HotSpot Therapeutics Eyes Clinic Following $65 Million Series B

Two years after Boston-based HotSpot Therapeutics launched, the company has secured $65 million in Series B funding. to advance the development of its allosteric therapies that target “regulatory hotspots” in the body into the clinic.

This morning, the company announced the financing that will be used to bolster is research and development of first-in-class allosteric therapies. HotSpot uses its SpotFinder platform to identify critical regions in proteins, the “regulatory hotspots” and then begins to design its first-in-class allosteric medicines to target them. Those regulatory hotspots, according to the company, are unique pockets on a protein, located remotely from the active site, that are both essential for protein function and entirely unique to each target. Using 3D structure insights from the uncovered pockets, the company designed in-house DNA-encoded libraries that include millions of “exquisitely tailored molecules.” They are then screened by using custom protein constructs, phenotypic screens and biophysics assays to demonstrate the differentiated properties of hotspot-targeted molecules.

The $65 million in financing will support the advancement of HotSpot’s lead programs into the clinic that target PKC-theta, which plays an important role in multiple autoimmune diseases, and S6 kinase, a metabolic enzyme involved in regulating hepatic insulin sensitivity and mitochondrial function. The company said it has made great strides in advancing the lead programs targeting S6K and PKC-theta, which are two genetically-validated targets that have been difficult to drug with active site inhibitors. These are seen as important targets by the company as they play roles in various diseases including nonalcoholic steatohepatitis (NASH), as well as metabolic, and mitochondrial diseases.

In addition to its lead programs, the financing will accelerate the discovery-stage pipeline targeting genetically validated transcription factors and E3 ligases, including CBL-B, the company said.

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HotSpot co-founder and chief executive officer Jonathan Montagu told BioSpace this morning that the company has made “really nice progress” with its SpotFinder platform. That progress has shown the company has the capabilities to “systematically identify and drug nature’s regulatory hotspots.”

“Now it’s about taking those insights and moving our allosteric molecules to the clinic,” Montagu said.

He added that since its launch, the company has proven that uncovering and targeting natural regulatory sites on proteins can lead to highly differentiated molecules across a number of important target families, which includes kinases, transcription factors and E3 ligases.

“Today’s financing will allow us to demonstrate the value of these molecules in patients,” Montagu added.

Montagu also touted the backing of the investors who supported the Series B. He applauded their financial support that will help the company realize its vision of developing these allosteric medicines.

The Series B 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. Atlas Venture and Sofinnova Partners, who supported the company’s Series A in 2018, also participated.

Along with the investments, HotSpot said Jill Carroll, a partner at S.R. One and Henry Skinner, of Tekla Capital Management have joined the company’s board of directors.

“Leveraging its proprietary SpotFinder technology platform, HotSpot is succeeding in critically important areas of biology that were otherwise considered intractable and undruggable,” Carroll said in a statement. “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.”