 Autism today is diagnosed behaviorally. There's no blood tests that a physician can order, nor to A, diagnose the condition, or B, determine which children are at risk for developing autism. Those don't exist in the marketplace, and that's what we're bringing to market. ["Demo Day"] What's up, everyone? We are at IndieBio Demo Day. We are back. And we are with John Slattery from BioRosa. Yeah, thanks for having me. I'm super excited to talk to you. Thank you. BioRosa is so important. So let's start by just giving a very basic understanding. So it's early stage diagnosis of autism, pediatrics, and children. So autism today is diagnosed behaviorally. There's no blood tests that a physician can order, nor to A, diagnose the condition, or B, determine which children are at risk for developing autism. Those don't exist in the marketplace, and that's what we're bringing to market. By doing so, research continually shows that if children get diagnosed with autism early and they get into behavioral services early, they have better outcomes. But the same tools that we're developing for diagnosis, by understanding the biology of disease, we can actually have a resurgence in trying to figure out treatments that affect the biology to improve behavior. And we have some interesting and compelling data on that already, which is super exciting. And we're looking to further expand that with that extra amount of funding. So, OK, and let's, as we go into more of the nuance of this, because we are going to unpack that, I want to know you better. How did you get passionate about this? Yeah, so I was introduced to autism when I was about 16 years old. One of my best friends whose wedding I was in a couple years back, his brother has a severe form of autism to the point where I would go over to their house during high school, see holes in the wall where he would have aggressive episodes. It was very heart-wrenching that a family had to deal with a child that was so behaviorally impaired that it affected the whole entire family unit. He didn't interact with people normally. Kind of classic autism, we refer to it as communication and social impairment, restricted and repetitive interests. And he met kind of the cardinal symptoms of autism. He kind of had scripted speech. He could tell you just amazingly every single, if you walked into his room, every single flag from around the world was in his room. And he could tell you about anything and everything you wanted to know about each place on the earth. He would watch the same shows over and over again. He could not interact socially. So it just really put a passion in me, an intrigue, of what makes someone's brain function that way. And while he's so impacted and won't be able to have a job and won't be able to live a normal productive life in society, but there's these things that he could do that none of us could do. So I was like, by understanding autism, what could that mean for how the brain works? What could it mean in terms of better interacting or understanding how people interact with each other and just kind of getting a better understanding of brain function, which is really what got me started on a career in neuroscience. So that's kind of where it started. And then I was fortunate enough to be able to kind of bring things full circle and work on really cutting edge autism research in my hometown, Lerak, Arkansas is where I'm from. That's where Arkansas Children's Hospital is. And while most people were focusing on the genetic basis of autism or doing eye tracking technologies or brain imaging or EEGs, all these different things, this group in Arkansas said, huh, we think that autism is metabolic. And they started finding these peculiar abnormalities in the way cells communicate and the way that things like the mitochondria function and seeing all these different disturbances in biochemistry, which Jill James, who's a co-founder in our company said, huh, there's some really interesting peculiar biology going on here. I wonder if we can improve the biology of the disorder. And that was just her first question. And she realized that she could, and then she goes, okay, well, by changing the biology, does that also improve the child's behavior and function? And lo and behold, it was happening toward children were in clinical trials and responding. Then we started kind of going full street press on that and had some really, really interesting results, which we're hoping to further expand on with Biorosa. Awesome, that's such a good story of getting involved because, man, does it really take a just a profound sort of like wake up to like a serious heart and gut wrenching problem in a family to really be like, I am so passionate about like solving that. Yeah, and then clinically, when we saw all these kids, you know, we saw thousands of kids over the seven years that I was there from all around the world, it was pretty remarkable. We kind of created this multi-disciplinary autism clinic dedicated to the medical needs of these kids. These kids have a lot of comorbidities. They have GI problems, a lot of them have seizures. A lot of them are really medically fragile and we think that's because their metabolic systems are very