Triple Progress Analysis: Lymphoma, PK Inhibitors & Antibodies

SUMMARY

In this triple analysis report BioSeeker Group has analyzed three major and intertwined areas of cancer R&D, Lymphoma, Protein Kinase Inhibitors and Therapeutic Antibodies, which are all subjects to an extensive number of innovative drug candidates. This extensive 320 pages report compiles and analyzes 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

Published trial data show an increase in response rates when rituximab is combined with current chemotherapy regimens in both the first- and second- line settings in the treatment of lymphoma. In addition, rituximab show significant off-label usage. Already today it is clear that rituximab has generated substantial revenues for the companies involved in its development. A collection of emerging facts suggest that several of the new targeted therapies under development include agents that cannot just be added into treatment regimens with conventional drugs. A few of them might have isolated properties on certain biologic targets that may require to be modulated in particular ways before or after cytotoxic chemotherapy. Among the emerging therapeutic strategies, passive and active immunotherapies have clearly continued to be leading strategies. Small molecule kinase inhibitors are as well in the forefront

The commercial and therapeutic success of antibodies will force the industry to look into the next generation of therapeutic antibodies, preparing themselves for the second wave in the lucrative field of therapeutic antibodies. The first-generation formulations of therapeutic antibodies will be facing heavy competition from biogeneric companies as their profitable antibody drugs comes off patent in the future. Among the different strategies (e.g., antibody engineering, changes in primary structure, fusions, chemical modifications glycosylation, pegylation, polymer conjugates), the approach of miniaturizing and delivering antibody drugs is the most promising because it permits better release of active drugs.

The number of protein kinase inhibitor drugs has risen sharply, as the number of targets. The fiercest competition in kinase inhibitor drug development is found in hematological, breast, lung, prostate, and colorectal cancer. Several big pharma companies are out hunting for promising technology and drugs to complement their internal pipeline.

TABLE OF CONTENTS

1 Executive Summary

2 Methodology

3 Table of Contents

• 3.1 List of Boxes
• 3.2 List of Figures
• 3.3 List of Tables

4 Lymphoma Therapeutics

• 4.1 Introduction
  • 4.1.1 Disease Definition
  • 4.1.2 Etiology & Pathophysiology
  • 4.1.3 Epidemiology
• 4.2 Current Treatment Strategies
  • 4.2.1 Hodgkin's Disease
  • 4.2.2 Non-Hodgkin's Lymphoma
  • 4.2.3 Prognosis
• 4.3 Progress in Current Treatment Strategies
  • 4.3.1 HODGKIN
  • 4.3.2 NON-HODGKIN
• 4.4 Key Therapeutic Strategies
  • 4.4.1 Antibodies & Immunostimulation
  • 4.4.2 Small molecules: Apoptosis inducers & Kinase inhibitors
• 4.5 Current Drug Development: The Late Stage Pipeline
  • 4.5.1 Progress Analysis: aldesleukin
  • 4.5.2 Progress Analysis: Arsenic trioxide
  • 4.5.3 Progress Analysis: BiovaxID
  • 4.5.4 Progress Analysis: bortezomib
  • 4.5.5 Progress Analysis: LymphoCide
  • 4.5.6 Progress Analysis: FavId
  • 4.5.7 Progress Analysis: MyVax
  • 4.5.8 Progress Analysis: Nelarabine
  • 4.5.9 Progress Analysis: Genasense
  • 4.5.10 Progress Analysis: Marqibo
  • 4.5.11 Progress Analysis: Pixantrone
  • 4.5.12 Progress Analysis: CCI-779
  • 4.5.13 Progress Analysis: HuMax-CD4
  • 4.5.14 Progress Analysis: Bortezomib
• 4.6 Current Drug Development: The Early Stage Pipeline
  • 4.6.1 Progress analysis: bevacizumab
  • 4.6.2 Progress Analysis: CMC-544
  • 4.6.3 Progress Analysis: galiximab
  • 4.6.4 Progress Analysis: LY317615
  • 4.6.5 Progress Analysis: SGN-40
  • 4.6.6 Progress Analysis: Hu1D10
  • 4.6.7 Progress Analysis: SGN-30

