// R&D pipeline

Technology

1 – Immunostimulation Technology

TriMix – 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 tumor-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 tumor 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 tumor-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 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 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 tumor microenvironment modulating technology

Naked or packaged mRNA is delivered intratumorally directly into the patient’s tumor site, a direct access to the effector site of the therapy. This modality offers opportunities to develop tumor-lytic, tumor-modifying and immune stimulating products. Preliminary experiments with a tumor-lytic modality showed impressive anti-tumor responses in the injected as well as in the non-injected tumors.

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