Thiogenesis Therapeutics, Corp. (TSXV: TTI, OTCQX: TTIPF) has taken a significant step in its clinical development program by dosing the first two patients in its Phase 2 trial for TTI-0102, its lead drug candidate for MELAS, a rare and debilitating mitochondrial disorder. The trial, which launched at Radboud University Medical Center in the Netherlands, marks a meaningful advance for the company and offers new hope for patients with a disease that currently lacks approved therapies in both Europe and the United States.
The Phase 2 study is designed as a multi-country, multi-center effort, with sites in the Netherlands and France. It is a randomized, double-blind, placebo-controlled trial that will enroll 12 patients in total. Of these, eight will receive TTI-0102 and four will be given a placebo. Over a six-month period, the trial will evaluate the safety, tolerability, efficacy, and pharmacokinetics of the drug. An interim analysis is planned at the three-month mark to assess safety and early signs of clinical benefit.
The trial will focus on several key endpoints that reflect the daily challenges faced by people living with MELAS, including the 12-Minute Walking Test to measure physical endurance, the Fatigue Severity Scale to assess the impact of fatigue on daily life, and the WHOQOL-BREF, a tool used to evaluate quality of life.
According to Dr. Patrice Rioux, CEO of Thiogenesis, the dosing of the first patients is the culmination of extensive planning and signals the company’s commitment to addressing unmet needs in mitochondrial diseases. He emphasized the potential of TTI-0102 to address biochemical deficiencies that play a role in MELAS, specifically glutathione and taurine, which are often lacking in patients and contribute to disease progression.
MELAS, short for mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, is a genetic disorder most commonly caused by a mutation in mitochondrial DNA. It typically presents before the age of 20 and can lead to symptoms such as seizures, vomiting, muscle weakness, and fatigue. Over time, patients may lose motor skills and experience intellectual disability. The disease is considered an orphan condition, affecting an estimated 4.1 in 100,000 people.
A growing body of research suggests that oxidative stress and deficiencies in antioxidants like glutathione and amino acids like taurine are central to the disease process. These insights have informed Thiogenesis’ approach, which centers on boosting these critical molecules within cells.
TTI-0102 is an asymmetric disulfide prodrug that acts as a precursor to cysteamine, a thiol compound with established therapeutic potential. Thiols are known for their antioxidant properties and their role in key metabolic processes. By delivering cysteamine in a more tolerable and effective form, Thiogenesis aims to overcome the limitations of earlier thiol-based drugs, such as short half-life and gastrointestinal side effects.
One notable aspect of TTI-0102 is its classification as a prodrug. Prodrugs are inactive compounds that are metabolized in the body to release the active drug. This approach can improve bioavailability and reduce side effects. Because TTI-0102 is based on a previously approved active ingredient, it can leverage accelerated regulatory pathways in both the U.S. and Europe, potentially speeding up the development process.
Headquartered in Toronto, Canada, Thiogenesis Therapeutics is a clinical-stage biopharmaceutical company focused on developing sulfur-containing prodrugs for pediatric diseases with significant unmet needs. In addition to MELAS, the company is planning trials for other conditions, including Leigh syndrome, Rett syndrome, and pediatric metabolic-associated steatohepatitis (MASH). The company’s work in rare diseases and its focus on innovative thiol-based therapies position it as a notable player in the biotech sector.
As the Phase 2 trial for TTI-0102 progresses, Thiogenesis will be closely watched by both the investment community and the rare disease community. The company’s approach, targeting the underlying biochemistry of mitochondrial disorders, reflects a growing trend in precision medicine and could provide a much-needed option for patients with MELAS if the trial is successful.