Report: Triple Analysis: Melanoma, Antibodies and Vaccines in Oncology TOC

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