Our skin microbiome plays a crucial role in human health

Microbiome

The human skin serves as a barrier to the outside world and is also rich in microorganisms. These microorganisms, collectively known as the “skin microbiome,” play a crucial role in maintaining human health and skin appearance.

The microbiome is made up of many different types of microbes. It is a diverse community of bacteria, fungi, mites and viruses that, when in homeostasis, provides protection against disease and keeps the skin looking smooth and moist. Skin diseases or changes in underlying skin biology can arise from different causes. Many skin diseases are associated with disruptions in the skin microbiome (known as “dysbiosis”). Skin disease may also be caused by damage to the skin, or in other cases by missing or excess amounts of key proteins. These problems can then be made worse by dysbiosis and—in many cases—by a strong inflammatory response to the changes in the microbiome. A dual strategy that focuses on addressing both skin biochemistry and dysbiosis can lead to dramatic improvements in the skin. Azitra’s approach is to develop therapeutics with these dual effects. Azitra is developing products that address both disease and dysbiosis.

Azitra is solving the challenges of skin diseases through three strategies that leverage desirable bacteria naturally found in the skin microbiome such as Staphylococcus epidermidis (SE):

Commensals

Skin commensal bacteria offer many well-described and published benefits that can potentially be harnessed for therapeutic applications for skin diseases. These commensal bacteria, including many strains of Staphylococcus epidermidis (SE), have adapted to live with us and cross-talk with the human immune system to create homeostasis. In certain skin diseases or cases of dysbiosis, direct application of commensal bacteria like SE can treat dysbiosis or microbes associated with disease—as well as skin inflammation, tissue damage, or a weakened skin barrier. These properties are being harnessed by Azitra to create novel therapeutics for skin diseases—as in the case of cancer therapy-associated rashes (CTAR), which are skin diseases linked to chemotherapy and associated with dysbiosis and in particular elevation of the Staphylococcus aureus population that lives on the skin.

Product goals:

Treat dysbiosis and microbes associated with disease

Improve skin barrier function

Accelerate wound healing and tissue repair

Address cutaneous inflammation

Enhanced Commensals

The microbiome and specific strains that live with us can also be designed to provide effective therapy for skin by using the tools of genetic engineering. Azitra engineers commensal skin bacteria to deliver critical disease-modifying proteins directly to the target and through the stratum corneum of the skin. This approach constitutes a major platform technology that can be used to deliver different proteins and target multiple diseases.

These types of products are known as Live Biotherapeutic Products (LBPs) and are being developed as cost-effective topical applications with the potential to solve skin disease challenges. The advantages of such LBPs include the ability to directly address the cause of disease, ease of use, and topical application at the location of the skin problem—thus avoiding systemic therapy. Azitra is focused on LBPs that treat disease and control health care costs. Many diseases, including ichthyosis vulgaris and multiple orphan diseases such as Netherton syndrome, are the result of deficient or missing proteins in the skin. The microbiome (and specifically Staphylococcus epidermidis) can be engineered to deliver the proteins that can resolve the underlying disease cause, and also address the challenges of dysbiosis that frequently develops in these situations.

The benefits of this approach include slow, stable, consistent and effective release of protein, at the level of the target cell in the skin. Azitra has pioneered this work and established many of the foundation patents in the space. Azitra’s work is rapidly progressing to clinical testing and product introduction.

Key products:

Filaggrin to restore the skin barrier

LEKTI to restore missing protease inhibitor and treat Netherton syndrome

IL-10 to suppress inflammation

Bioactive compounds derived from skin commensals

Azitra has a discovery-stage platform focused on the identification and development of bioactive compounds that can be derived from commensal bacterial strains. These compounds can be used for treating disease and addressing skin appearance. Funded by the Department of Defense, Azitra is working with the skin microbiome team at the Jackson Laboratory in Farmington, CT to explore the products derived from S. epidermidis (SE) that can offer potential in skin disease. It has been well established that SE produces multiple unique biological products with potentially important therapeutic benefits. Azitra is pleased to be a critical element of the team exploring the promise of such products.

Target programs:

New antibiotic candidates targeting S. aureus

Compounds to inhibit biofilm of invasive organisms

Novel therapeutic candidates for atopic dermatitis and other skin diseases

Development of advanced biosensors

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