more selective and potent. Consequently, he adds, these drugs could be made at a lower dose, and they could produce fewer side effects. HotSpot will still need to demonstrate those properties in clinical trials, of course.
HotSpot, which was founded last year, isn’t the first company to pursue allosteric drugs. Montagu notes that efforts have been made to develop allosteric central nervous system disorders drugs that target G-protein coupled receptors (GPCRs). Foster City, CA-based Gilead Sciences (NASDAQ: [[ticker:GILD]]) is currently in mid-stage studies with an allosteric drug developed as a treatment for the fatty liver disease known as NASH. That drug, GS-0976, acquired from Nimbus Therapeutics two years ago, blocks Acetyl CoA Carboxylase (ACC), an enzyme that helps regulate the formation of fatty acids. Montagu and Harriman know that compound well. When both of them worked at Nimbus, Harriman was the head of its ACC program.
Even though the former Nimbus liver drug is allosteric, Montagu says HotSpot’s work is completely separate from Nimbus. SpotFinder was developed within HotSpot based on research done after leaving Nimbus, Montagu says. Most of the SpotFinder technology was developed in-house, which means HotSpot holds 100 percent of the rights to the platform and the molecules that come from it, Montagu says. Montagu says SpotFinder’s ability to discover and develop a pipeline of allosteric drugs sets HotSpot apart from others that have allosteric compounds.
So far, SpotFinder has identified non-active regulatory sites in more than 100 proteins, including those hit by its two lead compounds. One targets S6 kinase, a metabolic enzyme that could have applications treating NASH, metabolic, and mitochondrial diseases. Montagu acknowledges that Novartis (NYSE: [[ticker:NVS]]) and Pfizer (NYSE: [[ticker:PFE]]) have also pursued this target, but he says those efforts have focused on the active site of the protein.
The second lead compound targets PKC-theta, a protein associated with inflammation. This drug could have applications treating rheumatoid arthritis, psoriasis, and graft-versus-host disease, Montagu says.
The $45 million in new capital, HotSpot’s Series A round of financing, was co-led by Atlas Venture and Sofinnova Partners. Montagu says the cash will pay for preclinical work; the goal is to reach clinical trials in two to three years. He says HotSpot is open to partnerships with other companies interested in applying SpotFinder to their drug discovery efforts. But Montagu adds that his company’s main focus is taking its own molecules into clinical testing.
Photo by Jon Chomitz Photography
