A second generation fungerp analog SCY-247, shows potent in vivo activity in a murine model of hematogenously disseminated Candida albicans

Echinocandins are a first-line therapy for Candida infections through their ability to inhibit the synthesis of polymer s-(1,3)-D-glucan. However, there has been an emergence of multidrug-resistant fungal species necessitating the development of novel antifungal agents to combat invasive fungal infections. SCY-247, a second-generation glucan synthase inhibitor of the triterpenoid class (fungerps), is currently being developed as a potential therapy option. We determined the pharmacokinetics of SCY-247 following oral (gavage) administration in mice and evaluated the efficacy of SCY-247 in a murine model of hematogenously disseminated candidiasis caused by C. albicans Plasma concentrations of SCY-247 were measurable through the last collected time point in all dose groups. Mean concentrations of SCY-247 increased with dose levels, with concentrations of SCY-247 higher after multiple doses compared to a single dose. Treatment with SCY-247 resulted in decreased fungal burden and improvement in survival rates against C. albicans disseminated infection. Treatment with 10 mg/kg SCY-247 showed a significant reduction in CFUs compared to the untreated control (3-log decrease on average) (P=0.008). Similarly, SCY-247 40 mg/kg demonstrated a statistically significant reduction in kidney CFUs compared to untreated mice (average log CFU ± SD of 2.38 ± 2.58 vs 6.26 ± 0.51; P=0.001). Mice treated with SCY-247 at 40 mg/kg exhibited a 100% survival rate at the end of the study, contrasted with 62.5% (5 of 8) survival rate in untreated mice. The results of this investigation indicate that SCY-247 is a promising novel anti-fungal agent with activity against Candida infections.