Orion BioScience Inc. has developed a 'Soluble Antigen Array' (SAgA) therapeutic that displays multiple copies of aquaporin-4 epitope for targeted clearance of the auto reactive NMO-IgG antibody in patients with neuromyelitis optica (NMO). The product is intended to selectively clear NMO-IgG while limiting interaction with other non-NMO specific antibodies, thereby reducing side effects often seen with global immunosuppressants. Orion's SAgA technology displays multiple copies of AQP4 epitope along a flexible polymer backbone and will initiate endogenous reticuloendothelial clearance mechanisms through antibody agglomeration. Blindness is the primary clinical outcome of NMO induced attacks; however, severe attacks can also lead to extensive transverse myelitis and paralysis. The ten year mortality rate after initial diagnosis in patients with NMO is >25%, however, no dedicated NMO therapeutic is available. A majority of symptoms result from the binding of NMO-IgG to AQP4, followed by initiation of the complement cascade and eosinophil recruitment. Systemic corticosteroids such as prednisolone and methyl-prednisolone, and antibodies targeting B cells or complement clearance are the current course of treatment. However, the systemic toxicity and severe immunosuppression limit both the treatment window and dosing frequency. Previous results using the SAgA platform in the treatment of experimental autoimmune encephalomyelitis show that multivalent display of antigen and co-signal can alter the immune response and provide therapeutic benefit. Orion looks to further adapt this technology to provide a highly targeted (utilizing AQP4 epitopes specific to NMO-IgG binding) and highly potent (multivalent display increases binding avidity) to provide a superior therapeutic option to patients suffering from NMO. This SBIR grant focuses on two lines of investigation. The first is directed at establishing formulation and storage stability profiles of he synthesized SAgA materials. The second is evaluating binding specificity using SAgAs manufactured with individual and combinations of known AQP4 epitopes in NMO- positive and healthy patient sera. The proposed aims will position Orion to move forward into Phase II studies with one or more lead compounds for pre-clinical and IND enabling studies.
Thesaurus Terms: Address;Adrenal Cortex Hormones;Adverse Effects;Affect;Affinity;Age;Animals;Antibodies;Antigens;Aquaporin 4;Astrocytes;Autoantibodies;Autoimmune Diseases;Avidity;B-Lymphocytes;Bacterial Meningitis;Binding (Molecular Function);Biological Assay;Blindness;Blood Circulation;Businesses;Cells;Cessation Of Life;Clinical;Clinical Trials;Collaborations;Competitive Binding;Complement;Complement Activation;Complication;Development;Diagnosis;Disease;Disease Progression;Dose;Drug Formulations;Effectiveness;Environment;Eosinophil;Epitopes;Excision;Experimental Autoimmune Encephalomyelitis;Fda Approved;Flexibility;Frequencies (Time Pattern);Functional Disorder;Grant;Headache;Health;Human;Immune;Immune Response;Immune System;Immunoglobulin G;Immunosuppressive Agents;Individual;Innovation;Interferons;Investigation;Label;Lead;Lesion;Letters;Link;Liquid Substance;Methods;Methylprednisolone;Modeling;Mortality Vital Statistics;Multiple Sclerosis;Natural Immunosuppression;Neglect;Nerve Degeneration;Nervous System Trauma;Neuromyelitis Optica;Optic Nerve;Orphan Drugs;Outcome;Paralysed;Patients;Pb Clearance;Peptides;Pharmaceutical Preparations;Pharmacology And Toxicology;Pharmacotherapy;Phase;Phase 2 Study;Plant Roots;Polymers;Positioning Attribute;Pre-Clinical;Predisposition;Prednisolone;Prevent;Production;Programs;Progressive Multifocal Leukoencephalopathy;Receptor;Reporting;Rituximab;Secondary Infection;Serum;Signal Transduction;Site;Small Business Innovation Research Grant;Specificity;Success;Symptom Management;Symptoms;T-Lymphocyte;Technology;Therapeutic;Therapy Design;Toxic Effect;Transverse Myelitis;Treatment Duration;Tysabri;Universities;Vertebral Column;Vomiting;Water Channel;Woman;
