Q4 2024 Revolution Medicines Inc Earnings Call

February 26, 2025

Speaker Change: Good day and thank you for standing by. Welcome to the Revolution Medicine's Q4 2024 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session.

Speaker Change: To ask a question during the session, you will need to press star one one on your telephone.

Speaker Change: You will then hear an automated message advising your hand is raised.

To withdraw your question, please press star 11 again.

Speaker Change: 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 Asay, please go ahead

Speaker Change: Thank you and welcome everyone to our fourth quarter 2024 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.

Speaker Change: Dr. Steve Kelsey, our President of Research and Development, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call.

Speaker Change: 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.

Speaker Change: Actual results may differ materially from those in the forward-looking statements.

Speaker Change: For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the U.S. Securities and Exchange Commission.

Speaker Change: This afternoon, we released financial results for the quarter ended December 31st, 2024, and recent corporate updates. The press release is available on the investor section of our website.

Speaker Change: at RevMed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer. Mark.

Thanks, Ryan. Good afternoon, and thank you for joining us.

Speaker Change: Today I'll cover highlights of progress with our pioneering Rason Inhibitor Pipeline and outline important priorities for 2025, as well as markers of progress we expect going forward as we pursue these priorities.

Speaker Change: Jack Anders will then summarize our financial results and provide a forward-looking financial view.

Speaker Change: Our mission at Revolution Medicines, one that we have pursued for much of our 10-year history, is to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development, and delivery of innovative targeted medicines.

Speaker Change: This mission is anchored in three pillars, discovery, development, and delivery.

Speaker Change: First, our innovative clinical stage RASON inhibitors have shown our discovery capabilities to be among the most productive in the industry.

Speaker Change: Our extensive original research in RAS biology and advances in our technology platform have given us critical know-how and a deep pipeline of proprietary assets we expect will enable us to continue raising the bar for what's possible in treating patients with RAS-addicted cancers.

Speaker Change: Second, our first-rate development capabilities have advanced multiple assets through FIRST in Human Studies and progressed our LEAD program into late-stage development.

Speaker Change: We will continue strengthening these capabilities as we move into additional Registrational studies across our portfolio and across a number of tumor settings and lines of therapy

Speaker Change: Third, we are preparing to deliver our novel therapies to patients by building strong commercialization capabilities in support of a successful launch, subject to regulatory approval, for duraxone racib.

Speaker Change: Supporting our mission is an ambitious strategic roadmap for maximizing the impact our RAS-on inhibitor portfolio can have for patients living with RAS-indicted cancers, and our commitment to this level of ambition is reinforced by our track record of productivity and successful execution.

We've been pioneers in the RAS space.

Speaker Change: Scientific innovation within RevMed has resulted in the first three clinical stage Rasson inhibitors. A Rasson multi-selective inhibitor, a Rasson G12C selective inhibitor, and a Rasson G12D selective inhibitor, each with a unique and promising clinical profile.

Speaker Change: Last month, we introduced the international non-proprietary or generic names for these three compounds, each of which is centered on the shared phrase, On Rasib, that alludes to the novel Rasson mechanism of action for this new class of compounds.

Duraxone RASib or RMC6236, our groundbreaking multi-selective RASone inhibitor.

Eliron Racib or RMC6291, our distinguished G12C selective covalent inhibitor.

and Zoledon Racib, or RMC9805, our innovative G12D-selective covalent inhibitor.

Speaker Change: In 2024, we built on our record of execution. We made substantial progress in advancing this portfolio of RAS-focused investigational drugs.

Speaker Change: We reported compelling monotherapy clinical data with our first wave of RASOM inhibitors, particularly diraxone RASib in pancreatic ductal adenocarcinoma, or PDAC, and non-small cell lung cancer, and zoldone RASib in PDAC.

We also reported initial evidence of two promising combination strategies.

Speaker Change: First, we reported initial clinical proof of concept for the first-of-its-kind RAS inhibitor doublet with a combination of iliron RASib with duraxone RASib.

Speaker Change: These data are highly encouraging and increase our confidence in the innovative RAS doublet concept more broadly.

Speaker Change: We've already completed dose escalation on a second Rasson inhibitor doublet, Zoldon Rassib, combined with Daraxon Rassib.

Speaker Change: We will study both raston inhibitor doublets further as potentially compelling options for patients, particularly as we move into earlier lines of treatment.

Speaker Change: Second, we reported early safety and tolerability data for both duraxone-rasib in combination with pembrolizumab and ileuronrasib in combination with pembrolizumab, observations that are highly encouraging and potentially enable a path to develop therapies for first-line metastatic non-small cell lung cancer.

Speaker Change: In addition, we also entered discovery and clinical collaborations designed to expand the range of treatment strategies we can bring to bear for patients with RAS-indicted cancers.

Speaker Change: Such collaborations enable us to explore a range of combinations with inhibitors of novel targets exemplified by a PRMT5 inhibitor under our agreement with Tango and novel approaches such as bispecific antibodies under our agreement with Aethon Therapeutics.

Speaker Change: We also formed collaborations with leading industry, academia, translational research partners, such as the Breakthrough Cancer Organization, that presents a valuable opportunity to uncover new patient-centric scientific insights to further inform our ongoing commitment to transformative science.

Speaker Change: Last year, we also made progress in building the organizational capabilities needed for us to drive the next stage of our strategic plan. In particular, we deepened our late-stage clinical development presence by launching our first Phase III registrational trial.

Speaker Change: reaching commercial-scale manufacturing of duraxone RASAs, and strengthening our organizational capabilities in preparation for a potential first regulatory approval.

Speaker Change: and we formed select partnerships to help us fulfill our tireless commitment to patients as we prepare to deliver our novel therapies to patients broadly.

Speaker Change: For example, to ensure that we keep patient needs at the forefront as we advance these medicines, we now have a relationship with Pancreatic Cancer Action Network, or PANCAN, a distinguished organization devoted to improving the lives of people living with pancreatic cancer.

Speaker Change: And, we ended 2024 in an exceptionally strong financial position, allowing us to continue our ambitious patient-centric strategy.

Speaker Change: 2025 will be an important year for RevNet as we advance our strategy aiming to maximize the impact we can have for patients with RAS-addicted cancers.

Speaker Change: I'd like to outline the highest current priorities that we anticipate could drive significant company transformation and value creation and to identify some of the markers of progress to follow.

Speaker Change: Our first priority is to execute pivotal trials with duraxone racib monotherapy in patients with previously treated metastatic pancreatic cancer and non-small cell lung cancer.

Speaker Change: For the Global Phase III RAS-ELUT302 Randomized Control Trial currently underway in patients with second-line metastatic PDAC, enrollment is an important measure of progress.

Speaker Change: So far, we have seen very strong interest among patients and investigators with highly encouraging enrollment at the initial U.S. investigation centers and we are actively opening new U.S. sites in line with our plan.

