Celcuity at TD Cowen’s Oncology Summit: Exploring Gadotelisib’s Potential

On Wednesday, 28 May 2025, Celcuity (NASDAQ:CELC) presented at TD Cowen’s 6th Annual Oncology Innovation Summit, offering a strategic overview of its lead drug candidate, gadotelisib. The discussion, led by CEO Brian Sullivan and analyst Tara Bancroft, highlighted both the promising potential and the challenges facing the drug in the competitive oncology market. While the company is optimistic about its comprehensive approach to cancer treatment, concerns about market sentiment and safety remain.

Key Takeaways

• Celcuity’s gadotelisib targets the PAM pathway, crucial for treating certain cancers.
• Ongoing trials include a Phase 3 study for breast cancer, with data expected in Q3 and Q4 2025.
• The company emphasizes gadotelisib’s safety profile, noting lower hypoglycemia rates.
• Market adoption hinges on demonstrating superior efficacy and safety.
• A hazard ratio of 0.5 or below is seen as compelling for the drug’s success.

Operational Updates

Celcuity’s clinical trial pipeline is robust, focusing on various cancers:

• Phase 3 VICTORIA-1 study in ER-positive/HER2-negative advanced breast cancer, with wild-type cohort data expected in Q3 and PIK3CA mutant data in Q4 2025.
• Newly initiated Phase 3 study in first-line HR-positive/HER2-negative advanced breast cancer, beginning enrollment this quarter.
• Phase 1b study in metastatic castration-resistant prostate cancer, with top-line data expected later in June.

The company aims to redefine treatment paradigms through comprehensive PAM inhibition.

Future Outlook

• Anticipated Q3 data readout for the wild-type cohort of the VICTORIA-1 Phase 3 study.
• Expected Q4 2025 data readout for the PIK3CA mutant cohort of the VICTORIA-1 Phase 3 study.
• Top-line data for the Phase 1b prostate cancer study expected later this month.

Celcuity is committed to establishing gadotelisib as a leading treatment by proving its efficacy and safety.

Q&A Highlights

• A hazard ratio of 0.5 or below in the Phase 3 breast cancer study is considered highly promising.
• The company stresses the importance of relative PFS over absolute PFS for evaluating clinical activity.
• The Phase 1b study’s stringent criteria suggest a higher hurdle for demonstrating results, supporting gadotelisib’s potential.
• Gadotelisib’s safety profile shows a lower incidence of hypoglycemia compared to other PI3K inhibitors.

For more detailed insights, readers are encouraged to refer to the full transcript below.

Full transcript - TD Cowen’s 6th Annual Oncology Innovation Summit:

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Good morning, everyone. I’m Tara Bancroft. I’m one of the senior biotech analysts here at TD Cowen. I wanna thank you so much for joining our sixth annual oncology innovation summit. And so for our next session, we have a fireside chat with CellCuity, and it’s my pleasure to introduce Brian Sullivan, who is the CEO and cofounder.

So it’s a privilege to have you here, Brian, and thank you so much for for joining us.

Brian Sullivan, CEO and Co-founder, CellCuity: It’s my pleasure.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: I get started yes. Of course. And I just wanna remind anyone listening that you can email me questions at any time, Tara.Bancroft@TDSecurities.com, and I’ll I’ll make sure that I incorporate it into the questions. So, Brian, maybe you could start with just a a general update overview before we get into specific questions on Victoria one and more.

Brian Sullivan, CEO and Co-founder, CellCuity: Sure. Well, Daniel, as as a company, we started, and I started the company, to develop a platform to quantify signaling pathway activity in live tumor cells. And we’ve now since evolved to focusing on treating cancers involving the PI3K AKT M4 pathway, which we refer to as the PAM pathway. And this pathway is is probably of the most important oncogenic pathways. It’s most highly altered pathway, which correlates to its role as a cancer driver, and and we think it represents one of the largest untapped drug development opportunities in solid tumors.

