Summary of Conference Call for Celcuity's Victoria-1 Phase 3 Clinical Trial Results Company and Industry - **Company**: Celcuity - **Industry**: Oncology, specifically focusing on advanced breast cancer treatments Key Points and Arguments Clinical Trial Overview - The Victoria-1 trial is a global Phase 3 study targeting patients with hormone receptor (HR) positive, HER2 negative advanced breast cancer, including both PIK3CA mutant and wild type patients [9][10] - The trial involved 392 patients randomized into three arms: triplet regimen (gedatolisib, palbociclib, and fulvestrant), doublet regimen (gedatolisib and fulvestrant), and control arm (fulvestrant) [10][11] Efficacy of Gedatolisib - The gedatolisib triplet regimen showed a statistically significant improvement in median progression-free survival (PFS) of 7.3 months over fulvestrant, with a median PFS of 9.3 months and a hazard ratio of 0.24, indicating a 76% reduction in the risk of disease progression or death [13][15] - The doublet regimen also demonstrated a significant improvement of 5.4 months in median PFS over fulvestrant, with a hazard ratio of 0.33, representing a 67% reduction in risk [15] - Subgroup analyses indicated that the clinical benefits of the triplet regimen were consistent across predefined groups, including patients in the U.S. and Canada, where median PFS was 19.3 months for the triplet [16][18] Safety and Tolerability - The gedatolisib regimens were generally well tolerated, with low discontinuation rates due to treatment-related adverse events: 2.3% for the triplet and 3.1% for the doublet [21] - Adverse events were primarily low grade, with no new safety signals observed. Notably, hyperglycemia rates were lower than expected, with 9.2% in the triplet and 11.5% in the doublet [22] Market Opportunity - There is an estimated 37,000 patients who progress to second-line treatment after CDK4/6 inhibitors, with approximately 60% being PIK3CA wild type, representing a significant market opportunity [23] - The potential addressable market for gedatolisib is projected to be around $5 billion, with a smoother reimbursement process for IV-administered drugs compared to oral therapies [24] Future Milestones - Celcuity plans to submit a New Drug Application (NDA) for the Victoria-1 PIK3CA wild type cohort in the current quarter, with additional data presentations expected at major medical conferences later this year [25] - Top-line data for the PIK3CA mutation cohort is anticipated by late Q1 or Q2 2026 [25] Competitive Landscape - The results from the gedatolisib regimens are positioned to potentially establish a new standard of care for patients with advanced breast cancer, especially in comparison to existing therapies like Roche's everolimus [34][35] - The differentiation of gedatolisib is emphasized, particularly for the broader patient population, as it may address the needs of approximately 85% of patients who do not have specific mutations [35] Intellectual Property and Development Strategy - Celcuity holds multiple patents related to gedatolisib, extending exclusivity until at least 2042, which includes patents for the drug formulation and dosing schedule [50][51] - The company is exploring additional clinical development opportunities, including combinations with oral SERDs and indications in earlier lines of therapy [28] Additional Important Content - The PAM pathway is highlighted as a critical target in oncology, with evidence suggesting that comprehensive blockade of this pathway is essential for effective treatment [3][4] - The trial's design and statistical analysis were structured to maximize the potential for demonstrating statistical significance in overall survival with mature follow-up data [55] This summary encapsulates the key findings and strategic insights from Celcuity's conference call regarding the Victoria-1 Phase 3 clinical trial results, emphasizing the potential impact of gedatolisib in the treatment landscape for advanced breast cancer.

Summary of the Oncology Innovation Summit - CellCuity Fireside Chat Company Overview - **Company**: CellCuity - **Focus**: Development of a platform to quantify signaling pathway activity in live tumor cells, specifically targeting the PI3K AKT mTOR pathway, referred to as the PAM pathway, which is a significant oncogenic pathway and represents a large untapped drug development opportunity in solid tumors [4][5] Key Assets and Studies - **Lead Asset**: Gadotelisib, a pan-PI3K inhibitor - **Ongoing Studies**: - Phase 3 study in second-line patients with ER-positive, HER2-negative advanced breast cancer, data expected in Q3 for wild type cohort and Q4 2025 for PIK3CA mutant cohort [5][6] - Phase 3 study for first-line HR-positive, HER2-negative advanced breast cancer, enrollment expected to begin this quarter [6] - Phase 1b study in prostate cancer for metastatic castration-resistant prostate cancer, top-line data expected later this month [6] Differentiation in the Market - **Mechanism of Action**: Unlike other inhibitors that target single components of the PAM pathway, CellCuity's approach addresses multiple targets, which is crucial due to feedback loops that can lead to adaptive resistance [9][10] - **Potency**: Gadotelisib is reported to be 300 times more potent than other approved single-target PAM inhibitors and is the only drug effective in both tumor cells with and without PIK3CA mutations [11][12] Clinical Expectations and Comparisons - **Hazard Ratio (HR)**: A hazard ratio of 0.5 or below is considered compelling for the upcoming phase 3 wild type data [20] - **Comparative Studies**: Previous studies have shown HRs ranging from 0.59 to 0.68, with no study reporting an HR below 0.5 in similar patient populations [20][21] - **Phase 1b Data**: In the phase 1b study, 60% of patients had an objective response, with 49% progression-free at 12 months, indicating favorable results compared to existing therapies [38][39] Safety Profile - **Adverse Events**: Gadotelisib has shown a lower incidence of hypoglycemia compared to other drugs in the class, with a discontinuation rate of 4% in early studies versus over 26% for other drugs [48][49] - **Patient Tolerance**: Preliminary data suggests good tolerance among patients, with no discontinuations due to adverse events related to hypoglycemia [48][49] Market Opportunity and Administration - **Efficacy vs. Safety**: The primary factors influencing physician decisions will be efficacy and safety, with convenience being a secondary consideration [51] - **Infused vs. Oral Drugs**: Infused drugs are more common in oncology, and while oral drugs offer convenience, they can lead to compliance issues due to side effects [54][55] - **Financial Considerations**: Infused drugs may have less cumbersome reimbursement processes compared to oral drugs, which can expose patients to high co-pays [54][55] Conclusion - The upcoming data in Q3 and Q4 is highly anticipated, with expectations for significant insights into the efficacy and safety of CellCuity's lead asset, gadotelisib, in treating advanced breast cancer and prostate cancer [56]