Pharmacokinetics of AZD8630/AMG 104 inhaled anti-TSLP in healthy adults and asthma patients

AZD8630/AMG 104 is an inhaled fragment antibody targeting anti-thymic stromal lymphopoietin (TSLP) developed to treat asthma. This Phase1 study (NCT05110976) aimed to characterize safety, tolerability, pharmacokinetics (PK) and immunogenicity of AZD8630/AMG 104 in healthy volunteers and patients with asthma. The study consisted of two parts; part A was conducted in healthy volunteers including global, Chinese and Japanese cohorts consisting of single and multiple inhaled and IV dosing of AZD8630/AMG 104. Part B was a randomized, double-blind, placebo-controlled design evaluating multiple dose levels of AZD8630/AMG 104 in patients with moderate-to-severe asthma. Participants in Part B received placebo or active drug once daily for 28 days. Following inhalation, AZD8630/AMG 104 was steadily absorbed with a median Tmax observed at 5-10 hours. The systemic exposure of AZD8630/AMG 104 increased in a dose-proportional manner. Mean terminal half-life was 21-37 hours across cohorts. No differences were observed in PK due to ethnicity. Accumulation was 2- to 3-fold in serum at steady state. The incidence of anti-drug antibodies (ADA) was low; three individuals (2.4% of those dosed) developed treatment-emergent ADA during the study. Overall, AZD8630/AMG 104 was well tolerated and no safety concerns were raised. AZD8630/AMG 104 displayed dose proportional PK characteristics in the dose range studied and a half-life suitable for once-daily dosing. Together with low rates of immunogenicity following 4-weeks of dosing this data supports the ongoing development of AZD8630/AMG 104 as a first-in-class inhaled biologic treatment option for asthma patients.