CELC

I would now like to turn the conference over to Jodi Sievers, Corporate Communications and Investor Relations at Celcuity. Please go ahead.

Thank you, Matthew, good afternoon, everyone. Thank you for joining us to review Celcuity's first quarter 2026 financial results and business update. Earlier today, Celcuity released financial results for the first quarter ended March 31st, 2026. The press release can be found on the investor section of Celcuity's website. Joining me on the call today are Brian Sullivan, Celcuity's Chief Executive Officer and Co-Founder, Vicky Hahne, Chief Financial Officer, as well as Igor Gorbatchevsky, Chief Medical Officer, and Eldon Mayer, Chief Commercial Officer, who will also be available during Q&A. Before we begin, I would like to remind listeners that our comments today will include some forward-looking statements. These statements involve a number of risks and uncertainties, which are outlined in today's press release and in our reports and filings with the SEC. Actual events or results may differ materially from those projected in the forward-looking statements.

Such forward-looking statements and their implications involve known and unknown risks, uncertainties and other factors that may cause actual results or performance to differ materially from those projected. On this call, we will also refer to non-GAAP financial measures. These non-GAAP measures are used by management to make strategic decisions, forecast future results, and evaluate the company's current performance. Management believes the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the company's ongoing operations and prospects for the future. You can find the table reconciling the non-GAAP financial measures to GAAP measures in today's press release. With that, I will turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead, Brian.

Thank you, Jodi, and good afternoon, everyone. Thank you for joining our first quarter 2026 operating and financial update conference call. We continue to make great progress as we prepare for the potential approval and commercial launch of gedatolisib in the third quarter. Achieving these milestones would be a pivotal moment for the women with advanced breast cancer who need new therapeutic options. With the groundbreaking data we have previously reported from the wild-type cohort and the recent announcement of positive data from the mutant cohort of our VIKTORIA-1 study, we believe gedatolisib is well-positioned to become a new standard of care second-line therapy for patients with HR-positive, HER2-negative advanced breast cancer. It's been an eventful past few months for Celcuity.

Last week, we reported positive top-line results for the PIK3CA mutant cohort of the phase III VIKTORIA-1 clinical trial. We look forward to presenting detailed results at a late-breaking abstract oral session at the 2026 ASCO meeting on June 2nd. Given the timing of our ASCO presentation, we will not be answering questions regarding these results during the Q&A portion of our call. Second, this morning, we announced two important updates to our clinical development plan. First, we announced the expansion of our phase III VIKTORIA-2 trial to include a second study evaluating gedatolisib as first-line treatment in patients with endocrine-sensitive HR-positive, HER2-negative advanced breast cancer. We are now positioned to evaluate nearly all patients in the first-line setting, irrespective of their endocrine sensitivity or PIK3CA status.

This offers the potential to advance the standard of care for the approximately 90,000 women each year who are newly diagnosed in the U.S. with HR-positive, HER2-negative advanced breast cancer. Secondly, we also announced this morning that we are advancing the development of a gedatolisib formulation for subcutaneous injection and that we have submitted our first patent application to the United States Patent and Trademark Office. The subcutaneous formulation is aimed at supporting potential future indications for gedatolisib regimens that may result in duration of treatment periods greater than several years. Finally, we remain optimistic about the outcome of the FDA's review of our NDA.

Assuming our NDA is approved, we intend to submit the FDA a supplemental new drug application based on the results of the PIK3CA mutant cohort VIKTORIA-1 and to submit VIKTORIA-1 data for both the mutant and wild-type cohorts to other global regulatory authorities following the sNDA submission. Turning now to the top-line results for the PIK3CA mutant cohort. The primary efficacy analysis of gedatolisib combined with fulvestrant and palbociclib, which we refer to as the gedatolisib triplet, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared to alpelisib, which is a PI3K alpha inhibitor, and fulvestrant. The secondary endpoint of gedatolisib combined with fulvestrant, which we refer to as the gedatolisib doublet, which was not part of the primary efficacy analysis in a hierarchical order, demonstrated a statistically significant and clinically meaningful improvement in PFS compared to alpelisib and fulvestrant.

Both gedatolisib regimens were generally well-tolerated with manageable safety profiles and no new safety signals. When considered alongside previously presented data from the VIKTORIA-1 PIK3CA wild-type cohort, the gedatolisib regimens have now demonstrated the potential to improve the standard of care in a second-line setting regardless of the PIK3CA status of a patient's tumor. We believe the results from the VIKTORIA-1 study validate our pioneering approach to targeting cancers involving the PI3K, AKT, mTOR or PAM pathway. Researchers have sought for nearly 20 years to develop a drug that blockades this pathway comprehensively without inducing unacceptable levels of toxicity. VIKTORIA-1 represents the first phase III study that demonstrate that comprehensively blocking the PAM pathway can significantly improve outcomes for patients with PIK3CA mutations compared to therapies only targeting a single component of this pathway.

As we've previously reported, the VIKTORIA-1 PIK3CA wild-type cohort set several new benchmarks for clinical trials evaluating patients with HR-positive, HER2-negative advanced breast cancer. The hazard ratios for the gedatolisib triplet and doublet were more favorable than has ever been reported by any phase III trial for patients with HR-positive, HER2-negative advanced breast cancer. The 7.3 months incremental improvement in median PFS for the gedatolisib triplet over fulvestrant is higher than has ever been reported by any phase III trial for patients with HR-positive, HER2-negative advanced breast cancer receiving at least their second line of endocrine therapy. The 17.5 months of median duration of response for the gedatolisib triplet and 31% incremental increase in the objective response rate relative to the control for the gedatolisib triplet are the highest reported for an endocrine therapy-based regimen in the 2nd-line setting.

Both regimens were found to have a manageable safety profile that was well-tolerated by patients as evidenced by the 2% and 3% adverse event-related discontinuation rates for the triplet and doublet respectively. We've also previously reported safety and tolerability-related analyses. In particular, for patients who experienced dermatitis, we reported that measures to mitigate it were generally effective. The median time to improvement from first onset to a lower grade of stomatitis for patients with grade 2 or grade 3 stomatitis who received the gedatolisib triplet was 12 and 14 days respectively. To characterize the overall tolerability of the gedatolisib regimens, we reported results from patient-reported outcomes that capture a patient's perception of their overall well-being. Of particular note was the stability of the patient's assessment of their well-being relative to their well-being prior to starting treatment with gedatolisib.

Over the first eight cycles of treatment with gedatolisib, patients reported no degradation in their sense of well-being, which we believe provides meaningful evidence that patients treated with gedatolisib tolerate it well. Let's talk about our VIKTORIA-2 study. Results from the PIK3CA wild type and mutation cohort of our VIKTORIA-1 study demonstrated the benefit of gedatolisib combination treatment in the 2nd line setting of HR-positive, HER2-negative advanced breast cancer. These results confirm the role the PAM pathway plays in patients with or without PIK3CA mutations and the importance of multi-target inhibition of this pathway. Additionally, results from our phase I-B clinical trial provided strong evidence that the PAM pathway is also an important disease driver in treatment-naive patients with advanced breast cancer.

In the early phase study that we performed, we evaluated gedatolisib plus palbociclib and letrozole as first-line treatment in patients with endocrine-sensitive HR-positive, HER2-negative advanced breast cancer. Median progression-free survival, or PFS, was 48.6 months, which compares favorably to historical data of approximately 25 months for ribociclib plus letrozole. The objective response rate was 79%, which again compares favorably to historical data of 53% for ribociclib plus letrozole. In light of the positive results for the PIK3CA wild type and mutant cohorts of VIKTORIA-1 and the promising preliminary data for our gedatolisib triplet as first-line treatment, we have high confidence that we can successfully develop the gedatolisib triplet for nearly all patients in the first-line setting, irrespective of their endocrine sensitivity or PIK3CA status.

