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.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.