Cancer Antibodies: Competitive Positioning for Success

1 Executive Summary __________ 3
2 About Cancer Highlights ______ 5
3 Methodologies ______________ 7
4 Table of Contents ____________ 9
4.1 List of Figures _______________ 13
4.2 List of Tables ________________ 13
5 How to Use this Report ______ 18
6 Antibody Target Localization _ 20
7 The Cancer Genome Project and Antibody Targets ______ 25
7.1 Antibody Targets Present in the Cancer Gene Census and in the Catalogue of Somatic
Mutations in Cancer ________________ 25
8 Protein Expression Profiles of Antibody Drug Targets in Human _________________ 28
8.1 Expression in Normal Tissues and Cancer Tissues _________ 28
8.2 Expression in Human Cancer Cell Lines and Primary Cells __ 29
9 Pathway Analysis of Antibody Drugs _________________ 32
10 Protein-Protein Interactions Among Identified Antibody Targets ________________ 53
11 Available Biological Structure Data on Antibody Targets _ 57
12 Drug Target Profiles of Antibody Targets in Oncology ___ 60
12.1.1 Auxiliary Transport Protein Activity ___ 62
12.1.2 Carboxypeptidase Activity __________ 64
12.1.3 Catalytic Activity __________________ 65
12.1.4 Cell Adhesion Molecule Activity ______ 67
12.1.5 Chemokine Activity ________________ 76
12.1.6 Cofactor Binding __________________ 78
12.1.7 Complement Activity ______________ 80
12.1.8 Cytokine Activity __________________ 82
12.1.9 DNA Topoisomerase Activity ________ 85
12.1.10 Extracellular Matrix Structural Constituent ___________________ 87
12.1.11 G-Protein Coupled Receptor Activity __ 89
12.1.12 Growth Factor Activity _____________ 92
12.1.13 Hormone Activity _________________ 98
12.1.14 Hydrolase Activity _________________ 99
12.1.15 Intracellular Ligand-Gated Ion Channel Activity ______________ 100
12.1.16 Metallopeptidase Activity __________ 101
12.1.17 MHC Class I Receptor Activity ______ 102
12.1.18 Molecular Function Unknown ______ 103
12.1.19 Oxidoreductase Activity ___________ 111
12.1.20 Peptidase Activity ________________ 112
12.1.21 Protease Inhibitor Activity _________ 114
12.1.22 Protein Binding __________________ 116
12.1.23 Receptor Activity _________________ 117
12.1.24 Receptor Binding _________________ 141
12.1.25 Receptor Signaling Complex Scaffold Activity ________________ 144
12.1.26 RNA-Directed DNA Polymerase Activity_____________________ 145
12.1.27 Serine-Type Peptidase Activity ______ 146
12.1.28 T Cell Receptor Activity ____________ 148
12.1.29 Translation Regulator Activity ______ 150
12.1.30 Transmembrane Receptor Activity __ 151
12.1.31 Transmembrane Receptor Protein Tyrosine Kinase Activity _____ 154
12.1.32 Unclassified _____________________ 175
13 The Antibody-Target Interactome __________________ 176
14 The Progression and Maturity of Antibody Targets in Oncology: The Preclinical
Explosion ____________________ 180
14.1 Target Profiles of Cancer Antibodies in Pre-Registration or on the Market __________ 182
14.2 New Cancer Antibody Targets in Phase III Clinical Development __________________ 182
14.3 New Cancer Antibody Targets in Phase II Clinical Development __________________ 183
14.4 New Cancer Antibody Targets in Phase I Clinical Development ___________________ 185
14.5 New Cancer Antibody Targets in Preclinical Development _ 185
14.6 Development Profiles of All Identified Cancer Antibody Targets __________________ 189
15 Competitive Peer Group Profiling of Antibody Drugs by Cancer Indication ________ 199
15.1 Biliary Cancer ______________ 204
15.2 Bladder Cancer _____________ 204
15.3 Bone Cancer _______________ 204
15.4 Brain Cancer _______________ 204
15.5 Breast Cancer ______________ 205
15.6 Cervical Cancer _____________ 207
15.7 Colorectal Cancer ___________ 208
15.8 Endometrial Cancer _________ 210
15.9 Fallopian Tube Cancer _______ 210
15.10 Gastrointestinal Cancer ____ 210
15.10.1 Gastrointestinal Stomach Cancer ____ 211
15.11 Head and Neck Cancer _____ 211
15.12 Leukemia ________________ 212
15.12.1 Acute Lymphocytic Leukemia _______ 213
15.12.2 Acute Myelogenous Leukemia ______ 213
15.12.3 Chronic Lymphocytic Leukemia _____ 214
15.12.4 Chronic Myelogenous Leukemia ____ 216
15.13 Liver Cancer ______________ 216
15.14 Lung Cancer ______________ 217
