AsherBio

Flare Therapeutics Presents Comprehensive Real-World Data in Advanced and Metastatic Urothelial Cancer in Support of Therapeutic Targeting of PPARG at 2022 EORTC-NCI-AACR Symposium

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:

  • 65% of advanced urothelial cancers evaluated were classified as luminal, of which one in three were enriched for genetic alterations in PPARG, RXRA or FGFR3
  • PPARG amplification, including a gain of only one copy number, is associated with higher PPARG expression
  • PPARG expression levels were sustained in metastatic lesions compared locally advanced tissues and did not significantly vary by metastatic tissue site

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

AsherBio

Flare Therapeutics Presents Preclinical Data that Show Potential of Novel PPARG Inhibitors to Treat Urothelial Cancer at 2022 EORTC-NCI-AACR Symposium

– 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

AsherBio

Flare Therapeutics Appoints Amit Rakhit, M.D. as President and Chief Executive Officer

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.

We invite you to follow us on LinkedIn and @Flaretx.

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

AsherBio

Flare Therapeutics Appoints Adrian Jubb as Chief Medical Officer

Dr. Jubb’s research and clinical development experience strongly positions company for clinical excellence in advancing precision oncology pipeline

Cambridge, Mass. – April 26, 2022 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced the appointment of Adrian Jubb, MB ChB, PhD, FRCPath, as Chief Medical Officer. Dr. Jubb joins the Flare leadership team at a key inflection point as the company progresses from early drug discovery into clinical development.

“We are extremely fortunate to be growing Flare’s executive team with the addition of Adrian, who is vastly accomplished and brings a wealth of oncology clinical development experience,” said Abbie Celniker, PhD, interim Chief Executive Officer of Flare and partner at Third Rock Ventures. “Adrian’s leadership and deep drug development expertise will be invaluable as we enter our next phase of growth, advancing precision oncology programs from our drug discovery engine into the clinic.”

Dr. Adrian Jubb is a board-certified physician scientist with more than 20 years of research and clinical development experience spanning oncology, infectious disease and neuroscience. Dr. Jubb has devoted much of his career to the translational and clinical development of cancer medicines, including Avastin®, Tarceva®, Zelboraf®, and Cotellic®, as well as multiple investigational agents, including MetMAb, Apo2L, anti-LILRB4, anti-CD96 and anti-CD200R1. Most recently, Dr. Jubb served as Head of Clinical Oncology and Neurology at 23andMe, where he led teams accountable for the IND filings and first-in-human clinical trials for two immune-oncology checkpoint inhibitors. Prior to 23andMe, Dr. Jubb held roles as Chief Medical Officer of Immune-Onc Therapeutics, Vice President and Head of Early Development at Achaogen and Medical Director in Oncology at Genentech. He holds MB ChB (Hons), PhD, and BSc (Hons) degrees from the University of Leeds (UK) and is a Fellow of the Royal College of Pathologists in London.

“Flare’s approach to finding and drugging transcription factors may elucidate previously unexplored and meaningful treatment possibilities for cancer patients,” said Dr. Jubb. “In just one year of discovery, the Flare team has made remarkable progress identifying genetically defined targets and promising chemical matter to develop new therapeutic candidates. I am both honored and excited to join the talented team at Flare as they continue to build a portfolio and bring potentially transformative programs into the clinic.”    

About Flare Therapeutics

Flare Therapeutics is a biotechnology company opening up 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. Our 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, Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.

We invite you to follow us on LinkedIn and @Flaretx.


Contacts

 

Investors:

Sarah McCabe

Stern Investor Relations, Inc.

Sarah.mccabe@sternir.com


Media:

Michelle Thaler

Michelle Thaler PR, LLC

516-225-4313

MichelleThalerPR@gmail.com

AsherBio

Flare Therapeutics Appoints Daphne Karydas as COO and CFO, and Michaela Bowden, PhD, as SVP of Biology and Translation

Company expands leadership team across business and science as it advances precision oncology pipeline

Cambridge, Mass. – October 25, 2021 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced the appointment of Daphne Karydas as Chief Operating Officer and Chief Financial Officer, and Michaela Bowden, PhD, as Senior Vice President of Biology and Translation.

