Announcement • Jan 23
Thiogenesis Therapeutics, Corp. Announces the Presentation of Interim Data from Its Phase 2 (Eu) Clinical Study of Tti-0102 in Patients with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (Melas) At Mitocon 2026
Thiogenesis Therapeutics, Corp. announced the presentation of interim data from its Phase 2 (EU) clinical study of TTI-0102 in patients with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) at Mitocon 2026 - a leading international conference dedicated to mitochondrial medicine being held in Pisa, Italy. The poster, titled "TTI-0102 in MELAS: PK/PD Results from a Phase 2 Study - Preliminary Evidence of Safety and Efficacy in Mitochondrial Disease," was presented on January 23 as part of Mitocon's Late-Breaking News session, a distinction reserved for data of high scientific and clinical relevance selected by the conference's Scientific Committee. Phase 2 (EU) MELAS - Study Highlights. The randomized, single-blind, high fixed-dose, placebo-controlled exploratory Phase 2 (EU) study enrolled nine (n=9) patients with genetically confirmed MELAS, a devastating mitochondrial disorder with limited therapeutic options. Results presented at Mitocon demonstrated that weight-based dosing is critical to achieving optimal exposure and tolerability, consistent with long-standing clinical experience using cysteamine in concentrations comparable to approved formulations (Cystagon®? or Procysbi®?) in cystinosis. Key clinical, pharmacokinetic, and pharmacodynamic findings included: Clinical Outcome (Fatigue): Statistically significant improvement in patient-reported fatigue as measured by the total score of Modified Fatigue Impact Scale (MFIS) At an average dose of approximately 60 mg/kg/day, TTI-0102-treated patients demonstrated a mean reduction of up to 10% in total MFIS score compared to placebo (p < 0.001) Fatigue is a cardinal and functionally limiting symptom affecting patients with mitochondrial disease. Lower peak plasma cysteamine concentrations (Cmax) at this dose compared with fixed dosing and approved cysteamine formulations, supporting improved gastrointestinal tolerability. Pharmacodynamics (PD): Increased plasma pyruvate without lactate elevation, suggesting enhanced glycolytic flux; a metabolic state in which glucose is more efficiently converted into usable cellular energy rather than diverted into lactate production, consistent with improved mitochondrial energy handling; Decreased plasma tryptophan, potentially reducing oxidative stress associated with neurotoxic kynurenine pathway metabolites. These pharmacodynamic effects were dose-dependent, negligible below 40 mg/kg/day, optimal at approximately 60 mg/kg/day, and slightly reduced at higher doses. taken together, these pharmacodynamic findings are consistent with reduced oxidative stress and improved cellular energy metabolism, supporting the proposed mechanism of TTI-0102 In mitochondrial disease, based on thiol-disulfide exchange equilibrium, and providing biological rationale for the observed clinical improvement in fatigue. The study further demonstrated that fixed dosing resulted in gastrointestinal adverse events and treatment discontinuations in lower-weight patients, whereas weight-adjusted dosing mitigated these effects, supporting its use in future clinical trials. Weight-based dosing at 60 +- 5 mg/kg TTI-0102 (26 mg/kg cysteamine base equivalent) achieved sustained 24-hour cysteamine exposure with half the daily dose of Cystagon®? or ProcYSbi®? administered to patients with cystinosis, and lower peak concentrations. The Modified Fatigue Impact Scale (MFIS) is a validated, patient-reported outcome measure widely used in neurological and mitochondrial disorders to assess the impact of fatigue on physical, cognitive, and psychosocial functioning. Fatigue affects an estimated 71-100% of patients with mitochondrial disease and is frequently reported as one of the most debilitating symptoms. MFIS is frequently reported as one of The most debilitating symptoms. MFIS has been reported as one of the most severe symptoms. MFIS is a validated, patient- reported in neurological and clinical clinical clinical clinical clinical proof-of-concept in MELAS - Study - Preliminary Evidence of safety and Efficacy in Mitocon's late-Breaking News session, a designation of the conference's Scientific Committee.
