NT-0796 shows sustained easing of inflammation in Phase 1/2 trial

Drop in key markers seen in CSF of patients given oral therapy for 28 days

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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NodThera’s potential oral therapy for Parkinson’s disease, NT-0796, continues to show promise in countering damaging inflammation in treated patients, according to new findings from a Phase 1b/2a clinical trial.

Treatment with NT-0796 for 28 days safely reduced pro-inflammatory markers in the patients’ cerebrospinal fluid (CSF, the liquid surrounding the brain and spinal cord), closely reaching levels seen in healthy elderly people. Markers of nerve cell death, or neurodegeneration, also declined with treatment.

These findings, which confirm those seen earlier in elderly adults at seven days of NT-0796’s use, support the therapy’s potential as a disease-modifying approach for Parkinson’s. NodThera is planning to continue testing and open a Phase 2a/2b clinical study.

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Trial data were presented at the AD/PD 2024 International Conference on Alzheimer’s and Parkinson’s Diseases, held this month in Lisbon, Portugal.

“Our new findings in Parkinson’s disease, a condition with substantial unmet medical needs, are profound and highly encouraging. They bolster our confidence in the ongoing program, with Phase II studies now in advanced planning stages,” Alan Watt, CEO of NodThera, said in a company press release.

Parkinson’s disease is characterized by the loss of nerve cells that produce dopamine, a signaling molecule that plays a role in controlling movement. Evidence supports that brain inflammation is driven by the NLRP3 inflammasome, a multiprotein complex that normally works to detect cellular threats, but promotes nerve cells loss in neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

NT-0796 is designed to cross the blood-brain barrier and enter the brain, where it blocks the formation of the inflammasome complex. The goal is to halt inflammation and slow disease progression.

The blood-brain barrier is a semi-permeable membrane crucial to protect the brain and spinal cord from the outside environment. However, it can prevent the entrance of medicines that need to target the brain, such as those used to treat neurodegenerative diseases.

Over 28 days, NT-0796 lowered the levels of several pro-inflammatory markers in patients’ CSF, including IL-1beta, IL-6, CCL2, CXCL1 and CXCL8, the company reported. Additionally, levels of key neurodegenerative markers, including neurofilament light chain and soluble TREM, also were reduced.

NT-0796 seen as a safe and potentially disease-modifying treatment

Patients with acutely high levels of inflammation, seen as elevated levels of C-reactive protein and fibrinogen, showed significant CSF reductions in these markers. These findings are consistent with NT-0796’s wide anti-inflammatory effects previously observed in elderly healthy adults enrolled in the trial’s earlier stage.

NT-0796 was safe and well tolerated, with reported adverse events mainly being mild and transient. No serious adverse events were observed.

“This is the inaugural demonstration of an NLRP3 inhibitor’s potential … Given that existing Parkinson’s treatments primarily manage symptoms, our innovative, disease-modifying strategy presents a significant shift, aiming to stop the disease progression. NT-0796’s demonstrated efficacy in reducing neuroinflammation in patients heralds a substantial advancement towards halting this devastating disease,” Watt said.

NT-0796 levels in the CSF were sustained for more than 24 hours, supporting the therapy’s once daily dosing regimen.

“These results are particularly promising for the future of Parkinson’s disease treatment, providing a compelling approach to the modulation of inflammation in the brain, a key driver in the development of this disease,” said Thomas Foltynie, PhD, a professor of neurology at the UCL Institute of Neurology and a consultant neurologist at the National Hospital for Neurology and Neurosurgery in London.

“Such an approach has the potential to change the face of treatment — actually stopping the disease in its tracks, that would be of enormous value to those living with Parkinson’s disease,” Foltynie added.