August 2019

Advances in the fields of cell biology and regenerative medicine have led to the development of a variety of stem cell-based therapies for many cardiovascular, oncological, metabolic and musculoskeletal disorders. Driven by the revenues generated from stem cell therapies, the regenerative medicine market is anticipated to generate revenues worth USD 100 billion by 2030. With a promising pipeline of over 200 stem cell therapy candidates, it has become essential for developers to scale up the production of such therapeutic interventions.  Given that stem cell therapy manufacturing requires highly regulated, state-of-the-art technologies, it is difficult for stakeholders to establish in-house expertise for large-scale manufacturing of stem cell therapies. As a result, stem cell therapy developers have begun outsourcing their manufacturing operations to contract manufacturing organizations (CMOs) . Specifically, small and mid-sized players in this sector tend to outsource a substantial proportion of clinical and commercial-scale manufacturing processes to contract service providers. In addition, even big pharma players, with established in-house capabilities, are gradually entering into long-term business relationships with CMOs in order to optimize resource utilization and manage costs. According to a recent Nice Insight CDMO survey, about 55% of 700 respondents claimed to have collaborated with a contract service provider for clinical and commercial-scale product development requirements. Considering the prevalent trends, we believe that the stem cell therapy manufacturing market is poised to grow at a steady pace, driven by a robust pipeline of therapy candidates and technological advances aimed at mitigating challenges posed by conventional methods of production. Amidst tough competition, the availability of cutting-edge tools and technologies has emerged as a differentiating factor and is likely to grant a competitive advantage to certain CMOs over other players in the industry. Scope of the Report The “Stem Cell Therapies Contract Manufacturing Market, 2019 – 2030” report features an extensive study on contract service providers engaged in the development and manufacturing of stem cell therapies. The study features in-depth analyses, highlighting the capabilities of various stem cell therapy CMOs. Amongst other elements, the report includes: A detailed review of the contract manufacturing landscape for stem cell therapies, featuring a comprehensive list of active CMOs and analysis based on a number of parameters, such as year of establishment, company size, geographical location, number of stem cell therapy manufacturing facilities, source of stem cells (allogenic and autologous), types of services offered (culture development, stem cell identification / validation, stem cell banking, cryopreservation, logistics, fill / finish and regulatory filings), scale of operation (preclinical, clinical and commercial), types of stem cells (adult, embryonic and induced pluripotent) and therapeutic area (oncology and non-oncology).  An elaborate discussion of the various guidelines laid down by regulatory bodies related to stem cells and other cell-based therapies across various geographies, such as the North America (primarily the US), Europe and other regions. Elaborate profiles of the key players based in North America, Europe and Asia-Pacific that have a diverse range of capabilities for the development, manufacturing and packaging of stem cell therapies. Each profile includes an overview of the company, its financial performance (if available), information on service portfolio, stem cell therapy manufacturing facilities, and details on partnerships, recent developments and an informed future outlook.  An analysis of the recent collaborations (signed since 2015) focused on the contract manufacturing of stem cell therapies, based on various parameters, such as year of agreement, type of agreement, scale of operation, source of stem cells used, types of stem cells and location of companies entering the partnership. An informed estimate of the annual demand for stem cell therapies in terms of area (in square feet) dedicated to stem-cell related operations, based on various parameters, such as target patient population, price of the therapy, dosing frequency and dose strength. A detailed capacity analysis, taking into consideration the manufacturing capacities of various stakeholders (small-sized, mid-sized and large CMOs) in the market, based on data gathered via secondary and primary research. It also provides the distribution of global stem cell therapy manufacturing capacity by company size (small-sized, mid-sized and large), and geography (North America, Europe and Asia-Pacific) and scale of operation (preclinical / clinical and commercial). A detailed analysis to understand the relationship between the demand and supply in this field, comparing the presence of stem cell therapy developers and the availability / capability of contract manufacturers across different geographies. An analysis to identify the key performance indicators for service providers active in the domain, based on the information gathered via secondary research and primary research. One of the key objectives of the report was to estimate the future size of the market. Based on parameters, such as increase in number of clinical studies, target patient population, anticipated adoption of stem cell therapies and expected variation in manufacturing costs, we have provided an informed estimate of the likely evolution of the market in the mid to long term, for the period 2019-2030. In order to provide a detailed future outlook, our projections have been segmented on the basis of [A] source of stem cells (autologous and allogenic), [B] types of stem cells (adult, embryonic and induced pluripotent), [C] size of contract service provider company (small-sized, mid-sized and large), [D] scale of operation (preclinical, clinical and commercial) and [E] key geographical regions (North America, Europe and Asia and rest of the world). To account for the uncertainties associated with the manufacturing of stem cell therapies 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 opinions and insights presented in the report were influenced by discussions held with senior stakeholders in the industry. The report features detailed transcripts of interviews held with the following industry stakeholders: Brian Dattilo (Manager of Business Development, Waisman Biomanufacturing) David Mckenna, Professor and American Red Cross Chair in Transfusion Medicine, University of Minnesota Fiona Bellot, Business Development Manager, Roslin Cell Therapies   Gilles Devillers, General Manager, Bio Elpida Mathilde Girard (Department Leader, Cell Therapy Innovation and Development, YposKesi) 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.  

