All right, good morning, everyone. I'm Bijan Mekoba, Senior Research Associate here at Stifel. Welcome to Day 1 of our Target Oncology Forum. We're happy to have with us Tucker Kelly, the CFO of Deciphera Pharmaceuticals. Thanks for joining us. Bijan, thanks very much for hosting us today. We appreciate the opportunity. Yeah, of course. So if we could, let's start with where the company is with QINLOCK and the shift in sales that we've seen over the past year, specifically in the past two quarters. How should we be thinking about sales growth from here? Sure, thanks. So QINLOCK, for those of you who don't know, is our first approved product. It's approved right now in 40 countries around the world for gastrointestinal stromal tumors for patients in the fourth line setting. We launched in the U.S. in 2020 and in Europe in 2022. So we've got direct sales that we do in the U.S. as well as in key European territories as we've been on pricing and reimbursement. And we have a series of partners and distributors in other parts around the world helping us to bring QINLOCK access to patients in need of the drug. And as you say, Bijan, we had a really good 2023 with QINLOCK. I'll touch a little bit on the dynamics in the U.S. as well as in Europe. We're seeing growth in both parts of the business. I think your question really talks about the U.S. business. What we've seen is that since launch, we became very highly penetrated and really rapidly the standard of care in fourth line just for indication on label. Then we had two things that happened in early 2023 that we think created a shift that led to some unpromoted off-label utilization of QINLOCK. Those two things were that, first off, we had run a trial in an earlier line setting and just in second line in an all-comer population. That trial, while not positive, showed that effectively the PFS was very similar between QINLOCK and the comparator, sunitinib, but that QINLOCK had a significantly better safety and tolerability profile. So we had half the rate of related grade three, grade four adverse events. On the back of that, the NCCN guidelines were updated in the first quarter of last year to list QINLOCK based on that all-comer population as the preferred regimen for patients who are intolerant to sunitinib. The NCCN panel is an independent body that puts out guidelines for practicing physicians with recommendations on treatment algorithms. The second thing that happened is that we put out data showing that from that same phase 3 study in second line, we had patients that had a particular genetic profile. These are patients that have an Exon 11 primary KIT and Exon 17 or 18 KIT mutation as well. Those patients did much, much better on QINLOCK than they did on sunitinib. We had a PFS of 14.2 months to 1.5%. We had a 44%-0% response rate. At a landmark 30-month basis, twice the number of patients were alive on the QINLOCK randomized on them. Then they were on sunitinib. So we published that. We talked about that data at the ASCO Plenary session back in January, and then had a presentation at main ASCO and actually just followed up earlier this year with a publication in Nature Medicine highlighting that data. So we think those two things and awareness of physicians, though we then don't promote to it, led to an increase in off-label utilization, and that that really was responsible for what we saw as a really strong growth pattern last year, particularly in the U.S. Yeah. You know, as you mentioned, there were those two components that led to the off-label second line use. What insights can you share about which component was the larger driver? Yeah, it's a really great question when we frankly don't have a fantastic answer for it, because, again, it's not one we promote to. So we do try and understand what the prescribing patterns are that physicians may do. We think ultimately it's probably both. It's hard for us to get data on things like utilization of ctDNA that would maybe lead you to believe that it's more the 11, 17, 18 patients. But we certainly think the awareness matters. And so where, again, we can't be promoting to it because it's off-label, things like the update to the NCCN guidelines, which, again, today don't include anything about the mutational patients that have 11, 17, 18, but is really that broad sunitinib intolerant group of patients. You know, we think that could have a meaningful impact in terms of just awareness of the data. Then, again, things like publication, as we just did, the Exon 11, 17, 18 in Nature Medicine really drives greater physician awareness. We don't know, but we think it's probably both. It's also why we're running the INSIGHT trial, which is a prospective study that would confirm the data that we saw from the subgroup analysis and INTRIGUE in these Exon 11, 17, 18 patients. And now global sales. So ex-U.S. sales also saw some growth over 2023. And we're thinking about the markets that could come online this year. How do you anticipate that's going to impact sales? Sure. So, you know, we have built up our own commercial organization in Europe. We've done it with a really lean and efficient and highly effective team. As I mentioned, we launched initially in Germany in 2022, and we've been continuing to drive market penetration and physician adoption over the last two years now in Germany, which is, again, the largest market in Europe and the highest price market. So a really key core group for us as a business