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spk07: Good afternoon, ladies and gentlemen, and welcome to the Selcuity 3rd Quarter 2024 Financial Results 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 the call you require immediate assistance, please press star zero for the operator. This call is being recorded November 14th, 2024. I would now like to turn the call over to Apoorva Chalori. Please go ahead.
spk00: Thank you, operator, and good afternoon to everyone on the call. Thank you for joining us to review Salcuity's third quarter 2024 financial results and business update. Earlier today, Salcuity, Inc. released financial results for the third quarter ended September 30th, 2024. The press release can be found on the investor section of the website. Joining me on the call today are Brian Sullivan, Salcuity's chief executive officer and co-founder, Vicky Han, 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 table reconciling the non-GAAP financial measures to GAAP financial measures in today's press release. And with that, I would now like to turn the call over to Brian Sullivan, CEO of Zilkiuti. Please go ahead.
spk04: Thank you, Apoorva, and good afternoon, everyone. We continue to make great progress advancing the clinical development of gadotilisib this quarter. Overall enrollment in Victoria 1 Our Phase III clinical trial, evaluating getatilicib plus fulvestrin with and without palvocyclib in the second-line setting, remains robust and on track. We're very excited to announce that the PIK3CA wild-type cohort is 100% enrolled, an important milestone. It reflects the excellent execution by our clinical development and operations teams and great support from the investigators at our sites. And enrollment in the PIK3CA mutant cohort is on plan. Our Victoria 2 Phase 3 clinical trial that will be evaluating getatilicid plus fulvestrin and a CDK4-6 inhibitor in the first-line setting remains on track to enroll its first patient in the second quarter of 2025. And our Phase 1b2 trial evaluating patients with metastatic castration-resistant prostate cancer is ongoing and remains on track to report preliminary data in the second quarter of 2025. The primary endpoints for the Victoria 1 clinical trial 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 patient cohort and a PIK3CA mutant patient 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. Primary analysis for each patient cohort is triggered upon reaching a predefined number of progression events. With a PIC3CA wild-type patient cohort, the threshold number of events for both primary endpoints must be achieved before the primary analysis is triggered. Based on our current forecast of reaching the event thresholds that will trigger primary analysis, we expect to report top-line data for the PIC3CA wild-type cohort sometime in late Q1 2025 or Q2 2025. and to report top-line data for the PIK3CA mutant cohort in the second half of 2025. If the results from the PIK3CA wild-type patient cohort are positive, we would expect to file a new drug application, or NDA, with this data and follow up with a supplemental NDA or SNDA if the results from the PIK3CA mutant cohort are also positive. Obviously, the foundation of Geta-Telicib's potential future positioning will require that Geta-Telicib report a clinically meaningful median PFS benefit. Current median PFS benchmarks for patients pretreated with a CDK4-6 inhibitor are modest. Published reports of median progression-free survival for the SIRDs range from 2 to 3.8 months, and in patients with PIK3CA mutations, ranges between 5.5 and 7.3 months for the AKT and PI3K-alpha inhibitors. The two most recently approved therapies for this patient population reported between 2 and 3.5 months of incremental PFS benefit. The threshold KOL is generally considered to be clinically meaningful. In addition, we've consistently heard from oncologists that they greatly prefer to delay use of chemotherapy or ADCs until the benefit from endocrine backbone regimens is exhausted. We also think the get-up-to-lispsib safety profile may also favor its potential positioning in a future treatment landscape. Gadotilisib's treatment-related discontinuation rate was only 4% in the Phase 1b arm with the Phase 3 intermittent dose schedule, which is comparable to the 6% to 8% discontinuation rates for the CDK4-6 plus fulvestrant regimens. These results compare favorably to the treatment-related discontinuation rates reported in the Phase 3 studies for alpalisib plus fulvestrant, where 26% of patients discontinued, and everolimus plus eczemistane, where 24% of patients discontinued. The results for getatelicib are especially encouraging given that patients in the Phase 1b study did not receive prophylactic treatment for stomatitis. Since we are prescribing stomatitis prophylaxis in our Phase 3 trial, we would expect fewer stomatitis-related adverse events, which would further enhance getatelicib's already promising safety profile. We recognize that the treatment landscape is evolving with new potential therapies under development. 