The human body is home to a diverse community of symbiotic, commensal and pathogenic microorganisms, collectively known as the microbiota. This microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, interest in developing therapeutics targeting the microbiota has surged in recent years.
EnteroBiotix, a privately held Scottish biotechnology company, is a pioneer in this rapidly emerging field. They are developing orally-delivered encapsulated microbial therapeutics for use in a medical treatment called Faecal Microbiota Transplantation (also known as FMT or a stool transplant). Recently, they raised £500,000 in an oversubscribed seed round of investment. This money will be utilised to equip and staff their GMP manufacturing facility and, advance their product through the initial phases of regulatory clearance.
To find out more about EnteroBiotix and the revolutionary therapeutics they're developing, we spoke to their CEO, James Mcllory.
JR: Could you please provide us with an overview of your company EnteroBiotix and, why you do what you do?
JM: We are an award-winning, patient-centered biotechnology company focused on using the body’s own microorganisms to prevent and treat debilitating infections and diseases. Our lead product candidate is an orally administered microbial therapy for use in a medical treatment called Faecal Microbiota Transplantation (FMT). FMT is a highly effective treatment for a nasty infection of the gut caused by a bacteria called C.difficile (C.diff), with cure rates of around 90% reported in the medical literature. However, at the present time, the treatment is challenging for doctors to deliver as they have to source and screen donors and deliver the FMT through invasive medical procedures. To put things simply, EnteroBiotix is solving these problems with its orally delivered microbial products.
We are advanced in our plans to set up an MHRA-licensed GMP-compliant manufacturing platform. We will use this platform to develop allogenic (from a donor) and autologous (using a person’s own bacteria) orally delivered therapies, using standardised, quality controlled and quantifiable processes. We are developing technology that maximises the viability of bacterial samples and allows for site specific delivery into the colon. We have been fortunate enough to win several awards since our inception, recently coming first place in the 2017 Oxford Biostars biotechnology competition.
As for why we do what we do. Well, we are laser focused on improving patient care and improving translational research into this exciting field of science and medicine. Each member of our team is passionate about making an impact in the healthcare sector and we are looking to launch additional products and therapeutic programmes in the near future.
JR: How do you turn gut bacteria into a viable treatment?
JM: Well it largely depends on the type of therapy you are trying to derive from the gut community. Different companies and research groups take different approaches. We are initially focused on treating with a healthy whole community to maximise the microbial engraftment in the recipient. To do so we take donations from a reliable, healthy and regularly screened donor pool. These donations are processed within a GMP facility using a series of steps that we have developed in house and are then quarantined for future use.
FMT delivers many strains of bacteria from the donor sample into the patient but interestingly, only certain strains seem to stay in the recipient and the presence of these strains is associated with a clinical response. Indeed, some donors seem to be better suited for some patients than others. This means that it may be possible to use the results of successful FMT’s to inform the design of cultured cocktails of bacteria. This approach would be more scalable than traditional FMT as there would be no need for a constant donor supply. An advantage of developing medicinal products using human sourced bacteria is that they likely have a more favourable safety profile than bacteria that have been sourced from elsewhere.
JR: On a technical level, what will the recent £500,000 seed finance EnteroBiotix received enable?
JM: This seed funding will allow us to equip and staff our GMP manufacturing facility, as well as progress through the first phases of regulatory clearance with the MHRA. There are currently five full-time employees working at EnteroBiotix and we are seeking to expand the team to a total of nine by the end of the year. We also have an active R&D pipeline that is focussed on developing a closed process (where the faecal microbiota doesn’t come into contact with the external environment) that will allow us to work in anaerobic (oxygen free) environments.
JR: Interest in the microbiome is exploding right now. What do you see as the next key steps in bringing this science from the bench to the clinic?
JM: It is now clear that several infections and diseases are intimately linked to changes in the composition of the gut microbiota. In adult patients, FMT appears to hold the most promise, with several randomised controlled trials reporting efficacy in C.diff infection and Inflammatory Bowel Disease. The next phase with FMT will involve standardising the therapy and stratifying donors and patients. Future microbiome modulating therapeutics range from small molecules derived from the gut microbiome to consortia of bacteria. Whilst some companies have raised large sums of money to pursue these strategies, none have been proven in man. There have also been some spectacular failures. These hard lessons show that the workings of the microbiome are still very much a mystery. For the field of microbiome modulating therapeutics to truly take off as an area of medicine we will really have to understand the co-dependent and synergistic relationships between the bacteria and the host (our gut) The primary focus of the field has been on distilling the thousands of species we can identify down to single strains or highly effective handfuls of bacterial species, but time and again data comes out which reveals the importance of the community as a whole.
Our approach is to start with something that works and then work backwards. Using this approach, we will be able to take a more rational and designed approach to developing medicinal products derived from gut bacteria in a much more analogous way to how we have produced medicines in recent history with pharmaceuticals.