August 2019

With six approved and marketed drugs, namely POLIVY™ (2019), LUMOXITI™ (2018), BESPONSA® (2017), MYLOTARG™ (2017, reapproval), KADCYLA® (2013) and ADCETRIS® (2011), antibody drug conjugates (ADCs) have become recognized as a potent class of targeted therapeutic agents catering to oncology and hematological diseases markets. The success of such conjugated products can be attributed to their ability to effectively identify and eliminate disease associated cells / pathogens, while limiting off target toxicities. Presently, ADCs are considered a part of mainstream healthcare regimens, having generated significant enthusiasm within the medical science community across the world.  The growing popularity and therapeutic potential of ADCs can also be correlated with an exponential increase in the number of patents that have been filed / granted; the cumulative patent count has increased from 1,395 in 2009 to over 16,500 in the first half of 2019. With more than 200 ADCs in clinical / preclinical stages of development, the industry is gradually shifting from relying on conventional technologies to newer and more robust approaches to conjugate such complex biomolecules. Over the years, a number of well-funded start-ups / small companies, offering novel conjugation technologies, more potent warheads and advanced linker technologies, have been established. In fact, multiple licensing agreements / collaborations have been inked in the past few years between drug developers and technology providers to advance the development of pipeline ADC candidates.   Using ADCs in combination with other drug / therapy classes is an emerging concept and multiple companies are evaluating their proprietary ADC candidates in combination with other established therapeutic classes, such as immune checkpoint inhibitors, epigenetic modulators and monoclonal antibodies. In addition, several other companies have introduced certain novel types of conjugated drug molecules; example of such companies include Bicycle Therapeutics (bicycle drug conjugate), BlinkBio (tunable drug conjugates), Cellectar Biosciences (phospholipid drug conjugate), Centrose (extracellular drug conjugate), Esperance Pharmaceuticals (peptide conjugate) and Nordic Nanovector (radionucleotide conjugate). We expect the ADC therapeutics market to growth at a healthy rate in the mid to long-term, driven by the introduction of new combination therapies involving ADCs, innovative ADC development and conjugation technologies, applications beyond oncology and the expansion of existing marketing authorizations to newer geographies across the world. Scope of the Report The ‘Antibody Drug Conjugates Market (5th Edition), 2019-2030’ report features an extensive study of the current market landscape, offering an informed opinion on the likely adoption of these therapeutics over the next decade. It features an in-depth analysis, highlighting the capabilities of various stakeholders engaged in this domain. In addition to other elements, the study includes: A detailed assessment of the current market landscape of ADCs, providing information on drug developer(s) and technology provider(s), phase of development (marketed, clinical and preclinical / discovery stage) of lead candidates, target antigen, type of linker, type of payload / warhead / cytotoxin, type of antibody, antibody origin, antibody isotype, type of therapy (monotherapy and combination therapy), combination drug (if being evaluated as combination therapy), target indication(s), line of treatment, route of administration and dosing frequency. Elaborate profiles of the clinical stage companies (shortlisted based on phase of development of the lead drug) and their respective product portfolios; each profile features an overview of the company, its financial information (if available), detailed information on advanced stage pipeline candidates (featuring a drug overview, clinical development plan and key clinical trial results) and an informed future outlook. An analysis of the most commonly targeted therapeutic indications and details of ADC candidates being developed against them, highlighting key epidemiological facts about the diseases and currently available treatment options, other than ADCs. A list of key opinion leaders (KOLs) within this domain, featuring detailed 2X2 matrices to assess the relative experience of key individuals, who were shortlisted based on their contributions (in terms of involvement in various clinical studies) to this field. It also includes a schematic world map representation, highlighting the geographical locations of eminent scientists / researchers engaged in this domain. In addition, it presents an analysis assessing the credibility and (relative) level of expertise of different KOLs, based on number of publications, number of citations, number of clinical trials, number of