and for patients. In addition, we've been selling in France under an early pre-approval program, paid access program. And that has been going well. We've been doing that for a number of years. But expansion in additional geographies in Europe is really impactful for us. So what we saw last year is that we had Italy come online, again, with pricing and reimbursement finalized, and that started to contribute in the fourth quarter, but will now, in 2024, really get a full year of Italy contributing to the overall international business. And in addition, you know, we looked for other geographies to come online. So Spain is probably the largest one next that we would talk about. You know, we think that'll happen in 2024, and we'll start to see contribution from Spain. Again, another really, you know, important market in the European area. Beyond that, you know, there are some other territories that, you know, will continue to roll out and try and get pricing and reimbursement, and then dedicate resources where needed to try and service those markets. So that's areas like the Nordics, the Benelux countries themselves, and those are ones that we would anticipate commercializing directly. You know, in addition, there's obviously a larger group within the EU. We just signed in January this year a distribution agreement with a group called Genesis Pharma for Central and Eastern Europe. So again, that we expect to contribute here in 2024 as well, and gives us a much wider footprint that we aren't going to build on our own. You know, in countries like Poland and areas like that, that, you know, it's better for us to not necessarily build out that infrastructure, but to rely on really good seasoned partners. Beyond that, you know, we do have other territories that over time we'll look at. You know, we've licensed the product to Zai Lab in Greater China, but we don't have any right now infrastructure or partners and distribution partners in places like Latin America or the Middle East and North Africa. So those are other areas where over time we would look to try and expand the availability of QINLOCK. Yeah, it sounds like you have some relatively large markets online already. Some large markets that aren't online that should be coming online this year and later. Do you have an idea of what proportion of the ex-U.S. market you've captured so far? No, we don't. We haven't provided those estimates. A lot of it also depends on pricing, which is part of the extended negotiations that you have in different countries. So, you know, it's been approved, for instance, across the EU. But in each case, there are different regulations and HTA bodies and pricing bodies that you need to get approval from, both at the national level and even at the regional level. So it's harder to forecast exactly what that portion is. We do think the international business in total, which right now is trending in the sort of 25%-27% of total revenue. You know, we do think, you know, a strong contributor to our growth over time. You know, some pharma companies certainly can get that up to be sort of 50/50 with the U.S. You know, whether we can get all that way is less certain, given that we're not going to put up our own infrastructure in other parts of the world. But we do think it can continue to be a really meaningful source of growth for us, and also sets us up well for building out that infrastructure as we bring vimseltinib online and any other products we might be able to get approved. Yeah, perfect. Perfect. To move on to the INSIGHT trial. It's been open and rolling for some time now. I'm wondering, what can you share about the pace of enrollment? And at what point in the trial will you be able to give us an estimate on when it'll be fully enrolled? Sure. So, as I mentioned, this trial is designed to replicate the data we saw in the 11, 17, 18 patients from INTRIGUE. It's a very compact study. It's 54 patients. We had 52 patients in the subset analysis from INTRIGUE. So very similar size. Otherwise, we've kept really all the details very similar to what we had seen in INTRIGUE. So we're randomizing against sunitinib. We have made it more patient-friendly since we don't expect patients randomized to sunitinib to get as much benefit as they certainly do from QINLOCK. So it's a 2:1 randomization. And we're really pleased with how the initial physician and patient engagement and enrollment is going. So we're now, I think, about 41 sites that are active around the globe. So that includes North America, South America, Europe, and Asia as well. So we're doing really well on bringing on sites. There's a lot of enthusiasm among investigators for the trial. It's really going to be the first time to use precision medicine in a broad just patient population in order to try and find the right drug for the right patients. And we've seen in that data that I touched on earlier just how compelling that can be. And so the reaction from physicians and patients that we're engaging with is really strong. So, you know, our hope is to get that enrolled as quickly as possible, so that we can get to a label expansion and begin to promote for what we expect to be a really strong outcome based on the data we saw in INTRIGUE. So we don't have any timeline yet as to when we'll reach full enrollment or read that out. Our past practice has been that when we have kind of line of sight to full enrollment, we'll typically try and provide that guidance and