The study of epigenetics - changes in gene expression that occur without a change in a cell's DNA code - is becoming increasingly important as scientists explore how internal and external factors trigger cellular dysfunction and influence disease progression. Three main mechanisms - DNA methylation, histone modifications and changes in non-coding RNA - have been elucidated in epigenetics. Each in its own way may provide the industry with a greater understanding into the underlying mechanism of diseases, act as a potential source for biomarkers of disease and provide new targets for therapeutic intervention.

Besides everyday DNA analytical tools, epigenetic researchers have needed to adopt more complex technologies such as chromatin immunoprecipitation (ChIP) and DNA methylation methodologies as well as develop analytical tools to decipher the vast amount of epigenetic information. Advances in these technologies should enable epigenetic research to reduce cost and increase sample throughput making it more commercially attractive in the industry to discover biomarkers and validate novel epigenetic targets for diagnostic and pharmacological development.

Epigenetic medicine has arrived. The market is worth over $560 million derived from the sale of three anticancer products which target two epigenetic pathways - DNA methyltransferase (DNMT) and histone deacteylase (HDAC) - and around thirty epigenetic drugs are under development from more than a dozen biotechnology companies. These drugs focus mainly on the treatment of cancer, neurodegenerative and infectious diseases although research is underway to explore the role for epigenetics in cardiovascular, metabolic, ocular and other diseases. Whilst this market is still in its infancy KOLs believe it is on the cusp of a revolution, one which could change how patients are diagnosed and treated in the future.

Key features of this report:

Identify leading companies at the forefront of epigenetic research who will drive the market to develop a new generation of epigenetic therapies and diagnostics.
Provide case studies of these leading companies developing epigenetic therapies to treat cancer, neurodegenerative and infectious diseases.
Analyze the key trends and issues confronting the development of epigenetic therapies.
Review the alliances, mergers, acquisitions and business strategies adopted by biotechs and big pharma to capitalize on the latest epigenetic developments.

Scope of this report:

Identify the companies leading the field in epigenetic research across a range of therapeutic areas
Review their business strategies and the development of their epigenetic programs
Learn more about the latest developments in epigenetic research and how non-coding RNAs may open up another Pandora's box for epigenetic research.
Identify innovative pharmaceutical companies and discover the strategies they are adopting to tap into the epigenetic potential both as biomarkers of disease and targets for therapeutic intervention

Key Market Issues:

Declining industry productivity: It is a well documented fact that productivity in the pharma industry has declined during the past 15 years. The identification of new biomarkers of disease could aide the R&D process and support the preclinical and clinical development of small molecule therapeutics.
Innovative new drug classes: The identification of underlying mechanisms of diseases could identify new target
for small molecule therapeutic intervention that may be used alone or in combination with traditional therapies to
extend their usage.:

Key findings from this report:

New epigenetic therapies have entered the market. The first medicines were approved in 2006 for the treatment of cancer and a host of new small molecule therapies are now under development which are more selective and target different classes of chromatin modifying enzymes enabling a more targeted approach to treatment.
The ability of innovative companies to generate intellectual property is a key driver for the sector as the market become more competitive in this new area of science. The unraveling of the human epigenome will be the first step in identifying new epigenetic markers which may have potential as biomarkers an area of considerable interest for the pharmaceutical industry at the present time.

Key questions answered:

Which companies are the market leaders in the epigenetics industry, identified through therapeutic areas (cancer, infectious diseases, neurodegenerative diseases, metabolic, cardiovascular, ophthalmic, other diseases) and recent alliances with the pharmaceutical companies?
What are the key products of these companies and how do they exemplify the future direction of the epigenetic therapies?
How is the pharmaceutical industry approaching the need for new targeted epigenetic therapies and what strategies are they taking?

