Cancer is known to be one of the leading causes of death worldwide. In the US, 0.6 million deaths were reported to have been caused due to cancer in 2018 alone. Further, according to the International Agency for Research on Cancer (IARC), close to 17 million new cancer cases were reported in 2018, worldwide. By 2040, it is estimated that the aforementioned number is likely to grow to 27.5 million. It is worth mentioning that in the past five years, the United States Food and Drug Administration (USFDA) has approved more than 100 drugs for the treatment of different types of cancer. However, as the growing global population is gradually being exposed to a growing list of risk factors and cancer causing agents, there is a pressing need for more specific and potent drugs / therapies to combat this complex, life threatening clinical condition. Over time, conventional treatment options, such as chemotherapy, surgery and radiation therapy, have shown limited efficacy in treating late-stage cancers. In addition, the non-specific and highly toxic nature of these therapies have severe detrimental effects on patients’ quality of life.
Defects in deoxyribonucleic acid (DNA) repair have been shown to be one of the primary causes of cancer. Moreover, tumor cells that are characterized by impaired DNA repair pathways typically become reliant on alternative DNA repair pathways for survival. This phenomenon is commonly referred to as oncogene addiction. Inhibitors of such compensatory repair pathways have the potential to sensitize cancer cells to DNA damaging agents and other therapeutic regimens. On the other hand, the simultaneous inactivation of certain pairs of genes have been shown to cause cell death. This phenomenon is known as synthetic lethality. In cancers, where mutations have led to the loss of function of one gene, using a drug molecule that specifically targets the corresponding gene of the synlet pair has been demonstrated to be a viable and effective therapeutic regimen. Recent advances in biomarker research, including the development of companion diagnostics, in combination with modern molecular screening platforms, which include clustered regularly interspaced short palindromic repeats (CRISPR)- and RNA interference (RNAi)-based screening techniques, have led to the identification of a number of synthetically lethal gene pairs.
Currently, there are four approved (and marketed) poly-ADP ribose polymerase (PARP) inhibitor drugs, which have been shown to operate based on the concept of synthetic lethality. Further, several such drugs are being investigated for the treatment of a myriad of advanced oncological and non-oncological indications. A number of companies are engaged in this domain; moreover, both venture capital (VC) firms and government bodies are actively funding such research initiatives.
Scope of the Report
The ‘Synthetic Lethality-based Drugs and Targets Market, 2019-2030: Focus on DNA Repair (including PARP Inhibitors) and Other Novel Cellular Pathways’ report features an extensive study of the current market landscape and the future potential of the synthetic lethality-based therapeutics. It features an in-depth analysis, highlighting the capabilities of various companies engaged in this domain. In addition to other elements, the study includes:
- A detailed assessment of the current market landscape, providing information on drug developer(s) (year of establishment, headquarters and size of the company), phase of development (marketed, clinical, preclinical, and discovery stage) of lead candidates, type of molecule (small molecule and biologic), type of therapy (monotherapy and combination therapy), type of synlet target, target patient segment, key therapeutic area(s), target indication(s), and route of administration. In addition, the chapter includes a list of screening platforms that are being used by industry players to study synlet interactions between gene pairs.
- Detailed profiles of large players that are engaged in the development of synthetic lethality-based drugs (shortlisted on the basis of phase of development of pipeline products), featuring a brief overview of the company, its financial information (if available), detailed profiles of their respective lead drug candidates, and an informed future outlook. Additionally, each drug profile features information on the type of drug, route of administration, target indications, current status of development and an excerpt on its developmental history. In addition, the chapter includes tabulated profiles of small-sized and mid-sized players (shortlisted on the basis of the number of pipeline products), featuring details on the innovator company (such as location of headquarters, year of establishment, number of employees, and key members of the executive team), recent developments, along with descriptions of their synthetic lethality-based drug candidates.
- An analysis of the prevalent and emerging trends in this domain, as represented on the social media platform, Twitter, posted during the period 2010-2019 (till May), highlighting the historical trend of tweets, most prolific contributors, frequently discussed synlet targets, popular disease indications and a multivariate tweet benchmark analysis.
