Alnylam and Collaborators Present Pre-Clinical Data for RNAi Therapeutics for the Treatment of Respiratory Diseases Including Pandemic Influenza; Results Include Data on Anti-viral Activity of RNAi Therapeutics toward H5N1 Virus.

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it presented pre-clinical data at the American Thoracic Society (ATS) International Congress being held in San Diego, California, from May 19 - 24, 2006. Alnylam and its collaborators presented new data from several ongoing respiratory disease programs including pandemic flu, asthma, chronic obstructive pulmonary disorder (COPD), and idiopathic pulmonary fibrosis (IPF).

At the ATS meeting Alnylam presented pre-clinical data on identification of small interfering RNAs (siRNAs), the molecules that mediate RNAi, that demonstrate potent anti-viral activity across multiple strains of flu. In particular, Alnylam scientists and collaborators demonstrated in vitro anti-viral activity toward a human clinical isolate of the H5N1 virus. These potent effects toward H5N1 were achieved with multiple siRNAs that also showed anti-viral activity toward other flu strains. The Alnylam pandemic flu program, in collaboration with Novartis, is focused on the development of RNAi therapeutics targeting sequences that are common to all flu genomes, including those of avian origin such as the H5N1 strain.

"We and our collaborators are committed to exploring novel therapeutics for the treatment of many respiratory diseases," said Antonin de Fougerolles, Ph.D., Senior Director, Research of Alnylam Pharmaceuticals. "The pre-clinical findings we announced at ATS represent continued progress with our pandemic flu program, as we advance this effort toward the clinic."

Based on these results and other research, Alnylam also announced that its flu drug candidate will include two siRNAs targeting different genes within the influenza virus designed to achieve the broadest spectrum of anti-viral activity, while diminishing the likelihood of viral resistance.

Alnylam's research and development in respiratory diseases include human clinical trials for the company's lead clinical development program for respiratory syncytial virus (RSV). Alnylam recently presented safety results from its Phase I clinical trials with ALN-RSV01, an RNAi therapeutic for the treatment of RSV infection, demonstrating the drug was safe and well tolerated when administered intranasally to adult human volunteers.

"There is significant need for novel therapeutics to effectively treat respiratory viral infections as they are a leading cause of serious disease and mortality worldwide," said Ralph A. Tripp, Ph.D., of the Center for Disease Intervention, Department of Infectious Diseases, at the University of Georgia. "I continue to be encouraged by the progress Alnylam is making in the area of developing RNAi therapeutics for the treatment of these important diseases, such as RSV and pandemic flu."

Additional Alnylam Respiratory Disease R&D Presented at ATS

Asthma and Chronic Obstructive Pulmonary Disorder (COPD)

At the ATS meeting, Professor Maria Belvisi of the Respiratory Pharmacology Group, Airway Disease Section at Imperial College, in collaboration with Alnylam scientists, provided an update on research on RNAi therapeutics for the treatment of asthma and COPD. Pre-clinical studies in an inflammatory lung disease animal model demonstrated that respiratory delivery of an siRNA targeting IKK2 (also known as IKK-beta), a gene involved in inflammatory responses, can achieve potent in vivo silencing of the target gene in the lung. In addition, results showed robust silencing of the expression of pro-inflammatory cytokines such as TNF-alpha and IL-1beta. In vitro optimization of siRNAs targeting IKK2 was achieved, and siRNAs were generated that demonstrated robust and specific inhibition of IKK2 mRNA and protein, with no effects on a related family member, IKK1 (also known as IKK-alpha). These results offer the possibility of designing an RNAi therapeutic that is able to both selectively and locally inhibit IKK2 activity in lung for the treatment of respiratory diseases, such as asthma or COD.

Idiopathic Pulmonary Fibrosis (IPF)

At the ATS meeting, Alnylam collaborator Dr. Oliver Eickelberg of the University of Giessen Lung Center (UGLC) provided an update on the local delivery of siRNAs for the treatment of IPF, a pulmonary fibrotic disorder of unknown causes that can lead to death. In IPF, fibrotic scarring leads to loss of lung volumes, diminution in alveolar number and function with resulting reduced oxygen transfer. In this collaboration, funded by the BMBF (German Federal Ministry of Education and Research) under the Innovative Medicines program, lead siRNAs targeting multiple members of the TGF-beta pathway have been identified and are being evaluated in animal models of IPF.

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, and Novartis. 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 plans with respect to the discovery and development of an RNAi therapeutic for pandemic influenza or respiratory diseases and our views with respect to the potential for RNAi therapeutics, including an RNAi therapeutic for pandemic influenza or a respiratory disease, 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; 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 our products; the successful development of products, 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 "Certain Factors That May Affect Future Results" 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. We do not assume any obligation to update any forward-looking statements.