Speaker Change: With regulatory clearances in the EU and Japan in hand, we are also activating ex-U.S. sites to support the global strategy. We currently anticipate substantially completing enrollment in the trial this year to enable an expected data readout in 2026.

Speaker Change: for non-small cell lung cancer, I'm pleased to confirm that activation of investigational sites is now ongoing in the Phase 3 Resolve 301

Randomized Control Trial

Speaker Change: comparing duraxone rastib to docetaxel in patients with previously treated metastatic rast tumors.

Speaker Change: Our second priority is to advance diraxon RASib into earlier line randomized pivotal trials in patients with PDAC.

Speaker Change: We expect to initiate a trial in first-line metastatic disease, comparing a reference arm of patients treated by chemotherapy to two investigational arms.

Speaker Change: one with patients treated with duraxone racib monotherapy and one with patients treated with duraxone racib plus chemotherapy.

Speaker Change: Based on single-agent data and preliminary chemotherapy combination data, we are optimistic that both treatment arms containing duraxone racib have the potential to become important therapeutic options for patients living with metastatic pancreatic cancer.

Speaker Change: We plan to finalize the trial design later this year when we have sufficient safety and tolerability data from the currently ongoing Draxon Reactive Plus chemotherapy safety cohorts.

Speaker Change: Of course, we'll need to align with the relevant regulatory authorities, including the US FDA, before we can initiate the global randomized phase 3 trial in patients with first-line metastatic Tdac.

Speaker Change: As a further step in our ambition to serve patients with earlier stage disease, I'm also very happy to share that we are actively designing a registrational trial with diraxon rasib as an adjuvant treatment

Speaker Change: patients with respectable pancreatic cancer who have undergone surgery and perioperative therapy, often including chemotherapy.

Speaker Change: This population constitutes approximately 15% of newly diagnosed pancreatic cancer cases in the U.S. each year.

Speaker Change: We expect to move quickly on developing this program in parallel with our work to finalize the pivotal trial in first-line metastatic disease mentioned earlier. We anticipate that both of these pivotal trials will be initiated in the second half of this year.

Speaker Change: Our third priority is to generate sufficient data to inform development priorities for the mutant-selective inhibitors Elironracib and Zoldonracib, and prepare to initiate one or more pivotal trials, either as monotherapy or in a drug combination, and a number of options are under consideration.

Speaker Change: For example, we continue development of Zoldan Rasib, our innovative Rason G12D selective inhibitor for which the first in human clinical data

Speaker Change: including a favorable tolerability profile and encouraging anti-tumor activity in RAS G12d PDAC were reported at the TRIPLE meeting last quarter.

Speaker Change: A key mark of progress against this priority is generating additional clinical data that helps to qualify and prioritize these options, and we expect to share additional clinical safety and anti-tumor activity on this exciting compound in the second quarter of 2025.

Speaker Change: Another example is our ongoing efforts to identify and advance rational combination strategies with our RASON inhibitors.

Speaker Change: We are data-driven in prioritizing among multiple combination options for advancing into earlier lines of therapy.

Speaker Change: As noted earlier, we have already provided initial Encouraging Safety and Tolerability data for both Duraxon RACiB and Eleron RACiB in combination with Pemperlizumab.

Speaker Change: thereby enabling potential combination paths to pivotal studies in first-line metastatic non-small-cell lung cancer where pembrolizumab is the global standard of care.

Speaker Change: We also provided initial encouraging data on the combination of ilearonracib with diraxonracib in KRAS G12C colorectal cancer that provide initial validation of this innovative approach.

Speaker Change: We are actively enrolling and evaluating this RAS-on inhibitor doublet in combination with pembrolizumab. That is, as a triplet regimen in K-RAS G12C non-cell lung cancer as a potential chemotherapy sparing first-line treatment.

Speaker Change: And a trial evaluating a doublet of Zoled-on-Racib with Durax-on-Racib is currently in an expansion phase across a range of solid tumors at the anticipated single agent recommended phase two dose for each agent.

Speaker Change: We plan to evaluate emerging data for multiple ongoing studies to help us prioritize among a range of potential monotherapy and combination clinical development plan options.

Speaker Change: Based on this work, we expect to initiate one or more pivotal combination trials in 2026 that incorporate either Alir-on-Racib or Zold-on-Racib, likely based on a Ras-on inhibitor doublet, and anticipate sharing clinical data supporting these plans in the second or third quarter of this year.

Speaker Change: Our fourth priority is to regress our earlier-stage pipeline, including advancing next-generation innovations from our highly productive discovery organization.

Speaker Change: In particular, we currently expect to advance RMC5127, a Rathon G12V-selective inhibitor, to a clinic-ready stage this year.

Speaker Change: This will enable initiation of a first-in-human, dose-escalation, phase-one clinical trial in 2026 and a subsequent evaluation of a RAS-on inhibitor doublet with durexon RASes.

Speaker Change: based on a highly productive virtuous cycle between the preclinical and clinical sciences enabled uniquely by our platform and pipeline

Speaker Change: We are excited about other promising, next-generation preclinical programs that will continue to be areas of investment for us to sustain our innovation pipeline beyond the current development stage assets.

Speaker Change: Finally, we are growing our commercial and operational capabilities and increasing pre-commercial activities in support of a potential launch.

Speaker Change: We've experienced and talented executives leading our commercial and medical affairs teams, and these groups have already begun expanding our visibility in key settings, including clinical conferences, to reach leading oncology practitioners.

Speaker Change: It is clear that our presence and growing leadership role are being felt.

Speaker Change: We continue to expand key aspects of our organization to support a commercial launch by adding top talents, including our U.S. field teams.

Speaker Change: We expect to continue to partner with translational and clinical experts and leading patient advocacy organizations to complement our internal capabilities.

Speaker Change: We are resourcing our efforts to ensure that we have the best strategies, tactics, operational capabilities, and people to bring duraxone racib with urgency to patients with previously treated metastatic PDAC through a successful launch pending regulatory approvals.

Speaker Change: We see the U.S. as a core foundation and an important driver of potential long-term shareholder value.

Speaker Change: We are committed to retaining control of U.S. commercial rights as a main element of our current strategy.

Speaker Change: We also continue exploring strategies for serving patients outside the U.S., potentially including partnership opportunities, to help us determine the best approach to ensure global access.

Speaker Change: We're excited about the continuing momentum and remarkable opportunity we have in front of us and look forward to reporting on markers of progress as we advance programs throughout the year.

Speaker Change: I'll now turn the call over to Jack Anders, our CFO, to summarize our fourth quarter financial results and forward-looking guidance.

Jack

Thanks, Mark.

Mark Goldsmith: We ended the fourth quarter of 2024 with $2.3 billion in cash and investments.

Speaker Change: which includes $823 million in net proceeds from our upsized equity offering last December.

Speaker Change: We project that our cash and investment balance can fund planned operations into the second half of 2027 based on our current operating plan.

