Celcuity at Stifel Forum: Insights on Cancer Drug Trials

On Wednesday, 09 April 2025, Celcuity (NASDAQ: CELC) participated in the Stifel 2025 Virtual Targeted Oncology Forum. During the call, CEO Brian Sullivan discussed the company's progress in cancer treatment development, focusing on their lead drug candidate, gedatolisib. While Sullivan expressed optimism about upcoming trial results and potential regulatory advantages, he also acknowledged the competitive landscape in oncology treatments.

Key Takeaways

• Celcuity is advancing gedatolisib, a pan-PI3K/mTOR inhibitor, in phase three trials for ER-positive breast cancer.
• The Victoria-1 trial's design and patient enrollment progress were key discussion points.
• CEO Sullivan highlighted the drug's unique mechanism and potential for accelerated regulatory review.
• The company is preparing for potential commercialization pending successful trial outcomes.
• No specific financial results were discussed; the focus was on clinical progress and market opportunities.

Operational Updates

• Enrollment in the wild-type cohort of the Victoria-1 study is complete.
• The first patient enrollment in the phase three study for first-line ER-positive advanced breast cancer is expected this quarter.
• Preliminary top-line data from the phase 1b study in metastatic castration-resistant prostate cancer is anticipated towards the end of the second quarter.
• The patient ratio in the Victoria-1 study was approximately 60% with mutations and 40% without, slightly differing from initial projections.

Future Outlook

• Celcuity awaits top-line data from the Victoria-1 trial this quarter, which could influence their NDA submission.
• The company is seeking accelerated regulatory review pathways due to the drug's breakthrough designation.
• Successful trial results could lead to the commercialization of gedatolisib.

Q&A Highlights

• The Q&A session focused on the Victoria-1 trial's design, particularly its enrollment of second-line patients post-CDK4/6 inhibitor treatment.
• The trial includes different cohorts based on mutation status, with specific design elements tailored to these groups.

Readers interested in detailed insights can refer to the full transcript below.

Full transcript - Stifel 2025 Virtual Targeted Oncology Forum:

Brad Canino, Senior Analyst, Stifel: Morning, everyone, and thanks for continuing to join us on the Stifel two day virtual oncology event. My name is Brad Canino, senior analyst here. Very happy to do the next fireside with Celcuity. We've got Brian Sullivan, CEO. Brian, thanks so much for joining us.

Brian Sullivan, CEO, Celcuity: Oh, you're welcome. Happy to be here.

Brad Canino, Senior Analyst, Stifel: Perfect. And can we just kick off with an intro to the company and the state of the business as we're sitting here right in front of first pivotal data for the company?

Brian Sullivan, CEO, Celcuity: Yes. Yes. Well, sure. So I started the company with our chief science officer with the initial focus of developing a platform, that could quantify signaling pathway activity in live tumor cells. And and and we started working on the p I three k a k t PAM pathway and have sub subsequently evolved, to now focusing on how to treat cancers that involve, the PAM pathway.

It's the most important oncogenic pathway, at least amongst the most important pathways in our view, most highly altered. And so our lead asset, gadotelisib, it's a pan PI3 m two inhibitor. We have three studies in process, two in breast cancer, one in prostate cancer. We have an ongoing phase three study that will report, first data, this quarter in one of the cohorts, wild type cohort, and that study is treating second line patients who have ER positive breast cancer. We have a phase three study that we're just getting going now in first line patients with ER positive advanced breast cancer.

We expect to enroll our first patient this quarter as well. And then we have an ongoing study in metastatic castration resistant prostate cancer. That's a phase 1b study. Expect to have top line preliminary data from that towards the end of the second quarter.

Brad Canino, Senior Analyst, Stifel: How do you like to describe the how and the why GetItPulse differentiated from the suite of other pathway inhibitors? Sure.

