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–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
Cambridge, MA – March 14, 2023 – Flare Therapeutics Inc., a private biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced that it will give an oral presentation highlighting the discovery of its clinical candidate FX-909, at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida.
Presentation Details are as follows:
Abstract Title: Discovery of FX-909, a first-in-class inverse agonist of the peroxisome proliferator-activated receptor gamma (PPARG) lineage transcription factor, to treat patients with the luminal subtype of advanced urothelial cancer (UC)
Session Category: Drug Development Track Special Session
Session Title: New Drugs on the Horizon: Part 2
Presenter: Robert Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare
Date/Time: Sunday, April 16, 2023 from 3:00 to 4:30 p.m. ET
Location: Tangerine Ballroom 2, Convention Center
Flare is advancing FX-909 into the clinic in patients with advanced urothelial cancer (UC). FX-909 is a potent, selective, small molecule inhibitor of the PPARG lineage transcription factor. In pre-clinical models, FX-909 displays meaningful PPARG target gene silencing in UC cell lines as well as tumor regression in PPARG-amplified and RXRA-mutant UC xenograft models.
About Flare Therapeutics Inc.
Flare Therapeutics is a private 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 advanced 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
Cambridge, Mass. – February 2, 2023 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced that Robert Sims, Ph.D., Chief Scientific Officer and co-founder at Flare Therapeutics, will present a company overview at the upcoming Guggenheim Healthcare Talks Oncology Day on Thursday, February 9, 2023 at 2:45 p.m. ET in New York, NY.
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 what to optimize for in tuning 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. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.
Contacts
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
Media:
Michelle Thaler
Michelle Thaler PR, LLC
516-225-4313
Cambridge, Mass. – November 22, 2022 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced that Daphne Karydas, Chief Operating Officer and Chief Financial Officer of Flare Therapeutics, will present a company overview at 9:30 a.m. ET on Thursday, December 1, 2022 at the Piper Sandler 34th Annual Healthcare Conference being held in New York, NY.
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 what to optimize for in tuning 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. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.
Contacts
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
Media:
Michelle Thaler
Michelle Thaler PR, LLC
516-225-4313
Cambridge, Mass. – October 28, 2022 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today presented translational insights from a retrospective advanced urothelial cancer (UC) cohort in a poster titled, “Peroxisome Proliferator-Activated Receptor Gamma (PPARG) status defines the luminal lineage in molecular profiles of advanced urothelial cancers (UC)” at the 34th EORTC-NCI-AACR Symposium, being held in Barcelona, Spain. Molecular RWD, comprising of more than 3,000 genomic and transcriptomic profiles from advanced UC tissue, were utilized to evaluate the transcription factor PPARG, and its role as a master regulator of the luminal lineage associated with its expression and mutational status.
“To the best of our knowledge, this represents the largest RWD from patients with advanced and metastatic urothelial cancer, providing unique insights into the persistence of PPARG signaling through disease progression, independent of the treatment paradigm,” said Michaela Bowden, Ph.D., Senior Vice President of Biology and Translation at Flare Therapeutics. “Stratification of patients based upon their PPARG status serves as the foundation for our precision approach in identifying individuals most likely to respond to PPARG inhibition.”
Flare presented its novel PPARG program demonstrating robust preclinical activity in a poster presentation titled, “Novel inhibitors of the luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG) durably eradicate tumors in urothelial cancer animal models” on Wednesday, October 26th at same symposium.
Data highlights:
Flare is advancing a novel PPARG inhibitor through Investigational New Drug (IND)-enabling studies and expects to initiate its Phase 1 clinical trial in 2023 in individuals with locally advanced or metastatic UC.
About Advanced Urothelial Cancer
Muscle-invasive UC is a common type of bladder cancer, with about 20,000 individuals diagnosed each year in the United States alone, and significantly higher incidence rates in other regions of the world. This disease has high rates of recurrence and the five-year survival rate is approximately 5% in metastatic cases. The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC patients. Recurrent genetic alterations in PPARG, including focal amplification, missense mutations, and fusions, as well as hotspot mutations in its binding partner, retinoid X receptor alpha (RXRA) are characteristic of this molecular subtype.
