Thiogenesis has synthesized novel compounds, that are New Chemical Entities (“NCEs”) and act as precursors to thiols. Thiols are compounds that have a functional R-SH group, where S is sulfur and H is hydrogen. Highly reactive sulfur makes the R-SH component of thiols one of the most active functional groups in chemistry, these activities have been widely studied for several decades and provide thiols with vast therapeutic potential.

The lead compound, TTI-0102, is an asymmetric disulfide made up of two thiols that have been synthesized. It was created to address the obstacles that hinder thiol-active drugs, they typically have: short elimination half-lives, discomforting side effects and dosing limitations, any of which can lead to compliance issues.

The compound cysteamine, is a well-studied thiol with an active functional R-SH group and giving it multiple mechanisms of action with potential therapeutic benefits, including:

• Provides cysteine, which is a precursor to the important anti-oxidant glutathione - the lack of cysteine is usually the limiting factor in the human production of glutathione
• Precursor to the amino acid taurine, which has cytoprotective properties
• Binds to the ACE2 receptor, giving it important anti-viral properties
• Is an anti-inflammatory, potentially inhibiting cytokine storm in viral disease
• Acts as a mucolytic (mucus thinner)
• Promotes the production of brain-derived neurotropic factor (BDNF), a protein important in nerve growth and brain function

However, cysteamine bitartrate formulations were approved in 1994 as Cystagon^® (immediate release) and in 2013 as Procysbi^® (delayed release) - both for the treatment of cystinosis. Cystinosis is a life-threatening lysosomal storage disease where the transporter for the disulfide cystine is not functioning. It results in the toxic buildup of cystine in the lysosome of cells; it damages tissues and kidneys, often leading to transplantation. Cysteamine aids in the orderly removal of cystine from the lysosome.

Cysteamine causes unpleasant side-effects at peak blood concentrations. These include halitosis, body odor, nausea/vomiting, fatigue and gastrointestinal pain. The side effects and dosing limitations of cysteamine have historically been a major obstacle to the development of additional applications for thiol-containing drugs. TTI-0102, Thiogenesis’ lead compound, was created to reduce or eliminate side-effects, provide dosing flexibility and improve compliance.