Q4 2024 Celcuity Inc Earnings Call

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Unknown Executive: Thank you for watching.

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Unknown Executive: Good afternoon, ladies and gentlemen, and welcome to the Celcuity fourth quarter and full year 2024 financial results webcast conference call. At this time, all lines are in listen only mode.

Speaker Change: Good afternoon, ladies and gentlemen, and welcome to the South Giddy fourth quarter and full year 'twenty 'twenty four financial results webcast conference call. At this time all lines are in listen only mode. Following the presentation. We will conduct a question and answer session. If at any time during this call.

Unknown Executive: 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.

Speaker Change: If you require immediate assistance. Please press star zero for the operator, I would now like to turn the clock conference over pretty much Hillary with ICR healthcare. Please go ahead.

Apoorva Chaluri: I would now like to turn the conference over to Apoorva Chaluri with ICR Healthcare. Please go ahead. Thank you, operator, and good afternoon to everyone on the call. Thank you for joining us to review Celcuity's fourth quarter and full year 2024 financial results and business update. Earlier today, Celcuity released financial results for the fourth quarter ending December 31st, 2024. The press release can be found on the investor section of the website.

Hillary: Thank you operator, and good afternoon to everyone on the call. Thank you for joining us to review the acuity fourth quarter and full year 'twenty 'twenty four financial results and business update.

Hillary: Earlier today, So acuity released financial results for the fourth quarter ending December 31st 2020 for the press release can be found on the investors section of the website. Joining me on the call today are Brian Sullivan, <unk>, Chief Executive Officer, and co founder Vicky Hahn, Chief Financial Officer, as well as Igor Gorbachev D Chief Medical Officer, who will.

Apoorva Chaluri: Joining me on the call today are Brian Sullivan, Celcuity's chief executive officer and co-founder, Vicky Hahne, chief financial officer, as well as Igor Gorbatchevsky, chief medical officer, who will be available during Q&A. Before we begin, I would like to remind listeners that our comments today will include some forward-looking statements. These statements involve a number of risks and uncertainties, which are outlined in today's press release and in our reports and filings with the SEC. Actual events or results may differ materially from those projected in the forward-looking statements. Such forward-looking statements and their implications involve known and unknown risks, uncertainties, and other factors that may cause actual results or performance to differ materially from those projected.

Hillary: [noise] 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 SBC Ottawa.

Hillary: Actual events or results may differ materially from those projected in the forward looking statements.

Hillary: Such forward looking statements and their implications involve known and unknown risks uncertainties and other factors that may cause actual results or performance to differ materially from those projected.

Apoorva Chaluri: On this call, we will also refer to non-GAAP financial measures. These non-GAAP measures are used by management to make strategic decisions, forecast future results, and evaluate the company's current performance. Management believes the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the company's ongoing core operations and prospects for the future. You can find a table reconciling the non-GAAP financial measures to GAAP measures in today's press release.

Hillary: 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 type of format.

Hillary: Management believes the presentation of these non-GAAP financial measures is useful to investors understanding and assessment of the Companys ongoing core operations and prospects for the future you could find the cable reconciling the non-GAAP financial measures to GAAP measures in today's press release.

Brian Sullivan: And with that, I would now like to turn the call over to Brian Sullivan, CEO of Salcuity. Please go ahead. Thank you, Apoorva. And good afternoon, everyone. We appreciate your interest in Celcuity. Our team made significant progress executing our clinical development programs in 2024. We completed enrollment of the PIK3CA wild-type cohort in Victoria 1, our Phase 3 study, evaluating gettatilicid plus fulvestrin with and without palvocyclib as second-line treatment for patients with HR-positive, HER2-negative advanced breast cancer. We also completed selection of approximately 200 sites for Victoria 2, our Phase 3 study designed to evaluate Geta-Tulisib in combination with Fulvestrin and either RiboCyclob or PowaCyclob as first-line treatment for patients with HR-positive, HER2-negative, endocrine-treatment-resistant advanced breast cancer.

Hillary: And with that I would now like to turn the call over to Brian Sullivan CEO Upsell QD. Please go ahead.

Brian Sullivan: Thank you operator, and good afternoon, everyone. We appreciate your interest in cell acuity.

Brian Sullivan: Our team made significant progress executing our clinical development programs in 2024.

Brian Sullivan: We completed enrollment of the picture you see a wild type cohort in Victoria, One phase III study evaluating <unk> plus full restaurant with and without Paolo Circlip as second line treatment for patients with HR positive <unk> negative advanced breast cancer.

Brian Sullivan: We also completed selection of approximately 200 sites for Victoria to our Phase III study designed to evaluate <unk> in combination with full restaurant and then either ribas cyclic or policy clip as first line treatment for patients with HR positive her two negative Andrew can treatment resistant advanced breast cancer.

Brian Sullivan: Our phase one dose escalation portion of our study evaluating get up to listen in combination with Dara.

Brian Sullivan: Our Phase 1b dose escalation portion of our study evaluating getatolisib in combination with darolutamide for patients with metastatic castration-resistant prostate cancer is ongoing and remains on track to report preliminary data at the end of the second quarter of this year. And we reported overall survival data from our Phase 1b study for treatment-naive and CDK4-6 pretreated patients who received our Phase 3 dosing. In our view, each of these three programs has the potential to generate blockbuster levels of revenue. If these three programs ultimately result in regulatory approvals, we estimate that nearly 200,000 late-stage cancer patients globally would be eligible to be treated with ketotilicin.

Brian Sullivan: For patients with metastatic castration resistant prostate cancer is ongoing and remains on track to report preliminary data at the end of the second quarter. This year.

Brian Sullivan: And we reported overall survival data from a phase one b study for treatment naive and CDK four six pretreated patients who received our phase III dosing schedule.

Brian Sullivan: In our view each of these three programs has the potential to generate blockbuster levels of revenue.

Three programs ultimately result in regulatory approvals, we estimate that nearly 200000 late stage cancer patients globally would be eligible to be treated with scatter to listen.

Brian Sullivan: As a result of the progress we made in 2024, 2025 will be a transformational year for Celcuity as we anticipate reporting several important clinical data releases. For our Victoria 1 clinical trial, we anticipate reporting top-line data for the PIC3CA wild-type cohort in the second quarter of 2025. and top-line data for the PIC3CA mutant-type cohort in the fourth quarter of 2020. The primary endpoints of Victoria 1 are progression-free survival, or PFS, per RECIS 1.1 criteria, as assessed by blind and independent sensory review. This study is designed to independently evaluate a PIC3CA wild-type cohort and a PIC3CA mutant cohort.

Brian Sullivan: As a result of the progress we made in 2024.

Brian Sullivan: It's only 25 will be a transformational year for cell acuity as we anticipate reporting several important clinical data readouts.

Brian Sullivan: For our Victoria, one clinical trial, we anticipate reporting topline data for the picture you see a wild type cohort in the second quarter of 2025.

Brian Sullivan: The topline data for the picture you see a mutant type cohort.

Brian Sullivan: In the fourth quarter of 2025.

Brian Sullivan: Primary endpoints of Victoria, one or progression free survival or PFS.

Brian Sullivan: For resist one one criteria as assessed by blinded independent Central review.

Brian Sullivan: <unk> is designed to independently evaluate a pick through say a wild type cohort and the picture you see a mutant cohort four.

Brian Sullivan: for the PIC3C-AWILD type cohort. There are two primary endpoints that will be tested hierarchically, whereas the PIC3CA mutant patient cohort has a single primary endpoint. The primary analysis for each patient cohort is triggered upon reaching a predefined number of progression events. Patients we're evaluating in our Victoria 1 study have HR-positive, HER2-negative advanced breast cancer, whose disease progressed while on or after receiving treatment with a CDK4-6 inhibitor and aromatase. We recognize that the treatment landscape for these second or third line patients is evolving as a number of investigational therapies are under development. Our view is that the underlying biological drivers of HR-positive, HER2-negative advanced breast cancer will ultimately determine which regimens become standard.

Brian Sullivan: For the picture to say wild type cohort.

Brian Sullivan: There are two primary endpoints that will be tested hierarchically, whereas the picture you see a mutant patient cohort has a single primary endpoint.

Brian Sullivan: The primary analysis for each patient cohort is triggered and upon reaching a predefined number of progression events.

