Alnylam and Collaborators Present Pre-Clinical Research Findings on RNAi Therapeutics Targeting PCSK9

Alnylam Pharmaceuticals, Inc. has announced the presentation of new pre-clinical data from its hypercholesterolemia program, performed in collaboration with the University of Texas Southwestern Medical Center at Dallas, at the XV International Symposium on Atherosclerosis 2009 held in Boston, Mass. from June 14-18, 2009.

Alnylam’s ALN-PCS program is focused on using RNAi therapeutics targeting proprotein convertase subtilisin/kexin type 9, or PCSK9, as a novel strategy for reducing LDL (or bad) cholesterol.

The newly presented data include results with novel lipid nanoparticles (LNPs), developed in collaboration with Tekmira Pharmaceuticals Corporation and University of British Columbia and exclusively licensed to Alnylam that show significantly improved in vivo potency and the use of certain optimized dosing regimens that also improve potency and enhance durability. Further, the new research findings show that silencing PCSK9 with RNAi therapeutics results in no measurable decrease in HDL (or good) cholesterol.

“We are excited about the progress we’re making in our development efforts for ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. We remain convinced that this is an ideal target for the advancement of new medicines in this significant clinical indication,” said Kevin Fitzgerald, Ph.D., Director of Research of Alnylam.

He continued, “A key highlight from our presentation is new data with a novel LNP that markedly improves efficacy for systemically administered RNAi therapeutics with effective doses for gene silencing at approximately 0.1 mg/kg. We believe that these LNPs achieve a new benchmark for the systemic delivery of RNAi therapeutics.”

The new research findings presented at the meeting include the following:

• in vitro data on the selectivity of PCSK9-specific siRNAs (or small interfering RNAs, the molecules that mediate RNAi), with no apparent silencing of likely off-target genes within the same cell line;

• in vivo rodent data on novel LNPs, showing improved efficacy with an approximately 50% gene silencing effect at doses of approximately 0.1 mg/kg;

• in vivo rodent data on sustained durability for PCSK9 silencing with reduction in total cholesterol levels of approximately 50% using an optimized maintenance dosing regimen; and,

• in vivo non-human primate data showing the absence of any measurable decrease in HDL cholesterol with PCSK9 RNAi therapeutics.

Alnylam expects to file one additional investigational new drug (IND) application in 2009 from its development pipeline, with candidates including ALN-PCS, ALN-HTT for the treatment of Huntington’s disease, and ALN-TTR for the treatment of transthyretin (TTR) amyloidosis.