All right. Good afternoon, everyone. I'm Andrew Berens, Senior Biotech Analyst at Leerink Partners. Thank you for joining us on day two of our annual Leerink Global Healthcare Conference. We're very excited to have with us, Brian Sullivan, CEO of Celcuity. Thank you for joining us. You're welcome. Pleasure. You got a lot going on, Brian. We do. You took time for us. We appreciate it. No, it's my honor. This is what I need to do. For those that don't know Celcuity, can you give an overview of the company? Sure. Well, I started the company a while ago now to initially develop a platform with our chief science officer to isolate the activity and quantify the activity of live patient tumor cells so that we can help identify patients who might be responsive to particular targeted therapies. We began working in the PI3K space and identified what we felt was a fantastic drug, gedatolisib, pan-PI3K/mTOR inhibitor, and began developing that drug in 2021. Now we have, you know, essentially completed one phase III study. We have another one we'll report out soon in the second line study in breast cancer. We also have a first line study in process. I'm sure we'll talk about that as well in breast cancer. We have an early phase study in process in prostate cancer. Okay, great. Well, you guys entered a very dynamic space. Mm-hmm. with a lot of moving parts. Since you started your program, a lot has transpired and a lot of pieces have fallen into place. Others have fallen out of place. Mm-hmm. How would you say HR-positive breast cancer looks today? You know, first line, second line, adjuvant. What do you foresee? Sure. What's different, I guess, today than it was when you started your program? Well, I think the most important data set to be reported, to be frank, is ours, because we've validated the important role this pathway plays independent, irregardless of whether there's a PIK3CA mutation. Our early phase data demonstrated the important role this pathway plays in patients who are treatment naive, who've never received treatment, or in a late-line setting. I think if I look at the landscape going forward, I think essentially, you know, gedatolisib will change it. We hope to have studies that will demonstrate the activity of gedatolisib in the front line setting for women who have endocrine-sensitive disease as well as endocrine-resistant disease. We've already shown essentially unprecedented levels of efficacy in the second line setting in patients who lack mutations. We hope to kinda close the loop with our data set in the next few months when we report out our mutant setting. I think all the other studies have essentially been trying to optimize existing targets. I think the PAM pathway has really been kind of very, very suboptimally targeted to date and really have only shown modest efficacy in a subset of patients. We think our drug has the promise of offering you know optimal tumor anti-tumor control irrespective and you know in both front line and second line sttings. Okay. There certainly seems to be something, I'm gonna use the word magical, for lack of another term, but when you hit the PAM pathway with both, a PI3K drug as well as an mTOR inhibitor versus what you would see with individual. Would you agree? I mean, what is causing? Sure. -the bet- So- the better efficacy we've seen? There are two key features of this pathway. One is it plays a critical role in regulating the glycolytic system in a tumor cell, which essentially means it's regulating the uptake of glucose, which is the energy source or primary energy source for tumor cells. They're particularly dependent on glucose. They consume 100x more of glucose than a healthy cell. It's a very relevant pathway, and that's why gedatolisib has shown its ability to work independent of the mutation. Because it's so important, it seems to have built in these redundancy mechanisms. You have multiple targets that are required to be addressed to control it, to comprehensively shut it down. You have the four Class I isoforms of PI3K, you have mTOR one and mTOR two. That unless you control all of those or inhibit all those, targets and shut down this pathway, essentially this pathway can continue to function. Now, drugs that hit a single target have shown activity when the tumor has a mutation. Absent that, they really haven't shown, as meaningful activity. So that's been the riddle. How can you essentially address this pathway in light of its complexity? Also because of some of the safety, challenges associated with this pathway. Because it does regulate such important physiological activities, depending how you hit it, how often you hit it, the concentration required to address it can induce unacceptable levels of toxicity. Right. Okay. Obviously, there's been a lot of attempts for people to improve upon fulvestrant. Mm-hmm. That's fallen short. We just had the announcement yesterday. Mm-hmm. That another oral SERD was disappointing in the front line this time. Which, you know, I think for you guys, I think it was a double-edged sword in some ways. I think it was good in that it gives some stability to the front line. Mm-hmm. We have the same stability, I guess, in the second line, meaning that fulvestrant's not going anywhere. It doesn't look like AI's going anywhere, at least in the near term. Mm-hmm. I guess, how do you view kind of the news about another oral SERD? Well, look, you never root against another