Brian Sullivan: Patients were evaluating and our Victoria, one study of HR positive <unk> negative advanced breast cancer, whose disease progressed, while on or after receiving treatment with the CDK four six inhibitor and an aromatase inhibitor.

Brian Sullivan: We recognize that the treatment landscape for the second or third line patients is evolving as a number of investigational therapies or under development.

Brian Sullivan: Our view is that the underlying biological drivers of HR positive <unk> negative advanced breast cancer will ultimately determine which regimens become standard of care.

Brian Sullivan: Three Interconnected Signaling Pathways. Cyclin D1, CDK4-6, and PF3K-AKT mTOR pathways promote this disease. And we believe that simultaneous blockade of all three of these pathways offers the best opportunity to optimize anti-tumor control. And this suggests that a triplet that addresses these three disease drivers, whether in the first or second line setting, may have a long-term advantage versus a doublet or monotherapy that addresses just one or two of these signaling pathways. Additionally, a triplet that could treat all patients, regardless of PIK3CA or ESR1 mutational status, would have an even greater advantage. Current second-line treatment paradigm for HR-positive, HER2-negative patients with advanced breast cancer includes selective estrogen receptor degraders, or SERDs, like fulvestrin or elastitrin as clinical agents, or one of the three approved PAM inhibitors combined with endocrine therapy.

Brian Sullivan: Three interconnected signaling pathways yesterday Jens.

Brian Sullivan: Secondly, one CDK four six and P. S. K 8-K T M. Tor pathways promote this disease and we believe the simultaneous blockade of all three of these pathways offers the best opportunity to opera optimized anti tumor control.

Brian Sullivan: And this suggests that a triplet that addresses these three disease drivers weather in the first or second line setting may have a long term advantage versus a doublet or mono therapy that addresses just one or two of these signaling pathways.

Brian Sullivan: Additionally, the triplet that could treat all patients regardless of pick three C. A R. E. S. R. One mutational status would have an even greater advantage.

Brian Sullivan: The current second line treatment paradigm for HR positive <unk> negative patients with advanced breast cancer includes selective estrogen receptor degraders or surge like full restaurant or Alas a trend that's simple agents or one of the three approved Pan <unk> inhibitors combined with endocrine therapy.

Brian Sullivan: However, each of the PAM inhibitors only targets a single PAM node, such as PI3K-alpha, AKT, or mTORC1. which is suboptimal because the uninhibited PAM nodes can induce compensatory resistance. and patients who've received prior treatment with a CDK4-6. None of these single node PAM inhibitors have demonstrated efficacy. who have PIK3CA wild-type tumors, while only the PIK3KA and AKT inhibitor have reported benefit in patients with PIK3CA. And these results are consistent with the non-clinical data that shows these single node inhibitors are three to four times less potent in breast cancer cells without PIC3C-MU. then and those with.

Brian Sullivan: However, each of the Pam inhibitors only targets a single Pam node, such as BK Alpha AK T or I'm talk one.

Brian Sullivan: Which is suboptimal because he uninhibited Pam nodes can induce competence in Torrey resistance.

Brian Sullivan: And patients who have received prior treatment with the CDK four six inhibitor. None of these single node Pam inhibitors have demonstrated efficacy in patients who have picked through we see a wild type tumors, while only the pick a P. S VK alpha and AK T inhibitor ever reported benefit in patients with picture you see have mutations.

Brian Sullivan: And these results are consistent with the non clinical data that shows the single node inhibitors are three to four times less potent and breast cancer cells without picks through sand mutations than those with them.

Brian Sullivan: Now this is in sharp contrast to the non-clinical and preliminary efficacy data we've reported. Forget it.

Brian Sullivan: This isn't sharp contrast to the non clinical and preliminary efficacy data we've reported forget it to listen.

Brian Sullivan: So let's... In non-clinical studies evaluating breast cancer and prostate cancer cell lines, GADF-ellisib was found to be equally potent and cytotoxic in cell lines with and without PIK3CA or P10 mutations, and at least 300 times more potent on average in breast cancer cells than single-node PAMs. consistent with these non-clinical. The preliminary clinical endpoints re-reported in our Phase 1b breast cancer study that evaluated gettatilicib combined with palviciclib in either letrozole or filvestrin was comparable in both treatment-naive and second-third-line patients with and without PIK3CA mutations. And we think these results demonstrate that along with the ER and CDK4-6 pathways, we Pam pathway plays an intrinsic role as a disease driver in HR positive, HER2 negative, advanced breast cancer.

Speaker Change: In non clinical studies evaluating breast cancer and prostate cancer cell lines get it for less of a sound to be equally potent cytotoxic in cell lines with and without Pixar CAGR of pizza and mutations and at least 300 times more potent on average in breast cancer cells and single node Pam inhibitors.

Brian Sullivan: Consistent with these non clinical results.

Brian Sullivan: Preliminary clinical endpoints, we reported in our phase one b breast cancer study that evaluated gathered solicit combined with palace equipment, either Letrozole are for restaurant was comparable in both treatment naive and second and third line patients with and without picks receipt of mutations and we think these results demonstrate that along with the E. R. A T T K four six pathways.

Brian Sullivan: M pathway plays an intrinsic role as a disease driver in HR positive <unk> negative advanced breast cancer, that's independent of the presence of an activating mutation like victory yet.

Brian Sullivan: That's independent of the presence of an activating. And that's why we believe development of an optimized PAM inhibitor, like Getty. that targets all class 1 PI3K isoforms and mTORC1 and 2 to comprehensively blockade the represents one of the most important opportunities. improve the standard of care and HR positive HER2 negative advanced breast We think that gadifolicib's tolerability may also favor its potential positioning in a future treatment. Geta-Telusib's treatment-related discontinuation rate due to adverse events was only 4% in the Phase 1b arm with a Phase 3 intermittent dose schedule, which is comparable to the 6-8% discontinuation rates for CDK4-6 post-fluvestrum.

Brian Sullivan: And that's why we believe development of an optimized Pam inhibitor like God, It's Elisa.

Brian Sullivan: Targets all class one P O three K isoforms and M torque wanted to to comprehensively blockade. The Pam pathway represents one of the most important opportunities to improve the standard of care in HR positive her two negative advanced breast cancer.

Brian Sullivan: We think they've got a solicitor Tolerability may also favorites potential positioning and our future treatment landscape get us Elisa streetman related discontinuation rate due to adverse events was only 4% in the phase one b arm the phase III intermittent dose schedule, which is comparable to the 6% to 8% discontinuation rates for CDK four six plus for western regiments well we.

Brian Sullivan: Well, we don't have head-to-head data. These results compare favorably to the treatment-related discontinuation rates reported in the phase three studies for Opalypsin plus Fulvestrin, where 26% of patients discontinued, and Everolimus plus Examistate, where 24% of patients discontinued. The results for Gettifliss were especially encouraging, given that the Phase 1B study did not include prophylactic therapy for stomatitis. The most common treatment-related adverse event, forget it. Since we're prescribing stomatitis prophylaxis in our Phase 3 trial, we would expect fewer stomatitis-related adverse events, which would further enhance Getta's already promising tolerability. Of course, the foundation of GEDA's role in this treatment landscape will require the GEDA solicits to be well tolerated and report a clinically meaningful benefit measured in terms of the incremental improvement in both median PFS and the hazard ratio relative to Breast cancer KOLs and regulators generally consider an incremental improvement in median PFS of three months relative to its control to be clinically meaningful.

Brian Sullivan: Don't have head to head data. These results compare favorably to the treatment related discontinuation rates reported in the phase III studies for uplift surplus full restroom were 26% of patients discontinued and Everolimus plus examine staff were 24% of patients discontinue.

Brian Sullivan: The results forget it splits were especially encouraging given that the phase one B study did not include prophylactic therapy for stomatitis the.

Brian Sullivan: The most common treatment related adverse event forget it's Elisa.

Brian Sullivan: Since we're prescribing stomatitis prophylaxis in our phase III trial, we would expect fewer stomatitis related adverse events, which would further enhance ghettos already promising tolerability.

Brian Sullivan: Now of course, the foundation of get his role in this treatment landscape will require to get it supposed to be well tolerated and report a clinically meaningful benefit measured in terms of the incremental improvement in both medium PFS and the hazard ratio relative to standard of care.

