Stan­ford tri­al points to a new CAR-T drug, spot­light­ing a fresh tar­get for next-gen cell ther­a­pies

CAR-T re­searchers have had years to study CD19 pro­tein mol­e­cules as a tar­get in their suc­cess­ful leukemia stud­ies. But a small, ex­plorato­ry study at Stan­ford un­der­scores that there’s sub­stan­tial promise in ex­pand­ing their scope to in­clude CD22, of­fer­ing a new route to fol­low for pa­tients who re­lapse — or nev­er re­spond — af­ter be­ing treat­ed with the first round of cell ther­a­pies now hit­ting the mar­ket.

Crys­tal Mack­all

The re­search team re­cruit­ed 15 pa­tients for this tri­al who had ei­ther re­lapsed or nev­er re­spond­ed to CD19-tar­get­ed CAR-T ther­a­py, which in­volves ex­tract­ing a pop­u­la­tion of T cells from pa­tients and adapt­ing them with a chimeric anti­gen re­cep­tor so they would tar­get a pro­tein com­mon­ly found on the sur­face of leukemia cells. Ten of them had re­lapsed, with their can­cer cells no longer ex­press­ing CD19.

Af­ter step­ping up the dose from the first round, the re­searchers achieved re­mis­sion in 11 of the 15 pa­tients — a re­mark­able 73%. The re­mis­sions last­ed a me­di­an of 6 months with one pa­tient in re­mis­sion at 21 months, with signs that the can­cer cells were able to mu­tate to stop ex­press­ing CD22 and es­cape the ther­a­peu­tic as­sault.

“The take-home mes­sage is that we’ve found an­oth­er CAR T-cell ther­a­py that dis­plays high-lev­el ac­tiv­i­ty in this Phase I tri­al,” said Stan­ford’s Crys­tal Mack­all, who led the study. “But the re­lapse rate was al­so high. So this forces the field to get even more so­phis­ti­cat­ed. How much of a tar­get is need­ed for suc­cess­ful, long-last­ing treat­ment? What hap­pens if we tar­get both CD19 and CD22 si­mul­ta­ne­ous­ly?”

Stan­ford’s team re­port­ed progress with CD22 four days af­ter in­ves­ti­ga­tors at Seat­tle Chil­dren’s launched a com­bi­na­tion CAR-T tri­al us­ing a new cell ther­a­py that could si­mul­ta­ne­ous­ly at­tack CD19 and CD22, look­ing for a more po­tent and con­sis­tent strat­e­gy for acute lym­phoblas­tic leukemia that could con­ceiv­ably cut the re­lapse rate in half, while al­so tak­ing an­oth­er step down a path to­ward us­ing CAR-T in sol­id tu­mors — one of the Holy Grails that has emerged in the field.

(Ed­i­tor’s note: Af­ter we pub­lished this sto­ry, one of our read­ers point­ed out that Au­to­lus al­so just start­ed a PhI/II study us­ing a CD19/CD22 CAR-T.)

The small tri­al at Stan­ford is sig­nif­i­cant for a va­ri­ety of rea­sons. While No­var­tis and Gilead/Kite have be­gun the process of field­ing the first new ther­a­pies, the em­pha­sis in re­search cir­cles has shift­ed to cre­at­ing a new, safer gen­er­a­tion of CAR-Ts that can be far more durable. Al­so, Mack­all told The New York Times, it’s im­por­tant to un­der­stand that CD19, for all its re­mark­able ef­fect in of­fer­ing a bea­con for cell ther­a­pies, is “not some kind of uni­corn.”

More tar­gets ex­ist that will work here, she says. And that’s where re­searchers will turn next.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.