RNA Therapy: the next big thing after monoclonal antibodies?

Table of Contents

CHAPTER 1 EXECUTIVE SUMMARY

• Key findings
• Why RNA therapy?
• RNA therapy is not yet validated
• Longer-term sales driver
• High potential brings investment
• Can RNA therapy deliver on its promise?

CHAPTER 2 BACKGROUND TO RNA THERAPY

• Key findings
• Why the interest in RNA therapy?
  • RNA therapies hit the central dogma of biology
  • Gaining access to non-druggable targets
  • mRNA splicing yields further potential targets
  • Gene therapy also offers significant potential, but has fallen out of favour
• History/ discovery
  • Antisense silencing
  • Antisense technology has been available for over 30 years
  • Phenomenon of sense RNA also causing inhibition
  • Emergence of RNA interference
  • RNA interference discovered in 1998
  • Accelerated entry of RNAi-based products into the clinic

CHAPTER 3 RNA THERAPY & PIPELINE OVERVIEW

• Key findings
• RNA therapy triggers
  • Only one RNA therapy has reached the market to date
  • Mechanisms of gene silencing
  • RISC-independent silencing
  • RISC-mediated (RNAi) pathway offers greater potency
• Analysis of the RNA therapy pipeline by trigger
  • Late-stage pipeline largely consists of antisense oligonucleotides
  • Antisense RNA therapies are at a more advanced stage of development
  • Focus has shifted towards RISC-mediated silencing (RNAi) and siRNA
  • Next-generation structures maintain interest in antisense
  • Focus on antisense and siRNA, but variants are emerging
  • Pipeline is dominated by siRNA and antisense
  • Further silencing technologies are emerging
  • miRNA offers a wealth of additional targets

CHAPTER 4 DETAILED PRODUCT PIPELINE

• Key findings
• Pipeline by product
  • Late-stage pipeline
  • Vitravene (formivirsen): only marketed RNA therapy
  • Genasense (oblimersen): struggle to demonstrate efficacy
  • Mipomersen (ISIS 301012): setbacks, but strong profile
  • Alicaforsen: Phase III failure for Crohn' s disease
  • Bevasiranib: challenging Lucentis in the maintenance of AMD
  • Early-stage clinical pipeline
  • Pre-clinical pipeline
• Pipeline by company
• Discontinued products
• Forecast RNA therapy sales
  • Comparison to the uptake of monoclonal antibodies

CHAPTER 5 DELIVERY AND THERAPY AREA ANALYSIS.

• Key findings
• Therapy area analysis
  • Pipeline by therapy area
  • Novel technology requires high levels of unmet need
  • Therapeutic focus driven by delivery technology
  • Therapy area by trigger type
• Delivery remains key to success
  • Administration

CHAPTER 6 APPENDIX

• References
  • Journals
  • Websites
  • Datamonitor reports
• Abbreviations

List of Tables

• Table 1: RNA therapy pipeline, marketed to Phase III
• Table 2: RNA therapy pipeline, Phase II and Phase I
• Table 3: RNA therapy pipeline, pre-clinical
• Table 4: Discontinued RNA therapy products
• Table 5: Segmented RNA therapy sales to 2020, $m

List of Figures

• Figure 1: RNA therapy offers access to novel, disease-relevant targets
• Figure 2: RNA therapy pipeline by development stage
• Figure 3: Illustrative RNA therapy market to 2020, $m
• Figure 4: Market capitalization of leading RNA therapy companies
• Figure 5: Considerations for successful RNA therapy development
• Figure 6: The central dogma of biology and potential role of RNA therapy in relation to traditional ' drugging' approaches
• Figure 7: Technological advances expand the ' druggable' space
• Figure 8: Key milestones in RNA therapy
• Figure 9: RNA therapy pipeline by development stage
• Figure 10: RNA therapy pipeline by involvement of the RNA-induced silencing complex, RISC
• Figure 11: Classification of RISC-independent silencing triggers
• Figure 12: Cellular processes involved in gene silencing
• Figure 13: Classification of RISC-mediated (RNAi) gene silencing triggers
• Figure 14: RNA therapy pipeline by development stage, split by silencing trigger technologyFigure 15: RNA therapy pipeline by silencing trigger technology , split by development stage
• Figure 16: RNA therapy pipeline by development stage and company
• Figure 17: RNA therapy pipeline by company, split by development stage (largest weighted companies only)
• Figure 18: RNA therapy pipeline by company, split by trigger type (largest weighted companies only)
• Figure 19: Estimated RNA therapy market to 2020, $m
• Figure 20: Comparison of estimated RNA therapy sales versus initial growth of the monoclonal antibody market, $m
• Figure 21: RNA therapy pipeline by development stage and therapy area
• Figure 22: RNA therapy pipeline by therapy area, split by trigger type
• Figure 23: Challenges associated with RNA therapy delivery
• Figure 24: Administration routes used for RNA therapy