All right. We're gonna get started. Hi, everyone. I'm Tara Bancroft. I'm one of the Senior Biotech Analysts here at TD Cowen. Thank you for coming to TD Cowen's 46th Annual Healthcare Conference. For our next session, we have a fireside chat with Celcuity. From Celcuity, we have the CEO and Co-Founder, Brian Sullivan. Thank you so much for being here, Brian. It's such a privilege to have you.
Oh, my pleasure.
For everyone in the audience, if you do have a question, please feel free to raise your hand. I'll make sure your question gets heard. Brian, I guess to start off, can you just give us some high-level thoughts and a general overview before we,
Sure
get into details?
You know, Celcuity is a clinical-stage company, focusing on development of drugs that address the PAM pathway, PI3K/AKT/mTOR pathway. It's one of the most important pathways in oncology. We have three trials underway currently. We have a Phase 3 trial, evaluating Gedatolisib in combination with palbociclib and fulvestrant in women who've progressed on their prior CDK. We have data that we'll be reporting out, a second set of data reporting out in the next few months. We have a first line study, in process, with the same drug combination in women, who are treatment naive, who have endocrine-resistant metastatic breast cancer. We have a third study at an earlier phase, investigating Gedatolisib in combination with an androgen receptor inhibitor in men with castration-resistant prostate cancer. A lot of other stuff going on as well, but we'll talk about that.
You sure do.
Okay.
Let's start with talking about launch preparation. You had the NDA acceptance, PDUFA date in July. As that review is ongoing, I know you have the RTOR designation, maybe you could start by talking about the various benefits of that?
Yeah.
I know it's a somewhat uncommon thing to get.
Mm-hmm.
maybe you could familiarize us with the benefits-
Sure
of that package.
Sure. RTOR is stands for Real-Time Oncology Review. Essentially, it's really only given or used for drugs that, in the FDA's view, offer a promise of changing the standard of care landscape for patients. We weren't surprised by getting it because we had Breakthrough designation, and the Breakthrough designation reflects, you know, results from earlier phase studies. The benefit of RTOR program is that it allows you to begin submissions prior to your completion of your formal submission, of your final submission. We started providing the FDA datasets, you know, within one month after we had our data, and then provided that on a rolling basis.
We have a priority review. Essentially PDUFA will be six months after they accepted our NDA. We think it's unlikely that the review will come in prior to that PDUFA date. I say that because of the 20 or so RTOR reviews that have been done the past five or six years since they put this program in place, drugs that have a profile similar to ours, first-time submission, priority review, full approval, not just an Accelerated Approval, for the most part have gotten an approval decision along the line of at the PDUFA date.
Where you'll see the real advantage in terms of shortened timeframes is for supplemental NDAs. If our mutant data, which we expect to report out end of this quarter, early next, or sometime next quarter, is what we hope, then we would file a supplemental NDA. We would also seek RTOR and hopefully in that case, we would see a shorter approval timeline.
Okay, great. Maybe just briefly, you know, we exist in a, in a pretty volatile FDA environment, so maybe a little bit on your thoughts on confidence in approval in this kind of environment.
We haven't seen any change in our the type of interactions, the quality of the interactions, the timing of the interactions over the past year. We've been interacting with the same group, same people for the past five years, and the relationship has been very collaborative. All the meetings, we have regular interactions with the agency. All the interactions typically are scheduled, i.e., they're supposed to occur within a certain timeframe. There has been no diminution or delays that have occurred. From our standpoint, we wouldn't know there was an issue just based on what we're seeing. We don't expect any anomalous outcome that could be influenced by some of this other stuff that's going on.
Okay, great. Okay. How about launch preparation?
Mm-hmm.
Where are you at with that? Maybe some numbers on sales force, MSLs.
Mm-hmm
anything else.
Sure
T hat you're doing.