Brian Sullivan: So breast cancer Kols and regulators generally generally consider an incremental improvement in median PFS of three months relative to its control to be clinically meaningful and the current median PFS benchmarks, where patients pretreated with the CDK four six inhibitor patient population, we're evaluating for modest published reports from recent randomized trials.

Brian Sullivan: And the current median PFS benchmarks for patients pre-treated with a CDK46 inhibitor, patient population we're evaluating, are modest. Published reports from recent randomized trials of median progression-free survival for Fovestrin average 2.7 months in patients with ESR1 wild-type tumors and 3.8 months for oral SIRDS in patients with ESR1 mutants. Incremental Median PFS Benefit for Patients with ESR1 Mutations Treated with an Oral SIRT was one of 1.9 months. For patients with PIK3CA or AKT mutations, median PFS ranges from 5.5 to 7 months when treated with either an AKT or PI3K alpha. representing approximately 3.5 months of incremental median PFS benefit.

Brian Sullivan: Median progression free survival for restaurant average 2.7 months in patients with ESR, one wild type tumors and 3.8 months for oral surge in patients with Es are one mutant tumors.

Brian Sullivan: The incremental medium PFS benefit for patients with ESR, one mutations treated with an oral surgery.

Brian Sullivan: Was one of 1.9 months difference.

Brian Sullivan: For patients with pick three C. A R E. K T mutations median PFS ranges from five five to seven months when treated with either an 8-K T or P. S. K Alpha inhibitor, representing approximately 3.5 months of incremental medium PFS benefit.

Brian Sullivan: The rapid adoption and resulting annual run rate for each of these drugs, which is approximately 500 and 600 million respectively, illustrates the desire physicians have to switch to new therapies even when the incremental clinical benefit to their patients is modest. Now, a potentially more important data point than incremental PFS benefit to consider an advanced breast cancer when assessing the clinical benefit of one therapeutic regimen relative to another is the hazard ratio. Now, this is because recent randomized studies evaluating therapies for patients with HR-positive, HER2-negative advanced breast cancer. have enrolled widely heterogeneous patients. For instance, one study that evaluated an oral SIRD conducted primary analysis that included first and second line patients.

Brian Sullivan: The rapid adoption and resulting annual run rate for each of these drugs. So approximately 500 and $600 million respectively illustrates the desire for physicians have to switch to new therapies, even when the incremental clinical benefit to their patients is modest.

Brian Sullivan: There are potentially more important data point that incremental be less benefit to consider in advanced breast cancer when assessing the clinical benefit of one therapeutic regimen relative to another is the hazard ratio and that's just because recent randomized studies evaluating therapies for patients with HR positive <unk> negative advanced breast cancer have enrolled while widely heterogeneous.

Brian Sullivan: Patient populations for instance, one study that evaluated in the oral surgery conducted primary analysis that included first and second line patients in the same study.

Brian Sullivan: And the same study evaluated the combination of the oral SIRD with a CDK4-6 inhibitor that included both patients who were CDK treatment naive and those who had received prior CDK4-6. In another study evaluating an AKT inhibitor, the primary analysis included both patients who were CDK4-6 treatment-naive and those who had received prior CDK4-6 therapy. Well, since patients, physicians rather, make different treatment decisions for patients, depending on, among other factors, how many lines of therapy or which type of therapy they've received, results from these studies can be hard to interpret using absolute median PFS or incremental median PFS benefit alone.

Brian Sullivan: You added the combination of the oral surgery with the CDK four six inhibitor that included both patients who are CDK treatment naive and those who had received prior CDK four six therapy.

Brian Sullivan: And another study evaluating an 8-K T inhibitor primary analysis included both patients who were CDK four six treatment naive and those who had received prior CDK four six therapy.

Speaker Change: Well since patients physicians, rather make different treatment decisions for patients depending on among other factors, how many lines of therapy or which type of therapy they've received <unk>.

Speaker Change: Results from these studies can be hard to interpret using absolute median PFS or incremental medium PFS benefit alone.

Brian Sullivan: As a result, the top-line median PFS results from these studies don't provide sufficient clarity about the actual benefit a particular patient population may receive. Hazard ratio essentially factors out the differences in study populations and thus provides physicians with an objective. We not only hope to report a hazard ratio that is statistically significant, but one that compares favorably to the hazard ratio reported for other therapies available for these second-line patients. An additional factor, which we think may ultimately accrue to get a thalassob's advantage, particularly in the community physicians. is the fact that DETA is an infused therapy administered in office.

Speaker Change: As a result, the topline median PFS results from these studies don't provide sufficient clarity about the actual benefit that particular patient population. They receive hazard ratio essentially factors out the differences in study populations and provides patients physicians, rather with an objective benchmark.

Speaker Change: He is not only hope to report a hazard ratio that is statistically significant but one that compares favorably to the hazard ratio reported for other therapies available for the second line patients.

Speaker Change: An additional factor, which we think may ultimately accrue to get it to elicit advantage, particularly in the community physician setting is the fact that get it is an infused therapy administered in office in this perspective has been reflected in the feedback we're receiving from oncologists, both key opinion leaders and community physicians and market access stakeholders in conjunction with our preliminary.

Brian Sullivan: And this perspective has been reflected in the feedback we're receiving from oncologists, both key opinion leaders and community physicians, and market access stakeholders in conjunction with our preliminary market research. Particular note, the encouraging feedback we received regarding Geta-Telusib's IV route of administration. Physicians can monitor and manage patient compliance more effectively than they can with oral therapies, and this is relevant. particularly for oral therapies that induce unpleasant side effects. But these therapies, patient compliance can often be a challenge. And this preliminary research does suggest an IV administration will not be a barrier to utilization of Geddes Lisbon, in fact, may be an important advantage.

Speaker Change: A market research.

Speaker Change: Particular note, it's encouraging feedback received regarding gathered to subside the route of administration.

Speaker Change: Actions can monitor and manage patient compliance more effectively than they can with oral therapies and this is relevant.

Speaker Change: Particularly for oral therapies that induce unpleasant side effects, but these therapies patient compliance can often be a challenge and its preliminary research does suggest an IV administration.

Speaker Change: Will not be a barrier to utilization of get us listen in fact, maybe an important advantage due.

Brian Sullivan: Additionally, in-office administered therapies such as getitalicib fall into the medical benefit category, which has a more streamlined reimbursement process, than orally administered drugs, which fall into the pharmacy benefit category. Our market research suggests that this fact has several implications for oncologists, patients, and our company. First, oncologists view IV-administered drugs favorably, allowing them to recover additional costs associated with treating their patients in-office. Emergency is called an October 22nd when colleges have more autonomy, just like therapies they believe will benefit Third, the payer management process is less burdensome. And finally, patients typically incur lower out-of-pocket costs with an infused therapy, which is an important consideration for most patients.

Speaker Change: <unk> and office administered therapies, such as get Us Elisa.

Speaker Change: Paul into the medical benefit category for which has a more streamlined reimbursement process than orally administered drugs, which fall into the pharmacy benefit category.

Speaker Change: Our market research suggests that this fact as several implications for oncologists patients and our company first oncologists view IV administered drugs favorably, allowing them to recover additional costs associated with treating their patients in office.

Speaker Change: And colleges have more autonomy to select therapies, they believe will benefit their patients.

Speaker Change: Third payer management processes, less burdensome to navigate and finally patients typically incur lower out of pocket costs with an infused therapy, which is an important consideration for most patients for pharmaceutical companies payer contracting is less common and results in fewer price discounts.

Brian Sullivan: for pharmaceutical companies. Pair contracting is less common and results in fewer price. In a real-world setting, patient convenience is only a meaningful consideration for IV-administered drugs when the efficacy and safety profile of the alternative drugs are comparable, or when a patient lives a significant distance from a treatment. Otherwise, based on our market research, a well-tolerated therapy that offers a clinically meaningful benefit is preferred by oncologists relative to one that offers less efficacy but is more convenient. The fact that the most widely prescribed oncology drugs are administered in office reinforces this point.

Speaker Change: In a real world setting patient convenience is only meaningful it's the only meaningful consideration for IV administered drugs when the efficacy and safety profile of the alternative drugs are comparable or when a patient lives significant distance from a treatment site.

