Recently, the number of covid-19 infected people in China has continued to increase. This round of epidemic has affected 29 provinces, showing the characteristics of many points, wide range and frequent occurrence. As the most effective means of prevention, covid-19 vaccination still attracts much attention. Especially in the face of the constantly mutating covid-19 virus, the market has high hopes for covid-19 vaccine with high protective efficacy. Recently, two domestic covid-19 mRNA vaccines were successively approved for clinical trials.
In April 4th, Cansino Biologics Inc(688185) biological (6185.HK) Hong Kong stock announced that its New Coronavirus mRNA vaccine had been approved by the National Drug Administration's clinical trial. On the 3 day, 01093.HK also announced that its New Coronavirus mRNA vaccine SYS6006 had been approved by the State Food and Drug Administration for clinical research.
Previously, covid-19 mRNA vaccine developed by Walvax Biotechnology Co.Ltd(300142) / Aibo biology, Sri Lanka microorganism, Amy vaccine and other enterprises also entered the clinical trial stage.
According to Li Hangwen, chairman of Sri Lanka microbiology, told the 21st Century Business Herald that its independently developed covid-19 mRNA iterative vaccine is undergoing phase 2 clinical trials in Laos; In Brazil, s microorganism has obtained the approval of clinical phase I, II and III. At present, Sri Lanka microorganism is also trying to promote relevant work in China.
At present, the research and development of domestic covid-19 mRNA vaccine blooms at multiple points. Can we break through the barriers and catch up, so as to accelerate the approval of listing and clinical application?
Chinese pharmaceutical enterprises accelerate mRNA market layout
At present, there is no covid-19 mRNA vaccine approved for marketing in China.
Among them, the fastest progress is the biontech covid-19 mRNA vaccine introduced in Shanghai Fosun Pharmaceutical (Group) Co.Ltd(600196) . At the performance communication meeting of Shanghai Fosun Pharmaceutical (Group) Co.Ltd(600196) 2021 held not long ago, Wu Yifang, chairman and CEO of Shanghai Fosun Pharmaceutical (Group) Co.Ltd(600196) told the 21st Century Business Herald that the mRNA market has broad application prospects and is expected to become one of the areas with the most achievements in the next stage. Chinese Pharmaceutical Enterprises also have a relatively rapid layout. At present, Shanghai Fosun Pharmaceutical (Group) Co.Ltd(600196) 's fubitai is still in the process of national review and approval, and our corresponding preparations are also in progress. If there are further exhibitions, we will synchronize with you in time.
In addition, the fastest developing covid-19 mRNA vaccine in China is arcovax (arcov) jointly developed by the Academy of military medicine of Aibo Academy of biology and military sciences and Walvax Biotechnology Co.Ltd(300142) Co. Phase I clinical data were released at the beginning of this year.
At present, many Chinese enterprises are accelerating the layout of mRNA vaccine research and development.
Cansino Biologics Inc(688185) bio, which has previously approved covid-19 vaccine as an adenovirus vector, also entered the bureau to develop covid-19 mRNA vaccine. In the announcement on April 4, Cansino Biologics Inc(688185) Bio said that compared with the traditional vaccine technology platform, the mRNA technology industrialization platform has significant advantages in R & D process and production cycle, and is benchmarked with the international biomedical enterprises at the forefront of this field, After completion, it is expected to have important localization substitution value.
Preclinical research results show that this vaccine can induce high titer neutralizing antibodies against a variety of important variants identified by the World Health Organization (including current epidemic strains). Compared with the existing covid-19 vaccine developed based on the prototype strain, it has a wider spectrum and can more effectively protect the body from the infection of existing variants.
According to the announcement issued by the Shijiazhuang group, its New Coronavirus mRNA vaccine, "SYS6006", has been approved by the China drug administration and can be launched in China. According to the announcement, SYS6006 has independently developed mRNA vaccine against New Coronavirus variant strain. The vaccine can be stored for a long time at 2 to 8 degrees Celsius, and has good protective effect on the current major mutants including Omicron and delta.