Successful development in the first-line setting would offer the potential to advance the standard of care for the approximately 90,000 women each year who are diagnosed with late-stage HR-positive, HER2-negative advanced breast cancer in the U.S. To achieve this goal, we amended several important elements of the VIKTORIA-2 study design. First, VIKTORIA-2 will now evaluate the safety and efficacy of patients with endocrine-sensitive HR-positive, HER2-negative advanced breast cancer in addition to those with endocrine-resistant disease, which was the original study. Endocrine-sensitive patients represent approximately two-thirds or 60,000 of the 90,000 women in the U.S. newly diagnosed with advanced breast cancer each year. Current standard of care therapies for these patients provide median PFS of approximately 25 months.

Patients will be assigned manually according to their endocrine sensitivity status to either study 1 if they are endocrine resistant, or study 2 if they are endocrine sensitive, and subsequently be randomized to a treatment arm. Each study will have independent statistical analysis plans that will include separate primary endpoints. The primary efficacy analyses for both study 1 and study 2 of VIKTORIA-2 will evaluate the entire intent to treat population enrolled in their respective study. Primary endpoints for patient cohorts based on their PIK3CA status are no longer included. This revision of the primary analyses allowed us to reduce the sample size for study 1, the endocrine-resistant study, from 638 patients to 440 patients without affecting the power of the analysis.

Third, the control arms for Study 1 and Study 2 will evaluate ribociclib combined with either fulvestrant for Study 1 or letrozole for Study 2. Study 1 will enroll patients with treatment-naive endocrine-resistant advanced breast cancer, and these are women whose breast cancer progressed while receiving or within 12 months of completing adjuvant endocrine therapy. It's a more aggressive disease. The trial will evaluate the efficacy and safety of gedatolisib combined with palbociclib and fulvestrant in arm A and compare that to ribociclib combined with fulvestrant in arm B. We expect to have top-line data by the end of 2028 for this study. Study 2 is expected to enroll approximately 740 subjects with treatment-naive endocrine-sensitive advanced breast cancer.

These are women whose cancer relapsed or progressed 12 months or more after completion of adjuvant endocrine therapy, or those with de novo metastatic disease who've had no prior endocrine therapy exposure. The trial will evaluate the efficacy and safety of gedatolisib combined with palbociclib and letrozole and compare itself to ribociclib combined with letrozole. The clinical trial primary endpoints for the VIKTORIA-2 clinical trial are progression-free survival per RECIST 1.1 criteria as assessed by blinded independent central review. We expect top-line data for the study 2 in the under-consented patients to be available by 2030. Prior to finalizing this amended phase III trial design, we conducted a type B meeting with the FDA to obtain their feedback and to gain alignment on these planned amendments.

Knowing that our lifecycle plan would eventually include indications that may offer several years of progression-free survival benefit, we initiated a program to develop a subcutaneous formulation of gedatolisib that would enable a patient to receive gedatolisib as an injection, as an alternative to an infusion. This program is ongoing with the goal of demonstrating clinical equivalence to the current intravenous formulation of gedatolisib. This work has resulted in a submission to the United States Patent and Trademark Office of our first patent application for an injectable formulation of gedatolisib. Let's turn to our phase I-B/II trial that's evaluating gedatolisib in combination with darolutamide in men with metastatic castration-resistant prostate cancer. We presented data for the phase I-B portion of the study at a poster presentation at ESMO last year.

In this portion of the trial, 38 patients were randomly assigned to receive standard doses of darolutamide twice daily and either 120 milligrams of gedatolisib in arm one or 180 milligrams of gedatolisib in arm two. The combination of gedatolisib and darolutamide was generally well-tolerated in the trial and mostly low-grade treatment-related adverse events. No dose-limiting toxicities were observed in either arm, and no patients discontinued study treatment due to an adverse event. For all patients treated, the six month radiographic PFS rate was 67%, and the median radiographic PFS was 9.1 months. These results compare favorably to historical results of a 40% six-month radiographic PFS rate for patients with metastatic castration-resistant prostate cancer who are treated with an androgen receptor inhibitor as second-line treatment.

Enrollment of patients in the dose escalation portion of the trial is ongoing. We expect to provide a data update at an upcoming medical conference. As we near what we hope is an FDA approval for gedatolisib in 2026, our efforts to prepare for the potential launch of gedatolisib continue to ramp up per our strategic launch plan. We began laying the groundwork for a potential gedatolisib launch over 24 months ago. Last call, we mentioned that we had largely completed building the commercial organization, except for the sales force. I'm excited to report now that we have since hired and onboarded all of our oncology sales specialists. They're a very experienced crew. On average, these individuals have 24 years of experience selling pharmaceuticals and 16 years of experience in oncology.

They're an incredibly talented group of individuals who have a strong track record of successfully launching novel oncology therapeutics. Key efforts today include continuing our extensive outreach across the country to payers, strategic accounts, which include health systems, integrated delivery networks, and community oncology practices. We're also very encouraged by the results of research we've continued to field to gauge the willingness of community and academic oncologists to prescribe gedatolisib should it get approved. These results make us optimistic about the possibility of establishing gedatolisib as the new standard of care in the second-line setting for HR-positive, HER2-negative advanced breast cancer in the wild-type patient population. Now, with positive results from our study with patients whose tumors have PIK3CA mutations, we expect the gedatolisib combination regimens to be uniquely positioned to provide second-line therapy for patients regardless of their PIK3CA mutation status.

Based on the analysis of published epidemiological data, we estimate there are 37,000 patients in the U.S. receiving second-line treatment for HR-positive, HER2-negative advanced breast cancer. Using internal duration of treatment estimates and pricing assumptions consistent with currently available novel therapeutics for breast cancer, we estimate the total addressable market for gedatolisib in the second-line setting is more than $5 billion annually. Given the significant penetration our research is suggesting we can achieve, we believe it's reasonable to estimate that a second-line indication for gedatolisib can potentially generate peak revenue of up to two and a half billion dollars annually. The progress we've made today is encouraging, and we look forward to providing with updates over the next few quarters.

Gedatolisib is well-positioned to address critical needs in the second-line space with its unique mechanism of action and potential first-in-class best-in-class safety and efficacy profile. This gives us an exciting opportunity to advance potential blockbuster indications in breast cancer and prostate cancer, while also aggressively preparing for and potentially launching gedatolisib commercially should we receive FDA approval. Now I'd like to hand the call over to Vicky to review our finances.

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the first quarter 2026. Our first quarter net loss was $52.8 million or $0.97 per share, compared to a net loss of $37 million or $0.86 per share for the first quarter of 2025. Our non-GAAP adjusted net loss was $46.8 million or $0.86 per share for the first quarter of 2026, compared to non-GAAP adjusted net loss of $34.7 million or $0.81 per share for the first quarter of 2025.

Research and development expenses were $33.1 million for the 1st quarter of 2026, compared to $29.8 million for the prior year period. The $3.3 million increase was primarily due to a $3 million increase in employee-related and consulting expenses. The remaining increase was primarily due to a $5.4 million increase in manufacturing and other costs, partially offset by a $5.1 million decrease in clinical trial costs, which was primarily driven by decreased costs for the VIKTORIA-1 phase III clinical trial. Selling, general, and administrative expenses were $17.4 million for the 1st quarter of 2026, compared to $6.3 million for the prior year period.

