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The Bioverge Podcast: From Bugs to Drugs

Kareem Barghouti, co-founder and CEO of VastBiome, sits down with Neil to discuss how his company is using AI to map the gut microbiome to discover novel therapies.

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Kareem Barghouti, co-founder and CEO of VastBiome, sits down with Neil to discuss how his company is using AI to map the gut microbiome to discover novel therapies.

Available on SoundCloud, here.

Available on iTunes, here.

Full Transcript


Danny Levine (Producer)
Neil, we've got Kareem Barghouti on the show today. Who is Kareem?


Neil Littman (Host)
I am incredibly excited to welcome Kareem to the show. Kareem is co-founder and CEO of VastBiome, which is doing some really cool things in the field of the microbiome. They've built a deep learning artificial intelligence platform to really come up with a high throughput way to screen the microbiome to develop novel therapeutics. So, full disclosure, they are a buyer verge portfolio company, but I'm really excited to talk to Creon about his journey. I think they've approached building the company in what is now known as this tech bio way. You know, Kareem is not a scientist by training. He came previously from Google so that, they have a really interesting cross disciplinary team and approach to building the company.


Danny Levine (Producer)
There was a fair bit of excitement about the microbiome probably about 10 years ago. It catalyzed several drug development efforts. Where are we in terms of understanding the microbiome?


Neil Littman (Host)
Yeah, Danny, that's a really good question. I mean, I think we're still in the relatively early days of understanding the microbiome and it's interrelation with the rest of the body. I mean, it certainly plays a a, and has a huge influence on everything from how drugs are metabolized in the gut and the efficacy of specific medicines to, its role in wellness and its role in disease. It has an influence on there's been some research, which I want to talk to Kareem about linking the microbiome to the brain and the central nervous system. I think we're starting to understand that the microbiome plays a large role in human health and disease. By modifying the microbiome, you can modify wellness and hopefully modify diseases within the body.


Danny Levine (Producer)
There's such a big landscape here to unravel and learn about VastBiome is using AI to help map and understand the microbiome. How do you think AI changes that challenge?


Neil Littman (Host)
Yeah, I mean, I, I think, and we'll talk to Kareem about this, but my understanding is they're doing this in a much more methodical, systematic approach than what has done in the past and that it's really being powered by big data. You need this advanced AI discovery platform that they built machine learning to ingest and understand the complex interrelation ship between the vast amount of data that they're ingesting into the system. They're not just looking at the, the, the bugs within the gut, but they're actually looking at the genetic signatures of those bugs. I think in order to mass and understand and interpret all that data, it really needs to be powered by this AI discovery engine that best buy them has built. I am excited to talk to Creem about the specific inputs and outputs of that system.


Danny Levine (Producer)
What else are you hoping to hear from him today?


Neil Littman (Host)
Yeah, I, I'm always really interested in the founding story. So I'm interested in Kareem's inspiration for starting fast biome, interested to hear about how their approach to building a therapeutics pipeline is different from a more traditional biotech company. They very much are a, a, a platform technology, not a single asset biotech company. So I, you know, I want to dive into it, you know, Kareem's point of view about what that means to him.


Danny Levine (Producer)
Well, if you're ready,


Neil Littman (Host)
Let's do it. Hi Kareem. I'd like to welcome you to the show today and say a big, thank you for joining us.


Kareem Barghouti (Guest)
Good morning. Hi Neil. How are you?


Neil Littman (Host)
I'm doing great. I'm really excited to chat with you today. We are going to talk about the best biome, how you are studying the microbiome of the human gut and how this can lead to new biomarkers and potential therapies. I'd like to start with the microbiome itself, just so our listeners are all on the same page. So for those who are not familiar with the microbiome Kareem, could you maybe just sort of at a high level, describe what we mean when we talk about the microbiome.


Kareem Barghouti (Guest)
Yes. Another way to think about it is the gut bacteria. The microbiome as a whole is a social with many different types of bacteria around the, in and on our bodies. Specifically for what that spine is focused on is looking at the gut. People might be surprised to know that you have roughly three to six pounds of bacteria living inside of your gut. This bacteria has been connected into the biology of the host, the pet, the, your body, and basically a hundred and trillion microorganisms are co-habit habitating, just to give perspective that the amount of DNA and genes of the microbiome is a hundred times greater than the human DNA. There's a lot going on, and it's really under at this point, we don't know much about what exactly the microbiome is doing, and that's where the opportunity is to really understand how it's connected to our health.