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, estrogen, cyclin D1, CDK4-6, and PI3K-AKT mTOR, promote this disease. And we believe that simultaneous blockade of all three of these pathways is required to optimize anti-tumor control. And this suggests that a triplet regimen that addresses these disease drivers whether in the first- or second-line setting, may have a long-term advantage versus a doublet regimen or monotherapy that addresses just one or two of these signaling pathways. Additionally, a triplet regimen that could treat all patients, regardless of PIK3CA or ESR1 status, would have an even greater advantage. We believe that a triplet regimen that includes getotelicib is well-positioned to establish this new standard of care, And we're optimistic that the VICTORIO-1 data from our PIK3CA wild-type and mutant cohorts can live up to this potential. Feedback we're receiving from oncologists and market access stakeholders, in conjunction with our preliminary commercial launch-related activities, further reinforces our optimism about the potential for get a TELICIB. Of particular note is the encouraging feedback received regarding get a TELICIB's IV route of administration. This preliminary research suggests that IV administration will not be a barrier to utilization of gadathalysib and, in fact, likely offers important advantages, particularly from a market access and adherence to therapy perspective. 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 and delay indication alone could exceed $2 billion. Returning to our Victoria 2 study, Our site qualification activities to support activation of up to 200 sites across North America, Europe, Latin America, and Asia are on track. We're very pleased with the interest we're receiving from our current Victoria 1 sites as well as new sites that have expressed interest in participating in this study. We expect these activities will allow us to enroll our first patient in the second quarter of 2025. The Victoria 2 study is a global phase 3 open-label randomized clinical trial evaluating the efficacy and safety of getatolizib in combination with fulvestrin plus a CDK4-6 inhibitor as a first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer who are endocrine therapy resistant. Prior to the initiation of the Phase III portion of the trial, a safety run-in study will be conducted in 12 to 36 participants to assess the safety profile of getatolizib in combination with rivociclib and fulvestrin. Earlier this year, we dosed our first patient in our Phase 1b2 trial that is evaluating getotelicib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer. This study is ongoing, and we are on track to report preliminary data from this study in the second quarter of 2025. Just recently in October, the journal Cancers published results of our non-clinical studies in gynecological cancer cell line models, highlighting the differences between single-node inhibitors of the PI3K-AKT mTOR pathway and gadotilisib. The published manuscript is available online and on the publication sections of CellQD's website. The results from these studies are consistent with the non-clinical studies we published earlier this year that evaluated breast and prostate cancer cell line models. In all three tumor types, gadotilisib demonstrated superior potency and cytotoxicity compared to single-node PI3K-AKT mTOR inhibitors. And this December, We're looking forward to presenting one clinical poster and two non-clinical posters at the San Antonio Breast Cancer Symposium. Our clinical poster will present overall survival data from our Phase Ib clinical trial that evaluated getotelicib in combination with palbociclib and endocrine therapy. The two non-clinical posters will present data that further characterizes the mechanism of action of getotelicib and its effect on key breast cancer cell metabolic functions. Overall, we're very pleased with the progress we made this quarter advancing the clinical development of getotelicib. I'd like now to turn the call over to Vicki, who will review our financial results.
