Gene Therapy to Prevent Reactions to Allergens

Background & Unmet Need

• Allergen-specific Immunoglobulin E (IgE) is integral to the pathogenesis of allergic disorders
• Binding of allergens to IgE antibodies on the surface of mast cells and basophils in sufficient quantities can lead to activation of the allergic response
• IgE-mediated allergic disorders include allergic asthma, allergic rhinitis, atopic dermatitis, and food allergies
• Omalizumab (Xolair) is the only approved anti-IgE therapy, indicated for allergic asthma with ongoing clinical development for peanut allergy
• Omalizumab has numerous limitations, including the need for repeated injections (every 2–4 weeks) and high cost
• Unmet Need: Novel therapies for the management of allergic disorders

Technology Overview

• The Technology: AAV gene therapy that provides sustained delivery of anti-IgE antibodies for the prevention of IgE-mediated allergic reactions
• The DNA sequence encoding for omalizumab was inserted into an AAV gene transfer vector (AAVrh.10anti-hIgE) and introduced into mice
• A humanized murine model of peanut allergy was generated by reconstituting immunodeficient mice with peanut-allergic human blood mononuclear cells
• PoC Data: A single dose of the gene therapy was sufficient for persistent prevention of peanut-induced sever allergy, both for prophylaxis and therapy after mice exhibit the peanut-induced anaphylaxis-related symptomology
• The inventors have also developed novel human anti-IgE antibodies with demonstrated efficacy that are ready to be incorporated into the AAV platform for further testing

Technology Applications

• One-time preventative therapy for peanut allergy and other severe, IgE-mediated allergic disorders
• Gene transfer method could be applied to other agents that block allergic reactions (e.g., soluble IgE receptors, eosinophils, and basophils)

Technology Advantages

• One-time therapy avoids the need for repeated and costly injections of omalizumab
• Durable protection improves patient quality of life by alleviating anxiety and risk associated with travel and dining at restaurants