Kareem Barghouti (Guest)
To follow more examples. It's actually been a lot of great papers showing that your health and that the gut is actually associated with neurological disorders, gastrointestinal metabolic in UNE, and the list really goes on. There's a lot of talking to news. Now how gut health is connected to a lot of different has a lot of implications on our overall health. You'll see a lot of probiotics in stores today that I'm saying, promote your guts and you'll take these pills. Those products are meant to restore the health of your gut and a healthy gut can lead to all kinds of benefits, which I'm happy to talk about.


Neil Littman (Host)
Kareem, that there are so many points there that I want to dive into throughout our conversation. The, the, the microbiome is still a relatively nascent field within biology. As you mentioned, there's been a lot of emerging research over the past decade, linking the microbiome to both wellness and disease, but in terms of where we are in the trajectory of understanding the microbiome, I mean, how well understood do you think we are today in terms of understanding the function of the microbiome and how it interacts with the rest of the body?


Kareem Barghouti (Guest)
Yes. I know that's the question that is being asked to constantly even today, after all in the last decade, I would say we've seen the most advancements and trying to get a grasp of how the microbes are affecting human health, but again, a hundred trillion organisms that have co-existed with humans since the beginning of human life, yet we know really, not much about them and how they're supporting our health or how they could be damaging our health. There's a lot of research from academics and industry. Now we're trying to connect the dots yet. It's still early days to be honest, because it, because of a lot of the great research in term, whether they're doing mouse studies or doing even patients, other studying what type of microbiome profile they have, what bacteria lives in them and comparing different types of patients profile is see what's the difference.


Kareem Barghouti (Guest)
They are. There's some good correlations at the moment of the causation factors still early on. That's a big question that the field is trying to address. I'll give you a couple of examples. In cancer, you have patients who are being treated specifically for immune-oncology drugs, checkpoint therapies, and there are roughly 20, 30% of the population is responding well to those treatments and this other 70, 80%, they don't have a great response. So why is that? A lot of factors, of course, but one common factor we've identified in the field has identified a number of paper that's shown. This is that there tends to be a different type of profile of bacteria living in patients that respond well to the treatment and those that don't respond. They took that option, that opportunity to study further. What if we took the microbiome profile, those patients will respond as well and actually transplanted into a patient that didn't respond well, what would happen?


Kareem Barghouti (Guest)
Lo and behold, in the, literally this past, this year, we've seen the studies come out that those non-responders are starting to convert to responders. The only difference is just changing their microbiome profile. It's really amazing to see what is going on there. How's it working? These questions are on answered yet, but we're knowing we're realizing there is a connection. One of the short, another example is in obesity, they've done a very famous mouse model where you have these obese mice with their gut profile, and then you have these skinny mice. All they did was transplant the microbiome profile from the obese to the skinny vice versa. You start seeing a converging of the skinny mouse starts becoming obese and there'll be stops and becoming skinny. Why is their metabolism changing? Just because their microbiome profile is changing. There's a lot of these connections it's still early on.


Kareem Barghouti (Guest)
Last one I will tell you about is my personal story and why I'm actually building vest, bio. One of the examples, one of the reasons why, but I, I, I suffered with a severe case of eczema and I've gone to all the best doctors. You can think of all types of doctors from immunology to gastroenterology, dermatology, and so on. They couldn't give me any answers of how, why. Last couple of years, my skin has gotten really challenged. I went to a natural path doctor, and we talked about the gut and these microbes. We in over a year's time, we changed the diet. We tried to get some probiotics. We tried all different kinds of things to change my gut health. I'm about 80% recovered from what I used to be, how bad it used to be. So there's definitely something going on. The question is how, and what is it doing?


Kareem Barghouti (Guest)
That's where vast volume was trying to focus specifically on not just the microbes, but the molecules of the microbes make are the starting point for really understand the interactions between the gut and the human health.


Neil Littman (Host)
It's it's, it's really quite fascinating, quite amazing. I want to dive into a point that you mentioned, and it's really interesting that the safety and efficacy of medicines seem like they can be affected by the microbiome. How much variation is there in the microbiome of individual to individual?


Kareem Barghouti (Guest)
Yes. Even before you're born, when you're still in your mother's womb, you go, your mom's microbiome is already influencing your, your gut composition. How, what kind of foods and vital factors she has. There's a lot of factors that I'm trying to get this environmental factors, the living conditions, the diet all will influence your gut composition and profile comparing you or to your friends. Even your neighbors can have a different profile just by how you're living in your different habits. Once you're born, you have the first three years of your life. You don't have a fully, a strong foundation for a gut it's still being developed in the early days. Based on you are your lifestyle changes. You'll see change, you'll see differences in your gut profile. Now it's not, it's stable, it's a stable gut profile, and yet it can change pretty quickly, depending on the differences you do in your habits.


