david kyle simple biotech featured

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  • Each one of us has a universe inside our gut in the form of trillions of microorganisms, which makes our gut’s microbiome. They dictate our life from the time we are born and having a healthy gut microbiome is an important part of living a happy life. (0.15)
  • In recent years, due to changes in how we raise our children, researchers have observed that infants nowadays have lesser of these very important bacteria’s causing lifelong issues to them, as they grow. This is a very serious global issue and cannot be ignored. (0:31)
  • The guest for today’s Podcast is Chairman and Chief Science Officer of Evolve Biosystems, David Kyle. (1:39)
  • David Kyle’s biography appears to be very impressive, as he has accomplished is an outstanding entrepreneur, philanthropist, and published academic. (0:48)
  • David initially co-founded a company named Martek Biosciences that was acquired for 1.1 billion dollars. He also co-founded another company with the name of the Mother and Child Foundation. (2:53)
  • In addition, David has published over 70 scientific articles, 2 books and has done some NASA projects. (3:22); (4:39)
  • David then talks about his specialty i.e. lipids. Then moving on to DHA, which is considered as a primary building block of the human brain. (5:25)
  • The human body is not that capable to produce DHA so, the body needs to take DHA from the diet. (5:38)
  • Studies have found out that infants can get their DHA from their mother’s breast milk. (6:07)
  • 15% of the energy content of human milk is tied up in sugar structures that the infant could not de-construct. (7:55)
  • B. Infantis was surprisingly not present in the children of the US (8:58)
  • B. Infantis is a bacterium that is naturally found in an infant’s gut which further helps to absorb the nutrition in a better way (10:21)
  • David explains the differences between HMO (Human Milk Oligosaccharides) and B. Infantis (10:46)
  • David also talks about completing a survey that indicated that fewer than 4% of the babies nowadays have the protection intact and B. Infantis is absent in more than 96% of these babies (12:19)
  • David’s company is initiating some clinical trials in conjunction with Jansen which is a part of Johnson & Johnson i.e. primary prevention of atopic dermatitis using B. Infantis (12:40)
  • Also, working in conjunction with other companies as their primary prevention for type 1 diabetes using EVC001. Along with another foundation to prevent the problem of severe and acute malnutrition, and stunting in South Asia and Africa, all with the help of EVC001. (13:00)
  • Evolve Biosystems is one of the leading microbiome companies in the world. It was launched by the University of California and funded by a venture capital, Agen FoodTech, by some strategic partners like Johnson & Johnson and a few more. (13:19)
  • It is discussed that over the last 100 years, with the advent of artificial formulations in infant formula, there has been a reduction in the time that a baby is being breastfed. (15:12)
  • The discussion evolves around how does the baby gets B. Infantis in his body. B. Infantis is found to be present in the mother’s gut in very low concentrations and therefore, gets transferred in the form of a seed from the mother during the vaginal birthing process (15:27)
  • The B. Infantis then expands during the time of breastfeeding (16:01)
  • David talks about how antibiotics and cesarian section can cause a slow reduction in the diversity of the gut microbiome especially, B. Infantis of the mother over a while (16:24)
  • Furthermore, the discussion continues to fix the problem of not having a B. Infantis anymore in the human gut to protect from severe allergies, etc. (17:40)
  • Evolve Biosystem carried out some preliminary trials in which HMO and B. Infantis was provided to healthy adults (20:14)
  • What is Evivo? (21:00)
  • David talks about the product of Evolve Biosystem named Evivo, which is a commercial product that contains an activated form of B.infantis of a very specific strain EVC 001. It is therefore a gut symbiont. (21:06)
  • Then further explaining the 3 major functions of Evivo (21:35)
  • Evivo is sold in a single serving sachet and when feeding it to the baby it is mixed with some amount of breast milk (22:24)
  • There is also a sister product to Evivo suspended in some part of oil specially designed for very low birth weight babies (23:00)
  • David then talks about probiotics in generally that there are 10 to 15 different kinds of probiotics that exist (23:33)
  • Furthermore, discussing the different strains (24:35)
  • David explains the successful results of the first clinical trials of Evivo (B. Infantis) when given to a baby. the gut of the baby got remodeled in the first 4-5 days and much more from pooping pattern to a reduction in the fussiness and diaper rashes (26:15)
  • Evolve Biosystem has initiated with raising a lot of money such as 1 million dollars in seed funding in 2014, 9 million dollars in series A round in 2015, 20 million dollars in series B round in 2017, and recently completed series C round with 40 million dollars (28:27)
  • David talks about the goal and distribution ways of the company that every baby gets access to B. Infantis and makes it easily available to the mothers in the US, may from amazon, the e-commerce site of Evolve Biosystems, or the hospitals. Initiation of shipping of the product to Hong-Kong and Singapore too from now onwards (29:19)
  • David then moves on to make us understand the health economics in terms of the low birth weight babies and their weak immunities (31:40)
  • The more diverse the source of fiber content a person consumes in food, the more diverse and healthier the gut microbiome becomes (34:34)
  • Use antibiotics judiciously. (35:25)
  • Discussing how the probiotics are preserved especially while shipping, they are preserved in a cold environment and when the consumer receives the package in a day or two, they have to store it in their refrigerator till they use it (36:02)

