DDW recently hosted Where are the breakthroughs in mRNA drug discovery and development? In this webinar, sponsored by Elegen, attendees learnt about the breakthroughs in mRNA drug discovery and development. Watch this on demand now.
Due to technical difficulties, Carsten Rudolph, Managing Director and CEO of Ethris, was unable to participate in the Q&A. Below, he answers some questions asked during the session.
1. Can you explain how your technology fully prevents the aggregation and destruction of lipid nanoparticles (LNPs)?
Ethris’ technology prevents aggregation and destruction of LNPs. It is based on two pillars: First, our stabilising excipient that can be added to any LNP formulation and sterically prevents the LNPs to aggregate. The excipient is listed in the pharmacopoeia as an inactive ingredient and therefore can easily added to an existing formulation. We have shown that the excipient does not only work for our SNAP-tag lipid (SNaP) LNP, but also for the commercialised vaccines. For Ethris, the development of a fully stable formulation has always been a prerequisite as we are focused on delivering mRNA to the lung and for that you need to nebulise the formulation which induced a lot of stress.
Second, our formulation is more tightly packaged compared with the industry standard as we only require 50% of the lipids. Conclusively, we have a more stable, tightly packed LNP which is further protected by the excipient.
2. Do you know why your LNP formulation remains localised after administration?
That is a very good question. We believe that the effect is caused by our proprietary lipidoid that we use instead of a cationic lipid. The difference is that our lipidoid has four amino groups that can be protonated. Therefore, we believe that the charge is partly retained at the site of administration and in combination with a tightly packaged LNP leads to a locally retained effect of our SNaP LNPs.
3. How does your high performance liquid chromatography (HPLC)-free manufacturing process compare to the standard used by the field?
The main difference is that we only use tangential flow filtration (TFF) for downstream purification which reduces the process time by more than 50%, significantly reduces capital expenditures (CAPEX) when establishing a manufacturing facility and allows easily scalable production with up-and downstream processes connected. The process was developed because for inhalation of mRNA, you need a lot of material, so from the beginning on we were focused on developing a process that would allow us to produce larger quantities of mRNA. So far, we have produced three GMP batches with contract development and manufacturing organisations (CDMOs) and have a lot of inbound interest for licensing of the process especially from CDMOs that are trying to enter the mRNA space.