Genelabs Technologies today announced that a non-nucleoside compound from its internal Hepatitis C virus (HCV) drug discovery program has advanced into preclinical development.
The compound, designated GL60667, is the second Genelabs non-nucleoside compound to advance into preclinical development. Genelabs also announced that the company has further advanced GL59728, its first non-nucleoside preclinical development candidate. Genelabs plans to initiate Good Laboratory Practices (GLP) preclinical studies on GL59728 which, if successful, would enable the company to file an Investigational New Drug Application (IND) for the compound. Genelabs retains all commercial rights to its non-nucleoside compounds.
Genelabs based its decision to advance compound GL60667 on rigorous pre- determined standards, including various measures of potency, metabolism, pharmacokinetics and toxicity. Genelabs believes that compounds meeting these criteria should hold a competitive advantage over other non-nucleoside HCV inhibitors described in the scientific literature. GL60667 has demonstrated the following properties in in vitro assays:
- potency of approximately 40 nanomolar against an HCV replicon.
- potency of approximately 20 nanomolar for inhibition of the HCV polymerase.
- potency against the major genotypes of HCV, including genotype 1, the most common genotype in the United States and western Europe.
The concentration of GL60667 that is effective in reducing HCV replication is more than 100 times lower than the concentration that causes toxicity to various human cell lines, as demonstrated in a battery of tests conducted by Genelabs. Genelabs also has profiled the metabolic and pharmacokinetic properties of GL60667 in several different animal species. Extrapolating from this data, Genelabs believes the compound should be suitable for once-a-day dosing.
Separately, Genelabs advanced its first non-nucleoside preclinical candidate, GL59728, into IND-enabling studies based on favorable results from 1-day and 7-day toxicology studies in two animal species. Selection of a vendor for process development and large-scale synthesis is underway.