Celine Halioua On The Science and Business of Making Dogs Live Longer

25:23Save the dogs, save the world, right? Exactly. Yeah, that's the thesis. But I've never heard you actually go in depth on that idea of like what would it look like to create a human drug. Do you have like some conception of what that part of the business will look like in the future? Yeah. I mean we don't have like a drug candidate yet because I think some of the challenges was doing – the original insight of the company was that you cannot develop a human longevity drug today. And everybody thinks that's because of the biology. But it's actually not because of the biology. It's because of logistics and like financial norms.

25:56It's because running a lifespan extension study in humans would take forever. It would cost a billion plus dollars. By the time you're done running it, your patent would be expired. So you're not going to get any of the ROI of the drug that you just invested billions of dollars in developing. Oh, by the way, most human drugs fail. So multiply that number out by the failure rate before you actually get a drug approved. It's difficult in certain health care systems to do something like that. The ROI is usually higher for acute medicine drugs versus preventative drugs. And so all of those issues were preventing – the thesis was that these were the reasons, the real reasons why we don't have longevity drugs for humans today.

26:36But luckily those reasons don't exist in dogs because they have a shorter life. It's a cash-paced system. You're economically incentivized for your dog to be healthy today and five years from now. So you'll invest in preventative care much more easily and much more quickly. And so A, it was that you can go dogs first. and then while you can't go for humans and then b that actually by doing it in dogs it accelerates and i believe is the fastest way to a human longevity drug and there's two reasons for this one is the biological right so okay if like one of the reasons why we can't develop human drugs for longevity is because the failure rate you know the success rate of a dog of a new human drug is about nine percent and for a number of reasons but one of the big reasons is that we you know, prove and test and ideate new drugs in like mice, which don't really age in the way we do and mechanisms, right, that don't really exist in the way we do.

27:30And we translate over to humans and everything breaks, right? We've cured most diseases in mice or like versions of these diseases in mice. We haven't done that in humans versus in a dog, like a dog naturally ages over time. A dog naturally develops dementia. So they develop Parkinson's, they develop cancer like we do. They develop osteoarthritis like we do. So if our drug can successfully slow the rate of unhealthy aging in these dogs, it's not one-to-one that's going to work in a human, but it's certainly much more compelling than it working in a mouse, right? So then that makes the ROI more compelling, right?

28:07Maybe you are willing to run that billion-dollar lifespan extension study if the probability of success is 40 % instead of 9%, right? So that's the first one. But the second, and I think actually the thing I didn't appreciate when I started the company, but I appreciate much more now, is actually just the economic model of biotech. Most biotech companies never make money. Most biotech companies exist to be externalized R &D for big pharma to take an idea or an asset, bring it to a value inflection point, you see some efficacy, you show it's safe, you have a compound, a compound seems like it makes sense, and then sell it to big pharma.

28:47They're not actually, biotech isn't a commercialization engine in most cases. There are notable exceptions, right? But in most cases, you're exiting long before you bring that product to market versus for us. And so you're always having to think about your investment in the scope of what would have an ROI for a pharma company, right? And this is partially also because, again, developing a human drug is just so stupid expensive and it's so risky. For a dog drug, it's like 50 mil-ish all in to bring a dog drug from idea to approval, not including a team. And so it is much more reasonable to raise that money on the private markets.

29:21It's much more reasonable to fund the entire life cycle. And in the commercialization, we believe, and I guess we'll find out, that you can do it yourself because there isn't all that insurance payer, PBM crap that makes it so difficult to commercialize on the human side. So actually a small company can commercialize. And so I actually think the fact that we have the potential of being a revenue generating biotech, biopharma company means that then we have hopefully a bolus of cash that we can do whatever the fuck we want. We can go invest it in crazy incinerator uses of capital like human longevity.

29:57And that's fine because we have a cash engine. And so I think that plus the mission motivation, plus the team, plus the dog data set, I think is how we're going to be able to do that. Yeah. It makes a ton of sense, especially on the revenue generation side. It's like you now have a core business model that can help fuel these bigger and bigger moonshots that can be a part of the business. Yeah. And I mean, and it's not like I'm the first one to come up with, like that was the Tesla moonshot, right? Like a lot of these deep tech companies, like you You bring something to market. Whew, great. OK, now you bring the next thing.

30:24Now you bring the next thing. Each of the previous one's success funds the next most audacious, most audacious, most audacious next step. Yeah, to your point on Tesla, Tesla, I mean, the speed at which you can get cars to market, though, is more regular, right? Whereas, like, because of these clinical studies, you actually could be 10 years for a human, 20 years for a human. How are you thinking about timeline for these? So what do you expect the timeline to be in terms of like drugs are starting to fall into consumers' hands on the dog side and how long do you think the clinical studies could take for humans if you were to run something like that?

