CAMBRIDGE, Mass., Feb. 27, 2026 (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 the presentation of updated clinical data and associated biomarkers from the Phase 1A study of FX-909, a first-in-class orally bioavailable potent and selective small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of the luminal lineage, in locally-advanced or metastatic urothelial cancer (UC).

Matthew Galsky, M.D., FASCO, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, will present the late-breaking abstract in a rapid oral presentation titled “Updated clinical results and associated biomarkers from an ongoing phase 1 study of FX-909, a first-in-class peroxisome proliferator-activated receptor gamma (PPARG) inhibitor, in patients (pts) with advanced urothelial carcinoma (adv UC)” today at the 2026 American Society of Clinical Oncology Genitourinary (GU) Cancers Symposium in San Francisco, CA.

“These data offer encouraging signs that FX-909 may help shrink or control tumors in patients with advanced UC, with enriched responses in tumors with a luminal lineage as defined by PPARG overexpression. FX-909 is the first and only agent addressing the underlying transcriptional driver of urothelial cancer,” said Dr. Galsky. “As an oral agent with an acceptable safety and tolerability profile, FX-909 has the potential to offer a much-needed new therapeutic option for patients with advanced UC, and over time, may extend into earlier lines of treatment.”

As of the data cut-off date of November 10, 2025, 46 patients with advanced UC received FX-909 monotherapy across four once-daily dose levels (30 mg, 50 mg, 70 mg and 100 mg), with a median of three prior lines of therapy (range 1-8), including prior enfortumab vedotin and anti-PD(L)1 therapy in 35% of patients. Key highlights from the presented data include:

• Antitumor activity in biomarker-defined patients with PPARG^high tumors: Among efficacy-evaluable patients, and using a provisional tumor proportion score (TPS) cutoff of ≥60% to define PPARG^high status, 18 of 25 PPARG^high patients showed tumor regressions, including five confirmed partial responses. An additional confirmed complete response was observed in a patient with non-measurable disease.
• Reinforcement of luminal lineage biology and genomic context: PPARG^high tumors show strong concordance with luminal biology features providing a more enhanced means of identifying PPARG activated tumors beyond genomic alterations that are linked to the PPARG signaling axis.
• Acceptable safety profile observed: At the 30 mg and 50 mg dose levels, the most common grade 3 treatment-related adverse events (TRAEs) included anemia (18.9%), thrombocytopenia (16.2%) and fatigue (10.8%). Other common treatment-emergent adverse events included diarrhea (32.4%), hypertriglyceridemia (27%) and hyperglycemia (24.3%). The 30 mg cohort showed fewer grade 3 TRAEs (35.3%), longer time to onset (median 52 days; range 44–85), and fewer dose interruptions (29.4%) and dose reductions (11.8%).
• Emergence of meaningful clinical benefit: Among the 25 patients in the PPARG^high subgroup, five remained on treatment at the time of data cut-off. Three patients at the 30 mg dose were on treatment for 5.3+, 5.8+ and 12.7+ months, one patient at the 50 mg dose for 5.5+ months, and one patient at the 70 mg dose for 7.6+ months. The one confirmed CR with non-measurable disease remained on treatment for 8.4+ months (70 mg – reduced to 30 mg after two cycles) at the time of the data cut-off.
• Molecular responses confer clinical benefit: On-treatment declines in circulating tumor DNA (ctDNA) at cycle 2/3 were associated with clinical benefit. 25 advanced UC patients had paired baseline and cycle 2 or 3 plasma samples for ctDNA analysis using the CARIS Assure test. 80% (12/15) of the PPARG^high subgroup achieved a ctDNA complete response (3 CCR, 9 CPR) per LB-RECIST criteria ref - Gouda et al Ann Oncol (2024).
  

FX-909 is currently 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 PPARG^high 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 data in a biomarker-defined population from the randomized portion of the Phase 1B in mid-2026.

More information about the trial is available at clinicaltrials.gov using the identifier NCT05929235.

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 AR_ON, the transcriptionally active, hormone-bound androgen receptor. This approach offers the potential to overcome key vulnerabilities of conventional therapies that target AR_OFF 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.

Contacts:

Investors:
Sarah McCabe
investorrelations@flaretx.com

Media:
Timothy Cockroft
media@flaretx.com