Loyal CEO Celine Halioua on FDA-approved longevity drugs for dogs — and what it means for humans

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Yeah, we're hoping to get a real horse in the studio at some point. I can help with that. I have like three. No way. Wait, you actually have horses? Yeah. Yeah, I'm a crazy horse girl. Where? Pedaluma. Pedaluma? Do you live there? No, it's SF. Cool. But I do the anti-commute. Okay. What is that?

Like you drive up against the traffic to North Bay to go ride your horses. I've taken investor calls while on a horse. Almost fell off on an investor call while on a horse. Wait, walk me through like uh are they the same breed? Like what's the story with the three horses? Why three?

Um, horses are potentially the worst investment you could ever make. Um, I do not recommend them. They are worse. Um, I feel like there's some like seed valuation joke you could make here about horses. Anyhow, they tend to break themselves. They're like self-destructive.

We were thinking about getting a horse at one point. We wanted to race in the Kentucky Derby and give it like some funny name. We We were going to call it the ramp. Yeah. And we were and we were and we were running the numbers and it wasn't that crazy as a marketing Yeah.

get into it and you're like, "Okay, maybe it's like 100K for the horse and then a couple grand a month to like But it's such a funny stop. Someone's going to do it now that we do. " Dude, that color would look sick on a horse, though. Like, imagine the racing stripes. I love it. I love it. Anyway, sorry.

Uh, kick us off with an introduction on yourself and the company. Hi. Yeah. I'm Selene Hollywood. I'm the founder and CEO of Loyal, and we're developing drugs to extend uh dog lifespan. Amazing. Horses next. Horses next. Venture capitalist next. Humans eventually. Eventually.

Uh well yeah what uh what was the inspiration for the company? Did like did you know that you wanted to start with animals or was that purely like the FDA? No. So I actually was working at human longevity.

So I worked with a previous guest of y'all's Laura Deming at her venture fund for a few years and we were just frustrated because nobody was trying to develop a drug explicitly for lifespan extension right and we were like this is obviously like obviously we all promise. Yeah.

Everybody was promising it, but nobody was working on it specifically. Not directly. No, they're all kind of going these indirect paths. And so we became obsessed with how to do this. Um realized to do it in humans, it would take a lot of time, a lot of money, but you could do it in dogs. It's a super crazy market.

I hear one of you is a dog person. I am. I am. My dog was supposed to attend, but I have to leave right after and so he's busy was chasing squirrels. He's a 10-year-old Newfoundland, so he need Oh, wait. So you understand this because we're starting with I think Newland's on your Yeah.

On your uh homepage there's for a while at least. Yeah. No, newies are the [ __ ] Yeah. No, it was uh like the dog was uh pitched to me as like look every every day after year five is like a miracle. Uh because they're known to have extremely short lifespans.

And so I kind of set myself up for like look like I'm I'm not coming in you get a you get a golden retriever you're not thinking like yeah it's going to live for 40 years. So I just went into it thinking okay I'm getting a Newfoundland that's six to eight years or something and he's done very well. He's 10 years old.

Good job. We need to sequence your dog. I'll send you a saliva kit. We actually have an investor that has two giant new fees that they bring around everywhere on his plane. It's It's hilarious. And well, that's why he's living so long. Well, yeah, that helps. Do not take your dogs commercial.

But it I actually got convinced to take their term sheet because they sent me their Pinterest board, which was just Newies all the way down. I love Newies. They're the best dogs. Fully committed. They're so good.

Um, so yeah, uh, on the like the fact that there's never been a drug explicitly for longevity, is that just because like in order to have a drug, you need a like a problem or some sort of like it needs to be a treatment for a specific condition and and just death is not a condition.

And so is is that the right narrative? Yeah. Like the way to think about it is to be able to have a drug to approve to do something, you have to prove that the dug is doing that thing. And so if I gave you guys a longevity drug and I was like, "Oh, let's see if it extends your lipan. " Yeah.

I'd be following you for decades and the company's going to be long dead and all of that. It's also hard to prove that the drug was the catalyst for your life, right? It could have been, oh, they just got a lot of sun or they walked a lot or they There's a lot of variability, right?