30:58On the dog side, we'll hopefully have a drug approved in a year, year and a half. It really just depends on the manufacturing timeline. Got it. That's the problem, right? That's a determinant. If we're going to resummit manufacturing this year, hopefully we get it. If we don't pull it off, which is entirely possible, then it adds another at least six months to that cycle. So that's really the biggest determinant. That's where I'm spending all my time right now and working on it. Sorry. If anybody's listening to this and like really good drug manufacturing, hit us up because that shit is complicated.

31:29I really underestimated it. So that's on the dog side. Then we'll have a couple of products. Hopefully, we want to have five approvals by 2030 is the vision. So five dog approvals by 2030. um human i mean we haven't even begun to design this clinical trial um and i think there's a lot of questions right like do we explicitly look at mortality risk reduction right so like your reduced the risk of you dying in any one year and the ability of a drug to reduce that do we look at what we think are leading indicators of mortality risk reduction but still more general than disease like all of these things are going to determine so i can't really give you a timeline for a human longevity trial right now.

32:11I think actually the biggest issue is, I think we have a little bit of a catch-22 with what kind of drug you develop for human longevity because, again, of this patent issue, right? And you need something, like the bar is going to be so high for safety, you're really going to want to hit a mechanism that is like well understood and established. But if the mechanism and the API, the drug, are well understood and established, it probably doesn't have enough patent life left on it to be protected post-approval. And how long do you think a human study would be? Is that like a 10-year study? I mean, again, it depends what you're looking at, right?

32:43So it's like you have this tension between probability of success and ability to see a readout in a period of time. So you could run a 10-year lifespan extension study, but it's going to be in relatively older or high-risk individuals. If you're in older or high-risk individuals, the probability of success of that study in general is going to go down because those individuals might be too, quote-unquote, far gone down the aging process to be intervenable or to be intervenable with that type of mechanism. So then you can go earlier, right? Like I could start you in a longevity drug today. I feel pretty confident there are things I can give you today that would extend your lifespan significantly.

33:18But it's going to take us hopefully 50, 60 more years to see if it extends your lifespan and see how much it extends your lifespan relative to somebody on a placebo. And so that's the tension. It's like what's that right intervention point where you're intervening early enough that you actually do see biological efficacy but not so early that by the time the study reads out, the company is dead. You've been in longevity since it was niche. Like it feels like over the last, what, seven, eight years, this has become pretty mainstream, at least in Silicon Valley in terms of people talking about it as a topic.

33:53What aspects of longevity right now do you feel like are non-consensus that you expect to become more consensus in the future? The idea of FDA approved drugs for lifespan extension is the biggest thing. I think longevity is still synonymous with supplements or tests or I did this thing. and I optimize my resting heart rate. And to be clear, those things probably do help, but I don't think it's seen as a biological process that is intervenable just like any other biological process that occurs in someone. I think the minute we hopefully get a drug approved, that will change and it will be considered, like pathological aging, I think should be considered a disease space or is like anything else, right?

34:40Right. And with that will come like a quantification of are you aging in a like in a way that one would expect, like a detangling of the physiological decline of age and the chronological age. Obviously, chronological age is great. I'm happy I am 31 now and not like an idiot 21 year old anymore. Right. But I do sure wish that I had the ability to learn new languages as robustly as I did when I was 21 or, you know, be able to deal with the insult of low sleep. right um as well as i did when i was 21 oh my god the new dog has been sleeping with me every night because i don't have the heart to kick her out which is really bad i need to work on it but she literally like she's giant and she sleeps so chaotically and it's just right i feel like a new mother can you tell us a little about your new dog oh absolutely pull my arm um so i i um She just adopted a baby Roddy named Wilma slash Squishy, depending on how I'm feeling in the moment.

35:44I think she's just going to be a two-named dog at this point. Most of them are like hundreds of named dogs. I know. I think Harper has hundreds of names at this point. But she still has the predominant name of Harper. Like, I'm not sure which one's going to be the predominant. Is it Squishy? Is it Wilma? A Roddy named Squishy is pretty amazing. It's kind of hilarious, isn't it? And she is a Squishy. Like, her face is so, like, Squishy. Um, so I wasn't planning on adopting another dog. I've been pretty like traumatized after losing my senior Rottweiler Della last year. Uh, but one of the shelters that we do some work with at, at Loyal, um, the SFSPCA, I was like, oh my God, we had this really cute dog come in.

