Good afternoon, everyone, and thank you for attending Jefferies Healthcare Conference. My name is Kelly Shi, one of the biotech analysts here. Please join me and welcome Mr. Andrew Robbins, CEO from Cogent. Welcome, Andrew. Thanks, Kelly. Thanks for having me today. Appreciate it. Before we discuss your three pivotal programs in detail, could you give us a quick overview of your lead drug, bezuclastinib, or just like a simplified bezu, and the three indications for which it is being evaluated? Sure. Thanks. Thanks for the question. Just a quick reminder that I'll probably be making some forward-looking statements today, so just to point folks to our recent SEC filings for a full discussion of risk. So, again, as Kelly said, I'm Andy Robbins. I'm the CEO of Cogent. I'm excited to be here. We're a company that's focused on creating precision medicines for patients with rare, genetically driven diseases. Our lead program, as Kelly mentioned, is a drug called bezuclastinib, which is in clinical development, active clinical development, in three registration-directed studies for three different indications, known as first, the SUMMIT trial, which is for patients with the non-advanced form of systemic mastocytosis. Also, in the APEX study, which is for the advanced form of systemic mastocytosis, and then, last but certainly not least, the Phase III PEAK trial, which is for patients who are refractory or resistant to imatinib and have gastrointestinal stromal tumor. So we're excited. I expect we'll spend most of the day talking about those three indications and our progress, developing bezuclastinib for those patients. Just quickly, in addition, we have, what I consider to be one of the best small molecule research teams in the industry that's also working on a very exciting pipeline of other programs. Probably won't have too much time to get into those today, but, certainly look forward to talking about those at a future meeting. Terrific. Maybe we will start with the oncology indication GIST, given that ASCO just completed this week, and you presented updated Phase III lead-in data at ASCO in second line. What are the key highlights from the data presentation and the feedback? Sure. We're definitely very excited to present an update from the lead-in portion of the PEAK study at ASCO just a few days ago. So for folks that aren't familiar, when we say the PEAK study, most people think about our Phase III trial, which is a randomized study of sunitinib, the current standard of care in second-line, versus our combination of bezuclastinib with sunitinib in the active arm. We're planning to enroll just under 400 patients around the world with a primary endpoint of median progression-free survival. And so what we showed data from at ASCO, because that trial is blinded, so we won't be able to have results from that study until about the end of 2025. We did do a lead-in study where we are looking at some important parts of the pharmacokinetics of the drug in combination with Sutent. We enrolled 42 patients, a handful, seven patients, to be exact, in the second-line setting, which is the same population as the pivotal, but then a number of additional patients, the balance of the 42, in third, fourth, fifth-line setting, to again help us really understand the performance of the drug and the exposure of the drug in combination with sunitinib. All of these patients were diagnosed with metastatic GIST, and so we followed them for long-term follow-up on both safety and tolerability and activity. What we showed at the meeting is that the combination of bezuclastinib and sunitinib is very well tolerated, and a lot of that has to do with the profile of bezuclastinib as a very selective and potent KIT mutant inhibitor. So while we are very potent against mutations in the KIT gene, we do not have activity really outside of KIT against any other commonly closely related kinase, like VEGF, PDGFR, FLT3, et cetera, etc. So we also do not have significant clinical activity in the brain, and so the profile of our drug lends itself to be, number one, important for the use in these diseases driven by KIT, but two, and especially important in the GIST setting, a good partner for combining with other drugs like sunitinib. So number one, the safety and tolerability profile at ASCO was shown to be highly consistent with data we presented before, adding essentially no noticeable incidence or severity of tolerability challenges relative to what you'd expect from Sutent monotherapy. And then number two, we updated for the first time, the estimated median progression-free survival data for the populations. Number one, for the overall 42 patients, we showed just over a 10-month median progression-free survival, which in a highly refractory GIST population, all of the FDA-approved therapies have median progression-free survival in the four to six-month range. We also demonstrated an objective response rate of 28% for the entire population, and that's compared to historically approved drugs in the single-digit rate for objective response rate. Then maybe most interestingly, in the subset of patients who had only received prior imatinib, the classic second-line population, we demonstrated an objective response rate of 33% and a median progression-free survival of 19.4 months. So this is by far the longest PFS that's been reported in a resistant or refractory GIST population, and while it's a small N, we think it is supportive and increases the likelihood that the ongoing Phase III trial will eventually be successful. Terrific, super comprehensive. You highlighted safety and efficacy, but for investors not super familiar with the size of the market, if we laser focus in second line, and how does Bezu and the Sutent combo actually cover the in terms of a percentage of a patient population based on the sensitivity of tumor of mutation types? Right. So for, i t's a good question. So for patients whose gastrointestinal stromal tumors