Neobe and the Cancer Matrix
Using bacteria to treat a disease like cancer may not seem very intuitive, but there are very smart reasons for doing so. No one knows this better than Dr. Pedro Correa de Sampaio, co-founder of Neobe, a company doing just that. No, the name isn’t a reference to the Matrix movies (for those of us old enough to remember them). It’s derived from “neo” as in new and “obe” as in the end of microbe, which makes perfect sense since they synthesize bacteria from scratch.
We also talked to Pedro about traveling as a scientist, setting up his own biotech company and the need for science communication.
Keep up with Pedro’s work and advances on Linkedin and check out the website for Neobe.
We’re very much enjoying listening to Afonso Cabral’s album Morada, which you too can download from Bandcamp, or check out his website for more info about his music.
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Episode transcript
[Background intro music playing is "Entre as Palavras e os Actos" by Afonso Cabral]
Parmvir: Pedro Sampaio.
Pedro: Yes.
Parmvir: How are you doing?
Pedro: I'm doing okay. I'm doing good. I'm really enjoying seeing you guys in London.
Parmvir: It is good to see you again. It's, although we have to kind of explain ourselves and say we've known each other for close to 10 years.
Pedro: Wow. Has it been that long?
Parmvir: I think so, yeah.
Pedro: Oh my God. Okay.
Parmvir: Yeah. I think at least nine. But bizarrely we've only met in person.
This is our second time meeting in person I think.
Pedro: No. Is it? I could have sworn we'd met more times, but no I think you're probably right.
Parmvir: Yeah. So I mean we were part of a group of people who were into like online meetings way before the pandemic.
Pedro: Way before it was cool.
Parmvir: Yeah, absolutely. So yes, it's a pleasure to see you again, and for everyone listening, obviously this is the 2Scientists podcast and I'm your host, Parmvir Bahia.
And we're here to talk to Pedro today because despite having known each other for this long, we've never really talked about each other's research. So why don't we do that? Let's begin with how you got into cancer research.
Pedro: How I got into it. Wow. Um, it's genuinely what I always wanted to do.
I mean, when I was a kid, I knew I wanted to be a biologist of some sort. I knew that I was interested in life. So sort of in, in general. So basically I was, I was either going to be a conservational biologist and go sort of study animals into, you know, natural reservations somewhere, or I was going to be a molecular biologist and do lab research and the moment I went in that direction, which was pretty much immediately, cancer was always something that I was interested in and something that I wanted to understand better and something that I wanted to do something about basically.
Parmvir: Yeah.
So you are from Portugal.
Pedro: I am.
Parmvir: And you ended up in Cambridge for your PhD.
How did that come about?
Pedro: Weirdly, a lot of the career decisions I've made in my life happened almost serendipitously. I was finishing my degree in biology. At that point I was still studying general biology at university in Lisbon. I knew I wanted to go down this direction. I wanted to do research, I wanted to do cancer research, so I just started sending out a ton of emails all over the place to people who were doing research that I thought was interesting asking, can I come, sort of follow you around in the lab and learn from you? And this group that was at the time in Cambridge responded to me saying, oh, you know what? We actually have this project going where we are trying to basically build cancer blood vessels in the lab, but the student who is doing it is leaving and we need someone to take it on. Do you want to come have a chat?
And I went and had a chat, and that chat somehow turned into a masters, and that masters turned into a PhD. That turned into six years living in Cambridge and becoming a cancer researcher.
Parmvir: As you're talking about this, it sounds so easy because my PhD was the same. Like I literally sent out emails to two people and they both said, we want you to do a PhD with us. And it feels like for grad students these days, that is not the thing. Like they spend ages.
They have to have load of extracurriculars. They have to have research before they even get there. I'm like, what is going on, man? I would not get a PhD on the basis of my background now, if I were to apply to a program, I would not.
Pedro: Yeah. It's all so over-subscribed. We're finally now, which is a conversation that I'm sure we're gonna get to, understanding that doing a PhD doesn't necessarily just mean you become a PI or you're going to do something else with your life. There's all sorts of things that you can do with a PhD, which is great, and it's true, but that means that it's probably, you know, people are starting to realize this. So a lot more people are trying to get a PhD and it's a little bit harder to get into them.
I did send a lot of emails out. I didn't just send two, I sent a lot of them out. But it was just the fact that I was taking the initiative to go look for one of these positions at the time was what the person who eventually became my PI told me like, this is the kind of attitude that we want in the lab.
Parmvir: Yeah.
Pedro: So we liked that. We met you, you did well in your interview, and that was kind of it. If I, you know, had to combine that with writing 5,000 words on why I think becoming a cancer researcher is important, I'm not sure that I would've passed the threshold. .
Parmvir: So we, we have this horrible tendency to use a lot of vocabulary that people maybe don't know what is a PI?
Pedro: Oh God, you're absolutely right. That was, that was bad. A PI is a principal investigator, so that was my basically lab supervisor, the leader of the research group where I was doing my PhD and who was basically mentoring me thoughout.
Parmvir: Yeah. So after you ended up doing your PhD, you moved onto Houston and MD Anderson.
How was that in terms of like, a culture shift and what was the type of stuff you were researching there?
