Good day and thank you for standing by. Welcome to the Celcuity Phase 3 VIKTORIA-1 Topline results investor call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Brian Sullivan, CEO and Co-Founder of Celcuity. Please go ahead.
Good morning. Thank you for joining us today. Let's now turn to slide two. Before we begin, 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. The description of these risks, uncertainties, and assumptions is included in our SEC filings. Let's now turn to slide 3. Today is an important day for patients who have HR positive HER2 negative advanced breast cancer. The clinically meaningful improvement in both progression-free survival primary endpoints from the PIK3CA wild-type cohort of Phase 3 VIKTORIA-1 trial was unprecedented in this disease setting. Dr.
Igor Gorbatchevsky, our Chief Medical Officer, will be joining us today to present these exciting results. We're also pleased to have Dr. Rachel Layman, Professor of Medicine at the MD Anderson Cancer Center, join us to provide an overview of the treatment landscape for HR positive HER2 negative advanced breast cancer, and Eldon Mayer, our Chief Commercial Officer, will provide a brief update on our preparations for a potential launch of gedatolisib should we get FDA approval. Let's turn now to slide four. We founded Celcuity because we believed that a functional analysis of the signaling pathways in tumor cells could yield important insights that weren't available from genetic analysis alone. When we turned our attention to the PI3K AKT mTOR or PAM pathway about five years ago, I couldn't reconcile two facts. First, the PAM pathway has long been recognized as one of the most important cancer drivers.
At the same time, very few patients were benefiting from drugs that targeted this pathway. It made no sense to me that there weren't any blockbuster PAM inhibitors. We learned that the primary reason why PAM inhibitors have had limited impact despite the importance of the PAM pathway is because it is very difficult to safely and efficaciously inhibit this pathway and there's multiple components, each of which need to be inhibited to comprehensively blockade the PAM pathway's activity. Otherwise, if only a single component is targeted, adaptive resistance arises and 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 these components that were not efficacious, too toxic, or both.
The failures of these early generation PAM pathway inhibitors led drug developers to target single components 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 this pathway, the resulting drugs have typically only demonstrated efficacy in patient populations that have pathway mutations. Eventually, we developed two hypotheses that led us to gedatolisib. First, we didn't think the pathway's relevance as a cancer driver was a function of the presence or absence of a mutation.
It became clear, at least to us, that the PAM pathway's role as a cancer driver and its overall importance was independent of any specific pathway variants or mutations, and this meant that an inhibitor that could comprehensively shut down this pathway could potentially be efficacious in patients lacking common mutations such as PIK3CA. The second hypothesis was that a highly potent drug that avoided overexposure in key organs such as the liver and GI tract could potentially limit the incidence of the side effects associated with this pathway, such as hyperglycemia or diarrhea. Let's now turn to Slide 5. Until today, we're very thankful that the data from the PIK3CA wild-type cohort of our Phase 3 VIKTORIA-1 clinical trial has validated our hypotheses in patients with HR positive, HER2 negative, PIK3CA wild-type advanced breast cancer.
Gedatolisib plus fulvestrant and palbociclib, and gedatolisib plus fulvestrant, met the study's two primary endpoints by demonstrating statistically significant and clinically meaningful improvement in progression-free survival, or PFS, versus fulvestrant. Median PFS for the gedatolisib triplet was 9.3 months compared to only 2 months for fulvestrant, a 7.3 month incremental improvement in median PFS. The hazard ratio was 0.24, which translates to 4.2x higher likelihood of survival without disease progression than fulvestrant. Median PFS for the gedatolisib doublet was 7.4 months, again compared to only 2 months for fulvestrant, a 5.4 month incremental improvement in median PFS. The hazard ratio was 0.33, which translates to 3x higher likelihood of survival without disease progression than fulvestrant. Let's now turn to slide. I have to say we were genuinely amazed at these results.
