Alnylam Reports Pre-clinical Progress with RNAi Therapeutics in Neurological Disease

Alnylam Reports Pre-clinical Progress with RNAi Therapeutics in Neurological Disease

- New Paper in Human Molecular Genetics Demonstrates Normalization of Cellular Function with RNAi Therapeutic Targeting Mutant Gene for Dystonia -

CAMBRIDGE, Mass., Feb 07, 2008 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the publication of new research in the journal Human Molecular Genetics. The new study, performed in collaboration with scientists Xandra Breakefield, Ph.D., Bakhos Tannous, Ph.D., and Jeffrey Hewett, Ph.D., from Massachusetts General Hospital, describes the silencing of a key gene implicated in early onset torsion dystonia, known as mutant torsinA. Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal posture. Early onset torsion dystonia affects approximately 1 in 30,000 - 300,000 persons and, in certain ethnic populations, is prevalent at a frequency of 1 in 10,000.

"We are excited by these new data which demonstrate the ability of RNAi therapeutics to readily discriminate between a disease target of interest, such as mutant torsinA, and a closely related gene, such as wild-type torsinA, thereby providing an important approach for the treatment of genetic disorders," said Dinah Sah, Ph.D., Senior Director of Research at Alnylam. "We are encouraged by these results, as well as results we have seen to date with our other neurological RNAi therapeutic programs, such as Huntington's disease, Parkinson's disease, and others."

Patients with early onset torsion dystonia have a single copy of the wild-type torsinA gene and a single copy of the mutant torsinA gene. TorsinA is implicated in the cellular processing of proteins through the secretory pathway and this cellular function is disrupted by mutant torsinA. The newly published data (Hewett et al., Human Molecular Genetics Advance Access published February 7, 2008 doi:10.1093/hmg/ddn032) show that an siRNA potently and selectively silenced mutant torsinA in vitro, with no effect on the wild-type torsinA gene. The silencing of mutant torsinA by siRNA resulted in normalization of protein secretion. In contrast, siRNAs that suppress both the mutant and normal torsinA genes were not effective in restoring protein secretion, and in fact further impaired secretion. These findings demonstrate that selective inhibition of the mutant torsinA gene only is critical for treatment of dystonia, and that such an approach may be possible with RNAi therapeutics.

About RNA Interference (RNAi)

RNAi (RNA interference) 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 which 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 a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. 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. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including our views with respect to the potential for RNAi therapeutics, including using siRNAs to treat neurological diseases, 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: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and Alnylam's short operating history; as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.