Celcuity Inc (CELC) 2021 Q4 法說會逐字稿

Greetings, and welcome to Celcuity Fourth Quarter and Full Year 2021 Results Conference Call. (Operator Instructions)

As a reminder, this conference is being recorded. I would now like to turn this conference over to your host, Mr. Robert Uhl. Thank you, sir. You may begin.

Thank you, Laura. Good afternoon, everyone, and welcome to Celcuity's Fourth Quarter and Full Year 2021 Financial Results and Business Update Webcast and Conference Call. Thank you for joining us.

Earlier today, Celcuity Inc. released financial results for the fourth quarter and full year ended December 31, 2021. The press release can be found on the Investors section of our 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 the 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 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.

So with that, I would like to turn the call over to Vicky Hahne, Celcuity's CFO, to review the financial results prior to a business update.

Thank you, Robert, and good afternoon, everyone. I'll provide a brief overview of our financial results for the fourth quarter and full year of 2021. And I invite you to review our 10-K, which will be filed later today for a more detailed discussion. After my remarks, Brian will provide a corporate update that includes a presentation that can be found on our website or through the link in our earnings press release. Our fourth quarter net loss was $6.8 million or $0.45 per share compared to $2.6 million net loss or $0.25 per share for the fourth quarter of 2020. Net loss for full year 2021 was $29.6 million or $2.21 per share compared to $9.5 million or $0.92 per share for the same period in 2020. Because these quarterly net losses include significant noncash items, including stock-based compensation, the issuance of common stock and interest, we also include in our press release non-GAAP adjusted net loss for the quarter and full year ending December 31, 2021.

Our non-GAAP adjusted net loss was $5.6 million or $0.37 per share for the fourth quarter of 2021 compared to non-GAAP adjusted net loss of $2.1 million or $0.21 per share for the fourth quarter of 2020. Non-GAAP adjusted net loss for the full year 2021 was $21.4 million or $1.60 per share compared to non-GAAP adjusted net loss of $7.7 million or $0.75 per share for the full year 2020.

R&D expenses were $5.5 million during the fourth quarter of 2021 compared to $2.1 million for the fourth quarter of 2020. R&D expenses for the full year 2021 were $25.8 million compared to $7.7 million for the same period in 2020. The approximately $18.1 million increase during the full year of 2021 resulted primarily from a $10 million upfront license fee related to the execution of the Pfizer license agreement, which included $5 million of noncash expense for issuance of common stock. The remaining $8.1 million increase primarily resulted from expenses initially associated with the transfer of gedatolisib related activities from Pfizer to Celcuity and subsequently, the continued support and development of gedatolisib. General and administrative expenses were $0.8 million for the fourth quarter of 2021 compared to $0.4 million for the same period in 2020. G&A expenses for the full year 2021 were $2.6 million compared to $1.9 million for the prior year. The approximately $0.7 million increase in G&A during the full year 2021 compared to the full year of 2020, arose primarily from noncash stock-based compensation.

Net cash used in operating activities for the fourth quarter of 2021 was $6.1 million compared to $2.1 million for the fourth quarter of 2020. This was the result of non-GAAP adjusted net loss of $5.6 million and working capital changes of approximately $0.6 million, offset by $0.1 million depreciation expense. We ended the quarter with approximately $84.3 million of cash and cash equivalents compared to $11.6 million on December 31, 2020. We expect this cash to take us into late 2023 or early 2024.

And now I will hand the call over to Brian.

Thank you, Vicky. Good afternoon, everyone, and thank you for joining us today. As always, we appreciate your continued support of Celcuity. In my remarks, I'll first provide a brief update of key activities over the past few months and then provide a more detailed update of the clinical development program for gedatolisib. My remarks will include a review of the pivotal Phase III trial design we recently finalized. And this study will evaluate gedatolisib in patients with HR-positive/HER2 negative advanced breast cancer. I will refer to the slide number of the presentation that corresponds to my remarks, and then we'll open up the line for questions.