drug, right? To the extent that there's an opportunity to improve outcomes for patients, you want that to work. The fact it didn't work certainly creates clarity around how to think about improving the outcomes for those patients because you know what the components of a regimen would be, you know what the components of the control would be. That makes it very straightforward to take the next step. Again, if you think of breast cancer, three pathways, you need to close that circuit. We think gedatolisib is the only drug under development that we think can effectively close that circuit and create, we hope, but based on our early, you know, the phase III results, we think we have a very good chance to do that and create a very meaningful treatment benefit in the frontline setting. Look, let's go through the data you showed in the second line. Mm-hmm in the wild types. Right. The trial that's about to read out in mutants. Sure. You know, we reported out two primary endpoints. We reported out data for gedatolisib plus palbociclib and fulvestrant, compared that to fulvestrant. Reported nine point three months median PFS compared to two, so a seven point three-month delta. That was the biggest delta ever really reported with an endocrine therapy before in the second-line setting. The hazard ratio, 0.24, was the most favorable hazard ratio that had ever been reported in breast cancer. It was really unprecedented level of efficacy. That, again, just reflects the importance of the target and how well gedatolisib does in mitigating or inhibiting that activity. We also saw very significant activity for gedatolisib combined with fulvestrant, so a doublet versus fulvestrant. Again, absent the triplet, it would have been the best results reported in the second-line setting. We think that helped validate our hypothesis that it's important to control this pathway comprehensively, and then if you do, it can induce a very significant benefit, again, irrespective of the mutational status of PIK3CA. Okay. The data that are coming in the mutant population? You know, we expect to report that data end of this quarter, sometime next quarter. We've reported early phase data that is quite promising. Reported in a cohort of patients in a phase Ib study about 14.5 months median PFS. That would be a great result if we reported that. To be statistically significant in this study, based on the results that have been reported to date for our control, which is alpelisib + fulvestrant. Yep You know, 10 months would be statistically significant. It would also be clinically relevant because the true standard of care today in the PIK3CA mutant patients with PIK3CA mutations is capivasertib and fulvestrant. In the setting that we're in, that drug reported about five and a half months median PFS. You know, even if we just squeak over the line with a statistically significant study, we'd be nearly double what that drug has been able to offer patients. We think it would be very clinically meaningful. Given our early phase data, certainly we think the odds of being positive are high. We think they're also high of hopefully doing better than that, but we'll see. Right. Now, you know, over nine though in the wild types, and now you're adding in a tumor that should get an added benefit. Right. You would think that. Right Plus the data that you've shown. Right. I think, I recall in that Phase Ib reanalysis, there was actually a smaller group that actually did even better that was similar to which, the way you're- Right using it now. Right. No, I just wanna manage expectations. That was great data. It was 19 months median PFS in patients that have mutation. Small sample size, so you have to really caveat that. But I think what it just shows is gedatolisib, all the results we've reported to date for gedatolisib in either the early phase or later phase setting have shown, you know, very, very good results. Again, just demonstrates the relevance of the pathway and capability of gedatolisib. Now, I mean, obviously, large pharma has spent a tremendous amount of effort to broaden the oral SERDs. Mm-hmm as broad as they can get them, and they've run into some difficulty beating fulvestrant in the second line. Mm-hmm except for in ESR1 mutant patients. Now we haven't seen the data yet, but, you know, they said there was a numerical but not statistical trend. Mm-hmm In the front line beating AI. You know, would it be possible hypothetically to run a trial with gedatolisib plus an oral SERD and use that to beat fulvestrant or AI? It would be challenging because you have two changes to the study arm. You would need to control for both. Especially if one drug has already failed the comparison and not shown to be active statistically in a meaningful way, it would make the trial design very complicated. Okay. You'd have to run like a 3-arm trial. Right. I see. You've done a three-arm trial before. Yeah. Once you've done it once, you want to avoid it if you can. You've done two of them. Right, again. If you can avoid it, you want to avoid it. Okay. Let's talk about the front line. Sure. We have a Phase III in patients who are HR-positive, treatment naive, but are considered to be endocrine resistant. These are patients who didn't really get much benefit from their adjuvant endocrine therapy. They essentially had early breast cancer, and the disease recurred either while they were receiving their tamoxifen or within 12 months