All right. Good afternoon, everyone. Thanks again for joining us, and welcome to TD Cowen's 44th Annual Healthcare Conference. My name is Tyler Van Buren. I'm a senior biotech analyst here at TD Cowen. For our next fireside chat, very pleased to be here with Deciphera, and it's a pleasure to introduce Steve Hoerter, President and CEO, Matt Sherman, Executive Vice President and Chief Medical Officer, Dan Martin, SVP and Chief Commercial Officer. Steve, Matt, and Dan, thank you very much for being here. It's a pleasure. Thanks. Thanks for the invitation. Of course. If you guys have any questions, feel free to raise your hand, and I'll do my best to get them asked. But let's start with QINLOCK and the GIST franchise. You guys have experienced a nice inflection of growth over the past year, so maybe you could start by describing the factors that's contributed to that versus the prior year. Yeah, absolutely. Thanks so much for having us. Thanks for the question. So, you know, really pleased with the fourth line business. It's really the foundation core of our commercial business with QINLOCK right now. US performance has been really strong, a lot of great feedback from the marketplace. We penetrated the fourth line opportunity quite rapidly, following the launch a number of years ago, and we've been growing that business gradually through gradual increase in our average duration of therapy that we expected to see and have seen in the real-world setting. Then came 2023, where we had a number of events in the marketplace that were relevant for us. First was the presentation of the ctDNA analysis of the INTRIGUE study, first presented at a virtual plenary at ASCO in January, and then presented at the large ASCO meeting in Chicago in June. In between those two presentations, the NCCN guidelines listed ripretinib as an option for treatment in the second line for patients who are intolerant of sunitinib. So all of those are off-label uses, so we don't promote those. However, that created a degree of buzz and awareness in the space where we are confident that we saw an increased use of QINLOCK in earlier lines of use than the fourth line, which contributed to the significant, you know, uptick in revenue growth that we saw in quarters 2, 3, and 4 of last year. Do you expect this to continue throughout 2024, and what do you think the ultimate peak sales potential is? Yeah. So we expect 2024 to be another growth year for QINLOCK. 2023 was a record year for us, and we expect 2024 to be a growth year on top of that. You know, in terms of peak revenue opportunity, we've communicated that the fourth line opportunity alone we see a $175 to $200 million opportunity there. Now, of course, there is significant growth opportunity as it relates to the second line driven principally by our INSIGHT studies. So our hope is that through our phase III INSIGHT study, where we are looking to replicate the data that we presented from the ctDNA analysis of INTRIGUE, Matt can certainly go into more details about INSIGHT. But, if that is successful, and we're able to get an indication there, we think that that additional indication expansion will bring- will really double the peak sales opportunity, and that's just in the U.S. alone. So that would take us from $175 million to $200 million to upwards of $400 million in the U.S., and then, of course, that doesn't include the continued geographic expansion that we have had underway and will continue to have underway outside of the U.S. So, Matt, when are you gonna finish enrolling the INSIGHT study? Yeah, so the INSIGHT study. Yeah, thanks for the question, Tyler. You know, the INSIGHT study is the confirmatory phase III study that we're doing in the second-line GIST population, who harbor the exon mutations and the primary mutation in exon 11, plus the secondary resistant mutations in 17 or 18. This follows the data that, Dan was mentioning about the INTRIGUE, a second line study that we reported, last year at ASCO, and we published in Nature Medicine, so a top-tier journal in January this year, showing that we had this outsized treatment effect with a, a progression-free survival of 14.2 months versus 1.5 months for the control arm of sunitinib, and the response rate was 44% for ripretinib versus 0% for sunitinib. So really suggesting the standard of care there, sunitinib, really had very limited or no, no benefit in the subpopulation. So the INSIGHT study is in 54 patients. It's a 2-to-1 randomization, so the patients have the opportunity to be randomized to the active arm of ripretinib, and there's also a crossover as well, too. So the study's enrolling, actively enrolling patients. We have 34 active sites throughout the globe in 10 different countries, and we're really looking forward to completing enrollment in the study. Yeah. So, we haven't given guidance as to when we'll complete the trial. Of course, as we get closer to being able to project that, then we'll be able to update folks at that time. Yeah. So 34 active sites, 54 patients, so it's 1.5 patients per site, roughly, right? It can be two. Okay. All right, you talked about peak sales for the second-line opportunity. And you said you'd give an update, though, on enrollment later this year, right? With INSIGHT. Our practice has been on clinical studies and pivotal studies to provide updates on enrollment as we get close to full enrollment, and we have a sense of when we'll be able to read out the study. So I'm sure we'll have a qualitative update, Tyler, on how enrollment is going. As Matt was saying, we've been really pleased with the enthusiasm from the investigator community, and we expect to see continued strong advocacy