Celcuity - Earnings Call - Q2 2025

Executive Summary

• Celcuity reported a larger net loss on higher R&D as it advanced gedatolisib, while delivering pivotal VIKTORIA-1 PIK3CA wild-type topline data showing unprecedented hazard ratios (HR 0.24 triplet; HR 0.33 doublet) and PFS increments (7.3 and 5.4 months) vs fulvestrant, positioning for an NDA in Q4 2025.
• GAAP EPS of $(1.04) missed S&P Global consensus EPS of $(0.88)*; non-GAAP adjusted EPS $(0.93) was slightly below consensus as well, with no revenue recognized (pre-commercial stage).
• Liquidity materially improved: Q2-end cash/investments were $168.4M; pro forma cash of ~$455M after July/Aug financing extends runway through 2027; management also flagged access to another ~$116M (term loan + in-the-money warrants).
• Near-term catalysts: full VIKTORIA-1 WT data (later 2025), PIK3CA-mutant cohort topline by end-2025, NDA submission (RTOR rolling start in September, completion targeted Q4 2025), and first patient dosed in VIKTORIA-2 (front-line).

What Went Well and What Went Wrong

• What Went Well

  • Pivotal efficacy: VIKTORIA-1 WT cohort met both primary endpoints with unprecedented hazard ratios and PFS improvements vs control; CEO: “topline data… are potentially practice-changing”.
  • Regulatory momentum: FDA agreed to RTOR; rolling NDA submission to initiate September; completion targeted for Q4 2025.
  • Balance sheet and IP: $286.5M net proceeds from July/August offerings; new dosing-regimen patent extends exclusivity to 2042; CFO reiterated funding into 2027.

• What Went Wrong

  • Operating spend and losses surged: Q2 OpEx rose to $44.0M (+81% y/y), driven by R&D (incl. $5M milestone under Pfizer license), widening GAAP net loss to $45.3M.
  • Cash burn increased: net cash used in operating activities was $36.2M vs $18.1M in Q2 2024; pre-commercial model remains revenue-free.
  • Data/visibility gaps: full safety details (e.g., grade-specific TEAEs, subgroup analyses) reserved for upcoming conferences; investors await PIK3CA-mutant cohort benchmarks (management pointed to Capivasertib ~5.5m mPFS as practical comparator).

Transcript

Speaker 7

Afternoon, ladies and gentlemen, and welcome to the Celcuity Second Quarter 2025 Financial Results Webcast and Conference Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press *0 for the operator. I would now like to turn the conference over to Apoorva Chaloori with ICR Healthcare. Please go ahead.

Speaker 2

Thank you, operator, and good afternoon to everyone. Thank you for joining us to review Celcuity's Second Quarter 2025 Financial Results and Business Update. Earlier today, Celcuity Inc. released financial results for the second quarter ended June 30, 2025. The press release can be found on the Investors section of Celcuity's website. Joining me on the call today are Brian Sullivan, Celcuity's Chief Executive Officer and Co-Founder, Vicky Hahne, Chief Financial Officer, as well as Igor Gorbatchevsky, Chief Medical Officer, who will be available during Q&A. Before we begin, I would like to remind listeners that our comments today will include some forward-looking statements. These statements involve a number of risks and uncertainties, which are outlined in today's press release and in our reports and filings with the SEC. Actual events or results may differ materially from those projected in the forward-looking statements.

Such forward-looking statements and their implications involve known and unknown risks, uncertainties, and other factors that may cause actual results or performance to differ materially from those projected. On this call, we will also refer to non-GAAP financial measures. These non-GAAP measures are used by management to make strategic decisions, forecast future results, and evaluate the company's current performance. Management believes the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the company's ongoing core operations and prospects for the future. You can find the table reconciling the non-GAAP financial measures to GAAP measures in today's press release. With that, I would now like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

