Alnylam Accelerates RSV Infection Program and Provides Update on AMD Program; Rapid Progress with RSV Program Supports IND Filing by Year End.

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today updated its product pipeline guidance for the remainder of 2005. The company now expects to file an investigational new drug (IND) application for ALN-RSV01, its proprietary RNAi therapeutic candidate for RSV infection, with the Food and Drug Administration (FDA) by the end of the year, rather than in the first half of 2006 as previously forecast. In addition, given the reported efficacy in recent Phase III studies from competing drugs targeting vascular endothelial growth factor (VEGF) for the treatment of age-related macular degeneration (AMD), the company has made a strategic business decision to suspend further development of ALN-VEG01, its RNAi therapeutic candidate targeting VEGF for AMD, in order to allocate resources to other product opportunities.

"Our RSV program continues to generate compelling pre-clinical data, as was presented Sunday by Alnylam scientists at the RSV Symposium 2005," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "There exists a significant unmet medical need for novel therapies to effectively treat patients infected with RSV, and we are pleased to report that, based on the tremendous progress we have made with this proprietary program, we are able to move our therapeutic candidate into human clinic trials ahead of schedule. Based on our interactions with regulatory authorities we believe we have a clear path forward to conduct a Phase I safety study."

"We have also made an important business decision to put the development of ALN-VEG01, part of our Merck ocular collaboration, on hold," continued Dr. Maraganore. "ALN-VEG01 had been expected to advance into Phase I clinical trials in the second half of 2005. With the increasingly competitive landscape for VEGF-targeting AMD therapeutics on the market and in late-stage human trials, we have made the strategic decision to allocate resources to higher-value product opportunities, such as ALN-RSV01. However, Alnylam and Merck continue to work together on the discovery of other RNAi therapeutics for the treatment of ocular disease."

At the RSV Symposium 2005, held recently in the UK, Alnylam researchers reported that ALN-RSV01 selectively and potently silences the highly conserved RSV N gene, which encodes a previously non-druggable protein target required for viral replication. Data presented show both in vivo and in vitro efficacy in pre-clinical animal studies. Intranasally delivered ALN-RSV01 specifically inhibits RSV replication in animals and is active in the prevention and treatment of RSV infection. Additionally, Alnylam reported that the in-life phase of IND-enabling GLP toxicity studies of ALN-RSV01 has been completed with no significant toxicities seen to date. The abstract, titled "siRNA intervention strategies for Respiratory Syncytial Virus Infection" was awarded 'Best Abstract' of the symposium by committee organizers.

The Company is reiterating its financial guidance that it will end the year with greater than $75 million in cash, and remains on track to announce its third development program by year-end.

About Respiratory Syncytial Virus (RSV)

RSV is a highly contagious virus that causes repeated infections in both the upper and lower respiratory tract. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems and others. RSV infection typically results in cold-like symptoms but can lead to more serious respiratory illness such as croup, pneumonia, bronchiolitis, and, in extreme cases, death. RSV infection in the pediatric population accounts for greater than 100,000 hospitalizations per year in the United States. The development of childhood asthma is also known to occur after childhood RSV infection. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.

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 a breakthrough in biology known as RNA interference, or RNAi. The company, founded in 2002 by scientific pioneers in the field of RNAi, maintains a leadership position in fundamental patents, technology, and know-how relating to RNAi. Alnylam is applying its expertise in RNAi to address multiple therapeutic opportunities that cannot effectively be addressed with small molecules or antibodies, the two current major classes of drugs. The company's expertise in designing and optimizing RNAi therapeutics has enabled Alnylam to form major alliances with top-tier companies including Merck and Medtronic. The company's global headquarters are in Cambridge, Massachusetts, with an additional operating unit in Kulmbach, Germany. For more information, please visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning our future expectations, plans and prospects, and projections regarding the amount of cash we will have available in the future, 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 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; obtaining, maintaining and protecting intellectual property utilized by our products; 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 Form 10-Q filed 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.