Syntara (ASX: SNT) Reports Motor Improvement in Phase 2 Parkinson’s-Related Study

Syntara has reported a statistically significant difference in clinician-assessed motor signs between SNT-4728 and placebo in a 41-person Phase 2 study, adding a clinical signal to previously released imaging evidence that the drug reduced brain inflammation.

The result was recorded at week 24, or 12 weeks after treatment ended, in participants with isolated REM sleep behaviour disorder (iRBD). The condition is associated with a high risk of progression to Parkinson’s disease and related synucleinopathies, making it a potential setting for testing treatments before more advanced disease develops.

Participants who received SNT-4728 showed slightly improved motor function after the 12-week treatment period, while the placebo group worsened. By week 24, scores in the SNT-4728 group had improved further and those in the placebo group had continued to deteriorate, producing a statistically significant between-group difference with a p-value of 0.021.

The result was measured using Part III of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, which assesses features including slowness of movement, rigidity, tremor, gait and postural stability.

Clinical and imaging signals converge

The randomised, double-blind and placebo-controlled trial enrolled 41 participants, allocated three-to-one between SNT-4728 and placebo. The study was designed to assess safety and tolerability as well as exploratory efficacy.

The motor finding follows Syntara’s previously reported primary imaging result. After 12 weeks of treatment, imaging showed a statistically significant reduction in inflammation on one side of the putamen, a brain region involved in motor control. Twenty of the 30 participants receiving SNT-4728 recorded a reduction from baseline, with a p-value of 0.0145.

Syntara said the combination of imaging evidence and improved clinician-assessed motor scores supports further clinical development of SNT-4728 as a potential disease-modifying treatment in prodromal and early Parkinson’s disease. That interpretation remains exploratory given the study’s size and short treatment period.

Smartphone-based measurements of participant-performed motor tasks moved in the same direction as the clinician assessment, but the difference between treatment groups was not statistically significant.

Other measures also showed no marked changes over time. These included broader Parkinson’s assessments, cognition, quality of life and sleep behaviour questionnaires. Further analysis of digital endpoints and clinical, biological and imaging biomarkers remains outstanding.

Safety findings support further evaluation

No treatment-related serious adverse events were reported. All previously reported adverse events across the treatment groups were mild or moderate, according to Syntara.

SNT-4728 is intended to reduce neuroinflammation by inhibiting the MAO-B and SSAO enzymes in the brain. The study was funded through Parkinson’s Research Ventures and conducted with investigators in Sydney and Oxford.

The latest results provide a rationale for a larger and appropriately designed trial, potentially including patients with early-stage Parkinson’s disease. Syntara did not disclose the design, timing or funding requirements for any subsequent study in the announcement.