Celcuity Inc. Q1 FY2024 Earnings Call

Good afternoon, everyone, and thank you for joining the Celcuity First Quarter 2024 Financial Results Conference Call. I would like to now hand it over to Maria Yonkoski with ICR Westwicke.

Thank you, operator, and good afternoon to everyone on the call. Thank you for joining us to review Celcuity's First Quarter 2024 Financial Results and Business Update. Earlier today, Celcuity released financial results for the first quarter ending March 31, 2024. The press release can be found on the Investors section of the 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, who will be available during Q&A. Before I 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 core 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. And with that, I would now like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

Thank you, Maria, and good afternoon, everyone. We appreciate your interest in Celcuity. Our Phase III trial, VIKTORIA-1, remains on track to report top line data for the PIK3CA wild-type subgroup in the second half of 2024. Enrollment continues to proceed well. During the first quarter, in conjunction with an update related to our debt facility, we reported that the wild-type subgroup was more than 50% enrolled. Achieving this enrollment threshold during the first quarter gave us the right to draw down an additional $10 million tranche from our current debt facility. The patients we're evaluating in this study have HR-positive HER2-negative advanced breast cancer whose disease progressed while receiving treatment with a CDK4/6 inhibitor and an aromatase inhibitor. And patients are eligible for enrollment if they've received up to 2 prior lines of endocrine treatment. But we anticipate that most of those enrolled will be receiving second line treatment. And these patients typically remain on their first line CDK4/6 inhibitor plus letrozole regimen for a median of 18 to 22 months depending on the CDK4/6 inhibitor. And this compares to the 13 months median duration of prior treatment reported for patients enrolled in the comparable arm of our Phase Ib breast cancer study that evaluated gedatolisib combined with palbociclib and fulvestrant. Patients who received prior chemo in the advanced setting are not eligible for our Phase III study, unlike the comparable arm of our Phase Ib study, and this is relevant since the prognosis tends to be worse for individuals who have previously undergone chemotherapy for advanced breast cancer compared to those who are chemo-naive. Another difference in the Phase III eligibility criteria relative to our Phase Ib study is the allowance of patients with bone-only disease. Based on data from other Phase III trials, we expect that roughly 20% of the patients enrolled in our Phase III study will have bone-only disease. Our Phase Ib study did not allow bone-only patients, only those with visceral disease were enrolled. And this is relevant since patients with non-bone-only disease generally have worse prognosis than those with bone-only disease. By not allowing patients who have received prior chemotherapy in the advanced setting and by including those with bone-only disease, we're eliminating two factors in our Phase III study that correlate with worse outcomes. As we begin preparing for gedatolisib's potential position in the future treatment landscape, we will take into account the criteria oncologists use to select a cancer therapy. We think these criteria in order of importance are efficacy, then safety, then mode of administration. And this is consistent with guideline recommendations, which are based on efficacy and safety considerations, not mode of administration preference, especially in advanced breast cancer. The current second-line treatment paradigm for ER-positive HER2-negative patients with advanced breast cancer includes selective estrogen receptor degraders or SERDs, like fulvestrant or elacestrant as single agents or one of three approved PAM inhibitors combined with fulvestrant. However, each of the PAM inhibitors only targets a single PAM node, such as PI3K alpha, AKT or mTORC1, which is suboptimal because the uninhibited PAM nodes can induce compensatory resistance. In patients who have received prior treatment with a CDK4/6 inhibitor, none of these drugs have demonstrated efficacy in patients who have PIK3CA wild-type tumors, while only the PI3K alpha and AKT inhibitor have reported benefit in patients with PIK3CA mutations. And these results are consistent with the nonclinical data that shows these single node inhibitors are 3 to 4 times less potent in breast cancer cells without PIK3CA mutations than in those with them. This is in sharp contrast to the nonclinical and preliminary efficacy data we've reported for gedatolisib. In studies evaluating breast cancer and prostate cancer cell lines, gedatolisib was found to be equally potent and efficacious in cell lines with and without PIK3CA mutations and at least 300 times more potent on average in breast cancer cells than the approved single-node PAM inhibitors. Consistent with these nonclinical results, the preliminary efficacy we reported in our Phase Ib breast cancer study that evaluated gedatolisib combined with palbociclib and either letrozole or fulvestrant was comparable in both treatment-naive and second or third-line patients with and without PIK3CA mutations. And we think these results demonstrate that along with the estrogen receptor and CDK4/6 