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Preclinical Characterization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

Award Number: R43AG061995
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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Preclinical Characterization 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 # PAS-18-187 Project Summary Vivreon Biosciences is pleased to apply for NIA SBIR Solicitation #PAS-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 a series of functional safety pharmacology and in vitro efficacy screens to identify promising candidate compounds in our library of small molecule CRAC channel inhibitors. Upon successful completion of the program, our preclinical 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 CNS integrity, and demonstrates neuroprotection in a mouse model of microgliosis (experimental autoimmune encephalitis). The lead series inhibits microgliosis by blocking CRAC channel activity with nM potency; suppressing M1-like NF- ¿B activity, while preserving M2-like phagocytosis. We will now test select candidates from our lead compound series in innovative safety and efficacy screens using screening technology from patient-derived induced pluripotent stem cells (iPSCs). iPSCs will first be grown and differentiated into microHearts and screened for functional safety pharmacology to detect potential cardiac toxicity liabilities. Finally, iPSCs from persons with Alzheimer's disease will be differentiated into microglia-like cells to monitor the anti-neuroinflammatory capacity of our candidate drugs. The final aim for this proposal is the preliminary preclinical characterization of the first CRAC channel inhibitor for AD therapy and identification of key inflammatory cytokines that may be used as surrogate biomarkers for target engagement in future clinical studies.


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: 2022 ( Subtotal = $0 )
2022	2019	VIVREON BIOSCIENCES LLC	4940 CARROLL CANYON RD	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	1	2/22/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	VIVREON BIOSCIENCES, LLC	4940 CARROLL CANYON RD STE 110	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	1	1/27/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $270,902 )
2019	2019	VIVREON BIOSCIENCES, LLC	7558 TRADE STREET	SAN DIEGO	CA	92121	SAN DIEGO	USA	Aging Research	000	1	7/26/2019	NEW	$270,902
														Subtotal = $270,902

Grand Total All Awards = $270,902

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Preclinical Characterization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

Award Number: R43AG061995

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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