Delivering RNAi-Based Therapeutics & Diagnostics: Challenges & Opportunities

Published by: PharmaVision

Published: Jul. 1, 2009 - 225 Pages

Table of Contents

Chapter 1 RNA Interference & Delivery

Key Findings

Introduction

RNAi a Natural Phenomenon

Antisense technologies

RNAi silencing agents

RNA silencing pathways

microRNAs and antagomirs

miRNA gene silencing

Pros & Cons of RNAi Silencing Agents

RNAi R&D

High throughput in vitro screening

RNAi in vivo screening

RNAi diagnostic makers

RNAi Therapeutics

RNAi Diagnostics

RNAi Therapy - A Discovery Timeline

Major Scientific Challenges for the Development of RNAi-Based

Diagnostics & Therapies

Report Structure

Chapter 2 RNAi-Based Therapeutics: Pipeline Analysis

Key Points

Key Therapy Areas Covered by RNAi-Based Therapies

Product pipelines

RNAi for Diagnostics

RNAi Companies Analyzed in This Report

Chapter 3 RNAi-Based Therapies for Cancer

Key Findings

Introduction

RNAi delivery in cancer

RNAi-Based Therapies -siRNA

Case study: ALN-VSP (Alnylam Pharmaceuticals)

Case study: CALAA-01 (Calando Pharmaceuticals)

Case study: Dicer substrate RNA (Dicerna Pharmaceuticals)

Case study: Intratumoral siRNA (Genesis Research & Development

Corporation)

Case study: NPX delivery technology (Intradigm Corporation)

Case study: SNS-01 (Senesco Technologies)

Case study: Atu027 (Silence Therapeutics)

Case study: STP702 (Sirnaomics)

Case study: PLK SNALP (Tekmira Pharmaceutical Corporation)

RNAi-Based Therapies -shRNA

Case study: CEQ501 (Cequent Pharmaceuticals)

Alternative RNA Approaches to Develop Cancer Therapies

miRNA in Cancer

Case study: miRNAs (Mirna Therapeutics)

Case study: miRNAs (Regulus Therapeutics)

Case study: SPC2996 & EZN3042 (Santaris Pharma A/S/Enzon

Pharmaceuticals)

MiRNA-Based Diagnostics

mRNA Antagonists

Case study: LOR-2040 (Lorus Therapeutics)

Antisense

Case study: OGX-011 (Isis Pharmaceuticals/OncoGenex) &

LY2181308 (Isis Pharmaceuticals/Eli Lilly)

Case study: TF siRNA (siRNAsense A/S/Polyplus Transfection)

Conclusions

Our Opinion on RNAi-Based Therapies & Diagnostics for Cancer

Where the technology is now, its evolution, achievements and pitfalls

Competition

Potential future applications

Activity in the market, major players and winners

Chapter 4 RNAi-Based Therapies for CNS Disorders

Key Findings

Introduction

Neurodegenerative Diseases

Amyotrophic lateral sclerosis

Case study: SOD1 siRNA (RXi Therapeutics)

Case study: SOD1 shRNA (Oxford BioMedica)

Huntington’s Disease

Case study: ALN-HTT (Alnylam Pharmaceuticals/Medtronic)

Case study: AVV-HTT (Targeted Genetics Corporation)

Parkinson’s Disease

Case study: SNCA-siRNA (Alnylam Pharmaceuticals)

Case study: biotinylated siRNA (ArmaGen Technologies)

Other CNS conditions

Conclusions

Our Opinion on RNAi-Based Therapies for CNS disorders

Where the technology is now, its evolution, achievements and pitfalls

Competition

Potential future applications

Activity in the market, major players and winners

Chapter 5 RNAi-Based Therapies for Viral Infectious Diseases

Key Findings

Introduction

Respiratory Syncytial Virus

Case study: ALN-RSV01 (Alnylam Pharmaceuticals)

Hepatitis C

Case study:TT-033 (Oncolys BioPharma/Pfizer/Tacere Therapeutics)

Case study: miR-122 (Regulus Therapeutics)

Case study: SPC3649 (Santaris Pharma A/S)

Human Immunodeficiency Virus

Case study: rHIV7-shl-TAR-CCR5RZ (Benitec Ltd/City of Hope)

