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 III VIKTORIA-1 Additional Results Presentation. All lines have been placed on mute to prevent any background 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 one again. I would now like to turn the conference over to Brian Sullivan, CEO and co-founder of Celcuity. You may begin.
Good morning. Thank you for joining us. Dr. Igor Gorbatchevsky, 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 PIK3CA wild type cohort of our VIKTORIA-1 phase III clinical trial. 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 gedatolisib 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. The PAM pathway also cross-regulates other oncogenic pathways and impacts immune competent cells and 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, HER2 negative advanced breast cancer, and this process is not dependent on PIK3CA 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. Let's now turn to slide four. The challenge is that it's very hard to safely and efficaciously inhibit the PAM pathway. It has multiple components, each of which needs 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 PI3K-alpha, AKT, or mTORC1, 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 gedatolisib, we hypothesized that the pathway's relevance as a cancer driver was not a function of the presence or absence of a 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 hyperglycemia or diarrhea. Let's turn now to slide five. Gedatolisib'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 can achieve effective pathway shutdown with low nanomolar concentrations of drug in tumor cell models with or without PIK3CA mutations. 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 gedatolisib triplet and doublet especially important. The 76% and 67% reduction, respectively, in risk of disease progression or death and the 7.3 and 5.4 month improvement, respectively, over fulvestrant for the gedatolisib triplet and doublet were unprecedented. With these results, we believe the gedatolisib regimens have the potential to establish a new standard of care for these patients. Let's turn now to slide six. My pleasure now to introduce Dr. Igor Gorbatchevsky, our Chief Medical Officer. Igor will review the results that were presented on Saturday at the ESMO Congress in Berlin.
Thank you, Brian. Let's turn now to slide seven. VIKTORIA-1 is a randomized open-label global phase III study in patients with hormone receptor (HR) positive, HER2 negative advanced breast cancer. VIKTORIA-1 study included patients with both PIK3CA mutant and wild type disease. Today, we will be focusing on study design and review of the results that were presented for patients with PIK3CA wild type disease. Main eligibility criteria included both men and women and patients who had disease progression on or after treatment with a CDK4/6 inhibitor in combination with a non-steroidal aromatase inhibitor. Up to two lines of hormonal therapy were allowed. Prior treatment with agents targeting PAM pathways was prohibited, as well as prior chemotherapy for advanced breast cancer. However, treatment with chemotherapy in neoadjuvant or adjuvant setting was allowed.
Patients must have had measurable disease according to RECIST criteria, and patients with endocrine resistant therapy were also eligible for this study. In the end, 392 patients were randomized in an equal manner, 1:1:1, to receive therapy in two study arms and one control arm. Patients received standard doses of palbociclib and fulvestrant. Gedatolisib was given at 180 mg intravenously over a short infusion period on days 1, 8, and 15. This intermittent schedule, three weeks on and one week off, provides, in essence, two weeks off therapy for patients when patients can take time off between day 15 and 29 when the next cycle of treatment starts. In arm A, patients received triplet regimens of gedatolisib combined with palbociclib and fulvestrant. In arm B, patients received doublet regimens where gedatolisib was combined with fulvestrant. In a control arm C, patients received standard treatment fulvestrant.
The primary objective of this study was efficacy, which was assessed by comparing median progression-free survival (PFS) 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 prophylactic therapy with mouthwash based on steroid water-based prophylactic therapy, and prophylactic non-sedating antihistamine treatment was recommended, but not mandated in this study. Let's turn now to slide eight. 392 patients were randomized in this study. Most patients in the gedatolisib treatment arms received allocated therapy. Eight patients who were assigned to receive fulvestrant therapy did not receive it. 95% of patients in a control arm who received fulvestrant ultimately discontinued treatment due to disease progression. Radiologic disease progression was less common in gedatolisib treatment arms.
A small number of patients in each gedatolisib group discontinued study due to one or more adverse events that were assessed by investigators to be related to any of the treatment regimens. Let's now turn to slide nine. 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 this study had stage four disease, with 80% of patients having liver and lung metastases. Additionally, patients who received less than six months of benefit on their prior endocrine therapy were eligible and accounted for 15% of patients enrolled in this study. These patients are often referred to as endocrine therapy resistant and often excluded from studies evaluated in recent studies with third treatment. As expected, more patients in each arm received ribociclib than either palbociclib or abemaciclib as their prior CDK4/6 inhibitor.
