Flare Therapeutics Presents Comprehensive Real-World Data in Advanced and Metastatic Urothelial Cancer in Support of Therapeutic Targeting of PPARG at 2022 EORTC-NCI-AACR Symposium

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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.

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Friday, October 28, 2022
Information
Tags: 
Oncology, Health, General Health, Research, Science, Pharmaceutical, Biotechnology, IND, RXRA, Biotechnology, Drug discovery, Cancer, Retinoid X receptor alpha, Flare, Disease, Recurrence, Squamous cell carcinoma, Peroxisome proliferator-activated receptor gamma, Inflammation, Senior, HIV disease progression rates, Neurology, Neoplasm, Patient, Bladder cancer, FGFR3, RWD, Lists of diseases, Third Rock Ventures, Therapy, UC, Investigational New Drug, Knowledge, Incidence, Factor X, Pharmaceutical industry, PPARG, Biology
Geotags: 
MASSACHUSETTS, UNITED STATES, NORTH AMERICA, SPAIN
Organisation: 
FLARE THERAPEUTICS
Summary
Key Points: 
  • 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.
  • 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.
  • Flare Therapeutics is a biotechnology company pioneering a new therapeutic space with a novel approach to decipher the biology of transcription factors to develop small molecule medicines.


Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today presented 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 Symposium, being held in Barcelona, Spain. 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.

“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.

About Flare Therapeutics

Flare Therapeutics is a biotechnology company pioneering a new therapeutic space with a novel approach to decipher the biology of transcription factors to develop small molecule medicines. Based on insights from the seminal work of its scientific founders, Flare’s team has uncovered ‘switch sites,’ druggable regions that are key targets for transcription factor regulation, to address mutations that cause disease. Flare’s drug discovery efforts to target switch sites has rapidly advanced, resulting in an emerging pipeline of research programs that address well-validated genetically-defined transcription factors, initially focused on precision oncology with future potential in neurology, rare genetic disorders, immunology and inflammation. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.

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