Q4 2025 Celcuity Inc Earnings Call

March 25, 2026

<unk> fourth quarter and full year 2025 financial call at this time all lines are in a listen only mode.

Following the presentation, we will conduct a question and answer session. If at any time. During this call you required immediate assistance. Please press star zero for operator.

I would now like to turn the conference over to Joe D C versus corporate communications and Investor Relations at <unk>. Please go ahead.

Thank you John and good afternoon, everyone. Thank you for joining us to review <unk> fourth quarter and full year 2025 financial results and business update earlier today. So acuity incorporated released financial results for the fourth quarter and full year ended December 31 2025.

Operator: Good afternoon, ladies and gentlemen, and welcome to the Celcuity Q4 and full year 2025 financial call. At this time, all lines are in a 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 star zero for the operator. I would now like to turn the conference over to Jody Sievers, Corporate Communications and Investor Relations at Celcuity. Please go ahead.

Press release can be found on the investors section of <unk> website joining.

Joining me on the call today are Brian Sullivan.

<unk>, Chief Executive Officer, and cofounder, taking on Chief Financial Officer, as well as eager corporate Chatzky, Chief Medical Officer, and Eldon Mayer Chief Commercial 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 look.

Jody Sievers: Thank you, John, and good afternoon, everyone. Thank you for joining us to review Celcuity's Q4 and full year 2025 financial results and business update. Earlier today, Celcuity Inc. released financial results for the Q4 and full year ended 31 December 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, and Eldon Mayer, Chief Commercial 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.

These 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 may 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 companys current performance.

Management believes the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the Companys ongoing core operations and prospects for the future you can find the table reconciling the non-GAAP financial measures.

Jody Sievers: Actual events or results may differ materially from those projected in the forward-looking statements. Such forward-looking statements and their implications may 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 presentations 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 financial measures in today's press release. With that, I would like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

GAAP financial measures in today's press release, and with that I would like to turn the call over to Brian Sullivan CEO of <unk>. Please go ahead.

Thank you Jody good afternoon, everyone and thank you for joining our fourth quarter and full year of 2025 operating and financial update conference call.

Last year has laid the groundwork for what we expect to be a transformative year for <unk> as we prepare for the potential approval and commercialization of <unk> Melissa.

2025.

Remarkable progress achieving a number of clinical and regulatory milestones, while also significantly bolstering our balance sheet and these achievements and the groundbreaking data reported to date are foundational to our goal of establishing <unk> as a new standard of care therapy for patients with HR positive <unk> negative advanced breast cancer.

Among the key clinical and regulatory milestones achieved recently.

CEO of Celcuity. Please go ahead.

Brian Sullivan: Thank you, Jody. Good afternoon, everyone, and thank you for joining our Q4 and full year 2025 operating and financial update conference call. The past year has laid the groundwork for what we expect to be a transformative year for Celcuity as we prepare for the potential approval and commercialization of gedatolisib. In 2025, we made remarkable progress, achieving a number of clinical and regulatory milestones while also significantly bolstering our balance sheet. These achievements and the groundbreaking data reported to date are foundational to our goal of establishing gedatolisib as a new standard of care therapy for patients with HR-positive, HER2-negative advanced breast cancer. Among the key clinical and regulatory milestones achieved recently, first, the FDA accepted our new drug application, or NDA, granted it priority review with a Prescription Drug User Fee Act, or PDUFA, goal date of 17 July 2026.

<unk> first.

The FDA accepted our new drug application or NDA granted priority review with a prescription drug user fee act or <unk>.

Date of July 17, 2026, Andy.

The NDA was submitted under the Fda's real time oncology review program.

Is utilized for drugs offering substantial improvement over available therapies.

Thank you, Jody. Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2025 operating and financial update conference call. The past year has laid the groundwork for what we expect to be a transformative year for Celcuity as we prepare for the potential approval and commercialization of datopotamab.

In light of the unprecedented efficacy data from the victory <unk> cohort of the phase III, Victoria, one clinical trial.

We're optimistic about the outcome of the Fda's review of our NDA.

Second these data were presented at a late breaking oral presentation at the European Society for medical oncology and San Antonio breast cancer Symposium in December.

2025, we made remarkable progress achieving a number of clinical and Regulatory Milestones while. Also significantly bolstering our balance sheet, and these achievements, in the groundbreaking data, reported to date, our foundational to our goal of establishing get us, elicit as a new standard of care therapy for patients with HR positive for negative Advanced Breast Cancer.

More recently as data were published a few weeks ago in a peer reviewed manuscripts in the journal of clinical oncology.

And third we completed enrollment of the picture you see a mutant cohort of our phase III Victoria, One trial late last year.

Brian Sullivan: The NDA was submitted under the FDA's Real-Time Oncology Review Program, which is utilized for drugs offering substantial improvements over available therapies. In light of the unprecedented efficacy data from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial, we're optimistic about the outcome of the FDA's review of our NDA. Second, these data were presented at a late-breaking oral presentation at the European Society for Medical Oncology and San Antonio Breast Cancer Symposium in December. More recently, these data were published a few weeks ago in a peer-reviewed manuscript in the Journal of Clinical Oncology. Third, we completed enrollment of the PIK3CA mutant cohort of our Phase 3 VIKTORIA-1 trial late last year. Reporting results from this cohort of this Phase 3 trial will be another incredibly important milestone for Celcuity.

Among the key clinical and regulatory milestones achieved recently include, first, the FDA accepted our New Drug Application, or NDA, and granted it priority review with a Prescription Drug User Fee Act, or PDUFA, goal date of July 17, 2026.

Results from this cohort of this phase III trial will be another incredibly important milestone for <unk>, we expect to announce these results in a top line press release in the second quarter and to present full results at a medical conference in 2026, where we also intend to host an investor call.

The NDA was submitted under the fda's real time. When College you review program which is utilized for drugs offering substantial, improvements over available Therapies.

Given how close we are to this disclosure we will not be answering questions about trial progress offering additional guidance on expectations for the results of the pictures <unk> mutant cohort during the Q&A portion of our call.

Night of the unprecedented efficacy data from the picture ECA wild type cohort of the Phase 3 Victoria-1 clinical trial. We're optimistic about the outcome of the FDA's review of our NDA.

We've discussed previously the historic nature of the results from the picture you say wild type cohort of the Victorian one trial.

Second, all these data were presented at a late-breaking oral presentation at the European Society for Medical Oncology and the San Antonio Breast Cancer Symposium in December.

The new milestones achieved in HR positive for two negative advanced breast cancer.

More recently, these data were published, a few weeks ago, in a peer-reviewed manuscript in the journal of clinical oncology.

And just to recap.

Medium progression free survival or PFS for the got us, what's a triplet, which is get us Elisa albus equipment for bathroom.

And third, we completed enrollment of the pixel 3A, mutant cohort of our phase 3 Victoria, 1 trials.

With nine three months compared to only two months worth of investment and hazard ratio.

Brian Sullivan: We expect to announce these results in a top-line press release in Q2 and to present full results at a medical conference in 2026, where we also intend to host an investor call. Now, given how close we are to this disclosure, we will not be answering questions about trial progress or offering additional guidance on expectations for the results of the PIK3CA mutant cohort during the Q&A portion of our call. We've discussed previously the historic nature of the results from the PIK3CA wild-type cohort of the VIKTORIA-1 trial and the new milestones they achieved in HR-positive, HER2-negative advanced breast cancer. Just to recap, median progression-free survival or PFS for the gedatolisib triplet, which is gedatolisib, palbociclib, and fulvestrant, was 9.3 months compared to only 2 months for fulvestrant. The hazard ratio was 0.24.

Two four.

Overall these results several new benchmark for clinical trials evaluating patients in this disease setting.

Reporting results from this cohort of this phase 3 trial will be another incredibly important milestone for Celcuity. We expect to analyze results in a topline press release in the second quarter and to present full results at a medical conference in 2026, where we also intend to host an investor call.

<unk>.

Hazard ratio for <unk> was a triplet is more favorable than it has ever been reported by any phase III trial for patients with HR positive <unk> negative advanced breast cancer.

And second seven three months incremental improvement in median PFS for the guidance was put overflow restaurants.

Now, given how close we are to this disclosure, we will not be answering questions about the trial, progress, or offering additional guidance on expectations for the results of the Pick. 3cm mutant cohort during the Q&A portion of our call.

Is higher and has ever been reported by any phase III trial for patients with HR positive <unk> negative advanced breast cancer, receiving at least the second line of the regimen, including an androgen therapy.

We've discussed previously, the historic nature of the results from the pick. 3ca wild type cohort of the Victoria 1 trials, they achieved in HR positive for 2 negative Advanced Breast Cancer.

And just to recap.

Third <unk> is the first inhibitor targeting the <unk> pathway.

Median progression-free survival, or PFS, for the GALA-full subtriplet, which is gadocetuzumab, talazoparib, alpelisib, equipment for vestron.

To demonstrate positive phase III results in patients with her two positive her two negative picture, we see a wild type events breast cancer, whose disease progressed on or after treatment with the CDK four six inhibitor.

It was 9.3 months compared to only 2 months for Vestron, and the hazard ratio was 0.24.

Brian Sullivan: Overall, these results set several new benchmarks for clinical trials evaluating patients in this disease setting. First, the hazard ratio for the gedatolisib triplet is more favorable than has ever been reported by any phase 3 trial for patients with HR-positive, HER2-negative advanced breast cancer. Second, the 7.3 months incremental improvement in median PFS for the gedatolisib triplet over fulvestrant is higher than has ever been reported by any phase 3 trial for patients with HR-positive, HER2-negative advanced breast cancer receiving at least their second line of a regimen including an endocrine therapy.

Overall, these results set several new benchmarks for clinical trials evaluating patients in this disease setting.

Before us.

The $17 five months median duration of response and the 31% incremental increase in the objective response rate relative to control for the restaurant triplet.

First, the hazard ratio for the gedatolisib triplet is more favorable than has ever been reported by any Phase 3 trial for patients with HR-positive, HER2-negative advanced breast cancer.

Get them close to tripling of the highest reported for an endocrine therapy based regimen and second line HR positive <unk> negative advanced breast cancer.

Additionally, the results demonstrated that the clinical benefit of the data towards a triplet was consistent across.

And second, the 7.3 months, incremental Improvement in medium PFS for the get up to a trip but over a full Fast Trip. It's higher than has ever been reported by any phase 3 trial for patients with HR positive for 2 negative Advanced Breast Cancer receiving at least their second line of a regimen including an endocrine therapy.

Brian Sullivan: Third, gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients with HR-positive, HER2-negative PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with a CDK4/6 inhibitor. Fourth, the 17.5 months of median duration of response and the 31% incremental increase in the objective response rate relative to control for the fulvestrant triplet, for the gedatolisib triplet are the highest reported for an endocrine therapy-based regimen in second-line HR-positive, HER2-negative advanced breast cancer. Additionally, the results demonstrated that the clinical benefit of the gedatolisib triplet was consistent across all patient subgroups. One patient subgroup of note, patients enrolled in the United States or Canada, achieved median PFS of 19.3 months for gedatolisib triplet versus 2 months for fulvestrant, which resulted in a hazard ratio of 0.13.

All patient subgroups, one patient subgroup of note patients enrolled in the United States or Canada achieved median PFS 19, three months to get it to a triplet versus two months for full vesting.

Which resulted in a hazard ratio of 0.13.

Further analysis that included patients enrolled in the U S, Canada, Western Europe, and Asia Pacific, representing nearly 60% of those enrolled.

And third got off the list of is the first inhibitor targeting the pi3k akt, mtor pathway to demonstrate positive phase 3 results. In patients, with her 2 positive, her 2 negative Victory. Say a wild type Advanced Breast Cancer, whose disease progressed on or after treatment of the cdk, 46 inhibitor.

