Talking Biotech Podcast 358 - Extending Health and Life, Starting with Dogs === Kevin Folta: [00:00:00] Hi everybody. And welcome to this. Week's talking biotech podcast by collabrate. Now one thing we all have in common, whether you're a man or a woman, a sea urchin, or a great blue whale is aging. The progression of time causes changes in our physiology. Our ability to move our strength, most of all, susceptibility to various diseases and disorders. Now over the last three decades or so. Genes have been identified in model systems that seem to play a role in the process of animal senescence and with an understanding of these mechanical underpinnings of aging, we gain the potential to push back with lifestyle modification and potentially even pharmacological therapeutic intervention. So take a pill, slow the aging process. Time is moving fast and a pathway to solutions in humans might take seemingly forever, especially for those of us who are on the backside of that curve. [00:01:00] um, if we've lived for more than half a century, the cures can't come fast enough. So what other ways might we attack this problem that comes from too many trips around the. Today's guest is Celine Halioua. She's the CEO of loyal. So welcome to the podcast, Celine. Celine Halioua: Hi, great to be here. Kevin Folta: yeah, this is really cool. I'm really glad you're here. And I really think this is a fun topic for lots of reasons. So before we kind of get too much into what your company does and how you do it, can you just start out with very simple terms? What is this thing called Celine Halioua: aging? that's actually a very, uh, contentious question. Um, so maybe I'll say how I think about aging and the, the aging problem. Um, so the best metaphor that I've come up with, uh, which is it's it's suboptimal, because I don't have any car expertise, but is so rubber is used in various parts of your car and has the same physical properties, generally [00:02:00] speaking, asterisk, asterisk, uh, no matter where it is and it ages over time in relatively the same. But the kind of end state disease that you get, um, depending where that rubber is defers significantly, where it is. So if it's in the engine, it might be a gasket leak. If it's in the tire, it might be your tire cracking. And so the way you treat those endstage diseases, changing a tire changing, um, the valve are very different, but there's a preventative mechanism or an, a way to treat the aging of the car, which would be, for example, creating a rubber that's more resilient to heat and stress. So that would extend. The all cause health span of the car in delayed diseases indications, uh, that come, uh, later in, in the life of the car due to the degeneration of the rubber in both places. So really the way I think about aging is it's. Um, actually I, I think, uh, KM cable line tweeted does that recently, it's kinda like the. The, the precursor mal of all melodies and so far that [00:03:00] it underlies very phenotypically, uh genotypically et cetera, different diseases, these like Alzheimer's Parkinson's, uh, cancers, OS arthritis, dementia, all of these disorders. But the underlying mechanism is a way by which we pathologically age over time. What are the things that go wrong in our bodies that break down our bodies over time, that over decades lead to the age-related diseases that we then treat independently. So really the aging field, at least aging field, as I see it is trying to treat the way by which we age over time to be Amod. Uh, multi causal drug that treats multiple HLA diseases at the same time or prevents them or dampens them diseases that are today not considered to be biologically similar at. Kevin Folta: Yeah. And so let me just throw you my, my definition, maybe how I think about it just cause I think it's germane to your topic. And I, like, I always think of it as a normal part of development that when you look at humans or mice or dogs or whatever, they all kind of go through the same progression of being a little pink wormy thing to [00:04:00] kind of upright, to kind of gradually through these different phases, through an adolescence, through an adulthood and eventually into the senescence and that all of this is dependent upon specific. Gene expression metabolism, maybe epigenetic phenomena with that progression into a senescent phase, you kind of lift a gate where all of these other processes, like you mentioned, these different disease states now become more possible. And, and, and is that seem to be okay too? Celine Halioua: Again, this is a very contentious topic. I think the way I would think about it, another way I think about it is a deviation from optimal biological function. Right? So can we redefine what a disease quote unquote is? So, um, the other example I always use, um, and I really need to come up with less embarrassing examples is that, you know, when I was in college and I was 20 or 21 or whatever, and. go