Ubiquitin Enzymes: Key Targets and Future Market Potential, 2016-2030

Ubiquitin Enzymes: Key Targets and Future Market Potential, 2016-2030

The ubiquitin proteasome system (UPS) is one of the key protein degradation pathway involved in the control of protein homeostasis and turnover that mediates the regulation of several cellular processes. The UPS consists of two separate consecutive steps, ubiquitination and proteasomal degradation. Due to its involvement in multiple metabolic and regulatory functions, the UPS is considered as a vital part of the cellular machinery controlling protein homeostasis. Targeting specific components of the UPS in order to regulate cellular growth and metabolism in diseases is not a novel concept; however, advances in molecular signalling have revealed a number of potential enzyme targets within the UPS that, if successfully modulated, can lead to the development of highly specific drugs against a number of pathological and degenerative disease indications.

Many scientists and research groups are trying to unravel the hidden potential of this highly complex regulatory system in order to develop viable drug candidates. According to PubMed, there are close to 1500 publications related to ubiquitin enzymes from 2015 till date. A number of technical advances in this domain have led to the development of multiple technology platforms, research based assays, toolkits, probes, reagents and precursor compounds to support the different drug discovery programs of various academic and industry researchers. In fact, the current market landscape features contributions of not only big pharma companies but also small to mid-sized players and academic institutions.

A number of strategic partnerships have also been inked between various stakeholders to advance R&D activities in this domain. Results of preclinical and clinical studies have demonstrated the potential benefits of this class of therapies; the major highlight being their attractive safety profile. The burgeoning field of research has captured the interest of several venture capital firms and strategic investors. The upcoming market, primarily focused on oncological indications, is expected to prosper in the long term and witness the emergence of several successful drugs.

SCOPE OF THE REPORT
The “Ubiquitin Enzymes: Key Targets and Future Market Potential, 2016-2030” report provides an extensive study on the current landscape of the evolving pipeline of ubiquitin enzyme inhibitors and offers a comprehensive discussion on the future potential of this market. Ubiquitin enzymes have been implicated in various cellular processes, such as protein homeostasis, apoptosis, autophagy, DNA damage repair, cell cycle control and senescence. Due to their involvement in multiple metabolic and regulatory functions, any deviations in the normal functioning of the UPS has been shown to lead to the development of diverse types of diseases.

Initial research on the UPS led to the development of several proteasome inhibitors, such as Velcade®, Kyprolis® and Ninlaro®, which are already available in different regions across the globe. However, since these drugs target the entire protein degradation pathway, lack of target specificity renders them potentially harmful and their use has been shown to pose side effects in patients. Consequently, the focus is gradually shifting from proteasome inhibitors to targeting specific components of the UPS, primarily on ubiquitination enzymes. This is a relatively new segment of the overall market. With no marketed products, the UPS associated enzyme inhibitors / modulators market is still in its infancy. The report primarily focuses on four classes of enzymes that have been shown to possess therapeutic relevance; these include E1 activating enzymes, E2 conjugating enzymes, E3 ligases and deubiquitinases (DUBs).

Currently, the ubiquitin pathway based inhibitors pipeline comprises of over 45 molecules that are under development for the treatment of a variety of indications. In addition, there are several companies that are engaged in the development of screening and validation assays for lead selection, research tools and competent technologies in this field. This unexploited and promising market has its hopes pinned on multiple start-ups, which have received significant financial support from several strategic investors and venture capital firms over the last few years. Among other elements, the report provides the following information:
 The current state of the market with respect to the key players, phase of development of pipeline products (both clinical and preclinical / discovery), target enzyme classes and the key disease indications.
 Comprehensive profiles highlighting clinical trial details, key preclinical / clinical findings and future market opportunity for the clinical stage (phase I/II, phase II and phase III) ubiquitin enzyme inhibitors.
 Various investments and grants received by companies focused in this area in order to accelerate and support their R&D activities.
 Partnerships that have taken place in the recent past covering product development / commercialization agreements, research collaborations, clinical trial collaborations, license agreements, acquisitions and other such deals between stakeholders in the industry.

One of the key objectives of this report was to understand the current activity and the future potential of the market. The study provides a detailed market forecast and opportunity analysis for the period between 2016 and 2030. The research, analysis and insights presented in this report include a detailed description of ubiquitin enzyme inhibitors along with drug classes closely associated with them. To add robustness to our model, we have provided three scenarios for our market forecast, namely the conservative, base and optimistic scenarios, to account for future uncertainties. The opinions and insights presented in this study were influenced by several discussions conducted with experts in this domain. All actual figures have been sourced and analyzed from publicly available information forums and from primary research. All financial figures mentioned in this report are in USD, unless otherwise specified.

