AND TO MAKE A DECISION ON WHICH EXPERIMENT TO DO, YOU WANT TO ORGANIZE YOUR CONTENT, NORMALIZE AND COMPARE, TO UNDER- STAND WHICH COMPOUND INTERACTS WITH WHICH TARGET AND TRIGGER WHICH BIOLOGICAL EFFECT—THAT'S A LOT OF MANUAL WORK!    

REAXYS MEDICINAL CHEMISTRY Reaxys Medicinal Chemistry excerpts all the relevant Quantitative data ESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDS

REAXYS MEDICINAL CHEMISTRY THE WORLD OF MEDICINAL CHEMISTRY AT YOUR FINGERTIPS ESSENTIAL INFORMATION 2.4 M chemical compounds 9 M biological experimental results 5100 Pharmacological targets REAXYS MEDICINAL CHEMISTRY: THE MOST POWERFUL AND VERSATILE MEDICINAL CHEMISTRY DISCOVERY ENGINE RELEVANT ANSWERS Chemistry driven searches (Substructure/Similarity) Pharmacology driven searches (Target, Cell, Bioassay) Taxonomies-driven searches ACTIONABLE Intuitive and powerful user-interface No access barrier Flexible export (Manageable by user)

4 ANSWERING YOUR QUESTIONS AT EVERY STAGE OF YOUR RESEARCH WORKFLOW SOME OF THE KEY QUESTIONS THAT REAXYS WILL HELP ANSWER: DOES A COMPOUND EXIST? WHAT IS KNOWN ABOUT THE COMPOUND? IS THIS COMPOUND COMMERCIALLY AVAILABLE? HOW TO SYNTHESIZE THIS COMPOUND? WHAT IS KNOWN ABOUT THIS AREA OF RESEARCH? WHO ELSE IS WORKING ON THIS COMPOUND OR REACTION TYPE? REAXYS GIVES RELEVANT AND ACTIONABLE ANSWERS AND ALLOWS YOU TO MOVE YOUR RESEARCH FORWARD. UNDERSTAND Know and understand what others have done and how. Access the relevant and actionable information quickly with a dedicated solution. Discover information you didn’t realize you were missing. EXPERIMENT Design experiments without wasting time. Get existing compounds or find out how to synthesize them. Use experimentally measured data to move your research forward more quickly. REPORT & COMMUNICATE Share results with your peers. Gain insight and move on to new projects with confidence. Accelerate innovation and research progress REAXYS; CHEMISTRY DISCOVERY ENGINE SUPPORTS ENTIRE SCIENTIST WORKFLOW

5 Experimental procedures Synthesis plannerMarkush viewerSimilarity searching Reaxys Structure Flat File Reaxys APIs ELN interoperabilityeMolecules integration PubChem integration Content Expansion & Indexing Anaylsis and reporting Reaxys Tree Ask Reaxys smart search Molecular Formula Builder CONTINUOUS INNOVATION BY CHEMISTS FOR CHEMISTS

6 A Bibliographic Database >46 million records (from ~16,000 journal titles plus records from key patent organisations) A Substance Database > 78 million substances (total) ~ 57 million substances (unique) A Chemical Reaction Database > 36 million single- and multi-step reactions A Property Database > 500 million experimental properties in > 400 fields in > 130 subject areas Reaxys 2014 CONTENT: MANY DATABASES ALL IN ONE REAXYS 2014?

THE WORKFLOW SOLUTIONS THAT LEADING CHEMISTS PREFER TO USE 95% of the largest pharmaceutical R&D organizations and 70 of the top 100 chemistry universities have already chosen Reaxys POWERFUL SOLUTIONS ACROSS THE ENTIRE CHEMISTRY WORKFLOW Designed by chemists to help chemists of all kinds in all sectors, advance more quickly and confidently through their research 7

First product to offer both searchable FDA approval packages and EMEA EPARs Over 1.7M newly-searchable pages covering all of FDA history, over 50 years, and all EMEA content. First product to bring together: preclinical, clinical & post marketing safety Normalized terminology on searches, extracted data. Which experimental data translates, which does not and why? Over 2 million extracted drug safety and PK observations Normalized AE/Tox terminology mapped to Class, Target, Structural Chemistry. PHARMAPENDIUM

FDA APPROVAL PACKAGES: EXAMPLES OF ORIGINAL DOCUMENTS

PHARMAPENDIUM MAKE BETTER DECISIONS

FDA Approval Packages Preclinical, clinical – coverage over 50 years (including FDA Classic Collection; microfiche-converted content). FDA’s history of Drug Development in terms of Efficacy, Delivery (exposure) and Safety with accompanying experimental data. Over 1.1Million Pages newly-searchable. EMEA EPAR drug approval documents AERS database Post market data updated quarterly. Metabolic transformations extracted from literature. Toxicity Observations extracted from literature. Drug/Target associations. PHARMAPENDIUM KEY SOURCES

PHARMAPENDIUM PATHWAY STUDIO TARGETINSIGHTS EMBASEQUOSA MEDSCAN TAXONOMIES (CONTENT) INTEGRATION TEXT MINING A VISION FOR INTEROPERABILITY 13 Returns compounds with action on target Sort by compounds that inhibit the target Any result mapping to PharmaPendium indicates more data is available Attach adverse event data to compounds found in Reaxys Medicinal Chemistry with adverse events of known drugs containing the compound User analyzes pathways for a drug User ID’s potential adverse event in which a compound inhibits a secondary target Search all Reaxys Medicinal Chemistry compounds via Pathway Studio that inhibit the target Get adverse event data for known drug with compound Compound/target pair results sent back to Pathway Studio Return adverse event data

MINIMIZING RISK IN PHARMACOVIGILANCE

16 PHARMACOVIGILANCE Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. Increasingly important in today’s world of big data analysis and regulation

sends ICSRs frequently (monthly, or at least once a quarter) sends over 200 reports per million inhabitants per year sends reports from different areas - geographical and medical sends reports from vaccination and other public health programmes sends reports containing traditional medicines (herbals) sends reports with as much information as possible has performed a causality assessment of the reports. In addition there are quality assurance guidelines related to file format (preferably ICH E2B format), correct position of data, allowed values, correct spelling of ADR terms and drugs, and unique ID-numbers (i.e. no duplicates). WHO PROGRAM FOR INTERNATIONAL DRUG MONITORING THE OPTIMAL NATIONAL PHARMACOVIGILANCE CENTRE CRITERIA

18 WHAT ARE GOVERNMENTS DOING? GROWING REGULATORY PRESSURE AND FOCUS ON LITERATURE MONITORING IN EU & US