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Since the birth of Genentech for decades, the biopharmaceutical industry has seen numerous new technologies and countless new companies. Many of these technologies have been known from the beginning of their birth as revolutionary new breakthroughs in comparison with recombinant DNA, such as gene therapy, such as gene sequencing, gene editing, and RNA interference. But to this day, there is still no technology that can revolutionize the pharmaceutical industry.

Moderna Therapeutics’s mRNA therapy is also a new technology that claims to change the world. But this company has been very mysterious, until few outsiders knew Moderna in recent years. Moderna has raised more than 2 billion US dollars, valuation of 7.5 billion, but the question is whether the company’s product line can support such a high valuation? Can mRNA therapy become the next breakthrough in the pharmaceutical industry? This article will unveil the mystery of the largest unicorn in this field of biotechnology.

The adventure of mRNA

 

Derrick Rossi did not like Paris. He often took part in the party for a year and a half in Paris. He had barely had a complete sleep. This kind of indulgence was probably not what he wanted.

 

Rossi studied in Paris after completing his undergraduate and master’s degrees at the University of Toronto in Canada, but after spending more than a year in Paris, he began to realize that this did not seem to be a correct decision. After leaving Paris, Rossi stayed in Texas for a while and then went to PhD in Finland at the University of Helsinki.

 

Perhaps from an outsider’s point of view, this kind of study experience is somewhat tossing, but Rossi does not think so. This complex background makes him able to contact multiple research fields, and lays a solid foundation for future independent scientific research.

 

But until Rossi graduated, he had never done research in the field of stem cells. He only occasionally read the literature and felt that the era of stem cells seemed to have arrived. And as research deepens, anti-aging is no longer recognized as a pseudoscience.

 

Rossi had a hunch that there seemed to be a strong correlation between stem cells and aging. So after graduating from PhD, Rossi went to Stanford University for stem cell and aging research.

 

Rossi likes Boston very much and often rides his bicycle around the city. In 2007, half a year after Rossi became an assistant professor at Harvard Medical School, he finally had his own laboratory. Rossi’s main research direction was hematopoietic stem cells at the time, but after having his own laboratory, he began to hope to do some other, more interesting research.

 

The reason why this idea is there is because Rossi had read a Japanese scientist Yamanaka published a research paper that shocked the world. Many people may have been very familiar with the work done by Yamanaka at that time. Yamanaka is one of the main founders of induced pluripotent stem cell technology.

 

Prior to the induction of pluripotent stem cells, stem cell research has been very dependent on embryonic stem cells. While embryonic stem cells are derived from obsolete embryos, there are numerous ethical issues in these studies.

 

But Yamanaka’s induced pluripotent stem cell technology perfectly circumvents this problem. Initially, Yamanaka found that transfection of the four transcription factor genes Oct4, Sox2, c-Myc, and Klf4 into adult cells through lentiviral vectors can transform adult cells into pluripotent stem cells (iPS cells) similar to embryonic stem cells. This is a landmark study. Yamanaka also won the 2012 Nobel Prize.

 

However, Rossi feels that although iPS technology is extremely important for basic research, if the iPS technology is applied to the field of disease treatment, the technology still has many defects. For example Yamanaka uses DNA viruses as gene carriers to induce normal cell transformation, and DNA viruses may actually induce unexpected mutations in the cell genome.

 

Although lentiviruses are safer than some types of retroviruses, Rossi’s concerns cannot be completely unreasonable. This is actually one of the main reasons that almost destroyed the field of gene therapy in the past. The specific content can refer to the author’s previous article on gene therapy. Gene therapy, if it chooses certain types of viruses as vectors, can actually cause fatal side effects or induce patients to develop leukemia.

 

Therefore, Rossi felt that if the technique of Yamanaka was optimized and the genes were not introduced using virus vectors, it might be possible to avoid these problems. Rossi’s solution sounds very simple, that is using mRNA as a genetic material to express these transcription factors. Unlike DNA viruses, mRNA does not integrate into the genome of the target cell and therefore there is no risk of inducing cancer.

