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.”

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,900+ biopharma pros reading Endpoints daily — and it's free.

Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.