Well, good morning, everybody, and welcome to this next fireside chat session of the Guggenheim Biotechnology Conference. My name is Paul Jeng. I'm a member of the biotech research team at Guggenheim, and I'm very happy to kick off the day today with Deciphera Pharmaceuticals as our next presenting company. With us today is Steven Hoerter, CEO, and Tucker Kelly, CFO. Welcome. Thank you. Good morning. Thank you. Thanks for the invitation. Yeah, great. So, just to get started, you know, there's a lot of moving parts with the company this year, as you're continue to grow your commercial franchise as well as your early pipeline. But, I want to start our discussion with the program that's sort of at the transition of those two axes, which is your CSF1R inhibitor, vimseltinib. So last fall, you had some positive, you know, top-line data from the MOTION study. Can you sort of summarize the key highlights from that data and how that positions you to address the unmet need in TGCT? Sure, I'd be happy to. Thanks again, Paul, for the introduction and for the invitation as well to be at this year's conference. It's a pleasure to be here. So, we were very excited in Q4 of last year to report the top-line results from the phase 3 MOTION study. And Paul, as you said, this was the pivotal study for vimseltinib in a disease called tenosynovial giant cell tumor. The study achieved its primary endpoint, which is response as measured by RECIST at week 25, and also achieved all six key secondary endpoints, including which we reported on responses measured by tumor volume score and then other patient-reported outcomes. And the drug was well-tolerated. So, really an exceptional set of data, which we think positions the drug to be potentially best in class for the treatment of patients with tenosynovial giant cell tumor. And maybe I'll spend just a couple of minutes kind of unpacking the data that we reported and putting a little more color to it. So, this is a disease that occurs in the joints, in the major joints in the body, and one of the characteristics of the disease, these tumors weave their way into the joint space, which oftentimes makes RECIST as a measure, a two-dimensional measure of tumor size, more challenging for the radiologist. Despite that, of course, as I mentioned, we achieved a 40% response rate in the vimseltinib arm versus zero for placebo. That was highly statistically significant. One of the key secondary endpoints was response as measured by tumor volume score, and this is importantly a different way of measuring tumor size, measuring volume, as the name suggests, which we think is a really appropriate and meaningful measure of size of tumor in a disease like tenosynovial giant cell tumor. As you may know, the threshold for a response, for calling it PR, using RECIST is a 30% shrinkage in tumor. TVS, however, the bar is much higher. It's a 50% shrinkage or reduction in tumor volume that then triggers a partial response. And so in this study, vimseltinib demonstrated a 67% response rate as measured by TVS. So we think that really speaks to the power of this highly selective agent for CSF1 receptor and how meaningful the clinical activity is as measured by response rate. In addition, we reported on five other, excuse me, one other secondary endpoint, one other key secondary endpoint. There were a total of six key secondary endpoints, two of which we reported on. The other that we reported on was range of motion, and what we saw for range of motion was a 5x improvement in range of motion at week 25 versus placebo. This is an important measurement in this disease because of how the disease affects the joint and the ability of the patient then to use that extremity, whether it be their arm or their hip or their knee. And this can have a significant impact in terms of a patient's ability to get from a sitting to a standing position or even taking a step up a step of stairs, a flight of stairs. So we were very pleased to see that profound benefit, showing us that when we shrink tumor in these patients with vimseltinib, that it also has meaningful additional benefits for patients. Now, what we haven't reported on yet, but will be reported when the data is released, the full top-line data is released, excuse me, the full data is presented at a medical meeting in Q2, will be data on the other key secondary endpoints. So that includes other measures like measures of physical function, measures of stiffness, measures of pain, and, and also other measures of quality of life. So, what we have disclosed is that each of those endpoints were both clinically significant as well as statistically significant, but we haven't reported yet on the details of those endpoints. At the top line, we also reported, of course, on the safety profile of the drug, which is very consistent with the data from the much more mature phase I-II study, where we showed that the drug was, is well-tolerated in this patient population. There was a very low rate of treatment discontinuation due to treatment-emergent adverse events in the vimseltinib arm. That was only 6%. So it shows that the drug was well-tolerated. Now, also, at the end of last year, we reported updated data from the phase I-II study of vimseltinib in TGCT. This