Okay. It seems like we're ready. My name is Eva Fortea. I'm one of the Wells biotech analysts. For our next session, we have Brian Sullivan, CEO and Co-Founder of Celcuity. Thank you so much for being with us today. You're welcome. My pleasure. Cool. To start, can you give us just a little bit of the lay of the land and Celcuity past 12 months, future 12 months? Sure. Our lead candidate, the lead drug, is now actually an approved drug, REVTORPYK. It's a pan- PI3K/mTORC1/2 inhibitor. We recently received approval to treat patients who have progressed on their first line of endocrine treatment for metastatic disease. It's a second-line therapeutic option for patients who have no PIK3CA mutation detected. We have two regimens that were approved, gedatolisib or REVTORPYK with palbociclib and fulvestrant, or REVTORPYK with fulvestrant. We're in the midst of preparing for our launch. We expect to have commercially available drug by the end of this quarter. We've also initiated and are enrolling patients in two phase III studies for patients who are treatment-naive in the advanced breast cancer setting. There are two different groups of patient population of patients, one that is considered endocrine sensitive, one endocrine resistant. Total number of patients that potentially could be eligible over time would be roughly 90,000 annually, so a very significant patient population. We expect to have data from the endocrine-resistant population sometime late 2028, early 2029, and for the sensitive population, probably late 2029 or 2030. We have a phase I/II study underway, ongoing in prostate cancer, prosecuting a similar underlying biological hypothesis as we've done in breast cancer, which is that it's a hormonally driven disease, in this case, the androgen receptor pathway, that involves the PAM pathway, PI3K/AKT/mTOR pathway. We've reported initial data that, in our view, was favorable. We'll be providing an update with that data later this year at a medical conference. There you go. That's an overview. There you go. Plenty of stuff there. A lot of stuff. Oh, and we have another data set. We announced data for patients who have a PIK3CA mutation. We presented that data at ASCO. We submitted a supplemental NDA last month, and so we expect things go the way we hope that that supplement, that sNDA, would be approved sometime in the second quarter next year. Got it. Okay. Maybe we can start with the approval, REVTORPYK. I hope I'm pronouncing this REVTORPYK. REVTORPYK. That's. So maybe just we can start with the pushes and pulls of shifting the launch towards the third quarter. What are the gating factors? Sure. Well, we had always projected third quarter, so essentially we just provided more detail when we got the approval. As far as the timing of the launch and when the product will be commercially available, basically we are waiting to get initial feedback from the FDA on a post-approval supplement for our second manufacturer. The first manufacturer we have has relatively low capacity, and to support the launch, we want to have visibility and to confirm that we will have two manufacturers able to support the volume of what we anticipate the demand. This post-approval supplement was provided to the FDA or submitted to the FDA within a week after approval. So we expect to get some feedback before the end of this month. The process we have is very robust. The review and the NDA of our first manufacturer was very straightforward, really no meaningful information requests. We are very confident about the quality of the data that we submitted, the robustness of the process overall, and the capability of this manufacturer. It is just a matter of, to be frank, being cautious on my part to minimize the risk of potentially having a drug shortage in the midst of a launch, which obviously would not be a good thing. Got it. In the scenario where this second manufacturer would not be able to come online, would you have enough drug supply to actually launch at the end of the quarter? We just want line of sight on when that manufacturer would be approved, and so we just want to make sure there is no obstacle in that. Again, process is very robust, using the same process at the second manufacturer. The data generated in that process, there are probably 50 analytical methods that are used to assess, and in fact to determine adherence to the various specifications, to measure adherence to these specifications. All those metrics essentially line up. We are very confident, but again, it is the FDA, we are not in charge, and you do not know what you do not know. So we are just being extra cautious on that front. Got it. Maybe shifting the conversation a little bit to the EAP that you announced. It has been a few weeks now. Can you just give us some qualitative insights. Sure. Into the EAP? We're very pleased with the response. There are two components to an EAP. EAP is expanded access protocol. Essentially, think of it as a clinical trial, and we're supplying clinical trial materials, so that's why it doesn't interfere with our ability to launch. The challenge for some sites is that their processes