Thiogenesis Therapeutics, Corp. announced that the European Medicines Agency ("EMA") has accepted its Clinical Trial Application ("CTA") Part I - Scientific and Medicinal Product Documentation, for its lead compound TTI-0102, to commence a Phase 2 clinical trial for the treatment of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes ("MELAS"). The CTA Part I is the equivalent of an Investigational New Drug application in the US.

The Company anticipates initiating its Phase 2 clinical trial in MELAS in the second quarter of 2024 once it receives regulatory acceptance of the CTA Part II - National and Patient Level Documentation, which is in the process of being filed. The Phase 2 clinical trial is a multi-country, multi-center trial that will be conducted in leading institutions in France and the Netherlands. The trial is a randomized, double-blind, placebo-controlled study to assess the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of oral TTI-0102 for the treatment of patients with MELAS.

The trial will enroll a total of 12 patients, 8 patients will receive TTI-0102 and 4 patients will receive placebo. The primary endpoints of the study are to measure over a 6-month period, i) the "change in functional capacity" based on a 12-minute walking test, and ii) additional safety and tolerability endpoints. Secondary endpoints in the trial will measure fatigue, quality of life and a range of biomarkers (including the level of the antioxidant glutathione).

This comes after a successful study in healthy volunteers confirmed that TTI-0102 is a prodrug of a well characterized and previously approved cysteamine-based drug. MELAS is the most common of the larger group of conditions that are classified as genetic mitochondrial diseases. There currently are no approved drugs to treat MELAS, and are eager to investigate the potential of TTI-0102 to provide relief for these unfortunate patients.

Mitochondria are important organelles in cells that generate its energy to function. Mitochondrial encephalomyopathy with lact acidosis and stroke-like episode ("MELAS") is a rare, inherited mitochondrial disorder, most often caused by a mutation of m.3243A>G in the MT-TL1 gene in mitochondrial DNA. Initial symptoms usually include seizures, vomiting, headaches, muscle weakness, loss of appetite and fatigue.

Longer term the disease may cause a loss of motor skills and intellectual disability. MELAS usually presents itself before the age of 20. Oxidative stress plays an important role in mitochondria and is a potential pathological mechanism of mitochondrial disease, making it a viable target for the treatment of MELAS and other mitochondrial diseases1.

The prevalence of MELAS is not well understood; however, it has been estimated that it occurs in 1:20,000 people2, which would represent between 15,000 to 20,000 in the US and over 20,000 in the EU. Thiols, which have a functional SH group (containing sulfur and hydrogen) are versatile bio-active molecules that are known to be involved in key biochemical reactions and metabolic processes, making them promising candidates for a number of therapeutic applications. In particular, thiols are known to be precursors to important antioxidants such as glutathione, and to further reduce inflammation, as a result they have the potential to significantly reduce oxidative stress in the mitochondria.

The prodrug TTI-0102 was developed to address the challenges of first-generation thiol-active drugs, including their short half live, adverse side effects and dosing limitations. Update on Restructuring of Lock-up Agreement. Further to its news release of November 27, 2023, the Company announces that the Company announces that TTI-0102, a new chemical entity patented in 2021 in the US and other mitochondrial diseases.