674. Pre-Clinical and Phase I Safety Data for Anti-Pseudomonas aeruginosa Human Monoclonal Antibody AR-105

BACKGROUND: Anti-bacterial monoclonal antibodies can serve as a new treatment modality for difficult to treat infections. AR-105 is a fully human IgG1 monoclonal antibody (mAb) that binds to an extracellular polysaccharide epitope of Pseudomonas aeruginosa (PA) and was shown to mediate in vitro complement-dependent opsonophagocytic killing. AR-105 is currently being tested in a global Phase 2 clinical trial as an adjunctive treatment to standard of care antibiotics in ventilator-associated pneumonia patients. Here we present pre-clinical efficacy and clinical safety data for AR-105. METHODS: Efficacy in nonclinical studies against PA pneumonia was tested in prophylactic and therapeutic mouse models, either as a stand-alone therapy or in combination with antibiotics. Mice were dosed intranasally or by intravenous infusion with AR-105 post or prior to infection with PA and survival or lung bacteriology were monitored. In a clinical Phase 1 open-label study, 16 healthy volunteers received 2, 8, or 20 mg/kg of AR-105. Adverse events, immunogenicity, and pharmacokinetic (PK) profiles were evaluated for up to 84 days following administration. RESULTS: In the animal models, AR-105 reduced lung bacterial counts in a dose-dependent manner, and improved survival (80% in the treated group vs. 0% in the control group). Combination of AR-105 with antibiotics was more effective than monotherapy. In the Phase I study, no serious adverse events (AE) were observed in any cohort. Few AE were deemed related to the investigational drug, and all were mild and transient. AR-105 was found to be well tolerated in healthy volunteers with no anti-drug antibodies (ADA) detected. The PK profile was comparable with other human IgG1 mAbs, exhibiting a serum half-life of approximately 20 days. CONCLUSION: AR-105 was confirmed to be effective in PA pneumonia animal models, either as stand-alone therapeutic or in combination with antibiotics. In the Phase 1 clinical study, AR-105 was shown to be safe and well-tolerated, with a PK profile similar to that of other IgG1 mAbs. AR-105 is a promising drug candidate for therapy of PA pneumonia. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.