Good day and thank you for standing by. Welcome to Revolution Medicine's fourth quarter 2025 earnings conference call. After the speaker's presentation, there will be a question and answer session. To ask a question during your session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan Acey, Senior Vice President of Corporate Affairs. Ryan, please go ahead.

Thank you, and welcome everyone to our fourth quarter and full year 2025 earnings call. Joining me on today's call are Dr. Mark Goldsmith, our Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of Research and Development. Dr. Alan Sandler, our Chief Development 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. Before we begin, I'd like to remind everyone 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 annual report on Form 10-K that is filed with the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter and full year ended December 31, 2025, and recent corporate updates. The press release is 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.

Thanks, Ryan. Good afternoon, and thank you for joining us. We will keep our prepared remarks brief today, Highlighting the substantial progress and growing momentum for our pioneering RAS on inhibitor pipeline and outlining several important priorities for the year ahead. Jack Andrews will summarize our financial results along with financial guidance for the year ahead. At Revolution Medicines, we remain steadfast in our commitment to revolutionizing treatment globally for patients living with RAS-addicted cancers through the discovery, development, and delivery of innovative targeted medicines directed against these common mutational drivers of human cancers. As pioneers in the RAS targeting field with a singular focus on RAS-addicted cancers and a great deal of validating data behind us, we are well positioned to continue building on important scientific drug discovery and clinical breakthroughs that have the potential to change standards of care for patients. Our efforts throughout 2025 strengthened our leadership position as we advanced our robust pipeline that includes four novel investigational drugs that target the major oncogenic RAS drivers. Diraxon RASIB, our most advanced program, a groundbreaking RASON multi-selective inhibitor. Aliron RASIB, a differentiated, highly active, and well-tolerated RASON G12C selective inhibitor. Zoldon RASID, an innovative, highly active, and well-tolerated RASON G12Z-selective inhibitor, and our newest clinical compound, RMC5127, a promising RASON G12Z-selective inhibitor. We have eight ongoing or planned Phase III registrational trials and extensive clinical experience to date, with more than 2,500 patients having received one or more of our RASON inhibitors in the aggregate. This clinical work is built upon the foundation of a strong discovery and preclinical platform that continues pushing the boundaries. Our virtuous cycle of innovation fuels how we discover new ways of targeting RAS through our highly productive tri-complex platform, develop novel investigational drugs through robust and parallel clinical development plans, and systematically expand our commercialization and operational capabilities to deliver potential new therapies to patients globally. I'll provide an update on our clinical activities in pancreatic cancer, our most advanced clinical program. With more than 90% of pancreatic cancers being RAS-driven, there's a profound need for RAS-targeted therapies, which we aim to address with multiple registrational trials underway or that we plan to initiate in 2026. Draxon RASiv, our pioneering RAS-on multiselective inhibitor, has shown an unprecedented clinical profile across RAS mutations and lines of therapy, either alone or in combination with standards of care. Our broad conviction around Draxon RASID was further strengthened by the U.S. FDA designation of Draxon RASID as a breakthrough therapy and its award of one of the agency's first commissioner's national priority vouchers based on its potential to address significant unmet needs in pancreatic cancer. We're currently evaluating Draxon-Rasib in three randomized registrational studies in pancreatic cancer across lines of therapy. Resolute 302, a randomized registrational trial evaluating Draxon-Rasib monotherapy in second-line medistatic disease. As a reminder, Resolute 302 employs a nested trial design. The largest population of patients with tumors carrying a RAS G12 mutation in the core and the expanded population that includes patients with tumors carrying other RAS mutations and tumors without a detected RAS mutation. The trial employs hierarchical testing to maximize the probability of success in the core population and potentially enable a broad label not requiring biomarker testing. With global enrollment now complete, we expect a readout to occur in the first half of 2026. In earlier lines of therapy, two randomized registrational studies were recently initiated. Resolute 303 is evaluating both Diracxon RACIB monotherapy and Diracxon RACIB in combination with chemotherapy in first-line metastatic disease. Evaluating both monotherapy and combination approaches may enable treatment optionality for physicians and patients. RASOLUTE 304 is evaluating DRAXON-RACIV monotherapy in the adjuvant setting in patients with resectable disease after receiving conventional surgery and perioperative chemotherapy. The data we've collected to date support our strong conviction that these studies have the potential to establish new global standards of care across lines of treatment for patients living with pancreatic cancer. Zoldanrasib, our covalent G12D selective inhibitor, is another first-of-its-kind compound that has shown a highly differentiated safety and tolerability profile. We recently disclosed encouraging initial data from patients with metastatic pancreatic cancer receiving first-line treatment with the combination of zoldanrasib and fulfirinox. The initial safety and tolerability profile for the combination of both treatments was largely consistent with the well-known profile of modified fulferinox alone, and a high zoldan-racid dose intensity was maintained. As of the data cutoff date, 63% of patients achieved a partial response, either confirmed or pending confirmation. The disease control rate was 95%, and the vast majority of patients remained on treatment. With these data reinforcing confidence in this compelling G12D selective inhibitor, we plan to advance two first-line registrational combination studies this year. Today, we're pleased to announce that Resolute 305 has been initiated. Resolute 305 is a randomized, double-blind, placebo-controlled