Pandemic Influenza

Bioterrorism

Other Infectious Diseases

Conclusions

Our Opinion on RNAi-Based Therapies for Viral Infectious Diseases

Where the technology is now, its evolution, achievements and pitfalls

Competition

Potential future applications

Activity in the market

Chapter 6 RNAi-Based Therapies for Ocular Diseases

Key Findings

Introduction

Age-Related Macular Degeneration

Case study: AGN-745 (Allergan/Sirna Therapeutics)

Case study: VEGF-A165b sparing siRNA & Bevasiranib (Opko Health)

Case study: PF-4523655 (Quark Pharmaceuticals/Pfizer)

Diabetic Retinopathy & Diabetic Macular Edema

Glaucoma

Conclusions

Our Opinion on RNAi-Based Therapies for Ocular Diseases

Where the technology is now, its evolution, achievements and pitfalls

Competition

Potential future applications

Activity in the market

Chapter 7 RNAi-Based Therapies for Cardiovascular, Metabolic & Other Conditions

Key Points

Introduction

RNAi-Based Therapeutics for Cardiovascular Diseases

Case study: miR-21 (Regulus Therapeutics)

Case Study: MHC miRNA inhibitors (MiRagen Therapeutics Inc)

RNAi-Based Therapeutics for Metabolic Disorders

Case Study: ApoB SNALP (Tekmira Pharmaceutical Corporation)

Case study: MDR-04227 (MDRNA)

Case Study: PCSK9 siRNA (Alnylam Pharmaceuticals)

Case study: ApoB rxRNA and GeRP delivery (RXi Therapeutics)

RNAi-Based Therapeutics in Other Therapeutic Areas

Case study: ALN-TTR siRNA (Alnylam Pharmaceuticals)

Case study: HSP47 siRNA (Nitto Denko Technical Corporation)

Case study: QPI-1002 (Silence Therapeutics/Quark Pharmaceuticals)

Conclusion

Our Opinion on RNAi-Based Therapies for Cardiovascular, Metabolic

& Other Diseases

Where the technology is now, its evolution, achievements and pitfalls

Competition

Potential future applications

Activity in the market, major players and winners

Chapter 8 Challenges & Opportunities for RNAi-Based Therapeutics & Diagnostics

Key Points

Introduction

Stability & Efficacy Issues for RNAi Research

Stability

Efficacy

Safety Issues for RNAi Research

Intellectual Property

Delivering RNAi-Based Therapies

Challenges

Opportunities

Chapter 9 The Future of RNAi-Based Therapeutics & Diagnostics: Market Trends

Key Points

Key RNAi Companies

Leading RNAi-Based Therapeutic Companies

Leading miRNA-Based Therapeutic Companies

Leading RNAi-Based Diagnostic Companies

Recent Deals & Alliances

The Global RNAi-Based Therapy Market 2008-2014

Analysis parameters

Market forecast 2008-2014

Global RNAi-Based Therapy Market in 2020

Drivers and market trends

Summary & Conclusions

Acknowledgements

Bibliography & Endnotes

List of Figures

Figure 1: siRNA - RISC mediated gene silencing

Figure 2: miRNA - RISC mediated gene silencing

Figure 3: High throughput RNAi screening for functional genomics and target validation

Figure 4: Rapid lead generation

Figure 5: ArteMice© RNAi model

Figure 6: RNAi therapeutics applications

Figure 7: Stages of pharmaceutical development

Figure 8: RNAi research: a timeline

Figure 9: RNAi-based therapeutics: defining therapeutic areas

Figure 10: Number of projects in the different stages of pharmaceutical development

Figure 11: Number of projects in each therapeutic area

Figure 12: Proportions of naked and targeted/vehicle assisted RNAi species

Figure 13: Delivery routes for RNAi therapeutics

Figure 14: Current approaches for cancer treatment

Figure 15: Potential RNAi approaches for cancer treatment

Figure 16: RONDEL delivery platform

Figure 17: In vivo efficacy studies with CALAA-01

Figure 18: Dicer substrate processing

Figure 19: Intratumoral siRNA delivery mediated with A) liposome and B) nanoparticles