Pedro: The culture shift was huge. I mean, going from Lisbon to Cambridge to Houston, those are three very, very different places. But at that point I'd been living in Cambridge for six years doing my PhD. I was used to just getting on my bike and getting anywhere that I wanted to go within, you know, 10 to 12 minutes on a bike and suddenly I get to Houston and nothing that you want to do is, you know, less than 15 minutes away by a car.
Parmvir: Yeah.
Pedro: And I decided, when I initially moved to Houston, I was like, no, I don't agree with this!
I'm going to walk and I'm going to cycle [Parmvir cackles], and I walked for 45 minutes to the lab every day for about two months. And then I got a bike and that lasted for about an extra six months. And then I finally got a car and I never looked back. So, you know, just the fact of being in this huge sprawling city where you have to drive everywhere, where there isn't, there aren't the kind of downtown centers that we're used to as Europeans.
If you want to go to a museum, you go to the museum district. If you want to go to a bar, you go to sort of one of the bar areas of Houston, you kind of, you, you're always sort of traveling around and that was obviously a shift and, you know, 40 degrees, or I guess I should say, you know, a hundred degrees Fahrenheit.
Parmvir: Yeah.
Pedro: With a hundred percent humidity.
Parmvir: Yeah.
Pedro: For three months in the year took a while to get used to. [Parmvir laughs] Even coming from Portugal.
Parmvir: Yeah. Yeah. Same for us. Going to Tampa, I mean, exactly the same shift in culture, but I have to say like it feels like a more kind of pure American experience than had you moved to like the Northeast or somewhere, or to one of the bigger cities, right?
Pedro: Oh, yeah. I think so. And I loved it. I mean, it was certainly a, it was an adaptation, it was a steep sort of learning period. My first six months in Houston understanding how life works there. Understanding that if someone calls me saying, let's go for a drink a couple of blocks away, I am not just gonna walk there because that's gonna take me, you know, 35 minutes that I need to get in the car and get there. But I ended up completely falling in love with Houston, with it's multiculturality, with its artistic scene, its live music scene. It was a fantastic place to be.
And the science that I was doing there. I was working at a really exciting department at the MD Anderson Cancer Center, which is one of the leading cancer hospitals in the world. And I was doing really exciting research, understanding how cancer cells communicate with different parts of their microenvironment, which is basically everything that you have in a tumor that isn't a cancer cell.
Everything from blood vessels to the immune system to, you know, the collagen fibers that keep everything in place. How do those interactions govern the way that the tumor progresses and the way that a patient responds to therapies? And that was, that was really exciting to me.
Parmvir: Yeah, so I think, perhaps for a lot of people who think about cancer, they, they do think about the tumor and they think of this as a disease that is slowly kind of deteriorating the body in some way. But can you explain to us exactly what the problem is with a tumor and why it is so detrimental to the rest of our body?
Pedro: The problem with the tumor is that a tumor is part of us, right? A tumor is basically our own organism turning against us. It's not a pathogen that you can just treat with an antibiotic. It's your own cells that make up the organs in your bodies and your tissues that become mutated. It's genetic information changes. They become highly unstable. They start multiplying and dividing uncontrollably, and this changes the way that an organ is organized. It changes the function of the organ.
And then you have the problem of these cells starting to travel around and they build an initial tumor in say, your breast. And they, you know, make this lump that makes up the initial cancer. But then they go into circulation and they start traveling around and they get to your lungs, and they get to your brain and they get to your bones. And that's typically where they start doing the real damage and completely, you know, damaging the functionality of your tissues.
Parmvir: So David asks in your mind, what do you think is the biggest misconception that people have about cancer?
Pedro: That it is one thing. I think that's the main pet peeve of most people who work in cancer research is when someone comes to you and, and asks, so, why don't we have a cure for cancer yet?
Because cancer is not one disease. Cancer is a number of different diseases that are all very different. A breast tumor and a leukemia are both types of cancer that are completely different.
Parmvir: Yeah.
Pedro: And for some cancers, for some tumors we've taken great strides in the treatment of the disease and we've managed to, you know, increase the survival of patients that have these cancers.
And in some others we haven't because we detect them later, because they're harder to remove. And that's what people need to understand. We're not gonna have one silver bullet magic cure for cancer. We're going to have different treatments that are going to enable us to live with the disease for as long as possible.
Parmvir: Yeah. So how do you feel about various presidents in the US at some point declaring either a war on cancer, which was, I believe was Nixon and even...
Pedro: Biden's moonshots.
Parmvir: President Biden, you got the moonshot. Like what do you think when you hear these like this time we are going to fix it. Or do you feel that that's the impression that people get?
Because that's what I feel.
Pedro: I think it is counterproductive because on, on the one hand, I mean, I can't be mad at it. I can't be mad at, at, you know, the leader of the biggest country in the world saying, we're gonna take all of this financial power and we're going to put it into understanding and fighting this disease. This is obviously a fantastic thing.
Then as a cancer researcher, I obviously welcome it. But then it does lead to these awkward conversations where people come to you and go like, well, we've been putting so much money into fighting this disease for such a long time, why haven't we found a cure yet?
And that is the problem because people keep wanting to see a golden tablet that everyone's gonna take, and no one's gonna get cancer anymore. And they are completely ignoring the progress that has been done in so many different types of cancer, you know?
Parmvir: Yeah.