5 Therapeutic Antibodies

• 5.1 Key Developmental Strategies
• 5.2 Treating Colorectal Cancer
  • 5.2.1 Avastin
  • 5.2.2 Erbitux
• 5.3 Treating Lymphomas
  • 5.3.1 Rituxan
  • 5.3.2 Bexxar
  • 5.3.3 Zevalin
• 5.4 Treating Leukemias
  • 5.4.1 ALL
  • 5.4.2 CLL
  • 5.4.3 AML
  • 5.4.4 CML
  • 5.4.5 Campath
  • 5.4.6 Mylotarg
• 5.5 Treating Lung cancer
  • 5.5.1 Cotara
• 5.6 Antibody Deals on the Rise
  • 5.6.1 Antibody Deals in Phase III
  • 5.6.2 Antibody Deals in Phase II
• 5.7 New Approaches in Antibody Delivery and Design - The Next Generation
  • 5.7.1 How to Make Them Smaller and Different?
  • 5.7.2 Biomaterials in Sustained Delivery Applications
  • 5.7.3 Gene delivery - the Future?
• 5.8 Current Analysis of Antibodies in Clinical Development
  • 5.8.1 Prostate Cancer Therapeutics
  • 5.8.2 Breast Cancer Therapeutics
  • 5.8.3 Colorectal Cancer Therapeutics
  • 5.8.4 Melanoma Therapeutics
  • 5.8.5 Hematological Cancers Therapeutics
• 5.9 Antibodies in Phase III Clinical Development
  • 5.9.1 Progress Analysis: IGN 101
  • 5.9.2 Progress Analysis: MDX 010
  • 5.9.3 Progress Analysis: ONYVAX 105
  • 5.9.4 Progress Analysis: Ovarex
  • 5.9.5 Progress Analysis: Panitumumab
  • 5.9.6 Progress Analysis: RENCAREX
  • 5.9.7 Progress Analysis: Nimotuzumab
  • 5.9.8 Progress Analysis: TransMID
  • 5.9.9 Progress Analysis: Lintuzumab
  • 5.9.10 Progress Analysis: Zanolimumab
• 5.10 Antibodies in Phase II Clinical Development
  • 5.10.1 Progress Analysis: ABT-510
  • 5.10.2 Progress Analysis: BB 10901
  • 5.10.3 Progress Analysis: CP 675206
  • 5.10.4 Progress Analysis: CNTO-328
  • 5.10.5 Progress Analysis: Ecromeximab
  • 5.10.6 Progress Analysis: EMD 273063
  • 5.10.7 Progress Analysis: WX-G250RIT
  • 5.10.8 Progress Analysis: HGS-ETR1
  • 5.10.9 Progress Analysis: HuMax-CD20
  • 5.10.10 Progress Analysis: HuMax-EGFr
  • 5.10.11 Progress Analysis: Galiximab
  • 5.10.12 Progress Analysis: PROXINIUM
  • 5.10.13 Progress Analysis: RAV12
  • 5.10.14 Progress Analysis: SGN-15
  • 5.10.15 Progress Analysis: SGN-30
  • 5.10.16 Progression Analysis: VEGF-Trap
  • 5.10.17 Progress Analysis: MEDI 522
  • 5.10.18 Progress Analysis: Volociximab
• 5.11 Cancer Therapeutic Antibodies in Clinical Development

