eTheRNA immunotherapies and Quantoom Biosciences announce a strategic collaboration for the development of a novel RNA production system

28 Jun 2021
Ellen Simms
Product and Reviews Editor

eTheRNA immunotherapies NV (‘eTheRNA’), a clinical-stage company developing mRNA-based immunotherapies with in-house GMP-certified production and process development capabilities, and Quantoom Biosciences S.A. (“Quantoom”), a biotech company aiming to improve access to essential medicines through innovative bioproduction methods, have announced that they are to collaborate on the development of a revolutionary RNA production system (RPS) for both research and GMP-grade material.

Quantoom and eTheRNA will work together to build an advanced, small footprint technology platform for the production of affordable RNA-based therapies, that can be used either within existing facilities or rapidly deployed to areas of urgent need. Unlike large and costly existing RNA production plants, the RPS will manufacture RNA small modular units, which can be shipped easily across multiple geographic regions. The RPS is intended to be scaled seamlessly from small scale preclinical batches to mass production of GMP-grade RNA. The only requirement will be for the RPS to be located inside a suitable clean room with an uninterrupted utility supply.

Under the terms of the agreement, eTheRNA will transfer manufacturing technology to Quantoom with all materials and data necessary for the development of the novel RPS. Following completion of the RPS, Quantoom will be responsible for commercialization of the system on a worldwide basis, with sales-related royalties payable to eTheRNA. International sales and distribution are expected to commence in 2023 following RPS production in Belgium.

Bernard Sagaert, SVP Manufacturing and COO of eTheRNA, commented: “This cooperation aligns with our goals for RNA production; namely cost reduction, process scalability from small to large scale, portability and process automation. Currently, the global supply of RNA is hampered by the lack of dedicated production facilities and by the cost of constructing new plants. The RPS will revolutionize the way RNA is produced and distributed globally and we are excited to be able to work with a leading developer and manufacturer like Quantoom to bring this vision to the market.”

José Castillo, CEO of Quantoom Biosciences, commented: “We are delighted to enter into this collaboration agreement with eTheRNA, which has extensive experience in the field of RNA and like Quantoom, has a mission to change the RNA world. Through our combined knowhow, I am confident that Quantoom will be able to develop an open, integrated RNA platform that will enable manufacture of RNA-based vaccines and therapeutics at scale, resulting in affordable development and production of RNA-based drugs.”

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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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eTheRNA immunotherapies and Quantoom Biosciences announce a strategic collaboration for the development of a novel RNA production system