Phase I Clinical Trial Generates Data on Mechanism of Action, Safety and Tolerability
July 19, 2016 — 4D pharma plc (AIM: DDDD), a pharmaceutical company focusing on the development of live biotherapeutics, today provides the following update on the phase 1 clinical trial in respect of Blautix, its proprietary single strain live biotherapeutic for the treatment of Irritable Bowel Syndrome (IBS).
IBS is a functional bowel disorder characterised by discomfort, pain and changes in bowel habits, affecting 10-15% of the population.
Blautix is the first orally delivered live biotherapeutic to undergo a clinical trial. The trial was a first in man study and, as previously reported by the Company, over this period Blautix was found to be both safe and well tolerated, and achieved the primary objective of the trial.
The multiple dose phase of the trial involved twice daily dosing of 24 healthy volunteers and 24 IBS subjects with either Blautix (16/24) or placebo (8/24) over a 14 day period, with a further washout period of 19-23 days.
Throughout the trial symptoms were recorded and samples were taken. This additional data has now been analysed further, allowing 4D to investigate the pharmacological mechanism of action of Blautix and resultant changes to the microbiome, and to follow any changes in subject symptoms.
Whilst the trial was not designed to demonstrate efficacy, during the period of the trial subject symptoms were monitored. In common with other IBS studies, a strong placebo response was noted. However, following the dosing period, subjects treated with Blautix showed a greater response over placebo, with the majority reporting an overall improvement in IBS symptoms.
The pharmacological mechanism of action of Blautix is associated with a reduction in hydrogen levels in breath samples in pre-clinical models. During the study, breath samples from qualifying subjects treated with Blautix or placebo were analysed before dosing, after dosing and following the washout period. This analysis showed that a greater proportion of the Blautix treatment group (compared with placebo) exhibited a reduction in hydrogen breath levels following dosing. Although based on a relatively small sample size, this observation is in line with pre-clinical data and strengthens the evidence of the proposed mechanism of action for Blautix in the treatment of IBS.
Analysis of both volunteer and subject microbiomes was also performed prior to dosing, after dosing and following the washout period. This data has importantly shown that 4D is able to successfully deliver a single strain live biotherapeutic to the gut, as an increase in levels of the Blautix strain was observed in both volunteer and subject samples. Further analysis of the microbiome samples has also showed evidence that Blautix, which as with all our current programmes is a single strain, may induce changes in levels of other species in the microbiome. This ‘signature’ shows similarities to findings obtained in pre-clinical models.
Overall, the results of this trial are comparable to the pre-clinical results in humanised disease models, first reported on in January 2015. At that point our view was that the humanised disease models were expected to more faithfully reproduce the conditions in the gut of subjects, and therefore enable the effects of targeted therapeutics to be assessed more accurately. The results of this clinical study appear to confirm the translational power of the humanised disease models.
In conclusion, the findings of this first clinical trial are encouraging and provide a solid basis for progressing Blautix into larger clinical studies and further evaluation as a potential treatment for IBS.
Duncan Peyton, the Company’s Chief Executive Officer, commented: “This is a true first in the field of live biotherapeutics. 4D has been able to produce an orally delivered live biotherapeutic, and generate meaningful data surrounding mechanism of action, and safety and tolerability, with great efficiency. Whilst the primary rationale for the trial was safety and tolerability, and recognising that it is a phase 1 trial in a very limited number of subjects, the data trends towards the overall effectiveness of Blautix. This gives us confidence to progress to the next phase towards approval of a safe, effective treatment in IBS. These results also give us confidence in our platform, the direct relevance of humanised models and the overall approach we have adopted across our pipeline for diseases such as cancer, multiple sclerosis and asthma. What 4D has achieved to date is a direct result of incredible work of our people. I am excited by the prospects not only for Blautix, but also for our platform, our pipeline and the impact live biotherapeutics could have across the pharmaceutical industry.”
Further data will be presented in future publications and scientific meetings.