Financial Data and Key Metrics Changes - The fourth quarter net loss was $51 million or $0.97 per share, compared to a net loss of $36.7 million or $0.85 per share for the fourth quarter of 2024 [25] - The full year net loss was $177 million or $3.79 per share, compared to $111.8 million or $2.83 per share for the same period in 2024 [25] - Non-GAAP adjusted net loss for the fourth quarter was $38.4 million or $0.73 per share, compared to $32.3 million or $0.75 per share for the fourth quarter of 2024 [26] - Non-GAAP adjusted net loss for the full year was $150.8 million or $3.22 per share, compared to $101.9 million or $2.58 per share for 2024 [26] - Cash, cash equivalents, and short-term investments were $441.5 million at the end of fiscal year 2025, expected to finance operations through 2027 [30] Business Line Data and Key Metrics Changes - Research and development expenses for the fourth quarter were $37.6 million, up from $33.5 million for the prior year period [27] - R&D expenses for the full year were $145 million, compared to $104.2 million for the prior year [27] - General and administrative expenses for the fourth quarter were $11.6 million, compared to $3 million for the prior year period [28] - G&A expenses for the full year were $27.2 million, compared to $9.1 million for the prior year [28] Market Data and Key Metrics Changes - The total addressable market for gedatolisib in the second-line setting is estimated to be more than $5 billion, with potential peak revenue of up to $2.5 billion annually [18] Company Strategy and Development Direction - The company is preparing for the potential approval and commercialization of gedatolisib, with a PDUFA goal date of July 17, 2026 [5] - The company aims to establish gedatolisib as a new standard of care therapy for patients with HR-positive, HER2-negative advanced breast cancer [5] - The company is engaging with payers and strategic accounts to ensure access to gedatolisib for oncologists and their patients [16][17] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the FDA's review of the NDA based on unprecedented efficacy data from the phase III VIKTORIA-1 clinical trial [6] - The company believes that the positive results from the PIK3CA wild-type cohort will position gedatolisib favorably in the market [14] - Management highlighted the importance of the safety profile of gedatolisib, which does not induce clinically relevant hypoglycemia [11][70] Other Important Information - The company has completed enrollment of the PIK3CA mutant cohort of the phase III VIKTORIA-1 trial and expects to announce results in the second quarter [7] - The company is also evaluating gedatolisib in combination with darolutamide for men with metastatic castration-resistant prostate cancer [15] Q&A Session Summary Question: Status update on the mutant data - Management could not comment on the database lock status [33] Question: Details on the disclosure of mutant data - Management indicated that top-line data will be provided in a press release, with details at a medical conference [34] Question: Feedback from physicians on launch segments - Management stated that the sales force will reach out generally to doctors to help them understand the benefits of gedatolisib [43] Question: Will physicians use it off-label for mutants? - Management confirmed that there have been no discussions with doctors about off-label use [44] Question: Details on the top-line release of median data - Management confirmed that the release will include a statement regarding the achievement of statistical significance [48] Question: Key gating factor for frontline endocrine-sensitive trial - The key gating factor is completing the safety run-in [58] Question: Challenges in getting patients for infusions - Management believes that efficacy is the most important factor for physicians and does not expect significant patient pushback on IV administration [61] Question: Commercial advantages of having a label across metastatic breast cancer subtypes - Management aims to simplify decision-making for physicians by providing a biomarker-agnostic alternative [66] Question: Learnings from the launch of inavolisib - Management noted that gedatolisib does not induce significant glycemic disruption, allowing broader patient treatment [70] Question: European commercial strategy for gedatolisib - Management plans to submit a supplemental NDA after initial approval and explore partnerships for launching in Europe [78]

