HotSpot Therapeutics Secures $45M to Advance Drug Discovery Platform

HotSpot Therapeutics has secured $45 million to advance its drug discovery strategy that identifies so-called  “hot spots” in proteins, allowing for their precise targeted regulation.

Using this technology, HotSpot Therapeutics has identified hot spots in more than 100 proteins important for many diseases, including mitochondrial diseases.

“HotSpot is targeting natural regulatory sites on proteins that evolution has perfected over many millions of years.  This allows us to create medicines that work through exactly the same mechanisms, offering the same degree of precision and potency,” Jonathan Montagu, CEO and co-founder of HotSpot Therapeutics said in a press release. “Regulatory hotspots offer a privileged subset of allosteric sites that remain unexplored for drug discovery and represent a major opportunity to create first-in-class medicines across multiple disease areas.”

One of the first regulatory hot spots they identified was in the S6 kinase, a metabolic enzyme involved in pathways of insulin, the hormone that controls blood sugar levels. It also is important for mitochondria’s morphology and function. This allowed the development of new compounds capable of regulating the protein’s function.

Another protein, PKC-theta, which has an important role in several autoimmune diseases, also has been one of the first targets of HotSpot’s technology.

Conventional drug design relies on identifying the active site of a protein — the one controlling the protein’s function — and design a compound that targets it. However, this approach has limitations, including lack of specificity, i.e., targeting the active site and only that of the intended protein.

On the contrary, identifying regulatory hotspots is a distinct approach because they’re located away from the active site, also important for regulating the protein’s function. Moreover, they are specific for each protein.

Drug design targeting regulatory hot spots is highly selective and prompted with increased effectiveness, and because the compound is specific, its full power is not wasted in “off” targets.

“At HotSpot, we have developed the first and only technology platform to identify regulatory hotspots systematically across the entire proteome [the entire collection of proteins].  We then apply novel chemistry to design the first small molecules targeting the hotspot,” said Geraldine Harriman, PhD, chief scientific officer and also co-founder of HotSpot Therapeutics.

“For proteins without active sites, regulatory hotspots may offer the only way to rationally drug the target.  This allows us to expand the breadth of disease pathways that are accessible to intervention,” Harriman said.

The funding was provided by HotSpot Therapeutic partners Atlas Venture and Sofinnova Partners.