Alnylam Shares Higher Following New Pre-clinical Data on RNAi Therapeutics for Treatment of Hemophilia

Alnylam Pharmaceuticals, Inc. ALNY, a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data from its RNAi therapeutic program for the treatment of hemophilia and other bleeding disorders at the 54^th American Society of Hematology Annual Meeting being held December 8-11, 2012 in Atlanta. Alnylam scientists presented data showing that ALN-AT3, a subcutaneously administered RNAi therapeutic targeting antithrombin (AT), yields potent, dose-dependent, and durable knockdown of AT in non-human primates (NHPs) with an up to four-fold increase in thrombin generation. Alnylam's program in hemophilia comprises part of its ‘Alnylam 5x15' product strategy, by which the company aims to advance five programs in clinical development, including programs in advanced stages, by the end of 2015. In a poster titled “An RNAi Therapeutic Targeting Antithrombin Increases Thrombin Generation in Nonhuman Primates,” (#3370) Alnylam scientists showed that subcutaneous administration of ALN-AT3 in NHPs results in potent, dose-dependent, and durable knockdown in serum AT, resulting in significant increases in thrombin generation. Specifically, a single subcutaneous dose of ALN-AT3 led to potent knockdown of serum AT, with an ED50 of 1 mg/kg. AT suppression was durable, with effects lasting greater than six weeks after a single dose. In addition, weekly subcutaneous doses of ALN-AT3 in NHPs led to sustained AT knockdown of approximately 80% and greater than 90% at 0.5 mg/kg and 1.5 mg/kg, respectively. These data enable an estimation of an ED50 dose for weekly subcutaneous administration at 0.15-0.3 mg/kg at a volume of injection for human administration expected to be less than 0.5 mL/injection. Moreover, increased thrombin generation was closely correlated with AT reduction, with an up to four-fold increase in peak thrombin at 90% AT reduction. ALN-AT3 utilizes Alnylam's proprietary GalNAc-siRNA conjugate delivery approach enabling subcutaneous dose administration with potential for a once-weekly or twice-monthly dosing regimen. Alnylam expects to file an investigational new drug (IND) application for ALN-AT3 in mid-2013. In addition, results from Alnylam's ALN-AT3 program will be discussed at an upcoming RNAi Roundtable on conjugate delivery that the company will host on Friday, December 14 at 11:00 a.m. ET. The discussion will focus on progress with the company's proprietary GalNAc-conjugate platform to deliver RNAi therapeutics with subcutaneous dose administration. The roundtable will also include a review of the company's two leading conjugate programs: ALN-TTRsc for the treatment of transthyretin-mediated amyloidosis (ATTR) and ALN-AT3 for the treatment of hemophilia and other bleeding disorders. The webinar will be available live on the Capella section of the company's website, www.alnylam.com/capella, and will also be available for replay on the Alnylam website within 48 hours after the event.