Thanks, everyone, for continuing to join us at the Stifel Healthcare Conference. My name is Bradley Canino, senior biotech analyst here. I'm happy to be hosting another fireside here. I've got a good chunk of the team of Deciphera Pharmaceuticals up here with me. I've got Steven Hoerter, CEO, Matthew Sherman, CMO, and Dan Martin, CCO. Thanks so much for joining us today. Really appreciate it. Yeah, our pleasure. Thanks for the invitation. I guess to kick this off, Steve, you know, we're coming out of a quarter with some positive news on the phase III pipeline program, continued momentum in market for the sales for QINLOCK. I guess, how do you like to describe the investment thesis in Deciphera today? So we're—Thanks, Brad. We're really excited about where we are as a company, coming off of the Q3 report, now two weeks ago, along with the top-line readout of the MOTION study. And the foundation of that excitement is really rooted in the strong QINLOCK performance. And as you saw in the Q3 call and on the announcement, we continue to see good growth in that business coming not only from the U.S., but also outside of the U.S., as we continue to launch outside of the U.S., and in Europe, specifically. And we expect with the INSIGHT study, which is now underway, in a second-line selected population in GIST, that that will also serve as a future source of growth for that brand. So really pleased with the performance of QINLOCK. And then on top of that, we reported out the phase III MOTION study for vimseltinib in tenosynovial giant cell tumor, and those data were truly exceptional and really affirmed for us our belief and our view that this drug has best-in-class potential for the treatment of patients with tenosynovial giant cell tumor. And so we're well on our way to having a second approved product, and one which leverages our existing set of capabilities and infrastructure that we have in the U.S. and in Europe. And taken together, we think these two products, on a global basis, have the potential to benefit thousands of patients and also generate $1 billion or more in peak revenue. So we think it's a very compelling investment thesis, looking even just at these initial two products. And then, of course, coming behind that, we're a research-based organization. We have a rich portfolio and pipeline of earlier programs, and that rich pipeline will continue to fuel our growth into the future. But we think we've now achieved what relatively few biotechnology companies achieve, which is to actually make that transition to be a multi-product company. So we're excited to get the package in front of the FDA and the EMA next year, and then work with the regulators to bring that product to patients. Yeah. Okay. Maybe to drill in on QINLOCK sales, two consecutive quarters here with nice double-digit quarter-over-quarter growth. Just walk through what's driving that, given the stage we're at with the launch now, and which ones do you expect to be tailwinds continuing into next year? Yeah, thanks for the question, Brad. So, we have had continued success in the fourth-line setting. We've continued to execute, the team's done a great job, and to make sure that we remain the standard of care in that setting. What we have talked about leading into the second quarter of this year was that we saw gradual growth in that fourth-line setting as a result of a gradually increasing average duration of therapy. And then, over the last couple of quarters, Q2, Q3, were really record quarters for QINLOCK by any measure, very much demand driven. And we believe that that growth has been impacted by increased, unpromoted earlier line use, so off-label use, per physician decision. There were a couple of events that happened earlier this year that we think were really important for this. One was when we presented the ctDNA analysis from the INTRIGUE study, showing this dramatic treatment benefit in patients with a exon 11, 17, 18 mutational status, as well as the NCCN updating the guidelines with ripretinib as a second-line treatment option for patients who are intolerant of sunitinib. We think those two events really contributed to this increase in earlier line use. It's as we look ahead, we expect to continue to be the real dominant leader in the fourth-line setting. As it relates to this recent growth that we've seen in earlier line use, we don't know if that will persist. That's something that we'll continue to monitor and provide color on, as appropriate in the coming quarters. Yeah. Maybe two follow-up questions there. One is, how are you able to track the potential for some of that growth to be from earlier line? Because you said you think it's coming from there. And then the second, you know, the last comment you had is a little conservative. You're not willing to extrapolate forward yet, that this is gonna be something that continues to be a material driver. Why not? Yeah, great questions. So I'll take those in order. So, measurement of use by line of therapy is a bit challenging. You know, we get data on bottles. It's hard to know which bottle is used in which line of therapy. So we can't know that from our own data, and so we have to look to additional sources to try to understand that, and the data just aren't great for assessing this. So, really, it's been a product of two factors. One is we had a long-standing trend with our fourth-line business that we believed was very highly penetrated because of the success we had at launch with the high unmet need and the really strong product profile. So that provides a real sort of basis from which to