Written by Debjit Chakraborty, Senior Research Associate - BIS Research

The overall mRNA vaccines and therapeutics market have massively garnered immense attention from healthcare stakeholders due to the emergence of COVID-19. The applicability of mRNA technology has shown impressive outcomes in establishing effective COVID-19 vaccination strategies in different regions of the world. Unlocking the potential of mRNA technology for the development of COVID-19 vaccines has ushered in a new era of transformative medicine. In addition, mRNA technology is also being utilized for the development of novel therapies to treat life-threatening debilitating diseases, including cancer, rare diseases, and metabolic disorders, among others. The successful launch of mRNA-based therapies for these diseases in the upcoming years is expected to offer transformative care to patients, further offering value-based clinical outcomes. Further, with the mRNA-based therapeutic candidates for complex genetic and metabolic disorders advancing through the clinical trials, the overall market for mRNA vaccines and therapeutics market is expected to witness tremendous growth in the forthcoming years.

The mRNA vaccines and therapeutics market is evolving at a very rapid pace, with emerging companies entering the market. The overall mRNA vaccines and therapeutics ecosystem include more than 20 companies that are developing novel vaccines and therapies for COVID-19 and non-COVID-19 applications, respectively. These companies are massively investing in conducting research and development for unraveling the potential of mRNA technology to transform clinical outcomes.

This specific market within the healthcare ecosystem has a perfect blend of companies involved in the development and commercialization of mRNA-based COVID-19 vaccines. These companies include Moderna Inc., BioNTech SE, Arcturus Therapeutics Holdings Inc., Translate Bio, Daiichi Sankyo Company, Limited., Gennova Biopharmaceuticals Ltd., and Providence Therapeutics, among others. In addition, this market also has companies that are developing a novel mRNA-based vaccine and therapeutic candidates for various non-COVID-19 applications including, oncology, rare diseases, and metabolic disorders, among others. These companies include Silence Therapeutics, ethris GmbH, Arcturus Therapeutics Holdings Inc., BioNTech SE, CureVac N.V., VERSAMEB AG, and Verve Therapeutics, Inc., among others.

The latest market study by BIS Research, titled “Global mRNA Vaccines and Therapeutics Market” focuses on the application (COVID-19 mRNA vaccines and non-COVID-19 mRNA vaccines and therapeutics), mRNA type (nucleoside-modified mRNA, unmodified mRNA, and self-amplifying

mRNA), and regional analysis. The study offers an in-depth analysis of competitive assessment, country-level analysis, and potential market dynamics, which are shaping up the entire mRNA vaccines and therapeutics ecosystem.

During the report development, Debjit Chakraborty, Senior Research Associate at BIS Research collaborated with various stakeholders to gain a holistic understanding of the intricacies associated with mRNA vaccines and therapeutics.

Following is an excerpt from the conversation between our analyst and industry spokesperson.

Q: How do you perceive the mRNA vaccines and therapeutics?

A: Messenger ribonucleic acid (mRNA) is a powerful technology that offers transient drug exposure in the body, such as vaccines. Vaccines need very short exposure to therapeutic antigens. The mRNA technology is also being used for gene editing, which requires very short exposure of the therapeutic molecule, which is the gene editing complex. Other applications of mRNA technology include regenerative medicine, where regenerative cells are programmed. So, the introduction of transient therapeutic exposure is very powerful when mRNA technology is utilized. For vaccines, a delivery vector is required that can deliver the code, which is then expressed in the body.

mRNAs are very short-lived, and their half-life ranges between 10-13 hours. During the timeframe, mRNA-based modalities express antigens in the body based on the half-life of the protein. The entire drug exposure in the body roughly ranges between 24 – 48 hours. During this timeframe, the immune system recognizes the antigen, which further actives the immune response. So that brief 24 – 48 hours exposure is more than sufficient for the body’s immune system to activate. So, that is why it is a very powerful technology.

Another advantage of mRNA-based vaccines and therapeutics is the requirement of less manufacturing time and low cost when compared to other technologies. Further, the development of novel delivery technologies, particularly lipid nanoparticles (LNPs), has supported the development of mRNA-based modalities for various applications. So, with the advent of COVID-19, mRNA-based vaccines have shown great potential pertaining to the establishment of robust vaccination strategies.