EXAMPLE HIGHLIGHTS
1. Over 45 molecules targeting ubiquitin enzymes are currently in clinical / preclinical stages of development. 71% of the pipeline molecules are targeting oncological indications. Within oncology, hematological malignancies, such as acute myeloid leukemia (AML) and relapsed / refractory multiple myeloma (MM), are the primary focus areas. In fact, the two late stage molecules, idasanutlin and pevonedistat, are being developed for hematological cancers. Other indications such as Alzheimer’s disease, Parkinson’s disease, Friedreich's ataxia and Angelman syndrome are also gradually gaining interest of developers.
2. The innovation in this emerging field is primarily being led by start-ups / small companies. Notable examples include (in alphabetical order) Agilis Biotherapeutics, Aileron Therapeutics, Almac Discovery, Aperion Biologics, Ascenta Therapeutics, Carmot Therapeutics, CellCentric, Cleave Biosciences, Ensemble Therapeutics, Mission Therapeutics, Progenra, Proteostasis Therapeutics, UbiQ Therapeutics, and Vivolux. In addition, a number of large companies are also developing assets in this field. Prominent players under this category include (in alphabetical order) Amgen, Biogen, Daiichi Sankyo, Merck, Novartis Pharmaceuticals, Priaxon, Roche / Genentech, Sanofi and Servier.
3. Prominent academic players, including (in alphabetical order) the Dana-Farber Cancer Institute, Karolinska Institute, Mayo Clinic, Memorial Sloan Kettering Cancer Center, University of Oxford and University of Michigan, have entered into research collaborations with industry players to conduct further research for the development of various inhibitors.
4. Several strategic investors and venture capitalists have strongly backed the potential offered by this domain. We identified over 70 funding instances over the past few years. The total amount invested has been close to USD 1.2 billion; of this, 70% has been invested during the last five years alone.
5. Stakeholders have actively collaborated to advance R&D initiatives. We came across 72 collaborations categorized as product development / commercialization agreements, product licensing agreements, technology licensing, acquisitions, clinical trial agreements and research collaborations. Among these, development / commercialization agreements and research collaborations, with over 60% share, have been the most popular.
6. In addition, we came across around 20 technology / research platforms that are currently available to advance the development of ubiquitin enzyme inhibitors. It is worth mentioning that these platforms are a direct consequence of the intense research activity in this field. Examples include (in alphabetical order) DUBprofiler™, DUBprofiler™, PROTAC Technology Platform, Ubi-Plex™ and UbiPro™.
7. Overall, we expect the field to witness considerable success in the long term. Post the launch of the first wave of products, we predict the market to grow at an annualized rate of 71% till 2030.

RESEARCH METHODOLOGY
Most of the data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market will evolve across different regions and technology segments. Where possible, the available data has been checked for accuracy from multiple sources of information.
The secondary sources of information include
 Annual reports
 Investor presentations
 SEC filings
 Industry databases
 News releases from company websites
 Government policy documents
 Industry analysts’ views

While the focus has been on forecasting the market over the coming ten years, the report also provides our independent view on various non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

CHAPTER OUTLINES
Chapter 2 presents an executive summary of the report. It offers a high level view on where the ubiquitin enzyme inhibitors market is headed in the mid-long term.

Chapter 3 provides a general introduction to the underlying concepts of protein homeostasis, emphasizing on the importance of post translational modifications in cellular processes. The chapter covers details on the discovery of the UPS, the structure and function of ubiquitin, brief discussions on the various components of the UPS, fundamentals of the UPS machinery and a schematic representation of the ubiquitination process. In addition, we have discussed the therapeutic applications of the UPS, providing the necessary arguments and evidence supporting the gradual replacement of the currently available proteasome inhibitor based therapies with the emerging class of ubiquitin enzyme inhibitors.

Chapter 4 provides a comprehensive overview of the current landscape of the ubiquitin enzyme inhibitors market. It includes information on the potential drug candidates that are currently in different stages of development (both clinical and preclinical / discovery). It presents a detailed analysis of the pipeline of products in this domain, including information on the most commonly targeted indications, current phases of development, target enzyme classes and key players involved in this space. Additionally, we have provided details of several research platforms, precursor compounds and research tools developed / being developed by various companies in order to support R&D initiatives in this space.

Chapter 5 presents important insights extracted from the current pipeline. The chapter provides a grid analysis of the candidate drugs in the market based on their distribution by target enzyme class, therapeutic area and highest phase of development. It also highlights the most popular targets within the UPS pathway from among the four ubiquitin enzyme classes mentioned earlier. In addition, we have also included an overview of the developer landscape based on the size and the activity of the industrial / non-industrial players engaged in this market. Along with that, we have mapped the geographical presence of various companies involved in the clinical development of product candidates in this field.

Chapter 6 focuses on E1 activating enzyme and E2 conjugating enzyme based inhibitors. The chapter includes a brief discussion on the role of these enzymes in the UPS pathway, including their mechanisms of action, important enzyme families, targets under investigation, current challenges and opportunities, and other relevant parameters. The chapter also includes detailed profiles of advanced stage product candidates. Each profile covers information such as drug specifications, its mechanism of action, current status of development, ongoing / completed clinical studies, key preclinical / clinical findings and other associated details.