pathways, the PAM pathway plays an intrinsic role as a disease driver in HR-positive HER2-negative advanced breast cancer, that's independent from the presence of an activating mutation like PIK3CA. And that's why we believe development of an optimized PAM inhibitor like gedatolisib that targets all Class I PI3K isoforms, and mTORC1 and 2 represents one of the most important opportunities to improve the standard of care in HR-positive, HER2-negative advanced breast cancer. Now obviously, the foundation of gedatolisib's potential future positioning will require the gedatolisib report a clinically meaningful median progression-free survival benefit. The current median PFS benchmarks for patients pretreated with a CDK4/6 inhibitor are modest. Published reports of median PFS for the surge range from 2 to 3.8 months, and in patients with PIK3CA mutations, 5.5 to 7.3 months for the AKT and PI3K alpha inhibitors, respectively. The two most recently approved therapies for this patient population reported 2 to 3.5 months of incremental PFS benefit. The threshold that key opinion leaders generally consider to be clinically meaningful. In addition, we've consistently heard from oncologists that they prefer to delay use of chemotherapy or antibody-drug conjugates until the benefit from endocrine backbone regimens is exhausted. And this perspective was actually recently echoed by senior management from an ADC sponsor that characterized ADCs as creating a third pillar in the treatment landscape for HR-positive, HER2-negative breast cancer that sits between endocrine therapy-based regimens and classical chemotherapy. And these comments are consistent with the sponsor's drug development strategy in breast cancer, which includes development of an oral SERD and AKT inhibitor. We also think gedatolisib's safety profile may favor its potential positioning in a future treatment landscape. Gedatolisib's treatment-related discontinuation rate was only 4% in the Phase Ib arm with the Phase III intermittent dose schedule, which is comparable to the 6% to 8% discontinuation rates for CDK4/6 plus fulvestrant regimens. And these results compare favorably to the treatment-related discontinuation rates reported in the Phase III studies for alpelisib plus fulvestrant, where 26% of patients discontinued, and everolimus plus exemestane, where 24% of patients discontinued. The results we are getting are especially encouraging given that patients in the Phase Ib study did not receive prophylactic treatment for stomatitis. Since we're prescribing stomatitis prophylactic in our Phase III trial, we would expect fewer stomatitis-related adverse events, which would further enhance gedatolisib's already promising safety profile. And finally, in office-administered therapies, such as an infused therapy like gedatolisib, there are several key advantages relative to orally or self-administered drugs. In a real-world setting, convenience is only a meaningful consideration when the efficacy and safety profile of the alternative drugs are comparable or when a patient lives a significant distance from the treatment site. Otherwise, a well-tolerated therapy that offers a clinically meaningful PFS benefit will be overwhelmingly preferred by oncologists relative to one that offers less efficacy but is more convenient. Office-administered therapies, such as gedatolisib, fall into the medical benefit category, which has a far more streamlined reimbursement process than orally administered drugs, which fall into the pharmacy benefit category. And this has several implications. First, oncologists can recover additional costs associated with treating our patients. Second, oncologists have more autonomy to select therapies, and the payer management process is much less burdensome. Third, payer contracting is less frequent, which results in fewer price discounts for the pharmaceutical company. And fourth, patients typically incur lower out-of-pocket costs with an infused therapy, which is an important consideration for most patients. Beyond our breast cancer program, we're excited about the opportunity to develop gedatolisib for patients with metastatic castration-resistant prostate cancer, or CRPC. This past February, we dosed our first patient in a Phase Ib/II trial evaluating gedatolisib in combination with darolutamide, an androgen receptor inhibitor in CRPC patients previously treated with an AR inhibitor. Like HR-positive breast cancer, prostate cancer involves both a hormonal pathway and the PAM pathway. The role that the PAM pathway plays in prostate cancer has been well characterized non-clinically and in two other ongoing PAM inhibitors, which showed compelling proof-of-concept clinical trial data in two randomized studies. In each of the clinical trials for these other PAM inhibitors, clinically meaningful treatment benefit was reported relative to the androgen receptor inhibitor control arm in patients with CRPC. This is especially encouraging since gedatolisib is significantly more potent and efficacious than these PAM inhibitors in vitro. Primary objectives of the Phase Ib portion of the trial include assessment of the safety and tolerability of gedatolisib in combination with darolutamide and determination of the recommended Phase II dose of gedatolisib. We anticipate reporting initial preliminary data in the first half of 2025. And with that, I'll turn the call over now to Vicky Hahne, our Chief Financial Officer, to review our financial results.