fragile. So there's ways in which you can treat the biology to improve behavior, but one thing we really need to do and research showed over and over again is if you could diagnose earlier, it's gonna relate to a better prognosis for that child. And then that, that's the gatekeeper to opening up a whole new world in which we could start diagnosing different, treating it biologically and allowing these kids to actually respond to behavioral interventions in ways that they can't because their own biology is fighting against them in some ways. Yes, yeah. So let's talk about the actual metabolic markers. Okay, so let's talk about those and then let's talk about what you're making is able to detect that. Cool. Yeah, so these are really foundational biochemical pathways that are involved in every cell in the body. So they are involved in what we call one-carbon folate metabolism, which is a very complex interconnected set of pathways. They're involved in things that are extremely important for normal physiology and the developing brain is very vulnerable to anything. So if there's problems in these metabolic pathways or metabolic blocks, if you will, it's gonna greatly impact the brain more into effects on other parts of the body. And one thing that's really interesting about the brain is that even though it's only 2% of body mass, it receives over 20% of the oxygen to supply. So your heart's constantly pumping to make sure your brain's always getting glucose and oxygen and if there's metabolic blocks, it can impact cellular function and we're seeing problems in things that are related to gene expression like epigenetics. Folate metabolism, which every woman during pregnancy goes on folic acid supplementation because we know how important it is for neurodevelopment, but these kids are seeing, we're seeing problems in folate metabolism so they're not properly able to utilize folate the way they're supposed to. We're also seeing problems in things that we call redox which is the primary antioxidant in our cells is called glutathione. It's kind of this God molecule, if you will. So problems in glutathione can actually cause something referred to as oxidative stress. And oxidative stress is kind of this smoke and gun, if you will, of problems and that that impacts like your mitochondria, which are the central metabolic, regulators and that if there's problems there, well the developing brain requires a ton of energy in order to properly develop the way it's supposed to. So if you have oxidative stress impacting the mitochondria, it's gonna affect the way that the brain is able to develop and function because it's not getting the proper energy supply it needs. And then we're also seeing problems in what we call purine pathways and purines and pyrimidines are the building blocks for DNA. So all of these pathways are connected and we're seeing disturbances in all of them and the novelty of what we're doing is that we can take a small amount of blood and run marker and we do machine learning on the data but we get the signal from something called mass spec and do like a metabolomics approach. Then we can determine based on the metabolic signature which children have autism and which ones don't with really good accuracy. And the accuracy is actually just as good or better than behavioral diagnosis. We can't replace behavioral diagnosis until we're able to further validate our approach. But we think this may have the potential to be able to detect autism biochemically and put kids into services before they ever even develop symptoms of the disorder which would greatly improve their prognosis. We know that children that if they get diagnosed before age two, there's this period of synaptic pruning in the brain where if you get kids in early before that, it's kind of like a window that's shutting, right? There's this period of pruning and if you can get kids in before that shuts, certain kids actually recover from autism because you can diagnose and put them into very intensive behavioral interventions when the brain's very plastic. And then they actually can have a much better response potential. Unfortunately, most kids miss out on that window of opportunity. We're talking about like three years old. Yes, most kids, you know, a parent suspects a problem as early as 12 months. Most kids are not diagnosed until four, four and a half or even older. If you get them young, you can get the right behavioral therapies in. So tell us about the meta box signature. Can we talk about what are the specifics on that? I can't really talk about the specific markers, but yeah, it's involved in those pathways. Okay. And then machine learning helps us determine the critical pieces of those pathways that are necessary to predict which sample came from autism or not. And then the other really cool thing about this is not only is it kind of a binary distribution of yes, it came from autism or no, it didn't. The markers also, you know, autism is a spectrum disorder. And we're seeing that the severity of the metabolic phenotype of the child correlates with their behavioral phenotype so that we can actually see that how severe their metabolic system is impaired, that correlates with how behaviorally they're