We actually began preparation for the launch about two years ago when we brought on our chief commercial officer. In turn, that led us to build out the senior team reporting to him that would be responsible for key functions in the commercial department. We also developed essentially a company-wide launch plan that not only involves building out the team over time and have a plan for that, and the projects associated with establishing your infrastructure commercially, but also, you know, laying out the projects required for all of your other departments, whether it's, you know, IT. Huge number of systems you need to put in place that involve IT. You know, your safety department has to, you know, substantially change to be ready for commercial reporting of safety events.
HR, you know, finance, just every function essentially gets affected. We had a company-wide launch plan, or have one, and then we've been implementing against that. We've pretty much completed the hiring of the commercial organization by the end of last year, except for the sales force. We did hire the regional sales managers prior to that. Now we've identified, we know how many we need. We've already identified the great bulk of those that we would be making offers to. We would expect to begin bringing the sales reps on second quarter. I would say we're directly absolutely on track to being able to launch effectively around the time of the Gedatolisib.
Okay. Maybe a little on launch expectations, the cadence of what use could look like in the beginning. You're in a little bit of a unique situation where you expect to get approval in one segment.
Hmm
a little bit later another. However, the data is gonna be out for that.
Mm-hmm.
Just curious what types of patients?
Sure
And in how many you think it could be used right away.
Sure. You can think of this market as having three fairly discrete segments. obviously the most common one, or rather the broadest one is just to use PIK3CA status as the determinant, right? PIK3CA wild type patients are roughly 60% of patients. That's what we'll focus on. We'll have data in the mutants cohort. That data will actually, we think, be available, be public, prior to launch of Gedatolisib. That'll, you know, certainly be wind at our back if it's what we hope it is, for the launch. We'll be focusing on women, who are, you know, PIK3CA wild type. Our data is very favorable relative to drugs that are currently available.
We think we've done a very effective job at being able to analyze, you know, the physician, you know, healthcare practitioner profile. So we are able to prioritize, you know, where we should put our efforts, how to design the sales territories, how to define, you know, the call patterns that we want the reps to use. And also then how to, you know, build out the messaging and how to make these individuals effective proponents of Gedatolisib and recognize that these doctors are used to alternatives. So, you know, part of our job will be to help them understand the context of Gedatolisib and how it relates to what they've done or what they might do in the future.
Okay. I do wanna get into a little bit more on which segments.
Mm-hmm
and types of patients that it can be used in, and that you have-
Sure
Confidence it'll be used in. I think everyone in this room and listening, probably wants to hear expectations for the mutant data. The first question that I have is, you know, with the late Q1, Q2 guidance, we're really coming up on that very-
Mm-hmm
Very shortly. You know, what can you say about your confidence that that timeline will not be delayed? Are you very close or have reached events already?
We haven't changed our guidance, and I don't think we will be changing our guidance with our quarterly call. We're confident that that's the time bucket that we'll have data to report.
Okay. Got it. All right. Expectations, I think let's first start with the control arm.
Mm-hmm.
I know we have some benchmarks with BYLieve and EPIK-B5.
Mm-hmm
in the 7.3-7.4 range.
Mm-hmm.
Maybe talk about your expectations for, what we could see in the control arm, using those benchmarks?
Sure
others.
There's always a question of is there a risk that the control arm could over perform relative to whatever assumptions you were and how would that impact you? We think just based on data that's been reported with those two studies that reported almost exactly the same results.
Mm-hmm
We think it's unlikely that there would be a surprise on the high side of that. If you look at the data for another drug that hits this pathway called Capivasertib, you know, that drug reported 5.5 months in similar population. It also had a control fulvestrant that was about the same level that we would expect in the mutant population with our study. That drug has a similar hazard ratio as alpelisib, you know, roughly 0.5. That would be an example or rather that would be a case to say, "Okay, well, that further buttresses the idea that it's unlikely to be outperforming what that drug has done previously." That's one, that's about, you know, the foundation for any assumption you make about our drug. There's really kind of two aspects of expectations.
