Capital Markets Day Transcript - CELC 2025-10-20

Operator

Hello, and thank you for standing by. My name is Bella, and I will be your conference operator today. At this time, I would like to welcome everyone to Phase 3 Victoria 1 Additional Results presentation. All lines have in place a mute to prevent any backward noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star, then the number one on your telephone keypad. To withdraw your question, press star 1 again. I would now like to turn the conference over to Brian Sullivan, CEO and co-founder of Sucuity. You may begin.

Brian Sullivan, CEO

Thank you for joining us. Dr. Igor Gorbachevsky, our chief medical officer, will also be joining us today. We're excited to discuss the detailed data that was presented over the weekend at the ESMO Congress in Berlin for the PIC3CA wild-type cohort of our Victoria I Phase III clinical trial. Well, let's now turn to slide two. Before we begin, though, I must point out that some of our comments today contain forward-looking statements that are subject to risks, uncertainties, and assumptions. In particular, our expectations around gaditolisib are uncertain and subject to change. Should our expectations fail to materialize or should our assumptions prove to be incorrect, actual company results could differ materially from these forward-looking statements. A description of these risks and uncertainties and assumptions is included in our SEC filings. Let's turn now to slide three. The PI3K-AKT mTOR pathway, which we'll refer to as the PAM pathway, is one of the most important oncogenic pathways. It plays an important role in a number of critical cell functions, including cell metabolism, cell growth, proliferation, and survival. And the PAM pathway also cross-regulates other oncogenic pathways and impacts immune-competent cells in the tumor microenvironment. Multiple studies have demonstrated that the PAM, estrogen receptor, and CDK4-6 pathways play important roles in promoting tumor cell proliferation. Additionally, they're interdependent drivers of HR-positive or 2-negative advanced breast cancer, and this process is not dependent on PIC3CA mutation status. To maximize the efficacy, the evidence suggests simultaneous blockade of all three pathways is very important it's especially important to provide complete blockade of the PAM pathway. Doing so prevents cross-activation of the PAM pathway when both the estrogen receptor and CDK4-6 pathways are inhibited. And it can also restore or enhance sensitivity to both endocrine therapy and CDK4-6 inhibitors. Because of the critical role in oncogenesis, the ability to interact and cross-regulate other oncogenic pathways, we believe that the PAM pathway represents one of the most important targets in oncology.

Apoorva Chaloori, Head of Investor Relations

Let's now turn to slide four.

Brian Sullivan, CEO

The challenge is that it's very hard to safely and efficaciously inhibit the PAM pathway. It has multiple components, each of which need to be inhibited to comprehensively blockade it. Otherwise, if only a single component is targeted, adaptive resistance arises and the pathway shutdown is limited. Further complicating the challenge of drugging this pathway is the narrow therapeutic window that exists. There is a graveyard of drugs attempting to inhibit all of these components that were not efficacious, too toxic, or both. The failures of these early-generation PAM inhibitors led drug developers to target single components of the pathway, such as PN3K alpha, AKT, or mTORP1, as a strategy to avoid toxicity. However, by compromising on the biological imperative that requires comprehensive blockade of the pathway, the resulting drugs have typically only demonstrated efficacy in patient populations that have pathway mutations. Now, as we initiated our development for gadotilicid, we hypothesized that the pathway's relevance to the cancer driver was not a function of the presence or absence of the mutation. This meant that an inhibitor that could comprehensively shut down the pathway could potentially be efficacious in patients lacking common mutations, such as PIK3CA. Our second hypothesis was that a highly potent drug that avoided overexposure in key organs, such as the liver and GI tract, and was only dosed three times a month, could potentially limit the incidence of the side effects associated with the pathway, such as hypoglycemia or diarrhea.

Apoorva Chaloori, Head of Investor Relations

Let's turn now to slide five.

Brian Sullivan, CEO

Gatitalisib's differentiated mechanism of action and pharmacokinetic profile as a comprehensive PAM inhibitor results in a highly potent therapeutic that is shown in non-clinical models that it can achieve effective pathway shutdown with low nanomolar concentrations of drug and tumor cell models with or without PIC3CA mutations. And this opens up the opportunity to address an important unmet need for improved therapeutic options for the 37,000 patients with HR-positive HER2-negative advanced breast cancer whose disease progressed on or after treatment with a CDK4-6 inhibitor. The need for better options for these patients makes, we believe, the results for the getotelicid triplet and doublet especially important. 76% and 67% reduction, respectively, in risk of disease progression or death, and the 7.3 and 5.4-month improvement, respectively, overfulvestrant for the getothelicib triplet and doublet were unprecedented. And with these results, we believe the getothelicib regimens have the potential to establish a new standard of care for these patients.

Apoorva Chaloori, Head of Investor Relations

Let's turn now to slide six.

Brian Sullivan, CEO

My pleasure now to introduce Dr. Igor Gorbachevsky, our chief medical officer. Igor will review the results that were presented on Saturday at the ESMO Congress in Berlin.

