Vernalis Research Explained

Vernalis Research
Type:	Subsidiary
Predecessor:	Vernalis plc
Foundation:	2018
Location City:	Cambridge
Location Country:	United Kingdom
Key People:	Clare Searle (Finance Director) James Murray (Research Director)
Industry:	Pharmaceutical and Biotechnology
Products:	Pharmaceuticals
Owner:	Vernalis (R&D) Limited
Num Employees:	75
Parent:	HitGen
Homepage:	vernalis.com

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.

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 2 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 A_2A.^[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. 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]

Notes and References

1. Davis BJ, Roughley SD . Fragment-Based Lead Discovery . January 2017 . Annual Reports in Medicinal Chemistry . 50 . 371–439 . 10.1016/bs.armc.2017.07.002 . 9780128130698 .
2. Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H . Twenty years on: the impact of fragments on drug discovery . Nature Reviews. Drug Discovery . 15 . 9 . 605–19 . September 2016 . 27417849 . 10.1038/nrd.2016.109 . 19634793 .
3. Book: Hubbard RE, Murray JB . Fragment-Based Drug Design - Tools, Practical Approaches, and Examples . Experiences in fragment-based lead discovery . Methods in Enzymology . 493 . 509–31 . 1 January 2011 . 21371604 . 10.1016/B978-0-12-381274-2.00020-0 . 9780123812742 .
4. Web site: Recommended Cash Offer for Vernalis plc by Ligand Holdings UK (Ltd) (a wholly owned subsidiary of Ligand Pharmaceuticals Incorporated) . London Stock Exchange . 14 December 2018.
5. Web site: HitGen to Acquire Vernalis, a Leader in Structure-Based Drug Discovery . Businesswire . 3 December 2020.
6. Massey AJ, Stokes S, Browne H, Foloppe N, Fiumana A, Scrace S, Fallowfield M, Bedford S, Webb P, Baker L, Christie M, Drysdale MJ, Wood M . 6 . Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design . Oncotarget . 6 . 34 . 35797–812 . November 2015 . 26437226 . 4742142 . 10.18632/oncotarget.5929 .
7. Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ, Dymock B, Eccles SA, Finch H, Fink A, Hayes A, Howes R, Hubbard RE, James K, Jordan AM, Lockie A, Martins V, Massey A, Matthews TP, McDonald E, Northfield CJ, Pearl LH, Prodromou C, Ray S, Raynaud FI, Roughley SD, Sharp SY, Surgenor A, Walmsley DL, Webb P, Wood M, Workman P, Wright L . 6 . 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer . Journal of Medicinal Chemistry . 51 . 2 . 196–218 . January 2008 . 18020435 . 10.1021/jm701018h .
8. Book: Inhibitors of Molecular Chaperones as Therapeutic Agents . Michael Rugaard . Jensen . Andrew . Massey . Joseph . Schoepfer . Paul A. . Brough . vanc . 23 October 2013 . 213–240 . 10.1039/9781849739689-00213 .
9. Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, Patterson L, de Haven Brandon A, Gowan S, Boxall F, Aherne W, Rowlands M, Hayes A, Martins V, Urban F, Boxall K, Prodromou C, Pearl L, James K, Matthews TP, Cheung KM, Kalusa A, Jones K, McDonald E, Barril X, Brough PA, Cansfield JE, Dymock B, Drysdale MJ, Finch H, Howes R, Hubbard RE, Surgenor A, Webb P, Wood M, Wright L, Workman P . 6 . NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis . Cancer Research . 68 . 8 . 2850–60 . April 2008 . 18413753 . 10.1158/0008-5472.CAN-07-5256 . free .
