gedatolisib (PF-05212384) / Pfizer, Celcuity - LARVOL DELTA

Celcuity Presents Updated Results from the PIK3CA Wild-Type Cohort of the Phase 3 VIKTORIA-1 Trial at the 2025 San Antonio Breast Cancer Symposium (GlobeNewswire) - "For patients whose time to progression on immediate prior therapy was >18 months, representing nearly half of those enrolled, median PFS was 12.4 months (HR=0.17; 95% CI: 0.11-0.28) with the gedatolisib triplet and 10.0 months (HR=0.19; 95% CI: 0.12-0.31) with the gedatolisib doublet versus 1.9 months for fulvestrant. For patients enrolled in the U.S., Canada, Western Europe, and Asia Pacific, representing nearly 60% of those enrolled, median PFS was 16.6 months (HR=0.14; 95% CI: 0.09-0.26) with the gedatolisib triplet and 7.1 months (HR=0.36; 95% CI: 0.24-0.57) with the gedatolisib doublet versus 1.9 months for fulvestrant....The median time to definitive deterioration was 23.7 months (HR=0.39; 95% CI: 0.25-0.67; p = 0.0003) for patients treated with the gedatolisib triplet and not reached for the gedatolisib doublet (HR=0.37; 95% CI: 0.24-0.66; p = 0.0003) versus 4.0 months for fulvestrant."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant with or without palbociclib for second-line (2L) treatment of patients with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): updated results from the randomized, phase 3 VIKTORIA-1 trial (SABCS 2025) - "In preclinical studies, gedatolisib demonstrated superior potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus, regardless of PI3K-pathway mutation status, and combinations of gedatolisib + fulvestrant, with and without palbociclib, were active in treatment-naive and resistant cell lines. These updated results support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of patients with HR+/HER2-/PIK3CA WT ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Functional analysis of gedatolisib combined with fulvestrant and/or palbociclib in breast cancer cell models adapted to estrogen receptor and/or CDK4/6 inhibitors (SABCS 2025) - " Gedatolisib (pan-PI3K, mTORC1/2 inhibitor), inavolisib (PI3Kα inhibitor), capivasertib (AKT inhibitor) were tested as single agents or in combination with fulvestrant and/or palbociclib in treatment-naïve BC cell lines with or without PIK3CA mutations as well as in BC cell lines adapted to long-term treatment with fulvestrant and/or palbociclib. These results indicate that gedatolisib plus fulvestrant, with and without palbociclib, effectively controls the growth of treatment-naïve BC cells as well as BC cells adapted to palbociclib/fulvestrant treatment. Moreover, in contrast to the currently approved PI3Kα and AKT inhibitors, the gedatolisib/palbociclib/fulvestrant triplet is effective in BC cells with or without PIK3CA mutations. The combination of gedatolisib with ET and a CDK4/6 inhibitor is being evaluated in two ongoing Phase 3 clinical trials as first-line (VIKTORIA-2) or second-line (VIKTORIA-1) treatment of HR+/HER2- ABC with or without PIK3CA..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Celcuity to Present Updated Data from the PIK3CA Wild-Type Cohort of the Phase 3 VIKTORIA-1 Trial at the 2025 San Antonio Breast Cancer Symposium (GlobeNewswire) - "The presentation will include additional sub-group efficacy analyses and safety data."

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

MODULE 4: Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC (SABCS 2025) - "Sponsored by Genentech, a member of the Roche Group, Eli Lilly and Stemline Therapeutics Inc. Biological rationale for inhibiting AKT in HR-positive mBC; mechanism of action of capivasertib Key efficacy and safety data from the Phase III CAPItello-291 study evaluating capivasertib/fulvestrant for HR-positive, HER2-negative mBC progressing on endocrine therapy with or without a CDK4/6 inhibitor FDA approval of capivasertib for patients with PTEN/PI3K/AKT alterations and current role with regard to other evidence-based options Mechanistic similarities and differences between gedatolisib and currently approved therapies targeting the PI3K/AKT/mTOR pathway in HR-positive mBC; implications for antitumor activity Design, eligibility criteria and primary and secondary endpoints of the Phase III VIKTORIA-1 trial evaluating gedatolisib in combination with fulvestrant with or without palbociclib for patients with HR-positive, HER2-negative advanced breast cancer whose disease..."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Solid Tumor • HER-2 • PIK3CA • PTEN

Gedatolisib: "Both Co-Primary Endpoints Met: 7.3- & 5.4-month improvement in mPFS"; Breast cancer (Celcuity) - Investor Presentation

P3 data: top line • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology

Celcuity Announces Completion of Submission of Its New Drug Application to the U.S. FDA for Gedatolisib in HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer (GlobeNewswire) - "The NDA was submitted under the FDA’s Real-Time Oncology Review ('RTOR') program, which is intended to facilitate shorter regulatory review periods....The NDA submission is based on the positive clinical results for the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial."