Table of contents
- Innovations in Epigenetics
- Executive summary
- Introduction
- Application in R&D & technological advances
- Exploring new therapeutic targets
- Epigenetic market, leading companies & pharmaceutical strategies
- The future of epigenetics
Chapter 1 Introduction
- What is epigenetics?
- Epigenetics and phenotypes
- Epigenetics a new biological paradigm
- Epigenetics, genetics, genomics & pharmacogenomics
- Molecular mechanisms associated with epigenetics
- DNA methylation
- Histone modifications
- Nucleosome remodelling
- Non-coding RNA
- X chromosome inactivation
- Gene imprinting
- RNA interference
- Epigenetic basis of disease
- Epigenetic syndromes
- Angelmann syndrome
- Beckwith-Wiedemann syndrome
- Prader-Willi syndrome
- Why is epigenetics of interest to the pharmaceutical industry?
- Biomarker discovery & diagnostics
- Novel small molecule epigenetic therapeutics
- Novel antisense therapeutics
- Stem cells & regenerative medicines
- Conclusions
Chapter 2 Application in R&D & technological advances
- The application of epigenetics in drug R&D
- DNA methylation biomarkers
- Histone modification biomarkers
- Technological advances in epigenetics
- Chromatin immunoprecipitation
- DNA methylation technologies
- Non-coding RNA technologies
- Bioinformatic modeling
- Conclusions
Chapter 3 Exploring new therapeutic targets
- Potential new therapeutic targets
- Epigenetics in cancer
- DNA methyltransferase & DNMT inhibitors
- Case study: Vidaza (Celgene Corporation) & Dacogen (Eisai /J&J)
- Case study: Zebularine a research tool
- Histone acetylase (HAT) and histone deacetylase (HDAC)
- Case study: Zolinza (Merck & Co.)
- Case study: MGCD0103 (MethylGene/Taiho Pharmaceutical)
- Case study: PCI-24781 (Pharmacyclics/Servier)
- Histone demethylases and histone methyltranserases
- Case study: PG11144 & PG11047 (Progen Pharmaceuticals)
- Potential epigenetic based diagnostics
- Diagnostic DNA methylation cancer biomarkers
- Case study: Epi proColon (Epigenomics AG)
- The next generation of epigenetic cancer biomarkers
- Epigenetics in neurological disorders
- Case study: EVP-0334 (EnVivo Pharmaceuticals)
- Epigenetics in infectious diseases
- Case study: MGCD290 (MethylGene)
- Case study: siRNA targeting HIV-1 (Kevin Morris, Scripps, La Jolla)
- Epigenetics in metabolic disorders
- Epigenetics in cardiovascular disease
- Epigenetics in ocular disorders
- Case study: Kinase inhibitors (Otsuka Pharmaceutical/MethylGene)
- Case study: Kinase inhibitors/S-adenosyl methionine (SAM) (Epizyme)
- Conclusions
Chapter 4 Epigenetic market, leading companies & pharmaceutical strategies
- Epigenetic market
- Epigenetic therapeutic revenues: Now and the future
- Leading epigenetic companies
- 4SC AG, Planegg-Martinsried, Germany
- Celgene Corporation, Summit, New Jersey
- Curis Inc, Cambridge, MA
- Chroma Therapeutics Ltd, Oxon, UK
- Constellation Pharmaceuticals, Cambridge, MA
- EnVivo Pharmaceuticals, Watertown, MA
- EpiTherapeutics Aps, Copenhagen, Denmark
- Epizyme, Cambridge, MA
- Gloucester Pharmaceuticals, Cambridge, MA
- MethylGene, Inc. Montreal, Qué bec
- Pharmacyclics, Sunnyvale, CA
- Progen Pharmaceuticals, Brisbane, Australia
- Repligen Corporation, Waltham, MA
- SuperGen, Dublin, CA
- Syndax Pharmaceuticals, Waltham, MA
- TopoTarget, Copenhagen, Denmark
- Summary of epigenetic-based companies
- Recent alliances, mergers & acquisitions in epigenetics
- Pharmaceutical strategies in epigenetics
- GlaxoSmithKline, Middlesex, UK
- Novartis, Basel, Switzerland
