Pioneering Novel Thiol Compounds as Therapeutics for Mitochondrial Diseases

Intro

Thiogenesis Therapeutics is a clinical-stage biotechnology company developing cysteamine-based therapeutics (thiols) that reduce cystine accumulation and restore cellular redox balance, supporting mitochondrial energy metabolism in inherited disease.

TTI-0102 is a novel cysteamine prodrug designed to replace a burdensome daily regimen of multiple capsules with oral dosing in a powder format - potentially improving tolerability, bioavailability, and dosing burden relative to legacy cysteamine therapies.

Cysteamine is FDA-approved for nephropathic cystinosis, but existing formulations impose a high daily capsule burden, strict dosing requirements, and GI side effects, resulting in challenges with adherence. TTI-0102 is in late-stage development for cystinosis, building on an investigator-initiated study to inform a potential pivotal trial.

Beyond cystinosis, Thiogenesis is advancing TTI-0102 in Leigh syndrome spectrum, a primary mitochondrial disease and a rare pediatric condition with no approved therapies, via a Phase 2 trial with a leading U.S. children's hospital expected in 2026.

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Thiogenesis Therapeutics is a clinical-stage biotech company developing New Chemical Entities (NCEs) that are thiol compounds with strong antioxidant and anti-inflammatory properties.
Thiogenesis’ novel compounds have the potential to be used as new therapeutic drugs for inherited and acquired mitochondrial diseases, including metabolic diseases, such as type 2 diabetes, fatty liver disease, and cardiovascular disease.

Oxidative stress and mitochondrial dysfunction are critical underlying features of both inherited and acquired mitochondrial diseases.

Thiols are compounds that have an active sulfur-hydrogen (-SH) functional group that participates in several biochemical reactions independent of the core compound. Importantly, TTI-0102 is the best-in-class method of generating intracellular cysteine, which is the rate-limiting factor in the cell for the  synthesis of intracellular glutathione, a critical antioxidant.

Thiols are compounds that have an active sulfur-hydrogen (-SH) functional group that participates in several biochemical reactions independent of the core compound. Importantly, TTI-0102 is the best-in-class method of generating intracellular cysteine, which is the rate-limiting factor in the cell for the  synthesis of intracellular glutathione, a critical antioxidant.

Considered the master antioxidant, glutathione is medically important for its potential in alleviating oxidative stress and maintaining normal mitochondrial function. Glutathione has several key properties including that it has a specific transmembrane transporter allowing it to enter the mitochondria, neutralizes free radicals, maintains redox balance and supports other antioxidants in the antioxidant defense system.

Thiogenesis’ proprietary compounds have been engineered to address the issues that have long constrained the development of thiol-based drugs over several decades of promising research; their short-half life and dose limiting gastrointestinal side effects. TTI-0102 has already demonstrated in a human volunteer study that it is well tolerated at high doses. 

TTI-0102 is initially targeting pediatric diseases with unmet medical needs that have oxidative stress as a core component and for which there is no approved therapy. With regulatory approval, the Company anticipates the initiation of three human efficacy trials with leading research institutions: in the metabolic liver disease pediatric MASLD/MASH, and the inherited mitochondrial diseases MELAS and Leigh syndrome.

Thiogenesis’ proprietary compounds have been engineered to address the issues that have long constrained the development of thiol-based drugs over several decades of promising research; their short-half life and dose limiting gastrointestinal side effects. TTI-0102 has already demonstrated in a human volunteer study that it is well tolerated at high doses. 

TTI-0102 is initially targeting pediatric diseases with unmet medical needs that have oxidative stress as a core component and for which there is no approved therapy. With regulatory approval, the Company anticipates the initiation of three human efficacy trials with leading research institutions: in the metabolic liver disease pediatric MASLD/MASH, and the inherited mitochondrial diseases MELAS and Leigh syndrome.