Nasal Delivery of mRNA Therapeutics: A Novel Approach to Drug Development for Asthma

Overcoming the Challenges of mRNA Drug Development

Developing mRNA therapeutics for respiratory conditions presents unique challenges, particularly in terms of drug delivery and stability. Unlike more traditional drugs, mRNA molecules are fragile and require careful handling to ensure they remain effective by the time they reach the target cells.

“Based on the emerging data that we and other companies have generated and that other academic groups have generated, I believe that mRNA-based therapeutics have a bright future in respiratory medicine.”

— Thomas Langenickel

Ethris has made notable progress in addressing these challenges. Two key hurdles were thermostability and nebulizability. Ensuring the stability of mRNA drugs without the need for ultra-cold chain requirements was crucial for practical clinical use. Ethris addressed this by developing a formulation that allows storage in a refrigerator and maintains stability at room temperature.

Another challenge was the nebulizability of lipid nanoparticle (LNP) formulations, which tend to form particle aggregates during spraying or nebulizing. These aggregates can trigger unwanted immune responses and reduce transfection efficiency. Ethris overcame this by creating a formulation that delivers pristine LNPs to the respiratory tract, ensuring effective and safe local delivery.

“We again address that through formulation development so that we have a product that is nebulizable and delivers really a pristine LNP into the respiratory tract avoiding all these potential undesired effects that you could get,” Dr. Langenickel noted.

Broader Implications for Respiratory Disease Treatment

With the Phase I trial demonstrating the safety and pharmacology of ETH47, Ethris is now planning a human virus challenge trial in asthma patients. This next step aims to investigate the safety, antiviral efficacy and potential for improving virus-dependent asthma symptoms in a relevant patient population.

While the focus of much current research is on asthma, the potential applications of nasal mRNA delivery extend far beyond this condition. Chronic obstructive pulmonary disease (COPD), another condition characterized by frequent exacerbations often triggered by viral infections, could also benefit from similar therapeutic strategies. Additionally, mRNA therapeutics hold promise for other respiratory viruses, including influenza and respiratory syncytial virus (RSV), particularly in high-risk populations.

Dr. Langenickel envisions a future where mRNA therapeutics play a central role in managing a wide range of respiratory diseases. “We could envision developing mRNA therapies for COPD, and based on its broad antiviral properties, also for prevention of severe disease following infections with any endemic respiratory virus,” he notes.