Viral Vectors & Plasmid DNA: The Building Blocks of Complex Biologics

February 2019

Clinical trials represent an arduous step in the drug development process and are crucial to understanding the safety and efficacy profiles of novel therapeutic interventions. As these trials are prone to delays, and can even fail altogether, they impose an immense financial pressure on sponsors. Amongst several known challenges, patient recruitment is considered to be one of the rate limiting steps when it comes to getting drugs to the market. It is estimated that 80% of clinical trials do not meet their designated patient enrolment deadlines. In fact, around 37% of research sites fail to meet their subject accrual goals, while more than 10% don’t even enroll a single patient. In addition, retaining patients is also a matter of concern, considering that the approximate dropout rate across clinical studies is around 30%. Delays in product launch, due to inability of the sponsors to recruit / retain patients, are highly common and are estimated to result in an average loss of USD 8 million per day in opportunity costs, for a blockbuster drug. The abovementioned challenges have led several players in the pharmaceutical industry to outsource their patient recruitment-related needs to capable, specialty service providers. Employing contract service providers has been shown to expedite the patient recruitment process. Such service providers employ a variety of outreach methods, such as social media, mobile technologies, electronic health records (EHRs) and real-world evidence (RWE), and, over time, have attained a vital role in the successful conduct of clinical research. Although some big pharma players carry out patient recruitment in-house, the growing complexity of clinical trials and demand for niche patient populations for studies evaluating orphan drugs / personalized medicines is likely to prompt more developer companies to outsource various aspects of their clinical research-related operations in the foreseen future. In fact, the market has recently witnessed the establishment of several partnerships, which include agreements between study sponsors and patient recruitment firms (outsourcing deals) and partnerships between stakeholders aimed to combine their respective services portfolios related to patient recruitment and retention (service alliances). This niche services industry has also witnessed some consolidation as multiple smaller players have been acquired by more established entities, in an effort to expand geographical reach.   Scope of the Report The ‘Patient Recruitment and Retention Services, 2019-2030’ report offers a comprehensive study of the current scenario and future potential of the players providing patient enrollment and retention services. The study features an in-depth analysis, highlighting the capabilities of the various stakeholders in this domain. In addition to other elements, the study includes: A detailed assessment of the current market landscape of companies offering patient recruitment and retention services, including information on over 10 types of patient outreach methods employed, types of services offered ([A] patient recruitment (including pre-screening and Institutional Review Board (IRB) / Ethics Committee (EC) submission), [B] patient retention (considering various strategies, such as the use of study-branded gifts, study-branded reminders, providing education and support materials, reimbursement programs, transportation programs, patient engagement web site, patient reconnect programs, mobile applications to track patient engagement and others) and [C] other associated services (including site identification and selection,study feasibility / protocol development, project management, clinical trial monitoring and other services), year of establishment, geographical location, and size of company. The chapter also covers an analysis of the geographical reach and therapeutic expertise of service providers, along with details on the payment model, patient recruitment platforms / technologies used, and the various certifications / accreditations awarded by regulatory bodies. An analysis of the most active regions (in terms of patient recruitment activity), based on the locations of headquarters of companies engaged in this domain, featuring schematic world map representations that highlight key hubs across the globe. An insightful 2X2 representation of the results of a competitiveness analysis of various service providers (segregated into three peer groups based on their employee count (small-sized (1-50 employees), mid-sized (50-200 employees) and large (>200 employees)), highlighting capable players in this domain, based on their respective capabilities. Comprehensive profiles of patient recruitment and retention service providers, featuring information on the location of their headquarters, year of establishment, patient recruitment services / platforms portfolio, recent developments and a comprehensive future outlook. An analysis of the partnerships that have been established in the recent past, covering outsourcing agreements, service alliances, acquisitions, joint ventures, mergers, technology licensing and development agreements, and other forms of partnerships. A review of emerging trends in the industry, including the use of social media, mobile technologies, EHRs and RWE, to overcome the challenges associated with patient recruitment and retention. One of the key objectives of the report was to estimate the existing market size and review the potential growth opportunities for patient recruitment service providers over the coming decade. Based on several parameters, we have provided an informed estimate of the likely evolution of this market in the short to mid-term and long term, for the period 2019-2030. In addition, we have segmented the future opportunity across [A] therapeutic area (oncology, infectious diseases, cardiovascular diseases, CNS disorders, respiratory disorders, metabolic disorders, and others), [B] steps in patient recruitment process (pre-screening and screening), [C] phases of development (phase I, phase II, phase III and phase IV), and [D] different global regions (North America, Europe, Asia-Pacific and rest of the world). In order to account for the uncertainties associated with some of the key parameters and to add robustness to our model, we have provided three market forecast scenarios portraying the conservative, base and optimistic tracks of the industry’s evolution. The opinions and insights presented in this study were 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 Klaasen (Co-founder and Managing Director, Link2Trials) Hagit Nof (Chief Operation Officer and Business Development, nRollmed) Paul Ivsin (Managing Director, Seeker Health) 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.

