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]

Core Insights - Roche's investigational candidate giredestrant, in combination with palbociclib, did not meet its primary endpoint in the phase III persevERA study for ER-positive, HER2-negative breast cancer [2][3][8] - Despite missing the primary endpoint, the combination showed a numerical improvement in progression-free survival (PFS) [3][8] - The safety profile of the giredestrant and palbociclib combination was consistent with expectations and manageable [4][8] Study Results - The phase III persevERA study involved 992 patients and compared giredestrant plus palbociclib against letrozole plus palbociclib [2] - The study failed to achieve a statistically significant improvement in PFS in the intent-to-treat population [3] - Management remains optimistic about giredestrant's long-term potential and plans to explore its use with CDK4/6 inhibitors in future studies [5] Regulatory Developments - Roche's new drug application (NDA) for giredestrant in combination with everolimus is under FDA review, with a target action date set for December 18, 2026 [6][8] - If approved, this regimen could be the first oral SERD combination available in the post-CDK4/6 inhibitor setting [7] Clinical Development - Giredestrant is part of a broader clinical program with five phase III studies across various treatment settings [14] - The evERA study showed significant PFS improvement compared to standard therapy, marking the first positive phase III outcome for giredestrant [10][11] - The second phase III study, pionERA, is expected to report results in 2027 [12] Market Performance - Roche's shares have increased by 32.4% over the past six months, outperforming the industry growth of 20% [7]

Core Viewpoint - Genentech's Phase III persevERA study for giredestrant in ER-positive advanced breast cancer did not achieve its primary endpoint of statistically significant improvement in progression-free survival, although a numerical improvement was noted [1] Group 1: Study Results - The persevERA study evaluated giredestrant plus palbociclib against letrozole plus palbociclib in patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer [1] - The study enrolled 992 patients globally, with the primary endpoint being investigator-assessed progression-free survival [2] - Adverse events associated with the giredestrant combination were manageable and consistent with known safety profiles [1] Group 2: Future Developments - Genentech is committed to advancing giredestrant as a potential new standard-of-care endocrine therapy, supported by previous successes in the evERA and lidERA studies [1] - The FDA has accepted the New Drug Application based on evERA data, and lidERA data will be submitted in the coming weeks [1] - The pionERA study, which will evaluate giredestrant in combination with a physician's choice of CDK4/6 inhibitor, is expected to read out in 2027 [1] Group 3: Background on ER-positive Breast Cancer - ER-positive breast cancer accounts for approximately 70% of breast cancer cases, with 2.3 million women diagnosed and 670,000 deaths annually [2] - The complexity of ER-positive breast cancer treatment remains a challenge, with up to a third of patients experiencing disease recurrence after adjuvant endocrine therapy [2] - There is a significant need for more effective treatments to delay clinical progression and reduce treatment burden [2] Group 4: Genentech's Commitment - Genentech has been advancing breast cancer research for over 30 years, aiming to improve outcomes for patients [2] - The company is focused on identifying new biomarkers and treatment approaches for various breast cancer subtypes, including ER-positive breast cancer [2]

