About IBS

Irritable bowel syndrome (IBS) is a chronic and debilitating functional bowel disorder which affects around 10-15% of the population.

The condition is characterized by abdominal pain, bloating and changes in bowel habits. The causes of IBS are multi-faceted; however, it is becoming increasingly clear that the gut microbiota plays a key role in the condition. In particular, microbiome instability and reduced microbiome 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 (diarrhea), or IBS-M (mixed symptom), each of which account for roughly one third of the diagnosed 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 a lack of disease-modifying therapeutics, currently available approved treatment options are largely limited to targeting the predominant symptom at the point of presentation, which usually involves prescribing anti-diarrheals 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 and can in fact exacerbate the problem. There are no treatments specifically approved for patients with IBS-M, who fluctuate between predominant symptoms, and represent a significant unaddressed population.

New therapies are needed to address the significant unmet need in IBS, and the microbiome represents an attractive target to deliver safe and effective new treatments which address the underlying condition, not just the symptoms.

About Blautix®

Blautix is a single-strain Live Biotherapeutic candidate in development for the treatment of IBS-C and IBS-D.

Blautix has a distinctive metabolism which consumes intestinal hydrogen as an energy source, reduces levels of hydrogen sulfide, produces the short-chain fatty acid (SCFA) 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. Blautix has shown potential to treat all IBS patients, irrespective of traditional symptomatic sub-type.

A Phase Ib placebo-controlled study of Blautix enrolled 24 IBS patients and 24 healthy volunteers to asses safety, tolerability and preliminary signals of activity.

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. 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. Microbiome diversity is known to be deficient in IBS ; IBS patients receiving Blautix showed an increase in microbiome diversity, comparable to healthy controls.

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.

We conducted a Phase II randomized, double-blind, placebo-controlled, multi-centre trial of Blautix, in 353 patients with IBS-C or IBS-D. The study was conducted in US, UK and Ireland, and is the largest study of a Live Biotherapeutic to date.

Blautix demonstrated a safety profile comparable to placebo, with no treatment-related serious or severe adverse events.

The primary endpoint of the study was 'overall responder rate' in IBS-C and IBS-D cohorts compared to placebo. The 'overall responder' endpoint comprises concurrent improvements in both bowel habit and abdominal pain over the treatment period. Clinically meaningful positive trends were seen in overall responder rates relative to placebo in both IBS-C and IBS-D cohorts. Blautix is the first therapeutic to show activity in both major subtypes of IBS.

Furthermore, the demonstration of activity in both IBS-C and IBS-D indicates Blautix as a potential treatment options for patients with IBS-M (mixed), who frequently fluctuate between predominant symptoms and currently have no approved treatment options.

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.