Celine Halioua - Making dogs live longer so humans do too

There is enough science out there for a first-generation longevity drug. You're not going to go and make people live to 200 with anything that's out there right now. But I think you can get statistically increased lifespan and healthspan. The economic incentives are not currently aligned with human longevity, fundamentally. And one of the things I really liked about the dog longevity space is that we could be a completely evil company who didn't give a shit about dogs, and we would still be economically aligned to do the best thing for dog owners and for dogs themselves. I'm very, very cognizant of the fact that if I mess it up, I probably burn the space for everyone else. Oh God, man, I'm gonna get canceled. I just think the aging field is full of charlatans. Yeah, so my name is Celine Halioua. I'm the founder and CEO of Loyal. We are developing drugs to extend dog lifespan. Our goal is to get the first drug FDA approved explicitly for lifespan extension and healthspan extension in any species, but obviously in our case, going dogs first. We're working on a lot of drugs. I think the most kind of notable progress we've made is we've now twice earned RxE efficacy approval from the FDA. So basically we've hit the efficacy bar we needed from the agency to be able to bring our drug to market. There's other things we have to do before we can sell the drug, but efficacy is so stupid hard and it was a huge, huge lift to even earn that. And we're hoping to bring to product, to market our first product next year for senior dog lifespan extension. This will be a daily beef-flavored pill to hopefully extend the healthy lifespan of senior dogs. And if it's approved, it's, you know, over 15 million dogs in the US will be eligible day one.

You started your academic career as an artist. Moved into neuroscience, began a PhD in pediatrics, and then dropped out. Can you walk us through that journey?

I mean, how long do you have?

45 minutes.

Okay, I won't subject y'all to too much of it. Yeah, the super high level was I was never an academic kid. I was in fact actually like in the bottom 10 of my high school. So it's always really funny whenever there's high school reunions and everyone's like, how is it you? Who's running the company in Silicon Valley? Doesn't Grok— what happened here? But I don't know. I had this realization right before I started college that we don't— in my view, we don't really have free will because we can be living our lives and making our independent decisions, but then something can go wrong in our bodies. And you always, when you're young, think that doctors are magical and they can save you and save the day if something goes wrong. And then once you kind of have your first medical scare or know somebody who has their first medical scare, you learn that in many situations that's actually not the case, right? In many situations, there's just not anything that anyone can do for you, no matter how hard you try. And something about that discorrelation between effort and results, um, And the fact that I had met a number of brain cancer patients shadowing a doctor, and many forms of brain cancer, especially glioblastoma, are extremely deadly and often deadly very quickly. And just the realization that if you got diagnosed with disease, if your cells went rogue, that any plan you had for your life was just gone and your one life was gone. Or even if you believe in reincarnation, this life that you're in currently is gone. And I just didn't want to live in that world, like, fundamentally. Um, so I switched to neuroscience and from art, and I was like, okay, how can I like help people who are sick? And I kind of went through like the classical thing of, I'm gonna be a nurse, I'm gonna be a doctor, I'm gonna be a neurosurgeon, I'm gonna be a researcher. And that kind of drove you know, my— where I spent time as I was growing up academically. And that was how I landed in the aging field. It was completely coincidental. I didn't know anything about longevity or the field. I'm, you know, not actually particularly interested in immortality or radical lifespan extension. I just think about longevity and aging drugs as a way to reduce the risk of getting some of these diseases that are so deeply intractable with current technology when you're diagnosed. That is a more effective way, a preventative mechanism instead of waiting until somebody's sick to treat them. And then, yeah, I started my PhD, dropped out pretty quickly for a multitude of reasons that I'm happy to get into if they're interesting, and then ended up starting Loyal, which I'm sure we'll talk more about, but ended up starting a company, which I certainly did not think that starting a company was how I would have my impact on the world. But 5 years later, here we are.

Let's dig in a little more into dropping out. I'm also a fellow PhD dropout, so let's go. Tell us about the decision. You know, there's this moment when you enter the shining halls of academia and you feel a sense of optimism, a sense of purpose and excitement, and then walk us through that first day and then that last day of being an academic.

