Frontiers in Cancer Therapies: Focus on Transcription Factors, GTPases, Phosphatases and GPCRs, 2018-2030
Cancer therapeutics continues to be one of the most active segments, in terms of drug development efforts, within the pharmaceutical industry. In fact, in the past five years, USFDA has approved more than 70 drugs for the treatment of different types of cancer. However, there is still a pressing need to develop more specific and potent therapeutics to combat this complex, life threatening clinical condition. According to the National Institutes of Health, the economic burden of cancer care in the US was estimated to be over USD 147 billion in 2017. As the global population continues to increase, the number of cancer patients is likely to rise as well; by 2030, it is estimated that about 21.6 million people are likely to be newly diagnosed with the disease. Thereby, the overall global economic burden related to the disease is anticipated to increase significantly in the foreseen future.
Conventional cancer treatments, such as chemotherapy and radiation therapy are associated with several side effects. Their non-specific nature has been shown to have severe detrimental effects on patients’ quality of life. Current drug development initiatives are focused on targeted therapies against specific oncogenic mutations that are responsible for disease development and / or progression. Over the years, several targeted drugs have been designed against specific proteins, such as human epidermal growth factor (HER2), BCR-ABL protein kinase and vascular endothelial growth factor (VEGF). However, certain biological targets have long eluded drug development efforts and, for a considerable period of time, have been reported to be undruggable. One such target is Ras family, which has been identified to a play critical role in oncogenesis. Scientific literature suggests that the RAS gene is mutated across about 30% of cancer types; the mutation is known to be present in about 90% of pancreatic cancers, over 50% of colorectal cancers and 35% of lung cancers. Likewise, there are several other targets that have not yet been successfully drugged and researchers are making significant efforts to identify novel approaches to target them.
Advances in drug discovery and development technologies / platforms have increased the likelihood of targeting a number of the abovementioned types of biological targets. As a result, novel product development opportunities have emerged and are likely to benefit both drug developers and investors alike. Ongoing R&D is focused on the development of treatment modalities that can also combat complications, such as off target toxicities and disease relapse, which are associated with the current standard of care therapies. As various clinical stage candidates progress towards advanced stages of development, we expect the market to witness aggressive growth over the coming years.
SCOPE OF THE REPORT
The ‘New Frontiers in Cancer Therapies: Focus on Transcription Factors, GTPases, Phosphatases and GPCRs, 2018-2030’ report provides a comprehensive study on the current market and therapeutic potential of the various pharmacological interventions designed against difficult-to-modulate cancer targets. It features an elaborate discussion on the future potential of this evolving domain, focusing on phosphatases, transcription factors, small GTPases (specifically Ras family) and undruggable G-protein coupled receptors (GPCRs). One of the key objectives of the study was to review and quantify the future opportunity for the ongoing product development programs of both small and big pharmaceutical firms. Amongst other elements, the report features:
A detailed assessment of the current market landscape of drugs being developed against various undruggable cancer targets, featuring information on the developer, phase of development (clinical, preclinical or discovery stage) of product candidate(s), information on type of molecule(s), biological target(s), mechanism of action, route of administration, and key therapeutic indication(s).
Elaborate profiles of key companies (selected based on pipeline strength); each profile features an overview of the company, details on it product portfolio, technology overview (wherever applicable), detailed information on advanced stage pipeline candidates (featuring a drug overview, clinical trial information and recent developments) and a comprehensive future outlook.
A section on emerging technologies and platforms that are aiding the development of therapies capable of targeting biological molecules which were previously considered as undruggable.
A detailed publication analysis on more than 70 research articles that have been published between January 2014 and March 2018, highlighting the key focus areas (biological targets and indications) of the ongoing research activity in this field.
An analysis of the partnerships that have been established in this domain in the recent past, covering R&D agreements, license agreements, clinical trial collaborations, mergers and acquisitions, and other relevant agreements.
An analysis of the investments made at various stages of development in companies that are focused in this area, including seed financing, venture capital financing, debt financing, grants, capital raised from IPOs and subsequent offerings.
A compilation of key insights derived based on various parameters; these include [A] a bull’s eye analysis highlighting the distribution of pipeline candidates in terms of phase of development, type of target family and type of molecule [B] a three-dimensional and five-dimensional spider web analyses of candidate therapeutics based on different parameters, namely number of publications, grants awarded to promote development, active clinical trials, current phase of development and the number of companies developing drugs against various undruggable targets, and [C] a world map representation, depicting the most active geographies in terms of the presence of companies developing drug candidates against difficult-to-modulate cancer targets.
