Remember that billion-dollar drug idea that got little Nimbus on Gilead’s radar back in 2016? Well, the folks behind that drug are building a whole platform on a similar concept. And they’re not just tackling NASH, but a whole lineup of previously undruggable targets.
The venture, called HotSpot Therapeutics, came out Tuesday with news that it’s being backed by Nimbus’ lead investor — Atlas Venture — in a $45 million Series A round co-led by Sofinnova.
HotSpot was launched last year by Geraldine Harriman, the former Nimbus executive who led the company’s NASH program — the very one that earned the Boston biotech a $1.2 billion partnership with Gilead. That drug, at the time called NDI-01097, used a way (relatively new to pharma) to manipulate proteins outside the active site, going instead after something called “regulatory hotspots.” These, I’m told, are allosteric sites that the body uses to regulate protein function. Harriman says targeting these hotspots could be a boon for drug development, which is why she’s co-founded an entirely new venture on the concept.
“The active sites of proteins tend to look a lot like each other, so getting molecules that can be selective is a hurdle,” she said. “It takes a lot of effort and sometimes the problem isn’t solved. Regulatory hotspots, on other hand, are how nature controls the proteins — turning things on and off. And regulatory hotspots are unique to the protein.”
Shortly after the Gilead deal, Harriman, together with another ex-Nimbus exec Jonathan Montagu, formed HotSpot to harness what they know about regulatory hotspots to build a whole slew of drug programs. Montagu is serving as HotSpot’s CEO, while Harriman is CSO.
With its platform, the company says it’s identified regulatory hotspots in over 100 proteins spanning several pathways and diseases. Montagu says they’re homing in on immunology, immuno-oncology, and NASH.
Montagu says HotSpot has five programs in the pipeline, although they’re mum on details. We do know they’re targeting PKC-theta, which plays a role in autoimmune diseases, and S6 kinase, a metabolic enzyme involved in regulating hepatic insulin sensitivity and mitochondrial function.
Cementing its ties to Nimbus, HotSpot also sports the same chairman: Atlas Venture partner Bruce Booth.
“HotSpot’s elegant and systematic approach to allostery, focused uniquely on regulatory hotspots, sets it apart from everything else we have seen in the field,” Booth said in a statement. “From the outset, we knew that regulatory hotspots were critical to protein function and now we see vividly that the known footprint of the natural protein ligand accelerates our chemistry efforts. HotSpot is changing the way allosteric drug discovery is conducted in a profound way and Atlas is very excited about the launch of this company.”
Image: Jonathan Mantagu and Geraldine Harriman. HOTSPOT
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