8-K: Celcuity's Gedatolisib Achieves Unprecedented Phase 3 Results in Advanced Breast Cancer

Celcuity Inc. announced positive topline results from its Phase 3 VIKTORIA-1 clinical trial, demonstrating statistically significant and clinically meaningful improvements in progression-free survival for gedatolisib in HR+/HER2PIK3CA wild-type advanced breast cancer.

Summary

• The gedatolisib triplet (gedatolisib + palbociclib + fulvestrant) reduced the risk of disease progression or death by 76% compared to fulvestrant (hazard ratio [HR] of 0.24, 95% confidence interval [CI] 0.17-0.35; p<0.0001).
• The median progression-free survival (mPFS) for the gedatolisib triplet was 9.3 months, compared to 2.0 months with fulvestrant, representing an incremental improvement of 7.3 months.
• The gedatolisib doublet (gedatolisib + fulvestrant) reduced the risk of disease progression or death by 67% compared to fulvestrant (HR of 0.33, 95% CI 0.24-0.48; p<0.0001).
• The mPFS for the gedatolisib doublet was 7.4 months, compared to 2.0 months with fulvestrant, representing an incremental improvement of 5.4 months.
• The hazard ratios for both gedatolisib regimens are more favorable than any previously reported Phase 3 trial for patients with HR+/HER2advanced breast cancer (ABC).
• The incremental mPFS improvements are higher than any previously reported Phase 3 trial for HR+/HER2ABC patients receiving at least their second line of therapy.
• Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.
• Treatment discontinuation due to treatment-related adverse events for both gedatolisib regimens was lower than observed in Celcuity's Phase 1b trial and lower than observed in any Phase 3 trials for currently approved drug combinations in HR+/HER2ABC.
• The gedatolisib triplet and doublet were better tolerated than observed in the Phase 1b trial, including lower rates of hyperglycemia and stomatitis.

Sentiment

Score: 9

Explanation: The filing reports overwhelmingly positive and statistically significant Phase 3 clinical trial results for gedatolisib, demonstrating unprecedented efficacy and a favorable safety profile in a difficult-to-treat breast cancer population. This represents a major milestone for the company and the potential for a transformative new medicine.

Positives

• Statistically significant and clinically meaningful improvement in progression-free survival (PFS) for both gedatolisib triplet and doublet regimens.
• Gedatolisib triplet reduced the risk of disease progression or death by 76% (HR=0.24) compared to fulvestrant.
• Gedatolisib doublet reduced the risk of disease progression or death by 67% (HR=0.33) compared to fulvestrant.
• Median PFS for the gedatolisib triplet was 9.3 months, an incremental improvement of 7.3 months over fulvestrant (2.0 months).
• Median PFS for the gedatolisib doublet was 7.4 months, an incremental improvement of 5.4 months over fulvestrant (2.0 months).
• Hazard ratios for gedatolisib triplet and doublet are more favorable than any previously reported Phase 3 trial for HR+/HER2advanced breast cancer.
• Incremental improvements in median PFS are higher than any previously reported Phase 3 trial for HR+/HER2ABC patients receiving at least second-line therapy.
• Gedatolisib is the first PI3K/AKT/mTOR pathway inhibitor to demonstrate positive Phase 3 results in HR+/HER2-/PIK3CA wild-type ABC patients whose disease progressed on or after CDK4/6 inhibitors.
• Lower treatment discontinuation rates due to adverse events compared to previous trials and currently approved drug combinations.
• Better tolerated safety profile, including lower rates of hyperglycemia and stomatitis.

Risks

• Topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the clinical trial data.
• Unforeseen delays in the planned New Drug Application (NDA) for gedatolisib.
• Ability to obtain and maintain regulatory approvals to commercialize gedatolisib.
• Other risks detailed in the Annual Report on Form 10-K for the year ended December 31, 2024, and Quarterly Report on Form 10-Q for the quarter ended March 31, 2025.

Future Outlook

Celcuity expects to submit a New Drug Application (NDA) for gedatolisib to the U.S. Food and Drug Administration in the fourth quarter of 2025. Full data from the PIK3CA wild-type cohort of the VIKTORIA-1 clinical trial will be presented at an upcoming medical conference later this year. Topline data for the VIKTORIA-1 PIK3CA mutation cohort is expected by the end of 2025.