“We are thrilled to be growing Flare’s executive team with the appointment of these two outstanding and accomplished industry leaders, deepening our expertise in areas of business and science and positioning Flare for growth,” said Abbie Celniker, PhD, interim Chief Executive Officer of Flare and partner at Third Rock Ventures. “Daphne’s decades of experience in a range of financial leadership roles in the biopharma industry and her proven skills in developing and executing growth strategies will be invaluable as we evolve Flare and grow as an oncology platform and pipeline company. Michaela brings her own deep experience and a critical set of skills to lead successful biology and translational research, enabling multidisciplinary R&D strategies to bridge our leading edge oncology drug discovery to high-impact precision medicines in the clinic.”

Daphne Karydas, Chief Operating Officer and Chief Financial Officer

“I couldn’t imagine a more exciting time and opportunity to join Flare,” said Ms. Karydas. “I feel fortunate to have the opportunity to work with such a talented team focused on pioneering a dramatically new way to target transcription factors and bring new medicines to cancer patients in need. I look forward to using my experience building and leading finance teams and my operations capabilities to help a growing organization execute on its strategy, goals and mission to impact the lives of patients.”

Daphne Karydas brings to Flare over 20 years of financial and operations experience in the biopharmaceutical industry, most recently as Chief Financial Officer for Syndax Pharmaceuticals (Nasdaq: SNDX.) 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. Prior to joining Allergan, she served as Executive Director and Senior Healthcare Analyst at J.P. Morgan Asset Management and as a Portfolio Manager and Senior Healthcare Analyst at The Boston Company Asset Management, a BNY Mellon company. Earlier, Ms. Karydas was a Vice President at Goldman Sachs Asset Management focused on healthcare, as well as a member of Goldman Sachs’ healthcare investment banking team. Before joining Goldman Sachs, she was a Project Chemical Engineer at Merck & Co. where she focused on process development for novel vaccines. She currently serves on the board of Eucrates Biomedical Acquisition Corp. and LogicBio Therapeutics, each of which is a publicly traded company, and Elicio Therapeutics, a privately held biotechnology company. 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, PhD, SVP of Biology and Translation

“It is a privilege to be joining Flare at a time when there is an opportunity to develop and shape our R&D strategies to enable a ground breaking new approach to targeting transcription factors through the switch site,” said Dr. Bowden. “Flare’s innovative approach gives us the potential to create highly promising precision medicines for cancer, and I look forward to bringing my own unique perspective and R&D expertise to the amazing team at Flare.”

Michaela Bowden, PhD, is an accomplished scientist and leader with over 15 years of experience building multidisciplinary research teams at drug discovery organizations of all sizes. Dr. Bowden joins Flare from Bristol Myers Squibb (BMS) where she served as executive director of translational biology and led teams at research sites in Cambridge, Mass., and New Jersey focused on immuno-oncology drug development. Prior to BMS, she served in scientific leadership roles at Dana-Farber Cancer Institute and Novartis Institutes for Biomedical Research, as well as at a startup life sciences company in her native Ireland. Dr. Bowden has expertise in elucidating patient phenotypes associated with tumor heterogeneity and the tumor microenvironment, which have led her to developing novel biomarker approaches that define high risk patient segments unmet by current treatment regimens. She has technical experience from developing biotechnology platforms to leveraging state-of-the-art disruptive technologies to address key translational hypotheses that impact drug discovery, casting a broad collaborative net across a diverse network of oncology experts at the intersection of clinic, biopharma and biotechnology. Dr. Bowden was a post-doctoral research fellow at Tufts University in the areas of assay development, multiplexed diagnostics and next-generation sequencing. She has a BSc and PhD in Analytical Science and Microfluidics from Dublin City University.

About Flare Therapeutics

Flare Therapeutics is a biotechnology company opening up 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. Our drug discovery 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, Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.

We invite you to follow us on LinkedIn and @Flaretx.

