Microbiologist Alex Sakatos felt strongly that valuable science was not making it from the lab to the clinic. This led her to start Ancilia which is finding ways to protect good bacteria in our gut from attack by viruses. A great chat about an exciting field in biotech.
Click here to read full episode transcript.
Highlights from our interview:
Sal Daher Introduces Alex Sakatos, PhD
Ancilia is Creating Ways to Protect Healthy Gut Bacteria from the Viruses That Can Attack Them
“...these viruses could directly prevent the efficacy of bacterial therapies…”
Founding Story of Ancilia
“... we actually know very well the mechanisms by which bacteria become resistant to phages, and so we can actually directly engineer those bacteria to be resistant to our phages…”
“So yeah, a co-founder is so helpful because founding a company is very, very lonely.”
Alex Sakatos. PhD’s Decision to Become a Founder
“...I leaped from academia into entrepreneurship was because I felt that there's more potential to actually develop research into therapies that impact patients.”
“...I learned from being in academia...if you don't do it, it's not necessarily guaranteed that someone else will. So, I think that it's important for more scientists to take their work towards translation.”
Parting Wisdom from Alex Sakatos
Transcript of “Ancilia: Defending Healthy Gut Bacteria”
GUEST: FOUNDER ALEX SAKATOS, PhD
Sal Daher Introduces Alex Sakatos, PhD
Sal Daher: Welcome to Angel Invest Boston, conversations with Boston's most interesting angels and founders. I happen to be recording right now with a founder who is in New York City, so we're making a bit of an exception, but she is a very compelling founder and I am planning to invest in the company. Her name is Alex Sakatos, welcome, Alex.
Alex Sakatos: Thank you.
Sal Daher: I should say Dr. Sakatos, she's a PhD scientist and she's the founder of a company called Ancilia, which is working in a very, very important area. All of you must have heard that I have an early investment in Vedanta Biosciences. Well, Alex's company is working in the same area. So Alex, please tell us what Ancilia does.
Ancilia is Creating Ways to Protect Healthy Gut Bacteria from the Viruses That Can Attack Them
Alex Sakatos: Sure. So, as you, and probably many of you know, over the last decade or so, there's been a huge amount of interest in the development of bacterial therapies as something that Vedanta is, and many other companies are working on. And this interest has been spurred by research that's shown that there's differences in the bacterial composition in the gut of patients with disease. And so the idea is can we use bacterial therapies to restore these changes in the microbiome composition and treat disease. But although almost all the focus to date has been on these bacterial components of the microbiome, at least half the organisms in the gut are actually viruses, and most of these viruses are bacteriophages, which can directly attack and kill commensal bacteria strains.
Sal Daher: Commensal are bacteria that are present normally.
“...these viruses could directly prevent the efficacy of bacterial therapies…”
Alex Sakatos: Yes, exactly. So normal in healthy individuals. And so, you can see that this could present a significant problem for a couple of reasons. So first you can imagine that there's patients and people with disease, as we have found, have increases in these phages in their gut, and that actually can deplete and kill these healthy commensal strains, which can drive the changes in the microbiome composition and lead to disease. And then also, furthermore, these viruses could directly prevent the efficacy of bacterial therapies, because you can imagine that if you give someone a bacteria and they have a phage that attacks that bacteria, that phage is going to attack the therapy, prevent its colonization in the gut, and prevent its efficacy. So what we're doing is working to first identify these phages in the gut, and then develop specific phage resistant bacterial therapies to prevent phage predation and treat disease.
Sal Daher: Oh, excellent, excellent. If you don't mind my restating it, you can either give me thumbs up or thumbs down.
Alex Sakatos: Sure.
Sal Daher: So basically, we have this flora, this population of bacteria, fauna I should say of bacteria in our gut, which has amazing implications to our health. It controls things as diverse as our immune system, affects our moods, can have impact on cancers and all kinds of things, and also those bacteria can become problematic. People who are in the hospital, they can have infections because of the virus, there are phages that attack the healthy bacteria in the gut.
So there have been attempts to create therapies, treatments, for various problems using the gut bacteria. They extract gut bacteria, they re-engineer them, and they try to repopulate the gut with these engineered bacteria. And a major obstacle to those therapies is the attack that phages, bacteriophages that eat bacteria, and they destroy the bacteria, the new bacteria that you're trying to introduce into the gut. So what Alex is working on is creating a defense, creating a way to allow new bacteria to be introduced or to protect the gut's healthy bacteria from certain bacteriophages. Do I get at least a B?