trial that is evaluating Zoldan-Rasib in combination with investigators' choice of either gemcitabine, NAB-paclitaxel, or modified fulfirinox chemotherapy compared to investigators' choice of chemotherapy with placebo. Resolute 309 will evaluate the Rasson inhibitor doublet combination of zoldon Rassib plus diraxon Rassib, and we plan to initiate this trial in the second half of 2026. We plan to share clinical data from the initial trial of the zoldon Rassib plus gemcitabine nadpaclitaxel combination and the zoldon Rassib plus diraxon Rassib Rasson inhibitor doublet combination in PDAC at one or more medical meetings this year. A second area of focus in which we've shown continued clinical advancement is non-small cell lung cancer. With approximately 30% of non-small cell lung cancers harboring a RAS mutation, including 18% with non-G12C mutations, this tumor ties remains a key priority. To date, we've shown encouraging initial safety tolerability and anti-tumor activity in patients with RAS mutant lung cancers across our three lead compounds that supports their potential to establish new standards of care. And we are building a set of registrational trials accordingly. RESOL 301, our global randomized trial evaluating Draxon RAS monotherapy in previously treated patients, continues enrolling patients across sites both in the U.S. and globally. We anticipate substantially completing enrollment this year. We also expect to disclose our plans for advancing Draxon RASIB combination therapy in first-line non-small cell lung cancer this year. With Zoldon RASIB and Alira on RASIB, we've reported highly encouraging safety tolerability and anti-tumor activity data from previously treated patients with lung tumors harboring RAS G12D or G12C mutations, respectively. The Zoldan-Rasib monotherapy expansion cohort is fully enrolled, and earlier this year, Zoldan-Rasib was awarded breakthrough therapy designation, making it our third Rason inhibitor to have received this distinction. Building on these milestones, we are preparing to initiate Resolve 308, a first randomized registrational trial of Zoldan-Rasib in combination with standard of care as a first-line treatment for patients with metastatic RAS G12D non-small cell lung cancer. For earlier on RASIV, we continue to evaluate this compelling G12C selective inhibitor that has demonstrated a differentiated clinical profile in both G12C inhibitor-naive and G12C inhibitor-experienced lung cancer patients. We've reported encouraging results with monotherapy or combinations with either pembrolizumab or as part of a RAS-on inhibitor doublet with diraxon RAS-ib. And as we consider multiple approaches, we plan to share an update on a registrational strategy for aliron RAS-ib this year. The third area of focus, colorexal cancer, remains of high interest and engagement for the company. Approximately 50% of patients with colorexal cancer harbor a RAS mutation. Given the genetically complex and heterogeneous nature of the disease, combinatorial approaches are key to maximizing clinical impact. We have a range of studies underway, including evaluating RAS on inhibitor doublets and evaluating RAS on inhibitors with current standards of care and with other novel approaches. We plan to provide visibility into combination data in colorectal cancer this year as we work toward prioritizing registrational opportunities. Our development efforts include several clinical collaborations studying our RAS-on inhibitors with new targeted therapies in clinical development. Our collaboration with Tango Therapeutics is studying our RAS-on inhibitors in combination with Volpi Metastat, Tango's MTA cooperative PRMT5 inhibitor in patients with tumors carrying both a RAS mutation and MTAP deletion. We also recently entered into a clinical collaboration with Bristol-Myers Squibb to evaluate Diraxxon RAS in combination with NAGLAMetastat, its MTA cooperative PRMT5 inhibitor, in patients with pancreatic cancer whose tumors carry both a RAS mutation and MTAP deletion. This collaboration extends our commitment to evaluating novel targeted agents, such as PRMT5 inhibitors, that may be appropriate to combine with RAS-ON inhibitors in some settings. Our ongoing collaboration with Summit Therapeutics is evaluating our RAS-ON inhibitor with Summit's PD-1-VEGF bispecific antibody, ivermesimab, across multiple solid tumor settings. The first patient in this trial was recently dosed. We recently brought our fourth RAS-ON inhibitor, the RAS-ON G12D selective inhibitor RMC5127, into the clinic and announced that the first patient had been dosed in the first in-human trial. We expect to identify a recommended monotherapy phase 2 dose for this compound in the second half of 2026. As leaders in developing treatment strategies for patients with RAS-addicted cancers, we recognize the importance of continuing to invest in new approaches that advance the science and have the potential to further transform treatment paradigms. Our discovery team continues pioneering novel new approaches, including an innovative new class of RAS on inhibitors from our laboratory designed to overcome RAS-driven drug resistance and thereby extend the clinical benefit of RASLON inhibitors. As we disclosed in January, in preclinical pancreatic cancer and non-small cell lung cancer models that had developed resistance to durexone racids, treatment with a representative compound from this new class, RM055, drove deep and durable regressions. This year, we plan to share more information about this new class of compounds at a scientific meeting, and later in the year to begin clinical development of a first compound from this class as our fifth investigational clinical stage RAS-on inhibitor. As late-stage programs, notably Duraxon RAS-id, advance toward possible commercialization, we are committed to building a world-class, end-to-end, global oncology enterprise to deliver compelling targeted therapies to patients with RAS-addicted cancers. We have established a strong operational foundation to move with speed and agility to ensure a successful first commercial launch initially focused in the U.S. market. To that end, we have made key strategic hires to form a strong leadership team of professionals who have established track records and launched some of the most impactful oncology products in recent years. In addition to recently onboarding regional field sales leadership to support the U.S. launch, recruitment for our first field sales team is now underway. I'd now like to turn the call over to Jack Anders, our CFO, to summarize our fourth quarter financial results and forward-looking guidance. Jack?