Speaker Change: Otherwise based on our market research the well tolerated therapy that offers a clinically meaningful benefit is preferred by oncologists relative to one that offers less efficacy, but it's more convenient.

Speaker Change: The fact that the most widely prescribed oncology drugs are administered Gen office reinforces this point for instance in breast cancer Herceptin Prijedor Keytruda and in her two each recorded multibillion dollar peak revenues, while trading smaller patient populations and the potential populations, we seek to address with get to solicit and our two current breast cancer clinical trials.

Brian Sullivan: For instance, in breast cancer, Herceptin, Progetta, Keytruda, and in HER2, each recorded multi-billion dollar peak revenues while treating smaller patient populations than the potential populations we seek to address with Geddes-Lisib and our two current breast cancer clinical trials. If Yadath Elisib ultimately does receive FDA approval for both the PIK3CA wild type and mutant populations, we estimate the peak revenue potential for the second line indication could exceed $2 billion with just 40% market cap.

Speaker Change: If you Gotta solicit ultimately does receive FDA approval for both the picture you see a wild type and mutant populations. We estimate the peak revenue potential for the second line indication could exceed $2 billion with just 40% market penetration.

Speaker Change: Now turning to our first line breast cancer program.

Brian Sullivan: Now turning to our Firstline Breast Cancer Program. We've completed the selection of the clinical sites that will participate in our Victoria 2 study. Approximately 200 sites across North America, Europe, Latin America, and Asia Pacific are in process now of being activated.

Speaker Change: We've completed the selection of the clinical sites that will participate in the Victoria study approximately 200 sites across North America, Europe, Latin America, and Asia Pacific are in process now of being activated.

Brian Sullivan: We're very pleased with the level of interest our current Victoria 1 sites expressed in participating in the study, and we continue to expect to enroll our first patient in second quarter of 2025. Victoria II Studies, a global Phase III open-label, randomized clinical trial evaluating the efficacy and safety of gadotelizumab in combination with fulvestrin, plus investigator's choice of either ribosiclib or palvosiclib. As a first-line treatment for patients with HR-positive, HER2-negative advanced breast who are endocrine therapy resistant. Approximately 638 patients will be assigned to a cohort based on their PIK3CA mutation. Clinical trial endpoints are progression-free survival per RECIS 1.1 criteria as assessed by blinded independent central review.

Speaker Change: Are you pleased with the level of interests are current Victorian one sites express and participating in the study.

Speaker Change: And we continue to expect to enroll our first patient in second quarter of 2025.

Speaker Change: Victoria, who study is a global phase III open label randomized clinical trial evaluating the efficacy and safety <unk> got it's less of in combination with sylvestris, plus investigator's choice of either Rob or cyclical or policy club as a first line treatment for patients with HR positive <unk> negative advanced breast cancer.

Speaker Change: Who are endocrine therapy resistant.

Speaker Change: Approximately 638 patients will be assigned to a cohort based on the picture you see a mutation status clinical trial endpoints are progression free survival per resist one one criteria as assessed by blinded independent Central review primary PFS endpoint for each of the two cohorts will be evaluated independently.

Brian Sullivan: Primary PFS endpoint for each of the two cohorts will be evaluated independently.

Speaker Change: Prior to the initiation of the phase II portion of the trial safety run in study will be conducted in 12 to 36 patients to assess the safety profile of get unsolicited in combination with <unk> and full restaurant.

Brian Sullivan: Prior to the initiation of the Phase III portion of the trial, a safety run and study will be conducted in 12 to 36 patients to assess the safety profile of getatelicib in combination with ribociclib and fulvestrin. We estimate that 15,000 to 20,000 patients with endocrine therapy resistant advanced breast cancer are diagnosed each year in the United States alone. And since this population doesn't overlap with the patient population we're evaluating in our Victoria One study, an approval to treat these patients would increase the size of the addressable US market potential for Gettys illicit by up to 3 billion.

Speaker Change: We estimate the 15000 to 20000 patients with endocrine therapy resistant advanced breast cancer are diagnosed each year in the United States alone.

Speaker Change: Just as population doesn't overlap with a patient population that we're evaluating and our fixed rate one study and approval to treat these patients would increase the size of the addressable U S market potential forget us Elisa by up to $3 billion.

Brian Sullivan: Turning now to our prostate cancer. We remain on track with our Phase 1B trial that is evaluating the safety and tolerability of Getta in combination with darylutamine. patients who have metastatic castration-resistant prostate.

Speaker Change: Turning now to our prostate cancer program.

Speaker Change: We remain on track with our phase one B trial that is evaluating the safety and Tolerability of <unk> combination with <unk> in patients who have met the metastatic castration resistant prostate cancer.

Brian Sullivan: The underlying biology of prostate cancer has a lot of similarities to ER positive. Both are hormonally driven tumor types and both involve the PAM pathway. While the development of PAM inhibitors in breast cancer is further advanced than in prostate cancer, there is significant non-clinical evidence and emerging clinical data that suggests simultaneous inhibition of both the AR and PAM pathways. may be more. and treatment with an AR inhibitor alone. We expect to report out preliminary data from the Phase 1b dose escalation portion of the study towards the end of the second quarter of this year. Since we're at an earlier phase in this program, our focus is optimizing the dose and schedule for this tumor type and drug type.

Speaker Change: You're lying biology of prostate cancer is a lot of similarities to ER positive breast cancer, both or hormone really driven tumor types in both involve the Pam pathway.

Speaker Change: While the development of Pam inhibitors in breast cancer is further advanced in our prostate cancer. There are significant non clinical evidence and emerging clinical data that suggest simultaneous inhibition of both the E. R and Pam pathway may be more efficacious than treatment with an <unk> inhibitor alone.

Speaker Change: We expect to report our preliminary data from the phase one dose escalation portion of the study towards the end of the second quarter. This year.

Speaker Change: Since we're at an earlier phase in this program my focus as optimizing the dose and schedule for this tumor type and drug combination.

Brian Sullivan: The data set will include approximately 36 patients, half of whom will have received a 120 milligram dose of Getta, the other half a 180 milligram. each are administered on a three-week on, one-week-off schedule. We're comparing both the landmark PFS at six months and the safety profile of these two arms to each other and historical control data for second-line metastatic castration-resistant prostate cancer patients who are retreated with an androgen receptor inhibitor.

Speaker Change: The dataset will include approximately 36 patients half of whom will have received a 120 milligram dose of <unk>. The other half are 180 milligram dose each are administered on a three week on one week off schedule. We're comparing both the landmark PFS at six months and the safety profile of these two arms to each other and historical control data.

Speaker Change: For second line metastatic castration resistant prostate cancer patients who are retreated with energen.

Speaker Change: Energen receptor inhibitor.

Brian Sullivan: And finally, we were very excited to report last December. encouraging preliminary overall survival data from both first-line and second-line advanced breast cancer patients from our Phase 1B study that evaluated getatolysis. in combination with Paolo Ciclip and Andy Cameron. For the Phase 1, or rather the first-line patients, median overall survival was 77 months, which compares favorably to published Phase 3 data for Powasiclib plus Letrozole. But the second line cohort, median overall survival, was about 34 months, which compares favorably to recently published OS data results for Fulvester. Of course, you have to be careful making cross trial comparisons, especially since ours was just a single arm study, but certainly we view the data as very encouraging.

Speaker Change: And finally, we're very excited to report last December.

Speaker Change: Encouraging preliminary overall survival data from both first line and second line advanced breast cancer patients from our phase one study that evaluated get it's Elisa.

Speaker Change: In combination with policy club and endocrine therapy for.

Speaker Change: For the phase one for rather the first line patients median overall survival was 77 months, which compares favorably to published phase III data for polycyclic plus letrozole.

Speaker Change: But the second line cohort median overall survival was about 34 months, which compares favorably to recently published OS data results for full restroom.

Speaker Change: Of course, you have to be careful making cross trial comparisons, especially since ours is just a single arm study, but certainly we view the data is very encouraging.

Vicky Hahne: And with that, I'll now turn the ball, call over to Vicky Hahne to review our financial report. Thank you, Brian. And good afternoon, everyone.

Speaker Change: And with that I'll now turn the call over to Vicki Hahn <unk> to review our financial results.

