Novel Virus-agnostic Broad Spectrum Antiviral mRNA for Pandemic Preparedness

The COVID-19 crisis demonstrated that we are inadequately prepared against pandemic threats, resulting in substantial healthcare and economic costs, sociological tension and deaths. A significant bottleneck was the unavailability of a broad-spectrum antiviral, which still does not exist. Such a drug should be effective against many viruses, reduce initial transmission and be immediately available. The clinical stage drug candidate ETH47 fulfills all these criteria and has demonstrated outstanding protection in pre-clinical models. ETH47 is a first-in-class mRNA packaged in lipidoid nanoparticles (LNP) that encodes interferon lambda (IFNλ), an epithelial and tissue interferon that mediates a broad anti-viral state. This mechanism of action is virus-independent, unlikely to lead to resistance and ideal for pandemic preparedness. ETH47 can be self-administered as a nasal spray, is stable at room temperature and has demonstrated an excellent safety profile in a single ascending dose phase 1 clinical study and dose-dependent IFNλ production in the nasal lining fluid. In NoVir, the antiviral efficacy of ETH47 will be evaluated in healthy volunteers infected with influenza and in an established rhinovirus challenge study in asthmatic and COPD patients representing a vulnerable patient population who are particularly at risk in a new pandemic. In-vitro and in-vivo models will test the broad effect of ETH47 against respiratory viruses from the Paramyxo-, Orthomyxo and Coronaviridae families, and Bunyaviruses, which can cause hemorrhagic fever. We will demonstrate the protective effect of ETH47 against viruses with diverse infection routes including intravaginal, ocular and systemic infections and test in vitro additive or synergistic effects with approved antivirals. Following the success of mRNA vaccines, ETH47 is potentially a major innovation in mRNA technology, enabling the immediate protection of a substantial population at risk of pandemic threats throughout the EU.