Development and commercialization of microbiome-based therapeutics was the focus of a recent event in Boston (USA): the Microbiome Drug Development Summit 2018, organized by Hanson Wade. The Microbiome Insights team was in attendance – and here we share some of the highlights from this exciting event:
Jennifer Wortman, Senior Director, Bioinformatics, Seres Therapeutics
Unraveling Microbiome Signatures for Drug Design
Seres Therapeutics, one of the top 5 microbiome biotechnology companies in the world by funding, has a robust microbiome development pipeline. Their approach for addressing disease is to supply bacterial species that are associated with health in an attempt to change disease course.
Wortman explained the company has an extensive strain library isolated from healthy donors. They design consortia for their treatments using in silico design models (e.g. species and functions to reduce inflammation and increase epithelial barrier integrity) and by looking at species that are naturally co-occurring.
One product, SER-287, is an orally delivered community of purified Firmicutes spores associated with gastrointestinal health; it has efficacy in mild to moderate ulcerative colitis and is currently in phase 2B clinical trials. No serious drug-related adverse effects were noted in the trials. Research on SER-287 looks at engraftment: which species were absent at baseline but present after treatment? In all groups, they have seen engraftment of the spore-forming species following treatment: 19 species were more prevalent in patients achieving clinical remission; 13 species were more prevalent in patients not achieving remission.
Julia Cope, Director Scientific Operations, Diversigen
Microbiome Tools and Trends for the Pharmaceutical Industry
Cope spoke about the process for developing drugs to address various microbiome-linked diseases, including obesity, IBD, and cancer. To treat a disease, you need to know what to target. She cautioned that not all targets are likely to be bacterial in origin; researchers should also pay attention to viruses or fungal members of the microbiota.
Cope gave an example of four different studies that revealed four different microbiome-disease associations: taxonomy was similar but the specific biomarkers were different. She advised integrating as many cohorts as possible in order to prevent confounds.
Cathryn Nagler, President ClostraBio & Professor, University of Chicago
The Gut Microbiome, Immunity, and Allergic Disease
Nagler’s central question was whether we’ll be able to develop new microbiota-based strategies to regulate or prevent food allergies. She explained that certain populations of bacteria (classified as clostridia) make barrier-protective cytokines; they also stimulate the production of mucus, antibacterial peptides, etc.
Nagler’s data showed that lactobacilli were depleted in infants allergic to cow’s milk, with an increase in microbes that typically characterize an adult microbiome. Treatment with LGG increased tolerance of cow’s milk in these infants, and increased fecal butyrate. ClostraBio is engineering synthetic drugs to mimic the protective function of the health-associated bacteria.
Mark Smith, CEO Finch Therapeutics Group
Leveraging Reverse Translation to Develop Microbial Therapies
Smith described how broad-spectrum microbial interventions (i.e. fecal microbiota transplantation, or FMT) have good safety profiles in different therapeutic areas. Finch is using data from FMT trials to identify the bacteria linked with positive clinical outcomes, and then making these into bacterial cocktails for the treatment of disease. Smith described their product FIN-524 (developed with Takeda)--noting the challenges in understanding which organisms are driving the response.
An afternoon panel discussion, called Clinical Development of Microbiome-Based Therapeutics, covered a range of questions: clinical trial design in the development of microbiome-based therapeutics; key learnings from existing clinical programs for these therapeutics; and the relative importance of clinical efficacy and mechanism of action.
The panel discussed ‘hype’ in the media: some outlets inflate the importance of the scientific results, but companies need to temper the enthusiasm and stay focused on robust science. As for health professionals, they may be aware of this area but they are uncomfortable talking to patients about it until new products are approved and released into the market.
Regulation was another topic of interest: in particular, the need for flexibility in regulating new microbiome-related drugs. Panelists noted that there’s very little guidance in both the US and Europe, and it might make sense to develop guidelines or have guidance to expedite the development of some of these products. The Parallel Scientific Review is one mechanism that could help.
Evgueni Doukhanine, R&D Scientist, Microbiome, DNA Genotek
Establishing Techniques for Reproducible and Insightful Microbiome Studies
Doukhanine discussed the necessary steps to design microbiome studies for scalability and innovative analysis. Many people pay attention to the sequencing technology—but the bioinformatics pipeline is also a very important factor. For 16S, they have seen that depending on the bioinformatic pipeline, the relative abundance recovery is quite different. DNA Genotek has moved from collection kits into study design consultation.
Phil Strandwitz, Co-founder & CEO, Holobiome
GABA-Modulating Bacteria of the Human Gut Microbiota
Strandwitz gave an overview of the microbiota-gut-brain axis and described the identification of a bacterium from the human microbiota that’s completely dependent on GABA for growth; Holobiome is using it to identify and culture a panel of diverse GABA-producing bacteria with the hopes that they can modulate levels of this important neurotransmitter.