Immunomodulators - Therapeutic Needs, Pipelines & Prospects

Executive Summary 12
Modulating the immune system 12
Inflammatory and Autoimmune Disorders 13
Infectious disease 13
Cancer 15
Transplantation 16
Market Considerations and Forecasts 16
Trends and Opportunities 18

Chapter 1 Modulating the immune system 22
Summary 22
Introduction 23
Overview of the human immune system 24
Innate (non-specific) immunity 25
Cytokines: the chemical messengers 26
Lipid mediators of inflammation 27
Phagocytic and natural killer cells 28
Complement system 29
Inflammatory and acute phase responses 29
Adaptive (specific) immunity 31
B and T lymphocytes 31
Antigen-presenting cells 34
Biopharmaceuticals as immunomodulators 35
Delivery of biopharmaceuticals 37
Regulatory requirements (US) 38
Scope of this Report 39

Chapter 2 Inflammatory and Autoimmune Disorders 47
Summary 47
Introduction 48
The role of T cells in autoimmune diseases and allergies 50
Current therapies 51
Glucocorticoids 52
Nonsteroidal anti-inflammatory drugs 54
Nitric oxide (NO)-releasing NSAIDs 55
Therapies targeting proinflammatory cytokines 55
B cell-targeted therapeutics 56
Other therapies 56
Current drug targets 58
GPCRs 58
Chemokine receptors 59
LTB4 receptor 61
S1P1 receptor 62
Leukocyte surface antigens 62
Cytokines and their receptors 64
IL-1 and receptors 64
Other ILs and receptors 65
TNF proteins and receptors 66
BlyS (BAFF) and APRIL 67
Interferons 67
Other cytokines 67
Kinases 68
Other targets 69
Immunomodulators in clinical development (US) 70
Rheumatoid arthritis 70
Psoriasis 72
Multiple sclerosis 73
Inflammatory bowel disease 74
Systemic lupus erythematosus 75
Asthma and allergic rhinitis 76
Chronic obstructive pulmonary disease 79
Cardiovascular disease 79

Chapter 3 Infectious Disease 118
Summary 118
Introduction 119
Types of vaccines 120
Combination vaccines 123
Viruses 124
Influenza 124
New vaccines 126
HIV 130
New vaccines 132
Other immunotherapies 136
Hepatitis viruses 137
New vaccines 138
Other immunotherapies 139
Herpes simplex viruses 141
New vaccines 142
RSV 143
New vaccines and immunotherapies 144
Bacteria, fungi and parasites 146
New vaccines 146
Other immuotherapies 151

Chapter 4 Cancer 179
Summary 179
Overview of Cancer 180
Tumor immunity 182
Treatment of cancer 183
Overview of immunotherapies 185
Small molecule immunomodulators 186
Cytokines 187
Monoclonal antibodies 188
Recent trends 189
Prophylactic vaccines 191
Therapeutic vaccines 191
Tumor antigens targeted by vaccines 193
Antigen/adjuvant vaccines 195
Whole cell vaccines 196
Dendritic cell vaccines 197
Idiotype vaccines 198
Genetically-engineered vaccines 199
Immunostimulatory sequences 201
Adoptive T cell immunity 202

Chapter 5 Transplantation 266
Summary 266
Introduction to organ transplantation 267
Rejection mechanisms 268
Prevention of rejection 269
Small molecule immunosuppressants 270
Calcineurin inhibitors 270
Anti-proliferatives 272
Glucocorticoids 273
mTOR inhibitors 273
Novel small molecule drugs 274
Induction therapy with T cell antibodies 275
Polyclonal antibodies 275
Monoclonal antibodies and fusion proteins 276
Co-stimulatory blockers 277
New approaches to prevention of GVHD 278

Chapter 6 Market Considerations and Forecasts 285
Summary 285
Introduction 286
Overview of the AIID Market 287
Rheumatoid arthritis 289
Multiple sclerosis 290
Inflammatory bowel disease 290
Systemic lupus erythematosus 290
Psoriasis 291
Asthma and allergic rhinitis 291
Overview of the Viral Infectious Disease Market 291
Influenza 291
HIV 292
Hepatitis viruses 293
Herpes simplex viruses 293
RSV 294
Overview of the Cancer Market 295
Cytokines 297
Monoclonal antibodies 298
Prophylactic vaccines 298
Therapeutic vaccines 298
Overview of the Transplantation Market 299
Quantitative Market Analysis 300
The global pharmaceutical market 300
The global immunomodulator market 302
Immunosuppression in AIID and allergies 304
Vaccines for viral pathogens 306
Vaccines for cancer 306
Monoclonal antibodies for cancer 307
Recombinant interferons 308
Transplantation medicine 308
Geographical analysis 309

Chapter 7 Trends and Opportunities 313
Summary 313
Preclinical immunomodulator programs 314
Trends in vaccines 316
Trends in monoclonal antibodies 317
Future players in immunomodulation 318
Immunomodulators Patent Survey 320
Patenting Activity 323
Leading assignees 326
Patent citation analysis 331
Appendix 339
Research Methodology 339