Like the decisions you make, the yerba mate being pro or anti- longevity, um, whatever it is, right? All of these things vary. Aging. It's one of the most complex phenotypes, but we all go through it. Yeah. And it's the same thing is true in dogs.

But the good thing about dogs, at least when you're developing a longevity drug, is they age much faster. So you can see if something is working in a period of time that's much more reasonable and you can you can theoretically have a much more like isolated study. Is that right? Just because What do you mean isolated?

Well, I just imagine like it's easier to control factors in a dog's life versus like a bunch of like a dog is not going on a bender in Las Vegas. That is Yes. Yeah. So, so, so you can just be like, "Yeah, well, we know exactly what the dog's diet was pretty much every single day.

Maybe he got in a new cheeseburger once, but a human is is like using Diet Coke one day and then some alcohol and then this and then Bender and then Burning Man. Who knows? There's so many confounding factors.

Dogs didn't have like a cheeky cigarette habit earlier in their life that they don't talk about or No, it's true. Yeah, dogs just It's a lot It's still complicated, but it's much more simple. And then you also have these individual breed variances which teach you a lot about humans too, right?

Like why does a new have such a short lifespan versus a golden versus a chihuahua? You can study these things in a much more quickly way. Yeah. Why not why not mice though? I feel like there's a lot of mice studies works in mice. You know, I love mice. Uh I don't think mice are a multi-billion dollar market.

Oh yeah, that's the thing. The the commercial opportunity with dogs. If you ask a dog owner, how much would you pay to have an extra year of of healthy lifespan for your dog? Yeah. And I'm sure there's a wide range between like $1,000 and some people that are like, I would pay any price.

I will, you know, liquidate my 401k for another two years. It's actually really interesting like people um it's not actually really at all correlated to socioeconomic status or how much you know people cash people have in bank. they will spend anything.

A certain subset of the population will spend anything on their dog. Um, I've had people offer me $50,000 for the drug before, and I would like to note to the FDA that I said no. Uh, but I've actually gotten a lot of offers like this. The willingness to pay is insane.

The market is huge, and so we could hopefully make a multi-billion dollar company around this and then use that revenue to fund more research. Yeah. Uh, maybe into horses. I love it. Uh, yeah. What was the initial Yes. Yes, please. What was the initial target kind of the the the biotech side of the business?

Like how do you know what to target? How like how do you narrow it down? Like there's a lot of different life extensions, NAD and Telmir extension and just you know cardiac stuff. There's like a million different sub indications that people think about when they're thinking about their own longevity.

How do you narrow it down? What did you focus on? So the way we thought about it is we wanted something that was as broad as possible.

also as you know efficacious and relevant to the Chihuahua as it is to another dog right and even if they have different food or different behaviors or you know more inbred or less inbred that it still may work. So that was one. And two, you want something that's relatively simple, right?

Aging is so unbelievably comp complicated that when you add any additional variables, like things just become exponential really quickly. And so where we actually started is what you were talking about early with newies uh with the short lifespan of big dogs.

Um because it turns out the genetic driver of dog size, the thing that makes a newie grow really really big in puberty or makes a Chihuahua not grow big in puberty, also genetically controls the rate of aging of that dog. So your new maybe not your new but the average newie is actually aging at a much faster rate.

And so that was a really nice place to start because a it's something that everyone understands especially big dog lovers. They're like I know I know the heartbreak of losing a great dane or losing a large Labrador. Um and it was like simple mechanistically and it was applicable to a wide swath of the canine population.

Basically any dog over a certain weight would be eligible and has this problem, right? because they're not living as long as a chihuahua that lives for 16 years. Every other bigger dog has a somewhat shorter lifespan than that theoretical maxima. So I mean how do you explain what the drugs are actually doing?

So basically that's a black box unfortunately. Yeah. Basically the way to think about it is you know all puppies are born approximately the same size but a Great Dane puppy has super high levels of these proteins called growth hormone and IGF-1.

And these are circulating at really high levels and they're basically binding to their cells and saying grow divide growide. And that's why your burner puppy or new puppy is getting so big. That's normal. It happens in humans too, but it shunts down significantly once you're fully grown. In a big dog, it doesn't.