15.14.1 Non-Small Cell Lung Cancer ________ 217
15.14.2 Small Cell Lung Cancer ____________ 219
15.15 Lymphoma_______________ 219
15.15.1 B-Cell Lymphoma ________________ 220
15.15.2 Hodgkin’s Lymphoma _____________ 221
15.15.3 Non-Hodgkin’s Lymphoma _________ 221
15.15.4 T-Cell Lymphoma ________________ 223
15.16 Melanoma _______________ 224
15.17 Mesothelioma ____________ 225
15.18 Myelodysplastic Syndrome _ 225
15.19 Myeloma ________________ 225
15.20 Nasopharyngeal Cancer ____ 227
15.21 Neuroblastoma Cancer _____ 227
15.22 Oesophageal Cancer _______ 227
15.23 Ovarian Cancer ___________ 228
15.24 Pancreatic Cancer _________ 229
15.25 Peritoneal Cancer _________ 231
15.26 Prostate Cancer ___________ 231
15.27 Renal Cancer _____________ 233
15.28 Sarcoma _________________ 234
15.29 Supportive Care Indications _ 234
15.29.1 Chemotherapy-Induced Bone Marrow Injury ________________ 234
15.29.2 Chemotherapy-Induced Anemia ____ 235
15.30 Thyroid Cancer ___________ 235
16 Cancer Antibodies and Their Targets by Companies ____ 236
16.1 Australia __________________ 236
16.2 Belgium ___________________ 236
16.3 Brazil _____________________ 237
16.4 Canada ____________________ 237
16.5 China _____________________ 238
16.6 Cuba  238
16.7 Denmark __________________ 238
16.8 France ____________________ 239
16.9 Germany __________________ 239
16.10 Israel ___________________ 240
16.11 Italy ____________________ 241
16.12 Japan ___________________ 241
16.13 Netherlands ______________ 242
16.14 New Zealand _____________ 242
16.15 Norway _________________ 242
16.16 South Korea ______________ 242
16.17 Sweden _________________ 243
16.18 Switzerland ______________ 243
16.19 United Kingdom __________ 244
16.20 USA ____________________ 245
16.21 Non Industrial Bodies ______ 267
17 Disclaimer _______________ 268
18 Drug Index _______________ 269
19 Company Index ___________ 273
4.1 List of Figures
Figure 1: Primary Sub-cellular Localization of Drug Targets .................. 20
Figure 2: Visualization of Protein-Protein Interactions Among Antibody Drug Targets ................... 56
Figure 3: The Drug-Protein Interactome of Antibody Drugs in Oncology .................. 178
Figure 4: Direct Head-to-Head Targeting Interactome of Cancer Antibody Drugs ... 179
Figure 5: Competitive Peer Group Profiling Example ...... 203
4.2 List of Tables
Table 1: Primary and Alternate Localization of Antibody Drug Targets . 21
Table 2: Drug Targets of Cancer Antibodies Present in the Catalogue of Somatic Mutations in Cancer and in the
Cancer Gene Census ............... 26
Table 3: Available Protein Expression Profiles of Antibody Drug Targets ................... 30
Table 4: Pathway Summary ... 32
Table 5: Drug Targets Without any Identified Assigned Pathways ........ 32
Table 6: Pathway Profile According to BioCarta of Cancer Antibody Drug Targets .... 33
Table 7: Pathway Profile According to KEGG of Cancer Antibody Drug Targets ......... 41
Table 8: Cancer Antibodies Targeting Major Singaling Pathways ......... 52
4 Cancer Antibodies: Competitive Positioning For Success
14 Cancer Highlights No 2 Vol 8 2008| BioSeeker Group AB © 2008
Table 9: Protein-Protein Interactions Among Antibody Drug Targets .... 53
Table 10: Number of Available Biological Structures of Cancer Antibody Targets ...... 57
Table 11: Overview of Drug Target Profile Themes ........... 60
Table 12: Antibody-Protein Interactome Clusters ........... 176
Table 13: Fall Out in Terms of the Total Number of Drug Target Mixes, Drugs, Developmental Projects, and the
Presence of New Drug Target Mixes by Developmental Stage ............ 180
Table 14: Top 5 Pursued Cancer Antibody Targets .......... 181
Table 15: Target Profiles of Cancer Antibodies in Pre-Registration or on the Market ................... 182
Table 16: New Cancer Antibody Targets in Phase III Clinical Development .............. 183
Table 17: New Cancer Antibody Targets in Phase II Clinical Development ............... 184
Table 18 New Cancer Antibody Targets in Phase I Clinical Development ................. 185
Table 19: New Cancer Antibody Targets in Preclinical Development ... 186
Table 20: The Progression, Maturity and Competitive Comparison of Antibody Drug Targets in Development 189
