RARE Daily

HotSpot Therapeutics Raises $65 Million

May 21, 2020

HotSpot Therapeutics raised $65 million in a series B financing to advance development of its pipeline of first-in-class therapies with genetically validated mechanisms for the treatment of autoimmune diseases, rare diseases, and cancer.

Photo: Jonathan Montagu, CEO and co-founder of HotSpot

S.R. One led the financing round, which included investment from funds managed by Tekla Capital Management, MRL Ventures Fund, Solasta Ventures, and Brace Pharma (via affiliate Cleva Pharma), along with co-founding investors Atlas Venture and Sofinnova Partners.

HotSpot is focused on the discovery and development of allosteric medicines—targeting the natural control mechanisms of protein, the “regulatory hotspots” that are amenable to small molecule drug discovery.

Regulatory hotspots are privileged sites on proteins that are often difficult to identify but possess certain common features that can be uncovered through mining of expertly curated structure, sequence, and function datasets. HotSpot’s platform uses advanced machine learning techniques to discover the underlying fingerprints of regulatory pockets. Using 3D structure insights from the uncovered pockets, the company has designed in-house DNA-encoded libraries that comprise millions of tailored molecules. A proprietary screening paradigm using custom protein constructs, phenotypic screens, and biophysics assays is then used to demonstrate the differentiated properties of hotspot-targeted molecules. HotSpot says this allows it to design first-in-class allosteric medicines with superior pharmacology, selectivity and drug-like properties.

“We have proven that uncovering and targeting natural regulatory sites on proteins leads to highly differentiated molecules across a number of important target families, including kinases, transcription factors and E3 ligases,” said Jonathan Montagu, CEO and co-founder of HotSpot. “Today’s financing will allow us to demonstrate the value of these molecules in patients.”

The new financing will support the advancement of HotSpot’s lead programs to the clinic, including protein kinase C (PKC-theta) antagonists for Th2 and T-reg driven autoimmune disease and S6 kinase (S6K) antagonists for rare metabolic disease. The financing will also accelerate the discovery-stage pipeline targeting genetically validated transcription factors and E3 ligases, including CBL-B.

Author: Rare Daily Staff

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