One of the key objective of the report was to understand the primary growth drivers and estimate the future size of the market. Based on parameters, such as target consumer segments, likely adoption rates and expected pricing, we have provided an informed estimate of the likely evolution of the market in the short to long-term, for the period 2018 to 2030. To account for the uncertainties associated with the development of cancer therapeutics and to add robustness to our model, we have provided three forecast scenarios, portraying the conservative, base and optimistic tracks of the market’s evolution.
The research, analysis and insights presented in this report is backed by a deep understanding of insights gathered both from secondary and primary sources. The opinions and insights presented in this study were influenced by discussions conducted with several key players in this domain. The report features detailed transcripts of interviews held with Amotz Shemi (CEO, Silenseed), Brian Frenzel (President and CEO, Tosk), Miguel Vega (CEO, Allinky Biopharma) and Stephen Franklin (CEO, Evgen Pharma). All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.
1. Over 100 product candidates are currently under various stages of development against difficult-to-modulate cancer targets. Of these, 75% of the candidates are in preclinical / discovery stages. Amongst the drugs that are under clinical development, 2 are in phase III, 5 in phase II, 5 in phase I/II and 12 in phase I. Drugs in advanced clinical evaluation (phase II and above) are napabucasin (phase III), Rigosertib™ (phase III), BL-8040 (phase II), CX-01 (phase II), danvatirsen (phase II), GI-6301 (phase II) and siG12D LODER (phase II).
2. A significant portion (~38%) of the drug candidates are being developed to target transcription factors, which play a critical role in a vast array of cellular processes and have been shown to be associated with several disease pathways. Prominent examples of transcription factors that have been shown to play a role in tumorigenesis include brachyury, Myc and STAT proteins. Another important target family is GTPases, primarily mutant Ras proteins, that are being targeted by about 28% of the pipeline candidates. Other key target families that are being investigated include GPCRs (such as CXCR4), phosphatases (such as SHP2 and PP2A) and certain complexes resulting from protein-protein interactions.
3. Small molecules, representing 48% of the present pipeline candidates, have emerged as one of the prominent drug classes being evaluated against difficult-to-modulate targets. Other important types of therapeutic molecules under development include peptides (12%), oligonucleotides (10%), proteins (9%) and antibodies (7%).
4. About 70% of the product candidates are being developed to treat solid tumors. Of these, pancreatic cancer (23%) is the most common; other popular indications include breast cancer (21%), lung cancer (19%) and colorectal cancer (16%). Further, about 30% of drugs are being developed for the treatment of hematological malignancies, such as acute myeloid leukemia, Burkitt lymphoma, myelodysplastic syndromes, non-Hodgkin lymphoma and multiple myeloma.
5. The market landscape is characterized by the presence of large (7), mid-sized (34) and small-sized companies (63), most of which are located in North America. The large companies involved in this domain include (in alphabetical order) AstraZeneca, BMS, Eli Lilly, Novartis and Pfizer. Similarly, mid-sized companies that are actively contributing to the development of these therapies include (with at least one molecule in the clinical phase of development) AndroScience, Boston Biomedical, Heptares Therapeutics, Ionis Pharmaceuticals, Polyphor, Silenseed and Taiho Oncology. In addition, small companies, such as (in alphabetical order) A2A Pharmaceuticals, FIMECS, Janpix, Navire Pharma, Oncternal Therapeutics, Orum Therapeutics, Ractigen Therapeutics, Sanoosa, SyntheX, TheraPten Biosciences and Zelluna Immunotherapy, are actively involved in this domain as well.
6. In order to advance the development efforts, stakeholders in the industry have forged several strategic partnerships. Over 50% of the agreements that have been signed since 2014 were related to the conduct of R&D activities. These were followed by licensing agreements (26%), clinical trial collaborations (9%), and product development (6%) and commercialization agreements (6%). Examples of recently inked deals include collaborations between FIMECS and Takeda Pharmaceutical (April 2018), Moleculin Biotech and University of Warsaw (March 2018), Onconova Therapeutics and Pint Pharma (March 2018), Moleculin Biotech and Emory University (March 2018), and Arvinas and Pfizer (January 2018).