Thank you, Mark. We ended the fourth quarter of 2025 with $2.03 billion in cash and investments. In 2025, we entered into our innovative and flexible strategic partnership with Royalty Pharma, which provided us access to up to $2 billion in committed capital under the terms of the agreement. We received the first royalty monetization tranche of $250 million in June 2025, and there remains an additional $1.75 billion in future committed capital under this arrangement. Turn into expenses. R&D expenses for the fourth quarter of 2025 were $294.9 million compared to $188.1 million for the fourth quarter of 2024. The increase in R&D expenses was primarily due to increases in clinical trial and manufacturing expenses related to our multiple ongoing clinical development programs, and an increase in personnel-related expenses and stock-based compensation expense associated with additional headcount. G&A expenses for the fourth quarter of 2025 were $66.7 million compared to $28.2 million for the fourth quarter of 2024. The increase in G&A expenses was primarily due to increases in commercial preparation activities and personnel-related expenses and stock-based compensation expense associated with additional headcount. Net loss for the fourth quarter of 2025 was $364.9 million compared to $194.6 million for the fourth quarter of 2024. The increase in net loss was primarily due to higher operating expenses as described earlier. Net loss for the fourth quarter of 2025 also included specific non-cash charges of $33.7 million in stock-based compensation expense, $12.6 million in non-cash warrant expense related to a mark-to-market change in the fair value of warrants we inherited as part of our EQRX acquisition, and $11.9 million in non-cash interest expense related to the accounting treatment for our Royalty Pharma arrangement. Full-year 2025 financial results are available in our corresponding press release and also included in our Form 10-K that was filed with the SEC this afternoon. Turning to financial guidance, we would like to note that we are switching the forward-looking financial guidance we provide from GAAP net loss to GAAP operating expenses for fiscal year 2026. The switch to GAAP operating expenses is intended to provide expectations on our anticipated level of spend for 2026 in a more straightforward and easier to follow manner. As GAAP net loss includes certain non-cash items within non-operating income and expense, such as the change in fair value of the warrant liability and non-cash interest expense associated with our royalty pharma arrangement. With that said, we expect full-year 2026 GAAP operating expenses to be between $1.6 and $1.7 billion, which includes estimated non-cash stock-based compensation expense of between $180 million and $200 million. The increase in expected gap operating expenses for 2026 is a result of the progression and expansion of our clinical development programs, in particular, the multiple ongoing and planned registrational studies we have outlined as priorities. We also expect higher expenses in 2026 as a result of increased commercial preparation activities as we continue to build and expand our organizational capabilities in preparation for becoming a global commercial stage company. That concludes the financial portion. I will now turn the call back over to Mark.

