Pharmacokinetics (PK) of the anti-ST2 monoclonal antibody, astegolimab

Astegolimab is an anti-ST2 monoclonal antibody that blocks initiation of the ST2/IL-33 inflammatory cascade. The safety, tolerability and PK of subcutaneous (SC) astegolimab in healthy volunteers are characterised here. Two double-blind, placebo-controlled, Phase I studies randomised healthy adults (6:2) to receive single- (SAD; 2.1–420mg) and multiple-ascending (MAD; 70–210mg Q4W or Q2W) SC doses of astegolimab or placebo. Endpoints included AEs, immunogenicity, serum PK and soluble ST2 (sST2). 48 participants took part in SAD (astegolimab, n=36; placebo, n=12) and 32 in MAD (astegolimab, n=24; placebo, n=8). No serious or fatal AEs or withdrawals due to AEs occurred. 5/35 participants (14.3%) in SAD and 5/24 participants (20.8%) in MAD with post-baseline results who received astegolimab developed anti-astegolimab antibodies. Non-linear PK were observed in SAD; mean C_max and AUC_last increased more than dose proportionally over 2.1–420mg but were approximately dose proportional for ≥70mg. MAD C_max and AUC_tau were dose proportional for 70–210mg (Figure). Astegolimab was well-tolerated. PK data informed the dosing of a subsequent Phase II trial in patients with severe asthma (<ext-link>NCT02918019</ext-link>), which also reported dose-proportional PK for 70–490 mg astegolimab Q4W. Baseline sST2 levels were comparable in healthy volunteers and patients with asthma or COPD. PK in patients with COPD will be confirmed in pivotal studies (<ext-link>NCT05037929</ext-link>; <ext-link>NCT05595642</ext-link>). <fig><object-id>erj;64/suppl_68/PA2987/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>