- An analysis of close to 700 peer-reviewed scientific articles related to synthetic lethality, published during the period 2017-2019 (till May), highlighting the research focus within this niche industry segment. It includes an informed opinion on the key trends observed across the aforementioned publications, including information on target disease indications, synlet targets, and analysis based on various relevant parameters, such as study type (review article, research article and case report), research objective, year of publication, key research hubs, most popular authors, provision of grant support, and most popular journals (in terms of number of articles published in the given time period and journal impact factor).
- An analysis of various abstracts presented at the American Society of Clinical Oncology (ASCO) in the time period 2013-2019 (till May), highlighting several parameters, such as year of (abstract) publication, popular drugs, synlet targets, target cancer indications, popular authors, author designations, industry type (industry and academia) and most active organizations (in terms of number of published abstracts). In addition, this analysis features a multi-dimensional bubble chart analysis to assess the relative level of expertise of the key authors / researchers based on the number of publications, citation count and research gate score.
- An in-depth analysis of close to 750 grants that have been awarded to research institutes engaged in projects related to synthetic lethality, between 2014 and 2019 (till May), highlighting various important parameters associated with grants, such as year of award, support period, amount awarded, funding institute, administration institute center, funding institute center, funding mechanism, spending categorization, grant type, responsible study section, focus area, type of recipient organization and prominent program officers. It also features a detailed analysis on most popular synlet targets and target indications, along with a multivariate grant attractiveness analysis based on parameters, such as amount awarded, support period, grant type, number of synlet targets and number of indications under study.
- An analysis of the investments made into companies that have proprietary synthetic lethality-based drugs / screening platforms, including seed financing, venture capital financing, debt financing, grants, capital raised from IPOs and subsequent offerings.
- An in-depth benchmark analysis of over 230 synlet targets identified from various credible sources (research publications, government fundings, clinical studies, recent news / tweets and abstracts presented in global conferences), highlighting targets that have already been validated in clinical studies, preclinical studies and early-stage research (cases where there is no lead (therapeutic) candidate being investigated). Further, it highlights the long-term opportunities (for drug developers) associated with individual targets, based on their popularity across different portals.
- An analysis of the role of innovative companion diagnostics in synthetic lethality on the basis of several parameters, such as synlet target, drug candidate(s) being investigated, target biomarker(s), target disease indication(s) and assay technique used. It also includes case studies, highlighting those companion diagnostic tests that are available and are being used to evaluate the therapeutic efficiency of approved PARP inhibitors using the principle of synthetic lethality.
One of the key objectives of the report was to estimate the existing market size and identify the future opportunity for synthetic lethality-based drugs, over the next decade. Based on multiple parameters, such as target consumer segments, region-specific disease prevalence, anticipated adoption of the marketed and late stage drugs and the likely selling price, we have provided informed estimates on the evolution of the market over the period 2019-2030. The report includes potential sales forecast of drugs that are currently marketed or are in late stages of development (phase II and above). The report also features the likely distribution of the current and forecasted opportunity across [A] type of molecules (small molecule and biologic), [B] different target indications (breast cancer, colorectal cancer, fallopian tube cancer, gastric cancer, head and neck cancer, lung cancer, ovarian cancer, peritoneal cancer and others), [C] synlet targets (APE1 / Ref-1, Chk1, GLS1, PARP, Pol θ, PP2A and Wee1), [D] route of administration (oral and intravenous), and [E] key geographical regions (North America, EU5, Asia-Pacific and Rest of the World). To account for the uncertainties associated with the growth of synthetic lethality-based drugs market and to add robustness to our model, we have provided three market forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry’s growth.
The opinions and insights presented in this study were also influenced by discussions conducted with multiple stakeholders in this domain. The report features detailed transcripts of interviews held with the following individuals (in alphabetical order of company names):
- Simon Boulton (Vice President, Science Strategy, Artios Pharma)
- Yi Xu (Associate Director, Business Development, IMPACT Therapeutics)
- Norbert Perrimon (Professor, Department of Genetics, Harvard Medical School)
- Vivek Dharwal (Professor, Department of Biochemistry, Panjab University)
- Alfred Nijkerk (Chief Executive Officer, UbiQ)
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.
