Making Microbiome Therapeutics a Reality

Making Microbiome Therapeutics a Reality

What's in store for microbiome research?

March16th,2020
Microbiome Connect

We are only just starting to understand the full complexity of the microbiome and how it interacts with its human host, but this has not stopped biotechnology start-ups and the pharmaceutical industry developing drug-development pipelines targeting it. A number of companies are set to release phase III clinical trial data this year and market approval for the first drugs is drawing near, so it is an exciting time for the field.  We talked to the research leads for a couple of leading biotechnology companies to find out what they see as the future for this challenging area of research and how they are handling the unique problems that this most complex of targets presents.



Christopher Missling (left) is president and CEO of Anavez, a company that utilizes precision genetic medicine to treat severe and devastating neurological disorders. Bret Wallace (right) is director of research at Symberix, a company that aims to improve human health by pioneering the development of symbiotic drugs that work by controlling bacteria without killing them.




What do you see as the key issue(s) when translating preclinical models to the clinic setting in microbiome R&D?

Christopher Missling: This subject is not limited to microbiome R&D: In general, preclinical models demonstrate high variability when translated to clinical settings.

Bret Wallace: The biggest issues with preclinical models, which is becoming more and more evident, is the immense variability in the gut microbiome. There is significant emerging evidence that the gut microbiota is dramatically different from specie to specie. Indeed, there is evidence even in mice/rats, that the same species could have variability… even cage-mates can have different microbiomes! So, translating from standard rodent models eventually to humans could have obstacles simply based on gut microbiome. 

How does your company aim to address that issue?

Christopher Missling: By performing smaller proof-of-concept clinical studies with a focus on ‘big data’ with artificial intelligence (AI) and by utilizing whole genome exome sequencing (WGS and WES) analysis.

Bret Wallace: At Symberix, we’ve been developing a platform assay that can assess functionality of the gut microbiota by sampling tissue and intestinal content to quickly determine if a particular animal or patient could be responsive to our therapeutics. Additionally, we can generate “humanized” rodent models to more accurately reflect the human gut microbiota.

Which indications are you looking to treat? Which modality(s) are you using and what’s unique about your approach?

Christopher Missling: We are looking at neurodegenerative indications, including Parkinson’s disease and Alzheimer’s disease, and also neurodevelopmental indications like Rett syndrome. As stated before: the hallmark of our approach is performing smaller proof-of-concept clinical studies with a focus on ‘big data’ with artificial intelligence (AI) allowing us to utilize whole genome analysis.

Bret Wallace: Our main research focus is on drug toxicities caused by reactivation of toxic drugs by gut microbial enzymes. The axis of metabolism between liver and gut is quite significant, and while gut microbial metabolism is very common, it can regularly result in GI drug toxicities. Our main indication is in the chemotherapy space, with our lead program focusing on irinotecan-induced diarrhea and epithelial damage, which often results in drug stoppage and/or modifications.  

Kisaco Research  

Where are you up to in your drug development pipeline? What’s the major 2020 target you’re looking to hit?

Christopher Missling: We expect to read-out several different clinical studies in 2020: Two Rett syndrome clinical studies and one Parkinson’s disease dementia clinical study.

Bret Wallace: Our lead program is quite well developed, and this year we anticipate completing the standard ADMET studies, and are targeting Phase 1 clinical trials by end of year.

What’s the current major roadblock obstructing your R&D progress? Do you envisage resolving this in-house or will you be recruiting partners to solve this issue?

Christopher Missling: I don’t think there is a major roadblock. It just takes time to execute the clinical studies.

Bret Wallace:  Funding is probably the most common roadblock. Our technology is sound, but we currently are solely funded by non-dilutive funding, namely NIH-funded SBIRs. Eventually, we will seek external investors once we near clinical trials as those tend to be quite expensive!

I understand you’ll be speaking at Microbiome Connect: Human in Boston, June 3-4. Can you give us a quick overview of what you’ll be talking about?

Christopher Missling: Linking gut-microbiota biomarkers with improved clinical response in Alzheimer’s patients treated with ANAVEX2-73:

  • What are the correlations between the gut microbiota and the response of the drug in Alzheimer’s patients?
  • What is the hypothesised mechanism of action of the drug?
  • Linking high levels of two specific microbial families to improved ANAVEX2-73 response in Alzheimer’s patients.

Bret Wallace:   I’ll be discussing a new technology for Symberix, a diagnostic assay that can quickly assess a human patient’s responsiveness to our parallel therapeutic programs. In the emerging drug development paradigm of microbiome-targeted drugs, novel tools are necessary to determine effectiveness of therapies against gut function. The robust functional assay we’ve developed can overcome the inherent microbial variability and easily determine if our drugs will be effective on a patient by patient basis.