Alex Sakatos: Yes, no, that's pretty perfect. I think the idea is that it is a defense and similar to the way our bodies have defenses against viruses, bacteria have defenses against viruses, and we're trying to enhance that defense in patients that need it to improve the efficacy of these therapies.
Sal Daher: Okay. Would you care to tell us the founding story of Ancilia?
Founding Story of Ancilia
Alex Sakatos: Sure. I was at Deep Science Ventures, it's a London-based biotech incubator and venture fund. They recruit people with science and engineering backgrounds to scope out opportunities for company creation across biotech and pharma. And it was there that I started really looking into the field of the microbiome. I've always found it fascinating, I did my PhD in microbiology, so always interested in the space. Into looking at the landscape of the field I was struck by the fact that there has been so much interest and people doing very exciting things to develop therapies, but there has been very limited focus on the viral components, which seemed to be a critical gap in terms of getting these therapies to work in certain patient populations. And so that's where I was struck by the opportunity and also at the time brought in and reached out to certain leading academics in the field who've done a lot of work characterizing viruses in the gut, and have worked with them very closely thus far to do proof of concept experiments around the approach and the idea and have been really critical partners to advance the company.
Sal Daher: So, this group gave you some funding?
Alex Sakatos: Yes.
Sal Daher: Excellent. And then you decided to launch the company. Now tell us, how do you anticipate that this would go? So presumably you are looking for various types of bacteria that are resistant to phages. I mean, are you going to have your patented bacteria that you're going to discover? How is that going to work? Is it going to be trade secret? Are you going to have patents that defend your intellectual property? How is it that you're going to build your moat, so to speak, to keep competition out?
Alex Sakatos: Yeah, so definitely very focused on filing patents. So we have one provisional patent filed, we're filing another one, I'm actually in the midst of it, so in the next couple of weeks. And the idea actually, the approach, is to start with identifying the phages. So first we want to identify the problem, so we started with IBD, so inflammatory bowel disease is one of the most widely studied diseases, that's linked to changes in the flora in the microbiome. And so we identified phages in the gut that are linked to disease in IBD and we're starting with those targets working now to develop bacteria that are resistant to those phages.
Sal Daher: Okay. So, you went out and searched for the viruses that are creating all the problems and you have identified a set of viruses that are the ones that might be implicated in irritable bowel disease. And so the next step is that you're going to take various types of gut bacteria and expose them to the viruses, and you're going to find that some of them are killed off by the viruses, but there is some of them that are resistant, and then you're going to figure out some way of multiplying the resistant strain. So you're basically bacteria breeding; you're breeding bacteria like selective breeding of bacteria, like selective breeding of horses.
“... we actually know very well the mechanisms by which bacteria become resistant to phages, and so we can actually directly engineer those bacteria to be resistant to our phages…”
Alex Sakatos: So yes, we can enrich for phage resistant bacterial strains by exposing the bacteria to phages, as you said, and that is something that we're working on doing. But in parallel, we actually know very well the mechanisms by which bacteria become resistant to phages, and so we can actually directly engineer those bacteria to be resistant to our phages of interest by manipulating those mechanisms that are well characterized.
Sal Daher: So basically, gene editing, using gene editing techniques, to edit the genes of the bacteria to make them resistant to the bacteriophages.
Alex Sakatos: Right, exactly.
Sal Daher: Okay. So, it's more like GMO bacteria?
Alex Sakatos: Yes, yeah. GMO bacteria.
There's some negative connotations with that, but we like to say we're enhancing the immunity of the bacterial strains, because we're actually using the endogenous immune systems that bacteria use naturally and we're enhancing them against these virulent phages.
Sal Daher: Alex, the community that invests in biotech, I don't think there are many GMO skeptics in the community.
Alex Sakatos: That's certainly fair.
Sal Daher: It's a different set of people that might be investing in other things, but not biotech.
Alex Sakatos: That's very true.
Sal Daher: Excellent. And now, so your idea here then is to engineer some of these bacteria that are resistant to bacteriophages, and once you have that, you're going to look for some strategic player with whom you can make an alliance, are you going to be thinking of producing these bacteria and selling them yourself? You're going to create the business? What are your thoughts in terms of your business model? How is it that you're going to make money with these particularly talented bacteria?
Alex Sakatos: Yeah, so the idea is that it is a platform technology, and so we can use it to both develop therapeutics internally, but also as you say, develop key partnerships with other players in the field. So as you mentioned the beginning, there's a huge amount of companies interested in developing bacterial therapies to treat microbiome associated diseases. So, the idea is that we could work with those companies, we can identify phages, and improve the efficacy of certain therapies.
