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.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll