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New Class of Drug Candidates Developed by Santaris Pharma Can Potently Counteract Disease-Associated MicroRNAs

COPENHAGEN, Denmark--(BUSINESS WIRE)--Oct 15, 2008 - Santaris Pharma announced today promising new findings on the in vitro and in vivo activity of a new class of microRNA-targeted therapeutic candidates developed with its proprietary Locked Nucleic Acid (LNA) technology platform. The new findings were presented this week at 4th Annual Oligonucleotide Therapeutics Society (OTS) Meeting in Boston, Mass.

In both in vitro and in vivo models, including rodents and non-human human primates, Santaris Pharma's LNA- antimiR(R)'s demonstrated outstanding recognition and detection of disease-associated microRNAs due to their high specificity and affinity, bolstering the company's efforts to develop new LNA-based, microRNA-targeted therapeutics for human disease.

Santaris Pharma's LNA- antimiR(R) abstract was one of six presented by the company at the OTS meeting. Other abstracts included preclinical safety and pharmacokinetic data supporting its candidate therapies already in clinical trials, as well as data on cancer and hypercholesterolemia target identification.

"Santaris Pharma has made significant progress in advancing a rich pipeline of clinical and preclinical drug candidates targeting a variety of diseases where RNA plays an important role," said Henrik Orum, Santaris Pharma's chief scientific officer. "The breadth of the presentations being made this week underscore the value that our proprietary Locked Nucleic Acid technology holds for bringing antisense back to the forefront, and the potential that this holds for producing new drugs that are highly potent, precise, and capable of being delivered systemically. Furthermore our results demonstrate that the LNA technology is optimal for the development of microRNA antagonists. Our small single stranded oligonuclotide sequences are easily delivered to the cell and bind to microRNAs with even higher affinity than competing natural messenger RNAs."

Santaris Pharma currently has four human clinical trials underway examining the use of LNA drugs in a variety of indications: two ongoing Phase 1/2 trials being conducted with partner Enzon Pharmaceuticals in HIF1-alpha, one clinical trial with Santaris Pharma's Bcl-2 inhibitor in the treatment of solid tumours and combined with an antibody drug in non-Hodgkin's lymphoma, and finally an ongoing Phase 1 trial in Hepatitis C of the first microRNA drug ever to reach the clinic.

The presentations made by Santaris Pharma and its collaborators include the following:

Inhibition of PCSK9 Using Locked Nucleic Acid Oligonucleotides: Potential Treatment for Hypercholesterolemia

PCSK9 is involved in posttranslational regulation of the LDL receptor (LDLR) in liver and is considered a potential target for the treatment of hypercholesterolemia. Study results showed that PCSK9 mRNA can be effectively inhibited in vivo by both single and multiple doses of a short LNA oligonucleotide without negatively affecting liver function. The results confirm the therapeutic potential of LNA oligonucleotides for treating hypercholesterolemia through PCSK9 inhibition.

BioDistribution and Pharmacokinetic Properties of Locked Nucleic Acid Oligonucleotides Correlate with In vivo Pharmacology

One of the major challenges facing oligonucleotide therapeutics is the effective and broad delivery to target tissues. In the field of siRNA therapeutics, both chemical modification and liposomal formulation are being widely explored as means to overcome this challenge. In this presentation, Santaris Pharma researchers show that in preclinical models short, single stranded LNA oligonucleotides can be administered intravenously as naked molecules and are broadly taken up by a wide range of targeted tissues (e.g., kidney, liver, bone marrow, spleen, intestine, skin, lymph nodes, and pancreas).

Identification of Novel and Potent RNA Inhibitors against Different Cancer Targets, Based on Locked Nucleic Acid Technology

As part of Santaris Pharma's drug discovery program, company scientists designed, synthesized and screened libraries of short, single stranded LNA-antisense oligonucleotides targeting human ErbB3 and human beta-catenin, two important cancer targets. Based on the results from the in vitro screening, several potent new mRNA inhibitors with anti-cancer activities were identified, which will be further evaluated for their in vivo efficacy.

Assessment of the Subchronic Toxicity in Monkeys of Four Locked Nucleic Acid (LNA) Oligonucleotides with Therapeutic Potential

This study reviews the positive safety data gathered prior to initiation of a clinical study of SPC 3649, Santaris Pharma's micro RNA directed drug candidate currently undergoing human clinical trials for Hepatitis C.

Antagonizing microRNAs for therapeutics

LNA-modified oligonucleotides have proven outstanding in microRNA recognition and detection due to their high specificity and affinity. The Company reports that short, unconjugated LNA-antimiR oligonucleotides can be used as potent molecules for sequence-specific antagonism of disease-associated miRNAs in vitro and in vivo in rodents and non-human primates.

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.


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. Santaris Pharma's messengerRNA antagonists and microRNA antagonists are being developed to silence mRNAs and microRNAs associated with various diseases, including cancer, metabolic disorders and viral infections. 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 Pharma's Locked Nucleic Acid technology (LNA)

LNA is the first true conformational analogue of RNA (ribonucleic acid). The ribose sugar in LNA is 'locked' in the three-dimensional shape of RNA 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 unprecedented 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. As LNA drugs are resistant to degradation when given systemically, have long tissue half lives, and are taken up readily by many tissues they have greater potency than other oligonucleotide chemistries.

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 Pharma's 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
Randi Krogsgaard, +45 4517 9879
Director, Corporate Communications
Cell: +45 20488384

Posted: October 2008