Scynex­is finds it­self in the spot­light with a weapon that may fight a su­per­bug that’s scar­ing the world to death

When Mar­co Tagli­et­ti flew from Am­s­ter­dam to Mi­lan ear­li­er this week, a neigh­bor­ing pas­sen­ger hap­pened to ask what he did for a liv­ing. Up­on learn­ing he was an in­fec­tious dis­ease spe­cial­ist, the pas­sen­ger in­quired whether he had come across the re­cent re­port about this “dif­fi­cult-to-treat new fun­gus.” Up­on dis­em­bark­ing, Tagli­et­ti slid in­to his Uber, when his dri­ver pro­fessed an in­ter­est in his pro­fes­sion. The physi­cian’s an­swer pro­duced a now-fa­mil­iar re­sponse: Have you heard about Can­di­da au­ris?

Mar­co Tagli­et­ti

Such is the state of af­fairs. A com­pre­hen­sive re­port by the New York Times last Sat­ur­day put the spot­light on a stub­born, dif­fi­cult-to-di­ag­nose and treat fun­gal in­fec­tion: Can­di­da au­ris or C. au­ris. The large­ly drug-re­sis­tant mi­crobe, which thrives in peo­ple with com­pro­mised im­mune sys­tems, has emerged mys­te­ri­ous­ly across the globe, pop­ping up in Venezuela, Britain, the Unit­ed States and hav­ing tak­en root in In­dia, Pak­istan and South Africa.

Tagli­et­ti, who has helped bring 35 drugs to mar­ket with stints at For­est Labs, Stiefel Labs and Scher­ing-Plough, runs a small biotech out of Jer­sey City, New Jer­sey called Scynex­is $SCYX — os­ten­si­bly the on­ly US drug de­vel­op­er with an an­ti­fun­gal in late-stage clin­i­cal de­vel­op­ment for the oft’ dead­ly pathogen.

“The CDC has been ac­tu­al­ly been talk­ing about it for the last cou­ple of years, mak­ing dire pre­dic­tions…but ap­par­ent­ly no-one was lis­ten­ing,” Tagli­et­ti said in an in­ter­view with End­points News.

More than 1 in 3 pa­tients with in­va­sive C. au­ris in­fec­tion (for in­stance, an in­fec­tion that af­fects the blood, heart, or brain) die, ac­cord­ing to the CDC, which has deemed the pathogen a “se­ri­ous glob­al health threat.” As of Feb­ru­ary 28, the US agency has record­ed 587 con­firmed cas­es and 30 prob­a­ble cas­es this year.

“C. au­ris at­tach­es from per­son to per­son, to things, to clothes, to the walls. This is why the CDC is so con­cerned about this pathogen, its very sticky, very per­sis­tent and tends to spread,” Tagli­et­ti said, not­ing that the pub­lish­ing of the NYT sto­ry in­spired a se­ries of re­ports glob­al­ly that helped the fun­gus has per­me­at­ed the cul­tur­al zeit­geist.

“From what we know, we are the on­ly com­pa­ny as­sess­ing an in­ves­ti­ga­tion­al treat­ment in C. au­ris. I’m sure now, many oth­ers will fol­low.”

It has been decades since a fresh fam­i­ly of an­ti­fun­gals has come on to the mar­ket — at the mo­ment there are three class­es of an­ti­fun­gals in clin­i­cal use, in­clud­ing azoles and echinocan­dins.

The most pop­u­lar an­ti­fun­gals in use to­day were in­tro­duced in the 1980s and this class is in­creas­ing­ly los­ing its po­ten­cy, as fun­gal pathogens be­come more re­sis­tant. Scynex­is’s lead ex­per­i­men­tal drug — ibrex­a­fungerp — be­longs to a new class of an­ti­fun­gals called glu­can syn­thase in­hibitors, and has shown to be ef­fec­tive against a broad range of fun­gal in­fec­tions, in­clud­ing re­sis­tant strains, Tagli­et­ti said.

