Alnylam and Medtronic Present New Late-Stage Pre-clinical Data on ALN-HTT, an RNAi Therapeutic for the Treatment of Huntington's Disease

New Data Demonstrate Broad CNS Distribution and Robust Therapeutic Silencing of Gene Responsible for Huntington’s Disease
Continuous 28-Day CNS Infusion of ALN-HTT Found to be Safe and Well Tolerated

VANCOUVER, BC, CANADA | September 15, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and Medtronic, Inc. (NYSE: MDT), the world’s leading developer of medical devices, announced today the presentation of new pre-clinical research findings from their Huntington’s disease program at the 2009 World Congress on Huntington’s Disease held September 12-15, 2009 in Vancouver, British Columbia. Together, the two companies are developing a drug-device combination for the treatment of Huntington’s disease. The drug, ALN-HTT, consists of an RNAi therapeutic targeting huntingtin, the gene responsible for Huntington’s disease, and is delivered to the central nervous system (CNS) using an implantable pump infusion system developed by Medtronic.

The newly presented pre-clinical research, performed in collaboration with Professor Don M. Gash’s laboratory at the University of Kentucky College of Medicine, demonstrate that a small interfering RNA (siRNA) targeting the huntingtin gene achieves broad distribution in the CNS following continuous direct CNS administration. Further, direct delivery to the CNS resulted in robust silencing of the huntingtin gene mRNA, extending previously presented pre-clinical data. This silencing effect was achieved at substantial distances from the infusion site, an important step towards translating this delivery approach from animal models to the larger human brain. Additional pre-clinical studies showed ALN-HTT to be well tolerated following continuous direct CNS administration over a period of approximately one month.

“We are very pleased with these promising results in our Huntington’s disease program, as it continues to represent an exciting opportunity to combine innovative medicines with our state-of-the-art drug device delivery technology in an area of extreme unmet medical need,” said Gregory Stewart Ph.D., Director of CNS Drug Therapy R&D at Medtronic. “With no currently effective disease-modifying therapies for patients afflicted with Huntington’s, the convergence of Alnylam and Medtronic technologies could provide a novel treatment strategy for this devastating neurodegenerative disease.”

The new pre-clinical studies presented at this meeting employed direct delivery of ALN-HTT to the striatum using implantable infusion pumps and convection-enhanced delivery (CED), or continuous infusion under positive pressure. Specifically, the new data showed that direct CNS administration of ALN-HTT resulted in:

* broad distribution of the siRNA across the CNS, including the striatum and surrounding brain regions;
* silencing of the huntingtin gene mRNA by an average of approximately 45% in the putamen following continuous infusion over seven days, as well as reductions in the levels of huntingtin protein as demonstrated by immunohistochemistry;
* silencing of the huntingtin gene messenger RNA (mRNA) in the CNS at significant distances from the infusion site; and,
* a safe and well tolerated profile following continuous infusion over 28 consecutive days, with no clinical abnormalities, neurological behavioral signs, and no clinically significant findings in histopathological examination of the brain.

“We are very excited by our new findings as they represent a major leap forward in our Huntington’s disease program across multiple dimensions,” said Dinah Sah, Ph.D., Vice President, Research, CNS, and Oncology of Alnylam. “Indeed, in our new ALN-HTT research findings, we have extended our earlier data in more advanced pre-clinical studies including key findings on siRNA biodistribution in the CNS, therapeutic silencing of the disease-causing huntingtin gene in a manner supportive of scaled effects for the human brain, and safety assessment following continuous infusion in the CNS over approximately one month. In aggregate, these new studies – which were performed in collaboration with the University of Kentucky, one of the leading academic institutions for research on direct CNS delivery for neurodegenerative diseases – support our continued and combined efforts with Medtronic to advance this important innovation to patients.”

This research was done with the laboratory of Don M. Gash, Ph.D. at the University of Kentucky College of Medicine, whose team is internationally recognized for developing new therapeutic approaches to treating neurodegenerative diseases, and have unparalleled expertise in direct drug delivery to the brain.

In February 2005, Alnylam formed a collaboration with Medtronic to pursue the development of novel drug-device combinations incorporating RNAi therapeutics to treat neurodegenerative disorders. In July 2007, the companies advanced their collaboration on their Huntington’s disease program into development stages, following positive pre-clinical data generated under the initial joint technology development phase of the program. In addition, the agreement was revised as a 50-50 partnership in the United States.

About Huntington’s Disease

Huntington’s disease is an autosomal dominant neurodegenerative genetic disease that afflicts approximately 30,000 patients in the U.S., with an estimated 200,000 additional patients having a 50% risk of developing the disease. The average lifespan for patients after onset is approximately 10 to 20 years. There are currently no effective therapies available for the treatment 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 Medtronic

Medtronic, Inc. (, headquartered in Minneapolis, is the global leader in medical technology – alleviating pain, restoring health and extending life for millions of people around the world.

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 and is partnered with Cubist and Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington’s disease, and TTR amyloidosis. 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, Roche, Takeda, Kyowa Hakko, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 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, 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, please visit

SOURCE: Alnylam Pharmaceuticals, Inc.

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