Months af­ter an­oth­er lethal set­back, Juno fi­nal­ly opts to kill lead CAR-T

Juno CEO Hans Bish­op

Months af­ter one of the worst set­backs in the re­cent his­to­ry of drug de­vel­op­ment left a string of pa­tients dead, Juno has fi­nal­ly de­cid­ed that it will ter­mi­nate its lead drug pro­gram, hop­ing for a bet­ter out­come with an­oth­er CAR-T ther­a­py in its pipeline.

Juno CEO Hans Bish­op claimed $JUNO that its de­ci­sion to shelve JCAR015 was all due to the “un­ex­pect­ed” tox­i­c­i­ty that it dis­cov­ered af­ter the drug killed five pa­tients due to cere­bral ede­ma, or brain swelling. The sec­ond tal­ly of deaths, though, oc­curred in No­vem­ber, af­ter the com­pa­ny con­vinced the FDA to swift­ly lift a clin­i­cal hold on the drug by mak­ing the du­bi­ous claim that elim­i­nat­ing flu­dara­bine from the pre­con­di­tion­ing reg­i­men for pa­tients would re­solve the safe­ty is­sue that had al­ready killed sev­er­al late-stage can­cer pa­tients.

Flu­dara­bine is still com­mon­ly used in most CAR-T stud­ies, need­ed to help these cell ther­a­pies take ef­fect in pa­tients. This first wave of drugs ex­tracts T cells from pa­tients and then reengi­neers them to go af­ter can­cer cells, and progress has been reg­u­lar­ly marred by se­ri­ous safe­ty is­sues. But there’s still been no clear ex­pla­na­tion of why JCAR015 de­railed.

Shares of Juno dropped 8% Wednes­day evening on the biotech’s re­minder of its se­ri­ous­ly flawed ef­forts.

“We con­tin­ue to ex­pe­ri­ence en­cour­ag­ing signs of clin­i­cal ben­e­fit in our tri­al ad­dress­ing NHL, but we al­so rec­og­nize the un­for­tu­nate and un­ex­pect­ed tox­i­c­i­ty we saw in our tri­al ad­dress­ing ALL with JCAR015,” said Bish­op in a state­ment. “We have de­cid­ed not to move for­ward with the ROCK­ET tri­al or JCAR015 at this time, even though it gen­er­at­ed im­por­tant learn­ings for us and the im­munother­a­py field.”

Juno threw out sev­er­al vague fac­tors that may have trig­gered the deaths. But they all added up to a re­turn to Phase I to prove their point. And there was no time to go back to the draw­ing board. From the state­ment:

Through the in­ves­ti­ga­tion Juno iden­ti­fied mul­ti­ple fac­tors that may have con­tributed to this in­creased risk, in­clud­ing pa­tient spe­cif­ic fac­tors, the con­di­tion­ing chemother­a­py pa­tients re­ceived, and fac­tors re­lat­ed to the prod­uct. Al­though Juno be­lieves there are pro­to­col mod­i­fi­ca­tions and process im­prove­ments that could en­able Juno to pro­ceed with JCAR015 in clin­i­cal test­ing in adult r/r ALL, Juno would first need to es­tab­lish pre­lim­i­nary safe­ty and dose in a Phase I tri­al. As a re­sult of the tim­ing de­lay that would en­tail and Juno’s be­lief that it has oth­er prod­uct can­di­dates in its pipeline that are like­ly to pro­vide im­proved ef­fi­ca­cy and tol­er­a­bil­i­ty,

As just about every­one who fol­lows this field has ex­pect­ed for some time now, Juno is turn­ing to JCAR017, hop­ing to get back on track af­ter falling far be­hind the two lead­ers in the field: Kite and No­var­tis. In its state­ment to­day, Juno out­lined plans to launch a piv­otal study for r/r dif­fuse large B cell lym­phoma lat­er this year. The biotech, though, has now fall­en be­hind ri­vals by more than a year.

At one point Juno was con­sid­ered a con­tender for a pi­o­neer­ing ap­proval, run­ning neck-and-neck with Kite. Yes­ter­day, though, Kite post­ed im­pres­sive 6-month re­sults for its CAR-T ahead of its ap­pli­ca­tion for ap­proval, as Juno was just get­ting ready to for­mal­ly ter­mi­nate its trou­bled lead pro­gram.

Added Bish­op:

Look­ing for­ward in­to 2017, we con­tin­ue to be op­ti­mistic about the progress we are mak­ing with JCAR017 and our pipeline more broad­ly. We ex­pect 2017 will be a da­ta-rich year of key in­sights, based on up to 20 on­go­ing tri­als by year end, and we plan to present da­ta from these tri­als as ap­pro­pri­ate through­out the year.

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

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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David Meline (file photo)

Mod­er­na’s new CFO took a cut in salary to jump to the mR­NA rev­o­lu­tion­ary. But then there’s the rest of the com­pen­sa­tion pack­age

David Meline took a little off the top of his salary when he jumped from the CFO post at giant Amgen to become the numbers czar at the upstart vaccines revolutionary Moderna. But the SEC filing that goes with a major hire also illustrates how it puts him in line for a fortune — provided the biotech player makes good as a promising game changer.

To be sure, there’s nothing wrong with the base salary: $600,000. Or the up-to 50% annual cash bonus — an industry standard — that comes with it. True, the 62-year-old earned $999,000 at Amgen in 2019, but it’s the stock options that really count in the current market bliss for all things biopharma. And there Meline did well.

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Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.