Mm-hmm.
You know, one is what do we need to be successful? That's the statistical benchmark. Just, you know, based on how the math works, roughly 10 months or so, median PFS would be stat sig. You know, that would only be 10% or less better than what we reported in the wild type population. We, we think from a probability standpoint, that seems like a, a highly probable outcome, yeah, to at least hit that threshold. Then the question is the clinical significance. How meaningful is that number? Well, alpelisib is no longer really being used very frequently. Its market has primarily moved towards Capi, and Capi's reported 5.5 months mean in PFS. If we're offering at a minimum 10 months relative to 5.5 months, we think that's a great advantage.
We think our safety profile will also be an advantage. Certainly anything better than 10 months would be better. You know, one frame of reference is the phase 1B data that we reported at ESMO. This phase 1B study evaluated a very similar patient population as what we're evaluating now. In the wild type population, it reported 9.1 months for wild type.
That was almost exactly what we reported in the phase III study, which was 9.3 months. In the mutant portion of that study, patient population, we reported 14.6 months. We all know what we're gonna see in the phase III, but at least it gives us confidence that the 10-month number is highly probable. Essentially, it just leads you to kind of put a high number for your probability of success and gives a sense of what, you know, your range could be. I'm not assigning probabilities to other numbers, though.
Yeah, of course. I mean, within that range, though, I mean, 14 to 19 months, that's, it's quite a range, so maybe which of those different segments do you think that the phase III population most closely mirrors?
Well, I would love it if it mirrored the 19-month one, but, we'll see, right, in a few months. We'll see. I think it is a reasonable enough sample size that it gives a sense of what's possible.
Mm-hmm.
There's also one other number independent of our study that is useful to reflect on is that with all the other studies done, evaluating inhibitors of this pathway, where they've generated data, patients who lack mutations versus those that have mutations. They've seen significant difference in outcomes for patients, i.e., better outcomes for patients that have mutations versus those that don't. You know, alpelisib in this setting reported the same results as we reported in the wild-type setting. It's very much the case that it's reasonable, we think, to think that the drug will do better in a mutant than wild type. That's what our phase 1B data showed. So all those factors, I think, give us, you know, reason for optimism about what the outcomes will be.
Okay, how about making a comparison to mutant-specific inhibitors? I mean, do you need to be over that 11- 12 month range to be competitive with them and gain comfort in the second-?
You mean to be competitive with the five-and-a-half month Capivasertib?
I'm more so talking about, you know, Relay, Scorpion.
Oh. Again, those drugs, you know, maybe they get approved, maybe they don't three or four years from now.
Mm-hmm.
It's not a top of mind. I think there's. Ultimately, when you're assessing the potential for a drug, you know, it's a really a function of what the relevance is of the target, right? Typically, there's only so much biological potential for inducing an antitumor effect associated with a target. We saw with the SERDs, that is to see... What is it? The book, Eternal, you know, Eternal Optimism or something, where every SERD coming down that was reporting data was gonna be the one that reported a positive, wild type, result. You know, after five or six, you'd start to think that optimism would dim, and it doesn't seem to.
I'm not, you know, being critical of those SERDs other than to say this is an example where lacking a mutation, there's only so much potential you can get out of hitting that target. You can't get more than 100%. There's only so much potential, I think, that you can get when you hit a component of this pathway. Certainly, to optimize the impact of inhibiting this pathway, you should comprehensively inhibit it. We've shown non-clinically very clearly what the benefit is, then we've shown clinically what the benefit is. You know, I think whatever our drug can do, I think it would be better than whatever a single target drug could do.
Got it. I still wanna dig in a little bit more on what that mutant-specific target is. I mean, I know we've seen phase II data, but maybe you could tell us a little bit more about the impact of baseline with measurable, non-measurable disease.
Sure
how much that actually impacts-
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T he first three phases.
