Table of Contents
EXECUTIVE SUMMARY
CHAPTER 1
INTRODUCTION
Scope and Organization of the Report
CHAPTER 2
OVERVIEW OF EPIGENETICS
2.1. Definition of Epigenetics
2.2. Mechanisms of Epigenetics
DNA Methylation
Histone Modification
Other Mechanisms
2.3. Methods to Detect Differences in DNA Methylation
2.4. Targets for Current and Emerging Epigenetic Drugs
CHAPTER 3
DIAGNOSTIC COMPANIES IN EPIGENETICS
3.1. Companies Developing Epigenetic-Based Diagnostic Tests
Epigenomics
OncoMethylome Sciences
Orion Genomics
Other Diagnostic Activities in Epigenetics (DNA Methylation)
Diagnostic Activities in Epigenetics (Histone Modification)
3.2. Clinical Laboratories Offering Tests to Detect DNA Methylation Changes
3.3. Epigenetics/DNA Methylation Test Agreements
CHAPTER 4
MAJOR DISEASES/CONDITIONS TARGETED BY NEW AND/OR EMERGING EPIGENETIC DRUGS
4.1. Hematological Cancers
4.2. Solid Tumors
4.3. Other Emerging Disease Indications
CHAPTER 5
EPIGENETIC DRUGS ON THE MARKET AND IN DEVELOPMENT
5.1. Drugs Targeting DNA Methylation (DNA Hypomethylation Drugs)
Celgene’s Vidaza
Eisai’s and Johnson & Johnson’s Dacogen
SuperGen
5.2. HDAC Inhibitors
Merck’s Zolinza (vorinostat)
Celgene’s Istodax (romidepsin)
4SC
Acetylon Pharmaceuticals
Celleron Therapeutics
Chroma Therapeutics
EnVivo Pharmaceuticals
Johnson & Johnson Pharmaceutical Research & Development
Karus Therapeutics
MethylGene
Novartis
Oncolys BioPharma
Pharmacyclics
Repligen
Syndax Pharmaceuticals
TopoTarget and Spectrum Pharmaceuticals
5.3. Emerging Therapies Directed Against Other Epigenetic Targets
CellCentric
Constellation Pharmaceuticals
Epizyme
SuperGen
CHAPTER 6
BUSINESS CONSIDERATIONS IN EPIGENETICS
6.1. Epigenetics Markets
Diagnostic Epigenetic Market
Therapeutic Epigenetic Market
6.2. Major Challenges/Hurdles and Strategic Issues for Diagnostic Companies in Epigenetics
Need for More Biomarkers, Validation Studies, and Outcome Studies
Delivery of New Diagnostic Tests: IVD versus CLIA Laboratory
Penetrating the Market: Diagnostic Platform(s)
Health Economics and Reimbursement
Intellectual Property Issues
Penetrating the Market: Physician Education
Does the Test Affect Physicians’ Decisions?
Acceptance by Experts; Incorporation into Guidelines
Physician Education
6.3. Major Challenges/Hurdles and Strategic Issues for Therapeutic Companies in Epigenetics
Safety Concerns with Epigenetic Drugs
Certain Market Segments Becoming Highly Competitive (HDAC Inhibitors)
Development Issues Common to Other Emerging Cancer Therapies
Development Issues Common to Other Companies Focusing on Novel Targets
Issues Facing Companies as They Launch Novel Epigenetic Therapies
6.4. Evaluating DNA Methylation Markers for Non-Epigenetic Cancer Therapies
6.5. Evolution of Companies in Epigenetics
Diagnostic Epigenetic Companies
Agreements in the Epigenetic Therapy Market; Companies Entering and Exiting the Market
CHAPTER 7
EXPERT INTERVIEWS
7.1. Walter C. Ogier, President and Chief Executive Officer, Acetylon Pharmaceuticals
7.2. Nessa Carey, PhD, Scientific Director, CellCentric
7.3. Alan Drummond, PhD, Chief Scientific Officer, Chroma Therapeutics
7.4. Mark A. Goldsmith, MD, PhD, President and Chief Executive Officer, Constellation Pharmaceuticals
7.5. Kees Been, President and Chief Executive Officer
Dana Hilt, MD, Senior Vice President, Clinical Development and Chief Medical Officer, EnVivo Pharmaceuticals
7.6. Oliver Schacht, PhD, CFO, Epigenomics AG, CEO, Epigenomics Inc.
7.7. Robert Gould, PhD, President and Chief Executive Officer, Epizyme
7.8. Jeffrey M. Besterman, PhD, Executive Vice President, Research & Development and Chief Scientific Officer, MethylGene
7.9. Harry Schrickx, WW Vice President Business Development, OncoMethylome Sciences SA, President, OncoMethylome Sciences, Inc.
7.10. Kamran Tahamtanzadeh, Founder & CEO, PrognosDx Health
7.11. James R. Rusche, PhD, Senior Vice President, Research and Development, Repligen
7.12. Joanna Horobin, MD, President & Chief Executive Officer, Syndax Pharmaceuticals
7.13. Henri Lichenstein, PhD, Chief Development Officer, TopoTarget A/S
REFERENCES
COMPANY INDEX WITH WEB ADDRESSES
List of FIGURES
Figure 1.1. Number of Abstracts Per Year from PubMed Search for “epigenetic OR epigenetics OR epigenomic OR epigenomics”
Figure 2.1. The Epigenetic Pathway
Figure 2.2. The Increasing Structural Complexity of Genetic Information from the Double-Helical Structure of DNA, through Nucleosome and Chromatin Structures, to the Chromosome
Figure 2.3. Schematic of the Nucleosome Showing Types of Post-Translational Modifications That Can Occur and the Enzymes Responsible for Them
Figure 2.4. Proposed Mechanism of Action of DNA Methylation Inhibitors in Cancer Therapy
List of TABLES
Table 2.1. Methods Available to Analyze DNA Methylation
Table 3.1. Companies Developing and/or Offering Epigenetic-Based Diagnostic Tests
Table 3.2. Clinical Laboratories Developing and/or Offering Epigenetic-Based Diagnostic Tests for Cancer
Table 3.3. Epigenetic Agreements
Table 4.1. Incidence of Hematological Cancers in the United States
Table 4.2. Incidence of Selected Cancers (Solid Tumors) in the United States (2009)
Table 5.1. Companies Marketing and Developing DNA Methylation Inhibitors
Table 5.2. Companies Marketing and Developing HDAC Inhibitors
Table 5.3. Companies Developing Novel Therapies Targeting Sirtuins
Table 5.4. Companies Developing Other Emerging Epigenetic Therapies
Table 6.1. Reported 2009 Sales of Approved Epigenetic Drugs
Table 6.2. Selected Epigenetic Therapeutic Agreements
Table 6.3. Selected Companies That Have Out-Licensed Epigenetic Drug Technology/Compounds and No Longer Appear to be Active in the Epigenetics Field