and drink. Uh, I'd get up for class the next day at 8:00 AM and, you know, be fine. I actually would brag about how I never got hangovers. Uh, now I have one glass of wine at [00:05:00] like some cringy VC networking event and I feel it for two days later. Um, and I don't have a disease. I don't have, you know, a liver, uh, me metabolism disorder. I don't have anything like that, but I've lost a degree of resiliency to the toxin that is alcohol presumably due. To age. Right. And so it's really that deviation. Um, also things like I need to sleep eight hours a night now. Like that's what I really think where disease is going. Um, but what's necessary. There is to be able to quantify that. And that's actually a very hard problem. Kevin Folta: Okay. So, so that's good that we've kind of set up a couple different ways of thinking about what this aging process is so loyal. Your company works primarily in what organism, Celine Halioua: uh, dogs , as you might have guessed by a name. Kevin Folta: Yeah. No, that's a really, it's really cool. I was really happy to see that. Uh, and, and I really appreciate your website. It's really well done. So you're working on dogs and, you know, humans live to 80, you know, dogs. [00:06:00] If you're lucky you get. Makes it to 10 or 15, depending on whether it's a big dog or little dog, all that stuff, a breed, you know, you look at a mouse that lives a year, if it's lucky, right? So these are all mammals. We all have similar developmental progressions. What is it about the clock in each one of those organisms? And it, I guess it seems to be related to size because like whale lives longer than us. So what is it about the clock and size and how do these things inter. Celine Halioua: Yeah, well, so one of the reasons I became, I'm a huge animal lover to be clear. I grew up with 15 cats, three dogs. We used to rescue, uh, birds is broken rings, like the, the whole, the whole thing. Right. Um, but I, I became interested in dogs actually, because there is a switch in this size lifespan, dimorphism. Um, so the bigger a dog is on average, the shorter their lifespan. So a great day might live seven to nine. While Chihuahua might live, you know, 16 to 18, and it's actually a linear, inverse [00:07:00] relationship between the weight of a dog and their, uh, expected median lifespan. And that's really interesting because as you just mentioned, you don't really see that in other organisms, generally speaking, a bigger and organism is the longer their lifespan is. Um, and. We, I became interested in dogs in addition, for other other reasons, I'm sure we'll talk about, because it seems like we might have given big dogs accidentally an accelerated aging disorder. Um, when we were breeding for. For, uh, a size, right? So when we selectively bred dogs for the pheno hips that we wanted, you know, let's say friendly in terms of golden retrievers or curly hair, or really big, and, you know, for great Danes, uh, people didn't understand genetics, so they just inbred and they would bring breed, you know, sons to daughters and, you know, just cross lines, like crazy, which was very effective in getting the phenotypes. They wanted very quickly in a couple of generations, um, but was very ineffective in creating, um, robust, uh, Lines of dogs that didn't have negative [00:08:00] consequences of this in breeding. So most breeds of dogs have, you know, some disease or diseases that are associated with them and it's due to its in breeding or thought be due to in breeding. So yeah, dogs have this really interesting size lifespan dimorphism to an extreme level that we don't see in any other breed, our species, um, which I think can teach us a lot about pathological aging and, and the lack there. Kevin Folta: Yeah, it seems like somebody I'm, I'm almost certain I'm, I've read stuff that really talks about that dimorphism. And if people looked at things like gene expression or, you know, methylation state, epigenetic state between small dogs and big dogs to get any hints as to why they might age a little faster, Celine Halioua: Well, that's what we're trying to target with one of our, uh, drug programs. But yeah, we are also, so we're running a, uh, community driven science program called X thousand dogs, which is, um, sequencing, um, dogs of all sizes, all breeds, uh, which is looking at epigenetics. And so for context, for those who might not know what [00:09:00] epigenetics is, you have your genome, which generally speaking is static. Uh, over your lifespan. Um, and it's generally speaking same from cell to cell. Um, epigenetics can be thought of as the 3d structure of that genome. So how is it folded over? And the folding over into structure impacts the function, right? So genes that are activated or deactivated or patho, pathologically active or pathologically deactive, um, and it's thought to be quite relevant, um, and perhaps unpredictable to aging. So we don't have any