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spk00: Good day. My name is Christy, and I'll be your conference facilitator today. Welcome to the Revolution Medicine Second Quarter 2022 Earnings Conference Call. Today's call is being recorded. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a question-and-answer session. To ask a question at that time, please press star, then the number 1 on your telephone keypad. If anyone has difficulty hearing the conference, please press star zero for operator assistance. I would now like to hand the conference over to David Errington, Revolution Medicine's SVP of Investor Relations and Corporate Affairs, for opening remarks. David, you may begin.
spk04: Thank you, and welcome, everyone, to our second quarter earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer, Dr. Steve Kelsey, the company's President, Research and Development, and Jack Anders, our SVP of Finance and Principal Accounting Officer. As we begin, I would like to note that our presentation will include statements regarding the current beliefs of the company with respect to our business that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These statements are subject to a number of assumptions, risks, and uncertainties. Actual results may differ materially from these statements, and except as required by law, the company undertakes no obligation to revise or update any forward-looking statements. I encourage you to review the legal disclaimer slide of our corporate presentation or the earnings press release, as well as all of the company's filings with the SEC concerning these and other matters. With that, I will turn the call over to Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer. Mark?
spk07: Good afternoon and thank you for joining us. Today I'll provide an update on our corporate progress and our Senior Vice President of Finance, Jack Andrews, will provide highlights of our financial results. In the second quarter of 2022, Revolution Medicines continued building strong momentum in the discovery and development of innovative medicines on behalf of patients with a wide range of RAS-addicted cancers, which represent 30% of all human cancers. We are advancing a deep and cohesive portfolio of RAS-targeted therapeutics, led by our development stage RAS-on inhibitors. Recently, we reported significant progress across our pipeline, setting us up for an exciting period as our assets progress over the next 12 to 18 months. I'll now review a number of key achievements that reflect this recent progress regarding our pipeline of RAS-on inhibitors and RAS-companion inhibitors. First, we have advanced the first two drug candidates from our highly innovative RAS-on inhibitor portfolio into clinical development. In June, we began dosing patients in a Phase I 1b trial, evaluating RMC6236. our oral RAS multi-on inhibitor in patients with tumors bearing various KRAS G12D mutations. The first patient treated with this drug candidate has advanced pancreatic cancer bearing the common KRAS G12D mutation. RMC6236, a bold compound that we have shown preclinically, inhibits a wide range of RAS proteins that can drive cancer, is the first development candidate from our broad collection of RAS-on inhibitors to enter clinical development. And this step marks a significant milestone in our efforts to serve the unmet needs of patients with RAS-addicted cancers. Additionally, I'm pleased to report that study site activation is underway for a phase one 1B trial of our second oral RAS-on inhibitor drug candidate, RMC6291. And shortly, this study will begin dosing patients who have tumors harboring the KRAS G12C variant. Unlike RMC6236, RMC6291 is designed as a highly selective covalent inhibitor of the activated or RAS-on state of the KRAS G12C variant that is common in lung and colorectal cancer. We have previously reported extensive preclinical data demonstrating its differentiated and promising anti-tumor profile. RMC-6291 is the first of a robust series of mutant-selective RAS-on inhibitors that we intend to bring into the clinic. Our third RAS-on inhibitor drug candidate, RMC-9805, remains on track toward our goal of beginning clinical evaluation in mid-2023. We believe that RMC-9805 is the first oral covalent inhibitor of KRAS-G12D, the most common RAS variant causing human cancer. particularly pancreatic, colorectal, and lung cancers. Based on their preclinical profiles, we believe that, in aggregate, this first wave of RAS-on inhibitor drug candidates, RMC6236, 6291, and 9805, has the potential to help serve the vast majority of patients with RAS-addicted cancers. Second, in support of our goal to develop optimal treatment strategies directed to RAS-addicted cancers, we continue clinical evaluation of two class-leading RAS companion inhibitors, our SHIP2 inhibitor, RMC4630, and our mTORC1 selective inhibitor, RMC5552, both of which have shown clinical evidence of anti-tumor activity. These RAS companion inhibitors are designed to be deployed primarily as combination agents with direct RAS inhibitors. Our clinical collaborator, Amgen, recently reported encouraging preliminary evidence from its phase 1B code break 101 clinical study, suggesting promising and durable benefit from combining RMC4630 with its KRAS G12C inhibitor, Sotiracid, particularly in second-line treatment of patients with non-small cell lung cancer who are KRAS G12C inhibitor naive. We continue enrolling patients into our phase 2 study of this