The BIO CEO & Investor Conference kicked off Monday with a panel discussion exploring how latest research developments on the microbiome may help patients suffering from a range of gut, immune, and nervous system disorders. Major biopharma companies have engaged in significant deals that envision treatments to commercialize from this research and leading companies are pushing forward on clinical trials. The panel was moderated by C. Simone Fishburn, PhD, Editor, BioCentury Innovations. The panelists were:
- Pierre Belichard, PharmD, PhD, Chief Executive Officer, Enterome
- Mark Bodmer, PhD, Chief Scientific Officer, Evelo Biosciences
- Nick Conley, PhD, Board of Directors, Co-founder & Chief Executive Officer, EpiBiome
- Jeffrey Riley, Chief Executive Officer, President and Director, Synthetic Biologics
- Nikola Trbovic, PhD, Director R&D Technology Strategy, Genome Sciences & Technologies, Worldwide Research & Development, Pfizer Inc.
The moderator described the microbiome as a rapidly growing area of research, having gone from the fringe to mainstream, and gave several examples of recent deals and high profile funding opportunities. In 2015, $309M was spent on microbiome-related funding, having grown from $13M in 2013. Broadly, there are three areas of microbiome research: bugs from drugs, bugs as drugs and diagnostics. Drugs can be developed from metabolites of microbiotia, but treatments can also be developed by cultivating a specific makeup of microbiotia to treat disease.
Trbovic described microbiome drug development as a novel modality that spans across several therapeutic areas. He argued that there is evidence to suggest a causal relationship between the microbiome and human health.
Belichard described the story of the microbiome as originating with Louie Pasture, who sought to irradiate bacteria to improve human health. Our understanding of the germ theory and the microbiome has evolved since them, and our overreliance on antibiotics has caused us to have lost between 30-50% of the diversity in our gut. This loss is related to a series of diseases that relate to the immune system and the microbiome. Following a cohort of 100 patients with Crohn’s disease, Belichard observed a correlation that led his company, Enterome, to develop an accurate diagnostic that he anticipates will be on the market at the end of 2017. Doing gene sequencing of the bacteria in the gut, the company noticed patterns in inflammation and developed a drug that is not antibiotic based, but helps the patient get back to a health microbiome to fight Crohn’s disease.
Bodmer observed that the microbiome regulates the immune system. The gut contains 75-80% of all the immune cells in an organism, and is not only responsible for gut health, but for immune responses systemically. He pointed out that organisms and their microbiomes coevolved together, and laboratory researchers who spent their whole careers keeping microbiota out of assays are putting them back in. He sees parallels between the questions being asked of microbiome research now, and the rise of antibody therapeutics in the 1980s (e.g. how to regulate, lot stability, etc.). The promise of microbiome research is that drugs can be manufactured at a suitable cost, with suitable reproducibility.
Riley’s company is focused on the GI tract, and has several drugs headed into phase III. Diversity in the microbiome is important, he notes, and it has been damaged by the overuse of antibiotics. He cited research suggesting that just a single dose of antibiotics can have profound effects upon a child’s microbiome, and he suggested it was likely that most of the adults in the room had taken about 10 or more antibiotics in their lifetimes. His drug helps protect the microbiome by breaking down an antibody before it has negative impact. Their research found it had a70% reduction in C. Diff., as well as a reduction in VRE.
Conley discussed the use of phages to target certain species. His company, EpiBiome, can tell semi-quantitatively what is in a particular microbiome sample, and use viruses to target specific bacteria, leaving the rest intact. Giving some historical background, he mentioned that early research in the USA was stopped due to the discovery of penicillin, although Russia had pursued this line of research a little longer. Presently, antibiotic resistance is a serious problem, and as the problem grows, certain procedures like Lasik or vasectomies may become too risky due to antibiotic resistant infections. Today, we can better understand the functioning of phages with more advanced technologies. We should keep it mind that agriculture and antibiotics allow the world to sustain its population, so a lessening in the effectiveness of antibiotics could have profound consequences on the world.
Fishburn then asked Bodmer: Are we looking at another 20 year lag time before microbiome-based therapies become well-entrenched, mainstream technologies? What do you think the biggest bottleneck is?
Bodmer replied: “Don’t expect me to say it’s going to take a generation to get the products to market,” eliciting some laughter from the room. He said we can see from the data what we’re interested in; the fundamental biological activities are there, visible to us. The real challenge is that the biological activity we see with strains of bacteria are highly variable.
Fishburn then asked Trbovic about what he saw as the biggest risks in microbiome research. He responded that the challenges in live therapeutics are related to manufacturing, the regulatory path, and a lack of a thorough understanding of the mechanisms of action by which these bugs work. He also pointed to a correlation and causation challenge since there is so much variation in the microbiome between patients, and even within one patient week to week.
Riley says that he anticipates that regulatory challenges will be an obstacle for companies because, “a bug that’s friendly for me may be a pathogen for someone else.” It can be difficult to know for sure that microbiota will function in the same way for everyone.
A question from the audience to Riley was: Are you seeing enough FDA staffing to support the products in the pipeline? Riley said no because there’s a hiring freeze at the FDA. Until we hear from the current administration, there will be a slowdown. We need more FDA folks to define what needs to happen going forward. Currently, the FDA has issues with having a lot of inexperienced people fresh out of school, who do not stick around at the FDA long before transitioning to industry. Although acknowledging that the FDA has been facing challenges and needing additional resources, Riley also said the FDA has been helpful to work with in his experience.
Another question from the audience was: Has your micriobiome research led you to make changes in personal life, such as altering your diet? Belichard’s answer was “Eat fiber.” “No,” Riley, joked in reply. “Eat meat!” Conley’s answer was to recommend the audience read “The Good Gut” by Erica Sonnenburg and Justin Sonnenburg if they were interested in learning more about the role of diet in microbiome-based health. He pointed out that eating more purified fiber sources at the health food store isn’t enough to rescue your microbiome. He tried fermenting kefir for a while, as lactic acids may protect against cholera. He also pointed out that it’s too early for definitive answers, but encouraged participation in uBiome experiments to help expand our microbiome knowledge.
Fishburn concluded the panel asked what the group thought of the prospect of coming together and collaborating on issues of shared interest, such as helping the FDA develop a standardized approach. Bodmer said his company would be open to such an idea, although some could be shared, and other parts would have to remain proprietary.