CELC - NASDAQ

Good afternoon, ladies and gentlemen, and welcome to the Celcuity Fourth Quarter and Full Year 2024 Financial Results Webcast Conference Call. [Operator Instructions] I would now like to turn the conference over to Apoorva Chaloori with ICR Healthcare. Please go ahead.

Thank you, operator, and good afternoon to everyone on the call. Thank you for joining us to review Celcuity's fourth quarter and full year 2024 financial results and business update. Earlier today, Celcuity released financial results for the fourth quarter ending December 31, 2024. The press release can be found on the Investors section of the 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 could find the table reconciling the non-GAAP financial measures to GAAP measures in today's press release. And with that, I would now like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

Thank you, Apoorva, and good afternoon, everyone. We appreciate your interest in Celcuity. Our team made significant progress executing our clinical development programs in 2024. We completed enrollment of the PIK3CA wild-type cohort in VIKTORIA-1, our Phase III study evaluating gedatolisib plus fulvestrant with and without palbociclib as second-line treatment for patients with HR-positive, HER2-negative advanced breast cancer. We also completed selection of approximately 200 sites for VIKTORIA-2, our Phase III study designed to evaluate gedatolisib in combination with fulvestrant and either ribociclib or palbociclib as first-line treatment for patients with HR-positive, HER2-negative endocrine treatment resistant advanced breast cancer. Our Phase Ib dose escalation portion of our study evaluating gedatolisib in combination with darolutamide for patients with metastatic castration resistant prostate cancer is ongoing and remains on track to report preliminary data at the end of the second quarter this year. And we reported overall survival data from our Phase Ib study for treatment-naive and CDK4/6 pretreated patients who received our Phase III dosing schedule. In our view, each of these 3 programs has the potential to generate blockbuster levels of revenue. These 3 programs ultimately result in regulatory approvals. We estimate that nearly 200,000 late-stage cancer patients globally would be eligible to be treated with gedatolisib. As a result of the progress we made in 2024, 2025 will be a transformational year for Celcuity as we anticipate reporting several important clinical data readouts. For our VIKTORIA-1 clinical trial, we anticipate reporting top line data for the PIK3CA wild-type cohort in the second quarter of 2025 and top line data for the PIK3CA mutant type cohort in the fourth quarter of 2025. The primary endpoints of VIKTORIA-1 are progression-free survival or PFS per RECIST 1.1 criteria as assessed by blinded independent center review. The study is designed to independently evaluate a PIK3CA wild-type cohort and a PIK3CA mutant cohort. For the PIK3CA wild-type cohort, there are 2 primary endpoints that will be tested hierarchically, whereas the PIK3CA mutant patient cohort has a single primary endpoint. The primary analysis for each patient cohort is triggered upon reaching a predefined number of progression events. Patients we're evaluating in our VIKTORIA-1 study have HR-positive, HER2-negative advanced breast cancer, whose disease progressed while on or after receiving treatment, with a CDK4/6 inhibitor and an aromatase inhibitor. We recognize that the treatment landscape for these second and third-line patients is evolving as a number of investigational therapies are under development. Our view is that the underlying biological drivers of HR-positive, HER2-negative advanced breast cancer will ultimately determine which regimens become standard of care. Three interconnected signaling pathways: estrogen's cyclin D1, CDK4/6 and PI3K-AKT-mTOR pathways promote this disease. And we believe that simultaneous blockade of all 3 of these pathways offers the best opportunity to optimize antitumor control. And this suggests that a triplet that addresses these three disease drivers, whether in the first or second-line setting, may have a long-term advantage versus a doublet or monotherapy that addresses just one or two of these signaling pathways. Additionally, in triplet that could treat all patients, regardless of PIK3CA or ESR1 mutational status, would have an even greater advantage. The current second-line treatment paradigm for HR-positive, HER2-negative patients with advanced breast cancer includes selective estrogen receptor degraders, or SERDs, like fulvestrant or elacestrant as single agents, or one of the three approved PAM inhibitors combined with endocrine therapy. However, each of the PAM inhibitors only targets a single PAM node, such as PI3K alpha, AKT or mTORC1, which is suboptimal because the uninhibited PAM nodes can induce compensatory resistance. In patients who have received prior treatment with a CDK4/6 inhibitor, none of these single-node PAM inhibitors have demonstrated efficacy in patients with PIK3CA wild-type tumors, while only the PI3K alpha and AKT inhibitor have reported benefit in patients with PIK3CA mutations. And these results are consistent with the nonclinical data that shows these single-node inhibitors are three to four times less potent in breast cancer cells without PIK3CA mutations than in those with them. Now this is in sharp contrast to the nonclinical and preliminary efficacy data we've reported for gedatolisib. In nonclinical studies evaluating breast cancer and prostate cancer cell lines, gedatolisib was found to be equally potent and cytotoxic in cell lines with and without PIK3CA or P10 mutations, and at least 300 times more potent on average in breast cancer cells than single-node PAM inhibitors. Now consistent with these nonclinical results, the preliminary clinical endpoints we reported in our Phase Ib breast cancer study that evaluated gedatolisib combined with