Rare Daily Staff

Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, launched with $82 million in a series A financing.

Third Rock Ventures led the funding round with significant support by Boxer Capital, Nextech Invest, Casdin Capital, Invus Financial Advisors, and Eventide Asset Management.

Based on insights from the seminal work of its scientific founders, Chief Scientific Officer Robert Sims, Fraydoon Rastinejad, professor of biochemistry and structural biology, University of Oxford, and Steven McKnight, professor at the University of Texas, Southwestern, 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 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.

“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, interim CEO of Flare and partner at Third Rock Ventures.

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 percent of genes encode TFs, making TFs one of the largest families of regulatory proteins. Transcription factors generally perform their functions while in multiprotein 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. Despite their central role in diseases, fewer than 1 percent of TFs have been successfully targeted for therapeutics because conventional rules for drug design do not apply to transcription factors.

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.

The funding will support Flare’s 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.

“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, 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.”

Photo: Robert Sims, chief scientific officer, and co-founder of Flare

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