 

A year and a half later, Luigi Warren of Boss Rossi finally completed the experimental study. Rossi believes that this research result will surely cause a lot of turmoil in the academic field. However, he is not willing to end this topic after publishing academic articles. He hopes to commercialize the research results at the same time.

 

However, as a Harvard assistant professor with limited qualifications, he did not have enough social resources to support him in this matter. Moreover, he had no entrepreneurial experience before. Rossi did not know how to conduct the so-called commercialization. So he found his colleague Tim Springer and hoped to get some suggestions from Springer.

 

Springer has had experience in transforming some academic achievements, and he himself also feels that Rossi’s research is truly remarkable. So Springer decided to introduce a person to Rossi: Robert Langer.

This is probably the dream that countless young scientists dream about, because Boston has always said that if you want to start a biotech company, you must first see Robert Langer.

 

The birth of Moderna

 

Langer is a very successful scientist. He has published more than 1,000 academic papers and applied for more than 800 patents. Langer’s e-mail is also full of emails from young scientists around the world. This is actually because Langer once set up more than 20 companies. The company’s business ranged from the delivery system of anti-tumor drugs to hair gel for hair styling. It was all-embracing. These young scientists hope to get some entrepreneurial guidance and advice from Langer here.

 

Langer’s schedule is very full every day. He is very busy. He can reply to seven emails from his toilet. Therefore, most people can book an appointment with Langer for a very short time, about ten minutes or up to half an hour. However, Langer had two hours for Springer and Rossi.

 

One day in late May 2010, the weather was unusually warm. Rossi and Springer went to Langer’s office to meet him on the campus of MIT. Three people sat around Langer’s desk. Rossi took out his laptop and started to explain the experimental data to Langer.

 

Although it may sound simple to use mRNA to express proteins in cells, there are many obstacles in practical applications. For example, cells sense the invasion of foreign mRNA and activate the body’s innate immune system to degrade these foreign nucleic acids. This is also a good mechanism for self-protection of the body to prevent cells from being manipulated by intruders.

 

However, Rossi broke through the cell’s own defense mechanism by modifying the mRNA nucleotides to avoid intrinsic immune system recognition. When the mRNA that can express a specific transcription factor smoothly enters the interior of the cell and is translated into the corresponding protein, the adult cell can be successfully transformed into an iPS cell.

 

Rossi felt that inducing cell transformation in this way would be a remarkable achievement, but after Langer listened, he wasn’t very interested in the transformation of iPS cells. What he found interesting was the first part of the experiment. Rossi delivers mRNA into the interior of a cell.

 

And at this time, Langer has begun to imagine the unlimited potential of this mRNA modification technology. Langer said to Rossi, not only limited to iPS cells, you can apply this technology to any field.

 

Three days later, Rossi appeared in the Flagship Ventures office. Flagship is a very interesting company, because they will not only invest in some startups, they also have startups incubators, and they set up new companies themselves.

 

Flagship’s CEO is Noubar Afeyan. In the 1980s, Afeyan earned a Ph.D. in biochemical engineering from MIT. At that time, the biotechnology industry was just born a few years ago, and it is generally believed that the biotechnology industry originated from the establishment of Genentech in 1976.

 

When Afeyan was a graduate student, Genentech was only a very young company. Although the scale of the industry at that time was still very small, people had unlimited expectations for this field. It was hoped that this field could have explosive growth and greatly improve human health.

 

And in the decades since then, there have been countless new technologies, gene sequencing, gene therapy, antisense therapy, RNA interference, and stem cell therapy. Seeing him rise from a high building, he saw him feast him and saw that he had collapsed. During these decades, Afeyan witnessed the ups and downs of these technologies, so he would not be an overzealous person for the new technology.

