Nim­bus picks 4 pre­clin­i­cal tar­gets for the next chap­ter of its pi­o­neer­ing com­pu­ta­tion­al drug dis­cov­ery work

Big name part­ner­ships were crit­i­cal for Nim­bus Ther­a­peu­tics’ first decade. With a head-turn­ing $1.2 bil­lion — $600 mil­lion of which were paid with­in months — deal from Gilead and a re­turn­ing cus­tomer in Cel­gene, the biotech emerged as a pro­lif­ic pi­o­neer of com­pu­ta­tion­al chem­istry and struc­ture-based drug dis­cov­ery while the in­dus­try went through a seis­mic shift in its think­ing of the role that al­go­rithms play in en­gi­neer­ing new ther­a­pies.

Jeb Keiper

As the sec­ond of the ini­tial batch of pro­grams en­ter the clin­ic, Nim­bus is un­veil­ing the head­ings that will de­fine what it calls its sec­ond chap­ter.

Their team of 20-plus sci­en­tists has iden­ti­fied four new tar­gets — AMP­Kβ2, CTPS1, Cbl-b and WRN — which they have been prob­ing with aca­d­e­m­ic col­lab­o­ra­tors and ex­perts at Schrödinger. And this time around, they plan to keep all four in-house for at least a lit­tle longer, fo­cus­ing on re­cruit­ing new staffers and friend­ly re­searchers rather than buy­ers.

At the same time, Nim­bus has dropped its STING ef­forts af­ter a slew of biotechs reached for it and came up emp­ty.

“One of the com­pli­ments we’ve been paid by our peers in the broad­er drug dis­cov­ery and de­vel­op­ment com­mu­ni­ty has been in our abil­i­ty to se­lect re­al­ly in­ter­est­ing tar­gets that are quite com­pelling,” Jeb Keiper — the for­mer BD chief who took over as CEO from Don Nichol­son less than two years ago — told End­points News. “We care a lot about be­ing able to do that.”

Aside from the usu­al sus­pects in tar­get se­lec­tion, such as ge­net­ic val­i­da­tion and med­ical need, Nim­bus zoomed in­to ones for which a se­lec­tive, struc­ture-based ap­proach is par­tic­u­lar­ly help­ful, CSO Pe­ter Tum­mi­no said.

Pe­ter Tum­mi­no

In AMPK (AMP-ac­ti­vat­ed pro­tein ki­nase), that means find­ing ac­ti­va­tors se­lec­tive for the β2 sub­unit, which could trans­late in­to a bet­ter safe­ty pro­file as meta­bol­ic drugs. Sim­i­lar­ly, the chal­lenge in CTP is to find com­pounds se­lec­tive for the S-1 iso­form. Cbl-b (Cbl pro­to-onco­gene B) is an E3 ubiq­ui­tin lig­ase — a nat­ur­al pro­tein de­grad­er — that’s gar­nered at­ten­tion from both small com­pa­nies like Nurix and big ones like Roche. Fi­nal­ly, the goal with WRN (Wern­er syn­drome ATP-de­pen­dent he­li­case) is to come up with a new treat­ment op­tion for tu­mors vul­ner­a­ble to dis­rup­tions in DNA re­pair.

“What isn’t new is we’re look­ing for small mol­e­cule agents,” he said.

Al­though these are tar­gets of high in­ter­est, he added, much is still un­known about their struc­tures, and Nim­bus is work­ing with lead­ing bi­ol­o­gists to elu­ci­date them with tech­niques like cryo-EM and crys­tal­log­ra­phy.

These are “not things you can sim­ply out­source to con­tract re­search groups,” Keiper added. “You re­al­ly are do­ing fun­da­men­tal aca­d­e­m­ic dis­cov­ery work.” That’s the kind of spe­cial sauce — mix­ing dyed in the wool drug dis­cov­ery vet­er­ans with com­pu­ta­tion­al ex­perts — that Nim­bus be­lieves will keep it go­ing for many years more.

How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

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Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

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Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

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Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

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Busi­ness­es and schools can man­date the use of Covid-19 vac­cines un­der EUAs, DOJ says

As public and private companies stare down the reality of the Delta variant, many are now requiring that their employees or students be vaccinated against Covid-19 prior to attending school or to returning or starting a new job. Claims that such mandates are illegal or cannot be used for vaccines under emergency use authorizations have now been dismissed.

Setting the record straight, the Department of Justice on Monday called the mandates legal in a new memo, even when used for people with vaccines that remain subject to EUAs.

Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

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No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Andrea Pfeifer, AC Immune CEO (AC Immune)

Look­ing to repli­cate Covid-19 suc­cess in neu­ro, BioN­Tech back­ers bet on AC Im­mune and its new­ly-ac­quired Parkin­son's vac­cine

The German billionaires behind BioNTech have found a new vaccine project to back.

Through their family office Athos Service, twin brothers Thomas and Andreas Strüngmann are leading a $25 million private placement into Switzerland’s AC Immune — which concurrently announced that it’s shelling out $58.7 million worth of stock to acquire Affiris’ portfolio of therapies targeting alpha-synuclein, including a vaccine candidate, for Parkinson’s disease.