1. Make the right decisionswith data youcan trust

2. Instructionsforattendees The webinar hasn’t started yet. It will start at 5:05 pm when allattendees are connected. Thank you for your patience.  To connect to the audio conference, please go to the top menu and click on Communicate>Teleconference>Join Teleconference and select the phone number to call. Before starting We will mute your microphone during the webinar During the webinar Use the chat for questions At the End You can ask your questions orally We will answer them either in the webinar session or later on by email. 2 AurPASS

3. Prediction of Adverse Drug ReactionsMediated by Off-TargetsUsing AurPASS

4. Safety and Adverse Effects Every year about 2 million patients in the United States are affected by a serious adverse drug reaction. This results in approximately 100,000 fatalities, making ADRs the fourth leading cause of death in the U.S. The consequence is a huge burden on national economies, which is estimated to be $136 billion annually in the U.S. Over the past 10 years, 19 broadly used marketed drugs were withdrawn after presenting unexpected severe side effects, with Rofecoxib and Cerivastatin. 30/06/2011 4 AurPASS

5. What is an off-target or anti-target? Off-Targets and Preclinical Safety Pharmacology Case Studies of Drug Failures Related to Off-Target Activities Off-Targets in Gene Families Ion Channels GPCRs Nuclear Receptors Cytochrome P450 Transporters Delimiting the Chemical Space of Off-Targets Predicting Off-Targets Off-Targets in Gene Families 5 AurPASS

6. Aureus at a Glance Aureus is a knowledge and information management solutions provider for the Life Science industry located in Paris. Over the past 10 years the company has developed a unique knowledge production platform which stores, indexes and organizes critical chemical and bioactivity information including experimental in vitro and in vivo protocols from the public or private literature. Aureus employees 20 highlevelscientists (PhD and MSc) includingscientific and IT project leaders and documentation analysts Aureus is funded by institutional investors like CDC Entreprise, AXA Provate Equity, OTC Asset Management and is part of the OSEO Excellence innovation team. 07/04/2011 6 AurPASS

7. Aureus 10 YearsExperience of Building SAR Databases 6/30/2011 7 AurPASS

8. AurSCOPE Knowledge Databases Target Pharmacological Space 2002 2004 2005 2008 2009 Nuclear Receptor Protease GPCR Kinase Ion Channel 13,303 including 6,966 patents 32,588 including 15,281 patents 4,668 including 2,484 patents 4,226 including 1,060 patents 10,206 including 6,806 patents Publications Biological Activities 275,044 418,202 186,047 1,243,793 670,407 98,439 354,323 146,426 Unique Ligands 124,313 48,500 Biological Protocols 8 AurPASS

9. AurSCOPE Knowledge Databases ADME/DDI & TOX Off-Targets ADME/DDI 12,165 including 200 FDA Reviews 10,700 Publications 315,200 462,785 Biological Activities Unique Ligands 34,872 compounds including 4,050 metabolites Biological Protocols 9 AurPASS 107,646 compounds

10. AurSCOPE GPS : Global Pharmacological Database 2009 2010 2011 GPCR Ion Channel Kinase NHR Protease ADME Off Targets 30/06/2011 10 AurPASS

11. Make The Right Decision With Data You Can Trust AurPROFILER Data analysis & Navigation Medicinal Chemistry Space AurQUEST Data mining AurPASS Predict Biological Activities Spectra DDI Predict AurPASS 11

12. Filling the Gap Using AurPASS in silicoPredictions 12 Aureus Prediction of Activity Spectra for Substances AurPASS ADME Off Targets GPCR Ion Channel Kinase NHR Protease

13. Predicting New Activities on Selectedbig Pharma Drugs Off-Targets SelectedMoleculesfrom Pharma Pipeline 13 AurPASS

14. Over Forty Publications with Independent Confirmation of PASS Predictions… 14 AurPASS More References in aureus-sciences.com/ResourceCenter

15. AurPASS Training Set SAR data extracted from individual AurSCOPE databases Chemical & biological post-processing Chemical Structures Multilevel Neighborhoods of Atoms (MNA) descriptors SAR Base Diverse chemical structures and associated MNA descriptors Associated qualitative biologicalactivity types Prediction Algorithm PASS Bayesian approach Models Validation LOO and L20%O validations External dataset 15 AurPASS

