Human microbiome therapeutics is a hugely exciting new field of research with almost limitless potential. So far the growing industry's focus has largely been on the gut, but there are numerous opportunities in other areas too. In this new series we go Beyond the Gut, exploring the exploring the therapeutic potential of the skin and oral microbiomes, gut/brain axis, gut/liver axis and around cardiovascular diseases. We start here with the skin. Download the full Microbiome Therapeutics: Beyond the Gut series as a whitepaper here.
The Skin Microbiome
Many microorganisms, including bacteria, fungi and viruses inhabit the human skin. These define the skin microbiome and have an influence on cutaneous diseases, including acne, atopic dermatitis, and psoriasis. The four dominant phyla of bacteria existing on the skin are the Actinobacteria, Proteobacteria, Firmicutes and Bacteroidetes, with the rarer types of bacteria accounting for variability between individuals.
Where are we now?
The global skincare market includes many products, ranging from cosmetics to over-thecounter (OTC) drugs to prescription drugs. It is a market that is growing rapidly. GMR Data estimates that the dermatology market (OTC and prescriptions) reached USD 50.1 billion in 2018, and could reach up to USD 93.7 billion in 2028. Meanwhile, the cosmetic care segment was estimated at USD 148.8 billion in 2016. The largest regional market by far is the US with a market size of USD 14.1 billion.
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As our understanding increases, we are discovering opportunities to leverage the skin microbiome as a diagnostic, prognostic and/or therapeutic tool. As for skin care, the market is currently focused on prebiotics and probiotics. Nonetheless, consumer resistance to fundamental concepts (can bacteria be good?) has hindered growth. As such, some brands focus on the scientific concerns their products address whereas others focus more on holistic health.
Research areas and companies
There are many companies engaged in research and development on the skin microbiome. Some of them are developing platforms (like Azitra), some are developing therapeutics (like AOBiome) and some focus more on the cosmetic side of the market (like S-Biomedic).
Azitra leverage their expertise on the skin microbiome to discover and develop novel products for the treatment of adverse skin conditions and diseases. They have developed a technology platform which offers multiple product opportunities in consumer health products, pharmaceuticals and novel bioactive compounds. Their lead programs are focused on eczema (atopic dermatitis) and ichthyosis vulgaris, inflammatory skin conditions, dry or irritated skin and orphan skin diseases including Netherton syndrome.
AOBiome Therapeutics is a US-based company focusing on research and development around a single strain of class-defining, auto-regulating Ammonia Oxidizing Bacteria (AOB) which they believe has the potential to restore critical biological and biochemical processes. They have six ongoing clinical programs in acne, one of which has completed Phase 2 and the company expects to begin enrolling patients in two Phase 3 studies in the first half of 2019. The other five programs are all in Phase 2 development.
S-Biomedic is a German company active in the field of skin cosmetics. They use a targeted modulation-based technology to modify the skin microbiome which can be applied in both the dermatology and cosmetic industries. As such, they select and combine beneficial bacteria to generate products that accelerate the rebalancing of a diseased microbiome, restoring a healthy skin. Their first target is acne vulgaris.
Potential growth and discovery
The global acne drugs market size was valued at USD 4.1 billion in 2017 and was anticipated to grow at a compound annual growth rate (CAGR) of 4.2% in 2018. As such, research on Isotretinoin, a form of vitamin A, is being done in the hope of developing microbiome-based acne treatments. Research at the Washington University School of Medicine in St. Louis has showed that Isotretinoin shifts the skin microbiome of acne patients to resemble that of people with normal skin. Research on variations of Isotretinoin is particularly important since isotretinoin causes severe birth defects. The role of microbiota in skin aging, such as wrinkling and sagging is not completely understood, and offers a lot of potential. Also, research has shown a strong interdependent relationship between skin microbiota and host immune functions. Imbalance of the skin microbiome can influence keratinocyte regulation and homeostasis as well as the skin barrier function. This indicates potential in developing innovative cosmetics and transdermal drugs for wellbeing and beauty.
A recent paper published raised the possibility of surface microbes interacting with the deeper microbial components, which hypothesizes we could design cosmetics applied topically without needing penetration, and that have deeper effects in the dermal tissue and immune functions. Another future opportunity is designing cosmetics that stimulate a regeneration process within the epidermal layer. Several applications can be imagined here, including wound healing and innovative cosmetics that can influence the slowing of cellular aging.
Funding, investments and partnerships
A few companies in this space have secured significant funding. In May 2018, Azitra secured USD2.15 million in convertible debt financing to support its skin care products. The financing was led by new investor Connecticut Innovations and existing investor Bios Partners. An additional new investor, KdT Ventures, joined the syndicate. This financing brings the total raised by the company to USD5.4 million.
Another company, AOBiome, partnered with iCarbonX in 2017 and secured USD 30 million to advance its clinical research on topical inflammatory disorders. The funding comes from iCarbonX, a health data collection and analysis platform. Finally, Naked Biome entered into a partnership (and received an investment) from LEO Pharma in April 2018. The investment was for USD 500,000 and was a way for Leo Pharma, a renowned player in the skin care space, to tap into Naked Biome’s expertise in the skin microbiome.
Research in this space continues to build excitement in the community. Many of the opportunities being explored by both the academic and private communities in diagnostic, therapeutic or basic healthcare, could considerably change many of the things we take for granted today, notably our nutritional habits.
There are several microbiome pursuits currently in clinical development and advancements for future discoveries will continue to grow. Nonetheless, many of these innovations face challenges ahead. Regulatory agencies are occasionally sceptical of the claims being made by various companies in the microbiome space. As such, rigorous testing and clinical studies are a must for these treatments to make it through. Yet, reproducibility is a key concern, as our body reacts very differently to some of these products. Planning large scale studies around probiotics and prebiotics remains a very real hurdle, which shouldn’t be underestimated going forward.
By partnering with solid, reputable and ethical companies, smaller start-ups and universities can help to lead these innovations from lab to market.