- First interventional study to directly target neuroinflammation in patients with isolated REM Sleep Behaviour Disorder (iRBD) and interrogate the disease biology underlying patient progression to Parkinson’s Disease
- Statistically significant reduction in brain inflammation was observed unilaterally in the putamen (p-value 0.0145), with 20 out of 30 patients on active treatment (SNT-4728) recording a reduction from baseline
- The putamen is a key region underlying the hallmark motor symptoms of Parkinson’s Disease
- “To demonstrate statistically significant reductions in a short period of time is notable and suggests the drug may be modulating disease relevant neuroinflammatory pathways” — Prof Simon Lewis, Director of the Parkinson’s Disease Research Clinic at Macquarie University
- Full results from the study, including further digital and biological markers, will be available in Q3 2026
- Based on activity as a first-in-class neuro-targeted anti-inflammatory therapy in iRBD, a new provisional patent application has been filed
Syntara Limited (ASX: SNT), a clinical-stage drug development company, is pleased to announce preliminary analysis of the first tranche of data from its randomised, double-blind, placebo-controlled Phase 2 clinical trial of SNT-4728 in patients with isolated REM Sleep Behaviour Disorder (iRBD), a sleep disorder associated with a high risk of progression to Parkinson’s and related diseases.
The multi-centre study evaluated the safety and efficacy of SNT-4728, a first-in-class neuro-targeted anti-inflammatory therapy, in 41 patients (3:1 randomised) with iRBD. In addition to safety, endpoints of interest included improvement in symptoms and reduction of brain inflammation in regions associated with neurodegenerative conditions, assessed by brain imaging at baseline and after 12 weeks of treatment. Positron Emission Tomography (PET) imaging using the Translocator Protein (TSPO) was used to monitor the activation of microglia in addition to the measurement of other markers of neuroinflammation in the brain.
The trial demonstrated a statistically significant reduction in brain inflammation unilaterally in the putamen (p = 0.0145), with 20 of 30 patients receiving SNT-4728 demonstrating a reduction from baseline. The putamen is a key region underlying hallmark motor symptoms of Parkinson’s Disease (bradykinesia, rigidity, tremor) and is also linked to non-motor features such as impaired motivation. No statistically significant change in inflammation was detected in other predefined regions of interest (substantia nigra, caudate, occipital cortex). Broader analyses further validated the anti-inflammatory effect of SNT-4728 by identifying additional areas of statistically significant reduced TSPO signalling, including regions within the temporal lobe.
Professor Simon Lewis, Director of the Parkinson’s Disease Research Clinic at Macquarie University said: “SNT-4728 is being evaluated in a prodromal Parkinson’s population where progression to symptomatic disease is very slow and can take over a decade. Therefore, any measurable change over only three months of treatment is notable, and seeing a statistically significant reduction in TSPO signal in the putamen, a region central to motor symptoms, is encouraging and suggests the drug may be modulating disease relevant neuroinflammatory pathways. The further imaging and biomarker analyses still to come from this study will help our understanding of the durability and clinical significance of this effect.”
Dr Lynsey Bilsland, Managing Director of Parkinson’s Research Ventures, said: “Right now, no drug can stop or slow the progression of Parkinson’s. With SNT- 4728, Syntara have shown that they are able to modify a key process linked to Parkinson’s progression through short-term treatment many years before Parkinson’s is diagnosed. In this trial, participants gave their time in the hope of delivering something that will improve life with Parkinson’s for generations to come. Seeing such a high percentage of them have a positive response to the drug is encouraging and we look forward to reviewing the remaining results in the coming months as we continue our globally powered search for a cure.”
A once-daily oral dose of 15 mg SNT-4728 was selected for this study. Dose selection was informed by prior clinical trials completed by Boehringer Ingelheim1,2, which confirmed that the compound crosses the blood-brain barrier. Given SNT-4728’s dual inhibition of two enzyme targets (SSAO and MAO-B), the 15 mg dose is predicted to provide excellent target engagement for both enzymes in the brain, supporting meaningful reduction of brain inflammation.
Of the 41 patients with a median age of 68 years enrolled in the study, 38 (93%) were male; 37 (90%) were hyposmic/anosmic (reduced or loss of sense of smell), 19 (46%) had low colour discrimination and 39 (95%) had misfolded alpha-synuclein detected in cerebrospinal fluid, indicating the successful recruitment of an enriched iRBD population at high risk for phenoconversion to Parkinson’s and related diseases. In keeping with the excellent safety profile observed in prior Phase 2 studies, SNT-4728 was safe and well tolerated with no treatment related serious adverse events reported. Across the treatment arms, all the adverse events observed were either mild or moderate in severity.
Further analyses, expected to be available towards the end of Q3 2026, include full clinical and imaging datasets, digital and biological markers. The availability of the complete data set from the study will further inform the conclusions drawn from this exploratory study and enable a developmental path forward in the treatment of iRBD and the slowing of progression to Parkinson’s for this population of patients.
Based on the emerging evidence of SNT-4728’s activity as a first-in-class neuro-targeted anti-inflammatory therapy in iRBD, a new provisional patent application has been filed.
Syntara Chief Executive Officer Gary Phillips said: “This study pushes the boundaries of what is technically possible and, when complete, will amass a significant body of evidence in this world first interventional study in iRBD. It would not have been possible without the support from Parkinson’s Research Ventures who funded the study, the dedication of our two principal investigators, Prof Simon Lewis (Sydney) and Prof Michele Hu (Oxford), and the healthcare teams at the sites and, of course, the patients. The study has generated a great deal of interest in the wider Parkinson’s community and we look forward to working with our collaborators to deliver the remaining trial results in Q3 2026 and evaluate the path forward after this promising start.”
Previous studies have estimated that approximately 2% of people over 50 years of age are affected by iRBD. Significantly, long-term observational studies suggest that up to 90% of individuals with iRBD subsequently develop a neurodegenerative disease, including Parkinson’s Disease and Dementia with Lewy Bodies, positioning iRBD as one of the strongest recognised clinical predictors of these disorders.
