Everyone, and welcome to Citi's Back to School Biopharma Summit. I'm Eric Joseph, senior biotech analyst with the firm, and one of our first fireside sessions this morning is with Celcuity, and it's my pleasure to be joined by company CEO Brian Sullivan to discuss the company. Brian, thanks for joining us. You're welcome. Thanks for having me. Maybe for anyone less familiar with the company, Brian, we could perhaps have you start out by just providing some high-level remarks, and then we'll pop into Q&A. Sure. Our lead candidate is actually now an approved drug, REVTORPYK, which is a pan PI3K/mTORC1/2 inhibitor. We recently received approval for a second-line indication in HR-positive, HER2-negative advanced breast cancer. We are getting ready to launch this quarter. We also have two phase III studies in the first line setting in HR-positive breast cancer, one for patients who are endocrine sensitive, then another one for patients who are endocrine resistant. We have an additional study ongoing in prostate cancer that is in the early stage, phase I-D/II, and we expect to provide updated results towards the end of this year on that study. Okay. Okay, great. Let's pick up on the REVTORPYK launch. We are in this interim period before products ship and start to go out. Can you just frame where things are with respect to just from a product awareness standpoint among oncology providers and just the groundwork that has been put in place to support access? Sure. We began preparing for this launch 2.5 years ago, and that included primarily, initially at least, building out the organization, ensuring that we had the appropriate team. We finished building that organization except for the sales force last year, and then added the sales force members. We have 90 folks, oncology sales specialists, in the second quarter. They began profiling accounts, working with doctors prior to having approval. They could not educate doctors on the data, but they could get an understanding of the physicians' tendencies towards what they use to treat patients. They could lay groundwork for the accounts in other ways. Our market access teams have been working with national accounts, which are the payers, for the past 18 months. Because they have safe harbor, we could present data, we could familiarize them with the product. Similarly with strategic accounts. These are the Dana-Farber, US Oncology of the world. You can work with them because they create a lot of what are considered to be clinical pathways. They essentially define the treatment paradigm for not only their institutions, but they also offer these pathways to other institutions. With these strategic accounts, they have outweighed very significant influence beyond just the group of patients they may be treating at their facilities. Now, our sales force has been meeting with doctors with the data. We have had two phase III data releases. We released our wild type data July 24 or 25 rather, and then we released our mutant data. This is PIK3CA mutant data at ASCO. With those two data releases, because the data we believe was unprecedented in terms of the level of results that we were able to report, it got a lot of attention. Prior to the launch, we conducted an unbranded campaign to educate doctors, physicians about the importance of the PAM pathway, PI3K/AKT/mTOR pathway, as well as the importance of comprehensively inhibiting it. We cannot promote the drug, we cannot mention our drug, but we can educate them about the pathway and the relevance in particular of our mechanism of action. Now that we have approval, we have our sales force meeting with doctors. We have each of these oncology sales specialists as a business plan. They have a target number of doctors within their territory. They understand priority doctors and accounts to work with, and that has been going very well. You overlay that with other programs, whether it can include digital marketing or other ways of getting in front of doctors, and we assess that. We think we have created a significant awareness to date amongst not just the academics or the KOLs who I think have been following us because that's part of what they do, but also more importantly amongst the community docs who represent or rather treat approximately 80% of breast cancer patients. Okay, great. I know that having clarity on a second manufacturing site is a key step that you want to have in place before beginning shipments later this quarter. What's the approval status of that second site today, and how should we be thinking about the scale of market reach, how much of the market you can serve once you start shipping commercial product? Sure. The second site is really there to provide additional capacity. Our first site can provide the capacity we need for the initial launch. We want visibility in the approval, in the review process of the FDA. We submitted a post-approval supplement that contained the validation data for the batches that this manufacturer ran. The process is very robust. We've gone through a review just a few months ago for our CMC package and the processes and specifications and analytical methods. So very confident about that, and now it's just a matter of having initial interaction with the FDA to understand or to gain confidence that somehow something new isn't going to pop up. So we don't need them to be approved. We don't need that PAS to be approved. We just want line of sight that it'll follow a normal course. Can you say more about how that line of sight is provided, I guess the interaction that you- The interaction with the FDA. Okay. Once you submit, you will typically get information requests and those interactions essentially provide a perspective on that that we will assess. I mean, we have been interacting with the agency for five years on this particular drug, and a lot of familiarity with the individuals involved. Again, we just are somewhat being cautious. We are confident about the data. We just do not want to be blindsided. Okay. Got