Santaris Pharma


Santaris Pharma A/S is a biopharmaceutical company founded in 2003 in Copenhagen, Denmark with a small branch in San Diego, California that opened in 2009. Created by a merger between Cureon and Pantheco, Santaris Pharma A/S has become a leading clinical-stage biopharmaceutical company that develops RNA-targeted medicines using a Locked Nucleic Acid Drug Platform and Drug Development Engine.
The company was acquired by Roche in August 2014.
Santaris has the worldwide exclusive intellectual property rights to the therapeutic applications of locked nucleic acid technology. This includes ownership of over 60 patent types, which range from the chemistry to manufacturing and from therapeutic uses to drug design.
With their LNA technology, Santaris works on developing drugs for a wide range of diseases using microRNA and mRNA. Their research focuses on infectious disease and metabolic disorders. They also work on collaborations with pharmaceuticals to develop drugs for rare genetic disorders, cancers, cardiovascular disease, and immune and inflammatory diseases.

LNA drug platform

Santaris develops LNA-based drugs to efficiently develop, identify, and design drug candidates. Their drug platform is LNA, which is a modification of RNA containing an oxymethylene bridge between the 2’ oxygen and 4’ carbon in the ribose ring. This bridge forms a bi-cyclic structure that locks the ribose conformation, and is integral to the high stability and affinity of the LNA to its complementary RNA sequence. Santaris designs LNA oligonucleotides as antisense therapeutics to complement specific mRNA and microRNA sequences. Binding of the oligonucleotide to the target creates a stretch of dsRNA, and this prevents translation. LNA oligonucleotides are shorter than other antisense drugs, which allows them a higher target affinity and potency than regular RNA oligonucleotides. They are a novel therapeutic agents because of their resistance to endonuclease activity. LNA-drugs have many other favorable features: they do not need complicated drug delivery vehicles, manufacturing is scalable and cost-effective, the drugs are well tolerated, and there is potential for oral delivery.
Their developed technology enables them to go through trial phases in 18 months, which is shorter than normal trials because it is not protein bound. They do this by using a screening library to find base sequences, using well known targets, and using mRNA sequences to help develop oligonucleotides.

Drug candidates

Santaris Pharma A/S currently has two novel drug candidates for the treatment of solid tumors and lymphomas, EZN-2968 and EZN-3042. EZN-2968 is an inhibitor of a transcription factor, HIF-1α, that is involved in cells ability to undergo angiogenesis and other processes needed for cell survival. EZN-3042 is also an inhibitor, which acts against Survivin. Santaris is partnered with Enzon Pharmaceuticals for the development of both drug candidates, which are in Phase I clinical trials.
SPC-4955 is in Phase I trials and is a novel treatment for cholesterol. SPC-4955 inhibits the protein that is necessary for the formation of plasma LDL cholesterol particles. This has the potential to be used as treatment for patients with hyperlipidemia.
Their PCSK9 program also has the potential to treat patients with hyperlipidemia. It inhibits the protein which controls the number of receptors responsible for removing LDL cholesterol particles from the blood.
Santaris is developing a microRNA targeting drug for hepatitis C, miravirsen, which entered Phase II clinical trials in 2010. The drug targets miR-122, a host factor necessary for viral replication of the hepatitis C virus in host liver cells; because miravirsen targets a host factor rather than the virus itself, there are no indications of the virus developing resistance. The U.S. Food and Drug Administration has approved a multiple dosing study, by injection, to treatment naive patients for phase II testing.
Santaris has a collaboration with Shire to discover and develop new RNA-based medicines to treat rare genetic disorders.

Collaborations

Santaris Pharma A/S is the preferred partner for the development of mRNA and microRNA-targeted medicines because of the strategy and leverage its LNA Drug Platform. The importance of the collaborations with larger pharmaceutical companies is demonstrated by the cash income, and the opportunity for development of their LNA platform. Since 2006, Santaris has partnered with several pharmaceuticals companies who want to capitalize on Santaris's ability to develop LNA oligonucleotides for mRNA and microRNA targets.
Pfizer and Santaris have a collaboration to develop up to ten targets. Pfizer is responsible for the pharmacology and future development, and Santaris is responsible for design and delivery of the lead candidates. Their partnership with Enzon is for cancer drug targets and begin clinical stage programs and they paired with Shire for lead candidates of five rare, undisclosed genetic disorders. They are also partnered with miRagen to develop treatments targeting microRNAs associated with cardiovascular disease and with GlasoSmithKline for four viral disease programs and clinical trials.

Publications

Santaris employees have coauthored articles published in Nature and Science.
These have outlined the results of experiments using LNA oligonucleotides to down-regulate the expression of endogenous microRNAs in primates.

Timeline

Executives
Exiqon brought Santaris to court to obtain more rights of LNA technology in 2010. On Friday, October 7, 2011, all the allegations initiated by Exiqon against Santaris were dismissed by the arbitration court. The ruling furthermore confirms that Santaris holds exclusive worldwide rights to manufacture, have manufactured, and sell products that comprise LNA as active ingredient for studies performed with a purpose of developing LNA-based drugs for marketing approval. Exiqon does not have rights to manufacture or sell such products.
Isis Pharmaceuticals filed a patent infringement lawsuit against Santaris Pharma A/S in the United States District Court of the Southern District of California in September 2011. Isis' infringement suit against Santaris is based upon Santaris' activities providing antisense drugs and antisense drug discovery services to several pharmaceutical companies, which are activities not protected under the exemption from patent infringement for drug development.