are driven by a mutation in the KIT gene, many or the predominant primary mutation occurs in this, in exon 9 or exon 11. And essentially, all first-line patients are treated with a drug called imatinib or Gleevec, which is an amazing drug and is, it was a huge step forward in the treatment of GIST patients. But about half, 50%-60% of those patients eventually develop resistant and progress, largely due to mutations in either exon 13, 14 or exon 17 and 18. And now, historically, drugs like Sutent have been effective at helping patients with an exon 13 or 14 mutation, but not so much for patients with an exon 17, 18. So there's a clear pathway for resistance, even for patients who present with an Exon 13, 14 mutation. Interestingly, bezuclastinib is especially good at covering the Exon 17, 18 mutations, while not as good as covering 13, 14. But when you put bezuclastinib together with sunitinib, then you get pan-mutant coverage across both the ATP and activation loop mutation. So we think that running an active arm in the PEAK study, where the combo of our two drugs can cover all of the commonly characterized resistance mutations, will be able to demonstrate superiority over Sutent, which really only addresses about half of the commonly known resistance mutations. Terrific. Just one more question on safety. Sutent is known for causing hypertension, and so from your data set, and how does it look like for this toxic now? Yeah, the nice part about the combination is that what we've characterized is that it doesn't seem like bezuclastinib adds to the safety or tolerability of sunitinib. But unfortunately, and the reality is just that it doesn't improve the tolerability of Sutent. So it's important to have sunitinib as part of the combination because of that molecular profile, but the toxicity, tolerability, safety associated with Sutent will remain there. The nice part, though, is that around the world, the GIST-treating physician community has now been using sunitinib as the standard of care for 16 or 17 years, since originally approved. So they are very familiar with the safety and tolerability profile and have adopted standards of care and improvements in the quality of care to incorporate those known associated adverse events as part of a successful outcome for GIST patients. Okay. Terrific. On the day of your ASCO abstract release, you also announced the PEAK Phase III enrollment completion is now expected one quarter ahead of the previously scheduled time and in Q3 of this year. Could you talk about what is driving the enrollment ahead of schedule, and also maybe elaborate on the physician feedback? Should we expect also an updated timeline for the Phase III top-line data as well? Yeah, what's interesting is while, a nd, and you, you mentioned this a little bit before, what, what is a fairly large population of metastatic cancer patients, around the world and, and also here in the United States. In the U.S., we're, we're talking about, you know, approximately 2,500-3,000 patients a year, entering the second-line GIST setting, which, from a commercial perspective, is—would lead you to a total available market of somewhere between $700 million and $1 billion. There's really very limited clinical development, trying to advance novel drugs for these patients. With bezuclastinib plus sunitinib really being the main late-stage clinical development active program at this time, the nice part about the lead-in study that we referenced again at ASCO is we've presented data from that cohort of patients initially at ASCO last year, and then again at the CTOS meeting for connective tissue and sarcoma diseases in November of last year. The emerging data that demonstrates this safety and tolerability profile of the combination, along with the early signals that the combination was helping patients, really has mobilized the global GIST community of investigators and patient advocacy groups who we're partnering carefully and closely with to find these patients in desperate need of new therapies and get them involved in the clinical trial. So to your point, we have, after several months of, of higher-than-expected enrollment, we're revising our estimates of when we're gonna complete the trial to Q3 of this year. So we're literally a handful of months away from finishing a global phase III trial enrollment. We, at this point, are gonna leave in place our guidance that we continue to expect to see mature PFS data from that trial by the end of next year, 2025. Okay, great. At ASCO, I'm not sure if you're aware of some, like, a very early phase, but, pan-KIT inhibitor data presented at ASCO. Maybe you could share your thoughts on that in terms of your combo strategy. Yeah, we've seen. We certainly understand the interest to try to find novel molecules that hit all of the exon mutations I referenced before. But the tricky part is, so far, and I think even some of these early clinical programs you've referenced, when you find a molecule that can successfully inhibit across the KIT gene, typically, those molecules are highly promiscuous and have equal potency against off-target kinases like PDGFR, CSF1R, FLT3, VEGF, KDR. And what that does is, as you increase the exposure of the drug to inhibit the KIT mutations, you also, by definition, are increasing the exposure of these off-target kinase potencies, which leads to oftentimes challenging safety and tolerability profiles, which we'll sort of reserve judgment until we can see more data. We're definitely in favor of more effective, well-tolerated drugs to help patients in need. But right now, we're nearing the end of a registration program, and there's really no other drug that has even initiated or started a registration program. So we have at least a several-year head start on any other drugs being developed in this indication. Okay, makes sense. And, let us switch to systemic mastocytosis. I think Cogent is mostly well known for. And, maybe start with