So now please turn to Slide 4. We laid important groundwork to advance our gedatolisib breast cancer program during the past few months. In November, we entered into a clinical trial collaboration and supply agreement with Pfizer to provide palbociclib known commercially as Ibrance for use in our Phase III clinical trial at no cost to Celcuity. This will result in substantial cost savings for our Phase III study. In December, we presented updated Phase Ib data during a Spotlight Poster-Discussion Session at the 2021 San Antonio Breast Cancer Symposium. The updated data provided additional information about the characteristics of enrolled patients, the impact of the dosing schedule on efficacy, time to first response and duration of treatment. The promising antitumor activity and tolerability of the therapy in patients treated with the 3 weeks on, 1 week off, gedatolisib regimen, supports use of this dosing schedule in our pivotal study.

In January, the FDA granted Fast Track designation to gedatolisib for the treatment of patients with HR-positive/HER2-negative advanced breast cancer after progression on CDK4/6 therapy. Fast Track designation is granted by the FDA for products, which demonstrates the potential to address a serious unmet medical need. This designation should enhance our ability to interact frequently with the FDA to discuss our development plan. And most importantly, most recently, we finalized the design of our pivotal Phase III clinical trial for gedatolisib following very productive meetings with the FDA.

So now please turn to Page 5. To provide context for the trial design, I'd first like to briefly review why we believe gedatolisib has such great potential to provide more effective treatment for women with breast cancer. This potential reflects both the importance of the pathway target gedatolisib inhibits and its highly differentiated mechanism of action and pharmacokinetic profile. Gedatolisib targets PI3K/mTOR, which is considered one of the most important and complex pathways involved in cancer. Blockading PI3K/mTOR efficaciously and safely, however, is challenging because of its structural complexity and its linkage to T cell metabolic processes. Gedatolisib addresses the structural complexity of the pathway by inhibiting all 4 Class 1 PI3K isoforms, in mTORC1 and mTORC2. This is the optimal approach biologically because it avoids a cross activation of uninhibited subunits and resulting drug resistance that can occur with PI3K isoform specific or mTOR specific inhibitors. Completely blockading the pathway also enhances the potential to induce synergistic inhibition with other targeted therapies, such as CDK4/6 inhibitors.

Please turn to Slide 6 now. Gedatolisib's differentiated chemical structure and intravenous formulation results in a very favorable pharmacokinetic profile. The drug is potent at low or sub nanomolar concentrations and can maintain pathway inhibition with a tiny fraction of drug mass compared to approved oral PI3K inhibitors. This results in a safety profile that compares very favorably against approved isoform-specific PI3K inhibitors. And thus, we believe gedatolisib's unique properties position it to realize the significant potential first envisioned for PI3K therapies when the pathways critical role in cancer was discovered.

I'll now turn to Slide 8. Gedatolisib initial potential target patient population, these patients with HR-positive/HER2-negative advanced breast cancer whose disease progressed during treatment with a CDK4/6 therapy. We estimate this represents over 100,000 breast cancer patients globally on an annual basis.

Please turn to Slide 9. There are limited options for patients whose disease progresses on a CDK4/6 inhibitor, and the efficacy is also limited. Current standard of care treatment regimens include either a selective estrogen receptor degrader or SERD, such as fulvestrant or a regimen that combines an mTOR or PI3K alpha targeted therapy with an endocrine therapy. Finding more effective treatment for these patients is a significant unmet need.

Please turn to Slide 10. Development of oral SERDs to replace fulvestrant is one therapeutic strategy several pharmaceutical companies are pursuing to address this unmet need. Unfortunately, clinical studies evaluating 2 different oral SERDs reported data recently that suggest this approach may not offer the clinical improvement in median progression-free survival or PFS that was expected. We believe these results highlight the need for new therapeutic approaches. In particular, the data from the SERD clinical trials and from the trials of existing standard of care therapies suggest additional oncogenic pathway drivers and resistance mechanisms must be targeted.

Please turn to Slide 11. Available evidence indicates that resistance to CDK4/6 inhibition is a transient adaptive mechanism and most likely involves the PI3K/mTOR pathway. This data indicates that CDK4/6 signaling is restored in CDK4/6 resistant tumors when a PI3K inhibitor is applied. So continuing CDK4/6 inhibitor treatment in combination with a PI3K/mTOR inhibitor, in patients who progressed on their prior CDK4/6 inhibitor with both blockade, the reactivated CDK4/6 pathway and prevent adaptive activation of the PI3K/mTOR pathway. This suggests the limited efficacy induced by current standard of care therapies in patients who have progressed on a CDK4 therapy reflects the mechanistic inadequacy of relying on partial PI3K/mTOR and no CDK4 inhibition to address this very complex disease mechanism.