Vicki Hahn: Thank you, Brian and good afternoon, everyone I'll provide a brief overview of our financial results for the fourth quarter and full year 2024.

Vicky Hahne: I'll provide a brief overview of our financial results for the fourth quarter and full year 2024. And I invite you to review our 10k, which will be filed later today for a more detailed discussion.

Vicki Hahn: Invite you to review, our 10-K, which will be filed later today for a more detailed discussion.

Vicky Hahne: Our fourth quarter net loss was $36.7 million, or $0.85 per share, compared to $18.8 million net loss, or $0.65 per share, for the fourth quarter of 2020. 23.

Vicki Hahn: Our fourth quarter net loss was $36 7 million or <unk> 85 cents per share compared to $18 8 million net loss or <unk> 65 per share for the fourth quarter of 'twenty.

Vicki Hahn: 23 <unk>.

Vicky Hahne: Net loss for the full year, 24, was $111.8 million, or $2.83 per share, compared to $63.8 million net loss, or $2.69 per share, for the same period in 2023. Because these quarterly and full-year net losses include significant non-cash items, including stock-based compensation and non-cash interest, we also included in our press release non-gap adjusted net loss for the quarter and the full year ending December 31, 2024. Our non-GAAP adjusted net loss was $32.3 million or $0.75 per share for the fourth quarter of 2024 compared to non-GAAP adjusted net loss of $17.6 million or $0.61 per share for the fourth quarter of 2020.

Vicki Hahn: Net loss for the full year 24 was 111 million $111 8 million or $2 83 per share.

Vicki Hahn: The $63 8 million net loss or $2 69 per share for the same period in 2023, because these quarterly and full year net losses include a significant noncash items, including stock based compensation and noncash interest. We also included in our press release.

Vicki Hahn: non-GAAP adjusted net loss for the quarter and the full year ending December 31, two.

Vicki Hahn: 2024.

Vicki Hahn: Our non-GAAP adjusted net loss was $32 3 million or <unk> 75 per share for the fourth quarter of 2024 compared to non-GAAP adjusted net loss of $17 6 million or 61 per share for the fourth quarter of 2023.

Vicki Hahn: non-GAAP adjusted net loss for the full year, 'twenty 2024 was $101 9 million or $2 58 per share compared to non-GAAP adjusted net loss of $57 8 million or $2.44 per share for the full year 2023.

Vicky Hahne: Non-Gap Adjusted Net Loss for the Full Year 2024 was $101.9 million, or $2.58 per share, compared to Non-Gap Adjusted Net Loss of $57.8 million, or $2.44 per share for the full year 2024.

Vicki Hahn: Research and development expenses were $33 5 million for the fourth quarter 2024, compared to $18 1 million for the fourth quarter of 2023.

Vicky Hahne: Research and development expenses were $33.5 million for the fourth quarter of 2024, compared to $18.1 million for the fourth quarter of 2021. R&D expenses for the full year of 2024 were $104.2 million compared to $60.6 million for the prior year. Of the approximately $43.6 million increase in R&D expenses year over year, $30.7 million was related to ongoing activities supporting the Victoria I Phase III trial and the Phase I B2 prostate trial, along with the commencement of the Victoria II Phase III trial. The remaining $12.9 million increase in R&D expenses is related to increased employee and consulting expenses.

R&D expenses for the full year of 2024 were $104 2 million compared to $60 6 million for the prior year.

Vicki Hahn: Of the approximately $43 6 million increase in R&D expenses year over year, $30 7 million was related to ongoing activities supporting the Victorian one phase III trial, and the phase one b to prostate trial, along with the commencement of the Victoria too.

Vicki Hahn: <unk> III trial.

Vicki Hahn: The remaining $12 9 million increase in R&D expenses is related to increase increased employee and consulting expenses.

Vicky Hahne: General and Administrative expenses were $3 million for the fourth quarter of 2024, compared to $1.6 million for the same period in 2020. G&A expenses for the full year of 2024 were $9.1 million, compared to $5.6 million for the prior year. Of the approximately $3.4 million increase in G&A expenses, $2.6 million was related to increased employee-related expenses, and $0.8 million was related to professional fees, expanding infrastructure, and other administrative expenses.

General and administrative expenses were $3 million for the fourth quarter of <unk> 24, compared to $1 6 million for the same period in 2023.

Vicki Hahn: G&A expenses for the full year of 2024 were $9 1 million compared to $5 6 million for the prior year.

Vicki Hahn: Of the approximately $3 4 million increase in G&A expenses, $2 6 million was related to increased employee related expenses.

Vicki Hahn: Point 8 million was related to professional fees expanding infrastructure and other administrative expenses.

Vicki Hahn: Net cash used in operating activities for the fourth quarter of 2024 was $27 8 million compared to $18 5 million for the fourth quarter 2023.

Vicky Hahne: Net cash used in operating activities for the fourth quarter of 2024 was $27.8 million compared to $18.5 million for the fourth quarter of 2020. This was the result of non-gap adjusted net loss of approximately $32.3 million, offset by approximately $4.5 million of working capital changes.

Vicki Hahn: This was a result of non-GAAP adjusted net loss of approximately $32 3 million offset by approximately $4 5 million of working capital changes.

Vicky Hahne: Net cash used in operating activities for the full year 2024 was 83.5 million compared to 53.8 million for the full year 2023. This was a result of non-gap adjusted net loss of approximately $101.9 million offset by working capital changes of approximately $18.4 million.

Vicki Hahn: Net cash used in operating activities for the full year 2024 was $83 5 million compared to $53 8 million for the full year 2023.

Vicki Hahn: This was the result of non-GAAP adjusted net loss of approximately $101 9 million offset by working capital changes of approximately $18 4 million.

Vicki Hahn: We ended the year with approximately $235 1 million of cash cash equivalents and short term investments compared to $180 6 million on December 31st 2023.

Vicky Hahne: We ended the year with approximately $235.1 million of cash, cash equivalents, and short-term investments. compared to $180.6 million on December 31, 2023. The increase of $54.5 million in cash, cash equivalents, and short-term investments was the result of several financing activities that occurred in fiscal 2024 and yielded net proceeds of $138.4 million. The $138.4 million was partially offset by year-to-date operating cash use of $83.5 million and capital equipment purchases of $0.3 million.

Vicki Hahn: The increase up $54 5 million in cash cash equivalents and short term investments was the result of several financing activities that occurred in fiscal 2024 and yielded net proceeds of $138 4 million.

Vicki Hahn: The $138 4 million was partially offset by year to date operating cash use of $83 5 million in capital equipment purchases.

Vicki Hahn: 3 million.

Brian Sullivan: I will now hand the call back to Brian. Thank you, Vicky.

Brian Sullivan: I will now hand, the call back to Brian.

Brian Sullivan: Thank you Vicky operator could you. Please open the call for questions.

Unknown Executive: Operator, could you please open the call for questions? Thank you.

Les: Thank you Les.

Unknown Executive: Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question.

Les: Ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press the star followed by the number one on your Touchtone phone, you'll hear a prompt that your hand has it been a race should you wish to decline from the polling process. Please press the star followed by the number two if you are using a speaker.

Speaker Change: Or phone please lift the handset before pressing any key one moment. Please for your first question.

Speaker Change: Your first question comes from Maury Raycroft with Jefferies. Please go ahead.

Maurice Raycroft: Your first question comes from Maurice Raycroft with Jefferies. Please go ahead. Hi, thanks for taking my questions and congrats on the progress. Just wondering if you can provide an update on the current status of the event rate for Victoria 1, and are you expecting to achieve the required number of events any day now, or is there still some time left before reaching the final milestone to trigger the readout? So at this stage, we're not commenting on any of the specifics related to achieving our ability to report top-line data. So right now, we're just providing guidance on when we believe we'll have the top-line data.

Maury Raycroft: Hi, Thanks for taking my questions and congrats on the progress. Thanks.

Speaker Change: Just what I was just wondering if you can provide an update on the current status of the event rate for Victoria. One in are you expecting to achieve their required number of events any day now or is there still some time, what before reaching the final milestone to trigger the readout.

At this stage, we're not commenting on any of the specifics related to achieving our ability.

Speaker Change: Our ability to report topline data so you know right now.

Speaker Change: Providing guidance on when we believe we will have the topline data available.

