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Denise Kelly representing Seventure on what makes a successful microbiome company

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A growing number of start-up microbiome companies—from new players in the established probiotics industry, to university spin-outs focused on novel microbiome-based therapeutics—are looking for support and funding. In this competitive environment, how can a new company make the cut?

For the past several years Professor Denise Kelly has worked with Seventure Partners, a leading European Investor—which has the first venture fund, Health for Life, dedicated to investing in microbiome-focused start-ups, led by Seventure’s CEO, Isabelle de Cremoux. Kelly has participated in panels at both the Translational Microbiome Conference (Boston, USA) and the Global Engage Microbiome Futures event (New York, USA) and recently gave keynote lectures at the IHMC meeting in Killarney and the NeuroCon-X meeting in Prince Edward Island, Canada. Here, Microbiome Insights hears Prof. Kelly’s summary of what will set up a microbiome-based company for success.

Use strong science—and own it

Kelly says Seventure has looked at more than 400 companies in the microbiome sector. The first question she asks is whether the science behind the product or service is robust—a major factor for the Seventure Life Science team. She notes, “We are really fortunate that a lot of interest comes from tier one academics and the findings are published in high-impact journals”—so the science has been peer-reviewed and often validated by independent research, adding to its credibility.

Moreover, Kelly says the strongest scientific ‘package’ combines wetlab work with human studies that address potential mechanisms of action in humans. And she notes that companies generally need to have more than 16S data on hand: “We know so much about strain level impact; shotgun sequencing gets you a lot more information. But even then, the industry is moving towards a multi-omics approach—for example, including metatranscriptomics  and metabolomics, so we know ‘who’ occupies an ecosystem but also what they are doing.”

The next question about the science is whether it’s unique: Do competitors have something similar? Having a strong patent portfolio is crucial as it gives the company a distinct competitive advantage.

Build your revenue stream

Among all the possible life sciences areas in which VCs can invest, microbiome science is still in its early days—meaning they are likely to proceed with caution. Kelly says, “Investing in the ‘discovery’ phase is inherently risky; investors want to see that others have invested in the ideas as well.” She says the solution is to use as many resources as possible to build a company’s revenue space, including building multiple product opportunities and diversifying target disease indications—and importantly, building partnerships and licensing opportunities. Very competitive companies are also winning sizeable non-dilutive grants.

Get your regulatory ducks in a row

The science may look exciting now, but what’s the plan for bringing it to market? Many potential therapeutics in the microbiome area—for example, ‘bugs as drugs’—will face unique regulatory challenges. Kelly recommends connecting with regulatory advisors early on so the company can plan for the realities of getting past the hurdles. And even in cases where the regulatory path for a particular indication is relatively well-established, those at the helm of the company need to understand the complexities of the manufacturing process and how regulatory requirements need to be factored in.

Build relationships strategically

Kelly emphasizes that no successful company is built in a bubble: it needs supporters in order to build success. Companies need relationships with key people in academia and elsewhere—and not just a list of names to put up on the web page, but people who really care about what it’s doing and who are willing to jump in with advice and support.

Kelly says it’s especially important to engage with key opinion leaders (KOLs) with knowledge about the specific indication on which the product is focused. A company that demonstrates authentic engagement with these individuals has a better chance of leading the way in the therapeutic space.

Know when to keep your cards close

As a company is building, it’s important to strategize about how much to reveal—at what times, and to whom. She says, “Approach investors, such as Seventure, when you have a clear vision of your commercial opportunity. Although we invest in early stage start-ups, we appreciate companies that have a strong science package as well as a robust business plan that clearly sells the path to clinic and ultimately, to the marketplace.”

Having all these pieces in place won’t guarantee success—but Kelly says they will certainly make investors take a closer look. “The microbiome industry is moving very fast and the number of new start-ups continues to grow exponentially. At Seventure, we continue to build our portfolio and very recently our CEO, Isabelle de Cremoux, announced the first close of a new AVF fund with Adisseo, dedicated to innovation in Animal Health and Nutrition.”