Speaker 0

Thank you, Apoorva, and good afternoon, everyone. Thank you for joining our Second Quarter Financial Results Conference Call. The past few months have been eventful ones for Celcuity. We achieved several significant milestones, and we believe these milestones laid the foundation for us to potentially establish Gatotolistin as a new standard of care therapy for patients with HR-positive, HER2-negative advanced breast cancer. First and most importantly, of course, was the positive top-line data we reported from the PIK3CA wild type cohort of our Phase III, Victoria 1 clinical trial. In patients with HR-positive, HER2-negative, PIK3CA wild type advanced breast cancer, Gatotolistin plus fulvestrant and palbociclib, or the Gatotolistin triplet, and Gatotolistin plus fulvestrant, or the Gatotolistin doublet, met the study's two primary endpoints by demonstrating statistically significant and clinically meaningful improvement in progression-free survival, or PFS, versus fulvestrant.

The reported hazard ratios and improvements in median PFS are unprecedented in HR-positive, HER2-negative advanced breast cancer. We believe these data validate our hypothesis that the role of the PIK3CA, or PI3K-AKT mTOR, or PAM pathway as a cancer driver is not solely a function of the presence of a pathway mutation. The implications are profound for patients with HR-positive, HER2-negative advanced breast cancer, as we seek to advance Gatotolistin as a therapeutic option for patients with or without PIK3CA mutations in both the second-line and first-line settings. The second important milestone achieved was the dosing of the first patient in our Phase III, Victoria 2 clinical trial. This trial is evaluating Gatotolistin in combination with a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer.

The third milestone was the announcement of favorable preliminary top-line results from two early phase clinical trials, one evaluating Gatotolistin and darolutamide in men with metastatic castration-resistant prostate cancer, and a second one that evaluated Gatotolistin and trastuzumab biosimilar in patients with HER2-positive, PIK3CA-mutated metastatic breast cancer. The fourth milestone was the extension of our patent exclusivity for Gatotolistin into 2042 with the issuance of a new dosing regimen patent for Gatotolistin. Finally, we raised around $287 million through public offerings of convertible notes, common stock, and pre-funded warrants that provide the funding that should allow us to aggressively prepare for and launch Gatotolistin should we get FDA approval next year. I'd like now to turn to the Victoria 1 trial. Last month, we announced top-line results from this trial.

Median progression-free survival, or PFS, for the Gatotolistin triplet was 9.3 months compared to only two months for fulvestrant. That is a 7.3 months incremental improvement in median PFS. The hazard ratio was 0.24, which translates to 4.2 times higher likelihood of survival without disease progression for the Gatotolistin triplet than fulvestrant. For the Gatotolistin doublet, median PFS was 7.4 months, again compared to only two months for fulvestrant, with a 5.4 months incremental improvement in median PFS. The hazard ratio was 0.33, which translates to three times higher likelihood of survival without disease progression for the Gatotolistin doublet than for fulvestrant. These results established several new milestones in the history of drug development for this patient population. First, the hazard ratios reported for both the Gatotolistin 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, 7.3 and 5.4 months respectively, 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, Gatotolistin is the first PAM inhibitor to achieve a positive Phase III data result in patients with PIK3CA wild type tumors and whose disease progressed on or after treatment with a CDK4/6 inhibitor. For comparison purposes, it's important to note that several Phase III studies in this patient population have reported data recently. In these studies, the incremental improvement in median PFS ranged from 1.7 to 3.9 months, and the hazard ratios ranged from 0.55 to 0.73.

Both Gatotolistin regimens exhibited a favorable safety profile, including lower rates of hyperglycemia and stomatitis, and the rate of discontinuation of all treatment due to a treatment-related adverse event was lower than was reported in a Phase IB study in this patient population. In light of the favorable safety profile, more favorable hazard ratios, and longer incremental PFS for the Gatotolistin regimens than the other currently available or investigational agents, we believe both the Gatotolistin triplet and doublet each have the potential to establish a new standard of care for these patients. We're on track to submit a new drug application to the FDA in the fourth quarter of 2025 for Gatotolistin based on data from the PIK3CA wild type cohort, and we're looking forward to presenting the full data set later this year at an upcoming medical conference.

