癌治療におけるアポトーシス剤、抗体、およびワクチン

Abstract

Executive Summary

In this triple analysis report BioSeeker Group has analyzed three major and intertwined areas of cancer R&D, Apoptopic agents, Antibodies and Vaccines in Oncology, which are all subjects to an extensive number of innovative drug candidates. This extensive 350+ pages report compiles and analyzes in parallel the progress concerning drug development and competitive situation in the three mentioned key oncology areas. The report will not only provide a framework but also a careful identification and evaluation of drug candidates, technologies and competitors.

There are today over 190 apoptopic drugs in active development for the treatment of more than 40 different cancer indications. The top five pursued cancer indications are: breast cancer, leukemia, lung cancer, lymphoma and prostate cancer. A thorough target analysis of drugs in development reveals more than 130 candidate targets for triggering apoptosis in cancer cells. Competitive forces are reviewed, showing market leaders, active players and changes in the competitive landscape. There are only one big pharma company represented among the top 10 players in apoptopic drug development in oncology. The acquisition of Idun Pharmaceutical in 2005 by Pfizer is principal example of a further step in big pharma strategy to augment their internal research and development efforts with high-potential, externally sourced product candidates and technologies.

Apoptopic Agents Highlights

• In-depth competitive landscape assessment of the apoptopic market in oncology
• Thorough review of utilized targets in apoptopic drug development
• Thorough review of approved drugs
• Progress analysis of five major cancer indications, including players, drugs, clinical progress and pitfalls

Among the targeted therapies for cancer, immunotherapy is probably the most versatile treatment strategy for the eradication of tumors, metastatic spread or not. Main strategies of cancer immunotherapy aim at exploiting the therapeutic potential of tumor-specific antibodies and cellular immune effector mechanisms (vaccines).

Immunotherapy in Highlights

• In-depth competitive landscape assessment of the cancer immunotherapy market place; Including more than 200 immunotherapy drugs and pharmaceutical companies
• Thorough review of tumor antigen discovery, immunomodulating strategies and adjuvants
• Thorough review of antibody and vaccine delivery and technologies surrounding it - The next generation
• Progress analysis of six major cancer vaccine indications and late stage antibody development projects, including players, drugs, clinical progress and pitfalls

Table of Contents

1 Executive Summary

2 Table of Contents

• 2.1 List of Boxes
• 2.2 List of Figures
• 2.3 List of Tables

3 Methodology

4 Introduction to Apoptosis in Oncology

5 Apoptosis Competitive Landscape in Oncology

• 5.1 Countries & Players: Who are In the Lead?
• 5.1.1 Top 10 Players Dominate The Developmental Pipeline
• 5.2 Deals & Alliances in Apoptosis Drug Development
  • 5.2.1 Review of Deals and Alliances Initiated in 2006
  • 5.2.2 Review of Deals and Alliances Initiated in 2005
  • 5.2.3 Review of Deals and Alliances Initiated in 2004
  • 5.2.4 Review of Deals and Alliances Initiated in 2003
  • 5.2.5 Review of Deals and Alliances Initiated in 2002
  • 5.2.6 Review of Deals and Alliances Initiated in 2001

6 Approved Apoptopic Cancer Drugs: Performance

7 Target Analysis in Apoptosis

• 7.1 Targets of Late Stage Apoptopic Drugs in Development
  • 7.1.1 B-cell CLL/lymphoma 2
  • 7.1.2 Caspase 3
  • 7.1.3 CD4 molecule
  • 7.1.4 Cytosolic ovarian carcinoma antigen 1
  • 7.1.5 Eukaryotic translation elongation factor 2
  • 7.1.6 Farnesyltransferase, CAAX box, alpha
  • 7.1.7 Fc fragment of IgE
  • 7.1.8 Histone deacetylase 1
  • 7.1.9 Histone deacetylase 2
  • 7.1.10 Interleukin 13 receptor, alpha 1
  • 7.1.11 Phosphodiesterase 2A, cGMP-stimulated
  • 7.1.12 Phosphodiesterase 5A, cGMP-specific
  • 7.1.13 Protein kinase C, beta 1
  • 7.1.14 Steroid 5-alpha-reductase, alpha polypeptide 1
  • 7.1.15 Topoisomerase (DNA) I
  • 7.1.16 Topoisomerase (DNA) II alpha
  • 7.1.17 Tubulin, beta polypeptide
  • 7.1.18 p53 protein
• 7.2 Apoptopic Drugs and Their Targets According to Top 5 Cancer Indications
  • 7.2.1 Targets in Breast Cancer
  • 7.2.2 Targets in Leukemia
  • 7.2.3 Targets in Lung Cancer
  • 7.2.4 Targets in Lymphoma
  • 7.2.5 Targets in Prostate Cancer

