Vernalis Research

Vernalis Research develops and applies fragment and structure-based methods to drug discovery,[1][2][3] and has generated cell active lead compounds and development candidates against biological targets in oncology, neurodegeneration, anti-infectives and inflammation.

Vernalis Research
TypeSubsidiary
IndustryPharmaceutical and Biotechnology
PredecessorVernalis plc
Founded2018
Headquarters
Cambridge
,
United Kingdom
Key people
Mike Wood (Managing Director)
Clare Searle (Finance Director)
James Murray (Research Director)
ProductsPharmaceuticals
OwnerVernalis (R&D) Limited
Number of employees
75
ParentHitGen
Websitevernalis.com

History

Following the sale of Vernalis plc[4] on 10 October 2018, Vernalis Research became a subsidiary of Ligand Holdings UK Ltd, wholly owned by Ligand Pharmaceuticals, Inc. On 2nd December 2020, HitGen (Chengdu, China), acquired the entire issued share capital of Vernalis (R&D) Limited. [5]

Their scientists, based at Granta Park, Cambridge UK, integrate fragment-based approaches, structural biology, biophysics, assay technology, drug metabolism, pharmacokinetics, cheminformatics, molecular modelling and computational, synthetic organic and medicinal chemistry to enable drug discovery on both established and novel targets, progressing projects from target identification through to clinical candidate. They have generated lead compounds on enzymes, protein-protein interactions and GPCRs, leading to clinical candidates for targets such as Chk1,[6] Hsp90,[7][8][9][10][11] Bcl-2,[12] Mcl-1,[13][14] FAAH[15] and A2A.[16]

As well as an internal portfolio of drug discovery projects, Vernalis Research has a number of research collaborations on targets with large pharmaceutical companies and academic partners. Recently disclosed collaborations include those with Servier,[13][12] Daiichi Sankyo, Lundbeck[17][18] and Asahi Kasei Pharma. In 2014, the Company was awarded a Queen's Award for Enterprise, for outstanding achievement in International Trade, endorsing both the talent and capabilities of its research group, and recognition of the growing overseas earnings it has achieved.[19]

Vernalis Research has delivered a number of drug candidates into clinical development, some of which remained as part of the Ligand Pharmaceuticals, Inc. portfolio following the sale of the research business to HitGen. These include V158866, the lead molecule arising from an in-house FAAH research programme, which completed a phase II study in spinal cord injury patients in July 2015.[20] Additionally, luminespib (AUY922) is a novel intravenous Hsp90 inhibitor with the potential to target a range of cancers, which arose from a research collaboration starting in 2004, originally between Vernalis plc, the Institute of Cancer Research and Cancer Research Technology, and then with Novartis.[8] A further example is V158411, the lead intravenous molecule arising from an in-house structure-based Chk1 oncology research programme.[6]

