Preclinical and early clinical development of a novel drug for on-demand voiding

Active Cooperative Agreement Awarded Last action

Award ID
U44NS129628
Recipient
Awarding agency
Obligated
$7,975,004

Award facts

Completion date 92% complete
Originally
Place of performance
Research Triangle Park, Durham, NC, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Spinal cord injury, multiple sclerosis, parkinson's disease, spina bifida, and stroke, as well as complications due to aging and diabetes, can produce a loss of voluntary control over bowel and bladder function resulting in both fecal and urinary incontinence as well as retention in the same patient. The activities proposed in this application will enable dignify therapeutics to complete preclinical development of an on-demand, rapid- onset (< 5 min), short-duration (< 10 min), drug-induced, voiding therapy to restore voluntary control of bowel and bladder function for the patient populations listed above. This project will culminate in the filing of an investigational new drug application (IND) for DTI-117 and completion of a phase I clinical study. Neurokinin 2 receptors (NK2RS) are located at several sites in the defecation and micturition pathways, particularly the colorectal and urinary bladder smooth muscles. Preclinical in vitro and in vivo studies in several species, including human tissue, have shown that activation of NK2RS produces forceful colonic and bladder contractions. Our previous preclinical studies showed that when administered via intramuscular, intravenous, subcutaneous, intranasal, or sublingual routes, NK2R agonists, including DTI-117, rapidly induced transient increases in colorectal and bladder pressures that produced urination and defecation. DTI-117 is currently in preclinical development by dignify therapeutics. Under ninds create BIO optimization track award U44NS106685, efficacy, selectivity, and preliminary safety of DTI-117 has been established. A GMP-compliant synthetic route, physicochemical characterization, analytical methods, bioanalytical assays, in vitro characterization, and target selectivity for NK2RS versus multiple common drug targets have all been established. Preclinical efficacy, measured as rapid-onset defecation and urination, has been demonstrated, and in vivo pharmacokinetic profiles mimic in vivo pharmacodynamic profiles. General toxicity studies completed to-date indicate that DTI-117 is both safe and effective. The final step for preclinical development of DTI-117 is to file an investigational new drug application (IND) prior to initiation of clinical studies. FDA guidelines require that acceptable toxicological and safety profiles are demonstrated in preclinical studies conducted under good laboratory practice (GLP) conditions for inclusion in the IND. In parallel, drug substance and drug product must be manufactured according to strict FDA regulations. Completion of these activities as described in this application will enable an IND filing for DTI-117.

Transactions

Action Obligated Date
Amendment $94,793
Amendment $199,520
Amendment $199,520
Amendment $976,908
Amendment $0
Amendment $0
Amendment $1,473,895
Amendment $1,473,895
Amendment $1,473,895
Amendment $42,503
Amendment $42,503
Amendment $499,393
Amendment $499,393
Amendment $499,393
Original award $499,393
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Quick answers

Who received award U44NS129628?

U44NS129628 was awarded to Dignify Therapeutics, LLC by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on March 1, 2023.

How much is award U44NS129628 worth?

$7,975,004 has been obligated on U44NS129628.

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