affiliations and strength of professional network (based on information available on LinkedIn). An insightful competitiveness analysis of biological targets, featuring a [A] three-dimensional bubble representation that highlights the targets that are being evaluated for ADC development, taking into consideration the number of lead molecules based on a particular target, phase of development of candidate therapies, number of clinical trials and number of target disease indications, and [B] a five-dimensional spider-web analysis, highlighting the most popular biological targets based on a number of relevant parameters, including affiliated publications, grants received to support research on a particular target, number of industry players involved in drug development efforts based on a singular target and geographical distribution of associated clinical trials.  An analysis of the partnerships that have been established in the recent past, covering R&D collaborations, licensing agreements (specific to technology platforms and product candidates), product development and commercialization agreements, clinical trial agreements, manufacturing agreements, mergers and acquisitions, manufacturing and service agreements, and other relevant agreements.  An analysis of the investments made, including seed financing, venture capital financing, debt financing, grants, capital raised from IPOs and subsequent offerings, at various stages of development in companies that are focused on developing ADCs. An in-depth analysis of the various patents that have been filed / granted related to ADCs till May 2019. It includes information on key parameters, such as patent type, publication year, geographical location, issuing authority, assigned CPC symbol, emerging focus areas and leading industry / academic players (in terms of size of intellectual property portfolio). It also includes a patent benchmarking analysis and a detailed valuation analysis. A study of the various grants that have been awarded to research institutes engaged in projects related to ADCs, between 2011 and 2019 (till April), highlighting various important parameters, such as year of award, support period, amount awarded, funding institute, grant type, focus area, type of recipient organization, key project leaders, key regions and leading recipient organizations. An elaborate discussion on the various strategies that can be adopted by the drug developers across key commercialization stages, namely prior to product launch, during / post launch, including a timeline representation of the key strategies adopted by drug developers for the commercialization of their proprietary products.  An analysis of the key promotional strategies that have been adopted by the developers of marketed products, namely POLIVY™, LUMOXITI™, BESPONSA®, MYLOTARG™, KADCYLA® and ADCETRIS®. An assessment of the various therapeutics that are being evaluated in combination with ADCs. The study also presents the likely evolution of these therapeutics across different indications.  A review of the evolution of ADC conjugation technologies, highlighting the various approaches that have been adopted across different generations; in addition, it presents a review of the existing competition between various conjugation approaches that are available / under development. An overview of the studies conducted to better analyze non-clinical data and support first-in-human (FIH) dose selection in ADCs. The study presents findings from various ADC studies in different animal models. It also includes an analysis of the different methods used in estimating FIH doses. In addition, it highlights the possible FIH starting doses and estimated dose escalations required to reach human maximum tolerated dose (MTD). An elaborate discussion on various factors that form the basis for the pricing of ADC products, featuring different models / approaches that pharmaceutical companies may choose to adopt while deciding the price of their respective lead therapy candidates that are likely to be marketed in the coming years. A case study on manufacturing of ADCs, highlighting the key challenges, and a list of contract service providers that are involved in this domain. A case study on companies offering companion diagnostics that can potentially be used to make treatment related decisions involving ADCs, providing information on the geographical location of key diagnostic developers, affiliated disease biomarkers, assay technique involved, target indication(s), the type of sample required (tumor tissue, blood, bone marrow and others) and the drug candidates for which a particular test was developed. One of the key objectives of the report was to estimate the existing market size and identify potential growth opportunities for ADCs, over the coming decade. Based on several parameters, such as target consumer segments, region