They're unprecedented and established several new milestones in the history of drug development for HR positive HER2 negative advanced breast cancer. First, the hazard ratios reported for both the gedatolisib triplet and doublet were the most favorable ever reported by any Phase III trial, first line, second line, or third line in this population. Second, the incremental improvements in median PFS for the triplet and doublet were the highest ever reported by any Phase III trial for this patient population receiving at least their second line of therapy for advanced disease. Third, gedatolisib is the first PAM pathway inhibitor to achieve positive Phase III data in patients who have PIK3CA wild-type tumors and whose disease progressed on or after treatment with a CDK4/6 inhibitor. In light of this data, we believe the gedatolisib triplet and doublet each have the potential to establish a new standard of care for these patients.
Let's turn now to slide seven. We're obviously very encouraged by these results and the implications for our now enrolling Phase III first line trial and our other potential future clinical development plans. Since gedatolisib has the potential to address a number of additional unmet needs in a variety of additional settings, we're thankful that our intellectual property position is very strong. With a recently issued patent, we expect to have patent exclusivity with gedatolisib until 2042. Let's turn now to slide eight. It's my pleasure to introduce Dr. Igor Gorbatchevsky, our Chief Medical Officer. Igor joined us at the outset of our clinical development program for gedatolisib. He's done a fantastic job of building and leading the clinical development team that has delivered these trial results. Igor, you're up.
Thank you, Brian. Let's turn to slide nine. We all know that the most common type of advanced breast cancer is hormone receptor positive HER2 negative disease, and approximately 60% of patients will have PIK3CA wild-type breast cancer. Unfortunately, the currently approved therapies offer very limited efficacy, with median progression-free survival ranging from 2 to 4 months only. As Brian mentioned, the PAM PI3K/AKT/mTOR 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 PAM, hormonal, and cell cycle pathways play important roles in promoting tumor cell proliferation.
Additionally, they are interdependent drivers for hormone receptor positive HER2 negative advanced breast cancer, and this process is not dependent on PIK3CA mutation status to maximize the efficacy. The evidence suggests that simultaneous blockade of all three pathways is very important. It is especially important to provide complete blockade of the PAM pathway. Doing so will prevent cross-activation of the PAM pathway when both hormonal and cell cycle pathways are inhibited. It also can help to restore or enhance sensitivity to both endocrine and cell cycle targeting therapies. Because of this critical role in oncogenesis and ability to interact and cross-regulate other oncogenic pathways, we believe that the PAM pathway represents one of the most important targets in oncology today. Let's please turn to slide number 10. Gedatolisib is a very potent inhibitor and very potently inhibits all four isoforms of class I PI3K and both mTORC1 and mTORC2.
This enables gedatolisib to provide complete and comprehensive blockade of the whole PAM pathway. This means that there is a limited potential for adaptive resistance when a single target inhibitor is used. For example, when someone targets just a single isoform of PI3K, like the alpha isoform, or just AKT, or just mTOR. In several preclinical studies, gedatolisib inhibitor effect was 300x more potent compared to those targeting a single PI3K isoform or AKT or mTOR. This potency was the same in tumor cell lines regardless of PIK3CA mutation status. Preliminary data with gedatolisib also found that patients with or without PIK3CA mutations had objective response rates well over 50%. Let's turn to slide 11. VIKTORIA-1 is a randomized open-label global Phase III study in patients with hormone receptor positive and HER2 negative advanced breast cancer. VIKTORIA-1 included patients with both PIK3CA mutation positive and wild-type disease.
Today we are focusing on design and review of top-line results for Study 1 which included patients with PIK3CA wild-type disease. In this study, both men and women were eligible for enrollment. Patients must have had disease progression on or just right after treatment with a CDK4/6 inhibitor in combination with a non-steroidal aromatase inhibitor. Up to two lines of hormonal therapy was allowed and prior treatment with agents targeting the PAM pathway was prohibited as well as chemotherapy for patients' advanced breast cancer. However, patients could have received chemotherapy as part of their treatment regimen in neoadjuvant or adjuvant setting. Patients also had to have measurable disease according to the most recent RECIST version 1.1. In total, 392 patients were randomized equally 1:1:1 in three study arms. Two of them were treatment study arms and one control study arm. Patients received standard doses of palbociclib.