Yeah, so there was a couple of things. So I went to Oxford and I was very— I mean, I don't come from a ton of money. My mom told everyone that she ever met that I was going to Oxford, and everyone was so proud of me. And there's kind of this borrowing of credibility that you get when you get to go to an institution that— well known. And it was kind of a feeling I'd never had before. I went to UT Austin for undergrad, which is a great school, but it's not Harvard. It was really the first time I got to feel that. And I think it was the realization of a couple of things. One is that I struggled with how hierarchical, needlessly I felt like hierarchical, it was to the detriment of effectiveness. I think one of the things I really fell in love with about Silicon Valley is Silicon Valley fundamentally values ideas. And execution on those ideas. They don't care if you're 5'1" or 6'10" or 18 or 50. It's just who is building the future, who has a vision for the future. And it's pretty well accepted that it's actually often going to be someone who isn't in the standard norm with all the degrees and all the letters behind their names that's going to have the insight that leads to the future. And at least my experience of the university was very different. It was very all about kind of chasing the titles and the, you know, your ideas aren't as good as the person who's one level above you, which aren't as good as the person five levels above you. And that's really kind of flown into how I try to run Loyal today too, is not in such a hierarchical manner. And so then when I got the opportunity to join a venture fund, I was investing in longevity. Companies, I just, I don't know, I came to Silicon Valley and I was the dumbest person in every room and I was learning every day and messing up every day and it was just so stimulating in a way that I just felt like I was spending most of my time on bureaucracy at university. And so I don't know, I almost completed it. I was like 6 months away, which is kind of tragic. Maybe one day I'll finish it if they'll have me back after they hear this podcast. But— It was definitely the right decision for me.

Is there any comment you have on the through line or the central theme that has stayed true for you from all these different chapters of your life, from artist to researcher to now startup founder and investor?

I think the biggest thing was just finding the most effective way to have the impact I wanted to have in the world. And the impact I wanted to have on the world is increasing free will. And increasing our resilience to age-related diseases, right? I had a lot of different ways of working on that. Like at one point, again, it was nursing. Then it was, when I got a little more confident, I was like, "Oh, maybe I could be a doctor." And then I was like, "Oh, I'll be a neurosurgeon 'cause like you'll work on brain cancer and those are really bad. Then I'll be a researcher and like develop new drugs." In the end, it was kind of like Loyal ended up bringing together lots of different aspects of myself. I've always been a huge animal lover. I obviously have an affinity for the arts and consumer design, and then obviously the aging biology. And that felt like it was founder market fit in such a strong way that I had to do it versus everything else. When I spent time on it, I loved it. I loved doing research. Loved the idea of becoming a doctor, but it was really clear to me deep down that I wasn't 99th percentile, I wasn't world class. I didn't feel that personal fit to it. I never was going to get a Nobel Prize for research. And then when I started Loyal, I was like, oh, I think there's a pretty compelling case that I'm one of the better people to start this company relative to 100 other individuals. That's kind of been my philosophy ever since of where to spend my time.

So something you've talked a lot about with Loyal is how, you know, your hope is you're going to prove out the market for dog longevity, and then that can set up a base, right, for people to invest into human longevity as well. Can you say a little more about, like, what is it you think there is in the culture and in the psychology of investors that makes them not see the opportunity for longevity? Like, I just feel I've been thinking about this for so long, it's hard for me to understand, right? Like, there's all these diseases and we're talking about targeting the root cause of disease and the root cause of, you know, all illness, right? Just, yeah, help us understand like how you see that manifest and what the cause of it is.

I think part of it is that it doesn't, you know, one of the things I realized, um, is, and it was actually one of the things I was studying also at my PhD and kind of became like interesting personally to me, is you have to align economic incentives with the good that you wanna create. In the world, and the economic incentives are not currently aligned with human longevity fundamentally, right? Like the, you know, one, if you run, one of the things we're thinking about right now lightly is, you know, how would you do an equivalent of our, we're running a pivotal lifespan extension study called STAY over the next 5 years in dogs to hopefully show Lifespan extension, healthspan extension was our drug. We've been thinking about, okay, how would— what have we learned from this study and how would we run it in humans? And one of the fundamental challenges would just be the length of that study. And the length of the study impacts economics because if your study takes 10 years, 15 years to read out, well, 10 years is longer than any fund timeline or most fund timelines. Also, your like core patents are going to be about 20 years old, 20 years timeline, once a drug's on market, if you magically get it on market, who's getting the ROI from that investment in that aging drug? It's probably not the insurance company that's insuring you today. It's probably Medicare or Medicaid or whoever you end up being on the later years of your life. So you're paying for somebody else's ROI. And one of the things I really liked about the dog longevity space is that we could be a completely evil company who didn't give a shit about dogs and we would still be economically aligned to do the the best thing for dog owners and for dogs themselves, right? You know, VC, it's economically aligned for investors to back us because the time to ROI is well within a fund lifecycle. I like to call the dog owner-dog relationship as like a micro single-payer healthcare system because you're economically responsible for your dog today and for the rest of their life. So you're willing to invest to a degree in preventative care You are the one who's on the hook for when your dog eventually gets cancer. All of these things kind of come together in a way that makes it very aligned. And so to go back to your original question of why do I think VCs don't see the opportunity as much, I think it's partially limited mindset. I've gotten a million passes of why would you do dog longevity? That's so stupid, da, da, da, da, da. But I think also fundamentally, even if somebody's bought in. It doesn't fit super well into current financing structure for startups. And so that's why one of our theses is take the revenue that we generate with dog drugs and invest it into better longevity drugs for dogs, but also human longevity R&D.

