HCV is responsible for 60% of the cases of chronic hepatitis and 50% of cases of cirrhosis, end- stage liver disease, and liver cancer. An effective vaccine has proved elusive and the preferred therapy with pegylated interferon is effective in less than 50% of patients with genotype 1 and 75% of patients with genotypes 2 or 3. Clearly, new treatment alternatives are needed. Interest in HCV IRES RNA as a drug target is reflected by the increasing number of small and large pharma companies pursuing that goal. MetalloPharm has created a novel platform technology (metallodrugs) that has the potential to irreversibly destroy the HCV IRES RNA.
The specific aims are directed toward selection of a lead and back-up drug candidate for IND-enabling pre- clinical testing following validation of cellular mode of action against IRES RNA and uptake mechanisms;assessment of PK, toxicity and efficacy data;and exploration of methods to improve serum half life.

Public Health Relevance

Millions of people worldwide are infected with HCV, including a significant portion of the US population. HCV is responsible for 60% of the cases of chronic hepatitis and 50% of cases of cirrhosis, end-stage liver disease, and liver cancer. An effective vaccine has proved elusive and current therapy is effective in less than 50% of patients. Clearly, new treatment alternatives are needed. MetalloPharm has created a novel class of therapeutics (metallodrugs) that function by destroying a key molecule in the viral life cycle with the potential to halt the progression of, or completely eliminate the virus.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AA016712-04
Application #
8270019
Study Section
Special Emphasis Panel (ZRG1-IMST-K (11))
Program Officer
Wang, Joe
Project Start
2007-09-30
Project End
2013-11-30
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$813,038
Indirect Cost
Name
Metallopharm, LLC
Department
Type
DUNS #
140535845
City
Delaware
State
OH
Country
United States
Zip Code
43015
Bradford, Seth S; Ross, Martin James; Fidai, Insiya et al. (2014) Insight into the recognition, binding, and reactivity of catalytic metallodrugs targeting stem loop?IIb of hepatitis?C IRES RNA. ChemMedChem 9:1275-85
Joyner, Jeff C; Keuper, Kevin D; Cowan, J A (2013) Kinetics and Mechanisms of Oxidative Cleavage of HIV RRE RNA by Rev-Coupled Transition Metal Chelates. Chem Sci 4:1707-1718