combination, RMC4630-03, in patients with KRAS-G12C non-small cell lung cancer. Additionally, Sanofi is now recruiting patients in its Phase I-II dose escalation and expansion study, evaluating RMC4630 in combination with adagracid in patients with previously treated lung cancer bearing a KRAS-G12C mutation. Further, we expect to evaluate our Ras-companion inhibitors in combination with our own Ras-on inhibitors in the future. Now I'll shift to our corporate progress and comment on our focus for 2022 and 2023. In July, we successfully completed an equity financing raising gross proceeds of $265 million to strengthen the company's balance sheet and overall financial position to support the continued development and expansion of our product pipeline. Following this productive financing in the remainder of 2022 and 2023, The company will take a disciplined approach to ensure successful and timely execution of the multiple development stage activities currently underway or planned. Our top priority is to deliver on important milestones during this time. In this period, we intend to concentrate our development resources on our three most advanced RAS-on inhibitors, RMC6236, 6291, and 9805, and two clinical stage RAS companion inhibitors, RMC4630 and 5552. Importantly, we maintain our strong commitment to research activities that provide critical scientific insights to support our ongoing development activities and that also leverage our proven RAS inhibition engine to generate exciting new mutant-selective RAS-on inhibitors with distinct profiles. We expect to nominate our next RAS-on inhibitor development candidate in the second half of 2022, which will join a planned second wave of drug candidates, including RMC 8839, which we anticipate to begin clinical development after 2023. With this R&D strategy and our current cash, cash equivalents, and marketable securities extending operating runway through 2024, we expect to deliver on important milestones. In our Rasa on inhibitor portfolio, upcoming milestones are as follows. to provide evidence of first-in-class single agent activity for RMC6236 in 2023, to announce dosing of the first patient in a monotherapy dose escalation study of RMC6291 in the second half of 2022, and provide preliminary evidence of superior activity in 2023, and to announce dosing of the first patient in a monotherapy dose escalation study of RMC9805 in mid-2023. In our RAS companion inhibitor portfolio, upcoming milestones are as follows. To provide top-line data from the 4630-03 study of 4630 plus sotiracid in 2023. And to dispose additional evidence of single-agent activity for RMC5552 in 2023. In summary, we remain deeply committed to our science-driven approach to treating patients with RAS-addicted cancers. and our pipeline and R&D efforts have entered an exciting and important phase. The first wave of RAS-on inhibitors, which includes three differentiated drug candidates, has advanced significantly, with RMC-6236 now dosing patients, RMC-6291 preparing to begin dosing patients shortly, and RMC-9805 continuing progress toward the clinic. Our differentiated RAS companion inhibitors have shown evidence of single-agent clinical activity along the path towards strategic combinations with direct RAS inhibitors. And the first clinical evidence has now emerged in support of RMC4630 as a RAS companion inhibitor combined with a RAS inhibitor. As we intensify efforts to progress these assets to significant milestones in the coming period, we are also continuing to make a significant investment, pipeline expansion activities based on our productive RAS innovation engine. Building on this exciting company momentum, I'll now turn to Jack Anders, our Senior Vice President of Finance, to provide a financial update. Jack?
spk06: Thank you, Mark. We are pleased to have strengthened our balance sheet in July with the upsized public offering of common stock, raising gross proceeds of $264.5 million. Net proceeds were approximately $248 million. after deducting underwriting discounts, commissions, and estimated offering costs. Our cash and investment balance as of June 30, 2022, was $461.4 million, which does not include proceeds from the financing. As a result of the financing and concentration of our development resources as described earlier by Mark, we are updating our cash runway guidance. and now expect our current cash and investment balance to fund plan operations through 2024. We have updated our 2022 financial guidance and lowered the top end of our 2022 gap net loss range by $10 million. We now expect full year 2022 gap net loss to be between $260 and $280 million. We are also lowering our estimated non-cash stock-based compensation expense for the year and now expect full-year 2022 non-cash stock-based compensation expense to be between $30 and $35 million. Turning to the quarter, revenue from our collaboration agreement with Sanofi was $9.1 million in the second quarter of 2022 compared to $8.7 million in the prior year period. Total operating expenses for the second quarter of 2022 were $71.2 million and increased by 34% over the prior year period. The increase in operating expenses was largely due to expenses associated with our preclinical portfolio, increased headcount in related facilities and infrastructure costs, and stock-based compensation expense. Net loss for the second quarter of 2022 was $61.2 million, or 82 cents per share. And that concludes the financial update. I'll now turn the call back over to Mark.