Chapter 7 provides in-depth information on E3 ligases. The chapter includes a brief discussion on the role of E3 ligases in the UPS pathway, including its mechanism of action, important enzyme families, targets under investigation, current challenges and opportunities, details of screening assays and other relevant parameters. The chapter also includes detailed profiles of advanced stage product candidates. Each profile covers information such as drug specifications, its mechanism of action, current status of development, ongoing / completed clinical studies, key preclinical / clinical findings and other associated details.

Chapter 8 elaborates on DUB enzyme inhibitors. As in earlier two chapters, it discusses the role of DUBs in the UPS pathway, including its mechanism of action, important enzyme families, targets under investigation, current challenges and opportunities, details of screening assays and other relevant parameters. The chapter also includes detailed profiles of the drugs under advanced stages of development.

Chapter 9 provides details on the various drug classes that are closely related to the UPS; these include proteasome inhibitors, immunomodulatory drugs (IMiDs) and inhibitors of apoptosis proteins (IAP inhibitors). In this section, we have provided a brief introduction to the aforementioned competing drug classes, providing insights into their respective mechanisms of action and an overview of the molecules developed / being developed under each class of drugs.

Chapter 10 presents details on the investments and grants received by companies working in the field of ubiquitin enzymes and other closely associated product candidates. The analysis highlights the growing interest of the venture capital community and other strategic investors in this market.

Chapter 11 features an elaborate discussion on the collaborations and partnerships that have been inked amongst players in this market. We have also discussed the various partnership models that have been implemented, highlighting the most common forms of deals / agreements prevalent in this segment of the overall market.

Chapter 12 provides a comprehensive market forecast analysis, highlighting the future potential of the market till the year 2030. The analysis takes into consideration the molecules that are in relatively more advanced stages of development (phase I/II, phase II and phase III). The future sales potential and growth opportunity is based on the target patient populations, existing / future competition, likely adoption rates and price points.

Chapter 13 summarizes the overall report. In this chapter, we have provided a recap of the key takeaways from the study and our independent opinion based on the research and analysis described in previous chapters.

Chapter 14 is a collection of interview transcripts of the discussions that were held with key stakeholders in this market. We have presented the details provided to us by Martin Wiles (Vice President, Almac Discovery) and Gerald Gavory (Director of Biology, Almac Discovery), Zhihao Zhuang (Associate Professor, Department of Chemistry and Biochemistry, University of Delaware) and Katrin Rittinger (Research Group Leader, Francis Crick Institute).

Chapter 15 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.

Chapter 16 is an appendix, which provides the list of companies and organizations mentioned in the report.

LIST OF COMPANIES AND ORGANIZATIONS
The following companies and organizations have been mentioned in the report.

