Antibody Drug Target Atlas in Oncology

SUMMARY

Executive Summary

The elaborate advances towards the blueprinting of the altered molecular networks that lie behind cancer development have paved the way for targeted therapy in cancer. There are currently more than 400 antibody based drugs in development for the treatment of cancer. What and where they are targeting has to date only been a fragmented knowledge. First in place, BioSeeker has surveyed these antibodies and identified 132 antibody drug targets, belonging to 220 antibody drugs. In all they range from preclinical development to established therapy leaders in the market place. Drug targets and their associated antibodies have been analyzed by BioSeeker according to:

• 34 Different molecular functions of target
• 13 Major signaling pathways
• Cancer stem cells
• Conjugated antibodies
• Therapeutic effects: Anti-angiogenesis, Apoptosis and Protein Kinase Inhibition
• 31 Targeted cancer indications
• Availability of expression profiles of targets in human tissues, cancer tissues, established cell lines and primary cell cultures
• Antibody therapeutic companies

Single target analysis of the 132 antibody targets is performed, including targeted cancer indications, antibody drugs involved and their developmental stages. In total more than 420 clinical trials are included in this analysis, covering more than 30 different cancer indications plus diagnosis and supportive care.

This report serves as a serious reference for professionals interested in the development of oncology drug targets and selection/validation of targeting strategies.

TABLE OF CONTENTS

1 Executive Summary

2 About Cancer Highlights

3 Methodologies

4 Table of Contents

• 4.1 List of Figures
• 4.2 List of Tables

5 Antibody Drug Target Analysis in Oncology: What and Where Are We Targeting?

6 Antibody Drug Targets by Molecular Function

• 6.1 Carboxypeptidase Activity Targets
• 6.2 Catalytic Activity Targets
• 6.3 Cell Adhesion Molecule Activity Targets
• 6.4 Chaperone Activity Targets
• 6.5 Chemokine Activity Targets
• 6.6 Cofactor Binding Targets
• 6.7 Complement Activity Targets
• 6.8 Cytokine Activity Targets
• 6.9 DNA Topoisomerase Activity Targets
• 6.10 Extracellular Matrix Structural Constituent Targets
• 6.11 G-protein Coupled Receptor Activity Targets
• 6.12 Growth Factor Activity Targets
• 6.13 Hormone Activity Targets
• 6.14 Hydrolase Activity Targets
• 6.15 Intracellular Ligand-gated Ion Channel Activity Targets
• 6.16 Metallopeptidase Activity Targets
• 6.17 MHC Class I Receptor Activity Targets
• 6.18 Molecular Function Unknown Targets
• 6.19 Oxidoreductase Activity Targets
• 6.20 Peptide Hormone Targets
• 6.21 Protease Inhibitor Activity Targets
• 6.22 Protein Binding Targets
• 6.23 Receptor Activity Targets
• 6.24 Receptor Binding Targets
• 6.25 Receptor Signaling Complex Scaffold Activity Targets
• 6.26 Receptor Signaling Protein Tyrosine Phosphatase Activity Targets
• 6.27 RNA-directed DNA polymerase Activity Targets
• 6.28 Serine-type Peptidase Activity Targets
• 6.29 T Cell Receptor Activity Targets
• 6.30 Translation Regulator Activity Targets
• 6.31 Transmembrane Receptor Activity Targets
• 6.32 Transmembrane Receptor Protein Tyrosine Kinase Activity Targets
• 6.33 Transporter Activity Targets
• 6.34 Unclassified Targets

