Alnylam Submits IND Application for ALN-RSV01, an RNAi Therapeutic for the Treatment of Respiratory Syncytial Virus Infection; Represents First RNAi Therapeutic for Viral Infectious Diseases and Alnylam's Lead Clinical-Stage Program

Business Wire, Nov 1, 2005

CAMBRIDGE, Mass. -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) to initiate a human clinical trial of ALN-RSV01, its proprietary RNAi therapeutic for the treatment of patients with respiratory syncytial virus (RSV) infection. Following clearance of the IND by the FDA, Alnylam plans to initiate a Phase I safety study in healthy adult volunteers, representing the first program the company will have advanced to human clinical trials. Alnylam is also preparing to initiate a Phase I trial in Europe.

"Submission of our IND for ALN-RSV01 is a major milestone towards Alnylam's goal of developing and commercializing RNAi therapeutics to treat important diseases with significant unmet medical need. Pending IND clearance, we expect to initiate human clinical studies by year-end," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam. "ALN-RSV01, our first Direct RNAi program to enter the clinical phase, represents a novel approach for the treatment of RSV. This program is a clear example of the potential for RNAi therapeutics both to target previously 'non-druggable' targets and to treat major infectious diseases."

ALN-RSV01 is believed to be the most advanced RNAi therapeutic for the treatment of infectious diseases caused by a virus. It is also the only RNAi therapeutic known to be in development for the treatment of RSV infection, a major cause of respiratory illness in young children, the elderly and in immune-deficient patient populations.

"Effective antiviral drugs to treat RSV infection, particularly in pediatric populations, are greatly needed as RSV infection is the leading cause of infant hospitalizations in the United States," said John P. DeVincenzo, M.D., Associate Professor of Pediatrics at the University of Tennessee Health Science Center. "Based on the encouraging pre-clinical data for ALN-RSV01, and a novel mechanism of action demonstrating impressive antiviral target specificity, I'm excited about the potential of advancing this promising new therapy into clinical trials."

ALN-RSV01 selectively and potently silences the RSV nucleocapsid 'N' gene. This gene is among the most highly conserved genes in the virus and is essential for RSV replication. Data presented to date show both in vitro and in vivo efficacy of ALN-RSV01 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 scientists have reported completion of GLP toxicology studies for ALN-RSV01 without any significant toxicities being observed.

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 more 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 leading companies including Merck, Medtronic, and Novartis. 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.