BioMendics CEO Karen McGuire, PhD, on Disease-Modifying Strategies for EB Simplex

In a recent interview with Dermatology Times, Karen McGuire, PhD, CEO and co-founder of BioMendics LLC, discussed the substantial disease burden of epidermolysis bullosa simplex (EBS) and emerging therapeutic strategies aimed at modifying disease biology rather than managing symptoms alone. McGuire emphasized that the term “simplex” is frequently misunderstood and does not imply a mild disease course. Instead, it refers to the skin layer in which blistering occurs

“We call it localized just because of the body surface area affected,” she noted. “We don't call it localized because it's mild.”

Patients with EBS experience significant morbidity driven by recurrent blistering, chronic wounds, pain, infection risk, and impaired mobility. Even in localized disease, blistering of the palms and soles can be severe, with nearly half of patients reporting difficulty walking and reliance on mobility aids. Blisters may form beneath calluses, often requiring urgent care intervention for drainage, further compounding pain and infection risk. Although EBS may appear less severe than dystrophic EB, McGuire stressed that its impact on quality of life is substantial.

McGuire outlined BioMendics’ investigational therapy, TolaSure, and its novel mechanism of action. Current standard-of-care treatments for EB focus on symptomatic management, including wound care, pain control, and infection prevention. In contrast, TolaSure targets the underlying cellular pathology of EBS. The therapy is based on BioMendics’ mTORX platform, which uses mTOR inhibition to induce autophagy. By enhancing autophagic clearance of mutated and misfolded keratin proteins, the treatment aims to reduce the toxic accumulation of defective keratins within basal keratinocytes. This process strengthens intermediate filament networks, which are structurally compromised in EBS, thereby improving cellular resilience and reducing blister formation.

Key findings from the phase 1b/2 TAMES-01 trial supported the advancement of this approach. Through multifactorial analyses, investigators identified blistering as the primary driver of disease severity. Measurement of intact and ruptured blister surface area demonstrated a 96% reduction within 2 to 3 weeks of treatment, whereas placebo-treated patients showed fluctuating disease activity. Importantly, electron microscopy of perilesional biopsies revealed restoration of intermediate filament networks in treated skin, providing mechanistic validation that correlated with observed clinical improvements. Collectively, these findings suggest that targeting keratin homeostasis through autophagy induction may represent a disease-modifying strategy for patients with EBS, addressing both the biological root of blistering and its clinical consequences.