Gut Instinct: Leveraging the Microbiome and Human Immune System to Dramatically Transform Medicine

Innovation That Matters

By Hui Cai, Vice President of Corporate Alliances and Head of Corporate Communications, WuXi AppTec

The drive behind Simba Gill’s success comes from having a deep passion for science, following opportunities regardless of geographical boarders, as well as surrounding himself with talented people. He is also a big believer in humanity and globalization. This approach most recently led him to Evelo Biosciences, which is moving at an accelerated pace through the intersection of the microbiome and human immune system. Evelo is the first company to focus on characterizing and understanding the biology of the immuno-microbiome to develop next generation immunotherapies across multiple diseases.

Evelo, launched by Flagship Pioneering, has created a broad discovery, development and manufacturing platform that combines expertise in microbiology, immunology, pharmacology and computational biology. The start-up – which has identified several drug candidates for oral delivery, with the potential for many more – is using its platform to develop monoclonal microbial therapeutics to treat cancer, autoimmune and inflammatory diseases.   

Gill – an immunologist and evolutionary biologist by training and also a senior partner at Flagship –  has founded and led pioneering companies in the fields of antibodies, stem cells, directed molecular evolution, gene therapy, and immunodiagnostics.

I recently spoke with Gill, who shared Evelo’s strategy and how the start-up is poised to transform the way disease is treated, as well as why he thinks monoclonal microbial therapeutics will be an essential part of next generation medicines.

Hui Cai: Can you start with some background on Evelo’s strategy in terms of tackling the immuno-microbiome system?

Simba Gill: Evelo began life with a realization that the microbiome and human immune system  have evolved together over millennia. Our hypothesis is that there are naturally occurring monoclonal microbial strains that act through the gut to modulate systemic immunity. Our approach is to find these microbes and then develop them as pharmacological agents – in exactly the same way as one would develop a small molecule or an antibody, i.e., to think through PK/PD (pharmacokinetic/pharmacodynamic modeling), dosing, drug delivery, process development and manufacturing. This is a massive area of underappreciated biology that we are now beginning to tap into. This untapped biology will, over time, yield more and more opportunities for new ways to think about developing drugs, accelerating drug discovery and development and a new modality for treating disease.

Hui Cai: Was there also an ‘aha’ moment for you?

Simba Gill: When I started to first understand the importance of what I have just described it led to many excited and sleepless nights. We’ve completely missed, from Darwin until today, the fact that we haven’t evolved independently as a single species, but we’ve evolved together with the microbiome as a meta-species, or holobiont. It’s a massive unappreciated and generally untouched area of biology. We see it as the most exciting field in the whole of medical research today.

Hui Cai: For immuno-microbiome, why is Evelo the first company to do this?

Simba Gill: The first wave of microbiome companies took a relatively straightforward approach to treating disease, which was to look at creating a new healthy symbiotic ecosystem in the gut away from an unhealthy dysbiotic gut ecosystem. At Evelo we have the benefit of years of foundational research in the microbiome, including at Flagship VentureLabs and we are very deliberately going for the next wave difficult challenges and aiming to do the unreasonable. The field has evolved to the stage where it’s ready for the paradigm shift towards the development of monoclonal microbials aimed at modulating the immune system versus modulation of the microbiome itself.  The tools are available and we’ll be able to crack the puzzle, but you have to be brave to do what has never been done before.  As the first people in a bold new field we have courage but we also have enough experience and data behind us to be confident in what we are pioneering.

Hui Cai: This is an exciting emerging field. Are there any unique risks associated with funding a company in this space?

Simba Gill: I think the risk is very minimal. And I don’t say that lightly. The reason I think the risk is minimal is because the starting thesis for the idea is to build upon what naturally exists. The parallel I use is if you go back to the early days of biotech, we were very focused on finding naturally occurring cytokines and growth factors and figuring out how to manufacture them externally and then develop them as pharmacological agents. So, think about G-CSF, GM-CSF, Interferon alpha, Interferon beta, human growth hormone – those were naturally occurring human growth factors and cytokines which we knew had pharmacological properties, and if we could figure out how to manufacture them and develop them as pharmacological agents we would be successful. We think that is highly analogous to our situation. Once we find the relevant microbes we’ll be able to develop them safely and effectively as pharmacological agents. A key area we need to focus on will be in process development and manufacturing because they’re biological agents, the products will be defined by the process under which they are manufactured. I don’t see that as an area of risk; I see it as an area of focus that needs to be developed in a very robust, very scientifically-driven manner, without that one doesn’t have reproducible, reliable pharmacologically active product.

