Elasomeran

The mRNA therapeutics market has experienced explosive growth over the past few years. According to estimates by QY Research, the global mRNA therapeutics market reached a total sales value of RMB 248.4 billion (approx. USD 35 billion) in 2023. Preventive mRNA vaccines are projected to achieve a 20% penetration rate in the USD 50.3 billion vaccine market by 2025, corresponding to a market size of USD 10.1 billion. Meanwhile, mRNA cancer vaccines are expected to reach a 0.5% penetration rate by 2025. From 2023 to 2028, the mRNA vaccine and therapeutics market is forecasted to grow at a compound annual growth rate (CAGR) of 16.8%, reaching USD 101.8 billion by 2028 and RMB 574.3 billion (approx. USD 80 billion) by 2030, with a CAGR of 13.2% between 2024 and 2030. Mechanism of Action and Core Advantages of mRNA DrugsThe core advantages of mRNA therapeutics lie in their flexibility and high efficiency. These features make mRNA an ideal platform for diverse applications such as preventive vaccines, cancer immunotherapies, and protein replacement therapies. As a single-stranded long RNA molecule, mRNA delivers genetic information from DNA and undergoes translation to synthesize proteins, offering immense therapeutic potential. Principles of antigen-encoding mRNA pharmacology1mRNA production begins with in vitro transcription (IVT), using linearized plasmid DNA containing the target antigen coding sequence as a template. This DNA is usually obtained via PCR amplification or chemical synthesis and is linearized to prevent circularization during transcription. RNA polymerases such as T7, T3, or SP6 transcribe the DNA in a reaction mixture containing nucleoside triphosphates (NTPs), enzymes, buffers, and cofactors. The resulting mRNA molecules are structurally complete, featuring a 5’ cap, untranslated regions (UTRs), an open reading frame (ORF), and a poly(A) tail—elements essential for intracellular stability and translational efficiency. ·The 5' cap, added via co-transcriptional or post-transcriptional methods, is crucial for stability and translation initiation. ·The 5' UTR influences translation initiation efficiency. ·The ORF encodes the target protein and represents the functional core of the mRNA. ·The 3' UTR and poly(A) tail enhance stability and translation efficiency. Tuning mRNA drug dose pharmacokinetics1The synthesized mRNA must be purified and chemically modified to increase stability and reduce immunogenicity. Common purification methods include chromatography, precipitation, and filtration to eliminate impurities such as residual DNA templates, unincorporated NTPs, and enzymes. Chemical modifications serve to enhance translational efficiency and minimize immune responses. These include: ·Nucleoside modifications, such as replacing uridine with 1-methylpseudouridine, to improve translation and reduce innate immune activation. ·Phosphorothioate (PS) backbone modifications, which substitute sulfur atoms in the phosphate backbone to improve mRNA stability. ·2’-O-methylation of ribose sugars, increasing mRNA resistance to degradation and decreasing immunogenicity. These enhancements make mRNA therapeutics more viable for clinical applications. General procedures for LNPs preparation3To protect mRNA from degradation and enable efficient cellular delivery, it is typically encapsulated in delivery vehicles—most commonly lipid nanoparticles (LNPs). LNPs consist of ionizable lipids, helper lipids (e.g., DOPE), PEGylated lipids, and cholesterol, which work synergistically to form stable nanoparticles: ·Ionizable lipids form electrostatic complexes with negatively charged mRNA. ·Helper lipids contribute to particle stability. ·PEG-lipids reduce opsonization and extend circulation time. ·Cholesterol enhances membrane rigidity and prevents premature mRNA release. Other delivery systems under investigation include polymeric nanoparticles, viral vectors, and cell-penetrating peptides (CPPs), but LNPs remain the most clinically validated method to date. In vitro transcribed mRNA for therapeutics2Once administered, mRNA-loaded LNPs are taken up by antigen-presenting cells through endocytosis, including phagocytosis (mainly in immune cells like macrophages) and pinocytosis (common to most eukaryotic cells). The endocytic vesicles gradually acidify, triggering structural changes in the LNPs and facilitating mRNA release into the cytoplasm. The precise mechanisms behind endosomal escape are still under investigation. Inside the cytoplasm, mRNA is recognized by ribosomes and translated