after. It's a tough group of patients, unfortunately. Current standard of care for the most part that they get is only gives them about seven months median PFS. It's in some ways it feels a little bit like a second-line study in terms of the outcome that they're currently getting. That population is comparable in size to the second-line population we're treating. It represents about, you know, a third of all women who are treatment naive. We've been doing a safety run-in to evaluate gedatolisib with ribociclib, and we expect to report out the results of that and then any updates to the study design in the near term. Okay. What would be I mean, if one of the advantages of that subgroup is that it wouldn't be like a four year or five year- Right. No, exactly. That's why we prioritize that. Biggest unmet need, and in turn, that also typically corresponds to a relatively short trial. Whereas the endocrine sensitive population, you know, which is roughly 60,000 women who are either well beyond their time of treatment with an adjuvant endocrine therapy or de novo metastatic. They weren't diagnosed with early breast cancer. They just present with metastatic disease. The women treated with current standard of care, CDK4/6 + letrozole, get about 25 months. That's a longer study, right? Your control. You know, that's your control, and then your study arm would hopefully, in our case, be a lot longer than that. It's an important opportunity, we think to help these women just stave off progression as long as possible. The earlier you can do that, we think ultimately it's better for patients. That one B trial that you cited that had four arms, what did you see in the naive? Actually, these were really good results. We reported 48 months median PFS, 79% objective response rate. Very, very favorable and encouraging, and that's why we think ultimately it will make sense for us to launch a study in that setting. Okay. What's the gating factor for that now? We have a lot of stuff going on, you know, we're getting ready to launch a drug. We'll get an approval decision. You know, PDUFA date is mid-July. You know, we're sorting through things and we'll keep people updated. Right. What preparations have you made? How big a sales force do you need? We've largely completed the build-out of the organization, except for the sales force. Essentially you need market access, several teams in market access, a marketing team, commercial operations team, medical affairs. All those teams are built. The sales, the head of sales, regional team, regional manager team is built, and we'll bring on the sales force beginning in the Q2. There's a lot of infrastructure systems and process-wise that need to be built. Other organizations, other sub-organizations within different departments also need to be created essentially to handle the requirements of being a commercial organization. That's well on its way. We're kind of close to being ready to go and, you know, targeting hopefully an approval date mid-July. What size sales force do you think you need? We haven't disclosed that yet. But, you know, if you were to benchmark other companies that have drugs in the breast cancer space, you'd see they typically have around 90. It's a very manageable size, sales force in terms of how to reach the docs. Okay. The fact that it's intravenous would mean you can target a smaller group of- Well, no, I mean, actually pretty much every practice because, for instance, breast cancer, the largest drugs, most significant drugs are all IV. Every doc that treats breast cancer patients has to have a connection to an infusion center just 'cause a good chunk of their patients will need infused drugs. As it turns out, that's an important component of particularly in the community setting, an important part of their practice. They're well organized, and they have the infrastructure to do that. To be frank, you know, economically it helps support their practice, as well. From a market access standpoint, medically infused drugs are considered to be medical benefit, tends to get a less challenging reimbursement pathway than oral drugs. There are a lot of factors that are to the good for us by having an IV drug. We think, you know, ultimately that'd actually be a favorable factor for our launch. Okay. The feedback, I mean, as you've been doing your commercial. Mm-hmm assessments has been strong for the IV? It has. I mean, you do a lot of different testing of messages of appeal. You know, you present data. You do a lot of quantitative research, you know, where it's essentially without any prompts, just essentially giving information to docs and allowing them to, you know, evaluate the data and draw some conclusions from it. All of that research has been very favorable in terms of what at least we're seeing for preference for use of gedatolisib versus the current alternatives and the low impact we think having the drug administered as an IV will have on that preference. Okay. You wanna talk about the prostate program? It's interesting. The underlying biology of prostate cancer has some parallels to breast cancer. Both are hormonally driven tumors. HR-positive breast cancer is. These hormone pathways in prostate cancer, the androgen receptor pathway has been shown non-clinically and clinically to interact with the PAM pathway. In a way that essentially could be considered similar to what you see with breast cancer. We have a study that's