palbociclib and either letrozole or fulvestrant was comparable in both treatment-naive and second, third-line patients with and without PIK3CA mutations. And we think these results demonstrate that along with the ER and CDK4/6 pathways, the PAM pathway plays an intrinsic role as a disease driver in HR-positive, HER2-negative advanced breast cancer that's independent of the presence of an activating mutation like PIK3CA. And that's why we believe development of an optimized PAM inhibitor, like gedatolisib, that targets all Class I PI3K isoforms and mTORC1 and 2 to comprehensively blockade the PAM pathway represents one of the most important opportunities to improve the standard-of-care in HR-positive, HER2-negative advanced breast cancer. We think that gedatolisib's tolerability may also favor its potential positioning in a future treatment landscape. Gedatolisib's treatment-related discontinuation rate due to adverse events was only 4% in the Phase Ib arm with the Phase III intermittent dose schedule, which is comparable to the 6% to 8% discontinuation rates for CDK4/6 plus fulvestrant regimens. While we don't have head-to-head data, these results compare favorably to the treatment-related discontinuation rates reported in the Phase III studies for alpelisib plus fulvestrant where 26% of patients discontinued, and everolimus plus exemestane where 24% of patients discontinued. The results for gedatolisib are especially encouraging given that the Phase Ib study did not include prophylactic therapy for stomatitis, the most common treatment-related adverse event for gedatolisib. Since we're prescribing stomatitis prophylaxis in our Phase III trial, we would expect fewer stomatitis-related averse events, which would further enhance geda's already promising tolerability. Now of course, the foundation of geda's role in this treatment landscape will require that gedatolisib be well-tolerated and report a clinically meaningful benefit, measured in terms of the incremental improvement in both median PFS and the hazard ratio relative to standard-of-care. Now breast cancer KOLs and regulators generally consider an incremental improvement in median PFS of three months relative to its control to be clinically meaningful. In the current median PFS benchmarks for patients pretreated with a CDK4/6 inhibitor, the patient population we're evaluating, are modest. Published reports from recent randomized trials of meeting progression-free survival for fulvestrant averaged 2.7 months in patients with ESR1 wild-type tumors and 3.8 months for oral SERDs in patients with ESR1 mutant tumors. The incremental median PFS benefit for patients with ESR1 mutations treated with an oral SERD was a 1.9-month difference. For patients with PIK3CA or AKT mutations, median PFS ranges from 5.5 to 7 months when treated with either an AKT or PI3K alpha inhibitor, representing approximately 3.5 months of incremental median PFS benefit. The rapid adoption and resulting annual run rate for each of these drugs is approximately $500 million and $600 million, respectively, illustrates the desire for physicians have to switch to new therapies even when the incremental clinical benefit to their patients is modest. Now, potentially more important data point than incremental PFS benefit to consider in advanced breast cancer when assessing the clinical benefit of one therapeutic regimen relative to another is the hazard ratio. Now this is because recent randomized studies evaluating therapies for patients with HR-positive, HER2-negative advanced breast cancer have enrolled widely heterogeneous patient populations. For instance, one study that evaluated an oral SERD conducted primary analysis that included first and second-line patients. And the same study evaluated the combination of the oral SERD with a CDK4/6 inhibitor that included both patients who are CDK treatment-naive and those who had received prior CDK4/6 therapy. In another study evaluating an AKT inhibitor, the primary analysis included both patients who were CDK4/6 treatment-naive and those who had received prior CDK4/6 therapy. Well, since patients -- physicians rather, make different treatment decisions for patients depending on, among other factors, how many lines of therapy or which type of therapy they've received, results from these studies can be hard to interpret using absolute median PFS or incremental median PFS benefit alone. As a result, the top line median PFS results from these studies don't provide sufficient clarity about the actual benefit a particular patient population may receive. Hazard ratio essentially factors out the differences in study populations, and thus, provides patients -- physicians rather with an objective benchmark. We thus, not only hope to report a hazard ratio that is statistically significant, but one that compares favorably to the hazard ratio reported for other therapies available for these second-line patients. An additional factor, which we think may ultimately accrue to gedatolisib's advantage, particularly in the community physician setting, is the fact that geda is an infused therapy administered in office. And this perspective has been reflected in the feedback we're receiving from oncologists, both key opinion leaders and community physicians, and market access stakeholders, in conjunction with our preliminary market research. Of particular note is the encouraging feedback received regarding gedatolisib's ideal route of administration. Physicians can monitor and manage patient compliance more effectively than they can with oral therapies. And this is relevant, particularly for oral therapies that induce unpleasant side effects. For these therapies, patient compliance can often be a challenge. And this preliminary research does suggest an IV administration will not be a barrier to utilization of gedatolisib, in fact, may be an important advantage. Additionally, in office-administered therapies such as gedatolisib, fall into the medical