Financial Data and Key Metrics Changes - The fourth quarter net loss was $51 million or $0.97 per share, compared to a net loss of $36.7 million or $0.85 per share for the fourth quarter of 2024 [25] - The full year net loss was $177 million or $3.79 per share, compared to $111.8 million or $2.83 per share for the same period in 2024 [25] - Non-GAAP adjusted net loss for the fourth quarter was $38.4 million or $0.73 per share, compared to $32.3 million or $0.75 per share for the fourth quarter of 2024 [26] - Non-GAAP adjusted net loss for the full year was $150.8 million or $3.22 per share, compared to $101.9 million or $2.58 per share for 2024 [26] - Cash, cash equivalents, and short-term investments were $441.5 million at the end of fiscal year 2025, expected to finance operations through 2027 [30] Business Line Data and Key Metrics Changes - Research and development (R&D) expenses for the fourth quarter were $37.6 million, up from $33.5 million for the prior year [27] - R&D expenses for the full year were $145 million, compared to $104.2 million for the prior year [27] - General and administrative (G&A) expenses for the fourth quarter were $11.6 million, compared to $3 million for the prior year [28] - G&A expenses for the full year were $27.2 million, compared to $9.1 million for the prior year [28] Market Data and Key Metrics Changes - The total addressable market for gedatolisib in the second-line setting is estimated to be more than $5 billion, with potential peak revenue of up to $2.5 billion annually [18] Company Strategy and Development Direction - The company is preparing for the potential approval and commercialization of gedatolisib, aiming to establish it as a new standard of care for HR-positive, HER2-negative advanced breast cancer [5][19] - The company has engaged extensively with payers and strategic accounts to ensure access to gedatolisib upon approval [16][90] - The company plans to conduct a supplemental NDA submission for the mutant cohort following initial approval for gedatolisib [76] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the FDA's review of the NDA for gedatolisib, citing unprecedented efficacy data from clinical trials [6][17] - The company believes that gedatolisib's unique mechanism of action and safety profile position it well in the market [19][92] - Management highlighted the importance of efficacy as the primary factor influencing physician and patient decisions regarding treatment [62] Other Important Information - The company completed enrollment of the PIK3CA mutant cohort of the phase III VIKTORIA-1 trial and expects to announce results in the second quarter of 2026 [7] - Safety results from clinical trials indicated that gedatolisib was generally well-tolerated, with low rates of treatment-related adverse events [10][11] Q&A Session Summary Question: Status update on the mutant data - Management could not comment on the database lock status for the mutant data [33] Question: Details on the disclosure of mutant data - Management indicated that top-line data will be provided in a press release, with further details at a medical conference [34] Question: Feedback from physicians on treatment segments - Management stated that the sales force will reach out to doctors generally to explain how gedatolisib offers improvements over current alternatives [43] Question: Will physicians use gedatolisib off-label for mutants? - Management confirmed that there have been no discussions with doctors regarding off-label use [44] Question: Details on the top-line release of median data - Management stated that the release will include a statement regarding the achievement of statistical significance [48] Question: Key gating factor for frontline endocrine-sensitive trial - The key gating factor is completing the safety run-in for the trial [58] Question: Challenges in getting patients for infusions - Management believes that efficacy will be the most important factor for physicians and patients, and they do not expect significant pushback on IV administration [61] Question: Commercial advantages of having a label across metastatic breast cancer subtypes - Management aims to simplify decision-making for physicians by providing a biomarker-agnostic alternative [66] Question: Learnings from the launch of inavolisib - Management noted that gedatolisib does not induce significant glycemic disruption, allowing broader patient eligibility [70] Question: European commercial strategy for gedatolisib - Management plans to explore partnerships for launching gedatolisib in Europe while proceeding with regulatory activities [78]

Core Insights - Celcuity Inc. announced significant efficacy results from the Phase 3 VIKTORIA-1 clinical trial of gedatolisib, showing a 76% reduction in disease progression or death with the gedatolisib triplet compared to fulvestrant [1][5] - The trial focused on patients with hormone receptor positive, HER2 negative, PIK3CA wild-type advanced breast cancer who had previously progressed on CDK4/6 inhibitors and aromatase inhibitors [1][2] Efficacy Results - In the PIK3CA wild-type cohort, the median progression-free survival (PFS) for the gedatolisib triplet was 9.3 months, compared to 2.0 months for fulvestrant, representing a 7.3-month improvement (HR=0.24; p<0.0001) [3] - The objective response rate (ORR) for the gedatolisib triplet was 31.5%, while the ORR for fulvestrant was only 1% [3] - For the gedatolisib doublet, the median PFS was 7.4 months versus 2.0 months for fulvestrant, an improvement of 5.4 months (HR=0.33; p<0.0001) [3] Safety Profile - The gedatolisib triplet and doublet were generally well tolerated, with low-grade treatment-related adverse events (TRAEs) [4] - Common grade 3 TRAEs included neutropenia (52.3% for triplet, 0% for doublet, 0.8% for fulvestrant) and stomatitis (19.2% for triplet, 12.3% for doublet, 0% for fulvestrant) [4] - TRAEs led to treatment discontinuation in 2.3% of patients in the gedatolisib triplet group and 3.1% in the gedatolisib doublet group, with no discontinuations in the fulvestrant group [4] Regulatory Status - The U.S. FDA has granted Priority Review for Celcuity's New Drug Application for gedatolisib, with a Prescription Drug User Fee Act goal date set for July 17, 2026 [5] Background on Breast Cancer - Breast cancer is the second most common cancer globally, with over two million cases diagnosed in 2022 [6] - HR+/HER2- breast cancer accounts for approximately 70% of all breast cancer cases, and therapies targeting the PI3K/AKT/mTOR pathway are crucial for treatment [6][7] About Gedatolisib - Gedatolisib is a multi-target PAM inhibitor that comprehensively blocks the PI3K/AKT/mTOR pathway, differentiating it from single-target inhibitors [9][10] - It has shown comparable potency in both PIK3CA-mutant and wild-type breast tumor cells in early clinical data [9]