into proteins or antigens via the host cell's translational machinery. This process includes: ·Initiation: Ribosomal subunits and initiation factors recognize the 5' cap and start codon (AUG). ·Elongation: Ribosomes move along the mRNA, synthesizing polypeptides. ·Termination: Translation ends upon encountering a stop codon (UAA, UAG, UGA), and the protein is released. The nature of the protein or peptide encoded by the mRNA determines its therapeutic effect—be it to stimulate an immune response (as in vaccines) or to replace or modulate dysfunctional proteins (as in gene therapies). For mRNA drugs used as vaccines, the translated antigen proteins are degraded by proteasomes into peptide fragments, which are then presented via MHC class I molecules to cytotoxic T lymphocytes (CD8+ T cells), thereby activating a cellular immune response. Concurrently, secreted antigens can be taken up by antigen-presenting cells and presented through MHC class II molecules to helper T cells (CD4+ T cells), further stimulating B cells to produce neutralizing antibodies. Cytotoxic T cells recognize and eliminate infected or tumor cells expressing the specific antigen, directly clearing the source of infection or malignancy. Helper T cells secrete cytokines that regulate the magnitude and type of immune response and promote the proliferation and differentiation of B cells to generate antibody-producing plasma cells. This dual activation of both humoral and cellular immunity results in comprehensive immune protection. This feature of mRNA vaccines gives them a significant advantage in both prophylactic vaccination and cancer immunotherapy applications. mRNA has a relatively short intracellular half-life—typically around 7 hours—after which it is rapidly degraded by ribonucleases (RNases), resulting in the loss of its protein-coding capability. The protein products translated from mRNA may undergo post-translational modifications and exert their effects either within host cells or via autocrine, paracrine, or endocrine pathways. The transient expression nature of mRNA ensures a high level of safety and controllability within cells. The expressed proteins can serve diverse biological functions—for instance, antigens can stimulate immune responses, and therapeutic proteins can directly act on specific pathological processes. Furthermore, the transient nature of mRNA expression avoids the risk of genomic integration, thereby reducing the potential for insertional mutagenesis. These characteristics make mRNA therapeutics highly promising across a broad range of treatment areas. Key discoveries and advances in the development of mRNA as a drug technology1Regional Landscape of mRNA Drug DevelopmentThe United States is the global epicenter for mRNA drug development, home to the most active mRNA technology platforms and biopharmaceutical companies such as Moderna, BioNTech (which has U.S. operations), and CureVac (which maintains a U.S. subsidiary). The rapid growth of mRNA research in the U.S. is supported by a strong foundation in scientific research, ample funding, and a robust regulatory framework. The U.S. Food and Drug Administration (FDA)’s expedited review and supportive stance on mRNA technologies have positioned the country as a global leader in the development and commercialization of both mRNA vaccines and therapeutic mRNA-based drugs. Europe is another major hub for mRNA innovation, particularly in countries such as Germany, the United Kingdom, and France. BioNTech, headquartered in Germany, co-developed the BNT162b2 COVID-19 vaccine with Pfizer, marking the first mRNA vaccine approved globally. CureVac, also based in Germany, is a pioneer in applying mRNA technology to cancer treatment and infectious disease prevention. Leading academic institutions such as the University of Oxford and Imperial College London have made significant contributions to the basic research of mRNA technologies. Regulatory support from the European Medicines Agency (EMA) has further accelerated development in the region. In Asia, countries such as China and Japan have made notable breakthroughs in mRNA vaccine and therapeutic development, supported by favorable government policies and incentives. India and South Korea are also actively investing in mRNA capabilities and pursuing international collaborations to accelerate R&D progress in this field. Global Competitive Landscape of mRNA DrugsThe global mRNA drug market is currently dominated by a few leading players, including Moderna, BioNTech, and CureVac. These companies are at the forefront of mRNA technology innovation and clinical application. Thanks to their successful COVID-19 vaccine launches, Moderna and BioNTech have seen massive increases in market capitalization, rising from USD 6.58 billion and USD 7.68 billion at the beginning of 2020 to USD 36.18 billion and USD 25.25 billion, respectively, by the end of 2023. In addition, global pharmaceutical giants such as AstraZeneca, GSK, Merck, Eli Lilly, Sanofi, and Pfizer are actively expanding into the mRNA field, further intensifying market competition and accelerating development. Moderna Moderna is a U.S.