The Nobel Prize has finally gone to mRNA technology, which has gained fame during the global coronavirus pandemic.
On the afternoon of October 2, Beijing time, Sweden's Karolinska Institute announced that it will award the 2023 Nobel Prize in Physiology or Medicine to Katalin Kariko and Drew Weissman for their breakthrough discoveries in messenger RNA (mRNA) research. These discoveries have led to an unprecedented pace of vaccine development.
The novel coronavirus vaccine based on mRNA technology has brought global attention, and the technology has repeatedly been considered promising for the relevant researchers to win the Nobel Prize, which is finally expected in 2023.
In addition to the Nobel Prize, mRNA technology has already been commercialized: the global birth of the United States Moderna (mrN.US), Germany's BioNTech (BNTX.US), CureVac (CVAC.US) and other MRNA giants; On the domestic side, there are Stone Pharmaceutical Group (1093.HK), Kangxinuo Biological (688185.SH; 6185.HK), Watson Biologics (300142.SZ), Smartfly Biologics (300122.SZ), Ameridien Vaccines (6660.HK), Beigene (BGNE.NS; 06160.HK; 688235.SH), Fosun Pharmaceutical (600196.SH; 02196.HK) and other listed companies have a heavy layout, and there are also new companies such as ABbot Biology and SMIL.
Remove obstacles to the clinical application of mRNA technology
According to Xinhua News Agency, with advances in molecular biology, vaccines based on parts of the virus rather than the whole virus are gradually being developed. However, viruses rely on body cells to replicate, and vaccines based on whole viruses, viral proteins, and viral vectors all require large-scale cell cultures. In some infectious disease outbreaks, rapid vaccine production requires intensive investment in cell culture. For this reason, researchers have long tried to develop vaccine technology independent of cell culture, but the process has been fraught with difficulties.
While collaborating at the University of Pennsylvania in the early 2000s, Corico and Weissman noticed that dendritic cells of the body's immune system recognize mRNA transcribed in vitro as foreign, causing it to activate and release inflammatory signaling molecules. They noted that mRNA carries genetic information that is not just A, U, C, and G bases, but also a wide variety of chemical modifications. The bases in mammalian cell RNA (ribonucleic acid) are often chemically modified, while mRNA transcribed in vitro does not have these chemical modifications. Is this base modification causing the difference?
To test the idea, they produced different mRNA variants, each with unique chemical modifications to their bases, and delivered them to dendritic cells. The results were striking: When base modifications were included in the mRNA, the inflammatory response was virtually eliminated. The results of this groundbreaking study were published in 2005. By discovering that base modifications can both reduce inflammatory responses and increase protein production, Corico and Weissman removed a key obstacle in the path of clinical application of mRNA technology. Based on this technology, mRNA vaccines against Zika virus and Middle East Respiratory syndrome coronavirus have been developed; In the wake of the COVID-19 outbreak, two base-modified mRNA vaccines encoding surface proteins of the novel coronavirus have been developed at a record pace.
East Asia Qianhai Securities research report pointed out that mRNA therapy will be modified mRNA template delivered to the cell, in the cell to produce proteins to stimulate the human immune system, so as to achieve the purpose of treating diseases. Compared with traditional therapies, mRNA technology uses human cells to directly express proteins in the body, so it is more effective, especially for some targets that cannot be patented. At the same time, the development cost of mRNA is low, which can greatly shorten the development cycle and cost of drugs and vaccines. The application field of mRNA technology is very wide, which can be used in preventive vaccines, therapeutic vaccines and therapeutic drugs.
In addition to the application of COVID-19 vaccine, the current pipeline of various companies shows that mRNA technology is mainly applied in the field of infectious diseases and tumors, and mRNA products such as influenza vaccine, respiratory syncytial virus (RSV) vaccine and rabies vaccine are all in the research and development stage. In addition, companies such as Modena are advancing mRNA technology in the treatment of hereditary rare diseases. Citic Securities Research report predicts that the non-COVID-19 mRNA market is expected to reach 28.1 billion US dollars in 2025, and the mRNA industry chain market has broad prospects.
