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Alnylam and Collaborators Present New Pre-Clinical Research Findings on RNAi Therapeutics Targeting PCSK9, a Genetically Validated Regulator of LDL Metabolism

New Data Include Use of Novel Lipid Nanoparticles with Markedly Improved Potency, Achieving a New Benchmark for Systemically Delivered RNAi Therapeutics

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun 18, 2009 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today 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. “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 measureable decrease in HDL cholesterol with PCSK9 RNAi therapeutics.

“I am very encouraged by these new data, which offer further support for an RNAi therapeutic strategy of targeting PCSK9 for the treatment of hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. “An RNAi therapeutic targeting this genetically validated gene has the potential to rapidly and durably lower LDL cholesterol, while preserving HDL cholesterol, and may also function synergistically with statins for the treatment of hypercholesterolemia.”

Human genetic studies have correlated increased levels of PCSK9 with an increased risk of cardiovascular disease (Abifadel et al., Nature Genetics, 34 (2): 154-6; 2003). Conversely, human genetic studies have confirmed a nearly 88% reduced risk of cardiac events in subjects with decreased levels of PCSK9 (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006). Alnylam is developing ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-PCS is a systemically delivered RNAi therapeutic comprised of an optimized siRNA encapsulated in an LNP.

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.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko Kirin. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington's disease, and TTR amyloidosis. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA-based therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to Alnylam's approach to discover and develop novel drugs, including ALN-PCS, which is unproven and may never lead to marketable products as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.

Contact: Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
Yates Public Relations
Kathryn Morris (Media), 845-635-9828

Posted: June 2009