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Bugs and Drugs: The Promising Microbiome Frontier

October 19, 2016
Tuesday at the 2016 BIO Investor Forum wrapped up with a panel discussion on the exciting potential of microbiome research, a relatively new but fast growing field in biopharama. Although still in an early phase, there has been growing excitement over the possibility of bringing new microbiome-derived drugs and therapies to the market.  With promising signs such as the $121M National Microbiome Initiative commitment from the White House, we can anticipate that this field will continue to garner attention in the coming years.

Getting microbiome-inspired candidates to become commercially viable therapeutics presents a number of challenges, including uncertainties in drug development and questions about intellectual property and regulatory pathways.

The panel, titled, “Translating Microbiome Research into Treatments”, was moderated by Andres Hurtado-Lorenzo, PhD, Director of Translational Research at the Crohn’s and Colitis Foundation of America.

The panelists were:

  • Nick Conley, PhD, Co-founder and Chief Executive Officer, EpiBiome

  • Colleen Cutcliffe, PhD, Co-founder and Chief Executive Officer, Whole Biome

  • Glenn Nedwin, PhD, MoT, Chief Executive Officer and President, Second Genome, Inc.

The panel discussion revolved around about current experiences in microbiome drug development and the promising future of microbiome therapies. After introductions, the panelists discussed their individual experiences with microbiome-based therapeutics and which recent developments they were most optimistic about.

Hurtado-Lorenzo noted that as an emerging field, it is not without its challenges. But he is hopeful that as the microbiome becomes more understood, cures will be created for intestinal and stomach diseases and beyond.

Cutcliffe’s company is working to build therapeutics of metabolic diseases. Nedwin mentioned that can have agricultural applications outside of the human body.

Hurtado-Lorenzo then asked the panel to define the microbiome for the audience and share what aspect of it they are most excited by.

Conley responded that he is most excited about a new development whereby bioluminescent genes can be transferred via phages into E-Coli 157 to make detection easier to identify. Cutcliffe replied that she is most excited about the potential of microbiome-based treatments in development to improve disease state.

Nedwin believes that an improved understanding of the microbiome will change the world of science in a profound way.  He said, “I believe the microbiome is the next paradigm shift”. He notes that we have coevolved with the various microbiota and rely on them more than we currently know. He explains that rather than the old understanding that bacteria are broadly harmful, we are starting to accept the idea that they are essential to our health; he notes: “They are keeping us alive”.

Hurtado-Lorenzo then asked what the panelists feel is the biggest challenge for companies working in the microbiome space.

Nedwin said that the biggest hurdle is identifying the specific bacteria to go after when it comes to research and also getting through regulatory hurdles. One of the biggest factors is that: “Nobody knows what a healthy microbiome looks like.”

Cutcliffe agreed that IP and regulatory hurdles are a huge challenge. What a healthy gut microbiome consists of is not yet defined. “It’s a pretty diverse target”, she explains.  It can be challenging to know which microbiota are helpful verses harmful.

“How about business challenges?” asked Hurtado-Lorenzo.

Cutcliffe explained that it is hard for small companies in the space to know what strategy to adopt when considering growth. Early stage startups in the space are asking themselves who to partner with: academia, big pharma, or other small startups?

Conley answered that a big issue in gaining investment traction right now is the fact that nobody has pulled this off successfully yet. Companies have no big products that they can point to in order to justify investment. “You’re really selling potential. Safety is a big issue. What’s a safe bacterium to someone who’s immunocompromised?” he said.

Hurtado-Lorenzo then asked the panel how building a microbiome company differs from running a pharma company.

Nedwin replied that first off, one must have an understanding of anaerobic bacteria to be successful in the space. Another big requirement is the ability to correlate the presence or absence of bacteria to metadata. He said, “You need good statistics to make the right correlations.”

Cutcliffe said that what makes studying and developing drugs based on the microbiome is that you often don’t go after a specific disease. Instead, there are properties of the microbiome that play a role in pillars of health rather than a specific disease. Your goal is first to gain a fundamental understanding of the microbiome and how it affects the host. She was also careful to warn that we should not overhype the field, as promising and exciting as it is.

