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

November 2019

According to experts in the healthcare industry, one in three adults are estimated to be suffering from some type of chronic clinical condition, such as multiple sclerosis, diabetes, rheumatoid arthritis and cardiovascular diseases. Chronic clinical conditions are considered to be among the leading causes of death and disability across the world.  Typically, in such cases, individuals are required to medicate on a daily basis. In addition to the cost of medication, such individuals are also burdened with a deteriorating quality of life, and often struggle with medication adherence.  According to the US Centers for Disease Control (CDC), the overall annual expense incurred by those living with chronic diseases is steadily growing and is currently estimated to be more than USD 3 trillion.  The development and commercialization of self-administrable dosage forms of drugs indicated to treat chronic clinical conditions has made a significant positive impact not only on the healthcare expenses borne by patients but also on compliance to prescribed therapeutic regimens. As the number of patients suffering from such disorders increase, the demand for more convenient and patient friendly drug delivery solutions is also on the rise.  Most self-injection devices / systems, such as autoinjectors and pen-injectors,  rely on prefilled syringes, which serve as primary drug containers in the aforementioned products. Moreover, despite having been in the market for more than three decades now, the overall interest in prefilled syringes continues to grow. In fact, the recent increase in use of biologics, which are usually administered via parenteral routes, has had a significant impact on the demand for prefilled syringes.  Over the years, significant improvements have been made to conventional prefilled syringes in order to further expand the scope of their applications. In this context, it is worth mentioning that dual / multi chambered syringes designed for the administration of lyophilized drugs are already available in the market. In such products, the syringe barrel is divided into two chambers, one of which contains the appropriate diluent for the prefilled (lyophilized) drug formulation. Likewise, there are multiple types of specialty syringes, including contrast agent containing syringes and flush syringes. Further, since the introduction and enforcement of the Needlestick Safety and Prevention Act in 2000, several medical device manufactures have developed add-on or integrated safety devices for prefilled syringes. In fact, by 2020, the incorporation of safety features in prefilled syringes is anticipated to be made mandatory across the world.  We are led to believe that the aforementioned developments are likely to fuel innovation and subsequent future growth in this market. Scope of the Report The ‘Prefilled Syringes Market (5th edition), 2019-2030’ report features an extensive study of the current market landscape of prefilled syringes and the likely future opportunities associated with such devices, over the next 10-12 years. It features an in-depth analysis, highlighting the capabilities of various stakeholders engaged in this domain. In addition to other elements, the study includes: An overview of the current market landscape of companies engaged in manufacturing prefilled syringes, providing information on year of establishment, company size, geographical location of the headquarters and manufacturing facilities, type of material used (glass and plastic), number of barrel chambers (single chamber and dual chamber), type of needle system (fixed needle system, luer lock and luer cone) and syringe volume.  An overview of the current market landscape of companies that are developing drugs in combination with prefilled syringes, featuring information on year of establishment, company size, geographical location of the developers, target indication, phases of development, type of drug molecule, route of administration, approval year (for marketed products), dosage details (for marketed products) and other approved dosage forms (for marketed products).  