Read an exclusive interview with Microbiotica CEO Mike Romanos published by Microbiome Movement
The interview covers the exciting developments in the microbiome space, Microbiotica’s progress over the past year, and a forward look at the Company’s aims in the next 12 months.
What do you think have been the most exciting developments within the microbiome space in the last year?
The microbiome represents a paradigm shift in biomedicine that affects how we think about health and disease and presents new modalities for therapeutic intervention. It is remarkable to consider our co-evolved microbiome as a major part of our physiology and representing our closest interaction with the external environment. The promise in biomedicine has been latent for more than 10 years, but in the last year successful translation has become very tangible. There are three areas I have been very excited about:
What is unique about Microbiotica’s approach and how are you using it to develop breakthrough medicines and biomarkers?
Microbiotica excels in rigorous identification of bacteria driving clinical outcomes as the starting point for therapeutics, biomarkers and novel targets. It is well known that animal models and in vitro screens have their limitations in drug discovery. We believe that in the microbiome particularly we should be mechanism-agnostic and see what the biology in patients is telling us. That way we can identify new mechanisms that have been pre-validated in patients and develop truly transformative therapies.
To do this is not simple. It requires (a) high-quality large patient data sets and samples, (b) the ability to identify and isolate the majority of the gut bacteria, and (c) bioinformatic tools including machine learning to associate groups of bacteria (“bacterial signatures”) to patient phenotype.
Microbiotica has leading tools in these areas that we believe allow an unprecedented level of precision in analysing gut bacteria that enable the identification of bacterial signatures missed by others. The science is based on over a decade of investment at the Wellcome Sanger Institute, led by Trevor Lawley (Microbiotica’s CSO), who addressed key barriers to translation, including the first design of defined bacterial therapeutics, mass isolation of gut bacteria, and comprehensive analysis of gut bacteria based on expanded reference genome collections.
These capabilities have attracted top quality collaborators, such as Genentech, Cancer Research UK, University of Cambridge and University of Adelaide, with clinical datasets and samples to feed the pipeline. We believe that armed with our platform and these clinical datasets we can make unique discoveries of bacterial signatures linked to biology that form the basis for highly differentiated defined live bacterial therapeutics and biomarkers.
What has Microbiotica achieved in the last year and how is Microbiotica applying these capabilities and what are the next goals for Microbiotica?
In the last year the company has made great strides. First we kept the operation running right through the pandemic while moving to our new facility in Chesterford Research Park, so we can now house all our scientists in the same building for the first time. Second we have significantly expanded and strengthened our executive team. Third and more importantly we have made great progress toward the clinic in our lead programs, both in Ulcerative
Colitis, in Immuno-Oncology and in our collaboration with Genentech. A key new strategic collaboration for us is with Cancer Research UK and Cambridge University Hospitals, which we signed in 2020 and which supports a major landmark clinical study in multiple cancers (MITRE). This gives us a great long-term position in Immuno-oncology.
How are your programs and products differentiated from others in the field?
We believe our programs are differentiated in that they use a precision medicine approach – they start with patient datasets and strong validation from the clinic, to which we add class-leading microbiome profiling. Out of this come products paired with highly predictive biomarkers to which we add mechanism.
It’s worth noting that we always identify multiple bacteria with differing mechanisms by this approach. As a result our products comprise consortia
of bacteria from each of the major three phyla all derived from clinical data. In the case of our Immuno-oncology program we have identified, we believe, the first universal signature of checkpoint inhibitor drug response in melanoma and lung cancer patients. The bacterial signature is so predictive that it has potential as a companion diagnostic and it gives us high confidence as we head to the clinic.
What progress have you made in your lead programs and what are your aims in the next 12 months?
In Ulcerative Colitis we started by analysing the excellent FMT study conducted by Sam Costello at the University of Adelaide. Applying our technology, we undertook a unique analysis of this study, isolating and banking all the bacterial species from the donors and identifying at the strain level bacteria engrafted in patients linked to remission. During 2020, we showed that our product (MB310) is efficacious in a mouse model of IBD and that the individual
bacteria had multiple therapeutic mechanisms demonstrated in cellular assays, including innate and adaptive immune-modulation and potent healing of damaged gut epithelium. We feel this has great promise to address the multiple pathologies of this disease and are very excited to take it into the clinic.
In Immuno-oncology we feel we have made remarkable progress using a similar clinic-first approach but this time based on melanoma patients receiving checkpoint inhibitor therapy. We based this on our completed MELRESIST study, identified a bacterial signature 91% predictive of drug response, then showed the signature was also predictive in an additional three data sets from around the world, and also in lung cancer. From this signature
we have identified nine bacteria that are most raised in abundance in responders and have shown them to be therapeutic preclinically, and having mechanisms profoundly stimulating cytotoxic T cell killing of tumours. The predictivity of the signatures gives us confidence for clinical efficacy of the product MB097, and also for the potential of a companion diagnostic for drug therapy.
We are very excited to take these programs to the clinic and have a laser-like focus on completing process development and manufacture ready for clinical trials in 2022.