For the full transcript of The Simple BioTech podcast Episode 12 Click Here

James (00:01): What if I were to tell you that each and every one of us has a universe inside of us, that controls our mood, how we age, and even what we’re alerted to a universe inside of our guts filled with trillions of microorganisms that make up our gut microbiome that dictate our lives from the moment we’re born. Having a healthy gut microbiome from birth is a massive part of living a long happy life. However, in recent years, because of changes to how we raise our children, researchers have noticed that infants of today have less and less of these extremely important bacteria causing lifelong issues for babies that are born today. This is a serious issue on a global scale, and it’s one that can’t be ignored. My guest today is an absolute stud in the world of biotech and is tackling this issue head on with evolve Biosystems.

James (00:59): In this interview, I get educated on the different strains of probiotics, why they’re so important, why children born today have less of them and why that is such a problem, as well as some tips for adults that have accidentally nuked their gut microbiome with things like antibiotics. If this type of podcast is interesting to you, and you’d love learning about the innovations that are happening in the world of biotech, please consider subscribing on Apple, Android, or whatever platform you’re listening on. It’s totally free and will help the simple biotech podcasts. Get the word out about an industry that doesn’t get enough attention. So without further ado, my guest today, chairman and chief science officer of evolve, Biosystems David Kyle, the human experience is changing and it’s going to happen a lot faster than you think the world is going to be a vastly different place in the next 10 to 20 years because of what’s happening in the biotech industry right now, welcome to the simple biotech podcast. My name is James rule, and I’m your host. The goal of the simple biotech podcast is to interview the researchers, founders, and investors that are working directly in the industry and to translate what they’re working on into simple and easy to understand language. If that sounds like something you’re interested in, let’s get started. Thank you so much for joining me today.

David (02:32): Thank you for the invitation James. I enjoyed your podcast before, and I hope I can provide some new insights for your listeners. I’m sure people are going to love this one before we get started.

Thank you so much for joining me today. Before we get too deep into things. I just want to give everyone a quick bio on you, David, because you’ve accomplished some seriously impressive things in your life. You’re an outstanding entrepreneur philanthropist and published academic. You co-founded a company that was acquired for $1.1 billion called MarTech. And the seriously impressive part about that is MarTech products are actually now found in virtually all infant formulas around the world. You also co-founded the U S chapter of the mother and child foundation, an organization dedicated to preserve and protect the health of pregnant women and their children through better nutrition. And lastly, but not leastly, you’ve also published over 70 scientific articles, edited two books. You’re the named inventor on over 350 patents of which over 100 have been issued worldwide. And you’re inducted into the U S technology hall of fame in 2009, for your contributions to science and industry David, that is a hell of a resume. Well, thank you very much. It’s been quite a journey. It’s a super interesting life that you’ve lived. So I’m curious what started at all, what sparked your entrepreneurial spirit and what got you interested in the world of biotech?

David (03:56): I’ll be happy to talk to her and talk to you about that. And, uh, some of the most reasonable activities I’m involved in, which are really quite exciting, but I basically had James, uh, three major paths in my career journey. I started off, as you indicated in the neck as an academic being trained in first in biology at the university of Victoria. I grew up in Canada. I did my PhD in biochemistry at the university of Alberta and in preparation for a life as a professor, I went on and did a postdoc in molecular biology and biochemistry, Michigan state university. But before I took the next step into academia, I thought I would check out the private sector. So I adjusted my journey and went into, went to work for the research Institute for advanced studies, which is part of Martin Marietta. At the time we worked on NASA projects, I’m very cool ones.

David (04:41): I don’t go into those in much detail, but, uh, that lasted a year or two before Martin Marietta decided to close down that entire unit. I was 1985 and this was a very fortuitous actually year and ending because that’s what started me on my, uh, my next two great adventures, the first one, uh, uh, MarTech bio-sciences. So I’ve always been entrepreneurial. I’ve started small companies when I was in school or when I was in university, I managed local commercial operations while I was completing my PhD. So at the close of the Riaz labs, several us got together and founded MarTech bio-sciences. And that was 1985, my gosh, 35 years ago. And it was a biotech company at the time built on sourcing unique materials from algae and my specialty lives was lipids. We quickly recognized that certain algae were very good producers of a compound called DHA.