Pedro: In breast cancer, for example, depending on the type of breast cancer that you have nowadays, if it's detected early, you can have pretty long survival rates, which you didn't, you know 30 years ago.
Parmvir: And I think this is part of the problem that a lot of people are hoping for a cure, whereas what scientists are kind of working towards now, is being able to manage as a chronic disease before we get to that stage. Right.
Pedro: Yeah, yeah. This is why I have a problem with, with a cure. Because a cure, this is what, this is what people imagine in their heads is you're gonna take one pill, you're gonna to get an injection.
Parmvir: Yeah.
Pedro: And you're never gonna get cancer, or you're gonna get, or your surgery, you're gonna get rid of your cancer. Most of the time, what we're aiming for is exactly that. Is taking tumor cancer, trying to get into a chronic disease. Something you manage.
Parmvir: Yeah.
Pedro: Something that you'll hopefully treat as effectively as possible in one go, but you're probably gonna have to keep coming back and maintaining it in check.
This is what we're gonna aim for.
Parmvir: So, going back to your work at MD Anderson, how would you summarize the research that you did there and do you feel like there was kind of like a particular idea that you think came out of what you were doing?
Pedro: Wow. I mean, I worked on so many different things.
That was what was exciting about my time at MD Anderson actually was that I had, I was in this really exciting place that was doing cutting edge research and I had the good fortune of being in a lab that was well funded and that gave me the freedom to just explore a number of different things.
So I initially did some work trying to understand how prostate cancer metastasizes, particularly how prostate cancer cells spread to the bone, which is a significant clinical problem. Uh, and again, I'm going to use this word a lot of times, the microenvironments, the interaction between cancer cells with their local environment, particularly blood vessels and how that influenced the way they spread.
I worked in a really exciting, I think, new field, which is the field of extracellular vesicles or exosomes, which are little sort of message boxes that cells sort of release into circulation and that they use to communicate with each other, which we used to think were just kind of like little dumpsters that the cells released information that they didn't need anymore. But it turns out it's actually quite useful and it can be used as a way to detect cancer. It can be used as a way to treat cancer. And I did some work on that, but the area that I was most excited about, was spatial biology, meaning understanding not just the different components that you have in a tumor, which we know.
We know that we have cancer cells, and cancer cells are heterogeneous, and you have the blood system and you have all different kinds of cells of the immune system. You have fibrolasts. All of these cells interact with each other, but the way that they distribute in space within the tumor, influences the way that they communicate with each other and influences the way that the tumor behaves.
Parmvir: Ooh.
Pedro: And that was something that I was really excited about, and particularly the fact that we developed this technology where we could use a bunch of different fluorescent markers to identify different cells within the tumor, and then take a bunch of pictures in the microscope and develop algorithms to exactly determine how they interact with each other spatially. Where do these cells usually sit within the tumor, and how does that influence the way the tumor progresses? And that's led into a lot of the research that I'm doing now, which is the way that immune cells that are trying to react against cancer cells interact with local obstacles within the tumor. Things like fibers of collagen, for example, that prevent them from coming in and how that influences the way that we can treat tumors with therapies that activate the immune system against it.
Parmvir: Yeah. So David is very actively writing something right now.
Uh, And also like as you're talking about prostate cancer, I know this is something that David works on with his collaborators, like the,
Pedro: I haven't worked on prostate cancer in a really long time, so go easy on me.
[Parmvir laughs]
Parmvir: So he says, you talk about algorithms. How much does computational biology and math biology help your work?
Pedro: So, I mean, they've helped my work and they've contributed to my work in a lot of different ways. In that particular project that I was talking about, which is one of the projects that I most enjoyed being a part of, I mentioned that we were developing markers, we're developing kind of fluorescent signals that identify different cells in the tumor. So we're talking about eight or nine different data points, which represent the cells that we're looking at in the tumor across each image. And we're taking hundreds of images per tumor, and we're looking at dozens of tumors in one go.
Parmvir: Yeah.
Pedro: So this is a lot of data. This is a lot of information to go through when you're trying to identify where each cell is in each tumor and turn this into something that you can actually extrapolate information from. You can't do this without mathematics. You can't do this without computational biology. So thank you David [Parmvir laughs] .
And you know, right now, and I'm sure we'll get into it at some point, what I'm doing involves sa lot of synthetic biology, meaning engineering, biology, taking bits of DNA and modifying them to do what we want them to do. And for that, having the right software and being able to use computational biology is also very important.
Parmvir: So that seems like a very good segue into what you are doing now because when we first spoke about you moving back to the UK, I was under this assumption that you were helping somebody else set up a company. And yet, when I talked to you later, it's like, Hmm, hang on. He's the CEO, that means that he's done this himself.
So what was this leap that took you from working as a postdoctoral researcher in somebody else's lab where obviously like you've got somebody else who's managing all the other people, they're bringing in the funding and so on, to all of a sudden now being essentially not just your own boss, but trying to set up a company yourself.
How did that come about?
Pedro: Oof. How much time do you have?
Parmvir: [Both laugh] How much time do you have? I know we've got lot more time than you do.
Pedro: Oh, no, it's fine. I basically already decided that I wanted to take a step away from academia and I don't want to, you know, make it a big deal. It was basically, I just felt that I wanted to do something more applied with my life.