for the study. Yeah. Yeah. Such a dramatic benefit, as Matt outlined. All right, vimseltinib. So you guys reported at the end of last year, top line phase III MOTION trial data, which was very successful. Maybe, for the audience, you could give the brief highlights of that data readout. Again, thanks. The MOTION phase III study is using our CSF1R inhibitor, vimseltinib, in patients with tenosynovial giant cell tumor, TGCT. This study was done in 123 patients, with a randomization of patients to vimseltinib versus placebo. And we're able to report that. We're very delighted to put out the top-line results in October last year, where we had met the primary endpoint of objective response rate by RECIST criteria, with a 40% response in the vimseltinib-treated patients versus 0% for the placebo-treated patients. In addition, we had six key secondary endpoints in the trial, and we were able to meet statistical significance for all six of those secondary endpoints. We did also, at the top-line results, readout, report in the first two of those, and the first one was, objective response rate by tumor volume score. So this is a different measure from RECIST, using the volumetric estimate of the tumor in the joint space because of its irregular shape and asymmetric growth. And weaving its way through the joint space, RECIST criteria are not exactly, the best criteria for looking at response. So using a volumetric score, we're up to 67%, TVS response, compared to 0% for placebo. And the last, so the next secondary endpoint that we read out was range of motion, and we had a fivefold improvement in range of motion. So in total, really great objective meeting the endpoints in the trial, and we're set to present more data from the Phase III trial in the second quarter of this year. What should we expect from the additional data that's gonna be presented next quarter? Yeah, importantly, in this disease, it's just not how the tumor responds, but how patients feel and function. And so we incorporated into the trial very important secondary endpoints, looking at patient-reported outcomes and quality of life. And these are the rest of the data that will be reported out from the trial. As we said, though, we did meet all the key secondary endpoints in terms of statistical and clinical meaningfulness. So, overall, it was a very, very positive trial. Okay. And later in the year, we're going to get another Phase I/II update. Felt like it was mature when we saw the last update in the fall, but now it's gonna be in, you know, incredibly mature, and obviously, the response rates continued to improve, as did duration of treatment. So, I guess we're going to have another year of follow-up, but what, what should we expect from that update? Yeah. So from the phase I/II study, which also has been in TGCT, TGCT patients, both from a dose escalation perspective and then in our expansion cohorts in previously untreated patients or patients who received a prior inhibitor of the CSF-1 receptor. We reported at CTOS last year, the best overall response rate is 72% in the patients in the dose escalation phases trial, as well as a 64% response rate in the patients who were previously untreated. In addition, the patients that received prior inhibition of the CSF-1 receptor had a 44% response rate. And also importantly, the duration of therapy in that population was quite prolonged. So in the dose escalation part of the study, where patients have been on the study the longest, the median treatment duration was 25 months. In the trial, the patient, who's still ongoing, it's the longest patient, has been now on the study for 4 years. With 1 year of follow-up, we'll be able to report out additional information in the trial in the second half. Okay. What are the gating items to filing the vimseltinib NDA and MAA submissions during Q2 and Q3, respectively? Yeah, the team is working really hard, Tyler, on pulling together all of the pieces of data and populating the modules for the filing of the NDA and then the MAA one quarter after. So we're really pleased with how tight the two filings are going to be, but it's really the usual and customary sorts of activities and writing that's going on right now as we prepare for those filings. Okay. And, I mean, you guys are absolutely intent to commercialize it, both in the U.S. and ex-U.S., right? That's absolutely the case. I mean, as Dan outlined, our great success with QINLOCK in the US, we have a really strong commercial team here, and we've invested in the 40 or so person organization in Europe for QINLOCK. That's allowed us to commercialize QINLOCK there, and with the nice overlap in the prescriber base between physicians who treat patients with GIST and those who treat patients with TGCT, it makes a lot of sense for us to commercialize on our own in Europe. And then we'll seek to work with distributor partners in other territories where we don't expect to, to build an organization on our own. I think a good example of that is our recent announcement of a distribution arrangement with a partner for Central and Eastern Europe, for QINLOCK, specifically. And we'd likely do something similar with vimseltinib in the future. For the key European markets, Western European markets, we intend to commercialize vimseltinib on our own. Based upon your interactions, does the EMA have a similar thinking as the FDA from a regulatory perspective for this indication in TGCT? Yeah, I think what one of the benefits I think that will accrue to us and the program is the fact that we have, as Matt was mentioning, a raft of secondary endpoints that really capture what it means to a patient to experience tumor shrinkage in