As Drug Resistance Grows, Amplyx Tests New Antifungal Drug

Xconomy San Diego — 

While fungal infections may seem like an annoyance rather than a serious health problem, sick people in hospitals and long-term care facilities are contracting potentially deadly infections that current treatments are failing to ameliorate, thanks to the evolution of many such germs.

One such fungus, Candida auris, like some bacteria, has become increasingly resistant to the drugs with which it was previously treated, causing infections across five continents, as the New York Times recently reported in an article about the rise of the “mysterious” worldwide health threat.

Now, a San Diego company is testing an experimental drug to treat life-threatening, invasive infections caused by not only strains of Candida, but also Aspergillis and rare molds.

Funded by over a hundred million dollars in venture investment, plus grants from the National Institutes of Health, Amplyx is enrolling patients in Phase 2 trials of its lead drug candidate, APX001A. The experimental drug attacks a fungal enzyme, Gwt1, interrupting the work of a protein that’s integral to the cell wall in fungi and, in doing so, damages that protective layer and clogs the cell in a way that leads to its death.

“This is not something we can sterilize our way out of,” Amplyx president and CEO Ciara Kennedy (pictured) said in an interview Friday. “We can do all the right things to decontaminate…but what we really need is new, innovative agents and new targets to address these types of infections.”

Three classes of antifungal drugs exist today. The use of polyenes dates back to the 1960s; azoles rose to prominence in the 1980s; and echinocandins came into use in the early 2000s, Kennedy said.

“The tools that doctors have relied upon for years are becoming less and less effective. What we’re doing is coming at these infections from a totally new angle, with a new target that hasn’t been addressed before, and that, I think, is the hope for the future, to really combat all the emerging resistance that we’re seeing,” she said. “We’re about due for a new class of antifungals. …I believe [APX001A] is the only novel mechanism, broad spectrum, [intravenous] and oral agent in development.”

As a treatment for Candida auris, at least, a study by the Centers for Disease Control and Prevention revealed that the experimental drug was active against samples of the pathogen collected from 100 different places, including some that are resistant to one or more current treatments.

“They have tested all the marketed drugs, and all the drugs in development,” Kennedy said. “By far, [APX001A was] the most active agent against the entire collection… We’re an order of magnitude more active, based on everything the CDC has published and everything we’re aware of, more active than anything they have tested.”

Amplyx has raised more than $118 million from investors, including a $67 million Series C financing round in 2017 led by Sofinnova Venture Partners.

Other companies are also vying to develop new antifungal drugs. Scynexis (NASDAQ: SCYX), a New Jersey-based spinout of Aventis (which has since merged with Sanofi), is in late-stage testing of ibrexafungerp, which it says can treat multiple fungal infections, including some that have demonstrated resistance to existing therapies. That drug uses the same mechanism as do the echinocandins, the most recent class of antifungal drugs, but Scynexis says it is still able to treat most echinocandin-resistant strains.

The CDC has been keeping an especially close eye on Candida auris because of its ability to spread easily in hospitals and long-term care facilities. Late last year the agency added the infection to its list of infections about which it must be notified. As of late February, the CDC had confirmed 587 cases in 12 US states, plus another 30 probable cases. Multiple cases have been reported in more than 20 other countries.

Amplyx is testing its drug for delivery both intravenously and orally. Kennedy anticipates data could be available as soon as year’s end from a Phase 2 trial in which the company aims to enroll 20 patients worldwide; Kennedy says enrollment is ahead of schedule.

“The big question on the table for us is, does all that great clinical data and the beautiful Phase 1 safety and [pharmacokinetics] data translate to cures in patients?” she said. “That’s what we’re doing right now.”