Table 21: Number of Cancer Antibody Drug Target Mixes Reported by Cancer Indication ........... 199
Table 22: Step 1 - Indication Profile of Peer Drugs .......... 200
Table 23: Step 2 - All Peer Drugs with Known Cancer Indications ........ 201
Table 24: Step 3 - Submarine Peer Drugs ... 202
Table 25: Step 4 -Target Overlap Drugs to Peer Drugs.... 202
Table 26: Drug Targets of Antibodies for the Treatment of Biliary Cancer According to Developmental Stage of
Antibody .......... 204
Table 27: Drug Targets of Antibodies for the Treatment of Bladder Cancer According to Developmental Stage of
Antibody .......... 204
Table 28: Drug Targets of Antibodies for the Treatment of Bone Cancer According to Developmental Stage of
Antibody .......... 204
Table 29: Drug Targets of Antibodies for the Treatment of Brain Cancer According to Developmental Stage of
Antibody .......... 205
Table 30: Drug Targets of Antibodies for the Treatment of Breast Cancer According to Developmental Stage of
Antibody .......... 206
Table 31: Drug Targets of Antibodies for the Treatment of Cervical Cancer According to Developmental Stage of
Antibody .......... 208
Table 32: Drug Targets of Antibodies for the Treatment of Colorectal Cancer According to Developmental Stage
of Antibody ...... 209
Table 33: Drug Targets of Antibodies for the Treatment of Endometrial Cancer According to Developmental
Stage of Antibody ................. 210
Table 34: Drug Targets of Antibodies for the Treatment of Fallopian Tube Cancer According to Developmental
Stage of Antibody ................. 210
Table 35: Drug Targets of Antibodies for the Treatment of Gastrointestinal Cancer (general) According to
Developmental Stage of Antibody .............. 211
Table 36: Drug Targets of Antibodies for the Treatment of Gastrointestinal Stomach Cancer According to
Developmental Stage of Antibody .............. 211
Table 37: Drug Targets of Antibodies for the Treatment of Head and Neck Cancer According to Developmental
Stage of Antibody ................. 212
Table 38: Drug Targets of Antibodies for the Treatment Leukemia (general) According to Developmental Stage
of Antibody ...... 213
Table 39: Drug Targets of Antibodies for the Treatment of Acute Lymphocytic Leukemia According to
Developmental Stage of Antibody .............. 213
Table 40: Drug Targets of Antibodies for the Treatment of Acute Myelogenous Leukemia According to
Developmental Stage of Antibody .............. 214
Table 41: Drug Targets of Antibodies for the Treatment of Chronic Lymphocytic Leukemia According to
Developmental Stage of Antibody .............. 215
Table 42: Drug Targets of Antibodies for the Treatment of Chronic Myelogenous Leukemia According to
Developmental Stage of Antibody .............. 216
Table 43: Drug Targets of Antibodies for the Treatment of Liver Cancer According to Developmental Stage of
Antibody .......... 216
Table 44: Drug Targets of Antibodies for the Treatment of Lung Cancer (general) According to Developmental
Stage of Antibody ................. 217
Table 45: Drug Targets of Antibodies for the Treatment of Non Small Cell Lung Cancer According to
Developmental Stage of Antibody .............. 218
Table 46: Drug Targets of Antibodies for the Treatment of Small Cell Lung Cancer According to Developmental
Stage of Antibody ................. 219
Table 47: Drug Targets of Antibodies for the Treatment of lymphoma (general) According to Developmental
Stage of Antibody ................. 219
Table 48: Drug Targets of Antibodies for the Treatment of B cell Lymphoma According to Developmental Stage
of Antibody ...... 220
Table 49: Drug Targets of Antibodies for the Treatment of Hodgkin’s Lymphoma According to Developmental
Stage of Antibody ................. 221
Table 50: Drug Targets of Antibodies for the Treatment of Non Hodgkin’s Lymphoma According to
Developmental Stage of Antibody .............. 222
Table 51: Drug Targets of Antibodies for the Treatment of T cell Lymphoma According to Developmental Stage
of Antibody ...... 224
Table 52: Drug Targets of Antibodies for the Treatment of Melanoma According to Developmental Stage of
Antibody .......... 224
Table 53: Drug Targets of Antibodies for the Treatment of Mesothelioma According to Developmental Stage of
