Clinical Data Demonstrate Favorable Safety, Tolerability and Pharmacokinetics
Additional Nonclinical Data Show APX001 is Effective Against a Broad Range of Pathogenic Fungi, Including Deadly Candida auris
SAN DIEGO – October 9, 2017 – Amplyx Pharmaceuticals, a company developing novel antimicrobial agents for life-threatening fungal infections, today announced that it presented results from two Phase 1 studies of APX001, plus new nonclinical data highlighting its breadth of spectrum, at IDWeek 2017 held in San Diego, CA.
APX001 is a broad-spectrum antifungal drug candidate with a novel mechanism of action for the treatment of life-threatening, invasive fungal infections caused by Candida, Aspergillus and rare, hard-to-treat molds, and strains that are resistant to standard-of-care antifungal therapy.
“We are very encouraged by the exemplary safety and pharmacokinetic data from both Phase 1 studies, which showed APX001 to be very well-tolerated with a favorable safety profile across all doses of intravenous (IV) and oral formulations tested,” said Michael Hodges, M.D., Chief Medical Officer of Amplyx Pharmaceuticals. “The ability to dose APX001 once-daily and switch from IV to oral administration are critical in optimizing care in patients with invasive fungal infections.”
Two Phase 1 studies, with a total of 166 subjects enrolled, were conducted to assess both IV and oral formulations of APX001. Both were randomized, dose-escalation, double-blind, placebo‑controlled studies to assess the safety, tolerability and pharmacokinetics of APX001 in healthy subjects following single and multiple doses. The Phase 1 studies were also designed to evaluate an IV loading dose regimen; the effect of food on APX001; and the drug-drug interaction potential of APX001.
APX001 data highlights from intravenous and oral administration Phase 1 studies:
All doses of APX001 tested were safe and well tolerated.
Most adverse events (AEs) were mild, transitory and resolved without intervention.
Target exposures of APX001 for efficacy against Candida and Aspergillus were exceeded.
The average plasma half-life of APX001 was ~2.5 days.
The oral formulation showed greater than 90% bioavailability.
At the conference, Amplyx also presented five nonclinical studies of APX001 that demonstrate efficacy against a range of pathogenic fungi, including the multidrug resistant superbug Candida auris, Cryptococcus neoformans, which causes cryptococcal meningitis, and Rhizopus delemar which causes invasive mucormycosis, an invasive fungal infection with some of the highest documented mortality rates. Notably, 16 strains of C. auris showed a greater susceptibility to the active moiety APX001A than other antifungal agents. When tested in an immunocompromised mouse model, mice treated with APX001 had a significantly higher percentage survival than those treated with the control drug anidulafungin.
“There is a critical need for new antifungals, yet developing new drugs is extremely challenging given the genetic similarity between fungi and humans – compounds that effectively target fungi often also interact with the human homolog and consequently result in toxic side effects,” said Ciara Kennedy, Ph.D., Chief Executive Officer of Amplyx. “Demonstrating safety in humans for a potential new antifungal is a major development hurdle. This is a significant milestone for the APX001 program. APX001 has shown impressive activity against drug resistant strains and has potential to address some of the most recently identified fungal threats, including multidrug-resistant C. auris.”
APX001 is the prodrug of APX001A, which is a first-in-class small molecule drug candidate that inhibits the highly conserved fungal enzyme Gwt1, compromising growth of major fungal pathogens, including Candida and Aspergillus. In many nonclinical studies, APX001A has shown broad-spectrum activity against common species of Candida spp., and Aspergillus spp., including multi-drug resistant strains and rare, hard-to-treat molds including Fusarium spp., Scedosporium spp., and fungi from the Mucorales order.
About Amplyx Pharmaceuticals
Amplyx Pharmaceuticals is developing novel, broad-spectrum antimicrobial agents for the treatment of life-threatening fungal infections in vulnerable, immune compromised patients. Amplyx’s drug discovery and development efforts have been supported by significant venture investment and more than $10 million in grants from the National Institutes of Health. For more information, please visit www.amplyx.com.
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Heidi Chokeir, Ph.D.
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