Additionally, we expect to release top-line data for the Victoria 1 PIK3CA mutation cohort by the end of 2025. Moving on, I want to share just a quick overview of the market landscape we see for Gatotolistin and how we're gearing up for a potential launch should we get FDA approval. We think the market looks very promising for Gatotolistin. We estimate there are 34,000 patients moving to second-line treatment after progressing on a CDK4/6 inhibitor, and roughly 60% of them are PIK3CA wild type. That's a very large opportunity, and there's also a significant need for more efficacious therapies than those currently available. Currently approved therapies only offer two to four months of median PFS. With Gatotolistin's unique mechanism of action and corresponding clinical benefit, it's well-positioned to address critical needs in the second-line space.

This unmet need has been verified in our market research, which shows that oncologists are hungry for options that are more effective and have a safety profile they can manage. As we've discussed on prior calls, efficacy and safety are the two primary criteria oncologists use to select therapies for their patients. This is also consistent with the criteria used by treatment guidelines such as NCCN to determine recommendation categories for drug treatments. Additionally, as an IV-administered therapy, we believe Gatotolistin will be very well received in the community practice setting where over 80% of patients are treated. Gatotolistin will fall under the medical benefit category, which means a typically smoother reimbursement process compared to oral drugs that fall under the pharmacy benefit category. For oral drugs, payers tend to manage claims more heavily, resulting in a more cumbersome prescribing and reimbursement process for practices.

Unlike oral drugs, IV-administered therapies also allow physicians to recover costs associated with the purchase and administration of therapy and to better ensure patient compliance with their treatment regimen. Finally, the breast cancer community is active, engaged, and well-supported by advocacy groups, which will help create awareness for new treatments in general, and we think for Gatotolistin specifically. As a result, we believe Celcuity has the opportunity to build a strong presence amongst medical oncologists to address this large underserved patient population. Based on our projections, we believe the addressable market potential for a standard of care second-line therapy to treat this patient population is roughly $5 billion. I'd like now to turn to our Phase III, Victoria 2 trial.

Last month, we announced that we dosed the first patient in Victoria 3 that's evaluating Gatotolistin plus a CDK4/6 inhibitor that the investigator may choose and fulvestrant as first-line treatment for patients who have endocrine therapy-resistant HR-positive, HER2-negative advanced breast cancer. The standard of care first-line treatment for most endocrine therapy-resistant patients includes any one of three approved CDK4/6 inhibitors combined with fulvestrant. Results from a recent trial suggest the median progression-free survival period for patients receiving one of these three regimens is only about seven to eight months, highlighting the significant need for more efficacious front-line therapy for these patients. We believe the positive top-line data from the PIK3CA wild type cohort of our Victoria 1 study augurs well for the Gatotolistin triplet in this patient population.

I'd like now to turn to our Phase IB2 clinical trial that's evaluating Gatotolistin in combination with darolutamide in men with metastatic castration-resistant prostate cancer. In late June, we announced encouraging Phase IB preliminary efficacy and safety data from this study, which enrolled 38 prostate cancer patients who were randomly assigned to either receive 80 milligrams of darolutamide twice daily combined with either 120 milligrams of Gatotolistin in arm 1 or 180 milligrams of Gatotolistin in arm 2. Gatotolistin was administered once weekly for three weeks and then one week off in both arms. The preliminary analyses for the combined arms show the six-month radiographic PFS rate was 66%, which compares favorably to published data for androgen receptor inhibitors in this setting. Additionally, the data highlighted the favorable safety profile of this novel combination. There were no treatment-related discontinuations, and less than 3% of patients experienced grade 3 stomatitis.

