EDP-323, a First-in-Class, Oral, RSV-Specific, Non-Nucleoside L-Protein Inhibitor Antiviral Rapidly Reduces Total RSV Symptoms, Lower Respiratory Tract RSV Symptoms and Viral Load After Human Viral Challenge

Abstract Background RSV impacts large populations of vulnerable children and adults despite available prevention strategies. No effective RSV treatments exist. EDP-323, a first in class, potent, oral, non-nucleoside small molecule inhibitor of RSV polymerase (L-protein) is in development to treat RSV infections. Methods A randomized, double-blind, placebo (PBO)-controlled study (NCT06170242) evaluated the efficacy, antiviral activity and safety, of EDP-323. Healthy volunteers were inoculated with RSV-A. After confirmed RSV infection or 5 days(D) later, randomized participants received EDP-323 600mg (n=47), 200mg (with 600mg loading dose; n=47), or PBO (n=47) once daily (QD) for 5D and were followed through 28D. Clinical symptoms were assessed QD using the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) and viral loads (VL) were assessed by qRT-PCR on nasal washes. We evaluated efficacy as area under the curve (AUC) effects in the intent-to-treat infected population (EDP-323 600mg n=26; 200mg n=23; PBO n=30). Results Participants showed rapid (within the 1st 24 hr) and statistically significant improvements in RiiQTM RSV symptoms (Figs 1,2) and VL after EDP-323 dosing vs PBO. Compared to PBO, there were 73% (P=0.0012), 61% (P=0.0010), and 67% (P 0.0001) RiiQTM total symptom score AUC reductions in 200mg, 600mg, and EDP-323 pooled recipients respectively. Lower respiratory tract disease scores (LRTD) AUC were reduced by 95% (P=0.0002), 73% (P=0.0088), and 85% (P=0.0002) respectively in the 200mg, 600mg, and Pooled EDP-323 recipients vs PBO. There were 87% and 85% VL AUC reductions in 200mg and 600mg recipients, respectively vs PBO (all P 0.0001). EDP-323 dosing groups showed similar efficacies. Frequencies of treatment-emergent adverse events (TEAEs) were similar across EDP-323 and PBO groups. No serious TEAEs, severe AEs, or AEs leading to treatment discontinuation or study withdrawal occurred. Conclusion EDP-323 rapidly and significantly reduced symptoms including lower respiratory tract symptoms as measured by the RiiQTM patient reported outcome tool, lowered viral load vs placebo in healthy RSV infected adults and was well-tolerated. These findings support EDP-323 as a potential once daily oral RSV treatment. Disclosures All Authors: No reported disclosures