FDA filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Celcuity…Provides Corporate Update (GlobeNewswire) - "Submission of a New Drug Application ('NDA') to the U.S. Food and Drug Administration ('FDA') for gedatolisib, based on data from the PIK3CA WT cohort, is on track to be completed during the fourth quarter of 2025."

FDA filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

In the third quarter of 2025, investors exercised warrants generating cash proceeds of $12.8 million (GlobeNewswire) - "The warrants were issued pursuant to a private placement that closed on December 9, 2022 and had an expiration date of 75 days from the release of the topline data from the PIK3CA WT cohort of the VICTORIA-1 Phase 3 clinical trial."

Commercial • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Deciphering Molecular Drivers of Primary Immunotherapy Resistance in Epithelioid Pleural Mesothelioma using a Patient-derived Explant Platform (IMIG 2025) - "Co-targeting of PD1 and PI3K-mTOR signalling, using pembrolizumab and gedatolisib (a dual PI3K/mTOR inhibitor), in PE-derived co-cultures failed to enhance tumour cell killing, most likely due to T-cell toxicity induced by pan-PI3K inhibition.Our PDE platform reveals that the density of IR-expressing CD8+ T cells and M2-like macrophages predicts pembrolizumab sensitivity in Epi-MPM. Our PDE platform reveals that the density of IR-expressing CD8+ T cells and M2-like macrophages predicts pembrolizumab sensitivity in Epi-MPM. In non-responders, distinct molecular pathways are activated, offering potential novel targets for future combination immunotherapy strategies. These findings highlight the broad utility of the PDE platform for deciphering molecular drivers of immunotherapy resistance in Epi-MPM, as well as a pre-clinical model to directly test the efficacy of new combination approaches to overcome patient tumour resistance."

Clinical • IO biomarker • Epithelioid Pleural Mesothelioma • Malignant Pleural Mesothelioma • Mesothelioma • Pleural Mesothelioma • Respiratory Diseases • Solid Tumor • CD163 • CD68 • CD8 • CD86 • HAVCR2 • PD-L1 • VSIR

Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1 (ESMO 2025) - "Hyperglycemia incidence was 9.2% and 11.5%, respectively, with grade 3 severity in 2.3% of pts in both geda groups. Conclusions These data support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of pts with HR+/HER2-/PIK3CA WT ABC."

Clinical • Late-breaking abstract • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Celcuity Stock Soars 39% On Positive Phase 1 Results For Gedatolisib-Darolutamide Combo (Nasdaq) - "Celcuity Inc. (CELC) jumped 38.83% to $72.11, up $20.15, after announcing encouraging Phase 1 results for its investigational therapy gedatolisib in combination with Nubeqa (darolutamide) for men with metastatic castration-resistant prostate cancer (mCRPC). Celcuity's Chief Medical Officer said the data compare favorably to existing treatments and confirmed that the company has begun enrolling patients in the updated Phase 1/1b trial to determine the recommended Phase 2 dose."

P1 data • Stock price • Trial status • Castration-Resistant Prostate Cancer

Phase I/II study of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2025) - P1/2 | "Background Preclinical studies demonstrated interaction between the androgen receptor (AR) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mechanistic target of rapamycin (mTOR) pathways through reciprocal negative feedback, whereby inhibition of one pathway cross activates the other. Conclusions Following promising safety results from Arms 1 and 2, the study was recently amended to include intermittent dosing Arms 3 (gedatolisib 240 mg) and 4 (300 mg), along with an optional weekly dosing Arm 5 (dose TBD). Two dose levels from Arms 1–5 may then be evaluated on both intermittent and weekly schedules in the randomized phase 1b stage to formally define the RP2D and optimal dosing strategy, with further clarification achieved in the phase 2 expansion."

Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

In a presentation of results from the PIK3CA wild-type (“WT”) cohort of the VIKTORIA-1 study at the European Society for Medical Oncology (“ESMO”) Congress, additional data from a Phase 1b clinical trial that evaluated gedatolisib in patients with HR+/HER2- ABC was included. (GlobeNewswire) - "For all analyzed patients with PIK3CA MT tumors (n=30), median PFS was 14.6 months and the ORR in response evaluable patients was 48%. Median PFS was 19.7 months and the ORR was 64% in patients with PIK3CA MT tumors who received the intermittent dose of gedatolisib used in the VIKTORIA-1 study...For patients with PIK3CA WT tumors (n=60), median PFS was 9.0 months and the ORR in response evaluable patients was 41%. Median PFS was 9.1 months and the ORR was 53% in patients with PIK3CA WT tumors who received the intermittent dose of gedatolisib used in the VIKTORIA-1 study."

