Thiogenesis Announces Leigh Syndrome Clinical Program

July 18, 2024 9:00 AM EDT | Source: Thiogenesis Therapeutics, Corp.

San Diego, California--(Newsfile Corp. - July 18, 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 potent antioxidants targeting unmet pediatric diseases, today announced that it has signed a Master Research Agreement with a leading U.S. pediatric hospital. In the agreement, the pediatric hospital will act as the Investigator in assessing Thiogenesis' lead compound, TTI-0102, in the rare mitochondrial disease Leigh syndrome.

Leigh Syndrome and TTI-0102

Mitochondria are critical intracellular "powerplants" that provide the cell with the energy it needs to function normally; the disruption of mitochondrial function can result in several complex and life-threatening conditions. Leigh syndrome is one such rare inherited genetic disease that results from the disruption of normal mitochondrial function. It is usually diagnosed in infancy and occurs in an estimated 1/40,000 live births. Initial symptoms of Leigh syndrome include impaired or weak sucking/breastfeeding capability, loss of motor and communication skills, significant respiratory issues, poor muscle development, loss of appetite and seizures (https://rarediseases.info.nih.gov/diseases/leigh). There is currently no cure for Leigh syndrome, and treatment is primarily supportive, focusing on managing symptoms and complications. Leigh syndrome is highly heterogeneous, involving mutations in both mitochondrial DNA ("mtDNA") and nuclear DNA ("nDNA") that adversely affect multiple mitochondrial respiratory chain complexes. TTI-0102 has been engineered to increase the intracellular levels of the antioxidant glutathione to combat abnormally high levels of mitochondrial oxidative stress, a key characteristic of Leigh syndrome, and thereby help restore normal mitochondrial function and potentially improve clinical outcomes for these patients.

Thiogenesis' lead compound, TTI-0102, is a prodrug that becomes active after oral administration, leading to a well-tolerated sustained release of its active ingredient that can last for over 24 hours. Its active ingredient, cysteamine, has been previously approved for the lysosomal storage disease nephropathic cystinosis. As a result, TTI-0102 is eligible for the accelerated 505 (b)(2) regulatory pathway in the U.S. and can use third party safety data from the previously approved drug, in this case generic cysteamine, for the safety component of its Investigational New Drug ("IND") application with the U.S. Food and Drug Administration ("FDA"). Thiogenesis has requested a pre-IND meeting with FDA, to establish the protocols for its proposed clinical trial in Leigh syndrome. After the pre-IND meeting, Thiogenesis will submit an IND to FDA, with the agreed upon protocols, for a Phase 2a proof-of-concept clinical trial using TTI-0102 to treat Leigh syndrome.

"Innovative therapeutic approaches that increase the availability of antioxidants to boost oxidative stress defenses, have shown the potential to yield meaningful clinical benefits for patients with mitochondrial diseases like Leigh syndrome and significantly enhance their quality of life," said Patrice Rioux, MD, Ph.D., Chief Executive Officer of Thiogenesis. "We also believe our proposed Phase 2a Leigh syndrome clinical trial will provide meaningful synergies with our recently announced MELAS Phase 2 clinical trial in Europe, both in the field of pediatric mitochondrial disease."

About TTI-0102

Thiogenesis' lead compound, TTI-0102, is a new chemical entity that 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 several therapeutic applications. 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 oral 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.

About MELAS

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 diseases. The prevalence of MELAS is not well understood; however, it has been estimated that it occurs in an estimated 15,000 patients in the US and up to 20,000 in the EU.

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 U.S., 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 syndrome, Rett syndrome and pediatric NASH.

Forward Looking Statements

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.

Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this news release.

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SOURCE: Thiogenesis Therapeutics, Corp.