Core Insights - Celcuity is a clinical stage company focused on developing drugs targeting the PAM pathway, specifically the PI3K/AKT/mTOR pathway, which is crucial in oncology [1] Group 1: Clinical Trials - The company has three ongoing trials, including a Phase III trial evaluating GEDA in combination with palbociclib and fulvestrant for women who have progressed on prior CDK therapy [1] - A first-line study is being conducted with the same drug combination for treatment-naive women with endocrine-resistant metastatic breast cancer [2] - A third study is in an earlier phase, investigating the drug combination with an androgen receptor inhibitor in men with castration-resistant prostate cancer [2]

Summary of Celcuity's Fireside Chat at TD Cowen's 46th Annual Healthcare Conference Company Overview - **Company**: Celcuity - **Focus**: Clinical-stage biotechnology company developing drugs targeting the PAM pathway, specifically the PI3K/AKT/mTOR pathway, which is crucial in oncology [3][3]. Key Trials and Developments - **Ongoing Trials**: - **Phase 3 Trial**: Evaluating Gedatolisib in combination with palbociclib and fulvestrant for women who have progressed on prior CDK therapy [3][3]. - **First-Line Study**: Same drug combination for treatment-naive women with endocrine-resistant metastatic breast cancer [3][3]. - **Earlier Phase Study**: Investigating Gedatolisib with an androgen receptor inhibitor in men with castration-resistant prostate cancer [3][3]. Regulatory Insights - **RTOR Designation**: Celcuity received Real-Time Oncology Review (RTOR) designation, which allows for early submission of data to the FDA, potentially shortening approval timelines for supplemental NDAs [11][11]. - **PDUFA Date**: The priority review is expected to conclude six months after the NDA acceptance, with expectations aligned with historical outcomes for similar drugs [12][12]. Launch Preparation - **Commercial Strategy**: A comprehensive launch plan has been in place for two years, focusing on building a commercial team and infrastructure across various departments [21][21][22][22]. - **Sales Force**: The hiring of sales representatives is expected to begin in the second quarter, aligning with the anticipated launch of Gedatolisib [22][22]. Market Segmentation and Patient Focus - **Target Patient Population**: The primary focus will be on PIK3CA wild type patients, constituting approximately 60% of the market. Data on mutant cohorts will be available prior to the launch, which could enhance market positioning [28][28]. - **Market Dynamics**: Celcuity anticipates a competitive landscape, particularly in the 20% of the market with ESR1 mutations, but believes it holds a significant advantage in the remaining 80% [78][78]. Efficacy and Safety Profile - **Efficacy Expectations**: The company aims for a median progression-free survival (PFS) of at least 10 months, which is statistically significant compared to existing treatments [43][43][45][45]. - **Safety Profile**: Gedatolisib shows a favorable safety profile with low rates of hyperglycemia (less than 10% overall, 2% grade three), contrasting sharply with competitors like alpelisib, which has an 80% hyperglycemia rate [64][64][66][66]. Financial Projections - **Revenue Potential**: Celcuity estimates a potential peak revenue exceeding $10 billion from Gedatolisib in breast cancer treatment, highlighting the significant market opportunity [95][95]. Conclusion - **Underappreciated Aspects**: The size of the patient population eligible for treatment and the potential impact of an effective drug targeting critical disease drivers are seen as key factors that could reshape investor perceptions [96][96].