Without a doubt, the microbiome industry as a whole is truly disruptive and represents a complete paradigm shift in human and animal healthcare. Says Kelly: “We are confronted with numerous modalities, ranging from nutritional products through to microbiome-based drug therapies which can modulate microbiome community function and structure, significantly impacting health status but also disease risk and disease progression. Personalized approaches to medical care are also envisaged, as predictive microbiome biomarkers are being sought—and these could provide more accurate diagnostic and prognostic patient read-outs, leading to more predictable and enhanced drug efficacy. The next five years will be very exciting for many, many reasons. Our knowledge base will continue to grow, but most importantly, we also start to see completion of phase II/III human clinical trials.”

On World Microbiome Day, Here Are Ten Microbiome Thought Leaders You Need to Know

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Day in and day out, the Microbiome Insights team is immersed in scientific work on the microbiome. But on this very first World Microbiome Day, we’re taking a moment to step back and consider what—and who—made this remarkable field what it is today.

Although microbiome science is relatively young, the newest discoveries are only possible because of the preceding decades of research in fields as diverse as microbiology, genomics, molecular genetics, infectious diseases, and ecology. In this way, every microbiome researcher stands on the shoulders of those who came before.

With the help of Microbiome Insights co-founders Dr. Brett Finlay (Professor of Biochemistry and Molecular Biology, and Microbiology and Immunology at the University of British Columbia) and Dr. Bill Mohn (Professor of Microbiology and Immunology at the University of British Columbia), and our Scientific Advisory Board member Dr. Janet Jansson (Division Director of Biological Sciences at the Pacific Northwest National Laboratory)—all of whom qualify as thought leaders in their own right—we’ve compiled a list of ten scientists who have built a foundation for today’s microbiome researchers. These are individuals who, through their hard work and vision, have inspired their contemporaries to think differently and, in doing so, have shaped the field of microbiome science into what it is today.

Carl Woese

Dr. Carl Woese (1928-2012) was a biophysicist turned evolutionary microbiologist whose influence on the microbiome field cannot be understated. He was the first to show that bacteria evolve—and he demonstrated the phylogenetic relationships that backed this claim. Through this work he redefined the taxonomic scheme used to describe all forms of life on Earth and introduced us to the three domains of life we recognize today: Bacteria, Archaea and Eukaryota. His legacy is still seen in state-of-the-art lab techniques today, as he established phylogenetic methods using small subunit RNA and culture-independent methods that allow researchers to characterize microbial communities without first culturing them.

Norman Pace & trainees, including David Stahl

Dr. Norm Pace is, among many other things, a Distinguished Professor of Molecular, Cellular and Developmental Biology at the University of Colorado as well as a member of the National Academy of Sciences, a Fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, and the American Academy of Arts and Sciences. His distinguished research career began with the breakthrough idea that, rather than trying to culture all of the unknown microbes of the world, one can instead scoop up genes from the environment and sequence them—essentially creating the many areas of microbiome study that are now among the most active in biology. Many trainees of his lab have gone on to make major contributions to many microbiome areas—in particular, Dr. David Stahl with his unique application of microbial ecology to environmental engineering.

James Tiedje

Dr. James Tiedje is a pioneer in the molecular exploration of soil and non-human environments. His work was instrumental in advancing many fields of microbiome research and addresses environmental concerns like climate change and bioremediation. His expertise in the field was even used for space exploration, as he designed experiments for the Viking Rover aimed at finding life on Mars. He is now a Distinguished Professor of Microbiology and Molecular Genetics and of Plant, Soil and Microbial Sciences as well as the Director of the Center for Microbial Ecology at Michigan State University.

Maria Gloria Dominguez-Bello

Dr. Maria Gloria Dominguez-Bello is Research Professor in the Department of Medicine at New York University whose work spans the fields of microbiology, anthropology, and agriculture. Collecting data from different populations across the globe, including populations in remote geographical areas, her work has focused on the immune and metabolic functioning of the microbiota through development, and how modern practices might impact this functioning. She is well known for her pioneering research on how Caesarean section birth impacts infant microbiome development, and possible microbiome ‘restoration’ techniques.

Martin Blaser

Dr. Blaser is Director of the New York University (NYU) Human Microbiome Program, and Professor of Microbiology at NYU School of Medicine. His early work with Helicobacter pylori confirmed its role in diseases like gastric cancer, providing one of the first examples for a bacterial role in these human diseases. He also brought attention to the importance of the early life microbiome and the dangers of antibiotics to a healthy microbiome and drug resistance—concepts covered for the general public in his highly praised book, Missing Microbes.

Jeff Gordon

How does the gut microbiome develop after birth, and how might this affect one’s nutritional status? These are the questions that drive Dr. Jeff Gordon, the Dr. Robert J. Glaser Distinguished University Professor at Washington University in St. Louis. He has shone a light on the role of the gut microbiota in metabolism and has taken on two pressing global health challenges: obesity and childhood malnutrition. By exploring interactions between the diet and gut microbiome he is discovering potential new ways of optimizing gut community development during the first few years of life.

Patrick Schloss

Dr. Patrick Schloss, now Professor in the Department of Microbiology and Immunology at the University of Michigan, took an interest in bacteria early in his career—not only the bacteria present in samples, but also what they were doing there. To answer this, he used gene sequencing and developed critical tools for analyzing microbiome data and making the interpretation of this data more accurate. With his flair for bioinformatics, his work has helped others make sense of the vast amounts of data generated by microbiome studies.

Stanley Hazen

Dr. Stan Hazen, chair of the Department of Cellular & Molecular Medicine in the Lerner Research Institute at Cleveland Clinic, changed the way researchers think about diet, the gut microbiome, and heart diseases by showing for the first time that a microbial metabolite (TMAO) was linked to cardiovascular disease. With his groundbreaking work in atherosclerosis and inflammatory disease research, he has impacted clinical practice and has laid the foundation for FDA-cleared diagnostic tests and cardiovascular disease drug development. Among his many accolades is his recognition as 2017 Distinguished Scientist by The American Heart Association for his many contributions to the field.

Eran Elinav

After completing his medical specialization as a doctor of internal medicine, Dr. Eran Elinav moved to the Department of Immunology at the Weizmann Institute in Israel. His work has uncovered the very personal links between humans, their diet, and gut bacteria. This has led to microbiome-focused research on personalized physiological responses to nutrition, and has garnered him several accolades including The Rappaport Prize for Excellence in the field of Biomedical Research.

Highlights of the Microbiome Drug Development Summit 2018 in Boston

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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:

DAY 1

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.

DAY 2           

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.

Banff Keystone Symposia on Gut Microbiota: Day Two Summary

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March 6, 2018 marked the second day of the joint Keystone Symposia in Banff, Canada: (1) “Manipulation of the Gut Microbiota for Metabolic Health” and (2) “Microbiome, Host Resistance and Disease”.

Morning sessions were split into two tracks. The first track covered microbiota and metabolic disorders, with two initial talks by François Leulier (Institut de Génomique Fonctionnelle de Lyon) on gut microbiota and host mutualism in chronic undernutrition, and Emily P. Balskus (Harvard University) on microbiota-drug interactions.

The complex development of early life gut microbiota and immune function was the topic covered by the second track. Maria Gloria Dominguez-Bello (Rutgers University) gave an overview of what we know about how C-section birth is linked with later-life disease through the gut microbiota, showing the associations that exist in human populations and the causal evidence that exists in mouse models. Andrew J. S. Macpherson (University of Bern) then gave a detailed account of early postnatal innate immune development, showing how the site of microbe administration shapes distinct repertoires of IgA and IgG antibodies from mature B cells, and how these antibodies are found in several sites through the host. Subsequent talks branched out to other immune-related topics linked to skin commensals, and also the gut-brain axis (i.e. a gut bacterial metabolite that causes behavioural abnormalities related to anxiety and autism spectrum disorder).

The evening’s sessions were divided into one track on gut barrier alterations and host metabolic disorders, and one on mechanistic microbiome function in physiology and aging. A highlight of the evening was the account given by Lora Hooper (University of Texas Southwestern Medical Center) of mechanisms linking circadian rhythm with adipose tissue development: in mouse models, she found a conventional microbiota drives immune system regulation of circadian rhythms, resulting in more long-chain fatty acid uptake on a high-fat diet, and ultimately an increase in adipose tissue. Participants in the evening session also heard a talk by Michiel Kleerebezem focusing on the microbiota of the small intestine and how a robotic capsule can be used to track the effects of a dietary intervention.

We’ll be tweeting again on Wednesday! Look for the conference hashtags, #KSmicrobiome and #KSgut.