Ventyx Biosciences has dosed the first patient in a Phase I trial of a central nervous system (CNS)-penetrant NLRP3 inhibitor VTX3232 to treat various neuroinflammatory conditions.

The two-part, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD), double-blind, randomised study will assess the tolerability, pharmacodynamics, safety, and pharmacokinetics of VTX3232 in adult healthy volunteers.

The trial will study various dose ranges for sampling serial cerebrospinal fluid and assessing brain exposure.

Preclinical studies suggested NLRP3’s potential as a central driver of neuroinflammation and therefore VTX3232 is expected to have the potential to treat various neuroinflammatory conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and others.

Topline results from the study are anticipated in the first half of next year.

Ventyx Biosciences CEO Raju Mohan said: “VTX3232 is our fourth internally discovered compound to enter the clinic and an exciting addition to our broad, wholly owned clinical-stage pipeline of orally delivered small molecules targeting large disease populations with high unmet need.

“We believe we are well positioned to explore the therapeutic potential of NLRP3 inhibition and its effect on IL-1β biology across both systemic and neuroinflammatory diseases with VTX2735, which is peripherally restricted, and VTX3232, a novel CNS-penetrant NLRP3 inhibitor that is chemically differentiated from VTX2735.”

Ventyx is also conducting a Phase II proof-of-mechanism trial of VTX2735 in patients with the familial cold autoinflammatory syndrome.

VTX2735 also has the potential to treat chronic inflammatory conditions, including dermatologic, cardiovascular, and rheumatic diseases.