Efficacy assessments of EL219, a next-generation polyene antifungal, in immunosuppressed mice infected with drug-sensitive and drug-resistant Aspergillus isolates

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Abstract
Invasive pulmonary aspergillosis (IPA), mainly caused by A. fumigatus, remains a life-threatening fungal infection, with rising reports of infections caused by resistant species such as Aspergillus lentulus and Aspergillus calidoustus . EL219 (formerly known as SF001) is a novel, next-generation polyene with enhanced ergosterol selectivity and reduced nephrotoxicity. We evaluated the efficacy of EL219 compared to liposomal amphotericin B (LAMB) in vitro using the Clinical Laboratory and Standards Institute M38 methodology and in immunosuppressed murine models of IPA caused by A. fumigatus , A. lentulus , and A. calidoustus . Immunosuppressed ICR mice were infected via inhalation ( A. fumigatus ) or via intratracheal instillation ( A. lentulus and A. calidoustus ), then treated intravenously once daily with placebo, EL219 (0.3, 1.5, 7.5, and 30 mg/kg), or LAMB (5 mg/kg) starting 16 h post-infection. Treatment lasted 4 days ( A. fumigatus and A. lentulus ) or 7 days ( A. calidoustus ). Survival through Day 21 and lung fungal burden at Day 4 were assessed. EL219 showed enhanced in vitro activity against A. lentulus and A. calidoustus compared to LAMB. EL219 significantly improved survival in a dose-dependent manner, with 30 mg/kg outperforming LAMB. EL219 also resulted in >5-log fungal burden reductions in A. fumigatus -infected lungs. EL219 demonstrated broad-spectrum efficacy, improved survival, and reduced lung fungal burden, supporting its potential as a novel therapy for IPA.
Funding Information
  • Elion Therapeutics (22775)

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