Regulus Therapeutics Appoints Dr. Stelios Papadopoulos to Board of Directors

Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) formed to discover, develop, and commercialize microRNA-based therapeutics, announced today the appointment of Stelios Papadopoulos, Ph.D., to its Board of Directors. With a strong background in science and a career that encompasses more than two decades of experience as a leading investment banker focused on the biotechnology and pharmaceutical sectors, Dr. Papadopoulos will complement Regulus Therapeutics’ Board of Directors, which is comprised of industry leaders in drug discovery and development.

"We are thrilled that Stelios has agreed to join the Regulus Board of Directors,” said John Maraganore, Ph.D., Chairman of Regulus and Chief Executive Officer of Alnylam. "Stelios has been an instrumental and legendary figure in the biotech industry for over two decades; a scientist by training, his influence on the growth of the biotech industry from a financing perspective has been matched by only a few. We believe that the combination of his scientific and financial expertise, coupled with his demonstrated commitment to the development of innovative medicines, will add a unique perspective to Regulus’ world-class Board and will strengthen our efforts in building the leading microRNA therapeutics company.”

"The breakthrough field of microRNA-based therapeutics represents an entirely new approach for developing high-impact innovative medicines, and Regulus has all the necessary components to establish a dominant position in the space,” said Dr. Papadopoulos. "I am looking forward to working with Regulus’ management and other Board members to build a leading company that is translating the science of microRNAs into novel therapeutics.”

"We are honored to have Stelios join our Board,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus Therapeutics. "Stelios comes to Regulus at a very exciting time of development. In less than a year we have been able to recruit some of the top minds in RNA research, establish collaborations with key academic institutions to further expand the biology of microRNAs, and form a strategic alliance with GSK, a leading pharmaceutical company. We look forward to Dr. Papadopoulos’ invaluable contributions as we continue to expand our therapeutic pipeline and bring lead microRNA therapeutic compounds closer to the clinic.”

Dr. Papadopoulos retired as Vice Chairman of Cowen and Company, LLC in 2006 after six years with the firm where he was an investment banker focused on the biotechnology and pharmaceuticals sectors. Prior to joining Cowen in 2000, Dr. Papadopoulos was an investment banker at PaineWebber Incorporated, most recently serving as Chairman of PaineWebber Development Corp., a PaineWebber subsidiary focusing on biotechnology. He also held positions in Equity Research covering the biotechnology industry at Drexel Burnham Lambert and Donaldson, Lufkin & Jenrette. He is a co-founder and Chairman of the Board of Directors of Exelixis, Inc. and director and co-founder of Anadys Pharmaceuticals, Inc. and Cellzome, Inc. Dr. Papadopoulos is also a member of the Board of Directors at Biogen Idec Inc and Vice Chairman of the Board of BG Medicine, Inc.

Before joining Wall Street, he was on the faculty of the Department of Cell Biology at New York University Medical Center and maintains his affiliation today as an Adjunct Associate Professor of Cell Biology. Dr. Papadopoulos is also deeply involved in the non-profit sector. He is a co-founder and Chairman of Fondation Santé, a charitable foundation for scientific and educational purposes. In addition, he serves on the Board of Visitors at Duke University Medical Center and he is a member of the Board of Directors of the National Marrow Donor Program. Dr. Papadopoulos holds a Ph.D. in biophysics and an M.B.A. in finance, both from New York University.

About microRNAs

microRNAs are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. microRNA-based therapeutics represent a new approach for the treatment of a wide range of human diseases. 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, metabolic disorders and inflammatory disease. Targeting microRNAs with novel therapeutic agents could result in novel and broadly acting treatments for human diseases.

About Regulus

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop, and commercialize microRNA-based therapeutics. Regulus aspires to translate one of the most important new discoveries in biology into a novel new approach for innovative medicine and to build the leading microRNA company. Created as a joint venture by Alnylam Pharmaceuticals and Isis Pharmaceuticals, Regulus benefits from oligonucleotide drug discovery expertise, an established technology, and a broad intellectual property estate created and consolidated by its parent companies for the development and commercialization of 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, Regulus has collaborations with academic researchers to build on the company’s understanding of more than 60 microRNAs. In April 2008, Regulus formed a major alliance with GlaxoSmithKline to explore microRNA therapeutics for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Regulus, founded in September 2007, maintains facilities in Carlsbad, California. For more information, visit www.regulusrx.com.

About Isis Pharmaceuticals, Inc.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 19 drugs in development. Isis’ drug development programs are focused on treating cardiovascular and metabolic diseases. Isis’ partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Ibis Biosciences, Inc., Isis’ majority-owned subsidiary, is developing and commercializing the Ibis T5000™ Biosensor System, a revolutionary system to identify infectious organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

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, 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, Roche, Takeda, and Kyowa Hakko Kogyo. 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. For more information, 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, 2007, and its quarterly report on Form 10-Q for the quarter ended June 30, 2008 and in Alnylam’s annual report on Form 10-K for the year ended December 31, 2007, and its quarterly report on Form 10-Q for the quarter ended June 30, 2008, which are on file with the SEC. Copies of these and other documents are available from Isis or Alnylam.