Thiogenesis Presents Phase 2 (EU) MELAS Data at Mitocon 2026

Executive Summary

• Thiogenesis Therapeutics presented interim Phase 2 (EU) data for TTI‑0102 in MELAS patients at the Mitocon 2026 conference, highlighting statistically significant fatigue improvement and favorable PK/PD profiles.
• Weight‑based dosing (~60 mg/kg/day) achieved sustained cysteamine exposure with reduced gastrointestinal adverse events versus fixed dosing.
• Pharmacodynamic signals (increased plasma pyruvate, decreased tryptophan) suggest enhanced mitochondrial energy metabolism and reduced oxidative stress, supporting progression to further trials (Phase 2a in Leigh syndrome).

Key Details

• Study Design: Randomized, single‑blind, high fixed‑dose, placebo‑controlled exploratory Phase 2 (EU) study; n = 9 genetically confirmed MELAS patients.
• Clinical Outcome – Fatigue:
• Mean reduction of up to 10 % in total Modified Fatigue Impact Scale (MFIS) score vs. placebo (p < 0.001).
• Improvement deemed clinically meaningful for a core symptom of mitochondrial disease.
• Pharmacokinetics (PK):
• Once‑daily, weight‑based dosing achieved sustained 24‑hour cysteamine exposure.
• Optimal dose identified at ≈ 60 ± 5 mg/kg/day, yielding lower Cmax than fixed dosing and approved cysteamine formulations, improving GI tolerability.
• Pharmacodynamics (PD):
• Increased plasma pyruvate without lactate rise → suggests enhanced glycolytic flux and more efficient cellular energy production.
• Decreased plasma tryptophan → potential reduction in oxidative stress via the kynurenine pathway.
• Dose‑response observed: negligible effects < 40 mg/kg/day, optimal at ~60 mg/kg/day, slight attenuation at higher doses.
• Safety/Tolerability: Fixed dosing caused GI adverse events and discontinuations in lower‑weight patients; weight‑adjusted dosing mitigated these issues.
• Dosing Comparison: Weight‑based 60 ± 5 mg/kg TTI‑0102 (~26 mg/kg cysteamine base) provides sustained exposure with ≈ 50 % of the daily dose required for Cystagon®/Procysbi® in cystinosis patients.
• Implications: Findings provide biological and clinical proof‑of‑concept for TTI‑0102 in MELAS, informing design of upcoming Phase 2a Leigh syndrome trial (MM‑COAST outcome framework).

Notable Quotes

“The results presented at Mitocon confirm that TTI‑0102 achieves meaningful biological and clinical proof‑of‑concept in MELAS when administered using appropriate weight‑based dosing… These findings directly inform the design of our Leigh program.” – Patrice Rioux, M.D., Ph.D., CEO & Co‑Founder

All non‑material boilerplate, forward‑looking statements, and company background sections have been omitted for brevity.