Drug Development.

Area of Science:

• Neuroscience and Pharmacology
• Mitochondrial Biology
• Drug Development

Background:

• Mitochondrial dysfunction is implicated in Alzheimer's disease (AD) and Parkinson's disease (PD) pathogenesis.
• SUL-238, a novel small molecule, enhances mitochondrial function in preclinical models.
• SUL-238 has shown potential in an AD mouse model, improving protein expression, reducing amyloid plaques, and enhancing memory.

Purpose of the Study:

• To assess the safety, tolerability, and pharmacokinetics of single oral doses of SUL-238 in healthy adults.
• To evaluate the cerebrospinal fluid (CSF) penetration of SUL-238.

Main Methods:

• Phase 1, randomized, double-blind, placebo-controlled, single oral ascending dose (SAD) study in healthy volunteers.
• Doses ranged from 50 mg to 2000 mg across 6 cohorts.
• Pharmacokinetic (PK) analysis, including food effect and CSF-to-plasma concentration, was performed.

Main Results:

• SUL-238 was safe and well-tolerated across all tested doses (50-2000 mg), with no dose-limiting adverse effects.
• Adverse events were mild to moderate and comparable between SUL-238 and placebo groups.
• Favorable PK profile observed, with high CSF penetration (mean percentages of 21.1% at 2 hours and 74.2% at 8 hours post-dose).

Conclusions:

• Single oral doses of SUL-238 (50-2000 mg) are safe and well-tolerated in healthy volunteers.
• SUL-238 exhibits a favorable pharmacokinetic profile.
• The drug demonstrates significant penetration into the cerebrospinal fluid, supporting its potential for neurological applications.