About Flare Therapeutics
Flare Therapeutics is a biotechnology company pioneering a new therapeutic space with a novel approach to decipher the biology of transcription factors to develop small molecule medicines. Based on insights from the seminal work of its scientific founders, Flare’s team has uncovered ‘switch sites,’ druggable regions that are key targets for transcription factor regulation, to address mutations that cause disease. Flare’s drug discovery efforts to target switch sites has rapidly advanced, resulting in an emerging pipeline of research programs that address well-validated genetically-defined transcription factors, initially focused on precision oncology with future potential in neurology, rare genetic disorders, immunology and inflammation. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.
Contacts
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
Sarah.mccabe@sternir.com
Media:
Michelle Thaler
Michelle Thaler PR, LLC
516-225-4313
Michelle@ThalerComms.com
– First data showing durable in vivo tumor regression in urothelial cancer (UC) animal models
– Data highlight the potential for novel small molecule inhibitors of key transcription factors to target and effectively treat advanced UC
Cambridge, Mass. – October 26, 2022 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today presented new preclinical data in a poster presentation titled, “Novel inhibitors of the luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG) durably eradicate tumors in urothelial cancer (UC) animal models” at the 34th EORTC-NCI-AACR Symposium in Barcelona, Spain. The data presented by Robert Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare, show that FTX-6746, a potent, selective, small molecule PPARG inhibitor (inverse agonist), drives robust PPARG target gene silencing in UC cell lines and drives tumor regression in PPARG-amplified and RXRA-mutant UC xenograft models.
“Targeting cell lineage-defined transcription factors with small molecules is a proven and effective therapeutic strategy, as demonstrated by estrogen and androgen receptor therapies for breast and prostate cancers. Our goal is to add PPARG to that list, to potentially enable treatment of urothelial cancers. Leveraging our deep expertise in transcription factor biochemistry, we engineered compounds capable of driving a powerful repressive conformation of PPARG with high specificity, thereby inducing significant pharmacological effects,” said Dr. Sims. “In preclinical models, FTX-6746 demonstrated a favorable therapeutic profile, suppressing PPARG target genes with durable tumor regression at well-tolerated doses. We are currently advancing a novel PPARG inhibitor through IND-enabling studies and plan to advance that therapeutic candidate into the clinic in 2023 in locally advanced or metastatic UC.”
Data highlights:
• FTX-6746 drives an enhanced repressive conformation to overcome UC mutations
• FTX-6746 counteracts the activating effects of recurrent PPARG and RXRA missense mutations in preclinical models of UC
• FTX-6746 treatment results in robust PPARG target gene silencing in cells (average 50% maximal inhibitor concentration (IC50) ~5 nM); in vitro growth inhibition is preferentially observed in cell lines with activated PPARG signaling
• Tumor growth inhibition or regression was observed in PPARG-amplified and RXRA-mutant UC xenograft models, with no tumor regrowth upon cessation of treatment
“Today’s data presentation demonstrates the strength and depth of Flare’s research platform and our teams’ ability to rapidly advance a first-in-class molecule in precision oncology,” said Amit Rakhit, M.D., Chief Executive Officer of Flare Therapeutics. “Flare is poised to transition to a clinical-stage company early next year with our lead molecule in the PPARG program. Given the high unmet medical need with poor survival in advanced stages of disease, novel approaches that provide alternative therapeutic options are needed for people living with bladder cancer.”
About Urothelial Cancer
Muscle-invasive UC is a common type of bladder cancer, with about 20,000 individuals diagnosed each year in the United States alone, and significantly higher incidence rates in other regions of the world. This disease has high rates of recurrence and the five-year survival rate is approximately 5% in metastatic cases. The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC patients. Recurrent genetic alterations in PPARG, including focal amplification, missense mutations, and fusions, as well as hotspot mutations in its binding partner, retinoid X receptor alpha (RXRA) are characteristic of this molecular subtype.