A detailed competitiveness analysis of the various prefilled syringes that we came across, taking into consideration the supplier power (based on the employee size of developer / manufacturer and their respective annual revenues) and key product specifications, such as number of chambers in the barrel, number of needle systems, volume of the barrel, technological advancement / user-friendliness and other distinguishing features. A list of marketed drugs / therapies and pipeline candidates that are likely to be developed in combination with prefilled syringes in the near future, shortlisted based on an in-depth analysis that takes into consideration various relevant parameters, such as route of administration, type of drug molecule, target indications, other available dosage forms (for approved drugs) and historical annual sales information (for approved drugs). An analysis presenting potential strategic partners (primarily drug developers) for prefilled syringe manufacturers (with regard to likely collaboration opportunities for combination product development) based on different parameters, such as pipeline strength, target therapeutic indication(s) and developer strength. An analysis of the various prefilled syringe combination product-related initiatives of big pharma players, based on parameters, such as current adoption (based on number of approved and under development prefilled syringe combination products) and likely future adoption (based on potential injectable product candidates in the pipeline that are likely to be delivered via prefilled syringes), target therapeutic area(s) and type of drug molecule. A review of the landscape of contract fill / finish services providers that offer services for prefilled syringes, featuring a list of active (large-sized) service providers and analysis based on a number of relevant parameters, such as year of establishment, company size, scale of operation (preclinical, clinical and commercial), type of drug molecule (biologics and small molecules), and geographical location of the service provider.  A detailed discussion on various safety features (add-on and integrated devices) installed in recent versions of prefilled syringes and the companies involved in developing and manufacturing such solutions. An informative summary of various guidelines established and issued by major regulatory bodies for the approval of prefilled syringes, across different countries / geographical regions.   Brief discussions of currently available specialty syringes, which include prefilled flush syringes, prefilled diluent syringe systems and prefilled contrast agent delivery systems.  A case study on companies that are engaged in the manufacturing of autoinjectors, featuring brief profiles of key players in this domain; each profile includes an overview of the firm, and information on its respective product portfolio. Elaborate profiles of prominent prefilled syringe manufacturers engaged in this domain, featuring a brief overview of the company, its financial information (if available), information on product portfolio, recent developments and an informed future outlook. Elaborate profiles of prominent prefilled syringe component manufacturers, featuring a brief overview of the company, its financial information (if available), information on product portfolio, recent developments and an informed future outlook. One of the key objectives of the report was to evaluate the current market size and the future opportunity within the prefilled syringes market. Based on various relevant parameters, such as the number of commercialized combination products, annual adoption rate, and expected pricing, we have provided an informed estimate of the likely evolution of the market over the period 2019-2030. In order to provide a detailed future outlook, our projections have been segmented on the basis of [A] therapeutic area (infectious diseases, autoimmune disorders, oncology disorders, neurological disorders, ophthalmic diseases, metabolic disorders and others), [B] type of syringe, [C] type of material (glass and plastic), [D] number of chambers (single chamber and dual chamber),  [E] type of drug molecule (antibodies, proteins, vaccines, small molecules, peptides, and others), and [F] key geographies (North America, Europe (the UK, France, Italy, Spain, Germany and the rest of Europe), Latin America (Brazil, Mexico, Argentina and the rest of Latin America), Asia Pacific (Japan, China, India, South Korea and the rest of Asia Pacific), and the Middle East and Africa (Saudi Arabia, UAE, Africa and the rest of the Middle East)).  The research, analysis and insights presented in this report are backed by a deep understanding of key insights gathered from both secondary and primary research. The opinions and insights presented in the report were influenced by discussions held with several players in this industry. The study includes detailed transcripts of discussions held with the following individuals: Matthew Young (Founder and Chief Technology Officer, Oval Medical Technologies) Kirti Maheshwari (Chief Technical Officer, Intas Pharmaceuticals) Gregor Kawaletz (Chief Commercial Officer, IDT Biologika) Kevin Cancelliere and Tibor Hlobik (Marketing Directors, West Pharmaceutical Services) Marco Pederiva (Marketing & Sales Director, Lonstroff) Anonymous (Chief Executive Officer, Small-sized Medical Device Company) 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.

