Development of Oral Small Molecule PCSK Antagonist

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44HL137449-01
Agency Tracking Number: R44HL137449
Amount: $682,343.00
Phase: Phase II
Program: SBIR
Awards Year: 2017
Solicitation Year: 2014
Solicitation Topic Code: NHLBI
Solicitation Number: PAR14-088
Small Business Information
1 GREAT VALLEY PKWY STE 8, Malvern, PA, 19355-1423
DUNS: 192526221
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (610) 400-1243
Business Contact
Phone: (610) 400-1243
Research Institution
Project Summary Abstract The epidemic of cardiovascular disease CVD is a global phenomenon that remains the number one cause of death throughout the world killing nearly million people per year a number that is expected to grow to million by A high cholesterol level is well known risk factors for heart disease Although blood cholesterol can be lowered using a number of marketed drugs of which statins are the leading drugs only of patients taking these drugs are achieving the low density lipoprotein cholesterol goals set by the National Cholesterol Education Program NCEP Furthermore patients with homozygous familial hypercholesterolemia who have markedly elevated cholesterol levels respond poorly to current drug therapy and are at very high risk of premature cardiovascular disease These and other patients will dramatically benefit from an aggressive treatment of hypercholesterolemia The long term goal of this work is to develop novel orally bioavailable drugs for cholesterol lowering Our therapeutic target is the protease proprotein convertase subtilisin like kexin type PCSK PCSK controls the degradation of the LDL receptor LDLR in the liver and thereby contributes to cholesterol homeostasis PCSK is synthesized as a precursor protein that undergoes processing Secreted PCSK binds to the LDL receptor LDLR and chaperones it to the degradation pathway To achieve our goal we identified nanomolar orally active small molecule PCSK LDLR antagonists and demonstrated its efficacy in animal model As part of this Phase II proposal we will undertake all the work required to characterize these compounds in multiple animal models for the proof of concept and conduct safety assessment in order to advance the lead compound toward IND enabling studies and clinical trials Project Narrative Heart disease is the leading cause of death for both men and women in the US A high cholesterol level is a well known risk factor for heart disease Our goal is to develop new cholesterol lowering drugs that have an effect on all individuals with high cholesterol levels including that segment of the population having very high cholesterol levels

* Information listed above is at the time of submission. *

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