NodThera has announced positive preliminary data from four subjects in the elderly volunteer stage of a phase Ib/IIa study evaluating the effects of its lead candidate NT-0796 on inflammatory and disease-specific biomarkers in blood and cerebrospinal fluid (CSF).
NodThera is a clinical stage biotech developing brain penetrant NLRP3 inflammatory inhibitor for treating chronic inflammatory diseases.
Alan Watt, chief executive officer of NodThera, said: “Taken together, these initial findings represent the first demonstration of modulation of neuroinflammation in a human population with the inflammation inhibitor NLRP3. In designing our Parkinson’s disease study, we intentionally chose to measure the effect of NT-0796 in the elderly volunteer population as a first stage, because age is a clear factor in increasing neuroinflammation.
“Demonstrating such rapid reductions in just seven days, in various neuroinflammatory biomarkers in the CSF, particularly NfL, is a striking result, as other drugs require months or even years to show reductions in these biomarkers. Our data provide clear validation of our strategy for bringing highly differentiated brain penetrant molecules into the clinic and justify our confidence in the potential of NT-0796 to treat diseases such as Parkinson’s disease and Alzheimer’s disease.”
Paul Matthews, head of the Department of Brain Sciences at Imperial College London School of Medicine, said: “These data, while still very preliminary, provide promising evidence of the inhibitory potential of NLRP3 to modulate neuroinflammation associated with Parkinson’s disease. This is an interesting area. Development of molecules based on this concept could lead to gradual changes in the treatment landscape for neurodegenerative diseases more generally.”
Significant anti-inflammatory effect in plasma and CSF for NT-0796 NodThera
Preliminary data from ongoing studies confirm previous findings from the first completed preclinical and human studies with NT-0796 showing excellent pharmacokinetics with the new capsule formulation.
Subjects in this study were cannulated and CSF samples were taken on the first day (pre-dose) and the seventh day after daily doses of NT-0796. Confirmed CSF drug levels were consistent with previous observations and various biomarkers of CSF inflammation showed a marked reduction.
Neurofilament light chain (NfL), synthesized exclusively in the central nervous system (CNS), decreased by approximately 25% over seven days in the most inflamed subjects and by an average of 13%. NfL is now recognized by the US Food and Drug Administration (FDA) as a major biomarker of neuroaxonal damage and neurodegeneration.
A full panel of cytokines, chemokines, and adhesion molecules known to be associated with neuroinflammation was determined in the CSF, with the most re-inflamed individuals showing the strongest reduction. As previously observed, subjects who were the most inflamed at baseline showed the greatest reductions in the main peripheral inflammatory markers, C-reactive protein (CRP) and fibrinogen. A consistent decrease in circulating levels of unstimulated IL-1β, IL-18 and TNFα was also seen in subjects on the seventh day compared to the first day.
The NodThera phase Ib/IIa study in Parkinson’s disease, previously announced in June 2023, is currently recruiting patients for this study. An innovative clinical biomarker panel was designed using NT-0796’s preclinical profile demonstrating modulation of cytokines, chemokines and gliosis markers relevant to neuroinflammatory diseases.