1. 3SBio
2. 5AM Ventures
3. Abbiotec
4. Abcam
5. AcelRx Pharmaceuticals
6. Aegera Therapeutics
7. Aeneas Ventures
8. Agilis Biotherapeutics
9. Aileron Therapeutics
10. Aju IB Investment
11. Alexion Pharmaceuticals
12. Almac Discovery
13. Amgen
14. Angelman Syndrome Foundation
15. Apeiron Biologics
16. Apple Tree Partners
17. ARCH Venture Partners
18. Arcus Ventures
19. Argenta Discovery
20. Argos Soditic
21. Arvinas
22. Ascenta Therapeutics
23. Ascentage Pharma
24. Astellas Venture Management
25. Astex Pharmaceuticals
26. AstraZeneca
27. Australasian Leukemia and Lymphoma Group
28. Avacta
29. Bavarian Research Foundation
30. Biogen
31. Biogenova
32. Bio-Techne
33. Biotechnology and Biological Sciences Research Council
34. BioTheryx
35. Boehringer Ingelheim
36. Boston Biochem
37. Boston University Technology Development Fund
38. BostonBiochem
39. BPS Biosciences
40. Business Development Bank of Canada
41. Business Development Corporation (BDC) Capital
42. C4 Therapeutics
43. Calculus Capital
44. Canaan Partners
45. Cancer Research Technology
46. Captor Therapeutics
47. Carmot Therapeutics
48. Cayman Chemicals
49. Celgene Corporation
50. Cell Signaling Technology
51. CellCentric
52. Cellivery Therapeutics
53. CellXplore
54. Celon Laboratories
55. Chinese University of Hong Kong
56. Cisbio Bioassays
57. Clarus Ventures
58. Cleave Biosciences
59. CMEA Ventures
60. Cobro Ventures
61. Columbia University
62. Comprehensive Cancer Center of Wake Forest University
63. Connecticut Innovations
64. Cormorant Asset Management
65. Curis
66. Cyclofluidic
67. Daiichi Sankyo
68. Dana-Farber Cancer Institute
69. Debiopharm
70. Desjardins Venture Capital
71. Deutsche Bank
72. Domain Associates
73. Dr. Reddy's
74. Draper Esprit
75. Draper Fisher Jurvetson
76. E3X Bio
77. Edmond de Rothschild Investment Partners
78. EG Capital Group
79. Elan Pharmaceuticals
80. Elm Street Ventures
81. Encycle Therapeutics
82. Endeavour Vision
83. Ensemble Therapeutics
84. Enterprise Partners
85. Enzo Lifesciences
86. Erimos Pharmaceutical
87. Evotec
88. Excel Venture Management
89. Flagship Ventures
90. Focus Biomolecules
91. Forma Therapeutics
92. Foundation for Angelman Syndrome Therapeutics (FAST)
93. Foundation Venture Capital Group
94. Fox Chase Cancer Center
95. F-Prime Capital Partners
96. Francis Crick Institute
97. Genentech (Hoffmann-La Roche)
98. GlaxoSmithKline
99. GrowthWorks Capital
100. Halle University
101. Harris & Harris Group
102. Harvard Medical School
103. Hasso Plattner Ventures
104. Hatteras Venture Partners
105. HealthCare Ventures
106. Horizon Discovery
107. Human Genome Sciences
108. Hybrigenics
109. Imperial Innovations
110. Index Ventures
111. Innovate UK
112. Intrexon
113. Invenio Therapeutics
114. Investissement Québec
115. IP Group
116. Janssen Research & Development
117. Kamiya Biomedical Company
118. Karolinska Institute
119. Laboratorio Varifarma
120. Latterell Venture Partners
121. Life Technologies
122. LifeSensors
123. Ligand Pharmaceuticals
124. Lilly Ventures
125. Linköping University
126. Lurie Investment Fund
127. Majuven
128. Makoto Life Sciences
129. MaRS Investment Accelerator Fund
130. Mayo Clinic
131. Medical Research Council
132. Memorial Sloan Kettering Cancer Center
133. Merck
134. Meso Scale Discovery
135. Michael J. Fox Foundation
136. Millennium Pharmaceuticals
137. Miltenyi Biotec
138. MiRx Pharmaceuticals
139. Mission Therapeutics
140. Morningside Venture Investments
141. Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute
142. Multiple Capital
143. MVM Life Science Partners
144. Natco Pharma
145. National Cancer Institute
146. National Institutes of Health Small Business Innovation Research
147. New Enterprise Associates
148. New Leaf Venture Partners
149. New York University
150. Nextech Invest
151. Novartis Pharmaceuticals
152. Novitas Capital
153. Novus Biologics
154. Nurix
155. Nxt2b
156. Ono Pharmaceutical
157. Onyx Pharmaceuticals
158. OrbiMed
159. Osage University Partners
160. Oxford Bioscience Partners
161. Parkwalk Advisors
162. Peloton Therapeutics
163. Penn Pharmaceutical Services
164. PerkinElmer
165. Perrigo Company
166. Perseus
167. Pfizer
168. Pharmascience
169. Pharmion Corporation
170. Priaxon
171. Progenra
172. Promega
173. Proteologics
174. Proteostasis Therapeutics
175. Proteros Biostructures
176. Providence Investment Company
177. Quaker BioVentures
178. Queen’s University
179. R & D Systems
180. RA Capital Management
181. Remeditex Ventures
182. Rigel Pharmaceuticals
183. Roche
184. Roswell Park Cancer Institute
185. Sanofi
186. Sanofi-Genzyme BioVentures
187. Santa Cruze Biotech
188. Scottish Investment Bank (Investment Arm of Scottish Enterprise)
189. Selleckchem
190. Sequoia Capital
191. Servier
192. Sidney Kimmel Comprehensive Cancer Center
193. Sigma-Aldrich
194. Sofinnova Ventures
195. SR One
196. Statsyuk Research Group
197. Stemgent
198. Supergen
199. SV Life Sciences
200. Taiho Pharmaceutical
201. Takeda
202. Tensha Therapeutics
203. TetraLogic Pharmaceuticals
204. The Column Group
205. Thermo Fisher Scientific
206. Thiel Foundation’s Breakout Labs
207. Third Rock Ventures
208. Tocris
209. Tokyo Medical University
210. UbiQ Therapeutics
211. Ubiquigent
212. UBP Biotech
213. Université de Montréal
214. Universities of Toronto and Sherbrooke
215. University of Birmingham
216. University of Cambridge Enterprise
217. University of Delaware
218. University of Dundee
219. University of Florida
220. University of Glasgow
221. University of Liverpool
222. University of Michigan
223. University of Oxford
224. University of Rome “Tor Vergata”
225. University of South Florida (USF)
226. University of Texas
227. University of Toronto
228. VenGrowth Capital Partners
229. Vivolux
230. Walter and Eliza Hall Institute of Medical Research
231. Woodford Patient Capital Trust
232. Wren Capital
233. Yale University
234. Yonsei University College of Medicine
235. Yorkville Advisors


1. PREFACE
1.1. Chapter Overview
1.2. Research Methodology
1.3. Chapter Outlines
2. EXECUTIVE SUMMARY
3. INTRODUCTION
3.1. Chapter Overview
3.2. The Concept of Protein Homeostasis
3.3. Importance of Post Translational Modifications in Cellular Functions
3.4. Discovery of the Ubiquitin / Ubiquitin Proteasome System
3.5. Ubiquitin: Structure and Function
3.6. Fundamentals of the UPS
3.6.1. Components of the UPS
3.6.2. Key Steps Involved in the UPS
3.7. Therapeutic Applications of UPS
3.8. Emergence of Ubiquitin Enzyme Inhibitors
4. UBIQUITIN ENZYME INHIBITORS: MARKET OVERVIEW
4.1. Chapter Overview
4.2. Ubiquitin Enzyme Inhibitors: Development Pipeline
4.3. Ubiquitin Enzyme Inhibitors: Distribution by Phase of Development
4.4. Ubiquitin Enzyme Inhibitors: Distribution by Therapeutic Area
4.5. Ubiquitin Enzyme Inhibitors: Distribution by Target Ubiquitin Enzymes
4.6. Ubiquitin Enzyme Inhibitors: Distribution by Geography
4.7. Ubiquitin Enzyme Inhibitors: Most Active Industry Players
4.8. Ubiquitin Enzyme Inhibitors: Research Tools, Key Technologies and Precursor Compounds
4.8.1. Research Tools / Key Technologies
4.8.2. Precursor Compounds
4.8.3. UPS Based Research Tools: Other Players
5. KEY INSIGHTS: THERAPEUTIC AREAS AND POTENTIAL TARGETS
5.1. Chapter Overview
5.2. Ubiquitin Enzyme Inhibitors Clinical Development Analysis: Therapeutic Areas
5.3. Ubiquitin Enzyme Inhibitors Clinical Development Analysis: Potential Targets
5.4. Ubiquitin Enzyme Inhibitors Clinical Development Analysis: Developer Landscape
5.5. Developers of Ubiquitin Enzyme Inhibitors: Geographical Presence
5.6. Ubiquitin Enzyme Inhibitors and UPS: Recent / Upcoming Conferences
6. E1 AND E2 ENZYMES AS THERAPEUTIC TARGETS
6.1. Chapter Overview
6.2. E1 Activating Enzymes as Drug Targets
6.2.1. E1 Enzymes: An Introduction
6.2.2. E1 Enzymes: Mechanism of Action
6.2.3. E1 Enzyme Inhibitors: List of Related Targets
6.2.4. E1 Enzyme Inhibitors: Development Pipeline
6.2.5. E1 Enzyme Inhibitors: Drug Profiles
6.2.6. E1 Enzyme Inhibitors Development: Challenges and Opportunities
6.3. E2 Conjugating Enzymes as Drug Targets
6.3.1. E2 Enzymes: An Introduction
6.3.2. E2 Enzymes: Mechanism of Action
6.3.3. E2 Enzyme Inhibitors: List of Related Targets
6.3.4. E2 Enzyme Inhibitors: Development Pipeline
6.3.5. E2 Enzyme Inhibitors Development: Challenges and Opportunities
7. E3 ENZYMES AS THERAPEUTIC TARGETS
7.1. Chapter Overview
7.2. E3 Ligases: An Introduction
7.3. E3 Ligases: Mechanism of Action
7.4. E3 Ligases: Important Families
7.4.1. The RING Family
7.4.2. The HECT Family
7.4.3. SCF Complex
7.4.4. U-Box Family
7.4.5. RBR Family
7.5. E3 Ligase Inhibitors: List of Related Targets
7.6. E3 Ligase Inhibitors: Screening Methods
7.7. E3 Ligase Inhibitors: Development Pipeline
7.8. E3 Ligase Inhibitors: Drug Profiles
7.8.1. Idasanutlin / RG 7388 / RO 5503781 (Roche)
7.8.1.1. Drug Specifications
7.8.1.2. Mechanism of Action
7.8.1.3. Current Status of Development
7.8.1.4. Key Clinical Trials
7.8.1.5. Key Preclinical / Clinical Findings
7.8.2. AMG 232 (Amgen)
7.8.2.1. Drug Specifications
7.8.2.2. Mechanism of Action
7.8.2.3. Current Status of Development
7.8.2.4. Key Clinical Trials
7.8.2.5. Key Preclinical / Clinical Findings
7.8.3. HDM201 / NVP-HDM201 (Novartis Pharmaceuticals)
7.8.3.1. Drug Specifications
7.8.3.2. Mechanism of Action
7.8.3.3. Current Status of Development
7.8.3.4. Key Clinical Trials
7.8.3.5. Key Preclinical / Clinical Findings
7.9. E3 Ligase Inhibitors: Challenges and Opportunities
8. DUB ENZYMES AS THERAPEUTIC TARGETS
8.1. Chapter Overview
8.2. DUBs: An Introduction
8.3. DUBs: Mechanism of Action
8.4. DUBs: Important Families
8.4.1. USP / UBP Family
8.4.2. UCH Family
8.4.3. MCPIP Family
8.4.4. OTU Family
8.4.5. MJD Family
8.4.6. JAMM Family
8.5. DUB Inhibitors: List of Related Targets
8.6. DUB Inhibitors: Screening Methods
8.7. DUB Inhibitors: Development Pipeline
8.8. DUB Inhibitors: Drug Profiles
8.9. DUB Inhibitors Development: Challenges and Opportunities
9. ASSOCIATED DRUG CLASSES
9.1. Chapter Overview
