On October 19, 2023 Flare Therapeutics Inc., a biotechnology company targeting transcription factors (TF) to discover precision medicines for cancer and other diseases, reported that the first patients have been dosed in the company’s phase 1 study to assess the safety and tolerability of FX-909, a first-in-class small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of the luminal lineage (Press release, Flare Therapeutics, OCT 19, 2023, View Source [SID1234636154]). FX-909 is a highly potent and selective inhibitor of PPARG and has demonstrated tumor eradication in preclinical animal models of urothelial cancer at low oral doses.
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"We are excited to announce the dosing of patients in the first dose cohort of our Phase 1 clinical study of FX-909, marking a major milestone for Flare Therapeutics as we transition to a clinical stage company," said Michael L. Meyers, M.D., Ph.D., Chief Medical Officer of Flare Therapeutics. "Rooted in innovation and expertise in transcription factors, FX-909 has the potential to become a backbone therapy for advanced urothelial cancer. We believe PPARG’s role as a master regulator of the luminal lineage may represent a differentiated therapeutic option in advanced urothelial cancer, and we are excited to explore this novel mechanism in the clinic."
About FX-909
Flare Therapeutics’ lead investigational compound, FX-909, is a first-in-class novel, highly potent and selective small molecule that inhibits the transcription factor peroxisome proliferator-activated receptor gamma (PPARG) to treat patients with the luminal subtype of advanced urothelial carcinoma (UC) and potentially other solid tumors. Preclinical data for FX-909 has demonstrated robust anti-tumor activity, excellent PK/PD correlation, durable efficacy, and a favorable safety profile in mouse models of UC (PPARG-amp and RXRA-mut) at very low oral doses.
About the FX-909 Phase 1 Study
The ongoing phase 1 study is a first-in-human, dose-escalation and -expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma. The study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of FX-909. FX-909 will be given initially in a dose-escalation phase (Part A) to determine the recommended phase 2 dose. FX-909 will be given initially orally once daily in 28-day cycles. Part B will be a monotherapy expansion phase to further evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of FX-909 in patients with locally advanced (unresectable) or metastatic urothelial carcinoma. Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05929235).
About Advanced Urothelial Carcinoma (UC)
In 2020, there were an estimated 725,549 people living with bladder cancer in the United States alone, making it the sixth most common cancer overall, and fourth most common among men (SEER – 2020). Each year, there are more than 83,000 new cases diagnosed among men and women, and about 25% of those cases are classified as muscle-invasive UC (DRG 2020). Advanced UC has high rates of recurrence, where treatment outcomes have remained poor with typical five-year survival rates of 8% in advanced metastatic disease (SEER – 2020). The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC cases (Robertson, Cell 2017). Recurrent genetic alterations in PPARG are characteristic of this molecular subtype.