etherna Achieves Major Milestones in its Bio-Reducible LNP Platform

etherna immunotherapies NV recently announced breakthrough innovation in efficient in vivo extrahepatic delivery of mRNA to several key tissues, including to hematopoietic and progenitor stem cells (HSPCs) in bone marrow and to T cells. Key highlights of the data presented include:

• New rodent and non-human primate data on proprietary etherna vaccine LNPs that outperform by at least 5-fold the clinical benchmark LNP compounds for vaccine applications
• New rodent and non-human primate data using etherna liver LNP that outperform by at least 4-fold the clinical benchmark LNP compounds for liver repeat dose protein expression and gene editing applications
• New LNPs that have been optimized for efficient delivery of RNA payloads to hematopoietic stem and progenitor cells (HSPC) in the bone marrow, achieving mRNA payload expression in over 90% of all mouse bone marrow HSPCs using an untargeted LNP
• Other newly described and optimized LNPs that have shown efficient delivery to T cells in vivo in both mice and humanized mouse models, including demonstration of robust CAR-T mediated killing using both untargeted and CD8 antibody-targeted LNP
• Data to be presented by Antonin de Fougerolles at the 5^th annual mRNA-based Therapeutics Summit held in Boston on July 22^nd.

Nucleic acid-based therapeutics, including mRNA-based medicines, are rapidly reshaping the treatment landscape for genetic diseases, vaccines, and protein replacement therapies. While lipid nanoparticles (LNPs) have proven highly effective in liver-targeted applications, achieving robust delivery to extrahepatic cells remain a major challenge.

etherna’s proprietary library of bio-reducible ionizable lipids has been key in addressing this delivery challenge. In etherna’s recent Non-Human Primate (NHP) studies, the company’s proprietary LNP formulations demonstrated at least 5-fold improved mRNA expression compared to clinical benchmarks for both vaccine and liver repeat-dose protein expression applications. These LNP were also very well tolerated in NHP and this improvement in liver-directed expression was also demonstrated in a rodent transthyretin gene editing study where it significantly outperformed the LP01 clinical benchmark and where equivalent efficacy was seen at ¼ the LP01 dose. These results are further proof of the potency and translational potential of etherna’s proprietary lipid library.

etherna has now developed a novel LNP platform optimized for extra-hepatic delivery. This LNP platform is systematically optimized for increased mRNA expression through proprietary linker, tail, and headgroup chemistry modifications.

We have optimized an LNP formulation specifically for hematopoietic stem and progenitor cells (HSPCs). This formulation enabled a controlled shift in biodistribution away from the liver and toward bone marrow tissue. The resulting formulations achieved mRNA expression in over 90% of all bone marrow HSPCs, marking a transformative leap in the ability to deliver RNA therapeutics systemically to extrahepatic cell types.

This breakthrough was made possible through a structure activity relationship (SAR) optimization process which significantly enhanced the targeting of hematopoietic stem cells (HSCs). By adjusting lipid composition and systematically analyzing biodistribution outcomes, the research team unlocked a delivery profile that favors bone marrow uptake while maintaining stability, safety, and high transfection efficiency.

In addition, using a similar but slightly different approach, etherna scientists have optimized other LNP formulations for improved delivery to T cells. Efficient delivery to T cells using a passive targeting approach (consisting of just an ionizable lipid, helper lipid, cholesterol, and PEG lipid) was demonstrated in rodents. The addition of an anti-CD8 antibody on the LNP surface served to further increase in vivo uptake and mRNA expression in CD8+ T cells.

Importantly, we also demonstrated the ability of both our non-targeted and targeted T cell LNP formulations to deliver mRNA in a humanized mouse (mice reconstituted with human immune cells). When we used these formulations to deliver a CD19-CAR mRNA, a dramatic CAR-T-mediated killing of B cells was seen with both our untargeted and targeted LNP formulations. The level of CAR-T expression and activity seen using an unoptimized CD19-CAR mRNA was comparable to the current pre-clinical state of the art in the field, and we expect this to improve a further 3-5 fold upon incorporation of etherna’s proprietary mRNA designs.

These innovations represent a major advancement in the field of in vivo liver gene editing and therapeutic protein expression in hematopoietic stem cells and T cells. etherna’s breakthrough research offers a new treatment possibilities for hematologic disorders and beyond.

etherna is a leading RNA technology company headquartered in Niel, Belgium and Boston, USA, with decades of experience in the field. Specializing in customizable Lipid Nanoparticles (cLNPs), RNA chemistry, and process technologies, etherna empowers pharmaceutical and biotech partners at every stage of drug development. Our proprietary platforms drive discovery and address challenges in creating nucleic acid-based medicines, enabling transformative therapies to improve patients’ lives.

We welcome partners who are committed to pushing the boundaries of what’s possible in nucleic acid-based medicine therapeutics and delivery of payload to extrahepatic cell types. For more information, visit https://www.etherna.be/.