36:23Look how sweet she is. She has a snaggle tooth. You want to come meet her? And I kept on like putting it off, putting it off. I'm like, no, I'm traveling. No, I don't have time. And finally they got me to come in last weekend. and I went home with the dog. I didn't even bring a dog bed in my car because I was like, there's no way. And actually, I brought dog food with me because I was going to give it to the shelter. And yeah, that did not work out. I'm not shocked. You know, literally nobody is but me. I like to think that I'm like moderately self-aware, but I think on this variable, I was not at all.

36:59But she's super sweet. But I've never had a young dog before. Oh, wow. I've always adopted senior dogs. So your first dog was Wolfie. As an adult. Is that right? Yeah. As an adult. Okay. We had a bunch of dogs as kids. Were they all seniors when you were kids? No, but they were mostly just like random rescues we found on the side of the road. So you never had puppies? No. We never adopted a puppy. And I never did the puppy training thing. And also, yeah, ticks. So we had like a backyard, right? Like it's a little bit different than like city dog training. So, yeah, my white carpets are not white anymore.

37:33Well, we have an amazing trainer for you if you need it. Actually? Yeah. That would be great. She's in Oakland, but maybe she'd come out to you because you're a celebrity. I'll let you know. Thank you. Thank you. Shout out to Toby. Thanks, Toby. So going back to longevity, one of the things that people talk about is the idea of like a thousand-year human or there's, I think, these ideas. I see the eye roll. There's ideas that longevity can make us live like hundreds of years long. And it seems like that's probably unrealistic. What do you think are the better ways to think about longevity? I think the way to think about it is long tail outcomes that maybe five random people in this Japanese fishing village have lived to 115 and they still do the Sudoku every morning or whatever.

38:16Like I think those long tail outcomes becoming more like common outcomes. That's how I think about it. I think radical lifespan extension is going to require a subset of interventions that are going to be so very difficult. And I think completely possible, to be clear. Everything is, in theory, biologically possible. It's just how complicated is it? And specifically, what is the ratio between when you need to intervene, how extreme the intervention is, and are there near-term tradeoffs to that long-term intervention? I've heard some stats where it's like one in three people who are born today folks think will live longer than 100 years.

39:00So do you believe that? Or I guess how do you think that – what's life going to look like in 100 years from now? I think the biggest thing is we have a lot of societal norms around unhealthy aging and aging writ large that will hopefully push out over time. I think the issue with human is that so much of aging is environmental and behavioral and no drug is going to change that. It's going to help, but it's not going to change that. But if you keep that same ratio, you're hopefully just going to shift the curve over a little bit. And you're still going to have some people that live really long and really well because they go running every day and they're also genetically lucky.

39:38And maybe they don't live near a power plant, so they don't have all the carcinogens or whatever. and you're gonna have people who just get their shit out of the stick no matter what right um but hopefully everybody will move over to the right a bit i'm really excited about a world one of my favorite ideas is that you know you get very like what's the impact of increased cognitive flexibility and reduce cognitive aging in a society so you know people tend to crystallize as they age um We kind of consider this normal. Like, you know, it's like, oh, my racist grandpa. Right. Or like, well, I don't know what the thing is going to be that like millennials are considered like old school boomer for.

40:18Right. But I'm sure there will something that Gen Z's will look at us and be like, oh, my God, like they're so archaic. Why don't they understand how the world works? And it is interesting that you kind of have these like crystallizations within like cultural norms of society and of generations. And I do wonder if like a cognitive aging drug will change that. if it'll change your ability and like increase your ability to relearn something or change your priors or um adapt your worldview in a way that is i think actually just very biologically difficult with age and with with time i mean even something as simple like i think about this a lot it's like i don't listen to new music anymore i listen to like the stuff i like like new music from the same artists I like but I don't listen to like the new stuff um and you could say that's like social because I'm not like listening to the radio or not hanging out with like you know people at a time but I think it also is a little bit of a crystallization of preferences that like maybe aging drug would change do you think it's nostalgia too or like almost like a a love for what you already are like experiencing or like some draw to something that you know so well and it comforts you i just find it difficult now like i used to love the process of like my discover weekly and like learning new music and like adding new things to my like uh saved songs list and now i'm just like i could do that but that just sounds really painful i'm just gonna listen to this like 2000s album instead i'm gonna listen to the strokes right and i do think some of it's that but i think some of it's just like i think some of it is just a crystallization, right?