to approve a protocol involves conducting their own internal IRB process. Sometimes they'll have scientific committees, and so it can be kind of cumbersome. Given that the launch, the time when the drug will be available, that actually, this in sense is a number of sites that have these fairly extensive protocol review committees processes to use it. Essentially, the doctors that are in the best position to take advantage for their patients of the expanded access protocol are ones that rely on or are comfortable accepting a central IRB. The protocol is central IRB approval, and they don't have a second step involved, and they can move quickly so that essentially they're not putting patients on EAP and then a week later, commercial drugs available. Got it. How long would it take to transition these patients? Also, have you shared any numbers in terms of demand? We haven't. We'll provide updates on our normal quarterly updates. For the third quarter would be the time when that would occur. As far as transitioning patients, that's part of the protocols that they will be transitioned, but obviously we won't do anything that could interrupt their supply. I think from a practical standpoint, we would imagine that that cut-over would occur after they've received day 15 drug. Essentially our drug is administered on days one, eight, and 15, so roughly a two-week period, then there's a two-week gap. To the extent that there's any process involved in getting the drug to that site and available to that patient, that would make the most sense from a practical standpoint. Got it. Is the EAP only U.S.-based, or do you also have. It's just U.S.-based. Yeah. Okay. Got it. Let's talk a little bit about the label. What feedback have you gotten so far? For the triplet, we had 9.4 months PFS. Versus two months fulvestrant. Right. Can you put this into context? Sure. Two things, two perspectives to consider when you are trying to compare or to at least assess how our data compares to other data presented. We reported a hazard ratio of 0.24 for our triplet, gedatolisib, palbociclib, fulvestrant, 0.33 for the doublet. If you were to look at historically the trials done in breast cancer, HR-positive breast cancer, you would see that those results were more favorable than had ever been reported in breast cancer. Very historically important sets of data. The other way to look at that is to say, okay, most of the drugs evaluated in the second-line setting have been compared to endocrine monotherapy, let us say fulvestrant, which is what we used. You have a common control. Then you can assess on a relative basis the median PFS of, let us say, the drug regimen versus the control, fulvestrant. Our triplet offered 4.5x greater mean in progression-free survival than the control. If you were to look at the historical data for drugs that might be competitive to ours or ones, alternatives that are currently being used, you would see at best maybe 2x, 2x improvement relative to the control. From a differentiation standpoint, we think gedatolisib triplet and doublet have established a new benchmark in our view, and really that warrant them being standard of care for patients who lack a PIK3CA mutation. Got it. You also had data for the doublet, which was also meaningfully different. Again, it was very favorable and essentially now with two regimens. It is unusual when you are launching a drug to give physicians two alternatives. We think that really will optimize our ability to achieve our target penetration. Because as anybody knows, in this cancer setting, there is a wide range of patients, right? You will have some 35-year-old woman who are being treated and 75-year-old woman, and then every variation in between, a lot of different clinical characteristics or comorbidities that these patients may have. By giving the doctors an opportunity to select one versus the other, again, according to their analysis of the patient's profile, that is great. We think we maximize the likelihood that the doctor will find, will want to use gedatolisib as a backbone for that second-line setting. Got it. Based on the feedback, what type of patients do you expect would be getting the doublet versus the triplet? Our research indicates in the wild-type setting that we think it will be roughly an 85/15, 80/20 split. Because if you were to look at all the subgroup analyses done in the forest plot analysis for the triplet versus the doublet, you see very consistent greater response levels for the triplet than the doublet. Now, we have heard some doctors say they will start with the triplet and they will monitor the patients, and if they believe the neutropenia that palbociclib induces is a concern, they can discontinue the palbociclib and continue with the triplet because they know based on the data that the doublet offers their patients a good option. And vice versa. Some may start with the doublet, see how the patient does, and add palbociclib. We think, again, that flexibility, giving them that optionality will improve or increase the potential penetration that we can achieve. They are both good options for patients