mRNA Advances Allow Drug Development Focus on Rare Diseases (Part Two)

Chris Spivey, editorial director for Pharmaceutical Technology®, discussed messenger RNA (mRNA) advances at the leading scientific conference for the field, the 11th International mRNA Health Conference in Berlin, Germany, held Oct. 29– Nov. 2, 2023, with Thomas Langenickel, MD, chief medical officer at Ethris, a Germany-based biotechnology company specializing in next-generation RNA therapeutics and vaccines. In the second part of this interview Langenickel describes challenges with current pulmonary mRNA approaches.

The scientific and technical challenges lay in effectively managing stability through ambient temperature ranges, end-use stability and equal access throughout the supply chain, and the biological deployment conditions affecting ultimate biodistribution. Ethris has interim results on a technique to store lyophilized lipid nanoparticles (LNPs) at ambient temperatures successfully for up to six months. Mechanical stress (sheer forces) during manufacturing as well as shipping to and handling within the clinic (such as drawing drug product into the syringe) can create aggregation of LNPs or leakage of mRNA from the LNP. This can lead to increased immunogenicity, difficulties in nebulizing from clogging, and even batch failures during manufacturing itself.

Currently available vaccines injected into musculature show up in the brain, liver, spleen, and all major perfused organs, instead of more narrowly targeting, for example, lung tissue types. The Ethris manufacturing platform does not require high pressure liquid chromatography, which reduces costs but also some of the sheer forces mentioned earlier.

Langenickle has more than 15 years of experience in clinical development and translational medicine in cardiovascular and respiratory disease areas. He previously held the position of executive director and head of Respiratory Profiling at Novartis and served as medical director at Bristol-Myers Squibb.