Alnylam Announces Progress in Pre-clinical Programs at the 36th Annual Society for Neuroscience Meeting.

Encouraging Pre-clinical Data Support RNAi Therapeutic

Strategy for Neurological Diseases

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it presented pre-clinical data at the 36th Annual Society for Neuroscience Meeting being held in Atlanta, Georgia from October 14-18, 2006. Alnylam, in an alliance with Medtronic, Inc., and with its academic collaborators, presented pre-clinical data from four ongoing neurology programs including Huntington's disease, neuropathic pain, Parkinson's disease, and dystonia. Accumulating data show that small interfering RNAs (siRNAs), the molecules that mediate RNAi, can be administered in vitro and in vivo in animal models of neurological diseases to achieve therapeutic silencing of disease-causing genes.

"Data presented at the Society for Neuroscience meeting demonstrate in pre-clinical studies that RNAi provided a highly selective and effective inhibition of disease targets involved in pathologies of the nervous system," said Dinah Sah, Ph.D., Senior Director of Research at Alnylam. "We believe these results support our strategy of advancing RNAi therapeutics to treat serious neurological diseases and reflect the progress that Alnylam and our partners and collaborators are making in developing this promising therapeutic modality for significant unmet medical needs."

Huntington's Disease

In a poster titled "Widespread distribution of siRNAs targeting Huntingtin in the CNS after chronic intrastriatal infusion," Alnylam and Medtronic presented pre-clinical data demonstrating that siRNAs specific for the huntingtin gene, which is mutated in Huntington's disease, were administered in vivo to achieve silencing of the disease-causing gene. In addition, the majority of the siRNAs tested were effective at reducing levels of Huntingtin protein, and in reducing messenger RNA (mRNA) levels by at least 70 percent in cultured cells. Selected siRNAs were also found to be stable in rat cerebrospinal fluid. Additional pre-clinical studies by Alnylam and Medtronic showed that siRNAs administered into the brain were taken up by neurons in the brain region that is most affected in the early stages of Huntington's disease and that the huntingtin gene was silenced significantly in vivo in a relevant brain region after administration of siRNAs designed to target the huntingtin gene. Alnylam believes these findings support further studies of RNAi therapeutics for the treatment of Huntington's disease.

Neuropathic Pain

Alnylam collaborators Dr. Frank Porreca and Dr. Josephine Lai from the University of Arizona presented a poster titled "Small interfering RNA targeting NaV1.8 alleviates experimentally induced chronic pain." Results showed that intrathecal injection of an siRNA targeting NaV1.8, a disease target associated with neuropathic pain, provided more than 75 percent pain relief in a model of chronic inflammatory pain. The silencing of NaV1.8 mRNA was found to be dose-dependent and the siRNAs were found to be stable in cerebrospinal fluid. These in vivo results suggest that siRNAs can be used to silence NaV1.8 and provide pain relief.

Parkinson's Disease

Alnylam has designed and synthesized siRNAs that are specific to the alpha-synuclein gene, a gene associated with Parkinson's disease. In a poster titled "An inducible mouse model of synucleinopathy," collaborators Dr. Matthew Farrer and Dr. Jada Lewis at Mayo Clinic presented in vivo data demonstrating that siRNAs administered into the brain were effective in reducing alpha-synuclein levels. Two complementary methods showed significant lowering of alpha-synuclein mRNA levels in vivo, suggesting the applicability of RNAi therapeutics as a possible disease-modifying therapy for Parkinson's disease.

Dystonia

Alnylam has designed and synthesized siRNAs that are specific to the normal dystonia gene, torsinA, or the mutant form of this gene, which causes a debilitating movement disorder known as dystonia. In a poster titled "Knockdown of torsinA by RNAi decreases secretion of humanized Gaussia luciferase from control fibroblasts," Alnylam collaborator Dr. Xandra Breakefield and colleagues from Massachusetts General Hospital presented in vitro data demonstrating that siRNAs targeting the normal gene were highly effective in cultured cells, lowering torsinA mRNA as well as protein levels. Studies are ongoing to evaluate siRNAs specific for the mutant form of the torsinA gene in culture.

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Alnylam

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 building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. 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 Merck, Medtronic, Novartis, and Biogen Idec. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans, and prospects, including our views with respect to the potential for RNAi therapeutics, including using siRNAs to treat neurological diseases, 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: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; our ability to fund and the results of further pre-clinical and clinical trials; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales, and distribution of products; the successful development of our product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.