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.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

Endpoints Premium

Premium subscription required

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

Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by set­back with a fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,200+ biopharma pros reading Endpoints daily — and it's free.

Stephen Hahn (AP Images)

As he wraps stormy FDA tenure, Hahn ad­mits 'there was a sub­stan­tial amount of pres­sure' from White House — re­port

Last summer, as drugmakers rushed to test and deliver the first Covid-19 vaccines in hopes of taming a raging pandemic, FDA commissioner Stephen Hahn repeatedly reassured the public that he will fight for science and fend off any politicization. At one point in August — just before he would appear alongside President Donald Trump in a controversial event announcing the emergency use authorization of convalescent plasma — he told a reporter that “I’ve had absolutely no pressure from anyone.”

Bris­tol My­ers Squibb gets re­view date for Op­di­vo com­bo in gas­tric can­cer, look­ing to over­turn Keytru­da's 3-year lead

The past two months have been tough for Bristol Myers Squibb and its checkpoint inhibitor Opdivo after setbacks in lung and brain cancers. But in the battle against Merck’s Keytruda, any success matters — and now Bristol could be looking at a quick approval for Opdivo in an unmatched indication.

The FDA will launch a speedy review of a combination of Bristol Myers Squibb’s Opdivo and chemotherapy to treat first-line patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, the drugmaker said Wednesday. The agency set an action date of May 25 for the application.

Covid-19 claims an­oth­er PDU­FA vic­tim as Glax­o­SmithK­line push­es back planned PD-1 roll­out

Bristol Myers Squibb isn’t the only pharma giant that’s been standing in the FDA’s waiting line for site inspections.

GlaxoSmithKline is telling us today that their H2 2020 PDUFA deadline for the PD-1 drug dostarlimab — picked up in its Tesaro buyout — was pushed back due to a delay in the manufacturing site inspection needed for a regulatory decision. And that is forcing the company to revise its timeline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,200+ biopharma pros reading Endpoints daily — and it's free.

The IPO flood keeps ris­ing with 4 more biotechs and a SPAC on their way to Nas­daq

After a record year for biotech IPOs in 2020, forecasts were bullish on another strong year showing for public offerings — and 2021 hasn’t disappointed so far. Now, a clutch of four biotechs chasing rare disease and cancer and a New York SPAC are ready to join the party.

Three more companies filed to head to Nasdaq on Tuesday, as well as a SPAC, with an additional Dutch biotech filing Friday. All in all, early days indicate another big year, at least to start, with 12 companies either pricing or filing their IPOs in the first 20 days of January.

Ugur Sahin, BioNTech CEO (AP Images)

Covid-19 roundup: BioN­Tech of­fers da­ta show­ing Pfiz­er-part­nered vac­cine pro­tects against vari­ant; No­vavax at­trib­ut­es re­spon­si­bil­i­ty for PhI­II de­lay to OWS

Ugur Sahin and his team at BioNTech have proffered more evidence that their Pfizer-partnered Covid-19 vaccine can protect people from a much-feared variant of SARS-CoV-2.

Colloquially known as the UK variant, the B.1.1.7 lineage triggered alarms because it appeared more transmissible. Among a series of mutations on its spike protein — the key antigen that all frontrunners in the vaccine race targeted — N501Y was of particular concern because it’s located on the receptor-binding site.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,200+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.