The Future of RNAi Therapeutics: Drug Pipelines and Prospects

Table of Contents

Executive Summary

• RNAi in Infectious Disease
• RNAi in Cancer
• RNAi in Inflammatory and Other Diseases
• RNAi Companies: Technologies and Therapies
• Market Trends and Opportunities

Chapter 1 Introduction

• Summary
• Introduction
• Antisense technology
  • Antisense oligonucleotides
  • Ribozymes and DNAzymes
• Discovery of natural RNAi activated by dsRNA
  • Mechanisms of RNAi stimulated by dsRNA
    • Approaches to activate RNAi in mammals
• Discovery of micro-RNAs
• The potential for RNAi-based therapeutics
  • The promise of siRNA therapeutics
  • The promise of miRNAs therapeutics
• Optimizing siRNA design
  • On- and off-target activity
  • Immune system reactivity
  • Improving siRNA stability
• Optimizing siRNA delivery
  • Naked siRNA
  • Liposomes and lipoplexes
  • Polymer carriers/nanoparticles
  • Conjugates
• Optimizing shRNA delivery

Chapter 2 RNAi in infectious diseases

• Summary
• Introduction
• Respiratory viral infections
  • RSV virus
    • Clinical and biological features
    • Design of RNAi therapeutics
    • RNAi therapeutics in development
  • Influenza virus
    • Clinical and biological features
    • Design of RNAi therapeutics
    • RNAi therapeutics in development
  • SARS
    • RNAi therapeutics in development
• Chronic viral infections
  • Hepatitis viruses
    • Clinical and biological features
    • Design of RNAi therapeutics
    • RNAi drugs in development
  • HIV virus
    • Clinical and biological features
    • Design of RNAi therapeutics
    • RNAi drugs in development
  • HPV
  • HSV
• Viral hemorrhagic fever and Ebola
• Malaria

Chapter 3 RNAi in Cancer

• Summary
• Introduction
• Cancer types
• Treatment of cancer
• Approaches to RNAi in cancer therapy
  • Approaches to RNAi delivery
• Targeting microRNAs
• RNAi cancer therapeutics in development
  • Agents directed at established targets
  • Agents directed at novel targets
  • Agents directed at multiple targets
  • Agents directed at unspecified targets
  • microRNAs
  • DNAi therapeutics

Chapter 4 RNAi in inflammatory and other diseases

• Summary
• Introduction
• Inflammation/immune dysfunction
  • Current therapies
  • Allergies and respiratory diseases
    • RNAi therapeutics in development
  • Age-related macular degeneration
    • RNAi therapeutics in development
  • Other inflammatory conditions
    • RNAi therapeutics in development
  • Acute Renal Failure
    • RNAi therapeutics in development
• CNS diseases
  • Huntington' s disease
    • RNAi therapeutics in development
  • Parkinson' s disease
    • RNAi therapeutics in development
  • Other CNS conditions
• Cardiology and metabolism
  • Cardiovascular disease
    • RNAi agents in development
  • Type 2 diabetes
    • RNAi agents in development
  • Non-alcoholic steatohepatitis
• Other indications

Chapter 5 RNAi Companies: Technologies and Therapies

• Summary
• Alnylam Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Ambrilia Biopharma Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Angioblast Systems Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• AVI BioPharma Inc
  • Company description
  • Exon Skipping Pre-RNA Interference Technology (ESPRIT)
  • RNA splicing-related agreements
• Benitec Ltd
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• BioCancell Therapeutics Inc
  • Company description
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Calando Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Cequent Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Dicerna Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Generex Biotechnology Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Genesis Research and Development Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Green Cross Corp
  • Company description
  • Candidate RNAi therapeutics
• Gruenenthal Group
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Intradigm Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Isis Pharmaceuticals Inc
  • Company description
  • RNAi-related agreements
• Lorus Therapeutics Inc
  • Company description
  • Candidate RNAi therapeutics
• MDRNA Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Merck & Co Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Nucleonics Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Opko Health Inc
  • Company description
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• ProNAi Therapeutics Inc
  • Company description
  • RNAi-related technology
  • Candidate DNAi therapeutics
  • DNAi-related agreements
• Quark Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Regulus Therapeutics LLC
  • Company description
  • miRNA-related technology
  • Candidate miRNA therapeutics
  • RNAi-related agreements
• Rosetta Genomics Ltd
  • Company description
  • miRNA-related technology
  • Candidate miRNA therapeutics
  • miRNA-related agreements
• RXi Pharmaceuticals Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Santaris Pharma A/S
  • Company description
  • RNAi-related technology
  • Candidate miRNA therapeutics
  • RNAi-related agreements
• Senesco Technologies Inc
  • Company description
  • Candidate RNAi therapeutics
• Senetek plc
  • Company description
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Silence Therapeutics plc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Sirnaomics Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• siRNAsense AS
  • Company description
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Stelic Institute & Co
  • Company description
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Targeted Genetics Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• Tekmira Pharmaceuticals Corp
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
  • RNAi-related agreements
• ToleroTech Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• Topigen Pharmaceuticals Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics
• TransDerm Inc
  • Company description
  • RNAi-related technology
  • Candidate RNAi therapeutics

