Azitra, Inc. announced preclinical data from the Company?s platform and pipeline. The data are being presented on May 10, 2024, in two oral sessions entitled ?Engineered Staphylococcus Epidermidis as a Protein Delivery System for Treating Skin Diseases? and ?Staphylococcus epidermidis Strain Expressing LEKTI-D6 (ATR12-351) for Netherton Syndrome?

at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting in Baltimore, MD. The data in the two oral presentations showcase the preclinical development of ATR-12 and the clinical study design of a Phase 1b study in Netherton syndrome patients. In vitro data show that LEKTI (lympho-epithelial Kazal-type-related inhibitor) protein secreted by ATR-12 has nanomolar inhibition of a key protease that drives Netherton syndrome, kallikrein (KLK) 5 (IC50=26 nM).

Additionally, in human ex vivo Netherton syndrome models, ATR-12 supernatant reduces protease activity nearly 7-fold to levels comparable to healthy skin. Furthermore, in ex vivo human skin models, ATR-12 led to a higher amount of LEKTI delivery to the skin compared to topically applied LEKTI alone (6.1 µg/cm2 vs. 2.3 µg/cm2, p=0.008) after 24 hours and resulted in deeper biodistribution of LEKTI.

Application of ATR-12 in human skin cell culture reduced IL-36? by 92% compared to skin extracts induced to overexpress IL-36?. Topical application of ATR-12 to in vitro human skin treated with erlotinib reduced IL-36?

by 69%. In studies conducted in minipigs with abraded skin, topical application of ATR-12 resulted in 11.9 ng/cm2 of LEKTI on the surface of the skin vs. 2.6 ng/cm2 in the vehicle group at day 14.

ATR-12 application was safe and well-tolerated in GLP toxicology studies with minipigs. The oral presentation entitled ?Staphylococcus epidermidis Strain Expressing LEKTI-D6 (ATR-12) for Netherton Syndrome? also provides the study design for an active clinical trial of ATR-12 in Netherton syndrome patients.

The Phase 1b study (NCT06137157) is a multicenter, randomized, double-blind, vehicle-controlled study in adults (n=12) with Netherton syndrome. Patients will be treated twice daily with 109 CFU /g ATR-12 for 14 days. The primary objective is to assess the safety and tolerability of topical application of ATR-12, and the secondary objectives are to evaluate efficacy signals (e.g., investigator and patient global assessments) and to evaluate the skin pharmacokinetics of LEKTI.

Exploratory objectives include the evaluation of pharmacodynamic parameters, including anti-LEKTI response, cytokine responses, biomarkers such as KLK5, KLK7, IL-36?, trypsin-like activity, and chymotrypsin-like activity.