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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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