Quasi-Vivo TM Inter-connected Cell Culture

1. Quasi-VivoTM Inter-connected Cell Culture Dr Kate DarleyKirkstall Ltd. Presentation April 2010

2. Quasi-VivoTM Cell Culture Systems • About Kirkstall • Introduction to the Quasi-VivoTM system • Access to the Quasi-VivoTM system • System data • Future directions

3. Quasi-VivoTM Cell Culture Systems About Kirkstall • Launch of company, November 2006 • South Yorkshire Seedcorn Fund investment July 2007 • Licence with Pisa University and Collaboration begins with Sheffield University, October 2007 • Proof of Concept Testing complete, June 2008 • Second Round Seed Funding, September 2008 • Manufacture and first validation studies complete, November 2008 • First Product (kit) sales, February 2009 • Launch of Contract Research Service, April 2009

4. Quasi-VivoTM Cell Culture Systems Introduction to the Quasi-VivoTM system

5. Quasi-VivoTM Cell Culture Systems INTER-CONNECTED CELL CULTURE … • Cells/tissue connected in series/parallel • Nutrient/media flow-through system • Allows cell-to-cell signalling • Metabolites/drugs/compounds circulate in system • Vitality/cell differentiation maintained PROVIDES IN-VIVO LIKE (Quasi-vivo) CONDITIONS FOR CELL GROWTH

6. Quasi-VivoTM Cell Culture Systems INTER-CONNECTED CELL CULTURE …

7. Quasi-VivoTM Cell Culture Systems Chamber design • Minimises bubble formation and shear stress • Shape & dimensions similar to 24 well plates. Facilitates cell transfer …from seeding to the bio-module • Cell biologists familiar with conventional multi-well plates rapidly able to use ...the system Proprietary design/covered by three patents

8. Quasi-VivoTM Cell Culture Systems Experimental design • Basic - 2 chambers connected • In series/parallel • Complex – 32 chambers • connected in series/parallel

9. Quasi-VivoTM Cell Culture Systems PROVIDES IN-VIVO LIKE CONDITIONS FOR CELL GROWTH? VALIDATION I • In primary hepatocytes xenobiotic gene expression • is closer to in vivo. • Cells maintain differentiation over a longer periods Cell morphology static Quasi-vivo

10. Conventional In vitro EC50 Quasi-VivoTMEC50 Clinical Trial Result Quasi-VivoTM Cell Culture Systems VALIDATION II - Correlation with drug metabolism/toxicity in vivo? Improved Sensitivity for Toxicity Screening: Diclofenac A non-steroidal anti-inflammatory.Dose-response curve inHuman Primary hepatocytes

11. Quasi-VivoTM Cell Culture Systems Access to the Quasi-VivoTM system

12. ACCESS TO THE TECHNOLOGY Quasi-VivoTM Cell Culture Systems Products: The Quasi-Vivo™ 100 Kit Bio-modules, reservoir bottle, connecting tubes, Peristaltic pump (Kit). Services: Contract research Flexible service, labs service available in Sheffield or in your own lab

13. Quasi-VivoTM Cell Culture Systems WHO WE WORK WITH…. • Academic groups: UK universities, • France (Montpellier), Italy (Pisa), • EU framework 7 – InLIVEtox • Cosmetic industry – EU ban 2009 • Need for an alternative to animal testing • Chemical industry – REACH legislation • Registration, Evaluation, Authorisation • and restriction of CHemicals • Pharmaceutical industry- Lead discovery/lead optimization

14. KEY NOTE SPEAKERS: Prof David Tweats (University of Swansea) ‘Toxicity Testing in the 21st Century’ Prof Claus-Michael Lehr (Helmholtz-Institute, Saarland) ‘Drug delivery across biological barriers’ Dr Patrick Maurel (INSERM Montpellier) ‘Human hepatocyte culture and applications for drug discovery’ Dr David Standring (Idenix Pharma, MA, USA) ‘Preclinical drug discovery, in vitro/in vivo testing past and future’ Dr Robert Landsiedel (BASF) ‘Safety Research on Nanomaterials’ Prof Sheila Macneil (University of Sheffield) ‘3D Tissue engineering models for R&D’

15. Quasi-VivoTM Cell Culture Systems Thanks for listening & any questions… kdarley@kirkstall.org www.kirkstall.org