Hurtado-Lorenzo asked about R&D opportunities. “What are the most exciting disease areas for microbiome therapies?”

Conley felt that diabetes and cancer are exiting areas of research currently. Cutcliffe responded that the low hanging fruit is around treatments for C. Diff infections. She said there is strong evidence that fecal microbiome transplants are effective in treating that infection because “You don’t have to understand specific microbe entities, you just have to crowd out the existing bad bugs.”

Conley shared an experience whereby a colleague showed him a book on equine veterinarian medicine showing that fecal transplants been performed in horses as long as 100 years ago, and that this treatment is only now being rediscovered in humans.

Nedwin answered that ear infections could potentially be treated by transferring wax from the healthy ear to the other. But, he said, the gut is where there is the most promise for new treatments. 75% of immune cells interact with the gut, so any diseases that relate o the GI tract like IBD are promising areas of research. Also, anywhere on the body where it is easy to procure samples such as the skin or teeth, could be promising.

Cutcliffe was careful to points out that the skin poses a real challenge because of how dynamic the system is. There are factors that could influence the research such as the time of day when the sample was procured, to what products the patient used on their skin.

Hurtado-Lorenzo then asked the panel what they believe is the most effective way to target the microbiome.

Conley answered that he was a big pan of prebiotics. He said that there is a fair amount of data about how different sources of fiber help the proliferation of microbiome. He was also impressed by preliminary evidence of improvement in lactose tolerance be treating with large amounts of lacto-bacteria. As an anecdotal example, one of his housemates went from not tolerating dairy to eating pizza and cheesy pasta after taking probiotics, but went back to being lactose intolerant after stopping the probiotics.

Cutcliffe said that all methods of targeting the microbiome are worth pursuing. But there are two challenges. One is IP. There is a question of where can you create ownership. The second challenge is the regulatory speed at which you can start testing new potential treatments in humans.

Nedwin noted that one interesting approach to microbiome research that would make it easier for companies to deal with regulatory challenges is to identify the molecules produced by microbiota rather than try to patent treatments based on the microbiota themselves. He clarified that this approach may not be possible with all diseases or targets, however.

Hurtado-Lorenzo then asked what role the microbiome plays in precision medicine.

Nedwin answered that eventually we will be able to apply it to precision medicine, but that we are still far from being able to implement it with precision because the field is still so young.

Hurtado-Lorenzo asked how investors view microbiome therapies, and if there are differences in how they view them verses traditional therapies.

Nedwin said, "I’m fortunate that Second Genome has really good investors (Roche, Glaxo). If you can identify molecules out of microbiome research, it’s an easier path to discovery." Industry realizes they need a new paradigm as a new source of drugs. Venture firms are concerned about this, he said.

Cutliffe agreed that it’s a hot space right now and that investors seem excited for the same reasons we are. New data being generated that hasn’t existed before. However, there are no blockbuster products yet, so that is a risk that needs to be addressed. "Investment in the microbiome space is happening. It’s alive," she said.

Conley added, "As long the reward exceeds the risk, it’s certainly investable. I don’t think it’s that much different than any technology without much precedence."

Hurtado-Lorenzo asked if partnerships play a role for the panelists.

Conley answered, "We have partnerships with academic labs. It’s hard to do everything in-house. Cutliffe answered that she faces the same struggles with partnerships in this space as any other space. Most of the cutting-edge micobiome companies are startups. Nedwin replied that getting funds from partnerships are important because it helps to expand your base.

Hurtado-Lorenzo asked one final question regarding the future microbiome-based therapeutics in the next five years.

Nedwin answered that several companies have products in the clinics. "I think in a few years from now, you will see products on the market that originate from this field. It’s very exciting."

Cutliffe said, "These next few years will really help us to understand where we will have an impact and where the challenges are. There's no doubt in my mind that in decades and hundreds of years to come, the field will exist. We’re just beginning to understand it."

Conley replied, "Once we get the first big blockbuster, that’s when things will really start to evolve rapidly. It’s a matter of when, not if." He added that he is hopeful that in the next five years, investors will stop sitting on the sidelines and start getting involved.