Ventyx Biosciences announces results from VTX3232 study

Ventyx Biosciences (VTYX) announced results from its Phase 2 study of oral, once-daily VTX3232 in patients with Obesity and Cardiovascular Risk Factors. The 175- participant study examined VTX3232 versus placebo, alone or in combination with semaglutide, evaluating safety and tolerability as the primary endpoint, and effects on inflammation as the secondary endpoint. Participants treated with VTX3232 monotherapy in the modified analysis set 2 showed a 78% reduction in hsCRP at week 12 relative to baseline compared with a 3% increase in the placebo group. Participants treated with VTX3232 in the full analysis set 3 showed a 64% reduction in hsCRP at week 12 relative to baseline compared with a 3% increase in the placebo group. Participants treated with VTX3232 monotherapy also showed statistically significant reductions in IL-6 to levels associated with reduced cardiovascular risk. The study also evaluated the effect of VTX3232 on additional inflammatory biomarkers linked to cardiovascular risk, on liver steatosis and inflammation, and on metabolic parameters including lipid levels, glycemic control and weight loss. Notably, treatment with VTX3232 resulted in statistically significant reductions in lipoprotein, fibrinogen, and erythrocyte sedimentation rate. Significant reduction in liver inflammation, independent of steatosis, was also observed. Treatment with VTX3232 monotherapy did not result in weight loss, nor did VTX3232 in combination with semaglutide demonstrate incremental weight loss over semaglutide alone. VTX3232 was safe and well tolerated in the Phase 2 study with rates of adverse events comparable to placebo. VTX3232 demonstrated: 78% reduction in hsCRP with VTX3232 versus 3% increase in placebo; 64% reduction in hsCRP with VTX3232 versus 3% increase in placebo; 69% of patients achieved target hsCRP levels of less than2mg/L or lower. VTX3232 demonstrated statistically significant reductions in IL-6 to median levels of 1.60ng/L, below the threshold for CV risk of less than or equal to1.65ng/L. VTX3232 demonstrated statistically significant reductions in Lp, fibrinogen, and ESR. VTX3232 treatment was not associated with changes in other lipid parameters. Treatment with VTX3232 did not result in weight loss as a monotherapy or provide additional weight loss on top of semaglutide. The combination of VTX3232 and semaglutide demonstrated significant reductions in hsCRP, IL-6, fibrogen, ESR, Lp and liver inflammation over semaglutide alone. The combination of VTX3232 and semaglutide demonstrated a statistically significant reduction in liver inflammation as measured by cT1 for participants with greater than or equal to 5% baseline liver fat. Treatment emergent adverse events were comparable in the placebo versus VTX3232 groups, and comparable in the placebo + semaglutide versus VTX3232 + semaglutide groups. Grade 3 or higher TEAEs were balanced between the groups; placebo, VTX3232 placebo + semaglutide and VTX3232 + semaglutide. TEAEs leading to discontinuation were balanced between the groups with placebo, VTX3232 placebo + semaglutide and VTX3232 + semaglutide.