Financial Data and Key Metrics Changes - The company's net loss for Q3 2025 was $43.8 million, or $0.92 per share, compared to a net loss of $29.8 million, or $0.70 per share for Q3 2024 [19] - Non-GAAP adjusted net loss was $37.2 million, or $0.78 per share for Q3 2025, compared to a non-GAAP adjusted net loss of $27.6 million, or $0.65 per share for Q3 2024 [19] - Research and development expenses increased to $34.9 million for Q3 2025 from $27.6 million in Q3 2024, with a significant portion attributed to increased employee and consulting expenses [19][20] - General and administrative expenses rose to $7.9 million for Q3 2025 from $2.5 million in Q3 2024, primarily due to increased employee and consulting expenses [20] Business Line Data and Key Metrics Changes - The company achieved significant clinical and regulatory milestones, including the release of positive data from the PIK3CA wild-type cohort of the phase III VIKTORIA-1 study [4][5] - The median progression-free survival (PFS) for the gedatolisib triplet was reported at 9.3 months, compared to 2 months for fulvestrant, indicating a 7.3-month improvement [7] - The objective response rate for the gedatolisib triplet was 32%, with a median duration of response of 17.5 months, while the doublet showed an objective response rate of 28% and a median duration of response of 12.0 months [9][10] Market Data and Key Metrics Changes - The total addressable market for gedatolisib in the second-line setting is estimated to be between $5 billion and $6 billion, with potential peak revenues of $2.5 billion to $3 billion [17][18] - The company estimates there are approximately 37,000 patients in the U.S. with HR positive, HER2 negative, advanced breast cancer who have progressed after treatment with a CDK4/6 inhibitor [17] Company Strategy and Development Direction - The company is preparing for a potential launch of gedatolisib, having ramped up efforts following the positive data release [15] - The strategic launch plan includes building the organization and internal systems required to operate as a commercial stage company [15] - The company aims to establish gedatolisib as the new standard of care in the second-line setting for HR positive, HER2 negative, advanced breast cancer [17] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential for gedatolisib to address critical needs in the second-line space, highlighting its unique mechanism of action and favorable safety and efficacy profile [18] - The company expects to complete the NDA submission for gedatolisib by the end of Q4 2025 [26] - Management noted that the positive interim overall survival data could support the drug's approval process [38] Other Important Information - The company completed concurrent offerings resulting in net proceeds of approximately $287 million, which will support commercial launch preparations and other strategic initiatives [21][22] - The company ended the quarter with approximately $455 million in cash, cash equivalents, and short-term investments [20] Q&A Session Summary Question: Plans for additional data at the San Antonio Breast Cancer Symposium - The company plans to present additional subgroup analyses and efficacy data at the conference [24] Question: Impact of second-line data on enrollment in VIKTORIA II - Enrollment is on track, and investigators are excited about the results, which may positively impact visibility and credibility [24] Question: Real-time oncology review submission process - The submission for the wild-type cohort will be separate from the mutant submission, with potential for a real-time oncology review for the mutant data depending on the results [25][27] Question: Duration of therapy and pricing strategy - The company is analyzing the duration of therapy and pricing strategy, with benchmarks around $25,000 for similar therapeutics [28][29] Question: Plans for commercialization outside the U.S. - The company plans to find partners for commercialization outside the U.S. and is preparing for regulatory submissions in Europe and Japan [31] Question: Overall survival trends and regulatory implications - The interim overall survival analysis showed a favorable trend, which could support the drug's approval process [38]

Summary of BeOne Medicines FY Conference Call Company Overview - **Company**: BeOne Medicines (NasdaqGS:BGNE) - **Industry**: Biotechnology - **Key Achievement**: First year of profitability and recognized as one of the fastest-growing large biotech companies [3][4] Competitive Advantages - **Integrated Development**: Fully integrated CRO-free clinical development organization with over 3,600 professionals [4] - **Product Pipeline**: Deep product pipeline with 10 internally developed New Molecular Entities (NMEs) entering the clinic in 2024 and 16 to date [3] - **Cost Efficiency**: 70% of the cost to develop medicines is in clinical development; BeOne aims to reduce this through its integrated approach [4] Product Performance - **Brukinsa**: - Leading market share in the BTK inhibitor market with 47% year-over-year growth in the U.S. and 71% growth in Europe [6][8] - Demonstrated durable progression-free survival (PFS) with 74% landmark PFS at 72 months [6][7] - Significant real-world impact and prescription growth globally [8][9] Market Dynamics - **Fixed Duration Treatments**: - BeOne supports finite treatments that meet four criteria: deep response, sustained PFS, acceptable safety profile, and convenience [10][11] - Current market dynamics show continuous use BTK inhibitors capturing about 50% of the market, with opportunities for growth through fixed-duration offerings [11][12] Pipeline Developments - **Sonrotoclax**: - Designed to be more potent and selective than venetoclax, with a half-life of five hours [14][15] - Breakthrough designation in relapsed refractory MCL, with plans for global filing based on upcoming data [30] - Phase 3 study planned for multiple myeloma, targeting the translocation 11;14 population [32][33] - **BDK CDAC**: - A degrader molecule with a different mechanism, potentially effective against mutations that standard inhibitors cannot target [24][25] - Phase 2 cohort fully enrolled, with data expected in the first half of next year [26] Competitive Landscape - **Comparison with Competitors**: - BeOne's zanubrutinib shows superior response rates compared to pirtobrutinib and acalabrutinib in specific patient populations [20][21] - Ongoing head-to-head studies to validate BeOne's offerings against competitors [16][17] Future Outlook - **Clinical Trials**: - Upcoming data presentations at ASH for various products, including BDK CDAC and sonrotoclax [28][29] - Commitment to advancing solid tumor pipeline, particularly CDK4/6 inhibitors, with a focus on first-line breast cancer [34][36] Conclusion - BeOne Medicines is positioned strongly within the biotechnology sector with a robust product pipeline, innovative clinical development strategies, and a commitment to addressing patient needs through differentiated therapies. The company is actively pursuing growth opportunities in both hematology and solid tumors while maintaining a competitive edge against established players in the market.

