New Paper Published in Blood Shows Potent and Selective Induction of Liver Erythropoietin through Silencing of EglN Genes

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced the publication of new pre-clinical results in the journal Blood (doi: 10.1182/blood-2012-04-423715) that describe targeting the egg-laying nine homolog (EglN) pathway for the treatment of anemia using RNAi therapeutics. The new findings show that activation of hepatic erythropoietin production using systemically delivered siRNA targeting EglN prolyl hydroxylases leads to improved red blood cell production in pre-clinical models of anemia. New approaches that induce endogenous mechanisms for erythropoiesis could address unmet medical needs in the management of anemia in patients who are refractive to current therapies.

Anemia of chronic disease remains a major cause of morbidity in patients with chronic kidney disease, inflammatory disorders, and cancer. While administration of exogenous recombinant erythropoietin has transformed the management of anemia, significant unmet need exists in a subset of patients who become refractory to therapy due to underlying inflammatory disease and increased production of factors such as hepcidin, said Rachel Meyers, Ph.D., Vice President, Research and RLD at Alnylam. These new results described in Blood demonstrate the ability of an RNAi therapeutic targeting the EglN pathway to reactivate a natural developmental pathway of hepatic erythropoietin production. This approach would allow the body to produce endogenous erythropoietin, thereby obviating the need for exogenous administration of recombinant or mimetic versions of this hormone.

Specifically, data showed that a systemically administrated RNAi therapeutic targeting the EglN family of proteins achieved dose-dependent silencing of EglN genes in vivo in animal models. The research showed that EglN silencing resulted in sustained increase in circulating erythropoietin that was generated specifically by the liver. The induction of endogenous liver erythropoietin expression recapitulates a developmental pathway for red blood cell production known to exist in the fetus. This increase in erythropoietin was detectable out to two weeks after administration of a single dose of the RNAi therapeutic and was associated with a sustained increased in red blood cell parameters including reticulocyte count, hemoglobin and hematocrit. Further, RNAi therapeutics targeting the EglN pathway were found to significantly correct anemia in models of both renal failure and chronic inflammation. Other changes observed with RNAi therapeutic targeting EglNs, such as decreased production of hepcidin, were also demonstrated and could enhance the effectiveness of endogenous erythropoiesis by improving iron mobilization, thereby lowering the circulating erythropoietin levels needed to promote red blood cell production.

This research was conducted in collaboration with researchers at the Dana-Farber Cancer Institute and the David Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology (MIT).

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 Alnylams 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 (ALNY)
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, ALN-APC for the treatment of hemophilia, and ALN-TMP for the treatment of hemoglobinopathies. As part of its Alnylam 5x15" strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner 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 Huntingtons disease. The companys 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 applications in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylams VaxiRNA" 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 worlds 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 www.alnylam.com.

Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylams future expectations, plans and prospects, including without limitation, statements regarding Alnylams views with respect to the potential for RNAi therapeutics, including targeting the EglN pathway for the treatment of anemia using RNAi therapeutics, and Alnylams 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, Alnylams ability to discover and develop novel drug candidates, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for these product candidates, which may not support further development of such product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials for such product candidates, obtaining, maintaining and protecting intellectual property, obtaining regulatory approval for products, competition from others using technology similar to Alnylams and others developing products for similar uses, and Alnylams 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 Alnylams 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.

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and
Corporate Communications
or
Spectrum (Media)
Amanda Sellers, 202-955-6222 x2597

Source: Alnylam Pharmaceuticals, Inc.

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