metastatic and in earlier lines of treatment. We launched our initiative in non small cell lung cancer with our registrational study for dirazepammonotherapy, in previously treated patients with RAS mutant lung cancer. [indiscernible] point to clear opportunities to continue evaluating zodon RASM in patients with RAS G12D mutant non small cell lung cancer. As monotherapy and in combination. The three pairwise combinations [indiscernible] pembrolizumab valerunrasib plus temblizumab, and the Raso inhibitor doublet. Of the veironacid plus [indiscernible] both show acceptable tolerability and encouraging antitumor activity. And create options in the first line treatment setting. For patients with tumors harboring RAS G12C, we plan to pursue a chemotherapy sparing RASM inhibitor doublet treatment including the raline raline plus doroxon rasib along with checkpoint inhibitor. For patients with non G12C disease, we plan to develop diraxone rasib in combination with standard care chemotherapy. Along with checkpoint inhibitor. We believe each compound in our clinical stage RAS inhibitor portfolio has the potential to transform treatment for patients living with RAS mutant non small cell lung cancer.

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

Thanks, Wei.

We ended the first quarter of twenty twenty five with $2,100,000,000 in cash and investments, which we project can fund planned operations into the second half of twenty twenty seven based on our current operating plan. R and D expenses for the first quarter of twenty twenty five two hundred and five $700,000 compared to 118,000,000 for the first quarter of twenty twenty four.

The increase in R and D expenses was primarily due to increases in clinical trial related expenses and manufacturing expenses for our three clinical stage programs.

With doraxoneurasib being the largest driver of the increase given the program is now in two Phase III trials.

Personnel related expenses and stock based compensation expense also increased in 2025 due to additional headcount. G and A expenses for the first quarter of twenty twenty five were 35,000,000 compared to $22,800,000 for the first quarter of twenty twenty four.

The increase in G and A expenses was primarily due to increases in personnel related expenses and stock based compensation, associated with additional headcount. [indiscernible] commercial preparation activities.

Net loss for the first quarter of twenty twenty five was $213,400,000 compared to $116,000,000 for the first quarter of twenty twenty four.

The increase in net loss was due to higher operating expenses.

We are reiterating our 2025 financial guidance and continue to expect projected full year 2025 GAAP net loss to be between $840,000,000 and 900,000,000 which includes estimated noncash stock based compensation expense, of between $115,000,000 and 130,000,000 That concludes the financial update.

I'll now turn the call back over to Mark. Thank you, Jack. We are making meaningful progress as we successfully execute on our 2025 strategic priorities in pursuit of our goal to revolutionize treatment for patients with RAS addicted cancers. A key focus this year is executing on the diraxonerasib registrational studies in both previously treated pancreatic and non small cell lung cancers. I'm pleased to share that RASLUT-three zero two, our ongoing global Phase III trial in patients with second line metastatic pancreatic cancer continues its strong pace of enrollment in The U. S. Following regulatory clearances in The EU and Japan, we've also begun enrolling patients in those geographies. We are confident that we'll be able to substantially complete enrollment this year to enable an expected data readout in 2026. We are also currently activating study sites for RESOLVE-three zero one, our Phase three trial in patients with previously treated RAS mutant non small cell lung cancer. We're making good progress toward advancing Drax raspid into earlier line, randomized pivotal trials. With planning underway to initiate registrational trials for draxonraspib in first line and adjuvant pancreatic cancer in the second half of this year. Today, we've shared important data that create exciting opportunities for us, in both previously treated and first line metastatic non small cell lung cancer, and eventually earlier lines of treatment including treatment approaches that include our mutant selective inhibitors.

We continue to expand our clinical programs, and follow study patients to enable the initiation of one or more pivotal combination trials in 2026. Progressing our earlier stage pipeline, including advancing next generation innovations, continues to be an important priority. At AACR recently, RMC five thousand one twenty seven, our G12V, mutant selective RasOn inhibitor, was presented in the New Drugs on Horizon session. We continue to advance the program and expect to reach a clinically stage later this year, to enable the initiation of a phase one study next year. Finally, we continue to make substantial progress growing our commercial and operational capabilities and in advancing launch readiness activities in support of our first potential product launch. We are making good progress in building our commercialization capabilities in The United States across functions including onboarding, our US field medical team. We also recognize our important responsibility for ensuring patient access to doraxonerasib globally, pending regulatory approvals. I'm very pleased to announce that Anthony Mancini has joined RevMed as our Chief Global Commercialization Officer and member of our senior management team. Anthony, who will oversee the comprehensive commercialization strategy and operations for our portfolio brings substantial experience from his successful decades long career in the biotech and Biopharmaceutical Industry, Having Led Significant Product Portfolios, Launches And Organizational Builds, In The U. S. And major international markets as well as overseeing significant strategic partnerships.