spk02: Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the third quarter 2024. Our third quarter net loss was $29.8 million, or $0.70 per share, compared to $18.4 million net loss, or $0.83 per share, for the third quarter of 2023. Because these quarterly Net losses include significant non-cash items, including stock-based compensation and interest. We also included in our press release non-GAAP adjusted net loss for the quarter ended September 30, 2024. Our non-GAAP adjusted net loss was $27.6 million, or $0.65 per share, for the third quarter of 2024, compared to non-GAAP adjusted net loss of $17.3 million, or $0.78 per share, for the third quarter of 2023. Research and development expenses were $27.6 million for the third quarter of 2024, compared to $17.5 million for the third quarter of 2023. Of the approximately $10.1 million increase in R&D expenses, $6.3 million primarily related to activities supporting the Victoria 1 phase 3 trial, the phase 1B2 prostate trial, and the initiation of the Victoria 2 phase 3 trial. The remaining $3.8 million was related to increased employee and consulting expenses. General and administrative expenses were $2.5 million for the third quarter of 2024. compared to 1.4 million for the third quarter of 2023. Employee and consulting related expenses accounted for 0.9 million of the increase. Professional fees and other administrative expenses accounted for the remaining increase of approximately 0.2 million. Net cash used in operating activities for the third quarter of 2024 was 20.6 million, compared to $12.7 million for the third quarter of 2023. We ended the quarter with approximately $264.1 million of cash, cash equivalents, and short-term investments compared to cash, cash equivalents, and short-term investments of $180.6 million at December 31, 2023. The increase of $83.5 million in cash, cash equivalents, and short-term investments was the result of several financing activities that occurred year-to-date through September 2024 and yielded net proceeds of approximately $138.3 million. The $138.3 million was partially offset by year-to-date operating cash used of approximately $55.8 million. I will now hand the call back to Brian.
spk08: Thank you, Vicki. Operator, could you please open the call for questions? Thank you.
spk07: Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, Please lift the handset before pressing any keys.
spk09: One moment, please, for your first question. Your first question is from Mari Raycroft from Jefferies. Please go ahead.
spk05: Hi. Congrats on the progress, and thanks for taking my questions. For the timeline updates and clarifications around timelines, it sounds like it's primarily driven by event rates Can you talk more about whether you have any additional insights into the event rate and whether there could be a relationship with patient baseline characteristics? And just want to clarify if any of the shift was related to enrollment going slower than expected.
spk04: Hi, Mari. Thanks for your question. We think that as we updated last quarter, our last update, that the higher proportion of of mutated patients relative to our initial projection, 40% versus 35%, had a corresponding decrease in the rate of enrollment for the wild-type population. We factored that into the event projection or the timeline we provided in August. And so the recent update relates to and would only be a result of the rate of events occurring. And so not related to change in enrollment. We're actually a little ahead of where we thought we'd be when we reported in August. And so as far as factors that could drive that, it's really not appropriate for me to comment. I think the event rate is out of our control. It's certainly a function of how the patients are responding to therapies. The events that we can track are only an aggregate for all three arms. We can't track them by endpoint. So, we, you know, really have limited ability to do anything other than track them and try to forecast when we think we'll cross over the line for those two primary endpoints.
spk05: Okay. Yeah, that makes sense, and that's helpful. And also, just wanted to ask you a question just based on the treatment landscape evolving with Roche's approval of Invalisib in combo with Publicyclib and Profestrin. Just your thoughts on that for the frontline setting and how that approval could impact or affect use of gadalizib in the second line if approved for the mutation population.
spk04: Sure. Well, we think the study and the results were supportive of our hypothesis, which is that inhibition of all three of these pathways is beneficial and can significantly improve outcomes for patients. As far as the impact on GETA, you know, our current indication or the indication we'd be seeking is for patients who are endocrine treatment sensitive. And these are patients who will have received CDK4-6 inhibitor plus letrozole. And so our forecasts of the opportunity have been focused on or have been related to that population. And so we don't expect that approval for inovolucid to essentially compromise or reduce the population that we're treating in the second line. Our Victoria 2 study, though, will directly address the population that the Roche study was focused on, the Inevalisib study, except that our study will enroll 100% of the eligible patients who are endocrine treatment resistant, whereas the Roche study essentially only enrolled or treated what we estimate to be roughly 20% of the eligible of the patients who would be considered to be endocrine treatment resistant. Got it.
