Thiogenesis Therapeutics, Corp. announces positive results from its Phase 1 clinical study of oral TTI-0102 in healthy volunteers in Australia. The Phase 1, "Open-Label, Dose-Escalation Study - to Evaluate Safety, Tolerability and Pharmacokinetics of Oral TTI-0102 Compared to Cystagon® (cysteamine bitartrate) in Healthy Volunteers," demonstrated that TTI-0102, which acts as a precursor to the thiol-active compound cysteamine, was safe and well tolerated at dose levels ranging from 600 mg cysteamine-base equivalent to 2400 mg cysteamine-base equivalent with no serious adverse events.

The pharmacokinetic (PK) profile suggests the potential for once-a-day dosing at target therapeutic levels compared to four times a day dosing with Cystagon®. The results from this study will be used to support Thiogenesis' Investigational Medicinal Product Dossier (IMPD) submission in Europe and its Investigational New Drug (IND) submissions in the US for human efficacy trials in multiple disease indications. Summary of TTI-0102 Phase 1 Clinical Trial Data: Trial Design - The Phase 1 study enrolled 12 healthy volunteers that were dosed with 600 mg of Cystagon® as a control and patients were later given one of: 600 mg cysteamine-base equivalent; 1200 mg cysteamine- base equivalent; or 2400 mg cysteamine-base equivalent of TTI-0102.

Safety: As expected, the most common Treatment Emergent Adverse Effects (TEAEs) reported following the administration of 600 mg of Cystagon® was nausea. Following TTI-0102 administration, no nausea was reported, and the only moderately graded TEAE reported was abnormal skin odor in 3 participants in the 2400 mg cysteamine-base equivalent group. PK Profile - The target therapeutic levels of cysteamine for TTI-0102 in the 1200 mg cysteamine-base equivalent group was maintained for over 12 hours, therefore TTI-0102's PK data supports dosing twice-a-day and potentially once a day, depending on the indication.

The Cmax of cysteamine with dosing of 600 mg of Cystagon® was 3.19 ± 1.12 mg/mL compared to 3.49 ± 0.95 mg/mL with dosing of 2400 mg cysteamine-base equivalent of TTI-0102. The difference was not statistically significant (p=0.61) even at the maximum dose of TTI-0102. These results support the ability to administer a higher dose level of TTI-0102 without risking a higher Cmax of cysteamine that is associated with side effects.

The AUC for the dosing of 600 mg of Cystagon® was 7.32 ± 1.76 hr.mg/mL compared to 20.38 ± 4.27 hr.mg/mL for the 2400 mg cysteamine-base equivalent in the TTI-0102 group. The increase in the AUC was statistically significant, representing an increase of 278% (p<0.01). The higher blood level AUC achieved without increasing the Cmax results in an increase in the availability of TTI-0102 to tissue over time, again without an increase in the side effects associated with increased dosing of cysteamine.