That median PFS was $16 six months with regard to us a triplet versus one nine months fulfill restaurant, which resulted in a hazard ratio relative to <unk> of 0.14.

Forest the 17.5 months of median, duration of response and the 31% incremental, increase in the objective response rate relative to control for the Lesser and triplet for the get a solid triplet of the highest reported for an endocrine therapy based regimen and second line, HR positive for 2 negative Advanced Breast Cancer.

Thank you results show that capitalism triplet was generally well tolerated in the trial with mostly low grade adverse events study treatment discontinuation due to treatment related adverse events was reported in two three of patients treated with <unk>.

In December we presented additional safety analysis in an oral presentation at the San Antonio breast cancer Symposium.

Additionally, the results demonstrated that the clinical benefit of the data to a subgroup triplet was consistent across all patient subgroups. One patient subgroup of note: patients enrolled in the United States or Canada achieved a median PFS of 19.3 months with the use of triplet versus 2 months for fulvestrant.

Brian Sullivan: Further analysis that included patients enrolled in the US, Canada, Western Europe, and Asia Pacific, representing nearly 60% of those enrolled, found that median PFS was 16.6 months with the gedatolisib triplet versus 1.9 months for fulvestrant, which resulted in a hazard ratio relative to fulvestrant of 0.14. Safety results showed that gedatolisib triplet was generally well-tolerated in the trial with mostly low-grade adverse events. Study treatment discontinuation due to treatment-related adverse events was reported in 2.3% of patients treated with the gedatolisib triplet. In December, we presented additional safety analyses in an oral presentation at the San Antonio Breast Cancer Symposium. For patients who experienced stomatitis, we reported that measures to mitigate it were generally effective.

Which resulted in a hazard ratio of 0.13.

Patients who experience stomatitis.

We reported that measures to mitigate it generally effective medium time to improvement from first answer to a lower grade is dermatitis for patients with grade two or three summit title received the got of course a triplet.

Was 12% and 14 days respectively.

We also reported the guy to solicit did not induce meaningful changes in patient glucose levels.

Further analysis that included patients enrolled in the US, Canada, Western Europe, and Asia-Pacific, representing nearly 60% of those enrolled, found that median PFS was 16.6 months with the Gat solicited triplet versus 1.9 months for fulvestrant, which resulted in a hazard ratio relative to fulvestrant of 0.14.

Unlike other approved drug targeting <unk> alpha.

<unk> did not induce clinically relevant metric leucemia.

Quired, no dose reductions or withdrawals due to hyperglycemia.

To characterize the Tolerability of the <unk> regimens. We also reported results from patient reported outcomes to capture a patient's perception of their overall well being and these measures include a patient's assessment of their mobility ability to care for themselves the ability to conduct their usual activities or pain or discomfort and anxiety.

It is generally well tolerated in the trial, with mostly low-grade adverse events. Study treatment discontinuation due to treatment-related adverse events was reported in 2.3% of patients treated with the GATSO triplet.

Brian Sullivan: The median time to improvement from first onset to a lower grade of stomatitis for patients with grade 2 or 3 stomatitis who received the gedatolisib triplet was 12 and 14 days, respectively. We also reported that gedatolisib did not induce meaningful changes in patient glucose levels. Unlike other approved drugs targeting PI3K alpha, gedatolisib did not induce clinically relevant hypoglycemia and required no dose reductions or withdrawals due to hypoglycemia. To characterize the tolerability of the gedatolisib regimens, we also reported results from patient-reported outcomes that capture a patient's perception of their overall well-being. These measures include a patient's assessment of their mobility, ability to care for themselves, ability to conduct their usual activities, their pain or discomfort, and anxiety, depression.

Depression.

All of these assessments and then summarized as the patient's time to definitive deterioration and changes in well being relative to the measures reported prior to the patients starting treatment on the trial.

In December, we presented additional safety analyses in an oral presentation at the San Antonio breast cancer. Symposium for patients, who experience stomatitis, we reported that measures to mitigate it were generally effective in, medium time to improvement from first onset to a lower grade of stomatitis for patients with grade 2 or 3 Summit, Titus received the gut of or some triplet was 12 and 14 days respectively.

For the Atlas a triplet the medium time to definitive deterioration was $23 seven months versus four months of a restaurant.

We also reported the guts. Elicit did not induce meaningful changes in patient, glucose levels.

Hazard ratio of <unk> 39.

Additionally for the first eight cycles of treatment patient assessment of their wellbeing remains stable relative to the assessment prior to starting treatment with <unk>.

Unlike other approved. Drugs targeting pi3k Alpha. Got to listen, did not induce clinically relevant hypoglycemia and required. No dose reductions or withdrawals due to hypoglycemia.

Based on these assessments. We believe this provides meaningful evidence that patients treated with caterpillar.

Tolerated it well.

Let's turn now to our Victoria to study to the.

The phase III clinical trial, evaluating <unk>, plus the CDK <unk> inhibitor and for western.

Brian Sullivan: The result of these assessments is then summarized as the patient's time to definitive deterioration and changes in well-being relative to the measures reported prior to the patient starting treatment on the trial. For the gedatolisib triplet, the median time to definitive deterioration was 23.7 months versus 4 months for fulvestrant, with a hazard ratio of 0.39. Additionally, for the first 8 cycles of treatment, patients' assessment of their well-being remained stable relative to their assessment prior to starting treatment with gedatolisib. Based on these assessments, we believe this provides meaningful evidence that patients treated with gedatolisib tolerated it well. Let's turn now to our VIKTORIA-2 study, which is a phase 3 clinical trial evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer who are endocrine therapy resistant.

To characterize the tolerability of the, get it to us and regimens. We also reported results from patient, reported outcomes, that capture a patient's perception of their overall well-being. And these measures include a patient's assessment of their Mobility, ability to care for themselves, the ability to conduct their usual activities, their pain or discomfort and anxiety depression.

As first line treatment for patients with HR positive <unk> negative advanced breast cancer.

<unk> therapy resistant.

We're wrapping up the safety run in and we expect to provide an update on our final phase III study design and the second quarter.

The result of these assessments is then summarized as the patient's time to definitive deterioration and changes in well-being, relative to the measures reported prior to the patient starting treatment on the trial.

We believe the positive results from the picture <unk> Wild type cohort of our Victoria, One study augurs well for the potential efficacy data from the triplet <unk> in this patient population.

For the guy that solicited triplet, the median time to definitive deterioration was 23.7 months versus 4 months for Vestron.

The hazard ratio of 0.39.

Now, let's turn now to our phase <unk> clinical trial that is evaluating go to solicit the combination with Dara <unk> and engine receptor <unk> receptor inhibitor.

And we are evaluating this in men with metastatic castration resistant prostate cancer.

Additionally, for the first aid cycles of treatment, patients’ assessment of their well-being remains stable, relative to their assessment prior to starting treatment with gedatolisib. Based on these assessments, we believe this provides meaningful evidence that patients treated with gedatolisib tolerated it well.

We presented detailed data for the phase one portion of the study at a poster presentation at ESMO.

And in this portion of the Phase <unk> study 38 patients were randomly assigned to receive standard doses of <unk> twice daily.

Brian Sullivan: We're wrapping up the safety run-in, and we expect to provide an update on our final Phase 3 study design in Q2. We believe the positive results from the PIK3CA wild-type cohort of our VIKTORIA-1 study augurs well to the potential efficacy our gedatolisib triplet may induce in this patient population. Now let's turn to our Phase 1b/2 clinical trial that is evaluating gedatolisib in combination with darolutamide, an androgen receptor inhibitor. We're evaluating this in men with metastatic castration-resistant prostate cancer. We presented detailed data for the Phase 1b portion of the study at a poster presentation at ESMO.

Brian Sullivan: We're wrapping up the safety run-in, and we expect to provide an update on our final Phase 3 study design in Q2. We believe the positive results from the PIK3CA wild-type cohort of our VIKTORIA-1 study augurs well to the potential efficacy our gedatolisib triplet may induce in this patient population. Now let's turn to our Phase 1b/2 clinical trial that is evaluating gedatolisib in combination with darolutamide, an androgen receptor inhibitor. We're evaluating this in men with metastatic castration-resistant prostate cancer. We presented detailed data for the phase 1b portion of the study at a poster presentation at ESMO.

And let's turn now to our Victoria 2 study which is a phase 3. Clinical trial, evaluating get us a list of plus the cdk, 46 inhibitor and for veteran as first line treatment for patients with HR, positive for 2 negative Advanced Breast Cancer or endocrine therapy resistant.

120 milligrams has got us Elisa in arm, one or 180 milligrams of catalyst and arm two.

We're wrapping up the safety run-in, and we expect to provide an update on our final Phase 3 study design in the second quarter.

The six months radiographic PFS or our PFS rate was 67% and the median PFS for patients was nine one months for both arms combined and these results compare favorably to historical results of a 40% six months, our PFS survival rate for patients with metastatic castration.

We believe the positive results from the pick through, say, a Wildside cohort of our Victoria-1 study in August, well, to the potential efficacy or get it to listed, triplet may induce in this patient population.

Now let's turn to our Phase 1b/2 clinical trial. That is evaluating GOTO listed in combination with DUMI, an engine reception receptor inhibitor.

Resistant prostate cancer, who were treated with and energen receptor inhibitor a second line treatment.

The combination of <unk> was generally well tolerated in the trial with mostly low grade <unk> treatment related adverse events no dose limiting toxicities were observed in either arm and no patients discontinued study treatment due to an adverse event.

Brian Sullivan: In this portion of the Phase Ib/II study, 38 patients were randomly assigned to receive standard doses of darolutamide twice daily in either 120mg of gedatolisib in arm one or 180mg of gedatolisib in arm two. The six-month radiographic rPFS or RPFS rate was 67%, and the median RPFS for patients was 9.1 months in both arms combined. These results compare favorably to historical results of a 40% six-month RPFS survival rate for patients with metastatic castration-resistant prostate cancer who were treated with an androgen receptor inhibitor as second-line treatment. The combination of gedatolisib and darolutamide was generally well-tolerated in the trial with mostly low-grade treatment-related adverse events. No dose-limiting toxicities were observed in either arm, and no patients discontinued study treatment due to an adverse event.

Brian Sullivan: In this portion of the phase Ib/II study, 38 patients were randomly assigned to receive standard doses of darolutamide twice daily in either 120mg of gedatolisib in arm one or 180mg of gedatolisib in arm two. The six-month radiographic rPFS or RPFS rate was 67%, and the median RPFS for patients was 9.1 months in both arms combined. These results compare favorably to historical results of a 40% six-month RPFS survival rate for patients with metastatic castration-resistant prostate cancer who were treated with an androgen receptor inhibitor as second-line treatment. The combination of gedatolisib and darolutamide was generally well-tolerated in the trial with mostly low-grade treatment-related adverse events. No dose-limiting toxicities were observed in either arm, and no patients discontinued study treatment due to an adverse event.

And we're evaluating this in men with metastatic castration resistant. Prostate cancer. We present a detailed data for the phase 1. B portion of the study at a poster presentation at esmo

And in this portion of the Phase 1, B2 study, 38 patients were randomly assigned to receive standard doses of Dermite twice daily.

We're continuing to enroll patients in the dose escalation portion of the trial to evaluate higher doses of caterpillar to determine the recommended phase II dose.

And either 1,100 or 120 milligrams of glycine in arm 1, or 1,100 or 180 milligrams of data listed in arm 2.

As we near what we hope is an FDA approval. So we're got up to listen to in 2026, our efforts to prepare for the potential launch of <unk> continued to ramp up for our strategic launch plan.

We began laying the groundwork for a potential <unk> launch nearly two years ago and we've since largely completed building the organization, including our sales force and internal systems required to operate the commercial stage company.

