Dr. Patrice Rioux reports

THIOGENESIS ANNOUNCES ACCEPTANCE OF CLINICAL TRIAL APPLICATION - PART I IN THE EU FOR MELAS

The European Medicines Agency (EMA) has accepted Thiogenesis Therapeutics Corp.'s 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 United States. 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 multicountry, multicentre 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; eight patients will receive TTI-0102 and four patients will receive placebo. The primary end points of the study are to measure over a six-month period: i) the change in functional capacity based on a 12-minute walking test, and ii) additional safety and tolerability end points. Secondary end points 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 Dr. Patrice Rioux, MD, PhD, chief executive officer of Thiogenesis. "It will be the first time that TTI-0102, a new chemical entity patented in 2021 in the U.S. 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 diseases. The prevalence of MELAS is not well understood; however, it has been estimated that it occurs in 1:20,000 people, which would represent between 15,000 to 20,000 in the U.S. and over 20,000 in the European Union.

About TTI-0102

Thiogenesis' lead compound, TTI-0102, is an asymmetric disulphide and a prodrug that acts as a precursor to the thiol-active compound cysteamine. Thiols, which have a functional SH group (containing sulphur 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 Nov. 27, 2023, the company announces that 292,667 common shares have been formally cancelled as of Dec. 22, 2023, in connection with the restructuring of a lock-up agreement dated Feb. 10, 2021, and the appointment of Dr. Vince Stanton to the company's scientific advisory board.

About Thiogenesis Therapeutics Corp.

Thiogenesis Therapeutics is a clinical-stage biopharmaceutical company operating through its wholly owned subsidiary based in San Diego, Calif. The company is publicly traded on the TSX Venture Exchange. Thiogenesis is developing sulphur-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's syndrome, Rett syndrome, and pediatric NASH (non-alcoholic steatohepatitis).

We seek Safe Harbor.