Welcome everyone. Thank you for joining us today for the last day of JP Morgan's 41st annual Healthcare Conference. I hope you are enjoying the conference so far. It's my pleasure to introduce you Andrew Robbins, CEO of Cogent Biosciences. My name is Tarun Soni, and I'm a Healthcare Vice President here at the Investment Banking group at JP Morgan. Just housekeeping before we begin the presentation, if you have any questions, you can submit them via the portal or the traditional way of raising your hand and ask any questions. With that, Andrew, over to you. Thank you. Great. Thanks, Tarun. I appreciate the invite to be here at the J.P. Morgan conference to kick off the year. I'm excited to share sort of a forward-looking presentation about what does 2023 hold for Cogent Biosciences and potentially even after that. We're obviously very excited by the progress we've made, certainly with our lead drug bezuclastinib over the past year, as well as in building out what we think is emerging as one of the leading precision medicine companies in the industry. Before I really dive in, I just wanna remind people that I will be making forward-looking statements. For a more complete discussion of risk, I would ask you to review some of our recent SEC disclosures. As I mentioned, Cogent Biosciences is a company that's focused on inventing, developing and hopefully ultimately commercializing precision medicines for rare diseases that are driven by genetic mutations. Our lead product is a drug called bezuclastinib, which is a potent and selective inhibitor of KIT mutations, including maybe most importantly D816V, which is a point mutation that's known to drive a disease called systemic mastocytosis. We're developing the drug in two different subgroups of mastocytosis, both the advanced setting and the indolent or non-advanced setting. Additionally, we're also developing the drug in a global phase III trial at this point in a disease called gastrointestinal stromal tumors, which is a solid tumor indication that again is driven by mutations in the KIT gene. In addition to bezuclastinib, which I'll spend most of the time today talking about, we have put together what we feel is one of, if not the best small molecule research team in the industry focused on precision medicine and targeted therapies. Many of these folks have their roots from a company called Array BioPharma, where I worked for several years before it was acquired by Pfizer. The first 2 programs we've announced from this effort are a selective, pan-mutant FGFR2, FGF1 sparing FGFR2, and a hopefully CNS penetrant version of an oral ERBB2 compound. We'll talk a little bit about those drugs if we have time at the end. But in addition to those two, obviously the research team is working on a whole host of other early-stage programs, and we believe in 2023 we'll have an opportunity to talk more publicly about a couple additional programs after those two. We also feel very confident in our cash position, which is a luxury for a small cap biotech company these days with cash that we believe will get us into 2025. Just looking kind of at the portfolio or the pipeline at a high level view, as I mentioned before, we're running three clinical studies, APEX, SUMMIT and PEAK respectively in the mastocytosis indications in the GIST. We believe that each of those three trials, if successful, could serve as the basis for registration. We're excited about the stage of development that bezuclastinib's in and some of the encouraging signs of clinical activity we've seen already. As you can see below, as I already mentioned, we have a couple of publicly disclosed programs as well as sort of a not yet ready for primetime group of targets that our exceptional research team is working on. Turning back to bezuclastinib. This is a drug that we feel strongly has the potency to cover D816V, which is important again in driving mastocytosis, but has a couple of other very important molecular properties that we think will differentiate it and potentially position it to be best in class long term. Number one, it is molecularly designed to spare CNS activity, which you don't want in treating mastocytosis patients. Maybe two, and more importantly, it's highly selective against common anti-targets, kinases like PDGFR, FLT3, CSF1R, et cetera. As a highly selective, highly potent non-CNS penetrant drug that hits KIT mutant, it is ideally positioned to go after this disease. We had the opportunity over the last 12, 18 months, once we took control of the asset to undergo a reformulation where we feel we've really optimized the way that the drug works and is absorbed, to improve the bioavailability and get us to a place where we can move forward with an acceptable commercial presentation into the phase III GIST program. I don't think there was ever a doubt we already at the doses necessary to get to mastocytosis were fine, but that really helped us enable the phase III PEAK study. The other nice consequence of reformulating or optimizing the formulation is that we believe we've extended the intellectual property protection or protection against generic entries until 2043. We feel very happy about that. Taking a look first at the competitive landscape, which is a question that I think investors always have. It's actually pretty limited in both indications. On the left side of this slide you'll see gastrointestinal stromal tumor landscape, and