Bris­tol-My­ers claims the lead in a race to de­vel­op a TYK2 drug, hop­ing to dis­rupt a huge mar­ket for an­ti-in­flam­ma­to­ries

Bris­tol-My­ers Squibb’s TYK2 team has been show­ing off some Phase II da­ta they be­lieve puts them in the run­ning for leader of a small but promi­nent pack of de­vel­op­ers look­ing to ad­vance a new class of an­ti-in­flam­ma­to­ries that aim at pen­e­trat­ing some very big mar­kets.

As pub­lished in the New Eng­land Jour­nal of Med­i­cine and pre­sent­ed at the 27th Eu­ro­pean Acad­e­my of Der­ma­tol­ogy and Ven­erol­o­gy Con­gress in Paris, Bris­tol-My­ers’ ef­fort for BMS-986165 pro­duced some com­pet­i­tive re­sults in a key mid-stage study for mod­er­ate-to-se­vere plaque pso­ri­a­sis — a packed field where JAK in­hibitors have been mak­ing waves.

By nar­row­ly tar­get­ing TYK2 — and leav­ing the oth­er JAK fam­i­ly tar­gets out — with an al­losteric ap­proach, as op­posed to ATP bind­ing, the Bris­tol-My­ers group say they were able to safe­ly pro­duce a range of com­pet­i­tive PASI75 clear­ance rates of 67% to 75% for the three high­est dos­es of the oral drug in the dose-rang­ing study.

John Throup

“From my per­spec­tive the clin­i­cal da­ta we have bears out the strat­e­gy we set out to de­liv­er right in the ear­ly stages of the dis­cov­ery pro­gram,” says John Throup, the de­vel­op­ment lead for TYK2, who of­fered a pre­view of the da­ta that was on dis­play Wednes­day, along with dis­cov­ery chemist Ryan Moslin.

This was an in-house pro­gram from the very be­gin­ning at Bris­tol-My­ers. And they’re tak­ing it all the way through, look­ing to trip up pro-in­flam­ma­to­ry cy­tokine re­cep­tors, in­clud­ing the hot tar­get IL-23, IL-12 and Type 1 in­ter­fer­ons with what they be­lieve is a clear­ly safe oral drug look­ing to dis­tin­guish it­self from a very big — and grow­ing — field of ri­vals.

The drug is al­ready in two Phase III stud­ies for pso­ri­a­sis, which joint­ly re­cruit­ed 1,600 pa­tients with a planned read-out in mid-2020. And they’re ex­pand­ing the work in­to Crohn’s and lu­pus, keep­ing an eye on oth­er tar­gets they could add as well

“Pa­tients don’t need an­oth­er non-spe­cif­ic JAK in­hibitor,” adds Throup, not­ing the safe­ty is­sues that have come up for the class, which in­cludes baric­i­tinib and Xel­janz. And they be­lieve that they’ve al­so tak­en the right path in the clin­ic by avoid­ing the ac­tive bind­ing site and tar­get­ing the reg­u­la­to­ry do­main in TYK2.

Of course, this drug still has to sur­vive the big Phase III chal­lenge in much larg­er pa­tient pop­u­la­tions that are de­signed to spot­light any small safe­ty is­sue. And ri­val de­vel­op­ment groups fo­cused on TYK2 for Cel­gene and its part­ners at Nim­bus, which is still pre­clin­i­cal, as well as Pfiz­er — which a spokesper­son tells me has mapped four Phase II stud­ies for PF-06700841— aren’t like­ly to let Bris­tol-My­ers pass un­chal­lenged.

In the mean­time, Ab­b­Vie is hus­tling ahead with its reg­u­la­to­ry re­view of the IL-23 drug risankizum­ab for pso­ri­a­sis, con­vinced they have the da­ta need­ed to field a megablock­buster. And there are more in­jecta­bles like Cosen­tyx — and fil­go­tinib from Gilead and Gala­pa­gos — which is al­ready well es­tab­lished. 

Bring­ing a safe, ef­fec­tive oral drug could dis­rupt that fast-chang­ing mar­ket­place. But this is one bat­tle of the gi­ants where every­one will be fierce­ly de­fend­ing their turf.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Tillman Gerngross, Adagio Therapeutics CEO

An­ti­body leg­end Till­man Gern­gross is el­bow­ing his way in­to the Covid-19 R&D cru­sade: 'I don’t see this end­ing any­time soon'

One of the most influential — and outspoken — scientists at work in the field of antibody discovery is jumping into the frenzied race to create new therapeutics to treat and prevent Covid-19. And he’s operating with the conviction that the current outbreak now once again spreading like wildfire will create plenty of demand for what he has in mind.

Dartmouth professor and Adimab CEO Tillman Gerngross tells me he’s raised $50 million from a group of close VCs to spin out a new company — Adagio Therapeutics — with a full C-suite team assembled to hire up a staff and keep rolling toward the clinic.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

The $1B Mer­ck-Bay­er drug that di­vid­ed car­di­ol­o­gists in March gets pri­or­i­ty re­view

Three months after Merck published in the New England Journal of Medicine data that left doctors and investors divided over just how well its experimental heart drug worked, the FDA has handed that drug priority review. A decision is now due by January 20, 2021.

Merck first announced the drug, known as vericiguat, as a Phase III success last November. In 2016, Merck had paid $1 billion upfront for US rights to the Bayer-developed drug. Early projections foresaw a few hundred million a year in sales, but the unspecified late-stage success raised the possibility for far more. After all, Novartis’s flagship heart drug, Entresto, was earning $1.7 billion per year and was expected to reach up to $4 billion in annual sales.

GSK’s Shin­grix leader Guil­laume Pfe­fer has jumped on board Flag­ship to helm a biotech hy­brid as Afeyan’s lat­est CEO-part­ner

After spending 4 years in a senior post with GlaxoSmithKline’s star team positioning Shingrix for a blockbuster approval, Guillaume Pfefer is headed back to the biotech world — in style.

Pfefer has signed on to join Noubar Afeyan’s busy group of partners at Flagship, and he’s taking the helm of an upstart — which today is being merged with another Flagship startup — with some grand plans of its own. The announcement this morning notes that Pfefer will run Kintai Therapeutics, one of the grads of the Flagship labs.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Donald Trump and Anthony Fauci (AP Images)

Covid-19 roundup: Fau­ci fires back at White House cam­paign to un­der­mine him

Anthony Fauci has called the White House campaign to discredit him “a bit bizarre” and said he stands by his previous statements, even if he has since changed his views.

The NIAID chief — who has received an outpouring of support following reports that the Trump administration has sent a document akin to opposition research to multiple news outlets — spoke with his usual candor in interviews with The Atlantic.

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John Furey, Imvax CEO

A neu­ro­sur­geon spent the past 30 years de­vel­op­ing a neoanti­gen tu­mor vac­cine. Now he has $112M for a piv­otal test

As a neurosurgeon, David Andrews knew there wasn’t much he could do for his glioma patients after resecting — rarely fully — their tumor. Even with the best treatment and care available, median overall survival is just somewhere between 14 and 16 months.

Then in the 1990s, his mentor at Thomas Jefferson University introduced him to Renato Baserga, a pathologist who had been studying the effect of using antisense oligonucleotide to knock out the insulin-like growth factor type 1 receptor in cancers. As IGF-R1 drives tumor growth and metastasis, the preclinical reasoning went, implanting a molecule targeting the receptor together with the tumor material near lymph nodes can slow down the spread of the cancer.

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Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.