AsherBio

Flare Therapeutics Presents Data at AACR 2024 Annual Meeting Characterizing PPARG-Derived Immune Cell Patterns in Urothelial Cancer Patients After Anti-PD1 Therapy

— Data support the potential to explore lead Phase 1 monotherapy asset FX-909 in combination with an anti-PD1 agent —

 

Cambridge, MA – April 9, 2024 – Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today shared data identifying immunosuppressive cell phenotypes associated with high PPARG expression in urothelial cancer (UC) patients treated with anti-PD1 therapy in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024 taking place April 5-10 in San Diego, California.

 

“Translational insights from our single cell analysis shed further light on the role that PPARG expression plays in the immune cell phenotypes of advanced UC patients following anti-PD1 therapy,” said Michaela Bowden, Ph.D., Chief Development Officer at Flare Therapeutics. “The ongoing study of our lead asset FX-909 – which is currently being evaluated as a monotherapy in a Phase 1 clinical study – includes an exploratory biomarker approach to assess the effect of PPARG inhibition on the innate and adaptive immune response of the patients enrolled, and may inform the ability to expand this novel treatment into a potential combination treatment strategy in the future.”

 

The poster, titled, “PPARG-high circulating monocytes exhibit an immunosuppressive phenotype in urothelial cancer patients treated with anti-PD1,” offers a comprehensive analysis of PPARG expression in peripheral blood mononuclear cells (PBMCs) of advanced UC patients. PPARG has been previously associated with immune-mediated resistance and is upregulated in a variety of immune cells such as monocytes, macrophages, and lymphocytes, where it plays a role in their maturation and function.

 

Flare Therapeutics scientists showed that circulating classical monocytes harboring high levels of PPARG expression exhibited an immunosuppressive phenotype in UC patients who received anti-PD1 therapy. Findings corroborate molecular real-world data presented at the SITC 2023 Annual Meeting that demonstrated high PPARG expression in patients with muscle-invasive UC is associated with an immunosuppressive tumor microenvironment and shorter real-world progression-free survival to anti-PD1 treatment.

 

Additional key takeaways from the poster are as follows:

  • Researchers conducted single-cell RNA sequencing of PBMCs from UC patients treated with anti-PD1 therapy and healthy volunteers – evaluating over 75,000 cells and identifying nine major immune cell populations.
  • Among peripheral blood cells, the highest PPARG expression was observed within the classical monocyte (CM) population.
  • PPARG expression in circulating CMs was significantly increased in UC patients compared to healthy volunteers.
  • PPARG-high circulating classical monocytes in UC patients exhibit a transcriptomic profile associated with immunosuppression and M2 macrophage polarization.

 

About Flare Therapeutics Inc.

Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Flare Therapeutics’ proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced urothelial cancer that is currently in a Phase I study. For more information, please visit www.flaretx.com and follow us on LinkedIn.

 

Investors:

investorrelations@flaretx.com

 

Media:
Peg Rusconi
Verge Scientific Communications
peg.rusconi@vergescientific.com

AsherBio

Flare Therapeutics to Present Immune Profiling Data from Urothelial Cancer Patients Treated with Anti-PD1 Therapy at AACR 2024 Annual Meeting

Cambridge, MA – March 5, 2024 – Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced a poster presentation identifying immunosuppressive cell phenotypes 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 taking place April 5-10 in San Diego, California.

Presentation details are as follows:

Abstract Title: PPARG-high circulating monocytes exhibit an immunosuppressive phenotype in urothelial cancer patients treated with anti-PD1

Abstract Number: 5627

Presenter: Ani Phuong Nguyen, Director, Computational Biology, Flare Therapeutics

Date, Time: Tuesday, April 9, 2024, 1:30pm – 5:00pm PDT (4:30pm – 8:00pm EDT)

Location: Poster Section 15, Poster Board #6, San Diego Convention Center

About Flare Therapeutics Inc.

Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Flare Therapeutics’ proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced urothelial cancer that is currently in Phase I study. For more information, please visit www.flaretx.com and follow us on LinkedIn. 

Investors:
investorrelations@flaretx.com

Media:
Peg Rusconi
Verge Scientific Communications
peg.rusconi@vergescientific.com

AsherBio

Flare Therapeutics Presents FX-909 Phase 1 Dose Escalation and Expansion Clinical Trial Design at the 2024 ASCO Genitourinary Cancers Symposium

Cambridge, Massachusetts – January 26, 2024 – Flare Therapeutics Inc., a biotechnology company targeting transcription factors (TF) to discover precision medicines for cancer and other diseases, 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.

