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

– Data in Non-Human Primates Show Potent Reductions in LDL Cholesterol Lasting Over One Month After a Single Dose with No Effects on HDL Cholesterol –


CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar 15, 2010 - 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 scientists at the University of Texas Southwestern Medical Center at Dallas. The data were presented at the PCSK9 Conference: From Gene to Therapeutics held in Nantes, France from March 11-13, 2010. Alnylam has an ongoing development program 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 new data demonstrated durable reductions of cholesterol levels in both rodents and non-human primates with an RNAi therapeutic targeting PCSK9 using second generation lipid nanoparticle (LNP) formulations. Further, data also showed the ability to utilize siRNA combination approaches to achieve efficient silencing of separate and distinct genes to achieve cholesterol lowering.


“We are very encouraged by the progress we have made in our development efforts for an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. With an RNAi approach, both intracellular and extracellular PCSK9 levels can be reduced, thereby replicating the human genetics,” said Kevin Fitzgerald, Ph.D., Director of Research at Alnylam. “In addition to the markedly improved potency we demonstrated last year with second generation LNPs, we are now able to show that PCSK9 silencing effects are durable over a remarkably extended period of time. Further, these new data highlight our ability to investigate liver-specific silencing of target combinations in order to develop novel RNAi therapeutics for the treatment of hypercholesterolemia, as well as potentially other metabolic disorders.”


The new in vivo research findings presented at this meeting were performed using a systemically delivered RNAi therapeutic targeting PCSK9 and formulated in a second generation LNP, developed in collaboration with Tekmira Pharmaceuticals Corporation, The University of British Columbia, and AlCana Technologies, Inc. Data from these studies include:




  • in vivo non-human primate data showing durable silencing of PCSK9 for more than 30 days following a single dose administration, with reduction in LDL cholesterol levels of approximately 50%;
  • unlike results reported with monoclonal antibody strategies targeting extracellular PCSK9 (Chan et al., Proc. Natl. Acad. Sci. USA, 106(24): 9820-5, 2009), RNAi-mediated silencing of both intracellular and extracellular PCSK9 resulting in no lowering of HDL (or “healthy”) cholesterol;
  • in vivo rodent data demonstrating the ability to utilize a novel dual-targeting approach to silence PCSK9 and a second undisclosed gene involved in lipid metabolism with a single RNAi therapeutic, resulting in a reduction in total cholesterol of greater than 40%; and,
  • in vivo rodent data showing that injection of multiple siRNAs packaged in a single LNP formulation results in silencing of as many as 10 distinct target genes simultaneously.


“These new data continue to support the development of an RNAi therapeutic strategy of targeting PCSK9 for disease intervention in hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center. “Based on its novel mechanism and promising pre-clinical data observed to date, an RNAi therapeutic targeting PCSK9 has the potential to lower LDL cholesterol while preserving HDL cholesterol, and possibly function synergistically with statins for the treatment of hypercholesterolemia.”


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 a second generation LNP formulation. Alnylam expects to advance its ALN-PCS program toward the clinic with a goal of initiating a Phase I clinical trial in 2011.


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. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington's disease. 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. 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, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-PCS, its plan to initiate a clinical trial ALN-PCS, the timing of regulatory filings, and its expectations regarding the continued development of ALN-PCS, 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 the company's ability to discover and develop novel drug candidates, and successfully demonstrate efficacy and safety of its drug candidates, including ALN-PCS, in human clinical trials, as well as those risks more fully discussed in the “Risk Factors” section of its most recent annual report on Form 10-K 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, 617-551-8207




Amanda Sellers, 202-955-6222 x2597





Posted: March 2010