November 2019

According to the World Bank, more than 50,000 different types of medical devices are currently being used on a daily basis in healthcare facilities across the globe. In 2018, the global medical devices market was estimated to have reached a net worth of approximately USD 450 billion. It is also worth noting that, since January 2018, the USFDA approved over 130 medical devices. However, a relatively large proportion of developers lack the resources and technical expertise required to handle regulatory filings and effectively manage the processes associated with procuring marketing authorizations from regional regulators. Moreover, keeping up with evolving regulatory guidelines, rising costs of legal advice and increasing effort required for preparing of technical documentation, is difficult for companies with limited finances. In addition, establishing reimbursement strategies for medium to high-risk devices is also a complicated process and innovator companies usually do not have the expertise to deal with payers and insurance providers. According to a recent report, 68% of medical device companies reports prepared and submitted by in-house players are either rejected or were reported to have multiple major gaps in their clinical evaluation report (CER) and supporting evidences by the notified bodies. In fact. in a survey published in the 2016 edition of Global Medical Device Supply Chain, regulatory requirements were highlighted among the primary areas of concern within the medical device value chain. Furthermore, the implementation of highly stringent regulatory guidelines, specifically for devices posing medium to high risk to consumers, render them subject to rigorous quality assessments.  The aforementioned challenges have led many medical device developers, especially the smaller players and certain established companies as well, to outsource parts of their regulatory operations to capable contract research organizations (CROs). Generally, CROs are known to offer a number of benefits, which include cost benefits, reductions in time-to-market and, in this specific case, an in-depth and up-to date regulatory support. Given that the global demand for medical devices is increasing at a substantial pace, the opportunity for CROs with expertise in regulatory affairs management is also on the rise. In the foreseen future, the growing complexity of regulatory processes across various developing and developed geographies is likely to prompt more developers to outsource various aspects of their dealings with regulatory authorities. Moreover, in order to cope up with latest changes in medical device-related regulations, several legacy CROs are re-evaluating their operational models and business strategies. Owing to the anticipated rise in demand for such services, the contract regulatory services domain is likely to witness the entry of a number of new players in the foreseen future. Scope of the Report The ‘Contract Regulatory Affairs Management Market for Medical Devices, 2019-2030’ report features a detailed study on the current landscape of contract service providers focused on regulatory affairs management for medical devices. The study features an in-depth analysis, highlighting the capabilities of the various CROs engaged in this domain, across different regions of the globe. Amongst other elements, the report includes: A detailed review of the current market landscape of the medical devices regulatory affairs outsourcing market, featuring a list of over 400 CROs engaged in this domain, and detailed analysis based on a number of relevant parameters, such as year of establishment, size of employee base, geographical location, device class (class I, class II, and class III), type and size of clientele (medical device developers, medical device manufacturers, medical device research organizations, and others), types of services offered, ([A] regulatory management services (such as legal representation, notified body selection, project registration and clinical trial application, regulatory writing and publishing, regulatory document submission, product labelling related service, gap analysis, technical dossier set-up, vigilance & medical device report, risk management-related services), [B] additional services (such as biostatistics, consulting, clinical operations, post-marketing activities, quality assurance, reimbursement, training)), region(s) of operation wherein the company is offering regulatory management services, and popular therapeutic area(s).  A detailed discussion on the need for regulatory review / oversight across different stages of the medical devices supply chain, with emphasis on the optimization of the supply chain using upcoming tools / technologies (such as artificial intelligence, big data analytical, blockchain, internet of things and others). An elaborate discussion on the various guidelines established by major regulatory bodies for medical device approval across North America (the US, Canada and Mexico), Europe (France, Germany, Italy, Spain, the UK and rest of Europe), Asia-Pacific and rest of the world (Australia, Brazil, China, India, Israel, Japan, New Zealand, Singapore, South Africa, South Korea, Taiwan, and Thailand). The report also features an insightful multi-dimensional, heat map analysis, featuring a comparison of the contemporary regulatory and reimbursement scenarios in key geographies across the globe. Elaborate profiles of popular players that specialize in offering end-to-end regulatory services for medical devices across key geographies (North America, Europe and Asia-Pacific). Each profile features a brief