Igor Gorbachevsky, Other

Thank you, Brian. Let's turn now to slide seven.

Igor Gorbachevsky, Other

Victoria 1 is a randomized open-label global phase 3 study in patients with hormone-positive HER2-negative advanced breast cancer. Victoria 1 study included patients with both PIC3CA mutation positive and wild-type disease. Today, we will be focusing on study design and review of the results that were presented for patients with PIC3CA wild-type disease. Main eligibility criteria included both men and women and patients who had disease progression on or after treatment with CDK4-6 inhibitor in combination with non-steroidal ermitase inhibitor. Up to two lines of hormonal therapy was allowed. Prior treatment with agents targeting PAMP pathways was prohibited as well as prior chemotherapy for advanced breast cancer. However, treatment with chemotherapy in neoadjuvant or adjuvant setting was allowed. Patient must have had measurable disease according to received criteria, and patient with endocrine-resistant therapy was also eligible for this study. In the end, 392 patients were randomized in an equal manner, 1 to 1 to 1, to receive therapy in two study arms and one control arm. Patient received standard doses of palvocyclib and fulvestrant. Giditalisic was given at 180 mg intravenously over short infusion period on days 1, 8, and 15. This intermediate schedule, three weeks on and one weeks off, provides, in essence, two weeks of therapy for patients. One patient can take time off between day 15 and 29 when the next cycle of treatment starts. In arm A, patient received triplet regimen of gated elicit combined with palbacyclob and fulvestrant. And in arm B, patient received doublet regimen where gated elicit was combined with fulvestrant. In a control arm C, patient received standard treatment fulvestrant. The primary objective of this study was efficacy, which was assessed by comparing median progression-free survival between two treatment arms and control, arm A versus arm C and arm B versus arm C. Patients who were assigned to arm A or arm B received prophylaxis therapy with mouthwash based on steroid water-based prophylaxis therapy, and prophylaxis non-sedating antihistamine treatment was recommended but not mandated in this study.

Apoorva Chaloori, Head of Investor Relations

Let's turn now to slide 8. 392 patients were endomized in this study.

Igor Gorbachevsky, Other

Most patients in the gitatelisib treatment arms received allocated therapy. Eight patients who were assigned to receive full vestron therapy did not receive it. And 95% of patients in a control arm who received full vestron ultimately discontinued treatment due to disease progression. Radiologic disease progression was less common in Gatitalisib treatment arms. A small number of patients in each Gatitalisib group discontinued study due to one or more adverse events that were assessed by investigators to be related to any of the treatment regimen.

Apoorva Chaloori, Head of Investor Relations

Let's now turn to slide 9.

Igor Gorbachevsky, Other

Demographics and baseline characteristics of patients were generally well-balanced between all three treatment arms. All patients had advanced disease. 100% of patients who were enrolled in the study had stage 4 disease, with 80% of patients having liver and lung metastasis. Additionally, patients who received less than six months of benefits on their prior endocrine therapy were eligible and accounted to 15% of patients enrolled in this study. This patient often referred as endocrine therapy resistant and often excluded from studies evaluated in recent studies with SIRDS treatment. As expected, more patients in each arm received ribocyclob than either palbocyclob or abemocyclob a day prior CDK4-6 inhibitor.

Apoorva Chaloori, Head of Investor Relations

Let's now turn to slide 10.

Igor Gorbachevsky, Other

As we have previously announced, the gated elicit triplet regimen produces statistically significant and clinically meaningful improvement of 7.3 months in median progression-free survival over results achieved with the standards of care fulvestrant. So the triplet regimen, medium progression for survival was 9.3 months, which results in hazard ratio of 0.24, meaning that we saw 76% reduction in the risk of disease progression or death. This level of efficacy has not been seen before in patients who were previously treated with CDK4-6 inhibitor. Unlike in most other trial settings, the initial steep drop in PFS curves that results from rapid early disease progression appears have to be attenuated in this study as you can see in the Kaplan-Meier curve. The median progression-free survival of two months for fulvestrant arm is similar to that has been reported in multitudes of recently randomized phase 3 studies. The illicit doublet regimen also produced a statistically significant and clinically meaningful improvement of 5.4 months over standard of care for Vestrant. The hazard ratio was 0.33, which means we saw 67% reduction in the risk of disease progression or death. And again, this level of efficacy has not been previously reported in patients who have been treated with cell cycle inhibitor.

Igor Gorbachevsky, Other

Let's turn to slide 11.

Igor Gorbachevsky, Other

Subgroup analysis demonstrates that the clinical benefit of triplet was maintained across all subgroups that were predefined for analysis. All hazard pressure were less than one, and none of the confidence intervals overlapped one. Notably, for the patient who were enrolled in the United States and Canada, median progression-free survival was 19.3 months. Forget it, a list of triplets, and as you will see later, 14.9 months, forget it, a list of doublet regimen. Additionally, efficacy was observed regardless of which prior cell cycle inhibitor was used for treatment of this patient. Patients who received prior palbocyclic benefited as much or more than those who had prior ribocyclic or democyclic. This is the first time when randomized phase 3 study, the data shows the benefits of retreatment with palbocyclic.

