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New Findings Published in Nature Biotechnology Demonstrate Use of "Lipidoids" to Achieve Systemic Delivery of RNAi Therapeutics in Multiple Pre-Clinical Models
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication of a new study in Nature Biotechnology by Alnylam scientists and collaborators from the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT). The new research (Akinc et al., Nature Biotechnology advance online publication, 27 April 2008 (DOI:10.1038/nbt1402)) documents the design and synthesis of a new class of lipid-based molecules called "lipidoids", which were used to form novel nanoparticle formulations for systemic delivery of RNAi therapeutics. The results of the studies showed successful delivery of lipidoid formulations of small interfering RNAs (siRNAs), the molecules that mediate RNAi, in multiple animal species including mice, rats, and non-human primates that together demonstrate potent, specific, and durable effects on gene expression in multiple tissues, including liver, lung, and peritoneal macrophages. Further, the new paper demonstrates applications of the same technology for delivery of microRNA (miRNA) antagonists.
"The successful systemic delivery of RNAi therapeutics remains an important objective in our efforts to bring these innovative medicines to patients. We believe that this new research could pave an entirely new path for efficient delivery of RNAi therapeutics in a broad range of clinical applications," said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. "Further, this new work builds on our existing delivery efforts both in-house, and with collaborators including MIT, Tekmira, Protiva, and others."
"It is clear that more efficient delivery of RNAi therapeutics will require the discovery of new biomaterials and formulations. We believe the lipidoids we have developed greatly expand the collection of available delivery materials, and that they hold significant promise as delivery agents for both siRNA and miRNA therapeutics," said Daniel Anderson, Ph.D. of the David H. Koch Institute for Integrative Cancer Research at MIT. "We're excited about this work and optimistic that our continued collaboration with the team of scientists at Alnylam will lead to additional delivery solutions for RNAi therapeutics."
In the new research, Akinc et al. describe the discovery and synthesis of a novel class of lipid-based molecules called "lipidoids". These lipidoids were used to form entirely new formulations of siRNAs, enabling their delivery to a broad range of tissues in vivo. The lipidoid molecules were created through a new combinatorial synthesis scheme that allows for simple, high-speed production. The rapid synthesis enables the development of a large library of over 1,200 structurally diverse lipidoids, which can ultimately be customized for different RNAi therapies and drug delivery approaches. In an exclusive license agreement with MIT, Alnylam has secured all rights to the lipidoid technology for delivery of RNAi therapeutics for all uses.
In the study, researchers described the discovery of lipidoids and evaluated the delivery of lipidoid formulations with siRNA and anti-miRNA oligonucleotides in multiple animal species including mice, rats, and non-human primates. The lipidoid formulations demonstrated potent, specific, and durable effects on gene expression in multiple tissues, including liver, lung, and peritoneal macrophages. Specifically:
* in rats, significant, dose-dependent reductions in liver Factor VII mRNA levels were observed, with > 90% silencing at 5 mg/kg doses;
* in non-human primates, silencing of apolipoprotein B (apoB) mRNA was observed in a dose-dependent manner, with maximal silencing of apoB liver mRNA of up to 85% corresponding to a maximal reduction in serum apoB reduction of up to 74% relative to pre-dose levels; and
* in non-human primates, the effects were found to be durable where a single intravenous injection lasted for up to four weeks.
Further, the lipidoid formulations also proved effective for delivery of anti-miRNA oligonucleotides or "antagomirs" that are used to suppress miRNA activity. Also, the delivery technology was used to successfully deliver two different siRNAs at the same time, with no apparent competition between the two siRNAs, demonstrating the potential of a multi-targeting strategy for formulations of RNAi therapeutics.
Alnylam has established multiple industry and academic collaborators in an effort to address delivery of RNAi therapeutics in a comprehensive and systematic manner. In May 2007, Alnylam announced a collaboration with the David H. Koch Institute for Integrative Cancer Research at MIT. As part of this collaboration, Alnylam is sponsoring a five-year research program focused on the delivery of RNAi therapeutics with the exclusive option to license future RNAi technology resulting from the research sponsorship. Additionally, Alnylam has an agreement with Tekmira Pharmaceuticals Corporation related to Tekmira's planned business combination with Protiva Biotherapeutics, Inc. Upon the effective date for the Tekmira-Protiva transaction, the new agreement will expand Alnylam's access to key technology and intellectual property for the delivery of RNAi therapeutics with liposomal delivery technologies.
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, Inc.
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.
About the Koch Institute
The MIT Center for Cancer Research (CCR) has changed its name to the David H. Koch Institute for Integrative Cancer Research at MIT (Koch Institute – pronounced “coke”) effective March 2008. This name change is linked to generous funding received in support of the creation of a new building and endeavor, to be completed by the year 2010, to house expanded and innovative cancer research at MIT. Note that all CCR facilities and faculty members have been incorporated into the Koch Institute.
Alnylam Forward-Looking Statements
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 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 annual report on Form 10-K 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.
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Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Yates Public Relations
Kathryn Morris, 845-635-9828
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