Oral NLRP3 inhibitor shows major reductions in key inflammatory and cardiovascular risk markers — positioning VTX3232 as a potential new class of anti-inflammatory therapy.
Ventyx Biosciences, Inc. (Nasdaq: VTYX) announced promising Phase 2 results for its investigational oral therapy VTX3232, demonstrating robust reductions in systemic inflammation and cardiovascular risk markers among participants with obesity and related comorbidities. The once-daily treatment — tested both as a monotherapy and in combination with semaglutide — achieved statistically significant reductions in high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and lipoprotein(a) [Lp(a)], while maintaining a favorable safety profile.
Inflammation Reduction and Cardiovascular Benefits
In the 175-participant, randomized, placebo-controlled study, VTX3232 monotherapy reduced hsCRP by approximately 78% compared to a 3% increase with placebo (p<0.0001). Nearly 70% of treated participants reached target hsCRP levels below 2 mg/L, a threshold associated with significantly lower cardiovascular risk.
Treatment also produced meaningful reductions in IL-6 — reaching median levels below the cardiovascular risk cutoff of 1.65 ng/L — as well as improvements in Lp(a), fibrinogen, and erythrocyte sedimentation rate (ESR). Additionally, MRI data revealed decreased liver inflammation, suggesting potential utility in metabolic liver disease.
“An ~80% reduction in hsCRP within one week of dosing — sustained through 12 weeks — demonstrates the power of NLRP3 inhibition to address residual inflammatory risk,” said Raju Mohan, PhD, Chief Executive Officer of Ventyx Biosciences. “VTX3232 may represent a new generation of oral anti-inflammatory therapies capable of reducing cardiovascular events beyond the benefits of lipid-lowering agents.”
Combination Data with Semaglutide
In patients receiving VTX3232 alongside semaglutide, the combination produced additional improvements over semaglutide alone, including further reductions in hsCRP, IL-6, Lp(a), and liver inflammation. However, neither monotherapy nor the combination resulted in additional weight loss compared to semaglutide alone — highlighting the drug’s role as an anti-inflammatory rather than metabolic modulator.
“The combination results are particularly compelling,” said Mark Forman, MD, PhD, Chief Medical Officer of Ventyx. “They suggest that pairing VTX3232 with GLP-1 therapies could deliver deeper cardiovascular protection for high-risk patients already benefiting from weight loss treatments.”
Safety and Tolerability
VTX3232 was well tolerated throughout the 12-week study. Treatment-emergent adverse events were comparable to placebo across all groups, with no significant differences in severity or discontinuation rates.
Expert Perspective
Independent experts noted that the findings underscore a growing focus on inflammation as a key driver of cardiovascular disease.
“Elevation in C-reactive protein (CRP) is a strong predictor of future cardiovascular events,” said Dr. Peter Libby of Mass General Brigham Heart & Vascular Institute. “The robust CRP-lowering seen with novel NLRP3 inhibitors like VTX3232 offers a promising path to reducing residual inflammatory risk in patients already treated for cholesterol.”
Next Steps and Broader Potential
Ventyx plans to advance VTX3232 into further clinical development aimed at cardiometabolic disorders driven by inflammation, including atherosclerosis, heart failure, and metabolic liver disease. As a once-daily oral therapy, it could complement — or enhance — existing lipid-lowering and GLP-1-based treatments.
“The consistent safety, potency, and biomarker response seen in this Phase 2 study give us confidence to move rapidly into later-stage development,” added Mohan.
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