7 Antibody Drugs Targeting Signaling Pathways

• 7.1 Alpha6 Beta4 Integrin Signaling Pathway
  • 7.1.1 Description of Pathway
  • 7.1.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.2 Androgen Receptor Signaling Pathway
  • 7.2.1 Description of Pathway
  • 7.2.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.3 B Cell Receptor Signaling Pathway
  • 7.3.1 Description of Pathway
  • 7.3.2 Antibody Drugs by Target, Developmental Stage and Cancer Type
• 7.4 EGFR1 Signaling Pathway
  • 7.4.1 Description of Pathway
  • 7.4.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.5 IL-2 Signaling Pathway
  • 7.5.1 Description of Pathway
  • 7.5.2 Antibody Drugs by Target, Developmental Stage and Cancer Type
• 7.6 IL-4 Signaling Pathway
  • 7.6.1 Description of Pathway
  • 7.6.2 Antibody Drugs by Target, Developmental Stage and Cancer Type
• 7.7 IL-6 Signaling Pathway
  • 7.7.1 Description of Pathway
  • 7.7.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.8 Kit Receptor Signaling Pathway
  • 7.8.1 Description of Pathway
  • 7.8.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.9 Notch Signaling Pathway
  • 7.9.1 Description of Pathway
  • 7.9.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.10 T Cell Receptor Signaling Pathway
  • 7.10.1 Description of Pathway
  • 7.10.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.11 TGF-beta Receptor Signaling Pathway
  • 7.11.1 Description of Pathway
  • 7.11.2 Antibody Drugs byTarget, Developmental Stage, and Cancer Type
• 7.12 TNF-alpha Signaling Pathway
  • 7.12.1 Description of Pathway
  • 7.12.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type
• 7.13 Wnt Signaling Pathway
  • 7.13.1 Description of Pathway
  • 7.13.2 Antibody Drugs by Target, Developmental Stage, and Cancer Type

8 Antibodies Targeting Cancer Stem Cells

9 Targets of Antibody Conjugates

10 Antibody Drug Targets by Three Major Non Immunological Therapeutic Effects

• 10.1 Anti-Angiogenesis
• 10.2 Apoptosis
• 10.3 Protein Kinase Inhibitors

11 Antibody Targets and Drugs by Cancer Indications

• 11.1 Basal Cell Cancer
• 11.2 Biliary Cancer
• 11.3 Bladder Cancer
• 11.4 Bone Cancer
• 11.5 Brain Cancer
• 11.6 Breast Cancer
• 11.7 Cervical Cancer
• 11.8 Cervical Dysplasia
• 11.9 Colorectal Cancer
• 11.10 Endometrial Cancer
• 11.11 Esophageal Cancer
• 11.12 Fallopian Tube Cancer
• 11.13 Gastrointestinal Cancers
• 11.14 Head and Neck Cancer
• 11.15 Leukemias
• 11.16 Liver Cancer
• 11.17 Lung Cancers
• 11.18 Lymphomas
• 11.19 Melanoma
• 11.20 Mesothelioma
• 11.21 Myelodysplastic syndrome
• 11.22 Myelomas
• 11.23 Nasopharyngeal Cancer
• 11.24 Oesophageal Cancer
• 11.25 Ovarian Cancer
• 11.26 Pancreatic Cancer
• 11.27 Peritoneal Cancer
• 11.28 Prostate Cancer
• 11.29 Renal Cancers
• 11.30 Sarcomas
• 11.31 Thyroid Cancer