Please turn to Slide 12. Our Phase Ib study evaluated the hypothesis in the first- and second-line setting for women with advanced breast cancer. Women with HR-positive/HER2-negative advanced cancer who had not received prior therapy for advanced disease were treated with gedatolisib combined with the CDK4/6 inhibitor, palbociclib, and the aromatase inhibitor, letrozole. The median progression-free survival period for this patient cohort was 31.1 months and the objective response rate, or ORR, was 85%. These results compare favorably to published data for palbociclib in combination with letrozole from the PALOMA-2 study were median PFS of 24.8 months and ORR of 55% was reported.

Please turn to Slide 13. For patients who have progressed on prior CDK4/6 treatment, gedatolisib dosed on an intermittent schedule combined with palbociclib and fulvestrant reported data that compares favorably to published data with current standard of care regimens. The median progression-free survival period for this patient cohort was 12.9 months and the objective response rate was 63%.

Please turn to Slide 14. In light of encouraging results with gedatolisib combined with palbociclib and fulvestrant in patients who progressed on prior CDK4/6 therapy, we concluded that evaluation of this regimen in a pivotal Phase III study was warranted. The design of the clinical trial in the setting required us to take into account several important factors. First, standard of care in the second-line setting for HR positive/HER2 negative patients differs based on PIK3CA. For the 35% of patients with a PIK3CA mutation, they typically receive a PI3K-alpha inhibitor, alpelisib, combined with fulvestrant.

The 65% of patients who do not have detectable PIK3CA mutations, most commonly receive either fulvestrant as a monotherapy or everolimus plus exemestane. Given the different treatment options and outcomes for these 2 patient groups, formal testing of the efficacy of a regimen in each PIK3CA subgroup is warranted. To evaluate efficacy in advanced breast cancer, the standard primary endpoint is progression-free survival in the first- and second-line setting. And PFS as an endpoint, has supported the registration of nearly all recently approved FDA therapies for advanced breast cancer.

Please turn to Slide 15. Before finalizing our pivotal study design, we saw formal feedback from the FDA, which we received during 2 very productive and collaborative meetings. Now that we have the feedback, we finalized the trial design. Our pivotal study named VIKTORIA-1, is a Phase III open-label randomized clinical trial to evaluate the efficacy and safety in gedatolisib in combination with fulvestrant with or without palbociclib in adults with HR-positive/HER2-negative advanced breast cancer, whose disease has progressed after prior CDK4/6 therapy in combination with an aromatase inhibitor. This will be a multicenter international trial, which we expect to enroll at approximately 175 clinical sites across the U.S., Europe and Asia. We expect to initiate the VIKTORIA-1 clinical trial in the first half of 2022.

The clinical trial will enroll patients regardless of their PIK3CA status. While enabling formal testing of efficacy in both the PIK3CA wild-type and mutation subgroups. For patients who don't have confirmed PIK3CA mutations, there will be 2 investigational arms, gedatolisib combined with fulvestrant with or without palbociclib and the control arm.

Patients will be randomly assigned on a 1:1:1 basis to receive either gedatolisib, palbociclib and fulvestrant in Arm A, gedatolisib and fulvestrant in Arm B or fulvestrant monotherapy in Arm C as the control. Up to 351 subjects who lack PIK3CA mutations will be enrolled. The 3-arm design will also show the contribution of gedatolisib in the combination. Subjects who have PIK3CA mutations will be randomly assigned on a one-to-one basis to receive either the investigational therapy gedatolisib, palbociclib and fulvestrant in Arm D or alpelisib and fulvestrant in Arm E as the control. Up to 300 subjects who have PIK3CA mutations will be enrolled.

Three primary endpoints are progression-free survival per RECIST 1.1 criteria as assessed by blinded independent central review. In subjects who lack PIK3CA mutations, the PFS and subjects in the 2 investigational arms A and B, will each be compared to the control Arm C. In subjects who have PIK3CA mutations, the PFS of Arm D subjects will be compared to Arm E subjects. As I mentioned earlier, there are roughly twice as many patients who lack PIK3CA mutations as those who have them. Given this, data for the 2 primary end points for the subjects lacking PIK3CA mutations will be available earlier from the data for those who have PIK3CA mutations. Our current estimate is that the primary analysis for PIK3CA non-mutated patients would be available sometime in the first half of '24. And the data for the PIK3CA mutated patients would be available in the second half of 2024.

