#ASH17: The big los­er in CAR-T, Juno is mak­ing a bid to seize the fast lane to fron­trun­ner sta­tus

Juno Ther­a­peu­tics $JUNO may be play­ing catchup in CAR-T. But if the lat­est cut of its 3-month DL­B­CL da­ta at the top dose holds up, the biotech won’t be play­ing for sec­ond — or third — place.

In their ab­stract out for ASH this morn­ing, Juno ex­ecs spelled out a key piece of da­ta for the high dose arm of the ear­ly study on JCAR017. Ze­ro­ing in on that one snap­shot, re­searchers say they tracked an 80% over­all re­sponse rate and a 73% com­plete re­sponse rate at 3 months for the high dose among a “piv­otal core” group of 15 pa­tients.

Gilead’s Kite and No­var­tis saw a slight de­cline in the CR rates to the low 30s go­ing from 3 to 6 months, leav­ing Juno a win­dow for con­sid­er­able im­prove­ment.

To be sure, Juno still has a long way to go af­ter its lead JCAR015 proved to be a lethal, tox­ic dis­as­ter in what was in­tend­ed to be a piv­otal study. But the biotech isn’t at all con­tent to be re­main­dered to the sec­tion of the in­dus­try that counts the num­ber of pa­tients killed in a failed study. In­stead, Juno be­lieves that its fol­low-up pro­gram will prove that the big sums gam­bled on its tech­nol­o­gy will show that they came up with a bet­ter CAR-T, with a more ef­fec­tive man­u­fac­tur­ing process and a safer pro­file that will ul­ti­mate­ly carve out a big place for it­self in the mar­ket.

In­vestors liked what they were see­ing, dri­ving up Juno’s shares by 10% this morn­ing.

Sunil Agar­w­al

Every­thing is rid­ing on this one. There won’t be much chance for a third shot at suc­cess.

What’s dif­fer­ent this time?

“The anal­o­gy I’ll give you,” says R&D chief Sunil Agar­w­al: “Small changes in the an­ti­body world can make big dif­fer­ences; all CARs are not the same.”

There’s more to come at ASH, he adds, where they can re­view the re­sponse for a big­ger group of pa­tients. But the es­sen­tial ef­fi­ca­cy and safe­ty pro­file on dis­play to­day, he adds, isn’t go­ing to change.

Says Agar­w­al: “I think these da­ta con­tin­ue to sup­port a best-in-class pro­file.”

For one, there’s the switch to the 4-1BB cos­tim­u­la­to­ry do­main, which al­lows for a slow and steady ac­ti­va­tion that sets the foun­da­tion for a more durable re­sponse.

Hans Bish­op

But that’s a fea­ture that No­var­tis’ CAR-T shares as well. Juno CEO Hans Bish­op tells me the “pre­cise pro­duc­tion” val­ues used now in mak­ing the ther­a­py from cells ex­tract­ed from pa­tients is just far more pre­cise.

“We know CD4 and CD8 cells act dif­fer­ent, CD8 cells are more po­tent,” says Bish­op. Get­ting the right mix with a mea­sured ex­pan­sion of cells now is part of a pre­cise­ly arranged pro­duc­tion recipe that dis­tin­guish­es JCAR017 from the rest, he as­serts.

Bish­op isn’t talk­ing ex­act pric­ing yet, and won’t un­til much lat­er in the game. But he does want peo­ple to un­der­stand that to be com­pet­i­tive here in­volves beat­ing out some steep ex­ist­ing costs in treat­ing DL­B­CL or ALL. Safe­ty, he says, will play a big role in that.

The lat­est up­date on the da­ta re­mains with 1 pa­tient suf­fer­ing from cy­tokine re­lease syn­drome, and 14% with neu­ro­tox­i­c­i­ty run­ning from Grade 1 to Grade 4. That’s not a per­fect score, by any means, but in this world Bish­op feels the num­bers give Juno an ad­van­tage over worse is­sues with the mar­ket lead­ers.

Close to two thirds of the pa­tients in their study nev­er ex­hib­it­ed any signs of tox­i­c­i­ty, ei­ther cy­tokine re­lease syn­drome or neu­ro­tox­i­c­i­ty, which ul­ti­mate­ly de­stroyed Juno’s lead ther­a­py, JCAR015, af­ter it killed 5 pa­tients. In this world, any tox, Grade 1 or above, earns pa­tients a one-way trip to the hos­pi­tal, which doesn’t come cheap. By avoid­ing tox, Juno hopes to prove that most pa­tients can be treat­ed in an out­pa­tient set­ting, vast­ly re­duc­ing their over­all cost — which some ex­perts say may well range from $1 mil­lion to $1.5 mil­lion, all in.

It’s a com­pelling ar­gu­ment, and one that Juno has care­ful­ly craft­ed af­ter one of the worst clin­i­cal set­backs in re­cent his­to­ry. Their R&D work here will be care­ful­ly scru­ti­nized at every step. To get on to the mar­ket, they’ll have to pass muster at the hands of a group of reg­u­la­tors em­bar­rassed by their abrupt and in­ex­plic­a­ble de­ci­sion to lift the orig­i­nal hold on JCAR015 af­ter just a few days — al­low­ing more pa­tients to die.

Juno has a high bar to clear, but they’re tak­ing a run­ning leap at it.

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.
Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.