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]

Financial Data and Key Metrics Changes - The company is focused on developing targeted therapeutics for breast cancer, particularly ER positive HER2 negative breast cancer, which represents approximately 70% of breast cancer cases [2][3] - The lead asset, palazestrant, is in a first-line trial with a CDK4/6 inhibitor, ribociclib, and is expected to read out results in the second half of next year [4][13] - The market potential for the combination of these assets is estimated to be between $15 billion to $20 billion [6] Business Line Data and Key Metrics Changes - The company has two clinical stage assets: palazestrant and OP3136, targeting different mechanisms in breast cancer treatment [4][5] - The first-line market opportunity with ribociclib and palazestrant is projected to exceed $10 billion [20] - The second and third-line market opportunity is estimated to be over $5 billion, focusing on both ESR1 mutation positive and wild-type patients [9][33] Market Data and Key Metrics Changes - The company is uniquely positioned as the only next-generation endocrine therapy combining with ribociclib, following a shift in the standard of care due to compelling survival data [6][7] - The competitive landscape includes other agents like palbociclib and camazestrant, which have shown limitations in terms of toxicity and efficacy [19][20] Company Strategy and Development Direction - The company aims to differentiate its products by demonstrating superior progression-free survival (PFS) in both mutant and wild-type populations [32][49] - A new collaboration with Pfizer aims to explore the combination of palazestrant with atoramiciclib, a CDK4 selective inhibitor, to enhance treatment options [27][30] - The company is focused on executing pivotal trials and generating data to support its market position and future product launches [44][46] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readouts and the potential for positive outcomes in pivotal trials, which could lead to regulatory filings and product launches [46][47] - There is an acknowledgment of market fatigue regarding new data, but management believes that compelling evidence from upcoming trials will help regain investor confidence [50][52] Other Important Information - The company has a fast track designation from the FDA for palazestrant, indicating the potential for expedited review and approval [13] - Upcoming data presentations at ESMO are expected to provide further insights into the efficacy of the company's therapies [44][56] Q&A Session Summary Question: What will the company communicate going forward? - The company plans to highlight the compelling phase two data, particularly focusing on the wild-type population post CDK4/6 treatment [49] Question: How does the company view market perception? - Management noted that the market may not fully value the potential of their therapies, but they believe that upcoming data will clarify their efficacy [50][51] Question: What are the expectations for the Roche pivotal trial? - Management expressed hope for positive outcomes from Roche's trial, which could validate their approach and enhance market confidence [55][56]

Core Viewpoint - Celcuity Inc. announced that the FDA accepted its New Drug Application for gedatolisib in HR+/HER2- advanced breast cancer for review under the Real-Time Oncology Review program, facilitating an earlier evaluation process [1][2] Group 1: FDA Review and Application - The FDA's acceptance of the NDA for gedatolisib is part of the RTOR program, which allows for earlier submission of topline efficacy and safety results [1][3] - Celcuity plans to initiate a rolling submission of its NDA in September 2025, targeting completion by Q4 2025 [1][2] Group 2: Clinical Trial Results - The NDA submission is based on positive topline results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial [2] - The gedatolisib-triplet (gedatolisib, fulvestrant, and palbociclib) reduced the risk of disease progression or death by 76% compared to fulvestrant, with a median progression-free survival (PFS) of 9.3 months versus 2.0 months for fulvestrant, an improvement of 7.3 months [2] - The gedatolisib-doublet (gedatolisib and 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 improvement of 5.4 months [2] Group 3: Company Overview - Celcuity is a clinical-stage biotechnology company focused on developing targeted therapies for various solid tumors, with gedatolisib as its lead candidate [4] - Gedatolisib is a potent pan-PI3K and mTORC1/2 inhibitor, differentiating its mechanism of action from other therapies targeting PI3Kα, AKT, or mTORC1 [4] - The company is conducting multiple clinical trials, including the ongoing Phase 1/2 trial for metastatic castration-resistant prostate cancer and the Phase 3 VIKTORIA-2 trial for first-line treatment in HR+/HER2- ABC [4]

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]

Summary of Relay Therapeutics Conference Call Company Overview - **Company**: Relay Therapeutics (Ticker: RLAY) - **Focus**: Development of selective PI3K alpha inhibitors for breast cancer and vascular malformations Key Points on Breast Cancer Treatment - **Mechanism**: Relay Therapeutics is developing a selective PI3K alpha inhibitor, ROI 2,608, which has shown promising results in clinical trials - **Clinical Data**: - Achieved an **11-month progression-free survival (PFS)** in the second line of therapy combined with fulvestrant - Reported a **39% overall response rate** and a **67% response rate** in the kinase-only subset of patients [4][9] - **Patient Population**: Approximately **40%** of hormone receptor-positive, HER2-negative breast cancer patients have a PI3K alpha mutation, indicating a significant market opportunity [5] - **Comparison with Competitors**: - ROI 2,608's PFS is **2x** that of capivasertib, which has a PFS of **5.5 months** [10] - Relay's drug is positioned to have a better safety profile, addressing issues like grade three hyperglycemia and diarrhea seen with other treatments [12][13] - **Future Trials**: Plans to initiate pivotal trials in the post-CDK4/6 population, aiming to establish ROI 2,608 as a frontline therapy [8][20] Insights on Competitive Landscape - **Roche's Data**: Roche has shown an overall survival benefit with a **15-month PFS** in a triplet therapy setting, but concerns about toxicity remain [14][16] - **Patient Selection**: Relay's trials are designed to include a broader patient population, allowing for those with pre-diabetic conditions, which may enhance the applicability of their treatment [27] Vascular Malformations Opportunity - **Market Size**: Approximately **170,000** patients in the U.S. have PI3KCA mutation-driven vascular malformations, with **5,000 to 15,000** specifically in the PIK3CA-related overgrowth spectrum [46][47] - **Current Treatments**: - Sirolimus is used off-label, and alpelisib (Vijoice) has received accelerated approval but has shown significant side effects like hyperglycemia [50][54] - **Relay's Approach**: The company aims to provide a more effective and tolerable treatment option, starting with a **400 mg BID** dosing regimen in their studies [57] Regulatory Path and Future Studies - **Accelerated Approval**: There is potential for an accelerated approval pathway due to the lack of fully approved treatments in the vascular malformations space [55] - **Study Design**: The upcoming trials will utilize a randomized dose selection approach, starting at the oncology phase three dose [57] Conclusion - Relay Therapeutics is positioned to capitalize on significant unmet needs in both breast cancer and vascular malformations through innovative therapies that promise improved efficacy and safety profiles. The company is actively preparing for pivotal trials and regulatory discussions to advance its promising drug candidates.