spk07: Thanks, Jack. Revolution Medicines continues robust efforts to outsmart RAS-addicted cancers, and with recent scientific and business progress, we believe that the company is in an excellent position to fulfill our mission on behalf of cancer patients. This concludes our prepared remarks for today, and I'll now turn the call over to the operator for the Q&A session. Operator?
spk00: As a reminder, if you would like to ask a question during this time, simply press star, then the number one on your telephone keypad. Again, that's star one. Your first question comes from the line of Mark Fram with Cohen and Company. Your line is open.
spk11: Thanks for taking my questions. Prioritization and making sure you prove out SHP2 and the companions on one side and the RAS-ONs makes a lot of sense. But as you hopefully find some efficacy signals with the direct RAS inhibitors, how do you weigh the pros and cons of using your limited resources to rapidly expand out that positive signal with combinations versus, you know, using that as proof of concept for the platform and then kind of rapidly following behind with things like the G13C and more target, you know, specific inhibitors.
spk07: ...on inhibitor, which is our highest priority to move additional rats on inhibitors into the clinic or to expand out the workarounds the inhibitor that's been shown to be active as monotherapy? Is that your question? Okay. Yep. Yeah. You know, I'm not sure we're going to have to make a choice at that point. You know, clearly, once one has a clinical signal, the priority is going to be to move that asset forward and develop as quickly as possible a supporting package to move into, you know, a registration program aiming towards an approval So we'll do whatever it takes to pull that off. But I also think a fair point is that amongst these three initial RAS-on inhibitors that are going into the clinic, while they do cover the vast majority of RAS-addicted cancers in aggregate, there is also real opportunity for specialized additional inhibitors that are targeting specific mutants beyond those. And you mentioned KRS-G13C we talked about and included in our pipeline reference to other mutants that are of interest to us. So those are important too. I don't think they'll really compete for resources at that stage. We'll continue company growth. I think this decision to be very focused To be honest, it's to be very focused on five assets in the clinic. It's not as if we paired back to a small program. There's a lot going on, but we know that all eyes are on these first three RAS-on inhibitors and also to see the RAS-companion inhibitors mature. We just want to make sure that we are sufficiently focused. I think it's less about resources and more about concentrating our intellectual bandwidth and effort around those things at this stage.
spk11: Okay. That's helpful. And can you just remind us what you can view as gating from these initial trials with 6236 and 6291 before you might bring in the SHIP2 inhibitor and start dosing the combination?
spk07: Okay. Yeah, maybe that's a question Steve Kelsey wants to comment on. I think the question is, what would trigger expansion into combinations, which, you know, Mark didn't mention it, but I think we'd have to include both RMC4630 and 5552, and also, of course, anti-PD-1 immunologic checkpoint inhibitors.
spk08: Yeah, it's a great question. I think the current strategy is to start combination programs as soon as we can. And that of course then begs the question, what do we need to know before we can? And I think the very basics there are we really need to have just about enough information to believe we have a drug. There's not much point in combining with something that's inactive. And then at the sort of tactical level, we really need to have a very good sense of what the schedule is because it's very difficult to do combination studies if you're trying to test more than one variable. And we really don't want to be testing the schedule, different schedules in combination. So I think those are the two fundamental things that we really have to understand. But the reality is that all along, even though we have expectations with mutant rats having been validated as a target for single agent therapy, all along I think we believe that combinations are going to ultimately have the biggest impact. So starting those as soon as we can hopefully will give us a head start when we start looking at the optimal treatment measurements for getting into pivotal trials and particularly into the first-line space for any RAS mutant indication of which, as you know, there are really three major epithelial malignancies all crying out for better treatments like that.
spk11: Okay, thank you. Very helpful. Thanks, Mark.
spk00: Your next question comes from the line of Alex Stranahan with Bank of America. The line is open.
spk09: Hey, guys. Thanks for taking the questions. Just a couple from us. The combo data looked quite good from code rate 101, tolerability through the dose escalation, no grade 4 adverse events. I guess, could you give us a sense of what dose of RMC4630 is being taken forward in this context? I imagine your own study could help further inform this, but it sounds like perhaps the highest 200 mg dose could be the one you ultimately go with. And as a follow-up to that, is your expectation that response rates could even improve, say, beyond 50% in the G12C inhibitor naive patients at sort of the set dose in the expansion phase? And then my second question, you know, with your fifth RAS on asset nominated later this year, you know, how are you guys approaching which RAS variants to prioritize? Is it the size of the end markets, unmet needs, drug ability of the targets? potential for combos, I guess what's sort of leading your decision-making here.
