As­cendis Phar­ma of­fers pos­i­tive sur­prise as its tech not just equals, but im­proves out­comes in key study

Tech­nol­o­gy de­vel­oped by Den­mark’s As­cendis Phar­ma to re­lease a par­tic­u­lar drug with­in the body in a pre­dictable man­ner at reg­u­lar in­ter­vals with­out the need for mul­ti­ple sep­a­rate ad­min­is­tra­tions has been shown to work well in a late-stage tri­al in pe­di­atric pa­tients with growth hor­mone de­fi­cien­cy — val­i­dat­ing the com­pa­ny’s plat­form that is used across its port­fo­lio.

The tech­nol­o­gy, called TransCon or tran­sient con­ju­ga­tion, com­pris­es an un­mod­i­fied ap­proved drug, an in­ert car­ri­er that pro­tects it, and a link­er that tem­porar­i­ly binds the two. When bound, the car­ri­er in­ac­ti­vates and shields the par­ent drug from be­ing re­leased, but once the prod­uct is in­ject­ed in­to the body, phys­i­o­log­ic pH and tem­per­a­ture con­di­tions al­low for the pre­dictable dis­sem­i­na­tion of the ac­tive drug — this can be done dai­ly or even half year­ly. The tech can be used for sys­temic ad­min­is­tra­tion or lo­cal­ly in ar­eas that are dif­fi­cult to treat with con­ven­tion­al ther­a­py.

The 161 treat­ment-naïve-pa­tient-tri­al, called heiGHt, com­pared the once-week­ly TransCon growth hor­mone (hGH) against a dai­ly growth hor­mone — Pfiz­er’s Genotropin — in chil­dren with growth hor­mone de­fi­cien­cy, an or­phan dis­ease caused by the in­suf­fi­cient pro­duc­tion of growth hor­mone by the pi­tu­itary gland that is char­ac­ter­ized by short stature, meta­bol­ic ab­nor­mal­i­ties, psy­choso­cial chal­lenges and cog­ni­tive gaps.

TransCon hGH is de­signed to de­liv­er un­mod­i­fied hGH — the same growth hor­mone used in dai­ly ther­a­pies — at a pre­dictable rate over one week. Cur­rent­ly in the Unit­ed States and Eu­rope, pa­tients must con­tend with dai­ly hGH in­jec­tions re­sult­ing in thou­sands of in­jec­tions over time, which of­ten leads to poor pa­tient com­pli­ance, the com­pa­ny said.

Tri­al da­ta showed that As­cendis’ prod­uct not on­ly met the main goal of non-in­fe­ri­or­i­ty in an­nu­al­ized height ve­loc­i­ty (a mea­sure of speed of growth) at 52 weeks, but ac­tu­al­ly proved su­pe­ri­or to dai­ly hGH. These re­sults could con­sti­tute a home run, con­sid­er­ing var­i­ous an­a­lysts were ex­pect­ing just the non-in­fe­ri­or­i­ty bench­mark to be met.

Joseph Schwartz

In the pri­ma­ry analy­sis of the in­tent-to-treat pop­u­la­tion, TransCon hGH demon­strat­ed a sig­nif­i­cant­ly greater an­nu­al­ized height ve­loc­i­ty of 11.2 cm/year com­pared to 10.3 cm/year for the dai­ly hGH — the treat­ment dif­fer­ence amount­ed to 0.86 cm/year, hit­ting a p-val­ue of 0.0088. The ex­per­i­men­tal treat­ment be­gan to sur­pass the com­para­tor at a sta­tis­ti­cal­ly sig­nif­i­cant rate from week 26 on­ward.

As­cendis’ shares $AS­ND sky­rock­et­ed more than 64.6% in morn­ing trad­ing to $114.10.

“The stock is not cheap, but we do see room for sig­nif­i­cant up­side up­on pos­i­tive piv­otal da­ta that may be used for reg­is­tra­tion of the first long-act­ing growth hor­mone treat­ment, which has been a prized goal for many com­pa­nies over sev­er­al decades,” Leerink’s Joseph Schwartz wrote in a note in late Jan­u­ary.

The com­pa­ny, which has part­nered with Roche’s Genen­tech and Sanofi to eval­u­ate its tech­nol­o­gy for oph­thal­mol­o­gy and di­a­betes drugs re­spec­tive­ly, plans to sub­mit a mar­ket­ing ap­pli­ca­tion for its pe­di­atric GHD prod­uct in the first half of 2020.

“As­cendis’ man­age­ment con­tin­ues to de­liv­er with this best-case out­come for TransCon hGH in a Ph3 tri­al, fur­ther val­i­dat­ing the tech­nol­o­gy plat­form and with pos­i­tive read-through to oth­er clin­i­cal pro­grams and pipeline po­ten­tial. We al­so see the pos­i­tive Ph3 rais­ing the com­pa­ny’s pro­file as a po­ten­tial ac­qui­si­tion tar­get, as As­cendis of­fers bal­anced clin­i­cal pipeline with fair­ly de-risked pro­grams, po­ten­tial best-in-class as­sets, an emerg­ing new ther­a­peu­tics ver­ti­cal and plen­ty of op­tion­al­i­ty with­in the TransCon tech­nol­o­gy plat­form,” Cred­it Su­isse an­a­lysts wrote in a note.