on the right side, the mastocytosis landscape. Let's start on the left with GIST. I think people are very familiar with a drug called sunitinib. This is all in, by the way, imatinib-resistant GIST. imatinib is an exceptional drug that is highly effective for de novo patients with GIST. Really the drug development landscape is focused on developing in the second line for this disease. sunitinib is the current standard of care and has been as a monotherapy since about 2005. It is now a generic drug. You can see here it is very active against patients that develop resistance based on exon 13/14 secondary mutations, but it does not have potency against patients that have an exon 17 or 18 mutation. Interestingly, a drug called ripretinib, which many folks know has been developed by Deciphera, sort of has the opposite profile, where it is very potent against exon 17 and 18 mutations but does not seem to have sufficient activity as a monotherapy to cover patients that have resistance in exon 13/14. You sort of see the crisscross on sunitinib and ripretinib. I think people are aware, about a year ago, they announced when they ran a phase III trial, these two drugs head-to-head, the PFS tied, which maybe you'd predict from the different profiles. You can see the combination of our drug bezuclastinib and sunitinib. We again are a very potent inhibitor of exon 17/18, but because specifically of the tolerability profile of our drug, we're able to combine with sunitinib. We believe we cover all of the secondary resistance mutations, and the design of our trial is sunitinib versus the combination of bezuclastinib and sunitinib, and that's why we feel that the result of our phase III PEAK study is likely to get to a different result. There are a couple of first in human programs going after refractory GIST with individual drugs that look like they have many of these mutation coverage, but interestingly, they're several years behind where we're already enrolling patients in our phase III trial. Turning to the mastocytosis side of this chart, you can see that there are three drugs in the world that are known to be potent enough on D816V to get the job done, quote, unquote. Two of these drugs are owned by Blueprint Medicines, avapritinib, which is already approved, and their backup drug called BLU-263 or elenestinib, and then bezuclastinib. All of us are potent enough against the main target. You can see here, as I mentioned before, you don't want CNS activity, so that's nice for their backup compound in bezuclastinib. You also don't, in this disease, it's a monogenic disease, you don't wanna inhibit other kinases because all that provides is the toxicity associated with hitting those targets. That again is one step further why long-term we believe bezuclastinib will be positioned as best in class in these indications. From a commercial potential perspective, this is a, you know, new slide, the first time we're putting sort of a stake in the ground what we think this market looks like. These three indications together represents, in the U.S., a total available market of about $2.5 billion. You can kind of see the split between the advanced systemic mastocytosis, second line GIST, and non-advanced systemic mastocytosis. You know, at the bottom there in the orange box, you can see that if you do, sort of a proxy for global potential market, we think it's about a $3.5 billion market. Remember, in GIST, there's very limited competition in the second line if we, if our PEAK study is successful. In the systemic mastocytosis side of the asset, there's really only 1 other company. Yeah, they have 2 drugs, but I think eventually Blueprint will position 1 of those drugs as the choice going forward. We're very excited with this asset to continue developing for what we, see as a very attractive market with very limited competition, which is, I think a rarity these days in drug development. Quickly on systemic mastocytosis, I think people are fairly familiar with this disease by this point. It is a rare hematologic disorder. It is driven by a single point mutation in the KIT gene, as I mentioned before. About 90% of patients present with the indolent or non-advanced form of the disease, and only 10% present with the advanced form of the disease. We, and I think, the patients and investigators would agree with this, there's a need for more, effective therapies. There's essentially one old drug and one new drug that are approved for the advanced form of the disease and really nothing yet approved for the indolent form of the disease. The unmet need remains quite high for these patients. As I mentioned before, it's a disease that is driven and well accepted in 95% plus of patients by a single point mutation. Turning now to our advanced study. This is a trial called the APEX study. It's a two-part phase II trial. We are currently enrolling patients in part one, which is where we're exploring the appropriate dose to move forward into the expansion phase of the study. We have guided that the enrollment we feel is necessary to pick a dose in part one will be complete this quarter, Q1 of 2023, with results from that cohort of patients, probably in mid-year 2023. Once we pick a dose, we'll move into the expansion, and we believe we need approximately 80 patients, plus or minus. If that shows efficacy similar or numerically better to avapritinib with a notable tolerability advantage, we