ARGX-113

ARGX-113 is a first-in-class antibody fragment designed for the management of acute autoimmune crisis, which is defined as the sudden and severe onset of symptoms between periods of remission. ARGX-113 has been created to degrade circulating disease-causing autoimmune antibodies and has potential in many large and orphan indications: multiple sclerosis, systemic lupus erythematosus, myasthenia gravis and skin blistering diseases.

Clinical trials

  • Phase 1 safety trial in healthy volunteers completed. 
  • Data set from Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) studies showed favorable safety profile and specific IgG reduction of up to 85 % with a long duration of effect, with repeated dosing of the drug.
  • Myasthenia gravis (MG) and immune thrombocytopenia (ITP)  initial indications for Phase 2 studies. 

Mode of action

  • ARGX-113 binds FcRn, blocks IgG recycling (including disease causing autoantibodies) and increases IgG clearance: resulting in faster remission and drastically reduced length and seriousness of acute autoimmune crisis
  • Antibody fragment designed using ABDEG™ technology
 Nat Biotechnol 2005, Vacaro et al.

Target

  • Neonatal Fc receptor (FcRn):
    • Recycling receptor for IgG’s
    • Ability to rescue IgG from destruction
    • Responsible for maintenance of high concentration of IgG (including autoantibodies) in circulation
 Nature Review 2007, Roopenian and Akilesh

ARGX-113 related publications

 Intensive plasma exchange therapy..., Blanchette et al., Transfusion, 1984  Familial hypercatabolic hypoproteinemia caused..., Wani et al., PNAS, 2006  Infusion of Fc gamma fragments for treatment..., Debré et al., Lancet, 1993  Transcytosis and catabolism of antibody. Chetie and Ward, Immunol Res., 2002  Engineering the Fc region of..., Vaccaro et al., Nature Biotechnol., 2005  Complete FcRn dependence for intravenous Ig..., Li et al., J Clin Invest., 2005  Divergent activities of an engineered antibody..., Vaccaro et al., PNAS, 2006  Amelioration of experimental autoimmune..., Liu et al., J Immunol., 2007  Pharmacokinetic/pharmacodynamic modeling of IVIG..., Deng and Balthasar, Interscience, 2007  FcRn: the neonatal Fc receptor comes..., Roopenian et al., Nat Rev Immunol., 2007  Antibodies in myasthenia gravis, Eymard, Rev Neurol., 2009  The neonatal Fc receptor as therapeutic..., Liu et al., Ther. Apher. Dial., 2010  The neonatal Fc receptor as therapeutic target..., Sesarman et al., Cell Mol. Life Sci., 2010  History of outcome measures for myasthenia gravis, Burns, Muscle Nerve, 2010  Comparison of IVIg and PLEX in patients with MG, Barth et al., Neurology, 2011  Neonatal Fc receptor blockade by Fc engineering..., Patel et al., J Immunol., 2001  Autoantibody depletion ameliorates disease..., Challa et al., MAbs, 2013  A randomized, double-blind, placebo-controlled phase II..., Howard et al., Muscle Nerve, 2013  The multiple facets of FcRn in immunity, Stappleton et al., Immunol Rev., 2015  Fc Engineering of Human IgG1 for Altered Binding..., Greveys et al., J Immunol., 2015  Effect of therapeutic plasma exchange..., Guptill et al., Autoimmunity, 2016  Myasthenia Gravis, Gilhus, NEJM, 2016

Indications

  • Myasthenia Gravis (MG)

    Myasthenia Gravis is an auto-immune disease that leads to fluctuating muscle weakness and fatigue.  

    Myasthenia Gravis (pronounced My-as-theen-ee-a Grav-us) comes from the Greek and Latin words meaning "grave muscular weakness." The most common form of MG is a chronic autoimmune neuromuscular disorder that is characterized by fluctuating weakness of the voluntary muscle groups. The prevalence of MG in the United States is estimated to be about 20/100,000 population. However, MG is probably under diagnosed and the prevalence may be higher. Myasthenia Gravis occurs in all races, both genders, and at any age. MG is not thought to be directly inherited nor is it contagious. It does occasionally occur in more than one member of the same family.

    In the most common cases, muscle weakness is caused by circulating antibodies that block acetylcholine receptors. Alternatively, in rarer forms, muscle weakness is caused by a genetic defect in some portion of the neuromuscular junction that is inherited at birth, as opposed to developing through autoimmunity later in life or through passive transmission from the mother's immune system at birth.

  • Immune Thrombocytopenia (ITP)

    Immune thrombocytopenia is an autoimmune disease affecting platelets. 

    If symptoms occur they can range from mild bruising to severe bleeding. In children the condition usually goes away on its own, without any treatment. In adults it is usually a lifelong condition. Treatment may or may not be necessary and may include steroids, immunoglobulin and surgery.