In­scrip­ta push­es fund­ing to $260 mil­lion as they launch genome edit­ing plat­form

In­scrip­ta pre­sen­ta­tions can be­gin with the ad­vent of agri­cul­ture. Or even fur­ther back: The emer­gence of man.

Nan­di­ni Kr­ish­na­murthy

“We’ve come a long way, start­ing with nat­ur­al se­lec­tion,” In­scrip­ta mi­cro­bial di­rec­tor Nan­di­ni Kr­ish­na­murthy told a ses­sion this year at Syn­Bio­Be­ta, the new an­nu­al con­fer­ence for the syn­thet­ic bi­ol­o­gy field.

Be­hind her was a slide that’s re­curred in com­pa­ny pre­sen­ta­tions, show­ing from left to right across the bot­tom the clas­sic evo­lu­tion-of-man chart (the ‘hu­mor­ous’ kind that ends on an over­weight so­da-drinker), a pic­ture show­ing the de­vel­op­ment of corn from thin strand to bul­bous Iowan, and then a squig­gly pro­tein close-up of “di­rect­ed evo­lu­tion.” Be­low that runs an ar­row and a tick­er of how long each takes, from 10^9 years to 1.

“The ques­tion is how do you go from pre­cise­ly en­gi­neer­ing pro­teins to pre­cise­ly en­gi­neer­ing path­ways and genomes to har­ness the pow­er of bi­ol­o­gy?” she said.

Kevin Ness

It’s the kind of grand rhetoric and am­bi­tion you’ve come to ex­pect from a syn­thet­ic bio field that fea­tures Gingko Bioworks and a com­pa­ny billing it­self as the “Ne­spres­so ma­chine for DNA syn­the­sis.” In­scrip­ta keynot­ed the 2019 con­fer­ence to launch their Onyx plat­form for genome en­gi­neer­ing, and to­day they’ve an­nounced $125 mil­lion in Se­ries D fund­ing to com­mer­cial­ize that plat­form. It brings their to­tal fund­ing to $260 mil­lion. The pitch is sim­ple: Do for CRISPR what lap­tops and phones have done for su­per­com­put­ers.

“We’ve de­moc­ra­tized ac­cess to the foundry,” CEO Kevin Ness told End­points News, re­fer­ring to the mi­crotiter plates of­ten used for DNA-edit­ed cell lines. “We’ve cre­at­ed the equiv­a­lent of a desk­top com­put­er.”

The foundries are groups like Gingko and Zymer­gen that of­ten use their large fa­cil­i­ties to ed­it or­gan­isms for a ser­vice fee. In­scrip­ta is try­ing to put much of that sys­tem in the hands of re­searchers, a key cog they think will help un­leash emer­gent “bioe­con­o­my:” a world where genomes are edit­ed as much as they are read. The price, though, is not in­signif­i­cant: Around $350,000 to­tal.

In­scrip­ta first made a name when they un­veiled MAD7, an al­ter­na­tive CRISPR en­zyme to CAS9 and then gave it away for free to all re­searchers. They pitched it as an al­tru­is­tic ways of break­ing the li­cens­ing fees around CAS9 and help­ing move the en­tire field for­ward, but it was good busi­ness: In elim­i­nat­ing one bar to genome edit­ing, they widened the po­ten­tial mar­ket for their re­al prod­uct: Onyx. It was a sim­i­lar strat­e­gy to the one em­ployed Il­lu­mi­na – the genome read­ing com­pa­ny In­scrip­ta specif­i­cal­ly mar­kets them­selves around.

“We do for genome edit­ing what Il­lu­mi­na did for genome read­ing,” Ness said.

Ness has ex­pe­ri­ence on the genome-read­ing side, work­ing ear­ly in his ca­reer on PCR and lat­er co-found­ing 10x Ge­nomics, and In­scrip­ta em­ploys mul­ti­ple Il­lu­mi­na alum­ni, in­clud­ing their co-founder and first CEO: John Stuelp­nagel.

So how does it work?

A bi­ol­o­gist with the plat­form can se­lect the genes they want to knock out from In­scrip­ta’s com­put­er in­ter­face. In­scrip­ta then cre­ates the agents to knock out those genes at their man­u­fac­tur­ing fa­cil­i­ty and sends them to the bi­ol­o­gist’s lab. The bi­ol­o­gist ap­plies those agents to the cell lines, cre­at­ing thou­sands of dif­fer­ent lines that are “bar-cod­ed.” The bi­ol­o­gist can run what­ev­er ex­per­i­ment — ex­pos­ing them to a drug, say, or an agent — and the In­scrip­ta tech can see which cell lines sur­vived.

So far the plat­form is on­ly avail­able for E. Coli and S. cere­visi­ae and the com­pa­ny’s ex­po­sure out­side syn­thet­ic bi­ol­o­gy and bac­te­ria spaces has been lim­it­ed, but In­scrip­ta has found a big pro­po­nent in MIT’s Jim Collins. Collins has used the plat­form to cre­ate bac­te­ria cell lines with 5,000 dif­fer­ent gene ed­its. He then used those to test which genes con­ferred re­sis­tance.

It al­lowed us “to ex­plore the ge­net­ic de­pen­den­cies of an­tibi­ot­ic func­tion in un­prece­dent­ed de­tail.” Collins told GEN in Oc­to­ber.

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Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

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Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

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David Meek

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UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

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He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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