8 Apoptopic Drugs in Development: By Major Indications

• 8.1 General Drug Developmental Overview
  • 8.1.1 Apoptopic Drugs in Phase III Clinical Development
  • 8.1.2 Failed Apoptopic Drugs in Oncology
• 8.2 Progress Analysis - Breast Cancer
  • 8.2.1 Phase I Clinical Development
  • 8.2.2 Phase II Clinical Development
  • 8.2.3 Phase III Clinical Development
• 8.3 Progress Analysis - Leukemia
  • 8.3.1 Phase I Clinical Development
  • 8.3.2 Phase II Clinical Development
  • 8.3.3 Phase III Clinical Development
• 8.4 Progress Analysis - Lung Cancer
  • 8.4.1 Phase I Clinical Development
  • 8.4.2 Phase II Clinical Development
  • 8.4.3 Phase III Clinical Development
• 8.5 Progress Analysis - Lymphoma
  • 8.5.1 Phase I Clinical Development
  • 8.5.2 Phase II Clinical Development
  • 8.5.3 Phase III Clinical Development
• 8.6 Progress Analysis - Prostate Cancer
  • 8.6.1 Phase I Clinical Development
  • 8.6.2 Phase II Clinical Development
  • 8.6.3 Phase III Clinical Development

9 Immunotherapy in Oncology

• 9.1 Vaccine Strategies: Challenges & Opportunities
• 9.2 Key Antibody Developmental Strategies

10 Competitive Landscape in Cancer Vaccines

• 10.1 Countries & Players: Who are In the Lead?
  • 10.1.1 Top 10 Players Constitute Up to One Third of R&D: Big Pharma Not Included!
  • 10.1.2 Approved Cancer Vaccine Drugs: Performance
• 10.2 Deals & Alliances in Cancer Vaccines
  • 10.2.1 Recent Mergers & Acquisitions in Cancer Vaccines
  • 10.2.2 Deals in Prostate Cancer
  • 10.2.3 Deals in Breast Cancer
  • 10.2.4 Deals in Leukemia & Lymphoma
  • 10.2.5 Drug Delivery Deals in Cancer Vaccines
  • 10.2.6 Adjuvant Deals

11 Antibody Deals on the Rise

• 11.1 Antibody Deals in Phase III
  • 11.1.1 Deal Situation: MDX 010
  • 11.1.2 Deal Situation: WX G250
  • 11.1.3 Deal Situation: Zanolimumab
• 11.2 Antibody Deals in Phase II
  • 11.2.1 Deal Situation: Mapatumumab
  • 11.2.2 Deal Situation: GCR 3888
  • 11.2.3 Deal Situation: MDX 070
  • 11.2.4 Deal Situation: CDP 860
  • 11.2.5 Deal Situation: Tru-Scint OV
  • 11.2.6 Deal Situation: SC 1
  • 11.2.7 Deal Situation: PRO 70769
  • 11.2.8 Deal Situation: XR 303
  • 11.2.9 Deal Situation: HumaRAD-HN

12 Tumor Antigens

• 12.1 Tumor Antigens: General Comments
• 12.2 Antigen Discovery
  • 12.2.1 Classical Immunology Approach
  • 12.2.2 The Reverse Immunology Approach
  • 12.2.3 Company Platforms
• 12.3 Specific Antigen Processing Technologies Increasing Antigen Presentation

