The FDA has granted clearance for Encoded Therapeutics’ investigational new drug (IND) application for ETX101.

This clearance allows Encoded to begin clinical trials of the gene therapy candidate designed to treat Sodium channel protein type 1 subunit alpha (SCN1A)+ Dravet syndrome.

In addition, Australia's TGA granted approval under the Clinical Trial Approval (CTA) scheme for trial commencement.

An AAV9-mediated gene regulation therapy candidate, ETX101 is claimed to upregulate the SCN1A gene expression in GABAergic inhibitory interneurons, thereby addressing the underlying cause of Dravet syndrome.

Encoded plans to commence a two-part Phase I/II clinical trial, dubbed ENDEAVOR, in the US for such patients aged between six months and under three years old in the first half of this year.

The WAYFINDER trial, also a Phase I/II study, will additionally enrol patients aged three to under seven years in Australia.

Both ENDEAVOR and WAYFINDER are part of the international clinical development programme, named POLARIS, which is designed to analyse the efficacy and safety of ascending doses of ETX101 in infants, as well as young children.

POLARIS will also assess the preliminary impact of ETX101 on seizure burden and lasting neurodevelopment improvements.

Encoded has reached an agreement with the US regulator on the ENDEAVOR trial design, which allows for a smooth transition to a potentially confirmatory study on demonstrating preliminary safety and efficacy.

The POLARIS programme is supported by prior participant-focused drug development programmes, including Dravet ENGAGE, the ELUCIDATE biomarker discovery project, and the ENVISION natural history study.

Encoded Therapeutics chief medical officer Sal Rico said: “ETX101 represents a groundbreaking advancement in the therapeutic landscape for Dravet syndrome, with potential not only for seizure management but also for addressing the broader spectrum of non-seizure manifestations.

“ENDEAVOR and WAYFINDER are the first step in bringing a potentially one-time, disease-modifying gene therapy to the Dravet community, and we are excited to be partnering with leading experts in the care of patients with Dravet syndrome to begin clinical trials in the US and Australia in the coming months.”

In 2020, the company secured $135m in a Series D funding round to support initial trials of its gene therapy assets for SCN1A+ Dravet Syndrome.