The $11.1 million increase was primarily due to an $8.7 million increase in employee-related and consulting expenses, of which $6.6 million was due to commercial headcount additions and other launch-related activities. The remaining $2.4 million increase was primarily due to software costs, professional fees, and other administrative costs. Net cash used in operating activities for the first quarter of 2026 was $55.1 million, compared to $35.9 million for the prior year period. The additional cash in operating activities quarter-over-quarter of $19.2 million was primarily due to non-GAAP adjusted net loss of $12.1 million and working capital adjustments of $7.1 million. Cash, cash equivalents, and short-term investments were $387.1 million at the end of first quarter 2026.

We expect cash equivalents, and investments and drawdowns on our debt facility to finance our operations through 2027. I will now hand the call back to Jodi.

Thanks, Vicky. Before we turn the call to the operator for questions, I'll remind you, we will not be answering questions related to the VIKTORIA-1 mutant cohort data being presented at ASCO on June 2nd or providing additional guidance on our expectations for data at this time. Matthew, could you please open the call for questions?

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment please for your first question. Your first question comes from Maury Raycroft of Jefferies. Please go ahead. Your line is open.

Hi. Congrats on the progress, and thanks for taking my questions.

You're welcome.

Maybe starting off, just wondering if you can provide any perspective into the nature of questions and interactions with FDA that you're getting ahead of the PDUFA date. Have you submitted a draft label, and are you in labeling discussions at this point?

Yeah, we're not going to provide that level of detail about the interactions other than to say that there's nothing about the interactions to date that suggests that we will be off track for the PDUFA decision by July 17th.

Got it. Okay. Then wanted to ask about the subq formulation as well. Wondering if there's anything more you could say about what you're seeing with preclinical data in respect to comparability on PK/PD and dosing frequency. Can you talk more about timeline to move this version into the clinic and whether there could be any bridging efforts as it relates to the VIKTORIA-2 study?

Sure. As far as the internal work, I mean, we're not gonna be providing a play-by-play of the internal work. I can speak to the timeline and the steps. I mean, obviously the first step is optimizing the formulation itself. It's required and you work with multiple candidates to ensure you've optimized it. You have to transfer that to manufacturing, scale it, ensure you have stability, et cetera. Ultimately you end up with PK studies, you know, phase I, to confirm the PK profile and map its equivalence to the IV formulation. Finally, we expect the FDA to probably require equivalent study, phase III study.

They've laid out some guidance on that front. The goal is to have an subq form available, basically along the same timeline that we would expect to get an approval or hope to get an approval for the endocrine sensitive population.

Got it. Okay. That's helpful. Thanks for taking my questions. I'll hop back in the queue.

You're welcome. Okay.

Thank you. Your next question comes from Tara Bancroft of TD Cowen. Please go ahead. Your line is open.

Hi. Good afternoon. My question is, you know, not about the mutant data, more about some educational historical background. Because in thinking about, you know, the range for alpelisib and fulvestrant in a five to seven months, can you just, from your view of historical trials, some context around the bookends of that range from BYLieve cohort C to then cohort A and EPIK-B5 in terms of patient characteristics that you think most contributed to the difference there, just to help us understand?

I don't want to speak directly other than to say that, you know, there is always a certain amount of heterogeneity between trials, the patient populations that get enrolled. Anytime you are looking at potential results for a particular therapy, we think it is best to look at the range and not get overly fixated on trying to calculate a probability. It is just not practically possible. The data that has been reported is, you know, really the only we think data that can be assessed to understand, you know, what the performance of a drug like apalutide can do.

Okay, great. Thanks. Thank you. Your next question comes from Andrew Berens of Leerink Partners. Please go ahead. Your line is open.

Hi. Thanks for taking the questions, and congrats on the progress, Brian. Looking forward to seeing the data at ASCO in Chicago.

Thank you.

My questions are about the subQ announcement today. We've been trying to think of an analog of a small molecule that was given IV and then was changed to subcutaneous. You know, most of them are antibiotics, and there's not really a benefit going subQ there. Is there one that you could point us to to get an idea of the process, the regulatory process? Then also, would you expect that the, you know, the PK and the Cmax would change when you go from intravenous to subQ? We've heard some speculation about, you know, the mucositis maybe being related to Cmax. Just wondering if you think that would come down with a subQ version.

Yeah, thanks for the question. As far as the regulatory process, I think there's a general process that FDA requires to assess drugs that are injected in some form or other, injected or infused. We expect our program will follow those requirements. I outlined those in one of the prior questions, you know, essentially where you have to characterize the PK profile for a variety of reasons, but then also then characterize the equivalence from an efficacy standpoint.

To date, it appears that when you are introducing a new formulation, that has a different route, you know, even if it's, you know, still being systemically administered directly, you do need to demonstrate clinical equivalence. Based on some recent guidance, it appears that the FDA's position is that if you demonstrate equivalence in one indication, that that data will then, and that approval will allow that new formulation to be used for any other indications that may exist. So we expect that to be the path forward for us, and, you know, we'll take it from there.

Okay. What about the PK and the Cmax? Any insights on how it's different?

No, I mean, obviously from a development standpoint, I mean, the perfect world is you match PK profile as, as closely as you can, or at least you kind of focus on certain ranges. As far as speculating about the stomatitis effect like that, it's just too premature to get into that. It's certainly, we think a function of a Cmax. The fact that, you know, the concentration settles in after a few hours at a much lower concentration and basically remains stable. We think that's one of the reasons why patients have reported the drug to be very well tolerated, not affecting their quality of life.

You know, certainly there's ways of thinking about administering the drug or formulating it that would allow you to try to optimize that. Those are all will be elements of the development program that we'll be evaluating.

Okay. Well, congrats again on continuing to move the needle.

Thank you.

Thank you. Your next question comes from Stephen Willey of Stifel. Please go ahead. Your line is open.

Yeah, good afternoon. Thanks for taking the questions. Congrats on the announcement today. I know that we've seen frontline market share in the endocrine-sensitive setting, kind of largely influenced by longer-term OS data. Just curious as you were thinking about the sizing of VIKTORIA-2, kind of how this factored into the design and whether you might be able to provide just any preliminary powering assumptions on either OS or PFS in the primary. Thanks.

Well, OS becomes, in effect, the way to break the tie when you have three regimens that offer almost equivalent progression-free survival. That was, you know, the case with the CDK 4/6 drugs. Ribociclib then subsequently demonstrated that it offered a survival benefit. We'll be comparing ourselves to ribociclib, and if we offer a progression-free survival period that's superior to ribociclib, and we show that there's no decrement in overall survival, that would, in effect, achieve the goal of demonstrating that there's a clinical benefit for these patients. Certainly, for any study you do, you'd like to show that there's a survival advantage relative to what you're comparing to.

If we achieve PFS and show no decrement in OS, we'll have essentially satisfied, you know, certainly the regulatory requirements, and we think we'll satisfy the clinical expectations for a drug. Certainly, the drug has to offer a meaningful increase in incremental PFS. You know, three months on top of 10 is different than three months on top of 25. We're mindful of that and then design the study to reflect the expectations that you need more than three months to demonstrate a clinically meaningful benefit.

All right. Thanks for taking the question.

You're welcome.

Thank you. Your next question comes from Bradley Canino of Guggenheim Securities. Please go ahead. Your line is open.

Hey, Brian and team. Great to see the strong progress on my end as well.

You're welcome.