Let's now turn to slide 10. As we have previously announced, the gedatolisib triplet regimen produced a statistically significant and clinically meaningful improvement of 7.3 months in median progression-free survival over results achieved with the standard of care fulvestrant. For the triplet regimen, median progression-free survival was 9.3 months, which results in a hazard ratio of 0.24, meaning that we saw a 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 a CDK4/6 inhibitor. Unlike in most other trial settings, the initial steep drop in PFS curves that result from rapid early disease progression appears to 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 the fulvestrant arm is similar to that that has been reported in a multitude of recently randomized phase III studies. The gedatolisib doublet regimen also produced a statistically significant and clinically meaningful improvement of 5.4 months over standard of care fulvestrant. The hazard ratio was 0.33, which means we saw a 67% reduction in the risk of disease progression or death. This level of efficacy has not been previously reported in patients who have been treated with cell cycle inhibitor. Let's turn to slide 11. Subgroup analysis demonstrated that the clinical benefit of triplet was maintained across all subgroups that were predefined for analysis. All hazard ratios were less than one, and none of the confidence intervals overlapped. Notably, for the patients who were enrolled in the United States.
and Canada, median progression-free survival was 19.3 months for gedatolisib triplet and, as you will see later, 14.9 months for gedatolisib doublet regimen. Additionally, efficacy was observed regardless of which prior cell cycle inhibitor was used for treatment of these patients. Patients who received prior palbociclib benefited as much or more than those who had prior ribociclib or abemaciclib. This is the first time when a randomized phase III study, the data shows the benefits over treatment with palbociclib. Let's now turn to slide 12. Similar findings are seen for gedatolisib doublet regimen comparing this combination with standard of care fulvestrant. All point estimates for hazard ratio were less than one.
However, the upper limit of confidence interval includes one in a several characteristics group, most notably for those patients whose disease progression occurred within the first six months of treatment on their most recent therapy before inclusion in the study. Let's turn to slide 13. 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-free survival for triplet regimens was 11.1 months and 5.6 months for doublet regimen, resulting in a 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-free survival was 19.3 months for triplet and 14.9 months for doublet regimen, with a hazard ratio being 0.13 and 0.35, respectively.
Those patients who had visceral metastasis at the beginning of the study, median progression-free survival was 10.7 months for the triplet regimen and 7.3 months for the doublet, with a hazard ratio reflected in 0.21 for triplet and 0.03 for doublet regimen. In those patients who had disease progression occur within the first six months of treatment on immediate prior therapy before inclusion in the study, median progression-free survival was 7.4 months for the triplet regimen and 5.6 months for the doublet regimen, which resulted in a hazard ratio of 0.24 for the triplet and 0.98 for the doublet. For those patients who received palbociclib as their prior treatment, median progression-free survival was 16.6 months for the triplet regimen and 7.6 months for the doublet, which resulted in a hazard ratio of 0.21 for the triplet and 0.39 for the doublet.
While a definitive conclusion cannot be drawn from a subgroup analysis, these results may reflect the contribution of CDK4/6 inhibitor in the palbociclib-containing triplet regimen compared to the doublet, providing additional clinical benefits in certain patient subgroups who may have more difficult-to-treat disease. Let's turn to slide 14. Promising 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 prespecified 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 fulvestrant to receive therapy with either the triplet or doublet regimen. 80% of patients received the triplet regimen, and the rest of the patients received the doublet of those who crossed over. Let's turn to slide 15.
When we censored the time of crossover of those patients who received treatment with gedatolisib, the overall survival curves have even greater separation, with a trend towards significance in the interim analysis in both gedatolisib treatment arms. Let's turn to slide 16. Further assessment of efficacy, with the objective response rate for the gedatolisib triplet was 32% compared to 1% for control with fulvestrant, and the median duration of response was close to 18 months, exactly 17.5 months for the triplet regimen. For the gedatolisib doublet regimen, the response rate was 28.3%, and the median duration of response was 12 months. The median duration of response and incremental improvements relative to the control for the gedatolisib triplet and doublet regimen are the highest reported for the endocrine-based treatment regimen in the second-line patients with hormone receptor positive, HER2 negative advanced breast cancer. Let's turn to slide 17.