The 6-month radiographic, BFS or rpfs rate was 67% and the median rpfs for patients, was 9.1 months from both arms combined and these results, compare favorably to historical results of a 40 percent 6 months, rpfs survival rate for patients with metastatic castration resistant, prostate cancer who were treated with an androgen receptor inhibitor, a second line treatment.

We are fortunate to have attracted an incredibly talented group of individuals with strong track records of successfully launching novel oncology Therapeutics.

Key efforts today include extensive outreach across the country to Payors strategic accounts population health decision makers and various treatment settings, including health systems integrated delivery networks and community oncology practices.

Brian Sullivan: We're continuing to enroll patients in the dose escalation portion of the trial to evaluate higher doses of gedatolisib to determine the recommended Phase 2 dose. Now, as we near what we hope is an FDA approval for gedatolisib in 2026, our efforts to prepare for the potential launch of gedatolisib continue to ramp up per our strategic launch plan. We began laying the groundwork for a potential gedatolisib launch nearly two years ago, and we've since largely completed building the organization, including our sales force and internal systems required to operate as a commercial-stage company. We're very fortunate to have attracted an incredibly talented group of individuals who have strong track records of successfully launching novel oncology therapeutics.

Brian Sullivan: We're continuing to enroll patients in the dose escalation portion of the trial to evaluate higher doses of gedatolisib to determine the recommended phase 2 dose. Now, as we near what we hope is an FDA approval for gedatolisib in 2026, our efforts to prepare for the potential launch of gedatolisib continue to ramp up per our strategic launch plan. We began laying the groundwork for a potential gedatolisib launch nearly two years ago, and we've since largely completed building the organization, including our sales force and internal systems required to operate as a commercial-stage company. We're very fortunate to have attracted an incredibly talented group of individuals who have strong track records of successfully launching novel oncology therapeutics.

The combination of Geta and Solicitor have been derided, was generally, well, tolerated in the trial with mostly low-grade treatment-related adverse events. No dose-limiting toxicities were observed in the other arm and no patients discontinued study treatment due to an adverse event.

We're continuing to enroll patients in the dose escalation portion of the trial to evaluate higher doses in order to determine the recommended Phase 2 dose.

Each of these groups are expected to play a key role in providing oncologists access to get us Melissa for their patients.

We made strong progress engaging with these decision makers and we're very pleased with the feedback and the enthusiastic response efforts have yielded.

Now as we near what we hope is an FDA approval for GET up to less than 2026, our efforts to prepare for the potential loss of GET continue to ramp up for our strategic launch plan.

We're also very encouraged by the results of research, we fielded to gauge the willingness of community and academic oncologists prescribed us should it get approved.

We began laying the groundwork for a potential data. Solicited launched nearly two years ago, and we've since largely completed building the organization, including our sales force and its internal systems required to operate as a commercial-stage company.

These results make us optimistic about the possibility of establishing data to listen.

A new standard of care in the second line setting for HR positive <unk> negative advanced breast cancer in the wild type patient population.

We're very fortunate to have attracted an incredibly talented group of individuals who have strong track records of successfully launching novel oncology therapeutics.

Brian Sullivan: Key efforts today include extensive outreach across the country to payers, strategic accounts, and population health decision-makers in various treatment settings, including health systems, integrated delivery networks, and community oncology practices. Each of these groups are expected to play a key role in providing oncologists access to gedatolisib for their patients. We've made strong progress engaging with these decision makers, and we're very pleased with the feedback and the enthusiastic response these efforts have yielded. We're also very encouraged by the results of research we fielded to gauge the willingness of community and academic oncologists to prescribe gedatolisib should it get approved. These results make us optimistic about the possibility of establishing gedatolisib as the new standard of care in the second-line setting for HR-positive, HER2-negative advanced breast cancer in the wild-type patient population.

In February we reported positive results from our study with patients whose tumors have mutations.

It got up to what's a triplet will be uniquely positioned to provide second line therapy for patients regardless of the fixed <unk> mutation status.

Key efforts today include extensive outreach across the country to payers, strategic accounts, and population health decision makers in various treatment settings, including health systems, integrated delivery networks, and community oncology practices.

Based on analysis of published epidemiological data.

We estimate there are approximately 37000 patients in the U S with HR positive <unk> negative advanced breast cancer, who have progressed after treatment with the CDK four six inhibitor <unk>.

We've made strong progress engaging with these decision makers, and we're very pleased with the feedback and the enthusiastic response. These efforts have yielded

Using internal duration of treatment estimates and pricing assumptions consistent with currently available novel Therapeutics for breast cancer.

We're also very encouraged by the results of research. We fielded to gauge the willingness of community and academic, oncologists to prescribe, get us to sort of get approved.

Estimate the total addressable markets, we've got a philosophy in the second line setting is more than $5 billion.

And given the significant penetration our research is suggesting we can achieve we believe it is reasonable to estimate that our second line indications, who got to solicit can potentially generate peak revenue of up to $2 $5 billion annually.

And these results make us optimistic about the possibility of establishing data to listen as the new standard of care in the second line setting for HR positive for 2 negative Advanced Breast Cancer in the wild site patient population.

Brian Sullivan: Should we report positive results from our study with patients whose tumors have PIK3CA mutations, the gedatolisib triplet will be uniquely positioned to provide second line therapy for patients regardless of their PIK3CA mutation status. Based on analysis of published epidemiological data, we estimate there are approximately 37,000 patients in the US with HR-positive, HER2-negative advanced breast cancer who've progressed after treatment with a CDK4/6 inhibitor. Using internal duration of treatment estimates and pricing assumptions consistent with currently available novel therapeutics for breast cancer, we estimate the total addressable market for gedatolisib in the second line setting is more than $5 billion. Given the significant penetration our research is suggesting we can achieve, we believe it is reasonable to estimate that a second line indication for gedatolisib can potentially generate peak revenue of up to $2.5 billion annually.

And so we report positive results from our study with patients whose tumors have picked 3 cm mutations.

We're excited about the opportunity now.

We are approaching potential launch to advance multiple potential blockbuster indications over the years in breast and prostate cancer, while also aggressively preparing for potentially launching <unk> commercially should we receive FDA approval.

We got a solicited triplet that will be uniquely positioned to provide second-line therapy for patients regardless of the PIK3CA mutation status.

<unk> is well positioned to address critical needs in the second line space with its unique mechanism of action and potential first in class and best in class safety and efficacy profile.

Based on analysis of published epidemiological data, we estimate there are approximately 37,000 patients in the U.S. with HR-positive, HER2-negative advanced breast cancer who have progressed after treatment with a CDK4/6 inhibitor.

I'd like now to hand, the call over to Vickie to review of our finances.

It looks like we lost Vicky.

And using internal duration of treatment estimates and pricing assumptions consistent with currently available novel therapeutics for breast cancer, we estimate the total addressable market for gedatolisib in the second line setting is more than $5 billion dollars. And given the significant penetration our research is suggesting we can achieve, we believe it is reasonable to estimate that a second line indication for gedatolisib can potentially generate peak revenue of up to $2.5 billion dollars annually.

Brian Sullivan: We're excited about the opportunity now that we're approaching a potential launch to advance multiple potential blockbuster indications over the years in breast and prostate cancer, while also aggressively preparing for potentially launching gedatolisib commercially should we receive an FDA approval. Gedatolisib is well-positioned to address critical needs in the second line space with its unique mechanism of action and potential first-in-class and best-in-class safety and efficacy profile. I'd like now to hand the call over to Vicki to review our finances.

Okay.

Vicky is having trouble connecting.

We're excited about the opportunity. Now that we, uh, we're approaching, uh, potential launch to advance multiple potential blockbuster indications over the years in breast and prostate cancer, while also aggressively preparing for potentially losing data to a list of commercially. Should we receive an FDA approval?

I can review the remarks that she was prepared to give.

Operator, she is no longer on the line.

Yes, she is recollecting like now.

As well, positioned to address critical needs in the second-line space with its unique mechanism of action and potential. First-in-class, investing-class safety and efficacy profile.

Operator: It seems like we lost Vicky.

YouTube's like we lost Vicky.

Well.

Well why don't I continue.

Brian I apologize I think I'm back on.

Okay. So one is what's your take on it.

Brian Sullivan: Well, if Vicky is having trouble connecting, I can review the remarks that she was prepared to give. Operator, is she no longer on the line?

Yes.

Well good afternoon, everyone I will provide a brief overview of our financial results for the fourth quarter and full year 2025, our fourth quarter net loss was 51 million or <unk> 97 per share compared to $36 7 million net loss or <unk> 85 per share for the fourth quarter of two.

Well, if Vicki, uh, is is having uh, trouble connecting. Uh, I can uh, review the remarks that she was prepared to give.

Um, operator, she is no longer on the line.

Operator: Yes, she's reconnecting right now.

Uh, yes, she's reconnecting right now.

2024.

Net loss for the full year was 177 million or $3 79 per share compared to $111 8 million or $2 83 per share compared to the same period in 2024.

Well.

Brian Sullivan: Well, why don't I continue, so we don't delay everyone.

Vicky Hahne: Brian, I apologize. I think I'm back on.

Our non-GAAP adjusted net loss was $38 4 million or <unk> 73 per share for the fourth quarter of 2025.

Brian Sullivan: Okay. Why don't you get going?

Well, I—don't I, uh, continue. Uh, so we have to let everyone—Brian, I apologize. I think I'm back on.

Vicky Hahne: Yes. Well, good afternoon, everyone. I will provide a brief overview of our financial results for the Q4 and full year 2025. Our Q4 net loss was $51 million or $0.97 per share, compared to $36.7 million net loss or $0.85 per share for the Q4 of 2024. Net loss for the full year was $177 million or $3.79 per share, compared to $111.8 million or $2.83 per share compared to the same period in 2024.

Okay, so once you get going,

Yeah. Sorry.

Compared to non-GAAP adjusted net loss of $32 3 million or <unk> 75 per share for the fourth quarter of 2024.

non-GAAP adjusted net loss for the full year of 2025 was $150 8 million or $3 22 per share compared to non-GAAP adjusted net loss of $101 9 million or $2 58 per share for 2024.

Research and development expenses were $37 6 million for the fourth quarter of 2025 compared to $33 5 million for the prior year period.

Vicky Hahne: Our non-GAAP adjusted net loss was $38.4 million or $0.73 per share for Q4 2025, compared to non-GAAP adjusted net loss of $32.3 million or $0.75 per share for Q4 2024. Non-GAAP adjusted net loss for the full year of 2025 was $150.8 million or $3.22 per share, compared to non-GAAP adjusted net loss of $101.9 million or $2.58 per share for 2024. Research and development expenses were $37.6 million for Q4 2025, compared to $33.5 million for the prior year period.

Well, good afternoon, everyone. I will provide a brief overview of our financial results for the fourth quarter and full year 2025. Our fourth quarter net loss was $51 million, or $0.97 per share, compared to a $36.7 million net loss, or $0.85 per share, for the fourth quarter of 2024. Net loss for the full year was $177 million, or $3.79 per share, compared to $111.8 million, or $3.33 per share, for the prior year.

Of the $4 1 million increase in R&D expenses, $8 6 million was related to increased employee and consulting expenses of which $5 3 million related to commercial head count additions and other launch related activities. These amounts were partially offset by a four.

Our non-GAAP adjusted net loss was $38.4 million, or $0.73 per share, for the fourth quarter of 2025.

Compared to non-GAAP adjusted net loss of $32.3 million, or $0.75 per share, for the fourth quarter of 2024.

$4 5 million decrease primarily related to costs.

Porting ongoing activities for the Victoria, one phase III trial.

R&D expenses for the full year 2025 were $145 million compared to $104 2 million for the prior year.

Non-GAAP adjusted net loss for the full year of 2025 was $150.8 million, or $3.22 per share, compared to non-GAAP adjusted net loss of $101.9 million, or $2.58 per share, for 2024.

Of the approximately $40 8 million increase in R&D expenses in.