Brian Sullivan, CEO, Celcuity: Well, it's important to understand, the structure of the pathway, because that's really what drives, the approach that we've taken, our drug has taken, and that's what differentiates it from, the other drugs that have been approved in this space. So most pathways that people are familiar with involve a single target, that can lead to downstream inhibition of pathway signaling. But the PAM pathway, PI3KAKT mTOR pathway, has multiple targets or nodes. It must be targeted because each of them can cross activate the other in the absence of inhibition. And so when this pathway was first discovered twenty plus years ago, almost every major pharma had a pan PI3K mTOR inhibitor because the biological imperative essentially required you to comprehensively shut this pathway down hitting these various targets.

Otherwise you'd have a suboptimal if or no treatment effect. Know, GETA then is able to hit, at low nonamolar concentrations, all class one PI3 isoforms as well as mTORC one and two, the two mTOR complexes. Whereas the drugs that are approved hit what we refer to as single nodes, let's say p I three k alpha mTORC one, AKT. And while they've gotten approved, you know, we would argue based on the available data that it's a suboptimal approach because if we can look at the nonclinical data, we would see that GATA, is 300 fold more potent than these drugs, when you analyze breast cancer cells, prostate cancer cells, tumor cells, relative to these approved single node inhibitors. And and we think that just reflects, the the nature of the pathway and the importance of inhibiting it comprehensively to to induce, either half maximal or maximal effect.

Brad Canino, Senior Analyst, Stifel: And what is the rationale for get us hold to work in patients who don't have oncogenic alterations on the pathway that's being targeted by the mechanism?

Brian Sullivan, CEO, Celcuity: Sure. There are two factors I think that need to be, considered. One is that this the PAM pathway's role is is you know, think of it as as a junction, and it regulates, you know, various important, critical cell functions, including the regulation of of key metabolic processes that include glycolysis. And that's particularly important in tumor cells, which require a tremendous amount of energy and glucose, relative to normal cells to survive. So essentially they're hyperdependent on PAM pathway activity and the resulting regulation of glucose.

So that makes it a fundamental driver independent of the presence of an activating mutation, particularly in tumor types like HR plus breast cancer that involve other pathways that link to it. The other factor, that makes it possible for GET IT to be effective independent of activating mutations or or makes the pathway relevant is that it requires this comprehensive inhibition because essentially the critical role of this pathway has has led to this, you know, essentially redundancy of these other nodes. So the pathway can still function and perform, you know, these metabolic processes. It can adapt if, in a sense, one node is inhibited. And so in the absence of an activating mutation, you still need to comprehensively blockade it.

You may induce, and the data suggests that you get better effect even with a single node inhibitor, if you're only, hitting a single node inhibitor in, cells that have that activating mutation. Interestingly, though, GATA, again, with the various, cell lines that we've analyzed, has no difference in effect. You know, in fact, same potency and cytotoxicity whether or not a mutation is present. And and we think that just reflects the nature of the pathway's role as a regulator of of these these key metabolic processes that, if inhibited, essentially disrupt the tumor cell's ability to survive.

Brad Canino, Senior Analyst, Stifel: Yeah. And, obviously, with the availability of the single node inhibitors, patients are segmented between patients with PI3K alpha mutation and not, and the treatment paradigm has evolved based on that. Based on your phase one data, how close is the clinical activity between those two subgroups of patients with and without the path to mutations?

Brian Sullivan, CEO, Celcuity: So the nonclinical data, you know, is is almost identical. And the the preliminary clinical data clinical data that we have suggests they're very comparable, but there's probably a numerical advantage, relative to with with patients that have a PIK3CA mutation versus those that don't. You know, in our early phase data, the objective response rate in patients that lacked PIK3CA mutations was sixty percent sixty three percent, whereas in in patients that had a mutation, it was seventy three percent. You know, PFS rate at twelve months, forty nine percent in wild type patients, sixty percent in patients that had mutations. So a difference, and and we would expect, as we report out data, to see a numerical, difference.

It wouldn't be statistically significant difference, but but I think meaningful potentially clinically, in terms of, the effect size difference.

Brad Canino, Senior Analyst, Stifel: And the data you're describing are are from a triplet. Obviously, fulvestrant is there, an endocrine backbone agent, which pretty much every patient gets across all lines, but also a CDK foursix inhibitor. Right. The question is why is it important to continue that CDK foursix inhibition when these are patients who have progressed on that mechanism in the front line?