 

However, when Rossi found him and told him about his ideas, Afeyan felt that Rossi’s mRNA technology was not simple. Afeyan, like Langer, also feels that in Rossi’s experiment, mRNA technology is much more important than iPS cell induction.

 

Afeyan has been deeply attracted to mRNA technology after talking with Rossi. Within the cell, various therapeutic proteins can be produced, which will be a new way of drug production.

mRNA is translated into protein

 

That evening, Afeyan thought about Rossi’s research while he was driving home. He constantly wondered about the broad application prospects of mRNA technology. He was already very excited. When he returned home, he was very confident that the technology used by Rossi would bring a huge breakthrough to the industry. Afeyan feels that in his investment career for so many years, this is the most promising technology he has ever seen in the field of disease treatment.

 

Two weeks later, Rossi met another person, Ken Chien. Chien is a scientist at Harvard University and he mainly works in the field of cardiac stem cells. Chien and Rossi soon joined forces to conduct another experiment. They found that heart cells can quickly take this modified mRNA and translate it into protein.

 

Chien at this time also began to get excited. He has been studying ways to repair myocardial and vascular damage caused by myocardial infarction, and Rossi’s technology provides him with a seemingly feasible solution, so he also hopes to be able to enter, join them, and set up a new company.

 

So with the support of FlagshipVentureLabs, Rossi, Langer, Afeyan, and Chien gathered together to form Moderna. The concept of the company’s name comes from the abbreviation of Rossi: Modified RNA. Tim Springer also became one of the earliest investors and board members of the company.

 

In 2010, Rossi applied for a patent for the manufacture of stem cells using modified mRNA, and published related articles in September. At this time, in fact, the company still lacks a core figure, that is, the company’s CEO.

In early 2011, Stephane Bancel was the CEO of BioMérieux, a French diagnostic company. Afeyan has repeatedly tried to hire him to manage some startups, but Bancel has always refused. Bancel’s goal is clear, he can indeed try to manage a small company, the company’s business can also be a great risk. But one must be met, that is, if this company succeeds, it must be enough to change the world.

 

Fortunately, Moderna’s cake can be drawn large enough. One day in February 2011, Bancel accepted Afeyan’s invitation to meet with him at the Flagship. Afeyan told Bencel very straightforward that he wanted Bancel to manage a start-up company, and that the company had so far only a few people and only had one mouse experiment.

 

He told Bancel that although the company was small at the time, Moderna would only be able to create a drug candidate in a matter of weeks if mRNA technology could succeed.

 

In addition, from an economic point of view, because mRNA drugs are different from traditional drugs, if the technology can be successful, it will be possible to avoid the patents of already-marketed drugs and use this new technology to develop and target a variety of mature targets. Point of mRNA drug, this would be a very big market.

 

From a technical point of view, there is no carcinogenicity or risk of mutagenesis in mRNA drugs, which has a great advantage over gene therapy. And because of the rapid metabolism of mRNA drugs, patients may not need to receive treatment once or several times just like gene therapy. Patients need continuous use of mRNA drugs (except for vaccines), which will also allow them to make long-term profits.

 

If Bancel is willing to consider it from the perspective of public interest, the technical characteristics of mRNA drugs also enable them to get involved in rare diseases and develop drugs for these diseases. This is actually very similar to gene therapy.

 

After the end of the meeting, Bancel lost his thoughts. Although Bancel’s scientific background is not strong, he can clearly feel the value of this technology. His brain is working fast, thinking about Moderna’s scientific and business potential.

 

Shortly afterwards, Bancel called Afeyan and told Afeyan that he wanted to join the company. He said that if he refuses the job and refuses to manage an opportunity to become a company with the next gene Tektronix, he will probably never forgive himself.

 

From the outside, Moderna’s corporate building is just a four-story building with brick structure. It is not like a place where top scientific research is conducted. Part of the first floor of the building and the basement are the company’s laboratories. After Bancel took office, these laboratories were soon filled with scientists, and their task was to verify and optimize this mRNA technology.