“FlareTx has built a robust body of preclinical evidence that supports investigation of FX-909 in clinical trials in patients,” said Michael L. Meyers, M.D., Ph.D., Chief Medical Officer of Flare Therapeutics. “Results shown to date reveal that FX-909 eradicates tumors in urothelial cancer (UC) animal models at low oral doses. Our scientists have also leveraged high PPARG expression as a defining feature of luminal muscle-invasive UC (MIUC) to identify genetically defined populations and select the patients that may be more likely to benefit from a treatment like FX-909. In addition, we recently shared novel translational data correlating increased PPARG expression with an immunosuppressive tumor microenvironment (TME) and shorter real-world progression-free survival to anti-PD1 treatment.”

PPARG drives luminal cell identity and accounts for two-thirds of all advanced cases of UC. Targeting PPARG offers a novel approach to treating advanced UC that could pave the way to improved clinical outcomes in patients with a luminal subtype. Treatment of genetically defined UC xenografts with FX-909 has shown an 84% tumor growth inhibition at a dose expected to be equivalent to a 50 mg dose in humans – the starting dose in the Phase 1 clinical study.

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. Exploratory objectives include the evaluation of patient selection biomarkers from tissue and blood samples and association with clinical outcomes. In the US, approximately 10 sites are planned for Phase 1A and 12-15 sites for Phase 1B.

“While advanced bladder cancer and MIUC remain lethal diseases, we are starting to see a real renaissance in providing new treatment options, thanks to increasing knowledge of the underlying molecular pathways involved,” said Gopa Iyer, Genitourinary Oncologist & Early Drug Development Specialist, Memorial Sloane Kettering Cancer Center. “FlareTx’s novel mechanism of action offers the possibility of a much needed second line option for patients who demonstrate disease progression following standard-of-care platinum chemotherapy, immune checkpoint inhibition, and/or ADC-based therapies.”

Details for the presentation are as follows:

Poster Title: A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 in Patients with Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma

Abstract Number: TPS709

Presenter: Gopa Iyer MD, Memorial Sloane Kettering Cancer Center

Date, Time: Session B: Urothelial Carcinoma – Friday, January 26, 2024, 11:30 AM-1:00 PM PT; 5:45 PM-6:45 PM PT

Location: Moscone West Conference Center, San Francisco, California Posters, Exhibits, and Food Room

About FX-909

Flare Therapeutics’ lead investigational compound, FX-909, is a first-in-class, 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)

There are 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). 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 which represents approximately 65% of all advanced UC cases (Robertson, Cell 2017). Recurrent genetic alterations in PPARG are characteristic of this molecular subtype.

About Flare Therapeutics Inc.

Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced urothelial cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

Investors:

Anne Marie Fields

Stern Investor Relations

annemarie.fields@sternir.com

 

Media:

Marites Coulter

Verge Scientific Communications

marites.coulter@vergescientific.com

 

AsherBio

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

Cambridge, MA – November 3, 2023 – Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, 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.

“While immunotherapy approvals have changed the treatment landscape for MIUC, approximately 70% of patients will still succumb to refractory or acquired resistance,” said Michaela Bowden, Ph.D., Chief Development Officer at Flare Therapeutics. “These results offer a unique opportunity to further investigate an immune-mediated mechanism of action for FX-909 with the potential to combine with an anti-PD1 agent.”In the poster presentation titled, “PPARG amplification is associated with lack of response to anti-PD1 in Muscle-Invasive Urothelial Cancer,”

Molecular RWD, comprising 1,393 genomic and/or transcriptomic profiles from MIUC patients were utilized to evaluate baseline PPARG expression and amplification associated with anti-PD1 response in MIUC patients. Additional key takeaways are as follows:

  • Higher PPARG expression and PPARG amplification are negatively correlated with PD-L1 expression in MIUC.
  • Tumors with elevated PPARG levels and PPARG amplification exhibited a suppressive immune phenotype, typified by an inverse association with CD8+ T cell infiltration.
  • PPARG amplification is significantly associated with shorter real-world Progression Free Survival to anti-PD1.

FX-909, a first-in-class covalent PPARG inhibitor, entered the clinic this year and is currently being evaluated in a Phase 1 study. 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.

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.

About Flare Therapeutics Inc.

Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced Urothelial Cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

Investors:

Julie Seidel
Stern Investor Relations
julie.seidel@sternir.com 

Media:

Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com

AsherBio

Flare Therapeutics to Present New Translational Data in Support of Clinical Candidate FX-909’s Phase 1 Development at SITC 2023 Annual Meeting

Cambridge, MA – October 31, 2023 – Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, 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.