to, again, depending on the particular clinical profile, one might be more appropriate than the other. Got it. One of the main pushbacks we've heard has been the IV dosing versus oral. Yep. Maybe can you just for us and investors, can you provide a little bit more color on. Sure. The feedback you've gotten from KOLs? Just clarify the dosing and the fact that there's this two-week off time. I think there's a lot of attention paid to the fact that gedatolisib's infused, partially because there's been a lot of work done with oral SERDs. There've been five or six drugs that have been evaluated. Many of the KOLs have participated in that, so it's very top of mind. One of the hypotheses or theses for the rationale for that drug was that it was more convenient alternative than fulvestrant, which requires intramuscular shot once a month. That's fine. But in the research that we've done, which essentially weighs, or rather takes into account, or rather assesses community docs as well as docs treating patients in an academic center, we don't find that the infusion is going to be a barrier to take up. We do an assessment of the demand that they anticipate using based on response to various potential patients that they might treat. We ask what their perspectives are on various characteristics of the drug, whether it's the efficacy or safety profile, or the route of administration. We ask that question in two different ways. What we've found amongst, and this is a quantitative survey, we're not interacting. This is done through the Internet and on a blinded basis. They don't know the drug. We only find the IV is, quote, a negative factor in their consideration of use of the drug by 5%-8% of the doctors. For some doctors, it may be a barrier, but I think a very small percentage. For most doctors, roughly 60%, or not 60%, about 50%, it's a neutral factor. The balance, it's actually favorable, because they get to see these patients. These are second-line patients. Their survival projection is a couple years, so they can decline, unfortunately, quickly. There is an advantage in that, roughly, I think 30% of these doctors, in seeing these patients more frequently. So net, we don't view it as a barrier to achieving very significant penetration. Got it. Okay. That's more clear for us. Maybe just talking a little bit about the toxicity profile and there were these questions on the label. There was a little bit of higher adverse events than what we had seen at the presentation. So maybe, can you clarify. Sure. Where is this coming from, and also particularly for the stomatitis the prophylactic measures. Sure. There are two ways of assessing adverse events or categorizing them. What you will oftentimes see in publications, which is how we approached it, you will present treatment-related adverse events. The FDA essentially decides that they want to only look at treatment emergent, which says regardless of whether there may be a linkage or not, if an event occurred, it is going to be ascribed to the drug. Okay, that is their right. There was not very much variation, to be frank, between treatment emergent, treatment-related results that we presented. There was one difference in the discontinuation rate for gedatolisib. Again, treatment-related was very low, but treatment emergent was higher. We found that discontinuations of gedatolisib early on were higher early on, and they were primarily related to one region, and that was a function probably, in our view, of just more caution than was warranted. We found in the second study, or mutation study, same sites, but it took longer to enroll, and we had disproportionate number of wild type, that the gedatolisib discontinuation rate was 5%, 4%. Essentially very, very favorable overall. We think there is always some translation, or rather, it is very typical to essentially see some, couple percent here or there difference between the treatment-related characterization of safety data versus a treatment emergent characterization. Got it. Makes sense. Maybe just on the launch and how should we be thinking about the first few weeks or few months of launch? We are going to have a temporary J-code. How should we be thinking about reimbursement friction? Sure. So, temporary J-code. One of the biggest potential obstacles when you are launching, I should step back. Anytime you are launching a drug first time, there is a variety of friction points. Systems have to put in place order sets, essentially, which is information related to your drug into their electronic health records. That can take, depending on the account, a few weeks, it can take a couple of months, and that greatly facilitates prescription of the drug. That is one friction point. Another friction point is reimbursement and time to reimbursement. Our drug is a buy- and- bill drug. So essentially these accounts will take ownership of the drug when we ship it, and they will be obligated to pay us at the time they do. With temporary J-code, the reimbursement process, the time when they get paid by the insurance company, can be very extended because it is not a streamlined process without a J-code