Apoorva Chaloori, Head of Investor Relations

Let's now turn to slide 12.

Igor Gorbachevsky, Other

People are finding are seen for the solicit doublet regimen, comparing this combination with standards of careful vestment. All point estimates for hazard ratio were less than one. However, the upper limit of confidence interval includes one in a several characteristic group, most notably for those patients whose disease progression occurred within first six months of treatment on their most recent therapy before including on stagging.

Apoorva Chaloori, Head of Investor Relations

Let's turn to slide 13.

Igor Gorbachevsky, Other

When we compare triplet regimen and doublet regimen results for different subgroups of patients, there are several that show differences in median progression-free survival and hazard ratio comparing these two regimens. For example, It includes patients in pre- and perimenopausal status, where median progression for survival for triplet regimens was 11.1 months and 5.6 months for doublet regimens, and resulting in hazard ratio of 0.13 for triplet and 0.33 for doublet. For patients who were enrolled in North America, United States, and Canada, median progression for survival was 19.3 months for triplet and 14.9 months for doublet regimen with hazard ratio being 0.13 and 0.35 respectively. Those patients who had visceral metastasis at the beginning of the steady median progression-free survival was 10.7 months for the triplet regimen and 7.3 months for the doublet, with hazard ratio reflected in 0.21 for triplet and 0.3 for doublet regimen. In those patients who had disease progression occurred within first six months of treatment on immediate prior therapy before inclusion in the study, median progression-free survival was 7.4 months for triplet regimen and 5.6 months for doublet regimen, which resulted in hazard ratio of 0.24 for triplet and 0.98 for doublet. Those patients who received palbocyclib as their prior treatment, median progression-free survival was 16.6 months for triplet regimen and 7.6 months for the doublet, which resulted in hazard ratio of 0.21 for the triplet and 0.39 for the doublet. Well, definitive conclusion cannot be drawn from a subgroup analysis. These results may reflect the contribution of CDK4-6 inhibitor in palbocyclic containing triplet regimen compared to the doublet, providing additional clinical benefits in certain patient subgroups who may have more difficult to treat disease.

Igor Gorbachevsky, Other

Let's turn to slide 14.

Igor Gorbachevsky, Other

Cognitive trends for both the triplet and doublet regimens were seen in the interim overall survival analysis. However, the data is immature with only 67 patients or 48% of a pre-specified 140 events occurring at this time. These results are especially encouraging since the analysis includes 63 patients who crossed over from a control arm of Fulvestrand to receive therapy with either triplet or doublet regimen. 80% of patients received triplet regimen and the rest of patients received doublet of those who crossed over.

Igor Gorbachevsky, Other

Let's turn to slide 15.

Igor Gorbachevsky, Other

When we censored the time of crossover, those patients who received treatment with gaditalisib, the raw survival curves have even greater separation, with a trend towards significance in the interim analysis in both gaditalisib treatment arms.

Apoorva Chaloori, Head of Investor Relations

Let's turn to slide 16.

Igor Gorbachevsky, Other

Further assessment of efficacy with the objective response rate for the gaditalisib triplet was 32% compared to 1% for control with fulvestrant, and the median duration of response was close to 18 months, exactly 17 and a half months for triplet regimen. The gated elicit doublet regimen response rate was 28.3%, and the median duration of response was 12 months. The medium duration of response and incremental improvement relative to the control for gaditalisib triplet and doublet regimen are the highest reported for the endocrine-based treatment regimen in a second-line patient with hormone-positive HER2-negative advanced breast cancer.

Apoorva Chaloori, Head of Investor Relations

Let's turn to slide 17.

Igor Gorbachevsky, Other

The gaditalisib triplet and doublet regimen were generally well-tolerated in this trial. and resulted in discontinuation of study treatment due to treatment-related adverse events in a very few patients, 2.3 patients in a triplet regimen and 3.1 patients in the doublet regimen group compared to 0% of patients in a control arm. Safety profiles were generally consistent with individual agents with no new safety signal observed in this study. Most of patients experience adverse events of very low grade one and two severity, and few experience grade three adverse events, except of the patient who experienced hematitis neutropenia. Grade four adverse events only included neutropenia, which is associated with treatment with pulbocyclic. It is important to know that there was no increase in number of neutropenic adverse events with the gadget illicit triplet regimen compared to historical data for pulbocyclic combination with fulvestrant. There was a very minimal changes in neutrophil levels for patients in a doublet regimen, only 2% of patients, which confirmed further previously reported data that gadget illicit it does not induce neutropenia. All grade hyperglycemia levels were low with 9.2 percent observed in triplet regimen and 11.5 percent in a doublet regimen with all grade diarrhea of 16.9 percent in a triplet and 12.3 percent in a doublet regimen also was low and majority of those advance where of a low grade. And each of these results are quite unexpected for drugs that target PAM pathway.

