Epigenetics R&D Pipeline - Histone Deacetylases (HDACs) Offer the Most Promising Targets and Outnumber Other Classes of Epigenetic Targets

Epigenetics R&D Pipeline - Histone Deacetylases (HDACs) Offer the Most Promising Targets and Outnumber Other Classes of Epigenetic Targets

Summary

GBI Research, a leading business intelligence provider, has released its latest research, entitled “Epigenetics R&D Pipeline - Histone Deacetylases (HDACs) Offer the Most Promising Targets and Outnumber Other Classes of Epigenetic Targets”. The report is built using data and information sourced from proprietary databases, primary and secondary research and in-house analysis by GBI Research’s team of industry experts. The report provides an insight into the epigenetic targets being studied and the challenges, issues, trends and opportunities in epigenetic research. It also outlines the product pipeline and discusses late-stage R&D molecules, as well as profiles of the major companies currently active in epigenetic research and in-depth analysis of strategic consolidations.

Epigenetics refers to a regulatory system that selectively regulates gene expression in different cells without actually affecting the genomic makeup of the Deoxyribonucleic Acid (DNA) sequence. Epigenetics is emerging as a key determinant of cellular differentiation, and epigenetic regulation of gene expression has been seen to play a vital role in a number of diseases.

There are currently only four epigenetic-based drugs in the market, namely Vidaza, Zolinza, Dacogen and Istodax. They act by inhibiting either Histone Deacetylases (HDAC) or DNA Methyltransferase (DNMT). The last few years have seen a surge of research into epigenetic modification and its usefulness in the treatment of a wide range of disease conditions. Analysis of the product pipeline reveals that the majority of research is centered on histone modifications. Clinical trials targeting HDACs clearly outnumber any other class of epigenetic targets. New targets such as RNA, BET, E2HZ are also being explored. Early epigenetics research was largely focused on its application for the treatment of cancer, although researchers and pharmaceutical companies now understand its potential for neurodegenerative diseases, metabolic disorders and aging. The lack of selectivity and the toxicity of first-generation epigenetic-based drugs are the key challenges in epigenetic research that need to address. There is no clear consensus among researchers as to whether research should focus on developing better combinations or better specificity. Some pharmaceutical companies such as Phamacyclics are developing drugs that are target specific while others are involved in investigating epigenetic-based combination therapies and developing novel epigenetic-based drugs.

The massive potential of epigenetics, both from a therapeutic and business point of view, has attracted substantial interest from academia, investors, and pharmaceutical and biotechnology companies. Epigenetics has been one of the most widely studied areas in recent years and has emerged as a promising focus in drug discovery. Expectations are high, and fulfilling them while also addressing key challenges and issues could be possible with collaborative efforts from academia and pharmaceutical companies.

Scope

- Existing and new targets being explored in R&D
- Detailed epigenetic pipeline analysis
- In-depth discussion of the challenges, trends and opportunities in epigenetic research
- Analysis of epigenetic-based marketed products
- Profiles of the top companies active in epigenetics
- Information on strategic consolidation in the epigenetic space

Reasons to buy

- Identify the advantages of epigenetic therapies and understand market potential
- Gain an insight into the targets being explored in R&D
- Understand the key challenges, issues, trends and opportunities in epigenetic research
- Identify the key players best positioned to take advantage of the epigenetic therapeutics’ market potential