$26 7 million was related to increased employee and consulting expenses.

Vicky Hahne: Of the $4.1 million increase in R&D expenses, $8.6 million was related to increased employee and consulting expenses, of which $5.3 million related to commercial headcount additions and other launch-related activities. These amounts were partially offset by a $4.5 million decrease, primarily related to costs supporting ongoing activities for the VIKTORIA-1 Phase 3 trial. R&D expenses for the full year 2025 were $145 million, compared to $104.2 million for the prior year. Of the approximately $40.8 million increase in R&D expenses, $26.7 million was related to increased employee and consulting expenses, of which $13.1 million related to commercial headcount additions and other launch-related activities.

Of which $13 1 million related to commercial head count additions and other launch related activities.

The remaining $14 1 million increase was primarily related to activities supporting our ongoing clinical trials.

A development milestone payment under the license agreement with Pfizer and other commercial launch related activities.

General and administrative expenses were $11 6 million for the fourth quarter of 2025.

Commercial headcount, editions and other launch related activities, these amounts were partially offset by a 4.5 million decrease, primarily related to costs supporting ongoing activities for the Victoria 1 phase 3 trial.

<unk> to $3 million for the prior year period.

R&D expenses for the full year 2025 were $145 million, compared to $104.2 million for the prior year.

Of the approximately $8 6 million increase in G&A expenses.

$6 9 million was related to increased employee and consulting expenses.

Which five.

Related to noncash stock based compensation.

The remaining $1 7 million increase was primarily related to professional fees.

Vicky Hahne: The remaining $14.1 million increase was primarily related to activities supporting our ongoing clinical trials, a development milestone payment under the license agreement with Pfizer, and other commercial launch-related activities. General and administrative expenses were $11.6 million for Q4 2025, compared to $3 million for the prior year period. Of the approximately $8.6 million increase in G&A expenses, $6.9 million was related to increased employee and consulting expenses, of which $5.4 million related to non-cash stock-based compensation. The remaining $1.7 million increase was primarily related to professional fees, expanding infrastructure costs, and other administrative expenses. G&A expenses for the full year 2025 were $27.2 million, compared to $9.1 million for the prior year.

Of the approximately $40.8 million increase in R&D expenses, $26.7 million was related to increased employee and consulting expenses, of which $13.1 million related to commercial headcount additions and other launch-related activities.

Expanding infrastructure costs and other administrative expenses.

G&A expenses for the full year 2025 were $27 2 million compared to $9 1 million for the prior year of the $18 1 million increase in G&A expenses $14 9 million was related to increased employee related and consulting expenses of which $10.

The remaining $14.1 million increase was primarily related to activities supporting our ongoing clinical trials.

A development Milestone payment under the license agreement with fiser and other commercial launch related activities.

General and administrative expenses were $11.6 million for the fourth quarter of 2025, compared to $3.0 million for the prior year period.

$4 million related to noncash stock based compensation.

Of the approximately $8.6 million increase in G&A expenses.

The remaining $3 2 million increase was primarily related to professional fees expanding infrastructure costs and other administrative expenses.

Net cash used in operating activities for the fourth quarter of 2025 with $36 4 million.

The $6.9 million was related to increased employee and consulting expenses, of which $5.4 million related to non-cash stock-based compensation.

<unk> to $27 8 million for the fourth quarter of 2024 net cash used in operating activities for the full year 2025 was $153 3 million compared to $83 5 million for the full year 2024 cash cash equivalents and in short term.

The remaining $1.7 million increase was primarily related to professional fees, expanding infrastructure costs, and other administrative expenses.

Vicky Hahne: Of the $18.1 million increase in G&A expenses, $14.9 million was related to increased employee-related and consulting expenses, of which $10.4 million related to non-cash stock-based compensation. The remaining $3.2 million increase was primarily related to professional fees, expanding infrastructure costs, and other administrative expenses. Net cash used in operating activities for Q4 2025 was $36.4 million, compared to $27.8 million for Q4 2024. Net cash used in operating activities for the full year 2025 was $153.3 million, compared to $83.5 million for the full year 2024.

Documents were $441 5 million at the end of fiscal year 2025, and are expected to finance our operations through 2027.

G&A expenses for the full year 2025 were $27.2 million compared to $9.1 million for the prior year. Of the $18.1 million increase in G&A expenses, $14.9 million was related to increased employee-related and consulting expenses, of which $10.4 million related to non-cash stock-based compensation.

I will now hand, the call back to Jody.

Thanks, Vicky before we turn the call over to the operator for questions I'll remind you we will not be answering questions related to the progress or status of the mutant cohort of the Victoria, one study or providing any additional guidance on our expectations for data at this time John could you. Please open the call for <unk>.

The remaining $3.2 million increase was primarily related to professional fees, expanding infrastructure, costs, and other administrative expenses.

Net cash used in operating activities for the fourth quarter of 2025 was $36.4 million, compared to $27.8 million for the fourth quarter of 2024.

<unk>.

Thank you 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 Touchtone phone, you'll hear a prompt that their hands, it's been raised should.

Vicky Hahne: Cash, cash equivalents, and short-term investments were $441.5 million at the end of fiscal year 2025 and are expected to finance our operations through 2027. I will now hand the call back to Jody.

Net cash used in operating activities for the full year 2025 was $153.3 million, compared to $83.5 million for the full year 2024.

<unk> declined from the polling process. Please press star followed by the number too.

If you're using a speaker phone please lift the handset before pressing any keys one moment. Please for your first question.

Cash Cash equivalents and in short-term Investments, were 441.5 million at the end of fiscal year 2025 and are expected to finance our operations through 2027.

I will now hand the call back to Jodie.

Jody Sievers: Thanks, Vicky. Before we turn the call over to the operator for questions, I'll remind you we will not be answering questions related to the progress or status of the mutant cohort of the VIKTORIA-1 study or providing any additional guidance on our expectations for data at this time. John, could you please open the call for questions?

Our first question comes from the line of Marty Raycroft from Jefferies. Your line is now open.

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

Not sure if this fits within your criteria and offer on the status update but.

I'm wondering if with immune data if you can save the database lock is already in place that's something you can comment on.

Operator: Thank you. 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're using a speakerphone, please lift the handset before pressing any keys. One moment please for your first question. Our first question comes from the line of Maury Raycroft from Jefferies. Your line is now open.

Thanks, Vicky. Before we turn the call over to the operator for questions, I'll remind you we will not be answering questions related to the progress or status of the mutant cohort of the Victoria-1 study, or providing any additional guidance on our expectations for data at this time. John, could you please open the call for questions?

I can't comment on that.

Okay understood.

I know you've already commented on this in the past you, but if you could just recap how the disclosure is going to take place and what exactly you will share in the readout.

Thank you, ladies and gentlemen. We will now begin the question and answer session. Should you have a question, please press star followed by the number 1 on your touchtone phone. You will hear a prompt that your hand has been raised.

So, if you wish to decline from the polling process, please press star followed by the number 2.

Well as I indicated we will provide top line data in our press release and then we will provide details at <unk>.

If you're using a speakerphone, please lift the handset. Before pressing any keys, please wait one moment for your first question.

Upcoming medical conference.

Got it.

And then when thinking about.

Our first question comes from the line of Ray Croft, from Jeffries. Your line is now open.

Maury Raycroft: Hi, congrats on the progress, and thanks for taking my questions. Not sure if this fits within your criteria or not for the status update, but wondering if for the mutant data if you could say if the database lock is already in place. If that's something you can comment on.

When we could see more details at a medical conference can you say, if that's going to be my relatively soon or is it more likely going to be a second half update.

I think you'll just have to wait and see.

Brian Sullivan: No, I can't comment on that.

Uh, congrats on the progress and thanks for taking my questions. Um, not sure if this fits within your criteria or not for unst, status update but um, wondering if for the mutant data, if you could say if the database lock is already in place, if that's something you can comment on

Sorry, I can't provide any more details.

Maury Raycroft: Okay. Understood. I know you've already commented on this in the past too, but if you could just recap how the disclosure is going to take place and what exactly you'll share in the readout?

No, it can't comment on that.

Understood. Okay. Those were my questions I'll ask I'll hop back in queue. Okay.

Understood. And

Okay. Thank you.

Alright, Thank you Mark.

And I know you've already commented on this in the past too, but

Your next question comes from the line of Patter Bryan Kraft from BD Cowen. Your line is now open.

It it just recap how the disclosure is going to take place and what exactly you'll share in the readout.

Brian Sullivan: Well, as I indicated, we'll provide top-line data in a press release, and then we will provide details at an upcoming medical conference.

Hi, good afternoon, So I guess I'll shift to maybe a question on the launch I was hoping maybe you could give us some feedback what you're what you.

Well, as I indicated, uh, we'll provide Top Line data in a press release and then we will uh provide details uh at an upcoming medical conference.

Maury Raycroft: Got it. Okay. When thinking about when we could see more details at a medical conference, can you say if that's gonna be like relatively soon or is it more likely gonna be a H2 update?

You're hearing from physicians on which segments may be treated immediately upon the wild type of approval and which ones may be more gradual and just to get an idea of how you are planning ahead for cadence. Once you once you receive approval. Thanks.

Alright, now so as we launch we aren't going to be targeting a narrow casting our approach to doctors or patient segments. We believe.

Got it, okay. And then, when thinking about, um, when we could see more details at a medical conference, can you say if that's going to be relatively soon, or is it more likely going to be a second half update?

Brian Sullivan: I think you'll just have to wait and see, Maury. Sorry, I can't provide any more details.

And see. Sorry, I can't provide any more details.

Maury Raycroft: Understood. Okay. Those were the questions I'll ask. I'll hand it back to you.

Brian Sullivan: Okay.

Maury Raycroft: Thank you.

Get us listen regimens offer an opportunity to get the best option relative to whats available today and so we would expect our.

Brian Sullivan: All right. Thank you, Maury.

Understood. Okay. Those were the questions I'll ask. Okay, thank you.

All right. Thank you.

Operator: Your next question comes from the line of Tara Bancroft from TD Cowen. Your line is now open.

Your next question comes from the line of Apoorva Chaloori from TD Cowen. Your line is now open.

Sales force upon approval.

Tara Bancroft: Hi. Good afternoon. I guess I'll shift to maybe a question on the launch. I was hoping maybe you could give us some feedback on what you're hearing from physicians on which segments may be treated, you know, immediately upon the wild type approval and which ones may be more gradual. Just to get an idea of how you're planning ahead for cadence once you receive approval. Thanks.

Assuming that occurs.

Retail generally to doctors and essentially help them understand how that's most of them in the data.

Yes.

Can offer again, what we believe is.

An improvement in <unk>.

The alternatives are.

Currently available.

Hi, good afternoon, so I guess I'll shift to maybe a question on the launch. I was hoping maybe you could give us some feedback. Uh, what what you're hearing from Physicians on which segments, um, maybe treated, you know, immediately upon the, the wild type approval and which ones may be more gradual, um, just to get an idea of how you're planning ahead for for cadence. Once you once you receive approval, thanks.

Brian Sullivan: Well, thanks. Now, as we launch, we aren't gonna be targeting or narrowcasting our approach to doctors or patient segments. We believe gedatolisib regimens offer an opportunity to get the best option relative to what's available today. We would expect our sales force, you know, upon approval, assuming that occurs, you know, to reach out generally to doctors and essentially help them understand how gedatolisib in the data, you know, can offer, again, what we believe is an improvement in the alternatives that are currently available.

Okay, great, Thanks, and I guess in that feedback.

That you are hearing.

These discussions with physicians do you do you think or have any inkling, whether they would be willing to potentially use it off label and mutants ahead of us.

A potential mutant approval if the data are positive.

That's just not something that we have any conversations with doctors about okay. Okay alright. Thank you.