David (05:31): Now DHA is a primary building block of the human brain and the human brains about 70% lipid, but we, humans are not very good at making DHR cells. So we get it mostly from our diet and babies in utero, when babies are in utero, mom is literally dissolving the components of her own body, including things like DHA to provide these key building blocks to that growing baby’s brain. But in the first six months of postnatal life, the baby’s still doubles in size. Again, we’re wondering where is it getting the DHA from? But the answer became obvious. Then it became basically a light motif throughout my entire career. And that was that mom was providing it as a source in breast milk. Now, although infant formulas companies did a good job of providing general nutrition for the infant. It was missing certain components as specifics like DHA.

David (06:18): So we pioneered the feather simple concept of using this highest purity source of DHA, the alkaloids to be added to infant formulas in the late 1990s. And as you mentioned, MarTech went public in 1993 and went on to supply virtually every major infant formula company worldwide with DHA or economic asset for their formulas company was sold in 2011 for about 1.1 billion. But today virtually every infant nutrition product in the world contains TPHA. So James that’s what really got me at my first step into biotech and set me up for my third and my final adventure with evolve Biosystems.

James (06:55): Okay. Okay. So that makes sense. So your former research and all your, of your experience with breast milk and all the benefits that come with it, that’s what kind of inspired you to start evolve where you’re currently the CSO and chairman. So let’s talk a little bit about evolve.

David (07:17): That was the next part of my journey. So after MarTech, I decided to move to California, actually go into retirement. That didn’t last very long, a good friend of mine. Professor Bruce German at UC Davis told me about what he and four other interdisciplinary scientists had discovered while working on human milk at the foods for health Institute and UC Davis. And after telling me what they had discovered, it took me about five milliseconds to say I’m in. And that was the start of another incredible journey of discovery. This time again, propelled, which has been most of my life by the need to understand some enigmatic observations regarding human milk and James, the first one was, and you’ll find it the same 15% of the energy content of human milk was tied up in complex sugar structures that the infant could not deconstruct babies and adults do not have the genetic or metabolic machinery to deconstruct and use those that energy from those nuclear saccharides.

Daivd (08:12): So it didn’t make sense surely that she wasn’t being wasted. And the team soon discovered that these HMO’s were not lost at all, but they were consumed by a very specific gut bacteria called BN fantasy. We’ll talk about that quite a bit. Now that uniquely metabolize these sugars and converted them into smaller compounds, acetate, and lactate compounds that the baby could use, thereby making human milk, interestingly, a selectable growth medium for this one, what’s this one, organism, this one bacteria allowing it to dominate the gut microflora or the microbiome of that infant. It was a really cool discovery. You know, everybody said, well, why is nature doing this? Why does this as symbiosis set up for furthermore, the other odd and exotic observation was we quickly discovered that the infanticide couldn’t be found in Nina for our babies in the U S so the system seemed to be set up, but it was non-existent in the U S even those that are our gold standard babies vaginally delivered breastfed babies, but it was present and dominant in babies in many low and medium income countries around the world.

David (09:16): And that’s how they first discovered it. But our babies, I thought our babies were the healthiest ones in the world, and they don’t have this natural symbiosis. So maybe they aren’t. And as we investigate more, it became clear that this loss of the infanticide and the babies and the Western world, this massive change in the infant gut microbiome has only happened in the past 50 to a hundred years. And over that same time, as you know, the incidence of communicable diseases has dropped dramatically, primarily because of the advent of antibiotics and antibiotic uses in the 1950s, while the incidence of non-communicable diseases, ATP eczema, food allergies, asthma autoimmune diabetes has skyrocketed the other direction. So our first objective that evolved was to return that gut microbiome back to the way it was a hundred years ago, I eat dominated by the bee and fantasy. And what we saw James explained the natural linkage between breast milk and the infant gut microbiome, and what that was doing. It was very rewarding, finally understanding that, but that new knowledge is about to change the world.

James (10:19): Let me just clarify. So the bee and fantasy is bacterium that was naturally found in infants and they’re in their guts, correct. And that B infanticide basically would help the infants be able to absorb the nutrition better of the breast milk,

David (10:36): Correct. And even more and even more. Let me, um, talk about the one key discovery that this natural linkage between HMO and being fantasy demonstrated to us through the metabolism and the HMO through the metabolism of that HMO and the excretion of the acetate and the lactate. The gut pH was lowered by a whole pH unit to a value that prevents the colonization of opportunistic pathogens. Now, a lot of bacteria, they have optimal growth conditions. And when you drop the pH of the gut by one pH unit, things like E coli and Klebsiella, and you’ve probably heard of Clostridium and staphylococcus and streptococcus, they all stopped growing. So it turns out that this mechanism was actually a protection mechanism or what we call colonization resistance, and that colonization resistance preventing those opportunities, pathogens from getting into the gut also then prevented the erosion of the protective mucus lining of the gut.

