#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.

A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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David Grainger [file photo]

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While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.

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Jeffrey Kindler’s plan to take his biotech — which is developing a slate of non-opioid painkillers — public, is back on.

The Boston based company, led by former Pfizer $PFE chief Kindler, originally contemplated a $70 million to $80 million IPO last year— but eventually postponed that strategy. On Wednesday, the company revived its bid to make a public debut in a filing with the SEC — although no pricing details were disclosed.

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Scientists learned strands of DNA could occasionally appear outside of its traditional home in the nucleus in the 1970s, when they appeared as little, innocuous circles on microscopes; inexplicable but apparently innate. But not until UC San Diego’s Paul Mischel published his first study in Science in 2014 did researchers realize these circles were not only active but potentially overactive and driving some cancer tumors’ superhuman growth.

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We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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