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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA’s work­load buck­les un­der the strain, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

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