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the first quarter of 2024. Our first quarter net loss was $21.6 million or $0.64 net loss per share compared to $11.9 million net loss or $0.55 per share for the first quarter of 2023. Because this quarterly net loss includes significant noncash items, including stock-based compensation and interest, we also included in our press release non-GAAP adjusted net loss for the quarter ending March 31, 2024. Our non-GAAP adjusted net loss was $19.9 million or $0.59 per share for the first quarter of '24 compared to a non-GAAP adjusted net loss of $11.9 million or $0.55 per share for the first quarter of 2023. Research and development expenses were $20.7 million for the first quarter of '24 compared to $11.3 million for the first quarter of '23. Of the approximately $9.4 million increase in R&D expenses, $7.9 million primarily related to activities supporting the VIKTORIA-1 Phase III trial and the initiation of the prostate Phase Ib/II clinical trial, and $1.5 million was related to increased employee and consulting expenses. General and administrative expenses were $1.8 million for the first quarter of 2024, that compared to $1.3 million for the first quarter of '23. Employee-related expenses accounted for $0.3 million of the increase. The remaining increase of approximately $0.2 million resulted from professional fees and other administrative expenses. Net cash used in operating activities for the first quarter of 2024 was $17.1 million compared to $12.9 million for the first quarter of '23. We ended the quarter with approximately $177.7 million of cash, cash equivalents, and short-term investments compared to cash and cash equivalents of $180.6 million at December 31, 2023. The decrease in cash quarter-over-quarter of $2.9 million is primarily the result of a non-GAAP adjusted net loss of approximately $19.9 million, offset by a warrant exercise yielding $14 million in proceeds and working capital adjustments of approximately $3 million. I will now hand the call back to Brian.

Thank you, Vicky. Operator, could you please open the call for questions?

Your first question is from Maury Raycroft from Jefferies.

This is Yao on for Maury. So for the Phase III study, can you remind us how the primary analysis is going to be triggered in terms of events and maturity? And what were the PFS assumptions for treatment and control that went into the guidance of second half '24 top line data?

Sure. Well, the study primary analysis will be triggered by hitting an event threshold number of events, and that's independent of follow-up, although there are assumptions made about the follow-up period to derive an estimate of the timing when we would expect those events to occur and which informs the sample size assumptions. We haven't published the assumptions we used to do that analysis. But we have presented data, and there's publicly available data, particularly for fulvestrant, that suggests that 2 to 3.5 months would be the most likely in that range, probably centering around 2.7 for fulvestrant.

Maybe a quick follow-up. You recently said some KOLs think the bar for wild-type patients is 8 months PFS or 5-month delta versus fulvestrant. And there is one everolimus study in post CDK4/6 patients that showed PFS in that ballpark. So how does the current trial compare to the everolimus trial? And what in the current trial gave you confidence that you should show better PFS?

All the figures for PFS will be viewed comparatively since they relate to the control. Generally, key opinion leaders believe that a clinically meaningful benefit is around 3 months, with more being better. However, that is the minimum expectation. If you're asking about a specific study, could you clarify which one you mean?

Just I think you recently said one of the everolimus studies in the post-CDK4/6 patient that showed PFS in the I think maybe 6 to 8 months.

No. No, okay. That's why I asked. That's not correct. So there's been some retrospective analyses of everolimus that don't break out what their activity is between PIK3CA wild-type and mutant patients. But those are retrospective analyses. There are three of them if we aggregate the data and weigh it for the number of patients in each study; the median PFS was 4.2 months. But again, given that the nonclinical data would suggest everolimus is more likely to be more effective in patients with mutations than not with mutations, I think there's an open question about how effective everolimus is in the wild-type PIK3CA wild-type patients. And as I mentioned, there's been no randomized data that provides any informed information or credible data about the activity of the drug in patients who've received prior CDK4/6s.

Your next question is from Tara Bancroft from TD Cowen.

I have one clarifying question. Can you explain the reasoning that you have behind stratifying patients by 6 months on prior therapy versus 12, as these are chemo-naive patients, and that essentially implies that many will have a longer time on prior therapy? And do you expect that the prior therapy will be almost entirely all prior CDK4/6, or will it include others like everolimus or third too, if it's appropriate, as you know, the time on prior CDK4/6 specifically is important for outcomes. So it will be helpful to know.

The stratification factor for prior treatment duration was based on ESMO guidelines, which define androgen resistance in the advanced setting as patients receiving less than 6 months of progression-free survival on endocrine therapy. We believed this was a validated way to define the patient population. There is a clear distinction in responsiveness in the subsequent rounds of chemotherapy, which is why the guideline identified 6 months as the threshold. While some may want to consider more than 12 months, I would argue that most of the differentiation in outcomes likely happens within the 6-month timeframe. Consequently, you will observe a somewhat upward trend that closely correlates with prior treatment and is much more gradual compared to the curve for patients who have progressed on less than 6 months.

