Ligand Pharmaceuticals Incorporated (NASDAQ:LGND) announced that data from preclinical studies evaluating LG-7501 were featured in a poster presentation today at the 63 rd Annual Meeting of the American Association for the Study of Liver Diseases in Boston. Ligand is developing novel small molecule inhibitors of NS5B polymerase for the treatment of hepatitis C virus infection (HCV) using its HepDirect ™ liver-targeting technology platform. LG-7501 is a HepDirect prodrug designed for increased liver targeting, potentially improving clinical efficacy and safety.
In preclinical studies, Ligand evaluated the pharmacokinetics and liver targeting of LG-7501. LG-7501 is a HepDirect prodrug of 2’-C methylguanosine, a clinically validated NS5B polymerase inhibitor. HepDirect liver targeting of 2’-C methylguanosine and other active nucleosides may be an effective method to improve efficacy while reducing systemic side effects in HCV treatment. LG-7501 efficiently targeted the liver with reduced systemic distribution in preclinical models, providing proof-of-concept with a clinically validated HCV treatment.
The key findings include:
- LG-7501 has good oral bioavailability in two species.
- LG-7501 is rapidly metabolized to the active drug.
- LG-7501 converts to the active drug in the liver, resulting in greatly increased liver concentrations of the active drug while greatly reducing systemic distribution.
“Our HepDirect liver-targeting technology platform is an exciting example of Ligand’s diverse portfolio of un-partnered assets and technologies, and has applicability in preferentially targeting drugs to the liver across a range of new classes of compounds for diseases such as HCV,” commented Matthew W. Foehr, Chief Operating Officer of Ligand Pharmaceuticals. “Additionally, we are extremely pleased with the positive data generated in preclinical evaluation of LG-7501. HCV represents a significant and growing health concern, with few therapeutic options currently available for the approximately 180 million patients infected with the disease worldwide 1.”About Ligand’s HepDirect HCV Inhibitor Program HepDirect is a pro-drug technology that targets delivery of certain drugs to the liver by using a proprietary chemical modification that renders a drug biologically inactive until cleaved by a liver-specific enzyme. Antiviral therapies for the treatment of HCV often have significant undesired side effects related to systemic exposure of the compounds. The HepDirect technology may improve the efficacy and/or safety of certain drugs and can be applied to marketed or new drug products.
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