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Avila’s protein silencing drug AVL-181 shows promise in hepatitis C infection

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Monday, March 1, 2010, 18:23 This news item was posted in Clinical Trials category and has 0 Comments so far.

AVL-181, anti-viral drug to treat hepatitis C infection developed by Avila Therapeutics, Inc., will soon undergo clinical studies.

AVL-181 is a highly selective, small molecule hepatitis C virus (HCV) protease inhibitor. Pre-clinical studies showed that AVL-181 promoted complete viral clearance in vitro when used at clinically-relevant concentrations in combination with other HCV therapies.

Avila also showed that AVL-181 bonds selectively and irreversibly to HCV protease in vivo in a novel rodent model, thus silencing a key protein necessary for successful viral replication and resulting in a prolonged duration of action in vivo.

Avila is on track to advance into clinical development of AVL-181 next year, stated Katrine Bosley, chief executive officer, Avila.

The drug formed a highly specific covalent bond across HCV genotypes and clinically described drug-resistant mutant proteases and inhibits protease activity in cultured replicon cells for  over 48 hours after very brief exposure and removal of AVL-181.

AVL-181 also demonstrated potent and irreversible silencing of HCV proteases. This level of protease inhibition is directly correlated with the extent of target bonding. It durably inhibits the HCV protease for at least 10 hours in vivo after a single dose.

Covalent drugs inherently provide prolonged duration of action through this silencing of the disease target, and they can solve the critical therapeutic challenges of drugging difficult targets and addressing resistance mutations.

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. Nearly 170 million people worldwide are infected with hepatitis C virus, it is estimated. This includes nearly four million people in the United States.

When detectable levels of HCV persist in the blood for at least six months, a person is diagnosed with chronic hepatitis C.

Hepatitis C virus can cause serious liver disease, leading to cirrhosis, primary liver cancer and even death. Patients infected with the genotype 1 hepatitis C virus account for approximately 75% of the chronic hepatitis C patients in the U.S.

Human Genome Sciences’ clinical development pipeline includes novel drugs to treat lupus, hepatitis C, inhalation anthrax and cancer. The Company’s primary focus is rapid progress toward the commercialization of its two lead drugs, Benlysta (belimumab) for lupus and Zalbin (albinterferon alfa-2b) for hepatitis C.
Avila Therapeutics, Inc focuses on design and development of covalent drugs. This approach is called “protein silencing”.

The company is developing a pipeline of novel, proteinsilencing covalent drugs with a current focus on viral infection, cancer and autoimmune disease.

Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners.

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