Skin diseases are among the most common health problems worldwide. There are more than 3,000 known diseases of the skin and the most severe can limit life chances, cause disability and impairment, and death.
Also skin diseases impose a heavy burden on society, with financial, social and psychological consequences for patients and their families. The Global Burden of Disease project has shown that skin diseases continue to be the fourth leading cause of non-fatal disease burden worldwide.
Chronic and incurable skin diseases, such as psoriasis and eczema, are associated with significant morbidity in the form of physical discomfort and impairment of patients’ quality of life, while malignant diseases, such as malignant melanoma, carry substantial mortality. Despite this, skin disease historically has not attracted the investment in care or research that it undoubtedly requires.
Thankfully, awareness of the importance of access to care for skin disease is improving. In no small part, this is thanks to technological advances in research that were not available only a few years ago. This has deepened our understanding of the genetic make-up of skin disease and is leading to the creation of innovative new treatments.
This is where Azitra comes in. Azitra is a clinical-stage company that is developing novel therapeutics to treat adverse skin conditions by harnessing the human microbiome. Azitra has a discovery-stage platform focused on the identification and development of microbiome-based therapeutics and bioactive compounds that can be derived from commensal bacterial strains. These strains and their bioactive compounds can be used for treating disease and addressing skin appearance.
The human skin serves as a barrier to the outside world and is also rich in micro-organisms, which are collectively known as the skin microbiome. They play a crucial role in maintaining good 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 provide protection against disease, and keep the skin looking smooth and moist.
Azitra is solving the challenges of skin disease by using “good” bacteria naturally found in the skin microbiome, such as the commensal Staphylococcus epidermidis (SE). An abundant member of the skin microbiome, SE plays an important role in beneficial processes, such as tissue repair and immunity.
There is a robust body of published, high-impact evidence around SE, with articles in journals including Nature, Science and Cell. With significant venture capital support and funding in America from the National Science Foundation, National Institutes of Health and US Department of Defense, Azitra is working with the skin microbiome team at the Jackson Laboratory in Farmington, Connecticut, to explore treatments from SE that can address skin disease.
One of Azitra’s strategies is to reintroduce the bacteria that help keep the skin healthy and whose population may become limited during an infection. Another is to use SE to deliver biotherapeutic proteins to the skin. Direct application of commensal bacteria can treat dysbiosis, a microbial imbalance, or microbes associated with disease, as well as skin inflammation, tissue damage or a weakened skin barrier.
As we move into more clinical trials, we hope we can offer relief to patients suffering from debilitating skin diseases
These properties are being harnessed by Azitra to create novel therapeutics for skin diseases. This is the case with cancer therapy-associated rashes, which are skin diseases linked to chemotherapy and associated with dysbiosis, and with elevation of the Staphylococcus aureus population that lives on the skin.
Azitra’s product portfolio addresses the cause of skin disease and the consequences of dysbiosis. AZT-02 is designed for people with Netherton syndrome (NS), a serious genetic disorder for which there are few treatment options. Affecting one in 200,000 children, NS skin is sensitive, open, red, scaly and subject to excess shedding. Some 10 per cent of infants with NS die in their first year.
NS is caused by mutations in the SPINK5 gene, which makes LETKI protein. Applied topically, AZT-02 provides continuous delivery of functional LETKI, a protease inhibitor involved in regulating the rate of skin loss.
Julia Oh, assistant professor at the Jackson Laboratory, says: “There is increasing evidence the microbiome plays a vital role in many diseases and the potential of rationally designing microbes to express proteins that can treat a skin disorder such as NS is very exciting.”
Similarly, SE is being engineered by Azitra to deliver other beneficial proteins to the skin. For example, the delivery of filaggrin, which is key to skin structure and moisture, could help treat eczema and ichthyosis vulgaris, and interleukin-10 could help treat psoriasis.
Another of Azitra’s products, AZT-04, is a non-protein-expressing strain of SE, designed to treat skin with severe rash driven by excess levels of Staphylococcus aureus on the skin. The strain 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 for two days only. When the D-alanine is used up, the bacteria die and the products must be reapplied.
Azitra brings together a strong leadership team. Richard Andrews, president and chief executive, has enjoyed a successful career translating research and academic discoveries into product development and advanced clinical programmes. His work has primarily focused on skin disease, pneumonia and kidney failure, and he has helped to raise more than $130 million in equity funding for new ventures.
Travis Whitfill, chief scientific officer and co-founder of Azitra, has a background in molecular biology and biochemistry. He has co-founded a number of biotech and healthcare companies. He is a partner at Bios Partners, a healthcare-focused venture capital fund, and senior analyst at Bios Research, which provides research to institutional investors.
Trudy Grossman, vice president of research, is a world-class microbiologist who has led the development of a number of important therapies for skin disease. Senior director of product development is Gilles Dubé, with more than 15 years’ experience supporting drug discovery and developments. Before joining Azitra, Dr Dubé served as head of pharmacology and non-clinical development at two biotech companies. Roger Léger is vice president of chemistry, formulation and development.
Mr Whitfill says: “We are developing commensal organisms to serve as a unique, living delivery system for the cost-efficient production and topical delivery of important therapeutic proteins. We have shown that our proprietary strain of SE can be engineered for the delivery of therapeutic proteins, and can efficiently colonise both healthy and diseased skin. As we move into more clinical trials, we hope we can offer relief to patients suffering from debilitating skin diseases.”
With a strong technology platform and leadership team with a proven track record, Azitra is making good progress towards delivering much-needed therapies to alleviate skin diseases that have previously been overlooked, to the benefit of patients all over the world.
For more information please visit www.azitrainc.com