12 Expression Profiles of Antibody Drug Targets

• 12.1 Human Tissues and Cancer Tissues
• 12.2 Cancer Lines and Cells

13 Disclaimer

14 Drug Index

15 Company Index

16 Appendix I: Antibody Targets by Companies

List of Figures

• Figure 1: Antibody Pipeline Maturity by Molecular Function Classes of Targets 1(3)
• Figure 2: Antibody Pipeline Maturity by Molecular Function Classes of Targets 2(3)
• Figure 3: Antibdody Pipeline Maturity by Molecular Function Classes of Targets 3(3)
• Figure 4: Pipeline Maturation of Carboxypeptidase Activity Targets
• Figure 5: Number of Antibody Drugs per Cancer Indication and Carboxypeptidase Activity Target
• Figure 6: Pipeline Maturation of Catalytic Activity Targets
• Figure 7: Number of Antibody Drugs per Cancer Indication and Catalytic Activity Target
• Figure 8: Pipeline Maturation of Cell Adhesion Molecule Activity Targets
• Figure 9: Number of Antibody Drugs per Cancer Indication and Cell Adhesion Molecule Activity Target
• Figure 10: Pipeline Maturation of Chaperone Activity Targets
• Figure 11: Number of Antibody Drugs per Cancer Indication and Chaperone Activity Target
• Figure 12: Pipeline Maturation of Chemokine Activity Targets
• Figure 13: Number of Antibody Drugs per Cancer Indication and Chemokine Activity Target
• Figure 14: Pipeline Maturation of Cofactor Binding Targets
• Figure 15: Number of Antibody Drugs per Cancer Indication and Cofactor Binding Target
• Figure 16: Pipeline Maturation of Complement Activity Targets
• Figure 17: Number of Antibody Drugs per Cancer Indication and Complement Activity Target
• Figure 18: Pipeline Maturation of Cytokine Activity Targets
• Figure 19: Number of Antibody Drugs per Cancer Indication and Cytokine Activity Target
• Figure 20: Pipeline Maturation of DNA Topoisomerase Activity Targets
• Figure 21: Number of Antibody Drugs per Cancer Indication and DNA Topoisomerase Activity Target
• Figure 22: Pipeline Maturation of Extracellular Matrix Structural Constituent Targets
• Figure 23: Number of Antibody Drugs per Cancer Indication and Extracellular Matrix Structural Constituent Target
• Figure 24: Pipeline Maturation of G-protein Coupled Receptor Activity Targets
• Figure 25: Number of Antibody Drugs per Cancer Indication and Extracellular G-protein Coupled Receptor Activity Target
• Figure 26: Pipeline Maturation of Growth Factor Activity Targets
• Figure 27: Number of Antibody Drugs per Cancer Indication and Extracellular Growth Factor Activity Target
• Figure 28: Pipeline Maturation of Hormone Activity Targets
• Figure 29: Number of Antibody Drugs per Cancer Indication and Hormone Activity Target
• Figure 30: Pipeline Maturation of Hydrolase Activity Targets
• Figure 31: Number of Antibody Drugs per Cancer Indication and Hydrolase Activity Target
• Figure 32: Pipeline Maturation of Ligand-gated Ion Channel Activity Targets
• Figure 33: Number of Antibody Drugs per Cancer Indication and Intracellular Ligand-gated Ion Channel Activity Target
• Figure 34: Pipeline Maturation of Metallopeptidase Activity Targets
• Figure 35: Number of Antibody Drugs per Cancer Indication and Intracellular Metallopeptidase Activity Target
• Figure 36: Pipeline Maturation of MHC Class I Receptor Activity Targets
• Figure 37: Number of Antibody Drugs per Cancer Indication and MHC Class I Receptor Activity Target