So big dogs still have these super high levels of these growth hormones circulating around that are basically making the dog turn over at a faster rate. Um, so what the drug does is it inhibits those levels. It brings them down to a level that's seen naturally in dogs.

So think bringing a new level down to an Aussie shepherd or something similar. Um and this is like this idea that if you reduce growth hormone, if you reduce IGF-1 extends lifespan.

It's actually been shown all the way from worms to mice to um you know a multitude of organisms and there's even human centinarians that have the same genetic, you know, things that Chihuahua do. And our our body spiritually Chihuahua. So So is is is the like I think that's an insult.

Is the scientific like phrase like IGF-1 inhibitors essentially? Um, and are biohackers using that pro like the wild like against the FDA? Are they learnism from these sort of fringe biohackers and what what these end of one study is there anything to learn or just uh um well yes there's always things to learn.

Um you know it's funny people actually often will supplement growth hormone IGF-1 because it makes your muscles really big. Oh sure and it's very aesthetic. It's kind of like human growth hormone. Yeah, exactly. Exactly. Um, it does not increase function, but it does increase like muscle size.

So, a lot of people are might not be happy. Interesting. It doesn't correlate with strength at all. It's just like gives you the pump. I mean, yeah. You guys can't tell I'm on it. Yeah. Yeah. Yeah.

Well, I mean, yeah, plenty I think the people that are taking HGH are doing that specifically entirely for aesthetic reasons and they're they're post strength, right? Yes. Yes, they are post strength.

Um but but are there people in the bio in the biohacking community that uh swear by it or are they optimistic that it will have an effect on uh longevity for them? Yeah, I mean this mechanism is pretty consensus as a longevity mechanism.

It's not going to be as like this specific one, the big dog short lifespan isn't going to be as relevant to humans because like I'm not living twice as long as you guys, right? Um me being so short that I'm having to like sit on my feet. Sure. But a new does live twice as lives half as long as a chihuahua. Exactly.

Exactly. So, think of it as kind of like a biological hack to have a foot into a very um very very complicated biological problem. Yep. What's the current understanding of uh why women live longer than men? I mean, we just do less crazy [ __ ] It's just risk-taking. Yeah, it's risk taking. No way.

I suppose it's like heart attacks or something. No, I actually don't know. Um there's like a real reason, but I don't. Yeah, I like the idea that dudes are just wing seating. Dudes are just [ __ ] insane. Um so so walk me through the the actual process to commercialize and and you know grow the business.

Um I imagine the FDA has a number of different uh subgroups. Veterary medicine's one of them. Is that a more receptive faster pathway than just the traditional drugs for humans pathway? Are you accelerated there? Yeah. So the the FDA on the veterary side is super stringent, right?

It matters a lot in some ways, you know, almost more because a dog can't talk. So, you're really trusting the FDA and you're trusting your veterinarian that this like pill you're giving isn't going to like cause some disaster. Sure.

Um, but the nice thing with with canines is that the incentives are really really aligned, right? Like everybody wants dogs to live a longer, healthier life and preventative medicine is really where it is with dogs because, you know, there's no insurance.

Nobody's getting half a million dollar cancer cart therapies or whatever, right? It's it's it's always a dog owner having to pay out of pocket. So, most of the really successful dog drugs today are already preventative medicines. Think like heartworm prevention, right?

It's reducing the risk of your dog getting a disease that if you give the drug, you'll never see them get that disease, right? Flee and tick, same thing. There's a lot of categories of medicines like this. Um, so yeah, it's actually been really fun to work with them.

And in the new administration is like, well, it's a little complicated, like super prolongevity, right? And so it'll be interesting to see how that maybe impacts the human side where things are very regulated but also just a bit more complicated.

But it seems absolutely critical even just from a fiscal standpoint that we figure out how to get people to live longer and healthier. Yes. It's you know people when you talk about longevity they tend to be like oh but like you're just going to make the rich live longer.

And like the fact of the matter is the rich already live longer because they can also access better cancer meds, better, you know, doctors. I do like preventative screens all the time. The vast m majority of Americans could never afford that, right?

Versus like a daily cheap pill that broadly extends your quality of life and broadly extends your lifespan. It not only helps that individual to potentially prevent them or delay them developing cancer, it also helps their children who aren't going to have to become caretakers before their own careers have taken off.

