BioCryst Pharmaceuticals has announced the positive preclinical results of its adenine nucleoside analog targeting viral RNA polymerase, BCX5191, used for the treatment of hepatitis C.
BCX5191 has completed in vitro and in vivo studies, where it demonstrated potent and selective pan-genotypic antiviral activity against the hepatitis C polymerase enzyme, showing no inhibition of human RNA polymerase and no evidence of toxicity.
In preclinical models, BCX5191 has showed high oral bioavailability, and it was also found that after a single oral dose of the drug in rats, liver BCX5191 triphosphate levels exceeded the IC50 values for genotypes 1-4 through 24 hours.
At Cmax, the drug triphosphate level is found 100 times higher than the IC50, and this pharmacokinetic profile is anticipated to support once-daily dosing in clinical studies.
BioCryst Pharmaceuticals’ senior vice president and chief medical officer Dr William P. Sheridan said: "BCX5191 has met stringent preclinical criteria to advance to IND-enabling studies. We expect this programme to be ready to file for first-in-human studies during the fourth quarter of 2012."
Dr Sheridan added: "Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients."
The study showed that BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations (0.05-0.36µM) and is active in replicon cell assays for genotypes 1a and 1b.
The company is planning additional BCX5191 non-clinical experiments, including Good Laboratory Practices (GLP) non-clinical safety studies and in vitro evaluation of BCX5191 in combination with ribavirin.
Hepatitis C is a contagious liver disease caused by hepatitis C virus (HCV), leading to life-threatening liver problems, such as liver damage, cirrhosis, liver failure or liver cancer.
BioCryst Pharmaceuticals designs, optimises and develops novel small-molecule pharmaceuticals that block key enzymes involved in infectious diseases, inflammatory diseases and cancer.