Brian Sullivan, CEO, Celcuity: Right. So one of the most important, I think, findings over the over the past few years is is is a recognition of, the interconnected role that the three pathways play as a promoter of ER positive breast cancer. You know, the ER estrogen receptor pathway, CDK foursix pathway, and the PAM pathway. And it appears, just based on the data we've generated as well as any non various nonclinical models, These pathways are intrinsically involved, and inhibition of one can drive and cross activate, the other pathways. And so there's a significant amount of non clinical data that we've generated as well as others in various labs across the world that have found that tumor cells that become refractory, no longer sensitive to CDK4six inhibitors, pathway can be reactivated and then the cells resensitize to CDK4six inhibition in the presence of a PAM inhibitor.

In effect, you eliminate that escape route, you drive activity back down to that CDK4six pathway, and so you need to maintain that pressure. Essentially, you've got this circuit that needs to be closed in order to optimize control, and that explains why in our first line phase 1b data showed very, very, we think, impressive results, forty eight months median PFS, in treatment naive patients, which we think provides a pretty good demonstration of, again, the intrinsic role these three pathways play at at the outset of the disease. They are the driver of the disease, and and you can potentially optimize treatment or require to optimize treatment blockade of all three pathways either upfront on the first line, or if you didn't do it upfront in the frontline setting, then it's a second line, option for patients. And and that's what we're evaluating in our various studies.

Brad Canino, Senior Analyst, Stifel: So let's talk about the study Victoria one second line pivotal trial. What are the key design elements you'd highlight of that trial?

Brian Sullivan, CEO, Celcuity: Sure. So we're enrolling patients whose disease progressed after treatment with a CDK foursix inhibitor and an aromatase inhibitor. So these are second line patients. That's standard of care for for most patients. They're allowed to have had up to two prior endocrine therapies, but no chemotherapy in the advanced setting.

So we would expect most of these patients to be pretty much second line, patients. They can't have had, for instance, prior, PAM inhibitors. They're randomized according to PIK3CA status, we we're essentially enrolling all comers, but then assigning them to, you know, cohort one or cohort two depending on their PIK3CA status. And in the wild type set in the wild type cohort, we have three arms. We have a triplet, you know, geta, palbociclib, and fulvestrant, and we're comparing that to fulvestrant as the control.

And we also have a doublet. Get a fulvestrant, and we're comparing that to the control as well. Those are

Brad Canino, Senior Analyst, Stifel: What the hell? Oh, I think you're back.

Brian Sullivan, CEO, Celcuity: I'm back. Yeah.

Brad Canino, Senior Analyst, Stifel: You paused for a little while?

Brian Sullivan, CEO, Celcuity: Everything shut off. I I apologize. That was, very strange. So, well, let me get my camera back, I guess, here. Hold on one sec.

Brad Canino, Senior Analyst, Stifel: We've got the we've got the wheat background.

Brian Sullivan, CEO, Celcuity: Yes. I'm here.

Brad Canino, Senior Analyst, Stifel: There you are.

Brian Sullivan, CEO, Celcuity: Great. No. Literally, our our entire system shut off. So I think I was just describing the trial design. And Yeah.

Actually, let me I'm sorry. I've just gotta reconfigure my system here. Hold on. I've gotta go off camera because I I had some something screw up. No worries.

So I'm back. Sorry about that.

Brad Canino, Senior Analyst, Stifel: No worries. Okay. So trial design.

Brian Sullivan, CEO, Celcuity: So so it's an interesting trial design. And then in the mutant cohort, we have a triplet. Again, in this case though in the mutant cohort we're comparing to alpulipsib and fulvestrant as a primary endpoint. The two cohorts have independent statistical analysis plans, and then on the case of the analysis of the triplet versus fulvestrant and the analysis of the doublet versus fulvestrant, those are tested hierarchically. So we're sparing alpha on making the design very efficient statistically.

Brad Canino, Senior Analyst, Stifel: Okay. And how has enrollment progressed in this study relative to your assumptions, and what do you think that means?