41:57I don't want to like learn or adapt to new music. I want to stay in my one musical swim lane. So I think that's like an interesting potential. You know, I don't think the music thing particularly matters, but like giving a change how you view society or POVs on society. And then also like the burden of elderly sick parents. What does a society look like where our parents are healthier longer, are able to support us longer, where, you know, you, the word of child isn't responsible necessarily until later, much later in life to do that sort of caretaking, both financially, but also just from a responsibility and like physical standpoint.

42:41I think that could actually be a really big driver of increased socioeconomic equality, right? Because, you know, if God forbid our parents need to be in care, we can probably afford a home for them or support or nursing or whatever, vast majority of people cannot. I couldn't have five years ago, right? And that is a limiter of socioeconomic mobility, right? I'm very lucky that my parents have been healthy and I've been able to take huge career leaps and leave them and go and do things that have allowed me to build loyal and whatnot. Some people, their parents get diagnosed with cancer and they have to stay at home.

43:20There's no choice, right? And they cannot take the opportunity to move to Silicon Valley. It's really interesting to think about what does the future look like if people can live longer and healthier lives, like health insurance changes, life insurance changes, retirement planning changes. Yeah. I mean, it's one of the fascinating things of like, you know, you look at your 401k or whatever, you're trying to figure out like how many years can this get me, right? But it's like, oh, you can live to 85 if you pull X amount out per year. But it's like, okay, what about if I live to 100? Like, how do I even know what it's going to be?

43:49That's true. It's really interesting in terms of the implications of just like how we structure the world. You're about to max out your 401k tonight, aren't you? Yeah, seriously. Putting it up. I mean, well, I got to start microdicing some sort of drug to make me live longer at this point. Deal. It might be my kids' 401ks that they actually have to care about. We'll see if we get these drugs in time. Working on it. Yeah, seriously. At least our dogs will. At least Harper will. At least Harper will. I hope so, yeah. I really hope that we can get it to Harper. She's five now. Okay, yeah, yeah. So the next five years.

44:18We can pull that off. It'd be great. As a side note, it's interesting you're talking about microdosing. I was with my neighbor last night, and he's in his 60s, and he's gay. He lived in San Francisco during the 80s. And he got HIV when he was 24. And he had a few years where he didn't need drugs or anything, but then his doctor started microdosing him on the newest HIV drugs from the black market. so they literally had like a black market in downtown san francisco which is a warehouse and people would either have extra drugs or they had a partner who had the drugs and they passed away and they'd take all these drugs and then they'd farm them out to all the other people who lived in san francisco at the time so that they could essentially like micro dose them and what they ended up realizing was like this was actually a really good solution to like reduce aids that some of these doctors were doing before before time yeah it's super fascinating to like hear from him and he so he um he's had cancer i don't know i don't know because prep is another one of like the og like consumer marketed pharmaceuticals yeah i mean this was a drug that they had in the 80s so i think what he was saying was that it's become more of a cocktail over time yeah i mean i was just learning from him and i don't think he was an expert but uh it's just fascinating to hear his story of like he's had cancer twice and but he's like pretty much has it fully under control now and like hrv aids won't kill him which is crazy that's amazing but it's it's interesting to think about, I was thinking about like, what are the things that we should be microdosing today?

45:43Like, should I be microdosing like GLP-1s or something else? Like, what are the types of things that I should be taking or like, are other people experimenting with? I don't want to put you on the spot and ask you because it's like, maybe we shouldn't recommend this to people, but it's interesting to think about what could be out there. Yeah. I'm going to go no comment on that. Yeah. That's great. No, no, no advice to the people out there. In terms of advice, so do you have advice for founders that are coming up, just given your whole journey of like what you've experienced you've been through all kinds of shit well i do write a yearly lessons blog year five lessons year four lessons i missed one year sorry um gosh i think the big what would be some generalistic advice i think one of them is understand the incentives around you um i didn't understand people like venture making money what venture funds care about investor dynamics like how all that works because i just didn't know anything about this world right i didn't like Like I didn't even like have money in the stock market until like two years into Loyal.

46:42I just like didn't understand a lot of these aspects of life. And I'm not saying you have to to be a CEO, but you should understand the economic incentives of the people around you. I think it's really important and helps explain behavior. It also like I tried really hard to design a company that is economically incentivized to do the right thing and do the thing that's right for dog owners and people. And I think I've done so far a relatively good job of that. but you have to understand the complexities. So that's one. Two is don't try to make people into what you think they can be. Take people as they are today and be surprised if they change and grow.

