CAR-M era be­gins as Caris­ma dos­es first pa­tient

Last month, doc­tors at the Abram­son Can­cer Cen­ter in Philadel­phia in­sert­ed a nee­dle in­to a pa­tient with an un­treat­able tu­mor and be­gan draw­ing blood in­to a ma­chine.

The ma­chine fil­tered out every­thing but a spe­cif­ic set of im­mune cells that were then pack­aged, put on a plane and shipped, still warm, to a fa­cil­i­ty in Sun­ny­vale, CA. Over 24 days, tech­ni­cians ex­pand­ed the cells, armed them with a new kind of re­cep­tor and sent them back, now cryo­geni­cal­ly frozen, on a plane to Philadel­phia to be in­fused back in­to the pa­tient.

Saar Gill

It’s a fa­mil­iar process. A few de­tails aside, it’s played out thou­sands of times over the past half decade as pa­tients with dead­ly blood can­cers re­ceived CAR-T treat­ments, po­ten­tial­ly life-sav­ing in­fu­sions of ge­net­i­cal­ly tur­bocharged T cells. But for the first time, de­vel­op­ers used a dif­fer­ent im­mune cell, one they hope can un­lock a whole new set of pa­tients and in­cur­able tu­mors: macrophages.

Caris­ma Ther­a­peu­tics, the Uni­ver­si­ty of Penn­syl­va­nia spin­out, an­nounced to­day that they had dosed their first pa­tient with CAR-macrophages, or what they call CAR-M. Re­ly­ing on a bub­bly im­mune cell that eats pathogens and of­ten gath­ers around sol­id tu­mors, they hope it can bring the ben­e­fits of cell ther­a­py in­to places where CAR-T has con­sis­tent­ly failed.

Joshua Bauml

“CAR-T ther­a­pies have made huge ad­vances in the field of [blood can­cers], but there are ma­jor lim­i­ta­tions to uti­liz­ing the same tech­nol­o­gy in sol­id tu­mors,” Joshua Bauml, an on­col­o­gist at Penn Med­i­cine and lead in­ves­ti­ga­tor on the study, told End­points News. “And I think that this tri­al aims to over­come some of those in a very clever way.”

Biotechs and aca­d­e­m­ic re­searchers have man­aged to make CAR-Ts with re­cep­tors that go af­ter sev­er­al dif­fer­ent blood can­cers, in­clud­ing lym­phoma and mul­ti­ple myelo­ma. But ef­forts to ap­ply T cells in sol­id tu­mors have failed, in large part be­cause many such tu­mors have mech­a­nisms to keep T cells from in­fil­trat­ing their en­vi­ron­ment and de­stroy­ing can­cer cells.

Those en­vi­ron­ments, though, are of­ten swarm­ing with macrophages. That’s ac­tu­al­ly a bad thing: There are mul­ti­ple types of macrophages and tu­mors re­ly on ones that sup­press the im­mune sys­tem, ef­fec­tive­ly giv­ing the can­cer a walled-off com­pound in which to thrive.

Michael Klichin­sky

But near­ly a decade ago Uni­ver­si­ty of Penn­syl­va­nia hema­tol­o­gist Saar Gill and a grad­u­ate stu­dent, Michael Klichin­sky, fig­ured out that if you at­tached a CAR on­to a macrophage, those macrophages can en­ter the tu­mor’s en­vi­ron­ment like a Tro­jan horse. There it both di­rect­ly eats up the tu­mor and sends out sig­nals that turn bad macrophages in­to good macrophages that can kill can­cer cells and re­cruit oth­er im­mune cells to join the brigade.

Or at least it did in an­i­mal mod­els. The new tri­al is test­ing to see whether those re­sults can trans­late in­to hu­mans, be­gin­ning with 18 pa­tients who have can­cers that ex­press HER2 and have ex­haust­ed oth­er op­tions.

Caris­ma chose to start with HER2 be­cause there’s al­ready a swath of treat­ments that tar­get the re­cep­tor, CMO Deb­o­ra Bar­ton said. It helps stan­dard­ize an oth­er­wise high­ly ex­per­i­men­tal pro­ce­dure.

Deb­o­ra Bar­ton

“We don’t want to add any vari­abil­i­ty,” she told End­points.

The first group of pa­tients will re­ceive 5 bil­lion cells in 3 dif­fer­ent in­fu­sions over 5 days to en­sure noth­ing goes wrong. If that goes well, the sec­ond group will re­ceive all the cells at once. Bar­ton, though, said they have good ev­i­dence to sug­gest the ther­a­py is safe. It doesn’t re­quire the same in­tense con­di­tion­ing reg­i­men that CAR-T ther­a­pies do, and they don’t think it will trig­ger the cy­tokine re­lease syn­drome, the dan­ger­ous im­mune over-re­ac­tion that CAR-T can stim­u­late.

Bar­ton isn’t promis­ing the near-cu­ra­tive im­pact that the first CAR-T stud­ies showed. In­stead, they’re hop­ing to sim­ply show that it’s safe, that the CAR-Ms are get­ting in­to the en­vi­ron­ment around the tu­mor and that they’re hav­ing some ef­fect.

The study al­so serves as a test run for the month-long, cross-coun­try process man­u­fac­tur­ing need­ed to make the CAR-Ms. Caris­ma has checked all the lo­gis­ti­cal box­es, she said, but mak­ing a cell ther­a­py is nev­er an easy task. If it runs smooth­ly and proves safe, Caris­ma hope to move for­ward with a swath of CAR-M ther­a­pies for oth­er tu­mors and oth­er anti­gens.

“It’s a whole world of lo­gis­tics that we need to get in place, and we have it in place, but you know there are snow­storms and every­thing can hap­pen,” Bar­ton said. “Every­thing can go wrong and we’re tak­ing all mea­sures.”

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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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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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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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.

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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Busi­ness­es and schools can man­date the use of Covid-19 vac­cines un­der EUAs, DOJ says

As public and private companies stare down the reality of the Delta variant, many are now requiring that their employees or students be vaccinated against Covid-19 prior to attending school or to returning or starting a new job. Claims that such mandates are illegal or cannot be used for vaccines under emergency use authorizations have now been dismissed.

Setting the record straight, the Department of Justice on Monday called the mandates legal in a new memo, even when used for people with vaccines that remain subject to EUAs.

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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No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Andrea Pfeifer, AC Immune CEO (AC Immune)

Look­ing to repli­cate Covid-19 suc­cess in neu­ro, BioN­Tech back­ers bet on AC Im­mune and its new­ly-ac­quired Parkin­son's vac­cine

The German billionaires behind BioNTech have found a new vaccine project to back.

Through their family office Athos Service, twin brothers Thomas and Andreas Strüngmann are leading a $25 million private placement into Switzerland’s AC Immune — which concurrently announced that it’s shelling out $58.7 million worth of stock to acquire Affiris’ portfolio of therapies targeting alpha-synuclein, including a vaccine candidate, for Parkinson’s disease.