On Wednesday morning at the BIO Investor Forum, leaders from six companies at the forefront of microbiome innovation assembled to discuss the latest developments in microbiome-based approaches to improve patient outcomes, including microbiome transplants, bioengineered probiotics, next-generation antibiotics, and microbiome-based drug discovery platforms. Investments in microbiome-related companies have accelerated across the past three years, demonstrating high investor expectations for results.
The panel was moderated by Wenyuan Shi, PhD, Chief Executive Officer and Chief Scientific Officer of Forsyth Institute. The panelists were:
- David Berry, Flagship Pioneering
- Karim Dabbagh, Second Genome
- Glyn Edwards, Summit Therapeutics
- Paul Miller, Synlogic
- Lihi Segal, DayTwo
- Emma Taylor, Naked Biome
Shi introduced the topic by noting that we have entered a very exciting time in the world of microbiology. We’ve realized that 90% of the DNA we carry within us is not human DNA, but rather the DNA of the bacteria and fungi that live within us in a symbiotic relationship. This new understanding has caused a shift the way we think about medicine. There is a shift from thinking of all bacteria as “bad”. In the face of the antibiotic-resistance crisis, we are moving away from broad spectrum antibiotics and towards probiotics and narrow spectrum antibiotics.
Shi started the discussion started with a round of introductions from the panelists, during which, Taylor said that we recognize there’s a lot of risk in the microbiome area, including how to commercialize microbiome products, protecting the IP, and figuring out unclear regulatory pathways. She is a dermatologist by training and sees the potential for the microbiome to treat a variety of skin conditions. Edwards said that his company, Summit Therapeutics, is developing narrow-spectrum antibiotics that avoid disturbing the rest of the microbiome unnecessarily. After everyone introduced themselves, Shi pointed out the diversity of approaches to the microbiome being represented.
Shi then asked the panel how we can develop a message around the paradigm shift that the microbiome field represents.
For Taylor, there is a lot of risk in this area with an undefined regulatory path, and key questions included: What do healthy and diseased microbiomes look like? How can you ensure that live microorganisms work in all patients? Are products going to be mass-manufactured, or is this an individualized approach? How can you address concerns of investors and other stakeholders?
Edwards then replied that the easiest people to convert are the clinical microbiologists, who already get the microbiome. The FDA is harder, however; as soon as we start conversations about what claims we can make, we find that the regulator has no real idea. Sometimes there’s a blank expression on their faces, and the best you can hope for is it will be a review conversation. Edwards says our biggest issue is with investors. While there’s a huge unmet need for new antibiotics, investors have had the experience of “a bag full of hurt” with funding new antibiotics. His company is aiming to change that with new mechanisms of action and doing things in a new way.
Segal added that Day two has a machine-learning algorithm which helps patients understand how foods affect blood sugar spikes, and people just get it because it’s just a machine algorithm helping them figure it out now. For doctors, it’s all about “show me the outcome.” They want to see articles showing results in peer-reviewed journals. For messaging to be believe, Segal says companies need to careful with their claims, and avoid anything that is too far out. And this approach is working, as the field now has allies like Johnson & Johnson with their microbiome center, and Seventure, who has been a big funder of microbiome companies.
For Miller, the key is going from good, core science to developing a solid product.
Berry then added that in the early days of the microbiome, the key question was how to change people’s minds. He recalled meeting with a company at a JP Morgan conference years ago, and being told: “David, you are literally trying to sell us [feces].” However, nowadays, patents have been developed, there are products in Phase 3, and so on, showing that the microbiome is no longer an unknown. As he saw it, we’re at this precipice where we haven’t had critical mass of entrants into the field. The microbiome is a new organ that’s been discovered; imagine how excited investors would be if we just discovered the brain, or the liver. Berry said he doesn’t care that investors are slow to come around; for people who don’t want to get involved, too bad!
Dabbagah agreed, saying that from Second Genome’s perspective, it’s good that the investor field is generally looking at this as a field that is happening, and tough luck for those who are not there yet.
Shi also asked the panel how to manage investors’ expectations. Miller said that when you’re working with investors, they tend to high expectations that you’re going to be showing something very profound and very quickly. When we talk to investors and others from the outside who are looking in, it’s important to point out there isn’t just one single microbiome category. The key is defining yourself along the way. Berry added that the vast majority of investors who look at the microbiome imagine theoretical risks. They’re very good at making up stuff, and the last thing a company should do is do something just because an investor said so. They often have no clue.
Shi also posed the question to the panel that since a uniform voice and shared experience are so important, how can we connect and move field forward together? Berry disagreed with the premise, and said he actually sees no reason that the field needs to come together. The less broad interest, the more opportunity for individual companies. Also, we still need to work on the foundational science, as this is early days of the field. Doing good science is the best thing we can do. Segal also felt that it’s much too early for the approaches and tools to be standardized and shared. Miller said that the microbiome field will eventually become more comfortable getting our scientists coming together and talking so we won’t need to spend money solving the same problems. Taylor added that seeing the precedents set by other companies in the areas of IP and regulator claim acceptance can be very helpful.
Next, Shi asked the panel: Do we even have enough science to know what’s normal and not? Taylor said that the Human Microbiome Project (HMP) has helped lay the groundwork here in terms of helping define healthy and diseased microbiome in subjects. Edwards said we need to work methodically on basic science. Berry then added that he’s always been baffled by mechanism question, as it seems like we’re trying to hold the microbiome to a completely different standard than other therapeutic products. Anchoring the way we think about the microbiome in this way is like saying, “How can we take a promising new field and kill it before it starts?” Dabbagh added that while causal mechanisms are difficult to understand with so many genes within the microbiome (“Microbes have 5 million genes sitting in your gut. We can barely do that with the 25,000 (protein-coding) genes a human has”), we do understand some mechanisms now, and it’s just going to increase with more companies and academics operating in this space.
For his last question to the panel, Shi asked: What is the biggest hurdle? For Taylor, the answer to this question is trying to figure out the regulatory pathway, and matching the expectations of investors. She told the story of how one time she decided to cold call the FDA and trying to find answer to a question (regarding animal testing would be necessary), which her company’s board thought she was crazy to attempt, but they were more helpful that anticipated. She said this shows we can’t just assume that small molecule processes will apply to the microbiome, and we need to push the message that we’re operating in a different biological system. Edwards pointed out that resistance to gonorrhea antibodies is at 4.4% globally, and the health organizations recommend a new antibiotic when resistance reaches 5%. Therefore, after C. Diff, gonorrhea will be next focus. Berry said that we in the microbiome field haven’t improved patient outcomes yet. He thinks that the field will keep growing and reach that point very soon, but we should remember that we still haven’t done that yet.
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