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Discovery of NaV1.7 Inhibitors for the Treatment of Pain

Award Number: U44NS111779
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2022

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Discovery of NaV1.7 Inhibitors for the Treatment of Pain - PROJECT SUMMARY The objective of our program is to develop a safe and effective nonopioid analgesic for the treatment of neuropathic pain, such as pain associated with chemotherapy-induced peripheral neuropathy, that targets an isoform of the voltage-gated sodium ion channel, NaV1.7. Voltage-gated sodium channels are involved in the transmission of nociceptive signals from their site of origin in the peripheral terminals of DRG neurons to the synaptic terminals in the dorsal horn. Ten mammalian isoforms exist, NaV1.1–1.9 and NaX. NaV1.7 is the most abundant tetrodotoxin-sensitive sodium channel in small diameter myelinated and unmyelinated afferents, where it has been shown to modulate excitability and set the threshold for action potentials. Humans lacking functional NaV1.7 due to a rare genetic condition are unable to experience almost all types of pain. Efforts to develop systemic inhibitors of NaV1.7 have been complicated by the challenge of achieving selectivity over other NaV isoforms expressed in the diaphragm, phrenic nerve, heart and central nervous system that are critical for safety. SiteOne Therapeutics has discovered a series of potent, state-independent NaV1.7 inhibitors that exhibit >1000-fold selectivity over other human isoforms. Work conducted under this program will support advancement of a lead candidate into clinical development as a therapeutic for neuropathic pain.


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: 2023 ( Subtotal = -$2,262 )
2023	2021	SITEONE THERAPEUTICS, INC.	280 UTAH AVE STE 250	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	10/17/2022	EXTENSION WITH OR WITHOUT FUNDS	-$2,262
														Subtotal = -$2,262

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	7/28/2022	EXTENSION WITH OR WITHOUT FUNDS	$0
2022	2021	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/5/2022	EXTENSION WITH OR WITHOUT FUNDS	$0
2022	2020	SITEONE THERAPEUTICS, INC.	280 UTAH AVE	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	10/16/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $455,622 )
2021	2021	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/15/2021	EXTENSION WITH OR WITHOUT FUNDS	$455,622
														Subtotal = $455,622

Issue Date FY: 2020 ( Subtotal = $461,907 )
2020	2020	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/17/2020	NON-COMPETING CONTINUATION	$461,907
2020	2019	SITEONE THERAPEUTICS, INC.	351 EVERGREEN DR STE B-1	BOZEMAN	MT	59715	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/18/2020	NEW	$0
														Subtotal = $461,907

Issue Date FY: 2019 ( Subtotal = $226,176 )
2019	2019	SITEONE THERAPEUTICS, INC.	203 ENTERPRISE BLVD STE 3	BOZEMAN	MT	59718	GALLATIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/1/2019	NEW	$226,176
														Subtotal = $226,176

Grand Total All Awards = $1,141,443

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Discovery of NaV1.7 Inhibitors for the Treatment of Pain

Award Number: U44NS111779

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/15/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2022

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