For the subcu, sorry if I missed this on the call. I missed some of the prepared remarks. Is the formulation completed, and have you conducted animal models with it yet, or is this still in process?

Well, I mean, again, we're not gonna give play-by-play on each stage of the program other than to say that we have multiple candidates that we're advancing and we're, you know, in the middle of doing a variety of both stability studies to confirm and to characterize the formulation itself, as well as evaluating, you know, the other nonclinical parameters, including, you know, animal studies and work like that.

Okay. Maybe it'd be helpful, are there any certain properties about gedatolisib that support its translation to a subcu formulation that could give investors confidence?

Well, we're confident we'll be able to develop it. You know, every drug has its own challenges when it comes to, you know, converting it to a more concentrated form. I think part of the advance that we've made is that it requires invention, and which is good because it's not an obvious approach, and it's one that we think will certainly enhance our intellectual property position significantly. As far as, you know, signaling, you know, how to interpret the likelihood that we'll be successful, I would say we're very confident.

Just anything you can say about what you're seeing so far about predicted dose, not so much disclosure of the dose, but how that might shape the specific device that you can use for the patient and the administration time.

I think you're referring to the volume. You know, the dose itself will be the same, and it's just a matter of translating that dose into a smaller volume so it's injectable. We have targets internally. We have functional requirements that we're targeting. You know, so far, we fully expect to meet the functional requirements that would allow it to be an injectable form.

Okay, great. Thanks for taking the questions and look forward to seeing you at ASCO.

Great. Thank you.

Thank you. Your next question comes from Oliver McCammon of LifeSci Capital. Please go ahead. Your line is open.

Hi, Brian. Thanks for taking my questions. I'm just thinking about the endocrine sensitive study. I'm wondering if there are any learnings to take from the PALOMA trials experience in terms of being thoughtful about patient follow-up and powering for OS. Thanks again.

There's a lot of learnings from the PALOMA-2 and also from the MONALEESA-2 rival study. Believe me, we've taken in the learnings from the rival study more than the PALOMA study. We think, you know, there's certainly a way to design the study in a way that maximizes your opportunity to potentially demonstrate an overall survival advantage.

Thanks again.

Thank you. Your next question comes from Eva Fortea-Verdejo of Wells Fargo. Please go ahead. Your line is open.

Hey, good afternoon. Congrats on the progress and thanks for taking.

Our questions. Do you have any updated thoughts on the competitive positioning for gedatolisib versus other PI3K inhibitors in development, and how do you see this evolving with a subcutaneous formulation coming online? Thanks.

Well, I think, you know, details to follow, we did report that gedatolisib doublet, just in a head-to-head, a replacement for an existing PIK3CA approved drug, was, you know, statistically significantly and clinically meaningfully differentiated from a single target inhibitor. Ultimately, what we think we've been saying has been confirmed, which is that multi-target inhibition of this pathway is required to optimize antitumor control and that single target inhibitors are going to be limited. If you look at the data for alpelisib and capivasertib, you'd see that the hazard ratios that they have reported in patients who've had prior CDK treatment are very similar. You know, roughly 0.5 compared to fulvestrant.

We've demonstrated that we're superior to that. What we think that means is that, you know, the approach will be at a, you know, a disadvantage going forward, just from a benefit standpoint. That approach we do not believe offers the potential to provide comparable efficacy.

Got it. Thanks.

Thank you. Your next question comes from Gil Blum of Needham & Company. Please go ahead.

Good afternoon, everyone, congrats on the progress and the impressive results, Brian.

Thanks.

Just a couple of quick points from us. One, as it relates again to the potential for a sub-Q formulation, is there any chance that would change kind of the. You currently have a very specific schedule of dosing. Would there could be any changes to that, or how do you view this? I have a follow-on.

Sure. Those are factors that, you know, go beyond, you know, simply the formulation, because it gets to the overall PK profile of gedatolisib and what's required to, you know, sustain sufficient target engagement. I think that question is broader than simply sub-Q. I think it's, you know, relates more generally to how to administer, or rather how frequently, gedatolisib needs to be administered. You know, how we answer that question, if it's different over time, you know, will be the byproduct of, you know, studies probably involving the infused form because we have that now, and we can evaluate that.

You know, to the extent that we find ways to potentially alter the administration schedule, you know, that would be applied if that were to happen to a potential subcutaneous formulation.

Yeah, that makes sense. Just interesting to hear your thoughts of recent news from one of your competitors, Oncore Pharma, decided to move away from a PI3K selective mutant to an alpha specific, if you have any thoughts on that? Thank you.

Well, I, you know, I think, again, there's only so much biological potential that targeting, you know, the alpha, you know, PI3K alpha gives you. I think that's less a function maybe of the targeting and more a function of, you know, increasing the potential patient population that they're hoping to treat. You know, they had a more selective approach that essentially meant that they would have a smaller patient population, I would imagine they found some results that indicated they didn't need to be that specific. alpelisib is generally targets, and their indications include, you know, the 12 or 13 most common mutations. There's been some evidence of variation in response to those patients depending on their mutations.

You know, I'm not sure that that is dispositive in how you think about developing for that population. You know, they, you know, they've got data, I'm sure, that is guiding their decisions and again, but it is in the context of, you know, what we think is limited biological potential to induce a treatment effect when you limit targeting to the alpha isoform.

Thank you for all that, Brian.

You're welcome.

Thank you. Your next question comes from Kalpit Patel of Wolfe Research. Please go ahead. Your line is open.

Yeah. Hey, good afternoon, and thanks for taking my question. One from us, another one on this sub-Q formulation. You know, would you characterize gedatolisib's antitumor effect as being Cmax driven or AUC driven? How does that inform your confidence on the sub-Q formulation that it can achieve clinical equivalence to an IV?

You know, I mean, those are great questions, and I think every drug company tries to tease that out. There's been a lot of work that people have done to try to kind of determine whether a drug is more Cmax versus total volume, total exposure. You know, I think an argument could be made that it's both, that you get a benefit, the high Cmax in the gedatolisib case and then, you know, the sustained target engagement. You know, again, your roadmap is gonna factor in what we've seen to date. That's the best approach to take is see how close you can match that curve, knowing that it won't be exact, but there are other ways you can affect that.

You know, we're taking those other factors into account.

Okay. Got it. Thank you.

You're welcome.

Your next question comes from Sylvain Tuerkcan of Citizens JMP. Please go ahead. Your line is open.

Thank you for taking my question, and congrats on all the progress. I'm looking forward to ASCO. Maybe if I can ask around ASCO, not about the data, but in general, it seems it's a very important venue for you, especially with the PDUFA in the, in the wildtype patients ahead. What's your strategy there to interact with doctors? What sort of events do you have planned, and what is your messaging on the wildtype population here ahead of the approval? Thank you.

You're welcome. Well, we'll have an army of folks at ASCO, with that are, you know, mostly, there to, you know, medical professionals to be able to engage with doctors and exchange information. There's a lot of other work that can be done as well. Certainly, it's a big venue. A lot of doctors will have a good opportunity to communicate the results. No, we view it as a great staging ground to lay the groundwork for what we hope is a future launch over the summer. No, we're Very excited about the timing of ASCO and its alignment with the schedule we're on, we hope to get an approval.

Great. Thank you. Have you done already some payer feedback discussions and kind of around coverage? Do you have any comments around that?

We've had a lot of discussions. You know, we built our payer team, which includes, you know, a team focused on strategic accounts and then a team focused on payers, national accounts. We've been engaging at great depth and length with them, you know, for almost a year. Been very encouraged by the feedback we've gotten. Their formal review really doesn't take place until you have an approval and you submit a dossier. Along the way, you can certainly get their input about their expectations.

