Regulus Therapeutics to Present Multiple Platform and Pipeline Advancements at the Keystone Symposium on microRNAs

LA JOLLA, Calif.--(BUSINESS WIRE)--Regulus Therapeutics Inc. today announced that new pre-clinical data from its therapeutic programs will be presented at the jointly held Keystone Symposia “microRNAs and Non-coding RNAs and Cancer” and “microRNAs and Human Disease” held February 11-16, 2011 in Banff, Alberta, Canada. Regulus and its collaborators will present advancements from multiple programs including new data from Regulus’ oncology program showing anti-miRs targeting microRNA-21 provide a significant survival advantage in a mouse model of hepatocellular carcinoma.

“Altered Hepatic Energy Metabolism and a Lack of Obvious Adverse Findings After miR-122 Inhibition in Mice”

“Regulus is advancing several microRNA therapeutic programs to the clinic in multiple disease areas with our pharmaceutical partners at sanofi-aventis and GlaxoSmithKline and our extensive network of over 30 collaborations with leading academic laboratories,” said Kleanthis Xanthopoulos, Ph.D., President and CEO of Regulus. “We uniquely combine leading biology with proprietary chemistry and bioinformatics to discover and develop microRNA therapeutics in key disease areas of high unmet medical need.”

In a talk titled “MicroRNA-21 as a Novel Therapeutic Target in Hepatocellular Carcinoma,” Regulus scientists and collaborators from the University of California, San Francisco will demonstrate that microRNA-21 is highly expressed in many cancers and that inhibition with a proprietary, chemically modified oligonucleotide anti-miR reduced tumor burden and significantly increased survival. Experiments were performed using a mouse model of hepatocellular carcinoma (HCC) where the oncogene RAS was over-expressed in the hepatocytes. RAS signaling is among the most frequently dysregulated pathways in human HCC and when overexpressed in this model, it produces tumors that closely resemble human HCC. Mice were treated bi-weekly for 3 weeks with either an anti-miR against microRNA-21, a mismatched anti-miR control, or saline. Mice treated with anti-miR-21 did not develop obvious liver tumors; in contrast, mice injected with the control anti-miR or saline developed extensive liver tumors. Importantly, anti-miR-21 treated mice demonstrated a dramatic survival advantage (p<0.0001) over saline and control anti-miR treated mice. These findings suggest microRNA-21 is a promising therapeutic target for liver cancer and further highlights the potential of anti-miR-mediated inhibition of microRNAs. Liver cancer is among the top three leading causes of cancer-related deaths worldwide, with a median survival of approximately six months. HCC affects diverse populations and has varied etiology including hepatitis viruses B and C, aflatoxin B1 and alcohol. Therapeutic options are limited and more effective treatments are greatly needed.

In a poster titled “Tale of a Tumor Suppressor microRNA: miR-34a as a Paradigm,” Regulus scientists will present a characterization of the effects of delivering to cancer cells a microRNA mimic of microRNA-34a, a microRNA known to interact with the p53 pathway and to be down-regulated in many cancer types. Regulus scientists will demonstrate that introduction of a microRNA-34a mimic into cancer cells lacking p53 blocked cell proliferation. In the same cell line with the p53 pathway genetically reconstituted, introduction of microRNA-34a mimic led to an even more effective block of cell proliferation. These findings may aid in the selection of appropriate patient populations for future clinical trials involving a microRNA-34a mimic therapy.

In a poster titled “Human Glioma Growth is Controlled by microRNA-10b,” Regulus scientists and collaborators from Harvard Medical School will present data that inhibition by an anti-miR targeting microRNA-10b, a microRNA not expressed in the normal human brain and strongly up-regulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell cycle arrest and apoptosis.

In a poster titled “Altered Hepatic Energy Metabolism and a Lack of Obvious Adverse Findings After miR-122 Inhibition in Mice,” Regulus scientists and collaborators from Duke University will present data on long-term inhibition of microRNA-122 in mice. Long-term, 50-week anti-miR-122 treatment results in a significant and sustained decrease in total plasma cholesterol, consistent with the pharmacodynamic effects of microRNA-122 inhibition, with no obvious deleterious effects based on body weight, clinical chemistry, and histopatholgy evaluations. These findings support the ongoing development of anti-miR-122 for hepatitis C viral infection.

In a poster titled “Inhibition of Let-7 with anti-miR Oligonucleotides Improves Insulin Resistance and Increases Body Mass in a Diabetic Mouse Model,” Regulus scientists will describe the targeting in a mouse model of diabetes of the Let-7 family of microRNAs, which are highly expressed in the liver and adipose. In addition, Regulus scientists and collaborators from University of Hannover will present data on optimal anti-miR design for therapeutic use show longer anti-miRs targeting the microRNAs let7a and microRNA-21 are more potent than shorter anti-miRs that target only the seed region.

In summary, Regulus continues to advance its leading microRNA therapeutic platform and pipeline. Data will be presented at the Keystone Symposium by Regulus scientists and collaborators that further demonstrate the broad potential of microRNA therapeutics in several disease areas.

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 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 with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function, opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs please visit http://www.regulusrx.com/microrna/microrna-explained.php.

About Regulus Therapeutics Inc.

Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs. Regulus is using a mature therapeutic platform based on technology that has been developed over 20 years and tested in greater than 5,000 human subjects. In addition, Regulus works with a broad network of academic collaborators and leverages 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, immuno-inflammatory diseases, fibrosis, oncology, and cardiovascular/metabolic diseases. Regulus’ intellectual property estate contains both the fundamental and core patents in the field and includes over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In April 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In February 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. In June 2010, sanofi-aventis and Regulus entered into the largest-to-date strategic alliance for the development of microRNA therapeutics. This alliance is focused initially on fibrosis. For more information, visit http://www.regulusrx.com.

Forward-Looking Statements

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Regulus’ business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus. Any statement describing 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 party’s 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 Regulus, these statements are based only on facts and factors currently known by Regulus. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Regulus’ programs are described in additional detail in each of Isis’ and Alnylam’s annual report on Form 10-K for the year ended December 31, 2009 and their most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from either Isis or Alnylam.