Core Insights - Celcuity Inc. is a clinical-stage biotechnology company focused on developing targeted therapies for oncology, specifically for multiple solid tumor indications [2] Company Overview - The lead therapeutic candidate of Celcuity is gedatolisib, which is a potent pan-PI3K and mTORC1/2 inhibitor that blocks the PI3K/AKT/mTOR ("PAM") pathway comprehensively [2] - Gedatolisib's mechanism of action and pharmacokinetic properties are distinct from other therapies that target PI3Kα, AKT, or mTORC1 alone or in combination [2] Clinical Trials - A Phase 3 clinical trial, VIKTORIA-1, has completed enrollment, evaluating gedatolisib in combination with fulvestrant, with or without palbociclib, for patients with HR+/HER2- advanced breast cancer [2] - The company has reported detailed results for the PIK3CA wild-type cohort from the VIKTORIA-1 trial [2] - A second Phase 3 trial, VIKTORIA-2, is ongoing, assessing gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for HR+/HER2- advanced breast cancer [2] - A Phase 1/2 clinical trial, CELC-G-201, is also ongoing, evaluating gedatolisib in combination with darolutamide for patients with metastatic castration-resistant prostate cancer [2] Investor Engagement - Brian Sullivan, CEO and Co-founder of Celcuity, will present at various investor conferences and is available for one-on-one meetings [1][3] - Live webcasts of the presentations will be accessible on the company's website, with replays available shortly after the events [1]

Summary of Celcuity Conference Call Company Overview - **Company**: Celcuity - **Focus**: Development of gedatolisib, a drug targeting the PI3K/AKT/mTOR pathway, primarily for breast and prostate cancer treatment [3][4] Key Points and Arguments Drug Development and Clinical Trials - **Gedatolisib**: Identified as a promising drug for the PI3K/AKT/mTOR pathway, previously owned by Pfizer and now being developed by Celcuity [4] - **Current Studies**: Two ongoing studies in breast cancer (second-line and first-line metastatic) and a new study in prostate cancer [5] - **Data Validation**: Preliminary data from early-phase studies in prostate cancer is encouraging, supporting the hypothesis that the PI3K pathway is relevant in hormonally driven cancers [5][8] Regulatory and Commercialization Strategy - **NDA Submission**: Preparing for an NDA submission under an accelerated review process, with groundwork laid for commercialization [6][30] - **Market Research**: Positive feedback from market research indicates potential for significant market share in the second-line setting for gedatolisib [10][11] - **Sales Strategy**: Targeting community settings where 80% of patients are treated, while also prioritizing academic centers [33][34] Competitive Landscape - **Comparison with Roche**: Roche's combination therapy is seen as a strategic move, but Celcuity believes gedatolisib offers better tolerability and efficacy [12][16][18] - **Market Positioning**: Gedatolisib is positioned as a safer option with lower toxicity compared to existing treatments like everolimus, which has a high discontinuation rate [15][17] Clinical Data Insights - **Patient Population**: Focus on a diverse patient population, including those with and without specific mutations, which is expected to enhance the drug's applicability [38][40] - **Duration of Response**: Data suggests a potential duration of response of 19 months in the US, which could positively impact market modeling [21][22] Financial Outlook - **Cash Runway**: Current cash reserves and access to additional funding are expected to sustain operations through 2027, with hopes of generating meaningful revenue by then [46][47] Other Important Insights - **Regulatory Interactions**: Ongoing discussions with Japanese health authorities to align on data package expectations for regulatory submissions [36][37] - **Trial Site Selection**: Leveraging previous trial site experiences to enhance enrollment efficiency in ongoing studies [42][44] This summary encapsulates the critical aspects of Celcuity's conference call, highlighting the company's strategic direction, competitive positioning, and financial health as it advances its drug development efforts.