You can learn about the system and exactly what their requirements are and ensure that when it comes time to make decisions that everybody on these various committees is well informed and feels comfortable with getting and from their perspective, the proposition that it offers to their patients and and to the, you know, and relative reimbursement expectations. No, we've made a lot of we're, I would say, very, very well along in laying that groundwork and being in a great position, you know, once the approval comes to really move expeditiously with the various accounts I described.

Great. Well, thanks, yeah, so much for the color.

Thank you. Your next question comes from Chase Knickerbocker of Craig-Hallum. Please go ahead, your line is open.

Good afternoon. Thanks for taking the questions. Just wanted to maybe just assess kinda your current kinda commercial readiness. You know, in the past couple of months, there's been a couple of early oncology approvals relative to PDUFA date. Brian, I just wanna get your thoughts on kind of where you, where you think you sit from an innings perspective as kinda having your team ready for a potential launch in wild type. Thanks.

Sure. Again, there's all of these situations with some of these early approvals are, I would say, situationally based. You know, there was an approval recently for a drug that had a regular review, and it came in a few weeks early. You know, we have a priority review for a new drug, six-month review period. Historically, our priority reviews of drugs with priority designation occur pretty much in line with the PDUFA date. That's, that's been our governing assumption. Internally, you know, we've, you know, identified a launch-ready date that's before PDUFA, so we're make sure that we are ready to roll when we hope the approval decision comes.

Helpful. Thank you.

Thank you. There are no further questions at this time. I'd now like to turn the call back over to Brian Sullivan, Chief Executive Officer and Co-Founder, for closing comments.

Great. Well, thank you very much for your participation in our call. We appreciate the questions, and we look forward to seeing some of you at ASCO. Take care. Goodbye.

Ladies and gentlemen, this concludes today's conference. We thank you for participating and ask that you please disconnect your line.

Good afternoon, ladies and gentlemen, and welcome to the Celcuity Fourth Quarter and Full Year 2025 Financial Call. [Operator Instructions] I would now like to turn the conference over to Jodi Sievers, Corporate Communications and Investor Relations at Celcuity. Please go ahead.

Thank you, John, and good afternoon, everyone. Thank you for joining us to review Celcuity's Fourth Quarter and Full Year 2025 Financial Results and Business Update. Earlier today, Celcuity Inc. released financial results for the fourth quarter and full year ended December 31, 2025. The press release can be found on the Investors section of Celcuity's website. Joining me on the call today are Brian Sullivan, Celcuity's Chief Executive Officer and Co-Founder; Vicky Hahne, Chief Financial Officer; as well as Igor Gorbatchevsky, Chief Medical Officer; and Eldon Mayer, Chief Commercial Officer, who will be available during Q&A. Before we begin, I would like to remind listeners that our comments today will include some forward-looking statements. These statements involve a number of risks and uncertainties, which are outlined in today's press release and in our reports and filings with the SEC. Actual events or results may differ materially from those projected in the forward-looking statements. Such forward-looking statements and their implications may involve known and unknown risks, uncertainties and other factors that may cause actual results or performance to differ materially from those projected. On this call, we will also refer to non-GAAP financial measures. These non-GAAP measures are used by management to make strategic decisions, forecast future results and evaluate the company's current performance. Management believes the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the company's ongoing core operations and prospects for the future. You can find the table reconciling the non-GAAP financial measures to GAAP financial measures in today's press release. And with that, I would like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