He will contribute additional strength, both to our approach to The U. S. Market and to our evaluation of options for reaching patients internationally. Our vision remains to create the industry leading targeted medicine franchise for patients with RAS addicted cancers. This vision is built on three foundational pillars. First, our pioneering clinical stage RasOn inhibitors have shown our discovery capabilities, be among the most innovative and productive in the industry. Second, our first class development capabilities have been demonstrated by efficiently progressing multiple assets through first in human studies, and advancing into late stage development. Third, we are building high quality organizational capabilities to ensure we can successfully deliver products to patients. Underlying all of this is an exceptionally strong financial position that gives us the wherewithal to continue executing on our strategy, and solidifying our position as leaders in the treatment of patients with RAS addictive cancers. As we continue to deliver compelling clinical observations, and build on our track record of execution, we never lose sight of our primary focus, patients living with cancer. Before we open the call for the Q and A session, I'd like to thank the patients and caregivers, clinical investigators, scientific and business collaborators, advisors, and shareholders for their commitment.

Without this support, none of the progress we've made would be possible. I'd also like to recognize the extraordinary efforts of RevMed employees who embody tireless commitment to patients in the work they do every day. This concludes our prepared remarks for today. And I'll now turn the call over to the operator. For the Q and A session.

Thank you.

At this time, we will conduct a question and answer session. Participant. If you have further questions, you may rejoin the queue. To withdraw your question, please press 11 again. Our first question comes from the line of Michael Schmidt of Guggenheim. Your line is now open.

Hi, thanks for taking my questions and congrats all the progress. A lot of new information here to digest today. But yeah, I had a question on your first line non small cell lung cancer strategy. Obviously, very interesting new data disclosed today for some of the various doublets, and [indiscernible] based on your slide, it seems like for the KRAS G12C, first line patient population. You have sort of focusing in on a triplet of ileron, rasib, doraxone, and pembro. [indiscernible] the only combination where we haven't seen data yet today. But just looking at some of the other doublets, perhaps could you just comment on your confidence and tolerability of that triplet just based on some of the rash rates that were seen in some of the doublets and some of the dose reductions there.

Hi, Michael. Thanks for your question. Maybe Wei can speak to that.

For the question. So we're optimistic given the profile we've seen so far. Obviously, we're still in the dose optimization, and we have not yet defined the final dose for the triple combination. But I think have characterized the monotherapy fairly well. We've not seen any new safety signal emerging. And regarding safety signals that are known characterized, such as rash, [indiscernible] as well as the QTC. Both are within what we have expected to observe with a monotherapy. So I think when we have longer follow-up and defined the dose, we'll be sharing those prior to initiating our Phase III trial.

Thank you. Our next question comes from Mark Fram of TD Cowen. Your line is now open.

Hi, thanks for taking my questions.

Congrats on all the data sets today. Maybe just looking across the various combination data sets you presented, was struck by I mean, looks like the vast majority of the responders are still ongoing as of the last data cutoff. Again PFS is clearly immature, but maybe can you give us a sense of just kind of the average follow-up in those cohorts to maybe give a sense of where durability and PFS may be headed? And then kind of looking longer term, what type of dataset do you think you need to gather before you can kind of formally declare Phase III intent for these various combinations? Do you just need to get a little bit more data, get more comfortable on safety and select the final dose. Or is it you need real robust PFS estimates? Just kind of what's needed there.

Hey, Mark, thanks for your question. I think the first question really is something that refers back to the Swimmer Plus that we provided in December, and I think those are available, so I'd recommend taking a look at those in terms of follow-up time for those. We don't have an update today, on that because we done a fresh data cut, but the December data had had those duration of treatment parameters listed. Your second question your main question, I think, is about what's really gating now to the triplet, Steve, you want to comment on that?

Yes. I mean, let's be clear that we're there's a differentiation here between the GTOBSI program and the non GTOBSI program. The G12 the non G12C program is pretty much ungated It's more of a sort of operational execution type question. I think we've shown very conclusively that adding diraxone rasib to the KEYNOTE-one 89 schedule is tolerated and the efficacy is pretty impressive. So we don't think we need any more data to press ahead with that. We just have to grind through the the operational and regulatory milestones that you have to go through in order to get a study off the ground. As Wei alluded to, in his prepared remarks, the G12C program is currently gated by optimizing the dose of that Rasohn doublet, the combination of diraxonrasib and eleronrasib we have to because it's a novel combination and it's going into patients who have never received treatment for their their non small cell lung cancer. We really have to get the dose right get the dose right for satisfaction of the company, but also to the satisfaction of the regulator and the payers and the prescribers. So a little bit more refinement [indiscernible] is needed there.

