The overall goal of this SBIR proposal is to develop and commercialize a new approach for allergen specific immunotherapy as treatment for cat allergy. This proposal will provide a novel therapeutic for a very important inhalant allergen and serve as a model for the application of this approach to other key allergens. Effective treatments to induce "allergic tolerance" for inhalant allergy (allergic rhinitis and allergic asthma) represent a major unmet need, driven by the increasing prevalence and incidence of IgE mediated allergic airway disease. The cat allergen Fel d1 is ubiquitous because of the small size of the airborne cat dander. 17% of US population, age 6-59, is skin test positive for cat allergen Fel d1 and 60% of those individuals have symptoms when exposed to cat dander. With nearly 78 million cats in the US and 40% of asthmatics sensitive to Fel d1, exposure to cat dander is a major contributor to the high prevalence of asthma throughout the world. While conventional immunotherapy is effective in reducing asthma symptoms in some cases, patients with severe acute bronchospasm or chronic asthma can remain seriously compromised during the 3-5 year regimen and suffer from the poor compliance and adverse reactions. We propose to develop and test a cat allergen Fel d1- 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 a number of specific allergic diseases, including ultimately severe food allergy. Our hypothesis, based on body of data we have generated as well as that of others is that an allergen-human Fc(1 chimeric protein will function as immunogen but not an allergen and thus will provide a mechanistically distinct and more effective form of allergen specific immunotherapy. This proposal will outline the key experimental pre-clinical steps on the path to commercialization for this approach. We have identified a lead compound - Fel d1-human Fc(1 - and have demonstrated its therapeutic efficacy in both in vitro and in vivo models. Building on the success with this initial chimeric human 31-cat allergen protein for respiratory allergy, we wish to continue its development. In this proposal, we will create and express an optimal cat human chimeric fusion protein, confirm that the expressed chimeric protein retains the key feature of the allergen, e.g., full IgE binding plus the key functional property of the human Fc(, e.g., Fc(RIIb binding, document that the chimeric protein fail to induce allergic reactivity, and derive a high level expressing cell line ready to produce material for GLP toxicology. Tunitas Therapeutics, Inc. has negotiated an exclusive license with the University of California to develop chimeric allergen-Fc(1 proteins for the treatment of allergy. This proposal will provide the critical initial steps on the path to commercialization of this therapeutic. 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 Fel d1-Fc(1 protein immunotherapy conservatively targeted to fall in a similar range and the expectation that only the most severe cat-allergic individuals may initially choose to receive immunotherapy, annual US sales of $150 MM would be expected within several years. PUBLIC HEALTH RELEVANCE: Principal Investigator/Program Director (Last, First, Middle): Narrative: Cat allergen-human Fc-gamma1 chimeric proteins to treat cat allergy Effective treatments to induce allergic tolerance for inhalant allergy/asthma represent a major unmet medical need. With nearly 78 million cats in the US and 40% of asthmatics allergic to cats, exposure to cat allergen is a major contributor to the high prevalence of asthma throughout the world. The goal of this proposal is to develop and commercialize a novel approach for allergen specific immunotherapy as treatment for severe cat allergy.
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