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spk02: Greetings and welcome to the Q&A fourth quarter and full year 2021 results conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. 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.
spk04: Thank you, Laura. Good afternoon, everyone, and welcome to Cellcuity's fourth quarter and full year 2021 financial results and business update webcast and conference call. Thank you for joining us. Earlier today, Cellcuity Incorporated released financial results for the fourth quarter and full year ended December 31st, 2021. The press release can be found on the investor section of our website. Joining me on the call today are Brian Sullivan, Salcuity's Chief Executive Officer and Co-Founder, Vicki Hahn, Chief Financial Officer, as well as Igor Gorbachevsky, 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 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 Vicki Hahn, Self-Q&A's CFO, to review the financial results prior to a business update.
spk01: 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 92 cents per share for the same period in 2020. Because these quarterly net losses include significant non-cash 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 31st, 2021. Our non-GAAP adjusted net loss was 5.6 million or 37 cents per share for the fourth quarter of 2021 compared to non-GAAP adjusted net loss of 2.1 million or 21 cents 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 75 cents 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 of 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 non-cash expense for issuance of common stock. The remaining 8.1 million increase primarily resulted from expenses initially associated with the transfer of GDAD ELISIB-related activities from Pfizer to Salcuity, and subsequently the continued support and development of GDAD ELISIB. 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. GNA expenses for the full year 2021 were $2.4 6 million compared to 1.9 million for the prior year. The approximately 7.7 million increase in G&A during the full year 2021 compared to the full year of 2020 arose primarily from non-cash 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 we will hand the call over to Brian.
spk08: Thank you, Vicki. Good afternoon, everyone, and thank you for joining us today. As always, we appreciate your continued support of Cellcuity. 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 GetDell Elizabeth. My remarks will include a review of the pivotal Phase III trial design we recently finalized. In this study, we'll evaluate gadalilisib 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 four. We laid important groundwork to advance our gadalilisib breast cancer program during the past few months. We entered into a clinical trial collaboration and supply agreement with Pfizer to provide palvocyclib, known commercially as Ibrans, for use in our Phase III clinical trial at no cost to cell acuity. 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 anti-tumor activity and tolerability of the therapy in patients treated with the three weeks on, one week off, get a telicid regimen supports use of this dosing schedule in our pivotal study. In January, the FDA granted fast-track designation to get a tolicib 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 demonstrate 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 three clinical trial for getatolizib following very productive meetings with the FDA. So now please turn to page five. To provide context for the trial design, I'd first like to briefly review why we believe getatolizib has such great potential to provide more effective treatment for women with breast cancer. This potential reflects both the importance of the pathway target getatolizib inhibits and its highly differentiated mechanism of action and pharmacokinetic profile. Getotelizib 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 key cell metabolic processes. Getotelizib addresses the structural complexity of the pathway by inhibiting all four class I PI3K isoforms in mTORC1 and mTORC2. This is the optimal approach biologically because it avoids the 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 six now. Gadotilis'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 Gatotilisib's unique properties position it to realize the significant potential first envisioned for PI3K therapies when the pathway's critical role in cancer was discovered. I'll now turn to slide eight. Gatotilisib's initial potential target patient population is 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 nine. 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 SIRD, 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 SIRDs to replace fulvestrin is one therapeutic strategy several pharmaceutical companies are pursuing to address this unmet need. Unfortunately, clinical studies evaluating two different oral SIRDs 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 these third clinical trials and from the trials of existing standard of care therapies suggests additional oncogenic pathway drivers and resistance mechanisms must be targeted. Please turn to slide 11. The available evidence indicates the 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 mTOR 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 would 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 PSUK mTOR and no CDK4 inhibition to address this very complex disease mechanism. Please turn to slide 12. A phase 1b study evaluated this hypothesis in the first and second line setting for a woman with advanced breast cancer. Women with HR-positive HER2-negative advanced cancer who had not received prior therapy for advanced disease were treated with Gedetolizumab 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. where