Okay, I'm getting the high sign here. It's time to start. Let's get going with our next presentation. My name is Chris Raymond. I'm one of the senior biotech analysts at Piper Sandler. It's my pleasure to introduce our next company, Deciphera. Joining us today, we have President and CEO, Steve Hoerter, and also Tucker Kelly, both of them to my left, who Tucker is the EVP, CFO, and Treasurer. So this format is a fireside chat format, very informal. So if you have any questions from the audience, please just raise your hand. I'll make sure your question gets asked and answered. And if you don't wanna do that, just email me. If you don't wanna raise your hand, I'll be checking my email, and we'll again, we'll make sure your questions get answered. So, we've got about 24 minutes or so for, for questions. Maybe before we do that, Steve, if you wouldn't mind just walking us through, sort of the setup, the premise around Deciphera, for any investor who might not be familiar with the story, and, and, walk us through maybe the elevator pitch, if you will. Sure. Happy to, Chris. Thanks for the invitation to join again for this year's conference. It's been a great conference so far. So for those who don't know, the company, Deciphera, we're an oncology-focused, commercial stage, fully integrated now, oncology company, focused... It was founded initially on our deep insights into kinase biology, so we're a kinase inhibitor company. Our first product, QINLOCK, was approved by the US FDA in 2020 for the treatment of gastrointestinal stromal tumor, or GIST. The drug was then approved the subsequent year for the same indication by the European Medicines Agency, and it's been approved now in over about 30, probably upwards of 40 countries now around the world. The drug has been very successful here in the U.S. and also outside of the U.S. in this initial indication. So we're focused right now with QINLOCK really on expanding the geographic reach of the product in territories where it's not yet available, in addition to focusing on enrolling the phase III INSIGHT study, which is a study where we're seeking to expand the use of QINLOCK into an earlier line setting in a selected group of patients. So we're excited about the setup really for QINLOCK here going forward and see a dramatic opportunity to the upside for the brand over the long term. And coming right behind that is our second product, vimseltinib, a potent selective CSF1 receptor inhibitor. We reported the phase III pivotal study results just about three weeks ago now, where the study hit on the primary endpoint and all six of the secondary endpoints. Really exceptional data in patients with tenosynovial giant cell tumor. So we're on track to file a new drug application for this product in Q2 of next year here in the U.S., and then filing in Q3 with the European Medicines Agency. Taken together, we think these two products have the potential to generate $1 billion or more in peak revenue. So a very exciting and interesting initial commercial portfolio for the company. We're also a research-based company, so all of these products, QINLOCK as well as vimseltinib, came out of our own research efforts, and we have a deep pipeline in the clinic, which we may have an opportunity to spend some time talking about. Our ULK inhibitor, which is now the subject of a number of combination dose escalation studies, targeting autophagy as an escape mechanism in cancer. We have a pan-RAF inhibitor that's entering the clinic shortly, and then a pan-KIT inhibitor for which we expect to file the IND in the first half of next year. So, a really nice setup for us going into next year and going into the future now with what we believe will be a sustainable portfolio with QINLOCK and vimseltinib together, all while we invest proceeds from the revenue we generate with those two products into our own research engine. Awesome. Okay, well, I've got about an hour and a half worth of questions here that I'm gonna try to pack into 20-20 minutes or so. So maybe let's just jump in. So, yeah, so QINLOCK, if we can begin there. Obviously, you know, the first approved TKI for GIST, you know, approved in the fourth-line setting. At this time last year, discussion around the addition of the NCCN guidelines, you know, was still ongoing. That happened in March, I think, of this year. Maybe just say a few words about, you know, the INTRIGUE study, given that the, you know, the study assessed ripretinib in GIST patients previously treated with imatinib. It obviously didn't, you know, hit the primary endpoint, but, you know, just the setup and the reason behind the NCCN guidelines. Yeah, maybe, Chris, we can actually first take a little bit of a step back. You know, so the initial study that was the basis for the original approval for the product in the fourth-line setting was the INVICTUS study- Mm-hmm. where we showed a dramatic improvement in PFS, a tripling of overall survival in the fourth-line setting, irrespective of mutational subtype. So we took this, the drug into a second-line head-to-head study versus Sutent, the INTRIGUE study that you referenced. We reported those data out now a couple of years ago, where we showed that the study failed to meet the primary endpoint, and we showed that the drug, QINLOCK, demonstrated