The gedatolisib 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% of patients in the triplet regimen and 3.1% of 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 signals observed in this study. Most of the patients experienced adverse events of very low grade one and two severity, and few experienced grade three adverse events, except those patients who experienced dermatitis and neutropenia. Grade four adverse events only included neutropenia, which is associated with treatment with palbociclib. It is important to note that there was no increase in the number of neutropenic adverse events with the gedatolisib triplet regimen compared to historical data for palbociclib combination with fulvestrant.
There were very minimal changes in neutrophil levels for patients in the doublet regimen, only 2% of patients, which confirmed further previously reported data that gedatolisib does not induce neutropenia. All grade hyperglycemia levels were low, with 9.2% observed in the triplet regimen and 11.5% in the doublet regimen, with all grade diarrhea of 16.9% in the triplet and 12.3% in the doublet regimen also was low, and the majority of those events were of a low grade. Each of these results is quite unexpected for drugs that target the PAM pathway. Let's turn to slide 18. In conclusion, this finding validates further the PAM pathway as a molecular driver, even in a patient with PIK3CA wild type disease, and supports comprehensive PAM blockade with gedatolisib-based therapy as a potentially new standard of care for patients with advanced breast cancer. Thank you, and I turn back to you, Brian.
Thank you, Igor. Let's turn now to slide 19. Gedatolisib 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% of them are PIK3CA wild type. This is a very large opportunity. There is 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. Our market research shows that oncologists are hungry for options that are more effective and have a safety profile they can manage. With such a large underserved market, we see a chance to build a strong presence for Celcuity.
In light of the clinical benefit offered by the gedatolisib triplet and doublet, we're well positioned to address critical needs in this space. A couple of quick points on market dynamics. IV-administered drugs like gedatolisib 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. The breast cancer community is active, engaged, and well supported by patient advocacy groups, which will help create awareness for new treatments such as gedatolisib. Based on our projections, this patient population represents a potential $5 billion addressable market. Let's turn now to slide 20. We have three important milestones coming up.
First, we expect to submit a New Drug Application for the VIKTORIA-1 PIK3CA 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. Third, we hope to report top-line data for the VIKTORIA-1 PIK3CA mutation cohort by late Q1 or Q2 2026. Let's now turn to slide 21.
As we started getting ready to report results from the PIK3CA mutant cohort of the VIKTORIA-1 trial, we analyzed data from patients who were treated with the same drug regimen evaluated in the VIKTORIA-1 study: gedatolisib combined with fulvestrant and palbociclib. This included a total of 90 patients from the escalation arm B and expansion arms B, C, and D of our phase Ib study. Patients in escalation arm B and expansion arms B and C received a 180 mg dose of gedatolisib once weekly, while patients in expansion arm D received the same dose of gedatolisib, but only on days one, eight, and 15 of a four-week cycle, which was the same intermittent dose regimen patients in the VIKTORIA-1 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 gedatolisib.
For all patients with PIK3CA mutant tumors, median PFS was 14.6 months, and the objective response rate, or ORR, in response evaluable patients was 48%. Median PFS was 19.7 months, and the ORR was 64% in patients with PIK3CA mutant tumors who received the intermittent dose of gedatolisib. For all patients with PIK3CA wild type tumors, median PFS was 9 months, and the objective response rate in response evaluable patients was 41%. For patients with PIK3CA wild type tumors who received the intermittent dose of gedatolisib, median PFS was 9.1 months, and the ORR was 53%. We are very encouraged by the median PFS of 14.6 months found in the entire PIK3CA mutant subgroup, particularly given the high proportion of patients who received gedatolisib weekly, which we believe is a less effective dose schedule than the intermittent schedule.
