Sep 17, 2007 Press Release for Alnylam

Alnylam and Collaborators Publish New Research on the In Vivo Mechanisms for Systemic Delivery of RNAi Therapeutics

Sep 17, 2007

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sept. 17, 2007--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication of a study in the journal Nature Biotechnology by Alnylam and scientific collaborators from the Swiss Federal Institute of Technology (ETH) related to mechanisms for in vivo delivery of small interfering RNAs (siRNAs), the molecules that mediate RNAi. In the study, lipid-conjugates of siRNAs that facilitate in vivo systemic delivery (Soutschek et al., Nature 432, 173-178 (2004)) were found to associate with circulating lipoprotein particles and to achieve cellular uptake through receptors for low-density lipoproteins (LDL) and high-density lipoproteins (HDL), in addition to the mammalian homologue for a channel-like cell surface protein that mediates transport of siRNAs in nematodes and fruit flies.

"The discovery of specific uptake mechanisms for systemic delivery of RNAi therapeutics points to the opportunity of targeting siRNAs to cell types and tissues of interest in a rational manner," said Markus Stoffel, M.D., Ph.D., Professor for Metabolic Diseases at the Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) in Zurich. "We believe that these findings may lead to the design and optimization of siRNA conjugates that can facilitate simple, selective, and efficient delivery of RNAi therapeutics for multiple clinical applications."

In the new study (Wolfrum et al., Nature Biotechnology advance online publication, 16 September 2007 (doi:10.1038/nbt1339)) lipid-conjugates of siRNAs were found to associate with circulating LDL and HDL particles and to mediate their tissue biodistribution and cellular uptake in a manner dependent on certain LDL and HDL receptors, the LDL receptor (LDL-R) and the scavenger receptor class B, type 1 (SR-B1), respectively. Further, data were obtained demonstrating that LDL-R- and SR-B1-mediated delivery also required the mammalian homologue of the previously described Caenorhabditis elegans and Drosophila melanogaster siRNA transport gene called "systemic RNAi deficient-1" or SID-1 (Feinberg and Hunter, Science 301, 1545-1547 (2003)). These specific mechanisms for siRNA delivery were observed with multiple siRNA conjugates, including cholesterol-conjugated siRNAs. This is the first study to demonstrate a potential role for SID-1 in the systemic delivery of RNAi therapeutics in mammals.

"Delivery of siRNAs remains the most important objective in our efforts to bring RNAi therapeutics to patients with the broadest applications. These new findings on the involvement of LDL-receptor, HDL-receptor, and especially the channel-like cell surface protein SID-1 for specific cellular uptake of siRNAs may prove critical to our ongoing efforts to optimize delivery of RNAi therapeutics," said Victor Kotelianski, M.D., Ph.D., Vice President of Research for Alnylam.

"In addition to our efforts on liposomal delivery and other technologies, these new findings highlight siRNA conjugates as a very attractive technology for the advancement of RNAi therapeutics from the laboratory to the clinic," said Muthiah Manoharan, Ph.D., Vice President of Drug Discovery for Alnylam.

About RNA Interference (RNAi)

RNAi 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 influenza, hypercholesterolemia, and liver cancers, amongst other diseases. 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 Merck, Medtronic, Novartis, Biogen Idec, and Roche. The company, founded in 2002, maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including statements with respect to the design of a new class of siRNA conjugates the possibility of targeting siRNAs to specific cell types and tissues in a rational manner and the use of siRNA conjugates in advance of RNAi therapeutics, 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: our approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; our ability to attract and retain highly qualified employees; obtaining, maintaining and protecting intellectual property utilized by our products; our ability to enforce our patents against infringers and to defend our patent portfolio against challenges from third parties; our ability to obtain additional funding to support our business activities; our dependence on third parties for development, manufacture, marketing, sales and distribution of products; the successful development of Alnylam's product candidates, all of which are in early stages of development; obtaining regulatory approval for products; competition from others using technology similar to ours and others developing products for similar uses; our dependence on collaborators; and our short operating history; as well as those risks more fully discussed in the "Risk Factors" section of our most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing its views as of any subsequent date. Our does not assume any obligation to update any forward-looking statements.

CONTACT: Alnylam Pharmaceuticals, Inc.
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SOURCE: Alnylam Pharmaceuticals, Inc.