7. More than 80 funding instances, amounting to USD 915 million worth of capital, have taken place in order to support R&D in this space since 2014. Alexandria Venture Investment and Fidelity Management & Research Company have emerged as some of the most prominent investors (in terms of number of financing instances). It is noteworthy to highlight that the NIH has provided financial support, in the form grants, to over 40 research projects in the past two years.
8. Close to 70 players have designed and developed novel proprietary technology platforms to advance R&D efforts. Prominent examples of companies with technology platforms include (in alphabetical order) Allinky Biopharma, Aelin Therapeutics, Bio-Path Holdings, Captor Therapeutics, Eureka Therapeutics, FogPharma, InterAx, MiNA Therapeutics, Nuevolution, PHusis Therapeutics, Phylogica, Sanoosa, Silicon Therapeutics and SyntheX.
9. With several ongoing research initiatives and the likely approval of multiple late stage clinical candidates, the market is expected to witness an accelerated growth and be worth USD 11-12 billion over the coming decade. Specifically, by 2030, close to 70% of the market is likely to be driven by drugs targeting transcription factors, followed by GPCRs (~18%). The market, in the long term, is likely to be driven by five indications, namely pancreatic cancer (36%), colorectal cancer (14%), glioblastoma (12%), MDS (10%) and leukemia (10%). In terms of the geographical distribution, North America and the EU5 are expected to account for over 80% of the market.
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
News releases from company websites
Government policy documents
Industry analysts’ views
While the focus has been on forecasting the market over the coming twelve years, the report also provides our independent view on various technological and 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 2 provides an executive summary of the insights captured during our research. It offers a high-level view on the likely evolution of the drugs against difficult-to-modulate targets to treat various cancer indications in the mid to long term.
Chapter 3 provides a general overview of certain biological targets (along with descriptions of the broader target families) that are considered as undruggable and associated with various cancers. In addition, it features information on the currently available treatment modalities that are used to treat cancers. The chapter also highlights the key benefits offered by various targeted anti-cancer therapies. The focus of the report is on difficult-to-modulate phosphatases, transcription factors, small GTPases (specifically Ras family) and GPCRs.
Chapter 4 provides a comprehensive overview of the current landscape of therapies against difficult-to-modulate cancer targets. It includes information on over 100 drug candidates that are currently in various stages of (clinical / preclinical) development. It features a comprehensive analysis of the various pipeline molecules, highlighting affiliated drug developers, phase(s) of development, type of molecule, biological target, target protein family, target therapeutic indication(s), mechanism of action and route of administration.
Chapter 5 contains detailed profiles of active players (selected based on pipeline strength) that are involved in developing therapeutics against difficult-to-modulate targets. Each profile includes an overview of the company, its technology (wherever available) and details of its product portfolio. In addition, we have profiled the advanced phase drugs (phase II and above) that are in the pipeline of each of the companies included in this section. Drug profiles contain information on clinical development status, clinical trial details and recent developments.
Chapter 6 provides a list of technologies / platforms that have been developed to discover and / or develop therapeutics against various difficult-to-modulate cancer targets. It features a comparative analysis of the technologies, based on ongoing development activity related to a specific technology (in terms of number of drugs across different phases of development), number of partnerships established related to the technology and the size of the company. In addition, the chapter features a detailed logo landscape of various types of technology providers, distributed on the basis of their respective geographical locations.
Chapter 7 features a publication analysis highlighting the recent trends related to undruggable cancer targets in published literature. The chapter provides details on novel methods, as well as the attempts that are being made to add value to ongoing research efforts within this domain. In addition, it provides details on the various grants received by different organizations between 2017 to 2018.
Chapter 8 presents details on investments made into companies that are engaged in this domain. It includes a detailed analysis of the various funding instances that have taken place in the period between January 2014 to April 2018, highlighting the growing interest of the venture capital community and other strategic investors in this market.
Chapter 9 features an elaborate discussion and analysis of the various collaborations and partnerships that have been inked amongst stakeholders in this market. In this section, we have also described the different partnership models (including R&D agreements, technology / product licensing agreements, product development and commercialization agreements, clinical trial collaborations and merger / acquisitions) adopted by collaborating entities, highlighting the most common forms of deals / agreements that have been established in the period between 2014 to 2018.
Chapter 10 presents a comprehensive market forecast analysis, highlighting the future potential of the market till the year 2030. It includes sales projections of therapies against difficult-to-modulate cancer targets that have progressed to advanced clinical stages of development (phase I/II and above). The projections take into consideration the target patient population, likely adoption rates, existing / future competition from competing drug classes and the likely price of products. The chapter also presents a detailed market segmentation on the basis of target family, type of molecule, key therapeutic indications and geographical distribution. In addition, it provides information on the net present value of the aforementioned drug candidates.
