It was clear that microbiome companies have been advancing their programs as rapidly as ever, despite the changes brought about by the global pandemic. Service providers—including drug manufacturing organizations—have been busy during the past year, as they continue actively helping diagnostics and therapeutics companies find solutions to advance their products.
Many colleagues in the microbiome industry were able to gather in person once again for Global Engage’s 9thMicrobiome R&D and Business Collaboration Forum: Europe. The event had a wide-ranging program covering microbiome industry updates and was held in Rotterdam, the Netherlands, October 26-27, 2021. The presentations were a combination of live and virtual.
The six conference keynotes covered a range of topics: the gut ecosystem and how it is shaped by factors such as circadian rhythm, the effects of personalized diets generated using gut microbiome data, successful approaches for microbiome drug discovery and manufacturing, and how to modulate the skin microbiome to address conditions such as eczema and acne.
In one of the keynote lectures, Lihi Segal, CEO of Day Two spoke on “Microbiome science for diabetes care”. Diet is one of the key strategies for managing diabetes and metabolic disease, but dietary advice is rarely personalized and individuals struggle to make dietary changes over the long term. Segal says the company aims to help people achieve sustainable remission of diabetes through “precision nutrition”, which she defines as a combination of biology and food that supports
a positive health outcome. The product offered by the company in both the US and Israel involves shotgun metagenomic sequencing of the gut microbiome from a stool sample, using an algorithm to predict individuals’ blood sugar response to any food (without the use of a continuous glucose monitor), an app for making food decisions, and ongoing behavioural coaching from registered dietitians and other nutritional professionals. Reported outcomes from the product include a drop in A1C, weight loss, and reduced medication. Segal also noted that the company is amassing a large database of information on people with diabetes and metabolic disease, and said they are open to collaborating with partners who may want to use this data to develop other products.
Alex Stevenson, CSO of 4D pharma plc focused on live biotherapeutic products (LBPs) with his presentation, “Building for Success: Challenges and opportunities in a novel drug modality”. Stevenson highlighted two parameters for candidate LBPs: (1) correlation vs. causation – that is, whether the strain is associated with health or is shown to have activity related to disease mechanisms; and (2) ecology vs. pharmacology: whether the strain changes the overall environment in the gut or has specific, transient activity on human biology via the gut, without engraftment. 4D pharma’s approach is to develop non-engineered single-strain LBPs that are based on causation and do not require engraftment for activity. Stevenson believes oral, gut restricted LBPs can have therapeutic effects in organs and tissues away from the gut, and that mechanism of action is increasingly important to define for LBPs. He described the company’s MicroRx platform, which applies pharmaceutical thinking to LBP development with the aim of discovering candidate LBPs. Beyond discovery, a challenge Stevenson identified was GMP manufacturing of LBPs in a controlled, reproducible, scalable, and commercially viable manner. In recent years, the field has seen more activity and investment in dedicated LBP contract drug manufacturing organizations (CDMOs).
Christine Lang, CSO of Belano Medical, turned to the skin microbiota with “Microbiotic products – modulating and improving microbiomes for health and therapy”. Lang described the company’s aim to “re-balance disturbed microbiomes” in common skin diseases. She gave the example of atopic dermatitis, where Staphylococcus aureus makes up around 90% of the skin microbiota as compared to 0-5% on healthy skin; the latter is enriched in S. epidermidis. The two bacteria appear to be in ‘competition’, since in vivo S. epidermidis combats the inflammatory S. aureus and interferes with its biofilms. In looking to transfer this science into products, the company took a twofold approach of strengthening S. epidermidis and other commensals as the skin’s ‘natural defence mechanisms’ while replacing S. aureus. After using an in vitro bioassay to screen for lactobacilli that stimulate the growth of S. epidermidis, they settled on Levilactobacillus brevis DSM 17250, and later found in a pilot study that an extract from this strain impacted the skin microbiota and lowered measures of atopic dermatitis severity. As for removing S. aureus, their screening process led them to Lactobacillus gasseri DSM 25908, which uses co-aggregation as its mode of action to achieve selective removal of pathogens.
In a session on gut health and disease, speakers discussed promising bacteria, including Akkermansia muciniphila (developed by A-Mansia) and Christensenella minuta (developed by YSOPIA Bioscience) for metabolic disorders and obesity, as well as six-strain consortia (developed by MRM Health) to target disease mechanisms in IBD.
Project Manager, Claire Derlot made a presentation on taking LBPs through the clinic and getting the CMC strategy right.
Session on gut health and disease
In the session on gut health and disease, Marcus Claesson of APC Microbiome Ireland, University College Cork, discussed machine learning methods for identifying biomarkers for inflammatory bowel disease (IBD). For disease classification of individuals with IBD, the best outcomes were achieved by combining data from microbiota and genetics and diet, as opposed to any one of those factors alone. Subsequent work revealed that distinguishing disease state in IBD was possible using microbiota data alone, but only when using operational taxonomic units from two consecutive time points—perhaps due to low microbiota stability in this population.
Warren Flood, COO of Bio-Me, spoke about developing microbiome-based biomarkers for clinical use in general. He described the challenge of applying microbiome monitoring in a clinical setting—with adequate turnaround time, reproducibility, and ease of use—and explained how this challenge is addressed by the company’s Precision Microbiome Profiling pipeline for microbial assay development and validation.
In terms of preclinical data, Maria Wiese, Senior Scientist Integrator in the Department of Microbiology and Systems Biology at TNO showed how in vitro platforms can be used for screening of LBP candidates for gut microbiome restoration and inhibition of pathogens. She described the i-screen high-throughput model to study human gut microbiota, with advantages that include cost efficiency and using small amounts of test substrates.
Jiri Snaidr, Founder & CEO of vermicon AG made a case for how imaging can inform microbiome analyses and help support better products. Whereas most common microbiome measures are indirect, fluorescence In Situ Hybridization (FISH) is a direct measure that helps scientists visualize and map the genetic material in microbial cells. Snaidr sees FISH as a powerful way to gain insights into microbial ‘reality’ and an ideal complement to indirect methods such as sequence analysis. He described its applications in LBP development for research, quality, and process control.
Session on women and infant health
Several talks in the session on women and infant health described impressive studies on the role of the microbiota in both maternal and infant health. When it comes to promising ways of improving women’s health through the microbiome, a highlight was the talk by Nicoletta Di Simone of Humanitas University, Milan, reporting on the endometrial microbiota as a possible diagnostic tool for idiopathic recurrent pregnancy loss in women.
Anders Damholt, Head of Clinical Development at Chr/ Hansen talked about the efficacy of an oral probiotic on vaginal health and the microbial community in women. The company’s “Feminine Support” product is a ten-strain combination that includes the most dominant bacterial species in a healthy vagina. A pilot study showed the product to be safe and well-tolerated, with a reduction in vaginal pH and ‘normalization’ of the vaginal microbiota.
Biose Industrie has 65 years of experience in the development and production of live bacteria based drugs. The company offers lab development specialised in microbiology and is Drug GMP certified for the manufacturing of API, clinical batches and commercial products. https://www.biose.com/en/cdmo