Details for the presentation are as follows:

Abstract Title: PPARG amplification is associated with lack of response to anti-PD1 in Muscle-Invasive Urothelial Cancer

Abstract Number: 537

Presenter: Evisa Gjini, Senior Director, Translational Medicine, Flare Therapeutics

Date, Time: Friday, November 3, 2023, 9:00am – 7:00pm PDT (12:00pm – 10:00pm EDT)

Location: Exhibit Halls A and B1, San Diego Convention Center, San Diego

About Flare Therapeutics Inc.
Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced Urothelial Cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

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. FX-909 is currently undergoing investigation in a Phase 1 clinical study, a first-in-human, dose-escalation and expansion study evaluating safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity. 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 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.

Investors:
Julie Seidel
Stern Investor Relations
julie.seidel@sternir.com 

Media:
Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com

AsherBio

Flare Therapeutics Announces First Patients Dosed in First-in-Human Phase 1 Clinical Study of FX-909 in Advanced Solid Malignancies, Including Urothelial Cancer

Cambridge, Massachusetts – October 19, 2023 Flare Therapeutics Inc., a biotechnology company targeting transcription factors (TF) to discover precision medicines for cancer and other diseases, 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.

“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.

About Flare Therapeutics Inc.
Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced urothelial cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

Investors:
Julie Seidel
Stern Investor Relations
julie.seidel@sternir.com

Media:
Marites Coulter
Verge Scientific Communications
marites.coulter@vergescientific.com

AsherBio

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

– Approach has potential to identify patients likely to respond to PPARG inhibition through FX-909 –
– AI-powered, end-to-end learning model was developed in collaboration with PathAI –

Cambridge, Massachusetts – October 13, 2023 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, 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). These findings were shared at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held in Boston, Mass. from October 11-15, 2023.

“The digitization of pathology has ushered in a new era of AI and machine learning that can inform patient diagnosis and guide clinical decision-making. We are excited to be at the forefront of applying these innovative biomarker approaches to identify patients with advanced urothelial cancer that may potentially respond to PPARG inhibition,” said Michaela Bowden, Chief Development Officer at Flare Therapeutics. “High PPARG expression is a defining feature of luminal MIUC, accounting for approximately 65% of cases in the advanced and metastatic setting. The ability to further stratify patient subsets could offer a powerful tool to inform the path forward for therapy that could include Flare Therapeutics’ lead investigational compound, FX-909.”

The poster presentation, titled “AI Analysis of Histological Images Accurately Identifies Luminal Subtype Urothelial Carcinomas Characterized by High PPARG Expression,” analyzed H&E-stained slides from 367 unique primary MIUC cases obtained from the TCGA BLCA dataset and 42 MIUC cases from an independent dataset. An end-to-end additive multiple-instance learning model was deployed, resulting in excellent performance typified by AUROC values greater than or equal to 95%, correctly classifying advanced urothelial cancer of luminal subtype, across the test, validation and independent data sets.

“We conducted machine-learning driven analyses of digital images from H&E-stained tissues to identify patients with luminal MIUC,” said Michael Montalto, Chief Scientific Officer at PathAI. “We are highly encouraged by the initial results relative to current molecular approaches and look forward to collaborating with the Flare Therapeutics team to evaluate the performance of this novel algorithm in support of the FX-909 program. The model could have tremendous utility in helping to improve MIUC patient outcomes. It was a pleasure to work closely with the Flare Therapeutics team and apply our model to a real-world application.”

FX-909 is a first-in-class novel, highly potent and selective small molecule that inhibits PPARG to treat patients with the luminal subtype of advanced UC. The Company recently initiated clinical trials for FX-909.

About Flare Therapeutics Inc.
Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced Urothelial Cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

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). FX-909 is currently undergoing investigation in a Phase 1 clinical study, a first-in-human, dose-escalation and expansion study evaluating safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity. 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 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.

Investors:
Julie Seidel
Stern Investor Relations
julie.seidel@sternir.com

Media:
Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com

AsherBio

Flare Therapeutics to Present Biomarker Data for Clinical Candidate FX-909 at 2023 AACR-NCI-EORTC International Conference

Cambridge, MA – October 4, 2023 – Flare Therapeutics Inc., a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today 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.