These data indicate that the optimal Gatotolistin dose for this patient population may not yet have been reached. We believe it's important to explore additional dose options for Gatotolistin. As such, we amended the clinical trial protocol to enable exploration of additional doses in the Phase IB portion of this clinical trial to determine the recommended Phase II dose. In addition to announcing the encouraging preliminary data from our prostate cancer trial, we also announced encouraging data from an investigator-sponsored Phase II clinical trial. In this trial, 44 patients with HER2-positive PIK3CA-mutated breast cancer were treated with Gatotolistin plus standard doses of a trastuzumab biosimilar. No prophylaxis for stomatitis was administered. The median number of prior anti-HER2 therapies enrolled patients received in the metastatic setting was four or more. 86% of patients had received at least three prior anti-HER2 therapies, so these patients were heavily pretreated.

The overall response rate was 43%, and no patients discontinued Gatotolistin due to a treatment-related adverse event. Achieving 43% overall response rate in patients receiving a fourth or fifth line of anti-HER2 treatment for their disease is very encouraging and compares favorably to published data for other available therapies in this group of patients. It also suggests that Gatotolistin in combination with HER2 targeted therapy may be an effective and well-tolerated therapeutic option for patients with HER2-positive metastatic breast cancer. Now, I'd like to turn to a few corporate updates. First, the U.S. Patent and Trademark Office issued Celcuity a new patent covering the clinical dosing regimen for Gatotolistin in HR-positive, HER2-negative breast cancer patients. The patent extends Gatotolistin's patent exclusivity in the U.S. into 2042. With this added patent exclusivity, we expect to have a long runway to optimize the development of Gatotolistin.

Last but not least, we also completed concurrent offerings of convertible notes, common stock, and pre-funded warrants with net proceeds of $286 million and $0.5 million at the end of July and beginning of August. With our current resources and other financing arrangements, we believe we are well-positioned to advance multiple blockbuster indications in breast and prostate cancer and to aggressively prepare for and launch Gatotolistin commercially should we receive FDA approval. I'd like now to hand the call over to Vicky Hahne, our CFO, to review our finances.

Speaker 6

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the second quarter of 2025. Our second quarter net loss was $45.3 million, or $1.04 per share, compared to $23.7 million net loss, or $0.62 per share for the second quarter of 2024. Our non-GAAP adjusted net loss was $40.5 million, or $0.93 per share for the second quarter of 2025, compared to non-GAAP adjusted net loss of $22.2 million, or $0.58 per share for the second quarter of 2024. Research and development expenses were $40.2 million for the second quarter of 2025, compared to $22.5 million for the second quarter of 2024.

Of the approximately $17.7 million increase in R&D expenses, $6.6 million was related to increased employee and consulting expenses, $6.1 million was related to increased research and development costs, primarily attributable to activities supporting our ongoing clinical trials, and $5 million is related to an anticipated development milestone payment under the license agreement with Pfizer. General and administrative expenses were $3.8 million for the second quarter of 2025, compared to $1.8 million for the second quarter of 2024. Of the $2 million increase in general and administrative expenses, $1.6 million was related to increased employee and consulting expenses. The remaining $0.4 million of the $2 million increase resulted from professional fees, expanding infrastructure, and other administrative expenses. Net cash used in operating activities for the second quarter of 2025 was $36.2 million, compared to $18.1 million for the second quarter of 2024.

We ended the quarter with approximately $168.4 million of cash, cash equivalents, and short-term investments. However, on a pro forma basis, taking into account the net proceeds of our financing activities in Q3, cash, cash equivalents, and short-term investments as of the end of Q2 2025 was approximately $455 million. Additionally, existing financing arrangements are expected to give us access to an incremental $116 million of cash over the next few quarters, $80 million from our current term loan agreement, and $36 million from the exercise of soon-to-expire in the money warrants. As a result, we believe we have the resources and financing in place to fund our operations through 2027. I will now hand the call back to Brian.

Speaker 0

Thank you, Vicky. Operator, could you please open the call for questions?

