AOB, Inflammatory Conditions, and Systemic Effects

AOB, Inflammatory Conditions, and Systemic Effects

We have identified significant therapeutic opportunities caused by the adverse impact of the modern environment on human physiology. The human body relies on a system of multiple microorganisms, chemistries, and pathways which have evolved with humans for millennia, and that together are essential to human health. When these microorganisms are imbalanced, or dysbiotic, the human body can be more susceptible to disease. Due to the widespread use of surfactants, antimicrobials, antibiotics, and general “sterilization,” these vital microorganisms have been stripped out of the modern human body and the living environment. In parallel, the incidence rates of systemic and inflammatory diseases have risen over the course of modern history. However, populations that live closer to natural environments, without the use of chemicals and the focus on antimicrobials, have been shown to be healthier in many respects. For example, a recently published peer-reviewed article examined three populations of similar genetic background, an Amish cohort that lives both close to nature on farms in the rural United States and refrains from the use of modern technology such as modern hygiene products and technology, a Swiss population that lives close to nature on farms but otherwise utilizes modern hygiene products and technology, and a non-farm, Swiss cohort practicing a modern lifestyle. The authors observed that only 7.2% of children in the Amish group had been diagnosed with atopy, a predisposition toward developing certain allergic hypersensitivity reactions, as compared to 25.2% of children in the Swiss farm group and 44.2% of the non-farm Swiss children. We believe that restoration of the symbiotic relationship between bacteria and human beings will have a profound effect on human health.

AOB, whose sole source of energy is ammonia, play a critical role in the nitrogen cycle. In the presence of oxygen, AOB consume ammonia and produces nitric oxide, or NO, and nitrite (see Figure 1 below). NO is a key signaling molecule integral to the circulatory system, the central nervous system and systemic response in the human body and is involved across numberous biological systems. NO was proclaimed the “Molecule of the Year” by the journal Science and the 1998 Nobel Prize in Physiology or Medicine was awarded for discovering NO’s role as a cardiovascular signaling molecule and is a well-documented vasodilator with anti-inflammatory properties. AOB also modulates nitrite.

The metabolism of ammonia by AOB lowers local pH levels, and due to its unique metabolic activity, AOB has both first order and second order effects on the human body, including (i) rearrangement of the microbiome, including an observed local reduction in known pathogenic bacteria, (ii) reduction in local pH, and (iii) production of known anti-inflammatory and vasodilatory compounds. Although microbiomes are often difficult to characterize given the transient nature of bacteria, we have shown that the presence of AOB is correlated with a reduction in populations of bacteria that are commonly associated with disease including Staph.aureus and P.acnes, which are associated with eczema and acne, respectively. AOB’s anti-inflammatory and pH-lowering properties, and its ability to reduce levels of pathogenic bacteria, coupled with our earlier anecdotal feedback from the Cosmetic Product, led us to undertake our clinical trials described below.

The following figure shows the conversion by B244, our proprietary strain of AOB, of ammonia into nitrite and nitric oxide:

 The conversion by B244, our proprietary strain of AOB, of ammonia into nitrite and nitric oxide

We are using the same active ingredient, B244, a live single strain of Nitrosomonas eutropha, in different potencies and formulations tailored to each of our clinical trials, and we initially targeted inflammatory conditions that are not well served by current therapies either due to lack of efficacy or intolerable side effects. We currently have six programs conducting clinical trials: AOB101 for the treatment of acne; AOB102 for the treatment of atopic dermatitis, or eczema, and associated pruritus; AOB103 for the treatment of rosacea, AOB201 for allergic rhinitis; AOB202 for migraines and AOB203 for hypertension. In all of our clinical studies, we have observed a very favorable tolerability profile, with no signs of hypersensitivity reactions, inflammatory reactions, localized infections, bacteremia or sepsis or any serious adverse events.