Triple Analysis: Melanoma, Antibodies and Vaccines in Oncology

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 Melonoma Etiology and Pathophysiology

5 Key Therapy Strategies

• 5.1.1 Immunotherapy
• 5.1.2 Cancer Vaccines
• 5.1.3 Antiangiogenesis
• 5.1.4 Gene Therapy

6 Current Treatment Regimens

• 6.1 An Overview
• 6.2 Cytotoxic Drugs
  • 6.2.1 Dacarbazine
  • 6.2.2 Cisplatin
  • 6.2.3 Carboplatin
  • 6.2.4 Carmustine
  • 6.2.5 Melphalan
  • 6.2.6 Paclitaxel
  • 6.2.7 Tamoxifen
  • 6.2.8 Temozolomide
  • 6.2.9 Vinblastine/Vinorelbine
• 6.3 Biological treatments
  • 6.3.1 Virulizin
  • 6.3.2 Melacine
  • 6.3.3 Alfanative (Multiferon)
  • 6.3.4 Proleukin or (Macrolin)
  • 6.3.5 Ceplene Maxamine

7 Competitive Lanscape in Melanoma R&D

• 7.1.1 Phase I & II R&D Collaborations in Melanoma: Oxxon
• 7.1.2 Roche links Schering-Plough and Chugai Clusters Together - What Will the Outcome Be? 50
• 7.1.3 GlaxoSmithKline Brings Wyeth, Hayashibara, Cytokinetics and Coley Pharmaceuticals Together
• 7.1.4 GlaxoSmithKline and Sanofi-Aventis have a Joint Middle Man
• 7.1.5 R&D Collaboration Trends in Melanoma Projects

8 Current Melanoma Drug Development

• 8.1 Vaccines: Active Immunotherapy a Benefit or Not?
  • 8.1.1 Vaccine: Direct Immunization with Tumor Antigens
  • 8.1.2 Vaccines: Is the Development of Cell Therapy Stalling?
  • 8.1.3 DNA Vaccine
  • 8.1.4 Optimism for New Vaccine Adjuvants
• 8.2 Immunostimulants: The Push in Passive Immunotherapy
  • 8.2.1 Immuno-Biologicals: The Work Horse
  • 8.2.2 Immunostimulation by Gene Therapy
  • 8.2.3 One Small Molecular Drug Candidate
• 8.3 Antiangiogenesis- The Major Research Focus for the Next Decade?
• 8.4 Apoptosis Inducers: Moving into Market
• 8.5 Small Molecules Inhibiting Cell Growth Faces Difficulties
• 8.6 Other Biological Drugs

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 BiotypeRvector
  • 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

