Disease State Primer: Neuropathic Pain Q2 2012 Update Table of Contents Slide Number I. Introduction • Who is Lumleian and what is a disease state primer? • 3 – 6 • What is our perspective on Neuropathic Pain? • 7 – 9 II. Disease Overview and Care Paradigm 11 • What is Neuropathic Pain? • 12 • Presentation, diagnosis, classification • 13 • Epidemiology by geography and patient segment • 15 • Current care paradigm and clinical evidence • 17 – 23 • Emerging care paradigm • 24 III. Clinical Development Pipeline 26 – 27 • Disease mechanism overview • 28 - 30 • Clinical development pipeline mapping • 31 – 37 • Sodium Channels • 38 – 41 • Trp Channels • 42 - 44 • Cannabinoid • 45 - 47 • Vesicular release • 48 – 50 • NGF Antagonist • 51 – 53 • Other mechanisms (opioid receptors, P2X3, NE reuptake • 54 - 68 inhibition , Anti-TNFα, calcium channel blockade, combinations) IV. Commercial Landscape 70 • Global, US, EU, Japan market size and growth by brand • 71 – 74 • Wall Street consensus forecasts for pipeline assets • 75 • US growth decomposition: Rx volume, pricing, product mix • 76 – 78 • US promotional spending, marketing mix and brand messaging • 79 – 85 V. Appendix • Table of Acronyms • 87 – 88 • More about Lumleian • 89 – 91 2 Lumleian offers the requisite scale and depth of life science expertise required for our client’s most critical investment decisions; We offer universal information and real time knowledge. Expertise Based Universal Real-Time Decision Life Science Teams Information Knowledge Support Client Base • Experience • Data Mining • Disease State Primers • Academic and - Academic faculty - Regulatory filings - Disease overview Research Institutions - Bio-pharmaceutical - Scientific literature and care paradigm - Portfolio optimization • Early stage - Equity research - Patent filings - Clinical development pipeline - Commercial landscape - Out licensing strategy - Strategy consulting - Company filings • Asset valuation and press releases • Functional Drill Downs • Expertise • Transaction support • Secondary Data - In licensing assessments - 30+ clinicians • Royalty monetization and Ph.D. scientists - Industry pipelines - Early and late stage • Bio-pharmaceutical Companies • Analytics - Wall Street analysis - Preliminary due dilligence - Asset valuation - 5 Ph.D. economists - US TRx, pricing, - Real-time clinical data and statisticians promotional spend - Clinical strategy • Proprietary Analytics - In licensing strategy • Primary Research - Asset valuation • Early and late stage - Key opinion leaders - Epidemiologic forecasts - Portfolio optimization - Practicing physicians - Industry benchmarks • Early and late stage - Reimbursement • Drug Development - Preliminary due dilligence and commercial - Patient segment valuations • Life Science Investors - Promotional response models - Asset valuation • Healthcare professional - Clinical strategy and direct to consumer - In licensing strategy 3 To ensure real-time knowledge, across disease states, our team of 30+ clinicians and Ph.D. scientists maintain a comprehensive knowledge management platform, leveraging novel data mining technology and proprietary analytics. Universe of Public Data Mining Expert Validation Information1 and Analytics and Decision Support Scientific • Clinical trials • Conference presentations & Clinical: • Gene ontology • Industry pipeline databases • NIH grants • Scientific literature & citations Academic • Early stage technologies Tech Transfer: • Intellectual property filings • Leverage data mining technology to access • 30+ clinicians and Business • Business development transactions novel data sources Ph.D. scientists Development: • Venture capital investments - Focused by area • Standardize, collate, of expertise Regulatory: • Advisory committee transcripts and link data sources • FDA and EMA filings • 5 Ph.D. economists • Execute Lumleian’s and statisticians proprietary analytical Financial: • Company presentations models • Earnings announcements • Equity research coverage • Investor relations transcripts Competitive • Disease profiles Landscape: • Industry publications • Sales and Rx data • Treatment algorithms Notes: 1These are a representative sub-set of the publicly available data sources 4 Our efficient platform and our expertise based teams enable us to both deliver the highest quality product and tailor our offer, to specific client needs: either custom decision support or more standardized research and analytics, e.g. disease state primers. Decision Support Proprietary • Clinical strategy Analytics • Portfolio optimization - Pre-Clinical Functional - Clinical Drill Downs • Asset valuation • Transaction support • Epidemiologic forecasts - In licensing Disease • Real-time clinical data • Industry benchmarks - Out licensing