NodThera Demonstrates Reversal of Neuroinflammation and Inflammation in Parkinson’s Disease with Oral NLRP3 Inhibitor
- Phase 1b/2a study results published in Movement Disorders journal
- Oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796 reduces key neuroinflammatory and inflammatory biomarkers in first clinical demonstration of central inflammasome inhibition in Parkinson’s disease patients
- Results support potential of NLRP3 inflammasome inhibition as a disease-modifying approach in Parkinson’s disease
- Novel brain-penetrant molecule NT-0150 prioritized in pipeline for rapid progression into Parkinson’s disease
Philadelphia, PA, August 12, 2025 – NodThera, a leading clinical-stage biotech delivering a paradigm shift in the treatment of chronic inflammatory diseases through selective modulation of the NLRP3 inflammasome, today announces the full publication of positive data from its Parkinson’s disease Phase 1b/2a study evaluating the effects of NT-0796, its oral, brain-penetrant NLRP3 inflammasome inhibitor.
The data are published in Movement Disorders, the official journal of the International Parkinson and Movement Disorder Society, in a paper titled ‘Anti-neuroinflammatory and anti-inflammatory effects of the NLRP3 inflammasome inhibitor NT-0796 in subjects with Parkinson’s disease’. In this 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.
Taken together, 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.
Neurodegeneration remains a key focus for NodThera and the company is rapidly progressing its clinical development program in Parkinson’s disease, to run in parallel with the company’s lead program for NT-0796 in obesity, currently in Phase 2 development. NodThera’s next-generation oral NLRP3 inflammasome inhibitor candidate, NT-0150, which is optimized for brain penetration and exceptional central nervous system (CNS) exposure, has been prioritized 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 2 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. With the most clinically advanced NLRP3 pipeline, and multiple first- and best-in-class inflammasome inhibitors, NodThera is uniquely positioned now to advance an NLRP3-targeting neurodegeneration program, alongside our lead obesity program, that we hope will change the face of Parkinson’s disease treatment.”
Alan Watt, President and Chief Scientific Officer of NodThera, added: “These clinical results are striking, showing for the first time in Parkinson’s disease patients that we can effectively inhibit NLRP3 activity in the brain and reduce markers of neuroinflammation that have long been associated with disease progression. The consistency and speed of biomarker modulation we observed, much of it within seven days, is highly encouraging and opens the door to a fundamentally different, disease-modifying treatment strategy.”
For more information about NodThera please contact:
NodThera
Tel: +44 (0) 1223 608130
Email: [email protected]
ICR Healthcare
Amber Fennell, David Daley
Tel: +44 (0)20 3709 5700
Email: [email protected]
About NodThera
NodThera is a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases. Led by an experienced management team, NodThera is combining a deep understanding of NLRP3 inhibition, pharmaceutical neuroscience expertise and precision chemistry. Its two lead clinical candidates are oral, small molecule NLRP3 inflammasome inhibitors, which have demonstrated differentiated, potentially best-in-class clinical profiles with significant anti-inflammatory effects and high brain penetration, offering distinct opportunities to treat multiple indications. The Company is backed by top-tier investors including 5AM Ventures, Blue Owl Capital, Epidarex Capital, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. NodThera is headquartered in Philadelphia, Pennsylvania, with additional operations in Cambridge, UK. Learn more at www.nodthera.com or follow the Company on LinkedIn.