overview of the company, including information on company headquarters, year of establishment, number of employees, and therapeutic area expertise, financial information (if available), detailed description of service portfolio, and an informed future outlook. A benchmark analysis, highlighting the key focus areas of small-sized, mid-sized and large companies, comparing their existing capabilities within and beyond their respective peer groups, providing a means for stakeholders to identify ways to gain a competitive edge in the industry. An elaborate discussion on the various outsourcing business models adopted for regulatory affairs management, along with an insightful Harvey ball analysis of key considerations that need to be assessed by industry stakeholders while selecting a CRO partner. An analysis highlighting the key performance indicators used by sponsor companies to evaluate service providers that are active in the domain, based on information gathered via secondary research (for top-ten medical device players) and primary research. A survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing regulatory affairs management services to medical device developers.  One of the key objectives of this report was to evaluate the current opportunity and the future potential of the medical device regulatory affairs outsourcing market over the coming decade. We have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2019-2030. In addition, we have provided the likely distribution of the opportunity across different [A] types of regulatory affair management service offered (legal representation, project registration and clinical trial application, regulatory writing and publishing  and 6+ categories) [B] device class (class I, class II and class III), [C] therapeutic areas (cardiovascular disorders, central nervous system (CNS) disorders, metabolic disorders, oncological disorders, orthopedic disorders, ophthalmic disorders, pain disorders, respiratory disorders, and others), and [D] geographical regions (North America, Europe, Asia-Pacific and rest of the world). To account for the uncertainties associated with the growth of the medical device regulatory affairs outsourcing CRO market 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 (in alphabetical order of company name):  Tania Persson, Business Development Manager, A+ Science Alexa Foltin-Mertgen, Business Development Manager, AtoZ-CRO Troy Mccall, Chief Operating Officer, CROMSOURCE Christian Wolflehner, Managing Director, Clinical Trial Specialist, CW Research & Management Antal Solyom, Director, Medical Device Unit, HungaroTrial Nazish Urooj, Senior manager, Medical & Clinical Operations, Metrics Research C Omprakash, Technical Director and Partner, Vyomus Consulting  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.

November 2019

The human body is known to harbor numerous communities of microbes, including both beneficial and harmful species, which are collectively referred to as the microbiota. Likewise, the ecological system of commensal, symbiotic, and perhaps pathogenic microorganisms that reside within a host system is called the microbiome.  Research insights, generated primarily  from the Human Microbiome Project (2009) and other independent studies, have demonstrated that an imbalance in the microbiome (also known as dysbiosis) may lead to the development of several chronic clinical conditions, including Clostridium difficile infections (CDIs), irritable bowel syndrome (IBS), diabetes, Crohn’s disease and ulcerative colitis.  Given the role of the microbiota in both disease development and pathogenesis, the concept of microbiome-based therapeutics has generated significant enthusiasm within the medical science community, defining a new frontier in the field of medicine. The growing popularity and interest in the therapeutic potential of the microbiome is evident across scientific literature; commonly cited terms in this context include microbiome, microflora, microbiota, fecal microbiota therapy (FMT), microbiome diagnostics, or human microbiome, as observed on the NCBI’s PubMed portal, over the last three years.  Over time, the efforts of industry stakeholders and clinical researchers in this domain have led to the discovery of novel therapeutic strategies, including the establishment of a gut-brain axis, involving the human microbiome. Despite the evident increase in interest (of therapy developers and investors alike) in this field of research, there are currently no approved microbiome-based drugs / therapy products available in the market. However, there is a FMT in the market that is designed to modulate the microbial population within the gut for the treatment of recurrent CDIs. This treatment has been shown to be particularly beneficial to those who are non-responsive to standard-of-care therapies. In addition, a number of microbiome diagnostic tests are available for the detection of digestive and gastrointestinal disorders, inflammatory diseases and certain oncological indications. Further, several technology developers have started using next-generation sequencing techniques and other versatile bioinformatics tools for the characterization of important species of gut microflora. It is also worth mentioning that, in the last 4-5 years, there has been a marked rise in the number of new entrants in this field. Interestingly, several big pharma players have also become actively involved in this domain. Given the fact that there are several candidate therapies in late phases of clinical development, the microbiome-based medical products market can be expected to witness substantial growth