Brian Sullivan, CEO, Celcuity: Sure. So, you know, we've completed enrollment in the wild type cohort. We announced that in the fourth quarter. We actually were right on track 100% with our projection from over two years ago for the overall enrollment of the study. We found that, the mix and the ratio of patients who lacked mutations versus those who had mutations was, slightly different from what we had projected.

We thought it would be a sixty five thirty five ratio, Just, you know, there's certainly variance, and it turned out to be more of a sixty forty ratio. And and that meant that the wild type cohort took slightly longer to enroll than than our initial projection, slightly improved enrollment in the in the mutant cohort, but not substantially really changing things. But the overall enrollment, we're very pleased with. You know, very, very engaged sites, from around the world and and and and kind of pretty much, met our expectations.

Brad Canino, Senior Analyst, Stifel: In broad strokes, what effect size do you hope to see in these two different patient cohorts?

Brian Sullivan, CEO, Celcuity: Well, I mean, we'd like to see as big an effect size as possible. Certainly what I can speak to is the available data for fulvestrant as control. I think the data is fairly clear, least in our mind, patients who've received fulvestrant post CDK foursix, there have been four randomized studies that have a population similar to ours, and that data ranges from 1.9 months up to about two point eight months. Call it an average of, you know, say two point seven five months. So we think it's most likely, just based on the results from those studies, that your control would be in that two and a half to three month range.

And and then, you know, we obviously reported, in our preliminary study, much higher PFS than that. But we can't really, it's not appropriate for us to project. What we can talk about though, and I think what's relevant, is what's clinically meaningful. You know, what would be a win? I think a win, and certainly more is always better, but when you talk to KOLs or regulators, they define a clinically meaningful result as an improvement of roughly three months or more relative to your control.

Now there are different ways of measuring activity because I think in this setting now what you have are studies taking place that are enrolling a mix of populations. You've got some studies enrolling first line and second line patients together or with or without prior CDK foursix. And clearly those patients have far different prognosis, the results they would obtain from the same regimen are far different. And so the hazard ratio improvement will be very important to achieve as well. And again, we hope and expect that the preliminary data we have represents what what we'll see in the phase three, but but we'll see.

But the bar relative to what we've reported to date with our preliminary trial, you know, the phase one b trial, suggests we have, you know, pretty good margin of safety, margin for error to just to achieve a meaningful and an important result.

Brad Canino, Senior Analyst, Stifel: Yeah. And I would agree. The KOLs I've spoken with have suggested that three month delta as being a meaningful metric to think about. Now a lot of the conversations with investors I have today around the competitive intensity in this space, and and some of that includes the CDK plus oral SERD doublets, which have emerged with, I would say, at least high high single digit absolute PFS results. And the question to you, and I'd like to know how you like to answer this, is how do you see yourself competing in that?

With the with this in the space with these new benchmarks out there as well?

Brian Sullivan, CEO, Celcuity: Sure. You know, I I think, for instance, you're probably referring to the EMBER three study, and and that that's an example of a study that, to be frank, because of the way they designed it makes data hard to interpret, because the primary analyses, included patients who were first line and second line, and in the second line patients some had and some didn't have prior CDK. So if you were to talk to investigators, they'd say they don't know how to interpret that data. Now one way to interpret the data is to look at the hazard ratio. And the hazard ratio was, you know, point five eight, you know, in that range.

And so, you know, we we don't think it's unreasonable to think that we would, you know, beat that if if, you know, the early phase data that we reported is reported in in this setting. But we'll see. I think that that study had some other challenges that, again, may may limit the applicability of the data and utility of that going forward. But ultimately, you know, again, people will have to look at the relative contribution of the regimen compared to control because, you know, the absolute numbers are hard to use. You've enrolled first line patients, you're going to see a higher absolute top line median PFS number.

That's just the way it is. Fulvestrant, as a frontline therapy, will offer patients potentially ten to eleven, twelve months. If you include those patients in your analysis, well then, you know, you've essentially goosed the top line and and that doesn't necessarily represent what the second line patients would get. And and so, you know, that'll be one of our responsibilities when, you know, if we are commercializing this drug, to ensure that we present our data in a way that is very interpretable and helps oncologists understand the relative benefits or potentially ways of, you know, assessing the various datasets out there.

