Penn sci­en­tists cor­rect ge­net­ic flaw in mice fe­tus­es, ex­pand­ing in utero CRISPR reach to lung dis­eases

Re­mem­ber when re­searchers ap­plied CRISPR to ed­it genes of mice fe­tus­es while they are still in the womb, spar­ing them from death by liv­er dis­ease? The same team from the Uni­ver­si­ty of Penn­syl­va­nia has now test­ed the same idea — al­beit with a dif­fer­ent tech­nique — in ge­net­ic lung dis­eases.

In the bur­geon­ing world of gene edit­ing spawned by CRISPR, in utero treat­ment can be seen as a mid­point be­tween ear­ly em­bryo edit­ing (which pass­es the ge­net­ic al­ter­ations to fu­ture gen­er­a­tions) and edit­ing af­ter birth, which can be too late for pa­tients with cer­tain lethal dis­eases.

William Per­an­teau

It is one of these con­di­tions that study co-lead­ers Ed­ward Mor­risey and William Per­an­teau set out to thwart in their lat­est proof-of-con­cept study, pub­lished in Sci­ence Trans­la­tion­al Med­i­cine this week. Specif­i­cal­ly, they look at a gene tied to sur­fac­tants, a cru­cial lipopro­tein that re­duces lung sur­face ten­sion and en­ables nor­mal lung func­tion. An SFT­PC mu­ta­tion in hu­mans, as in mice, means new­borns are al­most cer­tain to die with­in hours of birth — and that’s what hap­pened with all of the mice in the ex­per­i­ment that were born with the mu­ta­tion.

The team, how­ev­er, man­aged to in­ac­ti­vate the mu­tant gene in some of the fe­tus­es, al­low­ing 7 (out of 87 treat­ed with CRISPR) to sur­vive be­yond 24 hours, in­clud­ing 5 that seemed to re­main healthy for sev­en days.

To specif­i­cal­ly de­liv­er the gene edit­ing reagent to the lungs, the sci­en­tists in­ject­ed it in am­ni­ot­ic flu­id so that with every in­hala­tion, CRISPR would get straight to the ep­ithe­lial cells lin­ing the air­ways. The in­jec­tion took place four days be­fore birth, the equiv­a­lent of hu­mans’ third trimester.

They note that this method re­sult­ed in “rel­a­tive­ly uni­form tar­get­ing of most of the ma­jor pul­monary ep­ithe­lial cell types,” a po­ten­tial ad­van­tage over post­na­tal in­hala­tions that tend to cause dif­fer­en­tial dis­tri­b­u­tion.

“Giv­en that many con­gen­i­tal lung dis­eases such as cys­tic fi­bro­sis and in­her­it­ed [sur­fac­tant pro­tein] dis­ease are gen­er­al­ly caused by mono­genic mu­ta­tions, they should be ide­al can­di­dates for gene edit­ing tech­nolo­gies,” the study au­thors write.

Ed­ward Mor­risey

Like any mouse study, of course, the re­sults are mere­ly signs that re­searchers could pro­ceed with cau­tion. And the re­searchers add that pre­na­tal gene edit­ing can ex­pose the moth­er to risks — some­thing they wouldn’t have to wor­ry about in post­na­tal edit­ing. But the re­searchers are clear­ly stoked about the po­ten­tial here.

“The abil­i­ty to cure or mit­i­gate a dis­ease via gene edit­ing in mid to late ges­ta­tion be­fore birth and the on­set of ir­re­versible pathol­o­gy is very ex­cit­ing,” Per­an­teau said in a state­ment. “This is par­tic­u­lar­ly true for dis­eases that af­fect the lungs, whose func­tion be­comes dra­mat­i­cal­ly more im­por­tant at the time of birth.”

Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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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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Daniel O'Day

No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.