Well, thanks. No. Um, so as we launched, uh, we aren’t, uh, going to be targeting or narrowcasting our approach to, to doctors or patient segments. We believe, uh, get us a list of residents offer, uh, an opportunity to get the best option relative to what’s available today. And so, uh, we would expect our

Thank you.

As a reminder, please ask one question and one follow up.

Next question comes from the line of Stephen Willey from Stifel. Your line is now open.

Yes. Good afternoon, thanks for taking my questions and sorry to Badger you, Brian on the top line release of the data but.

Uh, sales force, you know, upon approval. If—if assuming that ours, uh, you know, to reach out generally to doctors and, and, you know, essentially help them understand, uh, how to get it to us and the data, uh, uh, you know, can offer again. What we believe is, uh, uh, an improvement in, uh, the alternatives, uh, that are currently available.

Tara Bancroft: Okay. Great. Thanks. I guess in that feedback that you are hearing in these discussions with physicians, do you-

Tara Bancroft: Okay. Great. Thanks. I guess in that feedback that you are hearing in these discussions with physicians, do you.

Just curious if that will include any details just with respect to headline PFS numbers and risk reduction or was this just simply be a statement regarding the achievement of.

Brian Sullivan: Mm-hmm.

Tara Bancroft: Do you think or have any inkling whether they would be willing to potentially use it off-label in mutants ahead of a potential mutant approval if the data are positive?

Scott.

It will be the latter I mean, we're mindful of the embargo requirements.

Brian Sullivan: Yeah. Yeah. That, that's just not something that we have any conversations with doctors about.

Two.

We need to adhere to in order to.

Tara Bancroft: Okay. All right. Thank you.

<unk> be in a position to have.

Brian Sullivan: Thank you.

Okay, great. Thanks. And I guess in that feedback, that that you are hearing in, in these discussions with Physicians, do you do you think or have have any inkling, whether they would be willing to potentially use it off-label and mutants ahead of um, a potential mutant approval, if the data are positive. Yeah, that that that's just not something that we have any conversations with doctors about, okay, okay. All right. Thank you.

Thank you.

Podium.

<unk>.

Operator: As a reminder, please ask one question and one follow-up. Your next question comes from the line of Stephen Willey from Stifel. Your line is now open.

One of these medical conferences.

Okay, and then maybe just a question on prostate and then maybe just a quick one on <unk>.

I had a reminder, please ask 1 question and 1 follow-up.

Your next question comes from the line of Stephen Relief from Stifel. Your line is now open.

Stephen Willey: Yeah. Good afternoon. Thanks for taking the questions, and sorry to badger you, Brian, on the top line release of the meeting data. Just curious if that will include any details just with respect to headline PFS numbers and risk reduction, or will this just simply be a statement regarding the achievement of stat sig?

On the second my breast opportunity that you spoke to so in prostate just.

Curious how high you think you can push dose.

Yeah, good afternoon. Thanks for taking the questions, and sorry to badger you, Brian, on the top-line release of the meeting data. But... but

North of the 180 <unk> that is used in and the Victoria trial.

And then just curious.

What metrics I mean, obviously, there's a balance of safety and Tolerability you need to consider in terms of nominating a recommended phase two dose but.

Just curious if that will include any details just with respect to headline PFS numbers and risk reduction, or would this just simply be a statement regarding the achievement of, uh, static.

Brian Sullivan: It'll be the latter. I mean, we're mindful of embargo requirements, you know, that we need to adhere to in order to be in a position to have a podium presentation at one of these medical conferences.

Are there any efficacy metrics that youre going to be prioritizing I know you've shown us the radiographic PFS data, but.

Just curious how things like PSA response.

Maybe even a resist response for those patients with measurable lesions, how that kind of factors into it as a dose nomination.

Uh, it'll be the latter. I mean, we're mindful of the embargo, uh, requirements, uh, to, uh, you know, that we need to adhere to, uh, in order to, uh, be in a position to have, uh, coding presentation at, uh, one of these, uh, medical conferences.

Stephen Willey: Okay. Maybe just a question on prostate and then maybe just a quick one on the second-line breast opportunity that you spoke to. In prostate, just curious how high you think you can push dose kinda north of the 180 mg that is used in the VIKTORIA trial. Just curious, you know, what metrics I mean, obviously, there's a balance of safety and tolerability you need to consider in terms of nominating a recommended phase 2 dose. But are there any efficacy metrics that you're gonna be prioritizing? I know you've shown us the radiographic PFS data, but just curious how things like PSA response, maybe even a RECIST response for those patients with measurable lesions, how that kind of factors into dose nomination.

Sure.

Just to recap relative to what we announced previously we were pleasantly surprised by the safety profile of that the 180 milligram dose.

Okay, and then maybe just a question on frost date, and then maybe just a quick one on—on—on...

The on the second line pressed opportunity that you spoke to. So when prostate um just curious how high you think you can push dose,

Courted.

No dose limiting toxicities.

Very limited grade three.

Adverse events.

Kind of north of the 180 Megs that is used in in in the Victoria trial. Um, and then just curious, you know,

Hypothermia was.

Consistent with our breast cancer stomatitis was significantly.

Less frequent.

At that dose and these men and so that's what led us to <unk>.

Decide to.

To increase the dose or rather to evaluate higher doses.

And essentially we were using some standard.

Brian Sullivan: Sure. Well, just to recap, relative to what we announced previously, we were pleasantly surprised by the safety profile of the 180 mg dose reported. No dose-limiting toxicities, very limited grade three adverse events. Hypokalemia was, you know, consistent with our breast cancer. Stomatitis was significantly less frequent at that dose in these men. That's what led us to decide to increase the dose or rather to evaluate higher doses. Essentially, we're using some standard methodology to, you know, stepwise increase the dose. Basically, depending on, you know, achievement or levels of dose-limiting toxicities, you know, we'll keep going.

What metrics? I mean, obviously there's a balance of safety and tolerability you need to consider in terms of nominating a recommended Phase 2 dose. But are there any efficacy metrics that you're going to be prioritizing? I know you've shown us the radiographic PFS data, but, um, just curious how things like ESA response, um, maybe even a RECIST response for those patients with measurable lesions, how that kind of factors into dose nomination.

Methodology to stepwise increase the dose.

Basically depending on.

Achievement or levels of dose limiting toxicities.

Well, we'll keep going.

We're in the midst of that so I can't really comment on where it will end up.

But again, there's always a balance where we can.

Sacrifice.

Tolerability to such an extent that his self defeating.

But to the extent that we believe there's a dose response.

Debt.

Would lead to improve response at higher doses, we want to.

Explore where that might take us and so we would expect to have.

Sure. Well, just to recap relative to, uh, what we, uh, announced previously, we were pleasantly surprised by the, uh, safety profile, uh, at the 180 milligram dose. Um, reported, uh, no dose-limiting toxicities. Um, very limited, uh, grade 3, uh, adverse events. Uh, hyperosmia was, uh, you know, consistent with our breast cancer [data]; stomatitis was significantly, um, uh, less frequent, uh, at that dose, uh, in these men. And so that's what led us to, uh, decide to increase the dose or rather to evaluate.

Look at that data by the end of this year or sometime early next year.

Okay. That's helpful. And then maybe just lastly, with respect to breast I appreciate some of the color around.

Kind of the peak revenue opportunity here in the second line setting.

Brian Sullivan: You know, we're in the midst of that, so I can't really comment on where we'll end up. Again, it's always a balance. We can't sacrifice tolerability to such an extent that it's self-defeating. To the extent that we believe there's a dose response that would, you know, lead to improved response at higher doses, we wanna explore where that might take us. We would expect to have some look at that data, you know, by the end of this year or sometime early next year.

I think you mentioned just kind of using historical pricing and duration of therapy, obviously, the pricing is kind of readily available but.

Whats the duration of therapy estimate that you are using to inform the peak numbers that you mentioned.

Yes.

Most response. Uh,

If you just use a round number.

Net.

No.

10 months and again Thats our projection, that's just an assumption to drive an estimate.

That, uh, would, you know, lead to improved response at higher doses? We—we want to explore where that might take us. And so we would expect to have

You would.

Consistent with our modeling.

Some, uh, look at that data, you know, by the end of this year, or sometime early next year,

Stephen Willey: Okay. That's helpful. Maybe just lastly, with respect to breast, I appreciate some of the color around kind of the peak revenue opportunity here in the second-line setting. I think you mentioned just kind of using, you know, historical pricing and duration of therapy. Obviously, the pricing is kind of readily available, but what's the duration of therapy estimate that you're using to inform the peak numbers that you mentioned? Thanks.

The market.

Alright.

Thanks.

That's helpful, and then maybe just lastly, with respect to breast, I appreciate some of the color and—

Our next question come from the line of Joshua Bolin from Guggenheim. Your line is now open.

Hey, guys. This is Josh on for Brad I, just wanted to know with most of the commercial build complete for second line. What is the key gating factor in getting the frontline endocrine sensitive trial up and running.

Alright key gating factors.

Um, kind of the peak revenue opportunity here in the second-line setting. Uh, I think you mentioned just kind of using, you know, historical pricing and duration of therapy. Obviously the pricing is kind of readily available, but what's the duration of therapy estimate that you're using to inform the peak numbers that you mentioned?

Brian Sullivan: Well, you know, if you just use a round number, you know, of 10 months, and again, that's not a projection, that's just an assumption to derive an estimate, you would, you know, be consistent with how we're modeling the market.

Impeding the safety run in to.

Look back a little bit.

We are evaluating <unk> in combination.

With rapid cycle up as a potential CDK four six option for doctors to use in the treatment arm.

And because we haven't.

Evaluated data with recycled before we needed to evaluate it in a sufficient number of patients to make a decision.

Thanks. Um, you know, if you, you know, just use a round number, um, that, uh, you know, of, uh, you know, 10 months. And again, that's not a projection, that's just an assumption to drive an estimate. You, you, you would, uh, you know, be consistent with how we're modeling.

Uh, the market.

Stephen Willey: All right. Much appreciated. Thanks.

Much appreciated. Thanks.

About the dosing and.

Operator: Our next question comes from the line of Josh Bowen from Guggenheim. Your line is now open.

Yes.

How to move forward.

So that's wrapping up and.

Our next question comes from the line of Josh Bowen from Guggenheim. Your line is now open.

Just on those results we'll update.

Josh Bowen: Hey, guys. This is Josh on for Brad. Just wanted to know, with most of the commercial build complete for second line, what is the key gating factor in getting the frontline endocrine-sensitive trial up and running? Thanks.

The study design accordingly, and we expect to.

Provide.

An update on the study design.

Hey guys, this is Josh, Sean for Brad. Just wanted to know, with most of the commercial build complete for second line, what is the key gating factor in getting the frontline endocrine-sensitive trial up and running? Thanks.

Brian Sullivan: Sure. Key gating factor is just completing the safety run-in. Just to, you know, look back a little bit, we're evaluating data in combination with ribociclib as a potential CDK4/6 option for doctors to use in this, in the treatment arm. Because we haven't evaluated data with ribociclib before, we needed to evaluate it in a sufficient number of patients to make a decision about, you know, dosing and how to move forward. That's wrapping up, and you know, based on those results, we'll update the study design accordingly. You know, we expect to kind of provide an update on the study design in Q2 and proceed apace to begin enrolling the Phase 3 study.

In the second quarter.

And proceed at pace to begin enrolling the phase III study.

Our next question comes from the line of Gil Blum from Needham and company. Your line is now open.

Hi.

Thanks for taking our questions. So I'll try to keep this brief.

So a commercial question that we've gotten a couple times.

Surrounding potential challenges in getting patients to come in foreign infusions can.

Can you discuss a bit how you plan to to avoid based kind of challenges or are they actually challenges.

No. Thanks for the question.

We have.

Her discretion from from investors.