Speaker 7

Thank you very much. Ladies and gentlemen, we will now begin the question-and-answer session. Should you have a question, please press star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number two. If you are using a speakerphone, make sure to lift your handset before pressing any keys. Your first question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Hi, this is Amin Makarem for Maury Raycroft. Thank you for taking our questions and congrats on all the progress. A couple of questions from us. First, regarding the upcoming full data presentation later this year for PIK3CA wild type portion of the Phase III study, can you elaborate on what we should expect to see? Specifically, will you be sharing subgroup analysis such as PFS and OS for ESR1 wild type and mutant cohorts there? I have a follow-up.

Speaker 0

We'll be focused on our initial data presentation on the primary analyses, the primary endpoints, and then we would expect to present data at subsequent meetings, additional subgroup analyses.

Okay, sounds good. For the PIK3CA-mutated population, how are you thinking about the benchmarks for success here? Is there a specific hazard ratio or PFS delta that you are considering a meaningful threshold there and could be considered clinically meaningful?

Sure. I think there are two thresholds to consider when we're reviewing the data in that cohort. The first is the comparison to the control, which in this case is alpelisib fulvestrant. As it turns out, given what we think is the likely outcome based on historical data for alpelisib in this population of between, let's say, seven to eight months, a statistically significant result would also be a clinically meaningful result of a little less than three months. We think if we have a positive study, we'll also be reporting clinically meaningful results. Additionally, because alpelisib is probably no longer the primary option that physicians are relying on, we think from a practical standpoint, the benchmark data that physicians will consider will be the data for capivasertib AKT inhibitor. Capivasertib data is reported data in the post-CDK population of about five and a half months of median PFS.

If we're able to report positive results relative to alpelisib, those will be especially positive relative to capivasertib.

Okay, sounds good. Thank you.

You're welcome.

Speaker 7

Your next question is from the line of Tara Bancroft from TD Cowen. Please go ahead.

Hi, this is Frances on for Tara Bancroft. Just one question on our end. Since the full safety data isn't broken out in the top line, is there any more detail you can offer ahead of it? If there's better rates observed, was that overall rates or just grade 3 stomatitis?

Speaker 0

Sure. We will be providing that data at the upcoming conference. We were really only at this stage able to provide a general summary of what we saw, but the additional detail will be forthcoming.

Speaker 7

The next question is from the line of Andrew Behrens from Leerink Partners. Please go ahead.

Hi, good afternoon. This is Eason on for Andy. Congrats on all the progress and thanks for taking our questions. Just a two-parter if I can. We noticed across various pivotal trials in the HR-positive, HER2-negative breast cancer space, it's been mixed whether the PFS primary endpoint was based on BICR, as is the case in VICTORIA-1, or based on investigator assessment. First question is, can we expect the PFS analysis based on investigator assessment to be presented at an upcoming meeting later this year? Second, what is the company's understanding on the concordance between BICR versus investigator assessment based on what we've seen in prior HR-positive, HER2-negative trials, as well as how is this aspect evaluated by FDA and other regulatory agencies? Thank you.

Speaker 0

No, thanks. The selection of BICR for our study as the assessment method was a function of our study being an open-label study, and that just reflects that Gatotolistin is an IV-administered drug and you can't really have a plausible placebo. You use blinded assessment of the scans to ensure that you're eliminating the potential for investigator bias. That's why you see that the trials for the recent oral SERDs, the Emerald trial and the Veritech 2 trial, were also BICR studies because, again, it's not plausible to create a placebo for fulvestrant. BICR is the method that the FDA actually encourages or recommends when you do have an open-label study for that purpose. In this case, the investigator data is really simply collected as part of ongoing assessment, and it's more for exploratory sensitivity analysis.

It's not a fundamental analysis, and we'll be reporting data, as I indicated earlier, in a sequence as we move from one conference to another. To your question regarding concordance, I think I saw one study that showed the concordance between the hazard ratios of a BICR PFS and the investigator-assessed PFS were, I think, correlated well over 90%. It might even have been 95%. We do not expect to have any issues on that front. In the processes, we prepare for NDA doing sensitivity analyses, many of which are prescribed by the FDA in our discussions with them about our statistical analysis plan. All those sensitivity analyses are indicating that our data is very robust and we're very comfortable and confident about the package that we expect to submit to the FDA.