Thank you, Jodi, and good afternoon, everyone, and thank you for joining our fourth quarter and full year 2025 operating and financial update conference call. The past year has laid the groundwork for what we expect to be a transformative year for Celcuity as we prepare for the potential approval and commercialization of gedatolisib. In 2025, we made remarkable progress, achieving a number of clinical and regulatory milestones while also significantly bolstering our balance sheet. These achievements and the groundbreaking data reported to date are foundational to our goal of establishing gedatolisib as a new standard of care therapy for patients with HR-positive/HER2-negative advanced breast cancer. Among the key clinical and regulatory milestones achieved recently include: first, the FDA accepted our new drug application, or NDA, granted it priority review with the Prescription Drug User Fee Act or PDUFA goal date of July 17, 2026. The NDA was submitted under the FDA's real-time oncology review program, which is utilized for drugs offering substantial improvements over available therapies. In light of the unprecedented efficacy data from the PIK3CA wild-type cohort of the Phase III VIKTORIA-1 clinical trial, we're optimistic about the outcome of the FDA's review of our NDA. Second, these data were presented at a late-breaking oral presentation at the European Society for Medical Oncology and San Antonio Breast Cancer Symposium in December. More recently, these data were published a few weeks ago in a peer-reviewed manuscript in the Journal of Clinical Oncology. And third, we completed enrollment of the PIK3CA mutant cohort of our Phase III VIKTORIA-1 trial late last year. Reporting results from this cohort of this Phase III trial will be another incredibly important milestone for Celcuity. We expect to announce these results in a top line press release in the second quarter and to present full results at a medical conference in 2026, where we also intend to host an investor call. And given how close we are to this disclosure, we will not be answering questions about trial progress or offering additional guidance on expectations for the results of the PIK3CA mutant cohort during the Q&A portion of our call. We've discussed previously the historic nature of the results from the PIK3CA wild-type cohort of the VIKTORIA-1 trial and the new milestones they achieved in HR-positive/HER2-negative advanced breast cancer. And just to recap, median progression-free survival, or PFS, for the gedatolisib triplet, which is gedatolisib, palbociclib and fulvestrant was 9.3 months compared to only 2 months for fulvestrant and the hazard ratio was 0.24. Overall, these results set several new benchmarks for clinical trials evaluating patients in this disease setting. First, the hazard ratio for the gedatolisib triplet is more favorable than has ever been reported by any Phase III trial for patients with HR-positive/HER2-negative advanced breast cancer. And second, the 7.3 months incremental improvement in median PFS for the gedatolisib triplet over fulvestrant is higher than has ever been reported by any Phase III trial for patients with HR-positive/HER2-negative advanced breast cancer receiving at least their second line of a regimen, including an endocrine therapy. And third, gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase III results in patients with HER2-positive, HER2-negative PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with a CDK4/6 inhibitor. And fourth, the 17.5 months median duration of response and the 31% incremental increase in the objective response rate relative to control for the fulvestrant triplet -- for the gedatolisib triplet are the highest reported for an endocrine therapy-based regimen in second-line HR-positive HER2-negative advanced breast cancer. Additionally, the results demonstrated that the clinical benefit of the gedatolisib triplet was consistent across all patient subgroups. One patient subgroup of note, patients enrolled in the United States or Canada achieved median PFS of 19.3 months for gedatolisib triplet versus 2 months for fulvestrant, which resulted in a hazard ratio of 0.13. Further analysis that included patients enrolled in the U.S., Canada, Western Europe and Asia Pacific representing nearly 60% of those enrolled found that median PFS was 16.6 months with the gedatolisib triplet versus 1.9 months for fulvestrant, which resulted in a hazard ratio relative to fulvestrant of 0.14. Safety results showed that gedatolisib triplet was generally well tolerated in the trial with mostly low-grade adverse events. Study treatment discontinuation due to treatment-related adverse events was reported in 2.3 of patients treated with gedatolisib triplet. In December, we presented additional safety analyses in an oral presentation at the San Antonio Breast Cancer Symposium. For patients who experienced stomatitis, we reported that measures to mitigate it were generally effective. The median time to improvement from first onset to a lower grade of stomatitis for patients with Grade 2 or 3 stomatitis who received the gedatolisib triplet was 12 and 14 days, respectively. We also reported that gedatolisib did not induce meaningful changes in patient glucose levels. Unlike other approved drugs targeting PI3K-alpha, gedatolisib did not induce clinically relevant hypoglycemia and required no dose reductions or withdrawals due to hypoglycemia. To characterize the tolerability of the gedatolisib regimens, we also reported results from patient-reported outcomes that capture a patient's perception of their overall well-being. And these measures include a patient's assessment of their mobility, ability to care for themselves, ability to conduct their usual activities, their pain or discomfort and anxiety, depression. The result of these assessments is then summarized as the patient's time to definitive deterioration and changes in well-being relative to the measures reported prior to the patient starting treatment on the trial. For the gedatolisib triplet, the median time to definitive deterioration was 23.7 months versus 4 months for fulvestrant with a hazard ratio of 0.39. Additionally, for the first 8 cycles of treatment, the patient's assessment of their well-being remained stable relative to their assessment prior to starting treatment with gedatolisib. And based on these assessments, we believe this provides meaningful evidence that patients treated with gedatolisib tolerated it well. And let's turn now to our VIKTORIA-2 study, which is a Phase III clinical trial evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR-positive/HER2-negative advanced breast cancer who are endocrine therapy resistant. We're wrapping up the safety run-in, and we expect to provide an update on our final Phase III study design in the second quarter. We believe the positive results from the PIK3CA wild-type cohort of our VIKTORIA-1 study augurs well for the potential efficacy of gedatolisib triplet may induce in this patient population. Now let's turn now to our Phase Ib/II clinical trial that is evaluating gedatolisib in combination with darolutamide, an androgen receptor inhibitor, and we're evaluating this in men with metastatic castration-resistant prostate cancer. We presented detailed data for the Phase Ib portion of the study at a poster presentation at ESMO. And in this portion of the Phase Ib/II study, 38 patients were randomly assigned to receive standard doses of darolutamide twice daily and either 120 milligrams of gedatolisib in Arm 1 or 180 milligrams of gedatolisib in Arm 2. The 6-month radiographic PFS or rPFS rate was 67% and the median rPFS for patients was 9.1 months in both arms combined. And these results compare favorably to historical results of a 40% 6-month rPFS survival rate for patients with metastatic castration-resistant prostate cancer who are treated with an androgen receptor inhibitor as second-line treatment. The combination of gedatolisib and darolutamide was generally well tolerated in the trial with mostly low-grade treatment-related adverse events. No dose-limiting toxicities were observed in either arm and no patients discontinued study treatment due to an adverse event. We're continuing to enroll patients in the dose escalation portion of the trial to evaluate higher doses of gedatolisib to determine the recommended Phase II dose. Now as we near what we hope is an FDA approval for gedatolisib in 2026, our efforts to prepare for the potential launch of gedatolisib continue to ramp up per our strategic launch plan. We began laying the groundwork for a potential gedatolisib launch nearly 2 years ago, and we've since largely completed building the organization, including our sales force and internal systems required to operate as a commercial stage company. We're very fortunate to have attracted an incredibly talented group of individuals who have strong track records of successfully launching novel oncology therapeutics. Key efforts today include extensive outreach across the country to payers, strategic accounts and population health decision-makers in various treatment settings, including health systems, integrated delivery networks and community oncology practices. Each of these groups are expected to play a key role in providing oncologists access to gedatolisib for their patients. We've made strong progress engaging with these decision-makers, and we're very pleased with the feedback and the enthusiastic response these efforts have yielded. We're also very encouraged by the results of research we fielded to gauge the willingness of community and academic oncologists to prescribe gedatolisib should it get approved. And these results make us optimistic about the possibility of establishing gedatolisib as the new standard of care in the second-line setting for HR-positive/HER2-negative advanced breast cancer in the wild-type patient population. And should we report positive results from our study with patients whose tumors have PIK3CA mutations, the gedatolisib triplet will be uniquely positioned to provide second-line therapy for patients regardless of the PIK3CA mutation status. Based on analysis of published epidemiological data, we estimate there are approximately 37,000 patients in the U.S. with HR-positive/HER2-negative advanced breast cancer who've progressed after treatment with a CDK4/6 inhibitor. And using internal duration of treatment estimates and pricing assumptions consistent with currently available novel therapeutics for breast cancer, we estimate the total addressable market for gedatolisib in the second-line setting is more than $5 billion. And given the significant penetration, our research is suggesting we can achieve, we believe it is reasonable to estimate that a second-line indication for gedatolisib can potentially generate peak revenue of up to $2.5 billion annually. We're excited about the opportunity now that we're approaching potential launch to advance multiple potential blockbuster indications over the years in breast and prostate cancer, while also aggressively preparing for potentially launching gedatolisib commercially should we receive an FDA approval. Gedatolisib is well positioned to address critical needs in the second-line space with its unique mechanism of action and potential first-in-class and best-in-class safety and efficacy profile. I'd like now to hand the call over to Vicky to review our finances.

It seems like we lost Vicky.

Well if Vicky is having trouble connecting, I can review the remarks that she was prepared to give. Operator, is she no longer on the line?

Yes. She's reconnecting right now.

Well, why don't I continue...

Brian, I apologize. I think I'm back on.

Okay. So why don't you get going...

Yes. well, good afternoon, everyone. I will provide a brief overview of our financial results for the fourth quarter and full year 2025. Our fourth quarter net loss was $51 million or $0.97 per share compared to $36.7 million net loss, or $0.85 per share, for the fourth quarter of 2024. Net loss for the full year was $177 million, or $3.79 per share, compared to $111.8 million, or $2.83 per share, compared to the same period in 2024. Our non-GAAP adjusted net loss was $38.4 million, or $0.73 per share for the fourth quarter of 2025 compared to non-GAAP adjusted net loss of $32.3 million, or $0.75 per share, for the fourth quarter of 2024. Non-GAAP adjusted net loss for the full year of 2025 was $150.8 million, or $3.22 per share, compared to non-GAAP adjusted net loss of $101.9 million or $2.58 per share for 2024. Research and development expenses were $37.6 million for the fourth quarter of 2025, compared to $33.5 million for the prior year period. Of the $4.1 million increase in R&D expenses, $8.6 million was related to increased employee and consulting expenses, of which $5.3 million related to commercial headcount additions and other launch-related activities. These amounts were partially offset by a $4.5 million decrease primarily related to costs supporting ongoing activities for the VIKTORIA-1 Phase III trial. R&D expenses for the full year 2025 were $145 million compared to $104.2 million for the prior year. Of the approximately $40.8 million increase in R&D expenses, $26.7 million was related to increased employee and consulting expenses, of which $13.1 million related to commercial headcount additions and other launch-related activities. The remaining $14.1 million increase was primarily related to activities supporting our ongoing clinical trials, a development milestone payment under the license agreement with Pfizer and other commercial launch-related activities. General and administrative expenses were $11.6 million for the fourth quarter of 2025 compared to $3 million for the prior year period. Of the approximately $8.6 million increase in G&A expenses, $6.9 million was related to increased employee and consulting expenses, of which $5.4 million related to noncash stock-based compensation. The remaining $1.7 million increase was primarily related to professional fees, expanding infrastructure costs and other administrative expenses. G&A expenses for the full year 2025 were $27.2 million compared to $9.1 million for the prior year. Of the $18.1 million increase in G&A expenses, $14.9 million was related to increased employee-related and consulting expenses, of which $10.4 million related to noncash stock-based compensation. The remaining $3.2 million increase was primarily related to professional fees, expanding infrastructure costs and other administrative expenses. Net cash used in operating activities for the fourth quarter of 2025 was $36.4 million compared to $27.8 million for the fourth quarter of 2024. Net cash used in operating activities for the full year 2025 was $153.3 million compared to $83.5 million for the full year 2024. Cash, cash equivalents and short-term investments were $441.5 million at the end of fiscal year 2025 and are expected to finance our operations through 2027. I will now hand the call back to Jodi.

