Ventyx Biosciences Announces Initiation of Dosing in Phase 1 Trial of  Novel CNS-Penetrant NLRP3 Inhibitor

Ventyx Biosciences, Inc. recently announced the first subject has been dosed in a Phase 1 trial of VTX3232, a novel central nervous system (CNS)-penetrant NLRP3 inhibitor.

“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,” said Raju Mohan, Chief Executive Officer. “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.”

The Phase 1 trial of VTX3232 is a two-part, randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTX3232 in adult healthy volunteers. The trial will explore a broad range of doses and will include serial cerebrospinal fluid (CSF) sampling to assess brain exposure. Topline results from the trial are expected in the first half of 2024. There is a growing body of preclinical data suggesting NLRP3’s role as a central driver of neuroinflammation and thus we believe VTX3232 may have therapeutic potential in a range of neuroinflammatory conditions with high unmet medical need, including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS), among others.

In addition to VTX3232, we are also evaluating VTX2735, a peripherally restricted NLRP3 inhibitor, in a Phase 2 proof-of-mechanism trial in patients with familial cold autoinflammatory syndrome (FCAS). FCAS is the most common subset of cryopyrin-associated periodic syndrome (CAPS), a group of rare autoinflammatory conditions caused by gain-of-function mutations in the NLRP3 gene. Beyond CAPS, we believe VTX2735 may have therapeutic potential across a broad range of chronic inflammatory conditions that are characterized by NLRP3-induced excess IL-1β, including large dermatologic, rheumatic and cardiovascular disease.

Upon activation, NLRP3 acts as a “danger sensor” in the body, releasing the pro-inflammatory cytokines IL-1β and IL-18 and inducing uncontrolled, lytic cell death (pyroptosis). These processes lead to chronic inflammation, thereby implicating NLRP3 in a large number of systemic and neuroinflammatory diseases.

Ventyx is a clinical-stage biopharmaceutical company focused on developing innovative oral medicines for patients living with autoimmune and inflammatory disorders. We believe our ability to efficiently discover and develop differentiated drug candidates will allow us to address important unmet medical need with novel oral therapies that can shift immunology markets from injectable to oral drugs. Our current pipeline includes internally discovered clinical programs targeting TYK2, S1P1R and NLRP3, positioning us to become a leader in the development of oral immunology therapies. Ventyx is headquartered in Encinitas, CA. For more information, visit www.ventyxbio.com.