HotSpot Therapeutics, a biotechnology company pioneering the discovery and development of first-in-class allosteric therapies targeting nature's regulatory sites, today announced the completion of a $65 million Series B financing. The financing round was led by S.R. One, Limited and included 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. Concurrent with the financing, Jill Carroll, Partner at S.R. One, Limited, and Henry Skinner, PhD, Senior Vice President, Venture at Tekla Capital Management have joined the HotSpot Board of Directors.

"We are thrilled to have the support of a top tier investor syndicate to realize our vision of designing and developing first-in-class allosteric medicines," said Jonathan Montagu, CEO and co-founder of HotSpot Therapeutics. "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. Today's financing will allow us to demonstrate the value of these molecules in patients."

HotSpot Therapeutics is creating a new paradigm for allosteric medicines that exploits natural control mechanisms. Leveraging a deep understanding of protein structure-function, the SpotFinder™ platform identifies critical regulatory regions on proteins - "regulatory hotspots" - that are amenable to small molecule drug discovery. This allows HotSpot to design first-in-class allosteric medicines with superior pharmacology, selectivity and drug-like properties.

The Series B 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.

"It is with pleasure that we welcome Jill Carroll and Henry Skinner to the HotSpot Board, both with significant experience guiding early stage companies in the transition from drug discovery into clinical development," said Bruce Booth, DPhil, Chair of HotSpot's Board of Directors and Partner at Atlas Venture.

"Leveraging its proprietary SpotFinder™ technology platform, HotSpot is succeeding in critically important areas of biology that were otherwise considered intractable and undruggable," said Jill Carroll, S.R. One, Limited. "We are very excited to partner with this seasoned team to transform HotSpot into a clinical stage company and to bring first-in-class allosteric drugs targeting natural regulatory mechanisms to patients."

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 SpotFinder™ 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 (DEL) that comprise millions of exquisitely 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.

About HotSpot Therapeutics

HotSpot Therapeutics is targeting nature's regulatory mechanisms to create allosteric medicines that exhibit high precision and potency. The company leverages its proprietary SpotFinder™ technology, the first and only platform designed to identify and target "regulatory hotspots," a unique family of pockets that sit remote from the active site on a protein and are used by nature to control protein function. Using bespoke chemistry approaches, HotSpot is developing a pipeline of first-in-class small molecules for the treatment of autoimmune and rare diseases as well as cancer. The company has identified regulatory hotspots across multiple target classes including kinases, transcription factors and E3 ligases. HotSpot's lead compounds include the first and only allosteric inhibitors to target PKC-theta for autoimmune diseases and S6 kinase, a critical signaling node involved in the regulation of mitochondrial and metabolic function. To learn more, visit www.hotspotthera.com.