Thanks, Vicky. Before we turn the call over to the operator for questions, I'll remind you, we will not be answering questions related to the progress or status of the mutant cohort of the VIKTORIA-1 study or providing any additional guidance on our expectations for data at this time. John, could you please open the call for questions?

[Operator Instructions] Our first question comes from the line of Maury Raycroft from Jefferies.

Congrats on the progress. I'm not sure if this fits within your criteria or not for -- on the status update. But wondering if for the mutant data, if you could say if the database lock is already in place, if that's something you can comment on?

No, I can't comment on that.

Okay. Understood. And I know you've already commented on this in the past, too, but if you could just recap how the disclosure is going to take place and what exactly you'll share in the readout?

Well, as I indicated, we'll provide top line data in a press release, and then we will provide details at an upcoming medical conference.

Got it. Okay. And then when thinking about when we could see more details at a medical conference, can you say if that's going to be like relatively soon? Or is it more likely going to be a second half update?

I think you'll just have to wait and see, Maury. Sorry, I can't provide any more details.

Understood.

Your next question comes from the line of Tara Bancroft from TD Cowen.

So I guess I'll shift to maybe a question on the launch. I was hoping maybe you could give us some feedback of what you're hearing from physicians on which segments may be treated immediately upon the wild-type approval and which ones may be more gradual? Just to get an idea of how you're planning ahead for cadence once you receive approval?

Thanks. No. So as we launch, we aren't going to be targeting or narrow casting our approach to doctors or patient segments. We believe gedatolisib regimens offer an opportunity to get the best option relative to what's available today. And so we would expect our sales force upon approval, assuming that occurs, to reach out generally to doctors and essentially help them understand how gedatolisib and the data can offer, again, what we believe is an improvement in the alternatives that are currently available.

Okay. Great. And I guess in that feedback that you are hearing in these discussions with physicians, do you think or have any inkling whether they would be willing to potentially use it off-label in mutants ahead of a potential mutant approval if the data are positive?

Yes. That's just not something that we have any conversations with doctors about.

[Operator Instructions] Your next question comes from the line of Stephen Willey from Stifel.

Sorry to badger you, Brian, on the top line release of the mean data. But just curious if that will include any details just with respect to headline PFS numbers and risk reduction? Or would this just simply be a statement regarding the achievement of stat sig?

It will be the latter. I mean we're mindful of embargo requirements to -- that we need to adhere to in order to be in a position to have a podium presentation at one of these medical conferences.

Okay. And then maybe just a question on prostate and then maybe just a quick one on the second-line breast opportunity that you spoke to. So in prostate, just curious how high you think you can push dose kind of north of the 180 mg that is used in the VIKTORIA trial. And then just curious what metrics -- I mean obviously, there's a balance of safety and tolerability you need to consider in terms of nominating a recommended Phase II dose. But are there any efficacy metrics that you're going to be prioritizing? I know you've shown us the radiographic PFS data, but just curious how things like PSA response, maybe even RECIST response for those patients with measurable lesions, how that kind of factors into dose nomination?

Sure. Well, just to recap relative to what we announced previously, we were pleasantly surprised by the safety profile that the 180-milligram dose reported. No dose-limiting toxicities, very limited Grade 3 adverse events. Hypoglycemia was consistent with our breast cancer. Stomatitis was significantly less frequent at that dose in these men. And so that's what led us to decide to increase the dose or rather to evaluate higher doses. And essentially, we're using some standard methodology to stepwise increase the dose and basically depending on achievement or levels of dose-limiting toxicities, we'll keep going. But we're in the midst of that. So I can't really comment on where we'll end up. But again, it's always a balance. We can't sacrifice tolerability to such an extent that it's self-defeating. But to the extent that we believe there's a dose response that would lead to improved response at higher doses, we want to explore where that might take us. And so we would expect to have some look at that data by the end of this year, sometime early next year.

Okay. That's helpful. And then maybe just lastly, with respect to breast, I appreciate some of the color around kind of peak revenue opportunity here in the second-line setting. I think you mentioned just kind of using historical pricing and duration of therapy. Obviously, the pricing is kind of readily available. But what's the duration of therapy estimate that you're using to inform the peak numbers that you mentioned?

If you just use a round number that -- of 10 months. And again, that's not a projection. That's just an assumption to drive an estimate, you would be consistent with how we're modeling the market.

Our next question comes from the line of Josh Boen from Guggenheim.

This is Josh on for Brad. Just wanted to know, with most of the commercial build complete for second line, what is the key gating factor in getting the frontline endocrine-sensitive trial up and running?

Key gating factor is just completing the safety run-in. And just to look back a little bit, we were evaluating geda in combination with ribociclib as a potential CDK4/6 option for doctors to use in the treatment arm. And because we haven't evaluated geda with ribociclib before, we needed to evaluate it in a sufficient number of patients to make a decision about dosing and how to move forward. And so that's wrapping up. And based on those results, we'll update the study design accordingly, and we expect to kind of provide an update on the study design in the second quarter and proceed apace to begin enrolling for the Phase III study.

Our next question comes from the line of Gil Blum from Needham & Company.

I'll try to keep this brief. So a commercial question that we've gotten a couple of times is surrounding potential challenges in getting patients to come in for infusions. Can you discuss a bit how you plan to avoid these kind of challenges? Or are they actually challenges?

Thanks for the question. We heard this question from investors. We do -- we've done a number of rounds of market research where we not only engage with doctors on a qualitative basis where we're able to have conversations and have a back and forth, but also in a quantitative setting where it's noninteractive and doctors are essentially going stepwise through information prompts that we provide. And they both allow us to gauge how they interpret the data, how they think about that data relative to other regimens are currently available, what factors they like, dislike, how strong a factor that is are they neutral on different factors. And one thing that's very clear when we review the results of that research is that, a, the efficacy is clearly the most important factor for them as they're evaluating the regimen; and b, the IV administration shows up as a negative factor in meaningfully less than 10% of the responses we have in this research. Secondly, we also do research with patients. And again, that's primarily qualitative. And again, except in cases where we believe there's a geographic limitation for a patient simply clinics too far or if there's some other considerations, their mobility, we do not expect that there will be significant patient pushback on the IV. I mean we have some interesting anecdotes from these conversations that suggest that women take very seriously their obligation for their family to do everything they can to maximize the time that they can be with their family and to use what they believe are the best drugs that they may have an option to take. So we think all in, it just reinforces what we believe, which is in certainly a terminal disease like metastatic breast cancer, the most important criteria that's going to guide selection of therapy by both the physician and then the preference for the patient is going to be related to the efficacy that the regimen can induce and then also to how well tolerated the regimen is. And the feedback we've received, again, is very positive on that front as well. And so finally, as it relates to the administration route, again, we think that's going to be an exigent issue for only a small number of patients for the reason I mentioned, and we don't believe that it is going to restrict preference for physicians to prescribe the therapy.

And maybe as a follow-up, can you help us understand the commercial advantages of having geda label across metastatic breast cancer subtypes?

