Targeted Protein Degradation Market: Focus on Technology Platforms and Therapeutics: Distribution by Type of Protein degrader, Therapeutic Areas, Route of administration, Key Contributing Technologies and Key Geographies, 2021-2030

Overview

Targeted protein degradation is a revolutionary pharmacological concept that presents viable drug development opportunities and is anticipated to introduce a new paradigm in modern therapeutic interventions. Due to various reasons, conventional drugs / therapies have been limited in terms of their capability to target certain proteins of pathological significance. Presently, medical researchers engaged in the development of bifunctional protein degrader-based interventions claim that this upcoming class of drugs is capable of targeting biomolecules in the human proteome, which were previously considered undruggable. The concept of targeted protein degradation revolves around the use of small molecule leads, which are capable of recruiting the ubiquitin-proteasome system (UPS) to selectively eliminate a target biomolecule. In other words, protein degraders regulate biological pathways by selectively downregulating a target protein by degrading them; this process has been shown to be robust, more sensitive to drug-resistant targets and can regulate cellular functions that are not dependent on enzyme action. Moreover, drugs designed based on this relatively novel concept, have been shown to demonstrate a remarkable level of selectivity, high potency, oral bioavailability and differentiated pharmacology, compared to traditional enzyme inhibitors. As a result, this upcoming class of drugs has garnered significant interest within the medical science community. In fact, the growing popularity of targeted protein degradation is evident in the USD 5 billion in capital investments made into companies engaged in this field of research, since 2014.

Proteolysis targeting chimera (PROTAC), developed by Hashimoto Laboratory in 2008, was the first targeted protein degrader. The incessant efforts of researchers involved in this domain have resulted in significant progress towards understanding the physiochemical and biological properties of such bifunctional molecules. Presently, there are several other types of targeted protein degraders and molecular glues, which have been / are being developed for the treatment of a variety of clinical conditions, including acute myeloid leukemia, Alzheimer's disease, breast cancer, myelofibrosis, multiple myeloma, Parkinson's disease, prostate cancer, psoriasis, rheumatoid arthritis, and supranuclear palsy. It is worth noting that the R&D efforts in this field are supported by DNA-encoded libraries and other in silico hit discovery and characterization tools. In the last 4-5 years, there has been a marked rise in the number of new entrants in this market. Additionally, several big pharma players are also actively involved in this field, evaluating proprietary protein degrader-based therapeutic leads. The market has also witnessed substantial partnership activity over the last few years, with several technology developers involved in high-value licensing deals. Although, there are no approved protein degrader-based drugs / therapy products, the market is poised to witness healthy growth over the next decade.

Scope of the Report

The ‘Targeted Protein Degradation Market: Focus on Technology Platforms and Therapeutics (2nd Edition), 2021-2030: Distribution by Type of Protein degrader (degronimids, PROTACs, SARDs / SERDs, and specific BET and DUB inhibitors, and other inhibitors), Therapeutic Area (Neurological Disorders, Oncological Disorders, and Other Therapeutic Areas), Route of administration (Oral, Intravenous and Others), Key Contributing Technologies and Key Geographical Regions (North America, Europe, Asia-Pacific, Latin America, Middle East and North Africa, and Rest of the World)’ report features an extensive study of the current and future potential of protein degraders, offering an informed opinion on the likely adoption of these therapeutics and affiliated technologies, over the next decade. The focus of this study is on specially designed small molecule degraders, including degronimids, endosome targeting chimeras (ENDTACs), epichaperome inhibitors, hydrophobic tags, immuno-modulatory imide drugs (IMiDs), lysosome targeting chimeras (LYTACs), molecular glues, photochemically targeting chimeras (PHOTACs), proteolysis targeting chimeras (PROTACs), protein homeostatic modulators, selective androgen receptor degraders (SARDs), selective estrogen receptor degraders (SERDs), specific and non-genetic IAP-dependent protein erasers (SNIPERs), and specific bromodomain and extra-terminal motif (BET) inhibitors and deubiquitinase (DUB) inhibitors. In addition, the report features an in-depth analysis, highlighting the diverse capabilities of stakeholders engaged in this domain.  

Amongst other elements, the report includes:

