Ethris, a clinical-stage biotechnology company, has partnered with Lonza to develop room-temperature stable, spray-dried formulations of mRNA-based vaccine candidates designed for mucosal delivery. This collaboration comes after Ethris received $5 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to advance their innovative approach to RNA vaccines.
The partnership aims to overcome one of the most significant challenges in mRNA vaccine distribution: the need for ultra-cold storage. By developing spray-dried formulations that remain stable at room temperature, the companies hope to revolutionize vaccine accessibility, particularly in regions lacking cold-chain infrastructure.
Innovative Technology Platforms
Ethris brings to the collaboration its proprietary stabilized non-immunogenic mRNA (SNIM RNA) technology and stabilized lipid nanoparticles (SNaP LNP) platform. These technologies address several key challenges that have historically limited mRNA therapeutics, including immunogenicity, instability, and delivery issues.
Carsten Rudolph, Co-founder and Chief Executive Officer of Ethris, explained the company's approach: "Our SNIM RNA technology introduces chemical modifications in the RNA molecule to make it unrecognizable but functional to its therapeutic role."
The company has also developed a proprietary lipid nanoparticle platform that enables efficient transport of mRNAs through respiratory and intramuscular routes. A key innovation is their stabilizing excipient that prevents aggregation during nebulization, a critical factor for respiratory delivery.
Advantages of Spray-Dried Vaccines
Spray drying offers several significant advantages over traditional vaccine formulations. According to Rudolph, "Spray drying is the standard technique for inhaled drugs as it allows for easy adjustment of process parameters to achieve the optimal mass median aerodynamic diameter suitable for inhalation."
The process is highly scalable and can be run continuously, unlike lyophilization which is more complex to scale. From a patient perspective, spray-dried vaccines eliminate the need for cold chain storage, making them easier to transport globally and more convenient for patients.
Jan Vertommen, Vice President, Head of Commercial Development, Advanced Synthesis at Lonza, highlighted the potential of the collaboration: "Spray-drying represents a well-established technique that addresses solubility and other manufacturing and stability challenges... Combining the expertise of Lonza Bend site's particle engineering team with the innovative SNIM RNA of Ethris, there is great potential to target unmet medical needs in the field of non-invasive vaccine delivery."
Technical Challenges and Solutions
Developing spray-dried RNA formulations presents significant technical hurdles. The spray-drying process subjects the formulation to mechanical stress similar to nebulization, which can lead to lipid nanoparticle aggregation in standard formulations. Additionally, the heat exposure during the drying process can damage most LNP formulations.
Ethris has addressed these challenges through their specialized formulation technology. Their lyophilized LNP formulations have demonstrated stability at room temperature for more than 18 months, and they expect similar stability for their spray-dried formulations, though studies are ongoing to confirm this.
Focus on Respiratory Delivery
The initial focus of the Ethris-Lonza collaboration is to develop a first-in-class mRNA vaccine candidate against influenza delivered nasally. This non-invasive approach aims to provide localized immune responses comparable to intramuscular vaccines while potentially reducing virus transmission by generating mucosal immunity at the site of virus entry.
Ethris has already demonstrated clinical success with nasal delivery. In their first clinical trial, completed last year, they achieved protein expression at levels significantly higher than the predicted therapeutic window using a highly concentrated suspension. The company is now working on a spray-dried powder designed for high loading of mRNA and uniform distribution within the nasal cavity.
Broader Pipeline and Future Directions
Beyond vaccines, Ethris is developing treatments for respiratory diseases via nasal and inhaled routes. Their lead phase II ready program, ETH47, addresses asthma exacerbations and chronic obstructive pulmonary disease by encoding interferon lambda, a protein essential for viral immunity in the respiratory tract.
"Approximately 80 percent of acute asthma attacks are associated with virus infections," Rudolph noted. "ETH47 aims to induce a mucosal innate immune response at virus entry sites, as well as inhibit viral replication." The company plans to advance ETH47 into phase II trials in 2025.
Another program in development focuses on primary ciliary dyskinesia, a rare genetic disorder caused by structural defects or the absence of cilia lining the respiratory tract. Their products aim to deliver corrected mRNA designed to produce ciliary proteins in the respiratory tract, thereby restoring ciliary function.
Implications for Global Health
The development of room-temperature stable mRNA vaccines could have far-reaching implications for global health, particularly in addressing pandemic preparedness and vaccine equity. By eliminating the need for ultra-cold storage, these vaccines could reach populations in remote or resource-limited settings that currently have limited access to mRNA vaccine technology.
CEPI's investment in this technology reflects the organization's commitment to enhancing access to RNA-based vaccines by increasing thermostability. The technology would not only facilitate distribution to regions lacking cold-chain infrastructure but also offer an alternative for individuals with needle phobia.
The mucosal delivery approach might also stimulate a more robust immune response at the site of pathogen entry, potentially offering advantages over traditional intramuscular vaccines for respiratory diseases. This could be particularly valuable for addressing seasonal respiratory infections as well as emerging pandemic threats.
