FX-909 / Flare Therap - LARVOL DELTA

Inverse Agonists of Peroxisome Proliferator-Activated Receptor Gamma: Advances and Prospects in Cancer Treatment. (PubMed, J Med Chem) - "The first-in-class PPARγ inverse agonist, FX-909, is currently being studied in clinical trials for cancer treatment...These findings inform the development of anticancer agents that act as PPARγ inverse agonists. Furthermore, our discussion of the complex biological functions of PPARγ provides insights into the exploration of its role in various diseases."

Journal • Review • Bladder Cancer • Developmental Disorders • Genito-urinary Cancer • Oncology • Solid Tumor • PPARG

PPARG protein expression in advanced urothelial carcinoma and selection for response to FX-909, a first-in-class PPARG-targeting agent. (ASCO-GU 2025) - P1 | "These data show the IHC assay is sensitive and specific for the detection of PPARG expression in advanced UC with utility to identify patients with potential to respond to FX-909, a first-in-class PPARG-targeting agent4. 1. Sims R, AACR 2023, Fl; 2."

Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PPARG

Flare Therapeutics Inc., a GordonMD Global Investments LP Portfolio Company, Enters Strategic Discovery Collaboration with Roche (Businesswire) - "Flare Therapeutics Inc., has entered into a strategic discovery collaboration with Roche...Flare will lead discovery and preclinical activities targeting multiple transcription factor targets in oncology, while Roche will pursue the further preclinical and clinical development and commercialization of potential products from the collaboration, leveraging its industry-leading capabilities in oncology....Flare will receive a US$70 million upfront cash payment and is eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$1.8 billion and royalties. Additionally, Flare retains a right to co-fund development for one target under the collaboration in exchange for increased royalties in the United States for this target. Flare will retain ownership of its existing pipeline, including its lead clinical-stage program, FX-909, in advanced urothelial cancer, its prostate cancer program entering IND-enabling studies..."

Licensing / partnership • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

Flare Therapeutics Announces Strategic Discovery Collaboration with Roche to Address Previously Undrugged Transcription Factor Targets in Oncology (PRNewswire) - "Flare Therapeutics Inc...announced it has entered into a strategic discovery collaboration with Roche....As part of the collaboration, Flare Therapeutics will receive a US$70 million upfront cash payment and is eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$1.8 billion and royalties....Additionally, Flare Therapeutics retains a right to co-fund development for one target under the collaboration in exchange for increased royalties in the United States for this target. Flare Therapeutics will retain ownership of its existing pipeline, including its lead clinical-stage program, FX-909, in advanced urothelial cancer, its prostate cancer program entering IND-enabling studies, and other programs in discovery and early development in oncology and other therapeutic areas."

Licensing / partnership • Prostate Cancer • Urothelial Cancer

PPARG-high circulating monocytes exhibit an immunosuppressive phenotype in urothelial cancer patients treated with anti-PD1 (AACR 2024) - "Real-world samples (Discovery Life Sciences) were collected from patients who received prior Pembrolizumab. PPARG-high circulating CMs in UC patients exhibit a transcriptomic profile associated with immunosuppression and M2 macrophage polarization. FX-909, a first-in-class PPARG inverse agonist, is being evaluated in the clinic and the study includes an exploratory biomarker approach to assess the potential effect of PPARG inhibition on the CM immune-profile of advanced UC patients enrolled in the Ph1 study [4]."

Clinical • IO biomarker • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • MAFB • PPARG

Flare Therapeutics to Present Immune Profiling Data from Urothelial Cancer Patients Treated with Anti-PD1 Therapy at AACR 2024 Annual Meeting (PRNewswire) - "Flare Therapeutics...announced a poster presentation identifying immunosuppressive programming associated with high PPARG expression in urothelial cancer (UC) patients treated with anti-PD1 therapy at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024..."