say, "Hey, we think we're going to reach full enrollment in x quarter or x half." And then obviously update once we get to that full enrollment timeline and provide some guidance for top line readout. So the moment we're still earlier on in the enrollment curve and don't have a projection yet to share. Yeah, that's fair. As far as the size of the opportunity, how should we be thinking about the size of the INSIGHT trial opportunity in the U.S.? What proportion of that is going to be captured by the time you get an approval? And then are there any levers that you could pull on to increase the size of the opportunity? Yeah, no, we think this is a really impactful opportunity for us with QINLOCK. We think in the U.S., what we've said is we think that this can double at peak the revenue that we can do. So at peak, we think with the second line subpatient population only. So it doesn't include any of the patients that we might talk about that are intolerant to sunitinib, but just with the 11, 17, 18 population. We think the total could be $350 million-$400 million, and that effectively expanding into the earlier lines in even a smaller number of patients allows us to double that market. So two things about that. One is that we don't obviously include patients that we might treat in the second line, you know, in the fourth line setting. So we don't include the possibility, at least of retreatment. What you see is that the, you know, duration of therapy is going to be, we think, significantly longer in the second line in this group of patients in particular than what we see in the fourth line. Today, what we said is that the fourth line, we think at peak, we can probably get an average treatment duration of around 8.5 months. We're well on our way to doing that, you know, in the first couple of years of launch here. We think, again, good opportunity to grow the fourth line business in the U.S. But we do think expanding to the subpopulation will be really critical. That allows us to get, again, a smaller number of patients in the second line. This is about 15% or so of all second line patients. But with the treatment duration that, you know, we think will be out to about 20 months. I n the phase III study, we saw this group of patients have a 14.2-month PFS. And we think, based on our experience in the fourth-line, as well as literature, that in the real world, the average treatment duration, not just a median PFS, will be a bit above that. So at 20 months, those patients really contribute a lot to the overall commercial opportunity. And again, this all is excluding the benefit that we would get for label expansion and off-label utilization potential in Europe or other parts of the world. That's helpful. So now moving on to vimseltinib. I guess, can you give us a brief on its current status and then the cadence of events over the next six months? Sure. So vimseltinib is our second potential medicine. It is a CSF1R inhibitor, another small molecule. We reported out top-line results from our MOTION study, which is our registration-enabling phase III study at the end of last year, end of October. This is in patients with tenosynovial giant cell tumor, or TGCT. So we're very excited to hopefully become a multi-product company here. We are on track for our guidance that we projected at the time of top-line readout to file with the U.S. FDA the NDA now in the second quarter of this year, and then the EMA to file that MAA submission in the third quarter. So both of those remain on track. We're very excited to get what we think is a stellar data set on a program that we think has great commercial potential for us in front of regulators and seek to get a rapid approval and provide this to our salesforce to begin to help market this for patients with TGCT. So we're in really good shape for those regulatory submissions. Our team has got obviously experience with QINLOCK, and we're going to be utilizing that expertise and experience now for our second product, vimseltinib. Makes sense. And then I know we should expect some data disclosures later this year from the motion study, and then also from the phase 1, 2b. Can you talk more about those data disclosures and what we should expect from each of them? Sure. So what we showed at the top-line disclosure for MOTION, which is the phase III study, is we reported out on the primary endpoint, which was response by RECIST at week 25, as well as week 25 endpoint for tumor volume score, which is an enhanced way of measuring tumor growth or shrinkage in this disease, as well as range of motion, which is one of the other key secondary endpoints. We had a total of 6 key secondary endpoints. What we said at the top-line MOTION result was that we had met all 6 key secondary endpoints. They were all statistically significant and clinically meaningful. But we provided data on the first 3. So we had a response rate of 40% compared to 0% for placebo. We had a 67%-0% response rate for the tumor volume score. We had a 5 times improvement relative to placebo in active range of motion. So what we'll present coming up now will be, again, data just from part one of the study, and that'll be added to week 25. That'll be coming up here in the second quarter. And it'll importantly detail the other key secondary endpoints that we did not disclose the actual results for back at top line. And we think this really rounds out well the efficacy profile. So this is a disease that's non-malignant. It's