• Figure 38: Pipeline Maturation of Molecular Function Unknown Targets
• Figure 39: Number of Antibody Drugs per Cancer Indication and Molecular Function Unknown Target
• Figure 40: Pipeline Maturation of Oxidoreductase Activity Targets
• Figure 41: Number of Antibody Drugs per Cancer Indication and Oxidoreductase Activity Target
• Figure 42: Pipeline Maturation of Peptide Hormone Targets
• Figure 43: Number of Antibody Drugs per Cancer Indication and Peptide Hormone Target
• Figure 44: Pipeline Maturation of Protease inhibitor Activity Targets
• Figure 45: Number of Antibody Drugs per Cancer Indication and Protease Inhibitor Activity Target
• Figure 46: Pipeline Maturationof Protein Binding Targets
• Figure 47: Number of Antibody Drugs per Cancer Indication and Protein Binding Target
• Figure 48: Pipeline Maturation of Receptor Activity Targets 1 (2)
• Figure 49: Number of Antibody Drugs per Cancer Indication and Receptor Activity Target 1(2)
• Figure 50: Pipeline Maturation of Receptor Activity Targets 2 (2)
• Figure 51: Number of Antibody Drugs per Cancer Indication and Receptor Activity Target 2(2)
• Figure 52: Pipeline Maturationof Receptor Binding Targets
• Figure 53: Number of Antibody Drugs per Cancer Indication and Receptor Binding Target
• Figure 54: Pipeline Maturation of Receptor Signaling Complex Scaffold Activity Targets
• Figure 55: Number of Antibody Drugs per Cancer Indication and Receptor Signaling Complex Scaffold Activity Target
• Figure 56: Pipeline Maturation of by Receptor Signaling Protein Tyrosine Phosphatase Activity Targets
• Figure 57: Number of Antibody Drugs per Cancer Indication and Receptor Signaling Protein Tyrosine Phosphatase Activity Target
• Figure 58: Pipeline Maturation of RNA-directed DNA polymerase Activity Targets
• Figure 59: Number of Antibody Drugs per Cancer Indication and RNA-directed DNA polymerase Activity Target
• Figure 60: Pipeline Maturation of Serine-type Peptidase Activity Targets
• Figure 61: Number of Antibody Drugs per Cancer Indication and RNA Serine-type Peptidase Activity Target
• Figure 62: Pipeline Maturation of T cell Receptor Activity Targets
• Figure 63: Number of Antibody Drugs per Cancer Indication and T cell Receptor Activity Target
• Figure 64: Pipeline Maturation of Translation Regulator Activity Targets
• Figure 65: Number of Antibody Drugs per Cancer Indication and Translation Regulator Activity Target
• Figure 66: Pipeline Maturation of Transmembrane Receptor Activity Targets
• Figure 67: Number of Antibody Drugs per Cancer Indication and Transmembrane Receptor Activity Target
• Figure 68: Pipeline Maturation of Transmembrane Receptor Protein Tyrosine Kinase Activity Targets
• Figure 69: Number of Antibody Drugs per Cancer Indication and Transmembrane Receptor Protein Tyrosine Kinase Activity Target
• Figure 70: Pipeline Maturation of Transporter Activity Targets
• Figure 71: Number of Antibody Drugs per Cancer Indication and Transporter Activity Target
• Figure 72: Pipeline Maturation of Unclassified Targets
• Figure 73: Number of Antibody Drugs per Cancer Indication and Unclassified Target
• Figure 74: Antibody Pipeline Comparison of Targeted Signaling Pathways in Oncology
• Figure 75: Pipeline Maturation of Immunoconjugated Antibody Targets
• Figure 76: Number of Immunoconjugated Antibody Drugs per Cancer Indication and Target

