The study met its primary goal of establishing safety and tolerability of VTX3232 in patients with early-stage Parkinson’s disease
CSF and plasma exposures reinforce VTX3232’s potential as a once-daily oral therapy for neurodegenerative diseases
VTX3232 treatment resulted in significant reductions in NLRP3-related biomarkers in CSF and plasma, demonstrating sustained target engagement
VTX3232 is also being studied in a 12-week Phase 2 trial in participants with obesity and cardiometabolic risk factors; topline results expected in H2 2025
SAN DIEGO, June 17, 2025 (GLOBE NEWSWIRE) -- Ventyx Biosciences, Inc. (Nasdaq: VTYX) (“Ventyx”, the “Company”), a clinical-stage biotech company developing oral therapies for autoimmune, inflammatory and neurodegenerative diseases, today announced positive top-line results from its Phase 2a study of VTX3232, a novel, CNS-penetrant NLRP3 inhibitor, in patients with early-stage Parkinson’s disease (NCT06556173).
The study accomplished the primary objective of demonstrating safety and tolerability, with no drug-related treatment-emergent adverse events (TEAEs) observed throughout the dosing period. The trial also met pharmacokinetic and pharmacodynamic endpoints, demonstrating high drug exposures in plasma and cerebral spinal fluid (CSF) as well as clear evidence of target engagement in plasma and CSF, with potent suppression of NLRP3-related biomarkers.
“We are thrilled that our Phase 2a data show that a once-daily dose of VTX3232 can safely maintain plasma and CSF levels above the IC90 for IL-1b for 24 hours in patients with early Parkinson’s disease,” said Mark Forman, MD, PhD, Chief Medical Officer. “In addition, we observed biomarker changes in CSF and plasma that reflect potent NLRP3 inhibition by VTX3232.”
David Russell, MD, PhD, Principal Investigator on the trial and member of the Yale University Parkinson’s Disease Research Group, remarked, “This was a thorough and well-conducted trial demonstrating clear evidence of target engagement in the CSF and plasma, with significant reduction to near-normal levels or the limit of quantitation (LOQ) in downstream biomarkers of NLRP3 inhibition, including IL-1b, IL-6 and high-sensitivity C-reactive protein (hsCRP). Our investigators also noted clinically significant reductions in MDS-UPDRS Parts II and III. With the caveat that this was a small, open-label study, all patients reported a subjective sense of improvement. Exploratory microglial PET imaging revealed no acute changes - not unexpected given the short duration of the trial.”
“Neuroinflammation is recognized as a potential trigger for neurodegenerative diseases. By inhibiting NLRP3-mediated cytokine production and inflammatory markers in the CNS, VTX3232 provides a unique opportunity for a disease-modifying therapy for Parkinson’s disease,” said Raju Mohan, PhD, Chief Executive Officer. “We are delighted that this trial met its goals of establishing that treatment with VTX3232 was safe and well tolerated, with high exposure levels in CSF and clear reductions in NLRP3-related biomarkers in a Parkinson’s disease patient population. We have initiated internal and external planning discussions for a placebo-controlled Phase 2 trial in Parkinson’s disease and potentially in additional neurodegenerative disorders such as Alzheimer’s disease.”
The single-center, open-label Phase 2a study evaluated a 40mg oral daily dose of VTX3232 in ten patients with early-stage, idiopathic Parkinson’s disease over a 28-day treatment period. The primary objective of this study was to evaluate safety and tolerability. Key secondary objectives included characterization of VTX3232’s pharmacokinetic profile in plasma and CSF, and its pharmacodynamic activity, by measuring effects on plasma, and CSF biomarkers of NLRP3-inhibition at Day 28, including IL-1, unbound, biologically active IL-18, IL-6, and hsCRP (Tier 1 biomarkers). The study also incorporated exploratory markers of neurodegeneration (Tier 2 biomarkers), motor and non-motor aspects of Parkinson’s disease as measured by MDS-UPDRS, and a microglial PET imaging assessment using [18F]-DPA 714 binding to translocator protein (TSPO).
About VTX3232
VTX3232 is a CNS-penetrant, potent and selective inhibitor of the NLRP3 inflammasome. VTX3232 has an excellent non-clinical in vitro and in vivo safety profile including in 6- and 9-month chronic toxicology studies.
VTX3232 has completed a Phase 1 trial in healthy volunteers and has shown good safety and tolerability with once-daily doses achieving therapeutic CSF exposures and significant reductions in NLRP3-mediated biomarkers in plasma and in the CSF.
VTX3232 is also being studied in a 12-week Phase 2 trial in participants with obesity and cardiometabolic risk factors with topline results expected in H2 2025.
About Ventyx Biosciences
Ventyx Biosciences is a clinical-stage biopharmaceutical company developing innovative oral therapies for patients with autoimmune, inflammatory, and neurodegenerative diseases. Our expertise in medicinal chemistry, structural biology, and immunology enables the discovery of differentiated oral small molecule therapeutics for conditions with high unmet medical need, and our extensive experience in clinical development allows the rapid progression of these drug candidates through clinical trials.
Our portfolio of NLRP3 inhibitors includes VTX2735, a peripherally restricted NLRP3 inhibitor in Phase 2 development for recurrent pericarditis, and VTX3232, a CNS-penetrant NLRP3 inhibitor in Phase 2 development for neurodegenerative and cardiometabolic diseases. Our inflammatory bowel disease portfolio includes two Phase 2 compounds: tamuzimod (VTX002), an S1P1R modulator, and VTX958, a TYK2 inhibitor.