SBIR-STTR Award

New treatments are needed for severe asthmatics who do not respond to standard therapy with inhaled steroids especially those with a type low phenotype such as individuals with neutrophil predominant inflammation This solicitation is for the development and early commercialization of an inhalational formulation of the A apolipoprotein A I apoA I mimetic peptide that can be administered to asthmatic subjects in Phase I clinical trials and subsequently developed into a new treatment for severe asthma ApoA I is the major protein component of high density lipoproteins which mediates reverse cholesterol transport out of cells by interacting with the ATP binding cassette subfamily member ABCA ApoA I also has anti inflammatory anti oxidant and immunomodulatory properties NHLBI investigators have shown that systemic administration of the A apoA I mimetic peptide which is a bi helical peptide that recapitulates the helical structure of apoA I and mediates reverse cholesterol transport out of cells by interacting with ABCA attenuates the induction of airway inflammation mucous cell metaplasia and airway hyperresponsiveness in house dust mite HDM challenged mice In addition they have shown that apoA I has a protective effect in allergic asthma Apoa knockout mice which were sensitized and challenged with ovalbumin OVA have increased neutrophilic airway inflammation that was primarily mediated by increased G CSF expression with associated increases in type IFN TNF and Th IL A cytokines The increased neutrophilic airway inflammation in the OVA challenged Apoa knockout mice was inhibited by intranasal administration of the A apoA I mimetic peptide Lastly serum apoA I levels are positively correlated with FEV in atopic asthmatic subjects which suggests that circulating apoA I may improve airflow obstruction These murine and human translational studies serve as the conceptual basis for developing the A apoA I mimetic peptide into a novel inhalational treatment for severe asthma Project GoalsThe overall goal of this project is to prepare in both manufacturing processes and preclinical evaluation an inhalational A apoA I mimetic peptide that will be the subject of a future Investigational New Drug IND application to the US Food and Drug Administration FDA focused on the treatment of type low phenotype asthma patients such as those with neutrophil predominant inflammation Successful submission and allowance to proceed of the IND will enable the company to collaborate on the conduct of a clinical trial with intramural clinicians at the NIH Clinical Center at the company s discretion During review preference will be given to companies or teams with a demonstrated prior ability to successfully bring either a peptide therapeutic or an inhalational therapeutic to at a minimum Phase clinical studies in the US