FX-909 / Flare Therap - LARVOL DELTA

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). (ASCO-GU 2026) - P1 | "FX-909, a first-in-mechanism orally bioavailable PPARG inhibitor, demonstrates clinical proof-of-concept for targeting the master regulator of luminal lineage in heavily pretreated adv UC pts and may offer a novel therapeutic strategy for PPARGhigh adv UC. A randomized phase 1B expansion study is ongoing (NCT05929235). A combination study of FX-909/anti-PD1 is planned for early 2026."

Biomarker • Clinical • IO biomarker • Late-breaking abstract • Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • PPARG

A small-molecule inverse agonist of PPARγ for advanced solid tumors: a phase 1 trial. (PubMed, Nat Med) - P1 | "FX-909 demonstrated acceptable safety and tolerability with preliminary antitumor activity, supporting further clinical development in urothelial cancer. ClinicalTrials.gov identifier: NCT05929235 ."

Journal • P1 data • Diabetes • Fatigue • Genito-urinary Cancer • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • Urothelial Cancer • PPARG

Phase 0 intratumoral microdevice study of FX-909 in bladder cancer demonstrates on-target anti-tumor activity and immune modulation, enhanced in combination with anti-PD-1 (AACR 2026) - "Abstract is embargoed at this time."

Combination therapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Flare Therapeutics Presents Updated FX-909 Phase 1A Data in Late-Breaking Oral Presentation at 2026 ASCO Genitourinary Cancers Symposium (GlobeNewswire) - "As of the data cut-off date of November 10, 2025, 46 patients with advanced UC received FX-909 monotherapy....Among the 25 patients in the PPARGhigh 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....The company expects interim data in a biomarker-defined population from the randomized portion of the Phase 1B in mid-2026."

Late-breaking abstract • P1 data • Urothelial Cancer

FX-909-CLINPRO-1: A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Flare Therapeutics Inc. | N=75 ➔ 120 | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Sep 2026 ➔ Oct 2027

Enrollment change • First-in-human • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Oral Cancer • Solid Tumor • Urothelial Cancer • CD4 • PPARG

First-of-Its-Kind PPARG Inhibitor Shows Compelling Activity. (PubMed, Cancer Discov) - "A novel inhibitor of the protein PPARG, which is overexpressed in most cases of advanced urothelial carcinoma, led to tumor shrinkage in most patients with high PPARG expression who received the drug FX-909. In addition, some responding patients had elevated levels of CD4+ T cells and circulating chemokines and cytokines, suggesting that the drug attenuates PPARG-mediated immune suppression."

Journal • Oncology • Solid Tumor • Urothelial Cancer • CD4 • PPARG

FX-909 Next Steps (The Manila Times) - "FX-909 is currently being evaluated in a Phase 1B expansion study...The company expects interim efficacy data in a biomarker-defined population at the recommended Phase 2 dose in the first quarter of 2026...In the first quarter of 2026, the company expects to initiate enrollment of a Phase 1 combination cohort that will investigate the safety, tolerability, immunologic effects and preliminary efficacy of escalating doses of FX-909 in combination with standard dose KEYTRUDA (pembrolizumab) in patients with advanced urothelial carcinoma."

P1 data • Trial status • Urothelial Cancer

Flare Therapeutics Presents Correlative Biomarker Analysis from the FX-909 Phase 1A Clinical Study at SITC 2025 40th Anniversary Annual Meeting (The Manila Times) - "Baseline molecular profiling confirmed that PPARGhigh tumors are of luminal lineage and display a cold immune phenotype consistent with lack of response to anti-PD-1 inhibition; FX-909 treatment activated IFNy-induced inflammatory pathways in all patients evaluated, including important IO biomarkers of response such as CXCL9, CXCL10 and TNFa amongst others"

Biomarker • P1 data • Urothelial Cancer

Phase 1 Clinical Data Show FX-909, a First-in-Class Oral PPARG Inhibitor, Drives Immune Modulation and Pro-Inflammatory Cytokine Induction in IO-Experienced Patients with Advanced Urothelial Carcinoma (SITC 2025) - P1 | "We also thank Flare Therapeutics staff, CROs and Consultants.Ethics Approval This study was conducted in accordance with Good Clinical Practice guidelines. Institutional Review Board approval was obtained at each participating site, and all participants provided written informed consent.Abstract 1318 Figure 1Request permissionsFX-909 promotes IFNy- induced inflammatory responses in patients with advanced urothelial cancerAbstract 1318 Figure 2Request permissionsFX-909 induces T-cell expansion selectively in responding patients that are enriched for luminal lineage C2D1: Cycle 2 Day 1"

Clinical data • IO biomarker • Late-breaking abstract • Metastases • P1 data • Oncology • Solid Tumor • Urothelial Cancer • IFNG • PPARG

Safety and clinical activity of FX-909, a first-in-class oral small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of luminal lineage in patients with advanced urothelial carcinoma (AACR-NCI-EORTC 2025) - P1 | "FX-909 demonstrated a favorable safety profile and is the first small molecule targeting PPARG to show clinical antitumor activity in advanced UC. A randomized Phase 1B expansion study investigating FX-909 (30 or 50 mg QD) is ongoing in prospectively biomarker-selected pts with PPARG high advanced UC in the second line or beyond."

