Respira Therapeutics, Inc. — Department of Health and Human Services SBIR Phase I: NICHD

Description

ABSTRACT Asthma is prevalent in overof the pediatric populationwith most pediatric patients uncontrolled or poorly controlled in their diseaseExtensive inflammation of the airways in asthma is treated using inhaled corticosteroidsICSas a maintenance therapyHoweverthese drugs can suppress growth in childrenand fear of this outcome can lead to non adherence in pediatric patientsThis results in severe complicationsTo minimize the risk of growth suppressionrecommendations are that ICS therapy be titrated to the lowest effective doseHoweverthis is complicated by the poor delivery efficiency of currently marketed inhalerswhich deposit the majority of the doseandgtin the upper respiratory tractURTThis often results in delivery of sub therapeutic doses and leads to unwanted local side effectsIn childrenthis is further complicated by decreased inspiratory effort and lung volumeThe issues with poor delivery efficiency become magnified when one considers that the small airways contribute substantially to asthmaUnfortunatelythe poor delivery efficiency of marketed DPIs means that only a small fraction of the nominal doseandltreaches the small airwaysThere is an unmet need for a consistenthigh efficiency inhaled therapyThe objective of this project is to develop an inhaled drug product that enables efficient and reproducible delivery of inhaled corticosteroids to the small airways of pediatric asthma patientsthereby addressing important causes of poor controlOur approach consists of minimizing URT deposition by engineering low densityfine particles that can be readily dispersed at flow rates achievable by pediatric patients using a high resistance deviceWe will create novelaerodynamically smallandltmleucine carrier particles and form adhesive mixtures of these particles with nano sized ICS particlesLeucine carrier particles have micromeritic properties that fundamentally differ from the standard adhesive mixtures of micronized drug with coarse lactose carrier particlesHerethe agglomerates of drug and carrier remain respirable and have a small impaction parameterCharacterizationFor aerosol performance testing we will use Respira s proprietary AOSDPIa portablepassivecapsule based inhaler with a high resistanceenhancing deliveryTo assess aerosol deposition in the URTwe will use the Alberta Idealized ThroatAITmodelwhich provides excellent in vitro in vivo correlationsWe aim to achieve the following milestonesDemonstrate thatvalues of the leucine carrier particles are andltmpreferably less thanmDemonstrate efficient aerosol delivery of ICS with andgtof the delivered dose delivered past the AITDemonstrate that drug delivery using this approach has low flow rate dependenceDemonstrate environmental robustnesswith comparable aerosol performance atandRHOur ultimate goal is the development of a new drug productwith increased and consistent delivery to the entire respiratory tree and decreased off target effectsthus improving the health of asthma patients NARRATIVE Current inhalers used by pediatric asthma patients show poor drug delivery to the lungs because most of the medicine deposits in the mouth and throat of the patientand very little reaches the smallest airwaysThis project proposes the development of a new inhaler formulated using extra fine particles that are designed to bypass the mouth and throat and reach the small airways of the lungs