Celcuity Inc.

Good afternoon, ladies and gentlemen, and welcome to the CellQD fourth quarter and full year 2024 financial results webcast conference call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. I would now like to turn the call Conference over to Aparva Chaluri with ICR Healthcare. Please go ahead.

Thank you, Operator, and good afternoon to everyone on the call. Thank you for joining us to review Salcuity's fourth quarter and full year 2024 financial results and business update. Earlier today, Salcuity released financial results for the fourth quarter ending December 31, 2024. The press release can be found on the Investor section of the website. Joining me on the call today are Brian Sullivan, CellQD'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 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 core operations and prospects for the future. You can find the cable 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 Selcuity. Please go ahead.

Thank you, Apoorva, and good afternoon, everyone. We appreciate your interest in Selcuity. Our team made significant progress executing our clinical development programs in 2024. We completed enrollment of the PIK3CA wild-type cohort in Victoria 1, our Phase 3 study, evaluating getatelicib plus fulvestrin with and without palvocyclib as second-line treatment for patients with HR-positive HER2-negative advanced breast cancer. We also completed selection of approximately 200 sites for Victoria 2, our Phase 3 study, designed to evaluate getotelicib in combination with fulvestrin and either ribociclib or palociclib as first-line treatment for patients with HR-positive, HER2-negative, endocrine treatment-resistant advanced breast cancer. Our Phase 1b dose escalation portion of our study evaluating getotelicib in combination with darolutamide for patients with metastatic castration-resistant prostate cancer is ongoing and remains on track to report preliminary data at the end of the second quarter of this year. and we reported overall survival data from our Phase 1b study for treatment-naive and CDK4-6 pretreated patients who received our Phase 3 dosing schedule. In our view, each of these three programs has the potential to generate blockbuster levels of revenue. If these three programs ultimately result in regulatory approvals, we estimate that nearly 200,000 late-stage cancer patients globally would be eligible to be treated with ketotelicid. As a result of the progress we made in 2024, 2025 will be a transformational year for cell acuity as we anticipate reporting several important clinical data readouts. For our Victoria 1 clinical trial, we anticipate reporting top line data for the PIK3CA wild type cohort in the second quarter of 2025, and top line data for the PIK3CA mutant type cohort in the fourth quarter of 2025. The primary endpoints for Victoria 1 are progression-free survival, or PFS, per Rhesus 1.1 criteria, as assessed by blinded independent central review. The study is designed to independently evaluate a PIK3CA wild-type cohort and a PIK3CA mutant cohort. For the PIK3CA wild-type cohort, there are two primary endpoints that will be tested hierarchically, whereas the PIK3CA mutant patient cohort has a single primary endpoint. The primary analysis for each patient cohort is triggered upon reaching a predefined number of progression events. Patients we're evaluating in our Victoria 1 study of HR-positive HER2-negative advanced breast cancer whose disease progressed while on or after receiving treatment with a CDK4-6 inhibitor and an aromatase inhibitor. We recognize that the treatment landscape for these second- or third-line patients is evolving as a number of investigational therapies are under development. Our view is that the underlying biological drivers of HR-positive HER2-negative advanced breast cancer will ultimately determine which regimens become standard of care. Three interconnected signaling pathways, the estrogens, cyclin D1, CDK4-6, and PI3K-AKT mTOR pathways promote this disease. And we believe that simultaneous blockade of all three of these pathways offers the best opportunity to optimize antitumor control. And this suggests that a triplet that addresses these three disease drivers, whether in the first or second line setting, may have a long-term advantage versus a doublet or monotherapy That addresses just one or two of these signaling pathways. Additionally, a triplet that could treat all patients, regardless of PIK3CA or ESR1 mutational status, would have an even greater advantage. The current second-line treatment paradigm for HR-positive HER2-negative patients with advanced breast cancer includes selective estrogen receptor degraders, or SIRDs, like fulvestrin or elastitrin, as single agents, or one of the three approved PAM inhibitors combined with endocrine therapy. 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've received prior treatment with a CDK4-6 inhibitor, none of these single-node PAM inhibitors have demonstrated efficacy in patients who have PIK3CA wild-type tumors, while only the PIK PI3K-alpha and AKT inhibitor have reported benefit in patients with PIK3CA mutations. And these results are consistent with the non-clinical data that shows these single-node inhibitors are three to four times less potent in breast cancer cells without PIK3CA mutations than in those with them. Now, this is in sharp contrast to the non-clinical and preliminary efficacy data we've reported for gadotilisib. In non-clinical studies evaluating breast cancer and prostate cancer cell lines, gadotilisib was found to be equally potent and cytotoxic in cell lines with and without PIK3CA or P10 mutations, and at least 300 times more potent on average in breast cancer cells than single-node PAM inhibitors. Consistent with these non-clinical results, the preliminary clinical endpoints we reported in our Phase Ib breast cancer study that evaluated getotelicib