July 2019

The cancer therapeutics market is considered to be one of the most active segments within the pharmaceutical industry. In the past five years, the USFDA has approved more than 100 drugs for the treatment of different types of cancer. However, there is still a pressing need for more specific and potent drugs / therapies to combat this complex, life threatening clinical condition. It is also worth highlighting that, in the coming years, the number of cancer patients is anticipated to increase substantially along with the growing global population. According to the International Agency for Research on Cancer (IARC), close to 17 million new cases of cancer were diagnosed in 2018, worldwide. By 2040, it is estimated that the aforementioned number is likely to grow to 27.5 million. In fact, the global cancer burden is anticipated to increase by 70% in the next 20 years. Among the current initiatives focused on developing targeted anti-cancer therapies, T-cell therapies (specifically CAR-T, TCR and TIL therapies) have emerged as a promising option owing to their capability to eradicate tumor cells from the body with minimal treatment-related side effects. These adoptive T-cell therapies (ACT) are based on the principle of harnessing the innate potential of the immune system to target and destroy diseased cells. With the recent approval of KYMRIAH® (Novartis) and YESCARTA® (Gilead Sciences) for the treatment of CD19-positive relapsed / refractory leukemias and lymphomas, such ACTs have become a part of mainstream healthcare solutions. Encouraging clinical trial results and therapeutic response rates achieved across various hematological cancers and solid tumors have further inspired research groups to focus their efforts on the development of these novel therapies. So far, more than 150 academic and research institutes across the globe have made significant contributions to this field, mostly by convening the initial research on potential therapy candidates. In fact, multiple collaborations have been inked in the past decade between various therapy developers and academic / research institutes to advance the development of various pipeline candidates. The ongoing research activity in this field has also led to the discovery of several novel molecular targets. Further research and characterization of the aforementioned targets have significantly strengthened the research pipelines of companies engaged in this market. Driven by the availability of innovative technology platforms, lucrative funding and encouraging clinical trial results, the T-cell immunotherapies market is poised for success in the long-run as multiple product candidates are expected to be approved over the coming decade.  Scope of the Report The “Global T-Cell (CAR-T, TCR, and TIL) Therapy Market (4th Edition), 2019 – 2030” report features an extensive study of the current market landscape and the future potential of T-cell immunotherapies (focusing particularly on CAR-T therapies, TCR therapies and TIL therapies). The report highlights the efforts of both industry players and academic organizations. 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 T-cell immunotherapies with respect to type of therapy, type of developer (industry / non-industry), phase of development, target therapeutic indication(s), key target antigen(s), source of T-cells (autologous / allogenic), and route of administration. In addition, we have provided an overview of the competitive landscape, key challenges and anticipated future trends associated with CAR-T, TCR and TIL-based therapies. 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 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 T-cell therapies, along with profiles of key technology providers. Further, it includes a relative competitiveness analysis of different T-cell immunotherapy-based gene editing platforms, based on various parameters, such as ease of system design, cost of technology, level of toxicity and efficiency of technology. An analysis of the partnerships that have been established in the recent past, covering R&D agreements, license agreements (specific to technology platforms and product candidates), product development and commercialization agreements, manufacturing agreements, clinical trial collaborations, product supply management agreements, joint ventures and others. An analysis of the investments that have been made into companies that have proprietary T-cell based products / technologies, including seed financing, venture capital financing, capital raised from IPOs and subsequent offerings, grants and debt financing. A case study on other T-cell based therapies, apart from CAR-Ts, TCRs and TILs. It presents a detailed analysis of the approved / pipeline products in this domain, including information on the current phase of development, target therapeutic area(s), type of T-cells used and source of T-cells. 