 

Seeing here you may think that Moderna is ready to change the world for the benefit of all mankind and will become the next Genentech.

Moderna Office

Patent concerns

 

The concept of mRNA therapy is indeed very simple if it is simply from the so-called business plan. Many diseases in humans are caused by the inability of the patient to produce enough specific proteins, or defects in the produced proteins that lead to the formation of diseases. At this time, the doctor can inject mRNA into the patient’s body. After the mRNA is transported into the cell, it can be translated into the corresponding protein, so as to achieve the purpose of treating the disease.

 

Unlike gene therapy, this method does not require changing the patient’s genomic information. Furthermore, although recombinant DNA technology can be used to produce the desired protein in some patients, it is usually limited to a few exocrine molecules. The advantage of mRNA technology is that it can produce proteins inside the cell that can produce effects inside the cell.

 

The problem is that Rossi is not the first scientist to try to use this strategy, and the originality of the technology used by Rossi is not high.

In the early 1990s, some researchers have demonstrated that injecting mRNA into mice or rats can induce the production of corresponding proteins in mice. But the protein expression is very low, and mRNA can only be expressed in a very short time.

In addition, mRNA itself is also very unstable and difficult to develop into drugs. A few years later, scientists discovered that the mRNA synthesized in the lab could trigger an immune response after injection, resulting in a more dangerous inflammatory response. Therefore, some researchers began to try to prevent the mRNA from being injected into the body to produce an immune response through the structural modification of mRNA.

 

These studies are actually the basis of Rossi’s iPS experiment. In order to avoid inducing an inflammatory reaction, Rossi and Warren used pseudo-uridine and 5-methylcytidine to replace uridine and cytidine. Although Rossi’s experiment was successful at the time, there was actually a big hidden danger. Because this modification strategy actually comes from Katalin Karikó of the University of Pennsylvania and Drew Weissman.

 

In both the 2005 and 2008 articles, Katalin Karikó and Drew Weissman confirmed in vitro and in vivo experiments in mice that the use of pseudo-uridine and 5-methylcytosine can well avoid cell recognition. This type of mRNA molecule initiates an inflammatory reaction. And as early as 2005 they submitted a patent application for the application of the technology for therapeutic purposes.

 

Karikó and Weissman once founded a company, RNARx, and also successfully received US$900,000 in U.S. government funding. They have demonstrated in experiments in mice and monkeys that cyclical injection of mRNA drugs can increase the expression level of erythropoietin, and erythropoietin can be used to treat certain types of anemia.

 

However, due to the dispute between the researchers and the University of Pennsylvania’s patent authorization, the company’s commercialization has come to an abrupt end. Eventually, the University of Pennsylvania sold patent rights to Cellscript. Although Cellscript has said that they are interested in developing drugs for treatment based on this patent, they mainly use this patent to produce nucleotide modifications for various uses.

 

This patent of Karikó and Weissman actually poses a great threat to Moderna. In fact, early in the company’s establishment, the company’s internal disputes over patents have already become very clear-headed. In an internal report from Flagship in 2010, they clearly stated that if researchers could not find priming uridine and other modification strategies other than 5-methylcytidine, they might have to rely on it. The University of Pennsylvania grants patents to support the company’s technology.

 

Moderna is also trying to circumvent the patent risk, and this responsibility has also fallen to the company’s first employee JasonSchrum. The vast majority of nucleoside analogs tested by Schrum are unable to replace pseudo-uridine and 5-methylcytidine. But in the end he succeeded in finding a compound, 1-methyluracil. In 2014, Moderna obtained a patent license for the use of various nucleosides including 1-methyluracil.

 

But the University of Pennsylvania, as well as other companies that conduct research on mRNA therapy, also have patents in a number of nucleoside fields. Since companies in the field of mRNA therapy rarely disclose their own technologies, many companies do not understand the progress of scientific research in other companies in the field, and intellectual property rights may also be controversial.