This project that I was talking about, the spatial biology project, it was a huge collaboration between us and other groups at MD Anderson and mathematical biologists and companies. And it was very much like, okay, let's build this project around the problem that we are trying to solve, and let's have something that is an output from that. And I realize that this is what I enjoy doing, is trying to identify a problem, finding a solution for this problem that leads into a product, something that's going to actually come into the real world and make a change.
I was getting a little bit, you know, fed up of the whole cycle of publishing papers to get grants to publish paper, to get grants. Nothing against it: it's the way the system, well, somethings against it, but that's a different conversation [Parmvir laughs] . But you know, I can't do what I'm doing without all of the academic research that provides the foundations for the work that I'm doing.
But I just wanted to work on something that had real output.
Parmvir: Yeah.
Pedro: So I decided that I wanted to get to go into startups because I also didn't want to go into like a huge pharmaceutical company,
Parmvir: Mm-hmm.
Pedro: and just be a tiny little cog into a huge machine. I wanted to actually work on something that was a project that I could, you know, get some application out of.
And obviously the initial, the most logical way of doing that is to go work for a startup, which I did. And I worked with a really exciting, immunotherapy startup that was based in Canada at the time. And around that same time, I had gone to a conference where I met this company called Deep Science Ventures that is based here in the UK.
And what Deep Science Ventures does is they take scientists that have, you know, a background in a particular area that they're trying to address, and they train these scientists to solve a problem through building a new venture.
Parmvir: Mm-hmm.
Pedro: And one of the areas that they were interested in, there's that word again, was the tumor microenvironment.
Parmvir: Yep.
Pedro: They wanted to build new companies in collaboration with Cancer Research UK, which is the biggest funder of cancer research in the UK, as the name indicates, they were trying to build new companies to exactly try to come up with new solutions to tackle the tumor microenvironment and how it can create obstacles to cancer treatments, which was a hundred percent my jam.
Parmvir: Yeah.
Pedro: So we met in this conference in Miami through a mutual love of manatees. And
Parmvir: Love of manatees, did you say?
Pedro: Yes.
Parmvir: Okay.
Pedro: Kirsten, who's the director of the company was, you know, we were having a couple of drinks and chatting about science and one of the social gatherings of the conference, and we both started talking about manatees and getting excited about seeing manatees from the hotel that we were in.
And somehow that turned into, oh, what do you do by the way? Oh wait, we're starting, we're trying to start companies in that area. Don't you wanna come work with us? And I did. I decided, why not give it a try. I'm already working with a startup, which I'm really enjoying to do, but now I have the opportunity of turning my own ideas into a venture project. And that sounded super exciting.
And we were also starting to be involved in the middle of a once in a lifetime pandemic. And I was stuck.
Parmvir: Oh yeah, that thing.
Pedro: Remember that thing?
Parmvir: Yeah.
Pedro: Yes. And I was stuck in my childhood bedroom back in Lisbon [Parmvir laughs], without being able to travel or start to new job anywhere else.
So I was like, you know, why not? Let's give it a go. And it ended up turning out quite well. And I started the company in January, 2021.
Parmvir: Is it possible that it might not have happened without the pandemic, or do you think you still would've gone there?
Pedro: I think it could have happened without the pandemic.
I'm not sure that I would've had the balls.
Parmvir: Uhhuh .
Pedro: Oh, can I say that?
Yeah.
Parmvir: Yeah.
Okay.
Of course. We've had swearers on this show.
Pedro: Okay. Good.
I I was on the verge of moving to Canada to go work for this company,
Parmvir: Right.
Pedro: Which is a really exciting company and I'm still in touch with them, and I love what they're doing, which was, you know, a job that I was excited about that had some stability to it. Would I have dropped that opportunity for the possibility of starting a company without really knowing how well that was gonna work out?
Parmvir: Mm-hmm.
Pedro: Maybe not, I don't know. I can't say for sure, but the fact that I couldn't move,
Parmvir: Yeah.
Pedro: So I was stuck back at home and I had free time. I was like, why not give it a go? Let's see how this works, because obviously a lot of the work that you do in the beginning when you're starting a company, is done at your desk behind your computer.
Parmvir: Mm-hmm.
Pedro: You're talking to a lot of people. You're scoping the field. You're trying to define what exactly your strategy is going to be. You're building a business plan. And before I realized that I was hooked,
Parmvir: So I'm glad I didn't hallucinate that bit where you were actually working for somebody else. Yeah. But you started,
Pedro: No, no, no. That's true.
Parmvir: Very good. Very good.
So related to that, David says, what was the biggest challenge in your transition?
Pedro: I've had this conversation with people before. When you, when you go from, generally from academia to the industry, not necessarily building a startup, there's obviously a lot of challenges associated with it. But I think one of the biggest things is, if you, I don't know if you saw the Loki show.
Parmvir: Yes. It was great.
Pedro: When it was on Disney Plus, it was great, right? It was, yeah. I loved it too.
So the whole thing on Loki was about the Sacred timeline.
Parmvir: Mm-hmm.
Pedro: Right? And how they had to go back and pick people off who damaged the sacred timeline.
Parmvir: Uhhuh.
Pedro: Because anything that got out of the sacred timeline was completely going to destroy the world.
Parmvir: Yeah.