specific adoption rates and expected prices of such products, we have provided an informed estimate on the likely evolution of the market for the period 2019-2030. The report includes potential sales forecasts of ADCs that are currently marketed or are in late stages of development. Additionally, it provides forecasts of the overall ADCs market, wherein the current and upcoming opportunity is segmented across [A] type of payload (MMAE, DM4, camptothecin, DM1, MMAF and others), [B] type of linker (VC, Sulfo-SPDB, SMCC, VA, hydrazone linker and others), [C] target indications (breast cancer, lymphoma (HL, NHL, ALCL), leukemia (AML, ALL), urothelial cancer, lung cancer (NSCLC, SCLC), ovarian cancer and others), [D] target antigens (CD30, HER2, CD22, CD33 and others (HER4, TROP-2, EGFR, FOLR1, MSLN, CD142, CD79b, DLL3, CD37, Nectin – 4, LIV-1, c-MET, BCMA, CD25, CD19 and ENPP3)), [E] technology providers (Seattle Genetics, ImmunoGen, StemCentRx, Immunomedics and others), and [F] key geographies (North America, Europe and Asia Pacific). To account for the uncertainties associated with the development of these novel 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 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 the following individuals: Alan Burnett (Professor, School of Medicine, Cardiff University) Aldo Braca (President and Chief Executive Officer, BSP Pharmaceuticals) and Giorgio Salciarini (Technical Business Development Senior Manager, BSP Pharmaceuticals) Anthony DeBoer (Director, Business Development, Synaffix) Christian Bailly (Director of CDMO, Pierre Fabre) Christian Rohlff, (Chief Executive Officer and Founder, Oxford BioTherapeutics) Denis Angioletti (Chief Commercial Officer, Cerbios-Pharma) John Burt (Chief Executive Officer, Abzena) Jennifer L. Mitcham (Director,  SMARTag ADCs and Bioconjugates, Catalent Pharma Solutions) and Stacy McDonald (Group Product Manager, Catalent Pharma Solutions) Laurent Ducry (Head of Bioconjugates Commercial Development, Lonza) Mark Wright (Site Head, Piramal Healthcare) Sasha Koniev (Chief Executive Officer & Co-Founder, Syndivia) Tatsuya Okuzumi (Associate General Manager, Ajinomoto Bio-Pharma Services) Toshimitsu Uenaka (Executive Director, Eisai) and Takashi Owa (Chief Innovation Officer, Eisai) Wouter Verhoeven (Chief Business Officer, NBE-Therapeutics) Anonymous (Director, Business Development, Leading CMO) Anonymous (Chief Executive Officer, Leading CMO) 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.

August 2019

CAR-T cell therapies are based on the principle of harnessing the innate potential of the immune system to selectively target and destroy diseased cells. Encouraging clinical results reported across several completed and ongoing trials, coupled to lucrative financing, have inspired many biopharmaceutical developers and academic research groups to focus their efforts on this relatively novel class of cell-based immunotherapies. With two approved products, namely KYMRIAH® (Novartis) and YESCARTA® (Gilead Sciences), CAR-T cell therapies are presently considered among the most promising anticancer therapeutics available, with potential applications in treating other diseases as well. It is worth highlighting that 66% of the pipeline therapies are presently in the clinical stage.  Over 100 companies and 85 academic / research institutes are actively involved therapy development initiatives in this domain. The ongoing research activity in this domain has led to the discovery of several novel molecular targets, which can be exploited for cell therapy development. Further research and characterization of these targets has significantly strengthened the pipelines of stakeholder entities engaged in this market. Driven by the availability of innovative technology platforms, the CAR-T therapies market is poised for success in the long-run as several therapeutic leads have recently entered mid to late-stage (phase II and above) trials and are anticipated to enter the market over the next 5-10 years.   Scope of the Report The “CAR-T Therapies Market, 2019-2030 (2nd edition)” report features an extensive study of the current market landscape and the future potential of CAR-T cell therapies. The report highlights the efforts of both industry players and academic organizations working in this domain. Amongst other elements, the report features the following: An analysis of the prevalent and emerging trends in this domain, as represented on the social media platform, Twitter, highlighting the yearly trend of tweets, most frequently talked about product candidates, popular disease indications, target antigens, and prolific authors and social media influencers. A detailed assessment of the current market landscape of CAR-T cell therapies with respect to type of developer (industry / non-industry), phase of development, target therapeutic