or offered equivalent PFS to Sutent in the all-comer population with an improved profile with respect to the rate of Grade 3, 4 adverse events, so a better-tolerated agent in that INTRIGUE study. We collected peripheral blood samples from patients enrolled in the INTRIGUE study, and then we undertook an evaluation of the circulating tumor DNA from those peripheral blood samples, which then led us to a new insight in terms of a selected group of patients who have an outsized benefit to QINLOCK in the second-line setting versus Sutent. And that was the basis for us launching the new Phase III INSIGHT study. We also received Breakthrough Therapy Designation for the drug. So that news all occurred at the beginning of this year. In addition, as you referenced, in March, the NCCN updated the treatment guidelines, really reflective, we believe, of the initial INTRIGUE data readout in the all-comer population, and updated those guidelines to list QINLOCK use in the second-line for patients who are intolerant to sunitinib treatment. So that was the update to the guidelines. We've seen somewhat similar updates in other parts of the world. So the Chinese Society of Clinical Oncology earlier this year updated their treatment guidelines to include QINLOCK as a treatment option for a broader group of second-line patients with a primary KIT exon 11 mutation. So I think there's now been recognition broadly by the community based on the insight... Excuse me, based on the INTRIGUE data and also our subsequent analysis, that was the basis for insight that QINLOCK is clearly a very active drug in this disease, and we at the company are very much focused on advancing this new study to generate a label in this earlier line use. So Q3 is a pretty good quarter for QINLOCK. Maybe, you know, I know you guys have been very careful about not, you know, talking about off-label or quantifying it, but this is a question I get all the time from folks, is what, you know, what's the impact of the NCCN guideline? How do you quantify the benefit? What's the... You know, it's hard to say what's the TAM of a, you know, non-labeled opportunity, but it is one of these sort of interesting, sort of, you know, interim, sort of, say, it's approval, but it's a, it's an endorsement. I know you get this question, but how do you. When you get people to ask, asking you, how do you quantify that benefit? Or what is the ultimate, you know, opportunity without a label, but with having this NCCN, you know, inclusion in their guidelines? How do you answer that question? Sure. So maybe one thing is to step back and look at what we've seen historically with QINLOCK, predominantly in the fourth line setting. And as Steve mentioned, we got it approved in the middle of 2020. So we've got over three years of experience now with the product in the U.S. And what we saw, if you look, for instance, at 2022 and the first quarter of 2023, is, you know, a relatively kind of narrow band of kind of quarter-over-quarter growth, so averaging about 3%. And then in the second quarter of this year, we saw a 17% quarter-over-quarter growth and another 13% in Q3. So we saw a significant trend shift. We don't have perfect visibility into what line of therapy patients are on, but as we talked about just a few minutes ago, we had these two events in Q1, the 11, 17, 18 data in January, and then the NCCN update for the sunitinib-intolerant patients in March. So we strongly suspect that we're getting earlier adoption in second line. We don't promote to that obviously, but it seems to be a significant trend shift that's driven the US business. And we don't know which of those two things, or both, may be contributing to that, that uptake. So, it's hard to predict what will happen going forward, but we certainly have seen a market shift that resulted in, you know, nice growth in Q2 and Q3, in the US business, in addition to the overall growth that we're seeing from the international expansion. And just, I mean, again, I know you don't promote to it, but there's another dynamic that has been sort of interesting to watch is the payer reaction. You know, if it's in the NCCN guidelines but not on the label, what's your go-to-market approach, I guess? That's kind of an overused word, but how do you approach payers, you know, with that dynamic? And what's been the general reaction you've gotten from folks as these issues come up with patients? Yeah, so from a payer perspective, payers in the U.S. refer to the NCCN guidelines as they make decisions about reimbursement, for a product like QINLOCK. So again, as Tucker said, this isn't a use that we, we promote to. It's all based on physician decision. But yet, I think payers in the U.S. recognize that the, the treatment of oncology, patients can sometimes be an art, and, and, and they want to be open to, to data and open to what's in the treatment guidelines as they make those decisions. So we don't, we don't believe there to be today, based on the guideline listing, a significant barrier with payers to physicians who choose on their own to, to use QINLOCK outside of its label. Okay, maybe just on some of the data updates you've had. You had some interesting updates, I think, at CTOS a few weeks ago with ripretinib versus sunitinib in patients with