the non-advanced population, which takes a majority, I think, 80% of the total population. Could you help us to understand what is the biggest treatment goal for this patient group, and what is the biggest unmet needs for the patients considering the current treatment options? Right. So the large population, as you referenced, in the non-advanced mastocytosis setting, this is a patient population whose disease is fundamentally driven by a mutation, again, in the KIT gene. It's a point mutation known as D816V. And what it does is it causes overactive mast cells to create a wide variety of symptomatic problems for patients, leading to a noticeable impact in their quality of life. So across many different body systems, including the skin, gastrointestinal tract, the CNS, bone, fatigue, and general other symptoms, it really compromises the ability of non-advanced systemic mastocytosis patients to live effective, and happy lives. So the goal-directed therapy so far, up until very recently, the only choices that these patients have had is to use symptomatic therapies like antihistamines or beta blockers or other therapies that are designed specifically to cover up the symptoms that they're manifesting from their underlying disease biology. And using KIT mutant inhibitors is the first opportunity to really go after the modification of the underlying disease itself. So the goal is to give these patients a return to normal life. So to turn off the mutation, which is causing problems in the immune system, and if you can do that effectively with a well-tolerated drug, you can eliminate the symptoms. You can eliminate the primary symptoms that are a result of the mast cells. You can eliminate some of the secondary systemic symptoms that are a result of having the disease, and hopefully return patients to a normal quality of life. Terrific. At a recent AAAA I medical conference, you presented a Part 1B data from the registration enabling SUMMIT study. Numerical data looks very compelling, but this also triggers some investor discussion because you leverage a different symptom measurement system from the system used in the current approved drug. Maybe you could help us to understand the rationale you actually made this modification, and how, what is the impact on comparability to other system? Yeah, it's a great question, and one we get a lot. So as you're referencing, there's a company called Blueprint Medicines, who has created a patient-reported outcome questionnaire and developed a drug known as avapritinib, and successfully was FDA approved last summer. For a variety of reasons, they've chosen to keep their questionnaire and their tool as a proprietary tool to the company. So for mostly legal reasons, we were required to create our own version of a tool that would approximate the symptoms that non-advanced Systemic Mastocytosis patients struggle with. This is mostly a function of a process and time. It's not, it's not a science, it's not an unknown, but over the last two and a half years, we've gone very, we've followed a very close process in collaboration with the FDA, and we're now nearing the end of that process. So our questionnaire, which is known as MS2D2, is a series of questions that ask patients about their symptoms at baseline, and then throughout the conduct of a clinical trial, measures the, increase or decrease in those symptoms as compared to a cohort of placebo patients. Ultimately, the judgment of, of the effectiveness of the drug will be made on the mean improvement of that Total Symptom Score, which is a composite endpoint of items included in the questionnaire at a 24-week time point. So the step that we need to take next, after completing, Part 1 of SUMMIT, which was essentially the dose-finding, portion of the study, is to return to, our collaboration with the FDA, demonstrate to them that we've followed the process, and we've come up with a composite endpoint, known as Total Symptom Score, that includes the most frequent and bothersome symptoms reported by our patients, and then effectively measures how those change over time. So that process will, in our estimation, is on track to be concluded in the first half of 2024. We're acutely aware there's not many days left in that time period, so, we expect to have news on that in the very near future. Are you going to press release the newest update from a regulatory agency? Yeah, we, we are committed to making sure that the investor community is aware of the outcome of that in the first half of 2024. Great. And, could you also talk about the latest status of the registration of SUMMIT Part 2 study enrollment so far from the data perspective? Would you help us to set a bar, what would be a winning situation for bezu to show in Part 2? Yeah, it's also an excellent question. So SUMMIT Part 2, which is designed, if successful, to help serve as the basis for approval, is a study of 159 patients randomized 2-to-1 for bezuclastinib against placebo, and then measured as the primary endpoint, as I said before, on that mean improvement in Total Symptom Score at 24 weeks. Oh, go ahead. Okay, great. Oh, I was just gonna say that we started that trial in late February. The guidance is that the enrollment period for SUMMIT Part II will last until Q2 of 2025, and then based on, again, that primary endpoint, we'd expect to have the top-line results by the end of 2025. Terrific. And, assuming a trial success, for the registrational trial, and, what do you think about a current, patient awareness and, also, physician familiarity, with bezuclastinib? And, maybe it's too early to discuss, but, in the, for the future commercial plan, what would be your strategy, in terms of gaining a competitively advantaged position for bezuclastinib? Yeah, we're working very closely with across, you know, North America, Europe, and even other regions across the globe to conduct the SUMMIT trial. We know that the awareness of bezuclastinib in the minds of the