Thank you, Jack. 2025 was a pivotal year for RevMed, and 2026 is poised to be one of substantial impact as we seek to create the industry-leading global targeted medicines franchise for patients with RAS-addicted cancers. We believe that each asset in our pipeline has the potential to transform the treatment landscape for these difficult-to-treat cancers. With key milestones across our clinical programs, advancing new programs to the clinic, continued investment in innovation, and preparing for our first commercial launch, We are well set up for the future, building on our foundational achievements to date. Of course, none of the work we do would be possible without the partnership and ongoing support of health care providers, patients and caregivers, and investors, and the remarkable dedication and efforts of RedMed employees. With that, I'll turn the call over to the operator for the Q&A portion of today's call.

Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please limit your questions to only one follow-up question when prompted. Please stand by while we compile the Q&A roster. The question comes from Jonathan Chang of Lyric Partners. Your line is open.

Hi, this is Albert Agustinus on for Jonathan Chang. Thanks for taking our question. I was just wondering, could you please share your thoughts or clarify in your plans to advance the direct-sumeration combination in first-line non-small cell lung cancer this Are you still guiding towards the initiation of a registrational trial in this setting?

Thank you. high commitment first line maybe the reality is that there are a number of options available to us we continue to optimize direct somracid in combination with the combination partners that you might expect us to use for that indication and also do efficacy testing to get the requisite proof of concept required to invest in a large base for a trial. So as soon as we have that information and a plan to go with it, we'll be able to share it with you. And I think we've committed to providing more information on that.

Yeah, and if I could just add, I think the other element to this, of course, is that we just started dosing patients with libanesumab in combination with their RAS on inhibitors. That obviously has lung cancer.

Thank you. One moment for our next question.

The next question comes from Brian Chang of JPMorgan. Your line is now open.

Hey, guys. Thanks for taking our questions this afternoon. As we get closer to the top line for the second-line PDAC trial, what is your latest thought on the efficacy measure that we could get at the time of the top line? And just curious if you can provide a bit more color on the rates of events towards this upcoming top line.

Hi, Brian. Thanks for your questions.

You know, of course, we've entered the period in which we indicated we'd be providing a disclosure, so I don't think we'll be able to give you higher resolution today. but it doesn't seem like the right time to do that. It is an OS event-driven readout, and the study is powered for OS and for PFS, so we'll have an intro read on the expectations. Other than that, we are – and that will be the set of benchmarks that will be used in our analyses.

Got it. Thank you. Thank you.

One moment for your next question. Our next question comes from Michael Schmidt of Guggenheim. Your line is now open.

Hey, good afternoon. Thanks for taking my questions, and congrats on all the progress. Mark, I had one on your ongoing and planned studies in first-line pancreatic cancer. So obviously there's a lot of excitement among physicians and patients in the pancreatic cancer community around direxin racet. And we've heard from docs more recently that, you know, if approved, they think that over 90% of their second-line patients could go on directs and RASF within months of approval. And so when you think about that, to what degree do you think directs and RASF use in your first-line studies post-progression in the control arm could potentially impact OS outcomes in RASF 303 and 305? and how important is it to demonstrate OS in these studies in the first place?

Okay, thanks, Michael. I think I understand the question. To what extent does the availability of an approved diraxom racid with the second line label potentially provide in the – there is some – of course, the label would not necessarily indicate we wouldn't be able to speak, But there is some risk to have the ability to address that, both through timing, so I think during that period, yet.

Thank you. Thank you.

Our next question comes from Charles Zhu of Lifeside Capital. Your line is open.

Hey, good afternoon. I have a couple about your decision about this kind of thinking context with your ongoing collaboration with Ivan Nesimab.