 

Media Contact:

Kathryn Morris

The Yates Network LLC

914-204-6412

kathryn@theyatesnetwork.com

 

 

 

AsherBio

Flare Therapeutics Launches with $82 Million Series A Financing to Advance Precision Oncology Pipeline based on Novel Drug Discovery Approach for Transcription Factors

Company has pioneered ‘switch site’ approach to uncover druggable regions within well‑validated, but elusive, transcription factors that are master regulators of gene expression

Founded by global scientific leaders in the biology and structure of transcription factors

Financing led by Third Rock Ventures with significant support from world-class group of investors

 

Cambridge, Mass. – May 13, 2021 – Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, today announced its launch and Series A financing of $82 million. The Series A was led by Third Rock Ventures with significant support by Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. Flare is targeting transcription factors through ‘switch sites’ – newly identified druggable regions that control predictable and profound changes in gene expression – as a fundamentally new way to discover novel small molecule medicines to treat the multitude of diseases driven by transcription factor dysregulation.

“We created Flare to pursue the mission of conquering transcription factors which have been one of the most sought-after targets of drug developers based on the central role they play in cancer and other diseases,” said Abbie Celniker, PhD, interim chief executive officer of Flare and partner at Third Rock Ventures. “The outstanding scientific team and co-founders we have brought together have already made strong progress to show how the unique biochemistry of the switch site serves as key targets for transcription factor regulation, translating into powerful biology and a new path for life-changing medicines for patients.”

Flare’s switch-site based drug discovery approach has resulted in an emerging pipeline of drug programs targeting transcription factor dysregulation and mutations that are known to be pivotal drivers of cancer. The Series A will support Flare’s further advancement of its lead program in precision oncology toward the clinic. In addition, the company will continue to build its unique engine and proprietary assays to discover small molecules that target transcription factors at switch sites.

“Over the past decade, there has been a constant flow of scientific discoveries showing evermore pointedly how transcription factors play a central role in diseases, notably cancer. Yet, transcription factors have continued to be elusive for finding targetable sites for drug discovery, with less than 1% of transcription factors successfully targeted for medicines,” said Fraydoon Rastinejad, PhD, professor of biochemistry and structural biology, University of Oxford, and a scientific co-founder of Flare. “Flare’s team and innovative approach are well positioned to realize the enormous potential of targeting transcription factors as a gateway to many new medicines.”

Flare’s new drug discovery paradigm for targeting transcription factors is based on a broader understanding of the cooperative communication and allosteric interaction among the elements of the transcriptional molecular complex, which is distinct from the historically narrow focus on individual transcription factor domains in isolation. Seminal work by Flare’s scientific co-founders recently elucidated molecular mechanisms for targeting transcription factors, showing the way for Flare’s drug discovery team to recognize the broad potential to generalize these principles to the ‘switch site’ as a focal point for drugging transcription factors in a new way.

“I am excited to join the Flare team in testing our abilities to discover new, first-of-class medicines that act by modulating gene expression. Maturation of the fields of human genetics and the biochemistry of gene regulation now point us towards opportunities for therapeutic intervention using conventional, small molecule drugs,” stated Steven McKnight, PhD, professor at the University of Texas, Southwestern, and a scientific co-founder of Flare.

World class team of drug developers and transcription factor experts

“The Flare team has made rapid progress from recognizing and understanding switch site biochemistry to advancing several drug programs around genetically and biologically validated transcription factor targets for cancer,” said Robert Sims, PhD, chief scientific officer and co-founder of Flare. “Our early focus is on precision oncology based on the clear role that transcription factors play in cancer, and we look forward to expanding our future drug discovery in other areas such as neurology, rare genetic disorders, immunology and inflammation.”

The Flare team brings together experienced biotechnology leaders with decades of industry expertise and deep scientific, drug discovery and development skills. Company leaders include Abbie Celniker, PhD, interim chief executive officer; James Audia, PhD, distinguished scientist; Lorence Kim, MD, interim chief operating officer; Jeanette Kohlbrenner, interim chief people officer; and Robert Sims, PhD, chief scientific officer.

