LSP, Boehringer back mRNA immunotherapy player eTheRNA in €24M Series A

ETheRNA has raised €24 million ($26.5 million) in a Series A round led by LSP Life Sciences Partners and PMV. The round, to which Boehringer Ingelheim Venture Fund contributed, will enable eTheRNA to assess whether its off-the-shelf mRNA immunotherapy has a future in the treatment of melanoma and triple-negative breast cancer.

eTheRNA CEO Dirk Reyn

Brussels, Belgium-based eTheRNA plans to put most of the cash into preparing its immunotherapy for late-phase trials, a process that will entail running assorted preclinical and clinical tests. The drug, dubbed TriMix, is a combination of three naked mRNA molecules--caTLR4, CD40L and CD70--that act on dendritic cells in different ways. ETheRNA included caTLR4 to induce dendritic cells to present antigens to CD4 and CD8 T cells, a process that is expected to be complemented by the activity of the other mRNAs. CD40L and CD70 are included to help activate helper and cytotoxic T cells. 

"It provides us with a very well tolerated way of stimulating the immune system," eTheRNA CEO Dirk Reyn told FierceBiotech.

To date, eTheRNA has primarily tested its TriMix as part of an autologous treatment. In this format, TriMix is applied to a patient's own dendritic cells, which are then administered back into the body. The concept was tested in 39 patients with pretreated advanced melanoma in a Phase IIa trial. After 6 months, the disease control rate was 51%. One-fifth of patients experienced complete responses. Around one-third of patients suffered severe, life-threatening or disabling immune-related adverse events.

While drawing encouragement from the clinical data, eTheRNA is shifting its focus to an off-the-shelf version of TriMix, which Reyn thinks will be "much easier, much more straightforward, much more predictable" than the autologous approach. The development of this off-the-shelf product is the top priority for the freshly capitalized mRNA player. While there is no guarantee that the off-the-shelf product will match up to the efficacy of the cellular approach, Reyn has seen enough data to suggest it is a risk worth taking. 

"If you look at all the preclinical data that we have, if you use the cellular product or we use this mRNA and we inject it in the tumor, or in the skin, or in the lymph nodes, … we see exactly the same effect," he said.

The task of translating this performance into the clinic is being handled by a mix of academics and biotech entrepreneurs. CSO Kris Thielemans, who spun the company out of VUB in 2013, and his collaborators ushered eTheRNA through its early years. Last year, this team was supplemented by Reyn and others with more industry experience. "We're all ex-J&J, ex-Movetis people," Reyn said. The plan is to continue adding staff, with a view to growing headcount to around 20 during the course of the Series A.

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