In Arm A and B it's 125 mg daily for 21 days with seven days of treatment window. Fulvestrant in all three arms also was given as a standard dose of 500 mg twice during cycle one and every four weeks thereafter. Gedatolisib was given in the standard dose of 180 mg intravenously once weekly on days one, eight, and 15. This three weeks on and one week off schedule provides patients with virtually two weeks break in treatment. For example, from day 15 to the day one of subsequent cycle, patients will have two weeks of break. In Arm A, patients received triplet regimen of gedatolisib combined with fulvestrant and palbociclib. In Arm B, patients received doublet regimen of gedatolisib combined with fulvestrant and in control Arm C, patients received fulvestrant alone.
It's important to notice that patients in Arm C who had confirmed disease progression were able to cross over and receive active treatment with either gedatolisib triplet or doublet regimen. The primary objective of this study was efficacy assessed by comparing median progression-free survival between treatment arms. We had two co-primary endpoints, first one comparing efficacy in Arm A versus Arm C and second Arm B versus Arm C. Let's turn now to slide 12. As Brian mentioned, both primary endpoints were met. Each shows statistically significant and clinically meaningful improvement in progression-free survival relative to fulvestrant alone. For patients in arm A who received gedatolisib triplet regimen, median progression-free survival was 9.3 months compared to 2 months for the patients in arm C who received fulvestrant alone. This resulted in a hazard ratio of 0.24 and a very narrow confidence interval with a p value less than 0.0001.
This translates to 4.2x higher chance of surviving without disease progression. These results are very clinically meaningful with 7.3 months incremental improvement in median progression-free survival for triplet regimen. Let's now proceed to Slide 13 and review results of the second coprimary endpoint. For patients in arm B who received gedatolisib doublet regimen, median progression-free survival was 7.4 months compared to 2 months for patients in arm C who received fulvestrant alone. This resulted in a hazard ratio of 0.33 and a narrow confidence interval with a p value less than 0.0001. This translates to a 3x higher chance of surviving without disease progression for patients who received doublet regimen. These results are also very clinically meaningful with a 5.4 months incremental improvement in median progression-free survival for those who receive gedatolisib in combination with fulvestrant. Let's turn to Slide 14.
Obviously we are very excited this efficacy result was so favorable, but we're also as pleased to report that both gedatolisib triplet and doublet were well tolerated and the side effects were easily managed with available standards of care. The discontinuation of therapy due to treatment-related adverse events was lower in both gedatolisib triplet and gedatolisib doublet regimens compared to those results observed in arm B from our Phase 1b study in advanced breast cancer that we presented in prior years. Additionally, the safety profile for both regimens was better than observed in the overall Phase 1b study we presented earlier, including lower rates for stomatitis and hyperglycemia. Finally, the overall survival analysis shows positive trends and was favorable for both triplet and doublet regimens.
Although the data is immature at this time, we are very encouraged about this because a very significant portion of patients in arm C crossed over to receive active therapy as I mentioned earlier. Patients in arm C upon disease progression were able to receive either triplet or doublet gedatolisib regimens. The full results of VIKTORIA-1 PIK3CA wild-type cohort will be presented at the upcoming scientific symposiums later this year, and we are anticipating NDA submission in the fourth quarter of this year. We thank all patients, investigators, and site staff for participating in VIKTORIA-1 study. Now I'm turning back to you, Brian.
Thank you, Igor. Let's turn now to slide 15. My pleasure now to introduce Dr. Rachel Layman, Professor of Medicine at MD Anderson. Dr. Layman provides a unique perspective. She was one of the top enrollers in both our Phase 1b breast cancer study and the VIKTORIA-1 study, so she has a deep level of experience treating patients with gedatolisib. Let's turn now to slide 16, and Rachel, the floor is yours.
Thank you so much, Brian. Today I'll be presenting the current treatment landscape for patients with hormone receptor positive, HER2 negative advanced breast cancer following prior treatment with endocrine therapy and a CDK4/6 inhibitor. I'll be focusing on cancers without PIK3CA mutations. Unfortunately, after patients are treated with a first-line endocrine therapy combined with a CDK4/6 inhibitor, subsequent endocrine-based treatment regimens have not performed well. In an effort to improve outcomes for this patient population, multiple clinical trials of novel therapies have been performed. I will start by reviewing the data for novel endocrine therapy agents. This slide shows the oral SERDs which have been in development for years. Although the expectations were high, Phase
III studies evaluating oral SERDs against standard of care endocrine therapy showed no significant benefit for cancers that do not harbor ESR1 mutations. The Phase III studies with positive readouts are shown here.