Pedro: That's working in a start up [Parmvir laughs out loud].
Right? Like you've got a goal and it's a clear goal and you're moving straight ahead to reach that goal. There is no time to diverge from the sacred timeline. There's no, there's no time to be seduced by the shiny objects. Mm-hmm. . Right. And that was one of the things that I enjoyed the most about academia.
A lot of the projects that I ended up working with, were things that just, you know, I happened to come across and was like, oh, that's cool. Let's have a look at that.
I can't do that when I'm running a company.
Parmvir: Yeah.
Pedro: And I think that's the biggest change.
Parmvir: Yeah. I really enjoyed that metaphor [Pedro laughs].
I remember one of the other conversations we had at some point was that actually the first few months where essentially you were eyeball deep in legal documents that had nothing to do with science at all.
Pedro: I mean, it was the best way to learn how to do it.
Parmvir: Yeah.
Pedro: I was starting a startup from scratch and I had, you know, really great support from Deep Science Ventures and Cancer Research UK as I started, but I was, it was me and my co-founder. It was just the two of us, and we had to start the company, start the lab, equip the lab, get the experiments going, start building data.
We didn't really have enough bandwidth or money to go hire lawyers and give them a bunch of documents and say, fix this for me. I had to learn how to do it myself, and it took me forever.
Parmvir: Yeah.
Pedro: It took me like a day to go through one document that, you know, it had a lot of pages, but it was one document. But that's how I learned.
You know, we, we've got PhDs, the main thing that you learn to do how to be, when you get a PhD is, is how to solve problems if the problem is this legal document needs to be accepted by tomorrow, and you need to make sure that you agree with it and you need to understand all of this lingo that you've never dealt with before. You'll figure it out.
We learn new lingos all the time when you're working in science .
Parmvir: So, one of the things I wanted to ask you was how did you meet your co-founder?
Pedro: Through a common acquaintance. Someone reached out to me. So, okay, going back to the beginning, right. It would probably be useful at this point to actually explain what it is that my startup does. Um, it's called Neobe: Neobe as in neo and microbe, because what we're doing is we're engineering new bacteria, to go into tumors and take those barriers that I mentioned before that prevent immune cells from getting into the tumor and take them apart. So the point is, we get these bacteria into patients, we remove the barriers, kind of like microscopic Trojan horses. We open the walls to the immune system, the immune cells come into the tumor, and these patients can now respond to drugs that are already in the market that activate an immune response against the cancer cells.
Right?
Parmvir: Right.
Pedro: So I kind of put the idea together and the strategy together for the company. But I've never worked with bacteria before in my life.
Parmvir: Uhhuh.
Pedro: I don't know how to engineer bacteria. I've never done it before. So I needed to find someone who knew synthetic biology, who knew how to engineer microbes, who knew how to build a platform.
And I looked around for quite a few months, until someone I knew just happened to tell me: Hey, like there's this person, who has I think all of the skills that you need, and she's interested in a new challenge, why don't you talk to her? And I talked to her and we immediately hit it off .
Parmvir: I think Edward's drunk already.
Just clattering about in the corner there. Sorry. Carry on.
Pedro: No, that was it. I think we, we just, well, like we met, we immediately hit it off I thought like on first chatting to her, I immediately knew like, this is the person I want to work with. She had all of the skills that I didn't.
Parmvir: Yeah
Pedro: And we've just. I mean, I think if you want to start a company, one of the most important things is to have the right team.
And I think we had the right team from the beginning.
Parmvir: Yeah.
Pedro: We were just like completely complimentary in everything. Like I'm a cancer biologist, she's a bacterial engineer. You know, in terms of attitudes to science, in terms of what our soft skills are. We were very, very, very complimentary from the beginning.
So we just immediately started working really well together, and from the moment I met her, to us starting the company was three months.
Parmvir: Wow.
Pedro: Yeah.
Parmvir: What was her name?
Pedro: Annelise.
Parmvir: Annelise.
Pedro: Annelise Soulier.
Parmvir: Very good. So I'm glad you pronounced your, the name of your company because I've been reading it as Nee-o-bee, which sounds like a character from the Matrix.
Pedro: Which is what everyone says.
So I'm used to it.
Parmvir: I'm in good company. Then or in bad company, depending on company.
Pedro: No, no, no. You're in very good company.
Parmvir: So what was I gonna say? Oh yeah, so I mean, you've just said that you have no experience in dealing with bacteria and so on. So where on earth did this idea come from to get bacteria into, first of all, generate new ones and to put them into tumors?
Pedro: I mean, it came from the way that Deep Science Ventures kind of like encourage us to start new companies, which is through using first principles. It was, we started with the problem, what do we need? We need to remove these barriers to immune infiltration of the tumors. We need to find a way, where we can take apart these walls, so to speak, in the tumor without affecting the rest of the body.
The problem is that the walls, the fibrotic components of this barrier, which we call the extracellular matrix exist in every single organ of the body.
Parmvir: Yeah.
Pedro: So it's really hard to find a solution that will sort of open these walls up that will open ways to infiltration in the tumor and not in the rest, of the organism.
So I started kind of looking around, well, what can we do? How can we engineer something that actually responds to the tumor microenvironment, responds to the physiological conditions that you have in a tumor to kick out a drug that will take these fibers apart.
