2062. In Vivo Efficacy of CD388, a Novel Drug Fc-Conjugate (DFC), Against Seasonal Subtypes of Influenza in Prophylaxis in Immune Competent Mice, and in a Severe Immunodeficient (SCID) Mouse Model

BACKGROUND: Influenza remains a significant public health concern due to the limited efficacy of vaccines. Cidara has developed CD388, a multivalent conjugate of a dimeric neuraminidase inhibitor with a proprietary hIgG1 Fc domain engineered for extended half-life, currently in clinical development. Here we describe the efficacy of CD388 against a panel of geographically and temporally diverse influenza A and B subtypes in mouse prophylactic models, and against H1N1 in a SCID model. METHODS: Efficacy studies were conducted in BALB/c mice lethally challenged with influenza virus. CD388 was administered intramuscularly (IM), seven days prior to challenge. Animals were monitored daily for 21 days or longer for survival (< 20% BW loss). For SCID studies, mice were dosed with CD388 two hours prior to lethal challenge with influenza A H1N1. Oseltamivir and baloxavir were included as comparators. RESULTS: Across all influenza subtypes, CD388 treatment at ≤1 mg/kg resulted in 100% survival (Table 1). Daily BW measurements of treatment groups supported survival findings and showed a transient BW loss (generally between 5 and 15% of starting weight), before animals recovered weight. In SCID studies, the median time of death for vehicle treated animals was seven days. Treatment with oseltamivir (5 mg/kg, bid x5d) and baloxavir (15 mg/kg, bid x1d) at their human equivalent doses extended the median survival time to Day 10 and 16, respectively (Figure 1). In contrast, a single dose of CD388 at 1 mg/kg extended the median time of death to beyond Day 21. A dose response was evident at higher CD388 doses with the median time of death extended to Day 30 and 35 for 3 and 10 mg/kg groups, respectively. CONCLUSION: This data demonstrated a single IM administration of CD388 fully protected animals from lethal challenge against seasonal influenza A and B. Importantly, CD388 was found to be efficacious in a severe model of immune deficiency. This data supports the prophylactic use of CD388 to prevent seasonal influenza in individuals. [Figure: see text] [Figure: see text] DISCLOSURES: James Levin, PhD, Cidara Therapeutics: Stocks/Bonds Simon Döhrmann, PhD, Cidara Therapeutics: Stocks/Bonds Jason N. Cole, Ph.D., Cidara Therapeutics: Stocks/Bonds Karin Amundson, BSc, Cidara Therapeutics: Stocks/Bonds Allen Borchardt, PhD, Cidara Therapeutics: Stocks/Bonds Thomas P. Brady, Ph.D., Cidara Therapeutics: Stocks/Bonds Thanh Lam, PhD, Cidara Therapeutics: Stocks/Bonds Joanne Fortier, BSc, Cidara Therapeutics: Stocks/Bonds Amanda Almaguer, Bachelors, Cidara Therapeutics: Stocks/Bonds Leslie W. Tari, Ph.D., Cidara Therapeutics: Stocks/Bonds