Ventyx Biosciences has reported encouraging top-line outcomes from its single-centre Phase IIa trial of the central nervous system (CNS)-penetrant NLRP3 inhibitor, VTX3232, in individuals with early-stage Parkinson’s disease.
The open-label study met its primary objective of showing tolerability and safety, without any treatment-emergent adverse events related to the drug.
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It involved ten patients and a 28-day treatment duration with a daily dose of oral 40mg therapy.
The trial’s secondary objectives include the therapy’s pharmacokinetic (PK) profile characterisation in plasma and cerebrospinal fluid (CSF), as well as its pharmacodynamic (PD) activity by assessing the impacts on various biomarkers of NLRP3 inhibition.
Additionally, the trial included exploratory markers of neurodegeneration, evaluations of both the motor and non-motor aspects associated with Parkinson’s as determined by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and an assessment of microglial PET imaging by utilising [18F]-DPA 714 to attach to the translocator protein (TSPO).
According to the company, VTX3232 showed an excellent PK profile, exceeding the IC₉₀ for NLRP3 inhibition.
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By GlobalDataA high correlation between plasma and CSF exposures was observed.
The trial also showed that VTX3232 engaged its target by reducing biomarkers of NLRP3 inhibition such as IL-1β in plasma and IL-18 in plasma and CSF.
Downstream biomarkers, including IL-6 and hsCRP, were also decreased.
Furthermore, treatment with the therapy was associated with improvements in both motor and non-motor symptoms of Parkinson’s, according to MDS-UPDRS.
No acute changes were observed in exploratory PET imaging, which aligns with the short duration of the study.
These data support the continued clinical development of the therapy in Parkinson’s.
The company is planning a dose-ranging, placebo-controlled, double-blind Phase II trial in Parkinson’s, with potential expansion into other neurodegenerative conditions such as Alzheimer’s disease.
Ventyx Biosciences CEO Raju Mohan said: “We are delighted that this trial met its goals of establishing that treatment with VTX3232 was safe and well tolerated, with high exposure levels in CSF and clear reductions in NLRP3-related biomarkers in a Parkinson’s disease patient population.”
In 2023, the company reported positive data from a Phase II clinical trial of VTX002 for the treatment of active ulcerative colitis (UC).
