Santaris Pharma

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Santaris Pharma A/S
Industry
Founded2003
FateAcquired by Roche Pharmaceuticals
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. With its LNA technology, Santaris developed drugs for the treatment of cancers and tumours 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.[3]

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

Locked Nucleic Acid (LNA) drug platform[edit]

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.[6] [7] [3]

Drug candidates[edit]

Cancer drug candidates[edit]

In 2009, Santaris announced that two LNA based drugs EZN-3042, and EZN-2968 would be entering clinical trials.[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. Santaris partnered with Enzon Pharmaceuticals,[9] for the development of both drug candidates.

Metabolic disorders candidates[edit]

SPC-4955 was a drug intended for the treatment of high 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 a treatment for patients with hyperlipidemia.[10] SPC-5001 which targets PCSK9 program also has the potential to treat patients with hyperlipidemia. It inhibits the protein that controls the number of receptors responsible for removing LDL cholesterol particles from the blood.[10]

As of 2022, clinical trials on SPC-4955 have been discontinued by Roche.[11]

Infectious disease[edit]

Santaris developed a microRNA targeting drug for hepatitis C, miravirsen (SPC3649),[12] which entered Phase II clinical trials in 2010.[13] 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.[14] The U.S. Food and Drug Administration approved a multiple dosing study, by injection, to treatment-naive patients for phase II testing.[13]

Rare genetic disorders[edit]

Santaris had a collaboration with Shire to discover and develop new RNA-based medicines to treat rare genetic disorders.[15]

Collaborations[edit]

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.[16] It also partnership with Enzon for cancer drug targets, [9]Shire for lead candidates of five rare, undisclosed genetic disorders,[15] miRagen to develop treatments targeting microRNAs associated with cardiovascular disease,[17] and GlasoSmithKline for RNA-targeted medication.[18]

Publications[edit]

Santaris employees have co-authored articles published in Nature (2008),[19] and Science (2009).[20] These have outlined the results of experiments using LNA oligonucleotides to down-regulate the expression of endogenous microRNAs in primates.[citation needed]

Timeline[edit]

  • 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.[6]
  • 2005: Began a miRNA research and drug development program.[6]
  • 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.[12] Established commercial partnership with GlaxoSmithKline for global research and development and of up four programs in viral diseases.[21] Enzon files IND and completes two Phase I/II US studies of advanced cancer research with EZN-2968.[15]
  • 2008: Biotech grant of 45 million DKK, $9.33 million, from Danish Advanced Technology for microRNA antagonist research.[22] 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.[13] Study published in Nature that shows LNA-based drugs targeting microRNAs capacity in non-human primates.[19]
  • 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.[15] Advanced the 4955 into drug development, which is a compound that targets Apolipoprotein B and could decrease and manage high cholesterol into drug development.[6] Publication in Science showing how the breakthrough microRNA-targeted therapy SPC3649 is a promising new treatment for Hepatitis C.[20] Wyeth Pharmaceuticals and Santaris Pharma announce their partnership to develop RNA-targeted medicines.[23]
  • 2010: Santaris Pharma A/S and miRagen Therapeutics form an alliance to develop microRNA-targeted medicines for the treatment of cardiovascular disease.[17] Advanced SPC5001, which targets PCSK9, into drug development for the treatment of high cholesterol.[10] Received the Red Herring Top 100 Europe Award.[24]
  • 2011: Obtained license from Massachusetts General Hospital for intellectual property related to miR-33 regulations for cardiovascular disorder treatment.[25] Expanded collaborations with Pfizer Inc. directed on development of RNA-targeted medicines.[26] 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.[27]
  • 2013: Santaris Pharma A/S and Bristol-Myers Squibb form an alliance to develop new medicines targeting mRNAs and microRNAs through Santaris' LNA technology.[28]
  • 2013: Santaris Pharma A/S and RaNa 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.[29]
  • 2014: Santaris Pharma A/S and GlaxoSmithKline (GSK) sign an agreement, wherein GSK gains access to LNA technology for medicine development.[18]
  • 2014: Santaris Pharma A/S was acquired by Roche and renamed the Roche Innovation Center Copenhagen.[30]

Awards[edit]

  • 2008: Fierce 15 by Fierce Biotechnology. [1]
  • 2010: Red Herring Top 100 Europe Award. [24]

Corporate structure[edit]

Executives[edit]

  • 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[edit]

  • 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.[31]

  • 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.[32]

References[edit]