impaired, which is remarkable. So that allows for a really great opportunity of being able to get a baseline of how severely affected they are. Then if we start seeing changes in these markers over time, that correlates with a meaningful clinical response. We've actually seen that in clinical trials. It just needs to be done much more and at a greater scale so that we can actually start integrating it into clinical practice. And so is the metabolic test a, what is it, a small blood? Yeah, a very small amount. And what age would you recommend, are you recommending this? So we're doing a validation study in which we're putting our biomarkers and algorithms up against the current gold standard, which is that one-on-one interaction between a child and a therapist to validate it against, you know, what is the gold standard today, right? So what we're doing is enrolling children between the ages of 18 months and 60 months. So that way, if we detect a signal, we can be able to take those 18-month-olds before that period at age two or 24 months, put them into services faster, and we will have a chance of making sure that more children have a chance of an optimal outcome where certain children actually recover from their autism to where if you did a behavioral diagnostic test on them after we intervened during that time, they wouldn't meet qualification criteria for autism anymore. They fall off the spectrum. We wanna make sure more of those cases occur. And then we also feel that by addressing the biology of the disease or disorder, we actually have an even greater chance of children that miss out on that window of opportunity to really moving the needle on them to improve their systems and their body to try and really improve their quality of life and have a much better outcome than's possible today. And what is the behavioral therapy that is applied then? Yeah, so the leading autism behavioral treatment is called applied behavioral analysis. So it comes from- And would you take that? Would you work with that? Oh, absolutely. Yeah, okay. Yeah, one of our goals as a company is to align with one of the leading, applied behavioral analysis goes by ABA. One of our go-to-market strategies is to align with ABA partners to make sure that they can only do ABA once a child's been diagnosed, but there's a wait list all across the country and around the world depending on where you are and how high throughput the clinic is. Kids are waiting anywhere between three months and 24 months. So parents imagine- Need more training then. We need more training. So you have more kids that need to be evaluated for autism than there are practitioners that can do the diagnosis. So it just creates bottleneck and jam in the system. And we need the scalable diagnosis. Exactly. So that way if we diagnose earlier, well the only way the kids can begin at ABA which is covered by insurance in 48 states, then we can be able to have our test put them into ABA faster and so that way they don't have to wait anymore. If you have a high reason to believe that a child is at risk for autism, you can do a screening tool like ours and put them into services faster. It will unfortunately have to be self-pay until insurance covers it, but it's something that allows the opportunity to where insurance will cover some level of the treatment. We just wouldn't know how much. But it allows kids access to faster therapy when they need it the most, which is critical. Yep, yep. And then what is the, just give us a brief understanding of what even, what occurs with the child in ABA? Yeah, so it's something called discrete trial learning where it's basically like each behavior that a child has, you take that behavior, you basically deconstruct it and then teach the child bit by bit how to build the appropriate behavior and then reinforce them on doing appropriate behaviors to ensure that they're learning the correct way to interact with people and things and their surroundings. Interesting, so what, now I'm interested to hear your thought about this and I've kind of poked in this area of neurodiversity for a while and there are videos that you showed me to and that have been, we've seen now of children that have severe motor impairments where they're doing its stemming and things like that and that is okay, that's an absolute obvious like that is hurting them. Okay, and then there's the, maybe let's call it an opposite which is like they're obsessed with all of the flags and all of the countries in the room and they can tell you all these stats about figures, facts about them. How, if it's that maybe mild, if it, let's call it mild, if it is mild and they're just obsessed with a specific thing like that, maybe they're meant to be genius in that thing and so what, so yeah. Yeah, so I mean the type of autism that we're looking to truly move the needle on for kids are kids that they have, they will not be able to live an independent functional life, unfortunately. Until we do something that can dramatically improve their prognosis. There are things that are very interesting that we're starting to learn that some of these children, while if you test them on normal IQ tests, they'll bottom out and you'll think that the kid