Ventyx Biosciences, a clinical-stage biopharmaceutical company, is advancing its pipeline with multiple Phase 2 trials focusing on NLRP3 inhibitors for autoimmune, inflammatory, and neurodegenerative diseases. The company anticipates a transformative year in 2025 with key clinical data readouts from its NLRP3 inhibitor portfolio.
VTX3232 for Cardiometabolic Diseases
Dosing has commenced in a randomized, placebo-controlled Phase 2 trial of VTX3232 in participants with obesity and cardiometabolic risk factors. The trial aims to enroll approximately 160 subjects, randomized into four groups for a 12-week primary treatment period: monotherapy placebo, monotherapy VTX3232, combination semaglutide + placebo, or combination semaglutide + VTX3232. Key endpoints include safety and change in high sensitivity C-reactive protein (hsCRP). The trial will also explore biomarkers of inflammation and cardiometabolic disease, as well as body composition and liver fat imaging. Topline results are expected in the second half of 2025.
Activation of the NLRP3 inflammasome and resulting chronic inflammation has been linked to cardiometabolic diseases, including atherosclerosis, insulin resistance, and obesity. This Phase 2 trial is designed to identify the effects of NLRP3 inhibition on inflammatory and metabolic biomarkers, potentially informing future development of NLRP3 inhibitors in cardiometabolic diseases.
VTX2735 for Recurrent Pericarditis
A single-dose, open-label Phase 2 trial of VTX2735 in participants with recurrent pericarditis is expected to begin in January. The trial will enroll approximately 30 participants for a 6-week primary treatment period, followed by a 7-week extension period. Key endpoints include safety, change in the NRS pain score, and change in high sensitivity C-reactive protein (hsCRP). Topline results are expected in the second half of 2025.
Recurrent pericarditis is considered an autoinflammatory condition caused by over-activity of the innate-immune system, particularly the NLRP3 inflammasome and IL-1. VTX2735 has the potential to offer a safe, effective, and convenient oral therapy for patients suffering from recurrent pericarditis, especially those refractory to non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine.
VTX3232 for Parkinson’s Disease
Enrollment is progressing in an ongoing Phase 2 biomarker and imaging trial of VTX3232 in participants with early Parkinson’s disease. This trial is expected to enroll approximately 10 participants for a 28-day open-label treatment period. Key endpoints include safety, pharmacokinetics, and biomarkers in cerebrospinal fluid (CSF) and plasma. The trial also includes exploratory TSPO PET imaging as a marker of microglial activation. Topline results are expected in the first half of 2025.
In Parkinson’s disease, overexpression of IL-1b and IL-18 has been observed in CSF samples, suggesting that NLRP3 inhibition in the CNS may offer a disease-modifying therapeutic approach. This Phase 2 trial aims to generate data supporting this hypothesis by demonstrating the ability to modulate key inflammatory and disease-related biomarkers in the CSF, downstream of NLRP3 activation.
Financial Position
Ventyx Biosciences reported a cash, cash equivalents, and marketable securities balance of $252.9 million as of December 31, 2024 (unaudited). The company expects these funds to support operations into at least the second half of 2026.
