#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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Ken Frazier, AP Images

Why Mer­ck wait­ed, and what they now bring to the Covid-19 fight

Nicholas Kartsonis had been running clinical infectious disease research at Merck for almost 2 years when, in mid-January, he got a new assignment: searching the pharma giant’s vast libraries for something that could treat the novel coronavirus.

The outbreak was barely two weeks old when Kartsonis and a few dozen others got to work, first in small teams and then in a larger task force that sucked in more and more parts of the sprawling company as Covid-19 infected more and more of the globe. By late February, the group began formally searching for vaccine and antiviral candidates to license. Still, while other companies jumped out to announce their programs and, eventually and sometimes controversially, early glimpses at human data, Merck remained silent. They made only a brief announcement about a data collection partnership in April and mentioned vaguely a vaccine and antiviral search in their April 28 earnings call.

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Mark Genovese (Stanford via Twitter)

Gilead woos fil­go­tinib clin­i­cal in­ves­ti­ga­tor from Stan­ford to lead the charge on NASH, in­flam­ma­to­ry dis­eases

With an FDA OK for the use of filgotinib in rheumatoid arthritis expected to drop any day now, Gilead has recruited a new leader from academia to lead its foray into inflammatory diseases.

Mark Genovese — a longtime Stanford professor and most recently the clinical chief in the division of immunology and rheumatology — was the principal investigator in FINCH 2, one of three studies that supported Gilead’s NDA filing. In his new role as SVP, inflammation, he will oversee the clinical development of the entire portfolio.

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Bris­tol My­ers Squib­b's just-launched MS drug Zeposia makes the cut in key ul­cer­a­tive col­i­tis tri­al

In March, Zeposia became the third oral S1P modulator to secure US approval for multiple sclerosis. Now, the drug has succeeded in a key ulcerative colitis study.

The immunomodulator, akin to others in its class, controls lymphocyte trafficking by limiting the white blood cells to the lymphatic system, in the lymph nodes, and thwarting their ability to jam up lymph nodes — precluding their ability to penetrate the bloodstream and the central nervous system.

Stephen Isaacs, Aduro president and CEO (Aduro)

Once a high fly­er, a stag­ger­ing Aduro is auc­tion­ing off most of the pipeline as CEO Stephen Isaacs hands off the shell to new own­ers

After a drumbeat of failure, setbacks and reorganizations over the last few years, Aduro CEO Stephen Isaacs is handing over his largely gutted-out shell of a public company to another biotech company and putting up some questionable assets in a going-out-of-business sale.

Isaacs —who forged a string of high-profile Big Pharma deals along the way — has wrapped a 13-year run at the biotech with one program for kidney disease going to the new owners at Chinook Therapeutics. A host of once-heralded assets like their STING agonist program partnered with Novartis (which dumped their work on ADU-S100 after looking over weak clinical results), the Lilly-allied cGAS-STING inhibitor program and the anti-CD27 program out-licensed to Merck will all be posted for auction under a strategic review process.

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Hill­house re­casts spot­light on Chi­na's biotech scene with $160M round for Shang­hai-based an­ti­body mak­er

Almost two years after first buying into Genor Biopharma’s pipeline of cancer and autoimmune therapies, Hillhouse Capital has led a $160 million cash injection to push the late-stage assets over the finish line while continuing to fund both internal R&D and dealmaking.

The Series B has landed right around the time Genor would have listed on the Hong Kong stock exchange, according to plans reported by Bloomberg late last year. Insiders had said that the company was looking to raise about $200 million.

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Novus Ther­a­peu­tics plunges deep in­to pen­ny stock ter­ri­to­ry af­ter failed ear tri­al

After a more than 15-year run, a California-based biotech is exploring options, including a sale, after its lead experimental therapy failed an exploratory mid-stage study in patients with middle ear infections characterized by a build-up of fluid behind the eardrum.

The company, initially called Tokai Pharmaceuticals but which subsequently changed its name to Novus Therapeutics in 2017, saw its shares more than halve on Monday after the drug — OP0201— did not pass muster as an adjunct therapy to oral antibiotics in infants and children aged 6 to 24 months with acute otitis media (OM).