Details for the poster presentation are as follows:
Abstract Title: AI analysis of histological images accurately identifies luminal subtype urothelial carcinomas characterized by high PPARG expression
Poster Number: B016
Presenter: Stefan Kirov, Vice President, Computational Biology, Flare Therapeutics
Date/Time: Friday, October 13, 2023, from 12:30 to 4:00 p.m. ET
Location: Exhibit Hall D, Hynes Convention Center, Boston

About Flare Therapeutics Inc.
Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics’ integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential. Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced Urothelial Cancer that has entered the clinic. For more information, please visit www.flaretx.com and follow us on LinkedIn.

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). FX-909 is currently undergoing investigation in a Phase 1 clinical study, a first-in-human, dose-escalation and expansion study evaluating safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity. 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 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.

Investors:
Julie Seidel
Stern Investor Relations
julie.seidel@sternir.com 

Media:
Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com

AsherBio

Flare Therapeutics Named to Inc. Magazine’s Annual List of Best Workplaces for 2023

Cambridge, MA – May 9, 2023 – Flare Therapeutics Inc., a biotechnology company targeting
transcription factors to discover precision medicines for cancer and other diseases, has been
named to Inc. magazine’s annual Best Workplaces list. The list is a result of a comprehensive
measurement of American companies that have excelled in creating exceptional workplaces
and company culture, whether operating in a physical or virtual facility.

The Inc. Best Workplaces recognizes the companies that foster a unique culture that thrives in
the face of adversity, fosters employee growth and advancement at all levels, and redefines the
workplace and continues to enrich it.

“We are honored to be included in Inc. Magazine’s Annual List of Best Workplaces for 2023. At
Flare, we believe that our exceptional culture is a direct reflection of our people. By prioritizing
the well-being and success of our team members, we create a positive and collaborative work
environment where innovation and excellence thrive,” said Amit Rakhit, M.D., M.B.A., Chief
Executive Officer of Flare Therapeutics. “The team’s passion, creativity, and dedication shape
the way we work, interact, and achieve our goals and makes us excited to come to work every
day. We are immensely appreciative for all our employees who have contributed to the success
and culture of the company, and we look forward to advancing our business and delivering on
our mission to deliver cutting-edge medicines for patients.”

After collecting data from thousands of submissions, Inc. selected almost 600 honorees this
year. Each company that was nominated took part in an employee survey, conducted by
Quantum Workplace, which included topics such as management effectiveness, perks, fostering
employee growth, and overall company culture. The organization’s benefits were also audited to
determine overall score and ranking.

“Being named to Best Workplaces is an honor that only a small fraction of companies have
been able to claim,” says Inc. editor-in-chief Scott Omelianuk. “Proving to the world that you’re a
magnet for talent and have a culture that keeps teams engaged, productive, and proud to come
to work is a truly remarkable achievement.”

About Flare Therapeutics Inc.
Flare Therapeutics is a biotechnology company changing the paradigm in drugging transcription
factors with an initial focus in precision oncology. Flare’s proprietary engine is founded on the
identification of novel druggable pockets, or ‘switch sites’, within transcription factor complexes
that solve for where to drug and how to tune gene expression to discover small molecule
precision medicines for cancer and other diseases. The team has rapidly advanced an
emerging pipeline of assets and plans to advance its lead precision oncology program, FX-909,
a small molecule inhibitor targeting PPARG into the clinic in 2023 in individuals with locally
advanced or metastatic urothelial cancer. For more information, please visit www.flaretx.com.

About Inc. Media
The world’s most trusted business-media brand, Inc. offers entrepreneurs the knowledge, tools,
connections, and community to build great companies. Its award-winning multiplatform content
reaches more than 50 million people each month across a variety of channels including
websites, newsletters, social media, podcasts, and print. Its prestigious Inc. 5000 list, produced
every year since 1982, analyzes company data to recognize the fastest-growing privately held
businesses in the United States. The global recognition that comes with inclusion in the 5000
gives the founders of the best businesses an opportunity to engage with an exclusive
community of their peers, and the credibility that helps them drive sales and recruit talent. The
associated Inc. 5000 Conference is part of a highly acclaimed portfolio of bespoke events
produced by Inc. For more information, visit www.inc.com.

About Quantum Workplace
Quantum Workplace, based in Omaha, Nebraska, is an HR technology company that serves
organizations through employee-engagement surveys, action-planning tools, exit surveys, peer-to-
peer recognition, performance evaluations, goal tracking, and leadership assessment. For
more information, visit QuantumWorkplace.com.

