Ventyx Biosciences provides NLRP3 Inhibitor data, pipelne updates

Ventyx Biosciences will provide clinical and pipeline updates today during its virtual investor event. VTX3232: We completed a Phase 1 single- and multiple-ascending dose trial of VTX3232 in adult healthy volunteers to assess the safety, pharmacokinetics and pharmacodynamics of VTX3232. Separate cohorts were included in this trial in which serial cerebrospinal fluid sampling was conducted to assess drug exposure and target engagement in the CSF. VTX3232 was well-tolerated with no dose-limiting toxicities identified. All treatment-emergent adverse events were graded mild or moderate. VTX3232 exhibited a dose-dependent and dose-linear pharmacokinetic profile. Repeat doses of 3 mg QD maintained steady-state IL-1beta IC50 coverage in both plasma and CSF over 24 hours. Repeat doses of 40 mg QD exceeded steady-state IL-1beta IC90 coverage in both plasma and CSF over 24 hours. Robust, dose-dependent pharmacodynamic effects were observed in a whole blood ex vivo IL-1beta stimulation assay. Additionally, reductions in inflammatory biomarkers were observed in plasma and CSF samples. We believe these data support the potential for VTX3232 to emerge as a best-in-class CNS-penetrant NLRP3 inhibitor for the treatment of neuroinflammatory diseases. We expect to initiate a Phase 2a trial of VTX3232 in patients with early Parkinson’s disease during the second half of 2024. We also expect to initiate a Phase 2a trial of VTX3232 in subjects with obesity and certain additional risk factors for cardiovascular disease during the second half of 2024. VTX2735: We completed a Phase 2 trial of VTX2735 in patients with cryopyrin-associated periodic syndromes, or CAPS, a group of rare autoinflammatory conditions caused by gain-of-function mutations in the NLRP3 gene. This trial enrolled 7 patients with familial cold autoinflammatory syndrome, the most common subset of CAPS. Treatment with VTX2735 demonstrated clinically meaningful improvements in disease activity, including an 85% mean reduction in the Key Symptom Score during Treatment Period 1. Reductions in inflammatory biomarkers were also observed, consistent with improvements in disease activity. VTX2735 was well-tolerated and all drug-related adverse events were graded mild. We believe these data establish compelling clinical proof of concept for our peripheral NLRP3 inhibitor VTX2735. We plan to evaluate VTX2735 in cardiovascular diseases with an initial focus on the secondary prevention of major adverse cardiovascular events and recurrent pericarditis. VTX002: In October 2023, we announced positive results from the Phase 2 trial of VTX002 in patients with moderately to severely active ulcerative colitis. We believe these results establish VTX002 as a potential best-in-disease oral agent in UC based on its differentiated efficacy profile, including a high rate of complete endoscopic remission, and its potential best-in-class safety profile. At our virtual investor event, we will present data from the ongoing Phase 2 open-label extension. We believe these data continue to support the potentially differentiated profile of VTX002 in ulcerative colitis, with robust rates of clinical remission and endoscopic remission observed among participants completing 52 weeks of treatment with VTX002. At least half of the patients in the 60 mg treat-through group achieved clinical remission or endoscopic remission at Week 52. Activities are underway to prepare for a Phase 3 trial. We intend to identify a partner or other source of non-dilutive financing to support the pivotal Phase 3 trial of VTX002 in ulcerative colitis. VTX958: We are evaluating VTX958 in a Phase 2 trial in patients with moderately to severely active Crohn’s disease. We recently implemented a protocol amendment for the ongoing Phase 2 trial to streamline trial design and accelerate the detection of an efficacy signal. As a result of the protocol amendment, target enrollment in the trial was revised from approximately 132 patients to approximately 93 patients. The trial’s sole primary endpoint is now the change from baseline in the mean Crohn’s disease activity index score at Week 12. We anticipate completing randomization of the trial during the first quarter of 2024 and expect to report topline results from the Phase 2 Crohn’s disease trial during the middle of 2024.