Great. Thank you.

Speaker 7

The next question is from the line of Stephen Willey from Stifel. Please go ahead.

Good afternoon. Thanks for taking the question. I was just wondering how you're now thinking about launch readiness. You're going to be filing an NDA here in the fourth quarter. You've got breakthrough. Presumably, there's an RTOR pathway you can leverage. What are some of the comps that you look to in terms of the requisite amount of infrastructure build that you need? How do you think about scaling that infrastructure here over the near term and as we get into 2026?

Speaker 0

Sure. No, that's a great question. It's a couple of points to highlight. First, we began building our team last year. We hired our Chief Commercial Officer, Eldon Meyer, in the first quarter of 2024. He, in turn, brought on board a Head of Marketing, Head of Market Access, and Head of Commercial Operations. They focused on projects that have a long lead time, and there are a variety of those that can take up to 18 months to get done. Essentially, we've been working back from a launch date. You have to assume an earlier launch date or you're kind of aggressive on when you think that'll occur just so you're not blindsided and you're ready under any circumstance. As we've gotten closer to launch these past few months, we've begun hiring the individuals who report up to the heads of these various departments.

In turn, they've been taking on more projects. Now that we have our data, we have what we think is a clear path to an approval decision, where we can define with some degree of confidence a launch date, we'll be taking that next step. That'll involve additional infrastructure associated in the commercial operations area to support Salesforce, to supporting them as Salesforce. There are activities in the market access area, engaging with payers and strategic accounts in ways that are appropriate at this stage. In turn, you start to build out your Salesforce management structure, starting with Head of Sales and then regional management, which in turn requires you to define sales territories, number of territories, the geographic alignment, et cetera. All those projects are on track.

As far as how are we doing or what is our benchmark, we've been very deliberate about hiring folks in all of these key positions, people who have been involved in first launch of a company's drug, first drug launch for a company. That's critical because there's so much infrastructure and operational support activities that are required to be effective as a commercial organization. It's not a plug and play of somebody coming from Big Pharma who has never had to set up all of this infrastructure or to establish these processes and these functions from scratch. I think we've been very, very fortunate. We've hired a great team, incredibly experienced, very focused, and I think we're absolutely on track to having what we think.

We're optimistic about the launch and our ability to be very, very effective in communicating the benefits of what we believe are the benefits of Gatotolistin to medical oncologists.

All right. Thanks for taking the question.

You're welcome.

Speaker 7

Your next question is from the line of Gil Blum from Needham & Company. Please go ahead.

Hi, this is Gil Blum for Gil. Just a couple from us. Can you put into context the practical ramifications for physicians now that they may have optionality with both a doublet and a triplet? I have a follow-on.

Speaker 0

I think the primary goal of all these physicians is to optimize and delay as long as possible the progression of a patient's disease, and the triplet offers that to these doctors. Now, the triplet, because it includes palbociclib, also induces some myelosuppression, which for patients who could be elderly or have an immune system that may be more compromised, they may consider not to be appropriate. They'll have the option of still getting very, very, what we believe, extended incremental benefit in PFS. What we think having either regimen available does is allow us to have access to as broad a range of patients as possible. That's always great.

I think as we get into and describe results for different subgroups, that will help guide some of the decision-making for different subgroups for physicians and how they might want to think about the doublet versus the triplet as an example.

Thank you. Very helpful. Just as a follow-on to Steve's question, is there any consideration on commercial partnering strategy for a launch? It looks like it might be a very large investment just given the size of the market. Thank you.

No, we're expecting and planning to launch ourselves. We think we understand what's required. We know what's required. We have a very, very detailed operating plan and operating budget. We know what the headcount is and why we need to bring them on. The investment is not insignificant, but it's not ridiculous, to be frank. Relative to the size of the opportunity, it's very manageable. We have financed ourselves accordingly. That's the other part of the equation, obviously, is having sufficient capital to invest aggressively in a launch. We think we've set ourselves up very well with our balance sheet to do that. Just purely from a financial perspective and a financial return perspective, it makes absolute sense for us to be launching this ourselves and not to be partnering with somebody.