it. I know that an expanded access program is already open. Can you discuss the pull-through that you are seeing into that program currently and how patient eligibility is determined? Sure. We just put that in place a couple of weeks ago, and it is targeting, or it is limited to patients who would be otherwise indicated for the drug, essentially the patients who would be consistent with the label population. One of the challenges of any EAP, which is essentially considered a clinical trial, it is an expanded access protocol. Because it falls into that category of approach, each site needs to approve that protocol. For larger sites that may have their own IRBs, Institutional Review Boards, that process can be quite extended. Because the window of time that- I see. we won't be having product available, it's very difficult for some of these larger sites to actually take advantage of it. Whereas the community sites or smaller sites that essentially are willing to rely on a central IRB approval, which we have, the process is much easier. We've gotten a lot of interest. Patients are on the drug through this, and more importantly, I think it signaled to the community that we want to do everything we can to make sure product is available for their patients, and we'll work with them if it's possible for their institution to take advantage of the program. Okay. I guess for all the folks who are tracking estimates and so forth like that, from a reporting standpoint, I'm just curious whether EAP demand or any volumes get reflected as sales and whether you'd expect that to be a meaningful. No, they won't get reflected as sales. Okay. We're offering this drug. It's considered a clinical trial. We're providing this drug in the context of that clinical trial. It's, in effect, free of charge. Okay. Once the drug is commercially available, those patients will be transitioned to a commercially available product. Okay, great. I guess in the wild-type PI3K kinase setting where REVTORPYK is approved today, you're talking about a market here that's roughly the same size as HR-positive, HER2-negative breast cancer with PIK3CA alpha mutation, if you are excluding patients with ESR1 mutation, if I have that rough math correct. From a benchmarking standpoint, is it useful to look at the launch trajectories of other PI3K alpha products here? I'm thinking of TRUQAP, for example. Can we think about- Sure. in demand- Yeah, the analog. as a comp here for REVTORPYK? I think there are two profiles of companies that end up launching drugs these days. One is the major pharmaceutical companies or ones that are already in the market and maybe already in the indication that they're launching a new drug. Those companies will have an advantage and will be able to reach peak sales probably within 24 months. I think that would be the typical result, and we've tracked that. Whereas companies like ours, launching their first drug into a new space, the time to peak, based on the analogs that we've found, is closer to 36- 42 months, and 36 months is probably more realistic. I think when you think of it that way and you reflect on the importance of the time to peak on the actual early sales then the analogs of, let's say, a TRUQAP, aren't quite applicable. Okay. That's helpful. Just, you're approved with two regimens here, a doublet with fulvestrant and then a triplet with fulvestrant and palbociclib. What's your sense of which combo regimen docs are more likely to treat with here, and do you anticipate any payer pushback, payer limitations with respect to the use of a triplet regimen in any sense? Perhaps putting gedatolisib and palbociclib in a little bit of tension. Sure. So, two things. One is that by having two regimens, we've actually, I think, increased our ability to optimize the penetration of usage of gedatolisib, because there's a very heterogeneous population in breast cancer. 30-year-old women, in some cases up to 75 or 80-year-old women. So giving doctors two options that they can use to essentially optimize for their patient, depending on their characteristics, will be very helpful, and that's the feedback we've received. However, for the triplet, the research that we've done to date has suggested at least that we would expect roughly an 80/20 split between the triplet and the doublet. Part of that may be informed by the fact that some doctors have indicated they'll start with a triplet. They always have the option if they're concerned about the neutropenia from palbociclib to back off the palbociclib. Alternatively, we've had some doctors tell us that, well, they'll start with the doublet and then allow the patient to see how the patient's doing and then potentially add palbociclib once that patient has received a cycle of therapy or so. So I think that flexibility will be very helpful to the doctors, because again, they can select what they think might be best depending on the patient's profile. That's always a challenge with any regimen, especially in breast cancer where you have such a wide range of patient subtypes. From your discussions with docs, do you anticipate use of REVTORPYK in patients with an ESR, with ESR1 mutation? I guess, yeah. I guess, if they were to do that, would they use the doublet combination as per label, or would they kind of seek to perhaps do a novel combination with an oral SERD? I think it would be helpful just to step back and think about these segments. There is roughly 40% of patients that lack a PIK3CA mutation or an ESR1 mutation. They are double wild type. There is about 40% of patients that have a PIK3CA mutation, and they may have or have not an ESR1 mutation. Then there is 20% of patients that are PIK3CA wild type that have an ESR1 mutation. I think in the two groups of patients, PIK3CA wild type, ESR1 wild type, and the PIK3CA mutant, the gedatolisib regimens will be very, very competitive. They are highly differentiated in efficacy and safety profile, and we think that will comprise a significant proportion of the regimens