Obviously, one always has to think through classic issues as with any drug, so we have to run the relevant safety studies, etc…. But for the field, I’m incredibly confident that in the future, what we are doing will be an inherent core part of the pharmaceutical industry in the same way that antibodies have become widely accepted.

Hui Cai: Do you define Evelo as a platform or product company, or both?

Simba Gill: We see ourselves as a product and platform company, but we’re a multi-modal platform company. Our platform has applicability across almost every disease area you can think of. We’re primarily focused currently on oncology, inflammatory and neuro-inflammatory disease, but we will grow the platform and we see extending the product opportunities to dermatology, metabolism, cardiovascular diseases. It’s almost without limits because what we’re touching is essentially evolutionary biology. We hope to grow the platform as the leader, and then develop a whole series of products linked to an understanding of the immuno-microbiome. We’re not a microbiome company; we’re a company that is developing a platform and products based on an understanding of the immuno-microbiome.  It’s a subtle point, but it’s an important one.

Hui Cai: I noticed Evelo has several partnerships in place already, such as with Mayo and the University of Chicago. Are partnerships important to help Evelo advance its platform?

Simba Gill: We have already identified several microbes very quickly because they exist in nature and we know how to find them. The positive challenge we have is that we want to continue to invest heavily in the platform while moving forward many different products across many different therapeutic areas. It’s incredibly broad as a field and the potential constraints around developing the breadth of the platform and the breadth of the product opportunities are access to capital and pulling in the right leadership, the right capabilities as well as partnering with the right people. We can’t do all of this on our own because it’s just too big a field.  So, partnering is very important to what we’re doing. We’re in a very lucky position where we believe, for the right opportunities, the world is ready to finance, in a big way, totally transformative technologies.

Hui Cai: What do you think Evelo will look like in five years?

Simba Gill: In five years, what we want to have firmly demonstrated is clinical proof of principal that individual microbes can modulate the immune system in the oncology context, in broad immuno-inflammatory disease systemically –  diseases  like rheumatoid arthritis, psoriasis,  as well as in the neuro-inflammatory area and neurology in general, as well as gut-related inflammatory diseases – and the beginnings of showing that the platform can generate products that have applicability in other areas, whether that’s metabolism, liver disease or beyond.

In a future time period, we would like for Evelo to have really led the way in deciphering the whole set of interactions between the microbiome and the human immune system.  That requires a lot of data to be generated – which we’ll do with our own capabilities as well as with partners – and for that data to be analyzed and deciphered.  From that, there will be many new targets, and many new direct opportunities that we believe will have broad relevance.

Secondly, as quickly as possible in the future, we would like to have established monoclonal microbial therapies – individual microbes that are pharmacological agents –as a fundamental modality in the pharmaceutical industry, with huge relevance across many disease areas, and the ability to develop highly effective, safe, orally-delivered products at a price point which allows for drugs to be available to the whole world. That is very central to what we’re doing.

Hui Cai: What is your longer-term vision?

Simba Gill: We have a platform that allows us to develop important and safe medicines, very cost effectively and with high probabilities of success. We believe we have the leadership team to execute on this platform. Our mission is to develop medicines accessible to 7 billion today, growing to 10 billion to people tomorrow, versus the 300-500 million people currently addressed by the industry. That is our fundamental vision.

Hui Cai: Besides the microbiome, what other hot and upcoming areas do you see in the industry?

Simba Gill: Personally, I think one of the most exciting areas is the growing understanding of the neurology and the brain space. I think, secondly, the convergence of data and medicine. Combining these first two areas I founded a neurology data platform company called Blackfynn on the belief that the field of neurology is exploding and linking this to data and artificial intelligence presents an enormous opportunity. The third area that is incredibly interesting and exciting to me because it’s going to happen is germ-line gene therapy. We will fundamentally in our lifetime see germ-line gene therapy as part of human medicine. It will literally change everything forever.

Hui Cai: From an industry perspective, what are you most excited about?

Simba Gill: I’m most excited about, and always will be, global entrepreneurial activity. We are in one of the few industries in the world in which, from scratch, several companies worth $100 billion-plus have been created in the face of massive established incumbents.  So, the change in our industry will come from the new global players. I’m very excited about that because it will naturally force massive positive change on the industry.

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