Clinical • Late-breaking abstract • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FABP4 • PPARG

Safety and clinical activity of FX-909, a first-in-class oral small molecule inhibitor of peroxisome proliferator-activated receptor gamma (PPARG), a master regulator of luminal lineage in patients with advanced urothelial carcinoma (AACR-NCI-EORTC 2025) - P1 | "FX-909 demonstrated a favorable safety profile and is the first small molecule targeting PPARG to show clinical antitumor activity in advanced UC. A randomized Phase 1B expansion study investigating FX-909 (30 or 50 mg QD) is ongoing in prospectively biomarker-selected pts with PPARG high advanced UC in the second line or beyond."

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FABP4 • PPARG

Flare Therapeutics Presents Part A Data from FX-909 Phase 1 Study at AACR-NCI-EORTC International Conference (GlobeNewswire) - "Preliminary anti-tumor activity was also observed at all doses evaluated in advanced UC patients (4 PRs, 1 CR). Efficacy was enriched in patients with high expression of PPARG by immunohistochemistry. Tumor shrinkage was observed in 70% of the 20 UC patients with high expression of PPARG. FX-909 has an acceptable safety and tolerability profile....Based on the totality of the Part A data, 30 mg and 50 mg QD doses were selected for further optimization."

P1 data • Urothelial Cancer

FX-909 Next Steps (GlobeNewswire) - "A validated immunohistochemistry (IHC)-based test has been developed to identify patients eligible for enrollment in the expansion study. The company expects interim efficacy data in a biomarker-defined population at the recommended Phase 2 dose in the first quarter of 2026."

Biomarker • P1 data • Urothelial Cancer

Flare Therapeutics to Present Correlative Biomarker Analysis from the FX-909 Phase 1A Clinical Study at Upcoming SITC 2025 40th Anniversary Annual Meeting (GlobeNewswire) - "The presentation at SITC will build on the first disclosure of the part A data from the ongoing Phase 1 study for FX-909, which were recently presented at the AACR-NCI-EORTC International Conference, and include novel insights regarding FX-909’s immune modulatory mechanism of action."

Biomarker • P1 data • Urothelial Cancer

Flare Therapeutics Announces Clinical Trial Collaboration and Supply Agreement with Merck to Evaluate FX-909 in Combination with KEYTRUDA (pembrolizumab) in New Cohort of Ongoing Phase 1 Trial in Metastatic Urothelial Cancer (GlobeNewswire) - "Under the terms of the supply agreement, Merck will provide its anti-PD-1 therapy KEYTRUDA to be used in combination with FX-909. The Phase 1 study combination cohort is expected to begin enrollment in the first quarter of 2026 and will investigate the safety, tolerability, immunologic effects and preliminary efficacy of escalating doses of FX-909 in combination with standard dose pembrolizumab in patients with advanced urothelial carcinoma."

Commercial • Trial status • Urothelial Cancer

Flare Therapeutics to Present FX-909 Phase 1A Data in Oral Presentation at Upcoming AACR-NCI-EORTC International Conference (GlobeNewswire) - "FX-909 is...currently in a Phase 1B study for the treatment of locally-advanced or metastatic urothelial cancer (UC)."

P1 data • Urothelial Cancer

Structural Basis of PPARγ-Mediated Transcriptional Repression by the Covalent Inverse Agonist FX-909. (PubMed, J Med Chem) - "The crystal structure of PPARγ LBD cobound to FX-909 and the NCoR1 corepressor peptide reveals a repressive conformation shared by other covalent inverse agonists. These findings build on recent studies highlighting the pharmacological significance and clinical relevance of transcriptionally repressive PPARγ inverse agonists."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • NCOR1 • PPARG

Flare Therapeutics Announces Initiation of Phase 1B Study of FX-909 for Treatment of Metastatic Urothelial Cancer (GlobeNewswire) - "Flare Therapeutics...announced that it has dosed the first patients in its Phase 1B clinical trial evaluating FX-909, a first-in-class orally available small molecule inhibitor of PPARG, a master regulator of the luminal lineage, for the treatment of locally-advanced or metastatic urothelial cancer (UC)....FX-909 has achieved clinical proof-of-concept in a Phase 1A study, as a monotherapy, based on pre-specified criteria. The company expects to present these data at a scientific conference in 2025. The Phase 1B study will evaluate safety and efficacy to determine the recommended Phase 2 dose in a biomarker-defined population....The company expects to report efficacy data in a biomarker-defined population at the recommended Phase 2 dose in the first quarter of 2026."

P1 data • Trial status • Urothelial Cancer

Structural basis of PPARγ-mediated transcriptional repression by the covalent inverse agonist FX-909. (PubMed, bioRxiv) - "The crystal structure of PPARγ LBD cobound to FX-909 and NCoR1 corepressor peptide reveals a repressive conformation shared by other covalent inverse agonists. These findings build on recent studies highlighting the pharmacological significance and clinical relevance of transcriptionally repressive PPARγ inverse agonists."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • NCOR1 • PPARG

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