Figure 20: RNAi NPX delivery platform

Figure 21: SNS-01 in mouse lung model

Figure 22: AtuPlex proprietary delivery system

Figure 23: SNALP delivery technology

Figure 24: Cequent’s tkRNAi delivery system

Figure 25: LNA monomer structure

Figure 26: Polyplus transfection In-vivo-jetPEI system -RNAi delivery to the lung

Figure 27: Photochemical Internalization enhances siRNA’s gene silencing effect

Figure 28: RNAi applications in CNS disorders

Figure 29: Medtronic’s SynchroMed II implantable infusion pump

Figure 30: Alzet osmotic pump for brain infusion

Figure 31: Diffusion profile of pressure and diffusion delivery

Figure 32: Molecular schematic of ArmaGen’s molecular Trojan horse

Figure 33: RNAi viral infectious disease targets

Figure 34: PARI Pharma’s eFlow nebuliser

Figure 35: Tacere’s shRNA construct to target HCV

Figure 36: Benitec’s RNAi approach to HIV

Figure 37: Proof of concept Ebola siRNAs

Figure 38: RNAi ocular disease targets

Figure 39: RNAi applications in CV, metabolic & other disorders

Figure 40: miR-21 mechanism of action in myocardial infarction

Figure 41: ApoB SNALP preclinical data in mouse model

Figure 42: ApoB nanotransporter in mouse model

Figure 43: GeRP mechanism of delivery

Figure 44: NDT’s siRNA delivery platform

Figure 45: Mechanism of action of siRNA HSP47 in liver cirrhosis

Figure 46: Challenges and opportunities for RNAi research

Figure 47: Safety issues

Figure 48: RNAi-based therapeutics: market drivers

List of Tables

Table 1: Antisense drugs in clinical development

Table 2: Pros and cons of RNAi silencing agents

Table 3: Leading RNAi diagnostic companies

Table 4: Novel non-coding RNA

Table 5: Diseases targeted by RNAi-based therapeutics

Table 6: RNAi and RNA therapeutic & diagnostic companies discussed in this report

Table 7: Leading companies evaluating RNAi therapies for cancer

Table 8: Academic institutions with an interest in RNAi based cancer research

Table 9: Potentially pro-oncogenic and tumor suppressor miRNAs

Table 10: Identification of key tumor suppressor miRNAs

Table 11: Leading companies evaluating RNAi-based therapies for CNS disorders

Table 12: Academic institutions with an interest in RNAi for the treatment CNS disorders

Table 13: Leading companies evaluating RNAi-based therapies for viral infectious diseases

Table 14: Academic institutions with an interest in RNAi for the treatment of viral infectious diseases

Table 15: Leading companies evaluating RNAi-based therapies for ocular diseasess

Table 16: Academic institutions with an interest in RNAi for the treatment of ocular diseases

Table 17: Leading companies evaluating RNAi-based therapies for cardiovascular disease

Table 18: Academic institutions with an interest in RNAi for the treatment of cardiovascular disease, metabolic & other conditions

Table 19: Leading companies evaluating RNAi-based therapies for metabolic disorders

Table 20: Academic institutions with an interest in RNAi for the treatment of metabolic disorders

Table 21: Leading companies evaluating RNAi-based therapies for other conditions

Table 22: A seminal RNAi patents

Table 23: Summary of leading RNAi-based therapeutic companies

Table 24: Recent RNAi acquisitions & licensing deals

Table 25: Recent RNAi alliances

Table 26: RNAi-based therapies included in the market forecast

Table 27: Forecast of pipeline RNAi therapy products 2008-2014 (US$m)

Table 28: Forecast of pipeline RNAi therapy products 2015-2020 (US$m)

Abstract

• assess the commercial potential of RNAi-based therapies in all of the key therapeutic areas: cancer, CNS disorders, viral infectious diseases, ocular diseases, cardiovascular, metabolic and other conditions;
• identify key pharma & delivery specialists advancing RNAi-based therapeutics & diagnostics;
• gain an in-depth understanding of the technological & delivery issues which face companies developing RNAi-based therapies;
• evaluate the options available for chemically and structurally modifying RNAi silencing agents and delivering them to target tissues now & in the future;
• discover which companies are tackling efficacy and safety issues & are in a prime position to exploit new opportunities;
• analyze how the market will evolve over the next decade highlighting key trends, opportunities & challenges.

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