Development of SP-a derived peptidomimetics for the treatment of asthma - phase II - current treatments for asthma, while reducing exacerbations in a subset of patients by focusing on airway…

Development of SP-a derived peptidomimetics for the treatment of asthma - phase II - current treatments for asthma, while reducing exacerbations in a subset of patients by focusing on airway inflammation, do not eliminate them. Asthma exacerbations are a significant cause of morbidity and mortality in asthma as they can lead to airway injury, lung function decline and death. Exacerbations in more severe asthmatics are of particular concern, as health care costs and lost productivity account for $21 billion/year in US annual health care expenditures. There is no current innate immune modulator for the treatment of asthma. Thus, there is a critical need to develop new therapies to be used in the treatment of inflammatory lung diseases including asthma. We have discovered small molecules that mimic the effect of an endogenous lung protein, surfactant protein a (SP-a), in reducing airway constriction associated with asthma that causes symptoms and exacerbations. SP-a is a natural component of the lining fluid in the lungs and serves as a first line of defense against inhaled insults and pathogens. Many asthma patients have either very low levels of SP-a or damaged SP-a due to the inflammatory environment of the asthma lung. Full-length SP-a delivered directly to the lungs is not feasible due to its size and structure. Our company, raesedo INC., was founded on the principle that we can create custom modifications of the active region of SP-a that are delivered in small peptidomimetic form that have improved pharmacokinetic properties and stability. These SP-a derived peptidomimetics represent a new class of asthma therapeutics. During phase i, raesedo INC. And the university of arizona, worked to meet the milestones proposed: design, synthesize and optimize peptidomimetics and to characterize the bioactivity of the peptidomimetics at specific cellular targets to identify lead compounds. Raesedo INC.'s objectives for the phase II proposal are to advance aerosol development, pharmacology and evaluation of toxicity of our lead compounds (C867 and C892) in two large animal models through collaborations with the university of arizona and lovelace biomedical. The overall goal of this phase II proposal is to demonstrate safety and efficacy in the ragweed sensitized canine model of asthma. If successful, raesedo INC. Will be equipped to submit an IND application bringing a new class of asthma therapeutics to the FDA for approval.