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.”

Bruce Booth

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

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.