Dignify Therapeutics LLC — Department of Health and Human Services SBIR Phase II: NIA

Description

PROJECT SUMMARY Underactive bladderUABis a clinically important problem in the elderlyUAB is characterized by weak bladder contractions and incomplete bladder emptying that result in symptoms of voiding frequencynocturiaand incontinenceand it can lead to serious complications such as permanent bladder and kidney damageAging related UAB may affect almostof Americans overand nearly two thirds of incontinent nursing home residents exhibit UABGloballyincreased life expectancy is expected to increase the number of patients with UAB and lower urinary tract symptomsThe current standard treatment to achieve complete bladder emptying in UAB patients is intermittent catheterizationAlthough drug therapies are sometimes used to manage milder forms of UABthose currently available have poor efficacy and tolerability and may not be suitable for use in elderly patients due to multiple side effectsA safe and effective product that facilitates efficientcomplete voiding would provide a paradigm shift in the management of UABDignify Therapeutics is developing next generation potent and selective NK R agonists to produce on demand voiding as a treatment for UABDrug induced side effects such as hypotension are a particular concern in the elderly as they can lead to mental confusionpoor mobilityand debilitating fallsThusa selectiveshort duration NK R agonist would be desirable for use in this populationIn Phase Itwo next generation NK R agonists were identified that have optimized selectivityimproved pharmacokineticPKprofilesand improved therapeutic indicesIn this Phase II projectprototype formulations for convenient administration several times a day will be developed and tested for efficacy and improved side effect profiles in adult and aged preclinical animal modelsPrototype intranasalINand orally disintegrating tabletODTformulations of optimized NK R agonists will be developed and manufactured for preclinical studiesQualified bioanalytical methods for plasma detection will also be developedThe therapeutic indexpharmacodynamicPDand PK profiles will be characterized following acute and repeated long term IN dosing in aged rats and optimized ODT and IN formulations will be characterized in anesthetized and awake dogsThe proposed Phase II project will allow Dignify Therapeutics to develop an optimizedon demandrapid onsetshort durationdrug inducedvoiding therapyto treat UAB in the elderlyThis optimized therapy will reduce the risk of deleterious side effects by providing greater target selectivity and a reduced duration of actionThis therapy would greatly improve the daily routine of elderly individuals with UABreduce UTIs and associated health risksand decrease overall healthcare costs