Novel ampk activator for treatment of congenital x-linked nephrogenic diabetes insipidus in pediatric patients

Active Project Grant Awarded Last action

Award ID
R44DK127798
Recipient
Awarding agency
Obligated
$2,095,545

Award facts

Completion date 89% complete
Place of performance
Seattle, WA 98199, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Nephrodi therapeutics (nephrodi) is advancing a first-in-class therapeutic, NDI-5001, for treatment of congenital x-linked nephrogenic diabetes insipidus (x-linked NDI). X-linked NDI is a rare pediatric orphan disease characterized by the production of very large quantities of dilute urine due to mutations in the type 2 vasopressin receptor (V2R) that prevent activation of the cyclic adenosine monophosphate (camp)/protein kinase a (PKA) signaling pathway. Individuals with x-linked NDI produce up to 20 l/d of dilute urine, almost 1 l/h 24-7-365. If left untreated, repeated episodes of severe dehydration may occur, eventually resulting in serious complications including dehydration-induced cognitive impairment, and children are especially vulnerable. The current therapeutic option for x-linked NDI patients is to drink as much water as they urinate and severely limit dietary sodium (0.5 g/d) and solute intake. The unmet medical need in x-linked NDI is enormous. Currently, there is no effective therapy for x-linked NDI. Nephrodi performed extensive efficacy, pharmacokinetic, formulation, and investigational new drug (IND)-enabling toxicology studies, initially during the phase 1 sttr, and subsequently with venture capital and a strategic partner. The nonclinical safety profile of NDI-5001 has been well characterized through the conduct of secondary pharmacology and pharmacodynamic studies, in vitro and in vivo genetic toxicology, in vitro and in vivo safety pharmacology, and pivotal 4-week repeat-dose toxicity and toxicokinetic (TK) studies in healthy rats and dogs. The NDI-5001 IND-enabling toxicology studies were conducted under GLP and adhered to principles set in place by the international council on harmonization (ICH). The NDI-5001 IND-enabling safety program is considered adequate to support a first-in-human single ascending dose (SAD), food effects, and multiple ascending dose (MAD) studies. Nephrodi's business plan is to develop NDI-5001 for the treatment of x-linked NDI. Nephrodi has been granted orphan drug designation (DRU-2022-9153) for NDI-5001 from the FDA. The goal of this phase 2 sbir application is to perform the additional, well-controlled, nonclinical studies necessary to support the pivotal clinical study in pediatric subjects with x-linked NDI. Nephrodi has the business infrastructure and domain expertise to establish human proof of concept for NDI-5001, an investigational new drug for x-linked NDI. We have a very strong IP position. Specific aim 1. GLP 39-week pivotal juvenile DOG (pre-weaning) toxicology studies. Specific aim 2. GLP male-only RAT fertility and early embryonic development (feed) study. Specific aim 3. Develop a liquid formulation suitable for pediatric populations for use in clinical trials. Completion of these aims will enable nephrodi to proceed to the pivotal study, post-phase 1, in pediatric NDI subjects with documented V2R mutations.

Transactions

Action Obligated Date
Amendment $998,617
Original award $1,096,928

Quick answers

Who received award R44DK127798?

R44DK127798 was awarded to Nephrodi Therapeutics, Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 15, 2020.

How much is award R44DK127798 worth?

$2,095,545 has been obligated on R44DK127798.

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