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Regulus Therapeutics Present New Pre-clinical Data from Multiple Therapeutic Programs at Keystone Symposium

Regulus scientists and collaborators demonstrate for the first time anti-miR delivery and microRNA target regulation in multiple cell types

CARLSBAD, Calif.--(BUSINESS WIRE)--Jan 15, 2010 - Regulus Therapeutics Inc. today announced that new pre-clinical data from multiple therapeutic programs were presented at the “RNA Silencing: Mechanism, Biology and Application” Keystone Symposium held January 14 – 19, 2010 in Keystone, Colorado. Regulus and its collaborators presented data showing microRNA target regulation by anti-miRs, as well as data from therapeutic programs focused on oncology, immune disease and hepatitis C virus (HCV) infection.

“The field of microRNA discovery and therapeutic development is growing exponentially and at a tipping point,” said Peter S. Linsley, Ph.D., chief scientific officer of Regulus. “The company's innovative chemistries and unique understanding behind the biology of diseases caused by microRNA dysregulation positions Regulus to lead the development of a new class of high-impact medicines based on microRNA.”


In a poster titled “microRNA mimics as cancer therapeutics,” Regulus scientists presented in vivo data demonstrating delivery of miR mimics and microRNA target repression in an orthotopic liver tumor mouse model. Using lipid nanoparticles developed by collaborators at Alnylam Pharmaceuticals, Regulus scientists demonstrated effective delivery of a miR-34a mimic to both the normal liver cells and human hepatocellular carcinoma cells growing as tumors within the liver. Microarray profiling of the livers from mice treated with the miR-34a mimic displayed a significant down-regulation of messenger RNA targets of miR-34a. Within the tumors, Regulus scientists saw a similar down-regulation of messenger RNA targets. When Regulus scientists further analyzed the down-regulated messenger RNAs for functional significance, it was discovered that several cell cycle progression and cellular division genes were over represented. This demonstrates the potential utility of a miR-34a mimic delivered by lipid nanoparticles for the treatment of liver cancer.

anti-miR target regulation in immune cells

Regulus, in an alliance with GlaxoSmithKline, presented data from immuno-inflammatory disorders program in a poster titled “Inhibition of microRNA function in macrophages by anti-miRs”. The study provided the initial demonstration of a pharmacological effect in immune cells by specific microRNA inhibition. The study showed that systemically delivered anti-miRs distribute to immune cells and show functional target regulation, as measured by a statistically significant de-repression of seed-matched messenger RNA transcripts. Characterizing microRNA targets using this approach is uncovering the role that microRNAs play in cells of the immune system, and opening the door for microRNA therapies in immuno-inflammatory diseases.

Autoimmunity and Cancer

In a presentation titled “Myeloproliferative disease, autoimmunity and cancer in mice with targeted deletion of miR-146a gene” Regulus scientists and collaborators from the California Institute of Technology demonstrated the biological role of miR-146a by establishing loss- and gain-of-function mouse models. miR-146a knockout mice are born normal, however at the age of 6 months they start to develop a spontaneous autoimmune-like disorder leading to premature death. The study showed additional immune phenotypes of miR-146a mutant mice, including loss of immunological tolerance and macrophage hyperresponsiveness to bacterial lipopolysaccharides. The study established that this microRNA is involved in determining immune cell fate. Moreover, aging miR-146a knockout animals develop frank tumors in the secondary lymphoid organs, suggesting that miR-146a can function as a tumor suppressor in the context of the immune system. Taken together, the findings suggest that miR-146a plays a key role as a molecular brake of inflammatory response and oncogenic transformation of the immune cells.


In a poster titled “Identification of miR-122 conserved targets in liver affecting cholesterol regulation” Regulus scientists presented expression profiling data from livers of anti-miR-122-treated cynomolgus monkeys, mice, and rats. The company is developing an anti-microRNA targeting miR-122 as a novel treatment for HCV infection. Regulus and other groups have shown that miR-122 inhibition in monkeys results in a potent reduction of plasma cholesterol levels. However, the molecular mechanisms contributing to this phenotype are not known. Analysis of the messenger RNA expression profiling data revealed target regulation in all species with a common set of up-regulated, seed-matched messenger RNA targets in pathways related to cellular transport. This research suggests miR-122 in hepatocytes might indirectly activate cholesterol efflux by suppressing targets that prevent transport.

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. Many 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. For more information, visit

Forward-Looking Statements

This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Regulus', Alnylam's, and Isis' business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus. Any statement describing Regulus', Alnylam's, and Isis' 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 Regulus', Alnylam's, and Isis' management 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, 2008, and their most recent quarterly reports on Form 10-Q which are on file with the SEC. Copies of these and other documents are available from Alnylam or Isis.



Contact: Regulus Therapeutics

Zachary Zimmerman, Ph.D., 760-268-6811


Russo Partners

Heidi Chokeir, Ph.D., 619-528-2217 (Media)



Posted: January 2010