1 Table of Contents
1 Table of Contents 6
1.1 List of Tables 9
1.2 List of Figures 9
2 Introduction 10
3 Epigenetics R&D Pipeline – Overview of Epigenetics 11
4 Epigenetics R&D Pipeline – Applications of Epigenetics 13
4.1 Epigenetics in Cancer 14
4.2 Epigenetics in Other Disease Conditions 14
4.2.1 Central Nervous System Disorders 14
4.2.2 Epigenetics in Aging 15
4.2.3 Diabetes and Obesity 15
5 Epigenetics R&D Pipeline – Mechanisms and Targets 16
5.1 DNA Methyltransferase 16
5.1.1 Histone Modifications 17
5.2 New Targets 18
5.2.1 Lysine-specific Demethylase 1 18
5.2.2 Enhancer of Zeste Homolog 2 18
5.2.3 Bromodomain and Extra-terminal Proteins 18
5.2.4 Ribonucleic Acid 19
6 Epigenetics R&D Pipeline – Marketed Products 20
6.1 Vidaza (azacitidine) – Celgene Corporation 21
6.1.1 Product Description 21
6.1.2 Mechanism of Action 22
6.1.3 R&D 22
6.1.4 Adverse Effects 22
6.2 Zolinza (vorinostat) – Merck & Co.Inc. 23
6.2.1 Product Description 23
6.2.2 Mechanism of Action 24
6.2.3 R&D 24
6.2.4 Adverse Effects 24
6.3 Istodax (romidepsin) – Celgene Corporation 25
6.3.1 Product Description 25
6.3.2 Mechanism of Action 26
6.3.3 R&D 26
6.3.4 Adverse Effects 26
6.4 Dacogen (decitabine) – Eisai Co., Ltd. 26
6.4.1 Product Description 26
6.4.2 Mechanism of Action 28
6.4.3 R&D 28
6.4.4 Adverse Effects 28
7 Epigenetic R&D Pipeline – Analysis 29
7.1 Epigenetics R&D Pipeline – Pipeline by Stage of Development 30
7.1.1 Epigenetics R&D Pipeline – Discovery 31
7.1.2 Epigenetics R&D Pipeline – Phase I 32
7.1.3 Epigenetics R&D Pipeline – Phase I/II 37
7.1.4 Epigenetics R&D Pipeline – Phase II 38
7.1.5 Epigenetics R&D Pipeline – Phase III 41
7.2 Epigenetics R&D Pipeline – Pipeline Analysis by Indication 42
7.3 Epigenetics R&D Pipeline – Pipeline Analysis by Mechanism of Action 43
7.4 Epigenetics R&D Pipeline – Late-stage Pipeline Molecules 44
7.4.1 LBH589 (panobinostat) 44
7.4.2 Belinostat 44
7.4.3 Entinostat 44
7.4.4 Vorinostat 45
8 Epigenetics R&D Pipeline – Challenges, Opportunities and Trends 46
8.1 Challenges in Dealing with Epigenetics 46
8.1.1 Physician Response to Epigenetic-based Therapies 47
8.1.2 Lack of Specificity of Epigenetic-based Therapies 48
8.1.3 Toxicity 48
8.1.4 Unknown Mechanism of Action 49
8.1.5 Better Combination or Better Specificity? 49
8.1.6 Technological Challenges 50
8.2 Opportunities in Epigenetics 50
8.2.1 Cancer Market Potential 50
8.2.2 New Indications 51
8.2.3 Resolving Toxicity and Specificity Issue will Increase Uptake of Epigenetic-based Drugs 51
8.2.4 Exploring New Target and Undefined Epigenetic Enzymes 51
8.3 Trends in Epigenetics Research 51
8.3.1 Shift to the New Potential Targets 51
8.3.2 Combination Therapies with Two or More Epigenetics Drugs with Different Mechanisms of Action 51
9 Epigenetics R&D Pipeline – Leading Players 53
9.1 Merck & Co., Inc. 54
9.1.1 Business Overview 54
9.1.2 Epigenetic Portfolio 54
9.2 Novartis AG 55
9.2.1 Business Overview 55
9.2.2 Epigenetic Portfolio 55
9.3 Syndax Pharmaceuticals, Inc. 55
9.3.1 Business Overview 55
9.3.2 Epigenetic Portfolio 56
9.4 4SC AG 56
9.4.1 Business Overview 56
9.4.2 Epigenetic Portfolio 56
9.5 GlaxoSmithKline Plc 57
9.5.1 Business Overview 57
9.5.2 Deals 57
9.6 Celgene Corporation 57
9.6.1 Business Overview 57
9.6.2 Epigenetic Portfolio 57
9.7 MethylGene Inc. 58
9.7.1 Business Overview 58
9.7.2 Epigenetic Portfolio 58
9.8 Pharmacyclics, Inc. 58
9.8.1 Business Overview 58
9.8.2 Epigenetic Portfolio 58
9.9 TopoTarget A/S 59
9.9.1 Business Overview 59
9.9.2 Epigenetic Portfolio 59
9.10 S*BIO Pte Ltd 59
9.10.1 Business Overview 59
9.10.2 Epigenetic Portfolio 59
9.11 Curis, Inc. 60
9.11.1 Business Overview 60
9.11.2 Epigenetic Portfolio 60
10 Epigenetics R&D Pipeline – Strategic Consolidation 61
10.1 M&A Deals 62
10.1.1 Celgene Corporation Completes Acquisition of Gloucester Pharmaceuticals 62
10.1.2 Celgene Corporation Acquires the Rights to Vidaza through the Acquisition of Pharmion Corporation 62
10.1.3 Eisai Co., Ltd Completes Acquisition of MGI Pharma Inc. 62
10.1.4 4SC AG Successfully Completes Transaction of Nycomed Oncology Projects 62
10.1.5 Astex Pharmaceuticals Enters into an Asset Transfer Agreement with GlaxoSmithKline 62
10.2 Licensing Deals 63
10.2.1 Celleron Therapeutics Enters into Licensing Agreement with AstraZeneca Plc 63
10.2.2 Spectrum Pharmaceuticals Enters into Licensing Agreement with TopoTarget A/S 63
10.2.3 CellCentric Enters into Licensing Agreement with Takeda Pharma 63
10.2.4 Cellzome Announces Second Major Strategic Drug Discovery Alliance with GlaxoSmithKline in Inflammatory Diseases 64
10.2.5 4SC Enters into Licensing Agreement with Yakult Honsha for Japan for Resminostat 64
10.3 Co-development Deals 64
10.3.1 Pharmacyclics Enters into Collaboration with Les Laboratoires Servier 64
10.3.2 Curis Enters into Co-development Agreement with the Leukemia & Lymphoma Society 65
10.3.3 Constellation Pharma Enters into Epigenetics Drug Discovery Collaboration Agreement 65
10.3.4 Leukemia & Lymphoma Society Enters into an Agreement with EpiZyme Inc. 65
10.3.5 Aphios Enters into Research and Co-development Agreement with VivaCell Biotech 66
10.3.6 EpiZyme Enters into an Agreement with Eisai 66
10.3.7 EpiZyme Enters into Co-development Agreement with GlaxoSmithKline 66
10.3.8 EpiTherapeutics Enters into Co-development Agreement with Abbott Laboratories, Inc 66
10.4 Expectations of Epigenetics Research in the Future 67
11 Epigenetics R&D Pipeline – Appendix 68
11.1 Market Definitions 68
11.2 Abbreviations 68
11.3 Sources 70
11.4 Research Methodology 71
11.4.1 Coverage 71
11.4.2 Secondary Research 71
11.4.3 Primary Research 71
11.4.4 Therapeutic Landscape 72
11.4.5 Geographical Landscape 75
11.4.6 Pipeline Analysis 75
11.4.7 Competitive Landscape 75
11.5 Expert Panel Validation 75
11.6 Contact Us 75
11.7 Disclaimer 75

