Thiogenesis Therapeutics, Corp. (TSXV: TTI, OTCQX: TTIPF), a clinical-stage biopharmaceutical company based in San Diego, has received clearance from the U.S. Food and Drug Administration (FDA) to move forward with a Phase 2a clinical trial of its lead drug candidate, TTI-0102, for Leigh syndrome spectrum (LSS), a rare and severe pediatric mitochondrial disease.
The FDA’s decision allows Thiogenesis to begin the trial in the second half of 2025, in collaboration with the Children’s Hospital of Philadelphia (CHOP). Dr. Zarazuela Zolkipli-Cunningham will lead the study at CHOP, a recognized center for pediatric mitochondrial medicine.
TTI-0102 is a new chemical entity and a prodrug, meaning it is designed to become active only after being metabolized in the body. It acts as a precursor to cysteamine, a compound that helps boost intracellular cysteine levels. Cysteine is essential for producing glutathione, the body’s primary antioxidant, which is especially important for patients with mitochondrial disorders like LSS.
The company aims to address the shortcomings of first-generation thiol-based drugs, such as short half-life and dosing limitations, by using TTI-0102’s unique chemical structure. The hope is that this approach will improve the drug’s effectiveness and reduce side effects. The upcoming trial will be conducted in two stages. In the first stage, nine patients, six receiving TTI-0102 and three receiving a placebo, will participate in a randomized, double-blind, placebo-controlled study lasting three months. This phase will include adults and adolescents with Leigh syndrome spectrum and will assess safety, tolerability, efficacy, and how the drug is processed in the body (pharmacokinetics and pharmacodynamics). The second stage is an open-label extension enrolling six pediatric patients aged five and older, all of whom will receive TTI-0102 for three months, with the same study endpoints as the first stage. If the results are positive and FDA approval is granted, Thiogenesis plans to move TTI-0102 into a larger, pivotal Phase 2b/3 trial for pediatric Leigh syndrome spectrum.
Leigh syndrome spectrum is a rare, inherited disorder that disrupts mitochondrial function, the process that generates energy in our cells. It’s usually diagnosed in infancy and affects about one in 40,000 births. Symptoms can be severe, including feeding difficulties, loss of motor skills, respiratory problems, muscle weakness, and seizures. There is currently no cure, and treatment is limited to managing symptoms.
The disease is highly variable, with more than 113 known genetic causes affecting mitochondrial respiratory chain function. TTI-0102 is engineered to combat the high levels of oxidative stress found in LSS, with the goal of improving mitochondrial function and, potentially, clinical outcomes for patients.
Dr. Marni Falk, Executive Director of the Mitochondrial Medicine Frontier Program at CHOP, commented on the trial’s significance, noting that boosting intracellular glutathione could help counteract oxidative stress in these patients. She highlighted preclinical research suggesting that compounds like cysteamine may bring meaningful benefits to those with mitochondrial diseases.
Thiogenesis focuses on developing sulfur-containing prodrugs as treatments for pediatric diseases with unmet medical needs. In addition to the cleared IND for LSS, the company is running a Phase 2 trial in Mitochondrial Encephalopathy Lactic Acidosis and Stroke (MELAS) and planning studies for Rett syndrome and pediatric Metabolic Dysfunction-Associated Steatohepatitis (MASH).
The company’s approach leverages the regulatory advantages of prodrugs, which can sometimes use existing safety data for faster advancement through the FDA’s 505(b)(2) pathway. This could help Thiogenesis get promising therapies to patients more quickly, provided the clinical results support their safety and efficacy.
As the Phase 2a trial for TTI-0102 gets underway later this year, investors and the rare disease community will be watching closely to see whether this new approach can make a difference for children affected by Leigh syndrome spectrum.