Kareem Barghouti (Guest)
For example, for myself, I told you when I changed my living lifestyle choices, my gut profile changed within a six month period. So there's a lot of differences yet. There's a lot of commonalities that you can, and that's the goal is trying to figure out what are the commonalities that are driving specific phenotypes in different patient populations.


Neil Littman (Host)
Karima, I want to circle back to what you're doing at best biome and, part of your inspiration for starting best biome sounds like it was born out of a very personal nature, right? Trying to come up with a, a better treatment to combat your, your eczema. Could you talk a little bit about sort of the, the history of VastBiome, your inspiration for starting yet, and sort of where you are today and in terms of the platform that you're building?


Kareem Barghouti (Guest)
Absolutely. A background, I don't come from the traditional scientific background myself, but I've always had an underground biology and always passionate about the intersection of health and technology. I spent most of my career in the commercial space and at Google actually most of my time, but then I, found this awesome opportunity to join a fellowship in Houston, Texas at the Texas medical center. That's where they put together a team through something called a bio-design program, which actually Stanford the group that coined that program. Essentially it takes four individual, the competency, complimentary skill sets, and with science medicine, business and computer science, and you have the opportunity to go look for unmet needs in healthcare. So great opportunity. You haven't met your team members, but hopefully things work out. That's always the tricky part in the beginning, but in Houston, people sometimes are not aware. It is the largest medical center community ecosystem in the country.


Kareem Barghouti (Guest)
You have over 16 institutions. Yet in some of the top institutions in the world from MD Anderson and cancer, Baylor college of medicine, and let's goes on. In this program, we spent a year looking for unmet needs, and we learned just across the street from us at MD Anderson, that the gut microbiome is influencing cancer, just as I spoke to you about in the papers that came out. With our backgrounds in pathology, computational biology, data science, and the business side, we thought, well, there's a lot of interesting opportunities to analyze the gut. The current tools are not necessarily giving us the best understanding of what's going on a gut. Most of these open source tools are giving a lot of false positives of what's actually in your gut. You're not, you don't even know what you're looking at. You're running all these analysis hoping to come out with a potential drug or insights that can lead to, different health complications.


Kareem Barghouti (Guest)
What inspired us aside from my personal story is all the team members came together because of the opportunity was very interesting. We all have a great careers in the past, but we wanted to build something meaningful and something that resonated with our personal stories. And so with VastBiome, what we're doing now, if we fast forward, it's been about three and a half years since then, is that we've built an end-to-end drug discovery pipeline, which is essentially from collecting patient samples directly from our clinical collaborators and ingesting it and curating and into this computational pipeline that starts with the bioinformatics side. Step one, try to figure out what's actually in your gut. Step two, can you predict which signatures, metabolomics, metagenomics, meta transcriptomics, and the clinical data, all wrapped in together to figure out what is your question you're asking? One case is we want to know whether a patient is going to respond or not respond to cancer treatment.


Kareem Barghouti (Guest)
What is the difference in patients responding versus not responding in terms of the gut profile? Once you create that list, then you want to go into, okay, now we have this list of genes that are coming from those bugs. I say, this it's actually very critical. Majority of the field is focused on looking at the species level of a strain level of what bacteria matter in your body. If you can get down to the gene, you'll have a lot more confidence in what you're looking at. Most of those papers that had been published has spoken about various different types of bacteria that are relevant to different health conditions. Some many cases, the common denominator is the genes. We did this, the sign, what genes matter, we can then predict. And then we started working with them. We actually express those genes, getting to the actual molecule that those genes are making.


Kareem Barghouti (Guest)
Those molecules are the starting point for trying to understand how they interact with the biology of the patient. Our goal is to build out with our data that we're ingesting at a large scale from collaborators and through private, and public data access, as well as computationally making the predictions and then going through our in vitro and experimental work to make sure that we know what we're looking at. We can understand back to the first point in that in terms of function, what these molecules are actually doing. So that could be your starting point. Think about it as a natural product drug discovery company. That's really what we are. Well, while there's been so much medicine that's been created in the natural product space from plants and the deep ends of the ocean, the famous one, everyone talks about penicillin, the last century, but we haven't thought about the gut as a natural product source.


