Since the launch of Adalimumab, the world's first fully human-sourced monoclonal antibody drug, in 2002, the global biopharmaceutical field has begun rapid development and still has great potential for growth over the 20 years. According to Frost & Sullivan, the global biopharmaceutical market grew from US$220.2 billion to US$297.9 billion from 2016 to 2020, and will grow to US$531 billion by 2025.
In the biopharmaceutical development process, cell strain development is the starting point and foundation of drug CMC, while selection of expression systems is the first step. Currently, two expression systems are competing for dominance: mammalian expression system and microbial expression system.
▲Market Share of Different Biopharmaceutical Expression Systems
Source: Trends in Biotechnology
In recent years, antibody drugs have gradually dominated the field of biopharmaceuticals. Due to the high complexity of the antibody structure, they are mainly produced by mammalian expression systems, so the proportion of mammalian expression systems in the field of biopharmaceuticals has increased linearly. However, such systems are difficult to operate, have high production costs, long preparation cycles, low yield, etc.
In comparison, the industrialized production technology of microbial expression systems is more mature, easier to cultivate, more productive, robust and cost-effective, all of which are ideal features in the biopharmaceutical production and development process. Moreover, with the rapid development of omics and systems biology and the acceleration of the application of synthetic biology, people's understanding of microorganisms has been raised to a new level, microbial expression systems have been continuously optimized and advanced, and the scope of application has been expanded. Even for some emerging therapeutic molecules, microbial expression systems are superior to mammalian expression systems. For example, nanobody products exhibits stable expression in a variety of expression systems because of their simple structure, small molecular weight and no need for glycosylation modification, while microbial expression systems have the advantages of being fast and convenient with reasonable cost, so naturally it has become the preferred expression system for nanobodies.
Jiangsu Yaohai Biopharmaceutical Co., Ltd. (“Yaohaibio”), located in Taizhou China Pharmaceutical City, is a pioneer in microbial expression system in the domestic market. Founded in August 2010, the company has been focusing on the microbiological sector from the start. In 2016, Yaohaibio completed a major transformation — becoming a biopharmaceutical CDMO company providing specialized microbial expression system services. Facts have proven that the transformation was very forward-looking.
The MAH system began to be piloted domestically in 2015, and was promoted nationwide at the end of 2019. During this period, dramatic changes have occurred in the ecological environment, production relationship and market structure of Chinese medicine, and the flexibility in separated production, research, and sales has provided a strong engine for growth of CDMO industry. Also, benefiting from the unabated popularity of biopharmaceutical research and development in recent years, the biopharmaceutical CDMO business has taken advantage of the momentum. According to statistics, between 2016 and 2020, the global biopharmaceutical CDMO market nearly doubled from US$9.4 billion to US$18 billion. The market is expected to continue to grow rapidly driven by the launch of innovative biopharmaceuticals and the higher accessibility of biosimilar drugs, and is promising to reach 46 billion dollars by 2025. While domestic biopharmaceutical CDMO market will reach RMB 45.8 billion at the time, with a compound annual growth rate of 38.1%.
Grab New Chances in mRNA and Seek for Steady Progress
Seizing this strategic opportunity in the industry, Yaohaibio has achieved rapid development and expanded its businesses with its professional strength. Currently, the company focuses its business on recombinant protein peptides, nucleic acid drugs, nanobodies, novel recombinant vaccines, etc., and is committed to constructing an open and integrated platform for production and researches, which can provide one-stop services from gene synthesis, sequence optimization, strain screening, process development, IND application and clinical sample production, NDA application and MAH commercial production, etc.
On February 16, 2022, Yaohaibio announced an important strategic decision: to launch a research-grade sample preparation service platform that includes four technical modules: RNADes (mRNA structure design and optimization platform), RNASyn (mRNA synthesis and modification platform), and RNAPur ( mRNA purification platform), RNAQua (mRNA quality analysis and control), serving throughout the life cycle from mRNA design to sample formation.
The COVID-19 pandemic has hit the industry hard in recent years, but the biomedical industry has ushered in new opportunities. Areas such as SARS-CoV-2 diagnostic reagents, COVID - 19 therapeutic agents, and preventive vaccines have developed rapidly, and a key technology — mRNA technology — become a hot issue. It is named one of the “Top 10 Breakthrough Technologies” of 2021 by MIT Technology Review, and became famous in its first application to the COVID-19 vaccine. Today, mRNA therapy has become a popular basic discipline and applied research direction, and studies on mRNA technology for infectious diseases, tumor vaccines, protein replacement therapy, and cell therapy is also in full swing.
This launch of the “RNASci” research-grade mRNA sample preparation service platform is Yaohaibio's strategic plan to develop gene therapy nucleic acid drugs based on its emphasis. It is also the company’s milestone of improvements, moving from a research-grade sample preparation service ecology to one-stop services of GMP-grade mRNA. Standing on a new “cusp”, Yaohaibio will comprehensively lay out mRNA technology and platform development in the future to help break through barriers to mRNA drug development and help more pharmaceutical companies accelerate the R&D, clinical trials and marketing of mRNA drugs, and benefit patients as soon as possible.
In addition, in order to build a technical barrier, Yaohaibio's Beijing R&D Technology Center is under steady construction, aiming to construct a technology platform for nucleic acid drugs and nanobodies, continuously consolidating the company's one-stop CDMO service capabilities in the fields of nucleic acid drugs and nanobodies.
Expansion of Production Capacity and Further Comprehensive Upgrading of Services
While Yaohaibio is developing rapidly, it is also favored by capital. Data from Pharnexcloud, a brand of Pharnex, show that the company has completed the A Round financing in March 2019 and the B Round financing of over RMB 100 million in November 2020.The injection of capital is not only a sign of excellent enterprise quality, but also a driving force for enterprises to move forward on the fast track of development.