Igor Gorbachevsky, Other

Let's turn to slides 18.

Igor Gorbachevsky, Other

In conclusion, this finding validates further the PAM pathway as a molecular driver in even in a patient with PIC3CA wild type disease and support comprehensive PAM blockades with gadotelisib-based therapy as a potentially new standard of care for patients with advanced breast cancer.

Apoorva Chaloori, Head of Investor Relations

Thank you, and I turn back to you, Brian. Thank you, Igor. Let's turn now to slide 19.

Brian Sullivan, CEO

Gadotelisib is addressing a significant unmet need for patients who have progressed on a prior CDK4-6 inhibitor. This is a significant patient group. We estimate there are roughly 37,000 patients who move on to second-line treatment after they've received treatment with a CDK4-6 inhibitor, and roughly 60 percent of them are PIK3CA wild type, and this is a very large opportunity. And there's also a very real and very important need here. Current second-line treatments for these patients are limited in terms of added progression-free survival benefit, and our market research shows that oncologists are hungry for options that are more effective and have a safety profile they can manage. And with such a large, underserved market, we see a chance to build a strong presence for cell acuity. In light of the clinical benefit offered by the gadatilisib triplet and doublet, we're well positioned to address critical needs in this space. And a couple quick points on market dynamics. Ivy-administered drugs like gadatilisib fall under the medical benefit category, which means a typically smoother reimbursement process compared to oral drugs under pharmacy benefits, where payers tend to manage claims more heavily. Additionally, unlike oral drugs, IV therapies offer the opportunity for practices to recover costs, which is particularly important in the community setting. And finally, breast cancer community is active, engaged, and well supported by patient advocacy groups, which will help create awareness for new treatments such as get it to listen. Based on our projections, this patient population represents a potential $5 billion addressable market.

Apoorva Chaloori, Head of Investor Relations

Let's turn now to slide 20.

Brian Sullivan, CEO

We have three important milestones coming up. First, we expect to submit a new drug application for the Victoria 1 PIC3CA wild type cohort indication this quarter. As we've previously disclosed, the FDA approved our application to the Real-Time Oncology Review Program, and this program allows sponsors to submit data on a rolling basis so that the FDA can begin its review more quickly. We've already provided two pre-submissions to the FDA, and we expect to complete our NDA submission this quarter. Second, we expect to present additional data at a major medical conference later this year. And third, we hope to report top-line data for the Victoria 1 PIC3CA mutation cohort by late Q1 or Q2 2026.

Apoorva Chaloori, Head of Investor Relations

Let's now turn to slide 21.

Brian Sullivan, CEO

As we started getting ready to report results from the PIC3CA mutant cohort of the Victoria 1 trial, we analyzed data from patients who were treated with the same drug regimen evaluated in the Victoria 1 study, gadatilisib combined with fulvestrin and polycyclics. This included a total of 90 patients from Escalation Arm B and Expansion Arms B, C, and D of our Phase I-B study. Patients in Escalation Arm B and Expansion Arms B and C received a 180-milligram dose of gadatilisib once weekly, while patients in Expansion Arm D received the same dose of gadatilisib, but only on days 1, 8, and 15 of a four-week cycle, which was the same intermittent dose regimen patients in the Victoria I study received. Overall, 72% of these patients had received prior treatment with a CDK4-6 inhibitor, and 71% received a weekly versus intermittent dose of gaditalisid. For all patients with PIC3CA mutant tumors, median PFS was 14.6 months, and the objective response rate, or OOR, in response-evaluable patients was 48%. Median PFS was 19.7 months, and the OOR was 64% in patients with PIC3CA mutant tumors who received the intermittent dose of getotilicin. For all patients with PIC3CA wild-type tumors, median PFS was 9 months, and the objective response rate in response-evaluable patients was 41%. For patients with PIC3CA wild-type tumors who received the intermittent dose of gadethylisib, median PFS was 9.1 months, and the OOR was 53%. We're very encouraged by the median PFS of 14.6 months found in the entire PIC3CA mutant subgroup, particularly given the high proportion of patients who received gadethylisib weekly, which we believe is a less effective dose schedule than the intermittent schedule. And while the sample size is small, median PFS from patients whose tumors had PIC3CA mutations and who received the Phase III intermittent get at the list of dose is promising and consistent with the results from the overall group, and we're looking forward to reporting Phase III data for this patient subgroup in 2026. If we report positive results in the PIC3CA cohort, as we hope, we believe we'll be well positioned to offer an all-comer therapeutic option that oncologists can consider for patients independent of the PIC3CA, ESR1, or diabetic status. And And given the importance of the PAM pathway and the breadth of patients getothelicib can potentially treat, getothelicib has the potential to become the new backbone drug required to optimize outcomes for patients. And this will position us well as we consider additional clinical development opportunities, such as combinations with oral SIRS and indications in earlier lines of therapy. Let's now turn to slide 22. Well, that ends the presentation portion of our day. Let's now turn to the Q&A session.