State Primers - Trial strategies - Commercial - Results - Clinical Development • Disease overview • In licensing • Patient segment and care paradigm assessments valuations • Clinical development - Pre-clinical • Promotional pipeline - Clinical response models - Healthcare professional • Commercial • Preliminary due dilligence - Direct to consumer landscape Customized - Scientific • Royalty monetization - Clinical Standardized - Commercial 5 What is a Lumleian’s disease state primer? What information is included in a disease state primer? • Lumleian’s objective and fact based perspective on the relative attractiveness of investing in a given disease state • Disease overview and care paradigm - Etiology, Diagnosis and patient segmentation, Global epidemiology, Treatment algorithm, Clinical evidence, Emerging care paradigm • Clinical Development Pipeline - Validated industry pipeline for all assets in clinical development, Select mechanism of action profiles, trial designs and evidence • Commercial landscape - Global, US, EU, Japan market and brand revenue, Pipeline forecasts, US growth decomposition, Promotional spend and messaging What disease states are planned for 2012? • Autoimmune: Inflammatory Bowel Disease, Lupus, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis • Cardiovascular: Hyperlipidemia • Central Nervous System: Alzheimer’s Disease, Depression, Pain, Schizophrenia • Endocrine: Type II Diabetes, Obesity • Infectious Disease: Gram Negative Bacteria, Hepatitis C Virus • Oncology: Breast, Colorectal, Leukemia(s), Lung, Lymphoma(s), Melanoma, Ovarian, Pancreatic, Prostate • Pulmonary: Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis Are disease state primers real-time, based on the latest validated scientific, clinical, and commercial data? • Quarterly primers are validated by our team: 30+ clinicians and Ph.D. scientists, 5 Ph.D. economists and statisticians • Primers are available at the end of quarter, incorporating new commercial and clinical data from the previous quarter - Particulary dynaimc disease states are updated around key medical conferences, e.g. HCV post EASL in April and post AASLD in November Do we create specific disease state primers and provide more in-depth functional information? • Yes, we plan to add disease states throughout ’12, per client interest • Yes, we are developing deep drills by function, e.g. Discovery, Clinical development, Business development, Commercial Why did we create our disease state primers? • We were frustrated by having to repeatedly validate, standardize, and collate pipeline and commercial data • Portfolio optimization requires a standard framework to compare “apples to apples” investment decisions across disease states • Our primers began as a training tool; We require every decision scientist create one from scratch before supporting clients 6 Executive Summary: Neuropathic Pain • Neuropathic pain is a debilitating disorder affecting 4-7% of the population worldwide and is often a consequence of common disorders such as diabetes, chemotherapy, shingles and HIV-treatment ‐ Associated with loss of intra-epidermal innervation by sensory fibers and hyperinnervation by sympathetic fibers, lack of control by inhibitory systems and inappropriate interpretation by CNS • Common manifestations include continuous pain, spontaneous breakthrough pain, pain in response to light Disease touch/movement or uncomfortable altered sensations Overview and • Associated with significant loss of quality of life such as major depression, sleep interruption, immobility, social isolation Care Paradigm and loss of employment • Currently treated by PCP following a neurological examination and can involve a referral to a neurologist ‐ Emphasis is placed on medical history, description of the pain, duration of symptoms and pain severity • Treatment paradigm involves first line therapy of anti-depressants or anticonvulsants with the addition of topical agents ‐ Opioids are occasionally used as a monotherapy or as an add on to existing treatment • It is estimated that approximately 30% of all NP patients are undiagnosed or under-treated • Low number of Phase I candidates partially attributed to withdrawal from CNS/Pain by large pharma or approval sought for alternative/multiple indications • Goals are to exploit peripherally restricted targets to reduce incidence of off-target effects and centrally mediated adverse events such as drowsiness and dizziness 2+ + Clinical • Targets with increasing interest include certain ion channel family subtypes (eg. Ca , Na , Trp) due to their restricted • The activity,global favorable tolerability and efficacy Development • NGF antibodies are progressing in Phase II for severe cancer-related pain with favorable results; however