As a type of asset-heavy enterprise, the size and production capacity of the R&D and production base of the biopharmaceutical CDMO is one of the important hard indicators in CDMO service competition and the basis for ensuring the smooth and stable delivery of projects. In order to meet the surging demand of the biopharmaceutical industry, Yaohaibio has greatly expanded its production capacity with the help of capital.
In March 2022, Yaohaibio's macromolecule drug development and industrialization service production line was officially put into use, indicating a further upgrade of its comprehensive service capabilities, consolidating its leading edge in CDMO service scale for microbial expression systems, and satisfying customers from pre-clinical to scale up production, and thus accelerate the development of biomedicine industry.
Currently, Yaohaibio has a GMP-compliant plant that is nearly 20,000m2. There are the production lines that meet the GMP requirements by NMPA, FDA and EMA, a perfect quality management system, and 3 major service platforms for technical process development, quality research and contract production. In terms of production capacity layout, the company has established 5 mature GMP-compliant production lines for microbial fermentation and purification. We have a 2-2000L fermentation system that can achieve high-density fermentation with the OD600 value up to 200 and a total fermentation scale up to 7,500L. There are also 2 drug product production lines, 3 technical service centers, and 1 modern quality research center. Both in the construction of technology platforms and the commercial production capacity layout, Yaohaibio is in a leading position in the country.
However, this is not the fulfilment of our “ambition”. As a local CDMO company, Yaohaibio is also laying the foundation for “going overseas” while further developing in China. Currently, Yaohaibio is actively preparing to build a new service base. After the project is completed, it will become the first domestic microbial expression system production line that meets the requirements for commercial production with the European Union, and will continue to expand the company's advantages of scale in the CDMO service area for microbial expression systems. Wang Manchao, General Manager of Yaohaibio, once said in an interview, “Yaohaibio is indeed an ambitious enterprise committed to establishing service processes, management systems and service capabilities that meet international standards. It can be said that we have always strived to be international.“ On the way to turning the blueprint into reality, Yaohaibio has taken one more step forward.
Serve attentively and reach high-quality cooperation
Whether it is the “Double-Ten Law” or the “Eroom's Law”, it reflects the industry's general belief that the cost of developing a new drug is getting higher and higher, while the success rate falls. Some pharmaceutical companies even have a tendency to be close to cost in terms of return on R&D investment, which cannot meet the needs of the rapid development of the pharmaceutical industry, so the industry is eager for a new model to reduce costs and increase efficiency in new drug development. At the same time, with the implementation of the centralized drug procurement policy, domestic pharmaceutical companies are becoming more and more stringent in controlling drug production costs; in addition, many biotech companies have begun to choose asset-light operating models in order to establish a clearer positioning and differentiated competitiveness. Therefore, cooperation with professional and excellent CDMOs may greatly improve R&D efficiency and accelerate project progress.
Yaohaibio has been devoted to microbial expression systems for more than ten years and has built a good reputation with excellent quality management and robust service system. The company is committed to providing comprehensive quality management services for the IND and clinical stages of the FDA, EMA, and NMPA, and pharmaceutical production that meets the commercialization stage of the NMPA; at the same time, it has rich practical experience and a mature platform the system, adhering to the service concept of “Serve with heart and create the future together”, Yaohaibio has attracted many well-known enterprises to cooperate with.
At present, the company has successfully served more than 100 projects, including 2 phase III clinical trials, 4 phase II clinical trials, several IND and phase I clinical projects, as well as several dual registration in China and US and Australian registration projects. It has become a long-term strategic partner for more than 300 high-quality customers, including Humanwell Healthcare, Tasly, Yabao, TopAlliance, Sinopharm, etc.
Particularly, it is worth mentioning that in January 2022, Yaohaibio's strategic partner Tasly Biopharma Holding Co., Ltd.'s B1344 clinical trial application was approved by the US FDA to be developed to treat non-alcoholic steatohepatitis (NASH). In this project, Yaohaibio mainly participated in many important technical supports and production tasks such as process amplification optimization, registration samples and phase I clinical sample preparation, and actively contributed to the smooth project progress of B1344 with mature quality management and service capabilities.
We believe the present is only the beginning of a farther journey of Yaohaibio. In the future, Yaohaibio will strengthen its innovation engine, extend the service chain, create a more excellent and comprehensive service ecology, meet the challenges, and continue to empower global new drug innovation with the mission of “establish global standards, promote new drugs development, and achieve a healthy life”, tying to become a one-stop CDMO service platform leading in technology and service.
Conclusion
CDMO carries the functions of specialized development and production, and is playing an increasingly important role in the pharmaceutical field. In the past, Europe and the United States occupied an important part of the global CDMO market share with their first-mover advantage; but in recent years, the domestic pharmaceutical industry has developed rapidly and the atmosphere of innovation has become stronger with a number of rapidly emerging CDMO companies. Companies such as Yaohaibio, which can provide professional, comprehensive and integrated services, can quickly smell the cusp and seize new opportunities. At the same time, against the backdrop of the accelerated precise division of labor in the industrial chain, Yaohaibio has made a distinctive feature through its rich accumulation in microbial expression systems, and is still continuously expanding the depth and breadth of its business. It is necessary not only to become a leader in the microbial expression system industry, but also to maintain the advantages. This may be the driving force that motivates Yaohaibio to keep moving forward and break through boundaries.
“Lead the Industry and Flourish the Country” is not only the interpretation of the company’s Chinese name “Yao Hai”, but also its determination to establish “global standards, promote new drugs development, and achieve a healthy life” as an engager and witness of the prosperity of China’s biomedicine industry.