Now please jump to Slide 18. The data from our Phase Ib study suggests that the anti-tumor effective gedatolisib when combined with palbociclib and fulvestrant is similar in patients with or without PIK3CA mutations. In each subgroup, while acknowledging the small sample sizes, the data compares favorably to recently reported prospective study data for the control therapies in comparable patient populations. Probability of progression-free survival at 12 months with the gedatolisib regimen was 48.5% in non-mutated patients compared to 10% in the recently reported EMERALD study for fulvestrant -- that included fulvestrant. In the mutated subgroup, the probability of progression-free survival at 12 months was 60% compared to 27% reported in the BYLieve study for the alpelisib regimen.

So to wrap up, we're more excited about the opportunity to develop gedatolisib than we've ever been. We've built an incredibly talented team of drug developers who've taken a fantastic drug to a pivotal Phase III clinical trial in a very short period of time. We're hopeful that this will only represent the first of what we think will be many opportunities for us to impact the lives of cancer patients.

Operator, I'd like to now open the call for questions.

(Operator Instructions) Our first question comes from the line of Maury Raycroft with Jefferies.

Congrats on the update today. My first question is just -- can you hear me?

I can hear you.

Okay. Okay. Great. First, I was wondering if you can talk about the conversation with FDA on the different stratifications for the Phase III that you have listed on Slide 16. How these factor into your hypothesis for gedatolisib? And are you powered based on any of these stratifications?

Well, I'll say a brief comment and then Igor can fill in the gaps. So the stratification variables are ones typically found in these studies. So there was nothing unusual about them. And we're following conventional statistical powering of those subgroups. Igor, maybe you could expound on that a little bit.

Yes. Thank you for the question. Certification factors used to make sure that arms are balanced for important clinical parameters in each study arm. That's primarily a goal for that. And in terms of study power, it is powered to detect statistical significance but also clinically meaningful difference between study arms, one that Brian mentioned as well as the control arm. That's median progression-free survival. This is the primary endpoint, as you see in the studies is the main goal with the study power.

Got it. Okay. That's helpful. And then based on the key eligibility criteria that you've got listed, how close do you think you'll be able to get with enrolling a patient population that's similar to Arm D where you show data in the Phase Ib study.

Go ahead, Igor.

I can answer this question. We believe that the results from Study 2151009 Arm D that will present to you -- will represent very well this global study involvement, and we believe it will be very close into real-world data as you will find information in the poster. Median number of prior treatment for these patients were 2 with a good number of patients receiving at least 2 number of prior treatments for advanced breast cancer. And that's a population that's very likely to be enrolled in Phase III as well.

Got it. That's helpful. And last question, I just wanted to ask about anything you're doing differently in the Phase III or proactively in the Phase III for managing tolerability, such as stomatitis in the study. If you can talk more about that.

I can answer this question as well. Yes, this study will include very detailed guidance on toxicity management as well as inclusion of prophylaxis that is accepted and expected as well for this patient population. So for example, steroid-based mouth wash would be mandatory for this patient in this study. And as we presented previously, in the Phase Ib study the prophylactic therapy was not used for all patients. So we believe that safety signal and profile in the Phase III study should be better.

Congrats, again.

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

Well. Maybe kind of a general one. It's pretty a pretty large study. Any assumptions you guys may have on total cost for a study of this size.

Sure. Well, I guess the way we look at that is, what is the current cash? Where does that take us? And basically, we think it gets us to roughly the first primary endpoint. And the study will get to the first primary endpoint, probably midway through the study, so that the activities will continue well after we get initial data. And so the trial costs are spread out over a much longer periods in just the first 2 years till we get the initial primary analysis.

Okay. That's very helpful. And maybe just a comment on alpelisib here. It looks like it's -- it's not that well tolerated. Do you have any additional comments, especially in comparison to gedatolisib?