feel confident that we can approach regulators for an approval. A few weeks back at ASH, we had an oral presentation on an interim look at the clinical data from APEX. This is a very short summary of that clinical presentation. You see here on slide 11 that we generated an objective response rate, which is measured by a composite endpoint called modified IWG-MRT-ECNM criteria of about 73% objective response rate in an admittedly small patient population, but we think this is very encouraging for clinical activity. If you take away some of the patients that had received prior avapritinib and look only at truly naive to KIT therapy patients, that objective response rate moves up to 89%. This drug is certainly clinically active, and I think now the question is, can we continue in a larger sample size to replicate these data and demonstrate a positive safety differentiation? Before I take a look at the safety and tolerability, there are many other surrogate endpoints that are interesting to review from a clinical activity perspective in this disease, namely, the levels and the reduction of a circulating serum tryptase, which is a marker of mast cell activity, the number of mast cell aggregates themselves in the bone marrow, and then, a newer measure, which is the frequency of the mutation in cells circulating in the blood. You can see here across the board, really, with maybe one exception, all patients are receiving significant benefit. Again, reminder that the objective response criteria in this disease is complicated. It's a composite. In order to achieve partial response, you would need to have a patient reduce below the dotted line on each of these charts, and then have other things happen. In order to be eligible for complete response, you would need to achieve levels that are denoted by the open circles, diamonds, and triangles. Again, we're seeing very rapid and deep responses across all measures of clinical activity, and that's encouraging us investigators and patients to continue the development of this drug. Looking now at the safety and tolerability from this study, we're again very encouraged, especially relative to what's expected for standard of care avapritinib. We reported no related cognitive effects in the trial at all. We reported no bleeding events of any kind, including obviously no intracranial bleeds. The vast majority of our treatment emergent AEs and treatment-related AEs are low grade and sporadic. You can see that there are a handful of grade three heme lab values that are denoted here. In all four cases, the two neutropenias, thrombocytopenia, and anemia, all of those patients resolved their counts back to or above baseline values without dose reductions. We're very excited about the tolerability profile that's emerging from bezuclastinib. Finally, what I'll say is we showed this, what I think is, again, a very encouraging chart about each of the patients at this point in the study that have had platelet counts measured. You can see on the X-axis, they're measured on day one of each cycle. If you just sort of pull your eyes back here on slide 14, you can see that the overall platelet health or the impact on platelets of bezuclastinib looks to be nonexistent. Platelets stay the same. If you really wanna look at it, they maybe sort of look like they're trending up a little bit. This, we believe, is very important because a significant proportion of the ASM population has a subset of disease called SM-AHN. Those AHN or other diseases are frequently diseases that have directed therapies that also cause heme toxicity, including things like azacitidine, decitidine, ruxolitinib, chemotherapy. In a commercial setting, if we can generate a profile that looks like bezuclastinib as a treatment is friendly to platelets or doesn't cause overlapping platelet toxicity, we think that we may be able to enable concomitant use with some of these AHN-directed therapies. We announced a few days ago that it is a strategic objective of ours this year to initiate a clinical investigation of bezuclastinib concomitantly used with some of these AHN-directed therapies. I'll say a word about SUMMIT, which I think people are very excited about, as are we. SUMMIT is our non-advanced systemic mastocytosis study. It's a complicated design, but at a high level here on slide 15, it's separated into the first part and the second part. The first part is really designed to do two things, pick the dose we think is appropriate for these patients while validating a patient-reported outcome tool that will be used for the measure of the primary endpoint in part two or the expansion phase. We are currently in part one. We expect to share clinical data after an unblinding from this part one in the second half of this year. Because the trial is blinded, we don't know what the data look like. We're waiting, I think with lots of other folks to see how this trial goes in the second half of the year. That'll be exciting, for us, for patients, for investigators. Turning now to GIST for a few minutes. I think GIST is also a pretty well understood indication in the investor community. There's about 4,000-6,000 newly diagnosed cases of GIST every year. Essentially, all of those patients are treated with imatinib, which is a fantastic drug. About 60% of GIST patients will develop resistance over time to imatinib, and that's where the conversation around drug development in GIST