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.

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.

Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,400+ biopharma pros reading Endpoints daily — and it's free.

Saurabh Saha at Endpoints News' #BIO19

On the heels of $250M launch, Centes­sa barges ahead with an IPO to fu­el its 10-in-1 Medicxi pipeline

Francesco De Rubertis made no secret of IPO plans for Centessa, his 10-in-1 legacy play. Barely two months later, the S-1 is in.

The hot-off-the-press filing depicts the same grand vision that the longtime VC touted when he did the rounds in February: Take the asset-centric mindset that he’s been preaching at Medicxi over the years, and roll up a bunch of biotech upstarts, with unrelated risk profiles, into 1 pharma company that can carry on the development at scale.