Azitra secures US patent for ATR-12 engineered microbiome therapy targeting Netherton syndrome

A new US patent covering an engineered live biotherapeutic for Netherton syndrome was awarded to Connecticut-based Azitra, Inc. (NYSE American: AZTR). As per the company press release, the firm received US Patent No. 12,606,610 B2 from the USPTO on April 21, 2026, covering compositions and methods for treating Netherton syndrome using LEKTI-expressing recombinant microbes. The Azitra ATR-12 patent covers microbes that secrete one or more domains of the lympho-epithelial Kazal-type-related inhibitor (LEKTI) protein and the methods of using those microbes to treat skin diseases, providing both composition-of-matter and method-of-treatment protection for the program.

Scientific basis and mechanism of the ATR-12 program

Netherton syndrome is caused by loss-of-function mutations in the SPINK5 gene, which encodes LEKTI, a serine protease inhibitor expressed in epithelial tissues. In the absence of functional LEKTI, unchecked serine protease activity in the skin leads to degradation of the cornified cell envelope, barrier dysfunction, chronic inflammation, and susceptibility to infection. The condition is estimated to affect approximately 20,000 patients globally, can be fatal in infancy, and carries profound lifelong morbidity for those who survive beyond early childhood. No therapy has received regulatory approval for the indication.

ATR-12 addresses the underlying protein deficiency through a microbiome-based delivery strategy. The asset uses an engineered strain of Staphylococcus epidermidis, a commensal bacterium naturally resident on human skin, that has been genetically modified to express and secrete a fragment of the human LEKTI protein. When applied topically, the engineered strain is designed to colonize the skin surface and provide local, sustained delivery of the missing protease inhibitor directly at the site of pathology. The approach bypasses the need for systemic drug exposure and leverages the skin’s existing microbial ecology as a therapeutic delivery vehicle.

The patent title, “Compositions and Methods for Treatment of Netherton Syndrome with LEKTI Expressing Recombinant Microbes,” reflects the dual scope of protection: the engineered S. epidermidis strain itself as a composition, and the therapeutic use of LEKTI-expressing microbes to treat skin diseases including Netherton syndrome. The breadth of the claims, as described by the company, extends to microbes secreting one or more LEKTI domains, which may provide coverage beyond the specific ATR-12 construct.

The ATR-12 program is currently being evaluated in a Phase I b clinical trial in adult patients with Netherton syndrome.

Context and competitive landscape

The issuance of the Azitra ATR-12 patent reflects a broader shift in dermatology drug development toward microbiome-based and precision delivery platforms, particularly for rare monogenic skin diseases where conventional small-molecule and biologic approaches have not produced approved therapies.

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Within the live biotherapeutic and engineered microbiome space for dermatology, ATR-12 occupies a distinct mechanistic position. The asset is not a conventional recombinant protein, a monoclonal antibody, or a gene therapy vector; it is a topically applied engineered bacterium designed to produce a therapeutic protein in situ. This approach has mechanistic parallels with other programs exploring the skin microbiome as a drug delivery substrate, though direct competitors using the same S. epidermidis LEKTI protein replacement strategy for Netherton syndrome treatment have not been publicly disclosed in the available data.

In the broader rare skin disease space, Krystal Biotech (Nasdaq: KRYS), based in Pittsburgh, Pennsylvania, has developed Vyjuvek (beremagene geperpavec), a topical gene therapy using a modified herpes simplex virus vector to deliver functional COL7A1 gene copies to skin cells in patients with dystrophic epidermolysis bullosa. Vyjuvek received US FDA approval in 2023 and represents the closest approved precedent for a topically applied, genetically engineered therapeutic in a rare, monogenic skin disease. The Krystal program uses a viral vector rather than a live bacterial platform, and targets a different disease and gene, but the regulatory and commercial pathway it has established is relevant context for Azitra’s development strategy. Both programs operate in the precision dermatology space defined by rare, genetically driven skin conditions with high unmet need and no prior approved options.

Timber Pharmaceuticals (NYSE American: TMBR), based in Short Hills, New Jersey, has been developing TMB-001, a topical isotretinoin formulation for congenital ichthyosis, another rare keratinization disorder. While the mechanism differs substantially from ATR-12’s engineered microbiome approach, the program competes in the same orphan dermatology development environment and illustrates the range of modalities being pursued for rare skin diseases.

Azitra has also disclosed a second advanced program, ATR-04, which uses a different engineered S. epidermidis strain for the treatment of EGFR inhibitor-associated rash, a condition affecting an estimated 150,000 patients in the US annually. ATR-04 has received Fast Track designation from the US FDA, and an investigational new drug application is open for that program.

Azitra’s broader platform comprises a library of approximately 1,500 bacterial strains, augmented by artificial intelligence and machine learning tools for strain screening and selection. The company has indicated that the platform is also being explored for applications in the consumer and cosmeceutical markets through filaggrin protein and peptide technologies, though those activities are separate from the clinical pipeline.


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