Randomized phase I trial outcomes show safe and sustainable inhibition of classical and lectin complement pathways by empasiprubart.

ABSTRACT: Activation of classical and lectin complement pathways contributes to several human diseases. Empasiprubart is a humanized recycling monoclonal antibody that inhibits both pathways by binding to the CCP2 domain of complement factor 2 (C2), an interaction that is dependent on both Ca²⁺ and pH. Here, we resolve the crystal structure of empasiprubart complexed with C2, providing the molecular basis of its Ca²⁺ dependency, and report a randomized, double-blind, placebo-controlled trial to assess the safety and tolerability (primary objectives) in addition to pharmacokinetics, pharmacodynamics, and immunogenicity (secondary objectives) of empasiprubart in 78 healthy participants (NCT04532125). A single intravenous (IV) dose of empasiprubart reduces circulating C2 levels by

SUBMITTER: Van de Walle I 

PROVIDER: S-EPMC12357863 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature