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New Biotech Creating Precision Cancer Therapies

DNA analysis graphic

(Gerd Altmann, Pixabay)

13 May 2021. A biotechnology company began work in public to develop new treatments that target proteins responsible for gene expression, beginning with cancer. Flare Therapeutics in Cambridge, Massachusetts, formed by life science investor Third Rock Ventures and operating in stealth mode up to today, is also raising $82 million in its first venture funding round.

Flare Therapeutics creates therapies addressing transcription factors, some 1,600 proteins in the human genome. Transcription factors bind to DNA and activate or limit gene expression, the process of translating genetic codes in DNA to RNA and proteins. Transcription factors are encoded by about 10 percent of human genes and implicated in one-third of cancer-causing genes, as well as one in five inherited diseases from haploinsufficient genes, where a functional copy of the gene is lost. Because transcription factors operate under complex conditions, with multiple proteins and chemical interconnections, they’re difficult to target directly for therapies.

The company’s technology is based on research by its scientific founders, particularly Fraydoon Rastinejad, professor of biochemistry and structural biology at University of Oxford in the U.K. Rastinejad work with one transcription factor revealed a biochemical process and structure in all transcription factors, particularly key pockets with amino acid residues critical to the protein’s structure and integration. These pockets, called switch sites, are targets for small molecule drugs for turning transcription factors on or off.

“Over the past decade,” says Rastinejad in a Flare Therapeutics statement, “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 one percent of transcription factors successfully targeted for medicines.”

“Clear role” of transcription factors in cancer

The company says it will first apply its switch site technology to precision cancer treatments that address specific cancer-causing mutations rather than the organs where tumors reside. “Our early focus,” says Flare Therapeutics’ chief scientist and co-founder Robert Sims, “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.”

Some neurological disorders are associated with haploinsufficient genes. Another of Flare Therapeutics’ co-founders is Steven McKnight, biochemistry professor at University of Texas Southwestern Medical Center in Dallas. McKnight’s work includes studies of transcription factors, including those involving neurodegenerative diseases. As reported by Science & Enterprise in July 2020, McKnight is a scientific co-founder of Nura Bio Inc., a biotechnology company developing therapies for neurodegenerative disorders.

Also among Flare’s scientific co-founders are Mitchell Lazar, who studies transcriptional regulation of metabolism and genetics behind metabolic disorders at University of Pennsylvania, and Stephen Frye, co-director of the Center for Integrative Chemical Biology and Drug Discovery at the University of North Carolina at Chapel Hill.

Flare Therapeutics is raising $82 million in its first venture funding round led by Third Rock Ventures in Boston. Joining the round are Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors, and Eventide Asset Management. Third Rock partners are filling in as the company’s interim CEO, chief operating officer, and chief people officer.

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