in place. They are reluctant to potentially become cash flow negative. The way to ameliorate that or mitigate that is to offer extended payment terms to those accounts. For instance, if it would normally take 60 days for them to get paid by an insurance company, but with a temporary J-code, it could be 120 days as an example, we will offer extended terms to them so they are not, in effect, cash flow negative, out of pocket by buying our drug. That has been found to be a good way to address concerns by these accounts. But any launch will typically, it does not go to 0- 60 in a week. There is a lot of work that is needed to be done, for instance, with strategic accounts, getting pathways characterized, with obviously insurers, getting them to put you on the formulary and hopefully, assign you a preferred status along the way. Those steps take time. Our team has been meeting with, and these are market access-related dynamics. Team has been meeting with these accounts for the past 18 months. Since we have had our data, we could present our data. They can do that. They are not treaters, so you have safe harbor to talk to them about the data. You cannot really get formal committee reviews until you have your label. So we submitted the dossiers and other materials that are required for them to do an assessment of the drug more formally immediately after the approval. That process is underway, and we are very, very satisfied with how that process is going at the national accounts and strategic accounts. Got it. Revenue might not be the best metric at the beginning to really assess how the launch is going. What other metrics are you going to provide to investors? Well, yeah, we'll provide some color. One drawback of having a buy-and-bill drug is that unlike, let's say, drugs that are shipped through a pharmacy, we won't have visibility into which doctor prescribed it or whether it's a new patient. The revenue will be the most important metric overall for assessing the launch. Then there'll be what you might call softer metrics, but they're activity metrics related to status with different insurers or status with strategic accounts. We'll provide color on that. The data that's more granular, that let's say oral drugs have, because they're mostly prescribed through pharmacies directly, is something we'll be able to get on a lagging basis, essentially two to three-month lagging basis, for accounts that represent roughly 40% of patients. It'll be helpful data internally. We'll be sorting through the best way to present it because, again, it'll be lagging, and we want to make sure the data's consistently available. It won't really be helpful to provide one-off data sets. Any data that we present, we'll want to make sure we can present consistently, and the reliability of it will be consistent as well. Very helpful. Maybe can you just provide some color on your pricing strategy and h ow should we be thinking about gross to net? Sure. We submitted our pricing to the various pricing compendium, or those are the organizations that payers, strategic accounts use to access the price for their systems that will vary depending on their system, and where they fall in the universe of, well, it is public, private, et cetera. Our price is $30,000 per cycle, or $32,500 per month. There are 13 cycles. It is a 20-day cycle, so 13 cycles in a year. Each vial is $10,000. We have reported that the average duration of treatment that we found in our VIKTORIA-1 study for the wild type was around 10 months. Each patient, we think, will generate or rather utilize 10 months, or rather utilize the drug for 10 cycles at that price. The gross to net, we estimate, will be about 80%, so 20% off of the wholesale acquisition cost, which we think is favorable. There are fewer hands that the drug goes through when it is a buy and bill than if it is an oral drug, going through PBMs and a bunch of other potential intermediaries. It is a more efficient distribution, which results in, we think, net roughly, a higher gross to net than you might otherwise get. Got it. Is this number of cycles for the triplet, for the doublet, or for both? They are somewhat comparable. From our perspective, our goal is that physicians use this drug because we think it offers their patients the best opportunity to be progression-free as long as possible. If they use the doublet, fine, great. If they use the triplet, fine. Essentially what we think the impact for us will be is that they are using our drug. Duration of treatment will be comparable, plus or minus a month or so. It is more important in our view, that by giving doctors an option, we think we have increased the number of patients, the percentage of patients that they will be willing to treat with our regimen. Got it. In terms of the launch, do you have any proxies that you can share with us the way we think about gedatolisib's launch? Well, we have 90 folks, 90 oncology sales representatives in the field today. They're managed by 10 in 10 regions. We have a team of MSLs that are also calling on doctors, coordinating with the regions and how they're going after those