VTX3232 / Ventyx Biosci - LARVOL DELTA

NLRP3 inhibition by VTX3232 tempers inflammation resulting in reduced body weight, hyperglycemia, and hepatic steatosis in obese male mice. (PubMed, Mol Metab) - "When combined with glucagon-like peptide-1 receptor agonism by semaglutide, NLRP3 inhibition by VTX3232 yielded additive metabolic benefits, highlighting complementary mechanisms of action. Together, these findings reinforce the biological rationale for targeting NLRP3 in inflammatory conditions such as obesity, expand on the role of NLRP3 in metabolic inflammation, and underscore the importance of continued investigation into the NLRP3 pathway as a central node in cardiometabolic disease."

Journal • Preclinical • Atherosclerosis • Cardiovascular • CNS Disorders • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • FGF21 • IL18 • IL1B • IL6 • NLRP3

Phase 2a Placebo-Controlled Study of VTX3232 Alone or in Combination With Semaglutide in Obesity (clinicaltrials.gov) - P2 | N=176 | Completed | Sponsor: Zomagen Biosciences Ltd. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Ventyx Biosciences Announces Positive Topline Results from Phase 2 Study of VTX3232 in Participants with Obesity and Cardiovascular Risk Factors (GlobeNewswire) - "VTX3232 monotherapy achieved ~80% reduction in hsCRP within the first week. VTX3232 monotherapy reduced IL-6 levels at Week 12 below the threshold for cardiovascular risk of ≤1.65ng/L1. Statistically significant reductions in Lp(a) and liver inflammation. No effect on weight either as a monotherapy or as add-on to semaglutide....The combination of VTX3232 and semaglutide demonstrated significant reductions in hsCRP, IL-6, fibrogen, ESR, Lp(a) and liver inflammation over semaglutide alone....Additional data will be presented at upcoming medical conferences."

P2a data • Obesity

NLRP3 Inhibitor VTX3232 Well Tolerated, Improves Parkinson Symptoms in Phase 2a Trial (NeurologyLive) - "Presented by lead author Richard Gregg, MD, managing member of REGregg Consulting LLC, VTX3232 was well tolerated with no drug-related treatment-emergent adverse events (AEs) among 10 patients with early PD. Notably, all reported AEs were considered mild or moderate in severity.....At steady state, the mean VTX3232 concentration 24 hours post dose was 107.2 ng/mL in plasma and 30.4 ng/mL in CSF, exceeding the IC90 for NLRP3 inhibition (~9 ng/mL) by more than 3-fold. By 28 days, interleukin (IL)-1β and IL-18 levels were reduced by 14% to 52% in both plasma and CSF. Downstream biomarkers, including IL-6, C-reactive protein, and serum amyloid A, decreased by 29% to 70%, with the largest reductions observed in participants with elevated baseline values."

Late-breaking abstract • P2 data • Parkinson's Disease

Safety, tolerability, pharmacokinetics and pharmacodynamics of VTX3232, a CNS-penetrant NRLP3 inhibitor, in participants with early-stage Parkinson's disease (MDS Congress 2025) - P2 | "Once daily administration of VTX3232 was well tolerated for 28 days in participants with PD. Drug exposure in CSF and plasma robustly inhibits NLRP3, exceeding the IC90 by >3-fold at trough. This positive Phase 2a study is a key milestone in advancing the development of VTX3232 and NLRP3 inhibition as a potential disease-modifying therapy for PD and other neurodegenerative disorders."

Clinical • Late-breaking abstract • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease • CASP1 • IL18 • IL1B • IL6 • NLRP3

Phase 2a Study of VTX3232 in Parkinson's Disease (clinicaltrials.gov) - P2 | N=11 | Completed | Sponsor: Zomagen Biosciences Ltd. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Ventyx Biosciences Announces Positive Top-Line Data from its Phase 2a Safety and Biomarker Trial Evaluating VTX3232 in Patients with Early-Stage Parkinson’s Disease (GlobeNewswire) - P2 | N=11 | NCT06556173 | Sponsor: Zomagen Biosciences Ltd. | "Ventyx Biosciences...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 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."

Biomarker • P2a data • Obesity • Parkinson's Disease

Phase 2a Placebo-Controlled Study of VTX3232 Alone or in Combination With Semaglutide in Obesity (clinicaltrials.gov) - P2 | N=176 | Active, not recruiting | Sponsor: Zomagen Biosciences Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Phase 2a Study of VTX3232 in Parkinson's Disease (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Zomagen Biosciences Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Mar 2025 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Ventyx Biosciences Reports First Quarter 2025 Financial Results and Highlights Recent Corporate Progress (GlobeNewswire) - "The Phase 2 open-label biomarker and imaging trial of VTX3232 in patients with early stage idiopathic Parkinson’s disease is on track to complete in the second quarter of 2025...The ongoing Phase 2, multicenter, open-label trial of VTX2735 in patients with recurrent pericarditis is expected to yield topline results in the second half of 2025...The ongoing Phase 2, multicenter, double-blind, placebo-controlled trial of VTX3232 in participants with obesity and cardiometabolic risk factors is expected to provide topline results in the second half of 2025."