Our lead assets are gadotelisib, pan p I three m two inhibitor. We have three studies, ongoing, two in breast cancer, one in prostate cancer. We have the an ongoing phase three study evaluating second line patients with ER positive for two negative advanced breast cancer. That one is one where we expect to report data in the third quarter for a wild type cohort. And then for a PIK3CA mutant cohort data, we expect to report fourth quarter of twenty five.

We also have a a phase three study that we’re just getting going that’s evaluating first line patients, HR positive, HER two negative advanced breast cancer. We expect to begin enrollment this quarter. And then we have an ongoing phase one b study in prostate cancer, a second line study for men that have metastatic castration resistant prostate cancer, and we expect to report top line data for that study actually later this month or later in June.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Great. And so I guess before we get into details on the data readouts that that are expected, I I think it would be helpful to kinda set the stage for the ways in which GETTA is actually differentiated in this space. There’s so much competition now going on, and so I think just also, like, mechanistically

Brian Sullivan, CEO and Co-founder, CellCuity: Sure.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: One of the things that KOLs are doing that we’re seeing is kind of bucketing it in with this PI three kinase class and and, like, the safety concerns that are associated with that. And so I wanna get your thoughts on on that and how it’s different from PI three k only class and and also some rationale for for how it could work in in wild type patients versus mutants as well. Well,

Brian Sullivan, CEO and Co-founder, CellCuity: a lot of ground to cover there. Well, you know, unlike most Yeah. Pathologies, you know, PAM pathways, multiple components or or targets have to be addressed. And and there are feedback and feed forward loops between the p k isoforms like p f k alpha or AKT or mTORC one that can cross activate the ones that are uninhibited. And and this essentially results in adaptive resistance when one inhibit one target is inhibited in the absence of the others.

Well, when the pathways roles in Oncadriver was first discovered, nearly every major pharma company initiated development of a pan p I three m two inhibitor because of the understanding of this adaptive resistance and that that was key to optimizing efficacy. And so the the the critical role the pathway plays in these metabolic processes makes it difficult to optimize pathway inhibition. And then safety issues also led to evolution of drugs that essentially just focused on single targets, let’s say p three k alpha, AKT, or mTORC one, as a way to, you know, get through what was believed to be a very narrow therapeutic window. And so there are these approved inhibitors that hit alpha, a three k, mTORC one, AKT. But these drugs aren’t haven’t been shown to be effective in patients lacking PIK three c m mutations, particularly in in in patients who have had prior CDK.

So unlike these other inhibitors, that really just address single targets, get inhibits all these targets at sub nanomolar or low nanomolar potencies and concentrations. And we’ve we’ve done analysis comparing how these approved single target PAM inhibitors and found that GET is 300 times more potent than the other drugs in vitro and and the only one that’s cytotoxic. And, also, important to point out, that GET is the only drug that has comparable potency and efficacy in in our in vitro studies in tumor cells with or and without PIK3CA mutations. And, again, that contrasts with the approved single node inhibitors that are three to six times less active in in tumor cells when they lack PIK3C mutation. So the mechanism is highly differentiated, and I think it’s just because the most recent drugs that have been developed and and approved happen to be single target inhibitors.

We we think we’ll reestablish the paradigm as requiring comprehensive PAM inhibition in order to optimize treatment of patients with dysregulated PAM activity.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. Definitely very great. Question.

Brian Sullivan, CEO and Co-founder, CellCuity: Yeah. I guess the other question was, okay. Why why, you know, why do we think, ghetto will work? What what’s the rationale for that, in in patients with these mutations? Well, it reflects two factors.

You know, the first factor relates to the PAM pathways role as a regular of of regulator of critical cell functions, including regulation of the glycolic process. And that’s that’s particularly relevant on tumor cells because they require tremendous amount of glucose relative to normal cells to survive. That’s their energy source. And that makes the PAM pathway a fundamental tumor driver independent of the presence of an activating mutation like PIK3CA, particularly in tumor types like HR positive breast cancer. The second factor just relates to this complex structure of the PAM pathway.