21 Appendix I: Treatment Guide Lines Melanoma

List of Boxes

• Box 1: Mechanisms which tumor cells use to evade an immune reaction
• Box 2: Introgen's INGN 241 Shows Vaccine Properties
• Box 3: Quick Facts - Oncophage
• Box 4: Oncophage - Designation and Status
• Box 5: Quick Facts - GM2-KLH Vaccine
• Box 6 Progenics reaquires rights to vaccine
• Box 7: Completed Melanoma Phase III trials
• Box 8: Quick Facts - NovaVac-M1
• Box 9: Quick Facts - SB 249553
• Box 10: Quick Facts - MJV 101
• Box 11: Quick Facts - Russian Melanoma Vaccine
• Box 12: Quick Facts - GV 1001
• Box 13: Quick Facts - N-Acetyl-GM3 ganglioside
• Box 14: Quick Facts: neu-glycolyl-GM3 ganglioside
• Box 15: Quick Facts - NY-ESO-1 ISCOMS
• Box 16 NY-ESO-1 and ISCOMATRIX
• Box 17: Quick Facts - F 50040
• Box 18: KpOmpA technology
• Box 19: Quick Facts - TransVax
• Box 20: Quick Facts - Canvaxin
• Box 21: Canvaxin - Designation and Status
• Box 22: CancerVax Milestone payment
• Box 23: Quick Facts - Dexosome
• Box 24: Important Milestones and License Fees
• Box 25: Quick Facts - M-VAX
• Box 26: Quick Facts -OncoVax
• Box 27: Quick Facts - Uvidem
• Box 28: Agreements Between Sanofi-Aventis and IDM
• Box 29: Quick Facts - Alvac-Mage1/Mage3
• Box 30: Quick Facts - Oxxon vaccine
• Box 31: Quick Facts - Therion's Melanoma Vaccine
• Box 32: Quick Facts - ImmunoVEX trimelan
• Box 33: Quick Facts - OncoVEX GM-CSF
• Box 34: Quick Facts - GVAX
• Box 35: Agreement Japan Tobacco and Cell Genesys
• Box 36: Predicted launch of GVAX
• Box 37: Quick Facts - Gp100 + MART-1 vaccine
• Box 38: Quick Facts - MAGE-3-TK
• Box 39: Quick Facts - Enhanzyn
• Box 40: Quick Facts - QS-21
• Box 41: Quick Facts - ZADAXIN
• Box 42: Quick Facts - Mobista
• Box 43: Quick Facts - ProMune
• Box 44: Quick Facts - Talabostat
• Box 45: Quick Facts - MDX-010
• Box 46: Quick Facts - Peginterferon alfa-2b
• Box 47:Quick Facts - BAY-504798
• Box 48: Quick Facts - EMD-273063
• Box 49: Quick Facts - Urocidin
• Box 50:Quick Facts - CP-675206
• Box 51: Quick Facts - ALLOVECTIN-7
• Box 52: Quick Facts - Cytokine, Gene therapy
• Box 53: Quick Facts - TG 1041
• Box 54: Quick Facts - Lenalidomide
• Box 55: Introgen's INGN 241 Shows Anti-angiogenesis Properties
• Box 56: Quick Facts - Sorefenib
• Box 57: Quick Facts - Vitaxin
• Box 58: Quick Facts . Bevacizumab
• Box 59: Quick Facts - Endostatin
• Box 60: Quick Facts - PI88
• Box 61: Quick Facts - Oblimersen
• Box 62: Quick Facts - Didemnin B
• Box 63: Quick Facts - INGN 241
• Box 64: Recent Identification of Molecular Pathways Underlying Activity of Introgen's INGN 241 Anti-Cancer Therapy
• Box 65: Quick Facts - KOS 953
• Box 66: Quick Facts - Temozomide
• Box 67: Molecular Pathways Underlying the Activity of Temozolomide's Anti-Cancer Therapy
• Box 68: Quick Facts - Pivanex
• Box 69: Quick Facts - Karenitecin
• Box 70: Quick Facts - Lomeguatrib
• Box 71: Quick Facts - PD 0325901
• Box 72: Quick Facts - SB 715992
• Box 73: Quick Facts - INO 1001
• Box 74: Quick Facts - CP 4055
• Box 75: Quick Facts - AP 12009
• Box 76: Quick Facts - Ecromeximab
• Box 77: Quick Facts - ILX 651
• Box 78: Quick Facts - Kahalalide F
• Box 79: Quick Facts - ABX MA1
• Box 80: Mechanisms Which Tumor Cells Use to Evade an Immune Reaction
• Box 81: M-VAX - Business & Market Bakground
• Box 82: Gardasil: Business & Market Background
• Box 83: The Principal Terms of Deal between AstraZeneca and Cambridge Antibody Technology
• Box 84: TNF in Cancer Treatments
• Box 85: Marrion's Drug Delivery Technology
• Box 86: Quick Facts - IGN 101
• Box 87: Quick Facts - MDX 010
• Box 88: Quick Facts - ONYVAX 105
• Box 89: Quick Facts - Ovarex
• Box 90: Quick Facts - Panitumumab
• Box 91: Quick Facts - RENCARNEX
• Box 92: Quick Facts - Nimotuzumab
• Box 93: Quick Facts - RENCARNEX
• Box 94: Quick Facts - Lintuzumab
• Box 95: Quick Facts - Zanolimumab
• Box 96: Quick Facts - ABT-510
• Box 97: Quick Facts - BB 10901
• Box 98: Quick Facts - CP-675206
• Box 99: Quick Facts - CNTO-328
• Box 100: Quick Facts - Ecromeximab
• Box 101: Quick Facts - EMD-273063
• Box 102: Quick Facts - WX-G250RIT
• Box 103: Quick Facts - HGS-ETR1
• Box 104: Quick Facts - HuMax-CD20
• Box 105: Quick Facts - HuMax-EGFr
• Box 106: Quick Facts - Galiximab
• Box 107: Quick Facts - PROXINIUM
• Box 108: Quick Facts - RAV12
• Box 109: Quick Facts -SGN-15
• Box 110: Quick Facts -SGN-30
• Box 111: Quick Facts - VEGF-Trap
• Box 112: Quick Facts - MEDI 522
• Box 113: Quick Facts - Volociximab

