The announcement of mutant strains has made global anti-epidemic efforts dare not relax their vigilance and actively seek countermeasures. Whether it is vaccines or special drugs, they are evaluating the effectiveness and protection of the mutant strains.
According to recent data released by BioNTech, the effectiveness of the two-dose mRNA vaccine for new mutant strains has been significantly reduced, but the effect of three-dose vaccination will reach the protection of the two-dose vaccine against the original virus. On the other hand, BioNTech stated that the company is simultaneously carrying out the research and development of the new vaccine, which is expected to be delivered before March next year.
The mRNA vaccine has made a big splash in the new crown epidemic. In fact, mRNA molecules have been discovered as early as 1961, but it has not been in clinical application until recent years, especially during the epidemic, in less than a year, a large-scale population was produced. vaccine.
It takes a long process for any technology to move from the laboratory to the market. Throughout the past development history, the virus pandemic is like a catalyst to promote the rapid iterative update of medical technology. The new crown epidemic has brought mRNA technology from basic research into The “real world” has achieved medical transformation and industrialization.
The “sense of smell” of capital is always very sensitive. Companies such as BNT have doubled their “worth” through the new crown vaccine. Since the epidemic, BioNTech has received multiple financings and its current market value is nearly 70 billion U.S. dollars.
mRNA vaccines are only one of the more advanced directions in the development of mRNA therapy. Compared with traditional drugs, mRNA therapy has unique advantages. Some analysts pointed out that the development path of mRNA technology is usually from infectious disease vaccines to cancer vaccines, and from local therapy to systemic therapy.
A few days ago, BioNTech CEO and co-founder Ugur Sahin, MD, received an exclusive interview with Caijing.com, sharing the latest data on vaccine research, the progress of new vaccine research and development, the difficulties of mRNA technology and the cooperation of multiple links, as well as development paths and expansion areas. He learned his experience and opinions.
The preliminary research results of the three-dose vaccine are announced, and the research and development of the new vaccine has started
Caijing.com: Previously, a set of data released by BioNTech showed that “For mutated strains, three doses of mRNA vaccine can achieve the effect of the previous two doses.” So is it necessary to update vaccines against new mutated viruses?
Ugur Sahin, MD:We need to further evaluate the data, so we cannot provide any conclusions and recommendations at this time.
Our preliminary experimental studies have shown that, compared with the two doses of vaccine, the titers of neutralizing antibodies to Omi Kiron produced by our third dose of the new crown vaccine have increased by 25 times; after the booster shot, it is against Omi Kiron mutant strains. The antibody titer of the vaccine is equivalent to the antibody titer against the mainstream virus type after two injections of vaccine, that is, it can provide high-efficiency protection.
It is still uncertain whether the market needs a new crown vaccine against Omi Keron (mutant virus).but weThe research and development of the new vaccine started on November 25,In the future, we need an improved vaccine that can provide higher protection and longer duration against Omi Keron.The first batch of Omi Keron customized vaccine is scheduled to be delivered within 100 days, that is, before March 2022, but it needs to wait for regulatory approval.
The purpose of developing an improved vaccine against Omi Keron is to induce a higher level of protection against the virus in the human body and a longer protection time. We will continue to collect laboratory data and analyze the effectiveness of the vaccine in the real world to evaluate the protective efficacy of the improved vaccine against the Omi Keron variant and propose the most effective way to prevent the epidemic.
Finance Network:Based on the existing mRNA technology platform, what is the time period for the development of new vaccines against mutant strains? Is it necessary to “form a mechanism for regularly changing vaccines like influenza viruses” for updated virus sequences?
Ugur Sahin, MD: Mutation is one of the characteristics of the virus, and so is the new coronavirus. This is a normal phenomenon. The key question is whether the mutated strain has immune escape (such as beta strain).At present, we are still not sure at what speed the vaccine will be adjusted and updated in the future, but the data will guide us when we need to update the vaccine.
We can adjust and produce an improved version of the vaccine. On the basis of obtaining regulatory approval, the delivery of the first batch of vaccines can be started in about 100 days at the earliest. The reason for this is that we have established a corresponding response model in advance to help evaluate the development, manufacturing, and supervision processes of specific variant strain vaccines. The purpose of this model is to be supported by extensive clinical data in preparation for submission to regulatory authorities.
The new formula vaccine has a longer storage time,mRNANeed to be delivered to the correct immune area
Caijing.com: At the beginning of the approval of BNT162b2, because the storage and transportation of vaccines need to meet high conditions, whether the vaccine is accessible has become a topic of widespread discussion. What is the current basic situation of storage and transportation?
Ugur Sahin, MD:Currently, the thawed, undiluted BNT162b2 vaccine can be stored at a refrigerator temperature of 2-8 for one month (31 days). Within these 31 days, the undiluted vial after thawing can still be transported for a total duration of no more than 12 hours. After the vaccine is diluted by normal saline, it can be stable for 6 hours at a temperature of 2-30, and the injection needs to be completed within 6 hours at room temperature.The low-temperature freezer is only used for long-term storage of more than a few months.
A vaccine with a new formula will be launched next year.Compared with the current vaccine that can be stored in 2-8 refrigerators for 31 days, the new formula vaccine can be stored under the same conditions for up to 10 weeks. After completing the first puncture (diluted by injecting physiological saline), the vaccine vial with the new formula can be stored and transported at a temperature of 2-30, and the injection can be completed within 12 hours. The product stability at the same temperature is 6 hours. The new formula vaccine for the currently approved population (people aged 12 and above) will be launched in phases starting in early 2022.