The three mRNA giants rose by the new coronavirus vaccine, and Baioenstein was sued for its patent
Among the mRNA three giants, the most well-known is Biontai, and its partners include the "cosmic pharmaceutical factory" Pfizer. In December 2020, an mRNA vaccine called COMIRNATY was approved for emergency use in the United States, becoming the first COVID-19 vaccine approved for use in the United States.
According to Pfizer's 2021 financial report, COMIRNATY's annual revenue exceeded $36 billion, becoming the new "pharmaceutical king" of the year. According to the 2022 financial report, Pfizer's annual revenue was $100.3 billion, the highest level in history, of which $37.806 billion was generated from new coronavirus vaccines, accounting for about 37% of the total revenue in the reporting period.
Biontec's partner in China is Fosun Pharmaceutical. According to the financial report of 2022, Fubitai has sold more than 15 million doses in Hong Kong, Macao and Taiwan. Since its launch until the end of February 2023, more than 31 million doses have been administered. In the pharmaceutical industry sales of more than 100 million pharmaceutical products or series, Fubitai ranks among them.
Founded in 2008 and headquartered in Mainz, Germany, Biontec was listed on NASDAQ in 2019. With the success of the commercialization of mRNA vaccines, its market value once reached hundreds of billions of dollars, but this figure has not been maintained for a long time, and its current market value is about 26 billion dollars.
Another company that once reached a market value of 100 billion dollars like Biontai is Modena in the United States, which was founded in 2010, began official operations in 2011, and listed on the Nasdaq in 2018. At the commercial level, Modena is currently relying mainly on the COVID-19 vaccine.
On December 18, 2020, the US FDA approved emergency use authorization for Modena's coronavirus vaccine Spikevax, the second COVID-19 vaccine to be approved for emergency use in the United States. According to the 2022 financial report, Modena's annual revenue reached 19.63 billion US dollars, and its revenue ranked 18th among global pharmaceutical companies. It is worth noting that Modena is increasing its investment in China.
On July 5 this year, the headquarters of the United States Modena company confirmed to the surging news reporter that on July 5, the company signed a memorandum of understanding and a related land cooperation agreement to create opportunities for Modena to research, develop and manufacture mRNA in China. Under the agreement, any drugs produced will be specifically targeted at Chinese patients and will not be exported.
Along with Biontai and Modena, there is the German CureVac company, whose official website shows that CureVac was officially established in 2000 and is the first company in the world to successfully use mRNA for medical purposes.
CureVac has chosen GlaxoSmithKline, one of the "Big Four vaccine giants", as its partner for mRNA and influenza vaccines. But the development has not been smooth. In June 2021, CureVac announced that the interim analysis of Phase III clinical trials of its candidate novel coronavirus vaccine showed that the initial effectiveness of the vaccine to prevent novel coronavirus disease was only 47%, failing to meet the statistical target of at least 50% of approval requirements. According to the official website, at present, its product pipeline is at the forefront of an mRNA novel coronavirus vaccine, which is in the second clinical stage. Currently, the company has a market capitalization of $1.534 billion.
It is worth mentioning that Modena and CureVac have both sued Pfizer and Biontec over their mRNA technology patents, arguing that the COVID-19 vaccine infringes their patents on basic mRNA technology.
In the wake of the COVID-19 pandemic, several giants have put mRNA technology on diseases that humans care more about, such as cancer. In October last year, when the founders of Biaoentai were asked in an interview when a cancer vaccine based on mRNA technology could be used in patients, they said it could be before 2030.
The layout of domestic mRNA companies is numerous, and the commercialization results remain to be observed
The prospect and potential of the 100 billion track of mRNA technology is unlimited, the mRNA novel coronavirus vaccine has been approved in China, and many listed companies have adopted the cooperative layout, but in terms of commercial returns, the road ahead for domestic enterprises is still misty.
