Itepekimab is a monoclonal antibody that targets interleukin (IL-33) and has 
been shown to reduce airway inflammation and associated tissue damage in 
preclinical studies. We assessed the safety, tolerability, pharmacokinetics 
(PKs), and pharmacodynamic profiles of single-ascending and multiple-ascending 
doses of itepekimab in two randomized, double-blind, placebo-controlled phase I 
studies. Healthy adults (N = 40) were randomized to the single-dose study and 
patients with moderate asthma (N = 23) to the multiple-dose study. Itepekimab 
was administered intravenously (0.3, 1, 3, or 10 mg/kg infusion) or 
subcutaneously (150 mg) in the single-dose study and subcutaneously (75 or 
150 mg weekly for 4 weeks) in the multiple-dose study. Itepekimab exhibited 
linear PKs across studies and dose-proportional increases in mean maximum 
concentration in serum and area under the concentration-time curve following 
single intravenous or multiple subcutaneous doses. Itepekimab demonstrated mean 
subcutaneous bioavailability of 59-73% and a long terminal half-life 
(30.0-31.6 days). IL-33 concentrations in most healthy participants and patients 
with asthma were undetectable at baseline. Following administration of 
itepekimab in both studies, total IL-33 concentrations increased and blood 
eosinophils decreased, both with durable effect. Itepekimab was well-tolerated 
in both studies with no detection of treatment-emergent anti-drug antibody 
responses.