Core Insights - The FDA has granted Breakthrough Therapy designation to zovegalisib in combination with fulvestrant for treating adults with PIK3CA mutant, HR+/HER2- locally advanced or metastatic breast cancer [1][2][3] Group 1: Clinical Data and Trials - The Breakthrough Therapy designation is supported by clinical data from the Phase 1/2 ReDiscover trial, which evaluated zovegalisib's safety, tolerability, pharmacokinetics, and preliminary antitumor activity [3][4] - Initial Phase 1/2 data for zovegalisib + fulvestrant at the 400mg BID fed dose will be presented at the ESMO Targeted Anticancer Therapies Congress on March 16, 2026 [1][4] - The ReDiscover trial included data from two doses: 600mg BID fasted (N=52) and 400mg BID fed (N=57), with the latter being the dose used in the ongoing Phase 3 trial [3] Group 2: Market Potential and Patient Impact - Approximately 40% of patients with HR+/HER2- advanced breast cancer have PIK3CA mutations, leading to limited treatment options after CDK4/6 inhibitors [2][8] - Zovegalisib has the potential to address a significant portion of the estimated 140,000 patients with HR+, HER2- breast cancer with a PI3Kα mutation annually in the U.S. [5] Group 3: Mechanism and Innovation - Zovegalisib is the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome limitations of traditional PI3Kα inhibitors [6] - The development of zovegalisib utilized advanced computational methods to elucidate conformational differences between wild-type and mutant PI3Kα [6]

Core Insights - Relay Therapeutics, Inc. (NASDAQ: RLAY) is highlighted as a promising biotech stock under $20, with a focus on its innovative drug development in precision medicine [1] Group 1: Company Overview - Relay Therapeutics is a clinical-stage precision medicine company that utilizes advanced computational and experimental technologies to enhance drug discovery [4] - The company’s Dynamo platform is designed to target previously difficult protein targets, aiming to develop small-molecule therapies primarily in precision oncology and genetic diseases [4] Group 2: Recent Developments - Oppenheimer upgraded RLAY from Perform to Outperform, setting a price target of $14, citing the upcoming VIKTORIA-1 trial readout for Celcuity's gedatolisib as a potential positive catalyst for RLAY's zovegalisib [2] - The firm anticipates that the VIKTORIA-1 results may not meet expectations, which could create a competitive benchmark for RLAY's zovegalisib-based regimen [2] - Interim clinical data presented at the 2025 San Antonio Breast Cancer Symposium indicated that zovegalisib combined with fulvestrant achieved a median progression-free survival of 11.4 months in second-line patients [3]

Core Insights - Relay Therapeutics announced interim clinical data for zovegalisib, an investigational allosteric, pan-mutant, and isoform-selective inhibitor of PI3Kα, showing promising efficacy in patients with metastatic breast cancer [1][10] Efficacy Data - The median progression-free survival (PFS) was reported as 10.3 months for all patients and 11.4 months for second-line (2L) patients [6] - Among patients with measurable disease, the objective response rate (ORR) was 39%, while the ORR for 2L patients was 47% [6] - Efficacy was consistent across various subsets, with a median PFS of 11.4 months and ORR of 44% for patients who received prior SERD [7] Patient Population - As of October 15, 2025, 118 patients were enrolled in the zovegalisib + fulvestrant arm of the ReDiscover study, with significant prior therapy levels noted [4] - Among the 64 patients receiving 600mg twice daily, 44% had two or more prior lines of therapy, and 29% had detectable ESR1 mutations at baseline [4] Ongoing Trials - The Phase 3 ReDiscover-2 trial is ongoing, focusing on zovegalisib + fulvestrant in PI3Kα-mutated, CDK4/6 pre-treated, HR+/HER2- advanced breast cancer [8] - The ReDiscover trial is also evaluating zovegalisib in combination with fulvestrant and CDK inhibitors [3] Company Overview - Relay Therapeutics is a clinical-stage company focused on developing precision medicine therapies for cancer and genetic diseases, with zovegalisib being its lead program [12] - The company utilizes its Dynamo platform to discover and develop mutant-selective inhibitors of PI3Kα, addressing a significant patient population in the U.S. [10][12]

Core Insights - Roche announced positive interim analysis data for giredestrant, a next-generation SERD, in its late-stage breast cancer study, indicating significant efficacy in reducing disease recurrence risk [1][3][10] Study Results - The phase III lidERA Breast Cancer study showed that giredestrant treatment reduced the risk of invasive disease recurrence or death by 30% compared to standard-of-care endocrine therapy [3][7] - At the three-year mark, 92.4% of patients treated with giredestrant were alive and free of invasive disease, compared to 89.6% on standard care [5][7] - The therapy also demonstrated a 31% reduction in distant recurrence-free interval, with safety profiles remaining manageable [5][7] Market Performance - Following the announcement of the positive data, Roche's shares increased by 3.6% [3] - Over the past year, Roche's shares have risen by 41.7%, significantly outperforming the industry growth of 7.2% [6] Competitive Landscape - Giredestrant is the first oral SERD to show superior invasive disease-free survival in the adjuvant setting, building on previous positive outcomes from the evERA Breast Cancer study [10] - Roche's breast cancer franchise includes established products like Herceptin, Perjeta, and Kadcyla, with recent approvals enhancing its portfolio [11][12] Ongoing Development - Roche is conducting an extensive clinical development program for giredestrant across five phase III studies, targeting multiple treatment settings and lines of therapy [13]

Core Insights - Roche (RHHBY) announced positive interim results from the late-stage lidERA Breast Cancer study for giredestrant, a next-generation selective estrogen receptor degrader (SERD) [1][4] - Giredestrant showed a statistically significant and clinically meaningful benefit over standard endocrine therapy in patients with ER-positive, HER2-negative breast cancer [5][8] Study Details - The lidERA study is a phase III, randomized, open-label trial involving approximately 4,100 patients with medium- or high-risk stage I-III ER-positive, HER2-negative breast cancer [2][3] - The primary endpoint is invasive disease-free survival (iDFS), with key secondary endpoints including overall survival and safety [3] Results and Implications - The study met its primary endpoint, demonstrating a significant improvement in iDFS with giredestrant compared to standard therapy, marking it as the first SERD trial to show such benefit in the adjuvant setting [4][8] - Although overall survival data were immature at the interim analysis, a positive trend was observed, indicating giredestrant's potential as a new treatment option for early-stage breast cancer patients [5] Roche's Breast Cancer Franchise - Roche's breast cancer portfolio includes Herceptin, Perjeta, and Kadcyla, with Kadcyla performing well due to increased demand from patients with residual disease [7] - The approval of the fixed-dose combination of Perjeta and Herceptin as Phesgo has further strengthened Roche's position in the market [7] - Roche's shares have increased by 27.8% year-to-date, outperforming the industry growth of 14.3% [7] Future Developments - Roche is conducting an extensive clinical development program for giredestrant across five phase III trials in various treatment settings [10] - The approval of inavolisib for breast cancer treatment has also bolstered Roche's franchise, indicating ongoing innovation in their product offerings [9]

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 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 - Vepdegestrant has shown statistically significant improvements in patient-reported outcomes (PROs) compared to fulvestrant, particularly in quality of life, pain, and daily functioning for patients with ESR1-mutated ER+/HER2- advanced or metastatic breast cancer [1][2][3] Clinical Trial Findings - The Phase 3 VERITAC-2 clinical trial demonstrated that vepdegestrant delayed deterioration in overall health status, pain severity, and various functioning domains compared to fulvestrant [2][3] - The trial enrolled 624 patients, with 270 having ESR1 mutations, and the primary endpoint was progression-free survival (PFS) [7][8] - Vepdegestrant was administered orally once daily, while fulvestrant was given intramuscularly [8] Company Collaboration and Development - Arvinas is collaborating with Pfizer for the co-development and commercialization of vepdegestrant, sharing development costs and profits [10] - The FDA has accepted the New Drug Application (NDA) for vepdegestrant, granting it Fast Track designation, indicating a significant unmet need in the target patient population [11] Additional Clinical Insights - Results from the TACTIVE-N Phase 2 clinical trial indicated that neoadjuvant vepdegestrant showed biological and clinical activity in postmenopausal women with localized ER+/HER2- breast cancer [5] - The data from the VERITAC-2 trial support vepdegestrant's potential as a best-in-class therapy for the specified patient group [4]

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]