Benitec Biopharma (ASX:BLT) has announced that BB-HB-331, a DNA-directed RNA interference (ddRNAi) therapy targeting the hepatitis B virus (HBV), demonstrated robust and durable suppression of HBV in vivo following a single administration.
Benitec is a clinical stage biotechnology company commercialising the patented gene-silencing technology, ddRNA - a combination of gene silencing using RNA interference coupled with the long term therapeutic potential of gene therapy.
BB-HB-331 is comprised of an AAV8 capsid and recombinant DNA engineered to express three short hairpin RNA (shRNA) that target and inhibit viral RNA expressed from three well conserved regions across multiple HBV genotypes.
The current in vivo study assessed the activity of BB-HB-331 in the PhoenixBio (PXB) mouse model, in which mouse liver cells have been replaced with human hepatocytes making the animals susceptible to HBV infection.
Once infected with HBV, mice were treated with a one-time systemic injection of BBHB-331. Weekly assessment of serum antigen levels, HBV viral proteins and extracellular HBV DNA were conducted for the duration of the 56-day study.
The key findings in the study were that a single BB-HB-331 treatment reduced serum HBV DNA by 1.83 logs, intracellular liver HBV DNA by 94.9 per cent, suppressed serum antigens, HBsAg and HBeAg, by 97.6 per cent and 92.6 per cent respectively, and decreased levels of HBV viral RNA and cccDNA.
According to the company, this in vivo experiment validates the BB-HB-331 in vitro findings previously observed in human hepatocytes isolated from the PXB mouse model.
Benitec’s Chief Scientific Officer, Dr David Suhy said: “These results demonstrate the utility of an approach that combines RNAi with gene therapy to treat HBV. In addition to these encouraging results, we note that the HBV serum DNA and antigen levels continued to drop through the predetermined conclusion of the study, and may not have reached their lowest levels. As previously communicated, Hep B represents a significant commercial opportunity and we will continue to apply key learnings from our clinical stage hepatitis C program to advance the Hep B program towards the clinic.”