This data only includes the ESR1 mutation population regardless of PIK3CA mutation study status, as this is the population that benefited from therapy. The hazard ratios were similar for all three drugs, ranging from 0.55 to 0.66, with lower hazard ratios being more favorable. Elacestrant is the only oral SERD currently FDA approved. The EMERALD trial improved the median progression-free survival by only 1.9 months. In the VERITAC-2 study, camizestrant improved median progression-free survival by 2.9 months, and finally, the Phase III EMBER-3 study enrolled patients with or without prior CDK4/6 inhibitor therapy. 30% of the study population did not receive a CDK4/6 inhibitor. Despite this, imlunestrant only improved progression-free survival by 1.7 months compared to standard endocrine therapy. Let's go to slide 17, please. Another approach to improve outcomes following first-line therapy was to continue a CDK4/6 inhibitor combined with a different endocrine therapy.
The Phase III postMONARCH clinical trial randomized patients to receive fulvestrant with or without the CDK4/6 inhibitor abemaciclib. All patients received a prior CDK4/6 inhibitor combined with an aromatase inhibitor in the metastatic setting and had any PIK3CA and ESR1 status. The results were positive with a hazard ratio of 0.73. However, there was less than a one-month improvement in progression-free survival with abemaciclib. The EMBER-3 study evaluated the oral SERD imlunestrant with and without abemaciclib. The study population in this trial was more diverse with only 65% of patients receiving a prior CDK4/6 inhibitor, and the study enrolled patients in the first, second, and third-line treatment settings. EMBER-3 also yielded positive results with a hazard ratio of 0.57 and absolute progression-free survival improvement of 3.9 months. Let's go to slide eight please. Slide 18 please. Here we will move to the PAM pathway targeting therapy.
To date, no prospective clinical trial in the post-CDK4/6 inhibitor setting has demonstrated benefit in cancers without a PIK3CA mutation. The most recently approved PAM pathway drug is capivasertib, an AKT inhibitor. However, no benefit was observed with the addition of capivasertib to fulvestrant in patients with PIK3CA wild-type breast cancer who had received a prior CDK4/6 inhibitor. Alpelisib is a PI3K inhibitor which is approved for the treatment of hormone receptor positive breast cancer with a PIK3CA mutation. The study leading to the approval of alpelisib was performed prior to wide availability of CDK4/6 inhibitors, and so most patients on this study did not receive a CDK4/6 inhibitor. Even so, patients without PIK3CA mutations did not benefit from the therapy and thus are excluded from the FDA approval of this drug. Everolimus is an mTOR inhibitor.
Results from Phase III studies were published more than a decade ago prior to the availability of CDK4/6 inhibitors among other therapies. Slide 19 please. Now let's look at how gedatolisib-containing regimens stack up against the current treatment landscape. First, I will show the median progression-free survival of the gedatolisib regimens along with the approved regimens for which we have Phase III data in the second-line setting. Again, for patients with hormone receptor positive, HER2 negative, and PIK3CA wild-type breast cancer following CDK4/6 inhibitor therapy. Fulvestrant provides a progression-free survival of only 2 months, while elacestrant has a 3.9 month progression-free survival when limited to the ESR1 mutant population. The two gedatolisib-containing regimens studied far outperformed the standard of care therapies with a median progression-free survival of 7.4 months when combined with fulvestrant and 9.3 months when combined with both fulvestrant and palbociclib. Slide 20 please.
Now let's include regimens with available data that are not FDA approved at this time. This slide shows the absolute improvement in median progression-free survival with each regimen when compared to standard endocrine therapy. Gedatolisib clearly provides the highest incremental progression-free survival with a 5.4 month improvement with doublet therapy and a very impressive 7.3 month improvement with triplet therapy. Incremental improvement in the other regimens range from 0.7 to 3.9 months. Slide 21 please. This slide shows the same data shown by hazard ratio. The lower the hazard ratio, the better the treatment efficacy compared to control, which is standard endocrine therapy. In this case, the hazard ratio for the triplet gedatolisib regimen is 0.24 and the doublet regimen has a hazard ratio of 0.33. These extremely favorable hazard ratios are rarely seen in oncology clinical trials and are unprecedented in this treatment setting.
