APOPTOSIS-BASED THERAPEUTICS: CELL DEATH TO MARKET BIRTH

Table of Contents

1 Executive Summary

1.1 Scope and Objectives of the Report

1.2 Methodology

1.3 Emerging World Market for Therapeutic Apoptosis Modulators

2 Introduction and Overview

2.1 Definition of Apoptosis

2.2 Apoptotic Stimuli and Targets

2.3 Molecular Pathways of Apoptosis

2.3.1 Bcl-2 Proteins

2.3.2 Caspases

2.3.3 Death Receptors

2.3.4 Inhibitors of Apoptosis Protein (IAPs)

2.3.5 Apoptotic Physiological Regulation Summary

2.4 Apoptosis-associated Diseases and Conditions

2.4.1 Cancer

2.4.2 Cardiovascular Disease

2.4.3 Rheumatoid Arthritis

2.4.4 Multiple Sclerosis

2.4.5 Thyroid Disease

2.4.6 HIV Infection

2.4.7 Sepsis and Multiple Organ Dysfunction Syndrome (MODS)

2.4.8 Alzheimer's Disease

2.4.9 Parkinson�fs Disease

2.4.10 Organ Transplant Rejection

3 Technological Issues for Apoptosis based Therapeutics

3.1 Key Drug Discovery Technologies

3.1.1 High Throughput Screening

3.1.2 Sequential High Throughput Screening

3.1.3 Combinatorial Chemistry and Parallel Synthesis

3.2 Target Identification and Validation

3.2.1 Genomics/Proteomics

3.2.2 Structural Biology

3.3 Compound Identification

3.3.1 Antisense

3.3.2 Recombinant Proteins

3.3.3 Small Molecule Mimetics

4 Apoptosis-based Drugs in Development

4.1 Caspase Activators and Inhibitors

4.1.1 IDN-6734

4.1.2 IDN-6556

4.1.3 MX1122

4.1.4 MX1013

4.1.5 VX-799

4.1.6 Pralnacasan (VX-740)

4.1.7 Executioner Caspases

4.2 Bcl-2 Modulators

4.2.1 Genasense

4.2.2 HA14-1

4.3 p53 Modulators

4.3.1 Advexin

4.3.2 INGN 241

4.3.3 INGN 251

4.3.4 SCH58500

4.3.5 ONYX-015

4.4 Inhibitors of Apoptosis Protein (IAPs)

4.5 Protein Kinase Pathway Modulators

4.5.1 Alkyl-lysophosphocholines: Perifosine

4.5.2 Bcr-Abl Tyrosine Kinase Inhibitor: Gleevec

4.5.3 Stress-Activated Protein Kinase (SAPK) Activator: TELCYTA

4.6 Mixed Lineage Kinase (MLK) Inhibitor: CEP-1347

4.7 Multiple Signal Transduction Regulators

4.7.1 Phenoxodiol

4.7.2 CO-501 (-lapachone)

4.8 TNF-Related Apoptosis Inducing Ligand (TRAIL)

4.9 Lysophosphatidic Acid Acyltransferase- (LPAAT-)

4.10 Nicotinic Acetylcholine Receptor (nAChR) Agonist

4.11 Heat Shock Protein 27 (Hsp27)

4.12 Factor 5A

4.13 Miscellaneous Mechanisms of Action

4.13.1 Angiogenesis Modulators

4.13.2 Antibodies

4.13.3 Antisense Agents

4.13.4 Proteasome Inhibitors

4.13.5 Specific Recombinant Antigen: MP4

4.13.6 Selective Apoptotic Anti-Neoplastic Drugs (SAANDs)

5 World Market Analysis

5.1 Market Overview

5.1.1 Market Definition

5.1.2 Major Drug Products

5.1.3 Competitor Companies

5.1.4 Costs of Drug Development

5.2 Total Emerging World Market Size and Forecasts

5.2.1 Total Global Market, 2003-2008

5.2.2 Total U.S. Market Size and Forecasts, 2003-2008

5.2.3 Total Western European Market Size and Forecasts, 2003-2008

5.2.4 Total Japanese Market Size and Forecasts, 2003-2008

5.2.5 Total Rest of World Market Size and Forecasts, 2003-2008

5.2.6 Geographic Shares of Total World Market, 2008

5.3 Caspase Activators and Inhibitors

5.4 Bcl-2 Modulators

5.4.1 Overall World Market

5.4.2 U.S. Market Size and Forecasts, 2003-2008

5.4.3 Western European Market Size and Forecasts, 2003-2008