Chapter 11 is a compilation of key insights derived from the study. It presents a review of the regional landscape of companies engaged in developing therapeutics for undruggable targets, based on their location and cumulative pipeline strength. The chapter also features a bull’s eye analysis, representing the distribution of drug candidates on the basis of their phase of development, target protein family and type of molecule. Additionally, the chapter features a spider-web analysis and bubble analysis, which highlight the activity of difficult-to-modulate targets. The parameters considered for these analyses include number of drug candidates, active clinical trials, publications, target indications and the companies that are involved in this domain.
Chapter 12 is a summary of the overall report. In this chapter, we have provided a list of key takeaways from the report, and expressed our independent opinion related to the research and analysis described in the previous chapters.
Chapter 13 is a collection of interview transcripts of the discussions that were held with key stakeholders in this market. The chapter provides details of interviews held with Amotz Shemi (CEO, Silenseed), Brian Frenzel (President and CEO, Tosk) Miguel Vega (CEO, Allinky Biopharma) and Stephen Franklin (CEO, Evgen Pharma).
Chapter 14 is an appendix, which provides tabulated data and numbers for all the figures included in the report.
Chapter 15 is an appendix, which provides the list of companies and organizations mentioned in the report.
LIST OF COMPANIES / LIST OF COMPANIES AND ORGANIZATIONS
The following companies and organizations have been mentioned in the report.
1. 1Globe Health Institute
2. 5AM Ventures
3. A2A Pharmaceuticals
4. AbbVie Ventures
5. Abilita Bio
7. Advent Life Sciences
8. Agence Nationale de la Recherche
9. Aileron Therapeutics
10. Akcea Therapeutics
11. Alaska Permanent Fund
12. Alexandria Venture Investments
14. Allinky Biopharma
15. Alta Life Sciences
16. Amadeus Capital Partners
18. Anima Biotech
19. Aptose Biosciences
20. ARCH Venture Partners
21. Arrakis Therapeutics
22. Arrowhead Pharmaceuticals
24. Aspire Capital Partners
25. Astellas Pharma
27. Aurigene Discovery Technologies
28. Avergen Pharmaceuticals
29. Baxter Healthcare
31. Baylor College of Medicine
32. Belfer CentreInstitute
33. BeyondSpring Pharmaceuticals
36. Bio-Path Holdings
37. Blueprint Medicines
38. Boston Biomedical
39. Boxer Capital
40. BridgeBio Pharma
41. Bristol-Myers Squibb
42. Broad Institute
43. BVF Partners
44. California Institute of Technology
45. Cambridge Enterprise
46. Canaan Partners
47. Canaccord Genuity
48. Cancer Research UK
49. Cantex Pharmaceuticals
50. Captor Therapeutics
51. Carmot Therapeutics
52. Casdin Capital
54. Centre for the Development of Industrial Technology
55. ChinaBio® Group
56. Circa Group
57. Circle Pharma
58. Clarus Securities
59. Cloud Pharmaceuticals
60. Codiak BioSciences
61. Cold Spring Harbor Laboratory
62. Columbia University
63. Commonwealth Scientific and Industrial Research Organisation
65. Confo Therapeutics
66. Cormark Securities
67. Cormorant Asset Management
68. Cosmo Bio
69. Cotinga Pharmaceuticals
70. CPS Capital
71. CytomX Therapeutics
72. D&D Securities
73. Dana-Farber Cancer Institute
74. Dementia Discovery Fund
75. Unites States Department of Health and Human Services
76. Dicerna Pharmaceuticals
77. Dual Therapeutics
78. EBD Group
79. EcoR1 Capital
80. Elements Capital Partners
81. Eli Lilly and Company
82. Emory University
83. Enzon Pharmaceuticals
85. Escend Pharmaceuticals
86. Eureka Therapeutics
87. EvoRx Technologies
88. Fidelity Management & Research Company
90. Flagship Pioneering
91. Frederick National Laboratory for Cancer Research
92. GBO, a joint venture of Onconova Therapeutics and GVK Biosciences
94. Glactone Pharma
95. GLG Pharma
99. GVK Biosciences
100. H. Lee Moffitt Cancer Center & Research Institute
101. Hatteras Venture Partners
104. Heptares Therapeutics
105. Indi Molecular
106. Innovate UK
107. Innovation Norway