Sal Daher: Yes, yes. I think that from an angel investor’s perspective, it is much more desirable for a biotech startup to find a strategic player who is interested in one aspect of its platform technology and license that out, and then use the funds from the licensing to help build out the rest of the company so that you don't end up having to raise hundreds of millions of dollars, reducing the interest of the angels to the smallest bacteria, microscopic size, and also your own interest as a founder.
Would you like to talk a little bit about the team?
Alex Sakatos: Sure. So, I'm the only full-time founder right now, but I've worked closely with bringing on David Espino, he's a bioinformaticist, did his postdoc at UC Berkeley, has had a huge amount of experience, publications, in doing analysis of the viromes. And then I've also worked closely with a founder at DSV, Matthew Cummings, who is serving as a board member and advisor. And then we're really focused right now on the academic collaboration. So, we have key academic collaborations at Wash U, at St. Louis, at University of Colorado, and starting one shortly with North Carolina state to complete these initial experiments to prove that our first therapy shows efficacy in mouse models. And so that's where the focus is to date.
Sal Daher: Okay. So, you're early on, so it's still building out the team on the academic side.
Alex Sakatos: Yes.
Sal Daher: Eventually you're going to need somebody who is more on the business side, but for now it makes sense that you'd be just doing the academic side, the science, because that's what's going to move the ball forward. I recently interviewed a very successful venture capitalist in Boston, his name is Russ Wilcox. And Russ is a seed stage investor in Boston, and too bad that I think they focus only on Boston companies, but otherwise I would connect you with Russ because I think this is his kind of company, it might interest him.
Alex Sakatos: Oh, interesting.
“So yeah, a co-founder is so helpful because founding a company is very, very lonely.”
Sal Daher: He's a deep tech guy. He is in the founding team that brought to market the e-reader, E Ink, e-reader, Kindle and all that. He brought the technology out of MIT Media Lab, Joe Jacobson, and so forth.
And his advice to founders was, get out and get yourself a co-founder. Instead of being in a room by yourself, putting stickies on the wall and saying, "I'm doing this." Get a co-founder, somebody who compliments your skills, somebody who you can work well with. Don't be so scared of getting the wrong co-founder, because, yeah, you can lose a little bit of equity that way, but you can have vesting schedules and all that stuff to protect you, make sure you get the right documentation for when you're bringing on a co-founder, so that if the co-founder doesn't work, you can pull the plug and the co-founder walks away with a small bit of the company, but doesn't hinder your future ability to bring in more capital and the co-founder of course end up with common equity, and then you can still bring in a group of preferred equity people above that. So yeah, a co-founder is so helpful because founding a company is very, very lonely.
Alex Sakatos: Yeah, no, I think that's for sure. Co-founders are important and look forward to building the team going forward. I think as to now, I view a lot of my academic collaborators as co-founders, they've done a lot of initial work and work closely with them. So it's been a fruitful collaboration thus far.
Sal Daher: Well, I think your academic collaborators might end up being advisors, your advisory board, your scientific advisory board, one of them might end up on your board, depending on the working relationship they have with you. But a co-founder is really a different thing, I mean, they're really going to bat for you and they are also coming in full time with you.
Alex Sakatos. PhD’s Decision to Become a Founder
So Alex, let's talk a bit about your decision to become a founder. You were a successful scientist, and scientists are people who sacrifice a great deal of their life in order to become scientists. It can be compared to priesthood or something, it's something that excludes you from everything else in order for you to become good at it because it's such a difficult thing. So how is it that you decided to leave the priesthood of science and immerse yourself in the sordid world of commerce, albeit of scientific commerce?
“...I leaped from academia into entrepreneurship was because I felt that there's more potential to actually develop research into therapies that impact patients.”
Alex Sakatos: Sure. So, I guess I'm not sure I really ever thought I would start a company. I don't think my aim was ever necessarily to start a company. I always loved science and I really loved the research and I liked the potential for impact that it could have on patients and on treating diseases. And I think the reason that I leaped from academia into entrepreneurship was because I felt that there's more potential to actually develop research into therapies that impact patients. And that really was my passion and interest. And that's how I thought starting a company was the best way to achieve that goal.
Sal Daher: Okay. Was there a particular event that got you thinking in terms of the impact of science on the treatment of people?
Alex Sakatos: I would say that's one of the main reasons I liked science from the beginning. I worked in a neuroscience lab before I went to grad school, and then in grad school, I did my PhD in microbiology, but in the school of public health, so I was really interested in the impact that the development of new therapies and treatments could have on a patients scale and on a population level. And I always liked to think about science, not just in terms of the experiment and the exciting new discoveries you can have, but how those discoveries could really translate into something that can help patients. And so that's why I wanted to make the transition into entrepreneurship to really make those developments into therapies and make those concrete.
