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.

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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UP­DAT­ED: New Kaiser analy­sis shows how lim­it­ing price ne­go­ti­a­tions to tar­get­ed drugs may bet­ter fo­cus up­com­ing leg­is­la­tion

As Congress considers whether to adopt sweeping new legislation to lower prescription drug prices across the board, the Kaiser Family Foundation is out with a new report on Monday showing how a more targeted approach on a subset of drugs might be a more efficient way to save government funds.

“This analysis shows that Medicare Part D and Part B spending is highly concentrated among a relatively small share of covered drugs, mainly those without generic or biosimilar competitors,” wrote Juliette Cubanski, deputy director of the program on Medicare policy at KFF, and Tricia Neuman, SVP of KFF. “Focusing drug price negotiation or reference pricing on a subset of drugs that account for a disproportionate share of spending would be an efficient use of administrative resources, though it would also leave some potential savings on the table.”

FDA lays the ham­mer on Emer­gen­t's Bal­ti­more plant af­ter J&J de­ba­cle, halt­ing all pro­duc­tion in un­usu­al move

Emergent BioSolutions has had a tough month: First, the CDMO ruined 15 million doses of J&J’s Covid-19 vaccine in March and then suffered the ignominy of the FDA seizing the reins. Now, as the agency receives a full accounting of the site’s problems, Emergent has slammed the brakes on all production at the FDA’s behest.

Emergent will cease manufacturing at its Baltimore plant until the FDA’s inspection and remediation of any findings is complete, the company said in a statement. Emergent will also quarantine existing materials that have already been manufactured. That stoppage started on Friday, four days after the initiation of the FDA’s inspection.

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Ovid cuts its loss­es on con­tro­ver­sial An­gel­man syn­drome drug, mak­ing its crush­ing de­vel­op­ment halt per­ma­nent

After a turbulent couple of years, Ovid is officially doing away with a program it had once championed in the face of heavy analyst skepticism.

Ovid has discontinued development of OV101, or gaboxadol, in Angelman syndrome and will not pursue further clinical trials for Fragile X syndrome, the company announced Monday morning. The news comes after Ovid had previously paused development in Angelman when the compound flunked a Phase III trial in December.

FDA slaps a hold on Mof­fitt’s next-gen CAR-T as reg­u­la­tors de­mand an­oth­er de­lay on clin­i­cal work — shares crater

Close to a year-and-a-half after tapping the brakes on one of its preclinical programs to do some added genetic engineering work on their next-gen CAR-T, Anixa $ANIX Therapeutics says the regulatory light is flashing red on their IND.

The San Jose, CA-based biotech — which changed its name from ITUS in 2018 — explained in late 2019 that they were taking a knee for at least a year so that researchers could go back and amp up the expression of follicle stimulating hormone on T cells to improve targeting of the FSH receptor on a specific set of ovarian cells. That required new vector engineering work by their partners at Moffitt Cancer Center.

Tillman Gerngross (Adagio)

Till­man Gern­gross' Covid-19 an­ti­body moon­shot scores $336M with the help of new ace CFO. Is an IPO next?

Less than a year into its existence, serial biotech entrepreneur Tillman Gerngross’ antibody play Adagio has raced ahead into a pivotal trial for its lead drug for Covid-19 on the back of some very promising preclinical data. Now, crossover investors led by Peter Kolchinsky at RA are rolling up the Brinks truck — and that could spell an IPO in the offing for Adagio.

Adagio has bagged $336 million as part of a Series C round led by RA Capital to advance lead single-shot antibody ADG20 through a pivotal Phase I/II/III trial for the treatment of mild to moderate Covid-19 patients at high risk of infection, the biotech said Monday.

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When is a drug re­al­ly a de­vice? Court knocks down FDA ap­peal in try­ing to sort that grey area

It’s always a surprise when a court has to step in to tell the FDA that it erred in performing one of its main duties: classifying whether a medical product is drug or a device.

But that’s what the US Court of Appeals for the District of Columbia did on Friday, making clear to the world’s top drug regulator that Genus Medical Technologies’ contrast agent barium sulfate (also known as Vanilla SilQ) should not be considered a drug, as the FDA had said, but a medical device.

Q1: A flood of in­vestor cash drove biotech's num­bers to new record highs, and the tor­rent of cash is mov­ing up­stream fast

If you thought biotech was booming last year, wait until you get a load of the numbers from Q1 2021.

On virtually every level, with one exception, the money engine was working around the clock in the first 3 months of this year. Venture capital has reached such a fever peak that the average B round now weighs in at an average mega-weight value of $100 million. The money flow is also finding its way to the mouth of the R&D river, where discovery work now merits the big bucks instead of cautionary seed funds.

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