-based biotechnology company headquartered in Massachusetts, founded in 2010. It is dedicated to developing innovative therapies based on mRNA technology. In December 2018, Moderna went public on NASDAQ, raising over USD 600 million at USD 23 per share—a record-setting IPO for a biotech company. Its market value surged more than 440% from USD 6.58 billion in early 2020 to USD 36.18 billion by the end of 2023. Moderna’s success is largely attributed to its breakthrough with the mRNA-1273 COVID-19 vaccine, which became the first COVID-19 mRNA vaccine to enter Phase I clinical trials and was granted Emergency Use Authorization by the FDA at the end of 2020. The company is also actively developing mRNA vaccines targeting RSV, HIV, Zika virus, Epstein-Barr virus, and more, aiming to launch up to 15 new products and advance up to 50 mRNA drug candidates into clinical trials within the next five years. BioNTech BioNTech is a Germany-based biotechnology company founded in 2008. It focuses on the application of mRNA technology in cancer immunotherapy, infectious disease vaccines, and protein replacement therapies. BioNTech successfully went public on NASDAQ in October 2019. Its market capitalization grew from USD 7.68 billion in early 2020 to USD 25.25 billion by the end of 2023, an increase of more than 220%. The BNT162b2 vaccine, co-developed with Pfizer, was the world’s first officially approved mRNA COVID-19 vaccine and has received emergency use authorization in multiple countries and regions. Beyond COVID-19, BioNTech is also advancing vaccines for tuberculosis, malaria, HIV, shingles, and influenza, while exploring mRNA applications in cancer treatment. CureVac CureVac, headquartered in Tübingen, Germany, is one of the pioneers in mRNA technology. Founded in 2000, CureVac has over 20 years of experience in developing and optimizing multifunctional mRNA molecules for medical use and was the first company to successfully apply mRNA in therapeutic contexts. In August 2020, CureVac went public on NASDAQ with a market capitalization of USD 18.105 billion. Its pipeline includes cancer immunotherapies (cancer vaccines), antibody therapies for rare diseases, and prophylactic vaccines for infectious diseases. Although CureVac’s mRNA vaccine candidates have lagged behind in development compared to its competitors, its deep technical expertise and innovation capacity continue to secure its relevance in the competitive landscape. ConclusionAs a revolutionary biotechnology platform, mRNA drugs have demonstrated enormous potential in prophylactic vaccination and cancer immunotherapy. With ongoing technological advances and deeper clinical research, the mRNA drug market is expected to enter a new phase of expansive growth. In the future, mRNA therapies are likely to play a critical role in the treatment of a wider range of diseases, offering patients more therapeutic options and hope. At the same time, progress in delivery systems and chemical modifications will provide a strong foundation for broader clinical applications. With the active involvement of global pharmaceutical giants and increasing policy support, the mRNA drug market is poised to maintain rapid growth and become a key direction in the development of the biopharmaceutical industry. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Reference 1.Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics--developing a new class of drugs. Nat Rev Drug Discov. 2014 Oct;13(10):759-80. doi: 10.1038/nrd4278. Epub 2014 Sep 19. PMID: 25233993.2.Liu C, Shi Q, Huang X, Koo S, Kong N, Tao W. mRNA-based cancer therapeutics. Nat Rev Cancer. 2023 Aug;23(8):526-543. doi: 10.1038/s41568-023-00586-2. Epub 2023 Jun 13. PMID: 37311817.3.Xiao Y, Tang Z, Huang X, Chen W, Zhou J, Liu H, Liu C, Kong N, Tao W. Emerging mRNA technologies: delivery strategies and biomedical applications. Chem Soc Rev. 2022 May 23;51(10):3828-3845. doi: 10.1039/d1cs00617g. PMID: 35437544.

