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Interpretation of the R&D route of mRNA vaccine giant Moderna
Interpretation of the R&D route of mRNA vaccine giant Moderna. At the end of 2020, the US FDA urgently approved Moderna and BioNTech/Pfizer’s two mRNA vaccines for the prevention of COVID-19 pneumonia (COVID-19).
In fact, long before the COVID-19 pandemic, mRNA vaccines have attracted a large number of pharmaceutical companies to participate in research and development with their unique advantages. Today, the success of mRNA vaccines in the COVID-19 field has greatly stimulated and promoted the development and expansion of mRNA technology.
mRNA, also called messenger RNA, is responsible for transmitting the genetic information stored in DNA and directing the synthesis of proteins in cells. The mRNA vaccine is to use mRNA to instruct cells to produce corresponding proteins, thereby preventing and treating diseases.
The mRNA vaccine has many significant advantages. The mRNA vaccine can simulate the natural infection process of the virus to activate the immune system and stimulate a potentially stronger immune response; multiple mRNAs can be packaged in the same vaccine to improve the applicability of the vaccine; mRNA The discovery and production of vaccines is faster than protein vaccines, and can respond more quickly to sudden epidemic infections; different mRNA vaccines can use the same production steps and facilities.
These unique advantages have allowed the rapid development of mRNA vaccines at an extremely alarming rate. There are currently not only a variety of new coronavirus mRNA vaccines, but also mRNA vaccines for rabies, Zika virus and other infectious diseases, cancer, autoimmune diseases, and rare genetic diseases. Under study.
Moderna was established in 2010 and is committed to developing innovative therapies based on mRNA technology. In December 2018, Moderna went public on the Nasdaq and raised more than US$600 million at a price of US$23 per share, setting a new record for biotech companies in IPO fundraising.
Nowadays, with Moderna’s success in the field of mRNA COVID-19 vaccines, its stock price has exceeded $230 since its listing for more than two years, and its total market value has reached $94 billion. It is only a matter of time before it is expected to pass the 100 billion mark.
In addition to the COVID-19 vaccine, Moderna also has a number of mRNA vaccines for infectious viruses, as well as more than 20 research projects for cancer vaccines, rare genetic diseases and other diseases. More than half of them have started clinical trials.
Today we summarize and introduce Moderna’s mRNA R&D pipeline.
Preventive vaccines for infectious diseases are the core business of Moderna. In addition to the mRNA-1273 for the prevention of COVID-19, two other mRNA vaccines against COVID-19 mutant strains are undergoing clinical trials.
Clinical trials of mRNA vaccines against cytomegalovirus, human metapneumovirus and parainfluenza virus 3 (hMPV/PIV3), Zika virus, respiratory syncytial virus (RSV), and H7N9 influenza virus have begun.
Preclinical research is under way for mRNA vaccines against Epstein-Barr virus, influenza virus, HIV, and Nipah virus.
Systemic intracellular therapy
The mRNA-3927 for the treatment of propionic acidemia has begun clinical trials, and the mRNA therapy for the treatment of methylmalonic acidemia, phenylketonuria, and glycogen storage disease type 1a is in the preclinical stage.
These four diseases are rare autosomal recessive inherited diseases. The correct mRNA is delivered systemically into the cell to express the protein that performs the correct function and realize the treatment of the disease.
Local regenerative therapy
The AZD8601 project is a local mRNA therapy encoding vascular endothelial growth factor (VEGF-A). Developed by Moderna in cooperation with AstraZeneca, it is used to treat heart failure patients who have undergone cardiac bypass graft (CABG) surgery. Phase 2 clinical trials are currently underway.
Systemic secretion and cell surface therapy
This category also requires systemic delivery therapy. Among them, mRNA-1944 for chikungunya virus has made the fastest progress. Phase 1 clinical trials have ended. After intravenous infusion, it can produce neutralizing chikungunya virus for a long time. Type antibody. The other three mRNA therapies encoding relaxin, PD-L1 and IL2 are still in the preclinical stage.
These two cancer vaccines were jointly developed with Merke and have entered clinical trials. They are a personalized cancer vaccine mRNA-4157 and a cancer vaccine mRNA-5671 that targets KRAS mutants.
The former enhances the effect of immune checkpoint inhibitors by stimulating T cell immune response. It can be used in combination with immunoassay inhibitors to improve the effect of cancer treatment. The latter encodes the main mutants of KRAS: G12D, G12V, G13D, and G12C, which are used for targeted treatment of non-small cell lung cancer, colorectal cancer, and pancreatic cancer caused by KRAS mutations.
Intratumoral Cancer Immunology
In the field of cancer immunology in tumors, Moderna has 3 therapies under development, injecting mRNA encoding pro-inflammatory cytokines into tumors to stimulate an inflammatory response, turning “cold tumors” into “hot tumors”, thereby improving immune inspections The therapeutic effect of some inhibitors.
These three therapies are mRNA-2416 encoding OX40L. The treatment of solid tumors and lymphoma is in clinical phase 1, and the treatment of ovarian cancer is in clinical phase 2. MRNA-2752, which encodes OX40L+IL23+IL36γ, is used to treat solid tumors and lymphomas and is in clinical phase 1. And MED1191, which encodes IL-12, is jointly developed with AstraZeneca to treat solid tumors and is in clinical phase 1.
(source:internet, reference only)