median PFS of 24.8 months and ORR of 55% was reported. Please turn to slide 13. For patients who had progressed on prior CDK4-6 treatment, get a telicib dose on an intermittent schedule combined with palacyclib and fulvestrin, reported data that compares favorably to published data with current standard of care regimens. The median progression of 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 for getatolizumab combined with palbociclib and fulvestrin in patients who progressed on prior CDK4-6 therapy, we concluded that evaluation of this regimen in a pivotal phase 3 study was warranted. The design of the clinical trial in this 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 status. For the 35% of patients with a PIK3CA mutation, they typically receive the PI3K alpha inhibitor, alpalipsib, combined with fulvestrin. The 65% of patients who do not have detectable PIK3CA mutations most commonly receive either fulvestrin as a monotherapy or everolimus plus examistane. Given the different treatment options and outcomes for these two patient groups, formal testing of the efficacy of our 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 sought formal feedback from the FDA, which we received during two very productive and collaborative meetings. Now that we have the feedback, we finalized the trial design. Our pivotal study, named VICTORIA-1, is a Phase III open-label randomized clinical trial to evaluate the efficacy and safety in getatilicib in combination with fulvestrin with or without palociclib in adults with HR-positive or 2-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 Victoria 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 two investigation alarms. Getatolizib combined with fulvestrant with or without palbociclib, and a control arm. Patients will be randomly assigned on a one-to-one-to-one basis to receive either getatolizib, palbociclib, and fulvestrant in arm A, getatolizib 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 three-arm design will also show the contribution of getatolizib in the combination. Subjects who have PIK3CA mutations will be randomly assigned on a one-to-one basis to receive either the investigational therapy, get a tolicib, pavaciclib, and fulvestrin in RMD, or alpalypsib, and fulvestrin in RME as the control. Up to 300 subjects who have PIK3CA mutations will be enrolled. Three primary endpoints are progression-free survival per RESIST 1.1 criteria, as assessed by blinded independent central review. In subjects who lack PIK3CA mutations, the PFS in subjects in the two 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 two primary endpoints for the subjects lacking PIK3CA mutations will be available earlier in 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 1b study suggests that the anti-tumor effect of Geta to Elicit when combined with Pabliciclip and Flavestrin 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 get-its-elicit regimen was 48.5% in non-mutated patients compared to 10% in the recently reported Emeril study for fulvestrin that included fulvestrin. In the mutated subgroup, The probability of progression-free survival at 12 months was 60% compared to 27% reported in the by-leave study for the epilepsy regimen. So to wrap up, we're more excited about the opportunity to develop Geta to Lissab 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 three 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.
spk02: At this time, we'll be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 to remove your question from the queue. For participants using speaker equipment, it may be necessary for you to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question comes from the line of Maury Raycroft with Jefferies. You may proceed with your question.
spk06: Hi, congrats on the update today. Thank you for taking my questions. My first question is just, hi, 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 three that you have listed on slide 16, how these factor into your hypothesis for good adolescent, and are you powered based on any of these stratifications?
spk08: 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.
spk03: Thank you for the questions. Certification factors used to make sure that arms are balanced for important clinical parameters in each study arm. That's primarily the goal for that. And in terms of study power, it is power to detect statistical significance, but also clinically meaningful difference between study arms, one that Brian mentioned, as well as a control arm. That's medium progression-free survival. This is a primary endpoint, as you see in the studies, is the main goal for study power.
spk06: 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 RMD where you show data in the Phase 1b study? Go ahead, Igor.
spk03: I can answer this question. We believe that the results from study 215-1109-RMD that we 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. Medium number of prior treatment for this patient were two with a good number of patients receiving at least two number of prior treatments for advanced breast cancer, and that's populations that are very likely to be enrolled in Phase III as well.
spk06: 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.
spk03: I can answer this question as well. Yes, this study will include very detailed guidance on toxicity management as well as inclusion of a prophylaxis that is accepted and expected as well for this patient's population. So, for example, steroid-based mouthwash would be mandatory for this patient in this study. And as we presented previously, in the Phase 1b study, this prophylaxis therapy was not used for all patients. So we believe that safety signal and profile in a phase three study should be better.