Brad Canino, Senior Analyst, Stifel: Alright. Okay. Now back to Victoria one, what toxicity profile do you hope to achieve? And is the rate of discontinuations an important metric you're looking at for the study result?

Brian Sullivan, CEO, Celcuity: Sure. I do think the rate of discontinuation is probably the best holistic measure of the overall tolerability of a regimen, and that's certainly the feedback we've received as we've done our preliminary commercialization preparation work, because it just captures whether patients can stay on the drug. In this setting, there are drugs out there, PI3K alpha inhibitor, mTORC inhibitor, that had twenty six, twenty four percent discontinuation rates, due to adverse, events. You know, in our preliminary data, our phase 1b data, with a phase three dose, the discontinuation rate was four percent. Now, if we look at the overall dataset from that, trial, hundred thirty eight patients, discontinuation rate was less than nine percent.

So I I think, you know, discontinuation rate of four to eight percent is certainly something we we think is reasonable, to expect. And and, again, based on the feedback we've received from investigators who've worked with and and treated patients with some of the other drugs in this class, they see a highly differentiated tolerability profile. And, again, you know, that's that's preliminary data. We'll we'll have to see. But it was very encouraging for us as we began activation or or selection of sites for our Victoria two study, the frontline study, that every Victoria one site, you know, the the study we hope to report data out, you know, this quarter, who we wanted to participate in our frontline study wanted to participate.

And and so, you know, we interpret that as favorable. The people had a good experience with the drug. The patients had a good experience in terms of general tolerability, and they must have seen something that suggests that they wanted to participate in ongoing development of the drug.

Brad Canino, Senior Analyst, Stifel: Yeah. Now one of the challenges of some of the competitive pathway inhibitors that we've seen launched recently in terms of interpreting their safety results is they have relatively strict criteria for who they select into the trials. And when the drug goes out in the real world, the toxicity rates generally start to creep How does your criteria for enrollment around parameters that can affect the safety profile compared to some of these recently launched drugs?

Brian Sullivan, CEO, Celcuity: Sure. So, you know, we have over, or I I think nearly 500 patients of data that's been reported publicly, so we haven't reported the phase three data. But referring to the published data for Ghetto, we have not had to create, for instance, a limiting HbAc1 level, for instance. So we've enrolled in those early phase studies patients who are prediabetic or type two diabetics. Uncontrolled diabetes, type one diabetics, we haven't been enrolled.

And as a result, and I think what you're referring to is hypoglycemia and given the role this pathway plays in regulating glycolysis, that has been the third rail, for drugs in this class. So we we don't, expect to see any difference between what we're enrolling and what we're experiencing in our phase three studies versus what the real world will show. And, there's there's enough patients who've who've been treated with the drug that we we think, you know, the

Brad Canino, Senior Analyst, Stifel: the profile, particularly around hyperglycemia, is is well well defined, well characterized. Got it. And maybe last question for me. Assuming we get positive results the next few months here, what could an NDA process for getetolasib look like? And given there still is an unmet need for a lot of these breast cancer patients, is there an accelerated timeline available for review?

Brian Sullivan, CEO, Celcuity: There is. We have breakthrough designation for this indication. Typically, breakthrough designation is given, A, based on available data you've presented to the agency and they'll review it, but also primarily because there's a significant unmet need. And that really hasn't changed. And so there's an a a pathway called real time oncology review, RCOR, that we'll, request.

And if that is is not, provided or granted, there's the accelerate, the priority review. You know, given the big unmet need, given the preliminary data, we we we think it's pretty reasonable to expect we would, qualify for some form of accelerated review.

Brad Canino, Senior Analyst, Stifel: K. Wonderful. Well, unfortunately, we're out of time. Brian, thank you so much for joining us. Look forward to hearing the news updates in the next few months.

Exciting time.

Brian Sullivan, CEO, Celcuity: Yes. It is. Thank you.

Brad Canino, Senior Analyst, Stifel: Alright. Bye now. Thanks, everyone, for joining in.

Brian Sullivan, CEO, Celcuity: You're welcome.

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