Nature Publishes Study by Santaris Pharma Scientists and Collaborators: LNA-Mediated MicroRNA Silencing in Non-Human Primates

COPENHAGEN, Denmark--(BUSINESS WIRE)--Santaris Pharma announced today the publication in Nature (Advance Online Publication (AOP) on www.nature.com/nature, March 26 2008) of a groundbreaking peer-reviewed study entitled LNA-mediated microRNA silencing in non-human primates. The paper is the first demonstration of microRNA silencing in non-human primates, providing an important validation of Santaris Pharmas emerging clinical program to develop a novel class of LNA-based therapeutics capable of silencing disease-associated microRNAs.

“In the study, we used a simple intravenous delivery of an unconjugated LNA-antimiR to antagonize the liver-expressed microRNA-122 in African green monkeys, which resulted in long-lasting, efficient and reversible decrease in total plasma cholesterol without any evidence of adverse reactions.”

The study authors, led by Dr Sakari Kauppinen, Director of MicroRNA Research at Santaris Pharma and visiting Professor at Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, used a high-affinity Locked Nucleic Acid-modified oligonucleotide (LNA-antimiR) to antagonize the liver-expressed microRNA-122 (miR-122) in rodents and non-human primates. Acute administration of the LNA-antimiR resulted in uptake of the compound in liver cells and formation of stable hetero duplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three intravenous doses of 3 mg/kg.

We are excited by the results from this study, which demonstrate the great promise that LNA technology holds for targeting microRNAs and exploring their function in vivo, said Sakari Kauppinen. In the study, we used a simple intravenous delivery of an unconjugated LNA-antimiR to antagonize the liver-expressed microRNA-122 in African green monkeys, which resulted in long-lasting, efficient and reversible decrease in total plasma cholesterol without any evidence of adverse reactions.

Even though further studies will be needed to optimize the dosing regimen and to assess the safety of LNA-antimiR compounds after long-term treatment, our findings represent an important step towards the development of LNA-based microRNA therapeutics, said Kauppinen.

MicroRNAs are small regulatory RNAs that play important roles in development and disease and, thus, represent a potential new class of targets for therapeutic intervention. Santaris Pharma has the proprietary worldwide pharmaceutical rights to the LNA technology, which was employed in the study published by Nature to target microRNAs. The use of LNA significantly enhances the potency of microRNA antagonists, while retaining target specificity, which is essential in silencing of specific microRNAs.

Dr Keith McCullagh, President and CEO of Santaris Pharma commented: In collaboration with Professor Peter Sarnow and Sylvia Schutz from Stanford University, we also show in the study published today in Nature that LNA-mediated silencing of microRNA-122 leads to efficient inhibition of Hepatitis C virus production in human liver cells, confirming previous work by the Stanford group on the importance of microRNA-122 for Hepatitis C replication. Now that we have confirmed that an LNA-antimiR oligonucleotide can effectively antagonize microRNA-122 in primates at low doses, we are encouraged to investigate the potential of LNA-mediated therapy in the treatment of HCV infection.

Santaris Pharma is preparing to advance its first LNA-antimiR compound, targeting miR-122, into human clinical testing in the first half of 2008. The first trial will be a Phase I safety and pharmacokinetic study in healthy volunteers.

The primate study was carried out in collaboration with the Connecticut based biotech company RxGen at the St. Kitts Biomedical Research Foundation.

About Santaris Pharma

Santaris Pharma is a Danish clinical stage biopharmaceutical company. The Company was formed in 2003 and has the exclusive rights to LNA technology, a 3rd generation antisense chemistry used to develop new classes of RNA medicines, called RNA antagonists and microRNA antagonists. Santaris Pharmas RNA antagonists and microRNA antagonists are being developed to silence RNAs associated with cancer, metabolic disorders and viral diseases. Santaris Pharma completed a Euro 40m second round of equity financing in May 2006 and a Euro 20m third round of equity financing in December 2007. Santaris Pharma has a global alliance with Enzon Pharmaceuticals of New Jersey to develop and co-commercialise a series of Santaris Pharma RNA antagonists for the treatment of cancer and a worldwide strategic alliance with GlaxoSmithKline for the discovery, development and commercialization of novel medicines against viral diseases.

About Santaris Pharmas Locked Nucleic Acid technology

LNA is an analogue of RNA (ribonucleic acid). The ribose sugar in LNA is locked in the RNA conformation by virtue of its rigid bicyclic structure. The result is that when incorporated into oligonucleotides, LNA conveys dramatically enhanced binding affinity to complementary RNA sequences. Drug molecules with multiple LNA substitutions therefore have truly outstanding potencies. The greater potency of LNA in binding complementary RNA sequences means that LNA oligonucleotide drugs can be made significantly shorter than previous antisense or siRNA drugs. These shorter RNA antagonist drugs are taken up efficiently by cells and tissues, thereby overcoming many of the delivery problems of RNAi to date. In addition to greater potency than other oligonucleotide chemistries, LNA drugs are resistant to degradation when given systemically, have long tissue half lives, are taken up readily by many tissues, and have improved therapeutic ratios over first and second generation antisense drugs.

About microRNAs

MicroRNAs are a newly discovered class of small regulatory molecules which control many biological processes in cells. In addition, microRNAs have been implicated in many diseases, such as cancer, viral infections, cardiovascular disease and neurological disorders and, therefore, represent a new class of targets for therapeutic intervention. Santaris Pharmas unique LNA technology enables development of short, synthetic RNA-binding molecules that can effectively antagonize disease-causing microRNAs and, thus may yield patient benefits unobtainable by other therapeutic approaches.

Santaris Pharma forward looking statements

This written announcement contains forward-looking statements, identified by the use of words such as "believes," "expects," "may," "will," "should", "potential," "anticipates," "plans" or "intends" and similar expressions. Such forward-looking statements involve risks, uncertainties and other factors that may cause actual results, events or developments to be materially different from the future results, events or developments indicated in this announcement. Such factors include, but are not limited to the timing, success and cost of clinical studies; the ability to obtain regulatory approval of products, market acceptance of and future demand for Santaris Pharma products and the impact of competitive products and pricing. These factors should be considered carefully and readers are cautioned not to place undue reliance on such forward-looking statements. No assurance can be given that the future results covered by the forward-looking statements will be achieved. All information in this press release is as of the date of this press release and Santaris Pharma does not intend to update this information.

Contacts

Santaris Pharma
Randi Krogsgaard, +45 4517 9879
Director, Corporate Communications
rmk@santaris.com

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