San Diego, California--(Newsfile Corp. - March 25, 2024) - Thiogenesis Therapeutics, Corp. (TSXV: TTI) ("Thiogenesis" or the "Company") a clinical-stage biotechnology company developing disulfides that are precursors to thiol-active compounds and that have the potential to treat unmet pediatric diseases, today 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).
"We are excited to be on the brink of initiating our first Phase 2 clinical trial," said Patrice Rioux, MD, Ph.D., Chief Executive Officer of Thiogenesis. "It will be the first time that TTI-0102, a new chemical entity patented in 2021 in the US and other countries, is going to be tested for efficacy in patients. 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 we are eager to investigate the potential of TTI-0102 to provide relief for these unfortunate patients."
About MELAS
Mitochondria are important organelles in cells that generate its energy to function. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes ("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.
1 Hayashi G, Cortopassi G. Oxidative stress in inherited mitochondrial diseases. Free Radic Biol Med. 2015 Nov;88(Pt A):10-7.doi: 10.1016
2 Gunnewiek et al. Mitochondrial dysfunction impairs human neuronal development and reduces neuronal network activity and synchronicity. bioRxiv 720227; doi: https://doi.org/10.1101/720227
About TTI-0102
Thiogenesis' lead compound, TTI-0102, is an asymmetric disulfide and a prodrug that acts as a precursor to the thiol-active compound cysteamine. 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 292,667 common shares have been formally cancelled as of December 22, 2023 in connection with the re-structuring of a Lock-Up Agreement dated February 10, 2021 and the appointment of Dr. Vince Stanton, Jr. to the Company's Scientific Advisory Board.
About Thiogenesis
Thiogenesis Therapeutics, Corp. (TSXV: TTI) is a clinical-stage biopharmaceutical company operating through its wholly owned subsidiary based in San Diego, CA. The Company is publicly traded on the TSX Venture Exchange. Thiogenesis is developing sulfur-containing prodrugs that act as precursors to previously approved thiol-active compounds, with the potential to treat serious pediatric diseases with unmet medical needs. Prodrugs are drugs that contain previously approved active ingredients and are modified so that they only become active when metabolized. For regulatory purposes prodrugs can use existing third-party safety data in regulatory submissions in the streamlined 505 (b)(2) regulatory pathway in the US, and its equivalent hybrid system in Europe, to proceed into human efficacy trials with regulatory approval. Prodrugs may enhance the profile of the active ingredient to increase its bioavailability and reduce side effects. The Company's initial target indications include mitochondrial encephalopathy lactic acidosis and stroke-like episodes ("MELAS"), Leigh's syndrome, Rett syndrome and pediatric NASH.
This news release contains certain forward-looking statements and forward-looking information (collectively referred to herein as "forward- looking statements") within the meaning of Canadian securities laws including, without limitation, statements with respect to the future investments by the Company. All statements other than statements of historical fact are forward-looking statements. Undue reliance should not be placed on forward-looking statements, which are inherently uncertain, are based on estimates and assumptions, and are subject to known and unknown risks and uncertainties (both general and specific) that contribute to the possibility that the future events or circumstances contemplated by the forward-looking statements will not occur. Although the Company believes that the expectations reflected in the forward-looking statements contained in this press release, and the assumptions on which such forward-looking statements are made, are reasonable, there can be no assurance that such expectations will prove to be correct. Readers are cautioned not to place undue reliance on forward-looking statements included in this document, as there can be no assurance that the plans, intentions, or expectations upon which the forward-looking statements are based will occur. By their nature, forward-looking statements involve numerous assumptions, known and unknown risks and uncertainties that contribute to the possibility that the predictions, forecasts, projections and other forward-looking statements will not occur, which may cause the Company's actual performance and results in future periods to differ materially from any estimates or projections of future performance or results expressed or implied by such forward-looking statements. The forward-looking statements contained in this news release are made as of the date hereof and the Company does not undertake any obligation to update publicly or to revise any of the included forward-looking statements, except as required by applicable law. The forward-looking statements contained herein are expressly qualified by this cautionary statement.
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