Your next question is from Bradley Canino from Stifel.

And good to see the reiteration of the second half '24 top line guidance. Brian, maybe another timing question, a layer on top of that. I'm just wondering how important is it for your strategy to be able to report the full data for the wild-type cohort at the San Antonio Breast Cancer meeting in December?

Ultimately, the most critical factor will be what the data indicates. It would be beneficial if we had the data to present, but I don't consider it essential. It's a secondary issue, and we don't have control over when it becomes available. There are additional factors to consider as well. So, we'll see how it unfolds. Nevertheless, it's something nice to have rather than a necessity, and the focus should remain on the data itself.

Okay. And then you also mentioned in your comments about the prior chemo and bone-only patient factors between your Phase II and Phase III. Could you point us to any data that might help quantify the degree of impact these factors can have on durability in PFS? Or any other comments on how you think about the potential directional impact?

Certainly. There is evidence across various tumor types indicating that patients who have undergone chemotherapy and are later treated with targeted therapy tend to have poorer outcomes compared to those who have not received prior chemotherapy. In breast cancer specifically, the data from the BYLieve study is particularly insightful. Cohort A included first-line and second-line patients who had not received chemotherapy, while Cohort C included patients with a history of chemotherapy, making it more pertinent to second or third-line treatments. Cohort A, which aligns more closely with the patient population we're studying, reported a progression-free survival (PFS) of 7.3 months, whereas Cohort B reported around 5.5 to 5.6 months. This represents roughly a 30% advantage in favor of chemo-naive patients, which serves as a relevant benchmark considering they are targeting a similar pathway. Regarding the impact of having only bone involvement, it's important to note that enrolled patients must have a measurable lytic lesion to assess PFS. In the PALOMA-2 study involving palbociclib, a follow-up analysis revealed that patients with bone-only disease experienced 38 months of PFS, which is 50% longer than that of patients with only visceral disease. This indicates that bone-only patients likely have a much more favorable prognosis and are more inclined to respond positively to targeted therapy, particularly therapies that include CDK4/6 inhibitors.

Your next question is from Chase Knickerbocker from Craig-Hallum.

This is Connor on for Chase. I just have one here today. Last quarter, you brought on Eldon Mayer to prepare for a commercial launch of data. Since then, what initiatives has he implemented or plans on implementing to prepare for the launch on your own?

Thank you for the question. I'm very pleased to have Eldon on the team. As those familiar with this field understand, the launch preparation period is quite lengthy. I believe launch preparation can be divided into two phases. The first phase is the 12 months prior to the launch, which is the most intense and costly period. This phase can truly begin once we have our Phase III data, allowing us to clearly define our product profile and conduct more targeted research for positioning and messaging in the market, along with compiling necessary documents for payers. Currently, we are in the timeframe leading up to 2024, specifically between 12 months and about 20 months before the launch. Our current focus is on building the initial team, specifically bringing in individuals to lead our marketing, business operations, and managed market efforts, and we are on track to identify and onboard these key people. Following this, we will conduct research and outline our overall plan. My goal by the end of this quarter is to develop a preliminary plan that will specify the organizational structure needed over the next 20 months, including budget considerations for that period and the first year of commercialization post-launch. We have also identified the cross-departmental dependencies that will need support for the launch, like IT, administrative, clinical operations, and medical affairs support. It's crucial that all this work aligns with our current understanding of the market landscape and how we anticipate it will evolve.

Your next question is from Gil Blum from Needham & Company.

So perhaps I should rephrase a couple of earlier points. Since you are enrolling patients with better expected outcomes, shouldn't this overall timeline for a study readout suggest that the increased benefit will be evenly distributed across the treatment arms? I assume this was factored into your calculations.

It did. But I would say though, there's a cap on the potential for fulvestrant. If you look at the data, I don't think there's any data that has been reported in this patient population that suggests that fulvestrant can do more than 3.7 months. If you aggregate the data that's been reported, you'd see it's about 2.7%. If you look at the error bars on the data that has been reported, the upper bound of the 95% confidence interval is around 3.8; you can nudge that up and round it to 4. But just given the mechanism and those results, we think that there's much less upside, I guess due to a more favorable patient population than there is by treating untreated disease mechanism, which is what we're doing with gedatolisib.

Thank you. There are no further questions at this time. Please proceed.

Great. Well, thank you again for participating in our call today and for your ongoing support and interest in our company. We're participating in a number of conferences in the coming months, and I look forward to interacting with many of you soon. I hope you have a great evening. Goodbye.

Thank you. Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect.