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

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

Paul Hudson, Getty Images

Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

A Kite deal that’s already become a burden on Gilead’s back just got heavier as a California jury has ruled Gilead must pay Bristol-Myers Squibb and Sloan Kettering $585 million plus a 27.6% royalty for patent infringement committed by its subsidiary. The ruling is almost certain to be appealed.

Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Paul Biondi (File photo)

Bris­tol-My­er­s' strat­e­gy, BD chief Paul Bion­di ex­it­ed the com­pa­ny — just ahead of the $74B Cel­gene deal close

Paul Biondi, who orchestrated billions of dollars in deals for Bristol-Myers Squibb over the 5 years he’s run their business development team, has exited the company. Biondi left last month, according to a company spokesperson, in pursuit of another — unspecified — external opportunity.

After 17 years with Bristol-Myers Squibb, Paul Biondi, Head of Strategy and Business Development, decided to leave the company to pursue an external opportunity. The company wishes him well in his new endeavors. Bristol-Myers Squibb  is actively searching for Paul’s successor, and will make an announcement, as appropriate.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

Arie Belldegrun at UKBIO 2019. Shai Dolev for Endpoints News

Kite Phar­ma's ex-CEO con­tra­dicts founder as CAR-T patent tri­al heats up, with con­flict­ing val­u­a­tions

Two days after Kite Pharma founder Arie Belldegrun told a federal courtroom that a meeting he had with a Memorial Sloan Kettering executive wasn’t about licensing their immunotherapy patent, Kite’s ex-CEO Aya Jakobovits said it was.

The admission came Tuesday during cross-examination in a patent infringement case that features two of the biggest cancer biotechs and some of the most well-known names in American medicine.

Jakobovits initially said she was not in attendance, didn’t know it was going to happen and didn’t know what took place, according to Law360. But then the plaintiff’s lawyer handed her a document – whose contents were not publicly revealed – and asked again if she learned after-the-fact that the meeting involved a potential patent license.

“Yes,” Jakobovits eventually said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.

On the heels of promis­ing MCL da­ta, Kite hus­tles its 2nd CAR-T to the FDA as the next big race in the field draws to the fin­ish line

Three days after Gilead’s Kite subsidiary showed off stellar data on their number 2 CAR-T KTE-X19 at ASH, the executive team has pivoted straight to the FDA with a BLA filing and a shot at a near-term approval.

In a small, 74-patient Phase II trial reported out at the beginning of the week, investigators tracked a 93% response rate with two out of three mantle cell lymphoma patients experiencing a complete response.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,600+ biopharma pros reading Endpoints daily — and it's free.