non-fatal. So how patients feel and function, these quality of life measures are really, really important. And we think this really substantially adds to the overall regulatory submission, but also importantly for the commercial opportunity. We hear consistently from physicians and patients that, you know, these types of secondary endpoints, so things like pain, stiffness, just overall quality of life, range of motion, those are really impactful and mean a lot in terms of their likelihood to prescribe or go on therapy and stay on therapy. So we're really excited about presenting that data. And then, as you said, we'll also have an update from the phase 1/2. That'll be later this year in the second half. And that really is showing long-term therapy. So the last update was at CTOS, which was in the fourth quarter of last year, where we showed really good duration of therapy and really good long-term safety and efficacy, which continues to trend nicely and improve over time. So what we'll have is, again, another update longitudinally of that study to show increased treatment duration at the time we had seen from the phase 1, 25 months of median treatment duration and 24 months in the phase II cohort A. So we'll have, and just under half the patients were still on drug at that time. So we'll have an update on things like duration, on efficacy measures, and obviously continued safety updates. And the safety profiles remain really as expected and quite favorable for this patient group. Yeah, and SpringWorks Therapeutics actually recently got an approval for nirogacestat and desmoid tumors, which is similar to TGCT, both are rare, benign sarcomas. They aren't life-threatening, but they do limit patients' function, reduce their quality of life. And then both of them are treated by off-label TKIs. I'm wondering, were there any learnings from the FDA's approval of nirogacestat that could be helpful for the vimseltinib filing? Yeah, no, it's a great question. We get that a lot as SpringWorks has launched now the drug in desmoid. There are, at a high level, some kind of key overlaps, like you mentioned, in terms of the disease states. There are obviously some key differences as well, and I'm not as well versed in desmoid. So we'll certainly watch the desmoid launch. From SpringWorks, it sounds like it's going well so far. You know, as far as the regulatory, you know, interactions, I think, you know, probably less impactful than what we do know, which is there is one drug approved for TGCT in the U.S. It's, unfortunately, an agent that has an off-target side effect unrelated to CSF1R inhibition that has severely limited its uptake of severe hepatotoxicity. We certainly have learnings from the submission that was made for pexidartinib and the approval that they got with the REMS in a black box, which we don't expect at all for QINLOCK, sorry, for vimseltinib, based on our data set. We do have a regulatory precedent that we think is useful in some ways and very distinct in others. Gotcha. Can you speak more about that? The key differences between the commercial performance of TURALIO and then how you intend to launch vimseltinib? Yeah. So TURALIO, otherwise known as pexidartinib, is marketed by Daiichi Sankyo. It's approved in Europe, but not in the U.S., but not in Europe. Sorry. And it has activity in TGCT patients from their phase III study. Unfortunately, what they saw is that they have a severe hepatotoxicity in a small number of patients. So outside of TGCT in the development program, they saw one fatality and a liver transplant. And within the phase III ENLIVEN trial that they had for registration in TGCT, they had about a 5% rate of severe hepatotoxicity. So these are elevations in AST and ALT, as well as increased elevations in bilirubin and so frank, or what they call cholestatic hepatotoxicity. So that's very distinct from what we and other CSF1R inhibitors have seen. There's no expectation that it is target related, and Daiichi said as much. As a result, they got a REMS and a black box warning. For patients, again, who don't die from their disease, who are often younger than traditional oncology patients. So TGCT patients are diagnosed in their 30s, 40s, 50s. And so the idea that they would trade off any potential benefits with pexidartinib for the low but very significant risk of things like severe liver injury has made it very challenging. In addition, physicians have to register for the REMS program. They have to be trained. What our claims data shows is that for a lot of physicians that see a smaller number of patients, you know, that's a real barrier. And they would rather use off-label imatinib, which is in the guidelines and has, you know, weaker efficacy but doesn't have these liabilities for pexidartinib. So, you know, pexidartinib does about $40 million a year in revenue just in the U.S. But that's really based on its limited duration in treatment and its small market share relative to what we see in the claims data as a very addressable patient population. And, you know, our market research and qualitative research since the MOTION readout has continued to confirm that with a better agent that doesn't have those liabilities and strong efficacy, that we think that's a winning strategy and a winning drug to help these patients, and that the experience that pexidartinib has had in the market, TURALIO, isn't necessarily what we would at all expect. Yeah. And just one final question on