You know, with with the various PIK3CA mutations and mTOR complexes that kinda cross activate each other, the pathway can continue to function if only a single node such as PFK alpha or AKT is inhibited. And so as a result, in in patients that lack mutations in particular, complete blockade is required of the pathway to induce an antitumor effect. And and and that’s required to be done at low nanomolar concentrations. You know? And this is another observation I think is important.

If the only relevant feature of this pathway was the presence of PIK3CA mutations, you wouldn’t expect to see any activity on wild type tumor cells in in vitro studies. But our studies with breast cancer cell line models and prostate cancer models and endometrial cancer models demonstrate that the potency and cytotoxicity of GATA, which again blockades this pathway completely, is nearly identical in tumor cells regardless of whether they have a a PAM pathway alteration. And our preliminary phase one b data, you know, provides demonstration of this where, you know, the objective response rates, p f PFS rate at twelve months was was, you know, comparable in the patient cohorts that had PIK3CA mutations compared versus those that lacked PIK3CA mutations.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. And with that setting the stage, I think now the most helpful thing would be to get into expectations for the phase three wild type data that you said are now coming in q three. So I guess what would be helpful is hearing what what you believe is would be kind of the the minimum HR that you would consider to be good data in in this wild type update. Not yes. For for hitting staff, you know, we know that you you have good powering and everything, but really in relation to other studies in the space, you know, we recently got, you know, Serena six, other marketed products even.

I know there’s there’s a range of HRs for other different studies that we’ve seen from Capitello at point five nine and Emerald three at point six eight. So Right. Some context there would would be great.

Brian Sullivan, CEO and Co-founder, CellCuity: Sure. Well, certainly, hazard ratio of point five or below, I think, would be considered very compelling. And as far as I know Mhmm. No study in patients that have HR positive or two negative advanced breast cancer who who are receiving endocrine therapies that include a portion of patients who’ve had prior treatment with CDK four six inhibitor has reported a hazard ratio below point five as its primary endpoint. And and in terms of specific references, I guess, you know, there’s been recent data, AMBER three data, HR for Imlunestrin.

You know, the oral SERD was point six two, in patients with ESR one mutations. It wasn’t active, in patients lacking those mutations. When Imlun was combined with Abemma, abemaciclib c d k four six inhibitor, the HR was point five seven for its primary endpoint. The Emerald study evaluated another oral SERD elastatran where no not active in patients lacking ESR one mutations, but in the patients that had ESR one mutations, the hazard ratio was about 4.55. You know, as far as the serine is six, I’m not sure that’s a relevant comparison because that really is a modified first line indication.

You know, the patients in that study were switched to an alternative endocrine therapy in oral SERD before their tumors progress. So they’re really just trying to optimize the endocrine backbone of that before progression sets in.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. And what what have you heard from KOLs of, like, what HR that they would want to see in order to use it? I know you said point five would would be highly compelling, but what what do you think you’re hearing from KOL specifically?

Brian Sullivan, CEO and Co-founder, CellCuity: I I I think when KOLs are evaluating results from a study and then trying to assess how those those results compared to other studies, they’re looking at a variety of factors. Certainly, hazard ratio is a critical one because it provides the relative reduction of risk, you know, for one drug to another that allows you to do some comparison if you’ve got similar patient populations. I think the delta in, you know, the PFS between the median the median PFS between the control arm and the study arm is very relevant. And I also think, you know, the ratio. You know, how much better was the study arm, you know, as a multiple of the control arm?

And so they’ll they’ll look at, you know, those those three factors and and draw a conclusion from that and come from there, make a decision. And, obviously, safety will be an important component of their assessment as well. But they’ll they’ll factor in, you know, those various efficacy metrics, the overall tolerability of the regimens, and and make a decision based on that.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. Okay. Thank you. So I guess the next thing I’d love to get your thoughts on is is the idea of absolute median PFS. Like, I know all of this is what you just said makes total sense that, you know, the street is kind of kind of settled on the importance of what the absolute number is.

So I’m curious what what you would say to that to us us doing that. And

Brian Sullivan, CEO and Co-founder, CellCuity: Sure. No. I I I think yeah. Obviously, it’s it’s very easy just to to evaluate top line numbers. But it to be frank, you know, the problem with using absolute median PFS is that it doesn’t take into account the performance of the control arm.

