Introduction to in vivo imaging for exploratory research in biomedical R&D. Year 2009. Beware of imitations!

1. TURNKEY SERVICES one-stop shop molecular imaging discovery imaging preclinical imaging Antonio 07Nov09 www.animascope.eu

2. EXECUTIVE SUMMARY Animascope is an R&D contract services company that specialises in multi-modality non-invasive biomedical imaging in vivo for discovery and preclinical exploratory research on animals in several therapeutic areas, onco, cardio, bones etc. In vivo visualisation of tissues, functions and dysfunctions, whole-body Cost-effective and time-effective approach Streamline discovery and preclinical studies Increase predictability of clinical outcomes Reduce experimental artifacts, Refine studies on animal models, Reduce the animal usage from 100% down to 20-30% To be earlier in the market Antonio 07Nov09

3. ANIMASCOPE INTEGRATED KNOWLEDGE TECHNOLOGY providers BIOMARKERS providers SOFTWARE providers FULL STUDY MANAGEMENT ANIMAL MODELS providers MANAGEMENT expertise Antonio 07Nov09 THERAPEUTIC expertise

5. Transversal Expertise, Integrated Knowledge

6. Turnkey Services, One-Stop Shop

7. Multi-modality Techniques

8. International Recognition

9. In Business since 2003 (700 k EUR sales)

10. First in the Market (2008, EU)

11. Operations in Geneva, Lyon, St. Etienne (France)Antonio 07Nov09

12. NON-INVASIVE IN VIVO IMAGING Whole-body 3D detection of tissues and molecules reached unprecedented sensitivity and speed providing exclusive pathophysiology and anatomy readouts Bridges the gap between preclinical and clinical R&D Imaging means Metrics Quantitative, Precise, Predictive Reduces experimental Artifacts (in vivo) Longitudinal Studies -Reduce Animal Usage (minus 70-80%) Reduction and Refinement of animal works are Cost and Time-effective on R&D Antonio 07Nov09

13. IMAGING IN DRUG DISCOVERY AND DEVELOPMENT Antonio 07Nov09

14. IMAGING IN DRUG DISCOVERY AND DEVELOPMENT Studies on Drug Delivery and Liberation (drug to target) Efficacy, Safety, Pathology (desiderable and undesirable effects) Ligand-Target interaction (receptors, enzymes, transporters) including Dose Occupancy relationships Dynamic Biodistribution and Kinetics Imaging is suitable for ADME studies of NCE and Biologics In vivo studies of peptides, antibodies, cell therapies, nanoparticles, nutraceuticals, materials. Studies of pathophysiology, phenotyping, translational research and model validation studies Antonio 07Nov09

15. REDUCTION OF ANIMAL USAGETIME COURSE – HISTOPATH / AUTORAD Groups A B C D Antonio 07Nov09 E 1 2 3 4 5

17. Reduced Variability: each is a self control

18. Reduced Artifacts: all are alive

19. Reduced Time for each experiment

20. Reduced Cost for the study

21. Reduced Ethical impactAntonio 07Nov09 E 1 2 3 4 5

22. X-RAY COMPUTED TOMOGRAPHY (CT) CT is well-suited for in vivo 3D analysis of Bone tissues at a high level of spatial resolution (10 µm). Using specific contrast media, can be used for anatomical and functional analysis of Soft tissues CT provides 3D anatomical images with spatial resolution 10-100 µm Antonio 07Nov09

23. MAGNETIC RESONANCE IMAGING (MRI) MRI provides anatomical, functional and metabolic images with or without the use of specific contrast media It is particularly suited for soft tissues such as brain and heart Routinely, spatial resolution varies around 100 µm in 3D Antonio 07Nov09

24. NUCLEAR IMAGINGPOSITRON EMISSION TOMOGRAPHY (PET)SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT) An increasing number of radio-tracers are available (positron or gamma-emitters), permitting 3D whole-body evaluationof biochemical pathways, ligand-receptor binding, antibody-antigen distribution and energy metabolism (molecular imaging) Spatial resolution is close to 1 mm Antonio 07Nov09

25. OPTICAL IMAGING Using fluorescent and bioluminescent probes, in vivo whole-body imaging provides images related to specific biochemical pathways (molecular imaging) It is also well suited for biodistribution analysis, cell trafficking and functional genomics studies The number of markers available is rapidly increasing while 3D technologies for Quantitative Tomography are emerging as the golden standard in this field Antonio 07Nov09

26. ULTRASONOGRAPHY (US)Echography Many applications, including development and reproductive medicine studies Provides 2D anatomical information Combined with Doppler analysis allows evaluation of functional parameters, particularly in the cardiovascular and muscular fields The spatial resolution ranges from 30 to 100 µm Antonio 07Nov09

