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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:
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
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
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
– 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
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
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
–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:
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:
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.
IRVING, Texas and CAMBRIDGE, Massachusetts, April 13, 2023 – Caris Life Sciences®(Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare, and Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced a multi-year strategic collaboration to accelerate precision medicine approaches across five of Flare’s therapeutic programs into clinical trials through advanced molecular profiling approaches that guide patient selection and participation.
The partnership reinforces Flare’s commitment to longitudinal testing, leveraging Caris’ comprehensive molecular tissue and liquid profiling services including whole exome sequencing and whole transcriptome sequencing for patients enrolled in Flare’s clinical trials, while also applying Caris’ data and analytics tools to bolster future clinical trial enrollment programs and companion diagnostics capabilities.
“We understand the importance of shaping translational insights early on as a major area of focus to help ensure efficient drug development at scale and clinical trial preparedness,” said Michaela Bowden, Ph.D., Chief Development Officer at Flare. “With access to Caris’ robust clinico-genomic real-world data, comprehensive molecular profiling and extensive precision oncology alliance network, we are well positioned to unlock the full potential of drugging transcription factors by further unraveling the molecular complexities of cancer at the patient level and successfully enter the next phase of our growth as a clinical stage company.”
Through comprehensive molecular profiling and the application of advanced artificial intelligence and machine learning, Caris has created the largest clinico-genomic database coupled with cognitive computing to unravel the molecular complexity of disease. Under the terms of the agreement, Flare will leverage Caris’ industry-leading next generation sequencing technology for the molecular testing of patients treated with Flare’s assets. In addition, Flare will receive access to Caris’ data insights and analytics capabilities to accelerate oncology drug discovery, identify novel biomarkers and optimize clinical positioning strategies for their pipeline. Flare will also leverage Caris’ biomarker-driven patient selection for clinical trials, allowing Caris the first option to develop a companion diagnostic for any drug candidate developed as part of the collaboration.
“This broad partnership with Flare will leverage Caris’ leading molecular science and technology solutions to support Flare’s novel approach to decipher the biology of transcription factors to develop small molecule medicines,” said Milan Radovich, Ph.D., Senior Vice President and Chief Scientific Officer of Caris Life Sciences. “The data accessibility and continuum across real world and clinical trial populations will provide Flare the necessary insights for successful molecule discovery and development.”
About Caris Life Sciences
Caris Life Sciences® (Caris) is the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare and improve patient outcomes. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced artificial intelligence (AI) and machine learning algorithms, Caris has created the large-scale clinico-genomic database and cognitive computing needed to analyze and unravel the molecular complexity of disease. This information provides an unmatched resource and the ideal path forward to conduct the basic, fundamental research to accelerate discovery for detection, diagnosis, monitoring, therapy selection and drug development to improve the human condition.
With a primary focus on cancer, Caris’ suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps patients, physicians and researchers better detect, diagnose and treat patients. The company’s latest advancement, Caris Assure™, is a blood-based, circulating nucleic acids sequencing (cNAS) assay that combines comprehensive molecular analysis (Whole Exome and Whole Transcriptome Sequencing from blood) and serial monitoring – making it the most powerful liquid biopsy assay ever developed.
Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Tokyo, Japan and Basel, Switzerland. Caris or its distributors provide services in the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com or follow us on LinkedIn.
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.
—Oncology industry veteran and skilled drug developer Michael L. Meyers, M.D., Ph.D. to join as Chief Medical Officer—
—Daphne Karydas, Chief Operating Officer and Chief Financial Officer, promoted to President and Chief Financial Officer and Michaela Bowden, Ph.D., promoted to Chief Development Officer—
—Jigar Raythatha appointed to Board of Directors—
CAMBRIDGE, Mass., March 30, 2023 — Flare Therapeutics Inc., a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced the appointment of Michael L. Meyers, M.D., Ph.D. as Chief Medical Officer, as well as the promotions of Daphne Karydas, formerly Chief Operating Officer and Chief Financial Officer, to President and Chief Financial Officer and Michaela Bowden, Ph.D., formerly Senior Vice President, Biology & Translation, to Chief Development Officer. In addition, Flare announced the appointment of Jigar Raythatha, venture partner at Third Rock Ventures, to its Board of Directors.
