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Clin Immunol ; 253: 109677, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37315681

RESUMO

Eblasakimab is a first-in-class monoclonal antibody under investigation for the treatment of atopic dermatitis (AD), which targets IL-13Rα1, a subunit of the Type 2 receptor complex. IL-13Rα1 stimulates phosphorylation of signal transducer and activator of transcription 6 (STAT6) to drive inflammation. This brief report investigates the mechanistic basis of eblasakimab and its effects on IL-13Rα1 signaling as part of a phase 1a, open-label, single ascending dose study. Single ascending doses of eblasakimab were administered by intravenous or subcutaneous injection to healthy male volunteers. The impact of eblasakimab on IL-13Rα1 receptor occupancy and STAT6 phosphorylation was assessed in participant blood monocytes. No serious treatment emergent adverse events were reported. Eblasakimab effectively blocked the IL-13Rα1 receptor and inhibited STAT6 phosphorylation with single doses of 3 mg/kg intravenously and 300 mg subcutaneously. Results support further clinical development of eblasakimab as a novel biologic for AD, with potential for 2- to 4-week dosing regimens.


Assuntos
Anticorpos Monoclonais , Interleucina-13 , Humanos , Masculino , Receptores de Interleucina-13 , Fosforilação , Fator de Transcrição STAT6 , Subunidade alfa1 de Receptor de Interleucina-13/metabolismo , Voluntários Saudáveis
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