- Merck & Co., Whitehouse, NJ
- Eisai Corporation of North America, NJ
- Takeda, Osaka, Japan
- Overall conclusions
Chapter 5 The future of epigenetics
- The future of epigenetics
- Epigenetic consortia; unraveling the human epigenome
- NIH's Roadmap Epigenomics Program initiative
- European Epigenome Network of Excellence
- Human Epigenome Consortium
- KOLs in epigenetics
- John Mattick, Institute for Molecular Bioscience, University of Queensland,
- Australia
- Overview
- Technology
- Applications
- Future
- Kevin Morris, Scripps Institue, La Jolla, CA
- Overview
- Technology
- Applications
- Future
- Monika Lachner, Max-Planck Institute of Immunobiology, Department of
- Epigenetics, Freiburg, Germany
- Overview
- Technology
- Applications
- Future
- Johnathan Whetstine, Department of Medicine, Massachusetts General
- Hospital Cancer Center
- Overview
- Technology
- Applications
- Future
- Peter Fraser, Head, Senior Fellow of the Medical Research Council, UK, The
- Babraham Institute, Cambridge
- Overview
- Technology
- Applications
- Future
- Summary of KOLs commentary
- Challenges
- Fundamental research
- Technological demands
- Financial constraints
- Intellectual property
- Opportunities
- Biomarker discovery & diagnostics
- Therapeutic intervention
- Regenerative medicines
- Conclusions
Chapter 6 Appendices
- Glossary
- Acknowledgements
- Index
- Index
- Bibliography
- Endnotes
List of Figures
- Figure 1.1: Timeline of epigenetics study
- Figure 1.2: Schematic of chromatin structure
- Figure 1.3: Schematic of epigenetic mechanisms associated with health and disease
- Figure 1.4: Epigenetic applications by the pharma industry
- Figure 2.5: Epigenetics in the drug discovery & development process
- Figure 2.6: Schematic of key technologies used in epigenetics
- Figure 2.7: Schematic of ChIP technology
- Figure 2.8: Epigenomics AG methylation specific PCR (MSP) methods
- Figure 3.9: DNA methylation targets for epigenetic cancer therapies
- Figure 3.10: Mechanism of action of HAT and HDAC
- Figure 3.11: Epi proColon high throughput colorectal epigenetic test
- Figure 3.12: Competitive pricing of Epi proColon
- Figure 3.13: EnVivo's HDAC project screening cascade
- Figure 3.14: Agouti mice and epigenetic manipulation
- Figure 3.15: Epizyme's rational design of small molecule HMT inhibitors
- Figure 4.16: Epigenetic therapies: product class and developmental phase
- Figure 4.17: Epigenetic therapies: therapy target and developmental phase
- Figure 4.18: CUDU-101 structure & design: combining multiple pharmacophores
List of Tables
- Table 2.1: DNA methylation PCR methods
- Table 2.2: Techniques to analyze DNA methylation
- Table 3.3: Examples of DNMT inhibitors: potential anticancer agents targeting epigenetic pathways
- Table 3.4: Examples of DNMT inhibitor research tools
- Table 3.5: HDAC inhibitors: potential anticancer agents targeting epigenetic pathways
- Table 3.6: Examples of HDAC inhibitor research tools
- Table 3.7: Histone modification and their effect on gene expression
- Table 3.8: Safety profiles of PCI-24781 rivals
- Table 3.9: DNA methylation sites associated with cancers
- Table 3.10: Validated and hypothetic miRNA targets for diabetes & obesity
- Table 4.11: Epigenetic therapeutic revenues ($m), 2009-2020
- Table 4.12: Preliminary clinical data for Pharmacyclics PCI-24781
- Table 4.13: Recent alliances, acquisitions and mergers in the epigenetic arena
- Table 5.14: NIH Epigenetic Roadmap - funded epigenetic projects

Pharmaceutical Market Research

Innovations In Epigenetics