Kareem Barghouti (Guest)
This is our chance now with the, the technologies of the genome, the genetic sequencing and metabolomics resources technologies, we can now actually figure out what's happening in our gut. We want to create this understanding of the gut and how it's all connected to our health, but also identify these genetic signatures and metabolomic signatures that could be starting points for biomarkers and therapies.


Neil Littman (Host)
Karim there's so much to dive into there. I want to go back to the founding story of . Cause I, I love this, right? I mean, you brought together really a cross disciplinary team of folks and you've built VastBiome in the spirit of what we call today, sort of a, you know, a tech bio company. I think this is still relatively a relatively new term. I I've talked about this before on the podcast with other guests, but I'd love your point of view in terms of, how you're going about building best buy, do you consider yourself a tech bio company? What does that mean to you? How do you fit in the broader ecosystem and how are you different than a traditional biotech that are developing therapies?


Kareem Barghouti (Guest)
Yeah. No good, great question. It's funny because this term like bar has really been building up in the last couple of years. I would say when we first started a company, we didn't know what that term meant. We actually thought we coined it internally to be fine on it. I come from a tech worlds and my colleagues are engineers as well. We thought it'd would be fun to use it just to flip it. There's a, I forget one of these venture firms that are started that actually branded it, that this is a tech biofield it's growing. And, and really to us, the way we think about tech bio and, essentially how we fit in, looking back to, again, natural product discovery in many cases have been accidental discoveries. We did not have a systematic approach or an engineered approach to basically standardize the process of how we find drugs in many cases, for example, in cancer, because that's what we're focusing on right now, 50% of the drugs in the market today are sourced from natural products.


Kareem Barghouti (Guest)
A lot of times we have no idea what the biology is behind it. We just know it works. That's not the best way to spend your time and trying to find the next big drug, because there's a lot of serendipity. If you may it's business in terms of how you discover these drugs. The tech bio, in our opinion is an opportunity to what if we create a systematic approach, you create a process and you have and specifically we target the specific on, on the microbiome space. The early days of microbiome companies saw small patient populations and looked at different types of commonalities across those patients ran mouse models. And they said, oh, that looks interesting. That's what we're going to go after and make a drug. We kind of expedite the process to think that we are, we know what the drugs could be without really understanding why and how it's happening.


Kareem Barghouti (Guest)
You can be definitely, there's been great wins that way. We hope those types of approaches so can be continue to be successful because we need the field to advance as a whole. At tech bio, in our opinion is more like you always hear the platform companies where you're not going to focus on its particular assets. You you're really going to bet on your technology is going to be fruitful and producing all kinds of pipeline of therapeutic potential candidates. You can continuously leverage a systematic approach. In our case, we use of course, deep learning and AI tools to predict which genes matter and what molecules are they producing. You really want to map out the entire microbiome and you have to use AI to do that. It's way too much information to really try to do on your own manually. We also use synthetic biology, you great companies like Ginko, I've shown how much advancements you can use in terms of manipulating these bucks to do what you want.


Kareem Barghouti (Guest)
Well, we're also using it in a cell-free approach. Our key value is we don't want to have to work with bugs anymore, but we rather use just the DNA and know what it does and then get to the molecule directly. It's a synthetic biology, the data science approaches, and then standardized process of, from the highlight sequencing technology that we use as well to know what's in our guts. In many cases, groups have looked at the same sample and derive complete different conclusions. Patient samples are stool samples, conclusions, because they don't have a systematic approach. For us, we are a hundred percent focus on let's build out the foundation and really know what's going on in our gut. Over time we can start picking some winners to advance our discovery pipeline,


Neil Littman (Host)
Korean blood, actually, that's a great segue into your discovery pipeline. You're working on developing potential therapies. I'm really curious about the inputs into your machine learning platform. VBX one, are you seeking samples from people with specific diseases to gain better insights into those conditions or to potential identify novel targets or therapies? I, it's, there's the age old saying, right? Garbage in, garbage out. What, what is, what is the, the data that you're putting into the system to come up with valuable outputs from the system?


Kareem Barghouti (Guest)
Yeah, absolutely. We first started, you're trying to be very lean. You have no cash, and you're just trying to think of how can I get involved in this space? We thought, well, let's go to the public domain and try to understand what data is available. The data to us is your S the patient's stool samples. We actually start with a Pacific patient indication, I guess, specific health indication in terms of what is there in our example is non-small cell lung cancer patients who are being treated with checkpoint therapy. We want to know why that 20, 30% are responding well, and what's the why the others are not. We look at their stool to get an idea of the composition. We look at their clinical metadata to understand what's their clinical history. Have they been taking antibiotics? Because if that's the case, you wipe out your entire gut and that's not really helpful.