assess a change in trend, which is what we've seen over the last couple of quarters, timed with these market events that I mentioned. In addition to that, we do have anecdotal evidence from some of our various market research instruments, but also importantly, just our engagement with KOLs. At ASCO, for example, while again, this is something we do not cannot and do not promote, you know, the interest in this analysis from the INTRIGUE study as well as the guidelines is certainly very high, a lot of energy for that. So, you know, taken together, we feel confident that the results the last couple of quarters have been impacted by these factors. Now, candidly, the reason that we have been somewhat cautious in our guidance, in the way we talk about the dynamic over the last couple of quarters, keep in mind that, you know, this is off-label. So as I mentioned before, it's not something that we promote, and we know that GIST is a promotionally sensitive market. So it's hard to predict if the impact of those recent trends are something that are going to persist the same way we would, you know, lean in and predict that if it was something we were able to go out and drive. In fact, you know, I think it's important to note this is really ties into one of the reasons we think it's so important to do the INSIGHT study, to be able to actually have a label-enabling study in that setting and be able to go promote and make sure that all GIST treaters across the academic and community, you know, continuum, are highly knowledgeable and aware of this information. Yeah. Well, Dan, you mentioned the reception from KOLs on the ctDNA data. Maybe to Matt, what is the status of the INSIGHT trial and the receptivity you're seeing as you're going and trying to opening up some of those sites? Yeah. So thanks, Brad. So it's really an exciting time to open up the INSIGHT study. So this is our confirmatory phase III study in the GIST population, second-line patients who harbor mutations in exons 11 and 17 and 18. And this is really based on the profound treatment effect we saw in the subset analysis from the INTRIGUE trial, where we had a progression-free survival of 14.2 months compared to only 1.5 months for the sunitinib treated arm. And the response rate, the objective response rate of 44% versus 0% for the sunitinib patients. So, you know, with that as a background, we announced back in August that we opened up our initial sites for the INSIGHT trial, and we continue to open up more sites and screen the first patients in that trial. The reception from the investigators is actually quite positive. They're really, you know, at the point in time now to incorporate precision therapy for the treatment of GIST patients. And so the ability to identify a highly selected and responsive subgroup of patients for the treatment with QINLOCK really will be practice-changing for them. Yeah. Now, as you mentioned, I think one of the reasons for running INSIGHT is predicated on really understanding that sunitinib is likely to do very poorly, unfortunately, in that patient populations, have a vastly inferior PFS. Is there a plan to conduct a futility analysis at any point to see if this is aligning with the post-hoc data you got out of INTRIGUE? So you know if it's worthwhile to continue to spend the resources into that trial. Yeah, there is no plan for an interim analysis because, of course, this is a small study. It's only 54 patients that randomized to ripretinib versus sunitinib. But because of the outsized treatment effect that we see, it takes only a few patients to confirm this in the follow-on INSIGHT study, so there will be no planned interim analysis. Okay. Maybe to Steven, as you've thought about this investment opportunity, you know, with this idea of likely having a ctDNA element on the label, you know, you've been involved in a lot of drug development in the past. Is this an attractive opportunity to be investing in when it's not currently done in the community today? Yeah, in my experience, when there is sufficient, when there's data that catalyzes the desire to test, then testing occurs. So in other words, you know, the data that we have from the INTRIGUE analysis is highly compelling, as Matt outlined, a 44% response rate versus zero in the sunitinib arm, a 17+-month PFS versus six weeks in the sunitinib arm. So that's the sort of data that I think will catalyze the adoption of ctDNA as a mechanism or a means to identify patients in the second line setting. I think it's also really important to remember that this is peripheral blood. It's a tube of blood that is drawn from a patient, and patients, of course, who are having blood draws all the time. This is not a requirement for a fresh tumor biopsy. So it's not an invasive procedure to draw a tube of blood. It's a rapid turnaround time of seven-10 days for physicians to get the information that they need to make their treatment decision. So there really aren't, in my mind, barriers to adopting ctDNA as a means to identify these patients. Okay. Based on the conversations that we've had with investigators and with physicians, as Matt was saying, they're excited about the potential to bring the treatment of GIST into the 21st century and to be able, for the first time, really, outside of PDGFR alpha, to identify patients who will respond to a drug like QINLOCK versus a drug like SUTENT. So, I think that level of enthusiasm will carry forward into the INSIGHT study and then ultimately, assuming success, into commercialization of QINLOCK for this specific indication. Okay. Yeah, and Brad, I mean, I would