1.1 List of Tables
Table 1: Epigenetic R&D Pipeline, Marketed Drugs, 2011 20
Table 2: Epigenetic Product Pipeline, Discovery, 2012 31
Table 3: Epigenetic R&D Pipeline, Phase I, 2012 32
Table 4: Epigenetics R&D Pipeline, Phase I/II, 2012 37
Table 5: Epigenetic R&D Pipeline, Phase II 38
Table 6: Epigenetic R&D Pipeline, Phase III, 2012 41

1.2 List of Figures
Figure 1: Epigenetic R&D Pipeline, Epigenetic Mechanism 11
Figure 2: Epigenetic R&D Pipeline, Approved Drugs that Target Epigenetic Mechanism, 2012 12
Figure 3: Epigenetic R&D Pipeline, Pipeline by Therapy Area, (%), 2012 13
Figure 4: Epigenetic R&D Pipeline, Vidaza Snapshot, 2012 21
Figure 5: Epigenetic R&D Pipeline, Zolinza Snapshot,2012 23
Figure 6: Epigenetic R&D Pipeline, Istodax Snapshot, 2012 25
Figure 7: Epigenetic R&D Pipeline Dacogen Snapshot,2012 27
Figure 8: Epigenetics R&D Pipeline, Pipeline by Stage of Development, 2012 30
Figure 9: Epigenetic R&D Pipeline, Pipeline Analysis by Indication, 2012 42
Figure 10: Epigenetic R&D Pipeline, Epigenetics by Mechanism of Action, 2012 43
Figure 11: Epigenetic R&D Pipeline, Challenges in Dealing with Epigenetics, 2012 47
Figure 12: Epigenetic R&D Pipeline, Single Drug vs. Combinations in Development 52
Figure 13: Epigenetic R&D Pipeline, Leading Players by R&D Programs, 2012 53
Figure 14: GBI Research Market Forecasting Model 74