Genelabs Technologies Announces Presentation of Data on Non-Nucleoside HCV Polymerase Inhibitor at 3rd International Workshop on Hepatitis C, Resistance and New Compounds
The oral presentation was given by Jill Bechtel, Ph.D. entitled, "In vitro antiviral activity and resistance profile of GL60667 (NVP-LDI133), a potent non-nucleoside inhibitor of HCV NS5B polymerase." The presentation contains studies performed by both Genelabs and Novartis scientists in connection with a license and research collaboration commenced in June 2006 between Novartis and Genelabs, covering Genelabs' non-nucleoside HCV polymerase inhibitors.
GL60667 is one of a number of non-nucleoside HCV polymerase inhibitors discovered by Genelabs. In the presentation, Dr. Bechtel outlined the ability of GL60667 in vitro to reduce HCV RNA levels after prolonged (20 day) treatment, described combination HCV treatment studies with other HCV agents, and characterized the resistance profile of GL60667.
The treatment of replicon cells with 0.56 uM and 2.8 uM GL60667 for 20 days resulted in a 4-5 log reduction in HCV viral RNA. In addition, combination studies showed GL60667 was additive with interferon (alpha) or ribavirin in inhibiting HCV replication, whereas the combination with an NS3 protease inhibitor or a nucleoside NS5b inhibitor was synergistic. Sequencing of the resistant clones isolated from GL60667 selection revealed an NS5b mutation previously identified as a site for resistance to earlier compounds in this series. Interestingly, several clones had no mutations in the NS5b region. Sequencing of the entire replicon revealed several amino acid changes in NS3, NS4a, NS4b and NS5a. Transient assays using replicons bearing these mutations demonstrated that an amino acid change in the NS3 helicase domain reduced the susceptibility to GL60667 by 6.7 fold. Additional experiments demonstrated that this mutation only shifted the potency of a select number of compounds in this series leading to the identification of the region of the molecule responsible for the resistance.
"The data presented today from both Genelabs and Novartis scientists demonstrate potent antiviral activity for site 1 non-nucleoside HCV polymerase inhibitors alone or in combination with other HCV agents and a favorable resistance profile," said Ronald C. Griffith, Ph.D., Genelabs' Chief Scientific Officer. "This data clearly support the further investigation of site 1 NNI inhibitors for the future treatment of HCV infection."
About Genelabs Technologies
Genelabs is a biopharmaceutical company focused on the discovery and development of novel compounds for infectious diseases. In addition to a late-stage vaccine candidate for hepatitis E virus partnered with GlaxoSmithKline, the company is advancing multiple partnered and proprietary compounds designed to selectively inhibit replication of the hepatitis C virus. For more information, please visit www.genelabs.com.
NOTE ON FORWARD LOOKING STATEMENTS AND RISKS:
This press release contains forward-looking statements regarding specific areas of further investigation for the treatment of HCV infection. 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, uncertainties and risks associated with the discovery and preclinical development of therapeutic 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 that may 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 Driscoll, 650-562-1477
Chief Financial Officer
Posted: June 2008