Core Insights - Thiogenesis Therapeutics, Corp. announced interim data from its Phase 2 clinical study of TTI-0102 for MELAS at Mitocon 2026, highlighting its potential in treating rare mitochondrial diseases [1][2]. Study Highlights - The Phase 2 (EU) study was a randomized, single-blind, placebo-controlled trial involving nine patients with genetically confirmed MELAS, demonstrating the importance of weight-based dosing for optimal exposure and tolerability [3]. - Fixed dosing led to gastrointestinal adverse events in lower-weight patients, while weight-adjusted dosing mitigated these effects, supporting its use in future trials [6]. Clinical and Pharmacological Findings - Statistically significant improvement in fatigue was observed, with TTI-0102-treated patients showing a mean reduction of up to 10% in the Modified Fatigue Impact Scale (MFIS) score compared to placebo (p < 0.001) [7]. - Weight-based dosing at approximately 60 ± 5 mg/kg achieved sustained 24-hour cysteamine exposure, with lower peak concentrations compared to fixed dosing and approved formulations [6][7]. - Increased plasma pyruvate without lactate elevation suggests enhanced glycolytic flux, indicating improved mitochondrial energy handling [7]. Future Implications - The findings provide a biological rationale for the observed clinical improvement in fatigue and inform the design of upcoming studies, including a Phase 2a study in Leigh syndrome spectrum [8]. - The MFIS is a validated measure for assessing fatigue in mitochondrial disorders, relevant for evaluating therapeutic benefits [9]. Company Overview - Thiogenesis Therapeutics is a clinical-stage biopharmaceutical company focused on developing thiol-based prodrugs for rare pediatric diseases, with TTI-0102 as its lead candidate [14].