benefit category, which has a more streamlined reimbursement process than orally administered drugs which fall into the pharmacy benefit category. Our market research suggests that this fact has several implications for oncologists, patients and our company. First, oncologists view IV-administered drugs favorably, allowing them to recover additional costs associated with treating their patients in office. And second, oncologists have more autonomy to select therapies they believe will benefit their patients. Third, payer management process is less burdensome to navigate. And finally, patients typically incur lower out-of-pocket costs with an infused therapy, which is an important consideration for most patients. For pharmaceutical companies, payer contracting is less common and results in fewer price discounts. In a real-world setting, patient convenience is only meaningful -- is only a meaningful consideration for IV-administered drugs when the efficacy and safety profile of the alternative drugs are comparable or when a patient lives a significant distance from a treatment site. Otherwise, based on our market research, a well-tolerated therapy that offers a clinically meaningful benefit is preferred by oncologists relative to the one that offers less efficacy but is more convenient. The fact that the most widely prescribed oncology drugs are administered in office reinforces this point. For instance, in breast cancer, Herceptin, Perjeta, Keytruda in HER2, each recorded multibillion-dollar peak revenues, while treating smaller patient populations than the potential populations we seek to address with gedatolisib and our two current breast cancer clinical trials. If gedatolisib ultimately does receive FDA approval for both the PIK3CA wild-type and mutant populations, we estimate the peak revenue potential for this second-line indication could exceed $2 billion with just 40% market penetration. Now turning to our first-line breast cancer program. We've completed the selection of the clinical sites that will participate in our VIKTORIA-2 study. Approximately 200 sites across North America, Europe, Latin America and Asia Pacific are in process now of being activated. We're very pleased with the level of interest our current VIKTORIA-1 sites expressed in participating in the study. And we continue to expect to enroll our first patient in the second quarter of 2025. VIKTORIA-2 study is a global Phase III open-label randomized clinical trial evaluating the efficacy and safety of gedatolisib in combination with fulvestrant plus investigator's choice of either ribociclib or palbociclib as a first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer who are endocrine therapy-resistant. Approximately 638 patients will be assigned to a cohort based on the PIK3CA mutation status. Clinical trial endpoints are progression-free survival per RECIST 1.1 criteria as assessed by blinded independent center review. Primary PFS endpoint for each of the two cohorts will be evaluated independently. Prior to the initiation of the Phase III portion of the trial, safety run-in study will be conducted in 12 to 36 patients to assess the safety profile of gedatolisib in combination with ribociclib and fulvestrant. We estimate that 15,000 to 20,000 patients with endocrine therapy resistant advanced breast cancer are diagnosed each year in the United States alone. And since this population doesn't overlap with the patient population we're evaluating in our VIKTORIA-1 study, an approval to treat these patients would increase the size of the addressable U.S. market potential for gedatolisib by up to $3 billion. Turning now to our prostate cancer program. We remain on track with our Phase Ib trial that is evaluating safety and tolerability of geda in combination with darolutamide in patients who have metastatic castration resistant prostate cancer. The underlying biology of prostate cancer has a lot of similarities to ER-positive breast cancer. Both are hormonally driven tumor types and both involve the PAM pathway. While the development of PAM inhibitors in breast cancer is further advanced than in prostate cancer, there's significant nonclinical evidence and emerging clinical data that suggest simultaneous inhibition of both the AR and PAM pathway may be more efficacious than treatment with an AR inhibitor alone. We expect to report our preliminary data from the Phase Ib dose escalation portion of the study towards the end of the second quarter of this year. Since we're at an earlier phase in this program, our focus is optimizing the dose and schedule for this tumor type and drug combination. The data set will include approximately 36 patients, half of whom will have received a 120-milligram dose of geda, the other half 180-milligram dose. Each are administered on a 3-week on, 1-week off schedule. We're comparing both the landmark PFS at 6 months and the safety profile of these 2 arms to each other and historical control data for second-line metastatic castration resistant prostate cancer patients who are re-treated with an androgen receptor inhibitor. And finally, we were very excited to report last December encouraging preliminary overall survival data from both first-line and second-line advanced breast cancer patients from our Phase Ib study that evaluated gedatolisib in combination with palbociclib and endocrine therapy. For the Phase I -- or rather the first-line patients, median overall survival was 77 months, which compares favorably to published Phase III data for palbociclib plus letrozole. For the second-line cohort, median overall survival was about 34 months, which compares favorably to recently published OS data results for fulvestrant. And of course, you have to be careful making cross-trial comparisons, especially since ours was just a single arm study. But certainly, we view the data as very encouraging. And with that, I'll now turn the ball -- call over to Vicky Hahne to review our financial results.

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the fourth quarter and full year 2024, and I invite you to review our 10-K which will be filed later today for a more detailed discussion. Our fourth quarter net loss was $36.7 million or $0.85 per share, compared to $18.8 million net loss or $0.65 per share for the fourth quarter of 2023. Net loss for the full year 2024 million was $111.8 million or $2.83 per share, compared to $63.8 million net loss or $2.69 per share for the same period in 2023. Because these quarterly and full year net losses include significant noncash items, including stock-based compensation and non-cash interest, we also included in our press release non-GAAP adjusted net loss for the quarter and the full year ending December 31, 2024. Our non-GAAP adjusted net loss was $32.3 million or $0.75 per share for the fourth quarter of 2024, compared to non-GAAP adjusted net loss of $17.6 million or $0.61 per share for the fourth quarter of 2023. Non-GAAP adjusted net loss for the full year 2024 was $101.9 million or $2.58 per share, compared to non-GAAP adjusted net loss of $57.8 million or $2.44 per share for the full year 2023. Research and development expenses were $33.5 million for the fourth quarter of 2024, compared to $18.1 million for the fourth quarter of 2023. R&D expenses for the full year of 2024 were $104.2 million, compared to $60.6 million for the prior year. Of the approximately $43.6 million increase in R&D expenses year-over-year, $30.7 million was related to ongoing activities supporting the VIKTORIA-1 Phase III trial and the Phase Ib/II prostate trial, along with the commencement of the VIKTORIA-2 Phase III trial. The remaining $12.9 million increase in R&D expenses is related to increased employee and consulting expenses. General and administrative expenses were $3 million for the fourth quarter of 2024, compared to $1.6 million for the same period in 2023. G&A expenses for the full year of 2024 were $9.1 million, compared to $5.6 million for the prior year. Of the approximately $3.4 million increase in G&A expenses, $2.6 million was related to increased employee-related expenses and $0.8 million was related to professional fees, expanding infrastructure and other administrative expenses. Net cash used in operating activities for the fourth quarter of 2024 was $27.8 million, compared to $18.5 million for the fourth quarter of 2023. This was a result of non-GAAP adjusted net loss of approximately $32.3 million, offset by approximately $4.5 million of working capital changes. Net cash used in operating activities for the full year 2024 was $83.5 million, compared to $53.8 million for the full year 2023. This was a result of non-GAAP adjusted net loss of approximately $101.9 million, offset by working capital changes of approximately $18.4 million. We ended the year with approximately $235.1 million of cash, cash equivalents and short-term investments, compared to $180.6 million on December 31, 2023. The increase of $54.5 million in cash, cash equivalents and short-term investments was a result of several financing activities that occurred in fiscal 2024, and yielded net proceeds of $138.4 million. The $138.4 million was partially offset by year-to-date operating cash use of $83.5 million and capital equipment purchases of $0.3 million. I will now hand the call back to Brian.