List of Figures

• Figure 1. Oxxon's R&D Collaborations in Melanoma
• Figure 2. Schering Plough's R&D Collaborations in Melanoma
• Figure 3. GlaxoSmithKline and Wyeth's R&D Collaborations in Melanoma
• Figure 4. Bristol-Myers Squibb's and Sanofi-Aventis' Collaborations in Melanoma
• Figure 5: Top 10 Countries in Cancer Vaccine Research
• Figure 6: Top 10 Companies' Clinical Trial Progress in Cancer Vaccine
• Figure 7: 2003-2005 Deals & Alliances in Cancer Vaccine
• Figure 8: Distribution of Cancer Vaccine Trials in Melanoma
• Figure 9: Distribution of Cancer Vaccine Trials in Breast Cancer
• Figure 10: Distribution of Cancer Vaccine Trials in Prostate Cancer
• Figure 11: Distribution of Cancer Vaccine Trials in Lung Cancer
• Figure 12: Distribution of Cancer Vaccine Trials in Colorectal Cancer
• Figure 13: Distribution of Cancer Vaccine Trials in Cervical Cancer

List of Tables

• Table 1: Critical Risk Factors for Development of Melanoma
• Table 2: Definition and Description of Stages of Melanoma
• Table 3: Prognosis of the 4 Stages of Malignant Melanoma
• Table 4: Deployed Strategies for Blocking Angiogenesis
• Table 5: Current Cytotoxic Drugs for Treatment of Melanoma
• Table 6: Development Milestones- Virulizin
• Table 7: Development Milestones - Melacine
• Table 8: Development Milestones - Alfanative
• Table 9: Development Milestones - Proleukin
• Table 10: Number of Collaborations and Drugs per Developmental Stage
• Table 11: Tumor antigen
• Table 12: In vivo gene therapy
• Table 13: Cell therapy based platform in pipeline as potential treatment of melanoma
• Table 14: Ex vivo gene therapy loading of antigen presenting cells
• Table 15: Overview of Immunostimulants in Development based on Type
• Table 16: Overview of Immuno-Biologicals
• Table 17: MDX-010's Collaborative History and Landscape
• Table 18: Overview of Gene Therapy Drugs for Immunostimulation
• Table 19: Anti-angiogenisis Drugs under Development
• Table 20:Selected Regulatory Progress of Sorafenib
• Table 21: Overview Apoptopic Inducer Drugs
• Table 22: Selected Regulatory Progress of Didemin B
• Table 23: Overview of Small Molecule Drugs
• Table 24: Overview of Various Biological Drugs in Development for Melanoma
• Table 25: Summary of Strategies Enhancing Antibody Function
• Table 26: Companies with Cancer Vaccine Drugs on Market
• Table 27: Antigen Classification
• Table 28: Platforms Used to Improve Antigen Presentation
• Table 29: Cancer Vaccines in Clinical Trials in Combination with Interleukin-2
• Table 30: Adjuvants in Cancer Vaccines
• Table 31: Synthetic Delivery Systems Deployed in Cancer in General and Cancer Vaccines in Particular
• Table 32: Potential Advantages in Local, Controlled-Release for Therapeutic Antibodies
• Table 33: Drug Delivery Companies with Cancer Focus
• Table 34: FDA Approved Polymer-based Drug Delivery Systems for Cancer
• Table 35 Top 10 Cancer Indications in Non-Antibody Based Cancer Vaccines
• Table 36: Discountinued Phase I to Phase III Cancer Vaccine Drugs
• Table 37: List of Phase I to Phase III Cancer Vaccines in Development for Melanoma
• Table 38: List of Phase I to Phase III Cancer Vaccines in Development for Breast Cancer
• Table 39: List of Phase I to Phase III Cancer Vaccines in Development for Prostate Cancer
• Table 40: List of Phase I to Phase III Cancer Vaccines in Development for Lung Cancer
• Table 41: List of Phase I to Phase III Cancer Vaccines in Development for Colorectal Cancer
• Table 42: List of Phase I to Phase III Cancer Vaccines in Development for Cervical Cancer
• Table 43: Antibody Therapeutics in Prostate Cancer
• Table 44: Antibody Therapeutics in Breast Cancer
• Table 45: Antibody Therapeutics in Colorectal Cancer
• Table 46: Antibody Therapeutics in Melanoma
• Table 47: Antibody Therapeutics in Hematological Cancer
• Table 48: MDX-010's Collaborative History and Landscape