HotSpot announces $65M Series B, as Nimbus pioneers look to keep up in a crowding field
In the decade since Nimbus Therapeutics built a company around computation and little-known phenomena like allosteric regulation, the industry has brimmed with algorithm companies and even a few chasing those same targets. Still, a couple of the old leaders think they can keep an edge.
“We’re very proud to have pioneered the field,” Gerry Harriman told Endpoints News. “And we’re also very proud to say our portfolio is full of targets that have allosteric inhibitors really for the first time that has ever been described.”
Harriman led Nimbus’s ACC program — the part that sold to Gilead for up-to $1.2 billion — before she and former Nimbus CBO Jonathan Montagu founded HotSpot Therapeutics 3 years ago. The idea was to take the same principles and technology that led to the Gilead-licensed drugs and unleash it on a suite of diseases.
Today Harriman and Montagu say they’ve developed a long list of targets, including two lead programs in autoimmune disorders and rare metabolic diseases. They’ve also secured $65 million to bring them forward, in a Series B round led by SR One, Limited. And more news could be coming soon.
“We’ve got a number of quite advanced discussions with Pharma,” Montagu told Endpoints.
In the four years since Nimbus sold its ACC program, Gilead’s NASH program has struggled, although the Nimbus drug remains in development, including Phase II trial. Interest in allostery has only grown in the last half decade. Black Diamond Therapeutics jumped in a little over a year ago from a stealth mode to a billion-dollar company with a $200 million IPO on its platform of allosteric cancer drugs.
These allosteric sites are sometimes known as hotspots (hence the biotech name), nodes that the body uses for its own internal mechanism of communication and regulation. These nodes can be difficult to find, much less target, but they hold significant potential as drug targets, both because they are a “natural” locus of activity and because they offer a way to drug proteins that lack the easy grooves.
“Potency, selectively, drug-like properties are the real advantages of this approach,” Montagu said. “And for those targets that don’t have active sites, it’s really the only way to build a first-in-class [drug].”
HotSpot is built around their computer platform that uses a slew of different algorithms to search for these allosteric sites. They go after proteins that genetics have shown drive disease. They start with the protein structure — of a kinase — and then build evolutionary maps that, with machine learning, allow you to scout out the common regulatory spots.
“We knew that a priori that not one single technology would allow us to a systematic uncovering of regulatory hotspots,” Harriman said. “So we put about a dozen different algorithms together that helps us to find the regulatory hotspots, determine if they’re druggable, understand the structure function, unveil these molecular fingerprints of fingertips.”
HotSpot will now look to get clinical data on two drugs by 2022. One is an allosteric inhibitor of PKC-theta, an enzyme pharma companies have with more conventional inhibitors, to little success. HotSpot will test it in auto-immune diseases driven by regulatory T cells and Th2 cells. The second is an inhibitor for S6 kinase, an enzyme that’s been studied as a treatment for obesity and that Hotpot will test on rare metabolic diseases.
But those, Montagu said, are only the first couple drugs they’re bringing forward in-house. The company is also working on drugging transcription factors, the DNA-regulating proteins that play a crucial role in a host of diseases but have been difficult to drug because they lack easy grooves into which you could sneak a small molecule. That program has generated interest from Pharma, Montagu said, as have some of their immuno-oncology findings.
”Even big companies find immuno-oncology challenging,” he said. “So we’d like to partner the I/O assets and address ourselves in the immunology space.”
Correction: The story has been updated to correct the status of the Gilead’s ACC drug.