Pioneering Novel Thiol Compounds as Therapeutics for Mitochondrial Diseases

Intro

Thiogenesis Therapeutics is a clinical-stage biotechnology company developing next-generation sulfur-based therapeutics (thiols) designed to restore redox balance and reduce inflammation; key drivers of inherited and acquired mitochondrial disease.

TTI-0102, is a novel cysteamine prodrug that improves on the limitations of legacy thiol therapies with enhanced tolerability, bioavailability, and dosing. Early clinical results demonstrate that TTI-0102 is well tolerated at high doses.

Cysteamine is an FDA-approved treatment for nephropathic cystinosis; however, current formulations are burdened by gastrointestinal side effects, strict dosing schedules, and adherence challenges. Thiogenesis expects to file an Investigational New Drug (IND) application in early 2026 for a pivotal Phase 3 trial of TTI-0102 in cystinosis.

Beyond cystinosis, TTI-0102 is being evaluated in a Phase 2 trial for MELAS and in planned studies for Leigh syndrome spectrum and other pediatric mitochondrial conditions.

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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.