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 the pricing of cell-based therapies. It features different models / approaches that a pharmaceutical company may choose to adopt to decide the price of a T-cell based immunotherapy 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 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 T-cell immunotherapies 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 over the period 2019-2030. The report includes potential sales forecasts of T-cell immunotherapies that are currently marketed or are in late stages of development. Additionally, it provides forecasts for the overall T-cell immunotherapies market, wherein both the current and upcoming opportunity is segmented across [A] type of therapy (CAR-T, TCR and TIL), [B] target indications (acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, melanoma, bladder cancer, lung cancer, head and neck cancer, multiple myeloma, sarcoma, chronic lymphocytic leukemia, ovarian cancer, esophageal cancer, colorectal cancer, nasopharyngeal carcinoma, hepatocellular carcinoma, acute myeloid leukemia, and renal cell carcinoma), [C] target antigens (CD19, BCMA, CD19/22, EGFR, NY-ESO-1, gp100, p53, EBV, MUC1, WT-1 and others) and [D] key geographies (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 individualss: Tim Oldham (Chief Executive Officer, Cell Therapies) Troels Jordansen (Chief Executive Officer, Glycostem Therapeutics) Wei (William) Cao (Chief Executive Officer, Gracell Biotechnologies) Victor Lietao Li (Co-Founder and Chief Executive Officer, Lion TCR) Miguel Forte (Chief Operating Officer, TxCell) Adrian Bot (Vice President, Scientific Affairs, Kite Pharma) Vincent Brichard (Vice President, Immuno-Oncology, Celyad) Peter Ho (Director, Process Development, Iovance Biotherapeutics) Brian Dattilo (Manager of Business Development, Waisman Biomanufacturing) Aino Kalervo (Competitive Intelligence Manager, Strategy & Business Development, Theravectys) Xian-Bao Zhan (Professor of Medicine and Director, Department of Oncology, Changhai Hospital) Enkhtsetseg Purev (Assistant Professor of Medicine, University of Colorado) 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.

May 2019

Biologics constitute a majority of the top selling drugs and presently represent one of the fastest growing segments of the overall pharmaceutical industry. In fact, since the launch of recombinant protein-based therapies around three decades earlier, the overall biologics market has grown at an annualized rate of over 12%. It is also worth highlighting that more than 5,000 biopharmaceutical product candidates are currently under development.  Despite the fact that biopharmaceuticals offer significant profit margins, the sponsors of such pharmacological interventions are plagued by high costs of development and complex production protocols. As a result, several start-ups / small-sized companies and certain pharma giants have begun outsourcing different aspects of their business operations to contract service providers. According to the 2017 Nice Insight CDMO survey, about 54% of 700 respondents claimed to have collaborated with a contract service provider for clinical and commercial-scale product development projects.  Contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) are known to offer significant benefits, such as reduction in capital investment, access to larger production capacities, reductions in time-to-market and reduced commercialization risk.  Specifically, fill / finish is the final step in the production process and is considered among the most crucial stages of drug product manufacturing. Biologics drug products require special procedures and equipment for fill / finish operations in order to ensure product integrity and safety. As this operation is heavily outsourced, the rise in demand for biologics has resulted in an equivalent need for flexible aseptic fill / finish technologies. Pharmaceutical drug manufacturers have not hesitated to collaborate with contract service providers to leverage the latter’s experience and expertise in the latest fill / finish technologies. Currently, over 115 companies are actively providing fill / finish services for biologics. In the recent past, many service providers have also forged alliances / acquired other players in order to enhance their service offerings.  Scope of the Report The ‘Biologics Fill / Finish Service Providers, 2019-2030’ report features an extensive study on the contract service providers offering drug product manufacturing services within the biopharmaceutical industry. The study features in-depth analysis, highlighting the capabilities of a diverse set of companies that claim to specialize in fill / finish operations. Amongst other elements, the report includes:  A detailed review of the overall landscape of contract fill / finish services market for biopharmaceuticals, featuring a list of active service providers and detailed analysis based on a number of relevant parameters, such as scale of operation (preclinical, clinical and commercial), type of biologics filled (peptides / proteins, antibodies, vaccines, cell therapies, gene therapies, viral products, oligonucleotides and others), year of establishment, company size and geographical location of the service provider, count and location of affiliated fill / finish facilities, number of additional services offered (lyophilization, labelling, quality testing, storage and distribution services), dosage forms handled (liquid and lyophilized), and types of primary packaging containers handled (ampoules, cartridges, syringes and vials),  including details on fill / finish capacity and fill volume range. A region-wise, company competitiveness analysis, highlighting prominent fill / finish service providers across various packaging types, based on supplier strength (considering experience and company size of the service provider), service strength (considering number of fill / finish facilities, number of continents where the aforementioned facilities are located, number of additional services offered and scale of operation) and types of biologics handled.      