“Our commitment to strengthening our team reflects the tremendous progress we have made to date and the pivotal year ahead of us as we transition into a clinical stage company,” said Amit Rakhit, M.D., M.B.A., Chief Executive Officer of Flare Therapeutics. “We are excited to welcome Michael to the team as Chief Medical Officer; his long-standing and renowned expertise in the field of oncology will be instrumental to the progress of our therapeutic programs and pipeline. Daphne and Michaela were the first two executives onboarded following Flare’s launch two years ago, and both have proven to be inspirational leaders in both internal and forward-facing capacities, bringing a diversity of perspectives and experiences that have proven invaluable.”
Michael L. Meyers, M.D., Ph.D., Chief Medical Officer
Before joining Flare, Dr. Meyers was Chief Medical Officer and SVP, Chief Development Officer at Syndax Pharmaceuticals. Previously, he had held senior-level roles at Johnson & Johnson (J&J), including Vice President, GU Oncology, Compound and Clinical Leader, and Vice President, Oncology Scientific Innovation in J&J’s London Innovation Centre. He has actively led numerous early- and late-stage oncology programs culminating in world-wide regulatory approvals and successful launches, including for ZYTIGA® (abiraterone acetate) in prostate cancer and VELCADE® (bortezomib) in multiple myeloma and non-Hodgkin’s lymphoma. He also led the medical affairs program at Aventis that investigated TAXOTERE® (docetaxel) in breast, prostate, gastric, head and neck and non-small cell lung cancers, among others. Dr. Meyers served on the faculty at Memorial Sloan Kettering Cancer Center, specializing in Clinical Immunology and Melanoma. He received his M.D. and his Ph.D. in Microbiology and Immunology from Albert Einstein College of Medicine in New York.
“I am thrilled to have the opportunity to apply my previous learnings from navigating clinical and regulatory milestones in oncology as we advance our lead program, FX-909, into a Phase 1 trial and further expand our library of compounds targeting transcription factors thought to be previously undruggable,” said Dr. Meyers. “I look forward to working with the impressive Flare team to progress the company’s precision oncology programs and bring much needed new therapeutic options to patients.”
Daphne Karydas, M.B.A., President and Chief Financial Officer
Ms. Karydas has more than 20 years of experience in financial and operations leadership roles, bringing an interdisciplinary approach to implementing growth strategies for biopharmaceutical and asset management companies. Prior to joining Flare Therapeutics in October 2021, Ms. Karydas was Chief Financial Officer for Syndax Pharmaceuticals. Previously, she worked at Allergan in roles as Senior Vice President of Corporate Financial Planning & Analysis and Strategy, where she oversaw the company’s long-term financial and business strategy until its acquisition by AbbVie in May 2020, and as Senior Vice President of Global Investor Relations and Strategy. Ms. Karydas received a BA and MS in chemical engineering from the Massachusetts Institute of Technology and an MBA from Harvard Business School.
Michaela Bowden, Ph.D., Chief Development Officer
Dr. Bowden is an accomplished research scientist with more than 15 years of interdisciplinary translational expertise spanning academia, biotech and biopharma. Prior to joining Flare in October 2021, Dr. Bowden was at Bristol Myers Squibb where she served as executive director of translational medicine and led the solid tumor team focused on addressing resistance to immuno-oncology therapies, supporting the next-gen drug development pipeline. She also held scientific leadership roles at Dana-Farber Cancer Institute establishing a multidisciplinary research model to meet future precision medicine-driven drug discovery needs. Dr. Bowden has expertise in patient-centric approaches to elucidating novel biology and biomarker insights to support clinical development, leveraging research partnerships across a diverse oncology network at the intersection of disruptive technology, real-world data and evidence and clinical diagnostics. Dr. Bowden has a BSc and Ph.D. from Dublin City University and continued her post-doctoral professional training at Tufts University and as a research fellow at Novartis Institutes for Biomedical Research, Inc.
