Well, good morning. Thank you, guys, for joining. Pleasure to have perhaps one of the more exciting breast cancer companies in the space, Celcuity. Brian, thank you so much for making time. You're welcome. We'll jump in sort of linearly and step by step, but I'll let you kick things off, and we'll go step by step. Great. Well, Celcuity's lead asset is called gedatolisib. It's a pan-PI3K/mTOR inhibitor. We have three phase III programs in process in HR-positive, HER2-negative breast cancer. The first two are in the second-line setting, and we initiated one in the first-line setting earlier this year. We also have a phase 1b/2 study in process in metastatic castration-resistant prostate cancer for the second line, reported promising data for that study at ESMO, as well as very, very exciting data, unprecedented data for one of the cohorts in our phase III study in second-line breast cancer. Excellent. Brian, I feel like what might be really helpful for just going through the session today is there's clearly so much innovation happening in the breast cancer landscape lately, and these are trials hitting with very meaningful hazard ratios. Historically, everyone was used to the moment you started looking at HR-positive breast, you'd think about letrozole, you'd think about adding a CDK4/6 to it, and that's about it, and then you move on to fulvestrant. But there's so much more happening now. So how do you see the treatment paradigm evolving? How do you see sort of mutation testing evolving? And so I want to start to fit in Celcuity separate from SERDs because there's multiple things happening sort of in parallel. Yeah, I think the best starting point is to think about the disease mechanisms involved in HR-positive breast cancer, the three pathways that are interconnected that essentially cooperate and promote the disease, the estrogen receptor pathway, CDK4/6 pathway, and what we refer to as the PAM pathway, PI3K/AKT/mTOR. And those three pathways need to be inhibited, to be blockaded in order to optimize tumor control. We had very, very promising data in the preliminary data in both the front-line and second-line settings before we announced this data, but it really highlighted how important it is to control comprehensively this PAM pathway. And if you do, as we demonstrated in at least the wild-type patients, patients who lack a mutation, you can establish a new second-line standard of care. And essentially now patients are getting some form of endocrine therapy with CDK4/6. We would expect then these patients to continue that treatment with our drug on top of it, and then the other drugs under development, to be frank, will be primarily, we think, third-line alternatives for these patients. Makes sense. Maybe it might be a good segue then to perhaps starting to look at the trial you guys ran, Victoria I. Sure. That's post-CDK4/6 setting, correct? Yes. The intention for the company remains in nominating that post-CDK4 setting? We actually have a study underway now, Victoria II, which is in the front-line setting. These are women who are treatment naive. They did not get a good response to their adjuvant therapy. They either recurred while they were receiving, let's say, their adjuvant tamoxifen or letrozole or within 12 months, and they're generally considered to be endocrine therapy resistant. That's about a third of all women who are ultimately diagnosed with metastatic breast cancer. Makes sense. So it's an important group, but a focus now. We'll get another data set for the patients with mutations, end of Q1, sometime in Q2. Right. Can I just clarify, if that's possible, Victoria I trial is post-CDK4/6, but CDK4/6 can happen in an adjuvant setting. So then do you get a first line? It'll be independent of when they receive their CDK4/6. So when you get approved for Victoria I, are you technically eligible for first-line patients as well? That was the eligibility criteria. We haven't gotten approved. We haven't finalized a label, but that would certainly make sense. Okay. So the current trial already technically opens it up for first line, and then this new one would potentially open it up for regardless of whether CDK4/6. Basically, these women, so women present with early breast cancer, most of them don't recur. About a third ultimately do. Some are diagnosed, about a quarter of them are diagnosed de novo. They didn't have early breast cancer, and so you have these different buckets of women with metastatic disease, and most of them won't have had adjuvant therapy. Some will, and so essentially you need to generate data for each of these settings, but with the data that we have now and the eligibility criteria that we used in that study, women who had adjuvant CDK in the early breast cancer setting would be eligible for this drug. Makes sense. Okay, excellent. Maybe let's start to get a little more specific. I want to go through both these trials in a fair amount of detail, I guess, but just ahead of that, I think historically a lot of folks have, at least when they're not looking at Celcuity properly, they look at it as a PI3K kinase, and that's about it. It's PI3K, but also it's an IV version of that, so just not spending incremental time. Could you remind us what the mechanism is? Because I think that lends itself into something. Right. This pathway is probably one of the most complex pathways in all of oncology. It has four isoforms of PI3K, alpha beta delta gamma, and it also has two complexes of mTOR, mTORC1 and mTORC2. Each of them essentially adaptively resists inhibition when a single component of this pathway is inhibited. So the real biological imperative is to comprehensively blockade it, which requires pan-PI3K inhibition along with inhibition of mTORC1 and mTORC2, and so the therapies that have been approved to date that address this pathway have been what we refer to as single-target inhibitors. They hit PI3K alpha or AKT or mTOR. In Geta, we've shown non-clinically, and then our clinical data supports this, it's 300 x more potent than these drugs in inhibiting this pathway. It's the only drug that hits this pathway that's cytotoxic, actually kills cells versus just creating cytostasis. It's a very, very differentiated molecule as a result, and that's why the