Stung by pa­tient deaths, a small Juno study points to a Goldilocks for­mu­la for CAR-T

For Juno, the hunt to find just the right mix­ture of T cells along with an ef­fec­tive reg­i­men to prep pa­tients for their CAR-T ther­a­py has had a lethal his­to­ry, tan­gling up de­vel­op­ment time­lines in a way that has ced­ed the lead in the field to ri­val Kite.

Stan­ley Rid­dell

But in a new, small study in­volv­ing one of their most ad­vanced CAR-Ts, an in­ves­tiga­tive team feels that they came up with just the right recipe. And that could have big im­pli­ca­tions for an­oth­er CAR-T pro­gram in which Juno holds high hopes for a come­back.

The drug in­volved in the study is called JCAR014, and the in­ves­ti­ga­tors say that they came up with a one-on-one mix of CD4+ helper cells with CD8+ killer cells that showed a re­mark­able abil­i­ty to wipe out can­cer cells that ex­press CD19, which has been the big ini­tial tar­get for all the play­ers in the van­guard of CAR-T work.

Sig­nif­i­cant­ly, the in­ves­ti­ga­tors al­so con­clud­ed that adding flu­dara­bine to cy­clophos­phamide (Cy/Flu) in a cock­tail to prep pa­tients cre­ates the right en­vi­ron­ment for the T cells to grow in the body. Half of the 18 pa­tients with non-Hodgkin lym­phoma who got the Cy/Flu com­bo had a com­plete re­sponse to the ther­a­py, com­pared to on­ly 8% of the group who re­ceived on­ly cy­clophos­phamide.

The team point­ed out that these re­sults could in­di­cate sim­i­lar out­comes for JCAR017, which is now in ear­ly stud­ies. Juno has tapped JCAR017 as a po­ten­tial “best-in-class” treat­ment for blood can­cers.

The mes­sage helped buoy the com­pa­ny’s stock to­day, send­ing shares up about 3%.

“With the de­fined com­po­si­tion treat­ment, we are able to get more re­pro­ducible da­ta about the ef­fects of the cells — both the ben­e­fi­cial im­pact against the can­cer and any side ef­fects to the pa­tient,” said Fred Hutch clin­i­cal re­searcher Stan Rid­dell, one of the se­nior au­thors of the pa­per, along with Dr. David Mal­oney. “We are then able to ad­just the dose to im­prove what we call the ther­a­peu­tic in­dex — im­pact against the tu­mor, with low­er tox­i­c­i­ty to the pa­tient.”

The ad­di­tion of flu­dara­bine to Juno’s lead CAR-T, JCAR015, was fin­gered for killing four pa­tients, a set­back for the biotech which trig­gered a brief but dam­ag­ing clin­i­cal hold by the FDA. The hold last­ed on­ly days, end­ing with the FDA sign­ing off on the biotech’s de­ci­sion to drop flu­dara­bine. But the hold end­ed up forc­ing Juno to de­lay its ex­pect­ed move to file for their first ap­proval back to 2018. Kite, mean­while, which is us­ing its own mix of T cells and Cy/Flu, has said it ex­pects to take the first batch of da­ta from its lead­ing study to the FDA af­ter an ini­tial re­view that comes in just a mat­ter of weeks.

This new study from Juno al­so rais­es ques­tions about its lead drug, JCAR015. If pa­tient out­comes are sig­nif­i­cant­ly low­ered by the ab­sence of flu­dara­bine, Juno’s first at­tempt at a com­mer­cial en­try against the com­pe­ti­tion could be se­vere­ly af­fect­ed.

CAR-Ts be­came a hot field a cou­ple of years ago, at­tract­ing hun­dreds of mil­lions in new in­vest­ments as the front run­ners raced to ad­vance new reme­dies for can­cer by adding a chimeric anti­gen re­cep­tor to a pa­tient’s T cells and then in­fus­ing them back in­to the pa­tient. But with Juno’s de­rail­ment and a re­cent de­ci­sion by No­var­tis to dis­solve its cell and gene ther­a­py unit and re­ab­sorb it in­to their big on­col­o­gy di­vi­sion, all eyes are on Kite now to see if it can claim the first ap­proval and mar­ket en­try.

The stakes are high.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.

Covid-19 roundup: Left out no longer, No­vavax se­cures largest Warp Speed deal yet: $1.6B

It looks like Novavax won’t be left out of Operation Warp Speed after all.

A month after the Gaithersburg, MD biotech saw its shares tumble when it was left off the first reported list of finalists for the White House’s Covid-19 vaccine accelerator, HHS and the Department of Defense have announced a $1.6 billion deal to scale up their Covid-19 candidate. It is the largest deal HHS has announced yet, eclipsing the $1.2 billion deal the administration reached with AstraZeneca in May.

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RA Cap­i­tal dou­bles down on Sid­dhartha Mukher­jee's vi­sion for a new cell en­gi­neer­ing ap­proach, lead­ing Vor's $110M Se­ries B

Vor Biopharma is muscling up.

CEO Robert Ang, who was reluctant to divulge the headcount when discussing his move from Neon Therapeutics to Vor last August, readily offered that the team has grown from 6 to 50 in less than a year. The biotech is moving to a larger office on Cambridge Parkway Drive in weeks, giving it more space to complete the IND-enabling work and manufacturing scale-up — conducted by a CDMO partner — in preparation for clinical trials planned for the first half of 2021.

Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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