Sure. I'll say a few words and Igor might provide some perspective as well. But that's one of the first piece of feedback we received from investigators and from clinicians when we started looking into gedatolisib and bringing it in-house. The alpelisib was approved as an option. It improved outcomes. But there was a very high discontinuation rate in the pivotal study that led to approval, 26%. In the more recent BYLieve study, the discontinuation rate was around 18%. It has very high grade 3, grade 4 hypoglycemia, which -- because it's an oral drug, means these patients can be -- potentially become very ill without seeing their doctor for an extended period of time. And from a clinician standpoint, that is very challenging for them and frustrating for them. So we've heard from a number of physicians that said if we just matched, and that's not the objective, but just using it as a reference. The efficacy with the safety profile that our drug has that we would be substantially preferred over that drug just on safety alone. Igor, did I miss anything there?

No, that's a good summary. As it's well published on the discontinuation rate for patients who treated with alpelisib could be quite high in double digits. And it's not only include hyperglycemia number of other toxicities that could lead to that and our preliminary data from Phase Ib study. And just a reminder, almost 500 patients and healthy volunteers have been treated with gedatolisib as a single agent or in combination with other therapies, safety profile has been established quite well. And based on feedback from experts and potential investigators, it compares -- again on paper. Of course, this will be first randomized study favorably to other PI3K/mTOR inhibitors.

All right. And maybe a last one, and I can understand that this might be a little hard to estimate. Considering the size of the study, have you guys thought of any COVID-proofing? I mean we've seen some pretty significant delays, especially in January.

Right. Well, the patients that we'll be enrolling are ones that are currently receiving treatment, and they've progressed. And so the standard practice for these patients is that they will be put on to new therapies. And the feedback we received from investigators is that these types of trials are ones that haven't been as effective. I mean obviously, it tends to be very situational, but we'll have a broad geographic dispersion of study sites. We won't be in Russia and the Ukraine. So we won't be impacted by what's going on there. But obviously, we can't predict the future, but if the current trend lines continue, having broad range of countries, a wide number of sites is really about the only steps you can take to mitigate any potential impact of reramping of COVID.

All right. I mean the thought came to me because it is an IV-administered drug and it should be administered in a hospital setting. Congratulations on having everything setup.

(Operator Instructions) Our next question comes from the line of Alex Nowak with Craig-Hallum Capital.

Brian, it looks like you've had 2 interactions with the FDA regarding the pivotal trial design. So maybe you could just speak to some of the feedback that you received and ultimately, how does the design of the pivotal study here change from what your initial conceptions were versus what we're seeing today?

Well, I think just briefly, I mean, we had very constructive collaborative discussions. And the whole point of it was to get their input on the final study design. We're pleased with the outcome. I mean the really -- the second study was really just to confirm what we talked about in the first. This is really our first interaction with the agency, and we want us to be as cooperative and collaborative as possible. And so we kind of accomplished our goals, and we're very, very happy with the outcome.

That's good. And is the plan to submit for -- or I guess, could you submit to FDA for approval based on that first or the second interim analysis? Or I guess how long do you need to run the study, get the bag in information before you have the right data set there to submit just to clarify.

Sure. Igor, why don't you touch on that?

Since the study in both mutated population and wild-type group patients is driven by events. Once number of events appropriate for analysis reached, we will initiate discussions with regulatory agencies. And based on this discussion filing could be based on the group of patients that has the results first.

Okay. Understood. And then just any update broadly regarding the FACT studies that are out there. Looks like the FACT 1 and 2 did get moved to the first half of 2023, just I'm sure those due to the Omicron variant, but just thoughts there and ultimately, how that affects the time lines for FACT 3, 4 and 5.

Right. So Omicron really did threw around some things. I mean that was a surprise, I think, to everybody as we've talked about on our last call, we saw activity pick up again back in February, but we lost those 3 months. And so had to push back when we expect to have data accordingly. The other studies got similarly affected. And -- because, again, these patients are coming in for specific procedure or biopsy, that tends to get a little bit more impacted than something that just required drug.

Congrats on finalizing the site design here.

Ladies and gentlemen, we have reached the end of today's question-and-answer session. I would like to turn the call back over to Mr. Brian Sullivan for closing remarks.

Well, thank you, everyone, for listening in and participating on this call. We'll be at the Canaccord and Needham conferences in April. I look forward to speaking hopefully with some of you then. If you have any additional questions, please feel free to contact us. Hope you have a good evening. Goodbye.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Enjoy the rest of your day.