Watson Bio-Vaccine Production Park. Figure/Enterprise Courtesy
In 2005, when Watson Bio was still an unknown company in Yunnan Province, it planted the seed of making a blockbuster vaccine in the world - the development of a pneumococcal polysaccharide conjugate vaccine. 15 years of difficult research and development, no flowers and applause, only countless failures and setbacks after the restart and continuous breakthrough. Fifteen years later, on December 31, 2019, Watson Bio's 13-valent pneumococcal polysaccharide conjugate vaccine (referred to as "13-valent pneumonia conjugate vaccine") was approved for marketing, breaking the decades-long technological monopoly of imported vaccines.
Since its establishment, the cumulative R&D expenditure invested by Watson Bio has exceeded 3 billion yuan, ranking first in its peers, and its independent research and development and production of vaccines have reached 7 varieties and 10 specifications. In 2020, Watson Biotech became the single enterprise with the highest output value of vaccine products in China, and the level of vaccine technology research and development leapt to the forefront of the world. Li Yunchun, chairman of Watson Biology, said: "Becoming the pride of China's vaccine industry and the pioneer of the world's vaccine industry is the vision of every Watson person."
Do not forget the original intention, forge ahead, fifteen years of wind and rain
As the most important vaccine product of Watson Biologics, the research and development time of the 13-valent pneumonia conjugate vaccine is as long as 15 years. "The development of this conjugate vaccine is really, very difficult, very difficult!" Recalling the research and development process of the past 15 years, Huang Zhen, vice chairman of Watson Biology, used three "difficult" words to express thousands of emotions in his heart. The company's production director Shi Jie also used "too painful" to describe the hardships of these 15 years.
In 2005, Watson Bio began product planning for pneumonia conjugate vaccines, and officially established the project in 2006. At that time, many of the world's top R& D teams were conducting relevant research, but their R & D difficulties exceeded expectations, and many R & D teams had to give up. "Multinational enterprises have not developed, what do you rely on as a domestic enterprise?" At that time, many people were skeptical about Watson's development of a 13-valent pneumonia conjugate vaccine. Yuan Lin, director of Watson Biotechnology, said.
But as a company, Watson Bio sees the value behind this product, and the senior management team with technical background values its medical value and social value.
In 2010, Pfizer successfully developed a 13-valent pneumonia conjugate vaccine, which quickly became the world's best-selling vaccine variety after its launch, with sales of up to $5.8 billion in 2019, known as the "king of global vaccines".
The success of Pfizer has also added greater difficulty to the research and development of Watson Biology. The import of 13-valent pneumonia conjugate vaccines has set up many barriers in intellectual property rights, and how to avoid infringement in research and development and production has become the first major problem. Watson's research and development team consulted many legal and medical experts at home and abroad, but there was no good solution. "We still have to have a fundamental innovation breakthrough in the process in order to avoid intellectual property risks and have multiple patents of our own." What's more, we eventually found a better way to produce than imported vaccines. Huang Zhen introduced that the most critical thing in the development of conjugated vaccines is the two technologies of polysaccharide antigen and binding protein, and the team finally decided to start with the binding protein and choose tetanus toxoid as the protein carrier. Because in the protein carrier, tetanus toxoid has the best immunogenicity and can also ensure production capacity.
"I joined the company in 2004, began to participate in the process research and development of the product in May 2005, and experienced the entire research and development process of the 13-valent pneumonia conjugate vaccine, from a young girl to a mother, and the full black hair of Teacher Huang (Huang Zhen) has also grayed. It's really not easy to get to this point, and there are mixed feelings. Yuan Lin always remembers the words that Huang Zhen once said to the R & D team: "As a scientific researcher, the development of a product will take several years or even more than ten years to produce results, to endure loneliness, not to forget the original intention, to have a calm mentality, to have a spirit of hard work in the laboratory." ”
Watson biological vaccine production line. Figure/Enterprise Courtesy
Rise strongly, break the monopoly, and win 40% of the market share
Out of confidence in the results of the phased research and development, and in order to quickly promote the clinical trial, the Watson Biological Research and Development Team decided to make appropriate adjustments to the clinical trial plan, and this adjustment turned the investment in the entire clinical trial into 75 million yuan. Huang Zhen has therefore stated to the company's senior executives and experts that if the clinical trial fails, he is willing to realize the shares of Watson Biology held by him for 75 million yuan and personally compensate the company.
"Mr. Huang completed the task without ambiguity, he often said, you will leave this matter to me, if it can't be completed, I am willing to bring it up to see you." These words actually show his determination and responsibility. Chairman Li Yunchun commented.
