On October 28, 2022 Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, reported that translational insights from a retrospective advanced urothelial cancer (UC) cohort in a poster titled, "Peroxisome Proliferator-Activated Receptor Gamma (PPARG) status defines the luminal lineage in molecular profiles of advanced urothelial cancers (UC)" at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, being held in Barcelona, Spain (Press release, Flare Therapeutics, OCT 28, 2022, View Source [SID1234622586]). Molecular RWD, comprising of more than 3,000 genomic and transcriptomic profiles from advanced UC tissue, were utilized to evaluate the transcription factor PPARG, and its role as a master regulator of the luminal lineage associated with its expression and mutational status.
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"To the best of our knowledge, this represents the largest RWD from patients with advanced and metastatic urothelial cancer, providing unique insights into the persistence of PPARG signaling through disease progression, independent of the treatment paradigm," said Michaela Bowden, Ph.D., Senior Vice President of Biology and Translation at Flare Therapeutics. "Stratification of patients based upon their PPARG status serves as the foundation for our precision approach in identifying individuals most likely to respond to PPARG inhibition."
Flare presented its novel PPARG program demonstrating robust preclinical activity in a poster presentation titled, "Novel inhibitors of the luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG) durably eradicate tumors in urothelial cancer animal models" on Wednesday, October 26th at same symposium.
Data highlights:
65% of advanced urothelial cancers evaluated were classified as luminal, of which one in three were enriched for genetic alterations in PPARG, RXRA or FGFR3
PPARG amplification, including a gain of only one copy number, is associated with higher PPARG expression
PPARG expression levels were sustained in metastatic lesions compared locally advanced tissues and did not significantly vary by metastatic tissue site
Flare is advancing a novel PPARG inhibitor through Investigational New Drug (IND)-enabling studies and expects to initiate its Phase 1 clinical trial in 2023 in individuals with locally advanced or metastatic UC.
About Advanced Urothelial Cancer
Muscle-invasive UC is a common type of bladder cancer, with about 20,000 individuals diagnosed each year in the United States alone, and significantly higher incidence rates in other regions of the world. This disease has high rates of recurrence and the five-year survival rate is approximately 5% in metastatic cases. The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC patients. Recurrent genetic alterations in PPARG, including focal amplification, missense mutations, and fusions, as well as hotspot mutations in its binding partner, retinoid X receptor alpha (RXRA) are characteristic of this molecular subtype.