meets criteria for maybe a mental retardation but if you actually test that child in a way in which they can interact meaningfully, like a storyboard where you actually can go with the child, I've seen kids that can't speak but the parent takes them over to a storyboard where they say what's 1,765 divided by 14, which I couldn't tell you off the top of my head. No way. But these kids will go over there and move the storyboard to the exact number and I can get out calculator and they're correct. So they are not children that are mentally retarded, they're a genius level. It's just they're trapped in and can't express it the way that they want to or the way we want them to. So imagine how stressful that must be to the child. If I couldn't interact with my surroundings and I couldn't communicate what I wanted to and I knew the answers, how would you respond? I'd be pretty upset and probably do things that appeared to be aggressive behavior or be a temper tantrum or something like that or just have a meltdown. I mean, that's a normal response. So maybe there's certain aspects of these kids that they're normal, but we consider their behavior abnormal. But what if we could improve their biology to make sure that what we consider abnormal can actually have a better chance at being normal? And create a more adaptive culture. Exactly. So interesting. I'm loving where the potentials of evolution in the most beautiful ways are evolving but also in the ones that are, like you initially started describing it with the inability to properly independently function in this society. Yeah, it needs to be tackled. It does, because I mean, the estimated cost of society per year on dealing with these super impaired kids is $30 billion a year. And the autism rates today in this country are one in 59. Wow. Back in the 70s, it was one in 5,000. Yes, it's moved up by two orders of magnitude. Yeah, and one in 42 boys in this country. And around the world, is it also moving that quickly? In westernized countries, yes. Why that is, we don't truly know. There's a new... Might have to do with the use of computer technology. There's some really interesting theories on it. We've written a few papers that kind of combine certain theories in terms of what might be going on but what we're seeing from a biochemical perspective, we're not saying that this is the cause. It's just something that can be leveraged as a better diagnostic tool, and something that can be used to monitor patient progress over time. So, you know, there's the bottom line with autism of what's causing it. The answer is many, many things. We can look at problems in the genome and know that there's hundreds of genes involved. Then there's also not nuclear DNA where you do looking at chromosomal microarrays and things like that to look for genetic polymorphisms. We're seeing problems in mitochondrial DNA. And not necessarily mitochondrial DNA point mutations but what we call heteroplasmy, where the amount of good mitochondria per cell is different in a patient with autism versus a patient that's normal versus a patient that has even diabetes. And then there's problems in this new emerging concept called the microbiome. And we seem to see problems there. I'm not saying that's causal, but it seems to be associated with autism, especially kids with autism that have GI disturbances. And there's really interesting data on trying to manipulate the microbiome in order to improve GI symptoms and behavioral symptoms. And we have some data that shows that our markers seem to move in response to even something that wouldn't even affect our targets, but their off-target, which is the microbiome. If they're producing small molecules that can affect our own metabolism, then by improving the microbiome, we can actually improve the way our own body functions and decrease certain problems with brain function that may be a result of problems in that gut ecosystem. There's, you're just listing all these variables that actually go into the equation and just to someone that cares a lot about nuance and multivariability is just so tough to actually calculate. Yeah, and that's one of the things that our algorithms use is a multivariate analytic approach to taking kind of disparate sources of information and being able to kind of pull it together of what's the signal from the noise and be able to leverage that in a useful way to try and monitor disease state and progression over time, as well as response. We feel that the same sort of approach with autism kind of being this amalgam of all these things that can go wrong during the wrong time during development leading to an increased risk in autism, that the same sort of thing can be applied to other disorders of their chronic disease. I'm a firm believer that the same sort of abnormalities that we're seeing in autism where it's problems with the mitochondria, problems with oxidative stress, problems with the gut microbiome, all of these things are interconnected systems when certain aspects of the body break down, it promotes other diseases. And one that we think really strongly seems to be associated with autism later in life. It's not autism, but it's a different phenotypic expression. It's actually