10. Brough PA, Barril X, Borgognoni J, Chene P, Davies NG, Davis B, Drysdale MJ, Dymock B, Eccles SA, Garcia-Echeverria C, Fromont C, Hayes A, Hubbard RE, Jordan AM, Jensen MR, Massey A, Merrett A, Padfield A, Parsons R, Radimerski T, Raynaud FI, Robertson A, Roughley SD, Schoepfer J, Simmonite H, Sharp SY, Surgenor A, Valenti M, Walls S, Webb P, Wood M, Workman P, Wright L . 6 . 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 . August 2009 . 19610616 . 10.1021/jm900357y .
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 . Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800 . Molecular Cancer Therapeutics . 9 . 4 . 906–19 . April 2010 . 20371713 . 10.1158/1535-7163.MCT-10-0055 . free .
12. Casara P, Davidson J, Claperon A, Le Toumelin-Braizat G, Vogler M, Bruno A, Chanrion M, Lysiak-Auvity G, Le Diguarher T, Starck JB, Chen I, Whitehead N, Graham C, Matassova N, Dokurno P, Pedder C, Wang Y, Qiu S, Girard AM, Schneider E, Gravé F, Studeny A, Guasconi G, Rocchetti F, Maïga S, Henlin JM, Colland F, Kraus-Berthier L, Le Gouill S, Dyer MJ, Hubbard R, Wood M, Amiot M, Cohen GM, Hickman JA, Morris E, Murray J, Geneste O . 6 . S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth . Oncotarget . 9 . 28 . 20075–20088 . April 2018 . 29732004 . 5929447 . 10.18632/oncotarget.24744 .
13. Kotschy A, Szlavik Z, Murray J, Davidson J, Maragno AL, Le Toumelin-Braizat G, Chanrion M, Kelly GL, Gong JN, Moujalled DM, Bruno A, Csekei M, Paczal A, Szabo ZB, Sipos S, Radics G, Proszenyak A, Balint B, Ondi L, Blasko G, Robertson A, Surgenor A, Dokurno P, Chen I, Matassova N, Smith J, Pedder C, Graham C, Studeny A, Lysiak-Auvity G, Girard AM, Gravé F, Segal D, Riffkin CD, Pomilio G, Galbraith LC, Aubrey BJ, Brennan MS, Herold MJ, Chang C, Guasconi G, Cauquil N, Melchiore F, Guigal-Stephan N, Lockhart B, Colland F, Hickman JA, Roberts AW, Huang DC, Wei AH, Strasser A, Lessene G, Geneste O . 6 . The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models . Nature . 538 . 7626 . 477–482 . October 2016 . 27760111 . 10.1038/nature19830 . 4472590 .
14. Szlávik. Zoltan. Ondi. Levente. Csékei. Márton. Paczal. Attila. Szabó. Zoltán B.. Radics. Gábor. Murray. James. Davidson. James. Chen. Ijen. 2019-08-08. Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity. Journal of Medicinal Chemistry. 62. 15. 6913–6924. 10.1021/acs.jmedchem.9b00134. 31339316. 198194567 . 0022-2623.
15. Pawsey S, Wood M, Browne H, Donaldson K, Christie M, Warrington S . 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 . June 2016 . 26987975 . 4875922 . 10.1007/s40268-016-0127-y .
16. Gillespie RJ, Bamford SJ, Botting R, Comer M, Denny S, Gaur S, Griffin M, Jordan AM, Knight AR, Lerpiniere J, Leonardi S, Lightowler S, McAteer S, Merrett A, Misra A, Padfield A, Reece M, Saadi M, Selwood DL, Stratton GC, Surry D, Todd R, Tong X, Ruston V, Upton R, Weiss SM . 6 . 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 . January 2009 . 19072055 . 10.1021/jm800961g .
17. Williamson DS, Smith GP, Acheson-Dossang P, Bedford ST, Chell V, Chen IJ, Daechsel JC, Daniels Z, David L, Dokurno P, Hentzer M, Herzig MC, Hubbard RE, Moore JD, Murray JB, Newland S, Ray SC, Shaw T, Surgenor AE, Terry L, Thirstrup K, Wang Y, Christensen KV . 6 . Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1) . Journal of Medicinal Chemistry . 60 . 21 . 8945–8962 . November 2017 . 29023112 . 10.1021/acs.jmedchem.7b01186 .
18. Christensen KV, Smith GP, Williamson DS . Development of LRRK2 Inhibitors for the Treatment of Parkinson's Disease . Progress in Medicinal Chemistry . 56 . 37–80 . 1 January 2017 . 28314412 . 10.1016/bs.pmch.2016.11.002 . 9780444639394 .
19. Web site: Vernalis Research «. Queensawardmagazine.com. 14 December 2018.