Enhanced in vitro potency of depemokimab for interleukin-5 inhibition versus mepolizumab

<bold>Background:</bold> Depemokimab is the first and only humanised anti-IL-5 antibody with enhanced binding affinity and high potency, resulting in an extended half-life, enabling 6-monthly dosing and sustained inhibition of broad inflammatory function. <bold>Aim:</bold> To assess relative potency of depemokimab and mepolizumab in vitro using 2 different cell types. <bold>Methods:</bold> TF-1 cell (human erythroleukaemia cell line expressing IL-5R) proliferation and IgE receptor (IgER)-mediated degranulation of human blood basophils was assessed following incubation with submaximal concentration (EC80) of IL-5 complexed with increasing concentrations of mepolizumab or depemokimab. <bold>Results:</bold> At submaximal IL-5 concentrations, depemokimab achieved a 24.9-fold (range 11.7–39.5) higher inhibition of IL-5-driven TF-1 cell proliferation and 31.0-fold (range 7.5–76.7) higher inhibition of IL-5-enhanced IgER-mediated basophil degranulation versus mepolizumab (Figure). <bold>Conclusion:</bold> Depemokimab demonstrated substantially higher potency than mepolizumab for both inhibition of IL-5-mediated proliferation in a human cell line and IgER-mediated human basophil degranulation. Depemokimab’s high affinity for IL-5 with resultant enhanced functional potency and prolonged half-life provide a mechanistic basis for understanding its clinical effects. The clinical implications are currently under investigation in randomised controlled trials. <bold>Funding:</bold> GSK <fig><object-id>erj;64/suppl_68/OA3644/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>