Kareem Barghouti (Guest)
We look at the blood, we want to see what are different multi-ethnic signatures in the blood that may be driving some type of phenotype. It's stool, metadata, blood, and metabolomics, metagenomics amount of transcriptomics across the board, all that needs to come together to start laying out the map to understand what are the associations who first step again, is to understand how are all these different biological signatures connected. From there, we can go into a specific indication and we say, okay, our question in our success so far with checkpoint patients, one example, the, we looked at, can you predict primarily by looking at the microbiome, the gut profile of these patients, why they responded and why they did it, what is the difference between responders and non-responders? We found particular genetic signatures. We thought, okay, those are from the public data. Well, then we ran our own study with our own patient samples.


Kareem Barghouti (Guest)
One of our collaborators, and we found that we're using the same model that we built off of that public data from these multiple different patient cohorts, were able to predict with 80% of accuracy, whether or not you going to respond to checkpoint therapy. Now, this is still early, there's been an N of 300 patients. To that point, we're trying to actually do a, we're going to be announcing soon, a very large study that will give us a much more confidence in our predictions, because we're going to have much of a larger data set we're going to be collecting. We start with the prediction of a biomarker as a companion diagnostic, and whether or not you respond to checkpoint therapy, but even take it a little further it's signatures. We find, we want to understand what molecules are making. We've identified when we knocked down those genes of those particular microbes, the phenotype in an in vitro setting changes quite significantly in regards to what type of immune cells are activated.


Kareem Barghouti (Guest)
We know, I like to think about as think of the genes as blueprints and these genetic blueprints. I give credit to my colleague, Peter, for coming on with us. I, we, the genetic blueprints are essentially a way to understand how to make the molecule that the genes produce once you ha. That's what I think we think of as a needle in the haystack. Now you have the needle, you actually have the tool to figure out what is it, what's the driver, but we still don't know how it works. What we've been able to do is say, okay, well, this gene matters. We actually produced what the molecule mix. We look in an in vitro setting. What if we knocked down the gene and then the, the immunological associations change quite rapidly. We've also been able to use those genes and molecules and run assays. The last piece of our pipeline is running these functional characterization assays.


Kareem Barghouti (Guest)
We need to know what these molecules actually do. In a biological setting, we have a number of assays, 312 data points per molecule, to really understand how is it connected to the health outcomes. We did this, one of our case study we talked about is we found a gene in detecting cancer patients that produce the molecule that is associated with in a cancer immunotherapy space. We identified a novel target directly tied to that molecule. So in a cancer setting. It's exciting to see that, but other than that, we've seen multiple what we call rediscoveries, where there's a number of clinical trials right now in the live biotherapeutic space for cancer drugs, and they're doing combinational therapies or monotherapies, and the genes we've discovered as our top 100 favorite clusters, gene clusters, out of the hundreds of thousands in your guts show up more than 50% of the time.


Kareem Barghouti (Guest)
It's exciting to see that we know where to look. Now, you have to figure out what to do with that information,


Neil Littman (Host)
Kareem, there there's one thread that I want to pull on just to make sure that I'm understanding things correctly and to clarify for our listeners. That there's a lot of potential with what you're doing. Part of it seems if I'm understanding correctly is in a, as a, as a diagnostic, cause you mentioned the companion diagnostics. You could actually take a sample from a patient who is being present, who would potentially be treated with a checkpoint inhibitor before they're treated, you could analyze their microbiome and you could then predict a priori before they're treated with the drug, whether they are likely to respond or not respond. To me that, I mean, that's fascinating, right? I mean, you could save, I think you had mentioned that only 30% of patients respond to checkpoint inhibitors, if you could correctly identify that patient population ahead of time. I mean, my goodness, I mean, all these cancer therapies have horrendous side effects.


Neil Littman (Host)
If you could say patients from taking a drug that is not going to work for them, I mean, that's a huge opportunity there. I just, I want to make sure that, that sounds like it's one part of the story. The next part of the story would be, you could actually come up with novel therapeutics that could be combined with a checkpoint inhibitor to increase the efficacy of those checkpoint inhibitors in patients who might not otherwise respond. Am I categorizing that correctly?


