Alnylam Presents First Ever Non-Human Primate Data with an RNAi Therapeutic Targeting PCSK9 Showing Significant and Durable Reductions in LDL Cholesterol Levels.

- New Findings for RNAi Therapeutic Targeting PCSK9 Presented at the XVI International Symposium on Drugs Affecting Lipid Metabolism -

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it presented new pre-clinical data from its hypercholesterolemia program at the XVI International Symposium on Drugs Affecting Lipid Metabolism held in New York City, October 4 - 7, 2007. This program is in collaboration with UT Southwestern Medical Center at Dallas and is focused on evaluating new approaches for reducing LDL cholesterol levels using RNAi therapeutics directed to the disease target proprotein convertase subtilisn/kexin type 9, or PCSK9, a target believed to be undruggable with conventional therapeutic strategies.

Alnylam scientists and collaborators presented new non-human primate data demonstrating PCSK9 antagonism with an RNAi therapeutic. Data presented at the meeting include the following:

* in vivo systemic administration of an RNAi therapeutic in non-human primates resulted in efficient silencing of the PCSK9 gene as measured by circulating PCSK9 plasma levels which were reduced by up to 70 percent of pre-dose levels;

* RNAi-mediated gene silencing was associated with rapid reductions in LDL cholesterol ("bad cholesterol") levels by 40 to 60 percent of pre-dose levels;

* reduction in circulating apolipoprotein B (apoB) levels - a constituent of the LDL particle - by 30 to 40 percent of pre-dose levels were also demonstrated;

* after a single intravenous injection, which was well tolerated in these studies, the RNAi therapeutic showed a durable biological effect with levels of LDL cholesterol decreased for up to three weeks; and

* therapeutic efficacy was observed with an overall decreased ratio of total cholesterol to HDL cholesterol ("good cholesterol") - a result which has been shown in humans to correlate with clinical benefit.

"We are very excited about the significance of these findings, which show for the first time a strong effect for acutely and durably improving cholesterol levels by antagonizing PCSK9 with an RNAi therapeutic in non-human primates," said Victor Kotelianski, M.D., Ph.D., Vice President for Research at Alnylam. "Although PCSK9 is well validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. It is gratifying to have obtained non-human primate efficacy data within one year of initiating our PCSK9 program, a clear positive for drug discovery efforts on RNAi therapeutics."

PCSK9 is an important gene involved in the metabolism of LDL cholesterol. The normal role of the PCSK9 protein is to break down the cell surface receptor for LDL; when there is less PCSK9 protein, there is more receptor on the cell surface to remove LDL from the bloodstream. In human studies, researchers at UT Southwestern Medical Center at Dallas have discovered that mutant forms of PCSK9 that have increased activity are linked with a familial form of hypercholesterolemia. Conversely, recent research published in the New England Journal of Medicine (N. Engl. J. Med. 354, 1264-1272, 2006) has demonstrated that other mutations in humans, including those that lower PCSK9 function, are associated with decreased cholesterol levels and an 88 percent risk reduction in cardiovascular disease.

"There is a clear unmet medical need for novel agents that can lower LDL cholesterol, and PCSK9 appears to be an excellent target for disease intervention in hypercholesterolemia," said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center at Dallas. "Based on its novel mechanism of action and pre-clinical data to date, an RNAi therapeutic targeting PCSK9 has the potential to lower LDL cholesterol, while possibly functioning synergistically with statins in the treatment of hypercholesterolemia."

Alnylam is developing ALN-PCS01, an RNAi therapeutic targeting PCSK9, for the treatment of hypercholesterolemia; ALN-PCS01 is a systemically delivered RNAi therapeutic comprised of an optimized small interfering RNA (siRNA) encapsulated in a cationic liposomal nanoparticle formulation. Alnylam expects to file one investigational new drug (IND) application this year from its portfolio of systemically delivered RNAi therapeutic programs, which include ALN-PCS01 and ALN-VSP01, an RNAi therapeutic for the treatment of liver cancers and potentially other solid tumors. As these are Alnylam's first systemic delivery programs, the timing of this IND will depend on many development efforts, including the results of GLP toxicology studies, which are currently ongoing.

In addition, at the International Symposium Third Annual Meeting of the Oligonucleotide Therapeutics Society held October 4-6, 2007 in Berlin, Alnylam scientists presented an overview of the company's development programs, including its lead program, ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection. ALN-RSV01 is in a Phase II trial to evaluate its safety and anti-viral efficacy in an experimental infection model. This blinded, placebo-controlled trial is currently enrolling subjects on schedule and the company goal is to announce top-line results by the end of this year, with complete data from this trial to be presented at a scientific meeting in early 2008.

About RNA Interference (RNAi)

RNAi 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, and 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 influenza, hypercholesterolemia, and liver cancers, among other diseases. 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, and Roche. The company, founded in 2002, maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including the timing for the filing of an investigational new drug application for, and statements regarding the development of, ALN-PCS01 and ALN-VSP01, 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 attract and retain highly qualified employees; 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 Alnylam's 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 quarterly 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.