Up to this point, hazard ratios for this population in the second-line setting have ranged from 0.55 to 0.73. Slide 22 please. This data supports the potential for gedatolisib to become the standard of care drug for second-line hormone receptor positive HER2 negative and PIK3CA wild-type advanced breast cancer. Gedatolisib is highly efficacious. It is associated with the highest incremental improvement in median progression-free survival over endocrine therapy that has ever been reported in this patient population. The hazard ratio for triplet therapy of 0.24 and doublet therapy of 0.33 are the most favorable reported for any study in hormone receptor positive HER2 negative advanced breast cancer. Additionally, gedatolisib is associated with preserved quality of life. Patients tolerated both gedatolisib containing regimens well with very low discontinuation rates.
In addition, the safety profile for triplet and doublet therapy was more favorable than that previously reported in the Phase 1B advanced breast cancer study. Of note, intravenous administration was not a barrier to use. Thank you very much. We can now go to slide 23 please.
Thank you, Rachel, for your very helpful summary of the treatment landscape. Let's turn now to slide 23. It's my pleasure to introduce Eldon Mayer, our Chief Commercial Officer. Eldon joined us last year, and he's done a great job of assembling a talented team and laying the groundwork for a potential commercial launch sometime next year. Eldon, please go ahead.
Thank you, Brian. Let's now turn to slide 24. I want to share a quick overview of the market landscape we see for gedatolisib, what we're doing to get ready, and how we're gearing up for a potential launch should we get FDA approval. Let's start with why we think the market looks promising for gedatolisib. First off, this is a sizable patient group. We estimate there are 34,000 patients moving to second-line treatment after CDK4/6 inhibitors, and roughly 60% of them are PIK3CA wild-type. That's a very large opportunity. There's also a real need here. As we heard earlier on this call, current second-line treatments for HR positive, HER2 negative advanced breast cancer 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, and with gedatolisib's unique mechanism of action and corresponding clinical benefit, it is well positioned to address critical needs in this second-line space. A couple quick points on market dynamics. IV administered drugs such as 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. Plus, the breast cancer community is active, engaged, and well supported by advocacy groups, which can help create awareness for new treatments. Based on our projections, this could represent a $5 billion served market revenue potential. Let's turn now to slide 25. All right, let's talk about how we're preparing for a potential launch in this market.
Our experienced teams are hard at work getting ready, and we're on track for a strong market entry if we receive FDA approval. We've been gathering valuable insights from key opinion leaders, and now with our clinical data in hand, we'll be investing more in those conversations to dig deeper into what these results mean for physicians and patients. Market access is a major focus for us to ensure patients have access to gedatolisib with a quick and seamless process when a physician orders it. We're actively engaging with health systems, payers, pathway decision makers, group purchasing organizations, or GPOs. We're also working hard to educate and build excitement around the importance of comprehensively blocking the PI3K, AKT and mTOR or PAM pathway. That includes having a strong presence at key oncology conferences and continuing to educate and raise awareness about these issues within the breast cancer and oncology community.
We're tackling the major long lead time initiatives such as setting up distribution, reimbursement and building patient support systems to name a few. We're ready to execute these at launch. Let's turn now to slide 26 and finally let's touch on our launch planning and infrastructure. With the teams we built, we're refining our strategic and tactical plans, especially now that we have Phase III clinical data to work with. The most critical piece is having a seasoned skilled team to execute and ready to ramp up, hiring quickly to make that happen. We're also staying close to oncologists through ongoing market research and working with key opinion leaders to ensure we're aligned with what oncologists and patients need so we can position gedatolisib as effectively as possible.
We're making great progress on the operational side across our company, building out critical infrastructure such as supply chain, IT systems, data and analytics, field support, and much more to ensure operational excellence. All in all, we've made major strides in getting ready to become a commercial stage company and we're pushing forward constantly to be fully prepared for a potential launch. Brian, back to you.
