The Next Wave of Asthma Therapeutics

The Next Wave of Asthma Therapeutics Biotherapeutics Inc (BTI) is an emerging biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel products for precision immunology. We have filed patent applications related to novel methods of suppressing inflammation during autoimmune disease, asthma, and allergy. The goal of this project is to develop the next wave of therapeutics for asthma that targets a new immunoregulatory pathway in immune and epithelial cells. Asthma is a significant public health concern afflicting over 25 million people in the U.S. with total health care expenses exceeding $80 billion/year. Current therapies for asthma are modestly successful but leave significant subpopulations of patients without adequate response. Type 2 asthma patients can develop steroid dependency and non-type 2 asthma has a lower responsiveness to current treatments. Recent attempts to target this population have been unsuccessful, with anti-TNF, anti-IL-17 receptor and chemokine inhibitors failing in clinical trials, while macrolides and methotrexate have shown mild improvement but at high side effect risk. Thus, there is an unmet medical need for safer and more efficacious asthma therapeutics. Regulatory T cells have gained increased recognition in the treatment of inflammatory and allergic diseases. Manipulation of Treg cells to restore their suppressive capacity has been postulated as a promising novel therapeutic approach. This SBIR Phase I application will develop a novel, oral, once-daily, immunoregulatory therapeutic for the treatment of asthma. The Specific Aims are to: AIM 1. Characterize the therapeutic efficacy and route of administration of the novel immunoregulatory drug candidate in two mouse models of asthma. We will use the ovalbumin plus lipopolysaccharides (OVA+LPS) and house dust mite (HDM)-induced mouse models of asthma, a neutrophilic model, and a mixed cellular phenotype model, to determine the therapeutic efficacy by airway resistance, lung histopathology, flow cytometry and cytokine expression. AIM 2. Determine the translational ability of the novel therapeutic candidate in human primary cells from asthma patients, by assessing cytokine and metabolic profile, plus suppressive Treg capacity in coculture studies in bronchial epithelial (HDBE) cells and PBMCs, respectively, from asthma donors and healthy controls. Expected successful outcomes are: i) ≥ 50% suppression of airway resistance and ≥ 50% decreased infiltration of neutrophils in the lungs of treated mice; and ii) ≥ 70% reduction in IL-8 and IL-6 expression in treated HDBE. Commercial Application: The impact of this new, oral, immunoregulatory asthma drug has the potential to disrupt an annual market estimated to reach $36 billion by 2029.