Epsi-gam is a genetically engineered bi-functional human fusion protein that is comprised of IgE and IgG1 domains. This molecule is designed to link the IgE receptor with an inhibitory receptor (FcγRIIb) on mast cells, basophils and IgE-producing B cells, thereby inhibiting their function. The FcγRIIb receptors can inhibit the cells’ allergic reactivity by sending internal negative signals that block the induction of the kinases necessary for cellular activation. One can think of the FcεRI as the gas pedal on allergic cells while FcγRIIb serves as the brake, with the brake having the ability to override the gas pedal. By making use this novel strategy that directly cross-link FcγRIIb to FcεRI receptors, Tunitas’ platforms make use of the natural FcγRIIb inhibitory pathway to inhibit human IgE-FcεRI signaling and thereby prevent allergic reactions.
Epsi-gam has been extensively studied in both human systems in vitro and in non-human primate animal systems. It blocks the effector phase of IgE on the skin, in the airway and systemically. Not only does this molecule interfere with the function of key allergic cells, it also blocks the production of human IgE antibodies. In clinical use, we anticipate that epsi-gam will be administered subcutaneously on an ongoing basis to address a number of serious allergic diseases, such as asthma, atopic dermatitis or any food and/or inhalant allergy. Phase 1 trials, recently begun in Australia, will evaluate epsi-gam’s safety and efficacy in single ascending dose and multiple ascending dose trial during 2016 and 2017. Following completion of these studies, Tunitas anticipates filing an IND with the US FDA.
Tunitas’ allergy vaccine platform consists of genetically engineered bifunctional human fusion proteins that are comprised of allergens and IgG1 domains. These vaccines are designed to provide a novel form of immunotherapy while maintaining a large margin of safety. As such, they offer a cost-effective way of treating millions of individuals with severe allergic reactions to inhaled or ingested substances, something that cannot currently be done through conventional immunotherapy. The human allergen proteins are linked to IgG1 or other ligands that trigger other inhibitory pathways and will bind to the key allergic cells that initiate a hypersensitivity response, leading to the inhibition of allergic reactivity. It is expected that these vaccines will prime antigen-presenting cells to modify their allergic response to a more balanced one more safely and effectively than conventional immunotherapy. Tunitas expects to nominate its first allergy vaccine clinical candidate, for cat allergy, in 2016 and to begin human clinical trials in 2018. A peanut allergy vaccine is expected to follow, with the potential for a large pipeline including vaccines to shrimp, milk, eggs and other serious food allergies.