Regulus Therapeutics and Collaborators Publish New Data on a Critical Role for miR-21 in Brain Tumors

Business Wire, August 19, 2008

CAMBRIDGE, Mass. & CARLSBAD, Calif. -- 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 publication of new research in the journal Molecular and Cellular Biology on the role of the microRNA known as miR-21 in regulating certain cancer cells (1). Researchers at Regulus Therapeutics, Brigham and Women's Hospital, and other collaborators discovered a new role for miR-21 in glioblastoma multiforme (GBM), the most malignant and aggressive form of glioma, a primary brain tumor.

Research performed in collaboration with Brigham and Women's Hospital in Boston and other researchers demonstrated that miR-21 is responsible for the regulation of multiple genes associated with glioma tumor cell death, migration and invasiveness. In the peer-reviewed research, scientists showed that increased miR-21 levels in tumor cells correlated with the grade or aggressiveness of the tumor; highest levels of miR-21 were associated with the most aggressive forms of GBM. To elucidate the role that miR-21 plays in GBM, anti-miR-21 compounds were used to inhibit miR-21 function in human tumor cells. Inhibiting miR-21 function affected the expression of genes associated with tumor invasiveness, proliferation, migration and other processes exploited by tumor cells. As a whole, these data correlated miR-21 regulation with the aggressiveness of the tumor, and suggest that miR-21 is involved in the regulation of many different cellular processes necessary for tumorogenesis.

"The over-expression of miR-21 is observed in a variety of cancers, including glioblastoma, breast, lung, colon and others. In this study we were able to identify genes affected by levels of miR-21 over-expression. Further, our studies show that blocking miR-21 function disrupted many of the pathways critical for tumor invasiveness and proliferation," said Peter Linsley, Ph.D., Chief Scientific Officer of Regulus Therapeutics. "This new research adds to a rapidly growing body of evidence suggesting that inhibiting the function of a single microRNA could have a profound effect on multiple disease-causing proteins, thereby interfering with entire cellular pathways and defining a new therapeutic approach for treatment of disease."

(1) Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol. 2008 Sep;28(17):5369-80. Epub 2008 Jun 30.

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 18 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[TM] 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.