We're pretty close. We have a range within which we're operating. And I don't think it'll take too long, but that's essentially what's gating the G12C first line non small cell lung cancer. Program.

And a subpart of that was is is PFS required Are we waiting for PFS? And I think that's a simple answer that PFS is really not driving that decision. We understand PFS based on the second line data and now we have confidence that the response rates are very competitive I think we're good to go from that perspective. Yeah, we should say, we should add that both from published literature and historical data and from our own pretty intense in house analysis, a response rate is a reasonable correlate of PFS in non small cell lung cancer. That has not been the case for pancreatic cancer, but for lung cancer it is. So we we're more confident about the link between our response rates that we've just disclosed in the lung cancer patients and predicted PFS that we will achieve. And of course, PFS in lung cancer more compelling as a regulatory endpoint unlike in cancer where we have to overall survival. So, it's got a lot lung cancer has got a lot lot more going for it.

Thank you. Our next question comes from Eric Joseph of JPMorgan. Your line is now open.

Thanks for taking the questions, and let me also just concur. Lots of data updates here and a lot to digest. Maybe Steve, could get you to expand a little bit on your last comment. The types of datasets [indiscernible] grant you confidence that [indiscernible] response rates would be a predictor for better PFS outcomes. Sort of outside of your own pipeline work I'm also curious to know whether you are continuing to enroll the frontline lung cancer cohorts [indiscernible] build upon the dataset that you are observing so far. And then we finally, the safety side, I know this is more than one question, but on the safety side, this non clinical, the subclinical QT signal that you're seeing with the right combinations, you're confident that it won't you know, become something greater with the triplet regimen? Thank you.

I think the first part was a question thank you, Eric. Think the first part was a question about the literature reflecting predictive utility of response rate for durability. Think we can provide? Some references offline that the way, it's something we've heard from investors for the last several years, why don't we use response rates more? So I think it's pretty generally well known and our observations are very consistent. That. Do you have anything you want to add to that, Anil? What was the second part?

Safety in the QT signal. Safety in the QT.

Safety question about the QT signal.

Concerns that it would be greater than the treatment. Do you want to comment on that? Yeah. We have not seen that be the case. Certainly, we've reported the QTC signal here. It's actually on par even lower than what we observed with the monotherapy Obviously, with longer follow-up, and larger patient sample, we do not expect there's going to be an enhancement of QT So I think QT is well within line of what osimertinib has reported. In their label.

And consistent with the larger earlier on and longer follow-up later on RACID data set that we showed at the beginning here, which I think makes that makes that point pretty clear.

The other question was on whether your continuing to enroll [indiscernible] Well, there's dose optimization ongoing, so pretty much answers that. [indiscernible] Thanks for taking the questions. Congrats on the on the updates.

Thank you.

Thank you. Our next question comes from Jonathan Chang of Leerink Partners. Your line is now open.

Hi, guys. Thanks for taking my question. How are you thinking about the duration of clinical benefit of doraxonerasib versus the mutant selective inhibitors like Zoltanrasib? And ElironRasib. What are the reasons for why one could be more durable than the other? And how could this and other factors impact how you're thinking about future development strategies? Thank you.

Thanks, Jonathan. Maybe I'll comment on that, and then if Steve or Wei wants to add anything to it, I don't think we have any direct head to head comparison, because the diraxonerasib study was done in tumors that carry different mutations, than the oliron Rasib study. So we really can't compare those, so we can't say which is superior to the other, and they're not matched for other prognostic factors as well. So I don't think we have any information on it.

You know, if you're wondering what what we might predict, I don't know. We'll see. And ultimately, we're combining these anyway, as both Wayne and Steve have talked about, and so one ought to get the benefit of whatever the pros are on each side of that. Is there anything more specific that you're trying to get at there?

I was just thinking about how in situations where you might be considering advancing the multi RAS or a mutant selective one or maybe the combination of both. How you might consider things like duration of clinical benefit and how long patients may stay on treatment. In addition to other considerations.

It's the number one consideration. Because that's the key driver of sort of patient experience, assuming that we obviously have a combination that patients can tolerate the time that they're on the treatment without having a miserable life. It's the number one consideration. The mechanisms of escape from the mutant selective inhibitors are very different from the mechanisms of escape from daraxomrasid. We have only disclosed mechanism of escape data for respite in pancreatic cancer, but it's very different pattern of escape from what's being disclosed for mutant selective inhibitors in non small cell lung cancer. And that's why we're so enthusiastic about the combination because all of those putative mechanisms of escape are covered by the combination. The novel RAS mutations that emerge on the mutant selective inhibitors are inhibited by diraxone rasid. And the putative amplification of mutant KRAS that we might see in lung cancer, which we have seen in pancreatic cancer, is suppressed by hitting the mutant harder with the combination of the two RAS on together. So we do expect the PFS to be longer with the combo than with either agent alone. And as we described, increase in response rate is a good harbinger of that.