spk05: Okay. That's helpful. Thanks for taking my questions. I'll hop back in the queue. You're welcome.
spk09: Your next question is from Brad Canino from Staple. Please go ahead.
spk06: Hi. Thanks for the updates. Maybe one heading into San Antonio. I know in the press release you've got an updated analysis. I want to Great to hear from you what the focus will be there. And then also at the conference, there's going to be a lot of data from oral SIRT and CDK doublets, including a phase three. I'd just like to ask if you consider these to be potential new combination therapies that could compete with Get a Toll Sib. And what are you keeping in mind as you plan to analyze the data from those at the meeting? Thank you. Sure.
spk04: Well, at the San Antonio conference, we'll have a number of objectives. I mean, one of them will be to present the three posters and update folks on, you know, the extended follow-up we've performed on the patients who were enrolled in the Phase 1b study, and then, you know, continue to provide information that helps people understand the mechanism of GETA and its impact on key metabolic functions. We'll also have objectives just related to general activities to support our two ongoing studies in breast cancer. But of course, we'll be tracking the data that comes out, the phase three data for the oral SIRD and then the other data. Most of these studies are seeking to treat a population similar to ours, so certainly very relevant to us, and we'll review the data accordingly. I think depending on which patient populations get enrolled, you have to peel apart the baseline characteristics, and depending on how they present the data, you'll need to do an assessment of the subgroups that maybe correspond to true second-line population that we're addressing, which is patients who received a CDK4-6 and an aromatase inhibitor who have received prior CDK4-6. And so that patient population is distinct. Some of these trials will be enrolling patients who have not had a CDK4-6 inhibitor That will tend to make it difficult to interpret without assessing the subgroups, you know, those who've received versus those who haven't received CDK4-6 inhibitors. And then, you know, there's certain characteristics that aren't necessarily representative of the type of population you might enroll in a phase three study. You know, for instance, patients with measurable disease versus non-measurable disease or valuable versus non-valuable tumors. You know, those factors can create have an impact on the response of patients to therapy. So it's always important when you look at these studies and you try to do a cross-trial comparison to try to normalize the data as much as possible to ensure that you're comparing likes to likes to the extent that, you know, the data is available to do that.
spk08: All right. Thanks, Brian.
spk09: The next question is from Tara Bancroft from TD Cowan. Please go ahead.
spk01: Good afternoon, and thanks for taking the question. So I was hoping to get a better idea of expectations. So first, I was hoping you could tell us what absolute MPFS number that you would like to see in the wild type triplet and doublet to have the highest level of confidence in success in the mutant population as well. And then, I guess, also related to what Brian asked. My question for the control arm expectations is, you know, given that we have the Ember 3 data coming up at San Antonio, it would be great to get your view on read-through from that, in particular in the control arm, you know, even though it's investigator choice, but it does include fulvestrants. So, you know, we've talked about this before with the post-monarch study, but how should we look at how the control arm performs and make any read-through here.
