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.”

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115M and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS-CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.