Flare Media:
Marites Coulter
Verge Scientific Communications
mcoulter@vergescientific.com

AsherBio

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

–FX-909 is highly potent and selective for the PPARG transcription factor, and demonstrates tumor eradication in preclinical animal models of urothelial cancer at low oral doses–

–Therapeutic efficacy of FX-909 assessed through gene expression profiling of normal skin tissue, potentially offers a less invasive surrogate biospecimen collection method compared to a traditional tumor biopsy–

Cambridge, Mass – April 17, 2023 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today 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.

“These initial findings suggest that FX-909 could become a backbone therapy for patient populations harboring the luminal subtype of UC, much like ER therapies in the luminal subtype of breast cancer,” said Rob Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare. “We are eager to continue advancing FX-909, which will be further evaluated in a Phase 1 trial that will begin later in the year. This will be a milestone moment for Flare, as we are the first company slated to enter the clinic with a small molecule inhibitor targeting the PPARG transcription factor for advanced UC.”

Flare is building a pipeline of potentially first-in-class therapies against genetically validated transcription factor targets, initially focused on cancer. Although challenging to drug, elusive transcription factors remain high-value targets across numerous disease categories, most notably oncology. Treatments that target cell lineage have become mainstay therapies in breast and prostate cancer, through the successful inhibition of the estrogen receptor (ER) and androgen receptor (AR) transcription factors. Similar to ER and AR, PPARG drives luminal cell identity and accounts for two thirds of all advanced UC, highlighting its potential as a therapeutic target.

The oral presentation, titled, “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),” shows that administration of FX-909 elicited durable tumor regressions in animal models of UC. The projected human starting dose of 50 mg/kg is also anticipated to be pharmacologically active.

Additional key takeaways are as follows:

  • FX-909 is a highly selective and potent covalent small molecule inhibitor of PPARG (cellular EC50, 1 nM), showing >2000-fold selectivity for PPARG over PPARA/PPARD (related transcription factors) – acting through a mechanism that promotes a repressive conformation of PPARG.
  • FX-909 inhibited cell growth in UC cell lines with activated PPARG signaling but had no effect on cell lines without activated PPARG.
  • 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.
  • FX-909 demonstrated predictable, on-target and reversible pharmacology in normal tissues at supra-pharmacologic doses, mimicking PPARG loss-of-function mutations with notable remodeling in adipose tissue and the normal urothelium.

The poster presentation titled, “Development of a surrogate tissue pharmacodynamic (PD) assay for potential clinical use with FX-909, a novel inhibitor of the urothelial luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG),” outlines the FX-909-dose dependent expression of PPARG target genes as markers of PD response in tumor, adipose and skin tissue from mouse xenograft, and normal rat and normal human skin preclinical models.

“Based on our observation of the consistent correlation of PPARG target gene expression patterns in tumor and normal tissues, we have elected to develop a normal skin PD biomarker assay to support early assessment of FX-909 biological activity in our Phase 1 study,” said Michaela Bowden, Ph.D., Chief Development Officer of Flare. “These findings reinforce the importance of uncovering valuable translational insights and applying them to further guide our drug development process, potentially enabling us to reduce the burden of repeated, invasive tumor biopsy collections for patients with late-stage cancer by offering surrogate skin biopsies as a viable alternative.”

Additional key takeaways are as follows:

  • In a rat pharmacology study, 30% of all genes that responded to FX-909 treatment in skin displayed a similar dose-dependent response profile in fat.
  • PPARG target genes including FABP4/Fabp4, AGT/Agt, IVT/Ivd and ARG1/Arg1 are repressed across different species and/or tissues, exemplified by dose-dependent suppression of FABP4/Fabp4 (atarget gene for PPARG) and showing a strong correlation (r=0.98, p value=0.003) between tumor and skin tissues.
  • Skin explant models bridge the interspecies translational gap for studying FX-909-mediated effects, where preliminary evidence shows on-target regulation of genes involved in known PPARG-mediated processes.

About Urothelial Cancer
Bladder cancer is the third most common cancer in men in the United States alone. 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. This disease has high rates of recurrence and the five-year survival rate is approximately 15% 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 cases. 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 changing the paradigm in drugging transcription factors with an initial focus in precision oncology. Flare’s proprietary engine is founded on the identification of novel druggable pockets, or ‘switch sites’, within transcription factor complexes that solve for where to drug and how to tune gene expression to discover small molecule precision medicines for cancer and other diseases. The team has rapidly advanced an emerging pipeline of assets and plans to advance its lead precision oncology program, FX-909, a small molecule inhibitor targeting PPARG into the clinic in 2023 in individuals with locally advanced or metastatic urothelial cancer. For more information, please visit www.flaretx.com.

 

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