Yet again, on November 5th and 6th, 2020 Microbiome Insights was a proud exhibitor at the 8th Microbiome Probiotics R&D and Business Collaboration Forum. This year, due to COVID-19, the conference was hosted virtually.
Over 300 leaders in the microbiome community gathered to discuss new advancements in microbiome research and potential challenges and opportunities on the path to commercialization.
Here are some of the highlights from the two conference days:
Gut Microbiota for Health & Disease
Ken Blount at Rebiotix Inc., a Ferring Company began by identifying the limitations of Fecal Microbiota Transplantations (FMTs) as standard of care for Clostridium difficile infections. While FMT has demonstrated efficacy, it is currently an unapproved procedure and, given it is the transplantation of fecal matter from a donor, there are significant risks. With that in mind, there is a need for standardized, safe Live Biotherapeutics Products (LBP) that can help realize the potential of microbiome-based therapeutics. Ken provided the latest update on the company’s portfolio of LBPs. The lead product, RBX2660, is a part of the clinical development program for recurrent C.difficile infections (rCDI). Early signs of RBX2660 being successful were evident in their Phase 1, Punch Open Label trial. At 24 months after treatment, 90% of RBX2660 subjects remained infection-free. The product has recently completed a Phase 3 trial, the first of its kind in the microbiome therapeutics industry. The preliminary findings announced by Rebiotix were positive, demonstrating a consistent reduction in rCDI among patients.
Skin & Cosmeceuticals
Dalida Chouchi at DSM addressed the main requirements for a probiotic as a novel cosmetic ingredient. A cosmetic product is defined by the site of application and function. It must be intended for external use and work to help keep the body in good condition. Dalida emphasized that it’s important to adhere to the correct terminology when defining a product as pre-, pro- or post-biotic. Out of 256 U.S. cosmetics carrying “probiotic” claims, only 10% are actually probiotics, the rest are postbiotics. One of the current skin microbiome commercialization challenges is that there aren’t safety guidelines for probiotic ingredients used in cosmetic applications. The caveat is probiotics being live microorganisms are dynamic, unlike classical cosmetic products. Previously, microbes have been viewed as potential pathogens from a regulatory perspective, so it’s important to demonstrate that the specific probiotic contains host-beneficial microorganisms and is safe to use.
Riccardo Sfriso at DSM spoke about the recent study on one of DSM cosmetic ingredients – ALPAFLOR ALP-CEBUM CB that looked at modulations of key bacteria. By looking at the relative abundance and applying differential abundance testing, it was identified that the ingredient upregulates beneficial bacteria such as S.epidermis and M.yunnanensis and downregulates pathogens such as S.capitis and S.kroppenstedtii. Overall, the study demonstrated visible improvement of skin condition and reduced redness.
Women’s Health & Infant Microbiome
Sharon Donovan at University of Illinois spoke about current infant microbiome research she is involved in. One of the main challenges of this area is access to only non-invasive approaches to studying infant human microbiome. With that in mind, to address nutritional regulation of intestinal development of human infants, Sharon and her colleagues developed a method of using exfoliated intestinal cells.
As a part of the “Metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response”, Sharon and her colleagues were able to identify microbiome differences in breastfed and formula-fed babies, with the former having high count of both Firmicutes and Bacteroides, and the latter had only Firmicutes at identifiable amounts. Drawing on the research that has been conducted on the ratio of Firmicutes and Bacteroides bacteria and obesity, Sharon and her colleagues hypothesized that formula-fed infants had obesogenic profiles.
Additionally, Sharon presented insights from one of her longitudinal studies (STRONG Kids 2 Cohort) studying breastfed, mixed- and formula- fed babies. The results from this study have shown that the microbiome is more diverse in breast-fed infants with mixed- and formula-fed infants having a more homogenous microbiome.
Sarkis Mazmanian at California Institute of Technology spoke on “Selective Modulation of enteric neurons alters the microbiome and gut physiology in mice”. He addressed the potential origins of Parkinson's disease (PD) and shared his research findings on the correlation vs. causation between PD and microbiome. In one of the studies, his team transplanted fecal microbiomes from Parkinson’s patients and healthy controls into mice and then looked at the effects of motor phenotypes. Mice that received the PD fecal samples had more pronounced motor deficits than mice with microbiomes transplanted from healthy controls. From his research Dr. Mazmanian developed hypotheses that either “the microbiome of Parkinson’s patients has more pathogenic bacteria” or it “may be missing important beneficial organisms compared to the general population”. Furthermore, the microbiome of mice with PD fecal samples was shown to deposit more amyloid proteins. One of the amyloid proteins is alpha-synuclein – which plays a major role in Parkinson's disease pathology. This discovery opens up a new area for PD therapeutics – one that can act through the gut and potentially prevent the aggregation of bacterial amyloids.
Skin & Cosmeceuticals
Pedro Dimitriu at Microbiome Insights presented data from the “Cinco De Mayo” study, which was done in collaboration with Amway. The study recruited 150 participants in total with samples collected from the forehead and cheek over three years, from 2017-2019. By sequencing the V1-V3 variable regions of the 16S rRNA gene, it was demonstrated that subjects’ skin microbiomes were stable over the two year period of the study, with a strong barrier function being a sign of a more diverse skin microbiome. Interestingly, a Corynebacterium sp. increased with age. The relative abundance of other skin commensals such as Staphylococcus and Cutibacterium correlated with physiological manifestations of skin health. Amway and Microbiome Insights continue to collaborate on various projects and build on the “Cinco De Mayo” findings.
Cancer & Business Collaboration – Regulations and Investment
Malcolm Kendall, our CEO and Co-Founder at Microbiome Insights, moderated a panel on venture capital with Eric de la Fortelle at Seventure Partners, Racquel Bracken at Venrock and Nina Kjellson at Canaan Partners.
Nina highlighted that the emergence of various tools and technologies that help advance microbiome research has been exciting for the Canaan Partners team. The firm is still cautious about investing into a microbiome company as they’re looking for a product that is “a diagnostic coupled to a more traditional pharmacological agent that results from the diagnostic informing the discovery of a metabolite or small molecule that can shift the microbiome and when given for a short period of time restore homeostasis in the host microbiome.”
Racquel at Venrock pointed out the main investment criteria for her firm are: is the mechanism of action clear? Does the company have the right team and is it focused on the right applications, on a disease where there is a real unmet need? With the recent successes with therapeutics aimed at tackling Clostridium difficile, Racquel thinks the microbiome industry is on an upswing and in 5 years will look back and see that microbiome drugs have had a big impact, but right now we are still sorting it out.
Eric de la Fortelle at Seventure Partners noted that the microbiome is a whole area of biology that has lain under our eyes, but we have only realized its importance recently, in the last 10 years - this is like discovering a new organ. Just like any new area of biology a lot of work is needed to understand how it connects with all the other organs and systems, like the immune system and this work will take 20 years or longer. Seventure’s strategy is to go in early and find the low hanging fruit, to identify companies that opportunistically find a short cut in biology that leads to a clinical result. In the end, classical pharmacology always wins. He likes to think of the microbiome sitting with one leg in therapeutics and the other leg in nutrition. Seventure is conversant and invests in both areas.