phase I-II study is comprised both of the phase 1 dose escalation, but also of two expansion cohorts. Cohort A is the same population that we treated in MOTION, and Cohort B is a population that has seen prior treatment with a CSF1 receptor-targeted agent. What we saw in that study, in that updated data, was very encouraging activity in this group of patients. So, with longer-term follow-up, we saw a 72% response rate as measured by RECIST in the phase I dose escalation part of the study, and then a 64% response rate, best overall response in Cohort A, in the phase II expansion. Now, one of the most important metrics we think that investors, and certainly we ourselves, are interested in is the duration of treatment. So, how long are patients staying on therapy with vimseltinib to treat their TGCT? And with the phase I-II study being the most mature set of data that we have, we think it's the best indicator that we have so far of what the real-world utilization might be of them upon approval. So in the phase I dose escalation part of the study, we saw a median duration of treatment of 25 months, so just over two years. And in cohort A in the phase II, it was a median of 21 months. And importantly, 47%-48% of patients as of the data cutoff remained on study. So, we will report later this year, updated data with almost an additional year's worth of maturity from the phase I/II, and that will help us to understand how that median duration of treatment has matured. It will also give us additional safety data with longer follow-up and additional efficacy data with longer follow-up. But we're certainly very encouraged by not only the phase I/II data that we reported last year, but we're really thrilled with the exceptional data from the MOTION study and how that now sets us up for an NDA filing in the U.S., which will occur in Q2 of this year, and then we expect the MAA filing to the European authorities in quarter three of this year. Got it. Great. Well, thanks for that overview. So then maybe looking ahead to a potential commercial launch for vimseltinib. Can you talk about sort of the sales force build-out that you would have to undertake? Do you have any initial strategy for high prescribers? And how does that marketing strategy extend to the community setting? Any other details that you have that you can share at this point? Yeah. So, one of the great things about vimseltinib and the upcoming launch that we'll have is that there's a high degree of overlap with our commercial effort in GIST. We've talked about a lot about the claims analysis that we've done, showing that we think in the US, there's sort of a 70%-80% overlap in terms of people who prescribe treatments for GIST and those for TGCT. So that fits in incredibly well with our current commercial presence, and we believe that's also the case in Europe as well. So today we've got just a little over 20 reps we call it with academic and community physicians. And so we've got a prescriber base since launch that's, you know, over 1,000 physicians. And so that sets us up really well for being able to put vimseltinib into the bag. We'll talk more as we get closer to the actual filing and approval about our go-to-market strategy. But in general, we think there's a core group of patients that are today already being seen by medical oncologists, where, again, we have this high degree of overlap, that we think will be really, attracted by the profile that vimseltinib brings with efficacy and safety. We've got a sales force that's already calling on these docs for the most part. So we think we will have to have some incremental, build there, but it's not gonna be significant. But we'll certainly add some reps, to try and get broader coverage, which will benefit not only the vimseltinib launch, but also, as well, our coverage of, QINLOCK in GIST. And so our key focus at the outset is on the medical oncologists, who today are seeing these patients, but we think there's a much broader opportunity beyond that. That goes to patients today that may not be getting a TKI or may not be seeing a medical oncologist, that are either at their PCP or at an orthopedic oncologist or orthopedic surgeon. Those are, I think, longer-term goals. Right now, we're gonna focus on the near term in front of us in terms of that 1,400 incident patients we can talk about today. But we think there's a larger prevalent pool and a pool of patients outside the medical oncologist that can help us grow the brand over time. Great. There is an on-market drug right now, pexidartinib, but you previously talked about how, you know, the REMS program and the black box have sort of hampered its uptake. How do you think that docs will initially position the two drugs? Do you think there's gonna be, you know, a rapid shift or something more gradual relative to the on-market pexidartinib? Yeah. So we, we see a very significant unmet medical need here in the U.S. and also in Europe. So pexidartinib, as you may know, is only approved in the U.S., it's not approved in Europe. And it wasn't approved in Europe because of the perceptions around the, the poor risk-benefit of the drug. And you alluded to and mentioned the REMS program and the black box warning, that's all related to the potential