It means that they can have more flexibility in pursuing doing the next great thing. I think actually like you know better health of the population is the one of the best great equalizers we could bring. Yeah.

How how closely does the does your business track to what I'm loosely familiar with in the biotech world where it's like uh you're in the lab, you develop the drug, then you test it on like dog, monkey, mice, something like that. You take that data through phase one, phase two, it's a multi-year process.

Uh the company might IPO and then get bought by Merc or Fizer at some point.

Uh like like that's what I think of when I think of biotech like drug like like yes we've created a new drug for like this very specific cancer but it's still a $10 million or hundred billion dollar outcome because it like it fixed this one thing and it became very profitable.

Is that the typical path or is it wildly different in veterary? Dude, your biotech contact is like on point. I'm actually super impressed. We had a bunch of biotech investors and founders on one day when Trump was doing the most favorite nation thing. They tried to get up on it. Mhm.

Uh which I don't really know where that went but anyway. Uh just it's okay. There was almost 100% tariff on us and then that got really no way. But that got taken away. It's been really interesting. It's been exciting. It's all a roller coaster. My cortisol is just like perfect. That's good for longevity. Yeah.

My personal longevity is not benefiting from the pill.

Um, so the way to think about it is if if you're comparing to human is you do um maybe backing up a little bit, the overarching themes of developing a dog drug is it takes like four to seven years basically by a combination of how effective and how lucky you are to get a dog drug approved.

Takes about 20 to$50 million um for context in humans it takes a decade to develop a human drug. It takes about a billion dollars to develop a human drug. So you're like orders of magnitude faster and orders of magnitude faster and cheaper. And then actually the coolest thing and you guys have been pretty lucky, right?

We've also been lucky, right? And like totally Where did you catch lucky breaks? Oh my god.

Like Well, I just feel like I I feel like uh average whenever you guys announce like any type of milestone, the average investor is basically sharing something to the effect of you guys don't realize like how rare this is like the speed at which you guys have been able to I mean it's kind of just like knock down these different milestones.

It's I mean we've gotten the first ever um efficacy approval uh for a longevity drug. We've created the first regulatory pathway for a drug to be approved for longevity for any species, right? Obviously, it's in dogs, but it's any species. And dogs actually are they're regulated by the same federal regs as human drugs.

So, it's a it was still a really huge lift. We've gotten the we're running the first ever lifespan pivotal FDA enabling clinical trial. Like all of these things are super super hard. We got um obviously we're like have a smart team, but yeah, you have to get really lucky too, right?

We got lucky that the drug when you pick a drug and you're like this is going to be our lifespan extension drug. It either is or isn't, right? And there's nothing I can do as CEO to make this drug work if it doesn't work. Well, you can try and take 10 drugs through the pathway at the same time potentially.

That's kind of what we're doing. We have like four in development, but that's really expensive, of course.

So, you have to you have to pick a couple candidates that have the most promise and luck comes in and that like you hope one of those is the one that you picked and you hope there isn't some like random toxicity find out at the 11th hour and that like totally nukes and especially with a longevity drug there's zero tolerance for adverse events.

There's zero tolerance for me turning your dog Yeah. Because it's not like you have a bad condition that you're trying to treat with some side effects or or you the average patient would be okay with some side effects. Yep. It's like you're the you're going from net neutral to it has to be better. Exactly. Exactly.

You can't reduce quality of life. I mean that much. I mean there's people like um what are some of the human uh the the drugs that human patients are taking. I feel like Peter and people are taking certain drugs that like like rap. Yeah. They like they they metformin like red reduces your like athletic performance.

They all have some like like metformin is like works by improving your metabolic fitness.

Um which um we actually have drugs that are actually our lead drug now is develop is uh improving metabolic fitness in senior dogs is a very like robust way like if you've ever intermittent fast or calorically restricted that's a way to improve your metabolic fitness. Um metformin just does that as a drug.

It's an old diabetes drug but yeah it has a bunch of like stomach side effects and also just when you give any drug for a long time bad things can happen. Yeah. There's also it can't if somebody were to reclassify it as a there's no incentive to reclassify metformin as a longevity drug because it's off patent, right?

