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a therapeutic effect that would match what we’d expect from a pharmaceutical product to actually treat severe diseases? And that has to do both with the mechanism underlying the effect, and understanding it. [Then there’s] the ability to scale up and produce such products—which is a higher level of complexity and stringency than the standard probiotics that are made as part of the food industry.
X: And some of the other challenges unique to the field?
MB: We’re not going to be able to apply the old mentality where we take a very complex system, and reduce everything to one simple protein. A significant amount of the benefit [from these drugs] will be from [achieving] the appropriate equilibrium of multiple strains [of bacteria] in the microbiome. So the challenge is going to be, what tools can we apply to manage that equilibrium? We’re very eager to help and to participate ourselves in developing that insight, and at the same time we’re beginning to invest in some of these tools that we can apply to precisely modulate the equilibrium that one would want to achieve in a healthy microbiome. Of course the other challenge has to do with engaging with the regulatory agencies, and discussing the most effective path forward for this class of products. That is going to be a new path that is going to have to be defined, and the first generation of products are going to have to do that.
X: What would be different about it?
MB: Some [study goals] would be the same—signs and symptoms based on the disease, and also providing some local benefit to tissue protection, or repair of the tissue, that may have been destroyed during the disease process. But the discussion is likely to be more active on gauging the mechanism by which that effect is being accomplished. Right now you deliver the drug to the patient, you measure the pharmacokinetics of the drug, you measure some biomarker readout, and you align that with the clinical signs and symptoms assigned to that drug, which are agreed to by the clinical community and regulatory agencies. The mechanism itself is going to be more complex here. How do you deliver live microbes? How do you reset the microbiome in the right equilibrium? What do those biomarkers look like? And how do you quantify those, and correlate them to the clinical benefit itself? That’s why if you look at the potential in the field, and where the investments are, those are all areas of significant investment from an intellectual perspective by key laboratories, as well as from a financial perspective on where the technology needs to be developed and where the successful technology would have that significant benefit.
X: So that means you’ll be watching Seres as it moves forward.
MB: I think they’re going to have a lot of attention. They are right there at the front, and [C. diff infection] is an indication that allows very specific readouts, specific effects, so I think they are positioned to really educate the broader field about this approach.
X: Seres is starting with C. diff, a type of bacterial diarrhea, rather than an autoimmune disease like IBD. What’s the difference, from a development perspective?
MB: I think [Seres] chose well. The mechanism [underlying C. diff] is known—it is associated with one specific bacteria. So it may be a simpler project to tackle with a clear readout. IBD is a more complex disease, so the ability to match the mechanism with a clinical benefit in a quantifiable approach is going to be more complex, and will require more investment and more time. It’s going to take a more precise and deeper clinical experiment relying on biomarkers, and ensuring the readouts match the therapeutic approach being taken.