Breast Cancer Therapeutics: How Innovation is Shaping Future Therapies

Table of Contents

Chapter 1: Executive Summary 1--1

• Breast Cancer Therapeutics 1--1
• Breast Cancer Technologies 1--3
• Breast Cancer Markets 1--3
• The Future and Breast Cancer 1--4

Chapter 2: The Need for Breast Cancer Therapeutics 2--1

• Epidemiology 2--1
• Breast Cancer Types and Stages 2--1
• Causes and Risk Factors 2--2
• Biomarkers and Diagnostics 2--2
• Awareness and Education 2--4
• Treatment Strategies 2--4
• Objectives and Scope 2--5

Chapter 3: Targets and Therapeutics in Endocrine Therapy 3--1

• Estrogen and the Estrogen Receptor 3--1
• Normal Estrogen Function 3--1
• The Estrogen Receptor 3--2
• Estrogen, The Estrogen Receptor, and Breast Cancer 3--3
• Estrogen and Breast Cancer 3--3
• The Estrogen Receptor and Breast Cancer 3--4
• Categories of Endocrine Therapy 3--4
• Selective Estrogen Receptor Modulators (SERMs) 3--4
• Mode of Action of SERMs 3--5
• Approved SERMs 3--5
• Emerging SERMs 3--7
• Raloxifene 3--8
• Arzoxifene 3--8
• Lasofoxifene 3--9
• Selective Estrogen Receptor Downregulators (SERDs) 3--9
• Mode of Action of SERDs 3--9
• Approved SERDs 3--9
• Aromatase Inhibitors 3--10
• Mode of Action of Aromatase Inhibitors 3--10
• Approved Aromatase Inhibitors 3--10
• Emerging Aromatase Inhibitors 3--12
• LHRH Agonists 3--13
• Mode of Action of LHRH Agonists 3--13
• Approved LHRH Agonists 3--14

Chapter 4: Innovative Therapy for Breast Cancer 4--1

• Targeting Growth Factors 4--1
• The erbB Receptor Family 4--1
• erbB1/EGFR 4--2
• erbB2/EGFR2/HER2 4--4
• Targeting Growth Factors (IGF) 4--5
• Targeting Angiogenesis 4--6
• Vascular Endothelial Growth Factor (VEGF) 4--6
• Targeting Farnesylation 4--8
• Targeting the MEK Pathway 4--9
• Targeting the mTOR Pathway 4--10
• Targeting Apoptosis 4--11
• Targeting DNA Synthesis and Repair 4--13
• Targeting the Proteasome 4--13

Chapter 5: Immunotherapy for Breast Cancer 5--1

• Cancer Vaccines and Breast Cancer 5--1
• Current Approaches in Cancer Vaccine Development 5--1
• Approved and Emerging Cancer Vaccines 5--2
• Approved Cancer Vaccines 5--2
• Emerging Breast Cancer Vaccines 5--2
• Adjuvants 5--6
• Approved and Emerging Monoclonal Antibodies 5--7
• Categories of Monoclonal Antibodies 5--7
• Naked Monoclonal Antibodies 5--7
• Conjugated Monoclonal Antibodies 5--8
• Approved and Emerging Monoclonal Antibodies 5--9
• Approved Monoclonal Antibodies 5--9
• Emerging Monoclonal Antibodies 5--13

Chapter 6: Chemotherapy for Breast Cancer 6--1

• Historical Timeline 6--1
• Chemotherapy Categorization 6--2
• Antimetabolites 6--2
• Mitotic Inhibitors 6--2
• Alkylating Agents 6--3
• Anthracyclines 6--3
• Topoisomerase II Inhibitors 6--3
• Approved Chemotherapy Drugs for Breast Cancer 6--3
• Emerging Chemotherapy Drugs for Breast Cancer 6--7
• Combination Chemotherapy 6--10

Chapter 7: Technology and Breast Cancer 7--1

• Gene Cloning and Characterization 7--1
• Gene Expression Profiling 7--2
• Proteomics 7--3
• RNAi 7--3
• Bioinformatics 7--4
• Population Genetics 7--4
• Biomarkers 7--5
• Diagnostics and Prognosis 7--7

Chapter 8: The Breast Cancer Market 8--1

• Endocrine Therapies 8--1
• Selective Estrogen Receptor Modulators (SERMs) 8--3
• Selective Estrogen Receptor Downregulators (SERDs) 8--5
• Aromatase Inhibitors 8--5
• Arimidex® 8--6
• Femara® 8--6
• Aromasin® 8--7
• Luteinizing Hormone-Releasing Hormone Analogs (LHRH Analogs) 8--7
• Innovative Therapies 8--7
• Immunotherapies 8--8
• The Chemotherapy Market 8--9

Chapter 9: Future Perspectives 9--1

• Therapeutic Potential 9--1
• Market Potential 9--2
• Breast Cancer Treatment and The Future 9--2
• Breast Cancer and The Patient 9--3
• Summary 9--3

Chapter 10: Expert Interviews 10--1

• James D. Winkler, Ph.D., Senior Director, Discovery Biology, Array BioPharma 10--1
• Dr. George Blackledge, Senior Oncology Physician, AstraZeneca 10--4
• Dr. Rene Bernards, Chief Scientific Officer, Agendia 10--6
• Dr. Thomas J. Schuetz, Chief Medical Officer and Senior VP of Medical Affairs, Therion Biologics 10--9