Speaker Change: This operating plan has been updated to reflect anticipated increased spend resulting from our growing confidence in the advancement of our clinical development programs.

Speaker Change: Turning to expenses, R&D expenses for the fourth quarter of 2024 were $188.1 million compared to $148.5 million for the fourth quarter of 2023.

Speaker Change: Please note the prior year quarter included $13.1 million in wind-down costs associated with the EQRX acquisition.

Speaker Change: The increase in R&D expenses was primarily due to increases in clinical trial-related expenses and personnel-related expenses associated with additional headcount.

Speaker Change: G&A expenses for the fourth quarter of 2024 were $28.2 million compared to $32.2 million for the fourth quarter of 2023.

Speaker Change: The decrease in GNA expenses was due to $13.8 million in eQRX wind-down costs in the prior year quarter.

excluding these non-recurring eQRX costs.

Speaker Change: G&A expenses increased in the fourth quarter of 2024, which was primarily due to increases in commercial preparation activities and personnel-related expenses associated with additional headcount.

Speaker Change: Net loss for the fourth quarter of 2024 was $194.6 million compared to $161.5 million for the fourth quarter of 2023.

Speaker Change: Please note, net loss for the prior year quarter included a total of $26.9 million in HRX wind-down costs.

Speaker Change: The increase in net loss was due to higher operating expenses, as described earlier.

Thank you.

Speaker Change: Full year 2024 financial results are available in our corresponding press release and also in our Form 10-K that was filed with the SEC this afternoon.

Speaker Change: Turning to financial guidance for 2025, we expect full-year gap net loss to be between $840 and $900 million, which includes estimated non-cash stock-based compensation expense of $115 to $130 million.

Speaker Change: The increase in expected gap net loss for 2025 is a result of increased expenses associated with the progression and expansion of our clinical development programs.

Speaker Change: We also expect higher expenses in 2025 as a result of increased commercial preparation efforts as we continue to build and expand our organizational capabilities in preparation for becoming a commercial stage company.

Mark Goldsmith: That concludes the financial portion. I'll now turn the call back over to Mark.

Thank you, Jack.

Speaker Change: In 2024, we continue to deliver compelling clinical observations and to build on our track record of effective execution.

Speaker Change: We have begun 2025 with the talent, capabilities, and financial capital to fuel our vision to create an industry-leading, targeted medicines franchise for patients with RAS-addicted cancers and to fulfill our responsibilities to patients, investors, and employees.

Speaker Change: The foundation we've established sets us up for long-term sustainable growth.

Speaker Change: in support of our aim to revolutionize treatment for patients with RAS-addicted cancers.

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

Speaker Change: Thank you. At this time, we will conduct the question and answer session. Each participant is encouraged to ask one question and a follow-up. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.

Our first question.

Speaker Change: It comes from the line of Ellie Murley of UBS. Your line is now open.

Speaker Change: Hi guys, it's Sam on for Ellie. Thanks for taking our question. I guess, can you walk us through the decision to move forward with the two phase 3 studies in the earlier line PDAC and I guess specifically what gives you conviction on the phase 3 in the adjuvant setting and can you talk a little bit about the role of RAF in this earlier line setting?

Yeah, thanks very much for your question.

Speaker Change: I think based on the data that we've already reported in pancreatic cancer, the monotherapy data, I think we have strong conviction that we ought to try to own the entire pediatrics space across all lines of therapy.

Speaker Change: So we've indicated that previously, and this is just further towards that goal.

Speaker Change: We've already previously announced that we intended to pursue a first line

Speaker Change: metastatic study and the question has always been what will be the composition of the of the various cohorts in that trial and we provide a little bit of clarity around that today and we'll continue doing so as the year progresses.

Speaker Change: The adjuvant is basically a study of patients who will have had their disease resected and represents an important opportunity to provide very significant long-term clinical impact for those patients.

Speaker Change: and the proof of concept that supports pursuing that particular indication is already provided by the second line and third line data that we've shown previously with model therapy.

Speaker Change: So, I think both of these are very rational and appropriate things for us to pursue and will further our goal of completely owning the PDAC space with this compound.

Speaker Change: Yeah, that makes a lot of sense. That's really helpful. And then I guess just a quick follow-up, can you just touch on how the frequency of RAS mutations might differ in the adjuvant setting versus maybe like the advanced or metastatic disease and how you're thinking about the overall opportunity there?

Speaker Change: I don't know that there's any evidence that those patients would have any different representation of RAS drivers than all other patients, which is essentially almost all pancreatic cancer patients have a RAS driver.

Speaker Change: and so there's no reason to believe that those patients would behave any differently in response to durexone racem.

Thank you for watching. Bye.

Thank you so much.

Thank you.

Speaker Change: Our next question will come from the line of Eric Joseph of JP Morgan. Your line is now open.

Speaker Change: The proposed terminal study in the adjuvant setting is also interesting to us and expansive to, you know, what we've generally thought about as being in scope in pancreatic cancer.

Speaker Change: You noted, Mark, that respectable PDAC is about 15% of overall cases, if I heard that correctly.

Speaker Change: Has this been a static metric? I wonder if you see this proportion sort of expanding at all with perhaps early detection initiatives? And then, you know, as it relates to the pivotal study, I guess, how should we be thinking about the

Speaker Change: regulatory bar that would need to be satisfied for registration? You know, is it PFS, OS? It would be great to hear your thoughts there. Thank you.

Thank you.

Speaker Change: Hi, Eric. Thanks for your question. I don't think that we can comment today on the second part of the question since we really haven't engaged.

Speaker Change: with regulatory authorities at the moment. So that will have to be something that we address in the future. But on the first question, I think I'll ask Dr. Waidlin, our Chief Medical Officer, to comment on

Speaker Change: you know, the estimated proportion of total PDAC cases that are currently considered respectable and whether that could evolve over time.

Yeah.

Thanks Mark

Speaker Change: It's a great question. I think in the short term, we don't expect a number to change because that detection is largely driven by whether there's any screening. Unlike breast cancer, colorectal cancer, there's no mammography or colonoscopy.

Speaker Change: and there's no pending test evaluating patients with pancreatic cancer. Now with blood tests for cTNA and so on, that's a much more long term to be established before it becomes standard care. That's why we don't, probably in the short term, we don't see that number change.

Speaker Change: Yeah, if I could just add to that, of course there are efforts underway to try to develop such...

screening tools that are largely based on circulating tumor DNA.

and to the extent that we can show further benefit.

Speaker Change: to patients who are diagnosed earlier in their disease that I think will further promote those efforts, but those are future events to occur. And of course, the possibility of even...

clearing a tumor to the point of cures.

Speaker Change: And so if it becomes possible to diagnose patients much earlier, then the possibility of even greater impact, as you point out, becomes much higher. But at the moment, we just have to focus on the patients who are diagnosed, and they do represent a significant fraction.

Speaker Change: Okay, great. Thanks for taking the questions, but I appreciate the color.

Thank you.

