Alnylam Announces Publication of Pre-clinical Results with an RNAi Therapeutic for the Treatment of Huntington's Disease

Alnylam Announces Publication of Pre-clinical Results with an RNAi Therapeutic for the Treatment of Huntington's Disease

- Data Show Broad CNS Distribution and Robust Therapeutic Silencing of Gene Responsible for Huntington's Disease -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - 新聞), a leading RNAi therapeutics company, announced today the publication of promising pre-clinical results in Experimental Neurology (doi:10.1016/j.expneurol.2011.11.020) related to its ALN-HTT program, an RNAi therapeutic drug-device combination for the treatment of Huntington's disease.

The findings - the result of a research partnership between Alnylam and Medtronic, Inc., and supported by CHDI - demonstrate that a small interfering RNA (siRNA) targeting the huntingtin gene, when administered by intrastriatal infusion with convection-enhanced delivery (CED), results in widespread distribution of the siRNA and significant silencing of the huntingtin mRNA throughout the striatum. Furthermore, administration of the RNAi therapeutic was well tolerated in these studies. The authors of the paper include researchers from Alnylam, Medtronic, and the University of Kentucky where the work was conducted.

"These published data represent important advancements in our Huntington's disease program across multiple dimensions. Indeed, these pre-clinical results extend our earlier reported data on siRNA biodistribution in the central nervous system and the degree and scope of therapeutic huntingtin gene silencing. We are also encouraged by the safety results following continuous intrastriatal infusion over approximately one month in this pre-clinical model," said Dinah Sah, Ph.D., Vice President, Research, at Alnylam. "In aggregate, these studies, which were performed in collaboration with the University of Kentucky, support our continued and combined efforts with Medtronic and CHDI to advance this important research effort."

The new pre-clinical studies employed direct delivery of the huntingtin-specific siRNA to the striatum using an implantable infusion system and CED. Direct delivery to the central nervous system (CNS) by intrastriatal CED for seven days resulted in broad distribution of the siRNA across the striatum and surrounding brain regions. This level of distribution of the siRNA resulted in the silencing of the huntingtin gene throughout the putamen by an average of approximately 45 percent, as well as reductions in the levels of huntingtin protein when evaluated by immunohistochemistry. This silencing of huntingtin occurred in a manner dependent on infusion rate and siRNA concentration.

A new pre-clinical model developed from these findings suggests that continuous CED of an siRNA targeting huntingtin has the potential to achieve physiologically significant coverage of the striatum of Huntington's disease patients with therapeutically relevant drug levels.

"We are very pleased with these early results in our research collaboration, which continues to represent an exciting opportunity to combine an innovative therapeutic strategy with state-of-the-art drug device delivery technology for Huntington's disease. A highlight of this study is that the pre-clinical results suggest scalability of RNAi therapeutic delivery to the striatum of Huntington's patients," said Gregory Stewart Ph.D., Distinguished Scientist, CNS Drug Therapy R&D at Medtronic. "The collaboration between Alnylam, Medtronic and CHDI marks an important effort to develop a novel treatment strategy for this devastating neurodegenerative disease."

This research was done in collaboration with the laboratory of Professor Don M. Gash, Ph.D. at the University of Kentucky College of Medicine in Lexington, Kentucky. Some of these findings have been previously presented at the 2009 World Congress on Huntington's Disease.

"These findings demonstrate the potential of RNAi therapeutics for the treatment of neurodegenerative diseases, and in particular, intraparenchymal CNS delivery of therapeutics as an important approach to drug delivery," said Professor Don M. Gash, Ph.D. at the University of Kentucky College of Medicine. "We look forward to the continued efforts in advancing this therapeutic approach to patients with Huntington's disease."

About Huntington's Disease

Huntington's disease is an autosomal dominant neurodegenerative genetic disorder that causes motor, cognitive, and behavioral dysfunction. It is estimated that 120,000 people in the U.S. have the genetic mutation that causes Huntington's disease and will experience symptoms during a normal lifetime. The average lifespan for patients after onset of motor dysfunction is approximately 10 to 20 years. There are currently no disease-modifying therapies available to slow the progression of Huntington's disease.

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. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific 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 leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and ALN-APC for the treatment of hemophilia. As part of its "Alnylam 5x15TM" strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntington's disease. The company's leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and Sanofi. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam's VaxiRNATM platform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, statements regarding Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-HTT, and Alnylam's expectations regarding its "Alnylam 5x15" product strategy, 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, without limitation, Alnylam's ability to discover and develop novel drug candidates, successfully demonstrate the efficacy and safety of its drug candidates, including ALN-HTT, in pre-clinical and human clinical trials, the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates, and Alnylam's ability to establish and maintain strategic business alliances, and new business initiatives, 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.