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

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Scripps reach­es $10M set­tle­ment with gov­ern­ment over al­le­ga­tions NIH grants weren't prop­er­ly ac­count­ed for

Scripps Research Institute has settled a case with the Justice Department alleging claims of misappropriated funds, the US attorney for the district of Maryland announced late last week.

Prosecutors said the institute improperly used NIH-funded research grants for non-grant related activities, including working on new grant applications, teaching activities and other administrative tasks. As part of the settlement, Scripps has agreed to pay $10 million.

Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.