for fatal hepatotoxicity, which is an off-target effect seen with pexidartinib. And so as a result of that effect, as a result of the REMS and the black box warning, that's why we believe we see... When we look at the claims data, we see a minority share of patients are getting treated with pexidartinib today. So, when we go out and test our product profile of vimseltinib, based on the phase I/II data, for example, which we've done historically, physicians rate them the highest among all of the options that they have today to treat patients, whether that's pexidartinib or off-label imatinib. Importantly, when we've asked physicians in market research what their preferred agent would be to treat patients with TGCT, all of them, in fact, selected the vimseltinib profile, and it was a blinded profile. So that gives us a lot of faith and belief in not only the unmet need, that physicians are waiting for a better option, patients are waiting for a better option, but it also speaks to the potential for vimseltinib to be a very meaningful addition to the armamentarium for physicians who treat these patients. It also speaks, we think, as Tucker spoke to a minute ago, what the commercial potential is for vimseltinib here in the U.S. and also around the world. One of the things we've noticed is that when we looked at the prescriber base and who's prescribing TKIs or not today in the medical oncology community, you know, we broke it down by sort of the highest prescribers and then the prescribers who were not seeing patients as frequently. You know, there's still a very thin concentration. Among the top prescribers, the average is only three, and then amongst the lower prescribers, the average is about one patient. But there's a stark difference between kind of the treatment patterns today. So, what we see is that in the higher prescribers, they have multiple patients, more likely to be the academic docs, maybe they were involved in the trials for pexidartinib. You know, you get a much higher share of physicians there who are currently using pexidartinib. So, that's like almost 60%, 54.5%. On the other hand, the lower prescribers are using it much, much less. So, there they're, they're using the vast majority with off-label imatinib, and there's only 15+% that are actually using today pexidartinib. So we think that just speaks to the fact that it's a very thinly distributed patient population, that the KOLs are really comfortable going through the REMS program and comfortable with the safety profile, and that the community out docs are very much not so, and they're still using off-label imatinib. So, we think in either case, that vimseltinib has the, the best profile, as Steve talked about before, the market research bears that out, but there is a, a disconnect today in the market in terms of who's prescribing what. Okay. And so then on the commercial market, you've recently been talking about a U.S. TAM of about $700 million or greater, which I believe is a slight upper revision from, you know, the $500 million that you were talking about before. So maybe can you talk about sort of the puts and takes of the estimate, and that goes into that TAM? Yeah, that's right. So this TAM is U.S. only, and it's based on what we see in the claims data, and that's 1,400 incident patients each year who are diagnosed with TGCT and are being seen by a medical oncologist in some fashion. And so the math is pretty straightforward. What we do is we look at those 1,400 patients as part of the TAM. We multiply it by what we see as the expected duration, and so the difference you mentioned from the 500 and 700 is that we now have updated data from vimseltinib, and that's from the phase I/II study that Steve mentioned, and there we see in our most mature cohort that, you know, the median treatment duration was 25.1 months. So before we've been anchoring to what we see in the claims data for imatinib usage, and that had been in 18 months. So the only difference between the 500 and 700 is just using the updated data based on our product profile. And beyond that, it's, it's using right now the pexidartinib price, which is $21,800 kind of wholesale a month, and that's how we come up with the, the $700 million, again, in the U.S. alone. The other thing to say about that is that, one, we think that there's opportunity over time for patients to continue to, to have treatment, whether it's continuous treatment like that, or if they get symptomatic relief, maybe they come off, and then they come back. This is not a disease that, unfortunately, for a lot of patients, is cured unless surgery is successful, and for patients right now, typically, that are on a TKI, that- that's always not been the case. So we do think there's a possibility of, you know, recurrent treatment over time, and we've been looking at that as part of the phase I, phase II cohort B. And then in addition, you know, we haven't talked about pricing any more specifically, but, you know, pexidartinib set a floor, we think. So, that, to us, is an indicator of, you know, a price that's, I think, well accepted by the market. We think we've got a better product profile, so there may be upside potentially as well on price after we do our market research and get closer