Genelabs Technologies Announces Presentation of Data on HCV NS4b Inhibitors at the Inaugural HCV Drug Discovery Meeting
The oral presentation was given by Christopher D. Roberts, Ph.D., Senior Director of Medicinal Chemistry at Genelabs, entitled "Targeting HCV NS4b Function: A New Approach to Anti-HCV Activity."
NS4b is an HCV protein that is believed to function by driving the formation of the "membranous web," the cellular scaffolding assembled by the virus in infected liver cells that is necessary for viral replication. Dr. Roberts outlined the discovery of compounds from an HCV replicon screen. Subsequently, HCV mutant replicons were raised that were resistant to these compounds and displayed consistent amino acid changes localized to a well-defined region of NS4b. "We believe that interfering with the assembly of this critical viral scaffolding can result in potent anti-HCV activity," said Dr. Roberts.
Multiple series of potent, proprietary compounds have resulted from the optimization efforts to date. The most active compounds display HCV replicon EC50 potencies under 100 nanomolar in both genotypes 1a and 1b, the most prevalent and difficult to treat HCV genotypes. Importantly, these NS4b compounds were also tested in combination with other classes of HCV antiviral compounds, including a NS5b polymerase nucleoside chain terminator, a NS5b polymerase non-nucleoside allosteric inhibitor, a NS3a protease inhibitor and interferon alpha, and shown to be additive in activity with each. When the HCV replicon was dosed for three weeks with an NS4b compound, the viral load was dropped by approximately 4 logs. Finally, in-vitro and in-vivo pharmacokinetic analyses demonstrated that compounds from this class have the potential to be well absorbed when dosed orally.
"With the clear threat of emerging viral resistance there remains the need to continue to discover and develop HCV treatments with novel mechanisms of action," said Ronald C. Griffith, Ph.D., Genelabs' Chief Scientific Officer. "Our NS4b program clearly fits this profile and our initial results show that this approach yields highly potent and orally bioavailable compounds that could play an important role in future HCV therapy. Future treatments for HCV are likely to involve combinations of antiviral drugs, and these data suggest that combinations of this new agent with interferon or other potential therapeutic drugs, such as nucleoside chain terminators, non-nucleoside inhibitors or protease inhibitors, may be feasible."
Forward Looking Statements
This press release contains forward-looking statements including statements regarding Genelabs' drug discovery efforts of its antiviral compounds for treatment of HCV. These forward-looking statements are based on Genelabs' current expectations and are subject to uncertainties and risks that could cause actual results to differ materially from the statements made, including, without limitation, the viability of NS4b as an HCV antiviral mechanism, the early stage of Genelabs' research programs and uncertainties associated with the preclinical development of compounds. Please see the information appearing in the company's filings with the Securities and Exchange Commission, including the most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, under the captions "Risk Factors," "Business Risks" and "Forward-Looking Statements" for more discussion regarding these uncertainties and risks and other risks which may affect the company or cause actual results to differ from those included in the forward-looking statements. Genelabs does not undertake any obligation to update these forward-looking statements or risks to reflect events or circumstances after the date of this release.
Genelabs Technologies, Inc.
Frederick W. Driscoll, 650-562-1424
Chief Financial Officer
Posted: April 2008