Parmvir: Yeah.
Pedro: So that we only do it in the tumor and you don't do it anywhere else.
Parmvir: Yeah.
Pedro: And there were a few different possibilities. We could, you know, I mentioned extracellular vesicles before. There's nanoparticles, there's viruses. None of these had the capability of actually acting as a single biological entity in the tumor that's gonna respond to a stimulus.
Parmvir: Yeah.
Pedro: And act in response to that stimulus.
And then I started reading about, bacterial therapeutics and I started becoming really excited about the field. I was aware of it, I'd read about it before, but I didn't realize just how far the field had gone since I'd last read about it, because I mean, this is a field that's been around since the beginning of the 20th century.
You had a British physician called William Coley that originally found that patients that had certain types of sarcomas and got bacterial infections went into full remission. This is data that has been there for over a hundred years and kind of went into oblivion for some time, but I think now as tackling the immune system and immune responses to cancer became such a big deal.
Parmvir: Mm-hmm.
Pedro: The field has had a bit of a resurgence. So there's a lot of companies that are doing really exciting things. Exactly using bacteria as therapies in cancer. And we're also in the golden age of molecular biology and synthetic biology. We've got all of these really exciting tools.
To build genetic circuits that, you know, transform bacteria into basically biosensors that get activated to do something in a particular environment. People are doing this in all sorts of things from climate science to agriculture.
Parmvir: Yeah.
Pedro: So why not take those principles and apply them to this?
Can we do it?
That's the question that I asked my co-founder and she said, yeah, I think we can do it. And we started a company.
Parmvir: So I mean the company currently is just the two of you, and we know that, oh, you have a third employee.
Pedro: I have a fifth employee.
Parmvir: Fifth?! Ooh. Going up in the world since we last spoke!
In any case, five people is still not enough to complete like a, a full scientific project and do all of the kind of the tests you need to do and then send it off into clinical trials.
So how does that work? Because you can't do this stuff by yourself, do you have external collaborators?
Pedro: I have external collaborators, and that was one of the most, I think, pleasant experiences in this whole journey that I've been through with what entrepreneurship is, is how easy it is to get really good collaborations.
Well, how easy, it's not easy, but how much people are actually excited about working together in collaborations. And I've got a number of collaborations with different academic institutions, both here in the UK and a couple of other countries, but particularly with a lab at the Barts cancer center here in London at Queen Mary University.
There's a research group there that is specifically interested exactly in how the extracellular matrix interacts with immune cells in cancer. And we kind of met in the early stages of me putting the company together and we started working together. We've got a joint PhD student, we've got a joint grant. So we do a lot of work with their group and we then have to work with contract research organizations for example as well. We don't have the logistics and we can't afford to have our own animal studies facilities, for example, so we work with companies that are hired to do those kinds of experiments.
Parmvir: Yeah.
So David asks: related to this, presumably while you're speaking with researchers, you're also speaking with the medical profession, right? And he says the medical field is quite conservative, so do you find a lot of resistance to your ideas from them?
Pedro: Yes. But you need to find the mavericks.
Parmvir: Right.
Pedro: And they are out there. We're not completely reinventing the wheel. There are other people that are doing these kinds of experiments out there. You need to go look for the doctors who are willing to take an innovative project to try to actually make a difference in the lives of cancer patients.
And there are thankfully clinicians in the UK who are doing clinical trials with these sorts of therapeutic modalities, and we've talked to them and they, you know, became really great supporters.
Others that we talk to are a little bit more resistant. But actually, you know, the large majority of people that we've talked to from clinicians to academic collaborators to investors, yes, we will very often have the odds: wait, really you're using bacteria to treat cancer.
But, you know, once we start getting into the science of it, most people will actually be really excited about it. And, you know, that doesn't mean that they don't understand the risks. There are obviously risks associated with it, but we're putting a lot of work into our platform to make sure that we're mitigating all of these risks from right at the beginning.
Thank you David. So I think the moment people understand that we're not just, you know, insane people that just decided, oh, we're gonna like take bacteria and put them into cancer patients. No, we're, we're building a platform where we're taking bacteria as a chassis, as a means to an end. And we're taking types of bacteria that are not pathogenic and we're using a lot of different genetic tools to modify them to make sure that they can't grow anywhere besides the tumor. And we we're, you know, putting measures in place to ensure that they're not able to grow in different organs, and we're making sure that they're only activated in the tumor. And we've got all of these things that we're adding to our products into our platform, that people look into and think, okay, this is, this is actually really interesting.
This is actually quite cool. And it could work.
Parmvir: Yeah. And I suppose this is probably bolstered by the fact that immunotherapies are, a very hot topic right now, particularly within cancer research. And essentially you are just giving people a pathway to kind of improve those therapies, right?
Pedro: Yeah, pretty much.
Because immunotherapies have been the biggest, I think, breakthrough in cancer research in the past 10 to 15 years. I was lucky enough to be at MD Anderson, you know, working in a lab that was collaborating with Jim Ellison when he won the Nobel Prize for it in, you know, 2018, I think it was.
Parmvir: Yeah.
Pedro: So, you know, it's a field that I've been excited about for a really long time, but as life-changing as they can be, when you look at patients that have solid tumors, and a solid tumor is basically anything that isn't a leukemia, a tumor of the blood. You look at patients that have solid tumors and only about 20% of them respond to immunotherapies.