spk04: Well, as far as what we'd like to see, I mean, we'd love to see two years. So I think what we think, and really it's not appropriate for us to provide a forecast. What we can do is just point people to the results we had in our Phase 1b study and point to the fact that in our Phase 3 study, we're enrolling a patient population that could be considered to have a more favorable prognosis than the patient population that was evaluated in the Phase 1b study. The patients in the Phase 1b study all had visceral disease, no bone-only patients. 20% of the patients had prior chemo. And their median duration of their prior treatment was around 13 months. Whereas in the Phase 3 study, we're not enrolling patients who've had prior chemo in the advanced setting. We are enrolling patients who have bone-only disease as long as they have a measurable lytic or lytic-blastic lesion. And those two factors, again, tend to correlate to improved response to targeted therapies. So net-net, we think we have a population that may certainly improve the odds of being able to replicate the data in the phase 1b. And the phase 1b data, we reported 12.9 months median PFS overall. Roughly 50% of patients were progression-free who were wild type at 12 months, whereas 60% on the mutant setting were progression-free at 12 months. And so we would hope to report results that were consistent with that. As far as the expectations or what's needed to have a clinical impact, You know, the KOLs we've spoken to, as well as the community physicians, very kind of uniformly indicated that the three-month median PFS delta relative to control would be meaningful. Certainly more is better than that, if that's possible. And so, you know, the data will come out and we'll see. Now, as far as, you know, what to think about the controls. In the past couple years, or three years, there have been four studies, one phase three, two phase three, two phase twos, randomized, that have evaluated fulvestrin in patients who've had prior CDK. Two of the studies reported 1.9 months median PFS for fulvestrin. One reported 2.1 months for fulvestrin, and the other reported 3.5. If you do a straight average or even a weighted average, taking into account the different population sample sizes, you find that the average results for fulvestrant in this population is about three months, where it ranges from two to three and a half. We think it would be very unlikely to see a result that was outside those boundaries going forward. As far as Ember 3, I think From what I know about the eligibility criteria, they've included patients who are CDK4-6 treatment naive as well as those who are CDK4-6 naive. And so it'll make the intent to treat MPFS reported difficult to interpret because for the most part, certainly in the U.S. and really in most of the developed countries, CDK4-6 treatment is standard in the front line. So the results for a mixed population won't necessarily be useful for investigators. They'll want to dig into the post-CDK patient results. And we'll see. I think it would be unlikely, given the other results that have been reported, that we'd see results outside that two- to three-and-a-half-month range, but we'll know in a couple weeks.
spk01: Okay, great. Thank you.
spk04: You're welcome.
spk09: Your next question is from Chase Knickerbocker from Craig Hallam. Please go ahead.
spk03: Good afternoon. Thanks for the questions. So Brian, just maybe as we're kind of obviously fully enrolled now in the first cohort in Victoria 1, maybe talk me through, obviously you're going to have a lot of similar trial sites in Victoria 2. Talk me through kind of your enrollment expectations for that study now that you have quite a bit of experience with what to expect from a lot of these trials. these sites from Victoria 1 and, again, kind of what you hear from investigators as far as, you know, kind of their excitement around Victoria 2 and to give more patients data?
spk04: Sure. I think, A, very excited that the sites in Victoria 1 that we wanted to partner with in this study, the Victoria 2 study, wanted to. So we're essentially batting, I think, about 1,000 on that front. And we think, you know, that reflects their experience with GETA. And so that's encouraging to us. And then the new sites that will be participating are familiar with the data that we've presented for the Phase 1b. They also are very familiar with the unmet need and the importance of coming up with options for these patients. I think generally First-line patient studies are considered to be easier to enroll. There are more patients. They tend to have fewer comorbidities that could make them ineligible. And so we think our enrollment rate for Victoria 1 was very, very good relative to what has been reported for other studies. So we're very encouraged by that. We think it would be more likely than not that the enrollment rate for Victoria 2 would be at least as good or likely a little better than Victoria 1. So we'll see as we go, but we're on track to selecting the sites. We're on track to conducting the regulatory work that's required outside the U.S. so that we can get those sites activated and begin screening patients. and on track to being able to get our first patient by the second quarter. So, you know, so far, so good.
spk08: Thanks for the question, Brian.
spk09: You're welcome. Ladies and gentlemen, as a reminder, should you have any questions, please press the star key followed by the number one. There are no further questions at this time. Please proceed with closing remarks. Thank you.
spk04: Well, thank you very much for participating in our call today, for your ongoing support. We'll be participating at multiple upcoming investor conferences in November, and I look forward to interacting with many of you soon. I hope you have a great evening. Goodbye.
spk09: Ladies and gentlemen, this concludes the conference call for today. We thank you for participating and ask that you please disconnect your lines.
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