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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Amidst R&D reshuf­fle, Ver­tex ex­pands its pres­ence in Boston, aim­ing to be­come num­ber one

Vertex Pharmaceuticals has been one of the buzzier names in the bustling Boston biotech scene, but now the company is looking to vault to number one status — at least in terms of physical footprint.

At a ribbon cutting on Tuesday for its new Jeffrey Leiden Center for Cell and Genetic Therapies at the Boston Seaport, Vertex announced it would embark on a new project: The company will build a 344,000 square foot facility in the seaport to accommodate the company’s growing R&D needs, especially in its cell and gene therapies program.

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Clay Siegall (Photo by Dimitrios Kambouris/Getty Images for Gabrielle's Angel Foundation)

UP­DAT­ED: Clay Sie­gall re­signs from Seagen amid in­ves­ti­ga­tion in­to do­mes­tic vi­o­lence claims

A week after Seagen revealed that longtime CEO Clay Siegall was on leave due to an allegation of domestic violence, he has resigned.

Since that shocking revelation, more details about the claims have emerged into the public eye. As Endpoints News reported, Siegall was arrested on April 23. A police report about that night and a subsequent temporary restraining order described a pattern of abusive behavior against his wife and a physical altercation that left her with multiple bruises. Siegall denied the claims.

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Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.

FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.