6 Protein Kinase Inhibitors

• 6.1 Rationale for Development of Kinase Inhibitors in Oncology
• 6.2 Protein Kinase Targets - A Growing Family
• 6.3 Challenges in Protein Kinase Drug Discovery
  • 6.3.1 Enabling Structure-Based Drug Design is the Key
  • 6.3.2 Specific Kinase Inhibitors without Kinase Profiling?
• 6.4 Drugs according to Target
  • 6.4.1 Cyclin-dependent Kinase Target Inhibitors
  • 6.4.2 Aurora Kinase Target Inhibitors
  • 6.4.3 Cell Cycle Checkpoint Target Controls Inhibitors
  • 6.4.4 Tyrosine Kinase Receptor Inhibitors
  • 6.4.5 Other Serine/Threonine Kinase Target Inhibitors
• 6.5 Dual or Multiple Kinase Inhibitor Analysis
  • 6.5.1 Presentation of Drugs Targeting A to F Kinases
  • 6.5.2 Presentation of Drugs Targeting G to T Kinases
• 6.6 Targets According to Indication
  • 6.6.1 Breast Cancer
  • 6.6.2 Prostate Cancer: What Cannot be Found in the 'Groins'?
  • 6.6.3 Lung Cancer: A Need for Improved Survival Rates
  • 6.6.4 Colorectal Cancer: EGFR & VEGFR are Strong Targets but There are Others
  • 6.6.5 Leukemia: Show Me the Power of PKI
  • 6.6.6 Melanoma
  • 6.6.7 Lymphoma: We Are In
• 6.7 Growing Competition in the Field
• 6.8 Big Pharma Outlook: The Race is On
  • 6.8.1 Novartis Deals - Digs Deeper into Cell Cycle Inhibitors
  • 6.8.2 AstraZeneca - Wheeling and Dealing
  • 6.8.3 Pfizer's Long Look at OSI Pharmaceuticals
  • 6.8.4 GlaxoSmithKline Gains Momentum
• 6.9 Strategic Deals Creating Competitive Edge
  • 6.9.1 Mergers
  • 6.9.2 Astex - the PKI Switchboard
  • 6.9.3 Big Pharma's Darling
• 6.10 Current Protein Kinase Inhibitors in Therapy
  • 6.10.1 Mechanism, Target and Developmental History
  • 6.10.2 Approvals: Indications & Markets
• 6.11 Protein Kinase Inhibitors in Drug Development - A Progress Analysis
  • 6.11.1 Progress Analysis - Breast Cancer
  • 6.11.2 Progress Analysis - Prostate Cancer
  • 6.11.3 Progress Analysis - Lung Cancer
  • 6.11.4 Progress Analysis - Colorectal Cancer
  • 6.11.5 Progress Analysis - Leukemia
  • 6.11.6 Progress Analysis - Melanoma
  • 6.11.7 Progress Analysis - Lymphoma

7 Appendix I: Selected Company R&D Summarizes in Lymphoma

• 7.1.1 Accentia BioPharmaceuticals
• 7.1.2 Biogen Idec
• 7.1.3 Cell Therapeutics
• 7.1.4 Chiron Corporation
• 7.1.5 Cephalon
• 7.1.6 Eli Lilly
• 7.1.7 Favrille
• 7.1.8 Genentech
• 7.1.9 Genitope Corporation
• 7.1.10 Genmab
• 7.1.11 Genta
• 7.1.12 GlaxoSmithKline
• 7.1.13 Immunomedics
• 7.1.14 Inex Pharmaceuticals
• 7.1.15 Millennium Pharmaceuticals
• 7.1.16 Protein Design Labs
• 7.1.17 Roche
• 7.1.18 Sanofi-Aventis
• 7.1.19 Seattle Genetics
• 7.1.20 Wyeth