P2 data • Metabolic Disorders • Obesity • Parkinson's Disease

Ventyx Biosciences Expands SAB with Renowned NLRP3 Experts and Prominent Neurodegenerative and Cardiometabolic Disease Specialists (GlobeNewswire) - "Topline data from the Phase 2 study of VTX3232 in Parkinson’s disease are expected in Q2 2025.”"

P2a data • Parkinson's Disease

Ventyx Biosciences Highlights 2025 Pipeline Strategy and Provides Clinical Updates on its NLRP3 Inhibitor Portfolio (GlobeNewswire) - "First subjects dosed in a Phase 2 trial of VTX3232 in participants with obesity and cardiometabolic risk factors, with topline data expected in H2 2025...Topline data from ongoing Phase 2 biomarker trial of VTX3232 in participants with early Parkinson’s disease expected in H1 2025..."

P2a data • Trial status • Obesity • Parkinson's Disease

Phase 2a Placebo-Controlled Study of VTX3232 Alone or in Combination with Semaglutide in Obesity (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Zomagen Biosciences Ltd.

New P2 trial • Genetic Disorders • Obesity

Ventyx Biosciences Announces Initiation of Dosing in a Phase 2a Trial of VTX3232 in Patients with Early Parkinson’s Disease (GlobeNewswire) - "Ventyx Biosciences, Inc...today announced that the first patient has been dosed in a Phase 2a trial of VTX3232 in patients with early Parkinson’s disease....The Phase 2a trial of VTX3232 in early Parkinson’s disease is expected to enroll approximately ten patients for a 28-day open-label treatment period....We expect to report topline results from this trial in 2025."

P2a data • Trial status • Parkinson's Disease

Phase 2a Study of VTX3232 in Parkinson's Disease (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Zomagen Biosciences, Ltd

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Ventyx Biosciences Reports Second Quarter 2024 Financial Results and Highlights Recent Corporate Progress (GlobeNewswire) - "A Phase 2 obesity and cardiometabolic trial of VTX3232 and a Phase 2a trial of VTX3232 in patients with Parkinson’s disease are both expected to initiate in H2 2024."

New P2 trial • New P2a trial • CNS Disorders • Metabolic Disorders • Obesity • Parkinson's Disease

Ventyx Biosciences Announces Positive Preclinical Data for CNS-Penetrant NLRP3 Inhibitor VTX3232 Demonstrating Reversal of Obesity and Improvements in Cardiometabolic and Inflammatory Markers (GlobeNewswire) - "Treatment with VTX3232 resulted in decreased body weight and food intake compared to DIO control. Reductions in liver steatosis and triglycerides were also observed. Improvements in cardiometabolic parameters were observed with VTX3232, including reductions in cholesterol, insulin resistance, fasting blood glucose and HbA1c. Systemic inflammatory biomarkers, including IL-1β, IL-6, and fibrinogen, were reduced in the plasma of VTX3232-treated DIO mice....The combination of VTX3232 and semaglutide resulted in greater benefit on body weight, liver steatosis and metabolic parameters compared to VTX3232 or semaglutide alone. Systemic inflammatory biomarkers, including IL-1β, IL-6, and fibrinogen, were further reduced in the combination arm relative to DIO mice dosed with VTX3232 or semaglutide alone."

Preclinical • Metabolic Disorders • Obesity

Ventyx Biosciences Announces $100 Million Private Placement of Common Stock (GlobeNewswire) - "Ventyx Biosciences, Inc...announced today that it has entered into a stock purchase agreement for the sale of 11,174,000 shares of its common stock at an offering price of $8.95 per share in a private placement to certain qualified institutional buyers and institutional accredited investors. Gross proceeds of the private placement are expected to be approximately $100 million....Ventyx currently intends to use the net proceeds from the proposed private placement, together with existing cash and cash equivalents, to fund the clinical development of VTX3232, VTX2735, VTX002, and the preclinical development of other programs, research activities and working capital and other general corporate purposes."

Financing • CNS Disorders • Immunology • Inflammatory Bowel Disease

Ventyx Biosciences Reports Fourth Quarter and Full Year 2023 Financial Results and Highlights Recent Corporate Progress (Yahoo Finance) - "Activities are underway to support initiation of a Phase 3 trial of VTX002 in UC during the second half of 2024....Ventyx will host a virtual investor event on March 11, 2024, to provide key clinical updates on our NLRP3 portfolio, including...topline results from the Phase 1 trial of VTX3232 in healthy volunteers. We will also provide a clinical update from the ongoing open-label extension of the VTX002 Phase 2 trial in ulcerative colitis."

New P3 trial • P1 data • P2 data • CNS Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Ventyx Biosciences Announces Initiation of Dosing in a Phase 1 Trial of VTX3232, a Novel CNS-Penetrant NLRP3 Inhibitor (GlobeNewswire) - "Ventyx Biosciences, Inc...announced that the first subject has been dosed in a Phase 1 trial of VTX3232, a novel central nervous system (CNS)-penetrant NLRP3 inhibitor...Topline results from the trial are expected in the first half of 2024."

Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease