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Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

Award Number: R44AG055205
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2022

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Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease - Vivreon Biosciences, LLC 7558 Trade St. San Diego, CA 92121 vivreonbiosciences@gmail.com Vivreon Biosciences – NIA SBIR # PA-18-187 Project Summary Vivreon Biosciences is pleased to apply for NIA SBIR Solicitation #PA-18-187. Vivreon Biosciences is an innovative life sciences company that is developing a series of novel small molecule, Ca2+ channel inhibitors for the treatment of Alzheimer's disease (AD). Our lead compound series achieves neuroprotection by an entirely new mechanism – inhibition of Ca2+ release-activated Ca2+ (CRAC) channels to block microgliosis. Vivreon seeks NIA funding to bridge the gap between discovery and development. We will perform chemistry and biology experiments to identify and validate a new clinical candidate therapeutic drug. Upon successful completion of the program, our clinical candidate will be the first to specifically target the CRAC pathway for neuroprotection in AD, thus comprising an entirely new tool in the battle against AD. Vivreon has discovered a lead compound series with oral bioavailability that penetrates into the central nervous system (CNS) very efficiently, shows no neurotoxicity in the Irwin test of central nervous system (CNS) integrity, and demonstrates neuroprotection in a mouse model of neurodegeneration. The lead series inhibits microgliosis by blocking CRAC channel activity with nM potency; suppressing M1-like NF-κB activity, while enhancing M2- like phagocytosis. We will now expand our library of small molecule CRAC channel inhibitors by synthetic chemistry followed by pharmacology assays designed to identify a candidate with properties appropriate for AD therapy. The candidate therapeutic will be validated in a new humanized animal model of AD (5x-MITRG). The final aim for this proposal is identification and validation of the first CRAC channel inhibitor for AD therapy.


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 = $0 )
2023	2020	VIVREON BIOSCIENCES LLC	4940 CARROLL CANYON RD	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	5	10/28/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $193,392 )
2021	2021	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	001	5	3/11/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	003	5	6/30/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	5	2/17/2021	SUPPLEMENT FOR EXPANSION	$193,392
2021	2020	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	002	5	6/30/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $193,392

Issue Date FY: 2020 ( Subtotal = $1,249,999 )
2020	2020	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	5	5/20/2020	NON-COMPETING CONTINUATION	$1,249,999
														Subtotal = $1,249,999

Issue Date FY: 2019 ( Subtotal = $1,250,000 )
2019	2019	VIVREON BIOSCIENCES, LLC	7558 TRADE STREET	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	4	6/6/2019	COMPETING CONTINUATION	$1,250,000
														Subtotal = $1,250,000

Issue Date FY: 2018 ( Subtotal = $745,976 )
2018	2018	VIVREON BIOSCIENCES, LLC	7558 TRADE STREET	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	001	3	6/11/2018	NON-COMPETING CONTINUATION	$745,976
2018	2016	VIVREON BIOSCIENCES, LLC	7558 TRADE STREET	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	1	10/23/2017	NEW	$0
														Subtotal = $745,976

Issue Date FY: 2017 ( Subtotal = $746,325 )
2017	2017	VIVREON BIOSCIENCES, LLC	6990 CARROLL RD STE A	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	2	7/24/2017	EXTENSION WITH OR WITHOUT FUNDS	$746,325
														Subtotal = $746,325

Issue Date FY: 2016 ( Subtotal = $222,453 )
2016	2016	VIVREON BIOSCIENCES, LLC	6990 CARROLL RD STE A	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	1	9/15/2016	NEW	$222,453
														Subtotal = $222,453

Grand Total All Awards = $4,408,145

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Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

Award Number: R44AG055205

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2022

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