CAMBRIDGE, Mass., Aug. 05, 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 that it has dosed the first patients in its Phase 1B clinical trial evaluating FX-909, a first-in-class orally available small molecule inhibitor of PPARG, a master regulator of the luminal lineage, for the treatment of locally-advanced or metastatic urothelial cancer (UC). More information about the trial is available at clinicaltrials.gov using the identifier NCT05929235.
“The initiation of the Phase 1B expansion study marks an important milestone as we seek to improve the treatment of advanced urothelial cancer with our lead program FX-909,” said Doug Manion, M.D., FRCP (C), Chief Executive Officer and Board Member. “We are prospectively screening for patients with high expression of PPARG, the hallmark of the luminal lineage, which accounts for approximately 65% of cases of advanced UC. We believe our PPARG inhibitor approach in this defined patient population represents a significant step toward addressing the disease at its source. By introducing a novel nuclear hormone receptor therapy—akin to the critical roles AR and ER play in prostate and breast cancers, respectively—we are expanding the therapeutic landscape to directly target the cell of origin and address the underlying disease biology.”
FX-909 has achieved clinical proof-of-concept in a Phase 1A study, as a monotherapy, based on pre-specified criteria. The company expects to present these data at a scientific conference in 2025. The Phase 1B study will evaluate safety and efficacy to determine the recommended Phase 2 dose in a biomarker-defined population. A validated immunohistochemistry (IHC)-based test is being deployed to prospectively select patients with the lineage determining transcription factor that drives the initiation and progression of these tumor types. The study will evaluate 30 mg and 50 mg (QD) doses in a 2-stage design, enrolling approximately 40 patients in total.
The company expects to report efficacy data in a biomarker-defined population at the recommended Phase 2 dose in the first quarter of 2026.
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 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, a 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, leverages 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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