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.

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.