Cutaneous Delivery of LEKTI via an Engineered Strain of Staphylococcus Epidermidis for the Treatment of Netherton Syndrome

The study investigates ATR12-351, a topical ointment containing an engineered strain of S. epidermidis designed to deliver LEKTI protein for treating Netherton syndrome (NS). Preclinical tests showed that ATR12-351 significantly reduced trypsin-like activity in human skin extracts supplemented with KLK5 and increased LEKTI levels in tape-stripped skin models. In minipigs with abraded skin, ATR12-351 application resulted in elevated LEKTI levels without adverse safety findings and was not detected in the bloodstream. These results suggest ATR12-351 effectively delivers functional LEKTI throughout the epidermis, reducing KLK activity, and is safe for use, prompting the initiation of a clinical study in NS patients.