Finance Network:Nucleic acid drugs and vaccines need to emphasize two issues, namely delivery and administration. LNP is the current mainstream delivery system, and some company leaders pointed out to Caijing.com that “there will be more complete technologies in the future, such as RNA self-replication technology, etc.”. What is the current status and future of delivery technology?
Ugur Sahin, MD:The mRNA must be presented to the correct immune area, such as lymph nodes, where specialized dendritic cells can efficiently transmit T cells and directly attack dangerous cells.mRNA needs to be encapsulated in a delivery vehicle, such as lipid nanoparticles or lipid nanocomplexes. We have achieved the correct presentation of mRNA through the breakthrough progress made on the two vectors.This helps to ensure that dendritic cells and T cells get the correct information, understand the “enemy” information, and the target of the attack.
In addition, we use different forms of mRNA according to different application methods and purposes, and further optimize and study their combinations. In the production of therapeutic proteins, we will use modified RNA, namely modRNA. In our cancer vaccine platform, we use uridine RNA, or uRNA, which has the function of triggering an inflammatory response in the immune system to resist harmful factors and can provide optimized immunogenicity. Self-amplified RNA, or saRNA, replicates itself before producing protein, which makes the required dosage only a small part of the vaccine dose.
mRNAThe technology is suitable for testing various candidate vaccines, and demand promotes the acceleration of the research and development process
Caijing.com: mRNA molecules have been discovered as early as 1961, but they have not been used in clinical applications until recent years. Especially during the new crown epidemic, they were produced for use by large-scale populations in less than a year. Vaccine. The epidemic has accelerated mRNA therapy, especially related technology vaccines from theory to application?
Ugur Sahin, MD:In fact, we launched the first clinical trial of mRNA-based cancer vaccine therapy in 2013.
The new crown epidemic is a global crisis. The huge demand for vaccines has greatly accelerated the research and development process. In order to meet the public’s demand for the new crown vaccine, we have given a lot of resources to this.
At the same time, there are many other medical challenges that need to be solved urgently, such as cancer, malaria, tuberculosis and AIDS.
Caijing.com: What are the reasons for the emergence of emerging small companies such as BioNTech during the epidemic?In the development of the new crown vaccine, BioNTech andFosun PharmaandPfizerThe cooperation of many companies has attracted wide attention. Can such cooperation accelerate the development, production and supply of vaccines?
Ugur Sahin, MD:Using traditional vaccine development technology will take a long time to manufacture vaccines.mRNA is also very suitable for testing various candidate vaccines.In the preclinical stage of the first vaccine, we designed and tested more than 20 candidate vaccines, and finally selected the best four vaccines and conducted clinical studies.
In this unprecedented global epidemic, many factors have jointly promoted the accelerated R&D, marketing, production and supply of vaccines. For example, we have been conducting research on mRNA technology for more than 30 years. During this epidemic, we actively communicated with regulatory authorities. , To speed up the process of being approved for marketing, all of which have played an important role in accelerating the development, production and supply of vaccines.In addition, at the beginning of the epidemic, we integrated relevant resources and optimized the company’s internal processes. At the same time, we conducted early communication with regulators and the government, and shared our expertise with our partners.PfizerandFosun PharmaResources.
In the future, we will continue to complement our partners’ strengths in their respective professional fields, and launch new therapies as quickly as possible, such as the development of oncologyCombination therapyplan.
Caijing.com: Some people in the industry believe that “in theory, all protein-level diseases can be treated with mRNA alternatives.” What are the specific application areas of mRNA technology? In which areas is BioNTech currently making further explorations?
Ugur Sahin, MD:In the beginning, we developed personalized treatments for cancer patients, but mRNA technology is multi-functional, and we will continue to develop driven by medical needs.
In the next few years, we hope to further advance our 15 candidate products in the oncology field, which are currently undergoing clinical trials.Currently, we have 4 product candidates in the second phase of clinical trials. Two of the products are based on our existing mRNA cancer vaccine platform “FixVac”, and the other two products are based on the personalized cancer vaccine platform “iNeST”. We expect that in the next five years, more cancer pipeline candidates will enter the advanced clinical development stage, and we will strive for the first batch of candidate products to enter the market.
In addition, we expect to start clinical trials of vaccine candidates for malaria and tuberculosis programs in 2022. At the same time, we also hope to continue to advance HIV programs. We are also considering exploring the potential of mRNA in autoimmune diseases and regenerative medicine.
Caijing.com: Since the epidemic, BioNTech has received multiple financings, and its current market value is close to 70 billion U.S. dollars. Is the company’s investment in future pipelines/R&D overview?
Ugur Sahin, MD: What many people don’t understand is that it usually takes at least 1.5 to 2 billion euros to develop a new vaccine.The reason why we are able to respond to the new coronavirus so quickly and effectively is because we have invested more than $1 billion in research and development in the past 12 years.
We need to continue to invest heavily in research, development and production capacity, which requires financial support. Since the epidemic, we have made a capital increase for the research and development of the new crown vaccine. It is very important for us to be able to apply the successful development experience of mRNA vaccines to other projects. Therefore, we will continue to invest in our R&D projects and pipeline products in the future.
(Source: Caijing.com)
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