Irritable bowel syndrome (IBS) is a chronic and sometimes disabling bowel disorder which affects around 10-15% of the population, around half of whom receive drug-based therapies. The condition is characterised by abdominal pain, bloating and changes in bowel frequency. The causes of IBS are multi-faceted; however, it is becoming increasingly clear that the gut microbiota plays a key role in driving the disease. In particular, microbiome instability and reduced diversity are thought to contribute towards IBS symptoms and their fluctuation over time.
IBS sufferers are classified on the basis of their predominant bowel symptom into either IBS-C (constipation), IBS-D (diarrhoea), or IBS-M (mixed symptom), each of which roughly correspond to about one third of the overall IBS population.
Existing treatments for IBS focus on symptom management, and there are currently no available therapeutics which tackle the underlying causes of IBS. Due to the lack of effective therapeutics, clinicians resort to treating the most bothersome symptom at the point of presentation, which often involves prescribing anti-diarrhoeals or laxatives to address abnormal bowel motility. This in itself is problematic, since IBS patients frequently undergo reciprocal transitions between -C and -D over time, and thus targeting a specific symptom fails to address this.
New therapies are needed to address the significant unmet need in IBS, and the microbiome represents a very attractive target to deliver these medicines.
Blautix is a single-strain live biotherapeutic candidate in development for the treatment of IBS-C and IBS-D. The organism was originally isolated from a healthy individual and has a distinctive metabolism which utilises intestinal hydrogen as an energy source, reduces levels of hydrogen sulphide, produces acetate, and increases microbiota diversity and stability. Unlike existing therapies which only seek to address IBS symptoms, by targeting the microbiome Blautix has the potential to act directly on the underlying pathophysiology of disease to treat all IBS patients irrespective of traditional sub-types.
In 2016 we completed a Phase Ib study of Blautix, our live biotherapeutic candidate for irritable bowel syndrome. The trial was a placebo-controlled study and enrolled 24 IBS patients and 24 healthy volunteers.
The study met its primary objective of demonstrating that Blautix was safe and well tolerated. We were also able to obtain preliminary insights into the clinical effectiveness and mechanism of the drug. Encouragingly, 82% of Blautix-treated patients showed improvements in their IBS symptoms compared with 50% of patients receiving placebo. We also noted a greater proportion of the Blautix treatment group exhibiting a reduction in hydrogen breath levels – a biomarker of the drug’s activity.
Although based on a relatively small sample size, these observations are in line with preclinical data and strengthen the evidence of the proposed mechanism of action for Blautix in the treatment of IBS. Moreover, these encouraging early clinical results provide a solid basis for progressing Blautix into larger studies and further evaluation as a potential treatment for IBS.
Utilising our proprietary MicroDx platform, we have generated a robust clinical dataset on the microbiome profile of patients with IBS to identify those suitable for treatment with Blautix. In an observational study of 145 subjects (80 IBS patients and 65 healthy individuals) we compared the microbiome and urine metabolomic profiles of IBS patients and healthy individuals.
It was shown that the microbiome of IBS patients is significantly different from that of healthy individuals, with significantly lower diversity. Interestingly, there were no significant differences in the microbiota of IBS clinical sub-types (C, D and M), and all three groups have significantly reduced diversity compared with healthy subjects. These data support the use of Blautix in all of the three traditional IBS sub-groups.