5.4.4 Japanese Market Size and Forecasts, 2003-2008

5.4.5 Rest of World Market Size and Forecasts, 2003-2008

5.4.6 Geographic Market Shares, 2008

5.4.7 Analysis of Potential Competitors

5.5 TP53 Modulators

5.5.1 Overall World Market

5.5.2 U.S. Market Size and Forecasts, 2003-2008

5.5.3 Western European Market Size and Forecasts, 2003-2008

5.5.4 Japanese Market Size and Forecasts, 2003-2008

5.5.5 Rest of World Market Size and Forecasts, 2003-2008

5.5.6 Geographic Market Shares, 2008

5.5.7 Analysis of Potential Competitors

5.6 Mixed Lineage Kinase (MLK) Inhibitors

5.6.1 Overall World Market

5.6.2 Geographic Regional Markets, 2008

5.6.3 Geographic Market Shares, 2008

5.6.4 Analysis of Potential Competitors

5.7 Proteasome Inhibitors

5.7.1 Overall World Market

5.7.2 U.S. Market Size and Forecasts, 2003-2008

5.7.3 Western European Market Size and Forecasts, 2003-2008

5.7.4 Japanese Market Size and Forecasts, 2003-2008

5.7.5 Rest of World Market Size and Forecasts, 2003-2008

5.7.6 Geographic Market Shares, 2008

5.7.7 Analysis of Potential Competitors

5.8 SAPK Activator: TELCYTA

5.8.1 Overall World Market

5.8.2 Geographic Regional Markets, 2008

5.8.3 Geographic Market Shares, 2008

5.8.4 Analysis of Potential Competitors

5.9 Selective Apoptotic Anti-Neoplastic Drugs (SAANDs)

5.9.1 Overall World Market

5.9.2 Geographic Regional Markets, 2008

5.9.3 Geographic Market Shares, 2008

5.9.4 Analysis of Potential Competitors

6 Company Briefs

6.1 Access Oncology Inc.

6.2 Aegera Therapeutics Inc.

6.3 Alexion Pharmaceuticals Inc.

6.4 Amgen Inc.

6.5 Antisoma plc

6.6 Applied Molecular Evolution Inc.

6.7 Aventis Pharmaceuticals Inc.

6.8 AVI BioPharma Inc.

6.9 Celgene Corp.

6.10 Cell Therapeutics Inc.

6.11 Cephalon Inc.

6.12 Cyclacel Ltd.

6.13 Cyclis Pharmaceuticals Inc.

6.14 Dendreon Corp.

6.15 Endovasc Inc.

6.16 EntreMed Inc.

6.17 Gemin X Biotechnologies

6.18 Genentech Inc.

6.19 Genmab A/S

6.20 Genta Inc.

6.21 Hoffman-La Roche

6.22 Human Genome Sciences, Inc.

6.23 Hybridon Inc.

6.24 Idun Pharmaceuticals Inc.

6.25 ILEX Oncology, Inc.

6.26 Introgen Therapeutics, Inc.

6.27 ISIS Pharmaceuticals, Inc.

6.28 Keryx Biopharmaceuticals Inc.

6.29 Ligand Pharmaceuticals

6.30 Marshall Edwards Inc.

6.31 Maxim Pharmaceuticals

6.32 Millennium Pharmaceuticals Inc.

6.33 Novartis AG

6.34 Onyx Pharmaceuticals, Inc.

6.35 OSI Pharmaceuticals, Inc.

6.36 OXiGENE, Inc.

6.37 Peregrine Pharmaceuticals Inc.

6.38 Pharmos Corp.

6.39 Phytomedics, Inc.

6.40 Protein Design Labs Inc.

6.41 Schering-Plough Corp.

6.42 Senesco Technologies, Inc.

6.43 SuperGen, Inc.

6.44 Targeted Genetics Corp.

6.45 Telik Inc.

6.46 Vertex Pharmaceuticals Inc.

6.47 Xenova Group plc

6.48 Zentaris AG

7 Company Directory

List of Tables

Table 5-1 Companies Developing Apoptosis-based Therapeutics

Table 5-2 Total World Market for Novel Apoptosis-based Therapeutics 2003-2008

Table 5-3 Total U.S. Market for Novel Apoptosis-based Therapeutics 2003-2008

Table 5-4 Total Western European Market for Novel Apoptosis-based Therapeutics 2003-2008

Table 5-5 Total Japanese Market for Novel Apoptosis-based Therapeutics 2003-2008

Table 5-6 Total Rest of World Market for Novel Apoptosis-based Therapeutics 2003-2008

