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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

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WIB22: Chas­ing af­ter ever-evolv­ing sci­ence takes a drug hunter across the pond

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Like many scientists, Fiona Marshall would tell you that she loved the natural world growing up — going to look at crabs running around the beach near her childhood home, pondering about the tides. But one thing about biology, in particular, stood out: It was constantly changing, and changing very quickly.

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