27. MULTI-MODALITY IMAGING X-ray CT and PET Dual Modality Function & Anatomy Optimise and Customise Each Protocol Multi-modality imaging allows to collect, combine and compare multiple readouts within the same anatomical structure and experimental frame Animascope utilizes a wide set of non-invasive technologies, all the main imaging techniques X-Ray CT, MRI, PET/SPECT, US, OPTIC Antonio 07Nov09 Courtesy of Siemens

29. Cell Therapy, Gene Therapy

30. Development, Reproduction (Reprotox, Teratology)

31. Gastrointestinal

32. GenitoUrinary, Nephrology

33. Immunization, Vaccination

34. MusculoSkeletal

35. Metabolism, Nutrition

36. Neurobiology, CNSAntonio 07Nov09

38. BIOLOGICS, BIOPHARMACEUTICALS

39. Nanotechnology, Tracers, Biomarkers, Contrast Agents

40. Nutraceuticals, Functional Food, Dietary Supplements

41. Phytopharmaceuticals

42. Agrichemicals, Environment and Chemistry(risk assessment)

43. Biomaterials, Bio-compatible materials, other MaterialsAntonio 07Nov09

44. TURNKEY SERVICES Our turnkey services are based on integrated services and multi-disciplinary skills. Customisable services and full studies are available depending on customer needs. Every project is tailored to optimize outcomes and readouts PROTOCOL DESIGN Definition of biological parameters to be measured Choice of imaging modalities, contrast agents, tracers, biomarkers Design of image processing workflow STUDY MANAGEMENT Model Pre-conditioning Image acquisition Recording and traceability IMAGE PROCESSING Image handling and pre-processing Data analysis REPORTING Technical reporting Biomedical reporting Antonio 07Nov09

46. PRE-CONDITIONING OF ANIMAL MODELS

47. SOFTWARE DEVELOPMENT

48. CONSULTANCY

49. TRAINING Antonio 07Nov09

50. ANIMAL MODELS Several models can be utilised, disease models and normal controls, including xenografts, mutants, pre-conditioned animals Several species can be used, such as mice, rats, guinea-pigs, microcebus, rabbits, and larger species Antonio 07Nov09

52. Orthotopic cancer xenografts

53. MetastasisOther models: Angiogenesis, Diabetes, CNS disorders Arthritis, Autoimmune Encephalomyelitis Inflammatory Bowel Disease Antonio 07Nov09

55. Clinical Trial and IND preparation

57. Toxicology, CMC, Drug Safety support services

58. US Agent servicesAntonio 07Nov09 www.drugstomarket.com

60. Drugs (small molecule)

61. Biologics (large molecule)

62. Gene Therapy

63. Medical Devices

64. In vitro Diagnostics

65. Combination Products

66. Generics

67. Due Diligence

68. Strategic medical writingAntonio 07Nov09 www.drugstomarket.com

70. Anti-infectives

71. Anti-inflammatory and Immunological diseases

72. Central Nervous System

73. Dermatology

74. Respiratory

75. Women’s healthAntonio 07Nov09 www.drugstomarket.com

77. Daniel CHRISTIAEN

78. Mimoun NEJJARI

79. Bassem HIBA

82. EuroBio 2008 (Paris-F)

83. BioBusiness 2009 (Geneva-CH)

84. Molecular Imaging in Drug Dev. 2009 (London-UK)

85. Biosquare 2009 (Lyon-F)

86. BIO-Europe Spring 2009 (Milano-I)

87. CLARA 2009 (Archamps-F)

88. BioTrinity 2009 (Oxford-UK)

89. EuroPOLA 2009 (Paris-F)

90. ESMI 2009 (Barcelona-ES)

91. AFSTAL 2009 (Nantes-F)

92. Pharma Finance Zangani (Roma-I)

93. ECCP 2009 Eu Cancer Cluster (Toulouse-F)

94. ETS 2009 Eu Teratology Soc (Arles-F)

95. EUROBIO 2009 (Lille-F)

96. CLARA 2009 (Lyon-F)

97. BIO-Europe 2009 (Vienna-A)Antonio 07Nov09

98. ANIMASCOPE CONTACT Animascope operates in Geneva, Lyon, St. Etienne (France) Contact: Antonio SERVADIO, Scientific Business Development www.animascope.eu a.servadio@animascope.eu Skype: animascope.eu Mobile: +39 338 7949623 www.animascope.eu Current Animascope office located near Grenoble New imaging facility near Geneva Antonio 07Nov09

99. IMAGINE YOUR PHENOTYPE Antonio 07Nov09