Fresh from a $72M raise, Jeff Aron­in's new lead rare dis­ease drug is flagged as a fail­ure

Just a few days af­ter one of Jeff Aronin’s biotechs put out the word that they had raised $71.8 mil­lion to push their rare dis­ease drug in­to piv­otal tri­als, the com­pa­ny qui­et­ly flagged the treat­ment’s fail­ure in Phase II.

But they are go­ing for Phase III any­way.

Jeff Aronin

The clin­i­cal­tri­ page on the Phase II study of Cas­tle Creek’s on­ly drug was up­dat­ed on Oc­to­ber 22 and now reads that the tri­al was ter­mi­nat­ed af­ter an in­de­pen­dent da­ta mon­i­tor­ing com­mit­tee “sug­gest­ed that the study will not meet sta­tis­ti­cal ob­jec­tives.” The page al­so in­cludes a time­line with a wrap due in the mid­dle of Oc­to­ber.

Cas­tle Creek’s co-founder, Michael Der­by, re­spond­ed to an email query of mine to say that the tri­al “showed sev­er­al pos­i­tive trends in key ef­fi­ca­cy mea­sures and a be­nign safe­ty pro­file that strong­ly sup­port con­tin­ued phase 3 de­vel­op­ment of this po­ten­tial treat­ment, which is our plan.”

He added:

The de­ci­sion to ter­mi­nate the phase 2 study was made fol­low­ing a planned in­ter­im analy­sis by an In­de­pen­dent Da­ta Mon­i­tor­ing Com­mit­tee that in­di­cat­ed that the tri­al, as struc­tured and pow­ered, was un­like­ly to de­liv­er the lev­el of sta­tis­ti­cal ro­bust­ness need­ed to con­firm ef­fi­ca­cy as de­fined by the pri­ma­ry end­point. In light of this da­ta, we plan to use our most re­cent in­vest­ment to pur­sue the late-stage de­vel­op­ment of this in­ves­ti­ga­tion­al drug. Giv­en the un­met med­ical need for pa­tients with EBS, we are al­so al­low­ing pa­tients from the ter­mi­nat­ed phase 2 tri­al to con­tin­ue ther­a­py in an on­go­ing open-la­bel ex­ten­sion tri­al.

To be clear, all of the in­vestors in Cas­tle Creek, in­clud­ing the in­vestors in our most re­cent fi­nanc­ing, were briefed on the in­ter­im re­sults and the de­ci­sion to ter­mi­nate the tri­al. They ful­ly sup­port our plan to con­tin­ue de­vel­op­ment and to de­sign an ad­e­quate­ly pow­ered phase 3 ef­fi­ca­cy and safe­ty tri­al.

Aronin — best known for kick­ing up a ruckus af­ter cob­bling to­geth­er da­ta on an old, cheap steroid sold over­seas for around $1,000 a year and steer­ing it through an FDA ap­proval for Duchenne mus­cu­lar dy­s­tro­phy with plans to sell it for $89,000 a year — runs Paragon Bio­sciences, which in turn owns 6 sub­sidiaries in­clud­ing Cas­tle Creek.

Michael Der­by

In Cas­tle Creek’s case, they took an old drug that is mar­ket­ed in a va­ri­ety of coun­tries around the world for os­teoarthri­tis — 50 mg di­ac­ere­in — and re­for­mu­lat­ed the IL-1 be­ta an­ti-in­flam­ma­to­ry drug in­to a top­i­cal treat­ment for an ul­tra-rare frag­ile skin dis­ease called epi­der­mol­y­sis bul­losa. 

Fi­deli­ty Man­age­ment & Re­search Com­pa­ny and Val­or Eq­ui­ty Part­ners put up the mon­ey to fund late-stage de­vel­op­ment.

Back in 2014 the EMA added re­stric­tions on the use of drugs con­tain­ing di­ac­ere­in, cit­ing ad­verse events that in­cludes prob­lems with the liv­er. The FDA, in turn, pro­vid­ed the com­pa­ny with a rare pe­di­atric dis­ease des­ig­na­tion for di­ac­ere­in 1% oint­ment, just as they did when Aronin was de­vel­op­ing his steroid Em­flaza. Those des­ig­na­tions are worth quite a bit, as an ap­proval would war­rant an award of a pri­or­i­ty re­view vouch­er worth more than $100 mil­lion.

And there are some dis­tinct sim­i­lar­i­ties be­tween his lat­est rare dis­ease pro­gram and his score on DMD, which a num­ber of harsh crit­ics in Con­gress con­clud­ed was re­ward­ed for a suc­cess­ful plan to game the drug ap­proval sys­tem.

Aronin has many of his old crew at Marathon — dis­band­ed in the wake of the con­tro­ver­sy over de­flaza­cort — work­ing at Paragon. The biotech proved to be an in­spi­ra­tion for Mar­tin Shkre­li, the phar­ma bro who was cas­ti­gat­ed when he en­gi­neered a 5,000%-plus overnight price hike at Tur­ing for an old drug of his own.

“These guys in­vent­ed price in­creas­es,” Shkre­li com­ment­ed once, be­fore he was sen­tenced to 7 years in a fed­er­al prison for de­fraud­ing in­vestors at his hedge funds. “I lit­er­al­ly learned it from them.”

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.

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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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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Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.

Partners Innovation Fund

David de Graaf now has his $28.5M launch round in place, build­ing a coen­zyme A plat­form in his lat­est start­up

Long­time biotech ex­ec David de Graaf has the cash he needs to set up the pre­clin­i­cal foun­da­tion for his coen­zyme A me­tab­o­lism com­pa­ny Comet. A few high-pro­file in­vestors joined the ven­ture syn­di­cate to sup­ply Comet with $28.5 mil­lion in launch mon­ey — enough to get it two years in­to the plat­form-build­ing game, with­in knock­ing dis­tance of the clin­ic.

Canaan jumped in along­side ex­ist­ing in­vestor Sofinno­va Part­ners to co-lead the round, with par­tic­i­pa­tion by ex­ist­ing in­vestor INKEF Cap­i­tal and new in­vestor BioIn­no­va­tion Cap­i­tal.

Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.