The accelerated mRNA technology is the same as Moderna, whose market capitalization soared by $12.4 billion in a single day

In the past three decades, the research and development of oncology drugs has been in full swing, and the promotion of cancer treatment vaccines has never stopped. However, compared with the former's rapid progress, tumor treatment vaccines are slightly bleak.

In 2010, the world's first cancer treatment vaccine, Provenge, was once approved for marketing in the United States, but this did not become the beginning of the rise of tumor treatment vaccines.

Conversely, Provenge faded out of the market due to its mediocre efficacy and high price. Since then, the development of tumor treatment vaccines has stagnated, and latecomers have collapsed.

However, fortunately, with the maturity of mRNA technology, tumor vaccines are expected to get rid of failure and regain a new life.

On December 13, Moderna announced that its mRNA-4157 in combination with PD-1 inhibitor K for adjuvant therapy for postoperative recurrence prevention in melanoma met its primary endpoint of a Phase 2b clinical trial, which could reduce the risk of recurrence or death by 44%.

Affected by the news, Moderna's stock price staged a violent aesthetic, and its market value soared by $12.4 billion in a single day.

Behind the high expectations of the market, it may indicate that the value of mRNA technology, which is accelerating forward, will be further released.

01 

mRNA technology today, tomorrow, tomorrow

The Chinese name of mRNA is messenger RNA, and its core job is to transmit information: in the cell, it transmits genetic information from genes to protein synthesis factories that direct protein synthesis.

As we all know, in our human body, all kinds of proteins are substances that can influence the appearance, such as antigens and hormones.

This also means that, in theory, we could design mRNA drugs or vaccines that allow human cells to make a variety of proteins to treat or prevent.

Therefore, the preparation of new crown vaccines is only part of the role that mRNA technology can play. After the success of the new crown vaccine, mRNA vaccines have been widely tried in the prevention of other diseases.

However, mRNA technology can not only be applied to preventive vaccines, but also has many potential applications. For example, for the development of therapeutic vaccines.

The many advantages of mRNA technology, including the ability to rapidly develop and manufacture mRNA drugs and the ability of mRNA to encode whole antigens, make it promising for use as a cancer vaccine.

Many patients' tumors are resistant to current immune-targeted drugs, creating new opportunities for mRNA therapeutic vaccines.

Even, mRNA technology is not limited to vaccines, but can also be used as immunotherapy. Because mRNA drugs can theoretically also produce immune or immunomodulatory proteins, such as antibodies or cytokines, to achieve therapeutic effects.

Because of the vast power of mRNA technology, different players in this field are widely deployed. BioNtech summarizes its layout into three phases: today, tomorrow and the future:

"Today" corresponds to the new crown vaccine, "tomorrow" corresponds to the product that replaces traditional medicine, and the layout of "future" refers to the expansion of mRNA into a wider range of therapeutic fields such as autoimmunity and regenerative medicine.

Moderna is no exception, and the layout is quite vast. It is clear that mRNA players around the world are confident in the future of the technology.

02 

The gap between ideal and reality

Of course, the grand layout of many pharmaceutical companies is only an ideal stage, and there is still a long way to go before the successful landing.

Throughout the history of technology development, mRNA technology is still only in the early stages of development, if not for the sudden onset of the new crown epidemic, perhaps mRNA technology will still take a long time to successfully industrialize.

In this case, it is not an exaggeration to see mRNA technology as a track ripened by the epidemic. In addition to preventive drugs, whether it is a therapeutic vaccine or an immune drug, there are more or less certain challenges.

For example, the challenge in developing a therapeutic oncology vaccine lies in two things: how to find the right antigen and overcome the inhibitory microenvironment.

Antigens are the core components of cancer vaccines, and when tumor antigens are injected into the patient's body, they activate the body's immune system's specific immune response to kill tumor cells.

Ideally, the antigen selected for a cancer vaccine should be present in all cancer cells and necessary for cancer cell survival, not in normal cells.

However, it is not easy to find the perfect tumor antigen. On the one hand, tumor-associated antigens are autoantigens, so patients may already have central tolerance to these antigens; On the other hand, tumor-associated antigens are also present in normal cells, which leads to normal cells that may also be accidentally injured after the immune system is stimulated.

After the selection of antigens is completed, how to reverse the immunosuppression in the tumor microenvironment is also a science.

Because the function of cancer vaccines is inseparable from the participation of the immune system, but considering that many tumors themselves have the ability to suppress the immune system, the immune ability of the immune system with killing ability will be greatly inhibited around and inside the tumor. For example, CD8+ T cells are inhibited before they enter the tumor core.

Globally, no product has entered Phase 3 clinical trials. It can be said that the current attempts of mRNA technology in other fields can only be a long-term layout of pharmaceutical companies.

03 

Moderna may be the first to usher in a new era

However, it seems that a new breakthrough in mRNA technology is getting closer and closer.

The seed contestant is Moderna's tumor treatment vaccine mRNA-4157, a high-end customized product.

It first performed next-generation sequencing of cancer cells in patients' cancer tissues and blood samples to find the site of gene mutation;

Then, according to the unique characteristics of each patient's immune system and the specific mutations of the cancer, the neoantigen sequence that can best stimulate the body's immune response is selected;

Finally, vaccines capable of encoding each mutation were created and loaded onto a single mRNA molecule.

As the vaccine is injected into the patient's body, the instructions carried on the mRNA tell the patient's cancer cells to express the new epitope of choice, so that the patient's own immune system can recognize the tumor cells and kill them precisely.

Today, the design works pretty well.

On December 13, 2022, Moderna announced that its mRNA vaccine, mRNA-4157, in combination with PD-1 inhibitor K, achieved its primary endpoint of Phase 2b clinical trial for adjuvant therapy for relapse prevention after melanoma surgery, reducing the risk of recurrence or death by 44%.

At the same time, Moderna said it plans to start a phase III clinical trial of mRNA-4157 in 2023 and quickly expand to other tumor types.

This does not mean that mRNA-4157 has been successful, but at least it proves that mRNA technology is accelerating.

Of course, the players driving mRNA technology forward are not only Moderna, but also overseas players such as BioNtech, and even domestic potential stars, such as Si Microbes, Wiszin, Convinced Biology, Blue Magpie Biology, etc.

Looking forward to the future in the field of preventive vaccines, therapeutic vaccines and immunotherapies, mRNA technology can bring us more surprises.