Table of Contents
Executive Summary
Chapter 2 provides an executive summary of the insights captured during our research. It offers a high-level view on the current state of the synthetic lethality-based drugs market and its likely evolution in the short-mid term and long term.
Chapter 3 provides a general introduction to the DNA damage and associated repair systems in the human body. This section features a detailed discussion on the different types of DNA damage that have been identified so face, along with their respective causes. It also features detailed descriptions of DNA repair systems and associated biological pathways that are activated during the detection of damage within the cell’s genetic code. Further, the chapter includes a discussion on the potential therapeutic benefits of targeting defects in DNA repair pathways for the treatment of different disease indications, such as cancer.
Chapter 4 provides an overview of the concept of synthetic lethality, including details on the associated pathways and their respective mechanisms of action. Further, it includes a discussion on the conception, historical evolution, importance, applications and challenges related to the use of synthetic lethality as a therapeutic principle. The chapter also highlights the most popular types of screening approaches that are used in the identification of synlet gene pairs. Additionally, it includes an analysis of contemporary Google Trends (as of June 2019) and insights from recent news articles related to the concept of synthetic lethality.
Chapter 5 includes information on nearly 75 synthetic lethality-based drugs that are currently approved or under development for the treatment of various indications. It features a comprehensive analysis of pipeline molecules, highlighting phase of development (marketed, clinical, preclinical and discovery stage) of lead candidates, type of molecule (small molecule and biologic), type of therapy (monotherapy and combination therapy), type of synlet target, target patient segment, key therapeutic area(s) and target indication(s), and route of administration of the drugs that are being developed for the treatment of cancer. Further, the chapter provides information on drug developer(s), highlighting their year of establishment, location of headquarters and employee strength. In addition, the chapter highlights the various screening platforms that are being actively used by the industry to study synlet interactions between gene pairs.
Chapter 6 features detailed profiles of some of the large companies developing synthetic lethality-based drugs (shortlisted on the basis of phase of development of pipeline products). Each company profile includes a brief overview of the company, its financial information (if available), detailed descriptions of their synthetic lethality-based drugs, and a comprehensive future outlook. Additionally, each drug profile features information on type of drug, route of administration, indications, current status of development and an excerpt on its developmental history. In addition, the chapter includes tabulated profiles of small-sized and mid-sized players (shortlisted on the basis of the number of pipeline products), featuring details on the innovator company (such as location of headquarters, year of establishment, number of employees, and key members of executive team,) recent developments, along with descriptions of their synthetic lethality-based drug candidates.
Chapter 7 provides insights on the popularity of synthetic lethality on the social media platform, Twitter. The section highlights the yearly distribution of tweets, posted on the platform during the period 2010-2019 (till May), and the most significant events responsible for increase in the volume of tweets each year. Additionally, the chapter highlights the most prolific contributors, frequently discussed synlet targets, popular disease indications, and a multivariate tweet benchmark analysis in order to highlight the most popular tweets.
Chapter 8 provides a detailed analysis of close to 700 peer-reviewed scientific articles related to synthetic lethality, published during the period 2017-2019 (till May). The analysis takes into consideration target disease indications, synlet targets, and analysis based on various relevant parameters, such as study type (review article, research article and case report), research objective, year of publication, key research hubs, most popular authors, provision of grant support, and most popular journals (in terms of number of articles published in the given time period and journal impact factor). The chapter also features detailed valuation analysis for recent publications.
Chapter 9 features a detailed analysis of various abstracts related to synthetic lethality presented at ASCO in the period 2013-2019 (till May). The analysis is based on multiple parameters, such as year of (abstract) publication, popular drugs, synlet targets, target cancer indications, popular authors, author designations, industry type (industry and academia) and most active organizations (in terms of published abstracts). In addition, this chapter features a multi-dimensional bubble chart analysis to assess the relative level of expertise of the key authors / researchers based on number of publications, citation count and research gate score.