Speaker Change: Our next question comes from the line of Mark Fromm of TD Cohen. Your line is now open.

Speaker Change: You know, pancreatic docs also talk about borderline resectable disease, not just resectable. And then there's also, you know, within resectable, some patients get Whipple procedures, others don't get Whipples. Would you be looking to go after all surgeries?

Speaker Change: surgeries or just kind of certain subsets there, because, you know, there are some varying outcomes depending upon which one you fall in. And then similarly, with the current trial in late-line disease, you have this hierarchical analysis based on different RAS mutations.

Speaker Change: Would you also do that and enroll broadly or, you know, is that kind of introducing too much risk when you're moving lines, different subsets, and different mutations in there?

Thank you very much.

Speaker Change: Thanks, Mark. Is the second question also relating to receptible or was that referring to... Well, it's an adjuvant, but both the first line and adjuvant for that for that second part of it. I see. Okay, good. I think Wade can address both the definition of...

Wade: of Receptable and what we're thinking about right now and then also testing and whether or not to stratify.

Thank you.

So, first question regarding the patient population.

Speaker Change: First of all, I just want to caveat by saying that we have not had any authority interruption, so the final design is still

pending those contractions, but we would certainly...

Thanks for watching!

include as many patients that have had resection of their

primary disease.

and then have any type of perioperative disease, typically chemotherapy.

and that defined as broadly as possible.

Speaker Change: I think the final design is still pending health re-interaction, but that's our goal is to define the largest population where we believe drugs from Rasputin can really benefit.

Speaker Change: And then the second question about the mutation specifically, this is kind of, it's piggyback on Mark's earlier comment. We do see that RAS is...

Speaker Change: the cancer-initiating driver mutation. And so, first of all, I think the preference is, as far as we know, it's fairly consistent throughout the lines of therapy. And then in the active setting or the early disease setting,

Speaker Change: our approach in developing giraffes and rats is similar in the metastatic setting.

Speaker Change: which is as far as to cover as many patients that's actually eligible for our trial. And then that's including a potential for an old-comer approach to the entire population of pancreatic cancer patients.

Speaker Change: Okay, that's really helpful. And then maybe just a more strategic view, Mark, just based on how you balance with all of these different combinations, also monotherapy opportunities to move forward into

Speaker Change: earlier lines, just how do you balance, you know, moving quickly versus making sure you don't end up having to run too many redundant trials or setting bars that then make it difficult to get the best option for patients over the long term.

Thank you.

Speaker Change: Yeah, well that's a, you know, that's a hard question. That's what we grapple with every day, you know, in our strategic considerations. I think our primary motivation here is to serve patients.

Speaker Change: That means moving swiftly when we have something that we think will move the needle for patients. We really need to do so.

Speaker Change: given also the competitive environment from a business point of view, there's not a lot of opportunity for us to pause things and wait and see what we might offer that's better in that in place of that.

I think we just have to move.

Speaker Change: Swiftly to try to deliver against the unmet needs Of course to the extent that we generate data That tells us what to prioritize

Speaker Change: We'll use that information in making those prioritization decisions, but there could be certainly circumstances where we can't make such a decision, but we wouldn't hold off on pursuing a.

Speaker Change: a phase 3 registration trial because that would leave patients unserved and or it would leave opportunities for competition to step in and just to create new bars for us. We'd rather be the ones to create the bar.

and then try to beat the bar ourselves.

Speaker Change: rather than chasing chasing someone else. And given our current position,

Thank you.

Speaker Change: I think it's it's ours to lose. If we don't pursue these things we will be setting ourselves up for for a different scenario. We'd rather be

Speaker Change: be first to the table, or we can't be. So it's a challenging, challenging topic. It's

Speaker Change: falls into the category of an embarrassment of riches to a large degree because we can define multiple potential solutions to each of these situations.

Speaker Change: and but we have to work in real time because for patients this is a pressing matter. It's not something that they can wait years for us to sort out.

Speaker Change: Thank you. Our next question will come from the line of Michael Schmidt of Guggenheim. Your line is now open.

Michael Schmidt: Hey, thanks for taking my questions and congrats on all the progress.

Michael Schmidt: I had a follow-up on your first-line metastatic pancreatic cancer strategy. So it sounds like you've now committed to doing a single three-arm trial there for registration as opposed to two separate trials.

Michael Schmidt: How much more Phase I work needs to be done with the chemotherapy combination before initiating the study?

Michael Schmidt: Will you be able to share some of that data, perhaps later this year, be it as a monotherapy, perhaps in first line or in combination? And secondly, what are your latest thoughts on how to incorporate sodium racid into your pancreatic cancer registration strategy, perhaps relative to the rexanracid?

Thanks so much

Thank you, Michael.

So the first question is, are we continuing...

Michael Schmidt: evaluation of chemotherapy combination to support that third arm in the trial and the answer that is straightforward yes we're doing that work now we've collected some data but we need more and it mainly has to do with what regimen we we select

to move forward with.

Michael Schmidt: and that's primarily around safety. It's really not at this stage about primarily driven by efficacy because we already have confidence in the efficacy based on the

Michael Schmidt: monotherapy, second and third lines data that we've already you know shared.

Michael Schmidt: So, this is really just about safety and making sure that we can assure high enough

relative dose intensity during treatments, that there aren't long breaks.

Michael Schmidt: As you may know, even both forms, major forms of chemotherapy and pancreatic cancer often incur the liability of grade 3 or higher.

Michael Schmidt: adverse events that drive hospitalization that often results in discontinuation of anti-cancer treatment for some period of time.

And that's not ideal, particularly...

for a target therapy where

Michael Schmidt: as continuous coverage as possible is likely to have the greatest efficacy in the long run. So we just want to choose the best regimen and regimens to go forward with, and we need some more data to drive that, but it still is our intention.

Michael Schmidt: In 2025 to initiate that that trial so we're we're moving as quickly as we can to support that decision

Thank you.

Speaker Change: The second question is Zolan Rasset. Do you want to comment a way on Zolan Rasset and pancreatic cancer and

Speaker Change: How do we think about that relative to direct summerism? Sure. So in RAS, as you know, G12B has a prevalence rate of about 40% of pancreatic cancer. So it's the most common RAS mutation, or specific mutation in general, that's a driver of pancreatic cancer. So we had shared earlier phase one data showing that it's a highly active agent, largely following

Speaker Change: Those three cells are looking for the durability of these activities. And then I think our initial thinking is it will probably end up being a separate registration trial.

with Stan Lowen, Registration and Pass.

Speaker Change: and we're currently evaluating a combination with duraxone racid as a potential rathon doublet, a best-in-class option that could be substantially improved upon by hormonal therapy.

Speaker Change: as well as the chemotherapy plus gender care, the psilocytal message. So those are potentially two options we could really develop.

Thank you.

Speaker Change: Thank you. Our next question comes from the line of Ben Burnett of Stifle. Your line is now open.