Speaker Change: Got it okay.

Maurice Raycroft: Got it. Okay.

Brian Sullivan: And wondering if you can talk more about your plans following the second quarter readout. When do you expect to file the NDA and what are your thoughts on whether you would get priority review? Sure. So we would hope to initiate an RTOR request, a real-time oncology review request soon after we have our top-line data. FDA has to approve that request. Otherwise, if they don't approve that, we would seek to get a priority review. We think either of those programs would shorten the overall review time substantially. And we think because we have breakthrough status that we certainly would get good consideration of those.

Speaker Change: Wondering if you can talk more about your plans following the second quarter readout.

Speaker Change: When do you expect to file the NDA and what are your thoughts on whether you would get priority review.

Speaker Change: Sure.

Speaker Change: So we would hope to initiate.

Speaker Change: Initiate a artur request, so real time oncology review request soon after.

Speaker Change: We have our topline data are FDA has to approve that requests a otherwise if they don't approve that we would seek.

Speaker Change: Seek to get a priority review.

Speaker Change: I think either of those programs would would shorten the overall review time substantially and.

Speaker Change: And we think because we have breakthrough status that we certainly.

Speaker Change: Would we get a good consideration of those requests for.

Maurice Raycroft: for instance, and then if we if we have our tour. Status Granted, we would begin submitting within months of receiving that approval. And with the completion of the overall package within a quarter, a quarter. after we get our Got it. That's helpful. Okay. Thanks for taking my questions. I'll hop back in the queue. You're welcome. Thank you.

Speaker Change: For instance, and then if we if we have our tour.

Speaker Change: Status granted we would begin submitting a within months of receiving that Oh that approval.

Speaker Change: And with the completion of the overall package.

Speaker Change: Within a quarter over quarter and a half.

Speaker Change: After we get our topline data.

Speaker Change: Got it that's helpful. Okay. Thanks for taking my questions I'll hop back in the queue.

Speaker Change: Welcome.

Speaker Change: Thank you.

Brad Canino: The next question comes from Brad Canino with Stifel. Please go ahead. Hey, afternoon. Thanks for the questions, Brian.

Speaker Change: The next question comes from Brad <unk> with Stifel. Please go ahead.

Brian Sullivan: Hi afternoon, thanks for the questions Brian.

Brad Canino: First, could you just discuss what you're currently thinking about the extent of the data you would plan to share in the 2Q top line, and then how timelines might look for a medical meeting presentation? Sure, so we would expect to present medium PFS data for each of the three arms in the wild type cohort as well as corresponding hazard ratios for the two primary analyses. then follow that up with a complete presentation or fuller presentation of the data at the next available major And we're not really providing a specific estimate of which medical Yeah, that makes sense.

Speaker Change: First could you just discuss what you are currently thinking about the extent of the data you would plan to share the <unk> top line and then <unk>.

Brian Sullivan: Im lines might look for a medical meeting presentation.

Brian Sullivan: Sure.

Brian Sullivan: So.

Brian Sullivan: We would expect to present.

Brian Sullivan: The median PFS data for each of the three arms in the wild type cohort as well as corresponding hazard ratios with two primary analyses.

Brian Sullivan: And.

Brian Sullivan: Then follow that up with.

Brian Sullivan: With a complete presentation of full of presentation of the data at Oh that correspond. The next available major medical meeting and we're not really providing specific estimate of which medical meeting that would be.

Brian Sullivan: Yes that makes sense and then separately have you.

Brian Sullivan: And then separately, have you heard any feedback from investigators, as you're working on site startup for the frontline triplet, about the Dear Doctor letter sent by Roche for Inovolazib, about the life-threatening ketoacidosis? And what do you think this might mean for the opportunity in the mutant population where there is a bit of overlap with the Inovolazib label? Thank you. So, I'm not going to comment on Roche's situation as far as feedback from investigators. I think PI3K alpha inhibitors, as I think most of you know, have been known to induce high levels of hyperglycemia. And in the case of the inovulisib drug, it was only evaluated in patients who would be generally considered to be metabolically healthy.

Brian Sullivan: Feedback from investigators as you're working on site startup for the frontline triplet about the Dear Doctor letter sent by Roche for an evolved said about the life threatening kiosk ketoacidosis.

Brian Sullivan: What do you think this might mean for the opportunity in the mutant population, where there is a bit of overlap with the <unk> label. Thank you.

Brian Sullivan: Yeah.

Brian Sullivan: So I'm not going to comment on roche's situation.

Brian Sullivan: As far as.

Brian Sullivan: Back from investigators I think P S K Alpha inhibitors.

Brian Sullivan: As I think most of.

Brian Sullivan: You know you now.

Brian Sullivan: Have been known to induce high levels of hyperglycemia.

Brian Sullivan: And in the case of Vienna, Walesa drug it was only evaluated in patients who would be generally considered to be metabolically healthy. They they were not pre diabetic or it didn't have type two diabetes.

Brian Sullivan: They were not pre-diabetic or didn't have type 2 diabetes. The label itself, though, didn't restrict. of the population to that category of patients, while it did require pretty intense monitoring of glucose in the early cycles of treatment. What that means is that drug requires a fair amount of scrutiny to prescribe. And so I think the feedback we've received from investigators is that, you know, that imposes a burden on them to provide extra management of these patients, as well as on the patients, because they have to self-administer glucose testing. And so that drug right now is only approved to treat patients who are endocrine-treatment resistant in the frontline setting, so it really doesn't overlap with our second-line indication at all.

Brian Sullivan: The label itself, though it didn't restrict.

Brian Sullivan: Oh, the population to that cat.

Brian Sullivan: Category of patients.

Brian Sullivan: While it did require pretty intense.

Brian Sullivan: Our monitoring of glucose in the early cycles of treatment.

Brian Sullivan: Yeah.

Brian Sullivan: What that means is that drug requires a fair amount of scrutiny to to prescribe and and so I think the feedback. We've received from investigators is that you know that imposes a burden on them to provide extra management of these patients and as well as on the patients because they have to self administer glucose testing.

Brian Sullivan: And so that drug right now is only approved to treat patients who are under can treat resistant in the frontline setting. So it really doesn't overlap with our second line indication at all that overlaps with our Victoria to first line population.

Brian Sullivan: It overlaps with our Victoria II first-line population. So I think net-net for us, if we're able to report favorable data and if we're able to present safety data comparable to what we've reported in our early phase studies, we have the potential to have a significant advantage, because we would, if all goes according to plan, have the opportunity to treat patients independent of their status at PICC-3CA and metabolic status. You know, we would really only be restricted from treating patients who have uncontrolled type 1 diabetes. And so, you know, the easier it is for patients, doctors to administer drugs, the less potential requirement for patients to self-monitor.

Brian Sullivan: So I think net net for us if we were able to report favorable data.

Brian Sullivan: And if we're able to present data safety data are comparable to what we've reported.

Brian Sullivan: In our early phase studies.

Brian Sullivan: We we have the potential to have a significant advantage because we would.

Brian Sullivan: All goes according to plan have the opportunity to treat patients independent of their status it picks VCA and independent of there.

Metabolic status.

Brian Sullivan: We would.

Brian Sullivan: Really only be restricted from treating patients who have uncontrolled type one diabetes and and so you know the the easier it is for patients doctors to administer drugs of less potential requirement for patients to self monitor obviously, the lower the risk of severe adverse events that could require hospitalization are all.

Brian Sullivan: Obviously, the lower the risk of severe adverse events that could require hospitalization are all, you know, what everybody's looking for in a cancer drug. And so we think, you know, have a good potential opportunity to deliver that. And it potentially, based on what you just told me, would contrast with the situation with the Roche. Great. Thanks again. You're welcome.

Brian Sullivan: What everyone is looking for in a cancer drug and so we think you know we have a a good potential opportunity to deliver that and potentially based on what you. Just told me with contrast, with the situation with the restaurant.

Speaker Change: Great. Thanks again.

Youre welcome.

Oliver Mccammon: Thank you. The next question comes from Oliver McCammon with Lifesci Capital. Please go ahead. Hi. Thanks for the update and for taking my question. So, we've seen a number of readouts in advanced year positive breast cancer over the past few months.

Brian Sullivan: Thank you.

Speaker Change: The next question comes from Oliver Mccammon with lifecycle Oh. Please go ahead.