On March 22 this year, Shiyao Group's new coronavirus mRNA vaccine (SYS6006) was included in emergency use in China, and the speculation of the first mRNA vaccine finally had an answer. As for the commercialization of the vaccine, the group mentioned that the vaccine was launched in Shijiazhuang, Shanghai and Jiangsu provinces and cities.
Previously, the mRNA novel coronavirus vaccine was the first mRNA novel coronavirus vaccine cooperated by ABbot Biology and Watson Biology, which has already been in the phase III clinical trial stage. The vaccine is currently only licensed for emergency use in Indonesia and has not yet been approved for domestic use. Watson Biological also cooperated with Blue Magke Biological mRNA vaccine, 2023 semi-annual report mentioned that the company is actively promoting the vaccine marketing authorization drug registration application related work.
Cansino Bio, which has drawn attention for its COVID-19 vaccine based on adenoviruses, is also deploying an mRNA vaccine. The semi-annual report of 2023 shows that its mRNA novel coronavirus vaccine has completed clinical phase 2b trials. On August 7 this year, Concino Bio and Astrazeneca signed a "Product supply cooperation Framework agreement", Concino Bio said that the cooperation will focus on using the company's mRNA production platform to support its research and development of specific vaccines.
Hundreds of billions of private vaccine giant Zhifei biology is not absent from the mRNA track. As early as the evening of December 7, 2020, Zhifei Biology issued an announcement that the company intends to subscribe for 10.189% of the equity of Xinxin Biology with its own funds of 35 million yuan, and Xinxin Biology has built an industry leading technology platform in the field of mRNA, especially LNP delivery technology. The 2023 semi-annual report only mentions that the company is a participating company and does not mention any other information.
Another partner of the company is Beigene, and in July 2022, the two companies reached a global strategic cooperation. Under the terms of the agreement, Biologics will receive an initial payment from Beigene and will be entitled to additional payments and tiered royalties based on R&D progress, registration progress and commercialization milestones achieved under the mRNA-LNP collaborative research program. Beigene will have exclusive global development and commercialization rights for the mRNA-LNP products jointly developed by the two companies. In addition, by granting Beigene a non-exclusive license to use its proprietary LNP technology platform, Convinced Bio will receive an additional down payment and be entitled to additional milestone payments.
Ai Mei Vaccine mentioned in the 2023 semi-annual report that the company has developed bivalent mRNA novel coronavirus vaccine, so far, has applied for clinical approval in China, and carried out phase III clinical trial in Pakistan on March 25, 2023, which is currently in the final stage.
Si Microbe is also a star company on the domestic mRNA track. In July this year, it was reported that from July 21, 2023, Simicrobe's Tianci factory suspended trial operation, during which the relevant personnel were waiting for their posts, and only a small number of necessary personnel were retained to maintain the basic operation of the factory and on-site care. In response to the above news, Smicro Biotechnology responded to surging news reporters that it is mainly because of the existence of objective factors in the environment, and there will be no production demand for the new coronavirus vaccine in the near future, so the trial operation will be suspended first, and the main effort will return to research and development.
Subsequently, on August 24, SMirm's wechat public number issued a message saying that the company would carry out CDMO business, that is, foundry. At the end of September, a consumption restriction order of the People's Court of Pudong New Area of Shanghai showed that the consumption restriction measures were taken on SMIRm, and the SMirm and its legal representative Li Hangwen were not allowed to implement a number of high consumption and consumption behaviors that were not necessary for life and work.
From star enterprises that rely on mRNA technology for multiple rounds of financing to factory shutdown and legal representative limit, the industry has triggered a discussion on the survival of mRNA enterprises in the post-epidemic era. On the limit of high news, Si Microbe and Li Hangwen did not respond to the above news. Surging reporters noticed that on the evening of October 2, Li Hangwen forwarded the news of the Nobel Prize in the circle of friends, and captioned it: "The name is deserved, and I am proud of the road of my struggle."