Chapter 10 provides information on close to 750 grants that were awarded to research institutes engaged in projects related to synthetic lethality, between 2014 and 2019 (till May). The analysis also highlights important parameters associated with grants, such as year of award, support period, amount awarded, funding institute, administration institute center, funding institute center, funding mechanism, spending categorization, grant type, responsible study section, focus area, type of recipient organization and prominent program officers. It also features a detailed analysis on most popular targets and target indications, along with a multivariate grant attractiveness analysis based on parameters; such as amount awarded, support period, grant type, number of synlet targets and number of indications under study.
Chapter 11 presents details on various investments received by start-ups / small-sized and mid-sized companies that are engaged in this domain. It also includes an analysis of the funding instances that have taken place in the market, in the period 2017-2019 (till May), highlighting the growing interest of the venture capital (VC) community and other strategic investors within this domain.
Chapter 12 presents benchmark analysis of over 230 synlet targets identified from various credible sources (research publications, government funding, clinical studies, recent news / tweets and abstracts presented in global conferences), highlighting targets that have already been validated in clinical studies, preclinical studies and early-stage research (cases where there is no lead (therapeutic) candidate being investigated). Further, it also highlights the long-term opportunities (for drug developers) associated with individual targets, based on their popularity across different portals.
Chapter 13 presents information on various companion diagnostics tests that are commercially available / being investigated for drugs that are designed to exploit the synthetic lethality mechanism. The chapter analyzes the innovative companion diagnostics on the basis of several parameters, such as the synlet target, drug candidate(s) being investigated, target biomarker(s), target disease indication(s) and assay technique used. It also includes case studies, highlighting those companion diagnostic tests that are available and are being used to evaluate the therapeutic efficiency of approved PARP inhibitors using the principle of synthetic lethality.
Chapter 14 features a detailed market forecast of the likely growth of synthetic lethality-based drugs till the year 2030. We have provided inputs on the likely distribution of the current and forecasted opportunity across type of molecules (small molecule and biologic), target indications (breast cancer, colorectal cancer, fallopian tube cancer, gastric cancer, head and neck cancer, lung cancer, ovarian cancer, peritoneal cancer and others), synlet targets (APE1 / Ref-1, Chk1, GLS1, PARP, Pol θ, PP2A and Wee1), different route of administration (oral and intravenous) and key geographical regions (North America, EU5, Asia-Pacific and Rest of the World). To account for future uncertainties associated with the growth of synthetic lethality-based drugs market and to add robustness to our model, we have provided three market forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industry’s growth.
Chapter 15 summarizes the entire report. It presents a list of key takeaways and offers our independent opinion on the current market scenario. Further, it captures the evolutionary trends that are likely to determine the future of synthetic lethality-based drugs market.
Chapter 16 is a collection of interview transcripts of discussions held with key stakeholders in this market. In this chapter, we have presented the details of interviews held with (in alphabetical order of company names) Simon Boulton (Vice President, Science Strategy, Artios Pharma), Yi Xu (Associate Director, Business Development, IMPACT Therapeutics), Norbert Perrimon (Professor, Department of Genetics, Harvard Medical School), Vivek Dharwal (Professor, Department of Biochemistry, Panjab University) and Alfred Nijkerk (Chief Executive Officer, UbiQ).
Chapter 17 is an appendix, which provides tabulated data and numbers for all the figures included in the report.
Chapter 18 is an appendix, which provides the list of companies and organizations mentioned in this report.