TGCT. So that total package of data from the MOTION study, we think will be really helpful, not only as we take the data package to EMA for regulatory approval But then looking forward to eventual negotiations with HTA bodies in Europe and even candidly in the US, where we believe there'll be an opportunity for us to show broadly how vimseltinib benefits patients beyond just tumor shrinkage. So we're excited about the strength of the data, as Matt had mentioned, the fact that we achieved both clinical significance and statistical significance for all six of those key secondary endpoints in the study. So it's a really robust data package, both from a regulatory and commercial point of view. So you guys have done a ton of market research in this area? So maybe you could provide the brief highlights of that market research. Sure, absolutely. So, we have done quite a bit of work both market research as well as analytics using U.S. claims data. And that analytics has been really important to helping us understand the patient journey, the market size and structure. And some of the key insights align extremely well to an opportunity that we believe we're really uniquely set up to take advantage of. So, what we see is, in claims data, we identified 1,400 treatment incident patients who have the following attributes: they're diagnosed, they're being treated with systemic therapy, and importantly, they've recently seen a medical oncologist. The reason we believe all of those attributes are important, including the medical oncologist engagement, is we think this reflects the point where these patients are in their journey, where they're likely to be really good candidates for a product like vimseltinib. Also, it's where we have our experience and the capabilities that we've built within that medical oncology setting. So that 1,400 patient opportunity, just on a treatment incident basis, maps to a $700 million total addressable market, just in the US. And then in addition to that, we've identified 9,000 patients who have the same attributes, but on a prevalent basis. And these patients are either receiving TKIs today, or they're receiving pain and steroid medications to manage the, you know, really debilitating burden of their disease. And we think that's really important, again, because it signals where these patients are in their journey and the fact that they would be really good candidates for a disease-modifying agent, as opposed to something that's just palliating their disease symptoms. So we think that those patients will be our real target at launch. We see when we map those patients to physicians, as Steve said, there's a significant overlap with our GIST prescribing universe, about 70%-80% overlap, which really provides a unique opportunity for us, not only for a really capital-efficient commercial footprint, but also to launch into a physician community that we know really well. These are people that we've been building relationships with for multiple years now. And so, we think that there's opportunity beyond that core opportunity to grow this space over time because we see another 1,300 treatment incident patients who have the same attributes, except that they haven't reached an oncology office yet. They may still be in kind of that surgical part of their journey, but they are receiving systemic therapies to palliate their disease. So we think that through, you know, patient education, we may be able to drive more of those patients to raise their hand and welcome a consultation with an oncologist to more fully explore their options. And of course, none of that touches on the European opportunity or ex-US opportunity more broadly, those figures are just US. So we think, taken together, there is not only a significant opportunity at launch in the US and outside of the US, but also opportunity to grow the market over time. Okay, that's helpful. So why do you guys think you could sell $hundreds of millions with vimseltinib when TURALIO has essentially been a failure of a launch? Yeah. So it's a great question, and really, I think the question comes down to, is the performance that pexidartinib has, has demonstrated, is that a pexidartinib-specific issue, or is that a market-specific issue? And we feel really confident that this is a pexidartinib-specific issue. So not that pexidartinib doesn't have its strengths and, and its ability to help certain patients, but I think those who have, you know, read up on the story here in TGCT know that pexidartinib is the only approved agent in this space, and it has a history of the risk of fatal hepatotoxicity. And so the FDA put a black box warning on the label, required a REMS program with very intensive liver monitoring. And it's important to keep in mind that this is a patient population that otherwise is healthy. That this is not a lethal indication. It's a very locally aggressive and debilitating disease. However, it's not life-threatening, and thus, a patient really has to have pause when they're deciding, "Do I wanna go on a therapy that's gonna, you know, put me at risk of fatal liver tox?" And so that's been a real burden for the pexidartinib launch, and we can map the $700 million opportunity that I mentioned before in the U.S. alone, to the $30 or so million that pexidartinib has delivered quite easily in the data. Because that $700 million opportunity I mentioned is based on 1,400 patients, treatment incident patients, about half of which get a TKI today. That's about 700 patients. Only about a quarter of those are getting pexidartinib. So now you're down under 200 patients a year, and pexidartinib, pexidartinib also has a relatively short time on therapy