I think, you know, whenever you're looking at data sets, particularly early phase data sets, you know, when you're trying to project what that might imply for a future readout in a phase III setting, you need to pay attention to the composition of that population. One factor that can have a big impact on PFS is whether or not the patient has bone-only disease versus measurable disease. In pretty much every study that I've seen that has an endocrine therapy component or monotony, the results for patients that have bone-only disease can be three or typically three to four times better than the results in patients that have measurable disease.
For instance, PALOMA-3 broke out that data and said, "Wow," you know, "3x better results for patients with bone-only disease." We saw that, although a very small sample in our own study where the baseline was two months, bone-only was eight months. If you have a population in an early phase study that has a high proportion of patients with bone-only disease, then you need to factor in the impact that that would have.
If you've got a cohort of patients that are generating eight months of benefit from fulvestrant, well, that's gonna goose your numbers and can potentially make them not representative of what you'd see in a phase III study. You know, again, as people think about what the biological potential is of a, of a single component inhibitor of the PAM pathway, the prior results are probably more instructive than in those phase III studies than anything else.
Okay, great. Thanks. I wanna move on to safety. you know, before I ask more specific questions, I do feel like we came out of ESMO.
Mm-hmm
I n San Antonio with a little bit of misunderstanding and not. I'm not talking about from the street and investor perspectives, but really among KOLs.
Mm-hmm
on the impact of the safety profile that you saw in getta's data, maybe you could give us some context there.
Sure. Well, we were able to put some specifics. I think one of the big surprises for doctors was that Gedatolisib induces, you know, very, very little hyperglycemia. Drugs in this class are typically associated with inducing high levels of hyperglycemia, can turn oncologists into endocrinologists. It's very tricky to manage patients. It's particularly important in this setting because roughly 50% of women with advanced breast cancer are either pre-diabetic or diabetic, they're particularly sensitive to any impact on their glucose system, metabolic system. You know, we reported less than 10% overall, 2% Grade 3. You know, alpelisib induces, you know, 80% hyperglycemia. Orders of magnitude difference. That was a surprise to the good. I think the on the other side, stomatitis was higher than we had expected it to be.
Frank, we thought the dexamethasone would have bigger impact. As we dug into the data and then presented some of those results at San Antonio, this kind of makes sense. If you get stomatitis, it's gonna manifest quickly, first two doses, you know, days eight, days one and eight. It resolves to a lower grade within a couple of weeks. You don't really almost have any Grade 3 by the end of a second cycle in your overall population. That was the fact that the stomatitis was really not impacting patients' perception or experience of treatment burden was really demonstrated in the quality of life, patient-reported outcomes that we were able to report.
Probably the best metric for assessing how a drug is impacting a patient's sense of wellbeing is this one score that essentially asks patients to rate how they're feeling in five different parameters that are associated with their health and general sense of wellbeing. We showed no degradation over an eight-cycle treatment period, which was the follow-up period in that score. Essentially, from baseline to end, there was no change. If you had an adverse event that was seriously impacting their quality of life, their sense of wellbeing, you'd see a diminution in that, and we didn't. When you see only a 2% discontinuation rate, which is what we had for this, which we read out, that essentially says patients can stay on this drug.
Qualitatively, we've heard from investigators that have said their patients will say, you know, unprompted, "Wow, I don't feel like I'm on a cancer drug." This relates to the PK profile of the drug. We're only needing to drug these patients three times a month. The drug stays at sufficient concentration to induce a tumor, anti-tumor effect during that off period. 25 days out of 28, they're not getting the drug, which means they're only getting that hit with that Cmax concentration of drug three times a month. Whereas an oral drug is hitting the patient every day, typically, or at least 30 times 20 days a cycle. 20 times a cycle.