List of Tables

• Table 1: Molecular Functions versus Oncology Antibody Drug Targets
• Table 2: Cancer Antibody Pipeline Listed by Carboxypeptidase Activity Targets
• Table 3: Cancer Antibody Pipeline Listed by Catalytic Activity Targets
• Table 4: Cancer Antibody Pipeline Listed by Cell Adhesion Molecule Activity Targets
• Table 5: Cancer Antibody Pipeline Listed by Chaperone Activity Targets
• Table 6: Cancer Antibody Pipeline Listed by Chemokine Activity Targets
• Table 7: Cancer Antibody Pipeline Listed by Cofactor Binding Targets
• Table 8: Cancer Antibody Pipeline Listed by Complement Activity Targets
• Table 9: Cancer Antibody Pipeline Listed by Cytokine Activity Targets
• Table 10: Cancer Antibody Pipeline Listed by DNA Topoisomerase Activity Targets
• Table 11: Cancer Antibody Pipeline Listed by Extracellular Matrix Structural Constituent Targets
• Table 12: Cancer Antibody Pipeline Listed by G-protein Coupled Receptor Activity Targets
• Table 13: Cancer Antibody Pipeline Listed by Growth Factor Activity Targets
• Table 14: Cancer Antibody Pipeline Listed by Hormone Activity Targets
• Table 15: Cancer Antibody Pipeline Listed by Hydrolase Activity Targets
• Table 16: Cancer Antibody Pipeline Listed by Intracellular Ligand-gated Ion Channel Activity Targets
• Table 17: Cancer Antibody Pipeline Listed by Metallopeptidase Activity Targets
• Table 18: Cancer Antibody Pipeline Listed by MHC Class I Receptor Activity Targets
• Table 19: Cancer Antibody Pipeline Listed by Molecular Function Unknown Targets
• Table 20: Cancer Antibody Pipeline Listed by Oxidoreductase Activity Targets
• Table 21: Cancer Antibody Pipeline Listed by Peptide Hormone Targets
• Table 22: Cancer Antibody Pipeline Listed by Protease inhibitor Activity Targets
• Table 23: Cancer Antibody Pipeline Listed by Protein Binding Targets
• Table 24: Cancer Antibody Pipeline Listed by Receptor Activity Targets
• Table 25: Cancer Antibody Pipeline Listed by Receptor Binding Targets
• Table 26: Cancer Antibody Pipeline Listed by Receptor Signaling Complex Scaffold Activity Targets
• Table 27: Cancer Antibody Pipeline Listed by Receptor Signaling Protein Tyrosine Phosphatase Activity Targets74
• Table 28: Cancer Antibody Pipeline Listed by RNA-directed DNA polymerase Activity Targets
• Table 29: Cancer Antibody Pipeline Listed by Serine-type Peptidase Activity Targets
• Table 30: Cancer Antibody Pipeline Listed by T cell Receptor Activity Targets
• Table 31: Cancer Antibody Pipeline Listed by Translation Regulator Activity Targets
• Table 32: Cancer Antibody Pipeline Listed by Transmembrane Receptor Activity Targets
• Table 33: Cancer Antibody Pipeline Listed by Transmembrane Receptor Protein Tyrosine Kinase Activity Targets
• Table 34: Cancer Antibody Pipeline Listed by Transporter Activity Targets
• Table 35: Cancer Antibody Pipeline Listed by Unclassified Targets
• Table 36: Antibody Drugs Targeting Signaling Pathways
• Table 37: Signaling Pathway Analysis of Oncology Antibody Drug Targets
• Table 38: Targets Linking Antibody Drugs to the Alpha6 Beta4 Integrin Signaling Pathway
• Table 39: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the Alpha6 Beta4 Integrin Signaling Pathway
• Table 40: Targets Linking Antibody Drugs to the Androgen Receptor Signaling Pathway
• Table 41: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the Androgen Receptor Signaling Pathway
• Table 42: Targets Linking Antibody Drugs to the B Cell Receptor Signaling Pathway
• Table 43: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the B Cell Receptor Signaling Pathway
• Table 44: Targets Linking Antibody Drugs to the EGFR1 Signaling Pathway
• Table 45: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the EGFR1 Signaling Pathway
• Table 46: Targets Linking Antibody Drugs to the IL-2 Signaling Pathway
• Table 47: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the IL-2 Signaling Pathway
• Table 48: Targets Linking Antibody Drugs to the IL-4 Signaling Pathway