Chapter 6 Market trends and opportunities

• Summary
• Validating RNAi in the clinic
• From first-in-class to best-in-class
• Exploring alternatives to siRNAs
• Overcoming delivery challenges
• Moving beyond "druggable" targets
• Intellectual property considerations
  • Introduction to RNAi patents
  • Fire and Mello Patent
  • Tuschl Patents
  • Kreutzer-Limmer Patents
  • Benitec patents
  • Crooke / RNAi modification patents
  • Glover patent
  • RNAi target patents
  • miRNA patents
  • Effect of patents on infringing R&D
• Patent survey results
• Market value considerations
  • Commercial prospects
  • Summary of key indications
  • Forecasts
    • Wet AMD: bevasiranib and others
    • RSV infection: ALN-RSV01
    • Acute renal failure: AKTi-5
    • The RNAi bottom line
• Company details
  • Alnylam Pharmaceuticals Inc
  • Ambrilia Biopharma Inc
  • Angioblast Systems Inc
  • AVI BioPharma Inc
  • Benitec Ltd
  • BioCancell Therapeutics Inc
  • Calando Pharmaceuticals Inc
  • Cequent Pharmaceuticals Inc
  • Dicerna Pharmaceuticals Inc
  • Generex Biotechnology Corp
  • Genesis Research and Development Corp
  • Green Cross Corp
  • Gruenenthal Group
  • Intradigm Corp
  • Isis Pharmaceuticals Inc
  • Lorus Therapeutics Inc
  • MDRNA Inc
  • Merck & Co Inc
  • Nucleonics Inc
  • Opko Health Inc
  • ProNAi Therapeutics Inc
  • Quark Pharmaceuticals Inc
  • Regulus Therapeutics LLC
  • Rosetta Genomics Ltd
  • RXi Pharmaceuticals Corp
  • Santaris Pharma A/S
  • Senesco Technologies Inc
  • Senetek plc
  • Silence Therapeutics plc
  • Sirnaomics Inc
  • siRNAsense AS
  • Stelic Institute & Co
  • Targeted Genetics Corp
  • Tekmira Pharmaceuticals Corp
  • ToleroTech Inc
  • Topigen Pharmaceuticals Inc
  • TransDerm Inc
• Glossary
  • Abbreviations and acronyms

List of Figures

• Figure 6.1: RNAi by development stage
• Figure 6.2: RNAi by origin of material
• Figure 6.3: RNAi USPTO patents: therapy area
• Figure 6.4: RNAi WIPO patents: therapy area
• Figure 6.5: RNAi USPTO Patents: patent focus
• Figure 6.6: RNAi WIPO patents: patent focus

List of Tables

• Table 1.1: RNAi Oligonucleotide Indications - Infectious Disease
• Table 1.2: RNAi Oligonucleotide Indications - Cancer
• Table 1.3: RNAi Oligonucleotide Indications - Cancer (continued)
• Table 1.4: RNAi Oligonucleotide Indications - Cancer (continued)
• Table 1.5: RNAi Oligonucleotide Indications - Miscellaneous Disorders
• Table 1.6: RNAi Oligonucleotide Indications - CNS
• Table 1.7: RNAi Oligonucleotide Indications - Inflammation/Immune Disorders
• Table 1.8: RNAi Oligonucleotide Indications - Inflammation/Immune Disorders (continued)
• Table 1.9: RNAi Oligonucleotide Indications - Cardiology, Metabolism
• Table 5.10: Financial Details, year ending Dec 2007, (US$m): Alnylam Pharmaceuticals Inc
• Table 5.11: Financial Details, year ending 2007, (Can$m): Ambrilia Biopharma Inc
• Table 5.12: Financial Details, year ending Dec 2007, (US$m): AVI BioPharma Inc
• Table 5.13: Financial Details, year ending Jun 2007, (Aus$m): Benitec Ltd
• Table 5.14: Financial Details, year ending Dec 2006, (NISm): BioCancell Therapeutics Inc
• Table 5.15: Financial Details, year ending July 2007, (US$m): Generex Biotechnology Corp
• Table 5.16: Financial Details, year ending Dec 2007, (NZ$m): Genesis Research and Development Corp
• Table 5.17: Financial Details, year ending Dec 2006, (Wm): Green Cross Corp
• Table 5.18: Financial Details, year ending Dec 2007, (US$m): Isis Pharmaceuticals Inc
• Table 5.19: Financial Details, year ending May 2007, (Can$m): Lorus Therapeutics Inc
• Table 5.20: Financial Details, year ending Dec 2007, (US$m): MDRNA Inc
• Table 5.21: Financial Details, year ending Dec 2007, (US$m): Merck & Co Inc
• Table 5.22: Financial Details, year ending Dec 2007, (US$m): Opko Health Inc
• Table 5.23: Financial details, year ending Dec 2007, (US$m): Rosetta Genomics Ltd
• Table 5.24: Financial details, year ending Dec 2007, (US$m):RXi Pharmaceuticals Corp
• Table 5.25: Financial details, year ending Jun 2007, (US$m): Senesco Technologies Inc
• Table 5.26: Financial details, year ending Dec 2007, (US$m): Senetek plc
• Table 5.27: Financial details, year ending Dec 2007, (£m): Silence Therapeutics plc
• Table 5.28: Financial details, year ending Dec 2007, (US$m): Targeted Genetics Corp
• Table 5.29: Financial details, year ending Dec 2007, (Can$m): Tekmira Pharmaceuticals Corp
• Table 6.30: Common RNAi/Antisense Targets
• Table 6.31: Common RNAi/Antisense Targets (Contd.)
• Table 6.32: Targets of Antisense Oligonucleotides but not RNAis
• Table 6.33: WIPO RNAi Patents: Filing and Publication Dates
• Table 6.34: USPTO RNAi Patents: Filing and Publication Dates
• Table 6.35: WIPO RNAi Patents: Top Assignees
• Table 6.36: WIPO RNAi Patents: Top Assignees (Contd.)
• Table 6.37: WIPO RNAi Patents: Top Assignees (Contd.)
• Table 6.38: USPTO RNAi Patents: Top Assignees
• Table 6.39: Leading RNAi Oligonucleotide Originators
• Table 6.40: Key data: Forecasts for wet AMD, RSV therapy and acute renal failure ($m), 2012