combined with palbociclib in either letrozole or fulvestrin, was comparable in both treatment-naive and second- and third-line patients with and without PIK3CA mutations. And we think these results demonstrate that along with the ER 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 of the presence of an activating mutation like PIK3CA. And that's why we believe development of an optimized PAM inhibitor like gadotilicid that targets all class I PI3K isoforms and mTORC1 and 2 to comprehensively blockade the PAM pathway, represents one of the most important opportunities to improve the standard of care in HR-positive HER2-negative advanced breast cancer. We think that gadotelicib's tolerability may also favor its potential positioning in a future treatment landscape. Gadotelicib's treatment-related discontinuation rate due to adverse events was only 4% in the phase 1 BRM with the phase 3 intermittent dose schedule. which is comparable to the 6% to 8% discontinuation rates for CDK4-6 plus fulvestrin regimens. While we don't have head-to-head data, these results compare favorably to the treatment-related discontinuation rates reported in the Phase III studies for opalipsib plus fulvestrin, where 26% of patients discontinued, and everolimus plus eczema stay, where 24% of patients discontinued. The results for gadathelizib are especially encouraging, given that the Phase Ib study did not include prophylactic therapy for stomatitis, the most common treatment-related adverse event for Geta tolicid. Since we're prescribing stomatitis prophylaxis in our Phase III trial, we would expect fewer stomatitis-related adverse events, which would further enhance Geta's already promising tolerability. Now, of course, the foundation of Geta's role in this treatment landscape will require that Geta tolicid be well-tolerated and report a clinically meaningful benefit measured in terms of the incremental improvement in both median PFS and the hazard ratio relative to standard of care. Now, breast cancer KOLs and regulators generally consider an incremental improvement in median PFS of three months relative to its control to be clinically meaningful. In the current median PFS benchmarks for patients pretreated with a CDK4-6 inhibitor, patient population we're evaluating, are modest. Published reports from recent randomized trials of median progression-free survival for fulvestrin average 2.7 months in patients with ESR1 wild-type tumors and 3.8 months for oral SIRDs in patients with ESR1 mutant tumors. The incremental median PFS benefit for patients with ESR1 mutations treated with an oral SIRD was a 1.9-month difference. For patients with PIK3CA or AKT mutations, median PFS ranges from 5.5 to 7 months when treated with either an AKT or PI3K-alpha inhibitor, representing approximately 3.5 months of incremental median PFS benefits. The rapid adoption and resulting annual run rate for each of these drugs, approximately 500 and 600 million respectively, illustrates the desire physicians have to switch to new therapies even when the incremental clinical benefit to their patients is modest. Now, a potentially more important data point than incremental PFS benefit to consider in advanced breast cancer when assessing the clinical benefit of one therapeutic regimen relative to another is the hazard ratio. Now, this is because recent randomized studies evaluating therapies for patients with HR-positive HER2-negative advanced breast cancer have enrolled widely heterogeneous patient populations. For instance, one study that evaluated an oral SIRD conducted primary analysis that included first- and second-line patients, and the same study evaluated the combination of the oral SIRD with a CDK4-6 inhibitor that included both patients who were CDK treatment-naive and those who had received prior CDK4-6 therapy. In another study evaluating an AKT inhibitor, the primary analysis included both patients who were CDK4-6 treatment naive and those who had received prior CDK4-6 therapy. Well, since physicians make different treatment decisions for patients depending on, among other factors, how many lines of therapy or which type of therapy they've received, results from these studies can be hard to interpret using absolute median PFS or incremental median PFS benefit alone. As a result, the top-line median PFS results from these studies don't provide sufficient clarity about the actual benefit the particular patient population may receive. Hazard ratio essentially factors out the differences in study populations, and thus provides physicians with an objective benchmark. We just not only hope to report a hazard ratio that is statistically significant, but one that compares favorably to the hazard ratio reported for other therapies available for these second-line patients. An additional factor, which we think may ultimately accrue to Getta-Telissib's advantage, particularly in the community physician setting, is the fact that Getta is an infused therapy administered in office. And this perspective has been reflected in the feedback we're receiving from oncologists, both key opinion leaders and community physicians, and market access stakeholders, in conjunction with our preliminary market research. A particular note is the encouraging feedback received regarding Getta-Telissib's IV route of administration. Physicians can monitor and manage patient compliance more effectively than they can with oral therapies, and this is relevant, particularly for oral therapies that induce unpleasant side effects. For these therapies, patient compliance can often be a challenge, and this preliminary research does suggest an IV administration will not be a barrier to utilization of getathalysib, and in fact, may be an important advantage. Additionally, in-office administered therapies such as getathalysib fall into the medical benefit category, which has a more streamlined reimbursement process than