Clinical OMICS

JUL-AUG 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 18 of 51 July/August 2019 Clinical OMICs 17 are being sought by Axial. To date, the company has found about a dozen similar metabolites of interest. The goal is to develop a method that will reduce these metabolites from getting into systemic circulation. A "molec- ular sponge," noted David Donabedian, Ph.D., a co-founder and the CEO of Axial, is one of the methods the company plans to test. "Think of something that expands when you swallow it," suggests Donabedian, "and will absorb these metabolites as it passes through the gastrointestinal tract." The sponge would have a strong affinity to the metabolites of interest to Axial. The other method will use Bacteroides fragilis to help repair the leaky gut and reduce the passage of metabolites into the circulation. Skin in the game Naturally covered with commensal bacteria—most of which is harmless and some of which is helpful—the skin is an obvious place to start developing health products based on the microbiome. Although the skin is the larg- est organ of the body and readily inspected, much about it remains unknown. For example, it continues to challenge medical dermatology. To find new treatments for skin disorders, Travis Whitfill co-founded Azitra, a microbiome-oriented startup company that he now serves as CSO. Whitfill saw opportunity in the skin microbiome when many others were starting to crowd the gut microbiome space. In addition to representing a less crowded field, skin microbiome technology is, Whitfill said, less bur- densome from a regulatory perspective. Topical approaches pose fewer concerns than oral approaches. "Together," notes Whitfill, "these qualities were really appealing." Azitra is building a strategy based on the commensal Staphylococcus epidermidis to treat skin infections. An abun- dant member of the skin microbiome, S. epidermidis plays an important role in beneficial processes such as tissue repair and immunity. One of Azitra's strategies is to reintroduce the bacteria that may become limited during an infection. Another is to use the S. epidermidis to deliver biotherapeutic proteins to the skin. One of the products in the company's pipeline, AZT-02, was developed in collaboration with the Jackson Labo- ratory. AZT-02 uses S. epidermidis to deliver a therapeutic protein to the skin. This protein is LEKTI (lympho-epithelial Kazal-type related inhibitor), a protease inhibitor involved in regulating the rate of skin loss. Applied topically, AZT-02 provides continuous delivery of functional LEKTI. AZT-02 is designed for people with Netherton syndrome (NS), a serious genetic disorder for which there are few treat- ment options. Affecting 1 in 200,000 children, NS is caused by mutations in the SPINK5 gene, which is responsible for making the LEKTI protein. In NS patients, skin is sensitive, open, red, scaly, and subject to excess shedding. Similarly, S. epidermidis is being engineered by Azitra to deliver other beneficial proteins to the skin. For example, fil- aggrin delivery could help treat eczema and ichthyosis vul- garis, and interleukin-10 delivery could help treat psoriasis. Another one of Azitra's products, AZT-04, is a nonpro- tein-expressing strain of S. epidermidis. It is designed to treat rough, dry skin. The strain is an auxotroph, meaning that it requires a supplement added to the product to grow. In this case, the necessary addition is the amino acid D-alanine, which the bacteria can grow off of for only two days. When the D-alanine is used up, the bacteria die and the product must be re-applied. Such a product, Whitfill added, would be of great interest to certain patient populations, for example, cancer patients who take EGFR inhibitors and who sometimes develop a severe, often treatment-limiting rash. Azitra recently began a clinical study with AZT-04, which the company hopes to develop as a potential treatment. In just a few years, the work going on at these young microbiome companies has changed how we think about the microbiome, its role in health and disease, and how it might be altered to become the basis of new treatments. Whether it's skin rashes, gut infections, or ASD, the work going on at Avitra, Finch, and Axial (and many other micro- biome companies) is far from skin deep. Leveraging the skin microbiome to fill some of dermatology's unmet clinical needs is Azitra's goal. The company's products, which are based on the commensal bacterium Staphylococcus epidermidis, can provide the skin with either an unmodified version of the bacterium or an "enhanced" version that can deliver beneficial proteins to the skin. Azitra hopes to provide treatments for skin disorders such as psoriasis, atopic dermatitis, and Netherton syndrome.

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