Moderna Announces Advancements in mRNA Platform Science for Application Across Multiple Diseases at Science and Technology Day
Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messengerRNA (mRNA) therapeutics and vaccines, today announced new research findings as part of the Company’s fifth annual Science and Technology Day. Moderna continues to highlight investments in the expansion of the utility of the mRNA platform, characterization of the Company’s vaccines, biodistribution of vaccines, and using clinical data to predict vaccine dosing.
“Science and Technology Day gives us an opportunity to showcase our leadership in mRNA medicines. Having continuously invested in our mRNA platform for more than 10 years, Moderna is well-positioned to continue bringing innovative medicines to the world through next-generation technology, research and manufacturing. I’m particularly excited about the advances that our more than 700 experienced platform research scientists have made in delivering medicines to the lungs and intramuscularly for vaccines, and am confident that the financial resources and expertise Moderna has will ensure Moderna remains as the world leader in mRNA,” said Stéphane Bancel, Chief Executive Officer of Moderna.
Expansion of the utility of the mRNA platform
Multiple biological barriers must be overcome to deliver mRNA medicines and maximize their clinical potential. In most cases, the effective delivery of mRNA-based medicines is enabled by encapsulating the mRNA in tiny lipid (fat) droplets, known as lipid nanoparticles (LNPs) in order to protect it against degradation and facilitate uptake by cells. Moderna announces advances in developing numerous proprietary LNPs, each suited to target different cell types and optimized for different routes of administration. Moderna has invested in the development of LNPs for systemic, intramuscular, intratumoral, and pulmonary delivery of mRNA.
With Moderna’s focus on respiratory diseases, the Company has invested in designing mRNA delivery systems tailored to targeting pulmonary disease. For pulmonary applications, delivery of mRNA medicines directly to the lungs by inhalation is the preferred method of administration in order to maximize the concentration of the medicine locally in the lung. Moderna researchers have developed a new LNP formulation that addresses many of the challenges associated with lung delivery of mRNA. This pulmonary LNP formulation is delivered by inhalation, uses multiple lipids, and is able to target specific areas of the lung. Moderna’s optimization of pulmonary delivery of mRNA provides opportunities to address a range of unmet medical needs.
Moderna is collaborating with Vertex to deliver mRNA directly to the lungs via aerosolization to enable production of a functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein. CFTR is an important target for treatment because it is a defect in the CFTR gene that leads to buildup of thick mucus in the airways, chronic lung infections, inflammation and eventual respiratory failure. To date, the companies have completed IND studies that are supportive of advancing to clinical development. Vertex expects to submit an IND for this program in the second half of this year. In a second collaboration, the companies are collaborating to develop a portfolio of mRNA CF treatments, through the discovery and development of novel LNPs and mRNAs for the delivery of gene-editing therapies for the treatment of CF.
Characterizing Moderna’s mRNA
mRNA is inherently unstable, but with continued investments in innovative science, Moderna researchers have developed a detailed understanding of the reactions that drive instability and lead to mRNA inactivation and degradation. mRNA stability has practical implications for product storage and shelf-life.
In addition to known chemical reactions that contribute to mRNA instability upon storage of product, Moderna researchers have identified and elucidated another mechanism that leads to a loss in mRNA activity: the formation of lipid-mRNA complexes, known as adducts. Since mRNA must be intact to be translated, adduct formation renders mRNA untranslatable, leading to a decrease in the expression of the proteins needed to treat or prevent disease.
In addition to the clinical benefits of stabilizing mRNA integrity, manufacturing protocols that limit the formation of lipid-mRNA adducts can improve product shelf-life. It thus remains critical to ensure robust analytical methods and stringent manufacturing controls to ensure mRNA stability and high activity in LNP delivery systems. Moderna’s adduct formation research has led to the development of manufacturing processes designed to identify and mitigate lipid-driven impurities that would otherwise disrupt mRNA translation and reduce product shelf-life. As a result, new manufacturing controls have resulted in improved shelf-life, improved product activity, and higher storage temperatures.
With hundreds of millions of COVID-19 vaccines administered, numerous observational studies and in-depth animal research, current data supports the safety of vaccination relative to fertility, pregnancy, and breastfeeding. In addition to examination of real-world and observational data, Moderna reviewed guidelines from several health agencies, including the United States Centers for Disease Control and Prevention (CDC), the United Kingdom (UK) Health Security Agency, the European Medicines Agency (EMA)’s COVID-19 Task Force (ETF), the UK Joint Committee on Vaccination and Immunisation (JCVI). Taken together, current data supports the safety of COVID-19 vaccination for pregnant or breastfeeding women and suggests no safety concerns in regard to fertility. Currently there is no evidence that COVID-19 vaccines cause fertility problems in women or men. Observational data from vaccinated pregnant women has not shown an increase in adverse pregnancy outcomes and no increased risk for miscarriage has been seen.
Observational data from women who were breastfeeding after COVID-19 vaccination have not shown a risk for adverse effects in breastfed newborns/infants. As per the CDC, COVID-19 vaccination is recommended for people who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future.
Biodistribution of Moderna’s vaccine
To further characterize Moderna’s IM vaccines, biodistribution studies were conducted to demonstrate where mRNA goes in the body after injection. Studies demonstrate that injected mRNA remains predominantly at the injection site and in nearby draining lymph nodes. Furthermore, consistent with its transient nature, mRNA is undetectable in the body 5 days after injection, with minimal mRNA detectable after only 3 days.
Using Clinical Data to Predict Vaccine Dosing
Selecting an optimal dose for new vaccine candidates is important in reaching maximal vaccine efficacy at a desirable safety level. Well-informed decisions about dose selection can reduce the development time and expense for new candidates. Moderna presented an immunostimulatory/immunodynamic (IS/ID) modeling approach that simulates immune response by vaccination (IS) and the resulting measured immune response dynamics (ID). The model was developed, tested and shown to be effective using data from Moderna’s cytomegalovirus (CMV; mRNA-1647) and COVID (mRNA-1273) vaccines.
With the goal of maximizing immunogenicity and reducing risk of adverse reactions, Moderna will apply the model to support dose selection for upcoming clinical studies.
Science Day Webcast Information
Moderna will host its annual Science and Technology Day for analysts and investors at 9:00 a.m. ET on May 17. A live webcast will be available under the “Events and Presentations” in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for one year following the presentation.