On July 3rd, GlaxoSmithKline (GSK) and CureVac N.V. announced that they had restructured their existing partnership into a new licensing agreement, allowing both companies to prioritize investment and focus on their respective mRNA development activities.
According to the new agreement, GSK will receive full rights to develop, produce, and commercialize influenza and COVID-19 mRNA candidate vaccines (including combination vaccines) globally, while CureVac will receive a prepayment of 400 million euros and an additional milestone payment of up to 1.05 billion euros for development, regulation, and sales, as well as graded royalties. The new agreement replaces all financial terms in the previous cooperation agreement between GlaxoSmithKline and CureVac.
A pharmaceutical industry analyst from a securities firm told 21st Century Business Herald that the agreement reached this time is also based on recognition of mRNA technology. In recent years, with the gradual development of multiple key technologies including delivery technology, manufacturing processes, mRNA design, synthesis, and modification, the entire industry has also gradually developed, and has become known to the world due to this epidemic.
"I think the real reason why everyone is paying close attention to mRNA technology at present is not only that the outside world has seen the success of developing two types of mRNA COVID-19 vaccine products during the period of COVID-19, but also that the safety and effectiveness of COVID-19 vaccine have also brought great confidence and hope to this field. With the support of a large amount of funds, this track has developed rapidly," said the above analyst.
The application fields of mRNA technology are very extensive, including preventive vaccines, therapeutic vaccines, and therapeutic drugs. For example, on May 31st, American vaccine company Moderna announced that its mRNA respiratory syncytial virus (RSV) vaccine (mRESVIA) had been approved for market by the US Food and Drug Administration (FDA). This is the second commercial mRNA vaccine in the world after COVID-19 vaccine, and also the first non COVID-19 mRNA vaccine in the world.
CITIC Securities Research Newspaper also predicted that the non COVID-19 mRNA market is expected to reach US $28.1 billion by 2025, and the mRNA industry chain market has broad prospects.
Focusing on the development of new vaccines
In 2020, GSK and CureVac jointly announced a strategic cooperation agreement to jointly research, develop, manufacture, and commercialize up to 5 mRNA vaccines and monoclonal antibodies targeting infectious disease pathogens.
According to the agreement at the time, GSK would inject £ 130 million (approximately $160 million) in equity investment into CureVac, equivalent to a 10% stake in the latter, and pay a prepayment of £ 104 million (approximately $130 million). Given that the commercial standard production facility being built by CureVac is being certified in Germany, GSK will also pay CureVac a one-time cost of £ 26 million (approximately $32.94 million) for manufacturing capacity reservation. In addition, CureVac will be eligible for development and regulatory milestone payments of up to £ 277 million (approximately $350 million), commercial milestone payments of up to £ 329 million (approximately $417 million), and royalty fees based on product sales classification.
The reason for this collaboration is also based on the advantages of CureVac's mRNA technology platform. According to public information, CureVac's mRNA technology platform has shown potential in the development and production of mRNA vaccines and therapeutic formulations. Its independently developed RNAoptimizer platform aims to optimize the characteristics of mRNA products based on three core pillar technologies: protein design, mRNA optimization, and mRNA delivery. Users can customize the platform according to their needs, inducing them to undergo varying degrees of immune reactions against selected specific protein antigens, thereby potentially providing effective preventive vaccines to combat infectious diseases such as rabies, and providing immunotherapy for cancer patients.
The above analyst introduced that the mRNA technology platform has functions similar to operating systems on computers. Its design allows it to achieve plug and play with different programs. A program is a unique mRNA sequence that encodes proteins, and different mRNA drugs correspond to different mRNA sequences. The only change from a potential mRNA drug to another drug is the coding region - the actual genetic code that indicates ribosomes generate proteins, while other basic elements are the same. So by encoding different mRNA sequences and delivering them to the human body, it is possible to guide the generation of proteins with different functions, thereby regulating various human functions and achieving the effect of resisting viruses or treating diseases.
"Just like computer programming, as long as you master this development skill, you can develop almost any program. That is to say, we now have mastered the development technology of mRNA COVID-19 vaccine, which means that this technology can also be applied to the development of other drugs. Theoretically, you can develop any mRNA drug, and you can develop and produce vaccines. As long as this ability is verified, you can quickly apply this ability to the development and production of other products, including tumor drugs and rare disease drugs." said the analyst.