Company index

Drug index

List of Boxes

• Box 1 Possible Complications of Treatment
• Box 2 Updated REAL/WHO Classification for B-Cell Neoplasms
• Box 3 Subclassification of stage
• Box 4 Updated REAL/WHO Classification for B-Cell Neoplasms
• Box 5 Updated REAL/WHO Classification for T-Cell and Putative NK-Cell Neoplasms
• Box 6 Staging subclassification system
• Box 7 Study details
• Box 8: The Principal Terms of Deal between AstraZeneca and Cambridge Antibody Technology
• Box 9: Marrion's Drug Delivery Technology
• Box 10: Quick Facts - IGN 101
• Box 11: Quick Facts - MDX 010
• Box 12: Quick Facts - ONYVAX 105
• Box 13: Quick Facts - Ovarex
• Box 14: Quick Facts - Panitumumab
• Box 15: Quick Facts - RENCARNEX
• Box 16: Quick Facts - Nimotuzumab
• Box 17: Quick Facts - RENCARNEX
• Box 18: Quick Facts - Lintuzumab
• Box 19: Quick Facts - Zanolimumab
• Box 20: Quick Facts - ABT-510
• Box 21: Quick Facts - BB 10901
• Box 22: Quick Facts - CP-675206
• Box 23: Quick Facts - CNTO-328
• Box 24: Quick Facts - Ecromeximab
• Box 25: Quick Facts - EMD-273063
• Box 26: Quick Facts - WX-G250RIT
• Box 27: Quick Facts - HGS-ETR1
• Box 28: Quick Facts - HuMax-CD20
• Box 29: Quick Facts - HuMax-EGFr
• Box 30: Quick Facts - Galiximab
• Box 31: Quick Facts - PROXINIUM
• Box 32: Quick Facts - RAV12
• Box 33: Quick Facts -SGN-15
• Box 34: Quick Facts -SGN-30
• Box 35: Quick Facts - VEGF-Trap
• Box 36: Quick Facts - MEDI 522
• Box 37: Quick Facts - Volociximab
• Box 38: The Power of Ambit's Kinase Profiling
• Box 39: Summary Terms of the Exelixis Transaction

List of Figures

• Figure 1 Generalized Illustration, Depicting the Key Elements Involved in the Apoptotic Pathways
• Figure 2 Top 10 PKI Drug Developing Companies
• Figure 3 Clinical Trial Distribution in Breast Cancer for PKI Drugs
• Figure 4 Clinical Trial Distribution in Prostate Cancer for PKI Drugs
• Figure 5 Clinical Trial Distribution in Lung Cancer for PKI Drugs
• Figure 6 Clinical Trial Distribution in Colorectal Cancer for PKI Drugs
• Figure 7 Clinical Trial Distribution in Leukemia for PKI Drugs
• Figure 8 Clinical Trial Distribution in Melanoma for PKI Drugs
• Figure 9 Clinical Trial Distribution in Lymphoma for PKI Drugs

