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.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

Ted Love. HAVERFORD COLLEGE

Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.


Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.


Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Russ­ian sci­en­tist plans to one-up Jiankui He in cre­at­ing his own CRISPR ba­bies — Na­ture

If De­nis Re­brikov has his way, the world could be ex­pect­ing more CRISPR ba­bies soon.

The Russ­ian sci­en­tist has told Na­ture he is con­sid­er­ing fol­low­ing Jiankui He’s ex­am­ple in knock­ing out the CCR5 gene in em­bryos and im­plant­i­ng them in­to women — ex­cept do­ing it in a bet­ter way. It marks the first de­c­la­ra­tion of in­ter­est in con­tin­u­ing the work when re­searchers around the world are call­ing for sus­pen­sion of hu­man germline edit­ing and stricter stan­dards, fol­low­ing a glob­al back­lash against He’s claims that he fa­cil­i­tat­ed the birth of twin girls who had been CRISPR-ed as em­bryos.

Ab­b­Vie touts new da­ta for Hu­mi­ra suc­ces­sor; Gilead inks dis­cov­ery deal

→ Ab­b­Vie is tout­ing new pos­i­tive da­ta com­par­ing their ag­ing block­buster Hu­mi­ra with their hoped-for block­buster upadac­i­tinib. Over 48 weeks a larg­er pro­por­tion of pa­tients tak­ing the ex­per­i­men­tal drug ex­pe­ri­enced clin­i­cal re­mis­sion than in the con­trol arm with Hu­mi­ra. Their drug brought in $20 bil­lion last year, top­ping the scales in the num­ber 1 slot.

→ Gilead has turned to Van­cou­ver-based Ab­Cellera for its lat­est dis­cov­ery deal. Ab­Cellera will use its know-how in “sin­gle-cell screen­ing of nat­ur­al im­mune sources” to find an­ti­body can­di­dates for Gilead to pur­sue in the in­fec­tious dis­ease field. The deal in­cludes an up­front and mile­stones.