over the coming decade. Scope of the Report ‘The Human Microbiome Market: Focus on Therapeutics (including gut-brain axis targeting drugs), Diagnostics and Fecal Microbiota Therapies (3rd Edition), 2019-2030’ report features an extensive study of the current market landscape, offering an informed opinion on the likely adoption of microbiome-based medical products (including therapeutics, diagnostics and FMTs), over the next decade. The report features an in-depth analysis, highlighting the diverse capabilities of stakeholders engaged in this domain. In addition to other elements, the study includes: A detailed assessment of the current market landscape of microbiome therapeutics, providing information on drug / therapy developer(s) (such as year of establishment, location of headquarters and company size), clinical study sponsor(s) or collaborators, phase of development (clinical, preclinical, and discovery stage) of product candidates, type of molecule (small molecule and biologic), type of therapy (prebiotic, probiotic, and prescription drug), target indication(s), key therapeutic area(s), molecular / biological target (if available), mechanism of action (if available), route of administration, type of drug formulation (tablet, capsule, gel, lotion, cream, ointment, nasal spray and 4+ categories), dosing frequency (reported for clinical candidates only), and information on special drug designations (if any). In addition, the chapter highlights the various technology platforms that are being actively used for the development of microbiome therapeutics. Elaborate profiles of key players (established after 2005) that are engaged in the development of microbiome therapeutics (which are presently in both preclinical and clinical stages of development); each profile features a brief overview of the company, its financial information (if available), microbiome-based product portfolio, information on advanced stage (phase II and above) pipeline candidates (featuring a drug overview, current status of development, clinical trial information, and clinical trial end-point analysis) and an informed future outlook.  A discussion on the various types of diagnostic tests, specifically highlighting the importance of next-generation sequencing within this field of research, along with [A] a detailed review of the current market landscape of microbiome diagnostic tests, including the information on the developer(s) (such as year of establishment, location of headquarters and company size), stage of development (commercialized and under development), type of sample used (blood, feces, saliva and vaginal swab), target indication(s), key therapeutic area(s), result turnaround time, and purpose of diagnosis, [B] brief profiles of popular diagnostic developers, and [C] an indicative list of screening and profiling test kits, including information on the developer(s) (such as year of establishment, location of headquarters and company size), type of sample used (blood, feces, saliva and vaginal swab), key therapeutic area(s), and result turnaround time. A review of the historical evolution and other relevant aspects of FMT therapies, including details on the process of donor selection, therapy procedure, route of administration, important clinical guidelines, regulatory guidelines and insurance coverage, along with [A] a detailed assessment of the current market landscape of FMT therapies, providing information on FMT developer(s) (such as year of establishment, location of headquarters and company size), status of development (commercialized, clinical, and preclinical stage), target indication(s), key therapeutic area(s), and route of administration, [B] a geographical clinical trial analysis of ongoing / planned / completed studies of FMTs sponsored by non-industry players, featuring details related to specific FMT therapies and analysis based on relevant parameters, such as the number of registered trials, year of registration, current status, phase of development, study design, type of sponsor(s), target indication(s), key therapeutic area(s), key focus areas, number of patients enrolled and leading non-industry player(s), and [C] information on various stool banks (including year of establishment and location of headquarters), along with brief profiles of the most prominent stool banks located across the globe.   A detailed business portfolio analysis based on an attractiveness and competitiveness (AC) framework, highlighting the current market attractiveness and existing competition across the most popular disease indication(s) for which microbiome therapeutics are under investigation. An analysis of the varied microbiome-focused initiatives of big pharma players (out of top 20 established pharmaceutical players), featuring a [A] heat map representation that highlights microbiome therapeutics under development (in partnership with core microbiome product developers), along with information on funding, partnership activity,  and diversity of product portfolio (in terms of disease indication(s) being treated and focus therapeutic area(s)), and [B] a spider web representation of the individual competitiveness of the initiatives of big pharma players based on multiple relevant parameters. An analysis of the start-ups / small-sized players (established in the last seven years, with less than 50 employees) engaged in the development of microbiome therapeutics and diagnostics, featuring heat map representation based on parameters, such as number of microbiome therapeutics under development, diversity of product portfolio, funding information (including funding amount, number of investors and evolution of investment activity), partnership activity, disease indication(s) being treated and focus therapeutic area(s), and strength of intellectual property portfolio. An assessment of the most commonly targeted therapeutic indications and details of microbiome-based drugs that are being developed against them, highlighting key epidemiological facts about specific diseases, available methods of diagnosis, and currently available treatment options and their side effects. 