Liver mRNA-based immunotherapies

Objetivo

Primary liver cancer is the third cause of cancer-related death worldwide with about 900 000 new cases and 830 000 deaths worldwide each year and a 5-year survival of only 20%. Current systemic treatments, including checkpoint inhibitors and tyrosine kinase inhibitors, benefit only a minority of patients, and around 70% of FGF19-positive HCCs remain refractory to immunotherapy. In this PoC project, LiveRNA will develop a first-in-class liver-targeted mRNA platform. It will combine mRNA-cGAS with a hepatocyte-specific IL-2 mRNA construct. This construct reprograms dysfunctional intrahepatic CD8 T-cells into potent antitumor effectors. LiveRNA will demonstrate the safety and antitumoral activity of the mRNA-cGAS/mRNA-IL-2 combination in stringent preclinical models, benchmark it against standard of care, and define the most promising HCC (and related liver tumour) subtypes for clinical translation. We will also provide a rationale for patient selection and future combination regimens. In parallel, the LiveRNA team will consolidate a freedom-to-operate-based IP position on mRNA-cGAS and IL-2-mRNA, establish a dedicated spin-off company, LiveRNA, and engage with investors and industrial partners to accelerate first-in-human development of this scalable, low-dose, liver-specific immunotherapy for patients with otherwise untreatable HCC.