David (11:31): And we found out through clinical data clinical trials, that in the absence of that natural protection mechanism, those opportunities, that passage, and set up a chronic inflammation that is recognized and seen within the first 40 days of life within the first month of life, these babies have chronic intera inflammation and it continues on and increases beyond those first 40 days that, that our gold standard vaginally delivered breastfed babies today are exhibiting major inflammatory responses, right in that critical a hundred day window where the majority of the immune training is actually occurring. So we believe that this can have lifelong consequences that may be presenting later in life as auto-immune disturbances or immune development, disturbances presenting as allergies. And as an they’re, like we’ve completed a survey and it’s about to be published. It should be out in the next couple of days, which indicated that fewer than 4% of the babies in the us today have this protection intact.

David (12:29): The bee and fantasy is missing over 96% of those babies. So it just to take this on a little bit further with this discovery, we are now in the next few months, initiating several more clinical trials, one in conjunction with Jansen part of Johnson and Johnson, where we’re looking at the primary prevention of atopic dermatitis using the B infantis strain that we’ve used for the last few years is called EBC zero zero one. We know that one works, there’s some issues about other strains, but in any case, we’re also in conjunction with a major pan-European team, looking at the primary prevention of type one diabetes using EBC zero zero one. And in conjunction with the Gates foundation, we’re looking at the prevention of severe acute malnutrition and stunting in South Asia. And Sub-Saharan Africa using EBC zero zero one. You know, today Evolv Biosystems is probably if not the leading, certainly one of the leading infant microbiome companies in the world.

David (13:25): And it’s just a little bit quick, just brief background. We were launched out of the university of California Davis. It was a spinoff were being funded by venture capital, primary ag and food tech. We have funded also by strategic partners like Johnson and Johnson and major philanthropic organizations, James, like the bill and Melinda Gates foundation and the Lee caching foundation that at least the venture capital arm of Lee caching foundation. So the company is really a science forward entity in this specialty, infant nutrition space. And so far, the team is very proud of making some incredible discoveries that have been published in top medical journals, like pediatric research in frontiers, in nutrition and BMC, pediatrics, and so on showing this crucial role in how important this be and fantasy combination with breast milk oligosaccharides in infant health and development within that first six months.

James (14:14): So basically the problem that evolved is solving is that babies don’t have as much be in fantasy anymore. And without that, it can produce issues throughout the rest of their lives. That’s a pretty serious issue. And, and I’m sure you have some theories about why children don’t have it as much. You mentioned that it’s something that’s happened within the past 50 years. Is there something, I mean, antibiotics, I guess some other possible reasons why there it’s not as common,

David (14:42): You know, the clues come from lots of sources. So let me answer that by reminding you, is that probably half the babies in the world still have those be in fantasy. They happen to be in low middle income countries where breastfeeding may go on for one to two years, which has probably from an evolutionary point of view, the way we’ve been providing nutrition, remember, but the human milk is the sole source of nutrition for babies in the first six months of life. So it’s been perfected over millions of years to provide all the nutrients needed for that baby. But over the last a hundred years, with the advent of artificial formulations, infant formula, there’s been a reduction in time in the rest of the world that we are breastfeeding, our babies. That’s one thing. The second thing is, and probably the most likely cause is that, well, let’s look at how being fantasy is actually transferred.

David (15:30): How does baby get beef and fantasy in the first place? It is normally found in the mom’s got at a very low concentration. And during the vaginal birthing process, as that baby is squeezed through the birth canal, mum will dedicate. It just happens naturally. It’s been happening for millions of years, and it’s kind of the quintessential fecal microbial transport oral to infant transport or transfer of a healthy gut microbiome to that baby. So the baby gets seated with a healthy gut microbiome for the mother. And then when being fed with the human milk, it creates a, an artificial or basically a selective growth medium for the bee and fantasies, allowing it to expand and provide all this benefits. So mom has to have it in the first place. It turns out that, um, the CDC tells us that the young woman who having her first baby today from the time she was born until the time she has her first baby has had on average 15 to 20 courses of antibiotics, aha antibiotics, maybe the culprit, different bacteria are very sensitive to antibiotics and she has every time she takes an antibiotic, she loses some diversity in our gut microbiome and B infanticide, probably one of the first ones to go.

