Nematode. Andy Murray

Com­pound nes­tled in par­a­sitic worm of­fers promise as an­tibi­ot­ic against ob­sti­nate su­per­bugs

A com­pound domi­ciled in­side the gut of a soil-dwelling par­a­sitic worm could be the chief in­gre­di­ent for a po­tent hu­man an­tibi­ot­ic de­signed to fight a class of stub­born su­per­bugs, new re­search sug­gests.

The tsuna­mi of an­tibi­ot­ic re­sis­tance is an acute glob­al threat. In the Unit­ed States, at least 2.8 mil­lion peo­ple get an an­tibi­ot­ic-re­sis­tant in­fec­tion each year, and more than 35,000 peo­ple die, ac­cord­ing to a re­cent re­port by the CDC.

The be­lea­guered field of an­tibi­otics is des­per­ate for a win­ner. For one of the biggest threats to glob­al health, the li­on’s share of an­tibi­ot­ic de­vel­op­ment is tak­ing place in a hand­ful of labs of small bio­phar­ma com­pa­nies or the halls of acad­e­mia, while big phar­ma large­ly fo­cus­es on more lu­cra­tive en­deav­ors. Mean­while, most fresh­ly ap­proved an­tibi­otics have been more po­tent ver­sions of ex­ist­ing class­es of an­tibi­otics. In short, the field is des­per­ate for fresh op­tions.

The com­pound, darobactin, is a prod­uct of Pho­torhab­dus bac­te­ria that was dis­cov­ered re­sid­ing with­in the gut of a ne­ma­tode.

Darobactin has the po­ten­tial to smoth­er Gram-neg­a­tive bac­te­ria, which cause in­fec­tions such as ty­phoid, cholera and the plague. The class of mi­crobes bran­dish­es a re­silient out­er mem­brane which as­sists them in sub­vert­ing most stan­dard an­tibi­otics. The last class of an­tibi­otics act­ing against Gram-neg­a­tive bac­te­ria was de­vel­oped in the 1960s, re­searchers not­ed in Na­ture.

Re­search on mice, con­duct­ed by a team of sci­en­tists led by Kim Lewis, pro­fes­sor of bi­ol­o­gy and di­rec­tor of the An­timi­cro­bial Dis­cov­ery Cen­ter at North­east­ern Uni­ver­si­ty, in­di­cat­ed that darobactin treat­ed E. coli and Kleb­siel­la pneu­mo­ni­ae in­fec­tions, sans any tox­i­c­i­ty.

The dis­cov­ery marks the first in­stance that the an­i­mal mi­cro­bio­me was found to har­bor an an­tibi­ot­ic that could be em­ployed in hu­mans, Lewis not­ed in a re­port pub­lished by North­east­ern ac­com­pa­ny­ing the Na­ture pub­li­ca­tion.

Ne­ma­todes and Pho­torhab­dus bac­te­ria share their din­ners, pri­mar­i­ly of the in­sect va­ri­ety. The ne­ma­tode sets its friend the Pho­torhab­dus bac­te­ria loose on say, a cater­pil­lar. The bac­te­ria ex­pels tox­ins in­to the unas­sum­ing cater­pil­lar, killing it — al­low­ing the con­niv­ing al­lies to share the spoils.

But, the Pho­torhab­dus must al­so fend off oth­er greedy din­ers — par­tic­u­lar­ly from with­in ne­ma­tode’s gut, which is typ­i­cal­ly brim­ming with the same Gram-neg­a­tive bac­te­ria that at­tack hu­mans. And be­cause the ne­ma­tode is the Pho­torhab­dus’s home, it makes sure what kills the gram-neg­a­tive pathogens doesn’t stran­gle its host.

“Since Pho­torhab­dus bac­te­ria live in the ne­ma­tode, and the ne­ma­tode is an an­i­mal just like we are, what­ev­er they make has to be non-tox­ic [for us],” Lewis said in the North­east­ern re­port.

That ad­di­tion­al ar­mor that Gram-neg­a­tive bac­te­ria en­joy is en­gi­neered by a pro­tein called Ba­mA, which acts as a guard, open­ing its gates cycli­cal­ly al­low­ing the pas­sage of fresh pro­teins to build that im­per­vi­ous pro­tec­tive shield. Darobactin makes a bee­line for Ba­mA and clogs that gate, thwart­ing the cre­ation of that cell wall and ren­der­ing the gram-neg­a­tive bac­te­ria vul­ner­a­ble to ex­ist­ing an­tibi­otics.

The re­searchers are now gun­ning to test the Ba­mA in­hibitor in hu­man tri­als.

This mech­a­nism of ac­tion po­ten­tial­ly re­solves the in­tractable prob­lem of pen­e­trat­ing the bar­ri­er of Gram-neg­a­tive bac­te­ria, they wrote in Na­ture. “There are on­ly two es­sen­tial pro­teins ex­posed on the sur­face of the out­er mem­brane – Ba­mA; and LptD17. There is lit­tle doubt that na­ture pro­duced more than one type of com­pounds act­ing against these tar­gets.”

The Na­ture ar­ti­cle in­clud­ed the con­tri­bu­tions of sci­en­tists from North­east­ern Uni­ver­si­ty, Pur­due Uni­ver­si­ty, and the J. Craig Ven­ter In­sti­tute from the Unit­ed States; Jus­tus Liebig Uni­ver­si­ty Giessen, the Ger­man Cen­ter for In­fec­tion Re­search DZIF and the Eu­ro­pean Mol­e­c­u­lar Bi­ol­o­gy Lab­o­ra­to­ry EM­BL in Ger­many; as well as the Uni­ver­si­ty of Basel in Switzer­land.

Im­age cred­it: Andy Mur­ray, A Chaos of De­light

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.

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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Stéphane Bancel, Moderna CEO (Andrew Harnik/AP Images)

A top an­a­lyst turns the spot­light on Mod­er­na, fu­el­ing a fast-and-fu­ri­ous Street race over the fu­ture of mR­NA

Bioregnum Opinion Column by John Carroll

Four months ago, one of the favorite talking points on the biopharma social media wave length was whether Moderna shares $MRNA were priced right or were wildly inflated.

After all, said the naysayers, the company had never actually pushed a treatment to an approval. Did messenger RNA really work, coding cells to make a drug or a vaccine? And how about all that chatter about how ‘secretive’ they are, or were?

Now, as CEO Stéphane Bancel and the top execs push the company to the forefront of a frantic race to develop the first vaccine to fight against the reignited wildfire spread of Covid-19, all those questions have been magnified — along with the stock price.

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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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