accounts. Our strategic accounts team, essentially a separate group of individuals, works from the top down. They're the folks that are coordinating with, let's say, the Dana-Farbers of the world, US Oncologies of the world, UPMCs of the world, to get incorporated into their pathways. Those accounts are particularly relevant, UPMC and Dana-Farber as an example, because not only are they making pathway decisions for their own system, but they also make those pathways available to other systems. Let's say UPMC will actually, their pathway document, ClinPath, will be something that systems that treat roughly 15% of all patients would be utilizing to guide their treatment guidelines. A lot of work on our teams around getting those pathway determinations finalized, hopefully, incorporating gedatolisib as a regimen. We'll provide updates as appropriate, any activity there that we think will be helpful for people to understand the status of the launch. Got it. In terms of PIK3CA mutant patients. You showed the data, you submitted the sNDA. Yep. You mentioned second quarter for potential approval. Can you maybe just put the data into context? This is a more competitive space than the wild-type patients. Sure. Also, how should we be thinking about incorporation of this data on label? The data that we reported at ASCO showed that the gedatolisib doublet and triplet offered 2x the median PFS benefit. Hazard ratio was 0.5. Essentially, it showed head-to-head the benefit of a multi-target PAM inhibitor versus a single target PAM inhibitor, single component PAM inhibitor. Our research indicates there will be significant preference for this regimen. It is not often that you get a 2x delta relative to an active control as this was. As far as the competition, I think there's potential competition or additional options coming out. We think the data very convincingly demonstrated the importance of multi-target inhibition of this pathway. There's the two drugs that hit in the second-line setting that are approved, that address this pathway. One's a PI3K-alpha inhibitor, alpelisib, Piqray. The other's an AKT inhibitor, TRUQAP, capivasertib. If you look into the data, you'll see that they offer very, very comparable efficacy compared to endocrine therapy. That's not surprising to us. We think there's limited biological potential when you're only inhibiting a single component. To the extent that there are other drugs coming down the pike that are hitting a single component, biologically, we think that that approach is obsolete. We think ultimately, if you can comprehensively inhibit this pathway, as our drug does, as REVTORPYK does, that that will induce a more favorable treatment effect. We've published a lot of non-clinical data in a variety of tumor cell lines, whether it's breast cancer, prostate, endometrial, ovarian, et cetera. Very consistently shown that gedatolisib is, in breast cancer in particular, 300 x more potent than a single-target inhibitor, whether it's an everolimus hitting mTORC1, or capivasertib hitting AKT, or alpelisib hitting PI3K-alpha. That just relates to the nature of this pathway. Very complex, multiple components. Inhibiting one component induces activity down the others and essentially cross-activates the others that are uninhibited. If you are able to shut this pathway down by hitting all these components, you don't need very much drug. 12 nM versus 6,000 nM, for instance, to induce a half maximal effect. It's very relevant. It's orders of magnitude better to comprehensively inhibit that. So we'll see what comes of these other drugs. But we think the underlying mechanism of action of gedatolisib is very relevant, and we think ultimately that's going to maintain as the standard of care for these patients. Very helpful. Maybe, can you share with us how you're thinking about duration of treatment for these PIK3CA mutant patients compared to the wild type and also commercial opportunity versus the wild type? 60% of patients do not have a PIK3CA mutation detected. That is the wild-type group that we have approval for. 40% have a PIK3CA mutation. The data that we presented for duration of treatment for the mutant is much more immature than the data we presented for the wild type. The mutant population with fairly short follow-up, average duration was in the 11-month to 12-month range, so it will be greater than the wild type. As that data matures, essentially when you are doing an average, what can really greatly impact or help your average duration is just that a lot of these patients are on drug for years. That obviously will boost up the overall average. We think net, the mutant population will represent 45% of the total market, 40%+ a little bit more on top because of the somewhat longer average duration of treatment. Got it. Maybe just on the survival benefit, we have not seen median overall survival for neither the wild type or the mutant patients so far, but when should we be expecting this, and how important do you think it is for doctors? Sure. There hasn't been a survival advantage shown for any drug in the second-line setting, and I think just the various