First In Vivo Demonstration of RNA Interference via Systemic Delivery is Published by Alnylam Scientists

Nov 10,2004

CAMBRIDGE, Mass., Nov. 10 /PRNewswire-FirstCall/ -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading therapeutic RNA interference (RNAi) company, today announced the first in vivo demonstration ever published of RNAi-mediated gene silencing in mammals by a method that potentially can be applied to systemic RNAi therapeutics for human disease. The research, published in Nature, represents a significant advance in the development of systemic RNAi therapeutics. Systemic delivery through the bloodstream potentially enables RNAi therapeutics to target virtually any gene involved in the cause of human disease, opening up the prospect for broad application of RNAi therapeutics to treat a wide range of diseases.

In the published research, Alnylam scientists demonstrated in vivo silencing of the gene for apolipoprotein B (apoB), a protein involved in cholesterol metabolism, and a consequent reduction in blood cholesterol levels. This was achieved using a specially engineered short interfering RNA (siRNA) that was given intravenously by a clinically relevant route of administration. siRNAs are the molecules within cells that trigger RNAi. To enable the synthetic siRNA used in the study to reach and enter appropriate cells, this siRNA incorporated proprietary chemical modifications designed to provide it with "drug-like" properties. Intravenous injection of the modified siRNA into mice resulted in silencing of apoB messenger RNA (mRNA) in liver and intestine, and reduced blood levels of both apoB protein and total cholesterol. In parallel experiments, the ability of siRNAs to silence the human apoB gene in a transgenic mouse model was also demonstrated. The apoB gene is highly relevant clinically and to date has not been amenable to targeting with traditional small molecule, protein, or antibody therapies.

"We have meaningfully advanced the field of RNAi in this first ever demonstration of RNAi mediated by systemically delivered siRNAs, providing tangible evidence of the broad potential for RNAi therapeutics," said Hans- Peter Vornlocher, Ph.D., Vice President of Research at Alnylam Europe AG. "We are excited that our research progress has been recognized by the prestigious journal Nature, as Alnylam continues our leading-edge therapeutic research to harness RNAi for a whole new class of medicines."

In this robust and well controlled study, Alnylam scientists generated the first in vivo evidence that a siRNA triggers RNAi-mediated degradation of its target mRNA in mice. Specific cleavage of the apoB mRNA at the predicted site was demonstrated, using sophisticated analytical methods. This confirmation of the specific mechanism of action of siRNAs reinforces their therapeutic potential to harness the natural catalytic process of RNAi for the treatment of disease.

"This significant research is a major step forward as we seek to develop systemic RNAi therapeutics for the broad-based application of RNAi to important diseases such as cardiovascular disease, diabetes, obesity, hepatitis, cancer, and many infectious diseases," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam Pharmaceuticals. "Alnylam remains committed to applying our scientific expertise and proprietary technologies to advance both direct and systemic applications of RNAi, including the continued improvement of systemic RNAi technology for human therapeutics."

Conference Call Information
Alnylam will discuss these results during its regularly scheduled earnings conference call, which will take place today, November 10, 2004, at 4:30 pm EST. The call may be accessed by dialing 800-260-8140 (domestic) or 617-614- 3672 (international) five minutes prior to the start time, and providing the passcode 34345993.

A replay of the call will be available from 6:30 pm EST on November 10, 2004 until November 17, 2004. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the access code 61185381. A live audio webcast of the call will also be available on the "Investors" section of the Company's website, An archived webcast will be available on the Alnylam website approximately two hours after the event, and will be archived for 14 days thereafter.

About RNAi
RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes that is potentially the basis for a new class of therapeutic products. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence and regulate such genes selectively through RNAi could provide a means to treat a wide range of human diseases. The discovery of RNAi has been heralded by many as a major breakthrough, and the journal Science named RNAi the top scientific achievement of 2002, as well as one of the top ten scientific advances of 2003.

About Alnylam
Alnylam is a biopharmaceutical company seeking to develop and commercialize novel therapeutics based on RNA interference, or RNAi. Growing from its foundation as the world's first company focused on RNAi therapeutics, the company's leadership in the field of RNAi is supported by its preeminent founders and advisors and its strengths in fundamental patents, technology, and know-how that underlie the commercialization of RNAi therapeutics. Alnylam is developing a pipeline of RNAi products using Direct RNAi™ to treat ocular, central nervous system, and respiratory diseases and Systemic RNAi™ to treat a broad range of diseases, including oncologic, metabolic, and autoimmune diseases. The company's global headquarters are in Cambridge, Massachusetts. For additional information, please visit

Forward-Looking Statements
Various statements in this release concerning our future expectations, plans, prospects and future operating results 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; 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 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.

SOURCE Alnylam Pharmaceuticals, Inc.

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