Alnylam and Regulus Receive Notice of Allowance from United States Patent and Trademark Office for New Patent Covering microRNA Therapeutics

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and Regulus Therapeutics Inc., a leading microRNA therapeutics company, announced today that the United States Patent and Trademark Office (USPTO) has awarded a notice of allowance for the Manoharan patent (application number 11/200,703), which covers several chemical classes of anti-miRs, antisense oligonucleotide inhibitors of microRNAs. This new patent in combination with Regulus’ existing intellectual property estate broadly covers approaches to developing microRNA-based therapeutics.

"Regulus Therapeutics is advancing a whole new frontier of pharmaceutical research through the discovery of microRNA therapeutics, which have the potential to block broad disease pathways as opposed to a single target,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus Therapeutics. "Our access to the pioneering research of our academic collaborators and Alnylam and Isis on oligonucleotide-based therapeutics, as evidenced most recently by the award of the Manoharan patent, has enabled Regulus to build a dominant intellectual property estate for microRNA therapeutics. We believe this is a strong foundation to advance our innovative approach to developing novel medicines to address the needs of patients.”

microRNAs are small, non-coding RNAs that regulate a large number of human genes; there are more than 700 microRNAs in the human genome that play a role in controlling expression of over one-third of all human genes. Abnormal expression and genetic mutation of microRNAs have been linked to numerous diseases including cancer, cardiovascular disease, metabolic disease, autoimmunity, and viral infection, amongst others. In 2005, Alnylam scientists and collaborators at The Rockefeller University were the first to describe antagomirs, which are part of a larger class of microRNA inhibitors known as anti-miRs (Krutzfeldt et al., (2005) Nature 438, 685-689). Anti-miRs were created to selectively inhibit microRNAs expressed in a broad range of tissues and to have pharmacological properties required for microRNA-based therapeutics. This research has created new drug discovery strategies focused on antagonizing microRNAs.

"We are pleased to have this important recognition from the USPTO regarding our discovery of antagomirs, a new class of anti-miRs and a novel invention in the field of microRNA-based therapeutics,” said Muthiah Manoharan, Ph.D., Vice President for Drug Discovery at Alnylam. "With this initial grant, we have received broad claims covering classes of anti-miRs with certain important chemical features for optimal delivery and in vivo pharmacology. Importantly, the inventive nature of these novel compositions was allowed independent of any specific microRNA sequence, thereby providing a broad set of patent claims that add to the innovations Regulus can employ in designing novel microRNA therapeutics, an entire new class of medicines.”

About microRNAs

microRNAs are a recently discovered class of genetically encoded endogenous RNAs, approximately 20 nucleotides in length, that are believed to regulate the expression of a large number of human genes. microRNAs have been described as being involved in the regulation of gene expression as part of physiology and development. The inappropriate absence or presence of specific microRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, cardiovascular, metabolic disorders and immuno-inflammatory disease. microRNA-based therapeutics represent a potential new approach for the treatment of a wide range of human diseases. Targeting microRNAs with anti-miRs could result in novel and broadly acting treatments for a number of serious human diseases.

About Regulus Therapeutics Inc.

Regulus Therapeutics Inc. is a biopharmaceutical company aiming to discover, develop, and commercialize microRNA-based therapeutics. Regulus aspires to translate one of the most important new discoveries in biology into a novel approach for innovative medicines and to build the leading microRNA company. Regulus was established by Alnylam Pharmaceuticals (Nasdaq: ALNY) and Isis Pharmaceuticals (Nasdaq: ISIS) in September of 2007, and benefits substantially from their RNA therapeutic drug discovery expertise, unique and established oligonucleotide-based technologies, and a broad and dominant intellectual property estate specific to microRNA-based therapeutics. Regulus’ patent estate includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNA for therapeutic applications. In addition, through its numerous collaborations with academic researchers, Regulus continues to expand its knowledge on the biological role of therapeutically relevant microRNAs. In April 2008, Regulus formed a major alliance with GlaxoSmithKline to explore microRNA therapeutics for immuno-inflammatory diseases. Regulus is headquartered in Carlsbad, California. For more information, visit www.regulusrx.com.

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 and is partnered with Cubist and Kyowa Hakko Kirin. 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 Kirin, 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 and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA-based therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

Forward-Looking Statement

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Isis’, Alnylam’s and Regulus’ business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus. Any statement describing Isis’, Alnylam’s or Regulus’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement, including those statements that are described as such parties’ goals. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Such parties’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause their results to differ materially from those expressed or implied by such forward-looking statements. Although these forward-looking statements reflect the good faith judgment of the management of each such party, these statements are based only on facts and factors currently known by Isis, Alnylam or Regulus, as the case may be. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis’, Alnylam’s and Regulus’ programs are described in additional detail in Isis’ annual report on Form 10-K for the year ended December 31, 2008, and its most recent quarterly report on Form 10-Q, and in Alnylam’s annual report on Form 10-K for the year ended December 31, 2008, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from Isis or Alnylam.

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