1 Table of Contents

1 Table of Contents 2
1.1 List of Tables 3
1.2 List of Figures 3

2 Executive Summary 4
2.1 Development of Targeted Therapies Remains a Focus across NHL Drug Development 4
2.2 NHL Shows a Moderate Level of First-in-Class Innovation 4
2.3 High Number of First-in-Class Pipeline Drugs with No Associated Deal 4

3 The Case for Innovation in NHL Development 5
3.1 Growing Opportunities for Biological Products 6
3.2 Diversification of Molecular Targets 6
3.3 Innovative First-in-Class Product Developments Remain Attractive 6
3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 7
3.5 Sustained Innovation 7
3.6 Report Guidance 8

4 Clinical Landscape 9
4.1 Disease Overview 9
4.2 Epidemiology and Risk Factors 9
4.3 Symptoms 10
4.4 Diagnosis 10
4.4.1 Biopsy 10
4.4.2 Flow-Cytometry and Immunophenotyping 10
4.5 Normal B-Cell Development and NHL Classification 10
4.6 Pathophysiology 17
4.6.1 BCL2 18
4.6.2 BCL6 18
4.6.3 Wnt/?-catenin Pathway 18
4.6.4 BCR Pathway 19
4.6.5 PI3K/Akt/mTOR Pathway 19
4.7 Patient Prognosis 20

5 Overview of Marketed Products and Treatment Algorithm for NHL 22
5.1 Marketed Products by Molecule Type and Mechanism of Action 22
5.2 Treatment Algorithm 23
5.2.1 Clinical Trial Response Criteria in NHL 26
5.2.2 Indolent NHL – Follicular Lymphoma 27
5.2.3 Aggressive NHL 33
5.3 Unmet Needs 45

6 Assessment of Pipeline Product Innovation 47
6.1 Non-Hodgkin Lymphoma Pipeline by Phase and Molecule Type 47
6.2 Non-Hodgkin Lymphoma Pipeline by Mechanism of Action 48
6.3 First-in-Class Pipeline Programs Targeting Novel Molecular Targets 51

7 Sigling Network, Disease Causation and Innovation Alignment 58
7.1 The Complexity of Sigling Networks in Oncology 59
7.2 Sigling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration 59
7.3 First-in-Class Target Matrix Assessment 63

8 First-in-Class Target Evaluation 66
8.1 Pipeline Programs Targeting Spleen Tyrosine Kise 66
8.2 Pipeline Programs Targeting PIK3CA and PIK3CB 69
8.3 Pipeline Programs Targeting PDPK1 71
8.4 Pipeline Programs Targeting EZH2 72
8.5 Pipeline Programs Targeting MDM2 74
8.6 Pipeline Programs Targeting PTPRC 76
8.7 Pipeline Programs Targeting CD40 78
8.8 Pipeline Programs Targeting IRAK4 81
8.9 Pipeline Programs Targeting CD22 82
8.10 Pipeline Programs Targeting BCL6 86

9 Deals and Strategic Consolidations 88
9.1 Industry-Wide First-in-Class Deals 88
9.2 Licensing Deals 90
9.2.1 Licensing Deals by Molecule Type 92
9.3 Co-development Deals 95
9.3.1 Molecule Type and Mechanism of Action 97
9.4 First-in-Class Programs not Involved in Licensing of Co-development Deals 100

10 Appendix 102
10.1 Abbreviations 102
10.2 Bibliography 103
10.3 Methodology 114
10.4 Secondary Research 114
10.5 Contact Us 115
10.6 Disclaimer 115