Cy­to­ki­net­ics ax­es lead drug af­ter it im­plodes in a PhI­II mus­cle tri­al for ALS, shares crater

Cy­to­ki­net­ics $CYTK lead mus­cle drug has crashed in a Phase III study for ALS.

The biotech re­port­ed this morn­ing that tirasem­tiv, de­signed to amp up the mus­cles of sick pa­tients, failed to hit the pri­ma­ry end­point on what’s called slow vi­tal ca­pac­i­ty, which mea­sures how much air can be ex­haled. And now the ther­a­py is be­ing shelved as the biotech’s stock craters, plung­ing more than 30% Tues­day morn­ing.

Robert Blum

The de­cline in SVC was slow­er in the drug arms com­pared to a place­bo, but it nev­er achieved sta­tis­ti­cal sig­nif­i­cance. The mid- and high-dose arms had the best re­spons­es, but it wasn’t enough. And now the South San Fran­cis­co-based biotech plans to shift fo­cus to a next-gen drug in the pipeline, where it feels it has a bet­ter shot at suc­cess, and kill the tirasem­tiv pro­gram.

That’s al­so bad news for Astel­las, which com­mit­ted $95 mil­lion in cash to Cy­to­ki­net­ics in or­der to get an op­tion on the drug as well as the ear­li­er-stage ther­a­py Cy­to­ki­net­ics will now turn to. Astel­las al­so in­clud­ed up to $100 mil­lion in mile­stones for the work.

While dis­ap­point­ing for in­vestors, it can’t be a big sur­prise to re­searchers in the field. Three years ago Cy­to­ki­net­ics re­port­ed that tirasem­tiv — which is de­signed to in­crease mus­cle sen­si­tiv­i­ty to cal­ci­um –flunked the pri­ma­ry and a range of sec­on­daries for ALS, scor­ing on­ly on SVC. Failed mid-stage drugs face tough odds when they are pushed in­to late-stage test­ing, as Cy­to­ki­net­ics knows all too well this morn­ing.

ALS re­mains one of the tough­est tar­gets in drug R&D, de­feat­ing mul­ti­ple at­tempts at ad­dress­ing a dis­ease that in­volves mo­tor neu­rons and the steady and re­morse­less de­cline of a pa­tient’s mus­cle ac­tiv­i­ty, lead­ing to death. Rilu­zole was the on­ly drug ap­proved for ALS in the US, ar­riv­ing in 1995, and re­mained in a class by it­self un­til Mit­subishi Tan­abe’s Rad­i­ca­va was added ear­li­er this year. Nei­ther come close to stop­ping the dis­ease.

Cy­to­ki­net­ics CEO Robert Blum not­ed:

We have de­cid­ed to sus­pend the de­vel­op­ment of tirasem­tiv. While we be­lieve that VI­TAL­I­TY-ALS demon­strat­ed phar­ma­co­log­ic ac­tiv­i­ty for the mech­a­nism of ac­tion, we al­so be­lieve that lim­i­ta­tions of tirasem­tiv may be ad­dressed with our next-gen­er­a­tion fast skele­tal mus­cle ac­ti­va­tor, CK-2127107.  Based on pre­vi­ous Phase 1 clin­i­cal stud­ies, we be­lieve CK-2127107 will be bet­ter tol­er­at­ed and po­ten­tial­ly more ef­fec­tive than tirasem­tiv in pa­tients with ALS and look for­ward to Phase 2 tri­al re­sults in 2018.

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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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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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.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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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.