results for the PI3K wild-type cohort were so encouraging, because typically these drugs, not typically, none of these drugs have shown activity, the ones hitting alpha or AKT in patients who lack the mutations. Our hypothesis was this pathway is important regardless of whether a mutation is present. It's regulating the energy source that these cells rely on to hyperproliferate. Essentially what that means is that if you can comprehensively blockade it, you should see anti-tumor effect, which is what we showed. Makes sense. And just remind me, what's the dosing frequency again? And there's no oral conversion possibility. No. And essentially, that's one of the features. You match it with the other cycle. Because with Geta, you dose these patients three times a month, days 1, 8, and 15 of a 28-day cycle, which means these patients are only getting Cmax concentration of drug three times a month. Right. The toxicity of this pathway, because it's so important to the metabolic function, both intracellularly and physiologically, it's very tricky to find that therapeutic window. Because Geta is so potent, essentially low nanomolar concentration can essentially shut down this pathway. We can dose it very infrequently, and as a result, the patients get much, much better or much less toxicity, much better safety profile than has been reported for other drugs that are addressing this pathway. And so essentially it's think of like the Miller Lite commercials, great taste, less filling, great efficacy, less toxicity. Makes sense. Fantastic. So on this Victoria I trial then, I want to start to get a little more specific on what to come next. Obviously, you hit the study I, which was in the wild-type patients. The second one in the mutants, when is that due? End of Q1, Q2. Okay. 2026. And the primary endpoint is PFS again? Yes. Has there been any interim on that? No. No. So essentially primary analysis, no interim. Okay. That's standard in this setting. You rarely see, and it's something the regulators really discourage. Got it. I guess when I looked at it, one of the questions I had was you have a Geta plus fulvestrant versus an oral PI3K plus fulvestrant versus a triplet arm, and that arm is particularly intriguing for me because it has CDK4/6 added onto Geta plus fulvestrant. Which arm are you most focused on? The triplet. The triplet was the data that we think is most relevant in the wild-type setting, reported hazard ratio of 0.24, which was a lower hazard ratio than it's ever been reported in breast cancer. And so we think the triplet is most likely to offer the best results. And really that relates back to what I said earlier about the role of CDK4/6 as a driver of this disease. When patients become resistant to it, no longer responding to CDK4/6 and endocrine therapy, it doesn't mean that pathway is not genetically transformed. And so when you add a drug like Geta, which shuts down that pathway comprehensively, you reactivate that pathway, which in turn resensitizes patients to CDK4/6 inhibitors. So even though they've progressed on that prior CDK, they require that CDK continued in order to optimize tumor control in that second-line setting. Makes sense. So as I think about that triplet arm, my first thought is let's say Geta does absolutely nothing. Even in that scenario, the triplet should work because post-Monarch, where Abemma was given in a post-CDK4/6 setting and showed up. Showed no activity. It was. It was never a hazard ratio. 9.9 months incremental benefit. I mean, so yeah, 0.9 months incremental benefit is. Right. My point being. You need the PAM inhibitor. The PAM inhibitor is central to the disease process. And with Geta, when we added just Geta to fulvestrant, you showed again higher, more favorable hazard ratios than had ever been reported. So just really highlighted how critical this pathway is independent of the status of PI3K. And the CDK4/6 is still required, but ultimately the results are driven by inhibition of this pathway. I guess the direction I was going with that is PostMONARCH exists. It shows something. It doesn't show zero per se. So if PostMONARCH adds something, and let's say Geta even at a very basic level adds a little something, theoretically that arm should be able to be active. And then the question. Absolutely. And then we turn to which CDK4/6 is it that's being used here, as well as what type of signal should we realistically expect from the Geta side alone? Sure. So we reported preliminary data for patients who have mutations of 14.6 months in patients in the second-line setting PIK3CA mutation. And that compares to data reported for alpelisib of around seven months. Alpelisib is a PI3K alpha inhibitor, or for capivasertib, which is an AKT inhibitor, the results for that drug median PFS was about 5.5 months. Right. So yeah, if we recapitulate that phase 1b data, the results would be obviously very, very significant. But we reported over nine months median PFS, nearly 10 months in the wild-type setting. If we just have a 10% incremental improvement in the triplet, in the mutant versus the wild-type, it would essentially be double what the current standard of care is offering because that's capivasertib. So I think the probability of success, to be frank, is very, very high. How do you see the doublet versus doublet? We'll see. I mean, again, the doublet in wild-type, 7.3 months, was essentially equivalent to alpelisib in the mutation setting. Yeah. So again, alpelisib in patients who lack mutations is not an active drug. So again, we think that augurs well for showing meaningful activity. Makes sense. In the mutant cohort. How big is the, and I realize you're not just a PI3 drug, but how big is that category right now? The overall second-line setting? Yeah. So you have about 37,000 patients. If you do the math, think about the duration of treatment, the cost. Those are mutants? Oh, the mutant is about 40% of the total. 