results yet on. Size, uh, lifespan dimorphism on that variable, um, yet, but it's definitely something we're looking at. Kevin Folta: Yeah. Maybe I should ask now. I kind of would hate to ask at the end, is this kind of citizen science thing still open and available. Celine Halioua: Yeah, so we are, um, we're not currently sending out kits, although we will likely reopen that portion of the study. But the other really key part actually is the survey questions. Um, so we ask people for photos of their dogs over [00:10:00] the, over their lifespan, and we ask people for information on how their dogs activity levels change in time and age. And it's actually incredibly, incredibly valuable. Uh, again, this problem of quantifying the aging process in a complex species. So the survey portion is a hundred percent open. If you wanna participate, you can just go loyal for dogs.com and click on X thousand. And we'd love to have you. We've had, um, over 130,000 survey questions answered so far by pet parents, which is pretty cool. Kevin Folta: That's cool. Cause I got four dogs and they range from yeah, they change from Chi. They range from Chihuahua to great ponies. That's Celine Halioua: uh, quite the span Kevin Folta: it's in size is inversely proportional to how long I want them to live. love the great ponies. They're Celine Halioua: such sweet dogs. Uh, uh, understand English we'll work on. Well, the, Kevin Folta: the, um, the big dogs are livestock guardians and they, they take good care of things out here on the farm. And, uh, but they're, you know, sweetest damn dogs. And I just, and they're [00:11:00] so such good workers, but it really ties in with the, maybe the next question, how much of this is related to the total number of calories they consume? Celine Halioua: Well, so that's interesting. The only as I'm sure, you know, one of the, the first mechanisms interventions to show lifespan extension was in the 1930s and rats, and they showed color restriction accents, rat lifespan, and it's been, you know, replicated over and over again. Um, in various model organisms, um, nothing is, you know, concrete in biology. We don't know if it's a nutrition based or there are some theories that it was about restricting a certain acid, but you know, generally speaking, we can say with relative. Uh, certainty that clerk restriction, generally speaking, extends lifespan. Sorry. I'm putting a lot. You know, asterisks in my sentences, like, like any good scientist, I guess. Um, and it's also the only intervention that as far as I know, um, has in a full, uh, finished study was the intention of looking at lifespan and healthspan and [00:12:00] dogs. So, um, Purina actually in the late nineties, ran a clinical study, um, where they did 25% color restriction in Labrador. Um, and they showed an approximately two year lifespan extension in these dogs. And these are already long lived dogs. Um, showed it approximately two year life span extension in these dogs and a non statistically significant, but pretty strong signal. Um, two year delay in the incidence of osteo arthritis and, um, certain forms of cancer. And I, I bring that up. That latter part is really important because osteo, arthritis and cancer mechanistically are, you know, about as different as they come. But under just aging theory, they're both driven by aging. They're both age associated diseases and to show even a non statistically significant delay in those diseases. In those dogs who also had lifespan extension is a really. You know, granted one study, um, but one study by a reputable partner, um, work showing that maybe this does translate out to a complex species, like the, like the. Um, and mechanisms are saying that we're looking at for some [00:13:00] of our drug programs too. We won't ally restrict dogs, but you know, and nobody wants to do that. Well, Kevin Folta: I, I, I, I think that the data are pretty good on, on that, where I've seen it over the years in a number of different organisms and it's pretty compelling. And I just was thinking in terms of, you know, Chihuahua eats a little bit, you know, whatever, how many calories a day, it seems like the great purines. You know, 10 times what the Chihuahua eats and the chihuahua's gonna make it a long time. The great Piase isn't is it just a question of how much coal you throw in the furnace and that the furnace is the same, you know, something, but this is just me spitballing ideas here. I just think it's so cool. You're talking about, um, lifespan and health span and what's the difference? Celine Halioua: Yeah. So, so if you. Lifespan extension, you actually are implying hell Spann extension. So lifespan is just the quantitative numbers of years lived. Um, Hells span is the quality of those years. Um, and the quantification of it, lifespan is just a quantitative numbers of years lived. So six or seven [00:14:00] years of age, uh, Hells Spann is the quantification of the