The huge potential of microbiome therapeutics - David Berry, Flagship Pioneering

At Biotech Week Boston, Xconomy Special Projects Editor Corie Lok sat down with David Berry, General Partner at Flagship Pioneering, for BWB TV. Here we pick out the key takeaways around the possibilities that microbiome therapeutics offer and where he sees the industry moving in the next ten years.

David Berry first took an interest in the human microbiome about a decade ago when it was ‘a really interesting area of untouched science’. As a General Partner at Flagship Pioneering - a venture capital firm specializing in ‘first-in-category life sciences companies’ – he explains what first excited him:

‘What we realised very early is that the microbiome is in fact an organ that hadn't previously been appreciated because it is not characterised as an organ in the traditional sense - ie how tightly it's held together.’

Jump forward ten years and Berry is now just as excited by the possibilities of the microbiome: ‘Now we appreciate it, we're able to understand it and develop drugs, and frankly it's giving us a complete new insight into disease.’

What's so exciting about the human microbiome?

‘It has the nice benefit of being the first organ we've discovered since about the 1860s.

It plays central roles in a number of diseases that have proven difficult to treat by more traditional approaches and more traditional targets. For example, clostridium difficile infection, or antibiotic associated diarrhoea more broadly, or ulcerative colitis; these have been areas where we've had challenges coming up with treatments that are durable, highly safe and remain consistently efficacious. I think part of that is we've been looking at only a subset of the biology.

As you get into the microbiome you realise there is this whole other piece of the biology that we just hadn't been aware of. If we can understand where this is really central, then that can be incredibly powerful.’

How can increased understanding of the microbiome organ be leveraged to create new therapeutics?

‘The interesting thing is, [the microbiome] is not just an organ, it's part of an organ system. Understanding the other part of that organ system - the immune system - allows us to figure out how they work together. The microbiome in this case offers a privileged way to engage with the immune system, by which I mean they have evolved together, the microbiome was shaped by the immune system. As a result, when you figure out the cues and the triggers that work in that context, you have an incredibly powerful tool to effectively naturally change the immune system. This can unleash a degree of immune control that has been difficult.

That's lending itself to bigger and bigger biologies that we're at the cutting edge of understanding - things like cancer, auto-immune disease, and food allergies. We're starting to get insights into how it might have connection with even psychiatric disorders and other neurological conditions.’

Where do you see microbiome therapeutics in 5-10 years?

‘We're only now understanding what the various modalities are.

There's opportunities in using elements that can shape the microbiome. There's an emerging field looking at the effectors that key members of the microbiome use to drive health or lack thereof and understanding those receptors.

We're going to see almost organ-unique types of therapeutics, like bacteria based therapeutics. We're going to see things that feel a bit more traditional like chemistries that can affect, or mimic, or take advantage, or block how the microbiome affects the host. We're also starting to see people using the microbiome almost as a delivery technique. These core biologies are central to all of it.’

What are the biggest challenges in developing these therapeutics?

‘The fundamental challenge is creating a new category of therapeutics. One has to figure out what the right ways are for developing this therapeutic, and what are all the standard rules to keep patient safety first and foremost to develop a proper ethical therapeutic...The FDA has been very keen to work with companies and figure this out in collaboration.

Despite facing challenges with its phase II trial, Seres has been given the green light by the FDA for a larger study because of the promise that has been seen and the understandings that the company's been able to get, around what the mechanisms are and what it means to treat a patient with a microbiome therapeutic.’