Index 340

List of Figures
Figure 7.1: Immunomodulators – Drug origins 314

List of Tables
Table 1.1: Immunomodulators Summary 41
Table 1.2: Indications by Category and Within-Category Count 42
Table 1.3: Recent Immunomodulator Deals 44
Table 2.4: Immunomodulators in US Clinical Development (Rheumatoid Arthritis) 82
Table 2.5: Immunomodulators in US Clinical Development (Psoriasis) 89
Table 2.6: Immunomodulators in US Clinical Development (Multiple Sclerosis) 92
Table 2.7: Immunomodulators in US Clinical Development (Crohn's Disease) 95
Table 2.8: Immunomodulators in US Clinical Development (Ulcerative Colitis) 98
Table 2.9: Immunomodulators in US Clinical Development (SLE) 99
Table 2.10: Immunomodulators in US Clinical Development (Asthma) 101
Table 2.11: Immunomodulators in US Clinical Development (Allergic Rhinitis) 106
Table 2.12: Immunomodulators in US Clinical Development (COPD) 108
Table 2.13: Immunomodulators in US Clinical Development (General Inflammation) 110
Table 2.14: Immunomodulators in US Clinical Development (Autoimmune Disorders) 113
Table 3.15: Immunomodulators in US Clinical Development (Influenza) 154
Table 3.16: Immunomodulators in US Clinical Development (HIV) 155
Table 3.17: Immunomodulators in US Clinical Development (Viral Hepatitis) 159
Table 3.18: Immunomodulators in US Clinical Development (Herpes simplex) 164
Table 3.19: Immunomodulators in US Clinical Development (Other Viruses) 165
Table 3.20: Immunomodulators in US Clinical Development (Bacteria, Fungi, and Parasites) 169
Table 4.21: Immunomodulators in US Clinical Development (Breast cancer) 203
Table 4.22: Immunomodulators in US Clinical Development (Prostate cancer) 207
Table 4.23: Immunomodulators in US Clinical Development (Non-Small Cell Lung Cancer) 212
Table 4.24: Immunomodulators in US Clinical Development (Ovarian cancer) 218
Table 4.25: Immunomodulators in US Clinical Development (Malignant melanoma) 221
Table 4.26: Immunomodulators in US Clinical Development (Head and neck cancer) 227
Table 4.27: Immunomodulators in US Clinical Development (Pancreatic cancer) 229
Table 4.28: Immunomodulators in US Clinical Development (Renal cancer) 232
Table 4.29: Immunomodulators in US Clinical Development (Solid tumours) 238
Table 4.30: Immunomodulators in US Clinical Development (Lymphoma) 244
Table 4.31: Immunomodulators in US Clinical Development (Non-Hodgkin's Lymphoma) 246
Table 4.32: Immunomodulators in US Clinical Development (Multiple myeloma) 250
Table 4.33: Immunomodulators in US Clinical Development (General Cancer) 253
Table 4.34: Immunomodulators in US Clinical Development (Colorectal cancer) 258
Table 4.35: Immunomodulators in US Clinical Development (Chronic Lymphocytic Leukaemia) 262
Table 4.36: Glossary - Immunomodulators in US Clinical Development 264
Table 5.37: Immunomodulators in US Clinical Development (Transplantation) 280
Table 6.38: World Population Data (2006) 286
Table 6.39: Inflammatory Disease Prevalences and Incidences (2006) 288
Table 6.40: Inflammatory Disease Summary (2006) 289
Table 6.41: World AIDS Statistics (2006) 293
Table 6.42: World Annual Cancer Incidence by Site (2002) 295
Table 6.43: Trends in cancer incidence, 1975-2000 296
Table 6.44: World Cancer Statistics (2002) 297
Table 6.45: World Pharma Market by Therapeutic Category, 2006-2011 301
Table 6.46: World Pharma Market by Region, 2006-2011 302
Table 6.47: Immunomodulator Analysis by Therapy Type (2006-2011) 303
Table 6.48: Immunomodulator Analysis by Indication (2006-2011) 304
Table 6.49: World Immunomodulator Market by Region, 2006-2011 310
Table 7.50: Preclinical Immunomodulators by Indication 315
Table 7.51: Preclinical Vaccines: Therapy Types 316
Table 7.52: Preclinical Vaccines: Top Indications 317
Table 7.53: Monoclonal antibodies in preclinical development 318
Table 7.54: Preclinical Immunomodulators: Top Originators 318
Table 7.55: Preclinical Vaccines: Top Originators 319
Table 7.56: Immunomodulator Patent Survey: Category Definitions 322
Table 7.57: Summary of Patents by Segment 322
Table 7.58: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (All Patents) 323
Table 7.59: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (Autoimmunity) 324
Table 7.60: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (Allergy) 324
Table 7.61: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (General Immunotherapy) 325
Table 7.62: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (Transplantation) 325
Table 7.63: US Immunomodulator Patents: Filing and Publication Activity, 1992-2007 (Vaccines) 326
Table 7.64: US Immunomodulator Patents: Assignee Summary 327
Table 7.65: US Immunomodulator Patents: Top Assignees 328
Table 7.66: US Immunomodulator Patents: Most Frequenty Cited Organizations 332
Table 7.67: Top-Cited Immunomodulator Patents, Entire Data Set (US Filings, 1992-2007) 334