eFFECTOR Therapeutics has dosed the first participant in the Phase Ib clinical trial of zotatifin (eFT226) to treat outpatients with mild to moderate Covid-19.

The trial is funded by a $5m cooperative deal from the US Defense Advanced Research Projects Agency (DARPA) and Defense Health Agency (DHA).

Zotatifin is designed to sequence-selectively block eukaryotic translation initiation factor 4A (eIF4A) mediated translation.

eFFECTOR added that the drug candidate is meant to hinder the translation of messenger ribonucleic acids (mRNAs) that encode various critical oncogenes and survival factors.

The double-blind, randomised, dose-escalation Phase Ib trial will study zotatifin in Covid-19 patients aged 18 to 65 years in an outpatient setting.

It is being carried out in partnership with the University of California, San Francisco (UCSF)’s Quantitative Biosciences Institute (QBI).

The safety and tolerability of the drug candidate are the trial’s primary endpoints.

Secondary goals include the antiviral activity of zotatifin determined as mean change in viral load over time, time to when viral load is not detectable and time to clinical resolution.

Initially, zotatifin will be given in two intravenous (IV) infusions one week apart.

eFFECTOR already completed toxicology and pharmacokinetic studies that showed the exposure and safety of zotatifin’s IV use similar to its subcutaneous use.

The company expects to switch to subcutaneous use, which is considered more favourable for treatment in an outpatient setting.

eFFECTOR Therapeutics president and CEO Steve Worland said: “We believe that positive clinical data from this trial would support the continued development of zotatifin as an antiviral treatment for SARS-CoV-2 and its emerging variants, such as the Delta variant, as well as potential future coronavirus strains that may emerge for which vaccines will be unavailable.”

As the drug candidate targets a human protein called host protein that is needed for viral replication, it could be less prone to resistance from viral mutations compared to therapies acting on virus-encoded proteins, Worland added.

In addition to Covid-19, zotatifin is being studied in a Phase I/II trial for solid tumours treatment.