Jigar Raythatha, Third Rock Ventures Partner, Board of Directors
Jigar Raythatha, venture partner with Third Rock Ventures, has joined the Board of Directors, bringing a wealth of expertise in precision oncology including previous leadership and board positions at Constellation Pharmaceuticals, Jounce Therapeutics and Triana Biomedicines, among others.
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.
Flare Therapeutics Contacts:
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
sarah.mccabe@sternir.com
Media:
Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com
–Financing round led by GordonMD® Global Investments LP and Pfizer Ventures, with participation from a world-class group of investors–
–Proceeds to support advancement of FX-909, a first-in-class PPARG inhibitor, into the clinic in 2023, along with continued development of Flare’s platform and pipeline of novel transcription factor targets in oncology–
Cambridge, MA – March 22, 2023 – 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. In conjunction with the financing, Craig D. Gordon, M.D., Founder, Chief Executive Officer and Chief Investment Officer of GordonMD® Global Investments LP, and Irena Melnikova, Ph.D., Partner at Pfizer Ventures, have joined the Flare Therapeutics Board of Directors.
“Our investor support is testament to the rapid progress our team has made since launch in advancing the only company focused on rationally designing transcription factor targeting therapies,” said Amit Rakhit, M.D., MBA, President and Chief Executive Officer of Flare Therapeutics. “This will be a pivotal year for Flare as we progress our first precision oncology program, FX-909, into the clinic, continue to expand our collection of druggable transcription factor targets, and build a pipeline of potentially first-in-class therapies against genetically validated transcription factor targets for cancer.”
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, as well as the advancement of a pipeline of novel transcription factor targets in oncology, including nomination of at least one additional development candidate from the company’s research pipeline in 2024.
“Transcription factors have long been viewed as prime therapeutic targets playing a key role in a broad range of diseases, particularly cancers, where they represent one-third of all oncogenes. While targeting transcription factors has the potential for incredible impact, their complex structure makes them notoriously difficult to drug, requiring a new approach and new thinking,” said Rob Sims, Ph.D., Co-founder and Chief Scientific Officer of Flare Therapeutics. “From the very beginning, we knew this would require a world-class, cross-disciplinary team to not only think creatively about how to design the platform, but also how to apply translational insights to ensure efficient drug development at scale.”
The Flare drug discovery platform is a powerful engine driving the systematic identification of switch sites, or druggable pockets within transcription factor complexes that dictate conformation and function. This is achieved through a broad and comprehensive approach that layers chemoproteomics, functional biochemistry, covalent chemistry and genetic insights to gain a deeper understanding of the structural underpinnings driving transcription factor function, and a proprietary library of compounds designed to modulate transcription factor behavior.
“Flare has taken on one of the most formidable challenges in drug discovery – drugging transcription factors,” said Craig D. Gordon, M.D., Founder, Chief Executive Officer and Chief Investment Officer of GordonMD® Global Investments LP. “The company is making impressive strides enabled by its platform, which to date has successfully identified more than 150 switch sites across the majority of transcription factor families, providing opportunities to treat a broad range of diseases.”
“We believe Flare’s differentiated and comprehensive approach to uncovering, targeting and systematically drugging switch sites on transcription factors may unlock the therapeutic potential of this class of targets, not only in oncology but in other indications as well,” said Irena Melnikova, Ph.D., Partner at Pfizer Ventures. “As a member of the board, I look forward to supporting the company in their mission to bring new medicines to patients in need.”
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.
Flare Therapeutics Contacts:
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
sarah.mccabe@sternir.com
Media:
Peg Rusconi
Verge Scientific Communications
prusconi@vergescientific.com
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