quality of life of those years. And so it's. I I in, from what we know, pretty damn difficult to extend lifespan, but not extend healthspan. So it's hard to take an old decrepit dog and drag out those old decrepit years, like zombie dogs. Um, but it is the first thing that people think of because it is how late stage disease, um, therapeutics often work. That's how, you know, a, a. Cancer certain cancer therapeutics like a chemotherapeutic isn't, you know, known for improv quality of life. It's really more about kind of giving the patient more time. And so the drugs that we're developing are specifically intended, and we really emphasize this to pet parents to extend health spans. So the number of quality years that they have with their pet. Um, so it's not just the years of the pet, but it's like how many years can Fido go and, you know, run around at the, at the. Kevin Folta: Yeah. So this is where your company really starts to intervene into the process. And we'll talk about that on the other side of the break, we're speaking with Celine Hollywood, she's the [00:15:00] CEO of lo and we'll be back with collaboratives talking biotech podcast in just a moment. And now we're back on the talking biotech podcast by collab. And we're talking with Celine HWA. She's the CEO of loyal, which can be found@loyalfordogs.com. Is that loyal F R or the number for. Celine Halioua: Uh, F Kevin Folta: R okay. I always wanna make sure the bottom line is, is that this is really exciting work because you're looking at this question of longevity, which is something we all worry about and healthspan and lifespan as we, either we age or our parents' age or whatever, or are looking at this all the time. And. The question now is, uh, what can we learn from dogs then possibly translate that to humans. And that's been really kind of where I see from your website, where your company's going. So let's talk a little bit about that. It there's been a lot of work that talks about, uh, methylation and epigenetic markers. All of these things we've discussed on the podcast before that really show similarities [00:16:00] between humans and dogs. And what does this tell us about potential translation of therapeutics that you may design for dogs to solve problems in other mamm. . Celine Halioua: Yeah, so we are committed to bringing forward our drug programs for, uh, pet parents, um, for a number of reasons. Um, we're very mission aligned. Um, there's an obscene amount of dog and cat people on this team. And if we ever didn't do that, I think, um, I would be quickly voted out of the, of the camp. Um, What we're really excited about is while we're developing these drug programs for pets and pet parents, what can we learn about translational aging, about aging in a complex species that's more broadly relevant, um, to understanding how human age humans age over time too. Um, so we do a lot of extra, I would say, parallel work that allows us to. Really again, this problem of a quantifying aging, that's really actually a huge part of it, right? There's actually a lot of [00:17:00] drug targets and mechanisms and whatnot that have shown lifespan, extension health span, extension, and complex in, in mice and other species. But we really need to understand is how do you actually quantify? How do you. Translate an aging program. Right? How do you quantify aging? How do you show a reduction in mortality risk? Um, how do you show an improvement in health span? Robustly? And that's something that we spend a lot of, a lot of time on. Um, and I think in the long term, we are absolutely wanting to develop, uh, drug programs that are. For humans. Um, and maybe cats too. I get a lot of questions. Like cats, cats have a really long lifespan. It's a little bit harder. Um and have you ever tried to give a cat a pill? Like good luck, you know, am I shorten a lifespan of the owner, but, um, that is, you know, maybe, maybe one Kevin Folta: day I would support programs to shorten a lifespan of cats. Celine Halioua: don't let people hear you say. I know Kevin Folta: there's a lot of cat people that just UN unsubscribed, but, um, I've never gotten along much with cats. I'm a dog guy. I love dogs. Um, I guess that's the other big question? What are some of the, um, biological [00:18:00] markers, like some of the diseases or states that happen to dogs as they age that are extremely common and maybe variable between species that make it a basis for something to. Celine Halioua: Yeah. So dogs are interesting in so far, they develop approximately, um, the same agely diseases at approximately the same time in their lifespan as humans do again. Uh, made, uh, scaled for the, the lifespan duration, the one big exception being cardiac disease. Uh, just because, I mean, we don't really know why, but my, my guess is just because, you know, certain forms of cardiac disease are very environmental lead driven in terms of diet and exercise in which dogs don't