Speaker Change: Hi, Thanks for the update and for taking my question.

Speaker Change: So we've seen a number of readouts in advanced <unk> positive breast cancer over the past few months can you just remind us of how closely we should be looking at patient baseline characteristics like measurable disease and treatment experience and some of these reference studies as we think about contextualize ing. These upcoming picked greasy a wild type data. Thanks again.

Oliver Mccammon: Can you just remind us of how closely we should be looking at patient baseline characteristics like measurable disease and treatment experience in some of these reference studies as we think about contextualizing these upcoming PIC3CA wild type data? Thanks again. Sure. No, that's a great question. The more heterogeneous the population that a study enrolls, the harder it can be to interpret the data. And I discussed this a bit in my remarks. And I think you've seen in some early phase studies in this setting, inclusion of patients who have non-measurable disease is an example, which makes it very difficult to assess a population that includes a significant proportion of patients of that type to those who are evaluating patients with measurable disease because of the impact it can have on progression-free survival and potentially tilting upward the median result.

Speaker Change: No that's a great question.

Speaker Change: The more heterogeneous population that study enrolls the harder it can be to interpret the data and I discussed this a bit in our in my remarks, and I think I think you've seen in some early phase studies in this setting inclusion of patients who have non measurable disease. As an example, which makes it very difficult to assess.

Speaker Change:

Speaker Change: A population includes a significant proportion of.

Speaker Change: Patients of that type two to those who.

Speaker Change: Our evaluating patients with measurable disease because of the the impact it can have on a progression free survival and potentially tilting upward.

Speaker Change: The median results.

Brian Sullivan: In the setting in registrational studies, I think we've seen some studies evaluate, as I alluded to earlier, multiple patient And again, it makes it hard to interpret those those results because the doctors need to understand what the data is for the patient that they're Treating And all of that said, I think, you know, the doctors will be paying very strict attention to the results, you know, within a patient population. and the best way to do that, certainly they'll be looking at the median PFS and whatever the incremental benefit is for patients, but just as important will be the hazard ratio because it really does allow you to more objectively compare.

Speaker Change: In the setting and in Registrational studies, I think we've seen some studies evaluate as I alluded to earlier, a multiple patient groups and again it makes it hard to interpret those those results because the doctors needs and understand what the data is for the patient that there.

Speaker Change: Treating and whether that patient as a second line patients that receive prior CDK or first line patient, who maybe Andrew can treat resistant may have different treatment options for them or different competitive or different alternatives that may have a different relative benefits depending on patient's profile.

Speaker Change: And all of that said I think you know the doctors will be paying very strict attention.

Speaker Change: To the results.

Speaker Change: Within our patient population.

Speaker Change: And the best way to do that certainly there'll be looking at the medium PFS in whatever the.

Speaker Change: Incremental benefit is for patients, but but just as important it will be the hazard ratio because it really does allow you to more objectively compare.

Speaker Change: Ah results I mean, obviously, you can't do head to head comparisons every dragon and the landscape, but the hazard ratio does does allow you to essentially net out some of these factors, which make it hard to interpret absolute PFS numbers or absolute incremental PFS and so you know again, it's always important to look at who is.

Brian Sullivan: results. I mean obviously you can't do head-to-head comparisons to every drug in in the landscape but the hazard ratio does does allow you to essentially net out some of these factors which make it hard to interpret absolute PFS numbers or absolute And so, you know, again, it's always important to look at who's being treated in a study because of the impact that can have on the results and the relevance when you're comparing it to other studies. But there are ways to try to get a beat on how one drug is performing. for patients relative to another drug by using the hazard ratio.

Speaker Change: Being treated in the study because the impact it can have on the results and the relevance when youre comparing it to other studies.

Speaker Change: But there are ways to try to get a bead on how.

Now one drug is performing.

Speaker Change: For patients relative to another drug by using the hazard ratio.

Speaker Change: Okay.

Speaker Change: Oliver.

Speaker Change: Oliver.

Speaker Change: Okay. Thank you well I guess, we didn't like my answer.

Unknown Executive: Well, I guess he didn't like my answer.

Speaker Change: No great answer and thanks for taking my Okay Youre welcome.

Unknown Executive: No, great answer and thank you for taking my question. Okay, you're welcome. Alright, thank you.

Speaker Change: Alright, thank you.

Frances Dovell: The next question comes from Tara Bancroft with a titty colon. Please go ahead.

Speaker Change: The next question comes from.

Speaker Change: Tara Bancroft with TD Colin Please go ahead.

Speaker Change: Hello. This is Francisco Lau on for Terra brand Croc, you mentioned in the second line plus opportunity could reach $2 billion can you elaborate regarding the assumptions that go into that number.

Frances Dovell: Hello, this is Frances Dovell on for Tara Bancroft. You mentioned the second line plus opportunity could reach $2 billion. Can you elaborate regarding the assumptions that go into that number?

Brian Sullivan: And then a quick follow up after that, do you expect to go into a quiet period ahead of the top line dated next quarter? Regarding the second-line opportunity, we estimate, and these estimates are based on third-party data that's available, that there are roughly between 30,000 and 35,000 women who are treated in the second-line setting after they've progressed on a CDK460. The pricing for drugs today that are proprietary, treating these patients, ranges up between I would say $15,000 to $20,000. That would be a price assumption to use for estimating the market. And then you can use anywhere between five to 12 months, you have to do sensitivity analysis to estimate then the corresponding serve market potential.

Speaker Change: A quick follow up after that do you expect to go into your quiet period ahead of the top line data next quarter.

Speaker Change: Yeah.

Speaker Change: Regarding the second line opportunity Yeah, we estimate and these estimates are based on third party data that's available there roughly between 30 and 35000, a woman who are treated in.

Speaker Change: In the second line setting after they have progressed on a CDK four six inhibitor.

Speaker Change: The pricing for drugs today and in this oh that our proprietary.

Speaker Change: Treating these patients you know ranges up you know between I would say 15000 to $20000. So that would be a price assumption to use for estimating the market.

Speaker Change: And then you can use anywhere between.

Speaker Change: Five to 12 months.

Speaker Change: What you have to do sensitivity analysis.

Speaker Change: To estimate than the corresponding served market potential and from there you can make an assumption about the penetration rate you know how how much how many of the patients will well if potentially we treat versus those who.

Brian Sullivan: And from there, you can make an assumption about the penetration rate, how many of the patients will potentially we treat versus those who are offering competitive or alternative therapies. And so net, we estimate the serve market potential for our drug would be about $5 billion. Obviously, we're not going to get all of that. But we think it's not unreasonable to certainly shoot for, let's say, 40% penetration if our data is favorable. And certainly that might be a goal of ours. And that translates to a $2 billion potential revenue opportunity.

Speaker Change: Our offering competitive alternative therapies and so net net yeah, we estimate the served market potential for.

Speaker Change: For our drug would be about $5 billion.

Speaker Change: Obviously, we're not going to get all of that but we think it's not unreasonable to certainly shoot for.

Speaker Change: Let's say, 40% penetration if if our data.

Speaker Change:

Speaker Change: Is favorable and certainly that what might be a goal of ours.

Speaker Change: And that translates to a 2 billion dollar potential revenue opportunity for us.

Speaker Change: And then I think your second question, just remind me Terra person.

Frances Dovell: And then I think your second question, just remind me, Tara person. Yes, it was just if you expect to go into a quiet period ahead of the top line data next quarter. We would, you know, but that's to be determined.

Speaker Change: Yes. It was supposed to do you expect to collect your quiet period ahead of the top line data next quarter.

Speaker Change: We would but that's to be determined.

Speaker Change: Okay.

Speaker Change: Wonderful. Thank you so much youre welcome.

Frances Dovell: Wonderful. Thank you so much. You're welcome.

Gil Blum: Thank you. The next question comes from... Gil Blum from Nidhum. and Corporation. Please go ahead. Hi, Brian. Thanks for taking our questions. So, maybe a bit to the side here. Recent reports for degraders have been a little bit, shall we say, disappointing, but activity has been seen specifically in ESR1 mutant population.

Speaker Change: Thank you.

Speaker Change: The next question comes from.

Speaker Change: Gil Blum from Needham and.

Speaker Change: <unk> Corporation. Please go ahead.