40%. So 60% wild-type, 40% mutant. Got it. But the overall market, essentially served market potential is around $6 billion. It's a very, very significant market and very, very significant number of patients. Makes sense. That's great. One last thing, as we do look at the doublet versus doublet, I want to look at efficacy, and there's signals suggesting there should be an efficacy signal, but there's some tolerability differences as well versus the stuff that's on the market currently. Could you elaborate on that? Sure. One of the major challenges in drugging this pathway is that it is related to the fact that this pathway regulates glycolysis. Right. And so if you hit it, you can induce high levels of hyperglycemia, which is very problematic. So in our wild-type cohort, we reported only about 10% all-grade hyperglycemia, 2% grade three hyperglycemia, very, very nominal levels. No patients discontinued, no dose reduction. And that compares to these other drugs where the hyperglycemia is significantly higher, requires some form of patient management, diabetes glucose monitoring. So we think that will ultimately be a very important component of how doctors are able to use the drug. Makes sense. Just before I proceed further, there's maybe just spending a quick second on your wild-type part of the study. I believe we've seen interim OS track pretty well. Is there another meaningful OS update coming at ASCO? Not at ASCO. The data would be available Q1 2027. Okay. Is there anything meaningfully new you're showing at San Antonio Breast this year? We'll have an update to the wild-type cohort. Okay. That update is on. December 11th. Just more follow-up? Not follow-up to PFS, but additional data related to either safety analyses, additional subgroup analyses, things like that. Okay. Got it, and I remember you and I spoke about this when some of the early PFS data came out, and one of the things that really stood out to me at least was how fast sort of the comparator arm drops and there's that rapid progressors, and in some ways, your median is more of how many of the rapid progressors you got versus the patients that actually do benefit. Is that something that clinicians sort of appreciate as well? Absolutely. I mean, these patients ultimately have other mechanisms involved in the disease, and just inhibiting the estrogen receptor pathway induces for half these patients no benefit at all, which means it's a challenging population to drug. And so the results that we reported in the wild-type setting were really fantastic, to be frank, because we eliminated that cliff. And so we had very, very few patients who were non-responsive. I think nearly all had a reasonably extended duration of benefit, certainly compared to fulvestrant. So, last two questions in the last couple of minutes. First, I was preparing for our conversation today, and I realized there might be a trial due next year, which is on the PI3K side head-to-head, inavolisib versus alpelisib, post-CDK4/6 setting. I guess what are you expecting there? Because is that the equivalent of your study too, basically with different molecules? Or is there a difference? It is. I mean, I think the inavolisib drug, it depends on the enrollment criteria, but the inavolisib drug has a lot of the same characteristics as alpelisib. If it's studied in an all-comer population, independent of their diabetes status, it would induce similar levels of hyperglycemia. If you exclude prediabetic and diabetics, essentially they get through the window where the drug can be tolerated. Efficacy, it's hard to say. They haven't reported out much data for that. It could very well be better results just because patients may be able to stay on the drug. So is this like a 0.85 better type of drug, would you argue? I would think regardless of those results, it just won't be as effective as a triplet where you're controlling the CDK4/6 pathway and then more comprehensively inhibiting this pathway. Right. All things being equal, I mean, we've done this work and published this work in a variety of tumor types. Geta is 300 x more potent than an alpha inhibitor. Essentially, this pathway is designed to adaptively resist inhibition of a single target. Right. So it's just a suboptimal way of addressing the pathway. Right. You could see a treatment benefit when there's a mutation present, but it's the second best alternative. Right. Right. So Brian, maybe in the last minute or so then, from a broader corporate strategy perspective, where do you see things going now? Because it's very quickly turning from a data story, which we just did for the last few minutes, to commercial launch, launch expectations. There's a whole different set of capital needs for that, but also even more importantly, the size of the team, the way it will change, whether or not you want to have strategic conversations or not. So there's a lot of decisions for you to make now about how you turn this into a large company and all the external stakeholders. Yeah. No, we're planning to launch the drug. We began the process of preparing for the launch Q1 2024 when we brought on our chief commercial officer. We've since built out pretty much the entire team that we require. How big a sales team do you need? If you look at this space, you'll see that in breast cancer, whether it's a large pharma or a small pharma, they'll have between 80 and 90 reps calling on these breast cancer docs. So it's not a ridiculous sales force. It's not a cardiology sales force. So we're ready. We basically have the organization built except for the sales team, and essentially you don't bring that team on typically, at least, and we're following this, and so you're about a quarter out from your expected approval date. Got it. I realize it's too premature to even talk about pricing, but would the construct have anything to do with how the currently marketed PI3Ks are? It sets some good benchmarks. I mean, the pricing, for instance, for these other drugs, the wholesale acquisition cost for these drugs is around $25,000 a cycle. So that's a benchmark. So it's attractive pricing. We haven't finalized our pricing, but we certainly think we offer a better proposition. I didn't realize they had 25. Yeah. Oh, interesting. Yeah. No, there's obviously gross to net discount. No, no, obviously. And also they're technically wild-type. Okay. Fantastic. Well, good luck into the part two and into all the OS updates next year as well. And we'll certainly stay in touch. Great. Well, thanks. Thank you. Nice to see you. Nice to see you. You too. Take care. You too. Take care.