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AB0443 Selective Immunomodulators of FC-Gamma Receptors (SIFS) to Inhibit Autoantibody-Mediated Pathology
  1. C.J. Bosques,
  2. J. Lansing,
  3. D. Ortiz,
  4. L. Rutitzky,
  5. N. Washburn,
  6. N. Bhatnagar,
  7. E. Kurtagic,
  8. A. Choudhury,
  9. T. Prod'homme,
  10. B. Schultes,
  11. S. Roy,
  12. G.V. Kaundinya,
  13. A.M. Manning
  1. Momenta Pharmaceuticals, Cambridge, United States

Abstract

Background Interaction of autoantibodies and immune complexes with Fcγ-receptors on leukocytes can lead to detrimental inflammatory events in autoimmune diseases including inflammatory synovitis. Modulation of Fcγ-receptor-mediated leukocyte activation could serve as an attractive strategy to limit acute exacerbations and recurrent disease symptoms in rheumatoid arthritis and multiple disease settings.

Objectives To develop best-in-class modulators of Fcγ-receptors and assess their activity in antibody-mediated pathogenic mechanisms active in autoimmune diseases.

Methods We designed a panel of novel recombinant multimeric-Fc drug candidates to modulate the activity of low affinity Fcγ-receptors. A comprehensive panel of physicochemical and pharmacological assays including in-vivo models of Immune Thrombocytopenic Purpura (ITP) and synovitis (Collagen Antibody-Induced Arthritis; CAIA) was used to select the candidate with optimal drug properties.

Results An optimal multimeric-Fc drug candidate was selected for development based on its attractive physicochemical and biological properties. This candidate demonstrated more than 40 fold higher potency than Intravenous Immunoglobulins (IVIg) in multiple in-vivo models of autoimmune diseases and more than 100 fold potency in different assays of immune cell activation.

Conclusions Selective Immunomodulators of Fcγ-receptors (SIFs) are effective inhibitors of various antibody-mediated pathogenic mechanisms. These novel agents may prove to have therapeutic value in the treatment of autoimmune diseases.

Disclosure of Interest None declared

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