P1 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

The topline efficacy data from the VIKTORIA-1 PIK3CA WT cohort established several new milestones in the history of drug development for HR+/HER2- ABC: (GlobeNewswire) - "The hazard ratios for the gedatolisib triplet and doublet are more favorable than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC; The 7.3- and 5.4-months incremental improvements in median PFS for the gedatolisib triplet and gedatolisib doublet over fulvestrant, respectively, are higher than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC receiving at least their second line of an endocrine therapy-based regimen...The gedatolisib triplet and doublet were generally well tolerated in the trial with mostly low-grade treatment-related adverse events ('TRAEs')."

P3 data: top line • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

The PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 trial is 100% enrolled and is expected to report topline data for this cohort in late Q1 2026 or during Q2 2026. (GlobeNewswire)

Enrollment status • P3 data: top line • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

In this Phase 1 study, 38 patients with mCRPC were randomly assigned to receive 600 mg darolutamide twice daily combined with either 120 mg gedatolisib in Arm 1 or 180 mg gedatolisib in Arm 2. (GlobeNewswire) - "In the amended Phase 1/1b portion of the clinical trial, up to six patients are planned to be enrolled in each of three arms and treated with different doses. Upon completion of Phase 1, up to an additional 40 patients will be randomly assigned to up to four Phase 1b cohorts to determine the recommended Phase 2 dose ('RP2D')...In the Phase 2 dose expansion study, which will include subjects from the Phase 1/1b clinical trial, up to 18 additional subjects will be enrolled to achieve a total of approximately 30 subjects treated with the RP2D."

Trial status • Castration-Resistant Prostate Cancer

Celcuity Inc…announced updated clinical results from the Phase 1 portion of a clinical trial evaluating gedatolisib in combination with Nubeqa (darolutamide), an androgen receptor inhibitor, in men with mCRPC whose disease had progressed on prior treatment with a next generation androgen receptor inhibitor. (GlobeNewswire) - "The six-month rPFS rate and median rPFS for patients from both arms combined was 67% and 9.1 months, respectively. For patients treated with 120 mg gedatolisib, the six-month rPFS rate was 74% and median rPFS was 9.5 months. For patients treated with 180 mg gedatolisib, the six-month rPFS rate was 61% and the median rPFS was 7.4 months...The combination of gedatolisib and darolutamide was generally well tolerated in the trial with mostly low-grade TRAEs. No dose limiting toxicities were observed in either arm."

P1 data • Castration-Resistant Prostate Cancer

Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting. (PubMed, Br J Cancer) - "These findings emphasize the critical role of the PI3K-AKT-mTOR pathway in chemo-radiation resistant HNSCC and highlight the therapeutic potential of PI3K inhibitors in a disease that is refractory to all conventional therapeutic approaches."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • NOTCH1

Celcuity Inc. (CELC)’s FDA NDA for Gedatolisib Accepted Under RTOR, Accelerating Review (Yahoo Finance UK) - "In August 2025, the U.S. FDA accepted CELC’s New Drug Application (NDA) for gedatolisib under the Real-Time Oncology Review (RTOR) program, allowing for a faster and more efficient regulatory process. The firm began its rolling submission in September and expects to complete it in the fourth quarter of 2025."

FDA filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Celcuity to Present Results from the Pivotal Phase 3 VIKTORIA-1 Trial at the 2025 European Society for Medical Oncology (ESMO) Congress (GlobeNewswire)

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Clinical-stage biotechnology company Celcuity Inc. (CELC) is set to present detailed results from its pivotal Phase 3 VIKTORIA-1 trial at the 2025 European Society for Medical Oncology or ESMO Congress, scheduled for October 17-21 in Barcelona. (RTTNews) - "The late-breaking oral presentation will spotlight efficacy and safety data from the PIK3CA wild-type cohort of the trial, which evaluates gedatolisib in combination with fulvestrant ± palbociclib for patients with HR+/HER2- advanced breast cancer."

Late-breaking abstract • P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial primary completion date • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PIK3CA • PTEN

Celcuity to Initiate NDA Submission of Gedatolisib in PIK3CA Wild-Type Cohort in HR+/HER2- Advanced Breast Cancer Under FDA’s Real-Time Oncology Review Program (GlobeNewswire) - "Celcuity is expected to initiate in September a rolling submission to the FDA of its NDA for gedatolisib, based on topline data from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial. Completion of the NDA submission is targeted for the fourth quarter of 2025."

FDA filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor Positive, HER2 Negative Advanced Breast Cancer. (PubMed, Clin Cancer Res) - "Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for ABC. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- ABC."

Journal • Breast Cancer • Dental Disorders • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • ER • HER-2 • PIK3CA