Sal Daher: I've seen this with other founding scientists or scientific founders, and they feel that they've developed something, they've discovered something, they're working on something that's so exciting to them, they say, "I imagine what impact it could have in the real world." Instead of just creating more science and letting somebody else do the work of translating that to the market.
“...I learned from being in academia...if you don't do it, it's not necessarily guaranteed that someone else will. So, I think that it's important for more scientists to take their work towards translation.”
Alex Sakatos: Exactly. And I think that the one thing I learned from being in academia for a while is that, if you don't do it, it's not necessarily guaranteed that someone else will. So I think that it's important for more scientists to take their work towards translation.
Sal Daher: Well, yes, the people who study innovation, professor Ed Roberts used to say that, innovation is the product of invention times commercialization. So if one of those is zero, there's no innovation. Because invention is not the same as innovation. Innovation is something which is not only new, but it is effective. It acts in the world, it is a new thing that has action in the world. And invention is something that can be abstract. I mean, you can invent something that works in the lab, but has no effect in the broader world. And the reality is that most scientific discoveries never have a practical application, so they remain just as inventions, discoveries, but they never become innovation. So that process of transferring things from the lab to the clinic is a very difficult one, and it's one that is a very noble one. I was just joking when I talk about sordid; you have to be slightly flowery languaged to keep people awake on a podcast when you’re talking about science so it's like, "Oh."
Alex Sakatos: Makes sense.
Sal Daher: But it's a very noble thing, particularly, this is being recorded in a time of COVID-19, everybody's on lockdown, we're recording online. And at a time like this, you think about how important it is for scientists to get their discoveries from the lab into a place where it can be used for the benefit of the population in general.
We're recording this in the very last day of April of 2020, and you think about, there's a lot of hope right now that there will be a vaccine that will allow everyone in society to return to their normal lives instead of just being hunkered down. A young person like you is not at risk right now, but the older population is 18, 20% of the population that's going to be on lockdown for a long time until there's an effective vaccine, until there's somebody who takes a discovery from the lab and commercializes it or brings it to the clinic.
Any of your parents entrepreneurs?
Alex Sakatos: No, no. My parents are both accountants. So pretty much the opposite.
Sal Daher: Both accountants. Oh, wow.
Alex Sakatos: Yeah, they were.
But I do have entrepreneurship in my family, on my father's side, well, I have two uncles that were tech entrepreneurs.
Sal Daher: Ah, okay, okay, okay, okay.
Alex Sakatos: So not totally out of the family line.
Sal Daher: Oh yeah. Hey, you can hit them up for funding too. And no, just joking aside, having a model. It just tells you that it's possible it can be done. And it's a noble thing. You think this person or that person, what they do is exciting and so forth, it is helpful to have that.
Anyway, Alex, are there any further thoughts that you have that you'd like to share with us?
Parting Wisdom from Alex Sakatos
Alex Sakatos: I got advice very early on in my career, which was from a really valuable mentor who just told me to do what you love and everything else will work itself out. And I've really tried to stick to that even as impractical as it can be at times. But I think it's really important, especially starting a company, is not easy, so you really have to enjoy it to stick with it.
Sal Daher: Okay. I think that is very true. Because you're not going to do this if your motivation is to make money. At some point you're going to look in and say, "Are you kidding me? I can go work for Merck, AstraZeneca blah, blah, and make many times more than I could ever make doing this, blah, blah, blah." So it's not going to get you through. In order for you to do this, it's got to be something that you're really passionate about and that you really love doing. And I can tell you're very, very passionate about this. And so I wish you well on the starting of the venture.
Alex Sakatos: Thanks so much.
Sal Daher: Let's stay in touch, keep us updated.
I hope you've enjoyed this excellent conversation with a promising young founder, Alex Sakatos, PhD. And I'm very grateful to you, Alex, for coming on the podcast, thanks.
Alex Sakatos: Thanks for having me. I really enjoyed it.
Sal Daher: Awesome, awesome. I hope that you will take also a little moment and go to iTunes and leave a review for this podcast, two or three iTunes reviews, I think it gets featured on the front page of iTunes, when the reviews pop up when the podcast is the current one, that podcast gets extra downloads, I've noticed. But anyway, this is Angel Invest Boston, I'm Sal Daher.
I'm glad you were able to join us. Our engineer is Raul Rosa. Our theme was composed by John McKusick. Our graphic design is by Katharine Woodman-Maynard. Our host is coached by Grace Daher.