And and for all clinical trials, it’s the relative difference between the study arm and the control arm that matters when assessing the clinical activity of these study drugs, not the absolute performance. And most of the studies in this setting use a very similar control, fulvestrant or or endocrine therapy. So so the relative comparison really is very important. And I think it may might be helpful. Let let’s take results from two hypothetical trials just to illustrate this.

Right? So imagine hypothetical trial one, right, where you have a study arm that reports nine months median PFS, and the control arm reports five and a half months median PFS. So in that hypothetical trial, then you have a study arm at median PFS. It was 1.6 times the five and a half month median PFS reported, for its control, and the incremental PFS was three and a half months. A lot of numbers there.

Sorry. Okay. So let’s consider a second hypothetical, trial. Well, the study arm reported seven and a half months, and the control arm reported two and a half months median PFS. So in in this second hypothetical trial then, study arm’s median PFS was three times two and a half month control, and and the incremental PFS was five months.

Well, I think most oncologists would select the regimen with seven and a half months median PFS that was three times longer relative to its control and offer five months incremental benefit over one that reported nine months p f meeting PFS. That was only one you know, roughly 1.6 times relative to its control and only offered three and a half months incremental PFS. And so that’s that’s why, again, it it’s just not the way decision making clinical decision making takes place. It’s just looking at the the one number out of context as as in most things in life. You know, the context matters.

So I know in this case, I think it’s obvious that the absolute PFS really just isn’t the right metric to use to establish some way of comparing one study regimen’s results to another regimen’s results in a in a clinical trial. Because, you know, you know, this example, I think, provides a pretty good illustration of that.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yes. Definitely. Thank you for that context. I feel like that’s that’s one of the most illustrative ways you you could have said that, so I I appreciate that. So I guess then, not to belabor this point, but I guess one of the things that I still think is is tougher to to get our minds around is, you know, the time that it’s taken to reach the study events.

Mhmm. Totally understandable. This is an event driven trial, of course, but to what extent can you have confidence that it’s not because the fulvestrant arm is outperforming, you know, like, post like you said, with with the five months, five point six or whatever it was in post monarch versus your expectations for three months, like, what underlies that and your confidence?

Brian Sullivan, CEO and Co-founder, CellCuity: No. It’s a great question. And oftentimes, you know, the differences in controls have nothing to do with the drug, right, or just randomness. It it really is more a function of which patients were enrolled, you know, what their tumor burden was, what the enrollment criteria were. So that that’s where you can get the variation, and that’s why it’s important that you you assess the relative performance of the study drug to the control.

So there have been four studies randomized that have used fulvestrant as control that have very similar enrollment criteria, to ours. And the average median PFS, for fulvestrant in those four studies was about two point eight months, two point seven months. So, you know, I think it’s pretty reasonable for us to expect between two and a half to three months, and that’s that’s just based on that data. You know, I don’t have any insight into anything. I just think, okay.

Those studies had very similar criteria Statistically, four different dips into that pool yield a very similar result. You know, the studies that useful vasodilator control like EMBER three and post Monarch didn’t have patient populations that were comparable to what we expect to enroll in VICTORIA one. For EMBER three, very complicated study because it enrolled, you know, four different subgroups of patients, you know, first line, second line with CDK prior treatment, not CDK prior treatment. So it’s very hard to get a beat on what what the the relevant subgroup that compares to to one we’re enrolling actually reported for for fulvestrant. Postmonarch study included a significant percentage of patients with non measurable disease, and and that results essentially in a significant upward skewing of progression free survival for those patients.

So it’s very hard to compare that, that that patient population to to ours. But the relative difference between the control and the study arm is is, again, as as I said earlier, is is what’s most relevant. So, you know, we’ll see. I mean, we’ll we’ll we’ll soon know, you know, how good our our reliance on this historical data is.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. Definitely. Okay. So I guess another that that all makes sense. You know, I I think one of the other things that I get, I I have a lot of conversations on with people is trying to understand it in context of the phase one data that you’ve gathered so far.