And is this an issue that is just— because there's another way of looking at longevity drugs where like, yeah, running a clinical trial to see if you extend healthspan is really difficult, but you could also just show reduced risk for heart disease, like pick your disease, and that you could potentially do over a shorter time period. But it seems like there's also just generally a distaste for preventative medicine more broadly. Is that also just an economic incentive thing, or am I describing it correctly?

I think it's probably right. I mean, I'm not as, um, as plugged into the human side anymore, but at a high level, yes. Like you have to think about when you're— there's also a reimbursement problem. Right. It is, you know, multiple orders of magnitude more expensive to develop a human drug than it is a dog drug. And it's probably going to be even more expensive to do a longevity drug. And so it does matter the reimbursement you're going to get and who's going to want to pay for it. One of the things we've thought about actually on the human side when we get there is going to single-payer healthcare systems because they have an economic incentivization to do preventative care for their populace. And again, it's not like that's not the case in the US either, but it's a little bit more convoluted. And you kind of see that in the startups that get started and get funding. Like there was this whole trend of these startups developing, you know, niche drugs for, you know, whatever gene therapy and it being $500,000 or $1 million per shot. Right. And now, now those are all struggling and failing. But that was kind of vogue. Versus the idea of a longevity drug, which is a cheap pill that the majority of people are on. In a lot of places, like startups weren't getting funded to do something with that big of a TAM.

You've also mentioned that, you know, you think these preventative drugs, that longevity drugs should be boring, right? Like these are simple things we take every day. I'm curious, the way you speak about it though, it seems like you have confidence that like it's more a market opportunity issue. People don't realize there's a market, right? Like there's market risk and then there's technical risk. When I think about longevity, I think about a lot of technical risk, right? Like, do we actually think we can build these things? Like, what gives you the confidence that if there is investment in this space, that we're going to be able to figure out all types of, you know, longevity drugs?

Yeah, I mean, it's difficult because I think a lot of the shots on goal— so I have a very specific way that I think about, or I hypothesize that we should tackle this field. And we'll see if I'm right or wrong. But like, my thesis has always been that we know people are going to want a longevity drug. We don't know the exact market, but like, you know, a drug that reduces— put another way, a drug that reduces all-cause mortality is obviously going to have a role in our healthcare system or in a healthcare system somewhere. Right. So one, two, we know that the biology of aging is modifiable. You know, there is decades of very, very strong research that shows translation ability of aging mechanisms, right, across organisms, right, suggesting that they can serve mechanisms, the most, like, well-understood being, you know, metabolic fitness improvement and caloric restriction. 3, we need to have safety, right? If I'm going to give you a drug today to hopefully keep you healthier longer in 20 years from now, it sure as hell better not kill you tomorrow, right? And safety is so, so, so, so crucial. And, you know, when you take all of these things together, I don't think, like, I think the way I really think of the field is what are the lowest hanging fruits that hit these requirements that allow us to bring a product to market for longevity that has the lowest efficacy risk, the lowest safety risk, and sufficient efficacy upside to obviously make it across the finish line. Right. And that's kind of how like that's what's informed, you know, the drug strategy that we've chosen. Like we're now doing undisclosed, but like I'll call them more like spicy medicines that we're working on. Right. But like our first drugs were, you know, very genetically validated, very like safe as milk, like all of these things that were like making it very, very clear that the ROI was positive. I think a lot of the field has gone instead, they've kind of skipped, I feel like, the low-hanging fruit and are like, let's go to the really complicated stuff. Let's go do senolytics, let's go do epigenetic reprogramming, let's go do this, that, and that. And I think that's an approach, and I think their approach is, their thesis is that it's gonna be so much more efficacious than like a caloric restriction mimetic could ever be, that it's going to actually accelerate things. You're gonna start seeing rejuvenation, and that's like where we need to go as a field. And it's actually not, you know, powerful or ballsy or whatever to go low-hanging fruit first. But I always worry about that because I think fundamentally you're still going to have— I think they'll create some great drugs, but I think there's always going to be this tension between efficacy and safety. And fundamentally, if you want to create the next statin or even the next rejuvenating drug, whatever that is, there is going to be a cap on the safety issues that people will accept. And characterizing that is difficult. So we'll see. It's the TL;DR. There's lots of different ways to go about it. Hopefully we're all right. But that was one of the reasons I went simple, simple and boring.