Thank you, Eldon. Let's now turn to Slide 28, please. We have three important milestones coming up the back half of this year. First, we'll present the full data at a major medical conference later this year. Second, we expect to submit a new drug application, or NDA, for VIKTORIA-1 PIK3CA wild-type cohort indication in the fourth quarter of 2025. Finally, we hope to report top-line data for the PIK3CA mutation cohort of the VIKTORIA-1 study by the end of 2025. Let's turn now to Slide 29. This ends the presentation portion of our day. We'll turn now to the question and answer session. Thanks to all of you who did send in questions. I should just mention that Dr. Rachel Layman will have to attend to patients in just a few minutes and will have to leave during Q&A. Hopefully she'll be available for your questions.
Let's open it up to questions, please.
Thank you. If you would like to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now start with our first question, and this is from Maury Raycroft from Jefferies. Please go ahead.
Hi, good morning. Much congrats on the data update and thanks for taking my questions. Wondering if you can provide additional context to the 2 month PFS data observed in the control arm. Do you believe this patient population exhibits greater endocrine resistance compared to recent trials. In the same setting?
What implications might this have for gedatolisib's effectiveness in a more sensitive population?
Thanks, Maury. On one hand, we weren't surprised by the results for the fulvestrant arm. There have been, I think, four fairly recent clinical trials, prospective trials, randomized, that reported 1.9 to 2.1 months median PFS for fulvestrant. There have been some outlier trials, but those results were really driven by differences in patient populations relative to a registrational study. This, we think, represents the current state and is representative of what patients can experience in the setting. What that means, I think, in translation, is that these patients are not going to respond to much endocrine therapy, that essentially they're untreated disease mechanisms, which we think we demonstrated in this VIKTORIA-1 trial. As far as the sensitivity, we had data in our frontline, in our Phase 1b study for endocrine sensitive patients, and in that study it was preliminary data.
In a sample size of 41 patients, we reported median PFS of 48 months with gedatolisib, palbociclib, and letrozole. That's obviously very encouraging data. Our VIKTORIA-2 study, which we're currently enrolling, is focused on enrolling patients who are considered to be endocrine treatment resistant. These are patients who progress almost immediately after or during their endocrine treatment for early breast cancer. Big unmet need for these patients. Most of these patients are only getting therapies that offer them about seven months median PFS. We're encouraged by the results here. Obviously, we have to get the results for the VIKTORIA-2 study to see what the effect is. Certainly, the data we have today is encouraging for us and makes us optimistic about those future results.
Got it.
That's helpful. Go ahead. Sorry. Yeah.
Maybe one other question, just on wondering if you could talk more about the favorable overall survival trend, what that means. Does that mean the trend's positive and even though it's immature and with crossover, can you add any more context to how your OS data compares so far relative to competitors at the same stage?
Sure.
I think what was very encouraging to us was that patients with the triplet showed a favorable trend, even though in the control arm, a significant number of these patients crossed over to receive gedatolisib therapy. While favorable OS, you know, positive OS is not required or hasn't been a benchmark that the FDA requires, they certainly expect to see no detriment to the overall survival trend for patients. There was a recent study that reported encouraging progression-free survival data but showed a fairly significant negative trend. I guess everybody is more sensitive to the overall survival data as a result. In that context we're particularly encouraged by what we've seen with the overall survival data. Got it. Okay.
Thanks for taking my questions.
You're welcome.
Thank you. We'll now take the next question. This is from Tara Bancroft, TD Cowen. Please go ahead.
Hi, good morning and congrats on these fantastic data. I was hoping you could talk more about the balance of the arms across mutational status and what consistency you might be seeing in those, especially in ESR1 mutant patients. If you could compare those relative to EMBER3 data specifically. Thanks so much.
Thanks. All that data, that type of data would be presented at later medical conferences. What we can say is that, you know, the demographic data, baseline characteristics data that we've reviewed suggests that, you know, these arms were all well balanced. We had stratification variables, factors that ensured for critical factors that these populations or the arms were consistent and representative. We don't expect to see any anomalies or anomalous accrual a ccording to m utational status or differences between arms.
Okay, great, thanks. I guess for that full data, are you thinking more on the ESMO timeline or San Antonio timeline or something else?
Just stay tuned.
Okay, great, thanks.