So I think, you know, it it’s clear from previous conversations why you would, you know, compare this dataset with one of the arms versus another in the phase one, but maybe just remind us again, like, how we can use the phase one data to kind of increase our confidence in the phase three or or make connections between the two?

Brian Sullivan, CEO and Co-founder, CellCuity: Well, you know, in our phase one b study, the results were were you know, we we view it as very favorable. In the wild type cohort, sixty percent of patients or so had an objective response. At at twelve months, forty nine percent of the patients were progression free, which, again, we we thought was, was very good relative to the the data from currently available therapies. The patient population we enrolled in the phase one b study actually was had more stringent requirements, to be frank, patients with more tumor burden than than what we expect to enroll in the Victoria one study. In particular, all a hundred percent of the patients in Victoria or rather than the phase one b study had had visceral mets, whereas we don’t expect that in Victoria one.

And in in fact, there were no bone only patients in the phase one b study. Bone only patients tend to, you know, be much more responsive or rather have much longer PFS periods because of just the nature of how bone mets progress relative to mets in solid solid organs. And in the Victoria one study, we we are enrolling patients who have bone only mets as as long as they have a measurable lytic or lytic plastic lesion. I guess another factor that that differentiates the phase one from the Victoria one that I think kinda represent gives a a sense that phase one b study had kind of a tougher hurdle to demonstrate results. In the phase one b study, patients were allowed to have prior chemo, so roughly a third of patients had prior chemo in the advanced setting.

We’re not enrolling patients who had prior chemo, but that that those patients were excluded in Victoria one. That’s relevant because patients who’ve had prior chemo in in the advanced setting tend to be less responsive to subsequent targeted therapy. So, you know, net net, I think the phase one b study actually is a good illustration. I think sometimes these phase one b studies can you know, are optimized to get quick enrollment, which means, you know, essentially allowing everybody that they can get just to get the data, which which is fair fair approach. But what I can do is create a skewing of of patients that may not be representative of of the population you’d enroll in a phase three study, and therefore, the results may not necessarily translate.

Now that’s why you see kind of a lot of phase three studies not replicate. We we’ve somewhat taken the opposite approach, and that well, we’ll soon see, we’ll see soon enough how, how that translates.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. Of course. And so, I guess, the you know, while we’re on this topic, can we think about how either the wild type data can read through to the mutant data and or how we should think about the the phase one context that we have? Like, how should we start now Sure. Thinking about the expectations of the mutant data?

Brian Sullivan, CEO and Co-founder, CellCuity: Right. Well, you know, on the margin, the the patients who had PIK three c mutations did better than the patients who lacked PIK three c mutations in our early phase study. And I would say it was a numerical superiority, not statistical superiority. So in in the in the mutant population, seventy three percent had an objective response versus sixty percent in wild type. You know, over sixty percent, were progression free at twelve months versus forty nine percent.

And from a regulatory standpoint, from a biological standpoint, it’s it’s harder to induce a treatment effect on patients that lack an activating mutation, which that’s been the history in this setting. None of the PAM inhibitors that have been evaluated in a phase three study and patients that have had really, some of them have had c d k four six inhibitor have demonstrated activity in patients lacking mutations. So if if we report favorable results that offer a clinically meaningful benefit, you know, we think that it’d be reasonable to assign a higher probability of success in our mutant cohort. We’ll have demonstrated ability to get over the, we think, the the the hardest hurdle to get over. And that patients with mutations tend to be more sensitive to these drugs this drug class, and we we think get a by inducing comprehensive inhibition of that pathway, we’ll certainly offer the potential for, you know, superior outcomes.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. And how about in terms of safety? I think, you know, the the fact that KOLs kind of unfairly bring up the p I three k class on its own and and kind of hold you to that bar. Can you give us some some context in in both the wild type and the mutant? Because the those comparisons to to CAPI and Inavo will will inevitably happen.