generally have those issues. They don't, you know, go to McDonald's and sit on the couch all day. Um, but that means. If something works, for example, in doggie dementia, which is a, you know, a real indication, um, or doggie cancer of which is the primary driver of dog death. Um, with age, it's not a [00:19:00] one to one to people to be clear, nothing think it's one to one to people, even in people. Right. But it's a, because that disease has developed over time. It's an induced disease. Like we so often see in mice, um, It's we learn a lot more about the mechanisms that may or not may or not be relevant to these diseases that are incredibly relevant to people. Um, and it's really important again, because these diseases fundamentally take time. So because we are gonna be following these dogs for years, because they're gonna be in clinical studies with us and they're gonna be hopefully out of the drug product, hopefully, you know, for, as a preventative mechanism for their dogs, aging, that gives us the opportunity to learn things. You know, potentially hundreds of thousands of dogs as they age or donate, um, or age slower, um, in a way that just wouldn't be possible, even at a CRO, right? It wouldn't be possible in a preclinical resource facility. It's really only possible at the scale that you get when you're in the clinic. Um, and in companion dogs, Kevin Folta: This, the other part of this to my [00:20:00] mind is that dogs are a reasonably recent species. And these are, you know, pretty recent vintage of genetics that separate them from their canine ancestors. And even within that, we have all of this species, not speciation B radiation you have so many different breeds that have been, uh, some of them very, even very recent. And how much is that helpful or a hindrance to the kind of work Celine Halioua: you. It's a little bit of both. Um, so the way to think about breeds is kind of like a founder population. Um, so in case you don't know what a founder population is and you know, in, in humans, there's some, you know, for example, like island populations, where they were, uh, off of, you know, a very small amount of humans then created the population that's there today. So you might have an. Overrepresentation of certain genes that might be positive or negative. Certain phenotypes of gene has, might be positive or negative that you don't see in a general population. And that's completely true for, for dogs. And so it's kind of both, right? Like [00:21:00] it's, um, like that's like the example of golden retrievers, uh, Goldens have two forms of cancer that are pretty highly represented in a breed that are more highly represented there than there are in other, um, other, uh, breeds of dogs, you know? To treat those dogs, uh, effectively for those cancers who probably need to develop a therapeutic that takes into account the driving genetics of the, the, the that's causing them specifically to get that cancer. But it might also be relevant to understanding those cancers in a more broad population. So like for example, There's some genetically associated dementias and par like early, early onset Parkinson's and curing early onset. Parkinson's probably won't cure, um, uh, uh, sarcastic Parkinson's, but it will give us some information about it. And it's kind of a nice, like thumb hold into or toe hold into a very, very complex disease. Wow. So Kevin Folta: dogs get Parkinson's. [00:22:00] Celine Halioua: Uh, there's evidence that they get some of the changes that you see in, um, in, in the CNS that's associated with Parkinson's. Kevin Folta: Yeah. Yeah. So changes in dopa, dopaminergic you never can say that, um, parts of the brain then, so they're seeing, okay. Well, that's interesting. I never knew that like, Celine Halioua: things like that. Yeah. Kevin Folta: Yeah. That, okay. So I guess the other interesting thought on this is have you found. Any associated genes or gene variants in all the genomic studies here that seem to associate with longevity or predisposition to disease and dogs. Celine Halioua: Yeah. So we haven't shared any of the data publicly yet. Um, but provisionally, uh, we've seen, so for example, with the, the golden retriever example, we have provisionally provisionally. Um, shown a provisional ability to, uh, be able to predict relatively accurately. Um, if a golden is going to develop that cancer, um, before they [00:23:00] have developed it, um, we haven't gone so deep into understanding what exactly are our models, you know, protein that off of, but at least it's a, a broadly applicable. And then with X thousand, we're still, um, we. Thousands of saliva swaps. So we're still sequencing them. Um, but that's exactly what we're looking for are those drivers that are associated really, the key thing was aging knows you need longitudinal data sets. You need data sets over time and you need to see the progression of aging in that organism. So kind of