Thank you. We'll now take the next question. This is from Andrew Berens from Leerink Partners. Please go ahead.
Hi, thanks. Congratulations on the transformational results.
Just wanted to ask a couple of questions. Questions on the future plans for the program. Can you just run through the rationale for the frontline trial? Specifically, the decision to target endocrine resistant population. With fulvestrant, just trying to put the results of the prior Phase 1b in context with that program, and then it really seems to be a large opportunity could be to combine gedatolisib with the oral SERDs and to help those drugs beat fulvestrant in a broader population, which as the doctor ran through, none of those agents have been able to do it. Are you considering running those trials? It really seems like that could unlock a lot of fundamental and strategic value. Thanks.
Sure. Okay, thanks Andy. As far as the rationale for the first-line trial, we initiated work to get this trial going last year, around the middle of the year. As we reviewed the unmet needs, we concluded that this population in particular was particularly underserved and that with median progression-free survival outcomes in the first-line setting for most patients only being 7 months. From a practical standpoint, that means you can enroll a study and get data from that study in a fairly reasonable timeline. We are addressing unmet need and it just is a practical population to evaluate. For a company at our stage of development, you have androgen-sensitive population gets a median PFS of roughly 25 months. It would be a much, much longer study.
Over time we think it would be appropriate to potentially go after because again, the preliminary data we showed in the endocrine-sensitive population was very, very encouraging. VIKTORIA-2 then in some ways mirrors, you could say, the population we enrolled here, endocrine-resistant. We are encouraged by these results and we'll have to wait and see how that translates into VIKTORIA-2, but certainly gives us reason to be optimistic. As far as future development opportunities, we think gedatolisib has shown that it can extend progression-free survival period when combined with hormonal therapy. To the extent that there are better ways or different ways of offering patients an oral SERD, we want to certainly explore that.
It'd be premature for us to really comment more specifically, but as we look longer term, we want to make sure that we position gedatolisib to be combined with as many appropriate drugs as possible so that we give patients the best opportunity to get the best efficacy and safety profile possible.
Okay, thanks and congrats again.
Thank you. You're welcome.
Thank you. We move to our last question today. This is from Oliver McCammon from LifeSci Capital. Please go ahead.
Congrats on the data and thanks for taking my question. Just considering some of the baseline characteristics in VIKTORIA-1 like prior CDK4/6 inhibitor use, measurable disease, et cetera. Can you remind us how heavily pretreated this patient population is versus some of the reference studies we've seen in the second or third line setting? I'm thinking specifically of things like EMERALD and CAPItello-291. Thanks again for the question.
Thank you, Oliver. Because of the enrollment criteria, we think, and we will disclose this data when we present the full data, but we've clearly enrolled mostly a second-line population and some third-line patients. We did not allow patients who had prior chemo in an advanced setting. Some of the other studies for the most part mirror this. To be frank, all these studies largely mirror this population. The number three study had, as Rachel alluded to, a very diverse population. In some ways you can think of them as having four subgroups of patients, first line and then second line with or without prior chemo or rather prior CDK. It's really hard to kind of assess directly. Again, the hazard ratio comparison provides a way to kind of evaluate the relative contribution of the study drugs on top of hormone therapy.
What's particularly interesting about this space is that for the most part, every study that's been run over the past, pick a number, 20 years, has essentially compared itself to endocrine monotherapy. You have the ability to kind of draw a bead on what the reasonable expectation is for these patients with endocrine monotherapy. Then what you'll see are some variations depending on whether patients are enrolled without measurable disease, which will happen in non-registrational studies, or patients may have received more prior chemo. For the most part, I think these populations really line up, except in cases where they're combined with first-line patients or patients who've not had CDK. That really is a very small proportion of patients today. The most representative trials and the ones most relevant are ones that really isolated patients with prior CDK.
Super helpful, and thank you again. Congrats on the data.
Oh, you're welcome. That wraps up our day. We appreciate you guys attending, and we look forward to providing these results in greater detail at an upcoming conference and to continuing our work to get ready for an NDA submission and to be able to get back with everybody with results from our mutant cohort. Look forward to chatting with some of you over the upcoming months. Thanks again.
Thank you. This concludes today's conference call. Thank you for participating, and you may now disconnect.