ONCOARENDI THERAPEUTICS LLC — Department of Health and Human Services SBIR Phase I: NHLBI

Description

DESCRIPTION provided by applicant Significance Approximately million Americans suffer from asthma which leads to about deaths per year and is responsible for estimated annual total direct and indirect costs of $ billion Despite the existing treatments for asthma predominantly combinations of inhaled agonists and corticosteroids CSs there remains a significant unmet medical need for new therapies which address two key issues approximately of patients are insensitive to current medicines and a significant number of patients up to have adherence challenges with the inhaled drugs due to inhaler misuse lack of use and or side effects There is compelling evidence implicating T helper Th cells in asthma via i the induction and maintenance of inflammation and ii the progression to the morphological changes associated with chronic disease Also there is growing published support that acidic mammalian chitinase AMCase a member of the chitinase family of hydrolases contributes to the Th driven inflammatory responses tissue injury and remodeling associated with diseases such as asthma Hypothesis We thus hypothesize that an oral AMCase inhibitor will alter the pattern of inflammation in CS insensitive asthmatics may augment the response to CSs in severe asthmatics and will also be effective in Th mediated asthma as well as avoiding the adherence issues with inhaled medicines Innovation Our company OncoArendi Therapeutics initiated a Drug Discovery Program focused on developing potent and selective orally active AMCase inhibitors for asthma and other Th associated diseases After synthesizing and testing more than compounds we have selected a clinical candidate to progress into development for asthma Our lead candidate OAT is very selective has high potency excellent oral bioavailability in rodents with long terminal half life low clearance and high volume of distribution and activity in two standard models of asthma In addition OAT has moderate plasma protein binding across species no significant inhibition of CYP enzymes or hERG and is negative in the Ames genotoxicity test OAT has first in class potential with no known competition from other BioPharmaceutical companies We propose to file an IND for this novel oral small molecule AMCase inhibitor as a critical step towards the clinical development of this innovative asset to treat moderate to severe asthma patients The major goals of this Fast track proposal are Phase I Specific Aim Evaluate the effects of the clinical candidate OAT in a murine chronic model of asthma involving exposure to Aspergillus fumigatus which is not sensitive to inhaled CSs Phase II Specific Aim Translational medicine studies in human lung Specific Aim File an IND for OAT after completing the standard IND enabling studies OAT is the first of a new class of oral compounds AMCase inhibitors which have the potential to manage patients with moderate to severe asthma who are not adequately controlled by current medicines while significantly improving treatment adherence compared to standard inhaled therapy PUBLIC HEALTH RELEVANCE Asthma is a very common and serious lung disease that affects more than million people in the US with more than deaths per year There are established treatments for asthma however approximately of patients do not respond to these medicines In addition a large number of patients estimated to be as high as do not take their inhaler medicines every day as required which can make their disease worse People prefer to take oral medicines rather than drugs given via an inhaler There remains a significant unmet medical need in asthma for new therapies which address these two key issues We are developing a new type of oral drug to treat this population of asthmatics who do not get better with current medicines and also to help patients adhere better to taking their daily treatments for asthma