13 Immunomodulators & Adjuvants in Cancer Vaccines

• 13.1 Overview
• 13.2 Cytokines
  • 13.2.1 Vaccines in Combination with Interleukin-2
  • 13.2.2 Tumor Necrosis Factor
  • 13.2.3 Interferons
• 13.3 Adjuvants
• 13.4 Other Immunomodulating Strategies
  • 13.4.1 An Immune Response Modifying Protein
  • 13.4.2 Immunostimulatory DNA
  • 13.4.3 Ex Vivo Stimulated Immune Cells
  • 13.4.4 Fusion Protein Gain Potent Immune Response
  • 13.4.5 Macrophage and Natural Killer Cells Activation
  • 13.4.6 Selective Suppression of the Immune System to An Antigen
  • 13.4.7 TAP Technology

14 Cancer Vaccine Delivery

• 14.1 Viral Delivery
  • 14.1.1 Introduction
  • 14.1.2 Viral Constructs Put into Use
• 14.2 Bacterias
• 14.3 Cell Therapy: Dendritic-cell Based & Cancer-Cell Based Therapies
  • 14.3.1 Introduction
  • 14.3.2 Cell Therapy Strategies
• 14.4 Synthetic Delivery Systems & Strategies
  • 14.4.1 Introduction
  • 14.4.2 Biotransport™
  • 14.4.3 Biotype®vector
  • 14.4.4 DNAVax Gene Delivery System
  • 14.4.5 FusitAb™
  • 14.4.6 GeneDrug™
  • 14.4.7 Molecular Conjugates
  • 14.4.8 Naked DNA Delivery
  • 14.4.9 PVLP Technology
  • 14.4.10 Sphingosomal Drug Delivery Technology
  • 14.4.11 STEALTH
  • 14.4.12 Failed Liposomal Systems

15 New Approaches in Antibody Delivery and Design - The Next Generation

• 15.1 How to Make Them Smaller and Different?
• 15.2 Biomaterials in Sustained Delivery Applications
  • 15.2.1 Implants
• 15.3 Gene delivery - the Future?
  • 15.3.1 Delivery Vehicles for DNA
  • 15.3.2 Gene Delivery in Commercialization

16 Cancer Vaccines in Development: By Major Indications

• 16.1 General Oncology Overview
• 16.2 Progress Analysis - Melanoma
• 16.3 Progress Analysis - Breast Cancer
• 16.4 Progress Analysis - Prostate Cancer
• 16.5 Progress Analysis - Lung Cancer
• 16.6 Progress Analysis - Colorectal Cancer
• 16.7 Progress Analysis - Cervical Cancer

17 Antibodies in Clinical Development

• 17.1.1 Prostate Cancer Therapeutics
• 17.1.2 Breast Cancer Therapeutics
• 17.1.3 Colorectal Cancer Therapeutics
• 17.1.4 Melanoma Therapeutics
• 17.1.5 Hematological Cancers Therapeutics
• 17.2 Antibodies in Phase III Clinical Development
  • 17.2.1 Progress Analysis: IGN 101
  • 17.2.2 Progress Analysis: MDX 010
  • 17.2.3 Progress Analysis: ONYVAX 105
  • 17.2.4 Progress Analysis: Ovarex
  • 17.2.5 Progress Analysis: Panitumumab
  • 17.2.6 Progress Analysis: RENCAREX
  • 17.2.7 Progress Analysis: Nimotuzumab
  • 17.2.8 Progress Analysis: TransMID
  • 17.2.9 Progress Analysis: Lintuzumab
  • 17.2.10 Progress Analysis: Zanolimumab
• 17.3 Antibodies in Phase II Clinical Development
  • 17.3.1 Progress Analysis: ABT-510
  • 17.3.2 Progress Analysis: BB 10901
  • 17.3.3 Progress Analysis: CP 675206
  • 17.3.4 Progress Analysis: CNTO-328
  • 17.3.5 Progress Analysis: Ecromeximab
  • 17.3.6 Progress Analysis: EMD 273063
  • 17.3.7 Progress Analysis: WX-G250RIT
  • 17.3.8 Progress Analysis: HGS-ETR1
  • 17.3.9 Progress Analysis: HuMax-CD20
  • 17.3.10 Progress Analysis: HuMax-EGFr
  • 17.3.11 Progress Analysis: Galiximab
  • 17.3.12 Progress Analysis: PROXINIUM
  • 17.3.13 Progress Analysis: RAV12
  • 17.3.14 Progress Analysis: SGN-15
  • 17.3.15 Progress Analysis: SGN-30
  • 17.3.16 Progression Analysis: VEGF-Trap
  • 17.3.17 Progress Analysis: MEDI 522
  • 17.3.18 Progress Analysis: Volociximab

