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

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.