I didn't know that. Cuz I was because there's uh there's a lot of it's debated, right?

But there's a lot of evidence that like aspirin it could could be potentially beneficial for lifespan, but nobody would do the work to reclassify it because it's off patent and you could you could go and you could spend a billion dollars proving that it works and then everybody can just make it. Yep.

And this this is like um a niche thing that actually And so you can't even market aspirin as claim. No. No.

And this is a niche reason why Loyal made a lot of sense and why I was like, "Okay, I guess I'm going to go and do this is you're 100% you have this catch 22 when you're trying to develop a human longevity drug, which is you need something that is has a ton of safety both acutely, right?

So you took like five of them, nothing bad's going to happen. But also over a period of time, right? If I give it to you for a decade, is it going to increase your risk of colon cancer or something? The only way you know that is by giving it to that person for a decade.

By the time you have done that, the drug is generic. One of the really cool things about animal health is that you actually the FDA tries to incentivize people to develop and prove that new drugs work for animal medicine. So you actually can get 10 years of exclusivity from the FDA. Yeah.

if you develop a novel a generic drug for a novel use case in dogs. So we have actually both. We have unlicensed human drugs. We have generic drugs. But it means that you are able to go in and say, "Look, this might not work, but it's not going to do any harm.

" And that's so important when you're trying to create regulatory pathways, when you're trying to convince veterinarians to prescribe something that's never existed before, to convince dog owners to do something they've never done before, to be able to say wholeheartedly there's decades of data and we don't think this drug is going to do any harm.

That helps. Are you guys getting uh feeling any acceleration from various AI uh models? It seems like we have people on the show every week that are building AI for science, AI for drug development and foundation models dedicated to it. And yet you're here, you haven't said AI once. I have not said AI once.

And this was so funny. It was a meta point. We were like working on like loyal narrative stuff. And I was like, should I just like let go of my ego and like have an AI story?

And I was like there like anyhow there was there was no AI in the loyal story but like I really debated it because I was like man I wonder if this would like increase my valuation by like a factor of two. What about el good for dogs and that be good for horses and it be good for people.

No, but but that's saying something that you're actively doing all of this drug development and meanwhile there's companies coming out and they're making the claim at least to investors that they're going to be able to, you know, speed up drug development, do it more efficiently, etc.

So, I mean, so here's the problem because I'm sure you've tried to figure out how do we how do we unlock value here? Yeah.

So here's the problem with AI for drug development is I am like I'm not an AI person but like I am like in terms of like technically trained but I am you know sure the models are good enough that we gave them biological data they could infer things that human scientists couldn't.

The problem is we don't have those data sets like they they don't exist for a human. I can't like say okay here's like your model and if I give you the drug how is it going to react in this part of your body that part of your body how is it going to like uh get reduced over time?

how is it going to interact with this other drug you're on? We just don't have those data sets. Yeah, we saw this with AlphaFold. Like AlphaFold came out, protein folding solved. It turned the biotech markets didn't really move because it turns out that actually solving protein folding problems is like.

1% of the job to do to get a new drug to market. You got to recruit patients and then monitor them and then talk to the FDA and do clinical trials. Yeah, there's so much more to do. You know, like our our big longevity study that we're running in dogs right now, um I think the biggest risk to is actually operational.

It's data quality. It's dogs not dropping out. It's veterinarians complying, right? Like the biggest reason the study would fail is that if we have to throw out a bunch of data in five years because it doesn't adhere to the standards that are necessary, right?

Um so there's some interesting AI companies for like the beginnings of drug development. Like Chai discovery is one um that's trying to do basically better antibbody uh binding design. That's smart. I think that makes a lot of sense.

But I mean, I'd love to be proven wrong, but I think there there hasn't been like a moonshot for the the bio data gathering on the clinical side that would be necessary to like model you and see what works. Well, it's not a good Yeah, it's not a business. Yeah, it's not a business.

You're taking a even if somebody was able to raise a billion dollars with the idea, it's like would they would they'd come to you and be like, what do you need? And then they'd be like a services provider to like Yeah.