starts. You can see here on slide 17, there are three drugs approved as monotherapies sequentially second, third, and fourth line. Each of those drugs has what I would call very modest activity with the response rates below 10% and progression-free survivals of six months or less. There is a significant unmet need to find new therapies that can help patients that, for whom imatinib is no longer controlling their disease. You can see here on slide 18 our phase III trial design of the PEAK study. We've completed or we haven't completed. We enrolled patients in part one-A, and at CTOS this year in October, announced that we felt comfortable taking forward a dose into the part two of the randomized study. The patients from part one-A obviously are cancer patients who are receiving directed therapy, so they're continuing to receive these, this combination, and we will, we've guided that we'll present a clinical update from part one-A in the first half of 2023, which in addition to longer-term safety and tolerability data, will start to show some of the measures of clinical efficacy in part one-A. We're excited that we're now actively enrolling patients in part two. We've guided that we think a trial of this size and this indication will take about two years plus or minus to accrue and then probably another, you know, few quarters to wait for the PFS events to accrue in the study. PFS is the primary endpoint of this trial. It was not lost on us that about one week ago, our colleagues at Deciphera put out some new interesting data from the INTRIGUE study that did not meet its primary endpoint that showed, you know, maybe, I think to the outside world, surprising data in patients that had exon 11 primary mutations with only exon 17 or 18 secondary mutations. It's not surprising to us that makes perfect sense that ripretinib would work quite well in that patient population. As a reminder, they showed a progression-free survival in that subpopulation, a post-hoc analysis of about 14 months relative to about one month for sunitinib monotherapy in that patient population. We went back, as you remember, a predecessor company ran a phase I-II study of bezuclastinib and sunitinib that showed very encouraging data in a highly refractory patient population. Unlike INTRIGUE and Deciphera, that was run in a second line only, this data set you're seeing on slide 19 is many third, fourth, and fifth line patients included in these bars. In this phase I-II study, we reported a median progression-free survival of 12 months and an overall response rate of 20%. We went back and took a look where we could because the data is incomplete. We found six of these patients had that same signature with classic exon 17, 18 secondary mutation only without 13, 14 involvement. For that group of six patients, we actually see a median progression-free survival of 16.5 months. I think this is very encouraging that it's not just that, oh, ripretinib gets those patients. The combination of bezuclastinib, which itself is a very potent Exon 17, 18 inhibitor with sunitinib, I think is has the potential to be as or more effective than the ripretinib data from last week. Okay. Another question that folks have is, why don't other companies combine with Sutent? We think, again, this gets back to the specific tolerability profile that bezuclastinib has shown clinically here from the original phase I-II, and I'll pause here on slide 20 for a minute. Then from CTOS on slide 21, these are two distinct groups, first of 18 patients, second of 19 patients, that show a safety profile of the combination of bezuclastinib and sunitinib that looks very similar to the safety profile of sunitinib monotherapy. We're excited that as we continue to enroll patients with these two drugs together, it doesn't appear as though bezuclastinib is adding any concerning toxicities or tolerability challenges to Sutent monotherapy, which again, as a generic drug now is widely understood and has been used by investigators around the world for 15 or 20 years treating these patients. just, you know, quickly, we were encouraged by the data that Deciphera has put out. This on slide 22 are their data from the INVICTUS study, which is the fourth line trial that shows there's many patients that have Exon 17 involvement as a secondary mutation, many patients that have 13, and many that cross over. We are concerned or interested to see how they solve the problem of concordance between circulating DNA measurements in GIST and tissue sample mutation analysis, as well as sort of the, you know, current maturity of ctDNA not seeming to pick up DNA or KIT mutations in many of the patients that are tested. You know, we're interested to see how they solve that conundrum. What we show here on slide 23, again, I'm not gonna read every word or every number on this slide, we tried to put together why we think INTRIGUE as a holistic trial didn't work, why we think PEAK will, and it makes sense why the subset of the 17, 18 patients on INTRIGUE for ripretinib did work. You can see here when you come on as a 13, 14, you really need something to cover you. If you come on as a 17, 18, you need something that's gonna cover that mutation. That the individual sunitinib monotherapy or any KIT 17, 18 monotherapy, including avapritinib, ripretinib, and quite frankly, bezuclastinib, if we test it as a monotherapy, I don't think any of those drugs would help