iStock, Moor Studio BioNTech said in 2022 that it faced “threats of a groundless patent infringement suit” from a company that was “unable to bring to market any product to help in the fight against COVID-19.” Now, the mRNA biotech is buying that very company. BioNTech’s $1.25 billion all-stock acquisition of CureVac brings together two German companies that have spent the past three years trading blows in the courts. Having painted CureVac as a failed rival that was trying to profit from its success, BioNTech now faces the task of integrating the biotech’s 1,000 employees into its operations. BioNTech and partner Pfizer set out their views on CureVac in a lawsuit in 2022, claiming they faced “threats of a groundless patent infringement suit” from a company that was “unable to bring to market any product to help in the fight against COVID-19.” The partners’ lawyers took aim at CureVac’s vaccine development woes and its decision to start legal action. “Unlike BioNTech’s and Pfizer’s efforts, CureVac’s failed, as it was unable to develop a COVID-19 vaccine product,” the Comirnaty developers said. “After this failure, CureVac turned its attention to an attempt to profit from the success of BioNTech and Pfizer through threats of patent infringement.” Now, BioNTech and CureVac are cozying up together. The path from scientific rivals to legal adversaries to a single company was shaped by the diverging circumstances of the two companies during the pandemic. A 3-Year Legal Battle BioNTech and CureVac, along with Moderna in the U.S., pioneered the use of mRNA to treat cancer and protect against infectious disease. CureVac made the early running, advancing a prostate cancer vaccine into a Phase IIb trial that failed in 2017. Three years later, COVID-19 radically changed the fortunes of mRNA. Both BioNTech and CureVac launched vaccine development programs but BioNTech moved fastest. Boosted by Pfizer’s support, BioNTech’s candidate became Comirnaty, the best-selling COVID-19 vaccine. CureVac landed deals with Bayer and GSK , received cash from the German government and reportedly became a buyout target for the U.S. government in President Trump Donald’s first term. However, CureVac published clinical data on its vaccine candidate months after its rivals and the results fell well short of the bar set by Comirnaty and Moderna’s Spikevax. CureVac stopped development late in 2021 and, working with GSK, advanced a second-generation candidate into the clinic in March 2022. Then the lawsuits started. CureVac alleged Comirnaty infringed a European patent and three German utility models in the summer of 2022. Utility models give the same rights as patents but are granted in weeks, rather than years. The patent covers stabilized mRNA coding for a viral antigen. CureVac filed the application in 2002. One utility model, which CureVac filed in February 2021, covers a COVID-19 vaccine. The other utility models, which date back to 2015, address ways to boost protein expression. At the time, analysts estimated the lawsuit had $500 million of “potential upside” for CureVac. BioNTech and Pfizer filed a complaint in Massachusetts around the time CureVac began its legal attack in Europe, seeking a judgment of non-infringement by Comirnaty of three U.S. patents. The action came thick and fast across the rest of 2022. CureVac added another European patent to its lawsuit. Between them, BioNTech and Pfizer filed to invalidate one patent in Germany, took action against two patents in the U.K. and requested the cancellation of the three utility models. The legal action continued in 2023. In the first half of the year, a German court supported the validity of a CureVac patent in a preliminary opinion, BioNTech and Pfizer filed oppositions against a EU patent and CureVac submitted a counterclaim in the U.S. alleging infringement of six more patents by Comirnaty. CureVac opened another front in the legal fight in July 2023, claiming infringement of one patent and two utility models in a lawsuit in a regional court and expanding its counterclaim in the U.S. Over the following months, courts suspended infringement rulings for two patents and three utility models. Events began to turn against CureVac in December 2023, when a German court nullified its stabilized mRNA patent after an oral hearing. A written judgment with reasons for the nullification arrived in April 2024, followed swiftly by an appeal from CureVac. In the second half of 2024, courts in Germany and the U.K. ruled CureVac patents invalid and several utility models were withdrawn from the cases and canceled. Yet, the story twisted back in CureVac’s favor in March of this year, when the European Patent Office declared a CureVac patent valid. CureVac won another validity decision in May. The victories teed up a hearing into whether BioNTech infringed the patents. The court was scheduled to hear the arguments on July 1. Now, BioNTech is set to neutralize the legal threat by acquiring CureVac in the all-stock deal. Analysts were somewhat confused by the deal itself, but many noted that the removal of the litigation threat was a positive for BioNTech. “By acquiring CureVac, ongoing litigation related to BioNTech’s mRNA technology is likely to be resolved, potentially removing the possibility of damages that could have loomed prior,” BMO Capital Markets wrote. Integrating Rival Organizations It is unclear what the merger means for CureVac’s programs. CureVac has said its drug candidates “face direct competition from companies such as Moderna and BioNTech.” Soon, those direct competitors will be part of the same pipeline, assuming the deal goes through. As for CureVac’s employees, of which there were close to 1,000 at the end of last year, the future is also uncertain. BioNTech will integrate CureVac’s research and manufacturing site in Tübingen, Germany, into the larger company’s network of facilities. The integration will align with BioNTech’s ongoing group-wide transformation from pandemic warrior back to its oncology roots .