Santaris Pharma A/S
IndustryPharmaceuticals
Founded2003
HeadquartersCopenhagen, Denmark
ProductsRNA-targeted medicines, Locked Nucleic Acid (LNA) based drugs

Santaris Pharma A/S was a biopharmaceutical company founded in 2003 in Copenhagen, Denmark.[1] The company also had a branch in San Diego, California that opened in 2009.[2] 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.[3]

Santaris had gained worldwide intellectual property rights to the therapeutic applications of locked nucleic acid (LNA) technology. These rights included ownership of over 60 patent types, which ranged from chemistry to manufacturing and from therapeutic uses to drug design.[3] With its LNA technology, Santaris developed drugs for a range of diseases using microRNA and mRNA. Its research focused on infectious diseases and metabolic disorders. The company also worked on collaborations with pharmaceuticals to develop drugs that could treat cancers and rare genetic disorders, among other things.

In August 2014, Santaris was acquired by Roche for $450 million.[4] As a result, the Copenhagen site was renamed the Roche Innovation Center Copenhagen (RICC).[5] RICC houses Roche's RNA Molecule Research, which is part of Roche Pharma Research and Early Development.[6]

Locked Nucleic Acid (LNA) drug platform

Santaris developed drugs based on Locked Nucleic Acids (LNA) to facilitate the identification and design of potential drug candidates. LNAs are modified RNA molecules, featuring an oxymethylene bridge between the 2’ oxygen and 4’ carbon in the ribose ring. This structural alteration forms a bi-cyclic configuration that enhances the stability and binding affinity of LNAs to their complementary RNA sequences.

LNA oligonucleotides 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 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 activity, which contributes to their durability. Moreover, LNA drugs possess several advantageous attributes: they can be administered without the need for complex drug delivery methods, their production is scalable and cost-effective, they are well-tolerated, and there exists potential for oral administration. These factors collectively define LNA-based drugs as innovative therapeutic agents.[7] [4] [3]

Drug candidates

Cancer drug candidates

Santaris Pharma A/S had two novel drug candidates for the treatment of solid tumors and lymphomas, EZN-2968 and EZN-3042.[8] 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.[8] Santaris partnered with Enzon Pharmaceuticals [9] for the development of both drug candidates.

Metabolic disorders candidates

SPC-4955 is a novel treatment for cholesterol.[10] SPC-4955 inhibits the protein that is necessary for the formation of plasma LDL cholesterol particles. This has the potential to be used as a treatment for patients with hyperlipidemia. The PCSK9 program also has the potential to treat patients with hyperlipidemia.[10] It inhibits the protein that controls the number of receptors responsible for removing LDL cholesterol particles from the blood.

Infectious disease

Santaris developed a microRNA targeting drug for hepatitis C, miravirsen (SPC3649),[3] which entered Phase II clinical trials in 2010.[11] 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.[12] The U.S. Food and Drug Administration approved a multiple dosing study, by injection, to treatment-naive patients for phase II testing.[11]

Rare genetic disorders

Santaris had a collaboration with Shire to discover and develop new RNA-based medicines to treat rare genetic disorders.[9]

Collaborations

Santaris partnered with several pharmaceutical companies that wanted to develop LNA oligonucleotides for mRNA and microRNA targets. Pfizer and Santaris entered a collaboration pact in 2009, which was expanded in 2011.[13] It also partnership with Enzon for cancer drug targets, [9] Shire for lead candidates of five rare, undisclosed genetic disorders,[9] miRagen to develop treatments targeting microRNAs associated with cardiovascular disease, and GlasoSmithKline for four viral disease programs and clinical trials.[14]

Publications

Santaris employees have co-authored articles published in Nature (2008),[15] and Science (2009).[16] These have outlined the results of experiments using LNA oligonucleotides to down-regulate the expression of endogenous microRNAs in primates.