patients with an exon 13, 14 mutation. Really, it's the combination. It's covering all of the secondary resistance mutations that we think will deliver a different outcome in the PEAK study. Then I'm gonna turn it over to some Q&A on our two early-stage programs. We presented data on both of these at EORTC this fall. The first is an FGFR1-sparing pan-mutant FGFR2 inhibitor. People might say, "Why do we need another one of these? There's a company called Relay Therapeutics that has one." We took a graphic from actually Relay's presentation there in the bottom right that shows, when treated with an FGFR inhibitor, patients with FGFR2 mutations typically develop resistance in the gatekeeper and the molecular brake mutation, the 564 I and the 549 K. From our data, their drug doesn't seem to be very potent against those two mutations. We'll wait, and we'll take a look, but we think that, when first-line patients are treated with four double o eight, they are gonna develop resistance, based on that molecular profile. What we showed at EORTC is the drug we're designing and developing. This is an exemplar of the program that we hope to finish up a candidate very shortly, has very potent coverage across both of those additional mutations. An ERBB2 inhibitor, people will say, "Well, there's some competition there." We agree. What we're trying to do first is create a drug that covers some of the lesser, focused on driver mutations in ERBB2, like 310, 842, 755. These are driver mutations of about 5%-10% of solid tumors like uterine cancer, bladder cancer, gastric cancer. We noticed in the development of this program as we continue to work on it, that our drug also is very potent against YVMA insertions. That's interesting to potentially explore in the future. We think we can get to a clinical candidate that has significant clinical CNS penetration. That is the goal of this ERBB2 program. Just to wrap it up, 2023 is gonna be an exciting year for us. We have many catalysts coming up. I mentioned some of them, but I'll recap them here. Clinically, phase III PEAK lead-in data, that 19-patient subset, we'll have a clinical update from that trial this half, in the first half of 2023. From APEX, we're gonna complete enrollment in part one this quarter, then we'll have a corporate or a, you know, mid-year update on how that went with clinical data subsequent to the announcement that we're moving into part two, hopefully. In the second half of the year, we're going to unblind patients in part one of SUMMIT and share those data with the world. In addition, the research milestones we think we're on track to select a candidate from our FGFR2 program and move into GLP tox and the enabling studies in the first half of this year. We look like we're on track to get an ERBB2 clinical candidate by the end of this year, so that would sort of put us about six to nine months behind the FGFR2 program. We are committed to talking about two additional targeted programs, where we think our research team can bring to light something that positions these programs for best-in-class unprecedented biology targets. We're excited to talk about that. As I mentioned before, we have just under $290 million with no appreciable debt to speak of, and that balance sheet will position us into 2025. With that, maybe we can transition and take a few questions. Cool. Thank you. If you have any questions, just a reminder, you can ask it through the online portal or you may raise your hand here and we can start the Q&A. We'll repeat the question from the audience for our online audience. Thank you. Thanks, Andy. I have a question. We saw the recent Deciphera announcement, you know, from the subset of patients from the INTRIGUE study in second-line GIST. Could you please tell us what are the implications for Cogent and the PEAK study from this news? Yeah, that's an excellent question. First of all, I think it's encouraging, you know, from the perspective of the patient and the investigators that it looks like in a subset of patients ripretinib does have some pretty impressive clinical activity. You know, we congratulate our colleagues at Deciphera for pushing the field forward. We think about this in two ways. Number one, patients with that genotype, as presented a few slides ago, we think the combination of bezuclastinib and sunitinib can be quite effective for those patients as well. As a reminder, our PEAK phase III trial allows any patient progressing on a imatinib to enroll in our study because I think the combination really has utility across all genotypes of secondary KIT mutations in the second line. Secondly, again, talking to KOLs over the last week, we're sort of, we have an open mind about this, but we're concerned about the feasibility of conducting such a study because it is not current common practice to genotype patients after imatinib approval before initiating second line therapy. At a facility like a Sloan Kettering or a MD Anderson, I think it's believable that those institutions have already set up, you know, genetic sequencing, whether it's tissue or blood, to rapidly turn around. On a global basis, on a study that probably needs to screen upwards of 500 patients, I think there's an open question about the feasibility of conducting that. Especially if we can continue to bring out additional clinical data that shows that patients with this genotype have very strong responses to our