Parmvir: Right.
Pedro: And this is a number that has stayed pretty much static. It's not changed much since immunotherapies became a thing and a big part of the reason why these patients don't easily respond to immunotherapies is exactly because of all of the components that you have in a solid tumor; the microenvironment, again. And this is an area that I was really interested in. This is an area that I've been doing research in a while and I was convinced that if we tackle the microenvironment, if we modify it, we can get these therapies that currently only work for about 20% of these patients and we can make it work for twice as many patients. And that is the whole purpose for why we're doing what we're doing.
Parmvir: Yeah. So coincidentally, we caught up today with friend of the podcast, Anson MacKay, who is a former guest, along with his partner David Adger. And Ansen, unfortunately, during the Covid pandemic, got diagnosed with throat cancer and has since been diagnosed with stage four. And he actually is one of the people who has been responding to immunotherapy.
So his tumors are in the lungs, and I'm not sharing anything outrageous because he's actually created a blog sharing his experience. So why is it that some people respond to these things and other people don't? Why is it you need this push from the bacteria to help more people?
Pedro: Well there's a number of different reasons. Not all patients don't not respond for the same reason. Right? And one of the things that has become kind of common speak in the, in the area is kind of like the temperature of the, of the tumor, right?
Parmvir: Yes. Yeah, yeah, yeah.
Pedro: So some tumors are, we call them hot or immunologically hot because there's a lot of immune cells that can come into the tumor. You've got something like a melanoma that can be very inflamed. A lot of, you know, different components of the immune system can easily get into this tumor, and if you make sure that these, the right types of immune cells are active through immunotherapies, they tend to have a pretty good effect. Then you have patients that have cold tumors, and these are tumors that for different reasons, barely get any immune cells coming into the tumor.
And there the problem is that you just don't have enough new genetic material being created to produce an immune reaction, for example, there aren't, there's just not an immune reaction being triggered at the start.
Parmvir: Yeah.
Pedro: But somewhere in the middle you have a type of tumor that is called immune excluded, and these are tumors where you can clearly see an immune reaction.
There's a bunch of immune cells coming into the tumor, but they get trapped on the edges of the tumor.
Parmvir: Mm-hmm.
Pedro: Kind of like an army trying to get into a castle.
Parmvir: Right.
Pedro: Which is sort of being trapped on the outside.
Parmvir: Yeah.
Pedro: And those are the patients that we're going after. We don't think that our bacteria is gonna make immunotherapies work for every cancer patient.
We're specifically designing them to improve immunotherapies in patients that have tumors like this, where the immune cells are there, but the drugs that activate the immune cells are not working because they're not getting to the place where they're supposed to be.
Parmvir: Yeah. Okay.
Pedro: So if we use these bacterial Trojan horses to tear the walls of the tumor down, then the immune cell army can come in and can start attacking the cancer cells.
Parmvir: Yeah. So you've got the hot ones and you've got the ones that you're talking about where they're essentially trying to get into the tumor. Why is it that they don't get into this final subset, people who have the tumors that don't respond at all.
Why?
Pedro: The people who have the cold tumors?
Parmvir: Yeah.
Pedro: I mean, there's a number of reasons for that, but one of the main ones is so tumors by definition, we kind of went into it a little bit when we were going into what actually cancer is in the beginning, are by definition genetically unstable.
Parmvir: Yeah.
Pedro: They're constantly getting new mutations. And new mutations means, new genes, meaning new proteins being created, this is how biology works, right? To get all of these mutations, the mutations means that the protein that is formed out of a particular gene is different. You're creating new peptides.
These peptides can be used as antigens, basically be used as a compound that is recognized by your immune system as foreign.
Parmvir: Yeah.
Pedro: And this is what activates an immune response against cancer cells. Some types of tumors are not as genetically unstable as others. Yeah. So they're not generating that many mutations there that leads to new antigens being formed.
Parmvir: Okay.
Pedro: So that doesn't trigger as much of an immune reaction. And there are different strategies that try to deal with that particular issue. That's not what we're going after. We're going after the ones that have the immune cells, but they're so dense because they're such a fibrotic reaction happening that they just like physically can't go in and we're trying to shove immune cells into the tumor .
Parmvir: So, I mean, one of the, obviously the fundamental premises of what you're trying to do is that you are creating new bacteria, like in my mind I'm thinking like building with Lego. How does that work?
Pedro: It's kind of like building with Lego, but with DNA.
Parmvir: Right.
Pedro: So it's, so it's virtual Lego for a big part of the project. Again, why computer science is our friend [Parmvir laughs]. You know, we are literally building sequences of DNA, which we are designing in the lab because we have tools to be able to do this. There are a number of bacteria for which we have laboratory tools that we can use to put DNA into these bacteria and make them produce things based on that DNA.
So what we, what we do is literally design genetic circuits that we then get synthesized and then we put that DNA into the bacteria. So then we do kind of build them as Legos because there are different modules to add. So we design one sequence of DNA that we call a biosensor. That means the bacteria is only activated once it's under a particular physiological condition. Say for example, low oxygen.
Parmvir: Yeah.
Pedro: Because tumors are pretty hypoxic.
Parmvir: Mm-hmm.