key opinion leaders is very high. They're very interested in a drug that has a different profile than the only approved drug in this disease. And so we're excited to conduct this study. What we're finding is that even in the U.S., where there's a commercially available drug, we are not struggling to find patients who are willing, and their physicians are willing to consent them directly onto the SUMMIT trial without even trying the commercially available drug. So I think that's indicative of the confidence that investigators have in the profile of bezuclastinib and its ability to modify the underlying biology of this mutational disease. As we think forward to a potential successful trial, we understand that, of course, the time advantage is already with the approved option. But Cogent feel very strongly that in the end, the best drug with the best profile will have an opportunity to be used by the most patients, especially in a disease where the patients will have such a say, because really, the judgment of how effective the drug is, is how the patients feel. So we believe that over time, patients who get experience with the on-market drug, a small proportion of them may have their symptoms resolved completely, but we think a significant proportion of them will have lingering symptoms, as the data from the PIONEER study, as it's known, did not show complete resolution really in any patients of their symptoms. So when we have a different offering that comes to market, there will already be an installed base of patients who may be looking for something that will help them improve even further their quality of life, as we don't expect for complete resolution, using the on-market drug. Terrific. Maybe move to advanced population. Compared to non-advanced SM patients, how are the treatment goal different? And also, do you see bezuclastinib positioned differently in terms of competitiveness in the landscape to non-advanced patient population? We absolutely do. In the advanced setting, we're talking about the same competitor. So again, avapritinib, which is a drug marketed by Blueprint Medicines. In the advanced setting, they conducted a trial called the PATHFINDER study at a 200 milligram dose, which we acknowledge is a very effective dose at treating the underlying disease biology of advanced systemic mastocytosis. The problem is with a drug that is equipotent on PDGFR, also hits some other kinases and is very, very significantly CNS penetrant, the safety and tolerability profile of that level of avapritinib is challenging for patients to tolerate, with nearly ubiquitous peripheral and periorbital edema, with high levels of thrombocytopenia and neutropenia, high levels of cognitive impairment, and in many cases, evidence of intracranial bleeding. So the difference in our profile of sparing those off-target kinases and not having clinically relevant CNS penetration, is we can achieve similar levels of objective response rate and duration without putting patients through the tolerability challenges of the currently available option. That's the goal of the APEX study. Okay, great. And, also, you already mentioned the registrational APEX trial ongoing. Could you also comment on the enrollment progress so far and the top-line data on track by the end of 2025? Yes, that's right. APEX was started last spring. We're on track to complete enrollment in APEX Part II by the end of 2024, and that would put us in place to have top-line results in somewhere between the middle to second half of 2025. The next question, I hope this is a fair question for CEO. So you have a three registrational trials ongoing, and a readout next year. So if you have to size and rank the value creation for, each trial respectively, how would you rank them? Yes. You know, for us, and this is, you know, core to everybody who works at Cogent, our, our number one goal is to help patients. And each of the patients in each of these clinical trial populations is as important to us as the other. From a pure commercial value perspective, I think what Blueprint is showing, and credit to them, is that the non-advanced systemic mastocytosis population is a very large disease. They're growing that market rapidly, and we know, based on our experience enrolling SUMMIT, that they have not really tapped in yet fully to that market. So from a value driver, I believe non-advanced probably represents the largest commercial opportunity, but just as not far behind, and we think it's an under acknowledged or underknown part of our story. Again, as I referenced before, a potential $700 million-$1 billion U.S. oncology market with limited to no competition, and we are nearing completion of our registration trial, and that indication provides a very nice additional opportunity for bezuclastinib to provide commercial value. The ASM population is clearly smaller than each of those. It's a very rare disease, but potentially the most important to provide these patients that have a significant risk of mortality, a way to extend their life with a palatable safety and tolerability profile. So, I'm not gonna pick a favorite. I'd say all three are important, but, but hopefully, that helps a little bit. Yes, and lastly, importantly, and very quickly, to echo the point you brought up, like, upfront, you have a pipeline expansion. Just curious, in terms of therapeutic area to focus, would you stay with oncology or inflammatory disease, or maybe even brand-new space to break into? Our research capabilities are very focused in kinase inhibitor and small molecule discovery, so that would lend itself primarily to oncology indications, but not exclusively. As we pointed out with our lead asset in Systemic Mastocytosis, there are other rare diseases that are not malignancies that we would also entertain building new best-in-class molecules for. Okay, terrific. And, thanks again for great discussion. And, thanks everyone for attending this session. Great. Thanks, Kelly.