Clinical • Urothelial Cancer

A phase 1, first-in-human, dose-escalation and expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma. (ASCO-GU 2024) - P1 | "The study is currently enrolling patients in the US. Clinical trial information: NCT05929235."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • PPARG

Flare Therapeutics Presents FX-909 Phase 1 Dose Escalation and Expansion Clinical Trial Design at the 2024 ASCO Genitourinary Cancers Symposium (PRNewswire) - "Flare Therapeutics Inc...today announced a poster presentation outlining the Phase 1 clinical trial design of FX-909, a highly potent and selective inhibitor of PPARG, at the 2024 ASCO Genitourinary Cancers Symposium taking place from January 25-27, 2024 in San Francisco, CA....FX-909-CLINPRO-1 (NCT05929235) is a first-in-human, multicenter, open-label Phase 1 study designed to assess the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FX-909 given orally to patients with advanced solid malignancies."

Clinical protocol • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

PPARG amplification is associated with lack of response to anti-PD1 in muscle-invasive urothelial cancer (SITC 2023) - "FX-909, a first-in-class covalent PPARG inverse agonist that will be evaluated in a Ph1 trial this year, will offer an opportunity to investigate the impact of PPARG inhibition on the TME of MIUC patients. FX-909 combination with ICI therapy potentially provides a ‘one-two punch’ strategy to overcome resistance to immunotherapy in MIUC patients with high PPARG expression."

IO biomarker • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD8 • PD-L1 • PPARG

Flare Therapeutics Presents New Translational Data in Support of Lead Asset FX-909 for the Treatment of Muscle-Invasive Urothelial Cancer at SITC 2023 Annual Meeting (PRNewswire) - "Flare Therapeutics Inc...today revealed molecular real-world data (RWD) demonstrating that high PPARG expression in patients with MIUC is associated with an immunosuppressive tumor microenvironment (TME) and shorter real-world progression-free survival to anti-PD1 treatment. The translational data were shared at the Society for Immunotherapy of Cancer's 38th Annual Meeting (SITC) 2023 taking place November 1-5, 2023 in San Diego, California....The data presented today suggest that FX-909 in combination with ICI agents could potentially provide a new therapeutic strategy that helps MIUC patients with high PPARG expression overcome resistance to immunotherapy."

Real-world • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics to Present New Translational Data in Support of Clinical Candidate FX-909's Phase 1 Development at SITC 2023 Annual Meeting (PRNewswire) - "Flare Therapeutics Inc...today announced a poster presentation at the upcoming Society for Immunotherapy of Cancer's 38th Annual Meeting (SITC) 2023, taking place November 1-5, 2023 in San Diego, California."

Clinical data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics Announces First Patients Dosed in First-in-Human Phase 1 Clinical Study of FX-909 in Advanced Solid Malignancies, Including Urothelial Cancer (PRNewswire) - "Flare Therapeutics Inc...today announced 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. 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."

Trial status • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics Presents Novel, AI-Based Method Identifying Luminal Subtype of Urothelial Cancer Supporting Lead Asset FX-909 at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Flare Therapeutics...today announced a new study describing a robust artificial intelligence (AI)-based model in partnership with PathAI that accurately predicts luminal muscle invasive urothelial cancer (MIUC), characterized by high peroxisome proliferator-activated receptor gamma (PPARG) expression using H&E-stained slides. This approach supports the clinical development of the Company's first-in-class clinical candidate, FX-909, for the treatment of patients with advanced Urothelial Carcinoma (UC)."

Diagnostic • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics to Present Biomarker Data for Clinical Candidate FX-909 at 2023 AACR-NCI-EORTC International Conference (PRNewswire) - "Flare Therapeutics...announced a poster presentation highlighting an artificial intelligence-based model developed in partnership with PathAI that identifies the luminal subtype in Urothelial Carcinoma as a novel biomarker approach for its first-in-class clinical candidate FX-909 at the upcoming 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place October 11-15 in Boston, Massachusetts."

Biomarker • Urothelial Cancer

A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=75 | Recruiting | Sponsor: Flare Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Oral Cancer • Solid Tumor • Urothelial Cancer • PD-L1

A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=75 | Not yet recruiting | Sponsor: Flare Therapeutics Inc.

Metastases • New P1 trial • Oncology • Oral Cancer • Solid Tumor • Urothelial Cancer • PD-L1

Development of a peroxisome proliferator-activated receptor gamma (PPARG) immunohistochemistry (IHC) assay in advanced urothelial carcinoma (UC) may provide a precision approach to patient selection for FX-909, a first-in-class PPARG-targeting agent. (ASCO 2023) - "Sponsored by Pharmaceutical/Biotech Company"

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer • PPARG

Development of a surrogate tissue pharmacodynamic (PD) assay for clinical use with FX-909, a novel inhibitor of the urothelial luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG) (AACR 2023) - "Based on these preclinical data and confirmatory experiments in the ex vivo setting, a novel FX-909 signature is under development to predict target modulation in the tumor. The consistent correlation of PPARG target gene suppression in tumor and normal tissues across species provide a strong rationale for a surrogate biospecimen collection, such as a skin punch biopsy, to establish the PK/PD relationship between the dose and response to FX-909 in the clinic."

Clinical • PK/PD data • Genito-urinary Cancer • Oncology • Prostate Cancer • Skin Cancer • Solid Tumor • Urothelial Cancer • AR • FABP4 • PPARG

Discovery of FX-909, a first-in-class inverse agonist of the peroxisome proliferator-activated receptor gamma (PPARG) lineage transcription factor, to potentially treat patients with the luminal subtype of advanced urothelial cancer (UC) (AACR 2023) - "Predictable, on-target and reversible pharmacology was observed at FX-909 doses above 1 mg/kg, mimicking PPARG loss-of-function mutations with notable tissue remodeling in adipose tissue and the normal urothelium. These collective findings corroborate the role of PPARG as a key UC survival oncogene and suggest that FX-909 will be an effective therapy for patients with advanced UC harboring the luminal subtype."

Clinical • Metastases • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Urothelial Cancer • ER • PPARA • PPARG • RXRA

Flare Therapeutics Presents First Preclinical Data on Lead Asset FX-909, a Novel Small Molecule PPARG Inhibitor to Potentially Treat Urothelial Cancer, at the 2023 AACR Annual Meeting (PRNewswire) - "Flare Therapeutics...highlighted the first preclinical data from its lead compound FX-909, a novel, small molecule peroxisome proliferator-activated receptor gamma (PPARG) inhibitor to potentially treat patients with advanced urothelial cancer (UC), in an oral presentation and poster format at the AACR Annual Meeting being held in Orlando, FL from April 14-19, 2023....FX-909 administered orally twice a day caused tumor regression in PPARG-amplified and RXRA-mutant UC xenograft models at 1 mg/kg doses, and tumor eradication at 3 mg/kg doses."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics Announces Oversubscribed $123 Million Series B Financing (PRNewswire) - "Flare Therapeutics Inc., a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced a $123 million Series B financing co-led by GordonMD® Global Investments LP and Pfizer Ventures, with participation from existing investors Boxer Capital, Casdin Capital, Eventide Asset Management, Invus Financial Advisors, Nextech Invest and Third Rock Ventures and new investors Agent Capital, Eli Lilly and Company, Memorial Sloan Kettering Cancer Center (MSK), Novartis, Pavilion Capital and ShangBay Capital....Proceeds from the financing will support a planned clinical trial in 2023 for FX-909, a small molecule inhibitor targeting the PPARG transcription factor, in patients with advanced urothelial cancer..."

Financing • New trial • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Flare Therapeutics to Present Overview of Clinical Candidate FX-909 at AACR Annual Meeting (Businesswire) - "Flare Therapeutics...announced that it will give an oral presentation highlighting the discovery of its clinical candidate FX-909, at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida.... In pre-clinical models, FX-909 displays meaningful PPARG target gene silencing in UC cell lines as well as tumor regression in PPARG-amplified and RXRA-mutant UC xenograft models."

Preclinical • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer