Look­ing for the next big break­through in CAR-T, Mike Gilman de­buts Ob­sid­i­an with $49.5M round

Biotech en­tre­pre­neur Michael Gilman is now on to his fourth start­up Suzanne Kre­it­er, Boston Globe


Over the past cou­ple of years, the pi­o­neers in the CAR-T field have made some phe­nom­e­nal leaps for­ward, and been hit with some of the most dra­mat­ic set­backs in biotech. They’ve of­fered ad­vanced stage can­cer pa­tients a sec­ond lease on life, and run in­to daunt­ing hur­dles on the out­er lim­its marked by the graves of pa­tients. And now a biotech up­start is grad­u­at­ing from a sub­stan­tial — and very qui­et — seed ef­fort in a dri­ve to the clin­ic with a new tech specif­i­cal­ly de­signed to ad­dress the biggest chal­lenges in CAR-T.

En­ter Ob­sid­i­an Ther­a­peu­tics, the lat­est in a string of biotech launch­es un­der the guid­ing hand of se­r­i­al en­tre­pre­neur Michael Gilman — now on to his fourth start­up along­side his oth­er day job at Ar­rakis. And the crew there, with a staff of 20 set to grow to around 35 next year, have a $49.5 mil­lion round led by GV to fund the next stage of the jour­ney.

While the first two now-ap­proved CAR-Ts — en­gi­neered pa­tient cells redi­rect­ed to kill can­cer cells — were ap­proach­ing the mar­ket, Ob­sid­i­an was work­ing on a new tech­nol­o­gy that promis­es to fix some of the most im­por­tant lim­it­ing fac­tors that are hold­ing these ther­a­pies back.

“This is go­ing to be a big deal,” says Gilman, in what is fast be­com­ing a big field.

So lis­ten up.

Tom Wand­less

This all start­ed, Gilman tells me, with a phone call from Tom Wand­less, who had been a stu­dent in Stu­art Schreiber’s lab at Har­vard work­ing on a tech project picked up in the ’90s by Ari­ad, a com­pa­ny which gave Gilman his first job. The tech was lat­er out-li­censed to Bel­licum and Wand­less went on to set up his own lab at Stan­ford. Wand­less kept at it, and 20 years lat­er — in 2015  — he had an idea for a new biotech.

Gilman knows peo­ple who fi­nance that kind of stuff.

They launched the com­pa­ny about 18 months ago, play­ing their cards close to the vest be­fore wrap­ping the A round and set­ting up their vir­tu­al com­ing out par­ty for to­day.

In sim­ple terms, here’s what Wand­less and his team did.

Build­ing off some re­search work he’d done in the lab for years, the crew has been work­ing with what he calls desta­bi­liz­ing do­mains, mu­tants which can be en­cod­ed in a “syn­thet­ic bi­o­log­ic cas­sette,” pack­aged in a vec­tor and dis­patched to tin­ker with an en­gi­neered CAR-T cell, to con­trol pro­teins. Do­ing that, they in­tend to amp ef­fi­ca­cy and di­al down tox­i­c­i­ty threats through a small mol­e­cule op­er­at­ing sys­tem man­aged by the at­tend­ing physi­cian — ba­si­cal­ly us­ing eas­i­ly ac­cessed gener­ics and oth­er ap­proved drugs.

The plat­form is built around a com­mon bi­o­log­ic func­tion for the dis­pos­al of dys­func­tion­al pro­teins — mu­tat­ed pro­teins that are on­ly par­tial­ly un­fold­ed which are tagged by the body’s dis­pos­al sys­tem and tak­en out to the trash.

“The mag­ic is when you pro­vide a small mol­e­cule lig­and it folds up and looks like it’s sta­bi­lized,” says Gilman, “you can now use the small mol­e­cule to reg­u­late the sta­bil­i­ty of the pro­tein.”

This is what Ob­sid­i­an is call­ing an op­er­at­ing sys­tem for liv­ing med­i­cines, with po­ten­tial in gene ther­a­py as well.

If you can reg­u­late pro­teins, you can ac­com­plish three things that lim­it CAR-Ts to­day, all of which re­volve around the cur­rent spot­light in the clin­ic: Con­trol­ling the way this per­son­al­ized ther­a­py is dosed so you get max­i­mum ef­fect with man­age­able risks. The goal is dura­bil­i­ty with­out tox­i­c­i­ty, pre­vent­ing re­laps­es as cells are ex­haust­ed.

First, Gilman ticks off, you can pre­vent cy­tokine re­lease syn­drome — the tox­ic storm that oc­curs in pa­tients when a swarm of these en­gi­neered cells run in­to a galaxy of anti­gens as­so­ci­at­ed with a high tu­mor bur­den — by “man­ag­ing the pro­lif­er­a­tion of the cell in an or­der­ly fash­ion, so they don’t slip out of con­trol.”

You can re­place the “bru­tal” flu/cy pre­con­di­tion­ing reg­i­men now in com­mon use with a new ap­proach that would al­low a physi­cian to take the ther­a­py up to the right, safe max­i­mum lev­el for a par­tic­u­lar pa­tient, and then leave it there.

And you could po­ten­tial­ly go back to a well known, and high­ly tox­ic, pro-in­flam­ma­to­ry play­er like IL-12 and tame it for use in sol­id tu­mors, pow­er­ing up the ef­fect in or­der to make it work in sol­id tu­mors — one of the next big chal­lenges in CAR-T which would open up the mar­ket to a whole new lev­el.

At­las seed­ed the 18-month lab project, and is step­ping in­to the $49.5 mil­lion launch round along­side GV, the Google ven­ture arm lead­ing the round, Take­da Ven­tures, Ver­tex Ven­tures HC, Am­gen Ven­tures, Alexan­dria Ven­ture In­vest­ments, and Shang­Phar­ma In­vest­ment Group.

That sug­gests a few things about some of the most up­beat pos­si­ble fu­tures that await Ob­sid­i­an.

At­las is a ven­ture group that en­joys noth­ing bet­ter than see­ing its fledg­lings work with a well fi­nanced part­ner, if not ac­tu­al­ly do­ing a sale at an ear­ly stage of de­vel­op­ment. Gilman knows that as well as any­one, and he’s quick to ac­knowl­edge that there are a lot of pos­si­bil­i­ties for do­ing a part­ner­ship ear­ly on, with no need to nec­es­sar­i­ly recre­ate the en­tire CAR-T wheel at Ob­sid­i­an. But, he adds, if you’re will­ing to write a big enough check, you can do all the man­u­fac­tur­ing and every­thing that comes with that. And these days, there are sev­er­al in­vestors that spe­cial­ize in those kinds of checks.

Al­so, there are oth­er things this tech can be used for, leav­ing lots of work for the team no mat­ter what hap­pens with CAR-T.

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.

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.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 52,900+ biopharma pros reading Endpoints daily — and it's free.

Adding mar­quee in­vestors, Black­Thorn bags $76M to back an AI-dri­ven strat­e­gy for pre­ci­sion neu­ro med­i­cine

As ar­ti­fi­cial in­tel­li­gence and ma­chine learn­ing loom ever larg­er in drug dis­cov­ery and de­vel­op­ment, a biotech op­er­at­ing at the “nexus” of tech­nol­o­gy and neu­ro­sciences has cashed in with $76 mil­lion in fresh fi­nanc­ing.

The big idea at Black­Thorn Ther­a­peu­tics is to do for neu­robe­hav­ioral dis­or­ders what ge­net­i­cal­ly tar­get­ed ther­a­py has done for on­col­o­gy: Re­de­fine pa­tient pop­u­la­tions by the un­der­ly­ing bi­ol­o­gy — dys­reg­u­lat­ed brain cir­cuits, or neu­rotypes — in­stead of symp­toms, there­by find­ing the pa­tients who are most like­ly to ben­e­fit at en­roll­ment phase.

Turns out, Rudy Tanzi did­n't see much of a sto­ry about a hid­den link be­tween En­brel and Alzheimer's ei­ther

The Wash­ing­ton Post man­aged to whip up the quick­est in­dus­try con­sen­sus I’ve ever seen that one of its re­porters was pur­vey­ing overblown non­sense with a sto­ry that Pfiz­er was sit­ting on da­ta sug­gest­ing that En­brel could be an ef­fec­tive treat­ment for Alzheimer’s. 

In cov­er­ing that bit of an­ti-Big Phar­ma fan­ta­sy — there are lots of rea­sons to go af­ter phar­ma, but this piece was lu­di­crous — I not­ed com­ments in the sto­ry from some promi­nent peo­ple in the field crit­i­ciz­ing Pfiz­er for not pub­lish­ing the da­ta. I sin­gled out Rudy Tanzi at Har­vard and then ap­plied some added crit­i­cism for the things he’s done to hype — in my opin­ion — high­ly ques­tion­able as­sump­tions. You can see it in the link. 

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 52,900+ biopharma pros reading Endpoints daily — and it's free.

J&J gains an en­thu­si­as­tic en­dorse­ment from Pres­i­dent Don­ald Trump for their big new drug Spra­va­to

Pres­i­dent Don­ald Trump has lit­tle love for Big Phar­ma, but there’s at least one new drug that just hit the mar­ket which he is en­am­ored with.

Trump, ev­i­dent­ly, has been read­ing up on J&J’s new an­ti-de­pres­sion drug, Spra­va­to. And the pres­i­dent — who of­ten likes to break out in­to a full-throat­ed at­tack on greedy drug­mak­ers — ap­par­ent­ly en­thused about the ther­a­py in a meet­ing with of­fi­cials of Vet­er­ans Af­fairs, which has long grap­pled with de­pres­sion among vet­er­ans.

Fol­low­ing CAR-T pi­o­neer­s' foot­steps, Tes­sa launch­es Chi­na JV in $120M deal

These days just about every biotech se­ri­ous about glob­al de­vel­op­ment — and not just com­mer­cial­iza­tion — has a Chi­na strat­e­gy. Tes­sa Ther­a­peu­tics, a Bay­lor as­so­ci­at­ed out­fit based out of Sin­ga­pore, is no ex­cep­tion.

Tak­ing a page out of the CAR-T pi­o­neers’ play­book, Tes­sa is es­tab­lish­ing a joint ven­ture with Chi­na-Sin­ga­pore Guangzhou Knowl­edge City, which is ini­tial­ly putting down $40 mil­lion for a 13% stake with $40 mil­lion more to come in a sec­ond stage. The biotech, which now re­tains an 87% con­trol, is al­so rolling out its own con­tri­bu­tions in two phas­es, start­ing with $20 mil­lion and all its tech­nol­o­gy li­cense rights for Chi­na.

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.