advanced GIST and second line after, I guess it was after, imatinib. These were KIT exon 11 plus 17, 18 mutations. Maybe for those who missed it, you know, could you say a few words about, you know, that update and how the story sort of unfolded over the last 12 months? Yeah, sure. So the data that we presented at CTOS was really a reprise of the initial publication of the data, or presentation of the data that occurred at the ASCO Plenary Session series back in January of this year, and then again at the big ASCO this summer, where the data were presented. And what it showed in this selected group of patients was a dramatic response rate in the QINLOCK arm, over 40% response rate in patients who received QINLOCK with this select group of mutations in the second-line setting, versus a 0% response rate for patients who received sunitinib. Similarly, for PFS, it was a PFS of over 14 months for patients who received QINLOCK, versus a PFS of one and a half months for patients who received Sutent. We also saw a favorable trend in terms of overall survival. So this was the basis, these data, of course, were the basis for the original Breakthrough Therapy Designation that we received from the FDA at the beginning of this year, and also were really instrumental in our decision, of course, to launch the new phase III INSIGHT study. We also had additional data, longer term for the overall population, for overall survival, but also the safety data. And that, again, was very consistent with the original top-line analysis, showing that ripretinib is just a much better-tolerated agent than sunitinib. It had much higher rates and grade 3, grade 4 adverse events than ripretinib did. And again, those are the same data that we think were impactful for the NCCN to include ripretinib as the preferred option for patients in the second-line who are intolerant to sunitinib. ...So maybe a question on the competitive setup in the second-line setting. Obviously, sunitinib is there as an established competitor. There's also another KIT inhibitor, bezuclastinib, which is in development in combination with Sutent. You know, just maybe talk about how you see the setup with, you know—you've got obviously this outstanding data set in these KIT 11, 17, 18 mutation patients, but there's a diagnostic step required. You know, in fast-forward, you know, several years when it, you know, if and when you both have labeling in the setting, maybe just describe the setup there where you... You know, it's sort of a trade-off, right? You've got to go through the diagnostic protocol for yours, but you've got your outcomes. How do you see that setup sort of set up with, in a, you know, a bezuclastinib world for second line? Yeah. Let's first start with the diagnostic component to it. Mm-hmm. So, you know, as I mentioned earlier, that one of the beautiful components of this is the simplicity of the diagnostic. So it is a single tube of blood, drawn from a patient, sent off to the lab with a 7-10-day turnaround time. So there's not a need for a fresh tissue biopsy. This is simply peripheral blood that's drawn, put in a tube, and shipped off to the lab. And then the physician gets a report, once that sample has been analyzed, which then indicates the presence or absence of the mutations of interest. So it's a very low kind of threshold or barrier for a physician to test. What we've heard from physicians, anecdotally and qualitatively in research is based on the data, based on this 44% versus 0 response rate, the magnitude of the PFS benefit, there that's a real reason to, to take the simple step of drawing that tube of blood and waiting a week to see what the result is. We don't see the fact that there's a diagnostic component to this as being a barrier. If anything, we think physicians who treat these patients are excited about the potential now to bring the treatment of GIST into the twenty-first century, where we're actually able to identify the right patient for the right drug at the right time, and that's exactly what this approach does. So if you were to fast-forward and you assume success for competitor approaches, such as the one that you outlined, yeah, you know, the challenge that we see, at least with that approach, is that we're not doing what I just described, which is that approach does not select the right patient for the right drug. And what it then means, and the implication of that is that we're ending up giving patients drugs that they actually don't need. And so I think the field is gonna move pretty rapidly in a direction of true patient selection strategies with this disease, as opposed to sort of drug development from the 1980s or the 1990s, where we're just giving drugs to patients irrespective of their mutational profile. Excellent. Okay, great. So let's pivot maybe to vimseltinib. Mm-hmm. Obviously, you had some big news, a couple of weeks ago, the top line of the MOTION-3 phase III study. Before we jump into the data and the results, maybe just talk a little bit about TGCT as a, as, as an opportunity, vimseltinib's mechanism and, and sort of, just so the premise and the setup and, and how you've... You know, seems like you've changed the face of this disease a bit with these results. Not to overstate the, the results here but- No, we thought