We just have to wait for that data to mature in order for it to be worthwhile disclosing publicly because immature PFS data isn't helpful to anybody.

Yeah, and Steve's comments are entirely consistent with what we have reported in the preclinical context, and I think Wei showed two figures representative of a much larger data set that we presented over several scientific meetings that the combination does tend to deliver significantly greater benefit and including the figure on the right side of that slide, slide I'm not sure what it is in your deck, but that right figure shows the combination of the doublet plus anti PD-one, and it basically provided for no progression in any of the animals in that experiment across one hundred days. So think the totality of the evidence is supportive of what Steve suggested.

Got it. Thanks for taking the question.

Thank you. Our next question comes from Kelly Hsieh of Jefferies. Your line is now open. Hi, this is Clara on for Kelly. Thanks for taking our question. On the data. So for non small cell lung cancer with all the combination updates and it seems like you have really multiple paths to pursue the opportunity in long and you also have total pancreatic development as well as maybe other early initiatives such as G12V. So maybe from a resource allocation perspective, what are the key criteria driving priorities between all those developments and also for lung cancer specifically, how should we think about the cadence of pivotal combination trials? And you mentioned you might initiate combination trials in 2026. Thank you.

Okay. Thank you, Clara.

Let me start with the second comment about timing. Mean, we have provided some timing, and I think that's all we can provide today. We do have, of course, Draxo and Rastiv in non small cell lung cancer already underway in the three zero study, but then in terms of first line, and combination studies, we'd expect to begin rolling those out in 2026. Terms of resource allocation, I don't think there's a simple single word or sentence answer to to help clarify that for you.

Obviously a pretty complex and rich set of opportunities, It's sort of an embarrassment of riches that each clinical study we've done so far opens up pretty exciting new pivotal trials that we could consider doing. So it certainly does create some need for prioritization We start with the clinical data, the biological rationale behind the data, we look at the competitive landscape, As Steve pointed out, ultimately what's most important is to provide durable clinical benefit So that's a key characteristic that gets ranked in all of this. So many, many factors. And at this point, we're able to proceed with a large chunk of the of the priorities that we have defined we're basically moving everything forward right now that that is ready to be moved forward in 2025, and we'll continue to do that into 2026. Constantly looking at justification for the investments, but also trying to achieve the goal that we've alluded to several times here, which is to deliver significant changes on behalf of patients across RAS mutations, tumor types, and lines of therapy, and we think we're best positioned in the industry to do that.

Thank you.

Our next question is from Ellie Merle of UBS. Your line is now open. Hey, guys. Thanks for taking the question, and congrats on all the progress.

I'm just curious your latest thinking on a potential commercial strategy ex U. S. And your general philosophy around potential partnering And then just in terms of the designs for the pivotal combination trial or trials, Could you give us maybe any more color on when you might expect to meet with the FDA to the designs, and when we might be able to learn more about the specifics of the designs from our end. Thanks.

Hi, Ellie. Thanks for your question. On the second point, unfortunately, no, we don't typically sort of lay out the timeline for our future interactions or ongoing interactions with the FDA. Our pattern that we've tried to establish is once we definitize a plan, or close to a definitive plan, we often provide some sort of update, including the data to support whatever commitment we're making. But beyond that, I can't give you any further higher resolution answer to it. With regard to the ex US strategy, that's obviously very much on our minds, as I think it is on our investors. Since I first raised almost two years ago now, the possibility that we might engage with others to help us commercialize outside The U. S. While we would certainly focus on retaining The US US market We have had strong interest from multiple global pharma companies, We had concrete and productive dialogue with them, and without a doubt, we could enter an attractive partnership. And that's really creates a great deal of optionality for us. We've also felt no need to rush into such a partnership, and we've continued to use time to our advantage. We've continued tracking the portfolio, tracking the assets, progress trajectory, We've also tracked organizational progress and trajectory.

And all of those have continued to exceed our expectations. So now we're in the position to assess the pros and cons of all the options. That are available to us. And we have to make a strategic judgment which we're just not ready to make today. Which is what's the best approach for serving patients not only in The U. S. But also internationally, and that also serves our business. And we are continuing to look at that, but now through the lens of where we are in 2025, with a very different organization in terms of depth and breadth, programs, maturity programs, and also with the addition now of Anthony, who joins the team, it can bring a very broad commercial perspective to it as well. So we will complete that analysis at some point and continue to provide updates as appropriate.

Great, thanks.

Thank you.

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

You, operator. Thanks to everyone for participating today and for your continued support of Revolution Medicines.

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