47:17I think this has been a perpetual challenge of mine personally and professionally. And it actually like probably some of my worst blow ups was team members have been people who I thought I was doing the right thing by like pushing them or believing they can be X when actually they were telling me loud and clear they wanted to be Y. I think don't be emotionally attached to like the process or the how be emotionally attached to the what. You know, I think one example of this is like all the 996 stuff. That is like the canonical, like I'm attached to, emotionally attached to the how we get something done, not the what we're getting done.

47:52Like what matters is the end point. It's the building of a successful product that generates great revenue or whatever the end goal of your company is. It's not really how you get there. And in fact, how you get there is probably going to change a lot over time, over stages of the company, over what the company needs. And if you become real – if you define yourself around, I think all companies should operate in this one manner or I think our drug has to be this drug or whatever it is, you'll end up actually, I think, reducing the probability of success of hitting the end goal. So like Loyal's goals have always been very explicitly getting the first drug FDA approved for lifespan extension.

48:28It was not get X, Y, and Z compound approved for lifespan extension, right? It was just like something that's safe and efficacious, getting it approved for lifespan extension. And that actually, I think, saved Loyal's butt many times.

48:44And I think also just like finding your security. I don't think you can be insecure and run a good company. I think it's, I don't know, maybe it depends from company to company. But like I think it is – I found a lot of success from like not being particularly emotionally attached to who I am at any moment and instead like trying to understand who do I need to be tomorrow for loyal to succeed and leaning into discomfort, leaning into the change, leaning into however I might be suboptimal and like the implicit feedback I get from others in addition to the explicit so that I can continue to scale.

49:26Before this meeting, you mentioned that you wish you had someone vibe coding for you and building AI tooling for you. And I think for me, what was surprising about that was I think about your business as one that's maybe really defensible to AI, right? Like there's so many of these companies that it feels like this is a really hard business. Like anyone with a clawed code can go and recreate this type of a company. Yours is not that. But you're still using AI tools and stuff inside, it sounds like. Is that true? Oh, barely. I'm not really an AI girly. We use some. And we're actually working on it right now.

50:02Really curious. There's a lot of roles we have that are extremely labor intensive. And to be clear, I don't think we're going to replace those roles with AI. But we have a pretty stringent ratio between the CRAs, the clinical research associates, and the number of dogs in a study. And can that ratio become higher if there's tools? right so like instead of having to grow to team one-to-one with the clinical trial count can we grow to team you know two-to-one trial to person or whatever is there efficiencies that way and specifically i'm trying to figure it out now because i want to do that before we blow up the team uh i don't want to do the thing that is happening a lot across industry right now where you know whole teams are getting like sliced um i think it's just terrible for a multitude of reasons Um, so we're doing that.

50:48Um, but honestly, like a lot of, a lot of stuff is, is so regulated, the data sets often don't exist that it's actually, it's all very early for, for a company like us. So again, there's things you can do internally where you're getting a better intellectual worker, like will obviously help loyal. Um, but it's not like I can have like an AI agent do this job of this FTE. Like it's going to be augmenting to humans. As we wrap up, any shameless plugs for loyal or specific experts, people that you want to meet? You mentioned that manufacturing experts is one that you want to try and connect with.

51:28Is there anything else like that that's bopping around in your mind? With our Seriously announcement, we opened up our first merch drop. And so you can now go on merch.loyal.com to buy loyal merch. And this is great if you want to rep merch or whatever. But The reason why I care about it is because we're donating all of the proceeds to Muttville, which is the senior dog rescue where I adopted Della from. So if you want to rep loyal and donate money to a shelter that has done a lot of good for a lot of dogs out there. What are some of the examples of swag that you have there? We have a bandana for dogs.

52:00We have a really cute hoodie that I'm actually so excited for that says save the dogs, save the world on the arms. For humans, not a dog hoodie. For humans. No dog hoodies. Sorry. We only have the bandana for dogs. I mean, look, I guess you can put the stuff on the dog too, but I'm not endorsing. We have T-shirts. We have sweatshirts. All the kind of classical stuff. And the team are the models for it, which is really cute. So the team who built out the merch store are actually the team who model each of the pieces. That's so fun. Yeah. So I resisted a merch store for a while because it can sometimes be a bit of a negative meme.

52:37But I realized that you can just do it as a charity event. And that's actually the best way to do everything. It's amazing. Well, congrats on the racing series C and thanks so much for joining us today. Thanks so much for listening to the Village Global Podcast. You can check us out online at villageglobal.vc. We'd love to hear from you, your feedback, your ideas, your inspirations. You can email us at hello at villageglobal.vc.