Keep getting backer is, is just completing the safety run and, um, just to, you know, look back a little bit. Uh, we we were evaluating gotta in combination, uh, with rabbit as a potential, uh, cdk for 6, uh, option for doctors to use in in the, in the treatment arm, because we haven't, um, evaluated data with Robert before we needed to evaluate it in a sufficient number of patients to make a decision, um, about, uh, you know, dosing and and, uh, how to move forward. And so that's wrapping up and uh, you know, based on those results that we'll update, uh, the study design accordingly. And and, you know, we expect to kind of provide uh an update on the study design, uh, in the second quarter.

We do we've done a number of rounds of market research, where we not only engage with doctors on a qualitative.

And proceeded to Phase 2 to begin enrolling. The Phase 3 study.

Basis, where we're able to have conversations.

And you'll have a back and forth, but also in our quantitative setting runs non interactively and doctors are essentially going step wise through <unk>.

Operator: Our next question comes from the line of Gil Blum from Needham & Company. Your line is now open.

Our next question comes from the line of Gil Blum from Needham & Company. Your line is now open.

Gil Blum: Thanks for taking our questions. I'll try to keep this brief. A commercial question that we've gotten a couple of times is surrounding potential challenges in getting patients to come in for infusions. Can you discuss a bit how you plan to avoid these kind of challenges, or are they actually challenges?

Information prompts that we provide.

Uh, thanks for taking our questions. I'll try to keep this brief.

And they both allow us to gauge.

How they interpret the data how they think about.

We'll have data relative to other regimens that are currently available with factors they like dislike.

Strong.

A factor of that is it a neutral.

Uh so a commercial question that we've gotten a couple of times. Uh is surrounding potential challenges in getting patients to come in for infusions. Uh, can you discuss a bit how you plan to to avoid these kind of challenges or are they actually challenges?

Brian Sullivan: No, thanks for the question. You know, we have heard this question from investors. We've done a number of rounds of market research where we not only engage with doctors on a qualitative basis, where we're able to have conversations and, you know, have a back and forth, but also in a quantitative setting where it's non-interactive and doctors are essentially going stepwise through information prompts that we provide. You know, they both allow us to gauge, you know, how they interpret the data, how they think about that data relative to other regimens that are currently available, what factors they like, dislike, you know, how strong a factor that is, are they neutral on different factors.

On different factors and one thing that's very clear with me.

Review of the results of that research.

Is it a the efficacy is clearly the most important factor for them as they are evaluating the restaurant NV.

<unk> IV.

Our administration.

It shows up.

A negative factor in.

Meaningfully less than 10%.

No, thanks for the question. Um, you know, we, we, uh, have heard this question from, uh, from investors. Um, we do—uh, we've done a number of rounds of market research, where we not only engage with doctors in a qualitative, uh, basis—we're able to have conversations and, and, uh, you know, have a back and forth—but also, you know, in a quantitative setting where it's not interactive and, and doctors are essentially going stepwise through.

The responses we have in this research.

Secondly, we also do research with patients.

Information prompts that we provide. And, and, you know, they both allow us to gauge uh, you know.

And again, that's primarily qualitative.

And again, except in cases, where we believe is a geographic limitation offer a patient simply clinics too far or if there's some other considerations there mobility.

Brian Sullivan: One thing that's very clear when we review the results of that research is that, A, the efficacy is clearly the most important factor for them as they're evaluating the regimen. B, the IV administration shows up as a negative factor in meaningfully less than 10% of the responses we have in this research. Secondly, we also, you know, do research with patients. Again, that's primarily qualitative. Again, except in cases where we believe there's a geographic limitation for a patient, simply the clinic is too far, or if there's some other considerations, you know, their mobility, we do not expect that there'll be significant patient pushback on the IV.

We do not expect that.

There'll be significant patient pushback on.

How they interpret the data, how they think about uh, that data relative to other, uh, residents that are currently available. Uh, what factors? They like dislike, you know how strong, um, a factor that is that a neutral? Um, uh, on on different factors and 1 thing? That's very clear. And we um, uh,

Review the results of that research.

The IV I mean, we we have some interesting anecdotes from.

These conversations that suggested women take very seriously.

Sure.

Obligation for their family to do everything they can to maximize the time that they can be with their family and infused what they believe are the best drugs that they may have an option to take so we think all in just reinforces what we believe which is certainly up.

Is that, A, the efficacy is clearly, uh, the most important factor for them as they're evaluating the regimen, and B, uh, the IV, uh, administration, uh, it shows up as, uh, a negative factor and, uh, meaningfully less than 10% of the responses we, we have, uh, in this research.

Uh, secondly, we also, you know, do research with patients, and again, that's primarily qualitative.

Terminal disease like metastatic breast cancer.

The most important criteria, that's going to guide selection of therapy by both the physician and the preference for the patient.

It's going to be related to the efficacy.

The regimen can induce and then also to how how well tolerated the regimen as in the feedback. We've received again is very positive on that front as well.

Brian Sullivan: I mean, we have some interesting anecdotes, you know, from these conversations that suggest that women take very seriously their obligation for their family to do everything they can to, you know, maximize the time that they can be with their family and to use what they believe are the best drugs that they may have an option to take. So we think all in, it just reinforces what we believe, which is in certainly a terminal disease like metastatic breast cancer, the most important criteria that's gonna guide selection of therapy by both the physician and then the preference for the patient is gonna be related to the efficacy that the regimen can induce, and then also to how well-tolerated the regimen is.

And again, except in cases where we believe there's a geographic limitation for a patient simply clinics too far. Or if if there's some other, uh, considerations, you know, their Mobility? Uh, we we do not expect uh that they'll be significant patient push back on. Uh, the idea I mean we we have some interesting anecdotes, you know, from, um,

So finally.

As it relates to the administration route again, we think that's going to be an exigent issue for only a small number of patients for the reasons I mentioned and we don't believe that it is going to restrict.

Preference for physicians to.

Prescribed the therapy.

Thank you for all that and maybe as a follow up can you help us understand the commercial advantages of having get on label across.

Static breast cancer subtypes. Thank you sure.

Well as anybody to follow this space knows the one word that gets used to describe the landscape visits very complex a lot of activity.

Brian Sullivan: The feedback we've received, again, is very positive on that front as well. You know, finally, you know, as it relates to the administration route, again, we think that's gonna be an exigent issue for only a small number of patients, you know, for the reasons I mentioned, and we don't believe that it is going to restrict preference for physicians to prescribe the therapy.

And so what we hope to be able to provide and the way we expect to position. The drug is that we can.

Simplify.

The decision making process for these physicians.

By giving them an option that we believe for any patient subgroup of it.

The woman said, very seriously uh, their, uh, obligation, uh, for their family, uh, to do everything they can to, you know, maximize, you know, the time that, uh, they can be with their family and, and to use what they believe are the best drugs that, uh, they, they may have an option to take. So so we think all in just reinforces what, what we believe, which is, in in certainly a terminal, uh, disease like metastatic breast cancer. Uh, the most important criteria that's going to, uh, guide selection of therapy by both the physician and then the preference for the patient. Uh, it's going to be related to the efficacy that the regimen can induce. And then also to how how uh well tolerated the resident is and and the feedback we've received again is is very positive on on that front as well. And so, you know finally you know, as it relates to the administration route again we think that's going to be an exigent issue for only uh small number of patients. You know, for the reason I mentioned and and we we don't believe

Treating.

The best potential.

Risk benefit.

Uh, that is going to restrict uh preference for Physicians to prescribe the therapy.

Relative to the alternatives now doesn't mean there are available options that some doctors may select a preferred certain patient segments.

Gil Blum: Thank you for all that. Maybe as a follow-up, can you help us understand the commercial advantages of having gedatolisib label across metastatic breast cancer subtypes? Thank you.

Thank you for all that, and maybe there's a follow-up.

can I help us understand the commercial advantages of having, uh, get a label across

I think overall.

We'll be in a very strong position by being able to offer essentially a biomarker agnostic.

Brian Sullivan: Sure. Well, you know, as anybody that's followed this space knows, one word that gets used to describe the landscape is it's very complex, a lot of activity. What we hope to be able to provide and the way we expect to position the drug is that we can simplify the decision-making process for these physicians by giving them an option that we believe for any patient subgroup that, you know, they may be treating the best potential risk-benefit relative to the alternatives. Now, it doesn't mean there aren't, you know, available options that some doctors may select or prefer in certain patient segments.

Uh, metastatic breast cancer subtypes, thank you. Sure.

Alternative that doesn't require them to.

Yes.

<unk>, yes.

Some complex.

Decision, making around biomarker subgroups anything ultimately.

That's.

Hitting the easy button was issued isn't too.

Diminish.

<unk>.

Importance of the decision for the doctors, but particularly in the community setting.

The challenges of keeping up with.

The alternatives.

Ken makes it difficult for them too.

Okay.

Make the right decisions in some cases and so to the extent we can.

Brian Sullivan: We think overall, you know, we'll be in a very strong position by being able to offer essentially a biomarker-agnostic alternative that doesn't require them to, you know, evaluate, you know, some complex decision-making around, you know, biomarker subgroups. We think ultimately, you know, that, you know, hitting the easy button, which isn't to diminish the importance of the decision for the doctors. Particularly in the community setting, you know, the challenges of keeping up with the alternatives, you know, can make it difficult for them to make the right decisions in some cases. To the extent we can leverage the data that we have now and we hope to have with the mutant setting, we think that'll be a very significant advantage.

Leverage the data that we.

Half now and we hope to have a immune setting.

We think that will be a very significant advantage.

Well, yeah. Is anybody to follow this space knows 1? 1 Word that gets used to describe the landscape is, it's very complex, a lot of activity. And so what we, we hope to be able to, uh, provide. And the way we expect the position of the drug is that we can, uh, simplify, uh, the decision making process, uh, for these Physicians, uh, by giving them an option that we believe, uh, for any patient subgroup, uh, that, you know, they may be treating, uh, the best potential, um, uh, risk benefit, uh, relative to the Alternatives. Now, does it mean? There are, you know, available options that some doctors May select to prefer in certain patient segments, but we think overall, you know, we'll be in a very strong position by being able to offer essentially, a biomarker agnostic. Uh, uh, alternative that doesn't require them to, uh, uh, you know, evaluate, um, you know, some complex, uh, decision.

Our next question comes from the line of Oliver Mccammon from lifestyle capital. Your line is now open.

Thanks for taking my questions.

So switching gears a little bit we're roughly one five years into the launch of <unk> for the pick <unk> mutant endocrine therapy resistant setting I'm curious if there are any learnings from the launch label <unk> Kols feedback that you think are supportive of the positioning of <unk> in the Victoria to trial.

Making around, you know, biomarkers, subgroups anything. Ultimately, um, you know that, you know, hitting the easy button with which isn't to diminish. Uh, the importance of the decision for the doctors but particularly in the community setting, um, you know, the the challenges of keeping up with uh, the alternatives.

Uh, you know, can make it difficult for them to, uh,

uh,

Thanks.

make the right decisions in some cases. And so, to the extent we can, um,

Thank you.

So that they've reported very good data and unfortunately, though.

The patient population that really is appropriate to treat with that drug is fairly limited.

Leverage the data that we have now and we hope to have with the mutant setting. Uh, we think that'll be a very significant advantage.

The study only enrolled patients, who essentially where metabolically healthy patients who had an HPA C. One level below six and essentially.

Gil Blum: Our next question comes from the line of Oliver McCammon from LifeSci Capital. Your line is now open.

Our next question comes from the line of Oliver Mammon from Life Cycle. Your line is now open.

Oliver McCammon: Thanks for taking my questions. Switching gears a little bit, you know, we're roughly one and a half years into the launch of inavolisib for the PIK3CA mutant endocrine therapy-resistant setting. I'm curious if there are any learnings from the launch, the label, and/or KOL feedback that you think are supportive of the positioning of gedatolisib in the VIKTORIA-2 trial. Thanks.

Ruling out patients that were pre diabetic or diabetic type two diabetes.