That is what induces the, you know, the sense of burden that a toxic anticancer drug can impose on a patient. That's why we think the quality of life data is what it is that essentially for the 25 days out of 28, you're not on this drug, so to speak. Physiologically, the concentration is below a level, below the IC50 level for healthy cells. It's above the IC80 level for tumor cells, and that's this very specific window that Getta is able to fit in. That's what we think leads to a very, very favorable safety profile. We think we'll absolutely win on that basis.
Okay, great. Any reason to believe that mutant and wild type data would look any different in terms of safety?
No. I mean, in the early phase data, we kind of looked at that. That was part of our NDA submission to providing that analysis. There's no reason for it to be different physiologically, but there wasn't, you know, from an actual readout standpoint.
Okay, great. Okay, now I wanna talk about the overall market and, you know, aside from the few months that it's gonna be on the market with Wildtype, potentially without mutant yet, I think it's easier to talk about segmentation of patients.
Mm-hmm
in everybody. There's a lot of mutations, and, you know, PIK3CA, AKT, ESR1.
Yeah.
Can you break down your assumptions for what the peak use could be?
Mm-hmm
B ased on those segments? In particular, I'm curious what you're hearing and what you think about priority of mutations. Like if...
Mm-hmm
I f a
Sure
H as PIK3CA and AKT and ESR1, like, which mutation.
Sure
Treated first?
Right. So, you know, we've obviously done a lot of research with doctors, you know, quantitative and qualitative to, A, you know, get a feel for how they think about this, and then in turn prompt us to dig in and do some quantitative evaluation of those comments. What's very clear is that doctors do, at least today, prioritize the PIK3CA as the treatable mutation that they'll use to make a decision. So that's the 40% bucket that I mentioned earlier. Now, with ESR1 mutations, you get a further bucketization of the segmentation of this group. You know, ESR1 wild type, PIK3CA wild type patients, so essentially they lack biomarkers. That represents about 40% of the population.
Essentially 80% of the population is one where we think we have a very, very compelling advantage. For patients who lack mutations of any type or those AKT mutations, there really aren't great alternatives, and Gedatolisib really does offer a very, very meaningful benefit for them relative to what's available. Where you get more potential competition is in the patients that have ESR1 mutations and lack PIK3CA mutations. That's about, again, 20%. There'll be some drugs that are likely approved or some regimens by the end of this year. We think our data stacks up very well against their data. There'll be more relative competition. I guess I would say we have clear advantage in 80% of the market.
In the 20% of the market, we'll have a bit of a dogfight.
Even then, any idea of a potential third-line use? Would have you heard about
Sure. No, I mean, obviously, you know, doctors can decide to sequence the therapy. There's no reason why they if they elected to use an alternative regimen, why they wouldn't necessarily consider it as an alternative in the third line. Yes, I would say one other observation that's pretty clear from the research is that doctors do want to spare patients from chemotherapy as long as possible if there's an appropriate and efficacious, sufficiently efficacious endocrine alternative. We think our drug regimen offers that efficacious endocrine alternative. Even if it isn't used in the second line, we think the data would warrant use of it prior to, let's say, an HER2 or some other chemo.
Okay, great. I know you also have this frontline trial that's ongoing.
Mm-hmm.
maybe you could talk about what your assumptions for use there are, and in that, you know, there's a lot of discussion and debate about, lidERA and persevERA.
Mm-hmm
and how those regimens-
Mm-hmm
C an impact potential get a use in the frontline and even potentially second line.
Sure
I mportant.
Okay. Yeah, right. You have really talked about 3 different groups of patients. There are patients that are early breast cancer getting adjuvant treatment. That was the lidERA study. Really won't have any downstream effect on advanced breast cancer. Over time, you might see some diminution in the number of women who progress or rather who recur to metastatic disease, but you also have a countervailing factor, which is the increase in overall incidence of breast cancer. Net-net, I think, it'll be 10 years before you might see any effect, and if you do see any effect, it would be nominal. The other population, there are 2 populations of women who present with metastatic disease. The larger group, it's about 60,000 women a year, present with either, you know, endocrine-sensitive disease.