Operator

At this time, I would like to remind everyone in order to ask a question, press start, then the number one on your telephone keypad. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Murray Raycroft with Jefferies. Your line is now open. Please go ahead.

Murray Raycroft, Analyst — Jefferies

Hi, congrats on the update and thanks for taking my question. I was going to ask one on just the hyperglycemia. So, in the phase three, you're showing a lower rate than in the phase one B study. What do you think accounts for this difference? And we're wondering if the two studies use the same protocol and grading criteria.

Brian Sullivan, CEO

No, thanks for the question, Murray. They did use the same criteria, you know, same criteria used to evaluate diabetes and any changes in glucose. As far as the reason for the difference, it really is hard to say. I mean, this is a larger study, so I think you place more weight on the results from this study. You know, it's a global study, so potentially you had fewer patients that may have been obese or, you know, had glucose issues, which are, you know, obviously associated with many patients in the U.S. But other than that, I don't think we can pinpoint a specific reason for the results we showed for diabetes, or rather for hyperglycemia in the study.

Murray Raycroft, Analyst — Jefferies

Got it. Okay. And then I'll ask one more and then hop back in the queue. There was a lot of discussion around Roche's Everett data before ESMO. Now that we've seen the data, how do you think physicians would potentially use their regimen versus your regimen? Maybe if you can just comment on that.

Brian Sullivan, CEO

Well, I think the data showed that the drug was effective in patients who had ESR1 mutations and that the drug didn't add a benefit relative to its control in patients who lacked those mutations. And so, you know, based on that data, I would say that that drug will be an option that physicians consider. I think a lot of these physicians will have experience treating patients with everolimus, and they'll be familiar with that profile. I think the patients that that regimen would address, which would be patients who are ESR1 mutant, PIC3CA wild type, who are endocrine sensitive, comprises, you know, roughly 15% of the total patient population. And the reason, you know, why we think that is the population that that drug would be mostly limited to, just is based on, I guess, our belief that we'll show favorable results in the PIC3CA mutant pathway that would exceed those reported here. And then in the ESR-1 wild-type patients, we think our regimen is clearly differentiated results relative to those therapies. And so, even with this regimen there, which is great, it's another option for patients, we think, you know, we have the opportunity because we can, we think, more effectively address the needs of patients, roughly 85% of patients. We think, you know, we have the opportunity to become the go-to option for all these patients because we offer comparable efficacy in that small subgroup as the other regimen. But we think the familiarity and the experience that doctors will gain working with our regimen for the great bulk of their patients will, we would believe, likely lead them to rely on this regimen for all or for most of their patients.

Murray Raycroft, Analyst — Jefferies

Yeah. Thanks for taking my questions.

Apoorva Chaloori, Head of Investor Relations

You're welcome.

Operator

Your next question comes from the line of Tara Bancroft with T.D. Cowan. Please go ahead.

Tara Bancroft, Analyst — TD Cowen

Hi. Good morning. And congrats on the great data and the great feature at the conference. So my question, I guess, is if you could maybe elaborate a little bit more on the stomatitis events that you're seeing, like the timing of them, time to resolution, and, you know, I think with such a low discontinuation rate, I mean, it clearly suggests that it's not limited. I'm curious to hear also how it's managed and if it resolves while the patient stays on therapy and maybe, or if it necessitates some kind of dose reduction, anything along those lines. Thank you.

Brian Sullivan, CEO

Thanks, Sarah. So, we'll be reporting out more details on, you know, kind of safety profile of GATT at a future medical conference, including stomatitis. But in the meantime, we can say that we were a little surprised, to be frank, by the grade three stomatitis. We did expect it to be lower based on some results from prior studies. It's hard for us at this point to pinpoint the reason for that, although we think probably the leading contender for that would be potentially a lack of compliance up front with patients using the regimen. One disadvantage with our regimen for patients using a prophylaxis is, unlike with an oral drug that they might be using every day, there's not a daily reminder to use that prophylaxis. However, based on the analysis we did in our Phase 1b study, we found that even patients who, most of those patients didn't receive any prophylaxis, But the dexamethasone mouth wrench, which is used to treat stomatitis, was found to be effective in reversing stomatitis, again, which is, we think, one of the reasons why patients are able to stay on therapy even with that incidence of stomatitis, because ultimately, it resolves to a lower grade that allows them to stay on the treatment. We also think because GEDA is only dosed three times a month and only exposing patients to a CMAX concentration of drug, you know, three times during that month, that the general incident will be potentially less severe during the dosing window because essentially the GEDA's alicit concentration is reduced substantially over that dosing window, it stays well above the ICA level needed for target engagement. And so we think the average dose level the patient is exposed to throughout the treatment cycle is lower and less likely, you know, to initiate or to aggravate adverse events. And so that while estomatitis manifests, we think it's treatable and reversible. But we also think the general level of aggravation is one way to characterize it. the hematitis may expose the patient to, somewhat self-resolves because of the lower concentration the patient sees during, for the most part, throughout the treatment period.