Top-line da­ta for the fliGHt Tri­al, eval­u­at­ing TransCon hGH in sub­jects who switch from dai­ly hGH, are ex­pect­ed in the sec­ond quar­ter. The com­pa­ny is al­so eval­u­at­ing its tech­nol­o­gy for use in hy­poparathy­roidism and achon­dropla­sia.

Eli Casdin, Casdin Capital

Eli Cas­din backs Codex­is' plat­form tech with $50M eq­ui­ty buy

About a month af­ter Codex­is notched a deal with No­var­tis $NVS, the Cal­i­for­nia com­pa­ny $CDXS on Thurs­day said long-time in­vestor Cas­din Cap­i­tal is putting up $50 mil­lion in a pri­vate place­ment, which puts the New York-based in­vest­ment firm in con­trol of more than 5% of the pro­tein en­gi­neer­ing play­er’s stock.

Eli Cas­din start­ed his epony­mous in­vest­ment firm in 2012 and dates his re­la­tion­ship with Codex­is back to at least a decade. About three years ago, Cas­din Cap­i­tal be­gan in­vest­ing in the in­dus­tri­al biotech com­pa­ny, af­ter it piv­ot­ed its fo­cus to the life sci­ences — un­der the aus­pices of new chief John Nicols — away from the en­er­gy in­dus­try.

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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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.

In­vestors pony up $476M for the lat­est round of biotech IPOs to hit the Street

Three biotechs — and a genome se­quenc­ing play­er — have caught the lat­est tide to the Gold Coast of IPOs, round­ing out the first half of 2019 with 23 new drug de­vel­op­ers mak­ing it on Nas­daq.

Most of these com­pa­nies filed their IPOs al­most si­mul­ta­ne­ous­ly, though we’re still wait­ing on word of fel­low class­mate Bridge­Bio’s pric­ing af­ter CEO Neil Ku­mar set the terms at $14 to $16 a share on Mon­day in search of a $240 mil­lion (or so) wind­fall. If he’s suc­cess­ful, that would take the one-week haul past the $700 mil­lion mark, a fresh sign that in­vestors’ en­thu­si­asm for new­ly coined pub­lic biotechs hasn’t cooled.

In starved an­tibi­ot­ic field, Melin­ta soars as FDA grants speedy drug re­view

Such is the state of af­fairs in an­tibi­ot­ic land that the FDA agree­ing to pri­or­i­ty re­view an ap­pli­ca­tion to ex­pand the use of an an­tibi­ot­ic can rock­et up a stock more than two-fold.

On Wednes­day, Melin­ta Ther­a­peu­tics said its ap­proved an­tibi­ot­ic Baxdela had been grant­ed pri­or­i­ty re­view for use in com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia (CAPB). The FDA is ex­pect­ed to make its de­ci­sion by Oc­to­ber 24. Shares of the Con­necti­cut drug­mak­er $ML­NT cat­a­pult­ed, clos­ing up near­ly 224% at $6.41.

Robert Forrester, Verastem

Ve­rastem CEO For­rester steps to the ex­it as the board hunts com­mer­cial-savvy ex­ec for the be­lea­guered biotech

Robert For­rester is step­ping down as CEO of Ve­rastem On­col­o­gy $VSTM just 8 months af­ter the com­pa­ny nabbed an ap­proval for du­velis­ib, a PI3K drug with a sto­ried past — and what ap­pears as not much of a fu­ture.

The biotech put out word this morn­ing that For­rester will take an ad­vi­so­ry role with Ve­rastem while COO Dan Pa­ter­son steps up to take charge of the lead­er­ship team and the board looks around for a new CEO.

Ken Frazier appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

Who’s next in line to suc­ceed Ken Fra­zier as CEO of the Keytru­da-blessed Mer­ck?

When Merck waved off a looming forced retirement for Ken Frazier last September, the board cited flexibility in CEO transition as a key factor in the decision. Having Frazier — who’s also chairman of the company — around beyond his 65th birthday in 2019 would ensure they install the best person at the best time, they said.

The board has evidently begun that process with a clear preference for internal candidates, sources told Bloomberg. CFO Robert Davis, chief marketing officer Michael Nally, and chief commercial officer Frank Clyburn are all in the running, according to an insider.

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Brent Saunders at an Endpoints News event in 2017 — File photo

An­a­lyst call with Al­ler­gan ex­ecs stokes an­tic­i­pa­tion of a plan to split the com­pa­ny in ‘a month or two’

So what’s up at Al­ler­gan?

Ear­li­er this week the ubiq­ui­tous Ever­core ISI an­a­lyst Umer Raf­fat was on the line with com­pa­ny ex­ec­u­tives to probe in­to the lat­est on the num­bers as well as CEO Brent Saun­ders’ re­cent de­c­la­ra­tion that he’d be do­ing some­thing de­fin­i­tive to help long-suf­fer­ing in­vestors who have watched their shares dwin­dle in val­ue.

He came away with the im­pres­sion that a sig­nif­i­cant com­pa­ny split is on the way. And not on some dis­tant time hori­zon.