spk07: Thanks. Alex, thanks very much. I think maybe Steve can address the first two questions, the two-part question, and maybe then I'll comment on the rest.
spk08: Yeah, nothing has really changed from the last earnings call. The study designed for the RMC463003 study, which is the one that we are sponsoring, which is a global phase two study and it's completely restricted to patients who have not previously received the KRAS inhibitor. The plan all along was to do a safety run in at the 140 milligram dose level and then then dose escalate to 200 and keep expanding at the 200 dose level until we either got a very clear efficacy signal or that we ran into issues with polar ability of that dose level. And that's still the plan and we're still enrolling that study. It's moving along. We haven't disclosed any data as to where we are, but it's rolling along very nicely right now. Your question about whether or not the response rate is more than 50%. Well, I think we would say there are two things I think that we would say. One is, of course, it's possible that the response rate for the combination will be higher than 50%. you know, the initial signals that were presented at the World Lung Congress, even though the number of patients was very small, if you actually just look at the four patients who were treated at the 140 and 200 milligram dose level, which are the two doses being tested in the O3 study, there were only four patients who with lung cancer that were G12C naive and were treated at either of those two dose levels, and three of them responded. So that gives you a 75% response rate, even though the denominator is only four. So the confidence was around that 75%, extremely wide, of course. The other thing to bear in mind is, of course, that just increasing the response rate is probably insufficient, partly because Really what patients and investigators want is durability. And partly because any pivotal trial that we would do with that combination, response rate wouldn't be the primary endpoint. It would be progression-free survival. So we have to keep a very close eye not just on the percentage of patients with who have tumors that shrink, but also on the temporal endpoints as well. The number of patients with stable disease and the durability of that stable disease is just as important as the number of patients who have a restless PR.
spk07: And this is Mark, I'll comment on your second question, which was how will we choose which additional inhibitors we would advance, or how will we prioritize them? It's a very complicated question, or it's a simple question with a complicated answer. There are a lot of different dimensions to consider. The real strategy here, which I hope we conveyed, but it's worth reiterating, is that we're not taking the foot off the accelerator creating these new assets. That work is still very vigorous, and essentially what we're doing is creating a basket of additional development candidates. The first one in the basket is, of course, 8839 on G13C, but there are others that will come behind that, as you pointed out, our next one this year, and one would imagine there will be more to come after that. And so with that basket, we'll get to choose, and we'll prioritize. One of the important considerations here is we're going to learn a lot from 63-6, 69-1, and 9-8-0-5. And those are three very distinct molecules with very distinct features. And we will learn a great deal from the early clinical experience with those. And I think that may guide us. It may guide us as to genotypes where the unmet need remains the highest after we see something from these three. It may guide us to which genotypes are most sensitive to RAS inhibitors. It may guide us to covalency versus non-covalency, selectivity versus multiple targets, et cetera. So there are a lot of really important scientific and clinical questions buried into the signals that we'll get from these, and I'm sure that that will significantly impact us, probably more so than, let's say, market size or something like that, But I wouldn't rule that out as some consideration. But I think the main thing we focus on tends to be probability. What's the likelihood that a given asset will actually provide clinical benefit in a given situation? And that's the kind of information we'll learn from these first three, the first wave of grass on produce.
spk09: Thank you. Thank you.
spk00: Your next question comes from the line of Jonathan Chang with SBB Security. Your line is open.
spk03: Hi, guys. Thanks for taking my questions. First question, can you provide any color around the progress of the Phase 2 RMC463003 study? Earlier in the year, the guidance was for top line data in the second half versus 2023 now. Also, can you help set expectations for how much and what kind of data could be available in the top line disclosure?
spk07: Yeah, maybe I'll answer this, at least take the first crack at it, which has to do with our notation that we will provide the next data readout will be the top line data set and that we won't provide an interim readout at the end of this year. That was really driven primarily by the fact that the Code Break 101c data were going to be and now have been disclosed. And so, in essence, one's already gotten a glimpse of what things can look like on an interim basis. And it didn't seem to us and to a number of investors speaking to us that anybody would really care about another interim update. and that what was really needed is a more definitive answer. Does RMC4630 provide added value to sotiracid in second line non-small cell lung cancer? And we think that this study will do that, but we just didn't see any value in giving another sort of drip, drip, drip of data on it. I think that's the main issue. A secondary factor or second factor is the enrollment pace wasn't quite on. with what we expected initially, and so we will continue enrolling some patients into the first part of 2023. And so, again, not having every patient enrolled and having just a partial data set to us didn't seem like it was meritorious.