Apoorva Chaloori, Head of Investor Relations

Great. Thank you so much, Brian.

Igor Gorbachevsky, Other

You're welcome.

Operator

Your next question comes from the line of Andrew Behrens with Lebrank Partners. Please go ahead.

Andrew Berens, Analyst — Leerink Partners

Thanks. Congrats on the results and execution, Brian. Thank you. A couple of questions. I was wondering if you could comment on the agency's preference for BICR in an open label trial. And if you think Avera's use of local reads for their primary endpoint could become a regulatory issue for them. And then another one on the stomatitis. One thing we noticed was it seems like the rate was higher with the triplet in this trial versus the doublet and also higher than that seen in the prostate trial. I'm wondering if this is something that's magnified by the CDK 4.6 or choice of combination partner. And then just a question on the IP, because I've gotten a lot of questions on it from investors. Just can you run through what you currently have for GEDA and what potential strategies you're using to extend the runway?

Brian Sullivan, CEO

Okay. Thanks, Andy. So the first question relates to BICR, Blinded Independent Central Review. It's the guidance of the FDA as well as the European Medicine Agency that studies that are open label, where the investigators and physicians know what therapy they're prescribing or they're treating their patients with, should use a blinded reviewers of the scans to limit or eliminate the potential bias that could accrue to investigators who know which treatment they're providing. And so with a blinded independent review, you eliminate that bias, which obviously is why the FDA and EMA look for that. It is surprising to us when there are open-label studies that use investigator-assessed PFS. Based on our interactions with the agency, you know, we receive very, very, I guess, firm recommendations that we use blinded independent central review. So, I can't explain what other sponsors do or what their rationale was, but I do know that, you know, we followed the agency's recommendations. Regarding stomatitis and being higher in the triplet and doublet, and we do think there is some stomatitis that accrues to polycyclic. If you look at their Phase III studies, Paloma II and III, you see that there is some incidence of stomatitis. So, that's probably one area where there's a bit of an overlap of adverse events between Geta and Palo. It is interesting. You pointed out the results we reported in prostate cancer, where there was very little stomatitis overall. And so, we think that there seems to be some greater sensitivity for women with breast cancer than there is for men with prostate cancer, which, again, is at this time hard for us to explain. One further follow-up to the question that Tara asked regarding stomatitis. But I would say one of the reasons why we were surprised by the somatitis results is that we didn't hear much commentary from investigators throughout the course of the study. And, again, we've been working with investigators for over two years now, treating patients, and our medical team regularly interacts with physicians, you know, providing follow-up and questions. And we just did not hear very much about somatitis at all. And so, again, over the course of a study, you get exposed to questions about safety or how to mitigate adverse prevention. And really, there just was not much dialogue on that. So that somewhat is consistent with what we observed in the Phase I-B, which is that just the overall pharmacokinetic profile of GATA results in maybe a less difficult to or easier to manage, I guess, type of stomatitis or incidence of stomatitis than maybe the case with drugs that are prescribed on a daily basis, such as an oral drug where you're hitting CMAX every day. I guess, and finally, the third question you asked regarding intellectual property. So, we have a series of three patent families that we think will ultimately help extend exclusive period for GETA to sometime in 2042. The first layer of protection for exclusivity relates to our API patent and the drug substance product patent. And that patent will provide exclusivity through the end of 2034. We have a composition of matter patent related to our dosing formulation, or rather our drug formulation. And that involves a functional excipient, which essentially is what's required to ensure stability of the drug, and so it's not substitutable. Essentially, a functional excipient performs a role that's required to achieve, you know, the necessary parameters for it to be reliably produced and used in the clinic. And so, that patent will expire sometime in 2041. And then we also received earlier this year a patent for the dosing schedule that we used in this trial, three weeks on, one week off. And that schedule will be incorporated on the label, and, you know, that patent would be included in the orange book. And so, we think that patent will serve to prevent the agency from granting approval to any ANDA submission as a result. You know, essentially, these dosing patents are very strong and really serve as effective barriers to generics coming in. And so, you know, a combination of those patents, as well as other work that we're doing that could further extend the exclusive period, you know, give us confident that we have a very long runway, at least until 2042, to develop the gaditolicib for additional indications.

Andrew Berens, Analyst — Leerink Partners

Does the extra work that you're mentioning, does that potentially include a subcutaneous version?

Brian Sullivan, CEO

We're working on a lot of different things that we think will have the opportunity to, you know, improve the ability of Ganatolicit to provide a benefit to patients. And if we're successful in launching those, then, you know, that we think one of the results would be that we would extend the exclusive period as well.

