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

Clin Immunol. 2023 Jun:251:109629. doi: 10.1016/j.clim.2023.109629. Epub 2023 May 4.


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® and hemolytic assays were used to demonstrate 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 assessment in clinical trials.

Keywords: C1s; Classical pathway; Cold agglutinin disease; Complement; Therapeutic antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Complement Activation
  • Complement C1s* / metabolism
  • Complement Inactivating Agents / therapeutic use
  • Complement Pathway, Classical
  • Humans


  • Complement C1s
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal
  • Complement Inactivating Agents