  1. ^ a b c "Santaris Pharma - 2008 Fierce 15". Fierce Biotech. June 2008.
  2. ^ a b "MicroRNA Drug Developer Santaris Establishes Toehold in San Diego With Isis Veteran". Xconomy. September 16, 2009. Archived from the original on 2021-05-12.
  3. ^ a b c d "Developing LNA technology for new-generation cancer drugs" (PDF). SP2 Magazine. March 2006.
  4. ^ "Forbion Announces Sale of Portfolio Company, Santaris Pharma, to Roche for up to $450m". www.businesswire.com. 2014-08-04. Retrieved 2022-03-05.
  5. ^ "Roche | Pharma R&D - Copenhagen, Denmark". www.roche-dot-com-staging.cwp.roche.com. Retrieved 2024-05-12.
  6. ^ a b c d Weiss, B.; Davidkova, G.; Zhou, L. W. (March 1999). "Antisense RNA gene therapy for studying and modulating biological processes". Cellular and Molecular Life Sciences: CMLS. 55 (3): 334–358. doi:10.1007/s000180050296. ISSN 1420-682X. PMID 10228554.
  7. ^ 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)
  8. ^ "Santaris Pharma A/S: Another LNA-based RNA Inhibitor Enters Clinical Trials EZN3042". BioSpace. Retrieved 2024-05-12.
  9. ^ a b c "Enzon Pharmaceuticals and Santaris Pharma Enter into Global Collaboration to Develop Novel Cancer Therapeutics; Alliance Strengthens Both Companies' Oncology Pipelines" (PDF). Enzon Pharmaceuticals. July 27, 2006. Retrieved 2024-05-12.
  10. ^ a b c "Santaris advances a second drug from its cardiometabolic programme, SPC4955, into phase I trials to treat high cholesterol". test.pharmabiz.com. Retrieved 2024-05-12.
  11. ^ Bejar, Nada; Tat, Trinh T.; Kiss, Daniel L. (May 2022). "RNA Therapeutics: the Next Generation of Drugs for Cardiovascular Diseases". Current Atherosclerosis Reports. 24 (5): 307–321. doi:10.1007/s11883-022-01007-9. ISSN 1523-3804. PMC 8975710. PMID 35364795.
  12. ^ a b Chakraborty, Chiranjib; Sharma, Ashish Ranjan; Sharma, Garima; Doss, C. George Priya; Lee, Sang-Soo (2017-09-15). "Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine". Molecular Therapy - Nucleic Acids. 8: 132–143. doi:10.1016/j.omtn.2017.06.005. ISSN 2162-2531. PMID 28918016.
  13. ^ a b c Janssen, Harry L.A.; Reesink, Hendrik W.; Lawitz, Eric J.; Zeuzem, Stefan; Rodriguez-Torres, Maribel; Patel, Keyur; van der Meer, Adriaan J.; Patick, Amy K.; Chen, Alice; Zhou, Yi; Persson, Robert; King, Barney D.; Kauppinen, Sakari; Levin, Arthur A.; Hodges, Michael R. (2013-05-02). "Treatment of HCV Infection by Targeting MicroRNA". New England Journal of Medicine. 368 (18): 1685–1694. doi:10.1056/NEJMoa1209026. ISSN 0028-4793. PMID 23534542.
  14. ^ "Santaris Pharma A/S advances miravirsen, the first microRNA-targeted drug to enter clinical trials, into Phase 2 to treat patients infected with Hepatitis C virus" (PDF). Globa Life Science Ventures. 2010-09-22. Retrieved 2024-05-12.
  15. ^ a b c d Otmani, Malin (2013-09-04). "Shire extends partnership with Santaris Pharma". Nordic Life Science – the leading Nordic life science news service. Retrieved 2024-05-12.
  16. ^ Jarzemsky, Matt (2011-01-04). "Pfizer, Santaris Expand Collaboration Pact". Wall Street Journal. ISSN 0099-9660. Retrieved 2022-03-05.
  17. ^ a b "Santaris Pharma A/S and miRagen Therapeutics, Inc. Form Strategic Alliance to Develop microRNA-Targeted Medicines for the Treatment of Cardiovascular Disease". www.prnewswire.com. Retrieved 2024-05-12.
  18. ^ a b A/S, Santaris Pharma. "Santaris Pharma A/S announce agreement with GlaxoSmithKline (GSK) to develop RNA-targeted medicines". www.prnewswire.co.uk. Retrieved 2024-05-12.
  19. ^ a b 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.
  20. ^ a b 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.
  21. ^ "GSK, Santaris ink $700M development deal". Fierce Biotech. 2007.
  22. ^ Writer, GEN Staff (2008-05-15). "Santaris Pharma Consortium Receives $9.33M to Develop RNA Drug Compounds". GEN - Genetic Engineering and Biotechnology News. Retrieved 2024-05-12.
  23. ^ Taylor, Nick (January 13, 2009). "Wyeth partners with Santaris on RNA development". Outsourcing Pharma.
  24. ^ a b "2010 RED HERRING TOP 100 EUROPE WINNERS". Red Herring. Retrieved 2024-05-12.
  25. ^ Writer, GEN Staff (2011-02-28). "Santaris Pharma Licenses miRNA from MGH for Development in Cardiovascular Diseases". GEN - Genetic Engineering and Biotechnology News. Retrieved 2024-05-12.
  26. ^ John Carrol (January 4, 2011). "Pfizer ups ante on Santaris RNA discovery deal with $614M pact". Fierce Biotech.
  27. ^ "Santaris Pharma A/S Advances miravirsen, the First microRNA-Targeted Drug to Enter Clinical Trials, Into Phase 2 to Treat Patients Infected With Hepatitis C Virus". www.prnewswire.com. Retrieved 2024-05-12.
  28. ^ "Santaris Pharma announces a worldwide discovery alliance with Bristol-Myers Squibb for RNA-targeted medicines". www.prnewswire.com. Retrieved 2024-05-12.
  29. ^ "RaNA Taps Santaris LNA Chemistry for RNA-Targeted Drug Development". GEN - Genetic Engineering and Biotechnology News. 2013-07-08. Retrieved 2024-05-12.
  30. ^ "Roche to Acquire Santaris Pharma to Expand RNA Portfolio". Yahoo Finance. 2014-08-05. Archived from the original on 2015-07-08. Retrieved 2024-05-12.
  31. ^ "Exiqon A/S completes litigation against Santaris Pharma a/s". GlobeNewswire News Room. 2011-10-07. Retrieved 2024-05-12.
  32. ^ "Isis files patent infringement lawsuit against Santaris for antisense drugs". News Medical. September 26, 2011.
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