1 Table of Contents 1 Table of Contents 2 1.1 List of Tables 3 1.2 List of Figures 3 2 Executive Summary 5 2.1 A Complex and Poorly Understood Disorder, with Numerous Unmet Needs 5 2.2 Small Pipeline for Schizophrenia with Few Signs of Innovation 5 2.3 Extensive Pipeline for Associated Indications 5 3 The Case for Innovation 6 3.1 Growing Opportunities for Biologic Products 7 3.2 Diversification of Molecular Targets 7 3.3 Innovative First-in-Class Product Developments Remain Attractive 7 3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 8 3.5 GBI Research Report Guidance 8 4 Clinical and Commercial Landscape 9 4.1 Disease Overview 9 4.2 Epidemiology 9 4.3 Disease Etiology 9 4.4 Disease Pathophysiology 10 4.4.1 Susceptibility Genes 10 4.4.2 Neurotransmission Alterations 11 4.4.3 Phosphatidylinositol Signaling 11 4.5 Disease Symptoms 11 4.6 Indications Associated With Schizophrenia 11 4.6.1 Panic Disorder 11 4.6.2 Depression 12 4.6.3 Post-Traumatic Stress Disorder 13 4.6.4 Obsessive Compulsive Disorder 13 4.6.5 Cognitive Impairment 13 4.7 Diagnosis 14 4.8 Prognosis 15 4.9 Treatment Options 15 4.10 Overview of Marketed Products 16 4.10.1 Molecule Type and Target Analysis 16 4.11 Current Unmet Needs 17 5 Assessment of Pipeline Product Innovation 18 5.1 Schizophrenia Pipeline by Molecule Type, Phase and Therapeutic Target 18 5.2 Comparative Distribution of Programs between Schizophrenia Disease Market and Pipeline by Therapeutic Target Family 22 5.3 First-in-Class Pipeline Programs 23 6 Schizophrenia Pathophysiology and Innovation Alignment 32 6.1 The Complexity of Signaling Networks in the Central Nervous System 32 6.2 First-in-Class Target Matrix Assessment 32 7 First-in-Class Target Evaluation 37 7.1 Pipeline Programs Targeting D-Amino Acid Oxidase 37 7.2 Pipeline Programs Targeting Gamma-Aminobutyric Acid Receptor, Subunit Alpha 5 38 7.3 Pipeline Programs Targeting Glutamate Carboxypeptidase 2 40 7.4 Pipeline Programs Targeting Phosphodiesterase 9 41 7.5 Pipeline Programs Targeting Potassium Voltage-Gated Channel Subfamily C, Member 1 43 7.6 Pipeline Programs Targeting Probable G Protein-Coupled Receptor 52 44 7.7 Pipeline Programs Targeting G Protein-Coupled Receptor 78 45 7.8 Pipeline Programs Targeting Probable G Protein-Coupled Receptor 85 46 7.8.1 Pipeline Programs Targeting Pipeline Programs Targeting Probable G Protein-Coupled Receptor 173 47 7.8.2 Pipeline Programs Targeting Pipeline Programs Targeting Probable G Protein-Coupled Receptor 27 48 7.9 Pipeline Programs Targeting Sodium and Chloride Dependent Glycine Transporter 1 49 7.10 Pipeline Programs Targeting Trace Amine-Associated Receptor 1 51 7.11 Conclusion 52 8 Deals and Strategic Consolidations 54 8.1 Licensing Deals 55 8.2 Co-development Deals 60 8.3 First-in-Class Programs not Involved in Licensing or Co-development Deals 64 9 Appendix 65 9.1 Abbreviations 65 9.2 Bibliography 65 9.3 Research Methodology 71 9.4 Secondary Research 71 9.4.1 Marketed Product Heatmaps and Treatment Algorithm 72 9.4.2 Pipeline Analysis 72 9.4.3 First-in-Class Matrix Assessment 72 9.4.4 First-in-Class Target Profiles 72 9.4.5 Licensing and Co-development Deals 73 9.5 Contact Us 73 9.6 Disclaimer 73

1.1 List of Tables Table 1: American Psychiatry Association DSM-5 Schizophrenia Criteria 14 Table 2: World Health Organization ICD-10 Schizophrenia criteria 15 Table 3: Data for D-Amino Acid Oxidase as a Therapeutic Target 37 Table 4: Evidence for D-Amino Acid Oxidase as a Therapeutic Target 37 Table 5: Data for Gamma-Aminobutyric Acid Receptor, Subunit Alpha 5 as a Therapeutic Target 38 Table 6: Evidence for Gamma-Aminobutyric Acid Receptor, Subunit Alpha 5 as a Therapeutic Target 39 Table 7: Data for Glutamate Carboxypeptidase 2 as a Therapeutic Target 40 Table 8: Evidence for Glutamate Carboxypeptidase 2 as a Therapeutic Target 41 Table 9: Data for Phosphodiesterase 9 as a Therapeutic Target 42 Table 10: Evidence for Phosphodiesterase 9 as a Therapeutic Target 42 Table 11: Data for Potassium Voltage-Gated Channel Subfamily C, Member 1 as a Therapeutic Target 43 Table 12: Evidence for Potassium Voltage-Gated Channel Subfamily C, Member 1 as a Therapeutic Target 44 Table 13: Data for Probable G Protein-Coupled Receptor 52 as a Therapeutic Target 45 Table 14: Evidence for Probable G Protein-Coupled Receptor 52 as a Therapeutic Target 45 Table 15: Data for G Protein-Coupled Receptor 78 as a Therapeutic Target 46 Table 16: Evidence for G Protein-Coupled Receptor 78 as a Therapeutic Target 46 Table 17: Data for Probable G Protein-Coupled Receptor 85 as a Therapeutic Target 47 Table 18: Evidence for Probable G