evaluating gedatolisib combined with a very good androgen receptor inhibitor called darolutamide in men whose diseases progressed after they've received, you know, frontline or an androgen receptor inhibitor. We hope to show that we can improve the outcomes for these patients, these men. Early results for two different doses were favorable. We think we showed that we can induce a meaningful treatment effect. The safety data actually was very encouraging. It was surprising. It was better than we expected. It seems men have a different safety profile than women that receive gedatolisib. We thought it was important to evaluate potentially another dose to make sure we haven't ruled out that prematurely. We expect those results sometime by the end of this year. Okay. The combination partner you said is which? Darolutamide. That's a drug owned by Bayer. It's the most potent androgen receptor inhibitor, and it's also the best tolerated. Essentially, if you stack these up, it's really the best partner drug for gedatolisib. Because it's not used as widely as the two standards of care, enzalutamide or abiraterone, you're gonna switch all these patients. They won't have received this drug, and so it makes it a very good alternative to combine with. Okay. Are there any other tumor types that you think? there's been interesting work done in endometrial cancer. Gedatolisib actually reported very favorable data in endometrial cancer as monotherapy. there've been some other studies that have shown some activity hormonally driven. Roughly 80% are ER positive, of endometrial tumors are HR-positive. It's confounded a bit because PD-1 drugs have become a standard of care for many of these patients in the frontline setting. Not 100% clear how that may change the potential responsiveness to targeted therapy 'cause typically you move on to chemo after PD-1 drugs. that's an unknown. you know, there are other tumor types where other drugs have shown activity but potentially didn't develop further because of safety issues. We think, you know, we overcome those safety issues. There's some interesting threads to pull on, outside of, you know, breast or prostate. Okay. Can we talk a little bit about the IP? Obviously, I know you think the IV formulation. Mm-hmm Is gonna support the commercial launch for the reasons you mentioned. Is there any thoughts about a subcutaneous version? Sure. I'll talk about the IP. We think we'll have patent term exclusivity through 2042, you know, based on the dosing patent, that's critical to optimize outcomes. It's a three-week on, one-week off schedule. We have other patents that are shorter duration. As far as the potential for a subcu, we don't think it's relevant and meaning necessary to optimize penetration in the second line or in the endocrine-resistant population. Certainly, in a setting with patients who are endocrine sensitive, where you could potentially be offering 36 months or so of progression-free survival, it would make a lot of sense to think about a subcu form. You could get meaningful penetration. It's a very large market, long duration of treatment. You know, there's a there there independent of whether you have subcu with IV and you only have IV. You could potentially optimize penetration in a way that you wouldn't really have much impact on these other patient populations. Okay. Are there any difficulties formulating it potentially? Well, we haven't really gotten into detail yet on the status of any of those efforts, and we'll update people in the future. Okay. Outside the U.S., what's your thoughts there, where the doctors may not have as much incentive to use IV drugs and- Well, I mean, they have incentive to try to improve the outcomes of their patients. I think that's usually the primary criteria for selecting a drug for a patient is not the convenience. It's really the outcome for them and knowing that their patient's getting a drug. Ex-US, we won't market ourselves. We're, you know, obviously preparing to launch in the U.S.. We felt it's important to hold off having any discussions with a potential partner. We've had a lot of discussions but to actually move anything forward until after our data and the mutation cohort is available. In the meantime, we're laying the groundwork to submit an MAA, you know, that's the equivalent of an NDA in Europe, soon after we have our mutation data submission to the FDA, what would be a supplemental. We would submit that as a joint combined package. We've also gained alignment with the Japanese regulators on what additional data they would expect in addition to what we already have with VIKTORIA-1. You know, we're essentially in the major markets, the five major EU countries as well as Japan, that comprises the bulk of ex-US revenue. We're marching down the path without delay to get those drugs hopefully approved. Then, you know, the partner discussions can fall within that time period, and we think we could wrap that up. That's your 13-month review cycle. You're really talking about an approval late 2027 at best. Japan will be longer 'cause you're generating additional data. We have time to optimize, you know, our approach there and hopefully, you know, find the right partner, right overall approach. Okay. Let me see if there's any questions from the audience. Any questions? You asked all the right questions. Well, you guys have been very visible, so big news. Yeah. All good. Well, thank you. Thank you.