Contents:

Introduction Using Target Product Profiles in Your Market Strategy Report Contents Target Product Profile Methodology Etiology and Pathophysiology Overview Etiology The Immune Response Microbial Involvement. The Inflammatory Cascade Cytokines Lipid Mediators Cell Adhesion Molecules. Mitogen-Activated Protein Kinases Downregulation of the T-Cell Response Genetics Risk Factors Pathophysiology Location and Extent of GI Tract Involvement Complications of Crohn’s Disease Target Product Profile Discussion—Crohn’s Disease Target Product Profile Summary for Crohn’s Disease—2011 Assessing Drug Development Opportunities Physician Survey Results Efficacy Safety and Tolerability Delivery Estimated Patient Share Pricing Potential Forecasted 2016 Pricing Environment Competitors to Watch Emerging Product Profile

Methodology

Our Target Product Profiles are made up of two physician-defi ned profi les that highlight physicians’ expectations of emerging therapies in terms of how much better or worse the therapy performs relative to a comparator drug on key measures of effi cacy, safety and tolerability, and delivery. The profiles also provide physician insight on estimated uptake and use (i.e., patient share) of drugs matching the Target Product Profi les as well as key drugs already in the pipeline. Interviews with key thought leaders are used to identify a key drug development opportunity that is realistic and obtainable within the next ten years. To complete the profile of a product that is able to fulfill the key drug development opportunity and determine the product’s potential uptake, we conduct two surveys for every disease we cover, each with at least 60 U.S. physicians who have large clinical practices. The first survey asks physicians how they would expect a therapy fulfi lling the key drug development opportunity to perform on various measures of effi cacy, safety, and delivery. To qualify physicians’ willingness to accept varying trade-offs in efficacy, safety, or delivery, price points above and below a comparator therapy (generally the sales-leading agent in the disease) are used. Price is used to force physicians to make choices between must-have drug attributes and acceptable trade-offs. These prices do not necessarily refl ect the potential cost or reimbursement of a novel agent fulfi lling the key drug development opportunity. With these price points in mind, physicians are asked to profi le two theoretical therapies: - “Minimal Acceptable,” defined as a therapy that satisfies the key drug development opportunity being tested and is priced lower than the comparator drug. - “Major Achievement,” defined as a therapy that satisfies the key drug development opportunity being tested and is priced higher than the comparator drug. All physician survey responses are averaged together to create the two final Target Product Profiles, each of which has clearly quantified performance measures against efficacy, safety, and delivery end points. The second survey presents these two Target Product Profi les to a new set of at least 60 physicians and asks for their opinion on the market potential of each profi le. Survey results reveal both Target Product Profiles’ market potential in terms of prescription patterns (how many patients physicians would consider prescribing the theoretical product profi les), the line of therapy such theoretical products would be used, and which current drug(s) the theoretical products would replace. The results of each of these surveys are presented and analyzed in the Target Product Profiles section of this report.