combination as well. We'll see what happens in the future. I don't know that it's an open question anymore, that if you're a patient with that genotype, that taking ripretinib is a good idea or not. You know, I think that we plan to show results from that subgroup in our phase III trial as well. As I mentioned before, we're already enrolling patients in the phase III PEAK study, so we do have a bit of a head start. We're, we're encouraged by what we've seen on our combination in that genotype subgroup as well. Thanks, Andy. Given the timelines for the PEAK study, what would you anticipate would be the impact on Theseus as they come forward with a PAN approach? Yeah, just to restate for folks on the web, the question was, some of the earlier stage programs in GIST that are in first in human studies, what will happen to those based on what happens with PEAK? I think both Theseus and IDRx are developing drugs in that setting. It's an excellent question. I think it's interesting to have a drug that potentially covers many of the KIT mutations. We will point out neither of those drugs seem to hit D816V, which is an important KIT mutation. It's probably tough to call those drugs actual pan-KIT mutants since they are not relevant for mastocytosis patients. In the GIST world, I think if I put myself in the shoes of another company that's currently running proof of concept phase I trial, when we will likely have top-line results from a pivotal study in the second line in, let's call it sometime in 2025, designing a long-term registration strategy clinically, you probably have to factor in the performance of that combination. If PEAK wins and/or, you know, beats sunitinib monotherapy, it may be challenging in a second-line setting to find patients that are willing to randomize to sunitinib in the future when they're ready to run their phase III study. I imagine they're trying to figure that question out, and the specifics of their strategy will most certainly be driven by the performance of those drugs in a phase I study. Again, we're all for rooting for great activity for cancer drugs for patients. If they come up with a response rate and a PFS that looks similar to ripretinib or bezuclastinib-sunitinib combo, I think it might be tough sledding from a clinical strategy perspective for them. Thank you. Thanks. Great presentation and congrats on the wonderful data. I have two quick questions just on the GIST study that you're running. Given that, one of the competitors had announced that they showed pretty remarkable PFS and that I think it's the 16 and 17 exon mutants, is there any way that you have thought about modifying the study to where you can pre-specify that 16 and 17 population as potentially a separate population that if you were to succeed in that but not in the overall study, you could still get a label? That's the first question. The second one is, I think you talked about potential enrollment updates for the course of the year. When is the anticipated study readout? Okay. The first question was, have we thought in the last week or so since the Deciphera news about changing the design of the PEAK study to incorporate some of this new knowledge on exon 17/18 only patient performance? The second question was about timelines. We're talking about the PEAK study again. Is that right? Okay. I'll do the easy one first. The PEAK study, we believe will take about two years to accrue, that probably brings you to the end of 2024. Because the primary endpoint is progression-free survival, we're at the mercy of when events occur. I can tell you that in VOYAGER and INTRIGUE, those studies, I think, took about 12 months ± from the end of enrollment until they had top-line results. It's probably about a three-year, two-year enrollment, one year of waiting for events. That's my guesstimate. As we get deeper into the trial, we'll be able to refine those timelines. With regards to modification of the study, we are not going to change the inclusion criteria to require genotyping because we do think that is gonna be a significant headwind to actually enrolling a second-line GIST study around the world. Again, maybe not at Sloan Kettering and MD Anderson and Dana-Farber, but at the 150 or 200 sites, you actually need to find 400 patients in GIST. They're just simply not set up for the logistics of doing ctDNA rapid turnaround while patients whose tumors are growing rapidly off of imatinib progression are waiting. We're not planning to do that. We are planning to collect baseline ctDNA tissue whenever possible at both baseline and progression in our study because as a science-driven company, we're very interested in contributing to the understanding of the disease. The interesting part of this is, in a blinded study, we're not gonna have the results of that until obviously on the other end of TLR. We'll take a look at all kinds of subsets, but really the combination of our two drugs and the molecular profile of the combination, we think are gonna be helpful for all patients coming off imatinib. Anything other than that would be sort of downstream of the primary endpoint. Just to follow up to that, you said you would only be collecting tissue whenever possible. Baseline, why wouldn't you be collecting blood samples as well to check ctDNA? Just a clarification. I might have misspoke. We will be collecting tissue whenever possible in ctDNA in everybody at baseline and