9.2. Proteasome Inhibitors
9.3. Immunomodulatory Drugs
9.4. IAP Inhibitors
10. VENTURE CAPITAL INTEREST
10.1. Chapter Overview
10.2. Funding Instances: Distribution by Type of Funding
10.3. Funding Instances for Development of Ubiquitin Based Therapeutics
10.4. Rising Venture Capital Interest
10.5. Leading Players: Distribution by Number of Funding Instances
10.6. Most Active Venture Capital Firms / Investors
10.7. Funding Instances: Distribution by Focus Area
11. RECENT COLLABORATIONS
11.1. Chapter Overview
11.2. Partnership Models / Agreements
11.3. UPS Based Therapeutics: Recent Collaborations
11.4. Recent Collaborations: Distribution by Month / Year
11.5. Recent Collaborations: Distribution by Type of Model
11.6. Recent Collaborations: Distribution by Focus Area
11.7. Recent Collaborations: Most Active Companies
12. MARKET FORECAST AND OPPORTUNITY ANALYSIS
12.1. Chapter Overview
12.2. Scope and Limitations
12.3. Forecast Methodology
12.4. Overall Ubiquitin Enzyme Inhibitors Market
12.5. Ubiquitin Enzyme Inhibitors Market: Individual Forecasts
12.5.1. Idasanutlin (Genentech)
12.5.1.1. Target Patient Population
12.5.1.2. Sales Forecast
12.5.2. Pevonedistat (Millennium Pharmaceuticals)
12.5.2.1. Target Patient Population
12.5.2.2. Sales Forecast
12.5.3. HDM201 (Novartis Pharmaceuticals)
12.5.3.1. Target Patient Population
12.5.3.2. Sales Forecast
12.5.4. VLX1570 (Vivolux)
12.5.4.1. Target Patient Population
12.5.4.2. Sales Forecast
12.5.5. AMG 232 (Amgen)
12.5.5.1. Target Patient Population
12.5.5.2. Sales Forecast
13. CONCLUSION
13.1. Drugs Targeting Protein Modification Pathways Have Emerged as Valuable Therapeutic Options
13.2. Extensive Research is Being Carried Out to Address the Challenges Associated with Drug Discovery
13.3. The Evolving Pipeline Caters to a Wide Spectrum of Disease Indications
13.4. Targeted Therapies are Being Developed by Leveraging Inherent Specificity of Various UPS Components
13.5. Growing Partnerships and VC Support are Indicative of Lucrative Future Potential
13.6. Novel Technology Platforms and Therapeutic Concepts Will Act as Key Enablers to Drive Future Growth
13.7. Once Approved, Ubiquitin Enzyme Inhibitors are Poised to Achieve an Accelerated Growth
14. INTERVIEW TRANSCRIPTS
14.1. Chapter Overview
14.2. Martin Wiles, Vice President Business Development and Licensing, Almac Discovery
Gerald Gavory, Director of Biology, Almac Discovery
14.3. Katrin Rittinger, Research Group Leader, Francis Crick Institute
14.4. Zhihao Zhuang, Associate Professor, Department of Chemistry and Biochemistry, University Of Delaware
15. APPENDIX 1: TABULATED DATA
16. APPENDIX 2: LIST OF COMPANIES AND ORGANIZATIONS
LIST OF FIGURES
Figure 3.1 Protein Surveillance: Important Mechanisms
Figure 3.2 Post Translational Modifications: Common Types
Figure 3.3 Phosphorylation and Ubiquitination: Key Differences in Drug Discovery
Figure 3.4 Phosphorylation and Ubiquitination: Mechanism based Analogies
Figure 3.5 Ubiquitin: Types of Target Proteins
Figure 3.6 Genetic Evolution of the UPS in Eukaryotes
Figure 3.7 Key Components of the UPS
Figure 3.8 Ubiquitin-Proteasome Pathway
Figure 3.9 Modes of Ubiquitination
Figure 3.10 Ubiquitination: Biological Functions
Figure 3.11 UPS: Disease Development Process
Figure 3.12 UPS: Key Therapeutic Areas
Figure 4.1 Ubiquitin Enzyme Inhibitors: Distribution by Phase of Development
Figure 4.2 Ubiquitin Enzyme Inhibitors: Distribution by Therapeutic Area
Figure 4.3 Ubiquitin Enzyme Inhibitors: Distribution by Target Enzymes
Figure 4.4 Ubiquitin Enzyme Inhibitors: Distribution by Target Ubiquitin Enzymes and Phase of Development
Figure 4.5 Ubiquitin Enzyme Inhibitors: Distribution by Geography
Figure 4.6 Ubiquitin Enzyme Inhibitors: Regional Landscape
Figure 4.7 Ubiquitin Enzyme Inhibitors: Most Active Industry Players
Figure 4.8 UPS Based Research Tools: Other Market Participants
Figure 5.1 Grid Analysis: Distribution by Target Enzyme Class, Therapeutic Area and Phase of Development