a, we've done cross sectional studies. We did a 500 dog, um, health fan study, which is large and small, old and young dogs. And that's definitely interesting, but I think what we're really like the, like the best data sets are the same dog over time. Um, ideally multiples of that dog breed of that dog, similar environment. And then some that age faster, some of that age slower, some that get cancer, some don't cancer. Cause then you can start to differentiate between what's causing that or hypothesize Kevin Folta: what's causing that. Yeah, you could start 78 in me. Celine Halioua: yeah. I [00:24:00] mean, people are doing that Kevin Folta: oh, they are doing that. Oh, that's good. I guess the big, the drive of your company ultimately is to identify different therapeutic compounds that may be able to affect some of these mechanisms that are related either to, I guess, aging or age related disease onset, or maybe you could just speak to. Celine Halioua: Yeah. I mean, so exactly we want to, we wanna prove that you can develop a. um, for aging and that it doesn't have to be, you know, so most human, every human, uh, potentially, uh, aging company is, you know, developing it, not for aging, which makes sense. Right. It, it would take a really long time to show, um, a reduction in biological aging, in a human. Um, versus we can see that relatively a short period of time in dogs, but the risk of developing, you know, a broad cause aging drug for a specific indication is it just increases the rate of false or the, the risk of false fails. Um, [00:25:00] so for example, if a drug doesn't. If a, uh, let's say a drug is targeting. I mean, one of the canonical, um, unfortunate examples is, you know, unity, uh, which is incredibly mission motivated, great team they're they are developing, um, ESCE, uh, Lytics. So drugs that target esent cells, cells one earlier to zombie cells. Um, but because they can't go for broad cause aging for all sort of reasons, um, their first clinical study at least was in osteoarthritis, but then there's at least. Doubling in the risk there, right? Because it's not only does the drug work, is it at the right dose? Is it, you know, targeting analytic cells? Is it not killing other cells? Um, is it safe? Da da, da, da, but it's also is this specific disease that we chose driven by senescence and is this specific disease that we chose? Reverted or clinic having a clinically meaningful change. If we reduce, um, the senescent cell burden, are we reducing the esent cell burden often enough to have a clinically meaningful change? It's a dose sufficient for osteo [00:26:00] arthritis specifically. There's just all these other variables. It can meet even quantify, you know, pain is actually a pretty like pain in the ass thing to quantify, um, for a clinical study. And so there's all these other variables that actually make it really, really. Um, versus things like lifespan, lifespans, actually, an easy endpoint, like it's a long endpoint, but it's an E it's binary. Right? you can't really like, you know, screw up a, a form on like, what's your pain scale today. And like I'm in a bad mood. So my pain scale's like up two points or whatever. Um, and so it's really about increasing the probability of success of bringing forward a drug for. Kevin Folta: And when you're looking at different drugs, are you mostly focusing on compounds that have already been approved for use in animals or even, you know, other humans, whatever, uh, that have already been approved so you can test for their effect on, in other indications or are these new compounds that are being discovered? Celine Halioua: Um, so we are not doing small Molo discovery at the moment. Uh, we're primarily focusing on compounds where the safety profile is known. [00:27:00] The reason being. One of our core theories is that, um, and I don't think it's a particularly controversial take, is that an aging drug has to be baseline neutral and then hopefully positive. Like it hopefully helps. Right. But we cannot, we are not ethically, uh, justified, nor is the regulatory environment gonna be, uh, amenable to the idea of a drug that is developed for. You know, a, a preventative mechanism that then, you know, makes the person sick in six months, but like maybe prevents a disease they may or may not gotten in 20 years from now. Right. So safety is super important. It's like vaccines are another thing. The safety profile necessary for any vaccine is way higher than a, you know, even a, like a pain medication. Um, so safety profile has been super important to us. Um, and even with some of the proprietor drugs we're working for with now, it's drugs that the mechanisms like the on target. Uh, safety, the chemical class safety. It's all well known. It's also because, you know, if the dog eats the [00:28:00] entire jar of drug, uh, we don't want the dog to die. Right? Like maybe they can have some diarrhea. The pep parenting can be annoyed