 

Despite Moderna’s patent risk, Moderna’s early investors did not worry about it. Because they think that a company that can bring a huge breakthrough to the industry will inevitably have the strength and financial resources to balance it all.

 

While modified nucleoside chemistry is only part of the building of mRNA drugs, another problem that Moderna faces is even more deadly. It is to figure out how to get mRNA precisely into specific cells and tissues in the body. It can be said that this issue is also the most important factor that restricts the development of this technology.

 

There are many problems

 

For drug delivery of mRNA, the difficulties are mainly in two aspects, one is to reach a sufficient number of cells, and the other is to achieve sufficient protein net expression.

 

Many types of cells can spontaneously take up naked mRNA that accumulates in lysosomes via endocytosis, but only a fraction of these mRNAs can enter the cytoplasm. For most cell types, active uptake of mRNA is not only very inefficient, it is also very easy to reach saturation at low concentrations. In addition, naked mRNA is also easily degraded by extracellular RNase. Therefore, it is not feasible to use naked mRNA directly. It is necessary to find a suitable strategy to assist the translocation of mRNA.

 

In fact, as early as when Moderna was founded, Langer told Bancel that the size of Moderna was very small at the time and there was not enough money to build its own drug delivery system. It was only looking for external cooperation. Moderna probably saw more than a dozen technology platforms for drug delivery systems. One of these platforms belongs to Arbutus, but Moderna did not choose Arbutus but used Acuitas to gain access to the technology. Acuitas is a very small company, small to his global headquarters set up in the CEO’s usual home.

 

Another problem with mRNA delivery systems, which is the control of protein expression, is also very difficult to solve. Although lipid nanoparticles protect mRNA from degradation by extracellular enzymes, it is still very difficult for chemists to develop such drug delivery systems. Because if the dose is too low, it will not be enough to produce enough protein to treat the disease, and if the dose is too high, toxicity will occur.

 

Moderna scientists are of course very clear about the difficulty of these issues. Therefore, they searched the medical literature to find diseases that require only a small amount of protein to achieve therapeutic goals, thus avoiding the problem of toxicity caused by excessive doses.

 

But in fact such diseases are very rare. Moderna eventually found an extremely rare disease, Crigler-Najjar syndrome, with an incidence of approximately one in a million. This disease is probably a disease that Moderna thinks is the easiest to treat.

 

Crigler-Najjar was a very important research project within Moderna at that time. But even this project, Moderna, failed to prove that the therapy was effective.

 

At the 2016 JP Morgen Health Industry Conference, Bancel talked about Moderna’s bright future in a crowded conference room. He promised that the drug Crigler-Najjar developed in collaboration with Alexion Pharmaceuticals will enter clinical research in 2016.

Bancel promised publicly many times that Moderna will advance one hundred drugs through mRNA technology in the next decade, and Crigler-Najjar will be the first of its kind.

 

However, the preclinical data of the drug is too poor to meet the safety requirements of clinical trials. If a low-dose drug is used, the therapeutic effect is too weak. When repeated doses are available to achieve therapeutic effects, the drug will cause toxic reactions in experimental animals.

 

So when Moderna was looking for new and better dosage forms, the development of the drug ALXN1540 had stalled indefinitely. At the 2017 Morgen Health Industry Conference in 2017, Bancel did not mention the progress of the project. In July 2017, Alexion stopped the cooperation with Moderna.

 

Due to the frustration of the project, Moderna also shifted the company’s focus to other research areas, focusing on the development of a series of vaccines. Vaccines are probably the areas where mRNA therapy is most likely to succeed because currently, due to the limitations of various technologies, mRNA is only suitable for those diseases that are short-term use and are sufficient for therapeutic/preventive purposes. This is also to reduce the risk of toxicity caused by the drug delivery system itself.

