4.7 Article

Anti-C1s humanized monoclonal antibody SAR445088: A classical pathway complement inhibitor specific for the active form of C1s

Journal

CLINICAL IMMUNOLOGY
Volume 251, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2023.109629

Keywords

Complement; Classical pathway; Therapeutic antibody; C1s; Cold agglutinin disease

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The objective of this study was to characterize the complement-inhibiting activity of SAR445088, a monoclonal antibody specific for the active form of C1s. The results demonstrated that SAR445088 is a potent, selective inhibitor of the classical pathway of complement. In addition, it was found that SAR445088 has potential therapeutic effects in treating classical pathway-driven diseases.
The objective of this study was to characterize the complement-inhibiting activity of SAR445088, a novel monoclonal antibody specific for the active form of C1s. Wieslab (R) and hemolytic assays were used to demon-strate that SAR445088 is a potent, selective inhibitor of the classical pathway of complement. Specificity for the active form of C1s was confirmed in a ligand binding assay. Finally, TNT010 (a precursor to SAR445088) was assessed in vitro for its ability to inhibit complement activation associated with cold agglutinin disease (CAD). TNT010 inhibited C3b/iC3b deposition on human red blood cells incubated with CAD patient serum and decreased their subsequent phagocytosis by THP-1 cells. In summary, this study identifies SAR445088 as a potential therapeutic for the treatment of classical pathway-driven diseases and supports its continued assess-ment in clinical trials.

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