While the sample size is small, median PFS from patients whose tumors had PIK3CA mutations and who received the phase III intermittent gedatolisib dose is promising and consistent with the results from the overall group. We are looking forward to reporting phase III data for this patient subgroup in 2026. If we report positive results in the PIK3CA cohort, as we hope, we believe we will be well positioned to offer an all-comer therapeutic option that oncologists can consider for patients independent of their PIK3CA, ESR1, or diabetic status. Given the importance of the PAM pathway and the breadth of patients gedatolisib can potentially treat, gedatolisib has the potential to become the new backbone drug required to optimize outcomes for patients. This will position us well as we consider additional clinical development opportunities, such as combinations with oral SERDs and indications in earlier lines of therapy.
Let's now turn to slide 22. That ends the presentation portion of our day. Let's now turn to the Q&A session.
At this time, I would like to remind everyone, in order to ask a question, press star and 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 Maury Raycroft with Jefferies. Your line is now open. Please go ahead.
Hi. Congrats on the update, and thanks for taking my question. I was going to ask one on just the hyperglycemia. In the phase III , you're showing a lower rate than in the phase I b study. What do you think accounts for this difference? We're wondering if the two studies use the same protocol and grading criteria.
No, thanks for the question, Maury. 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'd place more weight on the results from this study. 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. Other than that, I don't think we can pinpoint a specific reason for the results we showed for diabetes and/or rather for hyperglycemia in the study.
Got it. Okay. I'll ask one more and then hop back in the queue. There was a lot of discussion around Roche's evERA 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.
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 lack those mutations. 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, PIK3CA wild type, who are endocrine sensitive, comprises roughly 15% of the total patient population. The reason why we think that is the population that that drug would be mostly limited to is just based on, I guess, our belief that we'll show favorable results in the PIK3CA mutant pathway that would exceed those reported here.
In the ESR1 wild type patients, we think our regimen is clearly differentiated results relative to those therapies. Even with this regimen there, which is great, it's another option for patients, we think we have the opportunity because we can, we think, more effectively address the needs of patients, roughly 85% of patients. We think 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. 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 of their or for most of their patients.
Yeah. Makes sense. Okay, thanks for taking my questions.
You're welcome. Thank you.
Your next question comes from the line of Tara Bancroft with TD Cowen. Please go ahead.
Hi. Good morning. Congrats on the great data and the great feature at the conference. 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. I think with such a low discontinuation rate, 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 or if it necessitates some kind of dose reduction, anything along those lines. Thank you.
Yeah. Thanks, Tara. We will be reporting out more details on the kind of safety profile of gedatolisib at a future medical conference, including stomatitis. 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 upfront with patients using the regimen. One disadvantage with our regimen for patients using it 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 Ib study, we found that even patients who, most of those patients didn't receive any prophylaxis, that the dexamethasone mouth rinse, 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 gedatolisib is only dosed three times a month and only exposing patients to a Cmax concentration of drug three times during that month, that the general incident will be potentially less severe during the dosing window because essentially the gedatolisib concentration is reduced substantially over that dosing window, stays well above the IC80 level needed for target engagement.
We think the average dose level the patient is exposed to throughout the treatment cycle is lower and less likely to initiate or to aggravate adverse events. While stomatitis manifests, we think it's treatable and reversible, but we also think the general level of aggravation is one way to characterize it, that stomatitis may expose the patient to, somewhat self-resolves because of the lower concentration the patient sees, for the most part, throughout the treatment period.
Great. Thank you so much, Brian.
You're welcome.
Your next question comes from the line of Andrew Berens with Leerink Partners. Please go ahead.
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. 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 CDK4/6 or choice of combination partner. Just a question on the IP because I've gotten a lot of questions on it from investors. Can you run through what you currently have for GATA and what potential strategies you're using to extend the runway?
Okay. Thanks, Andy. The first question relates to BICR, blinded independent central review. It's the guidance of the FDA as well as the European Medicines Agency that studies that are open label, where the investigators and physicians know which therapy they're prescribing or they're treating their patients with, should use blinded reviewers of the scans to limit or eliminate the potential bias that could accrue to investigators who know which treatment they're providing. 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, we receive very, very firm recommendations that we use blinded independent central review. I can't explain what other sponsors do or what their rationale was, but I do know that we follow the agency's recommendations.
Regarding stomatitis and being higher in the triplet and doublet, we do think there is some stomatitis that accrues to palbociclib. If you look at their phase III studies, PALOMA-2 and -3, you see that there is some incidence of stomatitis. That's probably one area where there's a bit of an overlap of adverse events between gedatolisib and palbociclib. It's interesting you pointed out the results we reported in prostate cancer, where there was very little stomatitis overall. 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.
I would say one of the reasons why we were surprised by the stomatitis results was that we didn't hear much commentary from investigators throughout the course of the study. We've been working with investigators for over two years now treating patients, and our medical team regularly interacts with physicians, providing follow-up and questions. We just did not hear very much about stomatitis at all. Over the course of a study, you get exposed to questions about safety or how to mitigate adverse events. There just was not much dialogue on that.
That somewhat is consistent with what we observed in the Phase 1b, which is that just the overall pharmacokinetic profile of gedatolisib results in maybe a less difficult to or an 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, finally, the third question you asked regarding intellectual property. We have a series of three patent families that we think will ultimately help extend exclusive period for GEDA 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. It's not substitutable. Essentially, a functional excipient performs a role that's required to achieve the necessary parameters for it to be reliably produced and used in the clinic, and that patent will expire sometime in 2041. We also received earlier this year a patent for the dosing schedule that we used in this trial, three week on, one week off. That schedule will be incorporated on the label, and that patent would be included in the Orange Book. We think that patent will serve to prevent the agency from granting approval to any ANDA submission as a result. Essentially, these dosing patents are very strong and really serve as effective barriers to generics coming in.
A combination of those patents, as well as other work that we're doing that could further extend the exclusive period, give us confidence that we have a very long runway, at least till 2042, to develop gedatolisib for additional indications.
Okay. Does the extra work that you're mentioning, does that potentially include a subcutaneous version?
We're working on a lot of different things that we think will have the opportunity to improve the ability of gedatolisib to provide a benefit to patients. If we're successful in launching those, we think one of the results would be that we would extend the exclusive period as well.
Great, thanks for taking all the questions. Congrats again.
You're welcome. Thanks.
Your next question comes from the line of Brad Canino with Guggenheim Securities. Please go ahead.
Hey. Good morning. This is Bridget Biancobrad. Congrats on all the ESMO updates and thanks for taking our questions. Just regarding the observed positive OS trend for VIKTORIA-1 at the interim analysis, I guess, how have you designed the study to ensure that it has the ability to demonstrate statistical significance with more mature follow-up? What is the competitive significance of reaching that outcome in the treatment setting?
You were fading a little in and out. Could you just maybe repeat a bit about your question regarding the overall survival data?
Sorry. I guess regarding the positive OS trend, how have you designed the study to ensure that it has the ability to demonstrate statSIG with more mature follow-up? What is the competitive significance of reaching that outcome in the treatment setting?
Sure. Okay. The primary endpoints were PFS, and the FDA requires at the 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 the patient's overall survival. One of the thresholds that they make very clear that you need to not trip is showing any decrease in the likelihood of survival for patients on the study therapy. We showed in this interim analysis a very favorable trend. I mean, obviously, it's immature, and so not going to achieve statistical significance. We're also encouraged by the sensitivity analysis that excluded the patients, censored patients who had crossed over. 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 reaching statistical significance is that the number of events and the size of the studies in the second-line setting in breast cancer tend to be smaller. The delta needed to show in survival between the study arm and control arms needs to be bigger as a result. It's more of a statistical hurdle, not necessarily a therapeutic hurdle. One strategy that we did employ 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. 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.
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.
Got it. Thanks so much.
You're welcome.
Your next question comes from the line of Stephen Willey with Stifel. Please go ahead.
Yeah. Good afternoon. Thanks for taking the questions, and I apologize for the background noise. Congrats on the conference.
That's okay. Thanks.