Ben Burnett: Great, thank you. First, I just want to add another quick question on Zoldyna Rasib. I guess, is there any more color you can provide on the data update being contemplated in the second quarter? Specifically, what are the key learnings that you hope to glean from these data?

Ben Burnett: Yeah, hi, Ben. Thanks for your question. We don't have any more color to provide on that today. We do intend to provide additional data on sold-on RASAs in the second quarter of this year. And I think we'll just have to wait until those data are available.

Ben Burnett: Okay, understood. And if I can maybe go back to sort of a previous question on the on the frontline metastatic pancreatic cancer

Ben Burnett: You know, it feels like there's been some debate as to the combined ability of toxin or acid with chemo.

Ben Burnett: Sounds like you guys are pretty confident that there's some combined ability potential here given the design that you're proposing in the frontline metastatic cancer setting. But I guess the question is, like, what are the overlapping...

Ben Burnett: talk signals that one should be concerned with when thinking about Doxan RASP and the data that's been provided thus far with the various chemos being contemplated.

Thank you.

Ben Burnett: Yeah, Ben, let me just clarify, though. I don't know that there's been a debate about the combinability. That really, I think, is...

Ben Burnett: That statement has been made a number of times, but I haven't heard that debate. Really the topic that we raised earlier this year is the one that I alluded to in one of the earlier questions, which is that chemotherapy alone

Ben Burnett: is a very difficult thing for pancreatic cancer patients to go through because the disease is so aggressive the chemotherapy has to be aggressive to go with it to go with it.

Ben Burnett: And that chemotherapy already today drives substantial side effects, adverse events.

Ben Burnett: that often result in holding the drug for some period of time and or hospitalization.

Ben Burnett: And that in and of itself, just for the chemotherapy, the standard care chemotherapy alone.

Ben Burnett: could have implications for the ultimate efficacy of a combination of chemotherapy with, um, with, uh, duraxone acid or with any, with any other targeted agent, to be honest.

Ben Burnett: So that's really the issue that we've raised. We haven't, not sure that there really has been any

meaningful public debate about whether or not they are combinable.

Ben Burnett: And so I don't think we have anything to add to that because that hasn't really been the core issue. Of course, we're evaluating that now.

Ben Burnett: and we're optimistic that we can develop a regimen that combines them, but we're keeping in mind this fundamental issue that the chemotherapy itself

Ben Burnett: is already essentially barely tolerated. And in fact, in most cases, not only results in some dose holds, but typically results in dose reductions as one moves from one cycle to the next. So that's the context for that.

Thank you.

Speaker Change: Our next question comes from Laura Prendergast of Freeman James. Your line is now open.

Laura Prendergast: Hey guys, I was wondering if you could provide a little bit more colorectal cancer data disclosure cadence.

Speaker Change: Now, should we be expecting any chemocombo data, EPFR inhibitor combo, doublet data this year? And then just, you know, any guidance on if or when there will be a registrational path for colorectal cancer, and then maybe, you know, beyond the big 3K RAS-driven tumors as well?

Speaker Change: Hi Laura, thanks for your question. We don't have any guidance provided yet on next disclosures about colorectal cancer. We of course are studying colorectal cancer. In fact, just in December we disclosed data from a study of accommodation of

Aaliyah Onrasset with Drax Onrasset and Patience.

Speaker Change: quite advanced colorectal cancer patients who have been previously treated with a G12C inhibitor.

Speaker Change: and really had no other options and we showed significant activity from the combination of a lirunracid with duraxunracid. So that was just six weeks ago or two months ago.

Speaker Change: But we don't have any guides to provide. We continue to study this, the variety of different combination strategies that might be.

Speaker Change: that might prove to be interesting and we're evaluating them and I think when we have information that starts to point to future strategies we'll share that.

Great, thank you.

Thank you.

Speaker Change: Our next question comes from the line of Kelly Shee of Jeffrey's. Your line is now open.

Speaker Change: Hey guys, this is Claire Elm for Kelly. Thanks for taking our questions. So for the phase one study in PDAC, as of the last update, the median overall survival was so immature after output 2D. So just wondering, do you have any plans to update the overall survival data this year?

Speaker Change: Hi, Clara. Thanks for your question. Yes, what we showed before was two different ways of looking at the data. One was...

Speaker Change: from an aggregate of multiple dose levels up to and including the 300-milligram cohort. And there we did show an overall survival estimate from the curves that was 14.5 months.

Speaker Change: subset, if you will, that particular dose cohort, because those patients have been enrolled more recently than had the patients with the earlier doses,

Speaker Change: that those curves were not very mature and so we didn't have an estimate of OS per se but we did have information regarding the six-month OS which was you know quite high depending which subset you looked at it was in the

Speaker Change: 97 to 100 percent range, which I think provided some pretty good look about what's going to come as these data mature, but of course we didn't have those data. So those do continue to mature.

Speaker Change: and I'm sure at one point, at some point we will have an estimate of that. We don't have that today and we we don't have any information to share but I would imagine at some point we'll share that information. We don't have a specific plan around it right now.

Thank you. Appreciate it.

Thank you.

Speaker Change: Our next question comes from the line of Chris Shibutani of Goldman Sachs. Your line is now open.

Speaker Change: You noted that you're exploring the potential for a chemotherapy-free triplet combination here. Just in terms of your priorities here, would you potentially also pursue a non-G12c frontline indication, or do you still have plans to explore that? And then for the triplet...

Speaker Change: Could that be one of the updates that we can expect in the second quarter or third quarter of this year? Thanks.

Speaker Change: Thanks, Kevin. I think we have Steve Kelsey, our president of R&D. Maybe he could comment on how we think about the first line of lung cancer. Certainly there are kind of multiple subsets, as you alluded to. Essentially, GCLC has now been defined as a sort of a disease in and of itself, and then there's everything other than GCLC. Maybe Steve could comment on that.

Sure.

Speaker Change: RAS mutant lung cancer into distinct sets depending on the type of RAS mutation. And I think that now G12c mutant lung cancer has established itself as a completely separate disease, probably requiring a G12c

Speaker Change: selected inhibitors. So right now, because we are acquiring and have presented preliminary data on the

Speaker Change: combination of a niromiracid with niraxamiracid in G12C mutant cancers, we would plan to move that chemo-free triplet into the G12C

lung cancer space

Speaker Change: And then the Duraxone RACiB would be prioritized for all other RAS mutant lung cancer.

Speaker Change: without a GTOF-C mutation, which is about, probably somewhere in the region of 17 to 18 percent of all non-small cell lung cancer right now.

The

Speaker Change: So I think that addresses your first question. Can you remind me of your second question?

Speaker Change: Just following up on that, so does that mean... Oh, DASA. DASA, yeah. Will we release... Yep.

Yeah, I don't think we've specifically guided with regards to...

