Drugs directed against RNA targets have the potential to transform the pharmaceutical industry and the field of human medicine, making drug discovery, development and manufacture more efficient, faster and less error prone than ever before. At the same time, this novel class of drugs offers the means to inhibit previously undruggable disease targets thus facilitating new therapeutics that can help patients with difficult or untreatable diseases live longer and better.

Santaris Pharma a/s is a leader in the field of RNA-targeted drugs, leveraging its proprietary Locked Nucleic Acid (LNA) chemistry and powerful Drug Discovery Engine to develop an array of innovative drugs in several different disease areas, both independently and in partnerships with major pharmaceutical companies. In contrast to some other RNA-targeting medicines, Santaris Pharma's LNAs can deliver on the promise of the technology today.

RNA targeted therapeutics exploit one of the fundamental properties of biology: the ability of single strands of DNA or RNA to specifically recognize and bind to one another using the simple rules described by Watson and Crick. With these rules and readily available genetic information, therapeutic oligonucleotides can be designed to seek out and bind specifically to disease-related RNAs. Once bound to the disease-related RNA, that RNA is degraded or rendered inactive, thereby ameliorating the diseased state.

RNA-targeted therapeutics powered by LNA

To become drugs, short chains of nucleotides (oligonucleotides) must have physical properties that allow them to reach their site-of-action in the diseased cell intact and in sufficient quantities for activity. Having reached the cell, they can bind to their RNA-target with sufficient strength to elicit the desired pharmacology. Although the need for these physical properties has been recognized for a long time, it is only with the discovery of the LNA chemistry (in 1997) that high affinity oligonucleotides have become available.

Chief amongst the many unique properties of LNA are its high biostability and remarkable target affinity that in turn enables strong pharmacological activity to be packed into shorter-than-usual-oligonucleotides. When administered systemically, these oligonucleotides are effectively delivered to a range of tissues where they elicit highly specific, potent and long lasting reduction of the RNA target with consequential relief of disease.

Most importantly, the strong pharmacology of LNA oligonucleotides is achieved without the complex and often toxic delivery formulations needed for delivery of the more complex structured double stranded siRNAs.

To date, Santaris Pharma has characterized several different LNA drugs in toxicology studies in rodents and non-human primates  - enough to commence multiple clinical trials. These studies have consistently demonstrated LNA oligonucleotides to be safe at doses that exceed the expected therapeutic doses in man. Currently, four LNA drugs are being tested in human clinical trials as novel medicines against a diversity of solid tumors, cancers of the blood and hepatitis C viral infection.