David (16:37): If she no longer has it, she can’t even transfer it anymore to her baby. So I think any biotic generational use of antibiotics as a real culprit. And of course the increase in Syrian sections, if baby is born by cesarean sections, there’s no possible way that mom could transfer, even if she had to be in fantasy from her gut microbiome to the baby’s gut microbiome. So it’s kind of a perfect storm of, of modern medical achievements and advancements. And again, the old story of unintended consequences, we had no idea. These medical advances are all great and important and useful, and we’re not going to stop using antibiotics and C-sections do save lives. Infant formula is important to terms of convenience in some cases or some cases where moms can’t provide the breast milk. So all of these are important, but now that we know the impact on the gut microbiome, the loss of the inhabitants, the solution becomes very simple. Let’s just add it back. What can it do?

David (17:29): Well, it’s too, you know, they’ve already suffered through this. They’re no longer infants. They can’t benefit from the products from evil and maybe they can, what can an adult and adult do at this point, who likely doesn’t have be, and fantasy who likely doesn’t have, you know, dealt with the consequences their entire life.

David (17:46): It does question a lot and it’s not just adults talking about themselves. It’s adults talking about my three-year-old daughters now. And she said, allergies, and now has asthma. Can I fix that with the band fantasy to be a little bit pithy, which I probably shouldn’t be. There’s good news and bad news. The bad news is that there’s a, a window of opportunity because these are all disruptions of normal immune development. And that immune development time window is generally in and around the first a hundred days of life. A lot of pediatric immunologists believed a while ago that it was the first thousand days of life, but really most of the imprinting takes place in that first a hundred days of life. And if that’s where the disruption occurs, then it’s a window that is open for nominal development and it closed after that time. So there really is nothing much you can do other than look toward the great treatments that the pharmaceutical industry has provided for those particular conditions.

David (18:41): The good news is for the parents of that daughter. There’s good news for the grandchildren because now that we understand what the problem is, and we know how to fix it, we can fix it in time. But there is an interesting question about adults. So remember when you caught it accurately, that being fed as this is intended to work with human milk and human milk oligosaccharides, and not many adults are consuming human milk, but in the absence of the HTML, the infanticide still has a capability of stripping certain glycans off of glycoproteins. What do you mean HMO? Oh, sorry, human milk oligosaccharides. These are the complex sugars found in human milk. They referred to as human milk oligosaccharides. So I might drop to the recreation HMO. So this little critter being fantasy has other ways of harvesting. Glycans are complex sugars that it consume itself.

David (19:28): And one is to strip off these glycans that are associated with many proteins that are decorated with sugars called glycoproteins. And so it can strip those off. And there are many of those glycoproteins and milk. And we were kind of curious when we saw individuals or moms were reporting that their babies were getting infant formula. They gave them the BN fantasy and they still showed some of the symptomatic relief that those, that the breastfed babies were getting now concluded that they were actually being Fontus was stripping off these glycans from the milk proteins and providing some benefit there as well, too. But with respect to us, older people HMO’s are now being manufactured by ton quantities around the world, presumably to be added to infant formulas at sometime in the future. So we did some preliminary trials and looked at BN fantasy and HMO’s provided to healthy adults though.

David (20:21): So these milk oligosaccharides that are being manufactured possibly in fantasy, that perfect symbiosis to healthy adults, what happens when we can significantly increase the B infantis carriage of those adults. Now we’ve not yet looked at using this as a using this natural mechanism as a potential therapeutic for adults. I take the infanticide every day. Then I think I can feel the differences is not scientific, but I think I can feel the difference in my gut when I stopped taking it for whatever reason. So it may have other impacts, but our focus James really is stay strictly focused on the newborn baby and the importance that we provide to the newborn baby

James (20:56): Building a better future for our children. That makes a lot of sense. So you guys have a product called E vivo. Can you tell me more about what that is exactly how it works?

David (21:06): Sure. So if vivo is a commercial product that contains, um, an activated form of being fantasy of a very specific strain, we’ll call it EVC zero zero one. So that you hear that that’s a specific strain. We’ll talk about strain differences in a minute, and it’s really more than it. Guts in biology. It’s more of a gut symbiote than it is a probiotic, right? In the classic sense of the word. So it’s, co-evolved with humans for millions of years. And, um, it has a set of unique genes, specifically designed to code for three functions. So we have to just remember the three functions that are, that is happening here. It’s capturing these milk oligosaccharides on the outside of the cell as transporting them into the cell and then deconstructing those sugars inside the cell, metabolizing them and excluding acetate and lactate, which incidentally are now usable by the baby.

