En­cour­ag­ing gene ther­a­py da­ta give uniQure an in­jec­tion of con­fi­dence as it preps PhI­II show­down with Spark

Gene ther­a­py com­pa­ny uniQure start­ed the week in style with the news that it’s dosed the first pa­tient in its Phase III tri­al — a cru­cial step to­ward its quest for the best-in-class, first-in-mar­ket ti­tle in he­mo­phil­ia B gene ther­a­py. And to­day it’s of­fer­ing an up­date on the kind of mid-stage da­ta it’s armed with.

Matt Ka­pus­ta

Mean Fac­tor IX lev­els hit 38% of nor­mal lev­els 12 weeks af­ter the three pa­tients tracked in the Phase IIb study re­ceived the one-time in­jec­tion, reach­ing what the com­pa­ny calls “the nor­mal range” and well above the 12% com­mon­ly re­gard­ed as suf­fi­cient to sub­stan­tial­ly re­duce spon­ta­neous bleeds.

It’s the first look at da­ta three months post-ad­min­is­tra­tion — sig­nif­i­cant be­cause most pa­tients don’t be­gin to start plateau­ing un­til that point, CEO Matt Ka­pus­ta tells me in a pre­view of the re­sults, which fol­lows an up­beat snap­shot in No­vem­ber on six-week da­ta.

So have they reached the peak in FIX lev­els? Prob­a­bly not, Ka­pus­ta said.

The best way to glean that is we ac­tu­al­ly did a Phase I/II study with the first gen­er­a­tion prod­uct that is near­ly iden­ti­cal to the AMT-061 and in­clud­ed pa­tients that were at the same dose. […] Of the 9 pa­tients that were off of pro­phy­lax­is, 8 of them had Fac­tor IX ac­tiv­i­ty that was high­er at 52 weeks or — their lat­est mea­sure­ment was high­er than what it was at 12 weeks. […] So we don’t know if that will con­tin­ue to be the case, but that’s prob­a­bly — look­ing at those ki­net­ics from the Phase I/II study sug­gests that there is po­ten­tial for mean­ing­ful in­creas­es go­ing for­ward.

Since the pa­tients be­gan dos­ing at dif­fer­ent times, uniQure al­so gleaned in­sights in­to the (slight­ly) longer term FIX ac­tiv­i­ties: 48% for the first pa­tient at week 16; 25% for the sec­ond pa­tient at week 14; and 51% for the third pa­tient at 12 weeks.

“It’s not un­usu­al to have a three, maybe four-fold mul­ti­ple be­tween your min­i­mum and your max­i­mum,” Ka­pus­ta says. “Here of course we’ve got about a two-fold. So in our view the vari­abil­i­ty is ac­tu­al­ly tighter.”

The new round of da­ta drew uni­ver­sal ap­plause from an­a­lysts, with Chardan spec­u­lat­ing that the com­pa­ny is now a prime takeover tar­get. Shares are up 4%.

A chief ri­val of Spark Ther­a­peu­tics — which is tap­ping in­to he­mo­phil­ia as a fol­low-up to its ground­break­ing gene ther­a­py for the eye — Lex­ing­ton, MA- and Am­s­ter­dam-based uniQure $QURE pleased in­vestors and an­a­lysts back in No­vem­ber when it re­port­ed mean FIX lev­els of 31% at six weeks.

While care­ful to note that “we don’t love com­ment­ing on oth­er peo­ple’s da­ta,” Ka­pus­ta cit­ed the high lev­els of FIX ac­tiv­i­ty, low im­muno­genic­i­ty — none of uniQure’s pa­tients have re­quired im­muno­sup­pres­sion so far — and the fact that it doesn’t ex­clude pa­tients with pre-ex­ist­ing an­ti­bod­ies to AAV vec­tors as rea­sons to be­lieve that they have a “high­ly com­pa­ra­ble if not po­ten­tial­ly an op­ti­mized or su­pe­ri­or tar­get prod­uct pro­file.”

But the re­al show­down will take place in the piv­otal stage, as uniQure catch­es up with a Phase III pro­gram that Spark part­ner Pfiz­er be­gan last sum­mer.

With 20 ac­tive sites across the US and Eu­rope, uniQure’s Phase III is ex­pect­ed to en­roll 50 pa­tients by the end of the year. Top-line da­ta on the pri­ma­ry end­point — FIX ac­tiv­i­ty af­ter six months — should be ready in late 2020, paving the way for a BLA sub­mis­sion in 2021, Ka­pus­ta said.

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.