Timeline

  • 2003: Santaris was founded through a merger of Cureon and Pantheco.[3]
  • 2004: Began cancer drug development – LNA-based drugs SPC3042 targeting Survivin and SPC2968 targeting HIF-1alpha.[7]
  • 2005: Began a miRNA research and drug development program.[7]
  • 2006: Partnership with Enzon for cancer therapeutics.[9]
  • 2007: Commencement of preclinical development of SPC3649, a microRNA-targeted drug for the treatment of Hepatitis C.[3] Established commercial partnership with GlaxoSmithKline for global research and development and of up four programs in viral diseases.[17] Enzon files IND and completes two Phase I/II US studies of advanced cancer research with EZN-2968.[9]
  • 2008: Biotech grant from Danish Advanced Technology for microRNA antagonist research for 45m DKK.[18] Santaris Pharma named one of the “Fierce 15” Biotech Companies of 2008 by FierceBiotech.[1] Advanced to Phase 1 clinical trials for the treatment of HCV using a microRNA-targeted drug, SPC3649.[7] Study published in Nature that shows LNA-based drugs targeting microRNAs capacity in non-human primates.[15]
  • 2009: Establishment of a branch in San Diego, California, United States of America.[2] Formed collaboration with Shire to develop RNA-based medicines for the treatment of rare genetic disorders.[9] Advanced the 4955 into drug development, which is a compound that targets Apolipoprotein B and could decrease and manage high cholesterol into drug development.[7] Publication in Science showing how the breakthrough microRNA-targeted therapy SPC3649 is a promising new treatment for Hepatitis C.[16] Wyeth Pharmaceuticals and Santaris Pharma announce their partnership to develop RNA-targeted medicines.[19]
  • 2010: Santaris Pharma A/S and miRagen Therapeutics form an alliance to develop microRNA-targeted medicines for the treatment of cardiovascular disease.[14] Advanced SPC5001, which targets PCSK9, into drug development for the treatment of high cholesterol.[7] Received the Red Herring Top 100 Europe Award.[20]
  • 2011: Obtained license from Mass General Hospital for intellectual property related to miR-33 regulations for cardiovascular disorder treatment.[21] Expanded collaborations with Pfizer Inc. directed on development of RNA-targeted medicines.[22] Santaris made medical history with their 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.[23]
  • 2013: Santaris Pharma A/S and Bristol-Myers Squibb form an alliance to develop lead candidates against a limited number of targets
  • 2013: Santaris Pharma A/S and RaNa form an alliance to develop lead candidates against <10 of RaNA’s proprietary RNA targets for the treatment of human diseases
  • 2014: Santaris Pharma A/S was acquired by Roche and renamed the Roche Innovation Center Copenhagen.

Awards

  • 2008: Fierce 15 by Fierce Biotechnology [1]
  • 2010: Red Herring Top 100 Europe Award [20]
  • 2011: Finalist for 2011 Scrip Awards in the "Clinical Research Team of the Year" category.[24]

Corporate structure

Executives

  • J. Donald deBethizy – President & Chief Executive Officer
  • Henrik Stage, MS. – Chief Financial Officer & EVP Corporate Development
  • Henrik Ørum, MSc PhD – VP & Chief Scientific Officer
  • Michael R. Hodges, MD – VP & Chief Medical Officer
  • Troels Koch, PhD – VP & Chief Technology Officer
  • Bo Rode Hansen, PhD – VP, Alliance Management & Partnered Drug Discovery

Litigation

  • Santaris Pharma A/S vs. Exiqon A/S

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 confirmed that Santaris held exclusive worldwide rights to manufacture, have manufactured, and sell products that comprise LNA as active ingredients for studies performed to develop LNA-based drugs for marketing approval.[25]

  • 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 of the Southern District of California 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.[26]