Kareem Barghouti (Guest)
Yeah, that's correct. We think about the biomarker approach as the first step to get to the drug, but we're not a diagnostic company, but we can use that tool as a starting point to make sure that these diagnostics, these biomarkers can actually lead you to drugs. Let's use it as a, we like a stress test to make sure that that these biomarkers are truly valuable and relevant and then you can start understanding, okay, well, let's learn more about this cluster of genes and the mall. Cause a come from this gene by micro, what does it do then you can advance towards it that drove therapeutic side. To your point in terms of, yeah, there's a lot of opportunity to diagnostic side. There are companies who are looking at not just stool, but even your blood as a liquid biopsy company, but specifically the microbial DNA from the gut and the metabolites in your gut that flow into your bloodstream.


Kareem Barghouti (Guest)
From there, you can start diagnosing early on predicting early signs of cancer because the profile of the tumor in terms of the bacteria is different across different parts of your body. Knowing what microbes there are, is a great starting point for diagnostics, but then you can lead that towards, or what are these genes and these metabolites actually doing. That's where we go into therapeutic side.


Neil Littman (Host)
Let's talk about that for a minute. Where are you in terms of building out a pipeline?


Kareem Barghouti (Guest)
Yes. We are, we've done a number of these proof of concepts to see, are we finding relevant genetic signatures that could be immunomodulatory. And so that's been great. We've also done some strong in vitro work to show that we can find these genetic signatures that are relevant. We have not done the animal studies yet. The way we approach our, our company is we don't want to put a lot of eggs into one basket and upfront because we believe that the microbiome is challenged by not having standardized data, not having a real clear understanding of what the map looks like. Where we are today is in the next year or two, we're going to be establishing the clinically annotated chemical library that is directly associated with specific phenotypes of interest and that we've sourced and produced from them all the guts for prospective 70% of the bacteria in your gut.


Kareem Barghouti (Guest)
We cannot isolate or culture we can't actually use, but through our approach, we can access a hundred percent of the guts genes. By doing this, then you can produce the molecules and annotate them. Within that, at that point, you have a very valuable chemical library as a starting point for drug discovery. We're really focusing on the platform, build out right now with early signs of directions in the checkpoint therapy space of where we want to go move forward.


Neil Littman (Host)
Obviously checkpoint therapy spaces is in oncology cancer setting. We've talked about that there has been some interesting emerging research linking the microbiome to the brain and the central nervous system, which I actually found surprising. Can you maybe give a little perspective on that latest body of research is your immediate and long-term focus specifically within cancer or do you see opportunities in other areas?


Kareem Barghouti (Guest)
Yeah, I mean, it's really fascinating what's happening in the brain as well. Were focusing right now on a checkpoint. There is a market space because of our resources and our, our support team and all that data that's already been out there. So that's our starting point. We've got to prove ourselves first, but there is, we want to be with these disease agnostic over time. It was where we can reproduce our work across different disease areas. The neuro not neurological disorders is really open a lot of great literature showing the connection of how the gut influences your brain. It's actually, you've probably heard this many times before, but the gut is considered the second brain. And so what did it actually mean? Your gut and our brain might not be located very close to one another, right? However, they are connected. There's actually the nervous system.


Kareem Barghouti (Guest)
So the it's specifically the vagus nerve. That's a social with millions of these nerves that are communicating between your gut and your brain. They're sending signals and that the gut focus and in terms of the gastrointestinal and efforts, is to understand the inflammation of your gut. It's driving triggers to signal it to your brain, to let you know that something's wrong in your gut. When that happens, it actually can trigger your, your brain to have a psychological effect. So a lot of mood swings occur. You know, people call about being hangry. There's a reason why your mood changes when you've not fed. Your gut is not happy. A lot of also digestive concern issues occur in the gut, but also it basically breaks down how your gut is interact is absorbing the nutrients and how the brain needs to feed, use that to feed the body.


Kareem Barghouti (Guest)
Some areas I think was very compelling in the psychological space. There is groups of people who are taking CBT to actually help calm the nerves and to calm down. And that's actually ingested in the brain. If I start in the gut first, and then it signals to the brain. Autism is a really exciting area where it's not necessarily going to cure autism at the moment. If you can figure out what the microbiome is doing, but it might reduce the symptoms, the co-morbidities that occur. 70% of these autistic children have a lot of digestive issues. Well, why does the 30% not have that? They have a change and a difference in their gut, even Parkinson's some great work is happening there to understand how can we reduce these co-morbidities that occur with the symptoms that occur with patients who have these neurological disorders. Mental health, autism, anxiety, and all of that's connected to how you treat your guts.