Do you feel like you're naturally more sort of practical and conservative in that way? Or does your mind go to these kind of crazier therapeutics and you have to kind of bring yourself back down to earth to be practical?

I mean, so I came out of a gene therapy lab actually, and the first idea for a longevity drug at Loyal was a gene therapy. I raised the seed around a gene therapy. But the thing is, like, I'm very emotionally attached to the outcome of the company, which is getting the first drug FDA approved for lifespan extension in dogs. And I'm not emotionally attached to how we get there. So then when my team, when I hired them, were like, Celine, like, this gene therapy doesn't make sense for X, Y, and Z reasons, but like, here's this other approach. And, you know, they talked to me a lot of these things I'm talking to you guys about. I was like, well, obviously we should do that because it increases probability of success. You still are retaining efficacy. There's less safety risk, less all these other risks. And like, you know, yeah, I liked gene therapy, but I didn't exist to serve gene therapy. I existed to serve the end state, which is get a drug approved for lifespan extension. But I do think that's a very different type of thesis and kind of company formation. Versus a lot of companies in the longevity field, BioAge is an exception, but a lot of them have been started around a mechanistic thesis or like this type of longevity drug should be developed. And so that kind of just adds like inherent risk because not every mechanism is going to play out. And so when you're emotionally attached to a mechanism, it can— if your mechanism is wrong, there's nothing you can do. Fundamentally, unless you figure it out really quickly and pivot.

Just one thought that I'll share there is that this earlier theme of, of free will, of extending the human ability to— the human right to free will and the human right to individual agency, I think is reflected in the spirit of and business model of Loyal as a company. Because the only way you can control your destiny as a biotech and as a company is to have the capital structure to go and pursue what you'd like. And something we've chatted about in the past, and I know that we both really resonate with, is this idea that once you have the cash flow, free cash flows, and the balance sheet to go pursue novel mechanisms of action and have the investor support to go pursue other things, that's what allows you maybe to more effectively tackle the more intense radical therapeutic strategies and have a portfolio around different individually risky bets. Collectively strategically sound bets. And so that, that's something that I think you've done remarkably well as a CEO. So that's a really romantic connection.

I never thought about it that way, but you're totally right. Like, I've— yeah, I, I think that's totally right.

Celine, uh, something you've talked about in the past extensively through your online writings as well as through your other podcast interviews is, um, you know, the path of being a non-traditional founder. So question for you, how has being an outsider, which, you know, artist dropout, non-traditional background for biotech, shaped your approach to being a biotech CEO now?

I think the biggest difference that I probably have relative to maybe let's call it like the average biotech CEO is I don't consider myself the expert in any one thing and certainly not the scientific expert. You know, I'm obviously scientifically trained. I had the initial scientific insight and thesis and validated it that led to Loyal. You know, the biology that I promoted and pitched in our seed raise, albeit modifying it with gene therapies, is still the biology we're doing today, or still one of the programs we're doing today. At Loyal. And, you know, one of my first hires was a VP of aging biology to take the torch from me and lead the science better than I thought I could. And he did lead it better than I thought I could. And that's really been my philosophy for every corner of the organization. And I think— I'm sure there's plenty of leaders who lead that way who are, you know, much more credentialed than I am. But I think it was very easy for me to get out of my own way and let go of my legos and hire people who are better than me because I don't really— I think making me let go of fundraising might be difficult. I'm probably objectively the best person in the company at fundraising. I don't know if anybody at the company would fight me on that one. But the vast majority of things, my number one philosophy is hire somebody who's better than me and and who I can learn from on it. And then my job's to kind of be the interstitial fluid or the connective tissue between all of the functions, which is also something I'm very good at, right? I'm very good at connecting technical ideas, creative ideas with operational ideas, with veterinary ideas, clinical, and all of that. Like I have a lot of competency across like a very broad set. Again, I don't have the depth, but I have the breadth. And then I can bring it all together and like help all these very diverse skill sets work together. And so I think that's probably the biggest difference between how I've approached leadership from day one versus maybe somebody who came out of a PhD, discovered the biology that led to their company, and is the de facto expert on whatever receptor they're trying to modulate. That's great.