indication(s), key target antigen(s), source of T-cells (autologous / allogenic), route of administration, type of therapy (monotherapy / combination therapy) and patient segment (children / adults / seniors). Comprehensive profiles of marketed and mid to late stage clinical products (phase I/II or above); each profile features an overview of the therapy, its mechanism of action, dosage information, details on the cost and sales information (wherever available), clinical development plan and key clinical trial results. An analysis of the CAR constructs of clinical-stage CAR-T therapies based on the generation of CAR-T therapy (first generation, second generation, third generation and fourth generation), type of binding domain (murine, humanized, fully human and rabbit derived), type of vector and type of co-stimulatory domain used. A detailed analysis highlighting several key opinion leaders (KOLs) in this domain. It features a 2X2 analysis to assess the relative experience of certain KOLs, who were shortlisted based on their contributions (in terms of involvement in various clinical studies) to this field, and a schematic world map representation, indicating the geographical locations of eminent scientists / researchers involved in the development of CAR-T cell therapies. An analysis of the various CAR-T cell therapy focused clinical trials registered across the world, between 2009 and 2019, highlighting the year wise trend of initiation of such studies and distribution across different geographies. In addition, we have provided a detailed list of factors that have influenced the growth of CAR-T therapies, especially in China. An overview of the various focus therapeutic areas of therapy developers, including an assessment of the opportunity offered by oncological and non-oncological disease indications. A detailed discussion on innovative technology platforms that are being used for the development of CAR-T cell therapies, along with profiles of key technology providers. Further, it includes a relative competitiveness analysis of different CAR-T cell therapy-based gene editing platforms, based on various parameters, such as ease of system design, cost of technology, level of toxicity and efficiency of technology. A case study on manufacturing cell therapy products, highlighting the key challenges, and a list of contract service providers and in-house manufacturers that are involved in this space. An elaborate discussion on various factors that form the basis for pricing of cell therapies. It features different models / approaches that a pharmaceutical company may choose to adopt to decide the price of a CAR-T cell therapy that is likely to be marketed in the coming years.  A review of the key promotional strategies that have been adopted by the developers of the marketed CAR-T cell therapies, namely KYMRIAH® and YESCARTA®.  One of the key objectives of the report was to estimate the existing market size and identify potential growth opportunities for CAR-T cell therapies over the coming decade. Based on several parameters, such as target consumer segments, region specific adoption rates and expected prices of such therapies, we have provided an informed estimate on the likely evolution of the market over the period 2019-2030. The report includes potential sales forecasts of CAR-T cell therapies that are currently marketed or are in late stages of development. Additionally, it provides forecasts for the overall CAR-T cell therapy market, wherein both the current and upcoming opportunity is segmented across [A] target indications (acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, multiple myeloma, chronic lymphocytic leukemia, hepatocellular carcinoma and colorectal cancer), [B] important target antigens (CD19, BCMA, GPC3 and EGFR) and [C] key geographical regions (North America, Europe and Asia Pacific). To account for the uncertainties associated with the development of these novel therapies 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 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 the following individuals (in alphabetical order of company names): Tim Oldham (Chief Executive Officer, Cell Therapies) Vincent Brichard (Vice President, Immuno-Oncology, Celyad) Xian-Bao Zhan (Professor of Medicine and Director, Department of Oncology, Changhai Hospital) Troels Jordansen (Chief Executive Officer, Glycostem Therapeutics) Wei (William) Cao (Chief Executive Officer, Gracell Biotechnologies) Adrian Bot (Vice President, Scientific Affairs, Kite Pharma) Aino Kalervo (Competitive Intelligence Manager, Strategy & Business Development, Theravectys) Miguel Forte (Chief Operating Officer, TxCell) Enkhtsetseg Purev (Assistant Professor of Medicine, University of Colorado) Brian Dattilo (Manager of Business Development, Waisman Biomanufacturing) 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.