Andrew Berens, Analyst — Leerink Partners

Great.

Apoorva Chaloori, Head of Investor Relations

Thanks for taking all the questions, and congrats to God. Thanks.

Operator

Your next question comes from the line of Brad Canino with Guggenheim Securities. Please go ahead.

Rosie, Analyst — Guggenheim Securities

Hey, good morning. This is Rosie on for Brad. Congrats on all the ESMO updates, and thanks for taking our questions. So just regarding the observed positive OS trend for Victoria 1 at the interim analysis, how have you designed the study to ensure that it has the ability to demonstrate statistical significance with more mature follow-up? And then what is the competitive sense of reaching our outcome in a streaming setting?

Brian Sullivan, CEO

You know, you were fading a little in and out. Could you just maybe repeat a bit about your question regarding the overall survival data?

Rosie, Analyst — Guggenheim Securities

Oh, sorry. I guess regarding the positive OS trend, how have you designed the study to ensure that it has the ability to demonstrate that SIG with more mature follow-up, and what is the competitive significance of that breaching outcome in a stream and setting?

Brian Sullivan, CEO

Sure. Okay. So the primary endpoints were PFS, And the FDA requires a time of primary analysis that you do an interim look at overall survival to confirm or rather to determine whether there's any decrement to a patient's overall survival. One of the thresholds that they make very clear you need to not trip is showing any decrease in likelihood of survival for patients on the study therapy. We showed in this interim analysis, you know, a very favorable trend. I mean, obviously, it's immature, and so, you know, not going to achieve statistical significance. We're also encouraged by the, you know, sensitivity analysis that excluded the patient, censored patients who had crossed over. And so, you know, again, with overall survival analysis in these second-line studies, you haven't seen before positive OS data. You've seen favorable trends. One of the challenges to getting reaching a statistical significance is that the number of events and the size of the studies in the second-line setting of breast cancer tend to be smaller. And so the delta needed to show survival between the study arm and control arms needs to be bigger as a result. not, you know, and so it's more of a statistical hurdle, not necessarily a therapeutic hurdle. But one strategy that we did employ, though, to maximize the chance of potentially achieving statistical significance is that we had a statistical design that analyzed all the endpoints in a hierarchical manner. And the reason for that is that by testing and then only proceeding to the next analysis upon positive achievement of the endpoint in the prior analysis, you preserve your alpha. And so the benefit of that then with the results that we've reported is that we'll have the full alpha available when the final overall survival analysis is performed, which we estimate would be sometime in early 2027.

Igor Gorbachevsky, Other

Thanks so much.

Operator

Your next question comes from the line of Steven D. Wiley with STIFL. Please go ahead.

Steven Willey, Analyst — Stifel

Yeah, good afternoon. Thanks for taking the questions and apologize for going back on those. Congrats on that.

Brian Sullivan, CEO

That's okay. Okay.

Steven Willey, Analyst — Stifel

I was just curious. I know Igor kind of spoke to him in his review of the data, but just curious if you have any thoughts or hypotheses around what appears to be preferential activity of getta occurring in patients post-palbo. I think you see them in the triplet, you see them in Dublin. I think the inverse is true for Ebena. I'm just curious if you think that that's a byproduct of the CDK4-6 inhibitor itself. Is that a byproduct of just where these drugs are being used geographically in the site environment? I'm just curious if you have any thoughts there. I mean, just have a quick follow-up.

Brian Sullivan, CEO

Right. Well, I think it's hard to piece out the difference there. I mean, I think we can, you know, look at different patient characteristics. It's unlikely in a randomized study that we would see much difference in these patient characteristics unless we're starting physicians targeting treatment with palbociclib for different patients in a way that may be different than the population that received ribo, but we think that's unlikely. I would point out that the hazard ratio for both ribo and palbo, 0.22 and 0.21 were very similar. I think, you know, the median PFS was much higher with palbo. And again, that can, you know, potentially just be a bit of a statistical quirk because you're dealing with a smaller subgroup of data. I think the main takeaway is that I think, you know, there hasn't been before any data that has shown you can retreat patients with palbo with a different endocrine therapy and induce a benefit. And so, what this data kind of confirms is that there's a general role that the CDK4-6 pathway continues to play despite the patient's progression while they were on CDK4-6. Essentially, the tumor seems to adapt to reliance on other pathways. And so, that by blockading the PAM pathway and continuing to blockade the ER pathway, You know, our non-clinical model suggests that that reactivates the CDK4-6 pathway and thus resensitizes patients to CDK4-6 inhibitors. And this data suggests that it's a class effect. It doesn't really matter which CDK4-6 inhibitor patients will have received. Now, I suppose the caveat would be abemociclib, although the treatment, you know, the hazard ratio for abemociclib was still very, very good. I forget the number off the top of my head, but it's still very, very favorable relative to what's been reported previously. I think those results tend to be consistent with other drugs that follow a BEMA. There seems to be some difference in how patients who've received a BEMA respond to subsequent therapy compared to ribo and palo. And I'm not sure that that is something that we can readily explain.