• A detailed review of the current market landscape of targeted protein degradation-based therapeutics, including information on type of protein degrader (degronimids, ENDTACs, epichaperome inhibitors, hydrophobic tags, IMiDs, LYTACs, molecular glues, PHOTACs, PROTACs, protein homeostatic modulators, SARDs, SERDs, SNIPERs, and specific BET and DUB inhibitors), phase of development (clinical, preclinical, and discovery stage) of product candidates, target indication(s), key therapeutic area(s), type of biological target(s), associated ubiquitin ligase(s) (if available), target signaling pathway (if available), mechanism of action (if available), type of therapy (monotherapy and combination therapy), route of administration (oral, intravenous and others). In addition, it presents a list on drug / therapy developer(s) (such as year of establishment, company size and location of headquarters), clinical study sponsor(s) and collaborator(s). 
• An overview of the overall landscape of target protein degradation enabling technologies, featuring an analysis based on type of degrader. In addition, it presents a list of targeted protein degradation enabling technology developers and analysis based on various parameters, such as year of establishment, company size and location of headquarters. 
• Detailed profiles of prominent players engaged in the development of targeted protein degraders (shortlisted on the basis of phase of development of pipeline products). Each profile features a brief overview of the company, its financial information (if available), detailed description of their respective lead drug candidates, and recent developments and an informed future outlook. Additionally, each drug profile features information on the type of drug, current status of development, route of administration, target indications, and a brief summary of its developmental history. 
• Tabulated profiles of leading industry players (shortlisted on the basis of the number of candidates in development pipeline). Each profile includes details on the innovator company (such as year of establishment, location of headquarters, number of employees, and key members of the executive team), recent developments, along with information on respective drug candidates. 
• An in-depth analysis of completed, ongoing and planned studies of various targeted protein degraders, highlighting prevalent trends across various relevant parameters, such as current trial status, trial registration year, enrolled patient population and regional distribution of trials, type of protein degrader, phase of development, study design, leading industry and non-industry players (in terms of number of trials conducted), trial focus, target therapeutic area, key indications, and clinical endpoints.
• A detailed analysis of grants that have been awarded to various research institutes for targeted protein degradation projects, in the period between 2017 and 2020, on the basis of important parameters, such as year of award, amount awarded, administering institute center, support period, funding mechanism, type of grant application, purpose of grant award, activity code, emerging focus areas of the grants, study section, popular NIH departments, study section, and type of recipient organization, highlighting popular recipient organizations, popular program officers and regional distribution of recipient organizations.  
• A detailed publication analysis peer-reviewed, scientific articles that have been published between 2017 and Q3 2019, highlighting the research focus within the industry. It also highlights the key trends observed across publications, including information on type of publication, year of publication, study objective, popular keywords, type of protein degrader, biological target, associated ubiquitin enzyme, number of publications, type of publisher, leading players (in terms of number of publications), region, and key journals (in terms of number of articles published in this domain and impact factor of the journal). 
• An insightful analysis of the patents filed / granted for targeted protein degradation enabling technologies, since 2018, taking into consideration various parameters, such as type of patent, publication year, geographical location, type of applicant, issuing authority / patent offices involved, CPC symbols, emerging focus areas, leading players (in terms of number of patents granted / filed in the given time period), patent characteristics and geography. The chapter also includes a detailed patent benchmarking and an insightful valuation analysis.
• A list of key opinion leaders (KOLs) within this domain, and their assessment (based on the strength and activeness) represented in the form of 2×2 matrices. The chapter also includes a schematic world map representation (highlighting the geographical locations of eminent scientists / researchers) and an analysis evaluating the (relative) level of expertise of different KOLs, based on number of publications, number of citations, participation in clinical trials, number of affiliations and strength of professional network (based on information available on ResearchGate).
• An analysis of the partnerships that have been established in this domain, during the period 2014-2020, covering research agreements, product / technology licensing agreements, mergers / acquisitions, asset purchase agreements, R&D and commercialization agreements, IP licensing agreements, clinical trial agreements, product development agreements, and other relevant deals.
• An analysis of the investments in the form of seed financing, venture capital financing, debt financing, grants / awards, initial public offerings (IPOs) and subsequent offerings, made at various stages of development of the companies engaged in this field.
• A detailed deal structure analysis, highlighting cash flows and net present values of licensor and licensee, taking into consideration multiple likely scenarios of upfront, milestone and royalty payments.

One of the key objectives of the report was to estimate the existing market size and identify potential future growth opportunities of novel technologies for the development of targeted protein degraders. Based on the likely licensing deal structures and agreements that are expected to be signed in the foreseen future, we have provided informed estimates on the evolution of the market over the period 2021-2030. For estimating the future market opportunities for technology providers, we have considered the likely licensing deal structures and agreements that are likely to be established in the foreseen future. The future opportunity within the targeted protein degradation market has been segmented across [A] different types of protein degraders (degronimids, PROTACs, SARDs / SERDs, Specific BET and DUB Inhibitors, and other inhibitors), [B] therapeutic areas (oncological disorders, neurological disorders, and other therapeutic areas), [C] route of administration (oral route, intravenous route, and other routes), and [D] key geographical regions (North America, Europe and Asia Pacific). In order to account for future uncertainties associated with the growth of targeted protein degradation 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 influenced by discussions conducted with several stakeholders in this domain. 

The report features detailed transcripts of interviews held with the following individuals (in alphabetical order):

• Laura Itzhaki, Founder and Chief Scientific Officer, Polyprox Therapeutics
• Louise Bergeron, Vice President, Xios Therapeutics
• Martin Wiles, Vice President Business Development and Licensing, Almac Discovery & Gerald Gavory, Director of Biology, Almac Discovery
• Jason Brown, Scientific and Business Development Director, Ubiquigent
• Anonymous, Director of Oncology Research, Large Company
• Anonymous, Chief Scientific Officer, Very Small Company
• Paul Wallace, Chief Business Officer, Mission Therapeutics
• Katrin Rittinger, Research Group Leader, Francis Crick Institute
• Zhihao Zhuang, Associate Professor, Department of Chemistry and Biochemistry, University of Delaware

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.

Key Questions Answered

• Who are the leading industry and non-industry players engaged in this market?
• What are the key therapeutic areas for which target protein degraders are being / have been developed?
• Which geographies are the most active in conducting clinical trials on target protein degraders?
• What kind of partnership models are commonly adopted by industry stakeholders? 
• Which are the leading administering institute centers supporting the research related to this domain?
• What is the trend of capital investments in the targeted protein degradation market?
• How has the intellectual property landscape in this market evolved over the years?
• How is the current and future market opportunity likely to be distributed across key market segments