List of Tables

• Table 1 Drugs used in the treatment of lymphoma
• Table 2 Summary of Strategies Enhancing Antibody Function
• Table 3 Cancer immunotherapy strategies
• Table 4 Protein Kinase Targets in Clinical Trials for Lymphoma
• Table 5 Recent published studies Aldesleukin
• Table 6 Recent published studies Arsenic trioxide
• Table 7 Recent published studies BiovaxID
• Table 8 Recent Published Studies Bortezomib
• Table 9 Recent published studies epratuzumab
• Table 10 Recent published studies FavId
• Table 11 Recent published studies MyVax
• Table 12 Recent published studies Nelarabine
• Table 13 Recent published studies Genasense
• Table 14 Recent published studies Pixantrone
• Table 15 Recent published studies temsirolimus
• Table 16 Recent published studies Zanolimumab
• Table 17 Recent published studies Flavopiridol
• Table 18 Recent published studies bevacizumab
• Table 19 Recent published studies CMC-544
• Table 20 Recent published studies galiximab
• Table 21 Recent published studies LY317615
• Table 22 Recent published studies SGN-40
• Table 23 Recent published studies Apolizumab
• Table 24 Recent published studies SGN-30
• Table 25: Summary of Strategies Enhancing Antibody Function
• Table 26: Potential Advantages in Local, Controlled-Release for Therapeutic Antibodies
• Table 27: Drug Delivery Companies with Cancer Focus
• Table 28: FDA Approved Polymer-based Drug Delivery Systems for Cancer
• Table 29: Antibody Therapeutics in Prostate Cancer
• Table 30: Antibody Therapeutics in Breast Cancer
• Table 31: Antibody Therapeutics in Colorectal Cancer
• Table 32: Antibody Therapeutics in Melanoma
• Table 33: Antibody Therapeutics in Hematological Cancer
• Table 34: MDX-010's Collaborative History and Landscape
• Table 35: Overview of Targets in Commercial Development
• Table 36: Cyclin-dependent Kinase Targets in Development
• Table 37: Aurora Kinase Targets in Development
• Table 38: Cell Cycle Checkpoint Targets in Development
• Table 39: Epidermal Growth Factor Receptor Targets in Development
• Table 40: FMS-like tyrosine kinases and their Synonyms
• Table 41: Fms-related Tyrosine Kinase Targets in Development
• Table 42: Platelet-derived Growth Factor Receptor Targets in Development
• Table 43: Kinase Insert Domain Targets in Development
• Table 44: Drugs in Development Targeting the PI3K/Akt/mTOR pathway
• Table 45: Drugs in Development Targeting the Ras-Raf-MEK-ERK (ERK) pathway
• Table 46: Serine/Threonine Kinase Inhibitors in Development
• Table 47: Protein Kinase Targets in Clinical Trials for Breast Cancer
• Table 48: Protein Kinase Targets in Clinical Trials for Prostate Cancer
• Table 49: Protein Kinase Targets in Clinical Trials for Lung Cancer
• Table 50: Protein Kinase Targets in Clinical Trials for Colorectal Cancer
• Table 51: Protein Kinase Targets in Clinical Trials for Leukemia
• Table 52: Protein Kinase Targets in Clinical Trials for Melanoma
• Table 53: Protein Kinase Targets in Clinical Trials for Lymphoma
• Table 54: Drugs in Therapy - Mechanism & Targets
• Table 55: Current and Developmental History of PKI Drugs in Therapy
• Table 56: Approvals: Indications & Markets
• Table 57: Top 10 Drugs in Terms of Number of Clinical Trials
• Table 58: List of Cancer Indications Targeted by Protein Kinase Inhibitors
• Table 59: PKI Drugs in Development for Breast Cancer
• Table 60: PKI Drugs in Development for Prostate Cancer
• Table 61: PKI Drugs in Development for Lung Cancer
• Table 62: PKI Drugs in Development for Colorectal Cancer
• Table 63: PKI Drugs in Development for Leukemia
• Table 64: PKI Drugs in Development for Melanoma
• Table 65: PKI Drugs in Development for Lymphoma
• Table 66 Accentia BioPharmaceuticals anticancer pipeline
• Table 67 Biogen anticancer pipeline
• Table 68 Cell Therapeutics anticancer pipeline
• Table 69 Chiron Corporation anticancer pipeline
• Table 70 Cephalon anticancer pipeline
• Table 71 Eli Lilly anticancer pipeline
• Table 72 Favrille anticancer pipeline
• Table 73 Genentech anticancer pipeline
• Table 74Genitope anticancer pipeline
• Table 75 Genmab anticancer pipeline
• Table 76 Genta anticancer pipeline
• Table 77 GlaxoSmithKline anticancer pipeline
• Table 78 Immunomedics anticancer pipeline
• Table 79 Inex Pharmaceuticals anticancer pipeline
• Table 80 Millennium Pharmaceuticals anticancer pipeline
• Table 81 Protein Design Labs anticancer pipeline
• Table 82 Roche anticancer pipeline
• Table 83 Sanofi-Aventis anticancer pipeline
• Table 84 Seattle Genetics anticancer pipeline
• Table 85 Wyeth anticancer pipeline