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

[Operator Instructions] Your first question comes from Maury Raycroft with Jefferies. Please go ahead.

Hi, thanks for taking my questions and congrats on the progress.

Thanks.

Just wondering if you can provide an update on the current status of the event rate for VIKTORIA-1. And are you expecting to achieve the required number of events any day now, or is there still some time left before reaching the final milestone to trigger the readout?

So at this stage, we're not commenting on any of the specifics related to achieving our ability to report top line data. So right now we're just providing guidance on when we believe we'll have the top line data available.

Got it. Okay. And wondering if you can talk more about your plans following the second quarter readout, when do you expect to file the NDA and what are your thoughts on whether you would get priority review?

Sure. So we would hope to initiate an our TOR request, a Real-Time Oncology Review request, soon after we have our top line data. FDA has to approve that request. Otherwise, if they don't approve that, we would seek to get a priority review. We think either of those programs would shorten the overall review time substantially. And we think because we have breakthrough status, that we certainly -- we'd get good consideration of those requests. For instance, and then if we have our TOR status granted, we would begin submitting within months of receiving that approval, and with completion of the overall package within 1 quarter, 1.5 quarters after we get our top line data.

Got it. That’s helpful. Okay, thanks for taking my questions. I’ll hop back in the queue.

You’re welcome.

Thank you. The next question comes from Brad Canino with Stifel. Please go ahead.

Hi, good afternoon. Thanks for the questions, Brian. First, could you just discuss what you're currently thinking about the extent of the data you would plan to share in the 2Q top line, and then how time lines might look for a medical meeting presentation?

Sure. So we would expect to present median PFS data for each of the 3 arms in the wild-type cohort as well as corresponding hazard ratios for the 2 primary analyses. And then follow that up with a complete presentation, a fuller presentation of the data at the next available major medical meeting. And we're not really providing a specific estimate of which medical meeting that would be.

Yes. That makes sense. And then separately, have you heard any feedback from investigators, as you're working on site start-up for the frontline triplet, about the Dear Doctor letters sent by Roche for inavolisib about the life-threatening ketoacidosis? And what do you think this might mean for the opportunity in the mutant population where there is a bit of overlap with the inavolisib label? Thank you.