and next time they'll put it up higher. Uh, but we don't want, you know, severe adverse events to be basically possible. Is this drug, unless they do something. Kevin Folta: So when you're talking about using, um, already approved and things that are known to have good to tolerance already, are you trying to, uh, match those with, you know, potential targets that you're coming up with through genomic tests? Or how do you make that marriage between the test and the drug? Celine Halioua: Yeah, so it's a lot of, we have a biological hypotheses of what we think are speaking. Low hanging fruits, um, for treating aging and dogs. And then we pick programs and develop programs around. And we have a multitude of program. Um, our sequencing work that we're doing now is, uh, so we've been working on drugs for almost three years now, God. Um, and our sequencing work is relatively novel. Um, you know, we started [00:29:00] it this year, so that work hasn't driven into. The selection of the drug programs that we have currently lo one and lo two. Um, but I ably will play into our future programs Kevin Folta: and there's been a lot of work done in things as simple as worms, you know, like Gans, where they've identified genes directly associated with lifespan and have any of those really started to translate to things like dogs. Celine Halioua: Yeah. I mean, so mean Seattle against is I literally have to see against tattooed to my arm. Um, and a black six mass um, yeah, I mean, see against that was a, is actually one of the, the first I'm sure you know this, but like one of the first studies that really gave a lot of, uh, conviction that you could have a pharmaceutical intervention that's, you know, extending Healthman in lifespan because of course, chronical study showing, um, the knocking out of the girls hormone IGF one ortho. Um, showing it, you know, two to four X lifespan extension in GaN. So basically the idea that like one single intervention is sufficient to extend lifespan and healthspan, [00:30:00] um, in a, not that complex species, but you know, definitely not like a cell, uh, thing. So yeah, I mean, there's so much preclinical work that's been done. Um, and I, I think a lot of it's gonna be relevant to dogs and people. I mean, it's gonna have a fail rate similar to, you know, what. Anything. Right. Um, but the problem is I think gets translated out or much less gets translated out. Cause it's not really an aging industry currently. And so that's really kind of where the, the focus is now for. Kevin Folta: Well, one of the benefits that I see of your approach is that everybody loves pet and a puppy and, you know, loves a dog. And do you think that this has broader implications in terms of recruiting people into the interest of aging and aging Celine Halioua: science? Absolutely. I mean, I, it, one of the kind of challenges of the aging field has been. That at least the old garden field really kind of started with this super contrarian narrative around immortality and, uh, life, uh, lifespan, escape, velocity. [00:31:00] Thousand year lifespans and all of these things that we may or may not get, but are, you know, definitely controversial. Um, which at least for the kind of average, American to average individual has left a little bit of a bad taste. Um, and it's, you know, there, it, it brings up a lot of questions and ideas of what happens to socioeconomic equality in a world where they're rich live longer and all of these things, um, versus it's not controversial to extend dog lifespan, right. Um, even cat people. Love the idea of our pets living, you know, longer, healthier lives. Everyone thinks pets deserve the best quality of life we can give them. Everybody thinks pets should be happy. I mean, they're, they're, they're like our furry children in many ways. And so it's really kind of this. Less threatening way to introduce the ideas around. How do you develop a new medicine? What is biotech? What is, uh, pharma? Um, how does it impact your family and potentially help your family in a way that's way less stigmatized, politicized, um, and really kind of, without a lot of the [00:32:00] challenges and, um, You know, negativity that we sometimes see on the, the human side. Um, it also means that our advertisements and our brands are, you know, really good. I mean, billboards with dogs, you can't get better than that. Kevin Folta: No, I, you know what you are exactly. Right. I think when you talk about pharmaceuticals and that kind stuff, people go, oh, those scumbags and the big pharma, um, if you tell people you're gonna help their dog live longer, I think they're not gonna have a problem buying into Celine Halioua: it. Yep. Yep, exactly. And I, I really think there's an opportunity here too. Like once. Get people into the idea, get them thinking about it, then that can really help. Hopefully. Some of the perspectives on the human side too. Um, but even if we don't, at least