# Development of Nav1.7 Selective Inhibitors for the Treatment of Chronic Cough

> **NIH NIH R44** · SITEONE THERAPEUTICS, INC. · 2021 · $677,568

## Abstract

PROJECT SUMMARY
 Chronic cough, or cough that persists for more than eight weeks, is a condition that is often associated
with diseases such as chronic obstructive pulmonary disorder (COPD), asthma, idiopathic pulmonary fibrosis,
bronchiectasis or gastroesophageal reflux disease (GERD). In other cases, the etiology is unknown, although it
has been noted that the cough often first arises following a severe viral respiratory infection. Chronic cough has
significant physical, psychological, social and economic consequences that negatively impact quality of life.
Prevalence in the United States is as high as 11%, and in a majority of cases the condition is refractory.
 Compelling evidence supports the hypothesis that chronic cough arises from alterations in sensory
physiology that cause hypersensitivity to previously innocuous stimuli. The voltage-gated sodium ion channel
NaV1.7 is highly expressed in unmyelinated vagal nerve afferents that trigger cough through a sensorimotor
reflex circuit. Results from a published pre-clinical report show that reducing expression of NaV1.7 nearly
abolishes cough evoked by inhaled irritants, indicating that it is a promising target for reducing cough. SiteOne
Therapeutics has discovered potent and selective small molecule inhibitors of NaV1.7 that block vagal C fiber
activity in a dose-dependent manner. During a Phase 1 program, our team demonstrated that systemic
administration of an isoform-selective NaV1.7 inhibitor abolishes the cough response to inhaled irritants in
conscious guinea pigs. The objective of our Phase 2 program is evaluate safety, pharmacokinetic and efficacy
endpoints, and to advance an inhaled NaV1.7 inhibitor into IND-enabling development as a therapeutic for chronic
cough.

## Key facts

- **NIH application ID:** 10258238
- **Project number:** 2R44HL147776-02
- **Recipient organization:** SITEONE THERAPEUTICS, INC.
- **Principal Investigator:** John Cureton Hunter
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,568
- **Award type:** 2
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10258238

## Citation

> US National Institutes of Health, RePORTER application 10258238, Development of Nav1.7 Selective Inhibitors for the Treatment of Chronic Cough (2R44HL147776-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10258238. Licensed CC0.

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