Dignify Therapeutics LLC — Department of Health and Human Services SBIR Phase I: 300

Description

DESCRIPTION provided by applicant Spinal cord injury SCI can result in loss of voluntary control over bladder and bowel function often producing both incontinence and retention of urine and stools in the same patient This has a profound impact on the mental and physical health status and quality of life of patients as well as a large impact on health care costs For example urinary retention is generally irreversible and can be life threatening The only available pharmacotherapy consists of cholinergic agonists which have minimal efficacy and severe side effects Consequently patients catheterize themselves multiple times daily to empty their bladder Catheter use is associated with increased incidence of health problems predominately repeated urinary tract infections sepsis isolation depression and hospitalization An andquot on demandandquot safe and effective pharmaceutical alternative to catheterization would be a life changing improvement in the daily routine of bladder management for patients not to mention a significant reduction in individual and community health care costs Similarly andquot on demandandquot bowel control would provide substantial improvement in QOL for people with neurogenic bowel Dignify Therapeutics is developing an andquot on demand rapid onset short duration drug induced voidingandquot therapy using an analogue of neurokinin A Lys MeLeu Nle NKA aka DTI DTI is a potent and selective agonist of the NK receptor which induces powerful contractions of the human bladder and rectum in vitro and provides highly promising in vivo voiding efficacy safety and pharmacodynamic PD profiles in various dog and rat models following intravenous IV administration Presently the overarching objective of its development program is to discover a formulation that is more convenient than the IV formulation for people with SCI but maintains its therapeutic benefit Thus this Phase I application aims to compare onset of action duration of action potency and efficacy of DTI delivered IV with the following alternative routes subcutaneous SC intramuscular IM and intranasal IN using a simple but clinically relevant anesthetized acute spinal rat cystometry model It is important to quantify and understand the differences in efficacy potency onset and duration of action of these various routes of delivery because these factors will impact efficacy tolerability convenience and cost of product for the patient Thus a careful decision regarding formulation is critical to maximizing commercial and health care benefits Our Phase II application will test the preferred route s of administration i a translational chronic SCI animal model examine the effects of DTI on urethral activity determine the pharmacokinetic profile of DTI and conduct preclinical safety toxicology studies to establish the final formulation for clinical studies PUBLIC HEALTH RELEVANCE The ultimate aim of this project is to provide paraplegic patients a pharmaceutical alternative to facilitate voiding without the need for multiple daily catheterizations of their bladder to void urine Passage of a catheter into the urethra and bladder can be discomforting stigmatizing and is associated with urinary tract infections and various other complications Success of our project will restore patientsandapos dignity and improve their daily quality of life and health as well as reduce individual and community health care costs This grant will compare routes of administration of a novel compound intravenous intramuscular subcutaneous and intranasal to guide formulation selection for clinical development