David (21:53): So it’s actually bio transforming those digestible milk oligosaccharides into high energy compounds like acetate and lactate and no other product probiotics have those functional genes. Therefore can’t completely metabolize the 200 or so milk oligosaccharides that we find in human milk for consumers, there’s other commercial products out there they use for infants. Recently, adult probiotics have been repurposed and repackaged for inference, but again, they don’t have the milk metabolizing genes or capability back to the product for consumers. If vivo is provided as a single serving sachet, that mom would mix with a little bit of her breast milk. So she had opened the sachets, a small amount of powder mixed with the breast milk and provided directly to the baby, either with their fingertips, which most moms prefer or theirs. You can provide it with a little plastic syringe directly to the baby. It’s as simple as that, we also have a sister product James for use in hospital.

David (22:49): NICU is for preemie babies. And this is another story we’d like to talk about a little bit, and that’s what’s happening for the very low birth weight babies that are in hospital. And they’re being fed by tube. The vivo for hospital actually is the same activated DVC zero zero one strain, but it’s suspended in a small amount of oil. We call it medium chain triglyceride oil, which is used as an energy source in the NICU for babies. That simply makes it easier to add to a feeding tube. And when used with infant formulas, if mum is not breastfeeding and wants to have an environment that consumer sachet can easily just be opened and added directly to the infant formula itself and fed to the baby through the bottle. Okay.

James (23:27): Yeah. So you mentioned a few differences between the different types of strains. What did you mean by that?

David (23:33): Let’s just talk about probiotics in general. So probiotics have been referred to, and it’s kind of a genericized. If I can use that word genericized term, because there’s probably 10 to 15 different probiotics out there that are in commercial use right now, and they’re all completely different. And from a genetic structure, in fact, there’s probably more similarities between the human genome and the genome of a banana than there is between two different probiotics. So they’re not all the same, they’re all quite different. So bifidobacteria and fantasy is one that would be classified perhaps as a probiotic, quite different from all of the others. And the industry itself sometimes uses the term strains incorrectly when they’re really talking about species. So, so there’s very differences between species of these probiotics, but between strains, what we’ve discovered is that there are commercial strains out there that are also called B infanticide.

David (24:30): And what we’ve recognized is the there’s a significant difference. In fact, this paper just came out last week, looking at the difference of all of these commercial strains in terms of their genetic composition. And there are many out there most, in fact, out there that are missing key series of genes in what’s called the H five gene cluster. It really doesn’t matter what it’s called, but those genes code for the specific functions of the transport of those HMO’s from the outside of the cell to the inside of the cell. And so if those genes are missing, those quote strains of being fantasy will not be able to transport the milk oligosaccharides into the cell for deconstruction and conversion, to acetate and lactate. The paper shows that the phenotype of those organisms are unable to consume many of the milk oligosaccharides, unable to convert them into acid lactate and reduce the pH and therefore have the positive effects.

David (25:23): So we have to be careful in terms of strains. And so the strain that we have focused on all of our clinical trials, but done with, uh, both in term babies and preterm babies have been the EVC zero, zero one strain. So I keep representing that because we have to be careful as consumers, not to assume that all strains are the same, you know, the difference between one strain of being Landis and another strain is similar. If I can put the reference to something that’s a little more familiar to dogs, that’s like the difference, perhaps between a German shepherd and a Chihuahua they’re quite different. Got it.

James (25:55): And what results are you seeing so far with EVs zero zero one. And what metrics for success when you’re testing these, are you basically just testing the gut biome or other phenotypic results? You’re looking for,

David (26:09): First of all, the very first clinical trial they did just that just looked at the gut microbiome and ask, does it change? And the remarkable observation in that very first clinical trial of a few years ago was all we had to do was add B and fantasy. So the baby who was being breastfed and the gut microbiome remodeled within the first four or five days to be completely dominated by being fantasy, just as kind of we expected. And that’s when we discovered that in fact, it lowered the levels by 90% or more of the opportunistic pathogens. You call eye levels, went down. Other biomarkers, which are important in terms of clinical end points is that that Ecolab carries a lot of the antibiotic resistance genes that we have in our body today. And when you reduce the Ecolab levels by 90%, it actually reduce the antibiotic resistance gene carriage of these babies by 90% as well to the chronic inflation.