In terms of production capacity, Shijiazhuang Pharmaceutical Group said that the key production raw materials and auxiliary materials of mRNA technology have been internalized and replaced by localization, which can meet the demand of large-scale production capacity supply. According to the announcement of Shijiazhuang Pharmaceutical Group at the end of 2021, the total investment of mRNA vaccine industrialization project is 1 billion yuan, of which the annual production capacity of covid-19 mRNA vaccine is 1 billion. In addition, at the performance telephone conference of Shijiazhuang Pharmaceutical Group on March 23, sys6006 has conducted IIT research with a scale of 70 people. According to the preliminary data, the total antibody level of two doses of inactivated vaccine plus one dose of stone drug mRNA vaccine is more than 10 times higher than that of three doses of inactivated vaccine, which is equivalent to or even better than that of three doses of mRNA abroad.
In addition, according to Li Hangwen, chairman of Sri Lanka microbiology, told the 21st Century Business Herald that the covid-19 mRNA iterative vaccine independently developed by Sri Lanka is undergoing phase 2 clinical trials in Laos; In Brazil, s microorganism has obtained the approval of clinical phase I, II and III. At present, Sri Lanka microorganism is also trying to promote relevant work in China. It is revealed that Sri Lanka microorganism has completed the construction of 400 million agent production capacity.
can Chinese pharmaceutical enterprises break through barriers and catch up
Southwest Securities Co.Ltd(600369) medical analysis points out that mRNA technology is the commander to guide the human body to synthesize proteins necessary for life activities. Its main application fields include preventive vaccine, tumor immunotherapy, protein replacement therapy and regenerative therapy. Compared with traditional technologies, the common advantages of mRNA in the above fields include three aspects:
First, the indications in different fields are relatively wide. Due to the different proteins involved in different disease mechanisms of the human body, mRNA technology can suit the remedy to the case and make the human body its own "pharmacy";
Second, the R & D and production cycle is short and the cost is low. According to the research of KIS et al., taking mRNA vaccine as an example, its average R & D cycle is 0.8-1.5 years, and the process production and construction cycle is 2-4 years. The overall commercialization process is 10 times faster than the traditional path. The overall cost is 18 / 1;
Third, the therapeutic effect of mRNA technology is better. Covid-19 vaccine has the highest protection rate, and tumor immunity stimulates strong immunity of B and T cells.
Based on this, mRNA technology will have a huge market in the future.
However, there are three major technical barriers in the mRNA field, and foreign enterprises have become leaders, which will have some impact on late entrants.
Southwest Securities Co.Ltd(600369) analysis shows that in terms of pain points, the pain points to be solved by mRNA technology lie in reducing its own immunogenicity, the efficiency of protein expression in vivo and the final large-scale production. The resulting barriers are: on the one hand, in sequence design, mastering the platform computing ability is the core competitiveness, while 5-terminal capping and the modification of nucleotides in UTR region are the key. On the other hand, in the synthesis design of LNP delivery system, the synthesis technology of mRNA LNP is the most difficult part in the research and development of mRNA field, and it is the core patent link that Chinese enterprises need to master most. In addition, in terms of scale-up production, it is difficult to mass produce clean cap Ag (cap1), modified nucleotides and ionizable lipids in raw materials, and the microfluidic equipment used for mRNA LNP synthesis has the highest barrier in production equipment.
Li Hangwen told the 21st Century Business Herald: "delivery technology is the core barrier of the mRNA industry. How to accurately deliver in vitro transcribed mRNA to specific types of cells, i.e. targeted drug delivery, inhalation drug delivery, etc., still needs continuous efforts." It is understood that the covid-19 mRNA vaccines that have been on the market and are being developed are basically based on the LNP delivery system developed by the biomedical enterprise arbutus.
In this regard, the solution of s microorganism is to use LPP delivery system, which has been patented by many countries. Shen Haifa, chief microbiologist of Sri Lanka, introduced to the 21st Century Business Herald reporter that this is a virus like delivery platform with strong stability, which can realize accurate drug delivery, help stimulate the vitality of immune cells in the body, and then remove viruses in the body. "The LNP delivery system is like a 'soap bubble'. People experience 'floating' when entering, which affects the accurate delivery, and further improvement is still needed in terms of stability." Shen Haifa said.