just add to that, that you know, the KOLs have shared with us that just to keep in mind, just is really an archetype for tumors, where differential response to therapy is driven by the mutational status. And so they actually view ctDNA as a great tool in this space, not only because of the point Steve made, but also because you know, it's often the secondary resistance mutations that are driving progression post-imatinib. And so the idea of doing serial biopsies, you know, solid tumor biopsies, at that point in the patient's journey, just doesn't make a whole lot of sense to them. And then furthermore, given the polyclonal nature of the disease, the reality is that a solid tumor biopsy may miss, you know, the fact that there are certain tumors that are being driven by certain mutations, and other tumors in other locations of the body being driven by other mutations. So the ctDNA really lends itself to this new paradigm that Steve mentioned, the KOLs are so interested in pursuing. Yeah. Okay. At the start of the year, you gave some target sales for peak sales in the U.S. for QINLOCK. One of them was fourth line, $175 million-$200 million. If everything works out in the INSIGHT trial positively, does that start to cannibalize some of that target opportunity? Yeah. So it's interesting, when we put out the, guidance about fourth line being $175 million-$200 million opportunity peak just in the U.S., we set that as a foundation for, what impact could the INSIGHT study have for this, business? And we said that we believe the INSIGHT study would double the peak revenue opportunity from $175 million-$200 million to $350 million-$400 million. And I mean, I think the way we think about that is that, that additional revenue would come from two primary sources. One would be increased patient opportunity, more patients in the earlier line, as well as, increased duration of therapy. So we would assume about eight to eight in half months of peak in the fourth line, and we're estimating somewhere in the order of 20 months at peak in the, this second line selected population, because of just how well they do on ripretinib. And so, while we would expect some of the patients who would have received QINLOCK in the fourth line would now, under, in that scenario, receive it in the second line, they would actually be increasing their average duration of therapy on the order of 11-12 months. And so in that sense, you know, those patients, I wouldn't say they're cannibalized exactly, we think of it as sort of shifting from one line to the other, but, having incremental benefit for the good of the patient, but then also incremental revenue impact. Got it. Maybe switching over to ex-U.S., you know, I think there's been a pretty consistent growth pattern for that. What could change maybe next year that could alter the direction and growth, either up or down? The dynamic outside the U.S. is really driven by market access. So as you're well aware, you know, the first hurdle is getting regulatory approval, which we did at the end of 2021, and then the next step is on a country-by-country basis, unfortunately, going through the market access process, the pricing and reimbursement negotiations. So in Germany, we were able to price freely for the first number of months. We then got to a final negotiated price in Germany, which is just over EUR 18,000 per month. And we are in the process now of negotiating in other territories to get to final prices. We just completed our negotiations in Italy, and so the product is now, as of a few weeks ago, been launched in Italy. We're selling in France under a special post-approval paid access program, have not yet finalized price there. Spain is likely to come in the coming months, and then we would expect there will be other countries and other territories in Europe, where we will finalize price and reimbursement, and therefore, open up market access to the product. So unlike the U.S. market, where, you know, it's really straightforward, once we get regulatory approval, we price our drug, and then we launch our drug. In Europe, it's a very different process, which results in a very different trend in terms of how revenue evolves across the EU or the largest markets in Europe, which is really where our focus has been up until now. Yeah. In the markets where you have launched and gotten reimbursement, are you at the level of fourth-line penetration that you've been able to achieve in the U.S., which when I model out, is quite high? We don't believe so. So we take Germany, for example, which is the market where we have been launched for the longest period of time. We don't believe yet that we are at peak penetration in the fourth line setting. And that's, that is, in part, a function of the German healthcare system, where it's actually quite similar to the U.S., with a pretty thriving community or office-based physician practice in oncology. Whereas in other markets, like in France, it's more of a centralized practice of medicine, where patients just end up at specialist centers with their disease. Yeah. Okay. Maybe onto vimseltinib. Congratulations on the positive pivotal data there. What I want to know is, just kinda be walked through the scenario of how you're thinking about the, the pivotal data leading to a differentiated commercial outcome. Because I think it's really easy to point to TURALIO, the end market drug for this disease, and say it's only selling $30 million a year. So how do you go change that now with the data set in hand? Yeah, so from a product profile perspective, the MOTION data puts us in a