NodThera has shared positive data from its Parkinson’s disease Phase Ib/IIa study evaluating the effects of NT-0796, its oral, brain-penetrant NLRP3 inflammasome inhibitor. 

In the first publication to demonstrate the clinical potential of an oral, fully brain-penetrant NLRP3 inhibitor in Parkinson’s disease, NT-0796 was shown to be safe and well tolerated, with excellent central and systemic pharmacokinetics and high target engagement in both healthy volunteers and Parkinson’s disease patients. 

NLRP3 inhibition demonstrated a clear anti-neuroinflammatory effect through reductions of neuroinflammatory biomarkers. In cerebrospinal fluid (CSF), the NLRP3-relevant cytokine IL-1β was reduced along with relevant downstream markers including CSF CCL2, IL-6, IL-8 and CXCL1.  

Consistent reductions were also observed in the neuroinflammatory CSF biomarkers, sTREM2 and neurofilament light (NfL). Additionally, in subjects with evidence of systemic inflammation at baseline, NT-0796 drove reductions in systemic inflammatory markers including high-sensitivity C-reactive protein, fibrinogen, IL-6 and IL-18. 

The company says these data demonstrate the anti-inflammatory activity of NT-0796, support the hypothesis that central NLRP3 activity plays a crucial role in the neuroinflammatory pathology of Parkinson’s disease, and further indicate the potential of NLRP3 inhibition to target a key driver of the disease.  

The ability to control chronic low-grade inflammation by NLRP3 inhibition affords the opportunity to dampen down the immune processes that play a part in the initial phases of the disease, as well as those causing neuronal cell death, which ultimately manifests as clinical symptoms as the disease progresses. 

Pipeline in Parkinson’s and obesity

NodThera’s clinical development programme in Parkinson’s disease is running in parallel with the company’s lead programme for NT-0796 in obesity, currently in Phase II development.  

The company’s oral NLRP3 inflammasome inhibitor candidate, NT-0150, which is optimised for brain penetration and exceptional central nervous system (CNS) exposure, has been prioritised for further development in Parkinson’s disease, with Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies expected to commence in H2 2025, ahead of a planned Phase II trial. 

Daniel Swisher, Chief Executive Officer of NodThera, said: “This publication is highly significant for NodThera and our ambitions to change the Parkinson’s disease treatment paradigm through the modulation of neuroinflammation. The data generated by our team underscore the strength of science behind our approach and add to the growing body of evidence that chronic low-grade inflammation is not merely a consequence of Parkinson’s disease pathology, but a driver of it.”

Diana Turner, Senior Digital Content Editor, DDW