Chapter 11: Company Profiles 11--1

• Aeterna Zentaris Inc 11--1
• Agendia BV 11--5
• American Pharmaceutical Partners, Inc 11--8
• Array BioPharma Inc. 11--12
• AstraZeneca plc 11--16
• Bristol Myers Squibb 11--21
• Dendreon Corporation 11--25
• Eli Lilly and Company 11--29
• Genentech, Inc 11--33
• Genta, Inc. 11--38
• Igeneon 11--41
• Novartis AG 11--44
• Sanofi-aventis 11--49
• Therion Biologics Corporation 11--53
• ViRexx Medical Corp. 11--56

Chapter 12: References 12--1

TABLE OF EXHIBITS

• Exhibit 2.1 Risk Factors Associated with Breast Cancer 2--2
• Exhibit 2.2 Examples of Sub-groups of Breast Cancer Patients 2--3
• Exhibit 2.3 Pink Breast Cancer Ribbon 2--4
• Exhibit 3.1 Illustration of Estrogen Action 3--2
• Exhibit 3.2 Tissue Distribution of Estrogen Receptor �Eand 3--3
• Exhibit 3.3 Key Classes of Endocrine Therapy for Breast Cancer 3--4
• Exhibit 3.4 The Dual Role of SERMs on Breast and Uterine Tissue 3--5
• Exhibit 3.5 Approved SERMs for Breast Cancer Treatment 3--6
• Exhibit 3.6 Characteristics of the Ideal SERM 3--7
• Exhibit 3.7 Emerging SERMs 3--8
• Exhibit 3.8 Approved SERDs 3--9
• Exhibit 3.9 Approved Aromatase Inhibitors 3--11
• Exhibit 3.10 Emerging Aromatase Inhibitors 3--13
• Exhibit 3.11 Mode of Action of Zoladex® 3--14
• Exhibit 3.12 Approved LHRH Agonists 3--15
• Exhibit 4.1 Illustration of the Four erbB (EGFR) Receptor Sub-types 4--2
• Exhibit 4.2 Emerging Therapeutics Targeting erb1 (EGFR) 4--3
• Exhibit 4.3 Approved Therapeutics Targeting erbB2 (Her2/EGFR2/neu) 4--4
• Exhibit 4.4 Emerging Therapeutics Targeting erbB2 (and multiple erbBs) 4--5
• Exhibit 4.5 Emerging Therapeutics Targeting Angiogenesis 4--7
• Exhibit 4.6 Emerging Therapeutics Targeting Farnesyl Transferases 4--8
• Exhibit 4.7 Emerging Therapeutics Targeting the MEK Pathway 4--9
• Exhibit 4.8 Emerging Therapeutics Targeting the mTOR Pathway 4--10
• Exhibit 4.9 RAD001 Effects on Tumor and Vascular Cells 4--11
• Exhibit 5.1 Breast Cancer Vaccines in Clinical Development 5--3
• Exhibit 5.2 Mechanism of Action of Therion's Cancer Vaccines 5--4
• Exhibit 5.3 Mechanism of Action of Dendreon's Therapeutic Vaccines 5--5
• Exhibit 5.4 Adjuvants for Cancer Vaccines in Clinical Development 5--6
• Exhibit 5.5 Approved Non-conjugated Monoclonal Antibodies 5--8
• Exhibit 5.6 FDA-Approved Monoclonal Antibodies for Treating Cancer 5--10
• Exhibit 5.7 Mode of Action of Herceptin® 5--11
• Exhibit 5.8 Timeline of Herceptin® Development 5--12
• Exhibit 5.9 Emerging Monoclonal Antibodies for Breast Cancer 5--13
• Exhibit 6.1 Historical Milestones Associated with Chemotherapy Development 6--2
• Exhibit 6.2 Approved Chemotherapy Drugs for Breast Cancer 6--4
• Exhibit 6.3 Phase III Chemotherapy Agents 6--7
• Exhibit 6.4 Structure of Targaceutical® 6--8
• Exhibit 6.5 Select Phase II Chemotherapy Agents 6--9
• Exhibit 6.6 Gemzar and Paclitaxel as Combination Therapy 6--11
• Exhibit 7.1 Drug Targets Associated with Breast Cancer Therapeutics 7--2
• Exhibit 7.2 Tumor Marker Testing in Breast Cancer 7--6
• Exhibit 8.1 Key/Emerging Players in the Endocrine Therapy Market for Breast Cancer 8--2
• Exhibit 8.2 Sales of Endocrine Therapies for Breast Cancer (2003 and 2004) 8--3
• Exhibit 8.3 Sales of Nolvadex® (tamoxifen) from 2001 to 2004 8--4
• Exhibit 8.4 Sales of Approved Aromatase Inhibitors (2003-2004) 8--6
• Exhibit 4.10 Emerging Therapeutics Targeting Apoptosis 4--12
• Exhibit 4.11 Emerging Therapeutics Targeting DNA Synthesis and Repair 4--13
• Exhibit 4.12 Emerging Therapeutics Targeting the Proteasome 4--14