to launch. So we think that's the core initial market, that's $700 million. That obviously doesn't include the EU, where Steve mentioned there's no approved product or the rest of the world. And it doesn't include, we think, our areas for growth. So there's an additional 9,000 prevalent patients that have all the same characteristics. They're being seen by an oncologist in the last couple of years. They're diagnosed with TGCT. And so again, that with a new therapy that is well-tolerated, safe, and effective, could bring some of those patients back into the treatment funnel. And then beyond that, there are a lot of patients today who aren't seen by an oncologist. So we see about 1,300 incident patients each year that are not seen by an oncologist, but are treated typically by orthopedic surgeons or other physicians. So, again, these are other patients who can may well be amenable to having a systemic therapy. It doesn't include the, you know, primary patients from whom most of which surgery is curative. So, you know, we think this is a group of patients that are being medically managed and, and not necessarily getting surgical options. So, there's a lot of ways to, to win over time with with TGCT, and again, it's a great fit with our GIST franchise, and we think this initial core market is, is very, very readily gettable. Okay. And then maybe last on vimseltinib. So you recently talked about a proof of concept phase II for the drug in chronic GVHD. Maybe talk about the overall strategy in this setting. You know, would you sort of consider pursuing a third-line plus initially approval, or could you sort of go right into the early line settings and combinations? Yeah, we're really excited now to be able to potentially expand the program for them beyond TGCT and to pursue this new opportunity in chronic graft versus host disease, as we disclosed earlier this year. And that really has been driven by not only the strength of the data from the MOTION study and now being on our way to having potentially an approved product in vimseltinib, but it's also based on the fact that CSF1 receptor, targeting CSF1 receptor in chronic GVHD, is now very clinically validated as a target. You know, targeting these pro-inflammatory or pro-fibrotic macrophages in chronic GVHD has a significant benefit for patients. So what we've announced, as you referenced, is our plans to initiate an initial clinical POC study at the end of this year. And broadly speaking, we... You're right. We do see multiple opportunities in chronic GVHD. We see opportunities as monotherapy in later lines of treatment, but we also see opportunities in earlier lines, lines of treatment in combination. But the first step for us is to stand up this initial study to determine dose in GVHD, and then we'll determine, based on what we learn in the clinic, where we might head, whether it be as monotherapy or, in combination with another agent, or potentially both. But that will all be data-driven, based on what we see in the clinic. But it's an exciting, additional opportunity for us, for them, and we're enabled or, or can do that in, in part because of the very long IP runway that we have for vimseltinib. So, the composition of matter in the U.S. goes through 2034, plus PTE, so we believe we have very good IP coverage through the end of the decade, and that excludes secondary patents. So, we have a very long IP runway with the product, very similar case, in fact, with, with Qinlock, but we have a long IP runway with them, which gives us the opportunity now to make additional investments to benefit patients and also generate additional return for shareholders. Okay, so then let's talk about QINLOCK, which had another strong year of growth, $160 million roughly exiting 2023. You know, you're coming off about a year since the INTRIGUE data was added to the NCCN guidelines, as a recommended therapy in the second line setting. Do you have any visibility into contributions of off-label QINLOCK? How How much of that is in, you know, your last quarter versus, you know, additional growth in the fourth line setting? Yeah. So, we had, you're right, a really fantastic year with QINLOCK around the world in 2023, with $163 million of revenue. In Q4, the number was $46.7 million, so a strong contribution of just over $11 million from our ex-U.S. business, with the balance, roughly $35 million, coming from our U.S. business. We've seen a real change in the slope of that curve, particularly in the U.S. business in quarter three and quarter four of last year, which we think has been driven by an increase in unpromoted off-label use based on physician decision. So, importantly, this isn't a use that we can promote to because it is off-label, but we do believe that it's been triggered in part by the NCCN listing, that you referenced, which occurred in March of last year, where the drug is now listed as an option. QINLOCK is listed as an option for patients in the second line who are intolerant to sunitinib. In addition, as you know, we reported the data from the ctDNA analysis from the INTRIGUE study at the very beginning of last year. That was then again presented at ASCO in June. And so, there's been a lot of new data, in the second line with QINLOCK, showing the