Pedro: And then we have a completely different genetic sequence. That means that when that initial sequence is activated, this new sequence produces a drug. And then we have a different circuit. That means that that drug is secreted and released into the extracellular space of the tumor.
Parmvir: Okay.
Pedro: And we put all of these different genetic circuits together into one building block and we put it into the bacteria and suddenly this bacteria is now with different biological entity that does what we built it to do.
Parmvir: Okay. So the bacteria itself is kind of a shell of an existing bacterium?
Pedro: Yeah.
It's a, it's a chassis. Okay. Is what we call it.
Parmvir: Nice.
David, are you sending me more questions? Maybe? I might move on then.
Pedro: There's a lot of, there's, I see a lot of writing happening
Parmvir: Yes, there is.
Pedro: And I find it very intimidating. I don't know what's happening.
Parmvir: Yes. The only way I could get him, in front of a microphone really was to do the podcast in Spanish, so now he's got a whole other series of work he needs to do.
but yes. Um, what was I gonna say?
I always get to a point where I have a brain fart. Yeah.
Pedro: Sorry.
Parmvir: I've, I've been listening to like everywhere I've gone recently has been playing music, which is reminiscent of my kind of like high school and university education.
Pedro: Yes. And also it's reminiscent of me, of Houston, because my favorite club to go to in Houston was like an eighties club that they had on Friday night at Numbers in Houston.
Parmvir: I think you took us there!
Pedro: Yes, I did . That's correct. I forgot about that. Yes.
Parmvir: And that was a joy.
Pedro: Yeah.
Parmvir: But yes, actually that's something that we haven't spoken about is actually the reason we've got to know each other is because you care about scicomm and outreach and I mean, presumably you don't have the time for that now, but I guess that if you are having to speak to investors and so on, like, this is something that really requires you to be able to explain your science well?
Pedro: Oh, a hundred percent. I don't have time to do outreach, which is a shame because it's something that I love doing and I hope that I'll be able to do again at some point. I do every once in a while go get invited to go talk to, you know, groups of students and things like that, which I still enjoy doing because science literacy is essential, but also being able to communicate your science in a way that people understand is essential. And that is a lot of what we did at taste of science is something that I've been passionate about for a really long time. And because of that, it's something that I've been aware of for a really long time.
And that was, I think, really important to prepare me to talk about the company because like a big part of what I do these days is try to get funding. Try to get funding when you are a startup founder means talking to investors, pitching the company to investors, and being able to tell a good story, and explain to them efficiently why what you're doing is important and how it is that you're solving this particular problem. And being able to talk about science clearly has really helped me with this. And the reason I can do this is, is because I was so interested in science communication for so long.
Parmvir: Yeah. So we've talked a lot about your background, the basic research you did, setting up a company like that's a lot. David had another question, which was, you're a Portuguese citizen that's lived in the US and now works in the UK. What do you think you have that people with a more conventional background don't?
Pedro: Oh God.
Way to throw me in deep end David [both laugh] . Ah, yes, a Portuguese citizen trained in the UK actually. Yep. Who lived in the US for seven years and now works in the UK. I think multiculturalism right now is so kind of like ingrained into how I live my life these days that I think that really does help. Because I mean, one: we have five people in my startup right now. Every single person is from a different country.
Parmvir: Uhhuh.
Pedro: Being able to communicate with people from different backgrounds is super important, and that's something that I've had to learn how to do because I've lived in places that are so different from each other.
But I believe sincerely that that also translates into the science and into the work. Because if you know how to communicate with people from different backgrounds, if you are used to being able to adapt to different situations, that translates to how you run a company. That translates to how you run a scientific project because you are adaptable.
You know how to respond to challenges, you know how to solve problems. And you know, as silly as this may sound you know how to speak different languages.
Parmvir: Yeah.
Pedro: But I'm not talking about languages in the sort of
Parmvir: Linguistic sense.
Pedro: Linguistic sense. You know how to adapt the lingo that you need to adapt to talk to different people in different contexts.
And this is how, you know, going back to what you were asking me earlier, how I suddenly had to learn how to read legalese to make sure that I could get all of these documents together to get the company started. It's really good training.
Parmvir: Yeah.
Well, on that note, we wish you very much success with your company we'll be watching with close interest just because, not just because you're our friend, but because it's a very cool idea.
And we want to say thank you so much for your time today. We really appreciate it.
Pedro: Well, thank you. It's always great to talk to you guys and I'm happy that we got to meet while you're in London.
Yay,
There was also the time that I did inject myself with radioactive material, and I'm still not a superhuman, so I'm very disappointed by that.
Parmvir: Boo!
Pedro: Yeah. ,
Parmvir: Or maybe you are.
Pedro: Or maybe I am. It was, it was disappointingly, anti-climactic. I basically just had to fill in a health and safety form. That was it.
Yeah. But kids don't rummage through old syringes when you're trying to inject biological material.
Parmvir: Moral of the story.
Pedro: Yeah.
Parmvir: Okay, That's great.
Pedro: How about I do this because then I can look at you and talk into the microphone at the same time.
Parmvir: Super.
Pedro: There we go.
Parmvir: Uh, well done David.
Pedro: We're smart.
Parmvir: Yes. Really not [Pedro laughs] like I've been doing this for 10 years and I still fuck it up.