Core Insights - Celcuity Inc. announced significant efficacy and safety results from the Phase 3 VIKTORIA-1 clinical trial of gedatolisib for advanced breast cancer, showing a 76% reduction in disease progression risk with the triplet therapy compared to fulvestrant [1][3][6] Efficacy Results - The gedatolisib triplet therapy achieved a median progression-free survival (PFS) of 9.3 months, an improvement of 7.3 months over fulvestrant, with a hazard ratio (HR) of 0.24 [3][6] - The objective response rate (ORR) for the triplet was 31.5%, while the doublet showed an ORR of 28.3% [3][6] - For the gedatolisib doublet, the median PFS was 7.4 months, an improvement of 5.4 months over fulvestrant, with a HR of 0.33 [3][6] Safety Profile - Hyperglycemia occurred in 9.2% of patients on the triplet and 11.5% on the doublet, with treatment discontinuation due to adverse events at 2.3% and 3.1%, respectively [5][7] - The most common grade 3 treatment-related adverse events included neutropenia (52.3% for triplet), stomatitis (19.2% for triplet), and hyperglycemia (2.3% for triplet) [7] Clinical Significance - The results from the VIKTORIA-1 trial represent a potential new standard of care for patients with HR+/HER2- advanced breast cancer who have progressed after CDK4/6 inhibitor treatment [7][9] - Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to show positive Phase 3 results in this patient population [6][9] Future Developments - Celcuity has initiated a rolling New Drug Application (NDA) submission to the FDA, targeting completion in Q4 2025 [9] - The PIK3CA mutant cohort of the VIKTORIA-1 trial is fully enrolled, with topline data expected in late Q1 or Q2 2026 [9]

Core Insights - Recent advances in understanding the pathogenesis of venous malformations (VMs) highlight the PI3K/AKT/mTOR pathway as a key driver of disease proliferation, leading to increased off-label use of systemic rapamycin (sirolimus) for treatment [1][4] - A systematic review of 26 studies involving 98 patients treated with rapamycin for VMs supports the clinical potential of Palvella's QTORIN™ 3.9% rapamycin anhydrous gel, which is currently under evaluation in the Phase 2 TOIVA trial [2][3] Company Overview - Palvella Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for serious, rare genetic skin diseases without FDA-approved treatments [7] - The company is developing a pipeline based on its patented QTORIN™ platform, with QTORIN™ rapamycin being its lead product candidate [7] Industry Context - There is a significant unmet clinical need for effective treatments for cutaneous VMs, with no FDA-approved pharmacologic options currently available [2][6] - The estimated number of diagnosed patients with cutaneous VMs in the U.S. exceeds 75,000, highlighting the urgency for targeted therapies [5][6] Clinical Findings - The systematic review indicates that off-label use of rapamycin has shown efficacy in improving various clinical signs, including bleeding and quality of life, despite inadequate responses to standard treatments [4] - A targeted, topical formulation of rapamycin could provide clinical benefits by achieving therapeutic levels in the dermis while minimizing off-target effects associated with oral rapamycin [4] Regulatory Status - In April 2024, the FDA granted Fast Track Designation to QTORIN™ rapamycin for the treatment of VMs, indicating the potential for expedited development and review [5]

Core Insights - Celcuity Inc. announced positive topline results from the Phase 3 VIKTORIA-1 clinical trial for gedatolisib in combination with fulvestrant, showing significant improvements in progression-free survival (PFS) for patients with HR+/HER2- advanced breast cancer [2][5][9] Efficacy Results - The gedatolisib triplet (gedatolisib + palbociclib + fulvestrant) reduced the risk of disease progression or death by 76% compared to fulvestrant, with a median PFS of 9.3 months versus 2.0 months, representing an incremental improvement of 7.3 months [3][6][7] - The gedatolisib doublet (gedatolisib + fulvestrant) reduced the risk of disease progression or death by 67%, with a median PFS of 7.4 months compared to 2.0 months for fulvestrant, an incremental improvement of 5.4 months [4][6][7] Historical Significance - The hazard ratios for both the gedatolisib triplet and doublet are the most favorable reported in any Phase 3 trial for HR+/HER2- advanced breast cancer [7] - The incremental improvements in median PFS for both regimens are unprecedented for patients receiving at least their second line of therapy in this category [7][8] Safety Profile - Treatment discontinuation due to treatment-related adverse events for both the gedatolisib triplet and doublet was lower than observed in previous trials, indicating a favorable safety profile [6][8] - Lower rates of hyperglycemia and stomatitis were reported compared to earlier studies, suggesting better tolerability of the gedatolisib regimens [6][8] Future Developments - Full data from the VIKTORIA-1 trial will be presented at an upcoming medical conference, and Celcuity plans to submit a New Drug Application for gedatolisib to the FDA in Q4 2025 [5][9]