Q: Why are companies such as Moderna Inc. and BioNTech SE/Pfizer Inc. using nucleoside modified mRNA (mod-mRNA) to develop mRNA-based COVID-19 vaccines? Are there any underlying advantages associated with mod-mRNA?

A: The nucleoside modified mRNA (mod-mRNA) offers high protection to the RNA against the host immune system. When the body identifies RNA coming from outside, the cells recognize it as an infection induced by a virus. Usually, the RNA is transcribed in the nucleus, and from the nucleus, it is exported into the cytoplasm. If an RNA is introduced in the body from outside through the plasma membrane or endosomal compartments, the immune system gets activated since the body recognizes it as a viral infection. If an unmodified RNA is delivered into the body, the immune system will quickly react to it, further degrading the RNA. When it is delivered as a vaccine, it becomes important to ensure the expression of the antigens in the body by protecting the mRNA and restraining the immune system to hyper activate.

Q: What are the key differences between the mRNA-based vaccines developed by Moderna Inc. and BioNTech SE/Pfizer Inc.?

A: The sequence of mRNA is different in the vaccines developed by Moderna Inc. and BioNTech SE/Pfizer Inc. Although they both code for the same protein, they use different algorithms to optimize the codons. Depending on the algorithms utilized for the optimization of the codons, they produce different nucleic acid sequences. But, in the end, the two vaccines code for the same protein. Additionally, Moderna Inc. has its own manufacturing process, which is different from BioNTech SE/Pfizer Inc. The manufacturing process of the mRNA vaccines includes the transcription and purification processes. Further, lipid nanoparticles (LNPs) used in the two vaccines are different. So, these are the key differences between the mRNA-based COVID-19 vaccines developed by Moderna Inc. and BioNTech SE/Pfizer Inc.

Q: Currently, there are many mRNA-based therapeutic candidates that are being evaluated clinically, particularly for oncology and rare diseases? When do you think these therapeutics will be launched? Also, what is the potential of these mRNA-based therapeutics for the treatment of cancer and rare diseases?

A: It all depends on the success in the clinical trials. For instance, in cases of rare diseases, Moderna Inc. has not started any clinical trial. Moderna Inc. has some development programs which received investigational new drug (IND) approval from the FDA to commence the phase 1 clinical trials. Also, it is very important to analyze the data from the clinical trials to know more about the tolerability of mRNA therapeutics for rare diseases. Additionally, mRNA therapy for the treatment of rare diseases will require chronic dosing. The safety profile of the lipid nanoparticle (LNPs) mRNA drugs in case of chronic doses is still not known. Therefore, it all depends on the success of the clinical trials from phase 1 to phase 3. Pertaining to oncology, Moderna Inc. has shown some promising data from the clinical trials. It is progressing through the clinical trials, but it will take time to get commercialized in the market.

Q: Given the emergence of different SARS-CoV-2 variants worldwide, do you think that the mRNA-based COVID-19 vaccines are effective for the newer variants compared with the COVID-19 vaccines that are not based on the mRNA technology?

A: I do not have the clinical data of the mRNA vaccines against new variants of SARS-CoV-2. But, when the researchers took the convalescent sera from the mRNA vaccinated individuals and then tested against the new variants, these mRNA vaccines had less efficacy when compared with the original virus. I think that the mRNA vaccines will be effective in moderating the severity of the disease. For the Astra Zeneca vaccine against the South African variant, has an efficacy of less than 20 percent. But overall, the mRNA vaccines of Moderna Inc. and BioNTech SE/Pfizer Inc. are highly effective against the South African variant.

Q: Do you have any idea regarding the efficacy of mRNA vaccines developed by Moderna Inc. and BioNTech SE/Pfizer Inc. in context of Indian population as the clinical trials of these vaccines were conducted majorly in the U.S. and in some parts of Europe. What is your take on this?

A: I have no idea regarding this. We cannot speculate whether the mRNA vaccines in India will be useful. I know that Moderna Inc. and BioNTech SE/Pfizer Inc. are developing vaccines for the new variants. They will be testing the next-generation mRNA vaccines against these variants in the clinical trials. They have plans to keep updating their vaccines to just keep up with the emergence of novel variants.