Antibody .......... 225
Table 54: Drug Targets of Antibodies for the Treatment of Myelodysplastic Syndrome According to
Developmental Stage of Antibody .............. 225
Table 55: Drug Targets of Antibodies for the Treatment of Myeloma According to Developmental Stage of
Antibody .......... 226
Table 56: Drug Targets of Antibodies for the Treatment of Nasopharyngeal Cancer According to Developmental
Stage of Antibody ................. 227
Table 57: Drug Targets of Antibodies for the Treatment of Neuroblastoma Cancer According to Developmental
Stage of Antibody ................. 227
Table 58: Drug Targets of Antibodies for the Treatment of Oesophageal Cancer According to Developmental
Stage of Antibody ................. 228
Table 59: Drug Targets of Antibodies for the Treatment of Ovarian Cancer According to Developmental Stage of
Antibody .......... 229
Table 60: Drug Targets of Antibodies for the Treatment of Pancreatic Cancer According to Developmental Stage
of Antibody ...... 230
Table 61: Drug Targets of Antibodies for the Treatment of Peritoneal Cancer According to Developmental Stage
of Antibody ...... 231
Table 62: Drug Targets of Antibodies for the Treatment of Prostate Cancer According to Developmental Stage of
Antibody .......... 232
Table 63: Drug Targets of Antibodies for the Treatment of Renal Cancer According to Developmental Stage of
Antibody .......... 233
Table 64: Drug Targets of Antibodies for the Treatment of Sarcoma According to Developmental Stage of
Antibody .......... 234
Table 65: Drug Targets of Antibodies for the Treatment of Chemotherapy-Induced Bone Marrow Injury
According to Developmental Stage of Antibody ............. 235
Table 66: Drug Targets of Antibodies for the Treatment of Chemotherapy-Induced Anemia According to
Developmental Stage of Antibody .............. 235
Table 67: Drug Targets of Antibodies for the Treatment of Thyroid Cancer According to Developmental Stage of
Antibody .......... 235
Table 68: Antibodies with Drug Target Mix and Developmental Projects by Companies in Australia ................ 236
Table 69: Antibodies with Drug Target Mix and Developmental Projects by Companies in Belgium ................. 236
Table 70: Antibodies with Drug Target Mix and Developmental Projects by Companies in Brazil  237
Table 71: Antibodies with Drug Target Mix and Developmental Projects by Companies in Canada .................. 237
Table 72: Antibodies with Drug Target Mix and Developmental Projects by Companies in China  238
Table 73: Antibodies with Drug Target Mix and Developmental Projects by Companies in Cuba . 238
Table 74: Antibodies with Drug Target Mix and Developmental Projects by Companies in Denmark ................ 238
Table 75: Antibodies with Drug Target Mix and Developmental Projects by Companies in France .................... 239
Table 76: Antibodies with Drug Target Mix and Developmental Projects by Companies in Germany ................ 239
Table 77: Antibodies with Drug Target Mix and Developmental Projects by Companies in Israel . 240
Table 78: Antibodies with Drug Target Mix and Developmental Projects by Companies in Italy .. 241
Table 79: Antibodies with Drug Target Mix and Developmental Projects by Companies in Japan  241
Table 80: Antibodies with Drug Target Mix and Developmental Projects by Companies in the Netherlands ..... 242
Table 81: Antibodies with Drug Target Mix and Developmental Projects by Companies in New Zealand ......... 242
Table 82: Antibodies with Drug Target Mix and Developmental Projects by Companies in Norway .................. 242
Table 83: Antibodies with Drug Target Mix and Developmental Projects by Companies in South Korea ........... 242
Table 84: Antibodies with Drug Target Mix and Developmental Projects by Companies in Sweden .................. 243
Table 85: Antibodies with Drug Target Mix and Developmental Projects by Companies in Switzerland ............ 243
Table 86: Antibodies with Drug Target Mix and Developmental Projects by Companies in United Kingdom..... 244
Table 87: Antibodies with Drug Target Mix and Developmental Projects by Companies in the USA .................. 245
Table 88: Antibodies with Drug Target Mix and Developmental Projects by Non-Industrial Bodies .................. 267