Hack­ing in­to macrophage at­tack cir­cuits, Stan­ford sci­en­tists pitch a bet­ter ear­ly-warn­ing alert sys­tem for tu­mors

Af­ter years of fine tun­ing ways to en­list the im­mune sys­tem in the fight against can­cer, im­munother­a­py has tak­en the field by storm, with a No­bel prize and a pair of block­buster check­point drugs to boast. But can im­mune cells help in an even broad­er ef­fort — flag­ging ma­lig­nant tu­mors be­fore they are de­tectable by tra­di­tion­al in­stru­ments?

Push­ing the thresh­old of can­cer di­ag­noses to ear­li­er and ear­li­er stages of the dis­ease is one of the Holy Grails in on­col­o­gy, in­spir­ing mul­ti­mil­lion-dol­lar in­vest­ments in­to star­tups like Grail. This week, a team from Stan­ford has chipped in with their own pitch and some mouse da­ta to show for it.

Pi­o­neer­ing a new de­f­i­n­i­tion of the con­cept “im­mun­odi­ag­notics,” San­jiv “Sam” Gamb­hir of Stan­ford’s Ca­nary Cen­ter for Ear­ly De­tec­tion re­pur­posed macrophages to re­port the pres­ence of dis­ease or dam­aged cells, achiev­ing de­tec­tion of tu­mors as small as 4 mil­lime­ters in di­am­e­ter, out­per­form­ing “some of the most ad­vanced ear­ly tu­mor de­tec­tion meth­ods out there.”

Im­age: San­jiv “Sam” Gamb­hir. Steve Fisch, STAN­FORD

His tech­nique, re­port­ed in Na­ture Biotech­nol­o­gy, makes use of macrophages’ in­nate abil­i­ty to find (and eat) mal­func­tion­ing or dead cells. That’s sim­ple; the big chal­lenge is to hack the process in a way such that these im­mune cells emit a de­tectable sig­nal be­fore they be­gin to feast.

To do that, Gamb­hir’s team tagged a mol­e­c­u­lar mark­er to a gene pro­mot­er that awak­ens and ac­ti­vates the gene di­rect­ing the macrophage on­slaught in the pres­ence of a tu­mor.

“The mol­e­c­u­lar mark­er is called Gaus­sia lu­ciferase, and un­der cer­tain chem­i­cal cir­cum­stances, it glows,” Gamb­hir said in a state­ment. “So the idea is, we pick a gene that turns on when a macrophage sens­es a tu­mor cell, we link that gene’s pro­mot­er to Gaus­sia lucer­iferase and fi­nal­ly, we in­te­grate it in­to the macrophages.”

Macrophages have been a key im­mune cell type of in­ter­est, at­tract­ing a num­ber of biotechs to re­move the “don’t eat me” sig­nal that tu­mors of­ten de­ploy to pre­vent an at­tack.

There are, of course, lim­i­ta­tions with the method. For one, macrophages don’t just re­spond to can­cer­ous tar­gets, so a “hit” on this test rep­re­sents a call for oth­er, con­fir­ma­to­ry tests rather than a de­fin­i­tive di­ag­no­sis. But the ap­proach, which in­volves cre­at­ing a syn­thet­ic bio­mark­er, is a ma­jor de­par­ture from the tra­di­tion­al prac­tice, which re­lies on iden­ti­fy­ing bio­mark­ers in the body.

The syn­thet­ic na­ture of this tech­nique means the strat­e­gy can be ap­plied to mul­ti­ple in­stru­ments and im­mune cells — all pos­si­bil­i­ties that Gamb­hir is ex­plor­ing with his start­up, Ear­li.

Mov­ing for­ward, Gamb­hir plans to test the method in oth­er types of can­cers and an­i­mal mod­els, while re­fin­ing the tech­nique to home in on just tu­mor cells, not cells with oth­er types of dam­age.

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.


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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.