Neil Littman (Host)
It's really fascinating. Just how much is tied to the microbiome. I want to change gears just for a minute and talk about your business model. Understanding the pipeline is still very early and without giving anything away, what do you see as the business plan going forward? Are you looking to develop therapies, move them into the clinic yourself? Are you looking to seek partnerships, some combination thereof? What, what is your vision going forward?


Kareem Barghouti (Guest)
Yes. The short answer is that today, things as a startup, you have to evolve based on the literature science you have and things that as you adapt over time, you'll have a better understanding what direction you need to take. Today we like to say that we're not going to bet most of the risks upfront are on ourself. We want to work with a number of different collaborators who are the experts in clinical development and drug development to help us support the discoveries that we're doing in house. In the short term, we'll using the partnership approach specifically to help us validate our technology and continuously build out a pipeline. In parallel, we are now starting to identify what therapeutic areas do we want to keep in house completely. At one point we'll be able to go with our goal. As the VastBiome, the parent company is going to be going to up to phase one.


Kareem Barghouti (Guest)
We want to show phase one validation, and then we want have these just like the bridge bio con or the Roy vans of the world, that the hub and spoke model. We, it's not easy to do. There's a lot of challenges with it, but we'd like to investigate, explore, is that angle that we can take for therapeutic areas that are, might not be, that are going to be developed in the clinic. We'd like to bring on the experts to handle that part now. So we are a therapeutics first company. Now one piece that, it's still early, but over time, what can you do with all this knowledge that you've gained from the microbiome when you've truly mapped it out? If you can get to that point, you can unlock so many applications and that's why I'm cannot take on all those applications. Our hope is, in 10 years from now maximum 10 years from now, when you go to your doctor, you should be able to get a question to take your blood test and your stool tests.


Kareem Barghouti (Guest)
The insights that come out of that, it won't be invest by them giving you that readouts, but it will be powered by vast volume insights that these other companies can leverage our technology to develop those products. What are the backend of the microbiome space? Starting with therapeutics is where we're going to be our core business, but we're getting a lot of interest in a lot of groups saying, you guys know how the gut is working, or at least trying to figure it out. Can we leverage piggyback on what you've developed and we'll go do our own products, and then you can piggyback and getting access to our data. It's a data exchange in the end. Therapeutic first, but then really wanting to unlock the entire microbiome space to all researchers across.


Neil Littman (Host)
It's very quiet as you're talking, I couldn't help think about, the Intel inside model. It's like, fast forward 10 years, it's like best biome inside, but you're powering the engine for a lot of the stuff that's coming, coming, as you said, probably within the next 10 years, if not you're well, before that, Kareem, we could probably talk for the next two or three days about these topics, but I do want to be conscientious of your time for those who want to learn more about what you're doing at best biome. What, what, where can they go learn more, maybe get in touch with you and just even learn more about the microbiome space as a whole?


Kareem Barghouti (Guest)
Yeah, no, I mean, so definitely our websites, the first place to go in terms of who we are. I, if you want to reach out to us, you can always email me directly. It's Kareem, kareem@vastbiome.com. follow us on LinkedIn and Twitter. We're trying to be a little more active there, but yeah, that's the easiest way to connect with us. There's in terms of literature, there's really a lot of sources that you can go to. You can go into Google, you'll find a lot of great content on. It's see concerning because sometimes it's not very accurate information, but I think it's talking to different groups and understanding how the gut is affecting your health. Everyone should have some level of knowledge, whether you're in the research field or you're just a consumer trying to take care of yourself. I highly encourage everyone to try that out and you'll be very surprised to see what's happening in your gut to go take a test.


Kareem Barghouti (Guest)
You'll, you might be very interested to see that.


Neil Littman (Host)
If I'm going to go sign up one tomorrow. Well, Corinne, thank you so much for a really great conversation and really enjoyed having you on the show today.


Kareem Barghouti (Guest)
Great. Thank you very much, Neil, have a great day.


Danny Levine (Producer)
Well now, what did you think?


Neil Littman (Host)
I thought that was a great wide ranging conversation with Kareem. I mean, I, I, in fact, learned a lot about the microbiome and just, I mean, just the number of cells and bacteria that the human body has just Wharf. The number of cells that are nascent to the human body, right? Human cells are far outnumbered by bacterial cells and the microbiome so that, that is fascinating. The variation between individuals of the microbiome and the gut and how that can potentially affect how drugs are metabolized, the safety and efficacy profile. You heard Kareem talk about, you know, the early days of being able to change the microbiome to make checkpoint inhibitors, you know, more efficacious to even use the microbiome as a diagnostic tool, to understand whether a patient would respond to a checkpoint inhibitor ahead of giving them that drug. I mean, that stuff is just really fascinating.