the data was spectacular, and there's a huge unmet medical need for patients with TGCT or tenosynovial giant cell tumor. And these are patients who, though not gonna die from the disease, suffer from a lot of morbidity. And we've gotten a lot of qualitative research and patient input lately that just stresses how impactful the disease is on their lives. These are not metastatic tumors, but local tumors that occur in the joint area, so usually in the lower extremities, it'd be in the knee, or if it's in the upper extremities, it'd be in the elbow or the ankle or the wrist, sorry. And patients are diagnosed in their thirties, forties, and fifties, and they struggle to get diagnosed properly. And if it's not cured by surgery, which for a lot of patients it can be, it can become a lifelong series of, you know, multiple surgeries that have their own significant impact, and it weighs really heavily on patients. So, there really isn't a good option today. In the U.S. right now, there's one approved drug, which is pexidartinib, that has a black box and a REMS program based on significant hepatotoxicity that is expected to be off target, and that's severely limited its uptake. And what we see in our claims data is that most patients today that see an oncologist are getting an off-label imatinib, which is not a great CSF1 inhibitor, and that's the biological target, which is really clear. What we do know is that the biology of the disease is such that if you inhibit CSF1R, you're gonna be able to shrink these tumors and provide symptomatic relief. We think with vimseltinib, we've got a really selective agent that has performed incredibly consistently throughout the phase I, II, and now the phase III study, with a safety profile that we think is best in class and sets us up nicely to launch in the U.S. after approval and in Europe, where there's no approved therapy. Happy to dive into the data a bit more, but it's a great opportunity for a group of patients that in the U.S. today don't have a great option that they have to risk additional side effects for. Yeah. So let's maybe talk about that a little bit on the data. So you hit your primary endpoint, which was ORR at week 25, you know, strong stats, big, you know, in terms of the, you know, hitting that primary endpoint was a big win. But, you know, secondary endpoints like tumor volume score and range of motion also were measured. Maybe just give a sense of, of how, you know, physicians are viewing those. It would seem range of motion obviously is a key, you know, real-life measure. How do you plan to highlight these, you know, with physicians as you, as you market the drug? Yeah. So just to restate the data. So what we saw on the primary endpoint, which is response rate by RECIST criteria, was a 40% response rate versus 0% for the placebo arm. One of the key secondary endpoints was response as measured by Tumor Volume Score, which is a way to get, as the name suggests, a measure of the tumor volume as opposed to a two-dimensional measurement of tumor size. And we believe that TVS is a really important measure of response in this disease because the tumor itself is tumor that's woven into the joint, which makes it difficult to measure by RECIST. And the threshold for response when using TVS as a measure of response is a 50% reduction in tumor volume. So seeing a 67% response by TVS, we think is a really significant accomplishment and just demonstrates the, the power of the drug in this patient population. But as you point out, Chris, there were 5 other secondary endpoints that we included in the study. We reported on one additional secondary endpoint, and then we're saving the rest for a medical meeting. But one of those, which was range of motion, showed that treatment with vimseltinib resulted in a 5X improvement of range of motion over the placebo, or what we've seen with placebo. This is important because it can be, for a patient, the difference between being able to go from a sitting to a standing position, or the difference between being able to climb a set of stairs or not be able to climb a set of stairs. The other secondary endpoints that we have in the study are somewhat similar in that they really measure the impact on a patient's daily life. It could be pain consumption, but also their quality of life, and we think those will be very important measures as regulators, physicians who treat these patients, HTA bodies in Europe, as they think about the totality of the data now that we've generated for motion. And to have achieved, of course, not only the primary endpoint, but to have hit statistical significance on all six of the secondary endpoints with a well-tolerated safety profile, really is a kind of a best-case outcome from our perspective in terms of the data that's come out of MOTION. So we're really excited about now engaging with regulators and then eventually, getting to, post-approval, getting to a launch of this medicine around the world and getting it to the patients who need it. Okay, so speaking of launch and the market opportunity, you guys have talked about $500 million opportunity with, you know, the incidence of... Just the incidence of the 1,400 or so patients that are seen by an oncologist. There's also, however, this is kind of an odd indication