Speaker Change: when the data that justifies those clinical trials will be put together in a complete package. I mean, we are releasing

Speaker Change: data in tranches as we as we accumulate that data we've already I think

try to persuade you that

Speaker Change: Our Rasson inhibitors are combinable with Pembrolizumab, which of course is

you know, a fairly significant step.

Speaker Change: on the road to starting first-line trials in non-small cell lung cancer. It's an almost absolute prerequisite now for

Speaker Change: the starting trials in first-line non-stool cell lung cancer. And we can, not only can we combine our Ras-on inhibitors with pembrolizumab without incurring additional toxicity, but we can combine them at what we believe to be the full recommended

Speaker Change: phase 3 dose. We don't have to take a haircut on the dose in order to combine with pembrolizumab like some of the other RAS inhibitors have had to do. So, ultimately, you know, we are, as you know, still

aggressively enrolling

Speaker Change: The combination of the liromerasib and drexelomerasib in both colorectal cancer and non-sore cell lung cancer and waiting for the the sort of durability to mature as soon as that is mature then we can

Speaker Change: tell you about it, but of course, because it's durability data, I can't really give you a timeline for the maturation of that data. And of course, just behind that data set will be the combination of zolder acid with diraxone acid.

Speaker Change: in RAS mutant tumors as well. That was a little bit behind, and again, I don't have any guidance on when we can report that. But as soon as we have the...

Speaker Change: trials, the trial designs ready for public disclosure. We will also have the supporting data ready for public disclosure.

Great. That's really helpful. Thanks. I'll hop back into Qt.

Thank you.

Speaker Change: Our next question comes from the line of Jay Olson of Oppenheimer. Your line is now open.

Jay Olson: Oh hey, congrats on the progress and thank you for the update. For the study of daraxon racib in the adjuvant setting for resectable PDAC, how are you thinking about the dosing duration and could that be guided by ctDNA? And then I have a follow-up question on non-small cell lung cancer.

Thank you.

Speaker Change: You know, I think it's just a little bit early for us to get into the details of trial design, since, as we indicated, we're now committed to working on the trial design. You know, those are obviously questions that we'll be addressing, but they are core elements of the trial design. So, I would say, hold that question, and we ought to be addressing it in due course.

Speaker Change: Okay, understood. And then in non-small cell lung cancer, are you interested in earlier lines of therapy like the adjuvant setting or even neoadjuvant? And can you just talk about what your strategy might be there?

Speaker Change: Well, I can answer the first part of your question. Yes, we're very interested. I mean, we're...

Speaker Change: We obviously have a very rich pipeline that's going to be very relevant to RAS, the RAS mutant portion of lung cancer, which represents about 30% of non-small cell lung cancer, and in all lines of treatment. And you've heard about

Speaker Change: from Steve just a moment ago about strategy around first line. And I think we've just shown with our disclosure about our intention to pursue a

Speaker Change: an adjuvant trial in pancreatic cancer that we are we're committed to moving to these earlier lines. We don't have specificity around that right now.

Speaker Change: So, it's a little hard to explain a strategy until we have it well, sort of, well articulated, well thought through.

Thank you.

Speaker Change: And the pancreatic cancer is just a little bit ahead of lung cancer because it really has taken off and the unmet need is so...

Speaker Change: substantial and urgent that we're in a better position really to to push things in all directions there. But you'll hear about lung cancer over time as we

Speaker Change: as we're able to do so. Of course, importantly, we just announced today that we've initiated our second line, third line.

Speaker Change: non-small cell lung cancer study as we expected to do in the first quarter of this year but we're there now and that's happening so that's the first step in the right direction and as we develop both data and then the strategy that supports the data for various earlier lines we will we will share that.

Thank you.

Speaker Change: Our next question comes from the line of Joe Catanzaro of Piper Sandler. Your line is now open.

Speaker Change: Great, thanks so much for taking my question. Maybe one quick one from me as it relates to your comment, Mark, that chemo alone and frontline PDAC is an aggressive regimen. So for the frontline chemo combo, are you thinking that you'll design the regimen as just continuous combination therapy until progression? Or is there potential to use an induction maintenance idea?

Speaker Change: and maybe what the pros and cons of each approach could be. Thanks.

Speaker Change: Thanks for your question, Joe. I think that way we can comment on that on that question.

Speaker Change: Yes, again, because we have not had the regular interactions, I think right now we do not have the final study design. I think what we're doing right now in the exploratory studies, evaluating the combinations, really combining, adding drugs and RAS to the current standard care chemotherapy.

either Jamf vaccine or Folfirinox.

Thanks.

Speaker Change: I think, as we've discussed earlier, our primary goal is really to protect the dose and intensity of draconid acid because we think that's going to deliver the maximum chemical benefit to patients.

Speaker Change: And so how, one way or the other, what the final regimen that we develop will move into the first line setting. So other than that, I think it may be too early to share.

Speaker Change: Yeah, maybe if I could add a little bit to that, you know, we do expect that one arm of that trial will be monotherapy duraxone racid.

Speaker Change: doesn't matter so much. That's just nomenclature. But currently pancreatic cancer patients, first-line pancreatic cancer patients, typically try to pursue four to six cycles of chemotherapy.

Speaker Change: But many patients don't make it through four to six cycles of chemotherapy, either because they can't tolerate it, and so they stop, or because their disease progresses and they stop.

and so

Speaker Change: That's just something to keep in mind, is we want to make sure that patients actually get through their initial period, whatever that is.

Speaker Change: because the potential for having long-term benefit from direxome acid is implied by or suggested by the data from the previously treated patients. So again, we come back to the notion that

Thank you.

Speaker Change: you know, based on the history of that disease and how it's treated and the fact that we're now moving from sort of a generalized chemotherapy attempt to just kill cells to a more biologically driven

disease-modifying kind of strategy.

Speaker Change: that that will require a bit of a paradigm shift or it should require a paradigm shift in thinking about how you go about treating those patients and effectively we'll think of that combination arm as the Draxon Rassive arm to which we've added some chemotherapy.

Speaker Change: as opposed to the chemotherapy arm to which we've added some direct sulfur acid. And that's conceptually a very important thing to think about.

Speaker Change: It may or may not conform to the nomenclature we were using earlier.

Speaker Change: But that's again, as Wei said, those are things that we're actively engaged in thinking through and then of course we'll have to engage with regulators. Right now we're talking with advisors and trying to devise the most the most appropriate strategy.

Okay, got it. That's helpful. That's all for me. Thanks.

Thank you.

Speaker Change: Our next question comes from the line of Alex Stranahan of Think of America. Your line is now open.

Speaker Change: Hey guys, this is Matthew on for Alex. Thanks for taking our questions.

Speaker Change: Maybe a first quick one from us. I think in 3Q you mentioned that you expect to disclose data from the OER-ON-RAS at Pembroke combo in 1Q. I know you had safety tolerability data in December. Just curious if there were any update plans still for 1Q or whether the next updates would come.

and the Mutant Selector Inhibitor Update in 2Q or 3Q.

