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.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive PhI­II for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma. 

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.