108. InterAx Biotech
109. InteRNA Technologies
112. IOCB Tech
113. Ionis Pharmaceuticals
115. IRB Barcelona
117. Janssen Pharmaceutica
118. Jennings Capital
119. Jesse Brown VA Medical Center
120. KB Investment
121. Kura Oncology
123. Kymera Therapeutics
124. LA CELL
125. LB Investment
127. LGC LINK
128. LifeForce Capital
129. Lincoln Park Capital Fund
130. Lixte Biotechnology Holdings
132. Marina Biotech
133. Massachusetts General Hospital
134. Massachusetts Institute of Technology
137. Merck Sharp & Dohme
138. Methodist Hospital Research Institute
139. MiNA Therapeutics
140. Mirati Therapeutics
141. Mission Bay Capital
142. Moderna Therapeutics
143. Moleculin Biotech
144. MP Healthcare Venture Management
149. National Cancer Institute
150. National Center for Regenerative Medicine
151. National Health and Medical Research Council
152. National Institute of Biomedical Imaging and Bioengineering
153. National Institute of General Medical Sciences
154. National Institute of Neurological Disorders and Stroke
155. National Institutes of Health
156. National OncoVenture
157. National Research Council Canada
158. Navire Pharma
159. New Leaf Venture Partners
160. New York University
161. Nextech Invest
162. Nomura Research Group
163. Norwegian Radium Hospital Research Foundation
165. Novartis Institutes for BioMedical Research
167. O2h Ventures
168. Ohio State University
169. Olivia Newton-John Cancer Research Institute
170. OncoFusion Therapeutics
171. Onconova Therapeutics
173. Oncternal Therapeutics
175. Oregon State University
176. Orum Therapeutics
177. Osage University Partners
178. Oslo Cancer Cluster
179. Parkwalk Advisors
180. Partner Fund Management
181. Partners for Development Investments in Life Sciences
182. Partnership Fund for New York City
185. Permeon Biologics
188. PHusis Therapeutics
190. Pint Pharma
192. PowerOne Capital Markets
193. Proteros Biostructures
194. Purdue Institute for Drug Discovery
195. Qatar Investment Authority
196. RA Capital Management
197. Ractigen Therapeutics
198. RBC Capital Markets
199. Redx Pharma
200. Revolution Medicines
203. Rockefeller Institute
204. ROTH Capital Partners
205. Sanford Burnham Prebys Medical Discovery Institute
208. Scripps Research Institute
209. SEngine Precision Medicine
210. Seventure Partners
211. ShangPharma Investment Group
213. Silicon Therapeutics
214. Singh Biotechnology
215. Sirona Capital
216. Sloan-Kettering Institute for Cancer Research
217. Solidus Investment
218. Sosei Group
219. Spanish Ministry of Economy and Competition
221. Sumitomo Dainippon Pharma
222. SupremeCure Pharma
223. SV Health Investors
224. Syndax Pharmaceuticals
226. Taiho Oncology
227. Takeda Pharmaceuticals
229. Telethon Kids Institute
232. The Sapkota Laboratory
233. The University of Texas MD Anderson Cancer Center
234. The Wistar Institute
235. TheraPten Biosciences
237. Tokyo University of Science
240. United States Patent and Trademark Office
241. University of Barcelona
242. University of Basel
243. University of Bergen
244. University of California, Berkeley (Nomura Research Group)
245. University of California, San Francisco
246. University of Cambridge
247. University of Chicago
248. University of Dundee
249. University of Kansas, Lawrence
250. University of Minnesota, Twin Cities
251. University of North Carolina, Chapel Hill
252. University of Pennsylvania
253. University of South Florida
254. University of Texas Southwestern Medical Center
255. University of Tokyo
256. University of Toronto
257. University of Utah
258. University of Warsaw
259. University of Washington
260. United States Department of Veterans Affairs
261. United States Food and Drug Administration
262. VA Greater Los Angeles Healthcare System
264. Virginia Commonwealth University
265. Vitae Pharmaceuticals
266. Vividion Therapeutics
267. Warp Drive Bio
268. Whitehead Institute for Biomedical Research
269. Whitesun Healthcare Ventures
270. WI Harper Group
271. X4 Pharmaceuticals
272. Yale University
273. Zelluna Immunotherapy