progression. Thank you. Sure. Thank you, Andy. Another quick question. You know, we saw that, you know, one of your competitor recently provided guidance that the results of the HARBOR study of BLU-263 won't be presented until the second half of 2023. What are your thoughts about that? Yeah. That's also a great question. You know, again, it's maybe a better question for Blueprint. You know, the dynamics here are that they have a backup compound in ISM or the non-advanced mastocytosis setting that they announced in November that they were gonna share data from at ASH or around ASH. At ASH, they shared sort of a short qualitative update that they had a 40-patient clinical trial that looked favorable. They announced last week that they're going to share the results of that study in the second half of 2023. It could potentially be up to a year after they have the results of that new drug's patient data in hand before they share it with the patient community investigators and investors. I think we're puzzled by why we won't get a chance to see the performance of that drug earlier than that. We're, again, all in favor of more drugs helping patients. If we sort of think through the implications, if the HARBOR study in that 40-patient sample looks significantly better than avapritinib's PIONEER study, you know, I think the patients deserve to know that and go on that drug. If it looks worse, again, I think they also deserve to know that. We would just continue to monitor and wait to see those data. Again, based on the profile of BLU-263 not having really a differentiated selectivity profile from its parent drug, we think some of the same liabilities will follow that drug around as follow avapritinib around. Thanks, Andy. Just related to that, as a follow-up, we touched upon in terms of competition, you know, in the SM market compared to bezuclastinib. How do you say your asset is differentiated versus your close competitor, you know, Blueprint's assets, avapritinib, or, you know, the next generation, BLU-263? What kind of market opportunity do you see for your asset? Right. We actually think about our target product profile for bezuclastinib a little bit differently between the two indications. In the advanced setting, we acknowledge that avapritinib results from Pathfinder are very impressive from a clinical efficacy perspective, with a high percentage of patients achieving response and significant durability for patients that can tolerate the drug. What looks to be problematic from that profile is that the toxicity and tolerability that's associated with that drug at that clinical exposure is very challenging for patients. Our target product profile for bezuclastinib is to deliver clinical efficacy comparable to avapritinib high dose, but with a tolerability profile that's much friendlier to patients. In the non-advanced setting, because Blueprint designed a clinical trial that sacrificed 90% of their dose in clinical exposure to have a safety profile that's acceptable in a disease of morbidity, not mortality, their safety profile looks fantastic, right? Without having seen the full data set, it looks as good or better than placebo, it's very hard to imagine beating a safety profile like that. We will point out on a placebo-adjusted basis, their primary endpoint had an 11.4% improvement on the total symptom score, which is, we would call it modest at best. In the non-advanced setting, we think based on the profile of bezuclastinib, allowing us to preserve a clinical exposure similar to what we're testing in ASM or maybe identical, we think we can really drive patient benefit from a clinical efficacy perspective. Thanks, Andy. We have the last question, which is, how do you think about the attractiveness of this ASM market given avapritinib's launch? Yeah, that's also a great question. We, as many folks listening in, have watched the quarterly sales performance, and it looks like it's slowed or plateaued. I guess we'll see, you know, I think their guidance is in line with that for Q4. In November, I think Blueprint acknowledged that they're having challenges penetrating the SM-AHN market, which based on the PATHFINDER data, based on the emerging APEX data, looks to be representative of a significant majority of patients. We believe, as I mentioned before in my presentation, that a drug like avapritinib that seems to have a heme tox challenge at that clinical exposure of near 200 milligrams is difficult for hematologists and certainly community hematologists who don't see many of these patients per year to try to treat concurrently with a drug like azacitidine or decitidine or ruxolitinib or chemotherapy, because you don't wanna stack two heme-toxic drugs on top of each other. We believe, based on the emerging profile of bezuclastinib, that there is an opportunity for us to demonstrate, and we freely acknowledge we have to demonstrate this clinically, that concomitant use of bezuclastinib can be achieved with these AHN-directed therapies. If we can do that, then I think we unlock a significant proportion of the ASM market that avapritinib is just not well-positioned for. That really, I think, can drive us forward to what we believe in the U.S. is about a $300 million ASM market, maybe about a $500 million global market. Thank you, Andy. Thank you everyone for joining us. It was a great presentation, and have a great rest of the conference to everyone. Thank you.