Thank you.

Speaker Change: Okay, I was processing your question and I realized now what you're alluding to. We actually moved that update from Q1 of 2025 into Q4 of 2024.

Speaker Change: And so that was the update. We provided it earlier. We weren't sure if we were going to be able to do that, which is why we alerted folks it might come in 2025, but it actually came in 2024. And it was primarily, and it is primarily, a safety assessment.

Speaker Change: The issue with efficacy is that the patients who were treated, the vast majority of those patients, were actually previously treated patients who have already experienced

and Pemberlissa Mapp.

Speaker Change: So there really wasn't much potential for them to get a new boost of anti-tumor activity by retreating them with Pembrolizumab.

Speaker Change: And so looking at efficacy in that context, if you're thinking about it as additive Pembro plus diraxone racid, what you'd really just be seeing is the diraxone racid activity.

Speaker Change: This contrasts with where it would actually be used, which is in first-line patients who have not seen durax onracid or pembrolizumab before, and that would be a more appropriate setting for assessing efficacy.

Speaker Change: Makes sense. And then maybe a quick one on how you think about entertaining potential collaboration opportunities with the Rats on Rassive or any of your other assets.

Thank you for watching!

Come.

Speaker Change: Yes, I mean we certainly are both entertaining and actually engaged in

and collaborations.

Thank you.

Speaker Change: There have been many years of preclinical collaborations that have been underway and continue and have published papers and so on, and there are actually active

Speaker Change: clinical collaborations. We've mentioned, for example, that Tango Therapeutics will conduct a study

Speaker Change: of their PRNT5 inhibitor with one or several of our RAS inhibitors including direxome acid and that's a that is a clinical collaboration and we would imagine that that

range of combinations will be expanded over time.

Thank you.

Speaker Change: Our next question comes from the line of Ami Fadia of Needham & Company. Your line is now open.

Speaker Change: Hi, this is Zola on for Omni. Thank you for taking our questions.

Thank you so much.

Speaker Change: On SOLD and RASPB, what additional data do you need to see that would give you confidence to initiate the CBT combination trials? And will any of these updates include data from other indications such as Gatschek and CRC?

Speaker Change: Unfortunately we can't hear you very well so we're not sure what what those two questions were. Could you repeat that and maybe if we could get the volume adjusted up that would be helpful.

Speaker Change: Oh, sorry. I was asking what additional data do you need to see for Zolder and RASPF that would give you confidence to initiate the pivotal combination trials? And would any of these updates include data from other indications such as gastric and CRC?

Speaker Change: Okay, so the question is really about pivotal trials of salt oneracid in combination contexts.

Speaker Change: Well, we are currently evaluating soloneracid in combination with diraxoneracid, which

Speaker Change: we think is justified by the previous observations that Eleronracib plus Teraxonracib delivered compelling differentiated initial evidence of anti-tumor activity. And so we believe that same concept may hold for Zolonracib and we're evaluating it.

Speaker Change: We're also evaluating Zola Nerassa in combination with other agents, other standard of care agents.

Speaker Change: that would be appropriate for lung cancer or for colorectal cancer or for pancreatic cancer. So I think we have to generate that information. We've indicated that this is a high priority for this year. Much of that work is already underway.

Speaker Change: We expect to share some additional clinical data on zolon racid mid-year and we expect to develop at least one

Pivotal trial concept based on a heat-selective inhibitor.

Speaker Change: which could as well be a solenoid acid for 2026 and beyond.

Okay, thank you.

Thank you.

Speaker Change: Our next question comes from the line of Peter Lawson of Barclays. Your line is now open.

Speaker Change: Hey, good afternoon. This is Alex, on for Peter. Thanks for taking my question. I joined late, so sorry if this was addressed already, but how are you thinking about completion of the second line PDAC study, you know, and potential approval? And how could that impact, you know, if that could impact the control arm in your first line trial, you know, and the ability to show an OS benefit?

Yes.

Speaker Change: Yes, thanks for your question. There's always a downside to anything that has an upside, so rapidly completing that trial does create new barriers for a different trial.

Speaker Change: That doesn't stop us, though. We want to move forward as quickly as possible to complete that trial. And it is a very important opportunity for us to demonstrate an OS benefit from Durex on RASPID.

Speaker Change: which which we believe you know is a credible thing based on the

data that we've shown so far.

There's broad interest in this study.

Speaker Change: You're now talking about the 302, a Resolute Study. There's broad interest in that study by patients and investigators. The currently active sites, enrolling sites, are enrolling quite actively. We're very pleased with the progress there. We're also opening new sites.

Speaker Change: in the U.S. according to our plan, consistent with our plan, and we're opening sites in the U.S. right now. We do expect...

and are highly confident that we can complete.

enrollments of this study in 2025.

Speaker Change: There may be some stragglers from countries outside the U.S. that could roll over to 2026, but largely we do expect a complete enrollment, and that trial was here and we're moving as fast as we possibly can. As you point out, it does put pressure on that first-line trial.

Speaker Change: and frankly we think it'll put pressure on every future first-line trial that's sort of part of the

Speaker Change: Part of the intention here is to deliver changes in treatment benefit for patients.

Speaker Change: that moves the needle. That's what we want to achieve. But we are fighting ourselves a little bit on this, which means getting to an answer on our final trial design for the first-line trial as quickly as possible is important to do. We feel that urgency.

Speaker Change: and we currently expect to be able to do so to initiate the trial by the end of this year.

Speaker Change: Okay, thank you. And do you see any potential for an accelerated approval of some sort, you know, based on PFS in the first line setting?

Speaker Change: That's a question probably best addressed to regulators. I think that there is...

is not wild about accelerated approval in pancreatic cancer.

for a number of reasons.

Speaker Change: One of which is that the OS readout doesn't come that long after the PFS readout and so they're not

Speaker Change: particularly enthusiastic about giving somebody an approval and then finding out a month later that does or doesn't meet, you know, the OS bar. Just to exaggerate a little bit. So...

Speaker Change: I think generally speaking, we don't assume that there's an accelerated approval path based on PFS. On the other hand, there hasn't really been a drug that's moved the needle based on PFS.

Thank you.

Speaker Change: really ever, you know, in any meaningful way. And our ambition is to be able to deliver such data that will be determined by what the data show. But based on the Phase 1-2 data we've shown so far, we're encouraged by that possibility and how a regulatory body might look at those results. We don't.

Speaker Change: We of course can't can't predict we've designed the trial really around the OS

Speaker Change: which means that it's overpowered for PFS and the timing of the analyses, the first analysis, is actually driven by the number of OS events.

Speaker Change: And so it's an OS event-driven trial, but it is possible to achieve success on the PFS without having reached the mark on OS, or maybe being partially on the way there with evidence of a trend towards it without having reached it yet, in which case there would be a subsequent

Speaker Change: assessment of the data after, with a greater chance of achieving the OS at that point. What happens in that interim period?