vimseltinib, on the GVHD opportunity. What's the pitch for vimseltinib here? And then what do you need to see in a proof of concept to decide whether you're going to move forward with it in development? Sure. So we think this is a great lifecycle expansion for vimseltinib. It's an area we've been looking at for a while. What we think is a really good commercial opportunity for a company like us. The mechanism of CSF1R inhibition was validated in a registration study from another company last fall that showed good activity in chronic graft-versus-host with an antibody against CSF1R. So they had very good data. They're in the process of submitting to FDA for approval in chronic graft-versus-host. What we've announced is that we're going to be moving forward and initiating a proof of concept study in the fourth quarter of this year in GVHD. We think we've got a really good opportunity here because, one, now that a novel mechanism in the disease has been validated, we've got a very selective and specific CSF1R inhibitor. But importantly, it's a small molecule and not an antibody. And that's important for a couple of reasons. One is for patient convenience and compliance. It's always good. We have right now a twice-weekly dosing with a small molecule versus going and having to get an infusion. But also, importantly, the field of chronic graft versus host is also moving into combinations. And so there's a number of combinations being tested and being able to have another small molecule to complement the small molecules that really today are the backbone of treatment in chronic graft versus host, and whether that's a JAK inhibitor, steroids, or most recently, the ROCK inhibitor that Sanofi has that was launched a couple of years ago. You know, those all would be much better combined with a small molecule than having a small molecule antibody combination. So we think that it can provide some significant improvement over that. And so we look forward to getting the proof of concept study underway to try and show that we've got activity in chronic graft-versus-host. But we're very optimistic, given what the others have seen with the antibody. And, you know, we think this is a really good commercial opportunity in the third line setting. The ROCK inhibitor from Sanofi, which was approved 2.5 years ago, I think did about $350 million last year. So, you know, on top of what we see as a substantial opportunity in TGCT, we're really excited to move that quickly and try and find another avenue for growth with vimseltinib. Yeah. And just a couple of minutes left. So on the earlier stage pipeline, could you, how should we think about the next steps for each of the assets that you're having your earlier stage pipeline? Sure. So beyond QINLOCK and vimseltinib, we've got some great agents that we have in clinical or preclinical development. The most advanced is ULK inhibitor. We're in a series of dose escalation combinations there. Our goal this year is to report out data from that and have a recommended phase II dose to go to the expansion cohorts in the phase I combos in order to really test the efficacy hypothesis. So we'll have that, hopefully, in the second half of this year and be able to talk about next steps there. In addition, we have two other drugs that are either going into the clinic or being filed with the IND. So we've got our Pan-RAF inhibitor that will be dosing first patient here in the first half of the year. Then after that, we have a new Pan-KIT program. The goal there is to file the IND and initiate the phase I study later this year. So, you know, those programs we think are really exciting coming out of our proprietary drug development research engine. And we think complement nicely our later stage and commercial assets. Yeah. And then a final question on the Pan-RAF inhibitor. You know, how does it differentiate from other approaches being developed? I think degraders or other Pan-RAF inhibitors. And then how do you expect that to manifest in early data? Yeah, no, great question. There's certainly a number of other folks that are working on Pan-RAF inhibitors. We had had one actually years ago that we had through a research collaboration with Eli Lilly. But we think that 3084, our new Pan-RAF inhibitor that's going in the clinic now, has a set of properties, both biochemical in terms of its inhibition of the class 1, 2, 3 mutations, as well as fusions. And that gives it a best-in-class profile. So we've got some data in the deck from our corporate deck on the IC50s there that shows really good potency across the range of different areas that you need to have a good Pan-RAF inhibitor. In addition, it's got some really good biochemical and biophysical properties in terms of its ability to get at the tumor, to stay there, to not be kicked out by efflux pumps. And have good CNS penetration. We just had a poster at AACR here a couple of weeks ago showing the good brain activity of 3084. So we think there are some really good differentiating features. Obviously, we'll need to prove those out in the clinic. Preclinical profiles only get you so far. But we're really excited about it and eager to get the drug into the dose escalations and start to generate some good clinical data to prove out its profile. Well, we really appreciate that. We're just at time. So we've covered a lot. Really appreciate you taking the time to join us today. And, you know, we're excited for updates throughout the rest of the year.