Arie Belldegrun speaking at UKBIO19

Pa­tient death mars lat­est cut of da­ta from Al­lo­gene's off-the-shelf CAR-T

Al­lo­gene has been rid­ing high since AS­CO in May, when ear­ly da­ta showed their off-the-shelf CAR-T worked in a hand­ful of pa­tients and that no one re­ject­ed their for­eign cells. It was a key mo­ment in a field that could re­make cell ther­a­py and treat­ment for cer­tain can­cers.

On Wednes­day, though, the Arie Bellde­grun-found­ed biotech re­leased re­sults for their mul­ti­ple myelo­ma CAR-T and, al­though the re­spons­es were there, so was a red flag: Four pa­tients con­tract­ed a se­ri­ous in­fec­tion, and one of them died.

Al­lo­gene $AL­LO shares im­me­di­ate­ly fell from $33.79 to $28.78 Wednes­day morn­ing, al­though they would re­bound to $31.06 by the time mar­kets close.

The news is trag­ic on its own and a set­back for an ap­proach that Al­lo­gene is try­ing to prove can com­pete with or even out­per­form tra­di­tion­al mul­ti­ple myelo­ma CAR-Ts from J&J and Leg­end and from Bris­tol My­ers Squibb and blue­bird. Al­though Al­lo­gene and star­tups such as Po­sei­don have point­ed to the po­ten­tial for off-the-shelf ap­proach­es to be more scal­able and al­low for re­peat dos­ing, J&J and blue­bird have al­ready shown strong ef­fi­ca­cy in hu­man tri­als, set­ting the bar high.

Still, an­a­lysts were di­vid­ed on how large a role Al­lo­gene’s treat­ment played in the pa­tient’s death, or how con­cerned they should be if they are. The vol­un­teers in the Al­lo­gene tri­al were very sick, with many on their fifth-line of ther­a­py for a dead­ly can­cer, and pa­tients have died through­out the last decade of CAR-T tri­als, in­clud­ing in the blue­bird stud­ies.

Cowen’s Marc Frahm said it was “un­sur­pris­ing” news. “We would note that sev­er­al oth­er CAR T cell tri­als [saw] in­fec­tions in­clud­ing fa­tal events,” he wrote in a note to in­vestors.

The pa­tient was di­ag­nosed with se­vere pneu­mo­nia eight days af­ter re­ceiv­ing the ther­a­py, and in­ves­ti­ga­tors at­trib­uted it to the in­tense chemother­a­py pa­tients un­der­go di­rect­ly be­fore re­ceiv­ing the ther­a­py. They added that, as of the da­ta cut­off for the ab­stract, they had not seen oth­er ma­jor ad­verse events, in­clud­ing graft ver­sus host dis­eases — one com­mon and dam­ag­ing side ef­fect from oth­er form of cell trans­plants.

Jef­feries’ Biren Amin not­ed that, more broad­ly, “high in­fec­tion rate is a key fac­tor for mor­tal­i­ty in myelo­ma pa­tients.”

An­a­lysts, mean­while, were large­ly sat­is­fied with the ef­fi­ca­cy re­sults. Al­though it’s still ear­ly in Phase I, they ar­gued it showed the po­ten­tial to even­tu­al­ly com­pete with the J&J and blue­bird CAR-Ts.

In the high-dose arm of the dose-find­ing study, three out of five pa­tients re­spond­ed. One of the three had a strin­gent com­plete re­sponse and an­oth­er had a very good par­tial re­sponse.

That’s a pret­ty small sam­ple size to draw per­cent­ages from, but Frahm ar­gued it looked “sim­i­lar” to the rough­ly 65% VG­PR/CR re­sponse blue­bird saw in ear­ly stud­ies and the 88% VG­PR re­sponse J&J saw.

Amin said it showed high dos­es are need­ed for the ther­a­py to work. He said longer term, they’ll be look­ing for Al­lo­gene to match blue­bird’s Phase I re­sults. In that study, he not­ed, pa­tients across dose co­horts who had high BC­MA ex­pres­sion had an 89% re­sponse rate and a 22% com­plete re­sponse rate.

How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

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Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

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Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

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Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

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Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

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Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

UP­DAT­ED: Pan­el of neu­ro­science ex­perts lays out the com­pli­ca­tions with us­ing Bio­gen's new Alzheimer's drug

Treatment of early Alzheimer’s patients with Biogen’s new drug Aduhelm should closely resemble how the drug was studied in its pivotal clinical trials, according to new recommendations from a panel of neuroscience experts led by UNLV’s Jeffrey Cummings.

“Those considering aducanumab therapy should understand that the expected benefit is slowing of cognitive and functional decline; improvement of the current clinical state is not anticipated,” they wrote Tuesday in The Journal of Prevention of Alzheimer’s Disease, noting that some of their recommendations are more specific or more restrictive than the information provided in the FDA’s prescribing information.

Christophe Weber, Takeda CEO (Kyodo via AP Images)

Take­da flesh­es out CNS pact with pep­tide drug­mak­er, set­ting aside $3.5B in fu­ture mile­stones

One of a suite of drugmakers looking to reinvest in the neuroscience space, Takeda has been aggressive in signing on new partners to help build up its pipeline in that space. But sometimes the best partner is the one you already have.

Takeda will set aside $3.5 billion in future milestones and an undisclosed upfront payment to build out its drug discovery deal with Japanese peptide conjugate maker PeptiDream, adding neurodegeneration to the partnership’s list of CNS targets, the companies said Tuesday.

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George Yancopoulos, Regeneron

Re­gen­eron's lat­est ge­net­ics dis­cov­ery hooks As­traZeneca — now all-in on de­vel­op­ing small mol­e­cules for obe­si­ty

Just weeks after its widely lauded genetics research arm tagged a promising new target for obesity, Regeneron has signed up an industry heavyweight to collaborate with on developing new drugs that can potentially act as a game-changer in what has proven to be a tough field for developers.

The Regeneron Genetics Center published a paper in Science at the beginning of this month highlighting how their work sequencing the genomes of 650,000 people highlighted how people with at least 1 inactive copy of the GPR75 gene weighed on average 12 pounds less than the rest of the population with a 54% reduction in risk of obesity.

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