Episode 6: Biological Cartography; How Kallyope is Mapping the Gut-Brain Axis
Behind-the-scenes at Kallyope’s offices, and a conversation with CEO Nancy Thornberry.
In Episode 6, Lux Capital Managing Partner and Co-Founder Josh Wolfe sits down with Nancy Thornberry, CEO of Kallyope (a Lux portfolio company). Watch the entire episode above, and what follows is an edited version of the interview transcript.
Josh: Today we’re sitting down with Nancy Thornberry, CEO of Kallyope, a biotech company that’s developing a state-of-the-art platform to harness the potential of the gut-brain axis in order to treat diseases of significant unmet need. We’ll take you behind the scenes to show you how Kallyope mixes cutting edge biotech and computer science to target the gut-brain axis.
Josh: There were a ton of companies that started in this microbiome space, but you did something very different. Kallyope is focused on the gut-brain axis, which seems to be quite singular. What is the gut-brain axis in layman’s terms?
Nancy: The gut-brain axis is the bio-directional communication between the gut and the brain. It’s composed of neural circuits and composed of hormonal circuits. This axis has been implicated in a broad array of physiology and disease.
Josh: When people say that the way to a man’s heart may be through his stomach, it sounds like it also may be that the way to a man’s brain may be through his stomach.
Nancy: There’s no question that important aspects of physiology are mediated by the gut-brain axis, so we very much believe there’s a biochemical basis for things like a gut feeling, for example.
Josh: Now, let’s talk about some of the technologies. You’ve got computer science, you’ve got gut biology, you’ve got neuroscience, what are the sequences of steps that you have to take to come up ultimately with a gut-brain axis?
Nancy: We are leveraging a number of advanced technologies, many that have only been available in the past decade or five years or so in order to create a comprehensive map of gut-brain circuits. That really starts with having an understanding of the gut itself. Through single-cell sequencing, for example, which allows us to understand what every single cell type is that’s in the gut, with circuit mapping that allows us to understand how cells are talking to each other, and how gut cells are actually talking to cells in the brain. We use organoids, which are mini guts that are in a test tube, that enable us to translate our work more rapidly. There are a variety of different technologies that we’re using. I should also mention optogenetics and chemogenetics.
Josh: What is optogenetics?
Nancy: Optogenetics is a tool that was developed in neuroscience and allows us, once we identify a cell type in the gut that we think is important, to then get genetic control of that cell. For example, we can put a protein in there that’s sensitive to light and then we can use light to activate that cell and understand its function.
Josh: So you’re using external light to stimulate a cell and produce a response. It sounds like it’s something straight out of science fiction.
Nancy: It’s pretty remarkable technology and it’s so powerful because it does enable us to understand at a cellular level what the function is.
Josh: What’s the implication of all of this? You map the gut-brain axis, you develop an atlas, this is presumably now a treasure map to either develop drugs or targets.
Nancy: Yes.
Josh: What is the everyday person going to experience some years hence?
Nancy: Our goal is to take this incredible technology and data and use it to identify circuits that are involved in diseases of high, unmet need and then to target those diseases with gut-restricted molecules. Small molecules that would be orally delivered that will essentially target the brain via the gut, to hopefully result in breakthrough therapies for the treatment of these diseases.
Josh: One of the things we love at Lux is finding the rebel scientists, inventors and engineers who are, in some way, testing the boundaries and breaking the rules of what was conventionally understood to be possible. What scientific rules are you breaking at Kallyope?
Nancy: At Kallyope, we are taking a fundamentally new approach to target the brain via the gut.
Josh: How was it done historically?
Nancy: Small molecules were developed, which actually target the brain directly. They have to pass through the blood-brain barrier, and often they have off-target activity that results in side effects. We are instead targeting circuits from the gut to the brain with molecules that never leave the gut. So it’s a fundamentally new approach and allows us to really start to go after diseases that have historically been very tough to treat with small molecule therapeutics that target the brain.
Josh: Now, one of the founding scientists has used this analogy that I like a lot, which is the idea of playing a piano. In the same way that I might sit down at a piano and hit a note and it produces a sound or a chord and it produces a different sounds, the idea is that if you can use gut-restricted molecules, that you are basically targeting different notes that you can play in the brain. Is that an accurate description?
Nancy: Yes, it is. The circuitry between the gut and the brain can be complex. In feeding, for example, there are multiple circuits that essentially tell us that we are full. It’s important to understand the functions of the different cell types and then know how to manipulate them in such a way as to, for example, produce a feeling of fullness, that could have relevance for the treatment of obesity.
Josh: That would be amazing. Nancy, it is such a pleasure and honor to work with you. I am so excited we got to spend time and share a little bit about what you’re doing with the world. Thank you for coming by.
Nancy: Thanks so much, Josh, I enjoyed it.
Josh: That’s it from us today, I want to thank the rebel scientists and inventors at Kallyope for giving us a sneak peek of the future. And I want to leave you with a sci-fi book and a sci-fact book. Autonomous, a masterpiece on biotech and pharma, AI and robotics, intellectual property and what it means to be human. And the sci-fact book, Emeran Mayer’s The Mind Gut Connection, where you can read a lot more about the science that Kallyope’s working on. If you want to get in touch with us, reach out at Futura@Lux.vc, we’d love to hear your crazy ideas and inspirations.
This episode’s sci-fi and sci-fact recommendations:
Autonomous by Annalee Newitz (Sci-fi) and Emeran Mayer’s The Mind Gut Connection(Sci-fact).