in that there's got a sizable number of patients that are treated by non-oncologists. Maybe just talk about the launch dynamics in your commercial setup. It would seem the oncology part, you know, I wouldn't say it's easy, but it, it's you've known—you know what you're getting into. But getting at the other part of the market that's not seen by an oncologist, you know, it's probably not too really to ask this question, but what's the commercial plan there? Yeah. So we think we've got a really nice setup for commercializing vimseltinib, both in the U.S. and Europe. That core opportunity you mentioned, Chris, is really around those 1,400 patients that we see in the claims data today that are treated by an oncologist, have TGCT, and are getting some kind of pharmacotherapy now. But half of them are getting a TKI today, the other half are getting pain, steroid medication. But importantly, they're being seen and treated today by an oncologist. So it's a great fit for our sales force, which calls on the very same physicians. So we look in the claims data, and we've got an overlap of 70%-80% already for our calling effort based on KOLs in GIST. So that's really our core initial go-to-market strategy, is to be able to try and, one, replace imatinib and pexidartinib that are being used today as TKIs, and then provide a new option for those patients who, again, are being seen by an oncologist and treated with some kind of drug therapy, but not a TKI. And we think having a better, well-tolerated therapy with great efficacy is gonna really be able to convert those. So our goal is to try and initially maximize that 1,400. But as you mentioned, there's ways to grow with this product over time. The additional patients that we see in the prevalent pool, because, again, you don't die from TGCT, thankfully. We see about 9,000 of those patients that have been treated by an oncologist in the last couple of years. There are more that have ever been seen and treated, and diagnosed with TGCT, but that's sort of the more adjacent group. And so we think there's opportunity potentially to bring some of those patients back into the treatment paradigm, with a new option available to them. And then beyond that, again, there are patients who never make it to an oncologist. So we see those 1,300 patients you mentioned on an incident basis that are today being treated with some kind of drug therapy, but typically not a TKI, by surgeons, by orthopedic surgeons most often. And again, those are ones where we wouldn't necessarily expect to, you know, build a sales force to go after them or to try and convert orthopedic surgeons into using TKIs as kind of a drug therapy over, you know, a number of months or years. But we do think we can help, you know, increase referral patterns. We can find those patients, because again, they're looking for better options. You know, surgery works for a lot of patients, but for a number of them, either they're not amenable, or they've had one, and it isn't good, and there comes a lot of morbidity as well. So we think that beyond that core oncology, focus group at the outset, that there are ways that we can grow the brand over time, and that's a real upside, we think, to the $500 million TAM, which again, is just based on that 1,400 incident patients, today being seen by an oncologist. I got time for one more question, and it's another commercial one, I guess. You know, you guys, you mentioned, Steve, you know, this is a lifelong condition. You know, patients don't necessarily die, but they've got it for life. I think your data would indicate pexidartinib duration of treatment is 10 months or less. I think even off-label imatinib is 18 months. Mm-hmm. You guys have data going out 20 months, so far, right? So, how should we think about the duration of treatment? And, you know, it's obviously too early to get a sense of, you know, what the discontinuation sort of metric or dynamic would be. But, you know, is there any reason to think this wouldn't be, you know, like a rare disease where you get a patient on therapy and, like lysosomal storage disorder, they're on for life? So the phase I data, the de-escalation data, is the most mature, and the median duration of treatment in that group of patients is now out above two years, so over 24 months. And in fact, the patient on treatment the longest now has been on treatment for four years. In the phase II cohort A, which is the same group of patients that we've treated in MOTION, as of the last update, the median duration of treatment was 21 months. So we see there as being a potential for patients to receive a treatment like vimseltinib that's well-tolerated, has this great efficacy profile, being a long duration of treatment. And as you referenced, these patients don't die from their disease. There's the opportunity, over their lifetime, potentially, to have even more than one treatment intervention to the extent that they need it. So we see there as being a real meaningful opportunity to benefit patients, and we're excited to get the product and the data in front of regulators. Awesome. Great. Well, like I said, I got another hour's worth of questions, but I don't have any more time. So thanks for the great presentation. Lots going on. Yeah, thanks, Chris. Thanks, Chris.