Speaker Change: Hi, Brian Thanks for taking our question so.

Speaker Change: It might be a good fit to the side here.

Speaker Change: Recent reports for the Greeters have been a little bit shall we say disappointing.

But activity has been seen specifically in ESR one mutant.

Speaker Change: Population now, yes, I completely understand it's a different mechanism.

Brian Sullivan: Now, yes, I completely understand it's a different mechanism, but do you think the Victoria study has sufficient power to, I don't know, see an effect in that population, see if there's some overlap there? I'm just wondering here. Thanks. Sure. We think, you know, we haven't published this data because the sample size is relatively small, but we did not see in our preliminary Phase 1b data differences in activity associated with ESR1 status. We would hope to eventually report results that isolates activity between ESR1 mutant and wild type. patients.

Speaker Change: But do you think the Victoria study has sufficient powering to it.

Speaker Change: C N effect in that population and see if there's some overlap there just just wondering here. Thanks sure.

Speaker Change: Sure.

Speaker Change: We think.

Speaker Change: We haven't published this data because the sample size is relatively small, but we we did not see in our preliminary phase one b.

Speaker Change: Data differences in activity associated.

Speaker Change: Associated with our ESR one status.

Speaker Change: We would hope to eventually report results.

Speaker Change: That oh.

Speaker Change: Isolates activity between the ESR, one mutant and wild type.

Speaker Change: Patients.

Brian Sullivan: But but you know, obviously the most important mutation relative to our drug is the status of PIK3CA. And maybe in a similar vein, as it relates to patient activity towards prior CDK46, is this something we're also going to break out at that scientific meeting? as far as which particular CDK46 patients had previously. if it was, you know, if it was active in those patients, basically, they were we'll roll out data probably on a rolling basis. I mean, typically, you have a more narrow presentation of data, maybe at the first meeting, and then you follow on with additional details at later meetings.

Speaker Change: But you know obviously the most important mutation relative to our drug is a status of picture you see it.

Speaker Change: And maybe in a similar vein as it relates to.

Speaker Change: Patient activity towards prior CDK four six is something we're also.

Speaker Change: And a breakout.

Speaker Change: That scientific meeting.

Speaker Change: As far as which particular CDK four six patients had previously.

Speaker Change: As if it was.

Speaker Change: If it was active in those patients basically up shortly.

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

Brian Sullivan: And, you know, we'll kind of follow, I would expect that we would follow that that pattern. Thank you, Brian. You're welcome.

Brian Sullivan: Thank you Brian.

Speaker Change: Okay.

Speaker Change: Thank you.

Unknown Executive: Thank you.

Unknown Executive: The next question comes from Chase Knickerbocker with Craig Hallam Capital Group. Please go ahead. Good afternoon, thanks for taking the questions. Brian, actually, maybe one on the prostate study, being that that's, you know, two key data as well. Can you walk us through kind of the moving pieces and kind of the bar that you have there for, you know, either doing, you know, some more early to mid stage clinical work rather than, you know, moving that drug, moving the drug and prostate into, you know, later stage, more robust studies? Sure. So the population that we're evaluating will have progressed on a prior androgen receptor inhibitor, the next generation version of those drugs.

Speaker Change: The next question comes from Chase Knickerbocker with Craig Hallum Capital Group. Please go ahead.

Chase Knickerbocker: Hey, good afternoon, thanks for taking the questions Brian actually maybe one on on the prostate study being that that's you know two key data as well can you walk us through kind of the moving pieces and kind of the bar.

Chase Knickerbocker: That you have there for either doing some more early to mid stage clinical work rather than moving that drug.

Chase Knickerbocker: Moving to drug in prostate into later stage more robust studies.

Chase Knickerbocker: So so the population that we're evaluating a will have progressed on a prior androgen receptor inhibitor next generation version of those drugs.

Chase Knickerbocker: And if they're retreated with a different androgen receptor inhibitor in the second line setting, data suggests that, you know, they'll get in the five to five and a half month BMPFS. And so we'd be comparing ourselves to that. Since we don't have a head to head, you know, we establish our primary endpoint using landmark PFS at six months as the primary endpoint for that. And so we would, you know, compare statistically, whether we identify a difference between what our PFS rate at six months is relative. Historical Controls. One consideration for us since we're at a much earlier stage in development of this drug in light of the FDA's increased focus on dose optimization is that that's what we have to make sure we get right.

Chase Knickerbocker: And if they're retreated with a different androgen receptor inhibitor in the second line setting.

Chase Knickerbocker: Data suggest that they'll get in the five to five and a half months median.

Chase Knickerbocker: Median PFS benefit.

Chase Knickerbocker: Benefit.

Chase Knickerbocker: And so we'd be comparing ourselves to that since we don't have a head to head we are establishing.

Chase Knickerbocker: Stablish our pri.

Primary end point.

Chase Knickerbocker: Using landmark PFS at six months as the primary endpoint for that study and so we would compare statistically whether we identify a difference between what our.

Chase Knickerbocker: PFS rate at six months is relative to historical controls.

Chase Knickerbocker: You know one one consideration for us since we're at a much earlier stage in development of this drug and in light of how the FDA is increased focus on on dose optimization is that you know that's that's what we have to make sure we get right and so we will look at the data and make decisions accordingly.

Brian Sullivan: And so we will look at the data and make decisions accordingly. Obviously, one of the big components will be safety. Safety data is great, you know, you have flexibility potentially in your dosing. And those are all questions that we'll be addressing as we Got it.

Chase Knickerbocker: Obviously, one of the big components will be safety, if the safety data is great.

Chase Knickerbocker: You have flexibility potentially in your dosing and those are all questions that we'll be.

Chase Knickerbocker: Addressing us as we review our data.

Speaker Change: Got it thanks, Brian and maybe Vicky.

Vicky Hahne: Thanks, Brian. And maybe Vicky, as we think about kind of R&D over 2025, a couple moving pieces, obviously, with with some studies wrapping up and some studies starting, you know, is annualizing Q4 kind of the right way to think about 2025? Or just maybe, you know, what you budgeted for R&D in 2025? Some general thoughts? Unknown Speaker I'm Yeah, I think Looking at the R&D component, obviously, you know. relevant peg. I mean, we will continue to to increase some. kind of pre-launch activity. you know, 10% Great, thanks guys. Thank you.

Speaker Change: About kind of R&D over 2025, a couple moving pieces, obviously with with some studies wrapping up in some studies started.

Speaker Change: You know as annualized in Q4 kind of the right way to think about 25 or just maybe you know what you budgeted for R&D in 2025, some general thoughts.

Speaker Change: Okay.

Speaker Change: <unk>.

Speaker Change: Yeah I think.

Speaker Change: Looking at the R&D component obviously.

Speaker Change: Sure.

Speaker Change: Anticipating any type of additional commercial activities, if we do that that number would increase but.

In terms of the kind of the R&D and G&A spend.

Speaker Change: Q4 is that.

Speaker Change: Yeah relevant peg I mean, we will continue to to increase some.

Speaker Change: Kind of pre launch activities.

Speaker Change: Yeah, 10% or so.

Speaker Change: Yeah.

Speaker Change: Yeah.

Speaker Change: Great. Thanks, guys.

Speaker Change: Thank you.

Speaker Change: There are no further questions at this time I will now turn the call over to Brian Sullivan, The Chief Executive Officer and co founder. Please go ahead Sir.

Unknown Executive: There are no further questions at this time.

Brian Sullivan: I will now turn the call over to Brian Sullivan, the Chief Executive Officer and Co-Founder. Please go ahead, sir. Well, thanks again for participating in our call today, for your ongoing support.

Speaker Change: Well, thanks again for participating in our call today for your ongoing support we'll be participating in the Needham Conference and Stifel. So first of all oncology day in April and I look forward to hopefully interacting with some of you there.

Brian Sullivan: We'll be participating in the Needham conference in City Falls Virtual Oncology Day in April and look forward to hopefully interacting with some of you there.

Unknown Executive: Goodbye.

Speaker Change: Goodbye.

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

Unknown Executive: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation.

Unknown Executive: You may now disconnect.

Speaker Change: Yes.

Speaker Change: Okay.

Speaker Change: Yeah.

Speaker Change: Yes.

Speaker Change: Yeah.