Ventus Therapeutics has dosed the first subject in a Phase I clinical trial of its orally administered cGAS inhibitor, VENT-03, for the treatment of inflammatory and cardiometabolic diseases.

The intracellular pattern recognition receptor cGAS is activated after attaching to double-stranded DNA (dsDNA) in the cytoplasm.

The first-in-human trial will completely explore the pharmacodynamics, pharmacokinetics, and safety of VENT-03.

A range of single and multiple ascending doses are planned to be administered to healthy volunteers to gather comprehensive data. The results of this trial are anticipated in the second half of this year.

Ventus president and CEO Marcelo Bigal said: “cGAS has historically proven an elusive target despite significant industry efforts to develop a viable inhibitor. We have broken that cycle with the initiation of this Phase I clinical trial.

“We are eager to advance this therapeutic candidate and bring the potential of cGAS inhibition to patients suffering from inflammatory disorders with significant unmet needs. This trial continues our company’s momentum, being the second programme that we have brought to the clinic in the last six months.”

The cGAS pathway activation is linked to a variety of severe inflammatory and cardiometabolic conditions.

Ventus chief scientific officer Mike Crackower said: “The commencement of the Phase I VENT-03 trial demonstrates Ventus’ ability to drug a target that has been undruggable to date, made possible because of ReSOLVE.

“ReSOLVE, which combines machine learning with physics and computational chemistry, provided us with unique insights about the binding pocket that allowed us to design VENT-03 as a first-in-class cGAS inhibitor with excellent potency.”

In August last year, Ventus announced the dosing of the first participant in a Phase I clinical trial of its oral, brain-penetrant NLRP3 inhibitor, VENT-02.