We presented new pre-clinical data with ALN-HBV, an investigational RNAi therapeutic targeting the Hepatitis B Virus (HBV) genome for the treatment of HBV infection. The ALN-HBV siRNA targets a highly conserved site across genotypes A-J, mapping to the X open reading frame, which is downstream from the most prevalent integration hotspot targeted by siRNAs from other developers. ALN-HBV is thus expected to achieve potent knockdown of HBV surface antigen (HBsAg) expressed by both covalently closed circular DNA (cccDNA) and integrated HBV DNA. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in all rodent models.