AC-203 is an innovative topical therapeutic drug being developed by TWiB for the treatment of Epidermolysis Bullosa Simplex (“EBS”). Its development is based on diacerein, an active ingredient that has been used in a marketed osteoarthritis drug since 1990s. By delivering 1% diacerein ointment directly to the skin, AC-203 reduces the activity and expression of pro-inflammatory cytokines, particularly IL-1β, TNF-α, and TGF-β, and inhibits the activity of iNOS and production of nitric oxide. It is expected to modulate inflammatory responses, reduce blister formation, and help ease the daily burden of skin care for patients.

AC-203 has received Orphan Drug Designation from US Food and Drug Administration (“FDA”), European Medicines Agency, and Taiwan FDA. It has also been granted Rare Pediatric Disease Designation and Fast-Track status by the US FDA. As there are currently no approved therapies for EBS, AC-203 is expected to be the first-in-class therapeutic treatment for EBS patients.

Epidermolysis Bullosa Simplex (“EBS”)

Epidermolysis Bullosa, or EB, is a group of rare genetic skin disorders caused by genetic defects affecting proteins that normally hold the layers of skin together. EB is classified into several subtypes, of which EBS is the most common, caused by keratin mutations, with blistering occurring within the epidermis layer.

Junctional EB (“JEB”) results from defects in proteins of the basement membrane, often leading to more severe, early-onset disease. Dystrophic EB (“DEB”) is caused by collagen VII mutations, leading to deeper skin separation, scarring, and long-term complications. Kindler syndrome, a rarer subtype of EB, shows mixed levels of skin cleavage and progressive skin fragility. Together, these subtypes reflect the biological and clinical diversity of EB. It is estimated that there are approximately 500,000 EB patients worldwide, of whom around 70% have EBS.

The pathogenesis of EBS is mostly associated with mutations in keratin genes, particularly KRT5 or KRT14, which destabilize the basal keratinocyte cytoskeleton and make the skin extremely sensitive to friction. Clinically, EBS can be classified into localized, intermediate, and severe forms based on the severity of symptoms:

EBS is not only a disease of fragile skin but also represents a long-term medical and daily-life burden for patients. Recurrent blisters, erosions, infections, and associated pain and itching require patients to perform time-consuming wound care every day and limit many daily activities. These symptoms not only affect the patient’s quality of life but also impose significant psychological and financial burdens on their families. Since current treatments are primarily supportive and there are no effective therapies targeting the underlying cause, EBS remains a high unmet medical need.