Thanks for taking our questions.

You're welcome.

Speaker 7

Your last question comes from the line of Chase Knickerbocker from Craig-Hallum Capital Group. Please go ahead.

Speaker 8

Good afternoon. Thanks for taking the questions. Maybe Brian, just to start, could you give us your general thoughts on the competitive landscape in the mutant population? There's obviously some other actionable mutations in there with ESR, et cetera. Can you give us your general thoughts as far as the competitive environment there and how you see kind of gedatolisib fitting in?

Speaker 0

Right. I think two things. For PIK3CA mutation patients, we'll be reporting out that data later this year. Obviously, if our data is positive and shows benefit relative to alpelisib, we think that'll position us very well to establish gedatolisib as a new potential standard of care. We think that'll kind of speak for itself. As far as the ESR-1 mutations, we just don't think they'll be as relevant given the nature of the drug combination that we have. In the absence of inhibition of, let's say, CDK4/6 or the PI3K/AKT/mTOR pathway, potentially in ESR-1 mutant patients, data suggests that you can get some incremental benefit if you use an oral SERD to address that pathway. At the same time, we think if you are addressing the PI3K/AKT/mTOR pathway and CDK4/6, the relative difference in outcomes between the ESR-1 mutant and wild type patients is unlikely to be meaningfully different.

Speaker 8

Got it. Maybe just on the mutant side to dig in a little bit there. Obviously, the most recent approval there with alpelisib, can you just give us some thoughts as far as kind of how the market's changed in the last 10, 12 months and any relevant comparisons there?

Speaker 0

Sure. I kind of still use the generic name alpelisib. That drug's a PI3K alpha inhibitor. It's approved for treating patients who have a PIK3CA mutation in the first-line setting for women who have endocrine treatment-resistant disease, advanced disease. That's actually the patient population that we're addressing in our VIKTORIA-2 study. That population doesn't overlap at all with the population that we'll be addressing with the VIKTORIA-1 study results. The data does provide confirmation that in the front-line setting, treatment-naive patients have involvement of the PI3K/AKT/mTOR pathway in their disease, and they'll benefit. In this case, this drug has only shown favorable activity in patients that have a PIK3CA mutation. That drug also induces levels of hyperglycemia that can potentially limit its use to patients who are healthy metabolically, which means they are not prediabetic or not diabetic at all.

We would hope, and that's what our trial will evaluate, that gedatolisib can be effective in treating patients independent of their PIK3CA status and independent of their metabolic status and independent of their HbA1c levels or glucose levels. Ultimately, if our data from wild type recapitulates in the VIKTORIA-2 study and we show activity generally, we think we have another opportunity to establish gedatolisib as a potential standard of care.

Speaker 8

Thanks, Brian. Maybe just a little more if I could sneak it in. On the CMC portion of your filing, when you submit it in Q4, can you just remind us, you know, your manufacturer there, any specifics you're wanting to give as far as your kind of confidence around your CMC package?

Speaker 0

We're very confident about the CMC package. We have all the data. Our modules are complete for CMC. There's a very prescribed set of studies that are expected, analyses to be performed, a number of demonstrations of consistency of your process, and that's all been done. We're very confident just based on the robustness of the package that we've built and the data that we've generated that we should satisfy the FDA's requirements. We've also engaged directly with the FDA and ensured that there aren't any open questions based on an outline that we've provided to them of the data we expect to provide. We think we should be in good shape on that front.

Speaker 8

Great. Thanks, Brian.

Speaker 0

You're welcome.

Speaker 7

There are no further questions at this time. I'd like to turn the call back to Mr. Brian Sullivan for closing comments. Sir, please go ahead.

Speaker 0

Thank you for participating in our call today, and thank you for your ongoing support. I look forward to catching up with you at various conferences along the way. Take care.

Speaker 7

Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.