Armed with pub­lished an­i­mal da­ta, gene-edit­ing pi­o­neer In­tel­lia maps the road to an IND

One of the few pi­o­neers in the bur­geon­ing gene edit­ing field, In­tel­lia $NT­LA has di­rect­ed at­ten­tion to its IND-en­abling an­i­mal da­ta for some time. Now, it’s come out with a pub­lished sci­en­tif­ic study — com­plete with a few “un­der the hood” high­lights — to back the hype up.

The study, pub­lished in Cell Re­ports Tues­day, for­mal­ly sum­ma­rizes what In­tel­lia has been tout­ing since last March: the lipid nanopar­ti­cle tech­nol­o­gy it’s used to de­liv­er CRISPR/Cas9 gene edit­ing has proven to es­sen­tial­ly elim­i­nate all transthyretin (TTR) pro­teins in the liv­er of mice. The ef­fects of one dose last­ed for at least 12 months, sug­gest­ing that the gene edit­ing hap­pened not on­ly in nor­mal cells but the stem cell pop­u­la­tion of the he­pa­to­cytes.

Thomas Barnes

While the re­port cites a 97% tar­get pro­tein knock­down, In­tel­lia SVP of in­no­v­a­tive sci­ences Thomas Barnes ex­plained to me that was an av­er­age num­ber across mul­ti­ple co­horts. On a giv­en day in a cer­tain an­i­mal, the tech would like­ly be found to have achieved “quan­ti­ta­tive edit­ing” — ef­fec­tive­ly ze­ro TTR.

An­oth­er high­light from the study was that the CRISPR/Cas9 ma­te­r­i­al stayed in the body on­ly “tran­sient­ly,” low­er­ing safe­ty con­cerns. The safe­ty of the ade­no-as­so­ci­at­ed virus (AAV) de­liv­ery ve­hi­cle that some oth­er com­pa­nies use has been called in­to ques­tion in re­cent weeks. Ed­i­tas, one of In­tel­lia’s main ri­vals, lost some mo­men­tum be­cause of an AAV man­u­fac­tur­ing is­sue.

“You don’t re­al­ly want the Cas9 com­po­nent hang­ing around for­ev­er, or even for a very long pe­ri­od of time. You want them to be there just long enough to do the ed­its that they need to do, and then you want it all to go away,” Barnes said. “And that’s es­sen­tial­ly what we’ve shown our sys­tem can do.”

The pub­li­ca­tion comes as In­tel­lia is knee-deep in non-hu­man pri­mate stud­ies, which are sched­uled to wrap up in the first part of the year. Dur­ing the ro­dent study, re­searchers al­so did tests on rats which shed light on the rel­e­vant pa­ra­me­ters for re-op­ti­miz­ing the tech in larg­er an­i­mals. That has played an in­struc­tion­al role in the cur­rent tri­als by arm­ing re­searchers with knowl­edge of what ar­eas to play and tweak.

With a new lipid that’s been de­signed to be scal­able in com­mer­cial op­er­a­tions, In­tel­lia is ready to brace an IND in 2019, though Barnes was care­ful not to spec­i­fy a time just yet.

“This is a very im­por­tant mile­stone in the path of turn­ing LNP-based ap­proach­es in CRISPR in­to a tru­ly clin­ic-ready agent,” he said.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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