18 Disclaimer

19 Company Index

20 Drug Index

List of Boxes

• Box 1: Business & Market - PXD-101
• Box 2: Business & Market - MG-98
• Box 3: Business & Market - VX-680
• Box 4: Business & Market - Ceflatonin
• Box 5: Business & Market - Oblimersen sodium
• Box 6: Business & Market - motexafin gadolinium
• Box 7: Business & Market - 1D09C3
• Box 8: Business & Market - PCK-3145
• Box 9: Business & Market - ME-2
• Box 10: Mechanisms Which Tumor Cells Use to Evade an Immune Reaction
• Box 11: M-VAX - Business & Market Bakground
• Box 12: Gardasil: Business & Market Background
• Box 13: The Principal Terms of Deal between AstraZeneca and Cambridge Antibody Technology
• Box 14: TNF in Cancer Treatments
• Box 15: Marrion' s Drug Delivery Technology
• Box 16: Quick Facts - IGN 101
• Box 17: Quick Facts - MDX 010
• Box 18: Quick Facts - ONYVAX 105
• Box 19: Quick Facts - Ovarex
• Box 20: Quick Facts - Panitumumab
• Box 21: Quick Facts - RENCARNEX
• Box 22: Quick Facts - Nimotuzumab
• Box 23: Quick Facts - RENCARNEX
• Box 24: Quick Facts - Lintuzumab
• Box 25: Quick Facts - Zanolimumab
• Box 26: Quick Facts - ABT-510
• Box 27: Quick Facts - BB 10901
• Box 28: Quick Facts - CP-675206
• Box 29: Quick Facts - CNTO-328
• Box 30: Quick Facts - Ecromeximab
• Box 31: Quick Facts - EMD-273063
• Box 32: Quick Facts - WX-G250RIT
• Box 33: Quick Facts - HGS-ETR1
• Box 34: Quick Facts - HuMax-CD20
• Box 35: Quick Facts - HuMax-EGFr
• Box 36: Quick Facts - Galiximab
• Box 37: Quick Facts - PROXINIUM
• Box 38: Quick Facts - RAV12
• Box 39: Quick Facts -SGN-15
• Box 40: Quick Facts -SGN-30
• Box 41: Quick Facts - VEGF-Trap
• Box 42: Quick Facts - MEDI 522
• Box 43: Quick Facts - Volociximab

List of Figures

• Figure 1: Top 5 Countries in Apoptopic Cancer Research
• Figure 2: Top 10 Companies' Clinical Trial Progress in Apoptopic Drug Development
• Figure 3: Trial Distribution of the Entire Apoptopic Pipeline in Oncology
• Figure 4: Distribution of ApoptopicTrials in Breast Cancer
• Figure 5: Distribution of Apoptopic Drug Trials in Leukemia
• Figure 6: Distribution of Apoptopic Drug Trials in Lung Cancer
• Figure 7: Distribution of Apoptopic Drug Trials in Lymphoma
• Figure 8: Distribution of Apoptopic Drug Trials in Prostate Cancer
• Figure 9: Top 10 Countries in Cancer Vaccine Research
• Figure 10: Top 10 Companies' Clinical Trial Progress in Cancer Vaccine
• Figure 11: 2003-2005 Deals & Alliances in Cancer Vaccine
• Figure 12: Distribution of Cancer Vaccine Trials in Melanoma
• Figure 13: Distribution of Cancer Vaccine Trials in Breast Cancer
• Figure 14: Distribution of Cancer Vaccine Trials in Prostate Cancer
• Figure 15: Distribution of Cancer Vaccine Trials in Lung Cancer
• Figure 16: Distribution of Cancer Vaccine Trials in Colorectal Cancer
• Figure 17: Distribution of Cancer Vaccine Trials in Cervical Cancer