Last Oc­to­ber, the com­pa­ny ini­ti­at­ed a late-stage open-la­bel study called CARES in C. au­ris pa­tients. In a pre­sen­ta­tion on Fri­day, Scynex­is will present da­ta at a med­ical con­fer­ence on two pa­tients who were suc­cess­ful­ly treat­ed with the oral ibrex­a­fungerp from the on­go­ing study, which has en­rolled sev­er­al pa­tients so far.

The pas­sage of the lim­it­ed pop­u­la­tion path­way for an­tibac­te­r­i­al and an­ti­fun­gal drugs (LPAD) — es­tab­lished by the 21st Cen­tu­ry Cures Act — al­lows the FDA to ap­prove cer­tain an­ti-in­fec­tive prod­ucts on the ba­sis of lim­it­ed clin­i­cal da­ta. Scynex­is is work­ing with the FDA to sort out how much ibrex­a­fungerp da­ta will make the cut for C. au­ris, Tagli­et­ti said.

The drug is al­so be­ing test­ed for oth­er in­fec­tions. It is in a Phase III study for vagi­nal yeast in­fec­tions. Topline da­ta are ex­pect­ed in the first half of 2020, and if pos­i­tive, the com­pa­ny ex­pects to file a mar­ket­ing ap­pli­ca­tion in the lat­ter half of the year.

One of the biggest chal­lenges fac­ing the field of an­ti­fun­gal drug de­vel­op­ment is the lack of in­cen­tives, such as those af­ford­ed to com­pa­nies in the an­tibac­te­r­i­al and an­tivi­ral space, Tagli­et­ti said.

When the com­pa­ny ap­proached BAR­DA for fund­ing, they were told an­ti­fun­gals were not a pri­or­i­ty in Wash­ing­ton, he said. “I hope this aware­ness will now reach Wash­ing­ton.”

As su­per­bugs flour­ish, the in­dus­try play­ers con­tribut­ing to the ar­se­nal of an­timi­cro­bials are dwin­dling. Com­pa­nies in the an­tibi­ot­ic space have their own set of trou­bles.

Drug­mak­ers are en­ticed by green­er pas­tures, com­pared to the long ar­du­ous path to an­tibi­ot­ic ap­proval that of­fers lit­tle fi­nan­cial gain as treat­ments must be priced cheap­ly, and of­ten lose po­ten­cy over time as bac­te­ria grow re­sis­tant. Be­yond the in­cen­tives al­ready in place to push drug­mak­ers to de­vel­op an­tibi­otics, there have been calls to bring on “pull in­cen­tives,” or pol­i­cy mea­sures to in­crease the val­ue of a mar­ket­ed an­tibi­ot­ic by re­ward­ing drug­mak­ers on­ly af­ter their an­tibi­ot­ic is ap­proved by the FDA.

Tagli­et­ti does not see an­ti­fun­gals fac­ing a sim­i­lar hur­dle. “There is a (big­ger) need for an­ti­fun­gals, there­fore they will not go the same way an­tibac­te­r­i­al sales have gone. The last an­ti­fun­gal ap­proved in 2015 is mak­ing $150 mil­lion in its third year of sales…more than the last 4 or 5 an­tibac­te­ri­als com­bined.”


Im­age: Can­di­da Au­ris. Shut­ter­stock

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: 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.”

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Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?

Sanofi’s big week in­cludes a promis­ing PhI­II for an or­phan dis­ease drug, with plans for a pitch to the FDA

The biopharma R&D food chain is paying off with a plan at Sanofi to pitch regulators on a new drug for an orphan disease called cold agglutinin disease.

The pharma giant ushered out a statement Tuesday morning — after it spelled out plans to radically restructure the company, abandoning cardio and diabetes research altogether — saying that their C1s inhibitor sutimlimab had cleared the pivotal study.