Speaker Change: I think we'll just have to leave dangling because that's not really entirely up to us. In fact, it's not really up to us very much at all.

Speaker Change: Thank you. I am showing no further questions at this time, so I would like to turn it back to management for closing remarks.

Thank you. Bye.

Speaker Change: Thank you operator and thank you to everyone for participating today and for your continued support of Revolution Medicines.

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

Go to Beadaholique.com for all of your beading supply needs!

Ben Hanauzko, David Meade Emoji Lyrics

[music]

Mark Goldsmith: Mark Goldsmith, Ryan Asay, Stephen Kelsey, Erin Graves, Ryan Asay, Ryan Asay, Ryan Asay,

Music Music Music Music Music Music

Speaker Change: More movies Laptop movies Hickory dock Lights Subscribe To hear more movies Please, like, share, and comment Thanks, nice shot

Speaker Change: This is a story about a man who had a dream He had a dream that he was going to be a doctor He had a dream that he was going to be a doctor He had a dream that he was going to be a doctor

Music Music Music Music Music Music

Speaker Change: We are committed to impacting the communities of Respond2360 at all times.

Music Music Music Music Music Music

Speaker Change: To ask a question during the session, you will need to press star 1 1 on your telephone.

Speaker Change: You will then hear an automated message advising your hand is raised.

To withdraw your question, please press star 1 1 again.

Speaker Change: 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 Asay, please go ahead

Speaker Change: Thank you and welcome everyone to our fourth quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith, our Chairman and Chief Executive Officer.

Speaker Change: and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of Research and Development, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call.

Speaker Change: 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.

Speaker Change: Actual results may differ materially from those in the forward-looking statements.

for a full discussion of these risks and uncertainties.

Speaker Change: please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended December 31, 2024, and recent corporate updates. The press release is available on the Investors section of our website.

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

Thanks, Ryan. Good afternoon, and thank you for joining us.

Speaker Change: Jack Anders will then summarize our financial results and provide a forward-looking financial view.

Speaker Change: This mission is anchored in three pillars, discovery, development, and delivery.

Speaker Change: First, our innovative clinical stage RASON inhibitors have shown our discovery capabilities to be among the most productive in the industry.

Speaker Change: Second, our first-rate development capabilities have advanced multiple assets through FIRST in Human Studies and progressed our LEAD program into late-stage development.

Speaker Change: We will continue strengthening these capabilities as we move into additional registrational studies across our portfolio and across a number of tumor settings and lines of therapy.

We've been pioneers in the RAAF space.

Speaker Change: Last month, we introduced the international non-proprietary or generic names for these three compounds, each of which is centered on the shared phrase, On Rasib, that alludes to the novel RASOM mechanism of action for this new class of compounds.

Duraxone RASib or RMC6236, our groundbreaking multi-selective RASone inhibitor.

Speaker Change: Eliron Racib, or RMC6291, our distinguished G12C-selective covalent inhibitor and Zoldam Racib, or RMC9805, our innovative G12D-selective covalent inhibitor.

Speaker Change: In 2024, we built on our record of execution. We made substantial progress in advancing this portfolio of RAS-focused investigational drugs.

We also reported initial evidence of two promising combination strategies.

Speaker Change: First, we reported initial clinical proof of concept for the first-of-its-kind RAS inhibitor doublet with a combination of iliron RASib with duraxone RASib.

Speaker Change: These data are highly encouraging and increase our confidence in the innovative RAS doublet concept more broadly.

Speaker Change: We've already completed dose escalation on a second rasson inhibitor doublet, zoldon rassib, combined with diraxone rassib.

Speaker Change: We will study both raston inhibitor doublets further as potentially compelling options for patients, particularly as we move into earlier lines of treatment.

Speaker Change: Second, we reported early safety and tolerability data for both duraxone RASib in combination with pembrolizumab and iliron RASib in combination with pembrolizumab.

Speaker Change: observations that are highly encouraging and potentially enable a path to develop therapies for first-line metastatic non-small cell lung cancer.

Speaker Change: We also formed collaborations with leading industry, academia, translational research partners.

such as the Breakthrough Cancer Organization.

Speaker Change: that presents a valuable opportunity to uncover new patient-centric scientific insights to further inform our ongoing commitment to transformative science.

Speaker Change: reaching commercial scale manufacturing of duraxone RASAs, and strengthening our organizational capabilities in preparation for a potential first regulatory approval.

Speaker Change: and we formed select partnerships to help us fulfill our tireless commitment to patients as we prepare to deliver our novel therapies to patients broadly.

Speaker Change: For example, to ensure that we keep patient needs at the forefront as we advance these medicines, we now have a relationship with Pancreatic Cancer Action Network, or PAMCAN, a distinguished organization devoted to improving the lives of people living with pancreatic cancer.

Speaker Change: And, we ended 2024 in an exceptionally strong financial position, allowing us to continue our ambitious patient-centric strategy.

Speaker Change: 2025 will be an important year for RevNet as we advance our strategy, aiming to maximize the impact we can have for patients with RAS-addicted cancers.

Speaker Change: Our first priority is to execute pivotal trials with duraxone-racib monotherapy in patients with previously treated metastatic pancreatic cancer and non-small cell lung cancer.

Speaker Change: For the Global Phase III RAS-ELUT302 Randomized Control Trial currently underway in patients with second-line metastatic PDAC, enrollment is an important measure of progress.

Speaker Change: For non-small cell lung cancer, I'm pleased to confirm that activation of investigational sites is now ongoing in the Phase 3 Resolve 301 randomized control trial comparing duraxone rastab to docetaxel in patients with previously treated metastatic RAS tumors.

Speaker Change: Our second priority is to advance diraxon RASib into earlier line randomized pivotal trials in patients with PDAC.

Speaker Change: We expect to initiate a trial in first-line metastatic disease, comparing a reference arm of patients treated by chemotherapy to two investigational arms.

Speaker Change: one with patients treated with Duraxone RACiB monotherapy and one with patients treated with Duraxone RACiB plus chemotherapy.

Speaker Change: Based on single-agent data and preliminary chemotherapy combination data, we are optimistic that both treatment arms containing daraxon racib have the potential to become important therapeutic options for patients living with metastatic pancreatic cancer.

Speaker Change: Of course, we'll need to align with the relevant regulatory authorities, including the U.S. FDA, before we can initiate the global randomized phase 3 trial in patients with first-line metastatic PDAC.

Speaker Change: As a further step in our ambition to serve patients with earlier-stage disease, I'm also very happy to share that we are actively designing a registrational trial with daraxon rasib as an adjuvant treatment patients with resectable pancreatic cancer who have undergone surgery and perioperative therapy, often including chemotherapy.

Speaker Change: This population constitutes approximately 15% of newly diagnosed pancreatic cancer cases in the U.S. each year.

Q4 2024 Revolution Medicines Inc Earnings Call

Request a DemoDemo

RVMD

Revolution Medicines

Earnings