And since then.

Several dear Doctor letters.

For a very significant adverse events.

That have been reported.

And the.

Label requires fairly extensive glucose monitoring both by the physician as well as the patient while they're at home.

And so overall this is based on our assessment of the claims data.

Thanks for taking my questions. Um, so switching gears a little bit, you know, we're roughly one and a half years into the launch of an avoided for the PI3K CA mutant, endocrine therapy resistance setting. I'm curious if there are any learnings from the launch label and/or KOL feedback that you think are supportive of the positioning of ghetto in the Victoria-2 trial. Thanks.

Brian Sullivan: Well, thank you. You know, they've reported very good data, and unfortunately, though, the patient population that really is appropriate to treat with that drug is fairly limited. You know, the study only enrolled patients who essentially were metabolically healthy, you know, patients who had an HbA1c level below 6, and essentially, you know, ruling out patients that were either pre-diabetic or diabetic, you know, type two diabetes. It has since been, you know, several Dear Doctor letters for very significant adverse events that have been reported. You know, the label requires fairly extensive glucose monitoring, both by the physician as well as the patient, while they're at home.

Well, thank you. Um,

It appears those restrictions are having an impact on.

<unk>.

Usage.

In the clinic to date so.

So from a learning standpoint for us.

Sensually highly.

Highlights just how unique drug <unk>.

Addressing this pathway, but more importantly, our rather very importantly.

So, you know that they they've reported a very good data. And uh, unfortunately, though, uh, the patient population, that that really is appropriate to treat with that drug is fairly limited. Um, you know, the the study, uh, only enrolled patients, who essentially were metabolically, healthy, you know, patients who had an HPA C1 level below 06. And essentially, you know, ruling out patients that were either pre-diabetic or diabetic you know, type 2 diabetes.

We're not inducing the levels of.

Glycolic system disruption that can lead to hyperglycemia.

That requires.

Significant management or any management at all actually and we do not believe that the.

Brian Sullivan: Overall, based on our assessment of the claims data, it appears those restrictions are having an impact on the usage in the clinic to date. From a learning standpoint for us, I mean, essentially, it highlights just how unique a drug gedatolisib is. We're addressing this pathway, but more importantly, or rather very importantly, we're not inducing the levels of glycemic system disruption that can lead to hypoglycemia that requires significant management or any management at all, actually. We do not believe that patients who are pre-diabetic or type 2 diabetes will be restricted in their ability to receive treatment with gedatolisib.

Patients, who are pre diabetic or pre diabetic or type two diabetes will be restricted in their ability to receive treatment with cosmos.

So.

It really goes back to the drug and the overall safety profile and when you don't have safety profile by data when you hit this pathway.

And you know, they've since been uh you know, several dear doctor letters uh for a very uh significant Adverse Events uh that have been reported. And uh you know the label requires fairly extensive glucose monitoring both by The Physician as well as the patient uh, while they're uh, at home and and so overall, this this based on our assessment of the claims data, uh, it appears those restrictions are having an impact on, uh, the uh,

You run into challenges.

And really being able to treat a broad group of patients who are.

To treat patients in a way that does create some potentially significant adverse event risk.

Usage, uh, in the clinic to date. Uh, so from a learning standpoint for us, I mean, it essentially highlights just how unique a drug data is. We're addressing this pathway, but, but more importantly—or rather, very importantly,

Very helpful and just one sort of frontline follow up given the <unk> results. We saw recently your prior phase <unk> data that you've shared in frontline patients as well as the number of oral <unk> inhibitors looking at the frontline setting I'm curious what your level of interest as any frontline endocrine center.

Ah study.

Brian Sullivan: It really goes back to the drug and the overall safety profile. When you don't have a safety profile like gedatolisib, when you hit this pathway, you'll run into challenges in really being able to treat a broad group of patients or to treat patients in a way that doesn't create some potentially significant adverse event risk.

Of uh glycolic system disruption uh, that can lead to hypoglycemia uh that that requires uh uh significant management or or any management at all actually. And we we do not believe uh that the patients who have pre-diabetes who are pre-diabetic or type 2, diabetes will be restricted in their ability to receive treatment with glsen.

While it would be very logical given the very favorable data that is reported in that setting and our phase one study.

As a reminder to folks in that study sample size of 41.

We reported median PFS.

Over 48 months and an objective response rate of 79%.

And with.

With scatter to listen combined with probably stick with Microsoft So those those really compare very favorably to what's been published to date for our currently approved therapies. So I think there's a very strong case to be made.

And so, uh, it really goes back to the drug and and the the overall safety profile. And when you don't have a safety profile, I get a when you hit this pathway. Uh, you, you'll run as a challenges uh and and really being to able to treat a broad group of patients or uh, to treat patients in a way that uh, does create some potentially significant adverse event risk.

Oliver McCammon: Very helpful. Just one sort of frontline follow-up. Given the PERSEVERE results we saw recently, your prior phase one B data that you've shared in frontline patients, as well as the number of oral PI3K inhibitors looking at the frontline setting, I'm curious what your level of interest is in a frontline endocrine sensitive study.

For for Us.

Conducting a study in that space and.

We will keep people posted on our thinking.

Thank you for taking my questions.

Very helpful, and just one sort of frontline follow-up given the proverbial results we saw recently, your prior Phase 1b data that you've shared in frontline patients, as well as a number of oral PI3K inhibitors. Looking at the frontline setting, I'm curious what your level of interest is in a frontline, endocrine-sensitive study.

Our next question comes from the line of Eva for data from Wells Fargo. Your line is now open.

Brian Sullivan: Well, it would be very logical given the very favorable data that we've reported in that setting in our Phase 1b study. Just as a reminder to folks, in that study, sample size of 41, we reported median PFS of, you know, over 48 months and an objective response rate of 79% with gedatolisib combined with palbociclib and letrozole. Those really compare very favorably to what's been published to date for currently approved therapies. I think there's a very strong case to be made for us in conducting a study in that space. You know, we will keep people posted on our thinking.

Good afternoon. Thanks for taking our question a quick one from US do you have any updated thoughts on the European commercial strategy for <unk> in terms of like timing for a potential update or approach to partnering or how would you expect <unk> to sequence versus the U S.

Well, it would be very logical. Given the very favorable data, uh, that we've reported in that setting, uh, in our facial and view study. And just as a reminder to folks, uh, in in that study, uh, sample size of 41, uh, we reported meeting PFS of, you know, over 48 months and an objective response rate of 79%,

Sure.

So our current plan.

Our Grand plan comes to fruition.

Is that.

If we have as we hope and expect a positive readout with our mutant cohort.

Then follow up.

And, uh, we've got to listen combined with psych with and let results. So those those really compare, very favorably to what's been published to date, uh, for currently approved, uh, therapies. So, I, I think there's a very strong case to be made, uh, for, uh, for us, uh, and conducting a study in that space and, uh, you know, we we will keep people posted on our thinking

With a supplemental NDA, assuming we get the initial approval forget it's Melissa.

Oliver McCammon: Thank you for taking my questions.

thank you for taking my questions.

Operator: Our next question comes from the line of Eva Forte from Wells Fargo. Your line is now open.

Operator: Our next question comes from the line of Eva Fortea from Wells Fargo. Your line is now open.

Then once that NDA is complete with MBA packages is completed we would we will then utilize the documents and Samsung most documentation will translate but essentially use.

Our next question comes from the line of Eva Phora from Wells Fargo. Your line is now open.

Eva Forte: Good afternoon. Thanks for taking our question. A quick one from us. Do you have any updated thoughts on the European commercial strategy for gedatolisib in terms of, like, timing for a potential update or approach to partnering or how you expect EU to sequence versus the US?

Eva Fortea: Good afternoon. Thanks for taking our question. A quick one from us. Do you have any updated thoughts on the European commercial strategy for gedatolisib in terms of, like, timing for a potential update or approach to partnering or how you expect EU to sequence versus the US?

Information from.

The wild type and mutant datasets and the NDA modules overall.

Two.

Craig.

Submission.

Brian Sullivan: Sure. So our current plan, if our grand plan comes to fruition, is that if we have as we hope and expect a positive readout with our mutant cohort, we would then follow up with a supplemental NDA, assuming we get the initial approval for gedatolisib. Then once that NDA is complete or that sNDA package is completed, we would then utilize the documents, and essentially most of the documentation will translate. Essentially use the information from both the wild-type, the mutant datasets, and the NDA modules overall, to create an MAA submission in Q4 this year. That's roughly a 13-month process to potentially get it accelerated, but 13 months with a regular review.

In the fourth quarter this year.

Good afternoon. Thanks for taking our question, a quick one from us. Do you have any updated thoughts on the European commercial strategy for GA in terms of, like, timing for a potential update or approach to partnering, or how you expect EU to sequence versus the US?

That's roughly.

Roughly a 13 month process too.

[noise] potentially get it has accelerated the 13 months with a regular review.

So in the meantime, after we submit that would be the window of time.

That you would use to explore finding partners.

To collaborate with launching.

Not only in Europe, but potentially globally.

Simultaneously, we've also been engaging with the regulators in Japan.

And.

So identify the regulatory path forward for submission in Japan.

We think we've got it.

Gained alignment so far.

On that front and so even though we haven't identified a partner at this time.

We are not.

We're proceeding apace with.

Yeah.

Regulatory activities in the most significant markets, which would include the major five European countries as well as Japan.

Brian Sullivan: In the meantime, after we submit, you know, that would be the window of time that we would use to explore finding partners to collaborate with launching, you know, not only in Europe but potentially globally. You know, simultaneously, we've also been engaging with the regulators in Japan, and to identify the regulatory path forward for submission in Japan. We think we've kind of gained alignment so far on that front. You know, even though we haven't identified a partner at this time, we're proceeding at pace with regulatory activities in the most significant markets, which would include the major five European countries as well as Japan.

Sure. Um, so our current plan, um, if our grand plan comes to fruition, uh, is that, uh, if we have, as we hope and expect, a positive readout with our mutant, uh, cohort, uh, we would then follow up, uh, with a supplemental MDA. Assuming we get the initial approval for, get it listed, and then, once that MDA is complete, that MDA package is, is completed, we would, we would then utilize the, the documents and essentially, most of the documentation will translate, but essentially use, uh, uh, information from both the wild type and mutant, uh, data sets, uh, and, and the NDA modules overall, uh, to, uh, create a, an MMA submission, uh, in the fourth quarter, uh, this year. Uh, that's a roughly, a 13-month process, uh, to, uh, potentially get an accelerated— but, but 13 months, with a regular review. And so, in the meantime, after we submit, you know, that, that—

And so we will.

In this window have ample time to find the right partner without delaying at all our ability to house get a launched in those markets.

Got it thanks.

Would be, uh, the window of time, uh, that, uh, we would use to explore, uh, finding partners, uh, to collaborate with, uh, launching, you know, not only in Europe, but potentially globally, you know, simultaneously. Uh, we've also been engaging with the regulators in Japan, uh, and, uh,

Our next question comes from the line of <unk> Patel.

To identify, uh, the regulatory path forward, uh, for submission in Japan. We think, uh, we've, we've kind of—

From Wolfe Research your line is now open.

Yeah, Hey, thanks for taking the question one.

One from us on the meeting update.

Do you need to.

Both the doublet and triplet arms.

To file.

Later in the year or can you file on a successful hit on triplet alone.

Brian Sullivan: we will, you know, in this window have ample time to, you know, find the right partner without delaying at all our ability to have gedatolisib launched in those markets.

Brian Sullivan: We will, you know, in this window have ample time to, you know, find the right partner without delaying at all our ability to have gedatolisib launched in those markets.

Well without getting into any more detail just limit it to the study design the study design.

As the primary endpoint is a comparison of the triplet to epilepsy and so that.