Sure. Well, as anybody that's followed this space knows one word that gets used to describe the landscape is it's very complex, a lot of activity. And so what we hope to be able to provide and the way we expect to position the drug is that we can simplify the decision-making process for these physicians by giving them an option that we believe for any patient subgroup that they may be treating the best potential risk/benefit relative to the alternatives. Now it doesn't mean there aren't available options that some doctors may select or prefer in certain patient segments. But we think overall, we'll be in a very strong position by being able to offer essentially a biomarker-agnostic alternative that doesn't require them to evaluate some complex decision-making around biomarker subgroups. And we think ultimately, that hitting the easy button, which isn't to diminish the importance of the decision for the doctors. But particularly in the community setting, the challenges of keeping up with the alternatives can make it difficult for them to make the right decisions in some cases. And so to the extent we can leverage the data that we a, have now and we hope to have with the mutant setting, we think that will be a very significant advantage.

[Operator Instructions] our next question comes from the line of Oliver McCammon from LifeSci Capital.

So switching gears a little bit. We're roughly 1.5 years into the launch of inavolisib for the PIK3CA mutant endocrine therapy resistant setting. I'm curious if there are any learnings from the launch, label and/or KOL feedback that you think are supportive of the positioning of gedatolisib in the VIKTORIA-2 trial.

Thank you. So they reported very good data. And unfortunately, though, the patient population that really is appropriate to treat with that drug is fairly limited. The study only enrolled patients who essentially were metabolically healthy, patients who had an HbAC1 level below 6 and essentially ruling out patients that were either prediabetic or diabetic type 2 diabetes. And there's since been several dear doctor letters for very significant adverse events that have been reported. And the label requires fairly extensive glucose monitoring, both by the physician as well as the patient while they're at home. And so overall, just based on our assessment of the claims data, it appears those restrictions are having an impact on the usage in the clinic to date. So from a learning standpoint for us, I mean, it essentially highlights just how unique a drug geda is, a, we're addressing this pathway. But more importantly or rather very importantly, we're not inducing the levels of glycemic system disruption that can lead to hypoglycemia that requires significant management or any management at all actually. And we do not believe that patients who are prediabetic or type 2 diabetes will be restricted in their ability to receive treatment with gedatolisib. And so it really goes back to the drug and the overall safety profile. And when you don't have a safety profile like geda when you hit this pathway, you run into challenges and really being able to treat a broad group of patients or to treat patients in a way that does create some potentially significant adverse event risks.

Very helpful. And just one sort of frontline follow-up. Given the persevERA results we saw recently, your prior Phase Ib data that you've shared in frontline patients as well as the number of oral PI3K inhibitors looking at the frontline setting, I'm curious what your level of interest is in a frontline endocrine-sensitive study.

Well, it would be very logical given the very favorable data that we've reported in that setting in our Phase Ib study. And just as a reminder to folks, in that study, sample size of 41 we reported median PFS of over 48 months and an objective response rate of 79% with gedatolisib combined with palbociclib and letrozole. So those really compare very favorably to what's been published to date for the currently approved therapies. So I think there's a very strong case to be made for us in conducting a study in that space, and we will keep people posted on our thinking.

Our next question comes from the line of Eva Fortea from Wells Fargo.

A quick one from us. Do you have any updated thoughts on the European commercial strategy for geda in terms of like timing for a potential update or approach to partnering? Or how do you expect EU to sequence versus the U.S.

Sure. So our current plan, if our grand plan comes to fruition, is that if we have as we hope and expect a positive readout with our mutant cohort, we would then follow up with supplemental NDA, assuming we get the initial approval for gedatolisib. And then once that NDA is complete -- that sNDA package is completed, we would then utilize the documents and essentially, most of the documentation will translate, but essentially use the information from both the wild-type and mutant data sets and the NDA modules overall to create an MAA submission in the fourth quarter of this year. That's roughly a 13-month process to potentially get it accelerated, but 13 months with a regular review. And so in the meantime, after we submit, that would be the window of time that we would use to explore finding partners to collaborate with launching not only in Europe but potentially globally. Simultaneously, we've also been engaging with the regulators in Japan and to identify the regulatory path forward for submission in Japan. We think we've kind of gained alignment so far on that front. And so even though we haven't identified a partner at this time, we are not -- we're proceeding at pace with regulatory activities in the most significant markets, which would include the major 5 European countries as well as Japan. And so we will, in this window, have ample time to find the right partner without delaying at all our ability to have geda launched in those markets.

Our next question comes from the line of Kalpit Patel from Wolfe Research.

One from us on the mutant update. Do you need to hit both the doublet and triplet arms to file later in the year? Or can you file on a successful hit on triplet alone?

Well, without getting into any more detail, just limit it to the study design. The study design primary endpoint is a comparison of the triplet to alpelisib. And so that is the primary endpoint and that would form the basis for any potential regulatory submission. The analysis comparing the doublet to alpelisib is an exploratory analysis or secondary analysis.

Our next question comes from the line of Chase Knickerbocker from Craig-Hallum.

We'll be curious what you and your market access team have heard in your early prelaunch discussions with payers on a number of items around the profile of geda in wild type. Maybe kind of foremost amongst them, how that's solidified or altered any of your thoughts around potential pricing?

I guess just the overall reception to information that we've shared with payers and strategic accounts, which we're able to do on a safe harbor basis since they're not health care providers has been very, very positive. I think it's interesting to get the feedback they provide. They're in the business of helping ensure the individuals who they are insuring have access to therapies or ultimately responsible for treating and have access to the right therapies. And so we've been very pleased with how they've reacted to the data and their collaboration is how I would say it, in working with us to lay the groundwork to ensure that as early as practically possible geda rather patients would have access to this drug and the regimen.

Maybe just as a follow-up around the competitive environment. And we saw recently another acquisition of a mutant selective PI3K alpha inhibitor. Can you just refresh us on your thoughts on the potential future competition for you from that angle? And then just kind of generally on kind of the next-generation assets coming up in competition here?

Sure. No, thank you. Again, I think there's been -- since alpelisib received its approval, I guess, 7 years ago, there have been other -- a number of companies that have sought to potentially provide an alternative that would be safer than alpelisib. And that's a worthy project. But the underlying biological assumption that's really driving those projects, we think is not necessarily current. We think gedatolisib and the approach we've taken of inhibiting all Class I PI3K isoforms as well as mTORC1 and 2 is the approach that's required to optimize antitumor control -- to provide maximum antitumor control. And so we just think there's a biological limit on the benefit that a single target inhibitor like a PI3K-alpha inhibitor can induce. And having more as we've seen with SERDs doesn't necessarily yield different results. I think 5 Phase III reports later, I think we've seen very, very similar results. Now in this case, with this -- in this setting, I think it's reasonable to expect that based on the way these drugs are distinguishing their targeting between the mutant form of PI3K alpha and the wild-type form that they can improve upon safety profile relative to alpelisib, I think that seems pretty reasonable. But ultimately, I think there's going to be a limited biological potential to induce an optimal outcome for efficacy. And I think the results to date for geda certainly, we think, demonstrate the value and importance of providing comprehensive inhibition of this pathway as opposed to selective inhibition of this pathway. So as far as impact on us, we actually -- we think, again, that targeting approach will be obsoleted if the data we hope to report out soon is what we hope and expect.

There are no further questions at this time. I will now turn the call over to Brian Sullivan, Celcuity's Chief Executive Officer, for closing remarks. Sir, please go ahead.

Well, thank you for participating in our call today, for your ongoing support and look forward to reporting back to you soon. Take care.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.