And that's the hard thing like so we're building all these bio banks out um and so we're going to have you know potentially the one of the best data sets of translational aging um in a species that's the best model of humans that is in humans and so maybe we'll be able to do it from then but like I would it would feel disingenuous for me to say like yeah that's the strategy because just like no one knows like biology is like the ultimate black box and it's the ultimate humbler honestly.

What about peptides? Are dogs automplic yet? Are dogs on Ompic? Um, actually, so this is my favorite fun fact. Everyone is like, "Oh, are you just developing like Ozmpic for dogs? " And an answer is no. Mhm. Because people don't want their dog to not be hungry. Think about it, right?

You go home, your dog's super excited to see you, jumps on you, you're like, "Oh, my dog loves me so much. I'm the alpha male. " Your dog's probably hungry, right? And so when people give their dog Ompic or Ompic like drugs, it just takes all the joy. It takes all the joy away. The dog the dog becomes a cat. Oh no.

No, this actually I think about like my my most cherished memories with my dogs growing up. It was like my dad, my brother, and I making scrambled eggs for the dogs, right? It's like that was peak peak uh peak experience as like a you know 10-year-old. No, totally. Um it's a it's not a not a good market.

So like our other drug that's working on metabolic fitness to extend lifespan, which is very similar to how Ompic works.

um it is targeting you know improving metabolic fitness but it's a we make sure explicitly that the mechanism that we're hitting uh doesn't impact uh appetants and doesn't impact um like uh weight in general uh any book recommendations for us that's cute that you think I have time to read as a uh any uh movie recommendations must love dogs what you got for us dog related content I watched Love is Blind France last night okay love is blind really trying to turn off I'm sorry I you know I, you know, I want to be one of those like CEOs where I'm like, these are the esoteric hyperintellectual books I'm reading that like show that I'm smarter than you.

What? No, there's no shame. I was reading a book that there's only one copy. It's thousands of years old. It's a rare PDF. You don't have access to it. It's English, but you wouldn't you wouldn't understand. But like honestly, like Loyal is my all day every day.

Like I don't have What's the general routine like at Loyal for you? So, we're actually fully remote. Um, which I know contrarian contrarian. Um, but it actually works well because we have to hire people. We have to hire the best possible person for each skill set we need.

And often those people are not actually they're almost never in the Bay Area. I'm going to St. Louis after this. That's where we have a lot of team members. Uh, we have a lot of team members in Kansas. We have them in Florida, right?

And so it you get so much more benefit from hiring the right person for the right role than you do saying I'm gonna hire the second or third best person, but they're willing to move to SF. Right. Yeah. Yeah. So for me, I actually just like live at coffee shops.

Um I uh sit out of some of our investors offices, bring my dog. U maybe one day whenever I'm able to fly private, I'll bring my dog. Is Antonio Gracio the one with the two newies? No. Okay. Cuz Yeah. No, he does have a cute dog though. or his uh his partner does cuz it's it says you raised from Valor.

Um we got to hit the gong for you. Thank you so much. We're hitting the gong for me. Of course. I mean and all the dogs currently in getting studied. Just congratulations. What uh what's the next big milestone that people should be looking out for? The next big milestone.

I mean we're just trying to bring this damn drug to market honestly. Like that's a big one. Um hopefully in the next year or so. I mean pray for us. It's like the the hard stuff's behind us. Um, but there's a lot of hard stuff in front of us, too. So, well, good luck. Caught between the hard stuff. Yes.

As every entrepreneur is. It's It's a worthwhile goal. Anyways, well, I think we can close out the show with you because we actually have to uh hit the road. Well, first we got to tell you about eight. com. Yeah. Get a five. We got to put the animals on the on the eightle. You do have an eightlee. That's great.

We also got to tell you about Bezel. If you want a watch for your dog, go to getbzzle. com. Get him a Submariner. And if you want to And if you want to take your dog on a vacation, head over to Wander. Find your happy place. Book a fire hotel. Says, "When can we buy loyal stock? " I'm assuming you can't answer that.

We uh I SEC something. Okay. Sorry guys. Sorry guys. Private company become a venture capitalist someday in a very bright future, I'm sure. But thank you for tuning in with us today. We will be back tomorrow morning. I can't wait. Have a great afternoon. Goodbye. Love you. Bye.