Brian Sullivan, CEO and Co-founder, CellCuity: Sure. Well, you know, the the the biggest challenge with, drugging this pathway, is that it it controls these key metabolic processes. And so for instance, because the this pathway regulates the glycolic system, you can induce high levels of hypoglycemia depending on how the drug is delivered. If it’s orally delivered, processed to deliver, or this glycolic regulation takes place, you can induce very high levels of of hypoglycemia. And the early drugs developed in this indication, most of them didn’t get through the gate.

You know, the first one that did alpolypsin induced very high levels of hypoglycemia, a very tough drug for patients. Still very high levels of hypoglycemia reported for drugs in this class. Geta is able to have report has reported much lower in his preliminary studies and also in a variety of other studies in in different settings, about a a fraction, you know, a a two thirds less hyperglycemia than has been reported with these other drugs. You know, no patients have been discontinued. Over 500 have have published data for them.

None have discontinued due to adverse events related to to hypoglycemia. So the discontinuation rate is is another metric that we think is very important. You know, four percent of patients discontinued in in the early phase study who received the phase three regimen compared to, like, let’s say, alpulipsib, which was, you know, over, you know, twenty six percent. You know, CAPI, the AKT inhibitor is around thirteen percent. So so, you know, the the the preliminary data suggests patients tolerate the drug well.

Again, we’ll we’ll soon know soon enough whether those results translate to the phase three, but, you know, we’re we’re we’re optimistic just just because of the number of patients that have been treated with this drug and and that the profile has been consistent from from study to study safety profile.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Okay. And, you know, I know we’re we’re quickly approaching time here, but I do wanna give you a chance to talk about how you’re thinking about the evolving market opportunity. Like, I know that for the third space, I feel like especially on the street amongst investors, I feel like a big old wet blanket has been just placed on the entire class. And, you know, we get comments from KOL sometimes about the utility of IV versus oral. So in in the context of of how it’s been evolving, especially in the last six months, one year, how you’re thinking about how Geta fits in and will be used?

Brian Sullivan, CEO and Co-founder, CellCuity: Well, I I think, ultimately, the the the coin of the realm in oncology or really any drug treatment is the efficacy. And and then secondarily, would and very importantly, would would be safety. I think the route of administration, convenience is a factor, and certainly all things equal. Right? If you had same similar efficacy and safety, then then the tiebreaker becomes convenience.

But I think if if we are able to report superior efficacy and and and repeat the, safety results from from the earlier studies, I I think that will weigh most heavily, in decisions, that physicians make, as they’re considering, what drugs to treat. You know, I think in the community setting, again, these doctors are are used to infused drugs. I mean, the largest drugs in oncology are infused drugs, and breast cancer infused drugs are the largest drugs. You know, HER two positive patients receive Herceptin and Perjeta. They’re, you know, as a class, those two drugs are not reach peak revenues of $9,000,000,000.

And and so I it’s not really a foreign concept. And there are advantages for these doctors. They get to see the patients more frequently. These are these are sick patients, seeing them more frequently. Infused drugs ensure that the patients are compliant.

They’re getting their treatment. You know, one of the challenges with oral drugs, especially if they have induced some side effects that are unpleasant for the patient that can lead to inconsistent compliance taking the medication. And then, you know, because of the nature of this process, infused drug is a is a health medical benefit, So different reimbursement path, to be frank, much less cumbersome. And with these oncology drugs, it can be quite arduous for patients to get reimbursed, can expose patients to fairly high co pays. So there’s a certain financial toxicity.

So all these factors net net, I I think, again, it all hinges on efficacy and safety. And if we have that, I I think we will be in a position to have a, you know, garner significant share of the patient population, treat significant share of those patients.

Tara Bancroft, Senior Biotech Analyst, TD Cowen: Yeah. Definitely. So, I mean, I know I, for one, am really looking forward to the data in q three and q four and the prostate data, which we didn’t even get to. That’s coming very soon. But, you know, Brian, I just wanna thank you again as always for your time, for joining us, and educating us, and thank you everyone for for listening.

Brian Sullivan, CEO and Co-founder, CellCuity: Thanks for having

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