David (27:02): Again, these are biomarkers. What are I think your question is what are we seeing in terms of systematic outcomes with responses from moms that are either in clinical trials? There’s certainly an immediate change in stooling patterns. I don’t want to bore your listeners talking about pooping of babies, but in any case, it changes that composition, there is a reduction of fussiness or colicky that occurs in 60 to 70% of the moms that have reported back a reduction in diaper rash that are asleep times. We know this because what’s important in the gut. Microbiome is a, of course, that inhabitants of that gut microbiome, but it’s more what molecules those inhabitants are producing. It’s called the metabolome or the metabolic products of all of that ecosystem. And the metabolic products include things like elevation of required vitamins, elevation of molecules, like serotonin and things like that. So all of those things are happening in terms of long-term outcomes, looking at the primary prevention. Again, we’re not treating curing or mitigating a disease here where we organizing the gut microbiome to a situation where it’s, um, providing more health benefits and health outlets for that baby.

James (28:16): So some very impressive results so far, which brings me to kind of my next set. I am a, I’m a businessman I’m entrepreneur. And the story behind what you guys have done is extremely impressive. You guys have raised some serious money so far completing a $1 million seed funding round in 2014, $9 million series a round in 2015, a $20 million series B capital raise in 2017. And you most recently completed a $40 million series C round, which was co-led by the bill and Melinda Gates foundation. So there’s obviously people, very smart people think that this is a massive industry and that you guys are leading the charge. Yeah,

David (28:59): That’s exciting. And, uh, we’re very happy and proud to have all of the investors that we have. We’re in a different space. Something has, would be referred to more as a prevention space rather than a treatment space. So we’re outside the realm of the pharmaceutical companies and we’re actually outside the realm of the food companies. So we’re kind of in an unusual position, but our goal is still the same. Our goal is to ensure that every baby has access to be in fantasy else or one around the world. So they can benefit from this natural protection provided by that healthy gut microbiome, remembering that probably over half of the babies of the world already held this protection, which is great. We’re really only focusing on the areas where being fantasy is missing, which is most of the Western world. Interestingly, with the increased use of antibiotics in low and medium income countries, we’re starting to see this dysbiosis now in these low and medium in countries.

David (29:50): I think that’s one of the reasons why the Gates foundation is interested in what we’re doing because it’s early data suggests that dysbiosis in the high-income countries like the U S is presenting in these auto-immune disorders. The dysbiosis in these emerging countries is presenting as malnutrition and stunting. And so there’s a tremendous value here that we in generate. We’re talking about the market size of the addressable market is really all the babies in the world, but they’re not, it’s not all addressable. When we parse out where we think we can make an impact. We’re talking about 17 million babies, which is about less than a quarter of the babies that we believe is actually reachable worldwide.

James (30:31): You guys are, are addressing these. I mean, is this just going to be sold to at the supermarket infant or in a, um, a formula? Is this going to be given to babies at birth? What’s this going to look like on a global scale?

David (30:42): My vision is just make it available. So right now moms in the U S for example, can simply buy it on the, on either Amazon or they can go straight to our e-commerce site and buy it. We deliver it to hospitals. I’ll talk about that in just a second, but we are actually a shipping to not yet to Thailand, but we’re shipping to Hong Kong and Singapore, but I see as more data comes in in terms of health, economics and countries are starting to see declines in this spike of autoimmune disorders that are significant healthcare costs is that may be institutionally either from an insurance company’s point of view or from the government’s point of view, start being able to supply this to all babies at all, birthing hospitals. That would certainly be the easiest way for distribution. If I can take, I know we’re probably running out of time, but I just don’t want to spend a minute on the, in terms of the economics as well, too, with respect to the product in the NICU.

David (31:40): So we’ve done some clinical trials and got some data being generated, but these very low birth weight babies in the NICU, these are very fragile babies and a poorly developed gut, highly susceptible to overgrowth of opportunistic pathogens. And here in the U S james’ $26 billion a year is spent on pre-term the care of preterm infants and half of that $13 billion a year focused on only 60,000, these very low birth weight babies. And some of the data that we’ve had from hospitals now that have used this as standard of care for two plus years, have shown that, uh, vivo significantly improves not only the health outcomes of these very low birth weight babies in terms of, you know, one of the major issues with preterm babies is surgical interventions and mortality as a consequences of something called necrotizing enterocolitis again, which is an overgrowth bacteria, but the improvement of all of these other health markers for these babies, one of the institutions that have been using this over two years of reported a $23,000 per infant savings in using the vivo for their very low birth weight babies. So both the improved health of the infant and the health economics should drive the solution into all NICU’s. And I think the same to the healthy term infants that are born through insurance companies, or even governments when we get into medium and low income countries.

James (33:05): Well, it must be extremely exciting to be working on something that’s going to help. So many people, so many children while also probably going to make some serious money.

David (33:14): Exactly. But, you know, we’re always raising money. We’re raising more. In fact, we’re just wrapping up a series D round now, and to power, a number of key clinical trials and international and domestic market loans.