These are women who got their adjuvant or rather got their adjuvant tamoxifen or whatever, and it was years before they recurred, at least more than a year. Or they're de novo. They just were diagnosed for the first time with metastatic disease. They didn't have early breast cancer. The second group, it's about 35,000 patients, similar in size, actually, to the second line population, are women who have what's considered to be endocrine-resistant. These are women who didn't get much of a benefit from their adjuvant endocrine therapy. You know, they progressed while they were either receiving it or within 12 months. That's the study that we're doing right now, VIKTORIA-2. We're evaluating these women who today, if they're getting a CDK4/6 and fulvestrant, which is the standard of care for most of these patients-
Mm-hmm
O nly get about seven months median PFS. It's almost like a second-line study in some ways. You know, we have data from the endocrine-sensitive population in an early-phase study that was very, very promising. The women who are endocrine sensitive, you know, who kind of delayed recurrence from early breast cancer, when they are given the standard of care, which is CDK4/6 and letrozole, get about 25 months median PFS. We reported 48 months median PFS in that patient population. Small samples, I mean, 41 patients, not nothing, but at the same time, just single arm. 80% response rate. Clearly, we think it demonstrated, if nothing else, that this pathway, the PAM pathway, is relevant intrinsically in this disease. It's not an adaptive response to prior treatment.
That's consistent with the mutational pattern that you see. I mean, the percentage of patients with PIK3CA mutations really is no different in the first line versus the second line, i.e., it's a, it's an intrinsic mutation. This pathway, because of its role, we think is intrinsically involved in the disease.
Okay, great. kind of a tangent, I kinda wanna ask you, do you think persevERA is gonna work?
So if you were placing bets, I think you'd take into account two other studies. I mean, one would be a study with a SERD that had a similar hypothesis combining an oral SERD with a CDK4/6 inhibitor, comparing it to CDK4/6 and letrozole. That study didn't get through interim analysis, and the interim efficacy analysis resulted in the study being discontinued due to futility. You know, that obviously suggests that it's not a slam dunk.
Mm-hmm.
Not all oral SERDs are the same, but they all are in the same class, and there's, you know, only so much potential that you can get out of a target, even if one is better than the other. Second dataset relates to What was my other second dataset? was PARSIFAL study where they compared palbociclib and fulvestrant versus palbociclib and letrozole. The hypothesis was, well, more direct engagement of the target, hitting ER directly with the SERD would be more efficacious than, you know, the indirect effect on estrogen with the aromatase inhibition. Numerically, you know, the letrozole CDK palbo did better than fulvestrant. Not statistically significantly different, but it suggests that just having a good oral or rather a good SERD doesn't do much.
The other, I guess, third set of data that you'd point to would be that in patients' tumors lacking mutations, there really is no difference between an oral SERD and fulvestrant in terms of efficacy, and that's the patient population that you're treating in the first line setting. The question is, does the delay in onset yield a meaningful benefit? That's what we'll see. SOLAR-1 study didn't show it, we'll see. Certainly, it's a bit of a bank shot.
Okay, thank you. 1 more question before we go, what do you think is the most underappreciated aspect of Celcuity?
I think if people really step back and understood the size of the patient population that we think we'll eventually be able to treat, right? We have 37,000 patients that will be eligible in the second line. I think ultimately we will progress and with trials, and we think high probability of success in these trials in the first line setting. If you do the math on the potential impact in terms of treating that number of patients and the revenue that would generate, I mean, we have $10 billion plus higher of potential peak revenue with this drug just in breast cancer.
I think if people understood that and just fast-forwarded what the implications are of having effective drug that treats one of the three critical disease drivers, you know, that would potentially change their current view.
All right, Brian. Thank you so much for your time.
You're welcome.
A nd insights, and thanks everyone for listening.