LONDON, May 31, 2017 /PRNewswire/ -- INTRODUCTION
Cancer metabolism is based on the principle that cancer cells, as compared to normal cells, have different metabolic activities in order to support their enhanced energy and anabolic requirements. The pioneering discovery by Otto Warburg in the middle of the 20th century led to the observation that metabolic activity in tumor tissues leads to a ten-fold increase in production of lactate (from glucose) under aerobic conditions. This revelation generated a significant interest and led industry stakeholders to target metabolic pathways in an effort to find the treatment of cancer. In addition, several academic players have also initiated studies to explore the functional consequences of alterations in various metabolic pathways.
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The idea behind therapeutic strategies that target cancer metabolism is to limit / modulate the supply of crucial nutrients in cancer cells in order to induce cell death. Over the years, experimental and conceptual advances in this field have resulted in a better understanding of the role of metabolic pathways for the treatment of cancer. Owing to the complex nature of these pathways, innovation in this domain has been gradual. However, the knowledge that metabolic adaptations in cancer cells promote their malignant properties has led to the development of novel therapeutic approaches for cancer treatment; selective inhibition of altered metabolic pathways in cancer cells is believed to be a highly promising approach.
Currently, there are several molecules that are under preclinical and clinical evaluation. Extensive research is currently being carried out to explore the potential of certain enzymes of metabolic pathways to act as targets for the treatment of cancer. The alterations in metabolic pathways in cancer cells are often mediated by mutations in oncogenes and cell signaling pathways. However, with the recognition of specific enzymes within each metabolic pathway, it is anticipated that drugs targeting these enzymes are likely to have high efficacy in treating cancer with minimal side-effects.
Despite the fact that the field of cancer metabolism therapeutics is still in early stages, there are many active players in this area. A larger proportion of players (on the basis of number of molecules) are small-sized and start-up companies. In fact, well-known big pharma companies have come together with smaller players to support discovery and development of such therapies. Our research indicates that there are several players with mid / late-stage clinical candidates that are likely to enter the market in the coming decade; examples include Agios Pharmaceuticals, Celgene, Polaris Group, Bio-Cancer Treatment International, BERG Health, Cornerstone Pharmaceuticals, Taiho Pharmaceutical, Novartis and 3-V Biosciences.
A number of strategic and research collaborations have been inked between companies to progress research activities in this area. As clinical stage candidates progress towards advanced stages of development and companies continue to receive monetary support from different stakeholders, we expect an aggressive growth to unfold over the coming years.
SCOPE OF THE REPORT
The "Cancer Metabolism Based Therapeutics Market, 2017-2030" report provides an extensive study on the current landscape of the emerging pipeline of novel drugs that target metabolic pathways in cancer cells and offers a comprehensive discussion on the likely future potential.
The primary focus is on drugs that lead to metabolic reprogramming in cancer cells by altering / inhibiting the activity of key enzymes / transporters that are a part of glucose metabolism, amino acid metabolism, TCA cycle, lipid metabolism, nucleotide metabolism and pentose phosphate pathway. The scope includes novel products that are being specifically developed to target altered metabolic pathways and key enzymes / amino acids involved in the metabolism of cancer cells. Examples of such enzymes / amino acids include isocitrate dehydrogenase 1 mutant (IDH 1), arginine, glutamine, MTH1, L-type amino acid transporter 1 (LAT1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB3), choline kinase (ChoK), glucose transporter-1 (Glut-1) and hexokinase II. Specifically, certain drugs based on amino acid metabolism are being developed under the class of immuno-oncology drugs; these have been excluded from the scope of this document.
The overall pipeline comprises of 48 molecules that are under development for the treatment of a variety of oncological indications. Of these, 20 molecules are undergoing clinical evaluation while others (28) are in discovery / preclinical stages. This unexploited and promising market has its hopes pinned on multiple start-ups and small-sized companies, which have received significant financial support from strategic investors and venture capital firms in the recent past.
Amongst other elements, the report provides information on:
- The current state of the market with respect to key players, phase of development of pipeline products (both clinical and preclinical / discovery), target enzymes / metabolic pathways and the key disease indications.
- Comprehensive profiles of the clinical stage (phase III, phase II/III, phase II, phase II (planned)) molecules highlighting details on development of the drug, clinical trials, clinical trial endpoints, key preclinical / clinical findings, developer details including their financial performance (if available) and future market opportunity.
- 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, mergers / acquisitions and other such deals signed between stakeholders in the industry or with non-industrial players.
- Distribution of the pipeline through a schematic funnel analysis, an overview of the landscape of industry developers (small, mid-sized and large players) and the geographical distribution of the companies involved in the development of cancer metabolism therapeutics.
- Key targets, shortlisted based on dot-plot analysis, three-dimensional bubble analysis and five-dimensional spider-web analysis. Relevant parameters such as number of publications, grant programs, number of clinical trials, phase of development, and number of companies developing drugs for specific targets were considered for these analyses.
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 from 2017 to 2030. The research, analysis and insights presented in this report are backed by a detailed understanding of the therapies targeting cancer metabolism and other targets closely associated with them. To account for uncertainties associated with the development of novel therapeutics and add robustness to our model, we have provided three scenarios for our market forecast, namely the conservative, base and optimistic scenarios. 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.
1.1. RESEARCH METHODOLOGY
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 may evolve across different regions and sub-segments. Wherever 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 till 2030, 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 sources of information.
1.2. CHAPTER OUTLINES
Chapter 2 presents an executive summary of the report. It offers a high level view on the current state of the cancer metabolism based therapeutics market and its likely evolution in the mid-long term.
Chapter 3 provides a general introduction to the underlying concepts of cancer metabolism, emphasizing on the role of disrupting metabolic pathways in cancer cells. The chapter covers detailed information on the Warburg effect, mechanism of key metabolic pathways (amino acid metabolism, lipid metabolism, nucleotide metabolism, pentose phosphate pathway and TCA cycle), the role of target enzymes within each pathway and the challenges associated with targeting metabolic pathways. We have also provided a list of key targets that have been the focus of industry players.
Chapter 4 provides a comprehensive overview of the current landscape of the cancer metabolism based therapeutics market. It includes information on the drug candidates that are currently in different stages of development (both clinical and preclinical / discovery) and presents a detailed analysis of the pipeline products on the basis of target indications, therapeutic area, phase of development, type of molecule, target enzymes, route of administration and key players involved in this space.
Chapter 5 contains detailed profiles of the drugs that are being evaluated in advanced stages of clinical development (phase III, phase II/III, phase II, phase II (planned)). Each profile features a general overview of the drug and provides information on additional aspects, such as number of clinical trials, key clinical trial endpoints, clinical trial results, and an overview, financial performance and future outlook of the developer.
Chapter 6 provides a comprehensive market forecast, highlighting the future potential of the market till 2030. It includes future sales projections of molecules in phase III, phase II/III, phase II and phase II (planned) of development. The sales potential and growth opportunity is based on the target patient populations, existing / future competition, and the likely adoption rates and price points.
Chapter 7 presents details on the investments and grants received by the companies working in the field of cancer metabolism. The analysis highlights the growing interest of the venture capital community and other strategic investors in this market.
Chapter 8 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 9 is a compilation of certain key insights gained from the study. It features an analysis of the landscape of developers (small, mid-sized and large companies) that are active in this area and their geographical presence. It also provides a schematic representation highlighting the distribution of pipeline drugs and the targeted metabolic pathway within the field of cancer metabolism. We have also included a clinical validation analysis that was conducted to highlight the most popular targets / pathways based on the number of publications, grant programs, clinical trials, phase of development, and number of companies developing drugs for each target.
Chapter 10 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 11 is a collection of interview transcript(s) of the discussion(s) held with stakeholders in the field of cancer metabolism.
Chapter 12 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.
Chapter 13 is an appendix, which provides the list of companies and organizations mentioned in the report.
1. Of the total drugs targeting cancer metabolism, ~40% are being investigated in clinical stages of development. Examples of late-stage drugs include enasidenib (awaiting FDA approval), ivosidenib (phase III), ADI-PEG 20 (phase II/III), BCT-100 (phase II), BPM 31510 (phase II), CPI-613 (phase II), TAS-114 (phase II), IDH305 (phase II (planned)) and TVB-2640 (phase II (planned)).
2. Glycolysis, the most primitive pathway utilized by cancer cells to harness their energy requirement, has been extensively researched. It is followed by amino acid metabolism. Both these pathways capture over 20% of the pipeline each. TCA cycle is the third most popular pathway and accounts for 17% of the overall development pipeline.
3. During our research, we identified over 35 companies that are actively engaged in the development of drugs that target enzymes involved in various metabolic pathways. The overall market is distributed across different regions; majority of the players are located in the US (61%), followed by Germany (16%) and the UK (5%). Further, around 63% of the total companies we identified are small-sized players; examples include (in alphabetical order) 3-V Biosciences, Advanced Cancer Therapeutics, Aeglea BioTherapeutics, Bio-Cancer Treatment International, Calithera Biosciences, Cornerstone Pharmaceuticals, J Pharma, New Medical Enzymes, Polaris Group and Translational Cancer Drugs Pharma. Mid-sized players that are active in this area include Agios Pharmaceuticals, BERG Health, Forma Therapeutics and vTv Therapeutics. Established players that are actively involved in the development of both preclinical and clinical candidates include (in alphabetical order) AstraZeneca, Bayer, Celgene, Daiichi Sankyo, Genentech, Gilead Sciences, Merck KGaA, Novartis, Selvita and Taiho Pharmaceutical.
4. Several academic / research institutes are also conducting extensive R&D activities in this field. Examples of such institutes include (in alphabetical order) Cancer Research Technology (part of Cancer Research UK), European Molecular Biology Laboratory, Ludwig Institute for Cancer Research, MD Anderson Cancer Center, National Cancer Institute (NCI), University of Florida, University of Louisville's James Graham Brown Cancer Center, Wake Forest University and Weill Cornell Medical College.
5. Close to 40 deals have been signed over the last decade; these encompass product development and / or commercialization agreements (over 33%), research collaborations (26%), license agreements (20%), clinical trial collaborations (10%) and mergers / acquisitions (10%). In fact, several companies have entered into multiple collaborations; examples include Agios Pharmaceuticals, Celgene, Advanced Cancer Therapeutics, Merck KGaA, Polaris Group, AstraZeneca, BERG Health, Calithera Biosciences, Cornerstone Pharmaceuticals, FORMA Therapeutics, Janssen Biotech, Selvita and Sprint Bioscience.
6. Angel investors, venture capitalists and funding programs of various other organizations have provided monetary assistance to start-ups / small companies to pace up their R&D programs. Notably, close to USD 1.3 billion has been invested in this domain over the past few years.
7. With several promising candidates in the pipeline, the cancer metabolism based therapeutics market is expected to prosper in the long term; our outlook is highly optimistic as we expect the emergence of several successful drugs in the coming decade. Post the launch of the first wave of products, we anticipate the field to witness considerable success and grow at an annualized rate of ~100% till 2030.
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