Steven Willey, Analyst — Stifel

And then maybe just a follow-up on the prostate trial. I think it was noted that there's an intention to act in the protocol. I'm just curious as to, you know, I guess, A, what you're trying to achieve, and B, you know, whether or not the PSA data that you may or may not have seen from that trial seems to suggest that there is indeed a dose-dependent effect. I think there was a little bit of a step down in radiographic PFS with a higher dose of small patients who are just populating their cap strategy. And you're confident.

Brian Sullivan, CEO

Well, I think that's a great question. That's a question we're asking ourselves, in that how do we best identify the most appropriate dose? And so, on the one hand, you know, the number said that the lower dose did better than the higher dose. Small sample numbers, sample sizes. And so, you want to be careful about drawing too firm a conclusion. Given how well tolerated the combination was in these patients, you know, almost no diarrhea, hypoglycemia, stomatitis, you know, we felt that it was important to explore higher doses. because, you know, essentially when you're going into a new tumor type, you can't make assumptions that, you know, how patients respond or the dosing will be recapitulated in, you know, prostate in this case versus breast cancer. Clearly, there seems to be a different response to get from an AE standpoint for the men in prostate than the women in breast. Additionally, you know, prostate cancer presents mostly as bone-only disease. only roughly 20% of patients have any form of visceral metastases, which is the inverse of breast cancer, where most of these patients have some form of visceral disease. They may have a fair amount of bone disease participating, but there's infrequent, probably 20% of women who only have bone-only disease, no visceral mass. And so, because of that different presentation, we, again, want to make sure we fully analyze or are in a position to analyze the potential relationship of dose to response. And so, going to a higher dose, you know, would potentially allow us to tease out whether there is a dose response or not. We don't want to make a decision just on the basis of the two arms we evaluated, and, you know, in drug development, the last thing we want to do is go to a phase three with a suboptimal dose. And so, we just concluded that it's really important to make sure we step back, answer some questions now, you know, before you get to the phase three, and really be confident that we have a valid data set to support selection of what we hope, depending on the results, would be the dose used in a phase three study.

Steven Willey, Analyst — Stifel

You're welcome. Thanks.

Operator

Your last question comes from the light of Gilblom with Needham & Co. Please go ahead.

Gil Blum, Analyst — Needham and Co

Good morning, and thanks for squeezing me in. Allow me to also have my congratulations on the results. Maybe going back to the Roche data, just what do you think would be required, assuming there would be changes to the standard of care with the addition of oral SIRDS? Currently, all the studies are against fulvestrant. Would you think any additional studies would be required for slotting here, or this would be label dependent? Thank you.

Brian Sullivan, CEO

Hey, Gil, I'm not sure I quite understood the question. Are you asking me for a general comment on SIRDS, or are you asking a question as it relates to Getatelisib?

Gil Blum, Analyst — Needham and Co

As it relates to Getatelisib and the changes in, potential changes in the standard of care, does it relate to oral SIRDS?

Brian Sullivan, CEO

Okay. Well, you know, we think the data that we have will support registration. There's not going to be a look back on what therapies were used in the study. As far as going forward, you know, there's a bit of a to-be-determined aspect of this. On the one hand, you know, it's always important to demonstrate that a drug like GEDA can be safely combined with, you know, the various CERDs. So that would be one step to take just to ensure that physicians wanted to consider use of one oral CERD and combined with GEDA that, you know, they had data. They would need data to confirmed that it was safe for their patients for that to occur. And as far as the regulatory strategy and how to incorporate a CERD into a ghetto regimen, yeah, there's some complexity around that, and we're obviously still thinking that through. You know, with our Phase III data in wild type, you know, we want to see what we see in mutant. I mean, we feel confident about that, but, you know, until you get the data, you don't know. And that will allow us to more fulsomely understand how to think about the opportunity to, you know, do some work with oral surge and potentially create additional options for patients.

Gil Blum, Analyst — Needham and Co

Great. And as it relates to the additional data disclosures from the Victoria 1 study, would the proportion of ESR1 mutant patients be disclosed at some point or at a later stage?

Brian Sullivan, CEO

Thank you. So, we'll be reporting, you know, additional data, and those types of subgroup analyses are on the list.

Gil Blum, Analyst — Needham and Co

And congrats again.

Apoorva Chaloori, Head of Investor Relations

Thanks a lot.

Operator

That concludes our Q&A session. I will now turn the call back over to Brian Sullivan, CEO and co-founder of CellQuity, for closing remarks.

Brian Sullivan, CEO

Well, thank you for joining us today, and we appreciate your interest in CellQuity, and I look forward to speaking with everyone at some point in the future. Take care. Goodbye.

Operator

Ladies and gentlemen, thank you all for joining, and you may now disconnect. Everyone have a great day.