I was just curious. I know Igor kind of spoke to it in his review of the data, but just curious if you have any thoughts or hypotheses around what appears to be preferential activity of gedatolisib occurring in patients as opposed to palbociclib. I think you see it in the triplet. You see it in the doublet. I think the inverse is true for abemaciclib. 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 inside enrollment? I'm just curious if you have any thoughts there and just have a quick follow-up.
Right. I think it's hard to tease out the difference there. I mean, I think we can 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. 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 that the median PFS was much higher with palbo. That can 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 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.
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. By blockading the PAM pathway and continuing to blockade the pathway, our non-clinical model suggests that that reactivates the CDK4/6 pathway and thus resensitizes patients to CDK4/6 inhibitors. This data suggests that it's a class effect. It doesn't really matter which CDK4/6 inhibitor patients will have received. I suppose the caveat would be abemaciclib, although the treatment, the hazard ratio for abemaciclib, 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 abema.
There seems to be some difference in how patients who've received abema respond to subsequent therapy compared to ribo and palbo. I'm not sure that that is something that we can readily explain.
Understood. Maybe just a follow-up on the prostate trial. I think it was noted that there's an intention to add, I think, two higher doses to the protocol. I'm just curious as to, I guess, A, what you're trying to achieve with the higher dose, and then B, 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 at the higher dose. I know there's a small patient number that's populated in the Kaplan-Meier curve, but just curious on the higher dose strategy and your confidence in that.
Sure. No, I think that's a great question. That's the question we're asking ourselves, which is how do we best identify the most appropriate dose? On the one hand, the numbers said that the lower dose did better than the higher dose, small sample numbers, sample sizes. You want to be careful about drawing too firm a conclusion. Given how well tolerated the combination was in these patients, almost no diarrhea, hyperglycemia, stomatitis, we felt that it was important to explore higher doses because essentially when you're going into a new tumor type, you can't make assumptions that how patients respond or the dosing will be recapitulated in prostate, in this case, versus breast cancer. Clearly, there seems to be a different response to gedatolisib from an adverse events standpoint for the men in prostate than the women in breast. Additionally, 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. 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. Going to a higher dose 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. In drug development, the last thing we want to do is go to a phase III with a suboptimal dose.
We just concluded that it's really important to make sure we step back, answer some questions now before you get to the phase III, and really be confident that we have a valid dataset to support a selection of what we hope, depending on the results, would be the dose used in a phase III study.
All right. Thanks for taking the questions, and congrats again.
You're welcome. Thanks.
Your last question comes from the line of Gil Blum with Needham & Co. Please go ahead.
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 SERDs? 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.
Hey, Gil. I'm not sure I quite understood the question. Are you asking me for a general comment on SERDs, or are you asking a question as it relates to gedatolisib?
As it relates to gedatolisib and the changes in potential changes in the standard of care, as it relates to oral SERDs.
Okay. 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, there's a bit of a to-be-determined aspect to this. On the one hand, it's always important to demonstrate that a drug like gedatolisib can be safely combined with the various SERDs. That would be one step to take just to ensure that if physicians wanted to consider use of one oral SERD and combine with gedatolisib, they had data. They would need data to confirm that it was safe for their patients for that to occur. As far as the regulatory strategy and how to incorporate a SERD into a gedatolisib regimen, yeah, there's some complexity around that, and we're obviously still thinking that through with our phase III data.
In PIK3CA wild type, we want to see what we see in PIK3CA mutant. I mean, we feel confident about that, but until you get the data, you don't know. That'll allow us to kind of more fulsomely understand how to think about the opportunity to do some work with oral SERDs and potentially create additional options for patients.
Great. As it relates to the additional data disclosures from the VIKTORIA-1 study, would the proportion of ESR1 mutant patients be disclosed at some point or at a later stage?
We will be reporting additional data, and those types of subgroup analyses are on the list. Yeah.
Great. Congratulations again.
Thanks a lot.
That concludes our Q&A session. I will now turn the call back over to Brian Sullivan, CEO and co-founder of Celcuity, for closing remarks.
Thank you for joining us today. We appreciate your interest in Celcuity and look forward to speaking with everyone at some point in the future. Take care. Goodbye.
Ladies and gentlemen, thank you all for joining, and you may now disconnect. Everyone, have a great day.