that the doctors are prescribing. In that subgroup, that 20% portion that are PIK3CA wild type, ESR1 mutant, it will be more competitive. I think there is a very strong rationale to use the gedatolisib regimens, especially when you dig into some of the subgroups that we have reported on in terms of the duration of response, for patients with or without visceral mets. Characteristics like that allow you to see some fairly significant differentiation from the regimens that include an oral SERD. Okay. When we look at the results from study one of VIKTORIA-1, there is a little bit of discord in the PFS duration, on the triplet regimen versus the doublet. I am wondering whether, and I know there are some regional differences in that discord. I am wondering whether there are any implications from that signal as we think about the real-world duration on therapy with REVTORPYK here in the U.S. Sure. I actually think the population that we enrolled was a tougher population than the population you would see in the real world. In our eligibility criteria, we require patients to have measurable disease. In the real world, you would find roughly 20%-30% of patients with non-measurable disease, bone-only disease. Interestingly, when we look at the subgroups and look at patients who, for instance, don't have visceral disease or don't have measurable disease, the median PFS, the duration on therapy is significantly longer than those with measurable disease. That is consistent across the mutant and wild type subgroups. We actually think there is limited downside to the duration of treatment that we reported for the VIKTORIA-1 study, roughly 10 months duration of treatment average. In fact, if anything, there could be upside. Yeah. Given that the nature of the population that exists in the real world. Okay, great. Let's turn to the PIK3CA mutant opportunity here. You're expecting to file an NDA this quarter. No, we actually already filed that. Oh, excuse me. We filed that last year. Sorry. My bad. I guess, from a review standpoint, are you similarly expecting a priority review timeline for that? We haven't heard from the FDA on that. We're assuming sometime in the second quarter, and we'll see, once they do their review and we presume, hopefully, accept our submission. Okay. That's two months from the time of submission. And I guess, assuming approval, can you talk about the operational work that is still to be done, perhaps in support of an expanded launch, and whether there's any added scale-up to product capacity, manufacturing capacity to serve the wider eligible market? Sure. We have a production forecast that's linked to our sales forecast. One of the reasons why we're focused on having our second manufacturer, is to ensure that we have sufficient capacity because we expect to get significant penetration in this market. With the addition of an indication we expect in patients with these mutations, we would expect even greater volume. We're also working to validate two other manufacturers. We hope to exit 2027 with four validated manufacturers for REVTORPYK. Okay. I think there's going to be some interest from physicians who would seek to treat patients with mutant PIK3CA breast cancer, as soon as the product becomes available. Are payers-- Maybe you can speak to that interest, and then whether payers are likely to support access and reimbursement in the mutant PIK3CA population ahead of an expanded approval and what rule guidelines might have- Right. play here. We can't promote an off-label indication. But what can happen is that NCCN, if there's published data available, can make the decision to add, in this case, a recommendation for, let's say, in this case, the PIK3CA mutation population. If that were to occur, that would provide the level of evidence for payers to potentially make a reimbursement decision. But again, it's not something that we can really promote at all, and our focus is on getting the drug approved or getting the drug REVTORPYK approved for that patient population. Okay. Obviously, you're not done here with the development of gedatolisib in advanced breast cancer. You're running a frontline study, the VIKTORIA-2 trial. Can I just sort of get you to give us a snapshot of that trial- Sure. and sort of some rough guidance as to when you expect readouts from- Sure. from that study? There are roughly 90,000 women a year who are diagnosed with metastatic breast cancer and have not yet received treatment for that metastatic disease. 60,000 of them have what is considered to be endocrine-sensitive disease. These are women who had early breast cancer and were seemingly out of the woods, and unfortunately, it recurred a number of years later. They will typically get roughly 25 months of benefit from currently available therapy. We ran a phase I-B study in that population and reported median PFS of 48 months. Very, very extended time for these patients. That gives us optimism about the ability of gedatolisib, when combined with palbociclib and letrozole, to potentially improve the standard of care for that patient population. The second group of patients, roughly 30,000 or so, are considered to be endocrine resistant. These are women who did not get much benefit from their adjuvant, tamoxifen or letrozole, that they received after they were treated for their early breast cancer. They have a much tougher prognosis. They are only getting seven to eight months of benefit from the current standard of care therapies. It is a very significant unmet need for these women. That study is essentially separately powered, separately conducted within the overall protocol of VIKTORIA-2, and will have independent timelines. We would expect data from that population to be available earlier than the endocrine-sensitive population just because of the shorter duration of benefit expected in the control arm, in this case. I appreciate that you would expect a readout from the endocrine-resistant population a little bit earlier, but I guess from the expected PFS duration, I guess, from the control arm, we are thinking perhaps a readout in what timeframe do you think? Late 2028, 2029. 