Syntara (SNT) Status update summary

Study background and objectives

• SNT-4728 is a dual SSAO/MAO-B inhibitor developed for neuroinflammation, with a strong safety profile and prior development in other indications.

• The current phase II/2a trial targets prodromal Parkinson's disease, specifically patients with isolated REM sleep behavior disorder (iRBD), a high-risk group for developing Parkinson's.

• The study aims to demonstrate reduction in neuroinflammation using PET imaging as the primary endpoint, with additional biomarker and safety assessments.

• The trial is not powered for efficacy over placebo but seeks a within-subject signal to inform phase III design.

• Results for the primary endpoint are expected by end of June or in 2026, with further biomarker data later in the year or Q3/4 2026.

Mechanism of action and preclinical evidence

• SNT-4728 inhibits SSAO and MAO-B, enzymes implicated in neuroinflammation and neurodegeneration in Parkinson's disease.

• Preclinical studies show strong anti-inflammatory effects and reduction of microglial activation in animal models.

• The drug demonstrates excellent brain penetration, oral bioavailability, and once-daily dosing.

• PET imaging confirms high occupancy of MAO-B at clinical doses.

Clinical trial design and endpoints

• The phase II/2a trial enrolled 40–41 participants with confirmed iRBD, randomized 3:1 to drug or placebo.

• Primary endpoint is reduction in neuroinflammation measured by PET scan after 12 weeks of treatment.

• Secondary endpoints include digital and fluid biomarkers, safety, and tolerability, with follow-up to 24 weeks.

• The study is designed to inform power calculations and design for a potential phase III trial.

• First drug trial in iRBD aiming to provide evidence for early neuroprotective intervention in prodromal Parkinson's.