Regulus Therapeutics and Collaborators Publish Pre-clinical In Vivo Efficacy Data on microRNA Therapeutics targeting microRNA-10b in Models of Breast Cancer Metastasis

Regulus Therapeutics Inc. today announced the publication of new results in the journal Nature Biotechnology by Regulus scientists and collaborators. The new study demonstrated that systemic treatment of a microRNA therapeutic targeting microRNA-10b in tumor-bearing mice inhibits breast cancer metastasis. Cancer-related metastasis is a major cause of mortality and current cancer treatments have limited utility suppressing the metastatic spread of cancer cells. microRNA therapeutics targeting miR-10b represent a promising approach for the discovery and development of a novel anti-metastatic agent.

"We are very excited by our continued progress in developing microRNA therapeutics for the treatment of cancer. microRNAs are evolutionarily conserved regulators of gene networks and are often dysregulated in cancer. Targeting biological pathways by inhibiting microRNAs holds considerable promise as a novel therapeutic strategy for cancer and other human diseases,” said Peter S. Linsley, Ph.D., Chief Scientific Officer of Regulus. "The promising data in this Nature Biotechnology publication further validates Regulus’ microRNA product platform built on the integration of biology, chemistry, and bioinformatics. Working closely with our collaborators, the data generated from these efforts advance our understanding of microRNA biology in cancer. Further studies in additional animal models will help us determine the breadth of the therapeutic potential of anti-miRs targeting miR-10b.”

The new paper (Ma et al. (2010) Nature Biotechnology, advanced online publication, 28 March 2010 (doi:10.1038/nbt.1618)) describes the therapeutic targeting of microRNA-10b in an in vivo mouse model of cancer metastasis. Increased levels of miR-10b have been found to be associated with high-grade malignancy; miR-10b is also found to be highly expressed in metastatic breast tumor samples from patients. Indeed, the over-expression of miR-10b in non-metastatic breast cancer cells confers invasive and metastatic characteristics. In this study, miR-10b was targeted in vivo with an anti-miR-10b oligonucleotide in a mouse tumor metastasis model. Cancer cells were implanted in the mammary fat pad of mice, forming primary breast tumors that rapidly metastasize to the lung with 100% incidence. Mice treated with PBS or a control compound rapidly developed macroscopically visible pulmonary metastases. In contrast, an 86% decrease in macroscopically visible pulmonary metastases was achieved with the anti-miR-10b treatment. This therapeutic efficacy occurred in the absence of inhibition of growth of the primary tumor, demonstrating the specific effect of anti-miR-10b on the metastatic process.

"Most cancer-related mortality is caused by metastasis, which is inadequately addressed by current cancer treatments,” said Hubert C. Chen, M.D., Vice President of Translational Medicine. "Recent reports provide evidence that microRNAs are involved in cancer initiation, progression, and metastasis. Targeting miR-10b represents a promising approach for the research and development of a new anti-metastatic therapy for breast cancer.”

Cancer metastasis is a complex, multi-step process by which primary tumor cells invade adjacent tissue, enter the systemic circulation, and proliferate into a secondary tumor elsewhere in the body. Metastatic disease to the lung is common and frequently involves cancerous cells arising from primary breast tumors. Previous studies have shown miR-10b to be highly expressed in metastatic breast cancer cells and involved in the regulation of cell migration and invasion (Ma et al. (2007) Nature 449, 682-689).

In the field of microRNA therapeutics, Regulus controls fundamental patent rights related to miR-10b, including compositions of matter for various anti-miR compounds targeting miR-10b, and uses of these compounds as in vivo inhibitors of miR-10b activity.

About microRNAs

The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these new molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways.

About Regulus Therapeutics Inc.

Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines based on microRNAs. Regulus is targeting microRNAs as a new class of therapeutics by working with a broad network of academic collaborators and leveraging oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, cardiovascular disease, fibrosis, oncology, immuno-inflammatory diseases, and metabolic diseases. Regulus’ intellectual property estate contains both the fundamental and core patents in the field as well as over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. For more information, visit www.regulusrx.com.

Forward-Looking Statements

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, including statements regarding the therapeutic potential of targeting miR-10b. 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. 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 Regulus’, Alnylam’s, and Isis’ programs are described in additional detail in Alnylam’s and Isis’ annual reports on Form 10-K for the year ended December 31, 2009. Copies of these and other documents are available from Alnylam or Isis.