Scientific co-founders and advisors of Flare include world-renowned experts with decades of experience understanding the biology and structure of transcription factors.

  • Fraydoon Rastinejad, PhD, Flare co-founder, Wellcome-Trust Senior Investigator and Professor at the University of Oxford, is a world leader in the structure and function of transcription factors. Dr. Rastinejad has blazed a new understanding of how transcription factor complexes associate and cooperatively interact to facilitate DNA recognition. His scientific focus has included nuclear receptors and more recently bHLH-PAS proteins, where he demonstrated the bi-directional tuning of these transcription factors with synthetic ligands.
  • Steven McKnight, PhD, Flare co-founder and chair of the Flare scientific advisory board, Professor at the University of Texas, Southwestern, is a transcription factor pioneer and member of the National Academy of Sciences. Dr. McKnight’s notable work includes the discovery of leucine zipper transcription factors, unlocking the druggability of the non-nuclear receptor transcription factor HIF2A and co-discovery the phenomena of phase separation by low-complexity domains. He is also a successful serial entrepreneur, co-founding the transcription factor companies Tularik and Peloton.
  • Mitchell Lazar, MD, PhD, Flare co-founder, Willard and Rhoda Ware Professor at the University of Pennsylvania, is a pioneer for his modern approach to understanding the linkage between genetic, environmental, and circadian mechanisms to gene control and disease. Dr. Lazar is a member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences. Among his notable discoveries are linking circadian rhythms and metabolism via the nuclear receptor REV-ERB, the hormone resistin, and the importance of PPARG in adipocytes.
  • Stephen Frye, PhD, Flare advisor, Fred Eshelman Distinguished Professor and co-director of the Center for Integrative Chemical Biology (CICBDD) and Drug Discovery at the University of North Carolina at Chapel Hill, is a prolific medicinal chemist and chemical biologist and a leader in the chemical biology of chromatin and gene regulation. Through the CICBDD, Dr. Frye has helped foster numerous collaborative academic drug discovery projects including one program currently progressing through multiple clinical trials. Prior to joining UNC, he was the worldwide vice president of discovery medicinal chemistry at GlaxoSmithKline. At GSK, the teams led by Stephen successfully developed three FDA approved drugs: Avodart, Tykerb, and Pazopanib.
  • Robert Sims, PhD, Flare co-founder and chief scientific officer, is an industry leader in the drug discovery of gene control. Prior to joining Flare, Dr. Sims was an entrepreneur-in-residence at Third Rock Ventures and is a former founding scientist and senior vice president of research at Constellation Pharmaceuticals, where he helped establish its integrated epigenetics platform. At Constellation, Robert led the discovery and translational efforts of Pelabresib, a small molecule BET bromodomain inhibitor in Phase 3 for the treatment of myelofibrosis.

 

About Transcription Factors

Transcription factors (TFs) are DNA-binding proteins that can activate or repress DNA transcription and, therefore, control gene expression. There are up to 1600 TFs in the human genome and approximately 10% of genes encode TFs, making TFs one of the largest families of regulatory proteins. 1 Transcription factors generally perform their functions while in multi-protein complexes with interconnected biochemical activity. TF mutations are drivers of many diseases, including one-third of oncogenes in cancer and one-fifth of haploinsufficiency genetic diseases.2, 3 Despite their central role in diseases, fewer than 1% of TFs have been successfully targeted for therapeutics because conventional rules for drug design do not apply to transcription factors.

 

About Flare Therapeutics

Flare Therapeutics is a biotechnology company opening up 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. Our drug discovery 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, Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors and Eventide Asset Management. For more information, please visit www.flaretx.com.

 

1 The Human Transcription Factors, Cell, 172(4), 650-665, Feb 2018.

2 COSMIC tier 1 oncogene list, Catalogue of Somatic Mutations in Cancer, v92, Aug 2020.

3 V. T. Dang, V.T., et. al., Identification of human haploinsufficient genes and their genomic proximity to segmental duplications. Eur. J. Hum. Genet. 16, 1350–1357, June 2008.

 

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