Table 5-7 Total World Market Shares for Novel Apoptosis-based Therapeutics by Geographic Region 2008

Table 5-8 World Market for Bcl-2 Modulators 2003-2008

Table 5-9 U.S. Market for Bcl-2 Modulators 2003-2008

Table 5-10 Western European Market for Bcl-2 Modulators 2003-2008

Table 5-11 Japanese Market for Bcl-2 Modulators 2003-2008

Table 5-12 Rest of World Market for Bcl-2 Modulators 2003-2008

Table 5-13 Market Shares for Bcl-2 Modulators by Geographic Region 2008

Table 5-14 World Market for TP53 Modulators 2003-2008

Table 5-15 U.S. Market for TP53 Modulators 2003-2008

Table 5-16 Western European Market for TP53 Modulators 2003-2008

Table 5-17 Japanese Market for TP53 Modulators 2003-2008

Table 5-18 Rest of World Market for TP53 Modulators 2003-2008

Table 5-19 Market Shares for TP53 Modulators by Geographic Region 2008

Table 5-20 Market for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Table 5-21 Market Shares for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Table 5-22 World Market for Mixed Lineage Kinase Inhibitors 2003-2008

Table 5-23 U.S. Market for Mixed Lineage Kinase Inhibitors 2003-2008

Table 5-24 Western European Market for Mixed Lineage Kinase Inhibitors 2003-2008

Table 5-25 Japanese Market for Mixed Lineage Kinase Inhibitors 2003-2008

Table 5-26 Rest of World Market for Mixed Lineage Kinase Inhibitors 2003-2008

Table 5-27 Market Shares for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Table 5-28 Market for TELCYTA by Geographic Region 2008

Table 5-29 Market Shares for TELCYTA by Geographic Region 2008

Table 5-30 Market for SAANDs by Geographic Region 2008

Table 5-31 Market Shares for SAANDs by Geographic Region 2008

List of Figurs

Figure 5-1 Total World Market for Novel Apoptosis-based Therapeutics 2003-2008

Figure 5-2 Total U.S. Market for Novel Apoptosis-based Therapeutics 2003-2008

Figure 5-3 Total Western European Market for Novel Apoptosis-based Therapeutics 2003-2008

Figure 5-4 Total Japanese Market for Novel Apoptosis-based Therapeutics 2003-2008

Figure 5-5 Total Rest of World Market for Novel Apoptosis-based Therapeutics 2003-2008

Figure 5-6 Total World Market Shares for Novel Apoptosis-based Therapeutics by Geographic Region 2008

Figure 5-7 World Market for Bcl-2 Modulators 2003-2008

Figure 5-8 U.S. Market for Bcl-2 Modulators 2003-2008.

Figure 5-9 Western European Market for Bcl-2 Modulators 2003-2008

Figure 5-10 Japanese Market for Bcl-2 Modulators 2003-2008.

Figure 5-11 Rest of World Market for Bcl-2 Modulators 2003-2008

Figure 5-12 Market Shares for Bcl-2 Modulators by Geographic Region 2008 .

Figure 5-13 World Market for TP53 Modulators 2003-2008

Figure 5-14 U.S. Market for TP53 Modulators 2003-2008

Figure 5-15 Western European Market for TP53 Modulators 2003-2008

Figure 5-16 Japanese Market for TP53 Modulators 2003-2008.

Figure 5-17 Rest of World Market for TP53 Modulators 2003-2008

Figure 5-18 Market Shares for TP53 Modulators by Geographic Region 2008 .

Figure 5-19 Market for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Figure 5-20 Market Shares for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Figure 5-21 World Market for Mixed Lineage Kinase Inhibitors 2003-2008.

Figure 5-22 U.S. Market for Mixed Lineage Kinase Inhibitors 2003-2008

Figure 5-23 Western European Market for Mixed Lineage Kinase Inhibitors 2003-2008

Figure 5-24Japanese Market for Mixed Lineage Kinase Inhibitors 2003-2008.

Figure 5-25 Rest of World Market for Mixed Lineage Kinase Inhibitors 2003-2008 .

Figure 5-26 Market Shares for Mixed Lineage Kinase Inhibitors by Geographic Region 2008

Figure 5-27 Market for TELCYTA by Geographic Region 2008 .

Figure 5-28 Market Shares for TELCYTA by Geographic Region 2008

Figure 5-29 Market for SAANDs by Geographic Region 2008 .

Figure 5-30 Market Shares for SAANDs by Geographic Region 2008 .