The goal of this proposal is to develop and commercialize a novel approach for allergen specific immunotherapy as treatment for severe food allergy. Food allergy affects about 3.5% of the US population and 6% to 8% of young children. It is clearly on the rise. Peanut allergy, which affects around 1% of the population, is among the most severe food allergies, resulting in 30,000 emergency room visits and over 200 deaths per year. Standard allergen protein-based desensitization - immunotherapy as is employed for allergic airways disease - has proven unsuccessful and far too dangerous to use as treatment of severe food, e.g. peanut allergy. Thus treatment to prevent severe food reactions is a major unmet need. We propose to develop and test a peanut allergen (Ara h2)-human Fc(1 chimeric fusion protein as the prototype model for an entire platform of novel allergen-Fc(1 specific immunotherapeutic proteins designed for the treatment of severe food allergy. The Ara h2-Fc(1 protein is predicted to have a marked enhanced therapeutic index as the allergen portion will act as an immunogen to induce the benefits of standard allergen immunotherapy while the Fc(1 piece functions to block any allergic reactions. Thus the Ara h2-Fc(1 protein will act as an immunogen but not an allergen and thereby provide a safe and effective form of specific immunotherapy. Underlying this approach is an extensive body of science showing the ability of human Fc(RIIb inhibitory receptors to acutely inhibit allergic effector mechanisms. These studies on food allergy will build on our success with development of a chimeric human Fc(1-cat allergen protein for respiratory allergy. Tunitas Therapeutics, Inc. has negotiated an exclusive license with the University of California to develop chimeric allergen-Fc(1 proteins for the treatment of food allergy. The current proposal will provide the initial steps on the path to commercialization of this therapeutic approach using Ara h2, the dominant peanut allergen, as a model system. Specifically we will create the required gene, express the Ara h2-Fc(1 fusion protein in an optimized CHO cell system, and purify the resulting chimeric protein. We will then show that the expressed chimeric protein retains the key features of allergen IgE and Fc(RIIb binding. Finally, we will document that the chimeric protein fails to induce allergic reactivity in vitro or in vivo. The approval of a peanut-specific chimeric vaccine therapeutic would be an opportunity to administer a safe, effective course of immunotherapy to the vast majority of peanut-allergic individuals. The current cost of a course of immunotherapy is $1500-2500, with costs spread over a 3-5 year period. With a cost for a treatment course of Ara h-Fc(1 protein immunotherapy conservatively targeted to fall in a similar range and the expectation that only the most severe peanut-allergic individuals may initially choose to receive immunotherapy, annual US sales of $100-300 MM would be expected within several years. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page
Treatment to prevent severe food reactions is a major unmet medical need. Peanut allergy, which affects around 1% of the population, is among the most severe food allergies, resulting in 30,000 emergency room visits and over 200 deaths per year. The goal of this proposal is to develop and commercialize a novel approach for allergen specific immunotherapy as treatment for severe food allergy.