Nesimab. And on the context?

Understood. Thanks for taking the questions.

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

Thanks for taking my question. Congrats on all the progress. Maybe just first off on more of a bit of a housekeeping thing, can you just confirm whether any event thresholds have been reached in 302 to trigger interim analyses yet, or if just none of those have been hit yet? And then thinking more broadly about pancreatic cancer, you know, now you have several first-line trials either ongoing or, you know, getting started in the next handful of months. Just what is the kind of long-term vision you have for what the treatment paradigm in pancreatic cancer looks like in four or five years? You know, how do diraxin-rasib, zoldan-rasib, chemo all get sequenced, you know, for maybe the typical patient? First one, and then maybe Alan Sandler can landscape it.

My comment is I don't really have any answer to your question. When we are unblinded, that causes us to do an analysis, which then leads to your question about…

Thanks for the question. Well, I think we've set up very nicely with multiple studies to kind of have a major say as to what pancreatic cancer will look like in the next three to five years, you know, with our early studies looking at second-line therapy with Diraxxon-Rasiv, moving into the first-line setting also with Diraxxon-Rasiv, looking at it both with respect to monotherapy but also potentially in combination with chemotherapy. And then we're doing that with a more specific agent such as Zoltan-Rasiv or D, and looking at that as well in combination with chemotherapy versus chemotherapy in the frontline setting, but also the novel ability to combine it with Diracxon Rastad also in that first-line setting. This will provide patients with the optionality in first-line setting to actually potentially have a chemotherapy-free opportunity, as well as building upon the results that have been seen with chemotherapy alone. In addition, and potentially even more importantly, we have the opportunity to impact patients who have potentially curable pancreatic cancer by conducting 304, which is our adjuvant study for those patients who have had resected cancer in perioperative therapy. So we really are covering the gamut of patients with pancreatic cancer from second-line therapy all the way to resectable and potentially curable pancreatic cancer. And I think that covers probably three to five and maybe even a year or two beyond that as well. And then in addition, of course, as Mark mentioned earlier, there are other agents in our pipeline that we'll be looking at as well that will also potentially have an impact.

Thank you.

Our next question comes from Alex Stranahan of Bank of America. Your line is open.

Hey, guys. Thanks for taking our questions. With the Ivanesimab study now dosing patients, I guess, could you maybe speak a bit about the study design and which tumor types and lines of therapy you expect might enrich in the study as it enrolls? And longer term, how is this combo maybe emblematic of how you're hedging your RAS therapies alongside potential shifts in standards of care? Thank you.

Thank you for the question. And so the trial, as we pointed out, has been initiated, and that's the APEX study. It's a study that involves O3, and they're on RAS that covers O-RAS, the GCOD, as well. There's a standard dose isolation involving amnismab. And the dose isolation in the context of IVO?

Yes, just broadly, how you're thinking about CONVOs as standard of care involves across these treatment settings.

I think we're not holding anything up. With regard to non-small cell lung cancer, where temporal really is a dominant of the world, it will take more to knock that off than for there to be a real change.

That makes sense. Thanks so much for the call.

Thank you. Our next question comes from Ashika Gunawardin from Truist. Your line is open.

Hey, guys. Thanks for taking my question. I want to kind of go back to Albert's question at the beginning. specifically on Diroxone in frontline non-small PNR. I guess in previous calls, earnings calls, we've talked about, and you pointed out how Pembrol plus chemo is a backbone therapy, and it makes a lot of sense to consider that in combination with Diroxone-Rasib. But when you talked about other options today, I wanted to just get a little clarity here. When you talk about other options, do you mean other PD-1s in combination with chemo, other mechanisms, like maybe involving DD1 and CTLA-4, or are you thinking, are you considering chemo-free options here for the ideal regimen you want to take drugs on in the frontline non-sponsor With PEMBRO and chemo, or whether potentially IVO emerges during that period of time, I think that was the context for that narrow answer, is that we're now evaluating IVO, and so we'll have some of that information.

But in the meantime, as Steve had articulated, continuing the dose optimization and efficacy. So those are running in parallel.

I'm going to sneak a quick one in. Any thoughts on whether you will use your commissioner's priority review voucher for second-line PDAC once you have the RASL-302 data in hand? Thanks, guys.