List of Tables

• Table 1: Top 10' s Apoptopic Pipeline Drugs
• Table 2: Deals & Alliances in Apoptosis Drug Development in Oncology
• Table 3: Companies with Apoptopic Cancer Drugs on the Market
• Table 4: List of 120 Known Targets in Apoptosis Drug Development
• Table 5: Known Targets of Late Stage Apoptopic Drugs Development
• Table 6: Drugs with Bcl-2 as a Target
• Table 7: Drugs with Casp-3 as a Target
• Table 8: Drugs with CD4 molecule as a Target
• Table 9: Drugs with Cova-1 as a Target
• Table 10: Drugs with Eef-2 as a Target
• Table 11: Drugs with Fnta as a Target
• Table 12: Drugs with Fcer-2 as a Target
• Table 13: Drugs with Hdac-1 as a Target
• Table 14: Drugs with Hdac-2 as a Target
• Table 15: Drugs with IL13-RA1 as a Target
• Table 16: Drugs with Pde-2A as a Target
• Table 17: Drugs with Pde-5A as a Target
• Table 18: Drugs with Prkcb-1 as a Target
• Table 19: Drugs with Srd-5A1 as a Target
• Table 20: Drugs with Top-1 as a Target
• Table 21: Drugs with Top-2A as a Target
• Table 22: Drugs with Top-2A as a Target
• Table 23: Drugs with p53 protein as a Target
• Table 24: Breast Cancer Targets in Apoptopic Drug Development
• Table 25: Leukemia Targets in Apoptopic Drug Development
• Table 26: Lung Cancer Targets in Apoptopic Drug Development
• Table 27: Lymhoma Targets in Apoptopic Drug Development
• Table 28: Prostate Cancer Targets in Apoptopic Drug Development
• Table 29: Top 10 Cancer Indications in Apoptopic Cancer Drugs
• Table 30: Overview of Apoptopic Drugs in Phase III Clinical Development
• Table 31: Recently Ceased or Discountinued Phase I to Phase III Apoptopic Drugs
• Table 32: List of Phase I to Phase III Apoptopic Drugs in Development for Breast Cancer
• Table 33: List of Phase I to Phase III Apoptopic Drugs in Development for Leukemia
• Table 34: List of Phase I to Phase III Apoptopic Drugs in Development for Lung Cancer
• Table 35: List of Phase I to Phase III Apoptopic Drugs in Development for Lymphoma
• Table 36: List of Phase I to Phase III Apoptopic Drugs in Development for Prostate Cancer
• Table 37: Summary of Strategies Enhancing Antibody Function
• Table 38: Companies with Cancer Vaccine Drugs on Market
• Table 39: Antigen Classification
• Table 40: Platforms Used to Improve Antigen Presentation
• Table 41: Cancer Vaccines in Clinical Trials in Combination with Interleukin-2
• Table 42: Adjuvants in Cancer Vaccines
• Table 43: Synthetic Delivery Systems Deployed in Cancer in General and Cancer Vaccines in Particular
• Table 44: Potential Advantages in Local, Controlled-Release for Therapeutic Antibodies
• Table 45: Drug Delivery Companies with Cancer Focus
• Table 46: FDA Approved Polymer-based Drug Delivery Systems for Cancer
• Table 47 Top 10 Cancer Indications in Non-Antibody Based Cancer Vaccines
• Table 48: Discountinued Phase I to Phase III Cancer Vaccine Drugs
• Table 49: List of Phase I to Phase III Cancer Vaccines in Development for Melanoma
• Table 50: List of Phase I to Phase III Cancer Vaccines in Development for Breast Cancer
• Table 51: List of Phase I to Phase III Cancer Vaccines in Development for Prostate Cancer
• Table 52: List of Phase I to Phase III Cancer Vaccines in Development for Lung Cancer
• Table 53: List of Phase I to Phase III Cancer Vaccines in Development for Colorectal Cancer
• Table 54: List of Phase I to Phase III Cancer Vaccines in Development for Cervical Cancer
• Table 55: Antibody Therapeutics in Prostate Cancer
• Table 56: Antibody Therapeutics in Breast Cancer
• Table 57: Antibody Therapeutics in Colorectal Cancer
• Table 58: Antibody Therapeutics in Melanoma
• Table 59: Antibody Therapeutics in Hematological Cancer
• Table 60: MDX-010' s Collaborative History and Landscape