In fact, mRNA vaccines have many advantages over traditional vaccines and DNA vaccines. As mentioned above, since mRNA is not infectious and there is no genomic integration, there is no risk of infection or insertional mutations.

Second, mRNA can be easily metabolized by normal cellular processes, and half-life in vivo can be regulated by various modifications, and its production cost is also relatively low. It is for these reasons that the development of mRNA vaccines has been extremely rapid in the past few years.

Although Moderna has always been reluctant to publish the company’s experimental data, in February 2017, Moderna finally published the long-awaited paper on Cell. Preclinical results showed that the company’s mRNA protected mice from Zika virus infection, and all control mice died within 42 days of viral exposure, while experimental mice receiving Moderna’s mRNA vaccine survived.

 

Last year, Moderna published clinical data on a flu vaccine. Although there is no problem with these data from an experimental point of view, Moderna still has a big risk in these projects because Moderna does not own the patents for these mRNA vaccine drug delivery technologies.

 

As mentioned above, the patent right of the technology actually belongs to Arbutus, but Modera got a patent license from Acuitus, another company authorized by Arbutus, and whether Acuitas has the right to authorize Moderna to use this technology is also very Controversial things.

 

But in addition to the patent dispute and the difficulty of scientific research itself, Moderna’s corporate management model also has such a big problem, which will also limit the company’s development.

Overlord President

 

Bancel, 45, born in Marseille, France, holds a master’s degree from the University of Minnesota, and received an MBA from Harvard University in 2000. After graduation, Bancel entered the sales field and rose step by step at Lilly to take over Lilly’s Belgian subsidiary.

In 2007, 34-year-old Bancel became the CEO of a diagnostic company bioMérieux, a French company with approximately 6,000 employees and a market value of nearly $3 billion.

 

Bancel has an extraordinary talent for sales and management. After he took over as CEO, he did improve his profits. However, he also has an iron wrist, and he treats employees who do not perform well or who don’t like it, and they have a low tolerance for those who are not smart.

 

Bancel’s outstanding management talent also attracted Afeyan’s attention. Afeyan constantly tried to invite Bancel to manage some start-up companies, but Bancel rejected it because he felt the company’s landscape and vision were too small.

 

But Moderna is not the same. Although Bancel does not have experience in managing R&D, he is very confident in the future of mRNA drugs. I believe that Moderna will be successful.

 

So after he served as CEO of this company, he has been practicing this concept. Since Moderna must succeed, if an employee cannot help to complete this task, he is not suitable to stay in this company.

At the beginning of the company’s founding, the interior was in disarray. An early employee once said that after he failed in a simple verification experiment, he actually found himself fired. Another person who trained new employees also found that the person they trained was actually someone who replaced his position.

And the company also practices a rule: eliminate 10% of employees at the end. This is probably the biggest difference between Moderna and all other companies in the biomedical field, because most companies generally want to train their employees to grow with the company.

Moderna lost the director of two chemical departments within one year, and then the chief science officer and the director in charge of drug production quickly left. Within just a year of last year, the heads of the Oncology, Chemistry, Rare Diseases, and Cardiovascular departments also left.

If it is not scientific research or personnel management problems, probably few people are willing to leave. If Moderna’s technology really changed the entire biomedical industry, why would so many people choose to leave?

 

Unicorn Road

 

In fact, Moderna was able to become a company with such a strong ability to absorb gold, to a certain extent, it was due to coincidence.

 

In the first two years after the establishment of the company, Moderna’s account did not have much money and there was often a shortage of funds. At that time, the only goal of the company was to live.

 

However, in 2013, the era in which Moderna needed to live swiftly was gone forever. In that year, the company, which had only 24 employees at the time, signed a $240 million cooperation agreement with AstraZeneca to free Moderna from its financial difficulties.

 

For AstraZeneca, the signing of this agreement is largely due to the situation of AstraZeneca at the time. At that time, AstraZeneca’s several key drug patents were about to expire, and due to the failure of several clinical trials, it was decided to reorganize the R&D business and lay off more than 1600 scientists.