From the 7 price to the 9 price to the 13 price, from the selection of protein carriers to the purification of polysaccharides and the overcoming of the extraction process, in the past 15 years, the R & D team of Watson Biology has made a number of major technological breakthroughs, broken dozens of patented technology blockades, and finally successfully developed a 13-valent pneumonia conjugate vaccine, and a number of clinical trial indicators are better than imported similar products.
On February 23, 2019, the relevant departments organized an evaluation consultation meeting in Beijing, which was the most stringent assessment. Huang Zhen said that this is equivalent to the ancient examination of entering Beijing, and the significance is self-evident. Although I was fully prepared, everyone was still very nervous. Before Huang Zhen was ready to take the stage, Li Yunchun pulled him aside, straightened his tie, sorted out his suit, and patted him on the shoulder again. "It's actually a trust and an expectation for him, and he represents our entire team." Li Yunchun said. This scene, along with the successful listing of the domestic 13-valent pneumonia conjugate vaccine, is deeply engraved in the memory of every Watson person.
On the last day of 2019, Watson Bio's 13-valent pneumonia conjugate vaccine was approved for marketing by the State Food and Drug Administration. Watson Bio became the first company in China and the second in the world to have the "King of Global Vaccines" 13-valent pneumococcal conjugate vaccine listed. "I am proud of my motherland that China has broken the 10-year-long global monopoly on imported products." Huang Zhen said.
In April 2020, the domestic 13-valent pneumonia conjugate vaccine was officially launched, which confronted the imported vaccine. By the end of 2020, domestic vaccines will capture 40% of the domestic market share with a wider age range of adaptation. In the first three quarters of this year, about 4.0333 million doses of the domestic 13-valent pneumonia conjugate vaccine were approved, an increase of 21.75% year-on-year.
Technology is king, innovation is the foundation, and the investment in research and development is more than 3 billion
The successful development of a conjugate vaccine for 13-valent pneumonia is not the end point. Technological innovation is the strategic commanding height of Watson Bio's competition with global pharmaceutical giants, and it is also the core competitiveness. From the beginning of the establishment of Watson Biology, it has determined that technological innovation should be the core driving force for development, and continuous high investment in independent research and development. Over the past 10 years, Watson Bio has invested more than 3 billion yuan in research and development, ranking first in its peers. Institutional investors who follow Watson Bio have lamented that this is "based on strong confidence in scientific research strength, almost a tragic scale of investment." Among the human vaccine companies listed on the Gem Board, Watson Biologics ranked first in the number of invention patent applications in China. A scientific research team of hundreds of returnees, PhDs and masters showcased their talents on its vaccine development platform.
As a domestic monomer with the largest number of listed vaccine varieties and exclusive ownership of the world's two best-selling vaccine varieties, Watson Bio has set its sights on the future. Its research and development pipeline includes global blockbuster vaccines such as HPV vaccines and new crown vaccines. In the company's five-year plan, the goal is to lay out five new and best-selling vaccine varieties in the world. The management of Watson Bio believes that only by taking the lead in making breakthroughs in heavy vaccines can the company's core competitiveness be rapidly improved and gain market voice.
Among them, the research and development of the new crown vaccine has attracted much attention. In the three new coronavirus vaccine projects of Watson Biological Layout, the first novel coronavirus mRNA vaccine jointly developed by the Military Medical Research Institute of the People's Liberation Army Academy of Military Sciences of the Chinese People's Liberation Army and Suzhou Aibo Biology has made the fastest progress, and has now completed phase II clinical trials and entered the phase III clinical trial stage. The novel coronavirus vaccine (recombinant chimpanzee adenovirus vector) and the recombinant novel coronavirus vaccine have entered the phase II clinical trial stage.
Chairman Li Yunchun said that the global outbreak of the new crown epidemic has made the global vaccine industry the most competitive and developing industry in the world today, and the biggest driving force for its rapid growth comes from the rapid breakthrough of the world's cutting-edge technology in life sciences, the extraordinary research and development of the new crown vaccine in several technical routes, and the "explosive" amplification of vaccine production capacity. With the advent of the post-epidemic era, these breakthrough cutting-edge technologies, the platforms built by various technical routes and the amplified production capacity will find new breakthroughs, open up new growth space, and enter a wider range of fields, thus promoting major and subversive changes in the world's innovative vaccine research.
The global vaccine industry ushered in the "great reshuffle", in the face of great opportunities and severe challenges, Watson Bio "to become the pride of China's vaccine industry, the world's vaccine industry pioneer" vision remains unchanged, has always been towards the goal of "becoming the world's Watson" the dream of chasing the dream.
Beijing News reporter Wang Kara
Proofread by Yang Xuli