confounding factors that make that challenging. In the wild-type setting, we've presented interim OS analysis for both the wild type and mutant and showed favorable trends. In the wild type, we think the survival data will be confounded because we allowed crossover. Patients who were treated in the control arm with fulvestrant were allowed to cross over. Roughly 60% or so crossed over. So essentially, we're competing against ourselves in that OS analysis. Whereas in the mutant population, there was no crossover, so it's head-to-head. Again, promising but preliminary immature data in the mutant segment. If that analysis, we think, will have the best potential opportunity to show a possible survival benefit. But again, it's a high hurdle to meet, and it hasn't been met to date in the second-line setting in breast cancer. Got it. Very helpful. Maybe just with the last few minutes, just wanted to touch upon the first-line study. You included the endocrine-sensitive patient population e arlier this year. How are you thinking about the strategy there, and what gets you confident that you can succeed? There are 90,000 women each year who are diagnosed with metastatic disease is untreated, treatment-naive patients. 60,000 of them are endocrine sensitive. They get about 25 months of benefit from their current treatments, median progression-free survival. In a phase I-B study that enrolled 41 patients, we reported 48 months median PFS. Obviously compares very favorably to the reported data for the current standard of care. We're optimistic about that study. Certainly, the fact we have two positive readouts in wild type and mutant that showed very significant activity of gedatolisib gives us additional confidence. That's a longer study. We're enrolling, I think, 760 patients or so, or 780. We don't expect that data probably until late 2029, 2030, sometime. Endocrine-resistant population, worse prognosis. These are women who didn't get much benefit from their adjuvant endocrine therapy, their letrozole or tamoxifen. They're only getting about seven to eight months of median progression-free survival from their standard of care therapy. It's a lower bar to beat. In some ways you can think of it as almost a second-line study in the context of the data that we need to show. We think the data we've shown to date, if we repeat what we did in the second-line setting, in that setting, we'd have a positive readout, we think. We're optimistic about both studies, and we think having the quality and differentiation of the data that we showed in the second-line setting just augurs very well in the first-line setting. Importantly, this pathway, the PAM pathway, one thing that distinguishes it from, let's say, the estrogen receptor pathway, which can be affected by prior treatment and induce ESR1 mutations. PIK3CA status is stable, and it's intrinsic. That mutational status doesn't change over time. First-line patients with PIK3CA mutant is very similar to the second-line patients, so there's no transition. Our data from the first-line population was 80% wild type, it showed really that the extended progression-free survival we reported occur even though most of these patients lacked a mutation. We think that provides demonstration of the important role this pathway plays intrinsically in this disease. It's not a function of what patients received for prior treatment. Got it. You also mentioned earlier this year you were working on a sub-Q formulation. Yes. Maybe can you just give us the latest there? Sub-Q formulation we think is going to be most important for patients who are endocrine sensitive, patients who could be on this drug for several years. For obvious reasons, it would be more convenient for them to have the ability to have a shot, potentially self-inject. We don't think it's going to be as impactful or really very impactful on the second-line setting or the endocrine-resistant population. It'll help, but it's not determinative. We've begun that work. We began that work a while ago. We're advancing several candidates' formulations. There's a variety of criteria that we're using to evaluate those, so we're moving those through the pipe. The goal is to have an approved sub-Q formulation in time or to coincide with approval, we hope, of our regimen for the endocrine-sensitive population, in 2030 timeline. Got it. Very helpful. Are there any questions in the room? No? I'll ask one last on prostate. Yes. We have data coming up in the fourth quarter of this year. Yes. Maybe can you just g ive us a sense of what should we expect? Sure. We presented data probably last year. In our view, it was favorable. It showed, compared to historical data, a meaningful increase in percentage of patients that were progression-free at six months. In this update, we'll have data from an additional dose. We'll also provide some additional subgroup analyses that we think will be informative. Then we'll also update on our next step for the development of the drug in that setting. Got it. Perfect. Well, we're out of time. Thanks so much for joining us today. You're welcome. This was very helpful. My pleasure.