Gained alignment, uh, so far, uh, on that front. And so, you know, even though we haven't identified a partner at this time, uh, we are not, uh, we're proceeding at pace with, uh, regulatory activities in the most significant markets, which would include the major five European countries as well as Japan. Uh, and, uh, and so we will, you know, in this window have ample time to, you know, find the right partner without delaying at all our ability to get a launch in those markets.

Operator: Got it. Thanks.

Eva Fortea: Got it. Thanks.

Got it, thanks.

As the.

Operator: Our next question comes from the line of Kalpit Patel from Wolfe Research. Your line is now open.

The primary endpoint and I would form the basis for any potential regulatory submission.

Our next question comes from the line of Kalpit Patel.

The analysis can thank you.

From Wolfe research, your line is now open.

Kalpit Patel: Yeah. Hey, thanks for taking the question. One from us on the mutant update. Do you need to hit both the doublet and triplet arms to file later in the year, or can you file on a successful hit on triplet alone?

<unk> two epilepsy is an exploratory analysis.

Yeah, hey, uh, thanks for taking the question.

Or secondary got it thank you.

Welcome.

1 from us, on the mutant update. Um, do do you need to

Our next question comes from the line of Chase Knickerbocker from Craig Hallum. Your line is now open.

Hit both the dub and triplet arms.

Good afternoon, thanks for the questions will.

We will be curious what you and your end.

File on, uh, a successful hit on triplet alone.

Brian Sullivan: Well, without getting into any more detail, I'll just limit it to, you know, the study design. The study design as a primary endpoint is a comparison of the triplet to alpelisib. That is the primary endpoint and that would form the basis for any potential regulatory submission. The analysis-

And our market access team.

I've heard in your early prelaunch discussions with Payors.

Well, without getting into any more detail, just limit it to, you know, the study design, the study design, uh,

On a number of items around the profile of <unk> Wild type.

Maybe kind of foremost amongst them and how thats solidified or alter in any of your thoughts around potential pricing.

I guess, just the overall reception to information that we've shared.

Uh, as primary, uh, endpoint is a comparison of the triplet, uh, throughout the lipid. And so that, uh, is, uh, the primary endpoint. And it would form the basis for any potential regulatory submission.

Kalpit Patel: Okay. Thank you.

Brian Sullivan: Comparing the doublet to alpelisib is an exploratory analysis or secondary analysis.

With the payers and.

Now, the analysis comparing the doublet to Opal, lips of this, and exploratory analysis.

Strategic accounts, which we're able to do on our safe Harbor basis, since they're not health care providers.

Kalpit Patel: Got it. Thank you.

Brian Sullivan: You're welcome.

Or secondary analysis. Got it. Thank you.

You're welcome.

<unk> has been very very positive I think.

Operator: Our next question comes from the line of Chase Knickerbocker from Craig-Hallum. Your line is now open.

Interesting too to get feedback they provide.

Our next question comes from the line of Chase Nikkor-Butker from Craig-Hallum. Your line is now open.

Chase Knickerbocker: Good afternoon. Thanks for the questions. We'll be curious what you and your, you know, market access team have heard in your early pre-launch discussions with payers on a number of items around the profile of gedatolisib and wild-type, maybe kind of foremost amongst them, you know, how that's solidified or altered any of your thoughts around potential pricing.

They're in the business of helping insurers.

Individuals who they are ensuring have access to therapies or ultimately responsible for treating.

Access to the right therapies and so.

We've been very pleased with how they reacted to the data and there.

Good afternoon. Uh, thanks for the questions. Um, we'll be curious what you and your, uh, you know, market access team, um, have heard in your early pre-launch discussions with payers, um, on a number of items around the profile of GETA and wild type. Um, maybe kind of...

Yeah collaboration.

Good.

Foremost, amongst them—um, you know, how that's solidified or altered any of your thoughts around potential pricing.

And working with us to later.

Brian Sullivan: I guess, you know, just the overall reception to the information that we've shared with, you know, payers and strategic accounts, which we're able to do on a safe harbor basis, since they're not healthcare providers, has been very positive. I think it's interesting to get the feedback they provide. You know, they're in the business of helping ensure, you know, the individuals who they are insuring have access to therapies or ultimately responsible for treating, and have access to the right therapies.

Groundwork to ensure that.

As early as practically possible get a rather.

Patients will have access to.

So this this to this drug and the resident.

Maybe just as a follow up around the competitive environment and we saw recently another acquisition.

<unk> mutant selective <unk> inhibitor.

Can you just refresh us on your thoughts on potential future competition for you from that angle and then just kind of generally on kind of the next generation assets coming up.

Brian Sullivan: We've been very pleased with how they've reacted to the data and their, you know, collaboration is how I would say in working with us to lay the, you know, groundwork to ensure that as early as practically possible patients would have access to this drug and the regimen.

And.

And competition here.

Sure.

Thank you.

I think theres been.

Since uplifted.

This approval.

Seven years ago Theres been obviously the number of companies that have.

Soft too.

<unk>.

Provide an alternative that would be safer.

An awful upset.

That's us.

Uh, we we, I guess, you know, just the overall, uh, reception uh, to information that that we've shared uh, with uh, you know, payers and strategic accounts, which you're able to do on a safe harbor basis. Uh, since they're not Healthcare Providers, uh, has been very, very, uh, positive. I think, uh, it's interesting to to get the feedback they provide, you know, they're they're in the business of helping ensure, you know, the the, uh, individuals, uh, who, who they are ensuring have access to therapies, or or ultimately responsible for treating, uh, I have access to the right therapies. And so, uh, We've we've been very pleased, uh, with, with how they've reacted to the data and their, uh, uh, you know, collaboration, it's how I would, uh, say it. Um, in working with us to lay the, you know, groundwork to ensure that, uh, as, as early as practically possible, uh, get a rather, uh, patients would have access, uh, to this, this, uh, to this.

Worthy project.

Chase Knickerbocker: Maybe just as a follow-up, around the competitive environment. We saw recently another acquisition, of a mutant selective PI3K alpha inhibitor. Can you just refresh us on your thoughts on, you know, potential future competition for you from that angle? Just kinda generally on kinda the next generation assets coming up in competition here.

But.

The underlying biological assumption.

Driving those.

Projects.

We think is.

Oh no.

Not necessarily current we didn't get at Elisa and the approach we've taken of inhibiting all class one Patrick isoforms is all of them to or wanted to.

Maybe just as a follow-up, um, around the competitive environment. And we saw recently, another acquisition, um, of a mutant selective pi3k Alpha inhibitor. Um, can you just refresh us on your thoughts on, you know, the potential future competition for you from that angle? And then just kind of generally on kind of the Next Generation assets coming up. And

um,

in competition here.

Brian Sullivan: Sure. No. Thank you. Again, I think there's been, you know, since alpelisib received its approval, you know, I guess 7 years ago, there have been other, you know, a number of companies that have, you know, sought to potentially provide an alternative that would be safer than alpelisib, and that's a worthy project. You know, the underlying biological assumption that's really driving those projects, we think is not necessarily current. We think gedatolisib and the approach we've taken of inhibiting all class I PI3K isoforms as well as mTORC1 and mTORC2 is the approach that's required to optimize antitumor control, you know, to provide maximum antitumor control.

Is the approach that's required to optimize antitumor control.

<unk> provides maximum antitumor control and and so we just think there's a biological limit.

The benefit of that.

Single targeted inhibitor like yesterday off inhibitor can can induce and.

Having more as we've seen with serves doesn't.

It's a high yield different results I think.

Five phase III reports later I think we've seen very very similar results now in this case with this in this setting I think it's reasonable to expect that based on that the way. These drugs are.

Sure. No, thank you. I again, I think there's been, uh, you know, since epilepsy, uh, received its approval. You know, I guess 7 years ago, there have been other PE the number of companies that have, you know, sought to, uh, potentially provide an alternative that would be safer, uh, than opal lipid. Uh, and that's, that's a worthy project. Uh, but, uh, the underlying biological assumption, uh, that's really driving. Uh, those, uh, uh, projects. Uh, we think is, uh, uh,

Distinguishing they're targeting between the mutant form of <unk> Alfa and <unk>.

Whilst that form.

They can improve upon.

Safety profile relative to uplift, so I think that seems pretty reasonable, but ultimately I think there's going to be.

Brian Sullivan: We just think there's a biological limit on the benefit that a single target inhibitor like a PI3K alpha inhibitor can induce. You know, having more, as we've seen with SERDs, doesn't necessarily yield different results. I think, you know, five phase 3 reports later, I think we've seen very, very similar results. Now, in this case, you know, with this, in this setting, I think it's reasonable to expect that, based on the way these drugs are distinguishing their targeting between the mutant form of PI3K alpha and the wild type form, that they can improve upon safety profile relative to alpelisib. I think that seems pretty reasonable.

Unlimited.

Dialogical potential to induce an optimal.

Outcome for efficacy and I think the results today for data certainly we think demonstrate the value and importance of providing comprehensive ambition of this pathway as opposed to selective inhibition of this pathway.

Not necessarily current. We didn't get a solicited in the approach. We've taken of inhibiting all class 1, uh, PS3 isoforms as well. Then took 1 and 2, uh, is the approach that's required, uh, to optimize, uh, anti-tumor control, you know, to provide maximum anti-tumor control. And, and so we just think there's a biological limit, uh, on the benefit that, uh, a single target inhibitor, like a PS3 off inhibitor, can, can induce.

and uh,

So as far as.

The impact on us we actually.

We think again that targeting approach will be obsolete. It is.

With the data.

You know, having more as we've seen with serves doesn't necessarily yield different results. I think, you know, 5, uh, phase 3 reports later, I think we've seen very, very similar results. Now, in this case, you know, with this, in this setting, I think it's reasonable to expect that uh, based on the the way these uh, drugs are are distinguishing, their target.

We hope to report out soon is what we hope and expect.

Got it thanks, Brian.

Welcome.

There are no further questions at this time I will now turn the call over to Brian Sullivan <unk>, Chief Executive Officer for closing remarks, Sir. Please go ahead.

Brian Sullivan: Ultimately, I think there's gonna be a limited biological potential to induce an optimal outcome for efficacy. I think the results today for gedatolisib certainly demonstrate the value and importance of providing comprehensive inhibition of this pathway as opposed to selective inhibition of this pathway. As far as, you know, impact on us, we actually think again that targeting approach will be obsoleted if the data we hope to report out soon is what we hope and expect.

Well, thank you for participating in our call today for your ongoing support and look forward to reporting back to you soon.

Between the mutant form of pi3k Alpha and, and the wild type form, uh, that they, they can improve upon, um, safety profile relative to epilepsy that. I think that seems pretty reasonable, but, but ultimately, I think there's going to be, uh, a limited uh, biological potential to induce uh, an optimal. Um,

Take care.

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

Outcome uh for efficacy. And I think the results today for data certainly we think demonstrate the the value and importance of providing comprehensive and addition of this pathway as opposed to selective inhibition of this pathway. Uh so as far as uh you know, impact on us we we actually

We think again that targeting approach will be obsoleted, uh, if the data, uh,

Soon is what we hope and expect.

Chase Knickerbocker: Got it. Thanks, Brian.

Got it.

Brian Sullivan: Welcome.

You're welcome.

Operator: There are no further questions at this time. I will now turn the call over to Brian Sullivan, Celcuity's Chief Executive Officer, for closing remarks. Sir, please go ahead.

There are no further questions at this time. I will now turn the call over to Brian Sullivan. Q is Chief Executive Officer for closing remarks, sir. Please go ahead.

Brian Sullivan: Well, thank you for participating in our call today, for your ongoing support. I look forward to reporting back to you soon. Take care.

Well, thank you, uh, for participating in our call today. Uh, for your ongoing support. I look forward to reporting back to you soon.

Take care.

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

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

Q4 2025 Celcuity Inc Earnings Call

Request a DemoDemo

CELC

Celcuity

Earnings