potential role, again, outside of the label, that the drug could play in this disease, and that, as you know, was the basis, meaning the analysis of INTRIGUE, was the basis for us launching a new phase III study, the INSIGHT study, so that we can pursue a label in that genetically defined group of patients in the second line. That study is now up and running and actively enrolling patients, and we're still opening sites for that study, but that's going very well. But certainly, the data that we generated from INTRIGUE, we think, has created and generated enthusiasm among physicians. The other new piece of information, actually, just this year, kind of again, bolstering the case or the data for QINLOCK broadly in GIST, was the publication of the ctDNA analysis in Nature Medicine. That occurred just last month. And then we also reported at the ASCO GI Symposium, the final overall survival analysis from the INTRIGUE study in all patients in the ITT analysis, showing that there was no difference in overall survival between the QINLOCK and sunitinib arms when you look at the broad patient population. We also drilled down further to look at subsequent therapies that were given to patients in the third-line setting and whether that had an impact on PFS1 plus PFS2. What we saw was that there was no difference in PFS, whether patients got QINLOCK first and then went on to Sutent, or whether patients got Sutent first and then went on to regorafenib, which was the most commonly used agent after Sutent. So again, this is a large body of evidence now in over 450 patients, which demonstrates not only the clinical activity of the drug broadly, but also how well tolerated it is relative to Sutent. And we think that's an important set of data for physicians who treat these patients. So, we're excited about what we're seeing in terms of growth in the U.S.. Outside of the U.S., our focus on geographic expansion continues. So we launched in Italy in the fourth quarter. We still have not launched in many markets in Europe. We're still working through pricing and reimbursement. That includes in countries like Spain and Switzerland. While we're selling in France, we haven't yet finalized pricing reimbursement there, and there are many other markets in Europe where we will commercialize on our own, where we don't yet have an approved price and reimbursement. Lastly, we also announced earlier this year that we have a new distribution partner for Central and Eastern Europe, a company called Genesis. And so our focus and goal of continuing to expand our geographic reach for the product, we believe will be a continued source of growth. So we're excited about the growth that's ahead for the brand. We've already telegraphed to investors that we believe with a positive INSIGHT study and a label expansion in the second line, that we could double the revenue potential in the U.S. alone. As of the end of last year, out of our total revenues, only 25% of those revenues were coming from outside the U.S., so that just speaks to the additional incremental opportunity that we see outside of the U.S. to grow revenue. So we think we're on the front end of what will be a long-term growth opportunity in QINLOCK, and the strength of the data we think really speaks for itself. So we're excited about that, and now the potential to add vimseltinib to the bag for our sales organization, and with those two products together, we think they have the potential to deliver over $1 billion in peak revenue opportunity for the company. Okay. And then on the INSIGHT study you mentioned- Mm. Sounds like the study is enrolling, well, at this point. Do you have any line of sight at this point about possible, you know, top-line data for the study? We continue to hear great enthusiasm from investigators who are actively screening patients and now enrolling patients in the study. As we get to line of sight to full enrollment, it's only a 54-patient study, so a relatively small study to enroll. But as we get line of sight to full enrollment, we'll then certainly update investors as we get close to that point, so... and when we have better certainty as to when that might occur and when the study might read out. But we continue to be very encouraged by the enthusiasm. We think physicians are excited about now the potential, in the second line, to finally be able to select the right drug for the right patient at the right time. Certainly, using a simple blood draw, a tube of blood to do that, using ctDNA, seems to have broad appeal for physicians who treat these patients. We think things like the Nature Medicine paper will continue to drive enthusiasm. We've got 29 sites open on clinicaltrials.gov and continuing to activate new sites. And as Steve mentioned, it's, it's a relatively small study of 54 patients. So we, we really want to get the word out and make sure we get these patients as quickly as possible, and be able to get that label expansion so that our sales force can begin to really promote this and, and try and get this benefit to patients as quickly as possible. Gotcha. Okay, great. With that, I think we're up on our time, so I want to thank Steve and Tucker again for joining us, and thanks to the audience for listening in. Thank you. Thank you.