as a result of a number of issues, many of which I just touched on. And so, we can map that $700 million to the $30 million that they've done, you know, quite easily in the data, and that gives us great confidence, and has for quite some time, that this is really a pexidartinib issue, not a market opportunity issue. And we think that with a better product, best-in-class profile, we've put we've tested in a blinded fashion. We've taken the vimseltinib data, and we've tested it with physicians, and they've said that, "Yes, this is now the combination that we've been looking for." Meaning, you know, the efficacy of a potent CSF1R inhibitor, yet without the baggage that the only approved CSF1R inhibitor has, as it relates to the liver toxicity. What gives you guys confidence that vimseltinib will not have that same baggage upon approval? Well, the fact that we have no evidence of cholestatic hepatotoxicity in the clinical experience with the drug, and I think it's known quite broadly, that this is not an effect that is a non-target effect, meaning the cholestatic hepatotoxicity, it's an effect seen with a single drug with pexidartinib. So we continue to believe, as Dan was saying, in the best-in-class profile potential of the drug, and that we avoid this potentially fatal hepatotoxicity seen that's off target with pexidartinib, and we have the right blend of great efficacy, as Matt articulated, the firm and strong data now from the secondary endpoint, showing patient benefit as measured by PROs, together with a nice safety profile. We remain as confident as ever in the profile of the drug and the potential for the drug to benefit patients with TGCT. So, SpringWorks Therapeutics in the desmoid tumor space has received a lot of interest lately. As you guys know, they have their first approved product. Are there parallels between the desmoid tumor market and TGCT, in your opinion? So there may well be similarities and also differences. I mean, we certainly are not the right people to talk about, you know, SpringWorks and desmoid. I mean, certainly these are both diseases that are non-lethal diseases. These are diseases where there's the potential, at least, for long duration of treatment for patients, and where patients need to make their way to an oncologist for treatment. So those may be some of the similarities. But we, you know, we continue to see TGCT as a really exciting opportunity. We believe we've been really conservative in how we've mapped out what we see as the initial commercial opportunity here in the US and the opportunity for that to expand in the future. As you know, and as we announced earlier this year, we're now expanding the development program to take vimseltinib into chronic graft-versus-host disease. So adding yet another opportunity for us to benefit patients and extend the utility of this really potent and selective inhibitor. And that's all made possible, in part, by the fact that we have really strong IP for vimseltinib, with a composition of matter out to 2034, and with patent term extension, not counting secondary patents, but just with patent term extension, that would take our coverage out to 2039. So we have a really long runway to fully prosecute the opportunity in tenosynovial giant cell tumor and then also to explore use in GVHD, as I mentioned. That's great. Perfect segue. GVHD phase II kicking off by the end of the year. Mechanistically, why is it well suited for GVHD, and what existing evidence do you have to support that it will work? Yeah, so as we've highlighted, one of our goals this year is to begin the phase II proof of concept study of vimseltinib in chronic graft-versus-host disease. It's known that GVHD is a, an immune-mediated pro-inflammatory disease, requiring multiple signaling pathways, including B cells, T cells, and macrophages. Preclinical data was done or preclinical studies were done to show by knocking out macrophages, you can ameliorate or lessen some of the chronic fibrotic complications of graft-versus-host disease. And recently, Syndax has had some clinical proof of concept using an antibody to CSF-1 receptor showing that there was activity in GVHD. Our drug, of course, is an oral therapy, and the current standard of care for GVHD is using oral therapies, whether it's steroids, ibrutinib, Jakafi, or REZUROCK. So having an additional oral therapy to complement those other treatments could be very beneficial for these patients with chronic GVHD. You wouldn't try the acute setting, right? It would. You're just focused on chronic. Yeah, it's more of the chronic that leads to very, you know, debilitating complications for patients, particularly the fibrotic complications of the skin or in the lung. And so that's really where the opportunity is for, macrophage-driven signaling pathway. We'll talk more later this year about the GVHD opportunity and how we see the development path. We haven't yet disclosed a lot of details about this initial phase II study in GVHD, but at a very high level, we think there's both opportunity as monotherapy as well as in combination to treat patients with this disease. As Matt was saying, given the fact that the backbone or standard treatments that are used presently for these patients are all oral agents, we think there's a really nice opportunity to slot in an inhibitor targeting a different pathway, like vimseltinib, into this disease as an all-oral regimen for the treatment of these patients. Very interesting. All right, so let's get to the early-stage pipeline with a few minutes left. So you have an AULK inhibitor, Pan-RAF, Pan-KIT, GCN2 activator, which many people are familiar with. But if you had to point people to