Danny Levine (Producer)
It's interesting to hear that they started with the checkpoint inhibitors to see if they could find microbiome signals in the gut to detect differences between responders and non-responders, he characterized that as a small study, 300 patients, but what implications do you think that would have for the potential direction of this technology?


Neil Littman (Host)
Oh, I, I think it's huge. I mean, Kareem's were a downplay the diagnostic approach. Cause at the, at, at their core they're they are developing therapeutics, but I think that the diagnostic, potential here is enormously powerful, right? If you couldn't identify if a patient is going to respond to a particular drug, a priority that, that has huge implications, not just in terms of, market potential, but in terms of huge implications for the patient at the end of the day, right? I mean, if only 30% of patients respond to a given cancer treatment, but that means 70% are experiencing all these dramatic side effects. When you're talking about cancer medications, these side effects are, are terrible. If you could save 70% of patients from having to deal with and take medications that, aren't going to be effective for them. I mean, that is just enormous potential right there.


Neil Littman (Host)
Of course, what Corinne was really focused on is therapeutic potential of what they're doing. If you could actually pair, what, a future drug from best biome with a checkpoint inhibitor and increase the effect efficacy of the patients and go from a 30% response rate to a 70% response rate and have these drugs be more efficacious to a larger percentage of patients. I mean, that's a game changer as well. You know that there is enormous potential here. We are still in the very early days, right? We're still collecting data. We need to run, human clinical trials to prove all of this out. But the early signals are really powerful.


Danny Levine (Producer)
W you think about jeans and you think about blood, but what's the potential for using the microbiome to bring about a, an era of precision medicine?


Neil Littman (Host)
Yeah. I mean, I, I, I think very much so. I mean, you heard Karim talk about the individuality of the microbiome and how much it can vary from individual to individual. We heard them talk about his experience taking probiotics, right. To try to combat his eczema. I, I think that there's a lot of people, obviously the probiotics market is huge these days. Whether you're trying to prevent a reverse, some chronic disease or whether you're doing it to just increase the , health and wellness there's, there's potential there. Obviously what best biome is focused on is developing therapeutics to target specific diseases. But, again, the field is still relatively young, but there's an increasing amount of literature coming out of both academia and the industry that is supporting the role of the microbiome in terms of how it interacts to in both in terms of wellness and disease within the body,


Danny Levine (Producer)
He seems to want to move very deliberately about building a pipeline. What did you make of his approach?


Neil Littman (Host)
Yeah, I mean, I think it's a valid approach. I really, one of the things that we like to buy a roads, before we invested in the company was this idea of that the platform, right? And, and not betting too heavily on any single asset, but really building the core technology. Obviously you need proof of concept with a lead candidate, but then being able to sorta, rinse and repeat, once you have established that proof of concept, once you have established that the pipeline works, the ideas that you can spit out new drugs over time, but that, really focusing on the core foundation of the platform technology to me is really exciting. And, and to me, that is part of what makes them this puts them in this category of tech bio.


Danny Levine (Producer)
You talked about a kind of evolving business model with an early focus on partnering and establishing partnerships with experienced drug development companies while keeping certain therapeutic areas in house completely. What do you think of that?


Neil Littman (Host)
Yeah, I think that makes a lot of sense. That there's a lot of different directions. They could go, obviously they want to play to their core strengths, right? Their core strengths are not going to be, running, clinical trials across a variety of disease indications, right. They, they are, they are really focused on the early stages on coming up with novel, novel drugs, advancing them towards the clinic. I think the partnership strategy makes a lot of sense, that they are still a startup, they're not going to be able to do all of these things in parallel. The more they can prove out and validate their early therapeutic pipeline, partner that, and then focus one or two key IRAs. I, I, I think from a business perspective, it makes a ton of sense.


Danny Levine (Producer)
They're certainly not alone in looking at the microbiome. I suspect there's a bit of a, a race here. What do you think it'll take to be successful in this area?


Neil Littman (Host)
I think it'll really take clinical studies, right? More data proving out that what we're seeing in preclinical models, animal models, well actually translate to the clinic, right? I mean, that's where the rubber meets the road. I think the first wave of what we're seeing in terms of the microbiome or a lot of the probiotics and things like that, but, we need to run well controlled clinical trials to, establish, the they're there and to attend, to make sure that these things work as we think they're work. That you know, that will take time.


Danny Levine (Producer)
Well until next time.


Neil Littman (Host)
Thanks, Danny.


Danny Levine (Producer)
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