Companies Mentioned (Partial List)
A selection of companies mentioned in this report includes, but is not limited to:
- 3W Partners
- 5AM Ventures
- 6 Dimensions Capital
- 8VC
- Abbott
- AbbVie
- AbbVie Ventures
- Abingworth
- Adage Capital Partners
- Adams Street Partners
- Advanced Technology Ventures
- Agilent Technologies
- Agios Pharmaceuticals
- Alaska Women's Cancer Care
- Alexandria Real Estate
- Alexandria Venture Investments
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Allergan
- Almac
- Altitude Life Science Ventures
- Amadeus Capital Partners
- American Association for Cancer Research
- Amherst Fund
- Amoy Diagnostics
- Andera Partners
- Angel Investors
- Apexian Pharmaceuticals
- Apjohn Ventures Fund
- Apollo Munich Health
- Aptose Biosciences
- ARCH Venture Partners
- Arix Bioscience
- Arkin Holdings
- Artios Pharma
- Astellas Ventures
- AstraZeneca
- AtlasMedx
- Atrin Pharmaceuticals
- Austrian Science Fund
- AVICT
- Baylor College of Medicine
- BDC Capital’s Healthcare Venture Fund
- Beckman Research Institute
- BeiGene
- Beth Israel Deaconess Medical Center
- Biodesix
- Biogenex Laboratories
- BioMed Ventures
- BioMedical Catalyst Fund
- bioMérieux
- Biotechnology and Biological Sciences Research Council
- Boehringer Ingelheim Venture Fund
- Boston College
- Boxer Capital of the Tavistock Group
- Boyu Capital
- Breast Cancer Now
- Brigham And Women'S Hospital
- Broad Institute
- BVF Partners
- C4X Discovery
- Calibr
- Calico
- Calithera Biosciences
- Cambridge Enterprise
- Canaan Partners
- Canadian Cancer Society Research Institute
- Candiolo Cancer Institute
- Capital Midwest Fund
- CareNet Group
- Case Western Reserve University
- Caxton Alternative Management
- Cedars-Sinai Medical Center
- Celgene
- CellCentric
- Cellecta
- Cenova Ventures
- China Investment & Development
- China Summit Capital
- Chordia Therapeutics
- CITIC Private Equity Funds Management
- City of Hope National Medical Center
- Cleveland Clinic Lerner College of Medicine
- Clovis Oncology
- Cold Spring Harbor Laboratory
- Columbia University
- Columbia University Medical Center
- Cornerstone Parkwalk Advisors
- CRT Pioneer Fund
- CStone Pharmaceuticals
- Cyteir Therapeutics
- Daiichi Sankyo
- Dana-Farber Cancer Institute
- Decheng Capital
- Delphi Ventures
- Driehaus Capital
- DROIA
- Duksung Women's University
- EdiGene
- eFFECTOR Therapeutics
- Elevate Ventures
- Emory University
- Epic Sciences
- EpiCypher
- European Research Council
- Fast Track Initiative
- Flagship Ventures
- Fonds de solidarité FTQ
- Forward Informatics
- Foundation Medicine
- Frazier Healthcare Ventures
- Fred Hutchinson Cancer Research Center
- Fresenius Kabi
- Fund for Scientific and Technological Research
- Georgetown University
- GIC
- Google Ventures
- Grand Angels
- Green Pine Capital Partners
- Guangzhou YUEXIU Industrial Investment Fund
- Guardant Health
- Gurdon Institute
- H&Q Asia Pacific
- HAIBANG Ventures
- Harvard Medical School
- Harvard University
- Hopen Life Science Ventures
- Horizon Discovery
- HuagaiCapital
- IDEAYA Biosciences
- Ignyta
- IMPACT Therapeutics
- Imperial Innovations
- Indiana University
- Indiana Univ-Purdue Univ At Indianapolis
- IndieBio
- Innovate Indiana Fund
- Innovate UK
- Institute of Cancer Research
- Institute of Nano Science and Technology
- IP Group
- Israel Science Foundation
- Italian Association for Cancer Research
- JAFCO
- Janus Capital Management
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science
- Johns Hopkins University
- Jonathan Milner
- King Star Capital
- Kyoto University Innovation Capital
- Leica Biosystems
- Life Sciences Partners
- LifeNet Health
- Lightstone
- Lilly Asia Ventures
- Lixte Biotechnology
- LP. Joining Adage
- LUNGevity Foundation
- M Ventures
- Management
- Marie Curie Initial Training Network CodeAge project
- Massachusetts General Hospital
- Mayo Clinic
- MD Anderson Cancer Center
- Merck Ventures
- Metabomed
- MetaStat
- Ministry of Economy and Competitiveness
- Ministry of Education - Singapore
- Mission Bay Capital
- Mission Therapeutics