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 start-ups / small-sized companies (established in last seven years, with less than 50 employees) that are focused on developing microbiome therapeutics and diagnostics. An elaborate discussion on the various steps involved in the development and manufacturing of microbiome therapeutics, along with [A] an indicative list of contract manufacturers, along with details on year of establishment, location of headquarters, company size, scale of operation, facility location and microbiome production capacity, [B] an indicative list of companies with in-house manufacturing facilities for microbiome therapeutics, along with details on year of establishment, location of headquarters, and company size, [C] an indicative list of CROs that currently claim to have the necessary capabilities to offer various research services (such as screening, sequencing, characterization, analytical), along with details on year of establishment, location of headquarters, company size, and service portfolio details, and [D] an insightful Harvey ball analysis of key considerations that need to be taken into account by industry stakeholders while selecting a suitable CMO / CRO partner. An assessment of the emerging role of big data, highlighting efforts focused on the development and implementation of various algorithms / tools to analyze data generated from microbiome research along with [A] an insightful google trends analysis to demonstrate the rising interest of stakeholders in using big data tools to support microbiome research over the past decade, [B] a list of companies offering big data-related services / tools to support microbiome research, and [C] brief profiles of some of the popular companies that are engaged in this field of research. An informative case study on the various other applications of microbiome products, such as agriculture, animal health, plant health, food products, featuring a list of nearly 80 products, including probiotic supplements, cosmetics, and over-the-counter (OTC) products that are being used as dietary supplements. One of the key objectives of the report was to estimate the existing market size and identify the future opportunity for microbiome therapeutics, diagnostics and FMTs, over the next decade. The research, analyses and insights presented in this report are based on revenue generation trends based on the sales of approved / late stage (estimated) microbiome therapeutics, diagnostic products and FMTs. The report also features the likely distribution of the current and forecasted opportunity within microbiome therapeutics market across [A] type of therapy (prescription drugs, prebiotics, and probiotics), [B] type of molecule (small molecules and biologics), [C] target indication (acne vulgaris, atopic dermatitis, CDI, Crohn’s disease, diabetes, irritable bowel syndrome, lactose intolerance, nonalcoholic steatohepatitis (NASH), ulcerative colitis, and 5+ categories), [D] therapeutic area (autoimmune disorders, dental disorders, digestive and gastrointestinal disorders, dermatological disorders, infectious diseases, metabolic disorders, oncology, and others), [E] supply channel (hospital pharmacies, retail pharmacies, and online pharmacies), [F] key geographical regions (North America, Europe, Asia-Pacific and rest of the world), [G] leading drug developers, and [H] leading therapeutic products. In addition, it also features the likely distribution of the current and forecasted opportunity within microbiome diagnostics market across [A] target indication (Crohn’s disease, colorectal cancer, diabetes, irritable bowel syndrome, lung cancer, NASH, obesity, and ulcerative colitis), [B] therapeutic area (digestive and gastrointestinal disorders, metabolic disorders and oncology), [C] supply channel (hospital pharmacies, retail pharmacies, and online pharmacies), and [D] key geographical regions (North America, Europe, Asia-Pacific and rest of the world). In order to account for the uncertainties associated with the growth of microbiome 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 / organization names): Lee Jones (President and Chief Executive Officer, Rebiotix) Veronika Oudova (Co-founder and Chief Executive Officer, S-Biomedic) Colleen Cutcliffe (Co-founder and Chief Executive Officer, Whole Biome) Nikole E Kimes (Co-founder and Vice President, Siolta Therapeutics) James Burges (Executive Director, OpenBiome) JP Benya (Vice President, Business Development, Assembly Biosciences) Debbie Pinkston (Vice President, Sales and Business Development, List Biological Laboratories) Gregory J Kuehn (Vice President, Business Development and Marketing, Metabiomics)  Mark Heiman (Chief Scientific Officer and Vice President, Research, MicroBiome Therapeutics)  Alexander Segal (Vice President, Business Development, Universal Stabilization Technologies) Assaf Oron (Chief Business Officer, BiomX) Pierre-Alain Bandinelli (Chief Business Officer, Da Volterra) Alexander Lin (Associate General Manager, Chung Mei Pharmaceutical) Aaron Wright (Senior Scientist, Pacific Northwest National Laboratories) 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.