1. Why Outsource to Neurotar? A Business Development Proposal from Neurotar Ltd September 2010 Neurotar Ltd • www.neurotar.com

4. A c Cell erate: Faster, better informed preclinical decisions B eSure: Higher predictive power => Success in clinical trials Neurotar Ltd • www.neurotar.com “ The advantage of multiphoton intravital microscopy <...> is the capability to chronically image structure, function and the therapeutic response at high resolution with superior contrast and maximal physiological relevance .” Prof. Andrew Bullen, University of California San Francisco, USA Lead search Lead validation in vivo Ultimate lead validation in vivo Clinical trials Clinical trials time Lead search Lead validation in vitro High-throughput screening High Relevance High Resolution NEUROTAR’s in vivo microscopy Success due to increased predictive power Failure due to low predictive power High-throughput screening High Relevance Low Resolution Low Relevance High Resolution in vivo imaging in vitro microscopy

5. D eeTails: high definition picture in vivo Neurotar Ltd • www.neurotar.com “ Multiphoton microscopy <...> is the best high-resolution, noninvasive means of imaging in living animals <...> improving drug discovery and accelerating preclinical trials of clinical treatments.” Prof. Sharron X. Lin, Cornell University, New York USA Conventional low-resolution in vivo imaging NEUROTAR’S high-resolution in vivo microscopy

6. C eeMore: multiple parameters at once Neurotar Ltd • www.neurotar.com Mono-parametric imaging (one channel) NEUROTAR’s Multi-parametric imaging (2 channels or more) “ ... In vivo multiphoton microscopy has revolutionized the way that biomedical researchers can study physiology, pathophysiology, and drug action .” Prof. Kenneth W. Dunn, Indiana University Medical Center, USA

7. Power of Two: C eeMore D eeTails in vivo Neurotar Ltd • www.neurotar.com Low-resolution Mono-parametric High-resolution Mono-parametric High-resolution Multi-param etric Currently offered services: Neurotar’s advanced imaging services: “ Two-photon microscopy has opened a new era in the morphological and pathophysiological studies of the nervous system .” Prof. Clément Ricard, INSERM, France

8. Case study I : in vivo microscopy of A  plaques in AD End-point histopathology versus Neurotar’s in vivo microscopy Neurotar Ltd • www.neurotar.com “ Multiphoton microscopy will continue to be a powerful tool in understanding and combating Alzheimer's disease .” Prof. Brian J. Bacskai, Massachusetts General Hospital, USA 6 mice for 4 months Researchers’ time + animal use Σ 90 h 6 mice Breeding & handling 135 mice for 2-4 months Σ 300 hours 135 mice Researchers’ time + animal use 1 group = 15 mice Total 9 groups Histology (30h/group) Injections (3h/group) 1 group = 3 mice Total 2 groups in vivo imaging (6h/group) Surgery + injections (6h/group) Bonus: measurement of additional dynamic parameters accessible ONLY by NEUROTAR’s in vivo two-photon imaging (e.g., blood flow, Ca 2+ signaling, transient BBB breach, mitochondrial membrane potential, cell motility etc). Garcia-Alloza et al 2006 J Neuropath Exp Neurol Vasculature , A  plaques and neuronal fine processes Imaged in vivo Amyloid plaques visualized in fixed post-mortem sections

9. Case study II : in vivo microscopy in Stroke models Neurotar Ltd • www.neurotar.com “ At present, only 2-photon microscopy permits high-resolution, real-time imaging of structure and function within identified neurons in vivo.” Prof. Timothy H. Murphy, University of Alberta, Canada Longitudinal quantification of fine structural changes after stroke: Laser-induced thrombosis of cortical vessels (images by Neurotar): Vertical view: 50  m Winship and Murphy 2009, Neuroscientist

10. Case study III : in vivo microscopy in Migraine models Neurotar Ltd • www.neurotar.com Serduc et al., 2006 Int. J. Radiation Oncology Biol. Phys. In vivo two-photon images of BBB integrity and extravasation of fluorescent dyes Before and After irradiation. Vertical view In vivo two-photon images of reduced glutathione in meninges and cortex Horyzontal view Vertical view Sun et al., 2006 J. Biological Chemistry Imaging Blood-Brain Barrier Imaging Redox Deregulation “ Functional two-photon microscopy has allowed the mechanisms of neurovascular coupling to be studied in vivo in unprecedented detail . <...> It enables the interrelations between individual neurons, glial cells, and vessels to be examined.” Elisabeth M.C. Hillman, Columbia University, NY USA