New NIH vi­ral vec­tor flips the script on sick­le cell dis­ease gene ther­a­py

Re­searchers at the NIH have rolled out a new ve­hi­cle for sick­le cell gene ther­a­py with high­er speeds and bet­ter horse­pow­er, po­ten­tial­ly al­low­ing vast­ly more ef­fi­cient gene trans­fer and a much larg­er car­ry­ing ca­pac­i­ty. The best part? Un­like cur­rent sick­le cell gene ther­a­py mod­els, the NIH one doesn’t have to dri­ve in re­verse.

In mice and mon­keys, the new ve­hi­cle was up to 10 times more ef­fi­cient and had a car­ry­ing ca­pac­i­ty – the amount of DNA it can haul – of up to 6 times that of the con­ven­tion­al vec­tors cur­rent­ly de­ployed in gene ther­a­py tri­als across the coun­try. Most no­tably, the new vec­tor can read the ther­a­peu­tic gene se­quence for­ward rather than read­ing them back­ward — a counter-in­tu­itive trick re­searchers had used to over­come long-run­ning bar­ri­ers to gene ther­a­py but which sac­ri­ficed ef­fi­cien­cy. The re­sults were pub­lished open ac­cess in Na­ture Com­mu­ni­ca­tions.

John Tis­dale NIH

“Our new vec­tor is an im­por­tant break­through in the field of gene ther­a­py for sick­le cell dis­ease,” said study se­nior au­thor John Tis­dale, chief of the Cel­lu­lar and Mol­e­c­u­lar Ther­a­peu­tic Branch at the Na­tion­al Heart, Lung, and Blood In­sti­tute (NHLBI). “It’s the new kid on the block and rep­re­sents a sub­stan­tial im­prove­ment in our abil­i­ty to pro­duce high ca­pac­i­ty, high-ef­fi­cien­cy vec­tors for treat­ing this dev­as­tat­ing dis­or­der.”

Gene ther­a­py tri­als for SCD have launched the past few years, bring­ing a hand­ful of well-cov­ered cas­es of pa­tients re­spond­ing strong­ly to the treat­ment, even as more da­ta shows cur­rent tech­niques are no cure-all. One of the big­ger long­stand­ing ques­tions, though, is how to best de­liv­er the ge­net­ic fix.

The sim­ple ge­net­ic un­der­pin­nings of the dis­ease have been well-un­der­stood since the 1950s — one A-T sub­sti­tu­tion in the β-glo­bin gene — and re­searchers have ac­cord­ing­ly tar­get­ed it since the first gene ther­a­py re­search in the 1980s. But the par­tic­u­lar prob­lems of build­ing a prop­er vec­tor for the he­mo­glo­bin gene, in ad­di­tion to the myr­i­ad oth­er ob­sta­cles to gene ther­a­py broad­ly, have im­ped­ed progress.

The steps in gene ther­a­py for sick­le cell dis­ease. Na­tion­al Heart, Lung, and Blood In­sti­tute

Click on the im­age to see the full-sized ver­sion

The lentivi­ral vec­tor blue­bird bio has used to bring its sick­le cell gene ther­a­py to tri­al is a workaround to an ear­ly prob­lem unique to sick­le cell ther­a­py. RNA splic­ing – a nat­ur­al process crit­i­cal to prepar­ing the vec­tor – will re­move “in­trons” that are key to ex­press­ing the genes to pro­duce he­mo­glo­bin. De­vel­op­ers have been able to get around this by us­ing a vec­tor that reads the DNA back­wards, last gene to first. Most gene ther­a­py tech­niques read as you would a sen­tence, first word to last.

The re­searchers al­so not­ed their vec­tors were cheap­er to pro­duce.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Ludwig Hantson, Alexion CEO

Why pay $4B for a steady di­et of dis­ap­point­ment? Porges turns thumbs down on Alex­ion’s M&A strat­e­gy, of­fers some point­ers

When Alexion announced recently that it was paying $1.4 billion to bag Portola and its underperforming Factor Xa inhibitor reversal agent, you could hear the head-scratching going on around virtual Wall Street.

Why was Alexion going down the discount lane for new products? And why something like this? Analysts have been urging Alexion to get serious about M&A for years if it was serious about diversifying the company beyond Soliris and its successor drug. But this wasn’t the kind of heavy-impact deal they were looking for.

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Mil­li­pore­Sig­ma to build new $20 mil­lion, 12,000-square-foot lab in Switzer­land

On the heels of opening a new laboratory in Shanghai last week, MilliporeSigma is continuing its construction push.

The Merck KGgA life science subsidiary announced Wednesday its intentions to build a new $20 million lab in Buchs, Switzerland to support its reference materials business. It’s estimated that the new facility will be completed in December 2021 and open in early 2022 and is expected to be 12,000 square feet.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

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Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

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