How Microbiotica is getting closer to a blueprint of your body's bacteria
Dr Mike Romanos, co-founder and chief executive, outlines the revelatory new discoveries.
The microbiome is the undisputed life sciences star of the year so far.
“It’s like a whole new organ we’re discovering that controls every aspect of our biology,” says Dr Mike Romanos, CEO of Microbiotica.
He should know: earlier this month Microbiotica confirmed a £534million deal with Genentech, a member of the Roche group.
“We’ll be working with their new medicines pipeline in inflammatory bowel disease (IBD) to identify microbiome signatures of drug response, new targets and new drugs made up of live bacteria to correct gut microbiome imbalances,” says Dr Romanos of the collaboration. “The ‘live bacterial products’ are based on clinical response so have a good basis as a novel breakthrough therapy for this major disease.
“The funds comprise a significant upfront payment followed by milestone payments over the next few years.
“It’s a remarkable deal for an 18-month-old company.”
Indeed it is remarkable, even in the hectic world of life sciences. The vertical lift has been underpinned by Cambridge Innovation Capital which, with IP Group, co-led the initial £8million funding round when the firm was founded in December 2016 by CEO Dr Mike Romanos, CSO Dr Trevor Lawley and Professor Gordon Dougan.
In person, Dr Romanos pays generous tribute to his co-founders. A natural sciences degree from Cambridge and a PhD in molecular virology from Imperial College was followed by academic research and a first industry job in Wellcome Biotech. This led eventually to 10 years in international R&D leadership roles at GlaxoSmithKline, before he started Crescendo Biologics in 2009, where he was CEO and CSO for six years.
“I had worked with Gordon in bacterial vaccines at Wellcome Biotech,” he says. “He introduced me to Trevor in 2015, and said: ‘We may need some help with this’.
“In 2015 I left Crescendo and by the end of the year we had built a drug development and business strategy and secured the funding from Cambridge Innovation Capital and IP Group. Gordon had chosen a name, Mircobiotica, and I helped crystallise the concept and make it a reality.”
Many first-generation microbiome companies, often in the US, have been around for a while, but they are based around earlier technology which cannot overcome serious obstacles to designing new medicines.
The microbiome is all your single-celled organisms. These microbes are mainly in your gut, though we are discovering them now in other organs such as the lung and bladder. These microbes are crucial in programming and controlling the immune system, fighting off bacteria and viruses, controlling our metabolism and even controlling brain function. As our understanding of the link between the human microbiome and disease develops, it’s apparent these microbes have a significant effect on conditions including obesity, inflammatory bowel disease, diabetes, rheumatoid arthritis, cancer, autism, Parkinson’s and even depression. Microbiotica, based on the Wellcome Genome Campus, is uniquely able to improve the throughput and accuracy of characterising the bacteria in human microbial communities to properly understand these links.
“There are thousands of different gut bacteria in every person,” Dr Romanos explains, “and to design medicines or find markers of drug response you need to know which bacteria are present with great precision in many patients in order to make the biological correlation to health, disease or cure with certainty. This is the first key step to a medical application.”
For all the excitement in the field, this basic capability has been missing.
“The fundamental problem has been the inability to isolate and grow the majority of gut bacteria and then fully sequence their DNA. Doing this enables you to recognise the bacteria precisely when you see their DNA sequences in patients.
“The Sanger Institute supported Trevor long-term to address this problem, and in 2016 his group doubled the number of isolated gut bacteria with full genome sequences in one fell swoop. The number went from about 150 to 300.
“In fact since then it has become clear that many of the previous genomes available had errors. This kind of rigorous fundamental genome science is a hallmark of the Sanger Institute, which led the world in the Human Genome Project by doing 40 per cent of the total. This capability has been brought into Microbiotica and taken to a whole new industrial level. The precision in characterising the microbiomes in patients at scale is vastly increased as a result.”
Microbiome gene sequencing has been going for a decade but it’s only now that the scale of the task is being identified. What’s in your gut has a huge effect on your wellbeing and, with the average person hosting 2kg of microbiome, the potential is becoming manifest.
“With its industrial pipeline Microbiotica will eventually dwarf the number of isolated gut bacteria with matching genomes that we currently have or that the rest of the world has. There are currently about 300 in the public domain, Microbiotica has over 1,000, – growing to 5,000 in a few years.
“We can create the complete blueprint of all bacteria from one person, all isolated and banked. It’s never been done before, and Genentech were very impressed by that.”
It’s a massive step change.
“Until recently we didn’t realise how important the microbiome is. It’s involved in controlling every element of human biology. There’s no question that the microbiome represents a new paradigm in biology that must always be considered.”
Drug effectiveness depends on what’s going on in your gut, and the first disease to be tackled by the new science is IBD in the Genentech collaboration, though the company will also focus on other areas, including cancer, where drug efficacy has been linked to the microbiome.
“Genentech has a tremendous track record of making great drugs to address unmet needs,” continues Dr Romanos. “They have a whole pipeline of novel IBD drugs and want us to use our technology to identify microbiome signatures that will predict who will respond to their drug, who may have side effects, and who will not respond. We will get access to thousands of samples from their global clinical trials to do this work. When we identify responders with specific bacteria, we can develop those bacteria for delivery into the gut as therapies that can convert non-responders to responders. The only downside is that we will have thousands of faeces samples coming to us to do the analysis!”
Indeed this is a procedure that the squeamish might not like the sound of – a faecal transplant. You take a stool from a healthy person and bung it up the rectum of the IBD sufferer.
“Microbiotica’s medicines will be purified freeze-dried bacteria delivered in an oral capsule. We’ll make them for the clinical trials and once we have the product and the know-how we’ll consider the possibility of taking them to market.”
So Microbiotica will market the drug itself. It seems incredible that what would be a major goal for one firm is just a sideshow in the context of Microbiotica’s mission.
“We will have developed the knowledge to manufacture, develop and also potentially to market such products.”
There’s a significant shift in public consciousness riding shotgun with all this. Microbiotica’s analysis of the microbiome – and advances in mechanistic experiments in model systems with human bacteria – has suddenly exposed the structure and function of the microbiome in both diseased and healthy states.
“What we have now is the best tools, and we’ve got an incredible team together in Microbiotica. The field is very excited about this deal.”
They’re not the only ones.