So I'm not going to comment on Roche's situation. As far as feedback from investigators, I think PI3K alpha inhibitors, as I think most of you know, have been known to induce high levels of hypoglycemia. And in the case of the inavolisib drug, it was only evaluated in patients who would be generally considered to be metabolically healthy. They were not prediabetic or didn't have type 2 diabetes. The label itself though didn't restrict the population to that category of patients, while it did require pretty intense monitoring of glucose in the early cycles of treatment. What that means is that drug requires a fair amount of scrutiny to prescribe. And so I think the feedback we've received from investigators is that that imposes a burden on them to provide extra management of these patients, and as well as on the patients because they have to self-administer glucose testing. And so that drug right now is only approved to treat patients who are endocrine treatment resistant in the frontline setting. So it really doesn't overlap with our second-line indication at all. It overlaps with our VIKTORIA-2 first-line population. So I think net-net for us, if we're able to report favorable data and if we're able to present data -- safety data comparable to what we've reported in our early phase studies, we have the potential to have a significant advantage because we would, if all goes according to plan, have the opportunity to treat patients independent of their status of PIK3CA and independent of their metabolic status. We would really only be restricted from treating patients who have uncontrolled type 1 diabetes. And so the easier it is for patients -- doctors to administer drugs, the less potential requirement for patients to self-monitor, obviously, the lower the risk of severe adverse events that could require hospitalization, are all what everyone is looking for in a cancer drug. And so we think we have a good potential opportunity to deliver that. And potentially, based on what you just told me, would contrast with the situation with the Roche drug.

Right, thanks again.

You’re welcome.

Thank you. The next question comes from Oliver McCammon with LifeSci Capital. Please go ahead.

Hi, thanks for the update and for taking my question. So we've seen a number of readouts in advanced ER-positive breast cancer over the past few months. Can you just remind us of how closely we should be looking at patient baseline characteristics like measurable disease and treatment experience in some of these reference studies as we think about contextualizing these upcoming PIK3CA wild-type data? Thanks, again.

Sure. No, that's a great question. The more heterogeneous population that a study enrolls, the harder it can be to interpret the data. And I discussed this a bit in my remarks. And I think you've seen, in some early-phase studies in this setting, inclusion of patients who have non-measurable disease as an example, which makes it very difficult to assess a population that includes a significant proportion of patients of that type, to those who are evaluating patients with measurable disease, because of the impact it can have on progression-free survival and potentially tilting upward the median results. In the setting, in registrational studies, I think we've seen some studies evaluate, as I alluded to earlier, multiple patient groups. And again, it makes it hard to interpret those results because the doctors' needs, and understand what the data is for the patient that they're treating. And whether that patient is a second-line patient that's received prior CDK or first-line patient who may be endocrine treatment resistant, you may have different treatment options for them, or different competitive or different alternatives that may have different relative benefits depending on patient's profile. And all of that said, I think the doctors will be paying very strict attention to the results within a patient population. And the best way to do that, certainly, they'll be looking at the median PFS and whatever the incremental benefit is for patients. But just as important will be the hazard ratio because it really does allow you to more objectively compare results. I mean obviously, you can't do head-to-head comparisons to every drug in the landscape, but the hazard ratio does allow you to essentially net out some of these factors, which make it hard to interpret absolute PFS numbers or absolute incremental PFS. And so again, it's always important to look at who's being treated in the study because of the impact they can have on the results and the relevance when you're comparing it to other studies. But there are ways to try to get a beat on how one drug is performing for patients relative to another drug by using the hazard ratio. Oliver.

Oliver?

Thanks…

I guess, he didn’t like my answer.

No, great answer and thanks for taking my questions.

Okay, you’re welcome.

Thanks. The next question comes from Tara Bancroft with TD Cowen. Please go ahead.

Hello, this is Frances Duvall [ph] on for Tara Bancroft. You mentioned the second-line plus opportunity could reach $2 billion. Can you elaborate regarding the assumptions that go into that number? And then a quick follow-up after that, do you expect to go into a quiet period ahead of the top line data next quarter?

Regarding the second-line opportunity, we estimate, and these estimates are based on third-party data that's available, that there are roughly between 30,000 and 35,000 women who are treated in the second-line setting after they've progressed on a CDK4/6 inhibitor. The pricing for drugs today in this, that are proprietary, treating these patients, ranges up between, I would say, $15,000 to $20,000. So that would be a price assumption to use for estimating the market. And then you can use anywhere between 5 months to 12 months. You have to do sensitivity analysis to estimate then the corresponding served market potential. And from there, you can make an assumption about the penetration rate. How much -- how many of the patients will potentially re-treat versus those who are offering competitive or alternative therapies? And so net-net, we estimate the served market potential for our drug would be about $5 billion. Obviously, we're not going to get all of that. But we think it's not unreasonable to certainly shoot for, let's say, 40% penetration if our data is favorable. And certainly, that might be a goal of ours. And that translates to a $2 billion potential revenue opportunity for us. And then I think your second question, just remind me, Tara person?

