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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.

Contact:
Media:
Kathryn Morris
The Yates Network
914-204-6412
kathryn@theyatesnetwork.com


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