Santaris Pharma A/S was a biopharmaceutical company founded in 2003 in

Copenhagen Copenhagen ( ) is the capital and most populous city of Denmark, with a population of 1.4 million in the Urban area of Copenhagen, urban area. The city is situated on the islands of Zealand and Amager, separated from Malmö, Sweden, by the ...

Denmark Denmark is a Nordic countries, Nordic country in Northern Europe. It is the metropole and most populous constituent of the Kingdom of Denmark,, . also known as the Danish Realm, a constitutionally unitary state that includes the Autonomous a ...

. The company also had a branch in

San Diego San Diego ( , ) is a city on the Pacific coast of Southern California, adjacent to the Mexico–United States border. With a population of over 1.4 million, it is the List of United States cities by population, eighth-most populous city in t ...

California California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...

that opened in 2009. Created by a merger between Cureon and Pantheco, Santaris developed RNA-targeted medicines using a Locked Nucleic Acid (LNA) Drug Platform and Drug Development Engine. Santaris had gained intellectual property rights to the therapeutic applications of locked nucleic acid (LNA) technology. These rights included ownership of several patents, mostly with the chemistry and manufacturing of

therapeutic drugs Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

. With its LNA technology, Santaris developed drugs for the treatment of

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

and

tumours A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

using

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

and

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

. Its research focused on infectious diseases and metabolic disorders. The company also worked on collaborations with other pharmaceutical companies to develop drugs that could treat cancers and rare genetic disorders, among other things. In August 2014, Santaris was acquired by

Roche F. Hoffmann-La Roche AG, commonly known as Roche (), is a Switzerland, Swiss multinational corporation, multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, ...

for $450 million. As a result, the Copenhagen site was renamed the Roche Innovation Center Copenhagen (RICC). RICC houses Roche's RNA Molecule Research, which is part of Roche Pharma Research and Early Development. In 2023, it was closed due to a decision to move research to

Basel Basel ( ; ), also known as Basle ( ), ; ; ; . is a city in northwestern Switzerland on the river Rhine (at the transition from the High Rhine, High to the Upper Rhine). Basel is Switzerland's List of cities in Switzerland, third-most-populo ...

Switzerland Switzerland, officially the Swiss Confederation, is a landlocked country located in west-central Europe. It is bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. Switzerland ...

where Roche is headquartered. The former employees of the RICC were offered new jobs at the Danish pharmaceutical company

Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, with production facilities in nine countries and affiliates or offices in five. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S ...

Locked Nucleic Acid (LNA) drug platform

Santaris developed drugs based on

Locked nucleic acid A locked nucleic acid (LNA), also known as bridged nucleic acid (BNA), and often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The ...

(LNA) to facilitate the identification and design of potential drug candidates. LNA

oligonucleotides Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small fragments of nucleic aci ...

were engineered by Santaris as antisense therapeutic agents, designed to complement specific mRNA and microRNA sequences. This interaction leads to the formation of double-stranded RNA, preventing translation. Notably, LNA oligonucleotides are shorter than other

antisense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...

drugs, granting them greater target affinity and potency compared to regular RNA oligonucleotides. One of the distinctive qualities of LNA drugs is their resistance to

endonuclease In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...

activity, which contributes to their durability. Moreover, LNA drugs possess other advantageous attributes in comparison to other therapeutic agents: they can be administered without the need for complex drug delivery methods, their production is scalable and cost-effective, they are well-tolerated. These factors collectively define LNA-based drugs as innovative therapeutic agents.

Drug candidates

Cancer drug candidates

In 2009, Santaris announced that two LNA based drugs EZN-3042, and EZN-2968 would be entering clinical trials. EZN-2968 is an inhibitor of a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

, specifically

HIF-1 alpha Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awar ...

, which is involved in cells ability to undergo

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...

and other processes needed for cell survival. EZN-3042 is also an inhibitor, which acts against

Survivin Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the ''BIRC5'' gene. Survivin is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functi ...

. Santaris partnered with Enzon Pharmaceuticals, for the development of both drug candidates.

Hyperlipidemia

SPC-4955 was a drug intended for the treatment of high

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

. SPC-4955 inhibits the protein that is necessary for the formation of plasma

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

cholesterol particles. This has the potential to be used as a treatment for patients with

hyperlipidemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...

. SPC-5001 which targets

PCSK9 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes ( orth ...

program also has the potential to treat patients with

. It inhibits the protein that controls the number of receptors responsible for removing

cholesterol particles from the blood. As of 2022, clinical trials on SPC-4955 have been discontinued by Roche.

Hepatitis C

Santaris developed a microRNA targeting drug for

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...

(HCV),

miravirsen Miravirsen (INN; codenamed SPC3649) is an experimental drug for the treatment of hepatitis C, being developed by Santaris Pharma. As of 2017 it was in Phase II clinical trials. Miravirsen had been given by subcutaneous injection in early clinic ...

(SPC3649), which entered Phase II clinical trials in 2010. The drug targets

miR-122 miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 is highly expressed in the liver, where it has been implicated as a regulator of ...

, 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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

approved a multiple dosing study, by injection, to treatment-naive patients for phase II testing.

Rare genetic disorders

Santaris had a collaboration with

Shire Shire () is a traditional term for an administrative division of land in Great Britain and some other English-speaking countries. It is generally synonymous with county (such as Cheshire and Worcestershire). British counties are among the oldes ...

to discover and develop new RNA-based medicines to treat rare genetic disorders.

Collaborations

Santaris partnered with several pharmaceutical companies that wanted to develop LNA

for mRNA and microRNA targets.

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

and Santaris entered a collaboration pact in 2009, which was expanded in 2011. It also had a partnership with Enzon for cancer drug targets,

for lead candidates of five rare, undisclosed genetic disorders, miRagen to develop treatments targeting microRNAs associated with cardiovascular disease, and

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

for RNA-targeted medication.

Timeline

* 2003: Santaris was founded through a merger of Cureon and Pantheco. * 2004: Began cancer drug development – LNA-based drugs SPC3042 targeting Survivin and SPC2968 targeting HIF-1alpha. * 2005: Began a

miRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcri ...

research and drug development program. * 2006: Partnership with Enzon for cancer therapeutics. * 2007: Commencement of preclinical development of SPC3649, a microRNA-targeted drug for the treatment of Hepatitis C. Established commercial partnership with GlaxoSmithKline for global research and development and of up four programs in viral diseases. Enzon files IND and completes two Phase I/II US studies of advanced cancer research with EZN-2968. * 2008: Biotech grant of 45 million DKK, $9.33 million, from Danish Advanced Technology for microRNA antagonist research. Santaris Pharma named one of the “Fierce 15” Biotech Companies of 2008 by

FierceBiotech MidOcean Partners is a New York based alternative asset management firm that specializes in mid-sized private equity and alternative leveraged investments. The firm, founded in February 2003, is based in Midtown Manhattan. MidOcean was original ...

. Advanced to Phase 1 clinical trials for the treatment of HCV using a microRNA-targeted drug, SPC3649. Study published in Nature that shows LNA-based drugs targeting microRNAs capacity in non-human primates. * 2009: Establishment of a branch in San Diego, California, United States of America. Formed collaboration with Shire to develop RNA-based medicines for the treatment of rare genetic disorders. Advanced the 4955 into drug development, which is a compound that targets

Apolipoprotein B Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Its measurement is commonly used to detect the risk of Atherosclerosis, atherosclerotic Coronary artery disease, cardiovascular disease. Isoforms The protein occur ...

and could decrease and manage high cholesterol into drug development. Publication in Science showing how the breakthrough microRNA-targeted therapy SPC3649 is a promising new treatment for Hepatitis C.

Wyeth Pharmaceuticals Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, a ...

and Santaris Pharma announce their partnership to develop RNA-targeted medicines. * 2010: Santaris Pharma A/S and miRagen Therapeutics form a partnership to develop microRNA-targeted medicines for the treatment of cardiovascular disease. Advanced SPC5001, which targets PCSK9, into drug development for the treatment of high cholesterol. Received the

Red Herring A red herring is something that misleads or distracts from a relevant or important question. It may be either a logical fallacy or a literary device that leads readers or audiences toward a false conclusion. A red herring may be used intentiona ...

Top 100 Europe Award. * 2011: Obtained license from

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...

for intellectual property related to miR-33 regulations for cardiovascular disorder treatment. Expanded collaborations with Pfizer Inc. directed on development of RNA-targeted medicines. Advancement of miravirsen to Phase II trials, which is the first microRNA-targeted drug to enter clinical trials, and aims to treat patients infected with Hepatitis C. * 2013: Santaris Pharma A/S and

Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...

form a partnership to develop new medicines targeting mRNAs and microRNAs through Santaris' LNA technology. Santaris Pharma A/S and RaNa Therapeutics form an alliance to develop medicines against up to ten of RaNA's proprietary RNA targets, in a treatment that actively selects their protein expression. * 2014: Santaris Pharma A/S and GlaxoSmithKline (GSK) sign an agreement, wherein GSK gains access to LNA technology for medicine development. * 2014: Santaris Pharma A/S was acquired by Roche and renamed the Roche Innovation Center Copenhagen.

Awards

*2008: Fierce 15 by Fierce Biotechnology. *2010: Red Herring Top 100 Europe Award.

Litigation

*Santaris Pharma A/S vs. Exiqon A/S In 2010, Exiqon completed its litigation against Santaris for the supply of LNA. The court determined that both companies may supply the product for research and development of pharmaceutical products. Exiqon was made to pay partial costs to Santaris of DKK 2 million within two weeks. *Santaris Pharma A/S vs. Isis Pharmaceuticals Isis Pharmaceuticals filed a patent infringement lawsuit against Santaris Pharma A/S in the

United States District Court for the Southern District of California The United States District Court for the Southern District of California (in case citations, S.D. Cal.) is a federal court in the Ninth Circuit (except for patent claims and claims against the U.S. government under the Tucker Act, which are ap ...

in September 2011. Isis's infringement suit against Santaris is based upon Santaris's activities providing antisense drugs and antisense drug discovery services to several pharmaceutical companies.

References

{{DEFAULTSORT:Santaris Pharma a s Pharmaceutical companies of Denmark Pharmaceutical companies established in 2003 Danish companies established in 2003