References
  1. Davis BJ, Roughley SD (January 2017). "Fragment-Based Lead Discovery". Annual Reports in Medicinal Chemistry. 50: 371–439. doi:10.1016/bs.armc.2017.07.002. ISBN 9780128130698.
  2. Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H (September 2016). "Twenty years on: the impact of fragments on drug discovery". Nature Reviews. Drug Discovery. 15 (9): 605–19. doi:10.1038/nrd.2016.109. PMID 27417849.
  3. Hubbard RE, Murray JB (1 January 2011). "Experiences in fragment-based lead discovery". Methods in Enzymology. 493: 509–31. doi:10.1016/B978-0-12-381274-2.00020-0. ISBN 9780123812742. PMID 21371604.
  4. "Recommended Cash Offer for Vernalis plc by Ligand Holdings UK (Ltd) (a wholly owned subsidiary of Ligand Pharmaceuticals Incorporated)". London Stock Exchange. Retrieved 14 December 2018.
  5. "HitGen to Acquire Vernalis, a Leader in Structure-Based Drug Discovery". Businesswire. Retrieved 3 December 2020.
  6. Massey AJ, Stokes S, Browne H, Foloppe N, Fiumana A, Scrace S, et al. (November 2015). "Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design". Oncotarget. 6 (34): 35797–812. doi:10.18632/oncotarget.5929. PMC 4742142. PMID 26437226.
  7. Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, et al. (January 2008). "4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer". Journal of Medicinal Chemistry. 51 (2): 196–218. doi:10.1021/jm701018h. PMID 18020435.
  8. Jensen MR, Massey A, Schoepfer J, Brough PA (23 October 2013). Inhibitors of Molecular Chaperones as Therapeutic Agents. pp. 213–240. doi:10.1039/9781849739689-00213.
  9. Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, et al. (April 2008). "NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis". Cancer Research. 68 (8): 2850–60. doi:10.1158/0008-5472.CAN-07-5256. PMID 18413753.
  10. Brough PA, Barril X, Borgognoni J, Chene P, Davies NG, Davis B, et al. (August 2009). "Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone". Journal of Medicinal Chemistry. 52 (15): 4794–809. doi:10.1021/jm900357y. PMID 19610616.
  11. Massey AJ, Schoepfer J, Brough PA, Brueggen J, Chène P, Drysdale MJ, Pfaar U, Radimerski T, Ruetz S, Schweitzer A, Wood M, Garcia-Echeverria C, Jensen MR (April 2010). "Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800". Molecular Cancer Therapeutics. 9 (4): 906–19. doi:10.1158/1535-7163.MCT-10-0055. PMID 20371713.
  12. Casara P, Davidson J, Claperon A, Le Toumelin-Braizat G, Vogler M, Bruno A, et al. (April 2018). "S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth". Oncotarget. 9 (28): 20075–20088. doi:10.18632/oncotarget.24744. PMC 5929447. PMID 29732004.
  13. Kotschy A, Szlavik Z, Murray J, Davidson J, Maragno AL, Le Toumelin-Braizat G, et al. (October 2016). "The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models". Nature. 538 (7626): 477–482. doi:10.1038/nature19830. PMID 27760111.
  14. Szlávik, Zoltan; Ondi, Levente; Csékei, Márton; Paczal, Attila; Szabó, Zoltán B.; Radics, Gábor; Murray, James; Davidson, James; Chen, Ijen (8 August 2019). "Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity". Journal of Medicinal Chemistry. 62 (15): 6913–6924. doi:10.1021/acs.jmedchem.9b00134. ISSN 0022-2623. PMID 31339316.
  15. Pawsey S, Wood M, Browne H, Donaldson K, Christie M, Warrington S (June 2016). "Safety, Tolerability and Pharmacokinetics of FAAH Inhibitor V158866: A Double-Blind, Randomised, Placebo-Controlled Phase I Study in Healthy Volunteers". Drugs in R&D. 16 (2): 181–91. doi:10.1007/s40268-016-0127-y. PMC 4875922. PMID 26987975.
  16. Gillespie RJ, Bamford SJ, Botting R, Comer M, Denny S, Gaur S, et al. (January 2009). "Antagonists of the human A(2A) adenosine receptor. 4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines". Journal of Medicinal Chemistry. 52 (1): 33–47. doi:10.1021/jm800961g. PMID 19072055.
  17. Williamson DS, Smith GP, Acheson-Dossang P, Bedford ST, Chell V, Chen IJ, et al. (November 2017). "Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1)" (PDF). Journal of Medicinal Chemistry. 60 (21): 8945–8962. doi:10.1021/acs.jmedchem.7b01186. PMID 29023112.
  18. Christensen KV, Smith GP, Williamson DS (1 January 2017). "Development of LRRK2 Inhibitors for the Treatment of Parkinson's Disease". Progress in Medicinal Chemistry. 56: 37–80. doi:10.1016/bs.pmch.2016.11.002. ISBN 9780444639394. PMID 28314412.
  19. "Vernalis Research «". Queensawardmagazine.com. Retrieved 14 December 2018.
  20. Clinical trial number NCT01748695 for "A Safety, Tolerability and Efficacy Study of V158866 in Central Neuropathic Pain Following Spinal Cord Injury" at ClinicalTrials.gov
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