great position to have a clearly best-in-class agent from the tumor shrinkage endpoints of overall, overall response rate, objective response rate, or tumor volume score. Clearly, the drug shrinks tumors, and then with all of the secondary endpoints that show how that translates into really important and clinically meaningful benefit for the patient, we think—not to mention the really clean safety profile, we expect that to be a really strong best-in-class profile in the space. I think, we get the question about pexidartinib, and you know, the $30 million-$35 million per year that they've done. I think what's important to note, our analysis of the U.S. claims data, you know, shows very clearly that quite simply, pexidartinib was unable to penetrate the market opportunity. We see 1,500 incident patients and 9,000 prevalent patients who were diagnosed, treated systemically, and who have engaged with an oncologist. When we dig into those, we looked at the incident treatment year of 2022, 52% of those initiated on a TKI, the others initiated on prescription pain and steroid medications, really polypharmacy to manage the significant burden of their disease. Of the 52% that initiated on a TKI, only 27% of those were pexidartinib starts. That works out to about 14% of that core opportunity that we're focused on at launch. And if you add to that the fact that, you know, TURALIO actually has a rather short duration of therapy, in the claims data, only about 10 months. And by comparison, our median duration of therapy in our most mature data set from the phase I study that we just presented was 25.1 months. So based on these factors, you know, we've put together an estimate of a $500 million U.S. total addressable market, which, honestly may be conservative, because we assumed only 18 months duration of therapy in that calculation. And we assumed, to monetize that opportunity, the TURALIO WAC price of $21,865. Taken together, we think that, you know, not only will we have a best-in-class agent, we really understand the market, we understand where these patients are, who treats them, and we think we can penetrate the opportunity to a much greater extent than pexidartinib was able to. How critical will it be to not have a REMS program on your label like TURALIO has to achieve some of those goals you outlined? Yeah, it's a really good question. So first and foremost, you know, we believe the risk of fatal, fatal liver toxicity due to the cholestatic hepatotoxicity that drove TURALIO's black box warning in REMS program, you know, is certainly something that creates pause, right, in the minds of treating physicians as well as patients with TGCT. Cholestatic hepatotoxicity is something that has only been seen with pexidartinib. No other CSF1R inhibitor, be it small molecule or monoclonal antibody, has shown evidence of, of this adverse event. So, you know, we continue to have no evidence of cholestatic hepatotoxicity in our data, and that's part of the overall really compelling safety profile that we think will be a really important differentiator for vimseltinib, for both physicians and for patients. Yeah. Now, you outlined an interesting element where a lot of patients are starting TKIs, but it's predominantly imatinib. And another element of this thesis that you've proposed is you've got a sales force overlap with GIST. And I'm wondering, you know, when your sales reps are out, or you're seeing these physicians that you call on at GIST, at medical meetings, because obviously, you're not promoting vimseltinib, but are you hearing that they're using imatinib? 'Cause it's a question to me is if your in-place sales force can kind of work on that opportunity of converting imatinib to vimseltinib, or if there will have to be a sales force expansion to go out there and find the other physicians that are treating TGCT. Yeah, another really good and important question. So we've been doing quite a bit of work, recently to understand not just the size of the opportunity, but the structure of it. Meaning, where are these patients, and who are the physicians, and how concentrated versus diffuse is that opportunity? We've really learned a lot, and, you know, what's clear is that these 1,400 treatment incident patients and 9,000 treatment prevalent patients that, that I described before, importantly, they're seeing-- recently engaged with an oncologist. And that's really important because that's where we, that's where we operate. And many of these oncologists, actually, up to 70%-80%, as you mentioned, are the oncologists that we call on today. So we think that's really important from a couple reasons. One, these patients are at a point in their journey where they really are seeking additional options beyond surgery. We think that because of the overlap is so significant, we think that it affords a really capital efficient expansion, really incremental expansion to reach the opportunity, and frankly, the opportunity to leverage existing relationships with many of these treaters at launch. So, you know, for all these reasons, we think that this is a really unique fit into our portfolio. Just to circle back to one of the questions you asked in the beginning, when we're out there doing our market research, talking to physicians, do we hear them using imatinib? The answer is absolutely yes. I think one of the challenges is, and what we see in the data, is that pexidartinib abusers tend to be the academic providers who maybe were on the ENLIVEN study. They have the institutional support to deal with the REMS requirements and whatnot. And so often what