Do you use percentifying PDAC?

Oh, I see. Yeah, I think that's been made clear. It wouldn't really make sense if we wouldn't be operating under the CMPV in that second Thank you.

One moment for our next question. Our next question comes from Laura Prendergast at Stiefel. Your line is open. Hey, guys. Thanks for taking the question.

In a recent public appearance, Mark, you brought up the concept of treating beyond progression in PDAC, you know, from the angle of patients are progressing under XMRAC, and in the worst part due to amplification of the RAS target. It's supposed to be a pretty unique consideration in oncology, you know, where perhaps removing the drug upon progression of PDAC is one of the best interests of the patient. Let's not raise a few important questions at our end. You know, first, are investigators on the Phase 3 studies being first and second, like PDAC being encouraged to treat lung progression, is allowed to see protocols, and, you know, Infer, the question was about treatment beyond progression.

We have made the comment that we've heard a number of investigators. That's my general comments, but I don't know what the actual question is.

As it relates to the study protocols, was there any restrictions on how much, on whether or not this is a possibility on the first-line or second-line Phase III, and then how do you guys think this could impact the overall survival of those studies?

Yeah, okay. I do understand the question now. So, did we formalize this in the 302 study versus other studies? it's not in the 302 study because that study was already too far underway to make that modification the progression beyond that it is not permitted in the 302 study but as other studies come online we've encouraged investigators to evaluate that possibility and where it makes sense to continue continue treatment beyond progression particularly in the earlier line studies and so we'll be able to generate a lot more in got it thank you

Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open.

Oh, hey, guys. Congrats on all the progress. Thanks for taking our question. Since you're making a lot of headway in PDAC and non-small cell lung cancer, can you talk about your vision and strategy in colorectal cancer, and how are you prioritizing the CRC opportunity for RedMed? Is CRC an area that you would prefer to focus on with partnerships, for example, in combination with Ivanesimab? Or is CRC something that you plan to pursue independently? And from a BD perspective, would you consider in-licensing some molecules that have synergy with your RAS portfolio so you wouldn't need to rely on partnerships in CRC?

Yeah, Jay, thanks for your question. Maybe Steve and Kelsey can just comment in general on our approach to CRC, and if there's anything left on BD at the end, I can come back and comment on it.

Yes, I mean, colorectal cancer has never been deprioritized. Right from the start of direxom-rassin, zolom-rassin, disescalation studies, we included patients with colorectal cancer. I think what we found, which was hardly surprising because a number of other people have also found this both before and since, is that colorectal cancer is an incredibly complex and heterogeneous disease, each of those clones often containing multiple genetic abnormalities. And as a result, what happens is that two things happen, really. One is that overall response rates are lower than they are traditionally in the other RAS driven diseases, which makes rapid decision-making about future clinical development more complicated because now you have to wait for somewhat longer-term readouts like PFS. And secondly, it becomes an obligate combination play. You really, there really are no opportunities for developing a single agent in advanced. In the late-stage colorectal cancer, after chemotherapy has failed, it's such a heterogeneous and genomically complex disease, you need combinations, and in earlier lines of therapy, you really need to combine with combination chemotherapy, which is standard of care. So it becomes more difficult and more time-consuming to reach a point where there's a clear path forwards into pivotal trials and I think that's what we have found and it's got nothing to do with prioritization it's got it's really down to the biology of the disease and how that translates into early stage with regards to methodology I mean our our company is the you know we have made the decision to be a standalone global organization and we are not looking to change that on a disease or histotype, there may be opportunities for doing studies in collaboration with partners if the right partner – if we believe that's the right combination and we have the right partner, we may choose to do it as part of a clinical collaboration or maybe even as some other type of business arrangement. But right now, that's not the preferred or even and the base case plan, our plan is to figure out which combinations involving a RATSOI inhibitor are going to make the biggest impact and cover up the cancer and prosecute those to registration.

Your answer covered it pretty darn well.

You know, maybe the one last little piece is, would we bring in additional compounds into our pipeline? That's always possible. We have a very robust, which we evaluate other people's assets. We receive a lot of inbound proposals and occasionally we reach out to somebody else to learn more.

So that's all just a practical consideration.

Thank you.

The next question comes from Leo Timoshev from RBC. Your line is open.