Protein-Coupled Receptor 85 as a Therapeutic Target 47 Table 19: Data for Probable G Protein-Coupled Receptor 173 as a Therapeutic Target 48 Table 20: Evidence for Probable G Protein-Coupled Receptor 173 as a Therapeutic Target 48 Table 21: Data for Probable G Protein-Coupled Receptor 27 as a Therapeutic Target 49 Table 22: Evidence for Probable G Protein-Coupled Receptor 27 as a Therapeutic Target 49 Table 23: Data for Sodium and Chloride Dependent Glycine Transporter 1 as a Therapeutic Target 50 Table 24: Evidence for Sodium and Chloride Dependent Glycine Transporter 1 as a Therapeutic Target 50 Table 25: Data for Trace Amine-Associated Receptor 1 as a Therapeutic Target 52 Table 26: Evidence for Trace Amine-Associated Receptor 1 as a Therapeutic Target 52 1.2 List of Figures Figure 1: Innovation Trends in Product Approvals, 1987-2012 6 Figure 2: Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval, 2006-2013 8 Figure 3: Molecular Targets of Marketed Products 16 Figure 4: Schizophrenia Pipeline by Stage of Development and Molecule Type 18 Figure 5: Schizophrenia-Associated Indications Pipeline by Stage of Development and Molecule Type 20 Figure 6: Pipeline for Schizophrenia by Molecular Target 21 Figure 7: Pipeline for Schizophrenia-Associated Indications by Molecular Target 22 Figure 8: Molecular Target Category Comparison, Pipeline and Marketed Products 22 Figure 9: Molecular Target Category Comparison, Pipeline and Marketed Products 23 Figure 10: Molecular Target Category Comparison, Pipeline and Marketed Products 24 Figure 11: First-in-Class and Established Molecular Targets in the Pipeline for Schizophrenia 25 Figure 12: First-in-Class and Established Molecular Targets in the Pipeline for Schizophrenia-Associated Indications 26 Figure 13: Schizophrenia, Global, First-in-Class Pipeline Products - Part 1 27 Figure 14: Schizophrenia, Global, First-in-Class Pipeline Products - Part 2 28 Figure 15: Schizophrenia, Global, First-in-Class Pipeline Products - Part 3 29 Figure 16: Schizophrenia, Global, First-in-Class Pipeline Products - Part 4 30 Figure 17: Schizophrenia, Global, First-in-Class Pipeline Products - Part 5 31 Figure 18: First-in-Class Molecular Target Analysis Matrix (Schizophrenia Pipeline) 33 Figure 19: First-in-Class Molecular Target Analysis Matrix (Depression Pipeline) 34 Figure 20: First-in-Class Molecular Target Analysis Matrix (Panic Disorders Pipeline) 35 Figure 21: First-in-Class Molecular Target Analysis Matrix (Post-Traumatic Stress Disorder Pipeline) 35 Figure 22: First-in-Class Molecular Target Analysis Matrix (Obsessive Compulsive Disorder Pipeline) 36 Figure 23: First-in-Class Molecular Target Analysis Matrix (Cognitive Deficit Pipeline) 36 Figure 24: Pipeline Programs Targeting D-Amino Acid Oxidase 38 Figure 25: Pipeline Programs Targeting Gamma-Aminobutyric Acid Receptor, Subunit Alpha 5 39 Figure 26: Pipeline Programs Targeting Glutamate Carboxypeptidase 2 41 Figure 27: Pipeline Programs Targeting Phosphodiesterase 9 43 Figure 28: Pipeline Programs Targeting Potassium Voltage-Gated Channel Subfamily C, Member 1 44 Figure 29: Pipeline Programs Targeting Probable G Protein-Coupled Receptor 52 45 Figure 30: Pipeline Programs Targeting G Protein-Coupled Receptor 78 46 Figure 31: Pipeline Programs Targeting Probable G Protein-Coupled Receptor 85 47 Figure 32: Pipeline Programs Targeting Probable G Protein-Coupled Receptor 173 48 Figure 33: Pipeline Programs Targeting Probable G Protein-Coupled Receptor 27 49 Figure 34: Pipeline Programs Targeting Sodium and Chloride Dependent Glycine Transporter 1 51 Figure 35: Pipeline Programs Targeting Trace Amine-Associated Receptor 1 52 Figure 36: Industry-Wide Deals by Stage of Development, 2006-2014 54 Figure 37: Industry-Wide Deals by Stage of Development, 2006-2014 55 Figure 38: Licensing Deals by Region and Value, 2006-2015 56 Figure 39: Licensing Deals by Year, 2006-2015 56 Figure 40: Licensing Deals by Stage of Development 57 Figure 41: Licensing Deal Value by Molecule Type 57 Figure 42: Licensing Deal Value by Molecular Target 58 Figure 43: Summary of Licensing Deals, 2006-2015 59 Figure 44: Co-development Deals by Region and Value, 2006-2015 60 Figure 45: Co-development Deals by Year, 2006-2015 60 Figure 46: Co-development Deals by Stage of Development 61 Figure 47: Co-development by Stage of Development and Molecule Type 61 Figure 48: Co-development by Stage of Development and Molecular Target 62 Figure 49: Summary of Co-development Deals, 2006-2015 63 Figure 50: First-in-Class Programs for Schizophrenia and its Associated Indications with No Recorded Prior Deal Involvement, 2006-2016 64