Public information shows that GSK and CureVac currently have candidate vaccines for seasonal influenza and other diseases in Phase 2 clinical stage, as well as candidate vaccines for avian influenza in Phase 1 clinical stage. All candidate vaccines are developed based on CureVac's second-generation mRNA technology platform. So far, the relevant data on these candidate vaccines is positive, demonstrating their potential as a potential "best in class" new vaccine.
According to the new agreement terms, GSK will be fully responsible for the development and production of these candidate vaccines, and GSK will have the right to commercialize these candidate vaccines globally.
Need to break down mRNA technology barriers
At present, mRNA vaccines are known as rapidly developing cross era products, which are believed to revolutionize the production process of vaccines. In addition to multinational pharmaceutical companies, this has also attracted many domestic enterprises to accelerate their layout in this field. According to 21st Century Business Herald reporters, there are also many companies in China that are laying out the mRNA vaccine track, including Watson Biotech/Abbott Biotech, Microorganisms, Ruibo Biotech, Aimei Vaccine, Shiyao Group, Kangxinuo Biotech, Xinxin Biotech, Jiacheng Xihai, Ruike Biotech, Blue Magpie Biotech, Guanhao Biotech, and Sinopharm Biotech Funuojian.
However, multiple companies have also fallen through. For example, Smithsonian, founded in Shanghai in 2016, was one of the first companies in China to disclose COVID-19 mRNA vaccine to the outside world, and was known as one of the three swordsmen of domestic mRNA vaccine at that time. But starting from 2023, the funding chain for microbial transmission is tight. In July of the same year, Smithsonian announced that due to major changes in the external objective environment, there was no need for COVID-19 vaccine. In order to reduce the operating costs of the enterprise, its Tianci factory was suspended.
On June 25th, Watson Biotech also announced the termination of cooperation with its partner Suzhou Aibo Biotechnology Co., Ltd. to develop two mRNA vaccines. Including: novel coronavirus mRNA vaccine and herpes zoster mRNA vaccine.
"The layout of the mRNA market still has a long way to go in the future, and many new scientific and technological challenges need to be overcome. For example, researchers need to allow mRNA to enter target tissues and cells, while avoiding the immune system, because once the immune system is triggered, the reactions produced can limit the production of proteins, thereby limiting the therapeutic effect of mRNA drugs. Researchers also need to ensure that cells express enough proteins to achieve the expected therapeutic effect," a clinical expert told 21st Century Business Herald reporters, based on the experience of leading mRNA development companies overseas, MRNA drug development is a comprehensive work that involves multiple disciplines and technologies. A mature and efficient mRNA technology platform requires collaborative efforts from scientists and engineers from multiple disciplines to address unique challenges in mRNA drug development, including mRNA biology, chemistry, formulation and delivery, bioinformatics, and protein engineering.
According to research institutions, with the continuous breakthroughs in technology, the future market size of mRNA technology is enormous. From the current application fields of mRNA technology, it can be mainly divided into four main markets: preventive vaccine market, tumor immunity market, protein replacement therapy market, and regenerative therapy market. From the perspective of market size in various fields, it is expected that the market size will reach 32.6 billion US dollars by 2025, among which the market share of preventive vaccines is the largest, expected to reach 16 billion US dollars.
In promoting the breakthrough development of mRNA technology, the application of AI technology is also considered not to be ignored, as it can greatly improve the efficiency of mRNA drug research and development. For example, using deep learning models to predict the structure of mRNA is faster and more accurate than traditional methods, and further designing and optimizing mRNA molecular sequences to enable mRNA molecules to have high antigen expression as vaccines or high protein expression as drugs.
He Jianxing, Director of the National Respiratory Medicine Center at the First Affiliated Hospital of Guangzhou Medical University, previously told 21st Century Business Herald reporters that with the help of AI technology, massive mRNA molecules can be quickly calculated and screened, saving time and cost for complex high-throughput experimental screening, and thus discovering potential mRNA vaccines or drugs more quickly.
"AI technology can also mine new compound structures or optimize existing LNP structures (delivery systems) from known compound data, helping to design new LNP molecules and formulations. In the process of mRNA and LNP preparation, AI can analyze the process flow through machine learning methods, helping to improve the purity, stability, and efficacy of mRNA and LNP." He Jianxing pointed out that in the future, with the continuous deepening understanding of the sequence, structure, and function of proteins and mRNA molecules, generative AI will have the potential to quickly design new functional molecular sequences for vaccines or drugs based on the requirements of mRNA platforms.