16. AurPASS Off-Target Modules 16 Live Demo AurPASS

17. AurPASS Training Set SAR data extracted from individual AurSCOPEknowledgebases Chemical & biological post-processing Chemical Structures Multilevel Neighborhoods of Atoms (MNA) descriptors SAR Base Diverse chemical structures and associated MNA descriptors Associated qualitative biologicalactivity types Prediction Algorithm PASS Bayesian approach Models Validation LOO and L20%O validations External dataset 17 AurPASS

18. Selected Off-Targets and AssociatedADRs 6/30/2011 18 SAR information for these targets can be displayed in our portal aureus-sciences.com AurPASS

19. Content Description of Aureus Knowledgebases…. 6/30/2011 19 AurPASS

21. No mixtures

22. Inorganic and metalo-organicremoval

24. Target hierarchy

25. Target species, celllinesand tissues

26. Biologicalactivityparameters

27. Ligand action on targetAurPASS

28. 21 6/30/2011 Added Value of Aureus Data for Predictive Models AssigningActivity Classes Actives & Inactives Molecules & SAR Data AurPASSActivity Types Actives & Inactives PASS Training/Test Sets AurPASS

29. Encoding Chemical Structures: MNA Descriptors 22 MNA/2 C(C(CC-H)C(CC-C)-H(C)) C(C(CC-H)C(CN-H)-H(C)) C(C(CC-H)C(CN-H)-C(C-O-O)) C(C(CC-H)N(CC)-H(C)) C(C(CC-C)N(CC)-H(C)) N(C(CN-H)C(CN-H)) -H(C(CC-H)) -H(C(CN-H)) -H(-O(-H-C)) -C(C(CC-C)-O(-H-C)-O(-C)) -O(-H(-O)-C(C-O-O)) -O(-C(C-O-O)) MNA/0: C AurPASS MNA/1: C(CN-H) MNA/2: C(C(CC-H)N(CC)-H(C))

30. PASS Approach for Biological Activity Prediction Predicted values are “Probability Estimations” In all AurPASS modules, “Actives” are defined by a biological threshold less than 10 µM. The list of activities which are probable for a particular compound with the estimates for each activity of : Pa: probability to be active Pi: probability to be inactive Pa and Pi are calculated independently: Pa + Pi  1 Pa (Pi) can be considered as the probability of the compound belonging to classes of active (inactive) compounds 23 AurPASS

31. Internal Validation of AurPASS Off-Target Models AurPASS

32. AurSCOPE Databases are QuarterlyUpdated (4 releases/Year) Improvement of dataset over time in terms of diversity Updating/Testinggeneratedmodelswith new data External Validation of AurPASS Off-Targets Models 25 AurPASS Training Set Release n-1 Test Set Release n 3 monthslater AurPASS Ion Channels 47 938 Molecules 517 Activity Types Mean Accuracy of Prediction: 98% 2 244 new Molecules 113 Activity Types Mean Accuracy of Prediction: 90%

33. 6/30/2011 26 Can be downloaded from aureus-sciences.com/ResourceCenter

34. AurPASS Off-Target …is a desktop application licensed on a user basis. It contains the Aureus Off-Target dataset model. Off-Target Database …is the completedatabase accessible through the Aureus Web Portal and licensed on an annualsubscription mode AurPASS Product Line Aureus On Line Databases AurPASS Ion Channel Ion Channel 365 Targets / 130 000 Molecules AurPASS Kinase Kinase 1010 Targets / 190 000 Molecules AurpASS GPCR GPCR 555 Targets / 380 000 Molecules AurPASS Off Target Off Target 70 Targets / 107 000 Molecules 27 AurPASSOffers AurPASS

35. 28 For More Information Aureus Sciences www.aureus-sciences.com contact@aureus-sciences.com Tel: +33 1 40 18 57 57 Or Aureus Distributors AKOS (Germany) www.akosgmbh.de AriadneGenomics (U.S.) www.ariadnegenomics.com Patcore (Japan) www.patcore.com Pharmogo (China) www.pharmogo.com AurPASS

36. Thank you for your attention 174, Quai de Jemmapes 75010 Paris, FRANCE www.aureus-sciences.com 29