eTheRNA immunotherapies and Ghent University announce mRNA delivery collaboration and license agreement

The novel lipid nanoparticles for mRNA delivery will enhance thermostability, biodegradability and safety, paving the way for new off-the-shelf therapies

12 Jul 2021
Ellen Simms
Product and Reviews Editor

eTheRNA immunotherapies NV (‘eTheRNA’), a clinical-stage company developing mRNA immunotherapies for the treatment of cancer and infectious diseases, has announced a collaboration and license agreement with Ghent University.

Under the terms of the agreement, eTheRNA will receive exclusive worldwide rights to commercialize a new library of novel ionizable lipids, co-developed with the research group of Prof. Bruno De Geest from Ghent University, for a new generation of lipid nanoparticle (LNP) formulations. Ionizable lipids are a main driver of LNP activity, enhancing the entrapment and stabilization of mRNA into the LNP and facilitating the release of the mRNA payload into the cell cytoplasm where the mRNA is subsequently translated into the protein of therapeutic interest. The ionizable lipids in the new library have been designed for improved biodegradability and therefore offer a better safety profile. In addition, LNPs formulated with these ionizable lipids are expected to have favorable thermostability properties, reducing the need for cold chain storage of the final product.

Steven Powell, CEO at eTheRNA immunotherapies commented: “We are delighted to collaborate with the laboratory of Prof. De Geest from Ghent University with their valuable, combined expertise in chemistry, nanotechnology and immunology. One of the bottlenecks with current mRNA pharmaceuticals is the need for elaborate cold-chain logistics. This collaboration and license agreement gives us access to lipid nanoparticles with enhanced thermostability and improved safety profiles. The new ionizable lipids with improved properties will provide the basis for our second generation of LNPs that will be used to develop future prophylactic vaccines and tumor-microenvironment modulating therapies.”

Prof. Bruno De Geest, Ghent University commented: “I am delighted that my long-lasting collaboration with Dr. Stefaan De Koker from eTheRNA immunotherapies has culminated in this successful technology platform. I also wish to acknowledge support from the European Research Council (ERC) which enabled my lab to endeavor into this field of research.” Dr. Dominic De Groote, Business Development Manager at Ghent University added: “This partnership is the result of continuing efforts by Ghent University and Ghent University Hospital to become a leading academic and clinical center for the development of advanced therapy medicinal products (ATMPs). This LNP technology is part of our growing portfolio of ATMP related assets that we are actively developing from the bench to the bedside through our translational platform GATE.”

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The TriMix Technology

eTheRNA

Boosting immune response through the dendritic cell pathway in a targeted, safer and sustainable way eTheRNA’s TriMix contains three naked mRNA molecules: caTLR4 (that activates the immune system as it evokes dendritic cells to present antigens to the CD4/CD8 T-cells), CD40L (that induces the dendritic cells to initiate the antigen-specific action of the CD4 T-cells), and CD70 (that induces the dendritic cells to initiate the immune system of the CD8 T-cells). TriMix is unique in the way it uses these three mRNA molecules to circumvent some of the main obstacles faced by other immunotherapy concepts when attempting to induce the proliferation of T-cells into either mature helper T-cells or cytotoxic T-cells (i.e. the ultimate 'soldiers' of the immune system that fight cancer cells and infectious agents): The first attempts used specific antigens (unique molecules of the cancer cell or infectious agent) to induce an immune response. Many mediators for presenting the antigens are investigated: cancer cells, part of cells, DNA or proteins/peptides. To date, none of them yielded satisfactory results in the induction of an immune response that is sufficiently strong for resulting in a clinical response — not even when combined with adjuvants. Moreover, the safety aspects of some of these approaches (inclusion of genetic materials) remains an open question. The attention then shifted to using the patient's own dendritic cells as key mediator to trigger an effective immune response. Dendritic cells that were simply loaded ex vivo with tumor-associated antigens did effectively induce some immune response in patients, and even some clinical response - though unfortunately not sufficiently strong. TriMix overcomes these limitations by providing an additional triple boost: TriMix enhances the activation and maturation of dendritic cells, TriMix stimulates the processes that lead to activated helper T-cells, and TriMix also promotes the processes that result in activated cytotoxic T-cells. The mRNA constructs of the TriMix-based immunotherapy are coding for both the tumor-specific antigens as well as for three unique and crucial proteins that jointly stimulate the patient’s dendritic cells to produce a more potent and larger population of cytotoxic and helper T-cells. In preclinical and phase I/IIa studies in advanced melanoma, the TriMix cellular product - stand-alone or combined with a checkpoint inhibitor - demonstrated a unique capability for enhancing dendritic cells to elicit a powerful immune response, a promising clinical response and an increased disease-free survival rate. Thanks to the very good tolerability profile of this product, combination with other cancer drugs is a possibility.

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