we'll have, people will have a positive interaction with this, which is, especially in the re the current environment has been, you know, quite, quite negative for a lot of Kevin Folta: people. And we, we touched on this a little bit earlier when you talked about the goals, eventually being translation to humans, that kind of thing. But how much of this is really just a goal of let's, uh, have people who have dogs [00:33:00] and keep their companions alive longer and be healthier. And how, how close are we to tangible products that can help that process? Celine Halioua: Um, so REL relatively soon, um, we are aiming to have our first products in the market in two to three years. Um, uh, of course biology is hard, you know, et cetera, et cetera. Um, but it's actually a much faster process. Um, so a lot of people think that the regulatory barrier for pet pet drugs is lower. That's actually not true. Um, it's, you know, you still interact with the FDA. There's still a really high bar for efficacy safety. Um, the CMC packages are really hard, um, but just because of the. The the E the ease relatively speaking of doing a canine study, right? You can go straight into dogs, uh, relatively, simply as long as you know, the safety of your compound, um, allows us to have a faster development timeline, and it's cheaper development timeline, which is actually more, more relevant here. Kevin Folta: Yeah. I think that's what most listeners who have. Companion animals at home. Think about, because you know, [00:34:00] on the farm, you don't grow beef for 16 years, you know, or whatever, you know, it's lifespans are relatively shorter. So we don't worry about these kinds of things in a farm context, which is where most animals are raised. So thinking about this in terms of companion animals, and then potentially translating to humans, It's it's pretty exciting stuff. Do you think that this would be something that would be sold as kind of an over the counter supplement? Or is this something that a veterinarian would say, well, you've got a, uh, great Dan and they're more prone to this particular disorder. So we would advise this prescribing this drug because it may seem to help with that. Well, what do you. It's Celine Halioua: we're going for prescription. So all, all our products, if they become on market are gonna be FDA approved prescription drugs. Kevin Folta: So if, if people wanted to learn more about this, where would they look? Celine Halioua: Yeah. I mean, there's our website, although we're actually redoing the whole thing right now. So, um, it'll hopefully look a lot better. Uh, the [00:35:00] jog aging project is a really, really high quality, um, academic version of this. Um, so they're doing, you know, Thousands of dogs, tens of thousands of dogs in their kind of observational arm. And then they're doing aha micin intervention arm too. Um, so you can learn about it there. Um, and then one of the. , it's not aging specific, but one of the core theories of, again, what are the diseases and dogs that hurt dogs, where we can, you know, help dogs, but also learn about human aging is actually oncology. It's the OG area. This thesis has been applied. And so if you look at like the one health thesis, for example, you can find a lot about the thinking here. Kevin Folta: Okay. That helps a lot too. Yeah. I just think of this as a, uh, pet owner, a guy who, you know, has working animals who are also wonderful pets, um, They played dual role. And, you know, if it was up to me, I would keep 'em forever. I'm sad that they're gonna be gone before me. um, you know, which, which in all likelihood. Um, but it's one of these things that, you know, [00:36:00] we, we, we feel such reverence for these animals that we have in our homes and in our, in our space. And I think many people would be very excited. To, uh, learn more about your discoveries. Well, Celine Hollywood, thank you very much for joining me today on the podcast and do me a favor as you go forward and come up with new discoveries and help dogs live longer. Please put me on the top of the list to get some of the stuff. Let me know if you find anything really excellent that you want to tell the world about, because I would be happy to lend you a microphone again. So thank you very. Celine Halioua: Absolutely. Kevin Folta: Thank you. And there's always thank you for listening to another episode of the talking biotech podcast. Share this with a friend, share this with a dog lover. It it's an optimistic way of looking at how we're going to keep our companion animals alive longer and help them live longer, healthier lives, or at least healthier lives, if not longer. Right. You know, the, that health span a little bit longer and that's what's most important. This is a talking biotech podcast and we'll talk to you again next [00:37:00] week. Celine Halioua: You have a great podcast voice by the way? I Kevin Folta: do. I've never heard that before.