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.

Phase 3 VIKTORIA-1 HR+/HER2-/PIK3CA WT Trial Results Gedatolisib is an investigational agent and is not approved by any regulatory agency as a treatment for any indication. October 20, 2025 Forward-Looking Statements This presentation contains statements that constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to Celcuity's business, operations, and financial condition, and include but are not limited to our current beli ...

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]

Financial Data and Key Metrics Changes - The company reported a median progression-free survival (PFS) of about 10 months for RLY-2608, which is consistent with previous data and shows strong performance compared to competitors [3][4] - In second-line patients, the median PFS is around 11 months, indicating a solid efficacy profile [4] Business Line Data and Key Metrics Changes - RLY-2608 is specifically targeting HR-positive, HER2-negative, PIK3CA-mutated breast cancer, with a median PFS of 10.3 months in this population, nearly doubling the current standard of care [5] - The company is moving forward with a phase 3 trial for RLY-2608 based on the evolving data from the rediscover trial [4][10] Market Data and Key Metrics Changes - The total addressable market (TAM) for RLY-2608 in the U.S. and major global geographies is estimated to be between $2 to $3 billion, with approximately 30,000 patients in these regions [18] - The unmet medical need in the second-line setting has remained largely unchanged over the past decade, with PFS consistently reported between five to seven months for existing therapies [19][20] Company Strategy and Development Direction - The company is focusing on the development of RLY-2608 in both breast cancer and vascular malformations, prioritizing these areas due to their significant market potential [37][38] - There is an ongoing exploration of triplet combinations with other CDK4/6 inhibitors, which may lead to a frontline registration study in breast cancer [21][22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the safety profile of RLY-2608, which is expected to enhance real-world adherence and treatment duration compared to existing therapies [6][8] - The company is cautious about capital access and has reorganized to extend its cash runway into 2029, allowing it to reach key milestones in its clinical programs [38] Other Important Information - The phase 3 REDISCOVER-2 trial has been initiated, comparing RLY-2608 plus fulvestrant against capivasertib plus fulvestrant [10] - The company is also exploring the potential of RLY-2608 in treating PIK3CA-related overgrowth spectrum (PROS) and other vascular malformations, with a significant patient population identified [30][34] Q&A Session Summary Question: Can you provide an overview of the phase 3 REDISCOVER-2 trial? - The trial is a global randomized study involving 540 patients, comparing RLY-2608 plus fulvestrant to capivasertib plus fulvestrant, with a focus on second-line patients [10] Question: What are the expectations regarding the control arm of capivasertib plus fulvestrant? - The control arm is benchmarked against the CAPItella 291 study, which reported a median PFS of five and a half months in a similar patient population [15] Question: How does the company view the competitive landscape for NextGen PI3K inhibitors? - The company believes it has established a high bar with RLY-2608, showing superior clinical data compared to competitors, which have not demonstrated significant differentiation [28]