Yes. It was just if you expect to go into a quiet period ahead of the top line data next quarter.

We would. But that's to be determined.

Wonderful. Thank you so much.

You’re welcome.

Thank you. The next question comes from Gil Blum from Needham Corporation. Please go ahead.

Hi, Brian thanks for taking our question. So maybe a bit to the side here. Recent reports for degraders have been a little bit, shall we say, disappointing. But activity has been seen specifically in ESR1 mutant population. Now yes, I completely understand it's a different mechanism. But do you think the VIKTORIA study has sufficient powering to, I don't know, see an effect in that population, see if there's some overlap there? Just wondering here.

Sure. We think -- we haven't published this data because the sample size is relatively small, but we did not see in our preliminary Phase Ib data differences in activity associated with ESR1 status. We would hope to eventually report results that isolates activity between ESR1 mutant and wild-type patients. But obviously, the most important mutation relative to our drug is the status of PIK3CA.

And maybe on a similar vein, as it relates to patient activity towards prior CDK4/6, is this something you're also going to break out at that scientific meeting?

As far as which particular CDK4/6 patients had previously?

If it was, I mean, if it was active in those patients, basically if they were clinically responsive.

We'll roll out data probably on a rolling basis. I mean, typically, you have a more narrow presentation of data maybe at the first meeting, and then you follow on with additional details at later meetings. And we'll kind of follow -- I would expect that we would follow that pattern.

Thank you, Brian.

You’re welcome.

Thank you. The next question comes from Chase Knickerbocker with Craig-Hallum Capital Group. Please go ahead.

Good afternoon. Thanks for taking the questions. Brian, actually, maybe one on the prostate study, being that that's 2Q data as well. Can you walk us through kind of the moving pieces and kind of the bar that you have there for either doing some more early to mid-stage clinical work rather than moving that drug -- moving the drug in prostate into later-stage, more robust studies?

Sure. So the population that we're evaluating will have progressed on a prior androgen receptor inhibitor, the next-generation version of those drugs. And if they're re-treated with a different androgen receptor inhibitor in the second-line setting, data suggests that they'll get in the 5 to 5.5 months median PFS benefit. And so we'd be comparing ourselves to that. Since we don't have a head-to-head, we establish our primary endpoint using landmark PFS at 6 months as the primary endpoint for that study. And so we would compare statistically whether we identify a difference between what our PFS rate at 6 months is relative to historical controls. One consideration for us, since we're at a much earlier stage in development of this drug and in light of have the FDA's increased focus on dose optimization, is that that's what we have to make sure we get right. And so we will look at the data and make decisions accordingly. Obviously, one of the big components will be safety. If safety data is great, you have flexibility potentially in your dosing. And those are all questions that we'll be addressing as we review our data.

Got it. Thanks, Brian. And maybe, Vicky, as we think about kind of R&D over 2025, a couple of moving pieces, obviously, with some studies wrapping up and some study starting. Is annualizing Q4 kind of the right way to think about 2025? Or just maybe what you budgeted for R&D in 2025, some general thoughts?

Yes, I think looking at the R&D component, obviously, anticipating any type of additional commercial activities, if we do, that that number would increase. But in terms of the kind of the R&D and G&A spend, Q4 is a relevant take. I mean we will continue to increase some kind of prelaunch activities, 10% or so.

Great. Thanks again.

Thank you. There are no further questions at this time. I will now turn the call over to Brian Sullivan, the Chief Executive Officer and Co-Founder. Please go ahead, sir.

Well, thanks again for participating in our call today, for your ongoing support. We'll be participating in the Needham Conference and Stifel's Virtual Oncology Day in April, and look forward to hopefully interacting with some of you there. Goodbye.