At the time, AstraZeneca CEO Pascal Soriot faced great pressure just after taking office. Although Moderna was very small at the time, the ambition of Bancel’s determination to push a hundred drugs into clinical research within a decade seemed to give Soriot hope.

 

The signing of the agreement became a turning point for Moderna, and soon Moderna’s gold rush began in the investment field. It seems that all investment institutions want to invest in this company.

 

At the end of 2013, Moderna raised $110 million and quickly reached a cooperation agreement with Alexion. In early 2015, Moderna announced the completion of a new round of financing of US$450 million. In September 16th, Moderna completed a financing of US$475 million.

 

Moderna, on the other hand, was reluctant to disclose its own experimental data until some vaccine-related preclinical and clinical trials were published last year. Publishing academic papers in top journals is a very good way for outsiders to evaluate the strength of biopharmaceutical companies. However, Moderna’s interest in publishing academic papers has been limited.

This is due in large part to the fact that after 13 years, Moderna’s account has been running out of money, and it does not need to be financed by showing its research capabilities to the outside world. On the other hand, when investing institutions make investment decisions, they don’t know much about Moderna’s scientific progress.

Large investment institutions can see some of the company’s animal experiment data before investing, and small institutions can only take a cursory look at the data before deciding to invest millions of dollars.

Obviously, Moderna turned its financing into a seller’s market. If 10 investment institutions lined up to save you money, why did you spend time and effort to respond to one of the investors’ questions?

Before the release of any clinical trial data, Moderna’s valuation has soared to nearly 5 billion US dollars. In February of this year, Moderna completed a seventh round of financing of 500 million U.S. dollars. But the question is whether Moderna’s product lines and technologies can support a $7.5 billion valuation if there are so many problems.

 

Although the previous rare disease project failed, Moderna stated externally last year that they have solved the problem that caused the Crigler-Najjar project to fail. Moreover, Moderna treats two rare diseases: R&D programs for methylmalonic acidemia (MMA) and propionic acidemia (PA) performed well in animal experiments in mice.

 

Moderna also announced last year that AZD-8601, a research project that promotes heart tissue regeneration by raising VEGF levels, is safe in Phase I clinical studies. However, Moderna still does not disclose critical data, such as the level of protein expression? Since Moderna did not disclose this data, the outside world is still unable to judge the potential of the drug.

Last month, STAT unveiled a slide of Moderna’s 10-year vision that demonstrates how the company’s product line can hold up to $7.5 billion in valuations. The company predicts that two rare drugs will generate billions of dollars in revenue in the future, while the vaccine business will bring about 15 billion dollars in annual sales for the company. But many investors are unconvinced.

The incidence of methylmalonic acidemia is about one in 50,000, and the incidence of propionic acidemia is even lower. About 40 newborns in the United States are diagnosed with this genetic disease each year. And because only preclinical animal testing data, it is impossible to judge the efficacy of these drugs. Even if the market can be approved in the future, its annual sales will not reach US$1 billion.

 

Although Moderna’s vaccine may be safe, vaccines generally do not need to be reused. However, Moderna has not disclosed whether the repeated use of these vaccines will produce toxicity. These data are critical for the development of other mRNA drugs other than vaccines.

 

Perhaps Moderna’s vaccine programs do look promising, whether it’s preventive vaccines or therapeutic vaccines used in combination with Keytruda for tumor immunotherapy. But even if it can go public, whether a product line that includes Zika, flu, CMV, and cancer vaccines can generate $15 billion in annual sales, I believe different people will give different answers.

Just last month, Giuseppe Ciaramella, the director of the Moderna vaccine project, left. But despite the setbacks in personnel and scientific research, Moderna still has scientists who are reluctant to leave because they know what it will mean for the pharmaceutical industry if mRNA drugs succeed.

 

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