About Flare Therapeutics
Flare Therapeutics is a biotechnology company pioneering a new therapeutic space with a novel approach to decipher the biology of transcription factors to develop small molecule medicines. Based on insights from the seminal work of its scientific founders, Flare’s team has uncovered ‘switch sites,’ druggable regions that are key targets for transcription factor regulation, to address mutations that cause disease. Flare’s drug discovery efforts to target switch sites has rapidly advanced, resulting in an emerging pipeline of research programs that address well-validated genetically-defined transcription factors, initially focused on precision oncology with future potential in neurology, rare genetic disorders, immunology and inflammation. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.
Contacts
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
Sarah.mccabe@sternir.com
Media:
Michelle Thaler
Michelle Thaler PR, LLC
516-225-4313
Michelle@ThalerComms.com
Biopharma industry veteran to lead advancement of company’s transcription factor-focused pipeline into clinical stage and expand discovery efforts
Cambridge, Mass. – July 25, 2022 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced the appointment of Amit Rakhit, M.D., MBA, as President and Chief Executive Officer. Dr. Rakhit has over 20 years of life sciences leadership experience and joins at a pivotal time as Flare transitions into a clinical-stage company. He succeeds interim CEO Abbie Celniker, Ph.D., a partner at Third Rock Ventures, who will continue to serve as Chair of the Company’s Board of Directors.
“Flare’s pioneering approach to drugging transcription factors stands to profoundly impact medical practice globally for people living with cancer and other difficult to treat diseases. I am excited to join such a dynamic and experienced leadership team at this important inflection point for the company,” said Dr. Rakhit. “The team’s swift progress in identifying dozens of novel druggable pockets, or ‘switch sites’, within therapeutic transcription factor targets of interest and rapid advancement of the lead precision oncology program both inspired my belief in Flare and compelled me to join to help catapult the company into its next stage of growth.”
“Dr. Rakhit’s experience includes a rare mix of business acumen, clinical development expertise and passion for leading innovation in new treatment modalities that can benefit patients,” said Dr. Celniker. “His leadership and experience will be extremely valuable in driving the strategy forward as we transition our first precision oncology program into the clinic and grow our pipeline of discovery targets in multiple new therapeutic indications.”
For more than two decades, Dr. Rakhit has served in key leadership, clinical and operational roles in biotechnology and pharmaceutical companies spanning diverse therapeutic areas including rare disease, neurology, oncology and cardiology. Most recently, he has focused on launching and growing start-up biotechnology companies, overseeing clinical development and commercialization strategy in roles as CEO of Sporos BioVentures and President and Chief Medical Officer of Ovid Therapeutics. Earlier in his career, he was Senior Vice President and Head of Worldwide Medical Affairs at Biogen, Inc. where he led global external collaborations with key stakeholders and executed post-marketing development strategies for the launch and commercialization of key products in rare disease, including Spinraza®, and in neurology. Prior to Biogen, he held multiple roles of increasing seniority in global clinical development and medical affairs at Bristol-Myers Squibb, including spearheading global initiatives for Plavix®. Dr. Rakhit holds an M.D. from Tufts University School of Medicine and dual MBAs from Columbia University and London Business School. He completed his fellowship in pediatric cardiology at Harvard Medical School and was previously on staff at Boston Children’s Hospital.
About Flare Therapeutics
Flare Therapeutics is a biotechnology company pioneering a new therapeutic space with a novel approach to decipher the biology of transcription factors to develop small molecule medicines. Based on insights from the seminal work of its scientific founders, Flare’s team has uncovered ‘switch sites,’ druggable regions that are key targets for transcription factor regulation, to address mutations that cause disease. Flare’s drug discovery efforts to target switch sites has rapidly advanced, resulting in an emerging pipeline of drug programs that address well-validated transcription factors, initially focused on precision oncology with future potential in neurology, rare genetic disorders, immunology and inflammation. Flare Therapeutics was launched in 2021 and is backed by founding investor Third Rock Ventures, as well as Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.
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Contacts
Investors:
Sarah McCabe
Stern Investor Relations, Inc.
Sarah.mccabe@sternir.com
Media:
Michelle Thaler
Michelle Thaler PR, LLC
516-225-4313
Michelle@ThalerComms.com
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