// R&D pipeline


1 – Immunostimulation Technology


Boosting immune response through the dendritic cell pathway in a sustainable way. eTheRNA’s TriMix contains three naked mRNA molecules:

Activates the immune system as it evokes dendritic cells to present antigens to the CD4/CD8 T-cells

Induces the dendritic cells to initiate the antigen-specific action of the CD4 T-cells

Induces the dendritic cells to initiate the immune systems of the CD8 T-cells

TriMix is unique in the way it uses these three mRNA molecules to induce the proliferation of T-cells into either mature helper T-cells or cytotoxic T-cells – the ultimate ‘soldiers’ of the immune system that fight cancer cells and infectious agents. By combining TriMix with tumour-specific antigens or neoantigens the patient’s dendritic cells are stimulated to produce a more potent and larger population of antigen specific cytotoxic and helper T-cells compared to tumour antigens alone.

Initially, the TriMix technology was applied as an ex vivo product. The ex vivo product consists of dendritic cells extracted from the patient’s body, which are then, in the laboratory, modified with TriMix in combination with the tumour-specific antigen mRNA.
This cellular TriMix product is reinjected as an autologous product into the patient’s body.

In preclinical and phase I/IIa studies in advanced melanoma, the TriMix cellular ex vivo product – either as a standalone product or combined with a checkpoint inhibitor – was able to  induce dendritic cells to elicit a powerful immune response, which in turn resulted in a promising clinical response
and a prolonged disease-free survival rate.

eTheRNA is now turning this ex vivo approach into products that can be directly injected intranodally in the form of naked mRNA or intravenously, where the mRNA is packaged in lipid nanoparticles.

Lipid nanoparticles

Intravenous and intramuscular administration of mRNA in a packaged form. Lipid nanoparticles are used as a formulation vehicle to deliver mRNA to the lymphoid organs where they can transfect dendritic cells after intravenous and intramuscular administration. This modality is currently in preclinical development with very strong protective immune responses observed in in-vivo models. The aim is also to induce a specific immune response against antigens presented as mRNA in the vaccine.
Additional immune stimulation is achieved with TriMix included into the product.

2 – Oncolysis and tumour microenvironment modulating technology

For this therapy, naked or packaged mRNA is delivered intratumourally directly into the patient’s tumour, offering direct access to the site of action for this  therapy. This modality offers extensive opportunities to develop tumour-lytic, tumour-modifying and in general, immune stimulating products. Such tumour microenvironment modulating mRNA mixes have shown promising anti-tumour responses in the injected tumours as well as by-stander therapeutic effects on  non-injected tumours and are very amenable to additional enhancement of the immune responses by systemically provided check point inhibitor targeting drugs.

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