Thanks for taking my question. I wanted to ask a little bit on RMO55 and that class of molecules. I guess, does this address secondary mutations or does it really only work directly on RAS mutations themselves And I guess, said another way, are you seeing this line option, or can this be something that...

Yeah, thanks, Leo. Appreciate the question. All interesting ideas, but more to come.

Thank you.

Our next question comes from Ami Fadiya from Needham & Company. Your line is open.

This is Puna on for Ami. Thank you for taking our question.

I just want to understand how soon can you get to commercialization of data in case the first interim is positive what are some of the aspects within the commercialization preparation that you still need to work through thank you thank you for for those questions so i think you're asking about what have we done to repair and what does the timeline look like i think anthony can step into that yeah thanks for the question i think we're really pleased with how our launch readiness plan we're advancing and we continue to add highly experienced and talented members of the team and we're really achieving broad organizational readiness led by the US but also in Europe and in Japan so we're really pleased with the launch readiness across the board as Mark alluded to in his prepared remarks that launch readiness in terms of the US the first launch is actually proceeding quite well with leadership teams in place across commercialization and across functions, field-based leaders across meta-fairs, market access, marketing, and sales. And as Mark mentioned as well, we've now initiated the posting of our further extension of our field-based teams, our sales teams. So we're really, really pleased with how the launch readiness overall is coming together. And certainly as we get closer to filing and launch, we'll provide some more color.

Thank you. Thank you.

Our next question comes from Calbitt Patel of WUF Research. Your line is open.

Hey, thanks for taking the question. I guess how should we think about the disclosure of the pivotal update here in second-line pancreatic if for any reason you missed the interim PFS analysis and that does not cross the pre-specified boundary? Would you expect to provide an update at that point, or would you just wait for the OS-driven readout thereafter?

More power for PFS. So it's less likely than not crossing – not emphasizing that particularly, but it is one of the – and we'll just have to see what that looks like at that point in time.

Thank you.

Our next question comes from Sean McCutcheon of Raymond James. Your line is open.

Hey, guys. Thanks for the questions. Can you speak to the staggering of enrollment for RASLO 302, 305, and 309, and the 303 protocol components to ensure a representative sample of mutations in 303 and avoid an enrichment of non-G12D patients, and perhaps germane to that, as well, can you speak to your expectation for the G12D versus the G12V and G12R patients in the GNP arm, given G12D tends to be a bit more aggressive and chemo-resistant?

Got the general idea. There were a lot of specifics in that. The staggering of enrollment, just make sure we understood your question. Were you linking the staggering of enrollment of getting access to patients and enrolling?

Yeah, linking. So, obviously, 303 is all comers there versus 305 and 309 being G12D. So, the staggering as it relates to kind of shuttling the patients, you know, avoiding shuttling the G12D patients to the 305 and 309 study to comment on that?

I think some of this will be managed by the site selection O3-12b global trials. We're certainly mindful that we want to have a fair and equitable representation of all RAS mutants in the, or actually an old-comer population in the 303 study, and the G12d mutant population in 305 as well as 309. And the control arm do vary among these three, 305 specifically, just offer both GMP as well as Fofirinox versus 309 and 303. As you know, they're local regional preference for GMP and Fofirinox, so we have a variety of thoughts. The PDAC patients are metastatic patients. The U.S. alone, they're trying to, and we're still giving you nine points.

Give me back to Mutational.

Thank you.

Yeah, and just on the expectation for the – in the 303 study for G12D performance relative to G12D and G12R, given the, you know, respective expectations for each of those mutations being treated, understood.

Thank you. Our next question comes from Faisal Karzid of Jefferies. Your line is now open.

Hey, guys. Thanks for taking the question. I just want to ask, now that you've had the Commissioner Priority Review Voucher for a little bit, can you speak to what benefits you are either seeing now or expect to receive from that above and beyond what you'd otherwise get from programs like Breakthrough Designation and the Real-Time Oncology Review? Thank you.

Yeah, thanks for your question. We don't have much to offer on this particular point. We don't generally. You know, the main advantage that's...

Great, thank you.

Thank you. I am showing no further questions at this time. I would now like to turn it back to the Chairman and CEO, Mark Goldsmith, for closing remarks.

Thank you, Operator, and thanks to everyone else for participating today and for your Thank you for your participation in today's conference.

This does conclude the program, and you may now disconnect.