orally administered drugs, which fall into the pharmacy benefit category. Our market research suggests that this fact has several implications for oncologists, patients, and our company. First, oncologists view IV administered drugs favorably, allowing them to recover additional costs associated with treating their patients in office. Second, oncologists have more autonomy to select therapies they believe will benefit their patient. Third, the payer management process is less burdensome to navigate. And finally, Patients typically incur lower out-of-pocket costs with an infused therapy, which is an important consideration for most patients. For pharmaceutical companies, pair contracting is less common and results in fewer price discounts. In a real-world setting, patient convenience is only a meaningful consideration for IV-administered drugs when the efficacy and safety profile of the alternative drugs are comparable or when a patient lives a significant distance from a treatment site. Otherwise, based on our market research, The well-tolerated therapy that offers a clinically meaningful benefit is preferred by oncologists relative to one that offers less efficacy but is more convenient. The fact that the most widely prescribed oncology drugs are administered in office reinforces this point. For instance, in breast cancer, Herceptin, Progetta, Keytruda, and in HER2, each recorded multibillion-dollar peak revenues, while treating smaller patient populations than the potential populations we seek to address with Geddes-Lissib and our two current breast cancer clinical trials. If gadathalysib ultimately does receive FDA approval for both the PIK3CA wild type and mutant populations, we estimate the peak revenue potential for the second line indication could exceed $2 billion with just 40% market penetration. Now turning to our first line breast cancer program. We've completed the selection of the clinical sites that will participate in our Victoria 2 study. Approximately 200 sites across North America, Europe, Latin America, and Asia Pacific are in process now of being activated. We're very pleased with the level of interest our current Victoria 1 sites expressed in participating in the study. And we continue to expect to enroll our first patient in the second quarter of 2025. Victoria 2 studies, a global phase 3 open-label randomized clinical trial, evaluating the efficacy and safety of getothelicib in combination with fulvestrin plus investigator's choice of either ribociclib or palviciclib as a first-line treatment for patients with HR-positive HER2-negative advanced breast cancer who are endocrine therapy-resistant. Approximately 638 patients will be assigned to a cohort based on their PIK3CA mutation status. Clinical trial endpoints are progression-free survival per Rhesus 1.1 criteria, as assessed by Blinded Independent Central Review. Primary PFS endpoint for each of the two cohorts will be evaluated independently. Prior to the initiation of the Phase III portion of the trial, a safety run-in study will be conducted in 12 to 36 patients to assess the safety profile of getotelicib in combination with ribociclib and fulvestrin. We estimate that 15,000 to 20,000 patients with endocrine therapy-resistant advanced breast cancer are diagnosed each year in the United States alone. And since this population doesn't overlap with the patient population we're evaluating in our Victoria 1 study, an approval to treat these patients would increase the size of the addressable U.S. market potential for Geta Thalyssid by up to $3 billion. Turning now to our prostate cancer program. We remain on track with our Phase 1b trial that is evaluating safety and tolerability of Geta in combination with darolutamide. in patients who have metastatic castration-resistant prostate cancer. The underlying biology of prostate cancer has a lot of similarities to ER-positive breast cancer. Both are hormonally-driven tumor types, and both involve the PAM pathway. While the development of PAM inhibitors in breast cancer is further advanced than in prostate cancer, there's significant non-clinical evidence and emerging clinical data that suggests simultaneous inhibition of both the AR and PAM pathway may be more efficacious than treatment with an AR inhibitor alone. We expect to report out preliminary data from the phase 1B dose escalation portion of the study towards the end of the second quarter of this year. Since we're at an earlier phase in this program, our focus is optimizing the dose and schedule for this tumor type and drug combination. The data set will include approximately 36 patients, half of whom will have received a 120 milligram dose of GEDA, the other half a 180 milligram dose. Each are administered on a three-week on one week off schedule. We're comparing both the landmark PFS at six months and the safety profile of these two arms to each other and historical control data for second-line metastatic castration-resistant prostate cancer patients who are retreated with an androgen receptor inhibitor. And finally, we were very excited to report last December encouraging preliminary overall survival data from both first-line and second-line advanced breast cancer patients from our Phase 1b study that evaluated getatelicib in combination with palbociclib and endocrine therapy. For the phase one, or rather the first-line patients, median overall survival was 77 months, which compares favorably to published phase three data for palbociclib plus letrozole. For the second-line cohort, median overall survival was about 34 months, which compares favorably to recently published OS data results for fulvestrin. And of course, you have to be careful making cross-trial comparisons, especially since ours was just a single-arm study. but certainly we view the data as very encouraging. And with that, I'll now turn the call over to Vicki Hahn to review our financial results.