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

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.