spk08: Your second question? What readouts will we provide? Perfect. Dr. Kelty just provided the question and he can provide the answer. I mean, I think the answer I gave the last question probably sums it up as best I can really. The most obvious readout will be overall response rate because that is actually the end point of the study. But as I said, it's becoming increasingly important to us not just to look at response rate, but to look at durability. I think given that the study started enrolling last September, by the time we get the response rate data on the last patient in, the progression-free survival, the duration of progression-free survival data for the you know, the first transformations are relatively mature. So I think, you know, you can expect to see both absolute response rate data, durability of response, and progression-free survival from the cohort. And hopefully we will be able to make a meaningful comparison to the Codebreak 100 study, which was the pivotal trial of first single-agent psoriasis. We tried to, wherever possible, match the COBREC-100 study in the design of our study, specifically so that we can draw those comparisons. And I think that's hopefully what we'll be able to provide. Obviously, the other thing you'll see is the tolerability profile as well, because there's been a snapshot of that provided from COBREC-101C, but the heterogeneity of the patient population that was presented at the weekend doesn't really give you a robust assessment of the tolerability in that exquisitely defined G12C-naive non-sortial lung cancer population.
spk03: Got it. Thanks for taking my questions. Thank you.
spk00: Your next question comes from the line of Benjamin Burnett with Stiefel. Your line is open.
spk01: Hi, good afternoon. This is Neil Carnahan on for Ben. Thanks for taking our question. For the Phase 1 RMC6291 study, can you characterize enrollment criteria a bit? More specifically, will patients have been previously treated with a KRAS inhibitor, or will you be mainly pursuing patients that are KRAS inhibitor-naive?
spk07: Yeah, it'll be some component of both, I'm sure, but maybe Steve can Lay that out for us.
spk08: Yeah, the answer is that the eligibility criteria for the study right now are very similar to the COBRE 101 or COBRE 100. So in the initial phases of the study, pretty much anyone with any tumor harboring the DTLC mutation is eligible, irrespective of whether they've received the previous KRAS inhibitor or not. As we get into the later, the higher level dose escalations, certainly at the recommended phase two dose and schedule, we will be deliberately enrolling defined cohorts with, you know, based on criteria defined by tumor histotype and whether or not they have or have not received the KRAS G12C inhibitor. The primary population of interest for the study ultimately are obviously patients with lung cancer who have not received the G-tulsi inhibitor because that way you can make a comparison against the G-tulsi-off inhibitors. But there is some reason to believe that 69-1 might have activity in patients who are failing the G-tulsi-off inhibitor. That's not our primary focus as a single agent. It may become a very important focus when we start combining IMC 69-1 with other drugs in our portfolio, particularly IMC 63-6.
spk01: Great. Thank you. Thank you.
spk00: Your next question comes from the line of Noah Eisenberg with JPMorgan Chase. Your line is open.
spk10: Hi, guys. This is Noah on for Eric. Thanks for taking our question. We're just wondering, given some of the data at World Lung this past weekend, do you think the observed tolerability profile of combining KRAS inhibitors and PD-1s could be a class effect or specific to individual molecules?
spk02: Yeah.
spk07: Hi, Noah. Thanks for your question. You know, of course, it's a little bit hard to tell right now, but there have been a number of compounds, G12C inhibitors, that have shown a liver signal, which one would not be surprised, and that that would be exacerbated when it's combined with a checkpoint inhibitor that can cause inflammation in the liver, at least elevated LFT. So that additivity, I think, isn't surprising if you have monotherapy LFT abnormalities. Your question, though, is that due to a biological interaction between a G12C inhibitor and a PD-1 inhibitor? Is it due to chemical features? And we don't know, but given that many of the first-generation G12C inhibitors share either an entire chemical scaffold or chemical moieties related to one another, it's not too surprising if those compounds all have a similar effect within the liver. Now, you know, from our point of view, a big question is, does that lead through to our compounds, which is, of course, what we're focused on developing, and there really isn't chemical similarity. We've started from a completely different chemical starting point, binding to a completely different site on RAS and binding to a completely different state of RAS, RAS on versus RAS off. So there really isn't any obvious read-through, and since we don't have a good hypothesis as to why a generic G12C inhibitor biologically should cause LFT abnormalities to full stop, we don't have any hypothesis around that, we don't see any reason why that ought to read through to the RevMed Rapson inhibitor collection.