Figure 5.2 Ubiquitin Enzyme Inhibitors Funnel Analysis: Distribution by Target Enzyme Class and Phase of Development
Figure 5.3 Ubiquitin Enzyme Inhibitors Developer Landscape: Distribution by Developer and Phase of Development
Figure 5.4 Ubiquitin Enzyme Inhibitors: Geographical Presence
Figure 5.5 Recent / Upcoming Conferences: Distribution by Year and Geography
Figure 5.6 Recent / Upcoming Conferences: Regional Map
Figure 6.1 E1 Activating Enzymes: List of Related Targets
Figure 6.2 E1 Enzyme Drug Development: Major Challenges
Figure 6.3 E2 Enzymes: List of Related Targets
Figure 6.4 E2 Enzyme Drug Development: Major Challenges
Figure 7.1 Mechanism of Action: RING, HECT and U-Box Families
Figure 7.2 E3 Ligases: Important Families
Figure 7.3 Tumor Suppression by p53
Figure 7.4 Different Types of MDM2-p53 Interactions
Figure 7.5 MDM2 Mediated p53 Degradation Pathway
Figure 7.6 E3 Ligases: List of Related Targets
Figure 7.7 E3 Ligases: Screening Methods
Figure 7.8 E3 Ligase Drug Development: Major Challenges
Figure 8.1 DUB Enzymes: Important Families
Figure 8.2 DUB Enzymes: List of Related Targets
Figure 8.3 DUB Enzymes: Screening Methods
Figure 8.4 DUB Drug Development: Major Challenges
Figure 9.1 Proteasome Inhibitors: Related Side Effects
Figure 9.2 IAP Pathways and SMAC Mimetics
Figure 10.1 Funding Instances: Number of Instances, 2006-2016
Figure 10.2 Funding Instances: Amount Invested, 2006-2016 (USD Million)
Figure 10.3 Funding Instances: Distribution by Type, 2006-2016
Figure 10.4 Funding Instances: Distribution by Total Amount Invested, 2006-2016 (USD Million)
Figure 10.5 Funding Instances: Distribution by Range of Amount Invested by Type of Funding (USD Million)
Figure 10.6 Most Active Players: Distribution by Number of Funding Instances, 2006-2016
Figure 10.7 Most Active Venture Capital Firms / Investors: Distribution by Number of Instances, 2006-2016
Figure 10.8 Funding Instances: Distribution by Focus Area
Figure 11.1 Recent Collaborations: Distribution by Year
Figure 11.2 Recent Collaborations: Distribution by Type of Model
Figure 11.3 Recent Collaborations: Distribution by Focus Area
Figure 11.4 Recent Collaborations: Distribution by Focus Area and Partnership Model
Figure 11.5 Recent Collaborations: Most Active Players
Figure 12.1 Overall Ubiquitin Enzyme Inhibitors Market (USD Million): 2016-2030 (Base Scenario)
Figure 12.2 Ubiquitin Enzyme Inhibitors Market: Distribution by Therapeutic Area, 2025, 2030 (USD Million)
Figure 12.3 Ubiquitin Enzyme Inhibitors Market: Distribution by Target Enzyme Class, 2030 (USD Million)
Figure 12.4 Ubiquitin Enzyme Inhibitors: Distribution of Market Share, 2030 (USD Million)
Figure 12.5 Idasanutlin Sales Forecast (USD Million), Base Scenario
Figure 12.6 Pevonedistat Sales Forecast (USD Million), Base Scenario
Figure 12.7 HDM201 Sales Forecast (USD Million), Base Scenario
Figure 12.8 VLX1570 Sales Forecast (USD Million), Base Scenario
Figure 12.9 AMG 232 Sales Forecast (USD Million), Base Scenario
Figure 13.1 Overall Ubiquitin Enzyme Inhibitors Market Summary (USD Million): 2016, 2023, 2030
TABLE OF TABLES
Table 3.1 Ubiquitin: Structural Classification
Table 4.1 Ubiquitin Enzyme Inhibitors: Development Pipeline
Table 4.2 Ubiquitin Enzyme Inhibitors: Research Platforms
Table 4.3 Ubiquitin Enzyme Inhibitors: Precursor Compounds
Table 5.1 Ubiquitin Enzyme Inhibitors and UPS: Recent / Future Conferences, 2013-2017
Table 6.1 E1 Enzyme Inhibitors: Development Pipeline
Table 6.2 Pevonedistat: Current Status of Development
Table 6.3 Pevonedistat: Clinical Trials
Table 6.4 E2 based Inhibitors: Development Pipeline
Table 7.1 SCF Complex: Core Components
Table 7.2 E3 Ligase based Therapeutics: Development Pipeline
Table 7.3 Idasanutlin: Current Status of Development
Table 7.4 Idasanutlin: Clinical Trials
Table 7.5 AMG 232: Current Status of Development
Table 7.6 AMG 232: Clinical Trials
Table 7.7 HDM201: Current Status of Development
Table 7.8 HDM201: Clinical Trials
Table 8.1 DUB based Therapeutics: Development Pipeline
Table 8.2 VLX 1570: Current Status of Development
