IdeS

IgG depletion for auto-immune diseases.

IgG Mediated Auto-Immune Disorders

Multiple severe, fatal autoimmune diseases are driven by pathogenic IgG auto-antibodies, such as Immune Thrombocytopenia (ITP), Guillain-Barre, and many others.

IdeS is a potent enzyme that cleaves IgG into separate cleavage events.

IgG Mediated Auto-Immune Disorders

• Limited current pharmaceutical intervention w/ poor efficacy, relying on IVIG or Plasmapheresis
• IdeS reduces IgG levels by >99%, acting in minutes
• Proven in pre-clinical models for ITP, anti-GBM, Guillain-Barre, etc.
• WT IdeS (Imlifidase) from Hansa is approved for pre-treatment in non-HLA matched kidney donors. Has short PD and is highly immunogenic, limiting its use
• Cyrus IdeS is greatly improved for both half life and immunogenicity
• Cyrus IdeS half life supports acute use not possible with short PD Hansa WT
• Cyrus IdeS low immunogenicity and long half life in pre-clinical studies supports likely chronic use in IgG mediated autoimmune disease with superior dosing convenience and potency over anti-FcRn therapeutics

Competing approaches are slower acting and less potent

• FcRn blockers = novel MOA, inhibit IgG recycling, reduce IgG levels by 60-80% over a period of days. First approved 2021, Vyvgart from Argenx, for Myasthenia Gravis; Rystiggo from UCB in 2023

Cyrus IdeS: CYR 212 and 241

• Improved half life via novel protein engineering (See chart for CYR 212)
• 1000x reduced human antibody binding to IdeS via computational reengineering
• Drastically reduced T cell epitope interaction via hybrid computational / deep mutational scan approach

Curves showing length of time IdeS variants remain in the blood stream following administration in animals.