Alnylam and Yale University Scientists Demonstrate Therapeutic Silencing of Disease Target Associated with Acute Lung Injury Using RNAi.

Findings Published in Nature Medicine Show Potential for RNAi Therapeutic Targeting Angiopoietin 2

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today publication of data demonstrating that an RNAi therapeutic can silence angiopoietin 2 (Ang2), a key mediator in acute lung injury. In a paper published today in Nature Medicine, scientists from Yale University and Alnylam demonstrated inhibition of acute lung injury and cell death in animals with administration of small interfering RNAs (siRNAs), the molecules that mediate RNAi, targeting Ang2. These in vivo data showed silencing of Ang2 in the lung, and contribute to existing data demonstrating the potential for developing RNAi therapeutics that target diseases associated with the lung, such as respiratory syncytial virus (RSV) infection, influenza, and asthma.

"These results showed that we were able to design and synthesize siRNAs that, following pulmonary delivery in vivo, effectively silence Ang2, a very important target associated with acute lung injury," said Antonin de Fougerolles, Ph.D., Senior Director, Research at Alnylam and an author of the study. "The findings demonstrate a critical role for Ang2 in the pathogenesis of hyperoxic acute lung injury, and that silencing the Ang2 gene with RNAi may be therapeutically relevant."

The study published in Nature Medicine demonstrated that acute lung injury caused by cell death, high and potentially toxic concentrations of oxygen (hyperoxia), and the resulting excess fluid in the lungs (pulmonary edema), may be controlled by the Ang2 protein. Data showed that local intranasal administration in mice of an siRNA targeting Ang2 resulted in specific inhibition of messenger RNA (mRNA) by more than 60 percent. A proportionate drop in Ang2 protein levels was also observed. In addition, acute lung injury was reduced to near non-injury levels as measured by statistically significant reductions in lung inflammation and cell death. Importantly, mRNA levels of other genes were not affected by administration of the siRNA, including VEGF, Bcl-2 and [eth]-actin. The study was performed in the laboratory of Jack Elias, M.D., Chair of Internal Medicine at Yale University School of Medicine.

"Through this study, we have learned that Ang2 seems to be a mediator of cell death in the settings of high oxygen concentrations in the lung causing acute lung injury and pulmonary edema," said Dr. Elias. "In applying an RNAi approach, we were able to observe in mice that silencing of the Ang2 protein resulted in animals that lived longer and had evidence of decreased lung injury compared to animals with the protein intact."

"We are pleased with the leadership our scientists and collaborators have consistently demonstrated in pointing to the significant potential for RNAi therapeutics," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "Our commitment to scientific excellence through publication of RNAi therapeutic data in the world's top journals highlights what we believe are the industry's leading capabilities to translate the discovery of RNAi into a new class of innovative medicines."

About Angiopoietins

Angiopoietins are a type of growth factor that plays a key role in the angiogenic response whereby proteins stimulate the formation and maturation of blood vessels. Vascular endothelial growth factor (VEGF) stimulates growth of new immature leaky blood vessels. Angiopoietins 1 and 4 (Ang1 and Ang4, respectively) enhance angiogenesis by inducing vascular maturation and decreasing vascular permeability. Ang2 destabilizes blood vessels, enhances vascular leak and antagonizes Ang1 and Ang4. Ang2 can induce apoptosis in endothelial cells in the absence of other angiogenic stimuli. Beyond its role in the pathogenesis of acute lung injury and pulmonary edema, Ang2 has also recently been shown to play an important role in inducing inflammation and may also contribute to vascular leak in sepsis.

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 with respect to the potential for RNAi therapeutics, including therapeutics that silence Ang2 and/or treat RSV infection, influenza, asthma, and acute lung injury, 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.