Alnylam Publishes Pre-Clinical Research On Direct CNS Delivery Of RNAi Therapeutics

Main Category: Neurology / Neuroscience
Also Included In: Multiple Sclerosis
Article Date: 31 Dec 2008 - 1:00 PDT

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Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has published data in the journal Oligonucleotides demonstrating robust silencing of an endogenous oligodendrocyte gene with small interfering RNAs (siRNAs), the molecules that mediate RNAi, when administered by direct delivery to the central nervous system (CNS) in both rats and non-human primates.

"These data extend the successful delivery of siRNAs in vivo to an important additional cell type within the CNS," said Dinah Sah, Ph.D., Vice President, Research, CNS, and Oncology of Alnylam. "While previous studies have shown successful CNS delivery of siRNAs in neurons, this published study shows robust RNAi silencing of oligodendrocyte-specific genes. These findings suggest potential therapeutic applications for RNAi therapeutics in certain diseases demonstrating oligodendrocyte pathology such as progressive multifocal leukoencephalopathy (PML), multiple sclerosis, and cerebral palsy."

"This paper is a yet another proof point of our continued commitment to scientific excellence and also another example of Alnylam's scientific leadership in the RNAi therapeutics field," said Jack Schmidt, M.D., Chief Scientific Officer of Alnylam. "Indeed, this is the fourteenth paper Alnylam has published in 2008, well exceeding our goal of ten or more scientific papers published in peer-reviewed journals this year."

The research (Querbes et al. Oligonucleotides 18 December 2008; DOI: 10.1089/oli.2008.0165) conducted by Alnylam scientists, some of which was presented at the Keystone RNAi meeting earlier this year, demonstrated that in vivo silencing of an endogenous oligodendrocyte-specific gene by an RNAi therapeutic was dose dependent, durable, and mediated by an RNAi mechanism. Specifically, the data showed that:

-- siRNAs administered in a rodent model achieved successful delivery and silencing of an endogenous oligodendrocyte gene target (2′,3′-cyclic nucleotide 3′-phosphodiesterase or "CNPase") in a specific manner as compared with a control siRNA;

-- direct CNS delivery of siRNA in the rodent model silenced the CNPase mRNA by approximately 75 percent, as compared with a control siRNA, and was durable for up to one week;

-- increasing the infusion rate increased the distribution of CNPase mRNA suppression in white matter regions distant from the infusion site;

-- CNPase silencing was mediated by an RNAi mechanism as measured by 5'RACE; and,

-- direct infusion of an siRNA into the CNS in a non-human primate model resulted in silencing of the CNPase mRNA by 55 percent.

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 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, and Kyowa Hakko. 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 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, please visit http://www.alnylam.com.

Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam's future expectations, plans and prospects, 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 the company's ability to successfully research and develop products, 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.