spk06: Great. Okay, congrats again, and thanks for taking my questions. Thanks, Maureen.
spk02: Our next question comes from the line of Gil Bloom with Needham & Company. You may proceed with your question.
spk05: Hi, everyone, and good afternoon, and thanks for taking our questions as well. Maybe kind of a general one. It's a pretty large study. Any assumptions you guys may have on total cost for a study of this size?
spk08: Sure. Well, I guess the way we look at that is what is our 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 this study so that the activities will continue well after we get initial data. And so, you know, the trial costs are spread out over a much longer period than just the first two years until we get the initial primary analysis.
spk05: Okay, that's very helpful. And maybe just a comment on alpha-lucid here. It looks like it's not that well tolerated. Do you have any additional comments, especially in comparison to the beta-lucid?
spk08: Sure. I'll say a few words, and Igor might provide some perspective as well. But that's one of the first pieces of feedback we received from investigators and from clinicians when we started looking into Getatolizib and bringing it in-house. Alpalipsib 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 Bileaf study, the discontinuation rate was around 18%. It has very high grade three, grade four hyperglycemia, which because it's an oral drug means these patients can 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?
spk03: No, it's a good summary. As it's well published, The discontinuation rate for patients who are treated with Zolpallisib could be quite high in double digits, and it not only includes hyperglycemia and a number of other toxicities that could lead to that, and now preliminary data from Phase 1B study. And just a reminder, almost 500 patients and healthy volunteers have been treated with Gatotalisib 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's compared, again, on papers. Of course, this will be first randomized study favorably to other PA3K inhibitors.
spk05: 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. Thank you.
spk08: Right. Well, the patients that we'll be enrolling are ones that are currently receiving treatment and they've progressed. And so, you know, the standard practice for these patients is that they will be put on to new therapies. and the feedback we receive from investigators is that these types of trials are ones that haven't been as effective. I mean, it obviously 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, you know, the current trend lines continue, you know, having broad range of countries, you know, wide number of sites is really about the only steps you can take to mitigate any potential impact of, you know, re-ramping of COVID.
spk05: All right. I mean, the thought came to me because it is an IV-administered drug. It needs to be administered in a hospital setting. Okay. All right, thank you very much for taking our questions, and congratulations on having everything set up. Thanks.
spk02: As a reminder, if you would like to ask a question, please press star 1 on your telephone keypad. Our next question comes from the line of Alex Nowak with Craig Hallam Capital. You may proceed with your question.
spk07: Great. Good afternoon, everyone. Brian, it looks like you've had two interactions with the FDA regarding the pivotal trial design. So maybe if you just speak to some of the feedback that you received and ultimately how did the design of the study here change from what your initial conceptions were versus what we're seeing today?
spk08: 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 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.
spk07: 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 bagging information before you have the right data set there to submit, just to clarify?
spk08: Sure. Igor, why don't you touch on that?
spk03: Since the study in both mutated population and wild-type group patients is driven by events, one number of events appropriate for analysis reached We will initiate discussions with regulatory agencies, and based on these discussions, filing could be based on the group of patients that has the results first.
spk07: 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. I'm sure that's due to the on-the-counter. variant, but just thoughts there and ultimately how that affects the timelines for FAC 3, 4, and 5.
spk08: Right. So Omicron really did throw our wrench in 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 three months and so had to push back when we expect to have data accordingly. The other studies, you know, got similarly affected. And because, again, these patients are coming in for a specific procedure, you know, a biopsy, you know, that tends to get a little bit more impacted than, you know, something that just required drug.
spk07: Got it. Understood. Makes sense. Appreciate the update. Congrats on finalizing the study design here.
spk08: Thank you.
spk02: Ladies and gentlemen, we have reached the end of today's question and answer session. I would like to turn this call back over to Mr. Brian Sullivan for closing remarks.
spk08: Well, thank you, everyone, for listening in and participating in this call. We'll be at the Canaccord and Needham conferences in April. We'll look forward to speaking, hopefully, with some of you then. If you have any additional questions, please feel free to contact us. I hope you have a good evening. Goodbye.
spk02: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Enjoy the rest of your day.
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