Jonathan Montagu and Gerry Harriman (HotSpot)

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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,200+ biopharma pros reading Endpoints daily — and it's free.

Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Paul Hudson, Sanofi CEO (Photographer: Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi, Re­gen­eron’s Dupix­ent scores an­oth­er in­di­ca­tion with first-ever ap­proval for nodu­lar skin dis­or­der

Sanofi chief executive Paul Hudson told investors earlier this year that the Big Pharma was going to emphasize its sales kingpin Dupixent moving forward.

He wasn’t joking — the megablockbuster drug and sales king, recording just shy of $2 billion in sales this past quarter, has now officially secured its fifth indication from the FDA.

Sanofi and Regeneron, who jointly work on Dupixent development and commercialization, announced the new development on Thursday, saying that the FDA gave the all-clear to Dupixent to treat patients with prurigo nodularis, a rare autoimmune disorder characterized by a persistent, severe itch — and also visualized by hard, extremely itchy bumps known as nodules that form on the skin. The FDA noted in its announcement that it is the agency’s first approval for the disease.

Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,200+ biopharma pros reading Endpoints daily — and it's free.

Sens. Rand Paul (R-KY) and Cory Booker (D-NJ) (Olivier Douliery/Sipa USA (Sipa via AP Images))

Sen­ate pass­es bill to re­work an­i­mal test­ing re­quire­ments for drug de­vel­op­ers

The US Senate passed via unanimous consent on Thursday afternoon a bipartisan bill that would eliminate a federal mandate for animal testing for new drugs.

Touted as a much-needed modernization of FDA’s rules, co-sponsor Sens. Rand Paul (R-KY) and Cory Booker (D-NJ) have said the bill will stop lots of needless suffering of animals.

Pa­tient re­port finds con­sti­pa­tion con­di­tion not well man­aged, open­ing door for bet­ter ed­u­ca­tion from phar­ma

Advertising for constipation treatments often uses light-hearted humor in an effort to spur open discussions about the sometimes stigmatized topic. However, that may not be enough to get people to take the condition seriously, a new patient report from Phreesia finds.

Fewer than one-fifth (17%) of patients with constipation surveyed understand the longer-term health risks of constipation such as hemorrhoids and bowel incontinence. Many are trying to manage their condition with over-the-counter medicines, but often for much longer than recommended. An equal 68% say they use home remedies or OTC meds to manage constipation. But while 90% understand that OTCs are not intended for long-term use, 50% have used an OTC constipation medicine for more than a year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,200+ biopharma pros reading Endpoints daily — and it's free.