- Mitsubishi UFJ Capital
- Mizuho Capital
- Moffitt Cancer Center
- Morgan Noble
- Morgenthaler Ventures
- Morphic Therapeutics
- MPM Capital
- MS Ventures
- Mylan
- Myriad Genetics
- National Agency for Science and Technology
- National Cancer Institute
- National Human Genome Research Institute
- National Institutes of Health
- National League Against Cancer
- National Natural Science Foundation of China
- National Research Foundation of Korea
- Natural Science Foundation of Guangdong Province
- Natural Sciences and Engineering Research Council of Canada
- Nextech Invest
- Nippon Venture Capital
- Northeastern University
- Novartis Venture Fund
- Ofinnova Partners
- Ohio State University
- ONO Pharma
- OrbiMed Advisors
- Oregon Health & Science University
- Oriza Seed Venture Capital
- Osage University Partners
- Panjab University
- Pangaea Biotech
- Perceptive Advisors
- Personal Genome Diagnostics
- Pfizer
- Pfizer Ventures
- Pharmacyclics
- Phi Life Sciences
- Philadelphia Center
- PhoreMost
- Pontifax Fund
- Premier Pain and Spine
- Providence Investment Company
- Qameleon Therapeutics
- QIAGEN
- Qualifying Therapeutic Discovery Project Program
- RA Capital Management
- Rainbow Seed Fund
- Repare Therapeutics
- Resolution Bioscience
- Roche
- Roche Venture Fund
- Russian Foundation for Basic Research
- Sakarya University
- Sanford Burnham Prebys Medical Discovery Institute
- São Paulo State Foundation
- SBI Investment
- Scripps Research Institute
- Sectoral Asset Management
- Selvita
- SEngine Precision Medicine
- Senhwa Biosciences
- Sequoia China
- Shanks Lab
- Sheba Medical Center
- Shinsei Capital Partners
- Sierra Oncology
- SignalRx Pharmaceuticals
- Silicon Valley Bank
- Singapore Ministry of Education
- Singapore sovereign wealth fund
- Sloan-Kettering Inst Can Research
- Sloan-Kettering Institute
- SMBC Venture Capital
- Snap Bio
- Sofinnova Partners
- SOSV
- SR One
- SRI International
- St George Hospital
- St. Jude Children's Research Hospital
- Stanford University
- Sungent Bioventure
- SV Health Investors
- SV Life Sciences
- SyntheX Labs
- Taikang Insurance Group
- Takeda Venture Investments
- Tango Therapeutics
- Technion Research and Development Foundation
- Temple University
- Temple University of The Commonwealth
- Teneobio
- Terra Mafnum Capital Partners
- TESARO
- The Column Group
- The Institute of Cancer Research
- The Ohio State University
- The Royal Marsden NHS Foundation Trust
- Thermo Fisher Scientific
- Third Rock Ventures
- Thomas Jefferson University
- Tizona Therapeutics
- Touchstone Innovations
- U.S. Venture Partners
- uBiome
- UbiQ
- UCSF Helen Diller Family Comprehensive Cancer Center
- University College London Cancer Institute
- University Hospital Complex of A Coruña
- University Hospital Frankfurt
- University of Bergen
- University of California
- University of Castilla-La Mancha
- University of Chicago
- University Of Colorado
- University of Colorado Denver
- University of Florida
- University of Glasgow
- University of Health Network
- University of Iowa
- University of Kansas Cancer Center
- University of Kansas Medical Center
- University of Lodz
- University of Macau
- University of Miami
- University of Miami School of Medicine
- University of Navarra Clinic
- University of New Mexico
- University of Oklahoma Health Sciences Center
- University Of Pennsylvania
- University of Pittsburgh Cancer Institute
- University of Rome Tor Vergata
- University of South Alabama
- University of Texas
- University of Washington
- University of Wisconsin-Madison
- US Department of Defense
- US Department of Health and Human Services
- UT Southwestern Medical Center
- UTokyo Innovation Platform
- Vanderbilt University
- Venrock
- Versant Ventures
- Vivo Capital of Palo Alto
- Voyager Therapeutics
- Wellcome Sanger Institute
- Woodford Patient Capital Trust
- Worldwide Cancer Research
- WuXi AppTec Ventures
- WuXi Healthcare Ventures
- Yale School of Medicine
- Yale University
- Yunfeng Capital
Methodology
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