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.

Shares of Fennec Pharmaceuticals stock were cut almost in half early Monday as the company said manufacturing issues caused another FDA rejection of its reformulated version of sodium thiosulfate, which is intended to help kids who lose hearing due to chemo treatment.

The biotech had resubmitted an NDA for the drug to treat platinum-based, chemo-related ototoxicity in young children earlier this year. The first NDA was denied by the FDA last year, with the agency citing manufacturing issues with the biotech’s supplier.

Alvogen is handing off two of its subsidiaries to CEO Róbert Wessman and his healthcare investment firm Aztiq — who has now tied the two together in a massive biobucks deal.

In an alliance with Thailand’s PTT Group subsidiary Innobic, the two companies signed an agreement last week to buy a 100% stake in Alvogen Emerging Market Holdings Limited (AEMH) for $475 million from Alvogen, buying out shareholders such as CVC Capital Partners and Singapore’s Temasek. And now, the group is the majority shareholder of Alvogen’s former Asian subsidiary Lotus Pharmaceuticals and the only shareholder of Alvogen Malta, the owner of B2B pharma Adalvo.

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.