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Development of NaV1.7 Inhibitors for the Treatment of Chronic Cough

Award Number: R43HL147776
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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Development of NaV1.7 Inhibitors for the Treatment of Chronic Cough - PROJECT SUMMARY The objective of our program is to develop a safe and effective therapeutic for chronic cough. 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. 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. The Aims of this Phase I project are to evaluate a series of Nav1.7 inhibitors against physiological, pharmacokinetic, and efficacy endpoints in order to demonstrate the feasibility of developing a therapeutic candidate for chronic cough and to select a candidate for nonclinical development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Cardiovascular Diseases Research	000	1	8/26/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Cardiovascular Diseases Research	000	1	8/25/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $323,733 )
2019	2019	SITEONE THERAPEUTICS, INC.	203 ENTERPRISE BLVD STE 3	BOZEMAN	MT	59718	GALLATIN	USA	Cardiovascular Diseases Research	001	1	4/30/2019	NEW	$106,497
2019	2019	SITEONE THERAPEUTICS, INC.	203 ENTERPRISE BLVD STE 3	BOZEMAN	MT	59718	GALLATIN	USA	Cardiovascular Diseases Research	000	1	4/26/2019	NEW	$217,236
														Subtotal = $323,733

Grand Total All Awards = $323,733

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Development of NaV1.7 Inhibitors for the Treatment of Chronic Cough

Award Number: R43HL147776

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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