References

  1. 1 2 3 "Santaris Pharma - 2008 Fierce 15". Fierce Biotech. June 2008.
  2. 1 2 "MicroRNA Drug Developer Santaris Establishes Toehold in San Diego With Isis Veteran". Xconomy. September 16, 2009.
  3. 1 2 3 4 5 6 "Developing LNA technology for new-generation cancer drugs" (PDF). SP2 Magazine. March 2006.
  4. 1 2 Weiss B., Davidkova G., Zhou L-W. (1999). "Antisense RNA gene therapy for studying and modulating biological processes". Cell. Mol. Life Sci. 55 (3): 334–358. doi:10.1007/s000180050296. PMID 10228554. S2CID 9448271.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ "Forbion Announces Sale of Portfolio Company, Santaris Pharma, to Roche for up to $450m". www.businesswire.com. 2014-08-04. Retrieved 2022-03-05.
  6. ↑ "Roche | Pharma R&D - Copenhagen, Denmark". www.roche.com. Retrieved 2022-03-05.
  7. 1 2 3 4 5 6 "2010 Annual Report: A Pipeline of Opportunity". 2010. {{cite journal}}: Cite journal requires |journal= (help)
  8. 1 2 "Cancer". 2011. {{cite journal}}: Cite journal requires |journal= (help)
  9. 1 2 3 4 5 6 7 "Santaris, Shire Ink $380M+ Deal for Rare Generic Disorder Drugs". AllBusiness. August 25, 2009.
  10. 1 2 "Metabolic Disorders". 2011. {{cite journal}}: Cite journal requires |journal= (help)
  11. 1 2 Alan Franciscus (2010). "Hepatitis C Treatments in Current Development". HCV Advocate. Archived from the original on 2007-09-29.
  12. ↑ "New Hepatitis C Treatment Shows Promise". Drugs.com. 2009.
  13. ↑ Jarzemsky, Matt (2011-01-04). "Pfizer, Santaris Expand Collaboration Pact". Wall Street Journal. ISSN 0099-9660. Retrieved 2022-03-05.
  14. 1 2 "miRagen Therapeutics". June 23, 2010. {{cite journal}}: Cite journal requires |journal= (help)
  15. 1 2 Joacim Elmén (2009). "LNA-mediated microRNA silencing in non-human primates". Nature. 452 (7189): 896–899. Bibcode:2008Natur.452..896E. doi:10.1038/nature06783. PMID 18368051. S2CID 4308734.
  16. 1 2 Robert Lanford; Hildebrandt-Eriksen, ES; Petri, A; Persson, R; Lindow, M; Munk, ME; Kauppinen, S; Ørum, H (2010). "Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection". Science. 327 (5962): 198–201. Bibcode:2010Sci...327..198L. doi:10.1126/science.1178178. PMC 3436126. PMID 19965718.
  17. ↑ "GSK, Santaris ink $700M development deal". 2007. {{cite journal}}: Cite journal requires |journal= (help)
  18. ↑ "Santaris Pharma Consortium Awarded 45m DKK (€6m) by Denmark's Advanced Technology Foundation to Enhance Discovery of RNA Medicines". BusinessWire. 2008.
  19. ↑ Taylor, Nick (January 13, 2009). "Wyeth partners with Santaris on RNA development". {{cite journal}}: Cite journal requires |journal= (help)
  20. 1 2 "2010 Red Herring Top 100 Europe Winners". Red Herring. 2010.
  21. ↑ Navjot Rai (February 28, 2011). "Santaris Pharma A/S obtains an exclusive license from Mass General Hospital for intellectual property related to the regulation of miR-33 for the treatment of cardiovascular disorders". {{cite journal}}: Cite journal requires |journal= (help)
  22. ↑ John Carrol (January 4, 2011). "Pfizer ups ante on Santaris RNA discovery deal with $614M pact". {{cite journal}}: Cite journal requires |journal= (help)
  23. ↑ Navjot Rai (November 5, 2011). "Santaris Pharma A/S Phase 2a data of miravirsen shows dose-dependent, prolonged viral reduction of 2-3 logs HCV RNA after four-week treatment in Hepatitis C patients". {{cite journal}}: Cite journal requires |journal= (help)
  24. ↑ "The 7th Annual Scrip Awards". 2011. {{cite journal}}: Cite journal requires |journal= (help)
  25. ↑ Navjot Rai (2011). "Santaris Pharma A/S obtains favorable ruling in arbitration proceedings against Exiqon A/S". {{cite journal}}: Cite journal requires |journal= (help)
  26. ↑ "Isis files patent infringement lawsuit against Santaris for antisense drugs". September 26, 2011. {{cite journal}}: Cite journal requires |journal= (help)
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