happens, I think, is that analysts or investors will do a couple of calls to do doc checks with those KOLs, and they'll say, "Yes, I have a handful of patients, and they receive pexidartinib." We see a very different story when you look at the whole of the market in the data. And of course, you have to remember that imatinib, as Dan was saying, is listed in the treatment guidelines, but the level of evidence to support its use in this disease is very limited. These are all based on retrospective series of patients. Two manuscripts were published, which showed best response rates of between 19% and 29%, I think the number was. So I think this is a situation where there's a significant unmet medical need for a drug that is effective and also well-tolerated, and certainly, the data from MOTION supports that best-in-class profile. So we're excited to, as I was saying earlier, to get the drug out to regulators and then to get it to the patients who need it. Just to add why vimseltinib will matter to patients is not just the response rates that we were able to measure by RECIST criteria and by the tumor volume score, both objective response rates on the tumor itself, but it's how patients feel and function. Mm. So looking at their functional ability, their ability to have increased range of motion in their joints. We're able to show a fivefold increase in range of motion compared to the placebo-treated patients. In addition, we incorporated a number of patient-reported outcomes on pain and stiffness and physical function, and all of the secondary endpoints that we measured showed statistical significance compared to the placebo-treated patients. Really, it's the totality of data that will really have a major impact on the treatment of these patients. Yeah. Okay. Dan, I promise I will extend, expand my scope of due diligence for physicians. Maybe, I mean, you mentioned the secondary outcomes. A related question that I have is, in Europe, TURALIO was not approved. And I guess when you read the documents that outline the reasons for the rejection of TURALIO, what gives you the confidence that you can get vimseltinib approved in that market? Yeah, so the EMA, you know. So the TGCT presented the data to the FDA, which approved pexidartinib with a black box warning because of the associated fatal hepatotoxicity that was seen. But when it was presented to the EMA, the European Medicines Agency, they rejected the application. I mean, they felt that the data did show a benefit in terms of the efficacy, but it's really the safety profile, the risk of the hepatotoxicity, but also the absence of the secondary endpoints confirming the functional benefit or the impact on the patient's symptoms and patient-reported outcomes. And in that trial, in the ENLIVEN phase III trial that was conducted with pexidartinib, there was a lot of challenges in their collecting complete data sets for the patient-reported outcomes, and that, like, led to its rejection by the EMA. We, on the other hand, were very diligent in being able to collect our secondary endpoints and learn from their experience, so we had very rigorous evaluations of these self-reported, patient-reported outcomes, and that has, you know, led to our having these statistically significant, meaningful differences in our top-line results. Okay. Maybe if we expand on where else vimseltinib might be able to go, do you see other opportunities, that you're looking to pursue for the asset? Now that we're on the other side of the readout of the phase III study, yeah, we, we have been actively, actually in preparation for the readout, evaluating other potential indications, whether that could be expanding the reach within TGCT or looking at, at different indications entirely. You know, we know from competitor programs, that now this mechanism of action has been validated clinically in chronic graft versus host disease, as an example. There's certainly data preclinically that would, support the use of these agents, in, in fibrotic diseases like IPF. So we're very actively evaluating where else we might pursue, vimseltinib and explore its, ability to benefit patients, and also to, generate a return for shareholders. Given the very long IP runway that we have for vimseltinib, composition of matter takes us out to 2034 plus PTE. We think through the end of the next decade, we have very strong IP protection, so very ample runway for us to explore additional clinical opportunities for the product. Okay. All right, well, maybe we'll just close it out then on cash runway for Deciphera, and then what clinical milestones or even regulatory milestones that will get you through? Sure. So we at the end of the quarter of Q3 had $377 million in cash and cash equivalents, which we believe will take us into 2026. So ample runway to get to certainly filings for vimseltinib in the U.S. and in Europe, to get to approvals and introduction of the product in the U.S. at least, and potentially globally, depending on timelines. So that very importantly is all within our existing runway. During that time frame, of course, we expect to continue to see the QINLOCK business evolve with the conduct of the INSIGHT study and the potential to get us to, you know, a broader label for QINLOCK, all while we continue to advance the earlier stage clinical pipeline, whether it's our first-in-class ULK inhibitor or the pan-RAF inhibitor, for which we're due to file an IND, as was our milestone by the end of this year. Okay. Well, very good. Steve, Matt, Dan, thank you so much. Really appreciate it. Thanks, everyone, for listening. Thank you.