Moderna Spotlights Inhalable LNPs at Science and Technology Day

Moderna CEO Stéphane Bancel/Boston Magazine

Moderna held its first in-person Science and Technology Day since 2019 Tuesday morning, highlighting four of its main projects. Notably, the company shared information about its new inhalable lipid nanoparticles (LNPs), how it has improved vaccine stability by understanding mRNA in activation pathways, biodistribution and safety of intramuscular vaccine LNP and the mathematical modeling of vaccine immunogenicity and reactogenicity.

“We believe mRNA is a unique opportunity to change medicine forever,”  Moderna CEO Stéphane Bancel said at the start of the presentation. “We’re trying to maximize our impact on patients. We believe this will happen by building a platform so that we can scale and by obsessing about how fast we can expand the platform in terms of its applications for patients.”

The company is constantly moving ahead in mRNA research, priming the application of such technology to a wide variety of conditions. Moderna presented its current research concerning LNP engineering which has optimized the molecules in several parameters, including components, composition, structure and stability, and LNPs, which are suited to target different cell types and optimized for different routes of administration.        

“We have synthesized 2,000 novel delivery components to date, so those will be 2,000 unique molecules we have looked at for making better lipid nanoparticles. We’ve tested over 10,000 different composition and process variants and that has resulted in four different lipid nanoparticles that are now in clinic,” Moderna CSO Melissa J. Moore, Ph.D. said.

To that end, Moderna researchers have developed a new LNP formulation that could be inhaled and delivered directly to the lungs. The formula uses multiple lipids and can target specific areas of the lung, opening up a world of opportunities for the company to address unmet medical needs in pulmonary disease. Currently, Moderna is in collaboration with Vertex to deliver mRNA via inhalation in an effort to treat Cystic Fibrosis.

“In summary, we’ve developed this new LNP specific to the inhalation area. It has efficient delivery to the epithelium and it also has been enabled by aerosol delivery,” said Jean C. Sung, Ph.D., senior director of respiratory delivery and drug product development. “We were able to do this by using in-house systems and assays that we have developed to have higher throughput, specific to this route of administration, but also tools that can be applied more broadly. This LNP that we’ve designed does have high levels of protein expression that are localized to the airway epithelium, and it is suitable for development.” 

Moderna also highlighted its research in understanding how to improve the stability of mRNA technology, specifically. Over time, the company noticed that the shelf life of mRNA is reduced as it is stored in low temperatures. Moderna researchers identified a mechanism that contributes to this instability, which is the formation of lipid-mRNA complexes, known as adducts. To combat adducts, Moderna has designed manufacturing processes designed to identify and mitigate these impurities which have improved shelf life and product activity.

Moderna researchers also addressed a common question when it comes to their COVID-19 vaccine: where does the injected mRNA go? Biodistribution studies revealed that after injection, mRNA remains predominantly at the injection site and in nearby draining lymph nodes. After a period of five days, the injected mRNA is undetectable. Moderna also stated that its vaccine showed no evidence of fertility problems in men or women and has not shown an increased risk of adverse outcomes in pregnancy.

Finally, the company presented a mathematical modeling approach for selecting an optimal dose for new vaccine candidates in order to reach maximal vaccine efficiency. Moderna revealed an immunostimulatory/immunodynamic modeling approach that simulates immune response by vaccination and the resulting immune response dynamics. The model was validated and utilized using data from its cytomegalovirus and COVID vaccines.

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