Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it has named a new program to its pipeline: ALN-HBV for the treatment of hepatitis B virus (HBV) infection. The new ALN-HBV program derives from the company’s January 2014 acquisition of Merck’s RNAi assets, including their Sirna Therapeutics subsidiary. HBV infection afflicts 400 million people worldwide, with 1 to 2 million people in the U.S., and is a leading cause of liver disease and hepatocellular carcinoma (HCC) worldwide. Despite the use of nucleoside analog inhibitors of viral DNA synthesis and interferon therapies, less than 10% of patients achieve a cure 1. Reduction in HBV surface antigen (HBsAg) levels of over 0.5 log10 is the single best predictor of immunologic cure 2. An RNAi therapeutic targeting the HBV genome could have the potential to achieve a “functional cure” by effectively decreasing expression of tolerogenic HBsAg, in addition to inhibiting all steps of the HBV life cycle. In the most comprehensive proof-of-concept pre-clinical study results presented to date with an RNAi therapeutic for the treatment of HBV, Alnylam reported significant, multi-log reductions in HBV surface antigen (HBsAg) and HBV viral titers, and showed evidence for an immune-mediated therapeutic effect in chronically infected chimpanzees.
“Alnylam’s new ALN-HBV program is a mature, pre-clinical asset acquired through the company’s acquisition of Sirna from Merck. We are very encouraged by the data we are presenting for the first time today, which we believe constitute the most robust proof-of-concept pre-clinical data to date with an RNAi therapeutic for the treatment of HBV,” said Laura Sepp-Lorenzino, Ph.D., Vice President, Entrepreneur-in-Residence at Alnylam, and Project Leader of the ALN-HBV program. “We believe our ALN-HBV RNAi therapeutic represents a powerful mechanism for inhibiting all steps of the HBV life cycle: replication, assembly, secretion of virus, and secretion of sub-viral antigens. The Development Candidate for our ALN-HBV program will employ our Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, enabling subcutaneous dose administration with improved potency and durability, and a wide therapeutic index. We believe that an ESC-GalNAc conjugate can emerge as the best-in-class approach for RNA therapeutics targeting HBV, and we expect to name our ALN-HBV Development Candidate by the end of this year and file an IND or IND equivalent around the end of 2015.”