- FX-909, the first small molecule targeting PPARG to be tested in humans, showed monotherapy activity in advanced urothelial carcinoma with a favorable safety profile
- Strong safety, tolerability and efficacy data in a biomarker-defined advanced UC population supports further development of FX-909 in the ongoing Part B of the Phase 1 study
- On-demand webinar featuring company management and investigators, Xin Gao, M.D. and Matthew Galsky, M.D., now available
CAMBRIDGE, Mass., Oct. 24, 2025 (GLOBE NEWSWIRE) -- Flare Therapeutics Inc. (FlareTx), a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for oncology and other therapeutic areas, today announced part A data from the ongoing Phase 1 study of FX-909, a first-in-class orally available small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), the master regulator of the luminal lineage, in locally-advanced or metastatic urothelial cancer (UC). FX-909 demonstrated early signs of clinical benefit in patients with advanced urothelial carcinoma as a monotherapy with a favorable safety profile.
Xin Gao, M.D., Medical Oncologist and Clinical Investigator, Massachusetts General Hospital, presented these results in an oral presentation titled “Safety and clinical activity of FX-909, a first-in-class oral small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of luminal lineage in patients with advanced urothelial carcinoma” today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
“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. In the ongoing Phase 1B study, patients are being prospectively screened for high expression of PPARG, the hallmark of the luminal lineage, which accounts for approximately 65% of cases of advanced UC. I look forward to seeing the clinical activity data in this biomarker defined population,” commented Dr. Gao.
“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. We are encouraged by the preliminary clinical efficacy we are seeing for FX-909 and are focused on executing the ongoing Phase 1B study that will deliver data for our novel PPARG inhibitor in a biomarker-defined population of UC patients. We believe FX-909 may represent a significant step toward addressing the disease at its source by directly targeting the cell of origin and addressing the underlying disease biology, and we are eager to continue exploring the full potential of this agent,” remarked Dr. Michael L. Meyers, Chief Medical Officer at Flare Therapeutics.
Phase 1A Study
The Phase 1A open-label 3+3 dose-escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of FX-909 administered orally once daily (QD) in 28-day cycles and enrolled patients with advanced solid malignancies, including advanced UC. Data for 46 patients, including 36 patients with advanced UC, who were treated across four dose levels; 30 mg (12); 50 mg (15); 70 mg (13); and 100 mg (6) were reported as of September 17, 2025.
Key data highlights include:
- PK and PD support FX-909 as a pharmacologically active drug at all doses evaluated
- Preliminary anti-tumor activity was also observed at all doses evaluated in advanced UC patients (4 PRs, 1 CR)
- Efficacy was enriched in patients with high expression of PPARG by immunohistochemistry
- Tumor shrinkage was observed in 70% of the 20 UC patients with high expression of PPARG
- FX-909 has an acceptable safety and tolerability profile
- A cutoff for high expression of PPARG that predicts for luminal lineage was determined from the correlative biomarker analysis
Based on the totality of the Part A data, 30 mg and 50 mg QD doses were selected for further optimization. Prospective pre-screening to select for patients with a Tumor Proportional Score (TPS) cutoff of 60%, newly defined as PPARGhigh, is being implemented in the Phase 1 Part B study.
FX-909 Next Steps
FX-909 is currently being evaluated in a Phase 1B expansion study evaluating safety and efficacy in second line or beyond to determine the recommended Phase 2 dose in a biomarker-defined PPARGhigh locally advanced (unresectable) or metastatic UC patient population. The Phase 1 Part B study adopts a randomized 2-stage design. A validated immunohistochemistry (IHC)-based test has been developed to identify patients eligible for enrollment in the expansion study. The company expects interim efficacy data in a biomarker-defined population at the recommended Phase 2 dose in the first quarter of 2026. More information about the trial is available at clinicaltrials.gov using the identifier NCT05929235.
Webinar Information
An on-demand webinar with company management and investigators, Xin Gao, M.D. and Matthew Galsky, M.D., reviewing this data is now available on the Flare Therapeutics website and can also be accessed here: https://edge.media-server.com/mmc/p/wbj4uhqp. The poster presentation is also available on the Flare Therapeutics website under presentations & publications.
About Advanced Urothelial Cancer
Advanced urothelial cancer (UC) is an aggressive and challenging form of bladder cancer, representing approximately 25% of all bladder cancers diagnosed each year. In the United States, bladder cancer accounts for approximately 84,000 new cases each year, with urothelial carcinoma being the predominant histologic type. In advanced or metastatic stages, the disease is notably difficult to treat, with over 50% of patients experiencing disease progression within six to nine months of first-line chemotherapy. The five-year survival rate for metastatic UC remains poor, with estimates below 6%. While the introduction of checkpoint inhibitors and targeted therapies has expanded treatment options, clinical outcomes remain suboptimal, underscoring an urgent need for additional and more effective treatment options. Molecular subtyping has revealed that luminal tumors, or tumors that are characterized by high PPARG expression, comprise approximately 65% of advanced urothelial cancers. These luminal tumors are often or invariably characterized by activation of the PPARG (peroxisome proliferator-activated receptor gamma) pathway, which plays a critical role in maintaining tumor identity, promoting tumor growth, and contributing to immune evasion. Novel approaches such as PPARG inhibition are emerging as promising strategies to improve outcomes for patients that have UC with high PPARG expression. It is estimated that in the United States alone, there are approximately 14,000 new cases of advanced urothelial cancer with high PPARG expression diagnosed each year, based on the portion of luminal subtypes and overall incidence data.
About Flare Therapeutics Inc.
Flare Therapeutics is a clinical-stage biotechnology company exclusively focused on drugging transcription factors to fully unlock the therapeutic potential of this previously elusive target class. The company’s lead program, FX-909, is a first-in-class orally available small molecule inhibitor of PPARG, the master regulator of the luminal lineage, that is initially being developed for locally advanced or metastatic urothelial cancer. FX-909 has achieved clinical proof-of-concept in a Phase 1A study as a monotherapy and is actively dosing patients in a Phase 1B to determine the recommended Phase 2 dose in a biomarker-defined population. The second lead program, FX-111, is a novel and highly differentiated potent and selective degrader for ARON, the transcriptionally active, hormone-bound androgen receptor. This approach offers the potential to overcome key vulnerabilities of conventional therapies that target AROFF and has broad potential across prostate cancer at all stages. FX-111 is undergoing Investigational New Drug (IND)-enabling studies for initial development for the treatment of metastatic castration-resistant prostate cancer (mCRPC). These two programs, along with an earlier-stage portfolio targeting transcription factors involved in oncology and other therapeutic areas, leverage Flare Therapeutics’ integrated discovery platform of capabilities that identifies novel validated ligands to the undrugged proteome. For more information, please visit www.flaretx.com and follow us on LinkedIn.
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