Azitra, Inc. Shares Positive ATR-12 Preclinical Data and Netherton Syndrome Clinical Design at ASGCT Meeting

Azitra, Inc., a biopharmaceutical company focused on precision dermatology, has announced promising preclinical data regarding their innovative therapy, ATR-12, for treating Netherton syndrome. The findings were shared in two oral presentations at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting in Baltimore, Maryland, highlighting the use of engineered Staphylococcus epidermidis as a protein delivery system for skin diseases.

ATR-12, an engineered strain of S. epidermidis, is designed to express the missing lympho-epithelial Kazal-type-related inhibitor (LEKTI) protein in patients with Netherton syndrome. The in vitro studies have demonstrated that ATR-12 effectively inhibits the key protease kallikrein 5 (KLK5) associated with Netherton syndrome at nanomolar levels (IC50=26 nM). In addition, ATR-12 noticeably reduced protease activity in human ex vivo Netherton syndrome models to levels comparable to healthy skin.

In human skin models, ATR-12 provided significantly better LEKTI delivery compared to topically applied LEKTI alone, achieving a higher concentration (6.1 µg/cm2 vs. 2.3 µg/cm2, p=0.008) after 24 hours, along with deeper biodistribution. The application of ATR-12 also substantially reduced the pro-inflammatory cytokine IL-36γ by 92% in human skin cell cultures, and by 69% in vitro human skin treated with erlotinib.

Safety assessments of ATR-12 were conducted using minipigs with abraded skin. These studies indicated that ATR-12 was well-tolerated and safe, as shown by the delivery of 11.9 ng/cm2 of LEKTI on the skin surface compared to 2.6 ng/cm2 in the control group over 14 days. No adverse effects were observed in GLP toxicology studies.

Furthermore, Azitra is currently undertaking a Phase 1b clinical trial (NCT06137157) to evaluate ATR-12 in patients with Netherton syndrome. This trial is a multicenter, randomized, double-blind, vehicle-controlled study involving 12 adult participants. The primary goal is to assess the safety and tolerability of ATR-12 when applied topically, while secondary objectives include measuring efficacy signals such as investigator and patient global assessments and the skin pharmacokinetics of LEKTI. Exploratory goals involve evaluating pharmacodynamic parameters, cytokine responses, and biomarkers like KLK5, KLK7, IL-36γ, trypsin-like, and chymotrypsin-like activities.

Travis Whitfill, Azitra’s co-founder and COO, expressed enthusiasm about the preclinical data and the clinical strategy for ATR-12, emphasizing its potential as a proof-of-concept for using genetically engineered skin commensals to deliver essential proteins to the skin. The robust preclinical results set a solid foundation for the ongoing clinical study.

Azitra has secured clinical sites and identified patients for this Phase 1b trial and expects to present initial safety data by the end of the year. The company is committed to advancing precision dermatology through its innovative therapies and engineered protein delivery systems.