Parkinson's disease. There's a lot of really, really interesting data showing that patients with Parkinson's disease have problems with oxidative stress, they have problems with the mitochondria, they have problems with the gut microbiome, and that all these things kind of accumulate over time and that those problems end up breaking down neurons in the substantia nigra and dopamine production and all these different things. But that may be an output of the body. It may not be the initial causal factor. We think it, we consider it that way because you end up seeing behavioral symptoms of Parkinson's with rigidity and all these different things but what if it's actually starting in the gut and breaking down the metabolic systems of the mitochondria? What if that's actually the factors that happen way before the development of Parkinson's? And we actually see that patients that have Parkinson's, a lot of them have high rates of constipation. We see the same thing in autism. So I think we're gonna have a lot of lessons learned with what we learn from autism of being this kind of microcosm of all these things can go wrong at the wrong points during development leading to autism. But other factors of chronic disease across the lifeline, there may be similar shared mechanisms going on and what we are able to discover from autism we can apply to other things. Yes. And what other people learn can apply to you. Exactly. Yeah, the whole idea of like digitally diagnosing a developing disease is something that is so fascinating. So how does bioerosa get into the hands of parents? So the first thing we need to do is a validation study against the gold standard. So the last thing we wanna do is bring a product to market that has not been rigorously tested against the gold standard. Let's see. Reason being. Let's say it does succeed. Yeah, yeah, yeah. And then what, okay. Okay, because we don't want to bring a product to market that would not be rigorously tested. Totally. Because autism's a scary thing and nothing drives me more crazy than people trying to take advantage of desperate parents. Totally. That's, it makes me very angry. Worse. So we, upon validation, we will be able to bring our product to market as a screening tool where children that are looking to get assessed for an autism diagnosis at developmental centers, they will be able to get the bioerosa test while they're waiting in line, so to speak. And so that way all children will have access to the test. Our goal as a company is to make sure that's available to all children, whether they can afford it or not. And that for those that can afford it, it'll be $500 self-pay. And then until the entrance covers the cost of the test. We're also selling it to groups that are developing treatments for autism in biotech and pharma as well as academia. So that way we can hopefully accelerate drug development to bring the first FDA-approved interventions to market for these kids as well. And then like a scholarship system or something for those that cannot. Yeah, so I mean fundamentally what we're doing to try and improve lives for kids with autism, that's what it's all about. And then we wanna take some of our own money and put it back into more autism research from when we are profitable to make sure that we can accelerate novel new therapies because the problem's not going away and we need to change the system and make it better to improve patients' lives. What would be something to, do you think there's something else that we should tell people about what you're making, what you're building on the way out? Is there something else that's... Yeah, I mean we have the ability and opportunity at hand to be able to potentially prevent autism altogether. That's not to say that it's gonna work for every patient. And when we say autism, we're talking about those super severe kids that won't be able to live independent functional lives. The other side of the coin is that if we're able to have a better tool that we can bring clinicians to where they can monitor patient progress, we're able to help facilitate drug development, the millions of kids over 30 million that are affected by autism, that's 30 million children, there's over 100 million people affected by autism, like adults. So massive market opportunity, but we're looking to also work on facilitating drug development and discovery so that that way the people that are affected, we can also move the needle on them too and make sure that they have a more productive life. One of the worst things as a parent of a child with a super impaired kid is what's gonna happen when I'm gone? Who's gonna look after my child? Those are terrible fears for a parent to have. I made a promise to these families a long time ago that we're gonna do something to make sure that that's not as scary a thought in the future and that's exactly what we're aiming to do. I love it. Thank you so much. Sure, thank you. Thank you so much for working on this. It's my pleasure. Tackling this problem. Hey, these kids need better, the families need better, and we're aiming to do that. So, thanks for having me. Thanks for teaching us about it. Yeah, sure, man. Thank you. Thank you, awesome. Thank you. Thanks guys.