Table 8.3 VLX 1570: Clinical Trials
Table 9.1 Velcade: Case Study
Table 9.2 Kyprolis: Case Study
Table 9.3 Ninlaro: Case Study
Table 9.4 IMiDs: Pipeline
Table 9.5 Thalomid: Case Study
Table 9.6 Revlimid: Case Study
Table 9.7 Pomalyst / Imnovid: Case Study
Table 9.8 Types of IAPs in Human Malignancies
Table 9.9 IAP Inhibitors: Pipeline
Table 9.10 AT 406 / Debio 1143: Case Study
Table 9.11 Birinapant / TL 32711: Case Study
Table 11.1 Ubiquitin Enzyme Inhibitors and Associated Products: Recent Collaborations (2006-2016)
Table 12.1 Ubiquitin Enzyme Inhibitors: Potential Candidates
Table 12.2 Idasanutlin: Target Patient Population
Table 12.3 Pevonedistat: Target Patient Population
Table 12.4 HDM201: Target Patient Population
Table 12.5 VLX1570: Target Patient Population
Table 12.6 AMG 232: Target Patient Population
Table 15.1 Ubiquitin Enzyme Inhibitors: Distribution by Phase of Development
Table 15.2 Ubiquitin Enzyme Inhibitors: Distribution by Therapeutic Area
Table 15.3 Ubiquitin Enzyme Inhibitors: Distribution by Target Enzymes
Table 15.4 Ubiquitin Enzyme Inhibitors: Distribution by Target Ubiquitin Enzymes and Phase of Development
Table 15.5 Ubiquitin Enzyme Inhibitors: Distribution by Geography
Table 15.6 Ubiquitin Enzyme Inhibitors: Most Active Industry Players
Table 15.7 Recent / Upcoming Conferences: Distribution by Year and Geography
Table 15.8 Funding Instances: Number of Instances, 2006-2016
Table 15.9 Funding Instances: Amount Invested, 2006-2016 (USD Million)
Table 15.10 Funding Instances: Distribution by Type, 2006-2016
Table 15.11 Funding Instances: Distribution by Total Amount Invested, 2006-2016 (USD Million)
Table 15.12 Most Active Players: Distribution by Number of Funding Instances, 2006-2016
Table 15.13 Most Active Venture Capital Firms / Investors: Distribution by Number of Instances, 2006-2016
Table 15.14 Funding Instances: Distribution by Focus Area
Table 15.15 Recent Collaborations: Distribution by Year
Table 15.16 Recent Collaborations: Distribution by Type of Model
Table 15.17 Recent Collaborations: Distribution by Focus Area
Table 15.18 Recent Collaborations: Distribution by Focus Area and Partnership Model
Table 15.19 Recent Collaborations: Most Active Players
Table 15.20 Overall Ubiquitin Enzyme Inhibitors Market (USD Million): 2016-2030 (Base Scenario)
Table 15.21 Overall Ubiquitin Enzyme Inhibitors Market (USD Million): 2016-2030 (Optimistic Scenario)
Table 15.22 Overall Ubiquitin Enzyme Inhibitors Market (USD Million): 2016-2030 (Conservative Scenario)
Table 15.23 Ubiquitin Enzyme Inhibitors: Market Distribution by Therapeutic Area, 2025, 2030 (USD Million)
Table 15.24 Ubiquitin Enzyme Inhibitors: Market Distribution by Target Enzyme Class, 2030 (USD Million)
Table 15.25 Ubiquitin Enzyme Inhibitors: Distribution of Market Share, 2030 (USD Million)
Table 15.26 Idasanutlin Sales Forecast (USD Million), Base Scenario
Table 15.27 Idasanutlin Sales Forecast (USD Million), Optimistic Scenario
Table 15.28 Idasanutlin Sales Forecast (USD Million), Conservative Scenario
Table 15.29 Pevonedistat Sales Forecast (USD Million), Base Scenario
Table 15.30 Pevonedistat Sales Forecast (USD Million), Optimistic Scenario
Table 15.31 Pevonedistat Sales Forecast (USD Million), Conservative Scenario
Table 15.32 HDM201 Sales Forecast (USD Million), Base Scenario
Table 15.33 HDM201 Sales Forecast (USD Million), Optimistic Scenario
Table 15.34 HDM201 Sales Forecast (USD Million), Conservative Scenario
Table 15.35 VLX1570 Sales Forecast (USD Million), Base Scenario
Table 15.36 VLX1570 Sales Forecast (USD Million), Optimistic Scenario
Table 15.37 VLX1570 Sales Forecast (USD Million), Conservative Scenario
Table 15.38 AMG 232 Sales Forecast (USD Million), Base Scenario
Table 15.39 AMG 232 Sales Forecast (USD Million), Optimistic Scenario
Table 15.40 AMG 232 Sales Forecast (USD Million), Conservative Scenario
Table 15.41 Ubiquitin Enzyme Inhibitors Market Summary (USD Million): 2016, 2023, 2030

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