Flare Therapeutics Inc. has announced promising preliminary results from Part A of its Phase 1 study of FX-909, the first small molecule designed to inhibit the peroxisome proliferator-activated receptor gamma (PPARG). This significant announcement was made during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held on October 24, 2025, in Cambridge, Massachusetts.
The study reported that FX-909 demonstrated monotherapy activity in patients with advanced urothelial carcinoma (UC), coupled with a favorable safety profile. Dr. Xin Gao, a Medical Oncologist at Massachusetts General Hospital, detailed these findings in his oral presentation titled “Safety and clinical activity of FX-909, a first-in-class oral small molecule inhibitor of PPARG, a master regulator of luminal lineage in patients with advanced urothelial carcinoma.”
Dr. Gao stated, “These preliminary data show a first-in-mechanism drug with promising single-agent efficacy at all doses evaluated in a heavily pre-treated locally advanced and metastatic UC patient population. I believe this clinical proof-of-concept supports further development of FX-909.” The ongoing Phase 1B study is focused on patients screened for high PPARG expression, which is characteristic of approximately 65% of advanced UC cases.
Dr. Michael L. Meyers, Chief Medical Officer at Flare Therapeutics, expressed optimism regarding the results. He noted, “In the last decade, the advanced UC treatment landscape has evolved significantly, and the standard of care paradigm has changed. However, despite these advances, there is still a large unmet need for efficacious treatments with better tolerability and durability in this difficult-to-treat patient population.” He emphasized the potential of FX-909 in targeting the disease at its source.
The Phase 1A portion of the study utilized an open-label 3+3 dose-escalation design to assess FX-909″s safety, tolerability, pharmacokinetics, pharmacodynamics, and initial clinical activity. A total of 46 patients were enrolled, including 36 with advanced UC, and were administered four different dosing regimens: 30 mg, 50 mg, 70 mg, and 100 mg daily.
Key findings from the study indicated that the pharmacokinetics and pharmacodynamics supported FX-909 as an active compound at all evaluated doses. Notably, preliminary anti-tumor activity was observed across all dosing levels among advanced UC patients, with several patients achieving partial and complete responses. Tumor shrinkage was noted in 70% of the patients with high PPARG expression.
Looking ahead, FX-909 is currently being assessed in a Phase 1B expansion study aimed at determining its safety and efficacy in patients with locally advanced or metastatic UC classified as PPARGhigh. This study features a randomized two-stage design, and a validated immunohistochemistry test has been developed to identify eligible patients. Interim efficacy data from this biomarker-defined population is anticipated in the first quarter of 2026, with additional details available on clinicaltrials.gov under the identifier NCT05929235.
For those interested in further details, an on-demand webinar discussing the findings is available on the Flare Therapeutics website, alongside the poster presentation.
Advanced urothelial cancer is a formidable form of bladder cancer, making up about 25% of all diagnosed bladder cancers annually. In the U.S., bladder cancer contributes to approximately 84,000 new cases each year, with urothelial carcinoma being the most prevalent type. The advanced stages of this disease are notoriously challenging to treat, with a majority of patients experiencing progression shortly after first-line chemotherapy. The five-year survival rate for metastatic UC remains alarmingly low, highlighting the urgent need for more effective treatment options.
Flare Therapeutics Inc. is dedicated to targeting transcription factors to create precision medicines, with FX-909 being its lead program aimed at treating locally advanced or metastatic urothelial cancer. This innovative approach is part of a broader effort to unlock the therapeutic potential of transcription factors, a class of targets that has been difficult to address in oncology.