• Table 49: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the IL-4 Signaling Pathway
• Table 50: Targets Linking Antibody Drugs to the IL-6 Signaling Pathway
• Table 51: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the IL-6 Signaling Pathway
• Table 52: Targets Linking Antibody Drugs to the Kit Receptor Signaling Pathway
• Table 53: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the Kit Receptor Signaling Pathway
• Table 54: Targets Linking Antibody Drugs to the Notch Signaling Pathway
• Table 55: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the Notch Signaling Pathway
• Table 56: Targets Linking Antibody Drugs to the T Cell Receptor Signaling Pathway
• Table 57: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the T Cell Receptor Signaling Pathway
• Table 58: Targets Linking Antibody Drugs to the TGF-beta Receptor Signaling Pathway
• Table 59: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the TGF-beta Receptor Signaling Pathway
• Table 60: Targets Linking Antibody Drugs to the TNF-alpha Signaling Pathway
• Table 61: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the TNF-alpha Signaling Pathway
• Table 62: Targets Linking Antibody Drugs to the Wnt Signaling Pathway
• Table 63: Antibodies, Listed by Investigator, Developmental Stage, and Cancer Type, Targeting the Wnt Signaling Pathway
• Table 64: Cell Surface Markers of Identified Cancer Stem Cells in Human Tumors
• Table 65: Signaling Pathways Involved in Stem Cell Self-Renewal
• Table 66: Immunoconjugated Antibody Targets According to Molecular Function of Target
• Table 67: Immunoconjugated Antibody Pipeline According to Target
• Table 68: Antibodies in Oncology Reported to Affect Angiogenesis
• Table 69 Antibodies in Oncology Reported to Affect Apoptosis
• Table 70: Antibody Drug Protein Kinase Targets Ranked by Probability of Carrying at Least One Driver Mutation, Conditional on the Gene-Specific Selection Pressures
• Table 71: Antibodies in Oncology Reported to Act as Protein Kinase Inhibitors
• Table 72: Cancer Indicaions by Number of Known Antibody Targets, Number of Antibody Drugs, and Highest Developmental Stage
• Table 73: Antibody Pipeline by Targets in Basal Cell Cancer
• Table 74: Antibody Pipeline by Targets in Biliary Cancer
• Table 75: Antibody Pipeline by Targets in Bladder Cancer
• Table 76: Antibody Pipeline by Targets in Bone Cancer
• Table 77: Antibody Pipeline by Targets in Brain Cancer
• Table 78: Antibody Pipeline by Targets in Breast Cancer
• Table 79: Antibody Pipeline by Targets in Cervical Cancer
• Table 80: Antibody Pipeline by Targets in Cervical Dysplasia
• Table 81: Antibody Pipeline by Targets in Colorectal Cancer
• Table 82: Antibody Pipeline by Targets in Endometrial Cancer
• Table 83: Antibody Pipeline by Targets in Esophageal Cancer
• Table 84: Antibody Pipeline by Targets in Fallopian Tube Cancer
• Table 85: Antibody Pipeline by Targets in Gastrointestinal Cancers
• Table 86: Antibody Pipeline by Targets in Head and Neck Cancer
• Table 87: Antibody Pipeline by Targets in Leukemias
• Table 88: Antibody Pipeline by Targets in Liver Cancer
• Table 89: Antibody Pipeline by Targets in Lung Cancers
• Table 90: Antibody Pipeline by Targets in Lymphomas
• Table 91: Antibody Pipeline by Targets in Melanoma
• Table 92: Antibody Pipeline by Targets in Mesothelioma
• Table 93: Antibody Pipeline by Targets in Myelodysplastic syndrome
• Table 94: Antibody Pipeline by Targets in Myelomas
• Table 95: Antibody Pipeline by Targets in Nasopharyngeal Cancer
• Table 96: Antibody Pipeline by Targets in Oesophageal Cancer
• Table 97: Antibody Pipeline by Targets in Ovarian Cancer
• Table 98: Antibody Pipeline by Targets in Pancreatic Cancer
• Table 99: Antibody Pipeline by Targets in Peritoneal Cancer
• Table 100: Antibody Pipeline by Targets in Prostate Cancer
• Table 101: Antibody Pipeline by Targets in Renal Cancers
• Table 102: Antibody Pipeline by Targets in Sarcomas
• Table 103: Antibody Pipeline by Targets in Thyroid Cancer
• Table 104: Expression Profiles of Antibody Drug Targets in Oncology