spk10: Great, thank you. Very helpful. Thank you.
spk00: Again, if you would like to ask a question, please press star 1 on your telephone keypad. Again, star 1. Your next question comes from the line of Michael Schmidt with Guggenheimer Sehery's.
spk05: Hi. This is for Michael. Thanks for taking our questions, and congrats on the progress with the first two KRAS inhibitors. Starting off a question on 6236. You previously mentioned some preclinical rationale that 6G36 can be used as a targeted inhibitor for certain G12C mutants, G12 mutants, and also as a potential RAS companion inhibitor. Now that the compound is in the clinic, how would you prioritize the two strategies? Or are you going to evaluate them parallelly, you know, after 6G91 enters the clinic? And then a second quick question on 6291. It looks like you're evaluating both once and twice daily in upcoming phase one. So just what are some of the considerations to test both schedules? And does the preclinical PK data provide any rationale that one could be better than the other? Thank you.
spk07: Okay, thanks for your questions. The first question, which is what's the priority with RMC6236, to test it as monotherapy or to test it as a companion inhibitor? Well, that's pretty straightforward for us. You have to evaluate it as monotherapy and demonstrate that it's tolerated and active before you really qualify it to be used as a companion inhibitor. With that said, though, you don't necessarily require complete data package to convince you that you have a path forward to registration as a monotherapy before you start the RAS companion combinations. So, in other words, I think we'd start that fairly soon after we have some confidence around its anti-tumor activity and how well-tolerated and safe it is. I think we would look very much towards combinations with selected other RAS on inhibitors, but clearly phased in that way. The monotherapy is the thing to keep one's eyes on initially. And the second question was? The scheduling of 69-1. Daily versus BID dosing? I don't think we've ever talked much about BID dosing. Is there something behind that question that you're alluding to?
spk05: Yeah, it's just based on, you know, information on ct.gov, it looks like, you know, both schedules are, going to be evaluated, so sort of just want to, you know, get.
spk07: Yeah. So I think the question there is really just about how much continuous exposure one gets from daily versus twice daily dosing. You know, there was a really great visibility around this topic with regard to the first generation inhibitors, RAS off inhibitors, because if you're not covering them and keeping them trapped in the RAS-off form, you have a really easy escape mechanism, which is for the cell simply to shift the RAS-off pool over to RAS-on. And so, as a result, the general feeling in the field is that you need to continuously cover the entire RAS-off pool and try to keep it from converting to RAS-on at any point in time. And, of course, Maradi made a point of that, both with regard to the long half-life of Adagracid and then subsequently to BID dosing with the long half-life of products. You know, it's not entirely clear that that concept applies equally well to Ras-on inhibitors. It's really a little bit of a different mechanism. I mean, it's a dramatically different mechanism, but different dynamic. And so it's not really clear that that level of continuity is necessary. And secondly, it's not clear that RMC6291 given daily wouldn't provide that sort of continuous coverage. It may well. In fact, in mouse studies, it covers it very, very well. So I think that's really in the protocol. Steve can comment on this. But I think it's in the protocol simply acknowledging that continuous coverage is something we want to make sure we understand whether that's needed and make sure that we have a dosing schedule that could provide it if daily dosing is not sufficient.
spk08: Yeah, we quite often write into our protocols the option to evaluate alternative schedules right up front because it saves you having to write an amendment if you find out the PK is not tracking with your predictions and you have to go back and test another schedule. But I think, you know, to Mark's point, our preclinical data is, suggest that we can cover the targeting mice with once daily dosing and so whether or not we'll ever have to test a different schedule in the clinic remains to be seen. I think we need some clinical PK data first before we can decide. But it's definitely not a done deal. We're not necessarily going to test another schedule and even if we do, it's not necessarily going to be twice a day dosing.
spk05: Thank you.
spk00: As there are no more questions in the queue, I will turn the call back over to Dr. Goldsmith for his closing remarks.
spk07: Well, thank you, Operator, and thank you to everyone for participating today and for your continued support of Revolution Medicines. Have a good day.
spk00: This concludes today's conference call. You may now disconnect.
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