one or two of those programs or future data updates, which would they be? So we're excited about our early development pipeline. Tyler, as you're saying, we have an active program with our ULK kinase inhibitor, DCC-3116, that we're studying now in combination with our own QINLOCK agent in GIST patients, as well as with cetuximab in non-small cell lung cancer patients harboring the KRAS G12C mutation. So our goal this year is to identify recommended phase II dose, and then to move into the expansion component of the phase I/II trial for DCC-3116. But we also plan to have a first human trial with our pan-RAF inhibitor, DCC-3084, in the first half of this year. We'll be filing an IND with our pan-KIT second generation inhibitor, DCC-3009, in the second half of this year. And then for the GCN2 activator that you referenced, this is a research stage program where we presented initial data at AACR last year, as you may remember. And all of these programs have come out of our own research engine and remain wholly owned. So we're excited about, as Matt was saying, the breadth of the early-stage portfolio and how that complements now both our approved medicine in QINLOCK with the expansion opportunities that we see in the second line, and then, of course, vimseltinib coming up very soon, we hope, as our second approved medicine. On the Pan-KIT inhibitor, just roughly, how much larger could that opportunity be relative to QINLOCK in the second and fourth line? Yeah. So the way we view that program is it gives us, we believe, the opportunity to play in spaces where QINLOCK is not going to be able to benefit patients. So I think we've really clearly demonstrated in an all-comer population in the fourth line, that QINLOCK offers tremendous benefit for patients. We now have these data in a selected group of patients in the second line, so that's the basis for the INSIGHT study that we were talking about earlier. But that leaves a whole lot of white space, and just where there still remains a significant amount of unmet medical need. And so, our goal in designing DCC-3009, was to allow us to address those white spaces and the unmet need that exists for those patient populations. Whether that's in the rest of the second line population that we may not address with QINLOCK, or in the third line setting, these are all places where there are needs for better therapies for patients. Okay. And, just finally, on the Pan-RAF, what sort of patients do you think you'll go after with that program? Will you focus on, like, Class II and III, or potentially Class I, or all the above? So DCC-3084 is our Pan-RAF inhibitor, and we had designed this molecule to be potentially best in class as a RAF inhibitor, both from the physicochemical properties as a long residency time and a low efflux from tumor cells, also blood-brain penetration. And in the preclinical studies, it's shown to be active against all classes of RAF mutations, including Class I, II, III, CRAF heterodimers, as well as the fusion mutation as well, too. So, we'll be beginning the first human trial this year, and we'll look at the activity across all classes of mutation. Okay, great. Question? Are you done? Yeah, I've got a couple more. Go ahead. I was gonna ask what percentage of the population? For the webcast, what percentage of the INSIGHT study population are already capturing commercially with QINLOCK? So it's a good question. I think, if I'm understanding the question correctly, it's because we've noted some increased earlier line use, off-label, unpromoted, how might that be competing with or impacting the INSIGHT study? And we're not concerned about that. The level of energy that we've seen amongst our investigators has been really impressive. In fact, when we first showed them the results, showing this dramatic treatment benefit in this patient population for ripretinib, the term they frequently used was practice-changing. And so, we think that that energy and that interest in proving this out in a prospective study is really strong. You have to remember that, when it comes to the earlier line use, we think that a meaningful proportion of that is likely coming from the NCCN guideline component, which is in patients that are intolerant of sunitinib. It's hard for us to know exactly what percent of is coming from where, but frankly, that enables patients to receive the drug if patients are struggling with Sutent, which frankly, you could argue is actually third line. Given the interest in, you know, that population, which physicians tell us could be anywhere from 10%-20% of Sutent patients, we think that a considerable amount of this lift we've seen is likely coming from that, and given the interest level from investigators on the INSIGHT study, we're not concerned about that dynamic. Maybe just briefly, what's the latest on cash runway? Cash into the second half of 2026, so we ended Q4 with $352 million in cash. We're very well capitalized to take us into our vimseltinib launch, and we're excited to turn the page on the next chapter for the company. We're up on time here, but I'll end it with a final question. What do you guys believe is the most underappreciated aspect of the Deciphera story by investors? So I think investors are really just starting to understand the full potential of vimseltinib in TGCT. We spend a lot of our time in dialogue with investors as they understand the claims analysis that we've done and the benefit this drug could offer to patients, and I think that will be the area of focus for investors as we run into the lead up to the filing and then the eventual approval of vimseltinib. Great. Thank you very much. Thanks, Tyler. Thank you.