2029. Okay. Yeah. Okay. Got it. Okay. Maybe we could move to prostate cancer, right? With gedatolisib, which is where you're running a phase I-B study right now. You'll present some data there, I think, in the fourth quarter this year. I guess from a readout standpoint or a venue standpoint, how are you thinking about where those data might be presented? Are you targeting a medical meeting or. A medical conference- Okay. and we'll be at ESMO. Essentially, we'll be providing an update with some additional analysis of response by various subgroups, as well as some information from patients who received a higher dose than the first two doses, first two groups of patients that we evaluated. Okay. Compared with breast cancer, I guess, you see an overrepresentation of PTEN loss among various potential PAM alterations that you might see. You see PTEN loss overrepresented in prostate cancer- versus breast cancer. Can you talk about your confidence or what the preclinical data support in terms of gedatolisib being responsive or cancer cells with PTEN loss- Sure. being similarly sensitive to gedatolisib- Sure. versus breast cancer? Right. Yeah. It's interesting. Both breast cancer and prostate cancer have mutations of this pathway. PIK3CA is the primary one in breast cancer. PTEN loss, as you said, is the primary one in prostate cancer. And we've done a lot of non-clinical work to characterize the activity of REVTORPYK, gedatolisib, in breast cancer cells as well as prostate tumor cells. And we have not found significant differentiation in the level of activity in terms of potency and have maximal effect on limiting proliferation, as well as the cytotoxicity of the drug based on their mutational status. PTEN loss is roughly about 25% of patients, at least based on studies that have been reported out recently. And similar to the PIK3CA mutation, single-target inhibitors, such as TRUQAP, for instance, which hits AKT, have really only been found to be effective in patients that have PTEN loss. In effect, that's the mutation. Whereas our data suggests that the PTEN status won't be significantly relevant to the sensitivity or the responsiveness to REVTORPYK. And again, that relates back to the mechanism of action. By inhibiting all four isoforms of PI3K, mTORC1, 2, you are essentially shutting down that pathway, and the PTEN status then becomes not so relevant. Just coming back to the anticipated data readout at ESMO, can you just talk about the scope of the readout in terms of, I guess, volume of patients that you'll be reporting out on, and perhaps a sense of median follow-up? I don't know offhand what the median follow-up period is. I think the most relevant aspect of the data that we'll be reporting are the different subgroups and the new dosing level that we evaluated. Then we'll also be providing an update on our next steps for evaluating gedatolisib in that patient population. Would a subcu formulation be part of the discussion around next steps? Not so much with prostate cancer. A subcu formulation, which we've been working on, and we expect and are targeting getting approved in conjunction or around the same time that we would expect to get approval, let's say, in the androgen-sensitive population with breast cancer. Given the data that we've reported to date, given the duration of response that patients receive on standard of care, these patients could potentially be on this drug for a number of years. A subcutaneous formulation would clearly be a benefit to those patients. It would open up the market. We would have much higher potential peak penetration. With a subcutaneous formulation, we get that. We don't think the subcutaneous formulation in indications in the second-line setting or in the androgen-resistant population will be necessary to achieve near peak penetration. Certainly, when it's available, we would make it available broadly, wouldn't be independent of the patient population. But we don't think it's a key to achieving what we think is the peak potential in those settings. With prostate, again, that's at an earlier stage, and so most likely just the way the timelines will work, if our subcu formulation advances as we expect, it would be available in conjunction with potential. Again, a lot of things have to happen the way we want. But if those things do happen and we're successful in demonstrating in a phase III study that a geta regimen can offer a statistically significant improvement, then the subcutaneous formulation would be available to those patients as well. Got it. Okay. All right, great. Maybe just one last question before we wrap up. Just wondering what's next beyond these first broad sets of indications that you're in currently for gedatolisib, whether there's. Let me take a step back, actually. What I want to get to is just really a question around business development, whether there are additional indications for gedatolisib that you're pursuing or looking to pursue, or whether you might seek to expand the pipeline through BD. Sure. I would say two things. One, the development program we have in place is addressing two of the largest tumor types of all, right? Women with HR-positive breast cancer, as well as men with prostate cancer. Those indications alone, if you were to analyze the served market potential, are tens of billions of dollars. So we're addressing very important unmet needs in very significant populations. So that's a full plate. Now, we are also doing work, which we haven't disclosed, to expand the range of indications we could pursue, patient populations we may evaluate, or considering other drugs that could be consistent with our approach to treating solid tumors. Okay, great. I'll hold here for any questions from the room. All right, great. Well, we'll wrap it there. Thanks very much, Brian. Thank you, Eric. Okay, good seeing you. Thanks. Great. Thank you so much