Elaborate profiles of key players across key geographies (North America, Europe and Asia-Pacific), which were shortlisted based on our proprietary company competitiveness analysis. Each profile provides an overview of the company, information on its overall service portfolio, fill / finish facilities, financial performance (if available), and details on partnerships, expansions and recent awards and accolades, as well as an informed future outlook.  An analysis of the recent collaborations (signed since 2013) focused on the contract fill / finish services for biologics, based on various parameters, such as year of agreement, type of agreement, scale of operation of the project, focus area, types of services mentioned in the deal, types of biologics involved and location of facility where the project is to be executed.  A detailed analysis of the expansions undertaken (since 2013) by various service providers for augmenting their respective fill / finish service portfolios, based on a number of parameters, including year of expansion, type of expansion (capacity expansion and new facility), geographical location of facility, type of packaging container involved, scale of operation (as mentioned in the expansion terms), types of services and biologics involved, expansion details (in terms of new area added to existing facilities, if available) and most active players (in terms of number of instances). An estimate of the global, contract fill / finish capacity, by taking into consideration the capacities of various fill / finish service providers (as available on respective company websites), collected via secondary and primary research. The study examines the distribution of number of packaging units and volume of biologics filled, across various types of packaging containers (ampoules, cartridges, syringes, and vials), based on the size of the company / organization (small-sized, mid-sized and large)  and geography (North America, Europe and Asia Pacific). An informed estimate of the annual demand for fill / finish of biologics, taking into account the top 20 biologics, based on various relevant parameters, such as target patient population, dosing frequency, dose strength, type of packaging container and volume of the packaging container of the abovementioned products.  An analysis to identify the key performance indicators for service providers active in the domain, based on information gathered via secondary research (for top-ten pharmaceutical players) and primary research. A case study to highlight the benefits of using robotic / automated equipment for aseptic fill / finish processes; the study provides a list of equipment manufacturers providing robots suitable for pharmaceutical operations. A case study to highlight the role of ready-to-use packaging containers in aseptic fill / finish operations; the study provides a list of suppliers providing the ready-to-use components. A discussion on the potential growth areas, such as growing biopharmaceutical pipeline, increasing outsourcing of fill / finish operations, rising focus on self-administration enabling drug delivery devices and growing opportunities in Asia-Pacific region, which are likely to present in the coming years. One of the key objectives of the report was to understand the primary growth drivers and estimate the future size of the market. Based on parameters, such as growth of the overall biopharmaceutical market, cost of goods sold, direct manufacturing costs, share of drug product manufacturing costs, and outsourcing trends related to fill / finish operations, we have provided an informed estimate of the likely evolution of the market in the mid to long term, for the period 2019-2030. Our year-wise projections of the current and future opportunity have further been segmented on the basis of [A] types of primary packaging containers used for fill / finish (ampoules, cartridges, syringes and vials), [B] types of biologics (peptides / proteins, antibodies, vaccines, cell therapies, gene therapies, viral products, oligonucleotides and others), [C] company size (small-sized, mid-sized and large / very large), [D] scale of operation (preclinical, clinical and commercial), [E] key therapeutic areas (cancer, infectious diseases, autoimmune diseases, cardiovascular diseases and other indications), and [F] key geographical regions (North America (US, Canada), Europe (UK, France, Germany, Italy, Spain and rest of the Europe), Asia-Pacific (Japan, China, South Korea, India and Australia)). To account for the uncertainties associated with the fill / finish of biopharmaceuticals 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 also influenced by discussions held with senior stakeholders in the industry. The report features detailed transcripts of interviews held with the following industry stakeholders: Ales Sima, Business Development Manager, oncomed manufacturing  Gregor Kawaletz, Chief Commercial Officer, IDT Biologika Jos Vergeest, International Business Developer, HALIX Purushottam Singnurkar, Research Director and Head of Formulation Development, Syngene International All actual figures have been sourced and analysed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.