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Adenylyl Cyclase Type 5 Inhibition to Treat Myocardial Infarction

Award Number: R44HL142390
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2022

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Adenylyl Cyclase Type 5 Inhibition to Treat Myocardial Infarction - PROJECT SUMMARY/ABSTRACT The most significant advance in the treatment of Myocardial Infarction (MI) has been reperfusion therapy, which must be applied immediately after the MI diagnosis has been made. Despite the thousands of studies on drug therapies designed to reduce the size of the MI, most have failed in clinical trials. Our hypothesis is that a major reason why these drugs failed is that they must be administered before therapeutic cardiac catheterization is performed. This significantly limits their utility in the clinical setting. The current proposal is based on studies in the Adenylyl Cyclase type 5 (AC5) knock out mouse model, which is protected against myocardial ischemia, obesity, diabetes and has enhanced exercise capacity and lives longer than wild type. Our preliminary data demonstrate that pharmacological inhibitors of the AC5 enzyme have a unique advantage in that they reduce infarct size even when administered after coronary reperfusion. We have developed a novel, more potent and more selective AC5 inhibitor, C90, which is particularly attractive because it is a potent non-nucleoside adenine AC5 inhibitor and also is not toxic. We have a patent pending on C90 and selected this compound for clinical development based on efficacy, pharmacology and safety. Preliminary data indicate that C90 can reduce infarct size when administered after reperfusion by more than 50% in a mouse MI model. The goal of this proposal is to obtain proof-of-principle in mice, in Watanabe rabbits with atherosclerosis and in a large mammalian animal model for infarct size, cardiac function and complete IND-enabling pharmacology, ADME and toxicology 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: 2023 ( Subtotal = -$64,980 )
2023	2020	VASADE BIOSCIENCES INC	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	000	3	3/1/2023	NON-COMPETING CONTINUATION	-$64,980
														Subtotal = -$64,980

Issue Date FY: 2020 ( Subtotal = $715,042 )
2020	2020	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	000	3	9/5/2020	NON-COMPETING CONTINUATION	$715,042
2020	2019	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	002	2	9/16/2020	EXTENSION WITH OR WITHOUT FUNDS	$40,028
2020	2018	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	001	1	9/16/2020	NEW	-$40,028
														Subtotal = $715,042

Issue Date FY: 2019 ( Subtotal = $673,385 )
2019	2019	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	002	2	4/19/2019	EXTENSION WITH OR WITHOUT FUNDS	$673,385
2019	2018	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	000	1	11/12/2018	NEW	$0
2019	2018	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	001	1	11/27/2018	NEW	$0
														Subtotal = $673,385

Issue Date FY: 2018 ( Subtotal = $172,153 )
2018	2018	VASADE BIOSCIENCES INC.	16 E 27TH ST	BARNEGAT LIGHT	NJ	08006	OCEAN	USA	Cardiovascular Diseases Research	000	1	8/15/2018	NEW	$172,153
														Subtotal = $172,153

Grand Total All Awards = $1,495,601

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Adenylyl Cyclase Type 5 Inhibition to Treat Myocardial Infarction

Award Number: R44HL142390

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2022

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