Management Comments

• Sara Hurvitz, MD, Co-Principal Investigator: "Patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed while on, or after, treatment with a CDK4/6 inhibitor typically derive limited benefit from subsequent endocrine-based therapy. The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing. To my knowledge, we have not seen Phase 3 results in patients with HR-positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control."
• Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity: "The topline data from VIKTORIA-1 demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with CDK4/6 inhibitors. The 7.3 and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens are potentially paradigm shifting results. We are also very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well-tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event."
• Brian Sullivan, Chairman, CEO, and Co-founder of Celcuity: "The efficacy improvement relative to the control that each of the gedatolisib regimens demonstrated was historic for this patient population. We are excited about the potential opportunity to provide a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer."

Industry Context

HR+/HER2breast cancer is the most common subtype, accounting for approximately 70% of all breast cancers. While existing therapies target key oncogenic pathways, resistance to CDK4/6 inhibitors and current endocrine therapies is a significant challenge, leading to poor long-term survival rates for metastatic disease. Gedatolisib, as a multi-target PI3K/AKT/mTOR (PAM) inhibitor, is designed to overcome these resistance mechanisms by comprehensively blocking the PAM pathway. Its positive Phase 3 results in patients whose disease progressed on CDK4/6 inhibitors address a critical unmet medical need in this patient population, potentially offering a new, more effective treatment option where current options are limited.

Comparison to Industry Standards

• The hazard ratios for the gedatolisib triplet (0.24) and doublet (0.33) are more favorable than any previously reported Phase 3 trial for patients with HR+/HER2advanced breast cancer.
• The 7.3-month and 5.4-month incremental improvements in median PFS for the gedatolisib triplet and doublet over fulvestrant, respectively, are higher than any previously reported Phase 3 trial for HR+/HER2ABC patients receiving at least their second line of therapy.
• Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.
• Treatment discontinuation due to a treatment-related adverse event for the gedatolisib triplet and doublet was lower than observed in Arm D of Celcuity's Phase 1b trial in ABC patients and lower than observed in any Phase 3 trials for currently approved drug combinations in HR+/HER2ABC.
• The gedatolisib triplet and doublet were better tolerated than observed in the Phase 1b trial in ABC, including lower rates of hyperglycemia and stomatitis.
• A co-principal investigator noted that a "quadrupling of the likelihood of survival without disease progression relative to the study control" has not been seen before in Phase 3 results for this patient population.

Stakeholder Impact

• Patients: Potential for a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed on or after CDK4/6 inhibitors, offering significantly improved progression-free survival and a better-tolerated treatment option.
• Shareholders: Highly positive clinical trial results are likely to increase investor confidence and potentially lead to a significant increase in share price due to the strong efficacy data and clear path towards regulatory submission.
• Healthcare Providers: Gedatolisib could become a new standard of care for this specific patient population, providing a new tool in their treatment arsenal.

Next Steps

• Full data from the PIK3CA wild-type cohort of the VIKTORIA-1 clinical trial will be presented at an upcoming medical conference later this year.
• Submission of a New Drug Application (NDA) for gedatolisib to the U.S. Food and Drug Administration in the fourth quarter of 2025.
• Topline data for the VIKTORIA-1 PIK3CA mutation cohort is expected by the end of 2025.
• Management will host a webcast and conference call on July 28, 2025, at 8:00 a.m. ET to discuss the topline results.

Key Dates

Recommendation

The Phase 3 VIKTORIA-1 trial results for gedatolisib are exceptionally strong, demonstrating statistically significant and clinically meaningful improvements in progression-free survival that are described as "unprecedented" and "historic" for this patient population. The hazard ratios and median PFS improvements significantly outperform historical benchmarks for HR+/HER2advanced breast cancer patients who have progressed on prior therapies. Furthermore, the drug exhibited a favorable safety profile with lower discontinuation rates due to adverse events compared to existing treatments. As the first PI3K/AKT/mTOR pathway inhibitor to show such positive Phase 3 results in this specific, difficult-to-treat patient group, gedatolisib addresses a significant unmet medical need. The clear path to NDA submission in Q4 2025, coupled with the robust efficacy and safety data, positions Celcuity for substantial future growth and market penetration, making it a strong buy for investors.

Keywords

Celcuity, CELC, Gedatolisib, VIKTORIA-1, Breast Cancer, HR+ HER2-, PIK3CA wild-type, Phase 3 Clinical Trial, Oncology, PFS, Progression-Free Survival, FDA, New Drug Application, Biotechnology, Targeted Therapy, PI3K/AKT/mTOR inhibitor