Evaluation of Topical ATR12-351 in Adults With Netherton Syndrome

Netherton syndrome (NS) is a rare but severe autosomal recessive disease that affects the skin, hair, and immune system. NS presents at birth with red skin covered by fine scales, a specific hair shaft abnormality ("bamboo hair"), atopic lesions, and elevated systemic immunoglobulin E (IgE) levels. Patients often develop allergies and asthma, and the unfortunate prognosis for infants with NS is poor, with 10% mortality in the first 6 months of life and recurrent infections. There are no FDA-approved treatment options for NS. NS is caused by mutations in in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI). Absence of LEKTI causes unregulated activity of proteases in the kallikrein subfamily, causing excessive desquamation of skin.

ATR12-351 is a topical ointment containing a lyophilized version of a live biotherapeutic product (LBP), Staphylococcus epidermidis (SE) strain designated SE351. This strain has been modified to be auxotrophic and to express recombinant human LEKTI protein (rhLEKTI). ATR12-351 is intended to address the underlying cause of NS by replacing deficient/dysfunctional LEKTI. The treatment consists of applying ATR12-351 to affected areas, where rhLEKTI produced by ATR12-351 will counter the dysregulated skin serine protease activity observed in NS patients.

This first-in-human study is a randomized, double-blind, vehicle-controlled clinical study to assess the safety, tolerability, and pharmacokinetics (PK) of topical ATR12-351 in approximately 12 adult Netherton syndrome patients who will serve as their own control. This study will include a 14-day treatment period to investigate the safety and tolerability of ATR12-351 applied to the skin and will be followed a total of 84 days for safety. The results of this first-in-human clinical study will establish safety and tolerability as well as initial efficacy of ATR12-351 application in Netherton syndrome patients.