Wu Yifang also believes that since the global covid-19 outbreak, Chinese enterprises have shown their own advantages. For example, inactivated vaccines have been rapidly developed and listed, but there is still a gap in the research and development of some cutting-edge technologies. For example, in the field of mRNA vaccine and therapeutic drugs, multinational companies have long had layout reserves. He believes that Chinese pharmaceutical enterprises are in the process of catching up. "The application prospect of mRNA technology in the future is very broad. MRNA or one of the most fruitful technical fields in the next stage may even be the core hotspot." Wu Yifang said.
Accelerate the entry of vaccines into the new market
In fact, in order to help fight the epidemic, in the newly released "several policies and measures of Shanghai to fight the epidemic and help enterprises promote development" (hereinafter referred to as "measures"), Shanghai will take measures to support covid-19 virus prevention and control, and the R & D and industrialization of innovative products have attracted much attention. According to the measures, Shanghai will promote covid-19 virus vaccine, rapid detection reagents, specific drugs and other innovative products for epidemic prevention and control to quickly form effective production capacity, register for listing and put into application.
The Measures specify that Shanghai will support the R & D and industrialization of covid-19 virus vaccines, drugs and diagnostic products through the municipal special fund for strategic emerging industries and the special fund for high-quality industrial development, and provide post subsidy support for relevant products according to different clinical trial stages through the special fund of scientific and technological innovation plan, so as to help relevant enterprises speed up the progress of product approval, Promote the rapid formation of effective production capacity, registration, listing and application of innovative products for epidemic prevention and control.
With regard to Shanghai's support for the R & D and industrialization of covid-19 prevention and control innovative products, Li Hangwen told the reporter of the 21st Century Business Herald that at present, Sri Lanka microorganisms has built modern production plants in Zhoupu and Fengxian, Shanghai, which can realize large-scale quantitative production. Sri Lanka microorganism has successfully built an emergency mRNA vaccine technology platform system, committed to realizing the ability of "one product" to effectively neutralize "multiple variants", and providing a strong vaccine emergency guarantee for the national emergency response to various covid-19 variants.
In addition, at present, China is advocating people to strengthen the vaccination of covid-19 vaccine, and the advantages of sequential vaccination have been recognized by the academic circles. Sequential vaccination emphasizes the interval of vaccination with different technical routes. Earlier, Wang Huaqing, chief expert of immunization planning of China CDC, said that some countries in the Americas, Europe and Southeast Asia have begun to implement sequential immunization. Shao Yiming, member of the expert group of the vaccine research and development special class of the scientific research group of the joint prevention and control mechanism of the State Council, also said that sequential immunization is often used for viruses with strong variability and difficult to deal with.
Can mRNA participate in sequential inoculation? What effect will it have? Li Hangwen said that many studies have shown that the sequence of inactivated vaccine + covid-19 mRNA vaccine will significantly improve the level of neutralizing antibody in human body, so as to improve the efficiency of vaccine protection. As a scholar, Li Hangwen introduced that sequential vaccination can not only realize the complementary advantages between different vaccines, but also avoid side effects as much as possible. Individual constitution is different, which may have more side effects on a certain type of vaccine. In his opinion, at a time when the vast majority of Chinese people have been vaccinated with two inactivated vaccines, mRNA vaccine or sequential vaccination is one of the important choices.
Nowadays, mRNA has become the focus of attention in the field of biomedicine. Scholars closely combine mRNA with vaccine technology, nano delivery, immunotherapy and gene therapy, which provides new methods and ideas for solving infectious diseases, cancer and genetic diseases.
"In terms of modifying nucleosides to reduce side effects, Chinese enterprises are still at the international level, lacking nucleoside modification methods and patent protection with independent intellectual property rights. At the same time, there is still a lack of large-scale systematic and comprehensive comparative research on the relationship between the clinical effect, side effects and prognostic response of mRNA therapy. However, these will also become a new direction of efforts and research and development of Chinese Biomedical enterprises." Li Hangwen is very optimistic about the application prospect of mRNA technology. In his opinion, mRNA technology can be used to carry out all drug treatment in the future.
