Product Pipeline
Tunitas Therapeutics platform technology targets multiple approaches to treat allergic disease.
Allergen Vaccines
The first therapeutic platform consists of genetically engineered and expressed chimeric human Fcg—allergen proteins designed to provide a novel form of allergen specific immunotherapy with a large margin of safety. As such, it offers a cost-effective way of treating millions of individuals with severe food allergy, something that currently cannot be done with conventional immunotherapy. The same platform can also serve as a way to provide more rapid allergen immunotherapy in inhalant allergic disease. The chimeric protein consists of the allergen molecule linked to Fc portion of human IgG1. When the allergen portion is bound to its specific IgE on mast cells and basophils, the Fcg portion will simultaneously bind and co-aggregate with the inhibitory FcgRIIb and lead an inhibition of allergic reactivity. Thus, the chimeric molecule functions as an immunogen but not as an allergen. It will not trigger an immediate allergic response but, as with standard immunotherapy, will prime antigen-presenting cells to modify the existing allergic response to a more balanced one and thereby block the allergic response to that allergen.
GFD
The lead candidate is GFD, a chimeric Fcg molecule constructed with Fel d1, the dominant allergen from cats. GFD has shown efficacy both in vitro with human cells sensitized to cat allergen and in animal models including mice with humanized Fce receptors. This platform is designed to provide long-term antigen specific cures for allergy patients who would receive a treatment regimen of rapidly increasingly doses of the chimeric allergen protein in order to achieve allergic tolerance.
With grant funding from the NIAID and the Immune Tolerance Network, Tunitas are well along in the preclinical and clinical development of a clinical proof-of principal trial that will be completed in the first half of 2011 for Tunitas' cat allergy vaccine.
Peanut Allergen Vaccine
Tunitas' platform is most applicable in settings where there is a limited number of dominant key allergens, and particularly for the major allergenic foods that cause severe food allergy, e.g. peanuts, shellfish, egg and milk, since standard immunotherapy is simply too dangerous to be undertaken in this setting. A chimeric human Fcg—allergen protein targeting the major peanut allergens is in preclinical development.
GE2
The first therapeutic consists of a genetically engineered and expressed bifunctional human fusion protein that is comprised of the Fc portions of human IgE and IgG1 with a flexible linker interposed between the Fc pieces. This platform was designed to co-aggregate the high affinity receptor for IgE on basophils and mast cells with the inhibitory FcgRIIb receptor on these cells and thereby inhibit their function in an allergen nonspecific fashion. The lead molecule, GE2, has been studied extensively both in human systems in vitro and in animal systems, including non-human primates. This molecule blocks the effector phase of the IgE response in the skin, in the airway and systemically. Not only does this molecule interfere with basophil and mast cell function but also has been shown to inhibit the pro-allergic effects of IgE receptor bearing human Langerhans-like cells and blocks the production of human allergic antibody (IgE). This intervention is designed as a long-term parenteral (subcutaneous) therapy to be given on an ongoing basis. Based on demonstration of robust efficacy in a variety of models of allergic disease, GE2 is predicted to be effective in the treatment of a variety of human IgE mediated diseases such as allergic asthma, allergic rhinitis, and severe food allergy. An optimized construct has been stably expressed in CHO cells, and protein is ready to move into formal preclinical development.
EPL
The third therapeutic platform provides a novel method to deliver allergy gene vaccination. Delivering allergen genes to antigen presenting cells (APCs) has been shown to be a highly effective in driving immune responses away from allergic reactivity in animals. However effective gene delivery to APCs has not been previously accomplished. The platform consists of a genetically engineered fusion “carrier” protein, the Fc region of IgE fused to a defined stretch of charged amino acids, which targets APCs and carries the gene(s) of interest into them. The platform’s advantages compared to other gene vaccines are (1) targeting of APCs and (2) promoter directed expression in APCs. Benefits of the approach include (1) elimination of the need to administer any native allergen and (2) ease of production, since one protein would serve as a universal delivery vehicle for the different cloned allergen gene cassettes in the APC expression vector.