The overall goal of this phase 2 SBIR proposal is to develop and commercialize a novel biologic for allergen- specific immunotherapy as effective treatment for cat allergy/asthma. Cat allergy is common, with 17% of US population, age 6-59, being skin test positive for cat and 60% of those individuals have symptoms when exposed to cat dander Cat allergen, Fel d1, is particularly ubiquitous because of the small size of the airborne cat dander particles and is one of the key aeroallergens implicated in the current epidemic of allergic asthma. Presently, immunotherapy to treat cat allergy is problematic because it requires repeated visits to the allergists'office over a 3-5 year period and commonly elicits allergic reactions. The molecule that comprises our novel approach is a genetically engineered cat allergen-human Fc?1 fusion protein that is designed for a far greater safety profile so that it can be given as injectable immunotherapy (i) with greater safety, (ii) in a far more rapid time frame and (iii) without the pro-allergic effects of current allergen immunotherapy. In phase 1 of this SBIR, we created and expressed an optimal cat-human chimeric fusion protein and derived a current good manufacturing process (cGMP)-quality CHO cell line that is ready to produce material for good laboratory practice (GLP) toxicology. This phase 2 proposal comprises the studies that are expected to provide a strong Investigational New Drug (IND) application for full-scale Phase I/Phase IIa clinical trials upon completion. To achieve this, we will meet six key Aims.
Aim 1 : develop biochemical and cell-based assays for characterization of the material to be used for formulation development, GLP toxicology studies and in support of cGMP manufacture;these assays will be run under GLP SOPs with independent Quality Assurance monitoring.
Aim 2 : perform pre-formulation and stability experiments in preparation for transfer of the to a cGMP manufacturer.
Aim 3 : complete cell line development, master cell bank production, cGMP manufacture and purification, formulation and final sterile fill on the fusion protein drug product.
Aim 4 : develop an improved purification process, produce and formulate the material necessary for the proposed GLP toxicology studies.
Aim 5 : perform GLP toxicology in 2 species (rat and non-human primate) as required for IND filing.
Aim 6 : prepare and file an IND application with the FDA and work with that agency toward approval of this application. Successful completion of phase 2 would set the stage for the initiation of clinical trials to test the safety and efficacy of FDG in US-based trials. We envision the successful development of this fusion protein platform for cat allergy as not only an important new therapeutic for cat allergy/asthma but also as the sign post for development of this approach for the treatment of severe IgE mediated food allergy.
Effective treatments to for severe inhalant allergy represent a major unmet medical need with cat allergy being one of the key allergens involved. Symptomatic cat allergy affects 30 million people in the United States and is primary trigger for 30% (3 million) asthma cases as well. Cat allergen, because of the physical characteristics of the particles it is on is essentially ubiquitous in schools, public buildings and homes. Immunotherapy (allergy shots) works but it has a relatively low therapeutic index and poor compliance due to the need for multiple injections over a prolonged period of time with associated local and even systemic reactions. The goal of this proposal is to develop and commercialize a novel cat allergy vaccine that will be safer, faster and more effective than the current treatments.