James (33:25): Do you guys plan on going public anytime soon

David (33:29): IPO’s or even, um, the new spec approaches, uh, are interesting options and ones we’re certainly considering for the future, but at this time, our focus is simply to build more babies and microbiomes fixed.

James (33:40): Awesome. So you’ve been super informative. I like to end every interview with just a few fun questions. And this was a particularly interesting interview for me or relevant conversation for me, because I believe about 10 years ago, I completely new to myself with some antibiotics and my gut has never been the same. So if you don’t mind, could I ask you just a few questions, maybe some tips

David (34:03): Biotics do really mess up your gut microbiome. We’ve all known that. And as we take more courses of antibiotics, which we need to, in many cases to get over communicable diseases and important to do so, we have to remember that every course we take is decreasing our microbiome diversity by a significant amount. The question I think for adults is to maintain as high a gut microbiome, diversity as possible. Unfortunately, priding probiotics probably doesn’t increase your diversity, the diversity of the gut microbiome. And here’s my final thought. You have to feed those bacteria. And those bacteria in your gut are dependent on the, what we call fiber in food. The things that we don’t necessarily digest, we provide it there for our gut bacteria. And so the more diverse your source of fiber, the more diverse your gut microbiome would be. So take the course of antibiotics. If it makes you feel better to take a probiotic fine, but most important is probably get back into taking as many different or increasing your dietary diversity as much

James (35:03): As possible. So just increasing vegetables, you know, whatever you can do to just increase the variety of foods,

David (35:09): Correct. Don’t eat carrots all the time. Don’t eat peas all the time, mix them all up and get a variety of, uh, of fiber. And there’s actually fiber in animal products as well, too. So maintain as much of a diversity in your diet as you can, and that’ll establish or maintain as much diversity as possible in the gut microbiome and use antibiotics judiciously. You know, if you’ve got a little sore throat and you can get by without the antibiotics, remember a lot of the microbiome companies today are referring to the gut microbiome as an organ system. It is basically an malleable organ system, and you just nuked that Oregon system and likely in most cases, it comes back pretty much the same as his left, but the diversity has gone down by a percent or two. You mentioned earlier that [inaudible] would be eventually available, you know, globally.

David (35:59): I mean, my limited understanding of probiotics is they need to be kept refrigerated. They need to be in a cool place, or they get die. I mean, maybe that’s totally wrong, but how would that work with shipping those you’re absolutely right. They are live organisms, even though they’re gone into some sort of suspended animation as best we can make them go to sleep, but they still are alive. If they were dead, then it doesn’t matter. You can ship them at any temperature, so you really have to keep them cool. In fact, there are a lot of probiotics out there that are being sold that are not kept cool. And for the most part, they are probably mostly dead and maybe they work while they’re dead or not. I have no idea. Cool. Shipping is something that we can handle in our modern nations. And it’s a little more challenging in emerging countries, but we do ship cool to Singapore and Hong Kong.

David (36:44): There’s ways of handling the shipping to keep it cool and to storage to keep it cool. But we recommend when a mom would buy a vivo from us across the website, a we ship it in a cold chain and we suggest to mom, as soon as it gets there and it can get there in a day or two is to take it out, put the package that you’re going to use over the next 28 days in the refrigerator. If you’re getting some extra packages, put them in the freezer and just keeps quality. Good. Awesome. Well, that basically answered a lot of my other questions. I live in Thailand, as we talked about before the interview, and I don’t think there’s any way that I can get probiotics shipped to me, without them experiencing the beating heat of the Thai sun. There is ways it ends up costing more, but for your baby, and we’re talking about a very precious thing in your lifetime, and, uh, you may pay hundreds of dollars for a baby carriage or other sorts of things I added cost of having to ship cold and the potential benefits for this, my guess is that for most part, it’s going to be worth it.

James (37:41): And that’s a no brainer for sure. The happiness of your child. Yes. The health of your child for us as well. David, awesome interview. Thank you so much for joining me. I learned a lot and I’m sure the audience did as well. Thank you. If anybody in the audience wants any more information, they can always see our website at www dot evolve, biosystems.com or www.vivo.com or hashtag vivo bio.

James (38:05): Or evolved bio on Twitter and LinkedIn, if you got this far, I just want to say thank you so much for listening. If this was all interesting to you, I’d love to connect on Instagram and hear your feedback. I’ll also be posting clips from the latest episodes as well as anything else. I find interesting about the biotech industry. You can find me on Instagram at simple biotech. And if you’re interested in the companies that I’m looking at and the companies that I’m excited about, connect with me on angel list at angel dot slash James rule. That’s James R U H L E. Thank you so much and be safe out there.