In terms of your own confidence in your fundraising capabilities, what advice would you give to founders who are now navigating the journey of fundraising and what does it mean to be a great fundraiser?

I think the biggest thing is just, who was it? There was somebody who, oh my God, I'm blanking on her name. One of the co-founders of Maven has these really good blog posts and podcasts about executive communication and she targets especially people who are learning how to communicate up and manage up and that skill set. And one of the things she talked about that I thought was such a good framing is, you know, there's always explicit feedback, which, by the way, is very difficult to get from a VC. You know, we don't think your indication strategy is correct. We don't think you can be a good CEO. We don't think you're going to raise— like, whatever that explicit feedback is. That's when somebody is literally saying, this is my feedback for you. Usually it is very difficult in many situations, not just fundraising, to get explicit feedback. And she talks about this idea of, I believe she calls it implicit feedback, which is feedback loops from behaviors that give you an insight into what that person is thinking, even if they don't tell you. So you can kind of see, like, I like to talk to investor conversations in person because you can kind of see when people's eyes glaze over. And I'll always take a little note in my head like, oh, this is where I lost them, right? Or kind of being your own worst critic and constantly never being like, oh yeah, I nailed that pitch, but always thinking like, oh, how could I do it better? I remember when I raised the seed, nobody, obviously again, nobody gave me direct feedback. It was very rare. But in between each pitch, I would in the Uber be getting carsick changing the slides because I'd be like, okay, I lost this person here. This didn't flow that right there. He asked me this question here, which means that he probably wanted to understand that sooner and was holding it in and then was like lost. Like if you can create your own feedback loops, you'll get so much better so quickly. Like I think that is what I'm good at is learning very fast. And that's what's made me, like of course like Loyal's made sense and I know how to tell a loyal story and blah, blah, blah. And like, you're not gonna be able to fundraise for a stupid idea, you know, if no matter like, well, as I say that, I guess there's some people who do that like as a career, but at least I'm not that talented. But I think I am good at like understanding what people's point of views are and what their hangups are and hitting them front and then iterating very quickly to the audience and the dynamics of the round and the situation I'm in. That's great.

And just to quickly remind our audience, can you, cover the highlights on your fundraising history?

Yeah, so I started Loyal about 5 years ago. We've raised about $135 million to date. Um, our major investors are first round Valor, Bain, Khosla, Collaborative, Quiet. I'm probably forgetting somebody who's gonna get mad at me later, but Box, lots of people, Longevity Fund, obviously. Uh, and I think probably the thing that was like different about my fundraise is I've raised mostly from people who don't classically invest in therapeutics development. So there's a lot of education, there's a lot of responsibility in that education, and you also don't want to over-educate or not educate on things, or educate on things that don't matter because you just lose people. So there's a lot of judiciousness that goes into designing how do you talk to a generalist investor about something that's very, very technical where they don't have a specific background and maybe 5 out of 6 major components of your company.

So Celine, you've worked in pre-market spaces. What advantages come from entering a field before the market or the narrative for that field is defined?

So another recommendation, I'm reading a book right now about, um, the story of NVIDIA, and it turns out the CEO Jensen Huang talks about it as a $0 billion market. And I really, really like that. I think the way I think— so obviously there's never been an approved longevity drug. Obviously you can't go to your vet or your physician and be like, I'm going to, you know, can you prescribe me that longevity drug, please? And I'm obviously very excited about this idea of bringing a new category. I would say for every unit of excitement, I also have a unit of terror, fear, foreboding, because I'm very, very cognizant of the fact that if I mess it up, I probably burn the space for everyone else. So yeah, I mean, it's exciting. It's exciting to be able to define it. But to me, it's— it probably is one of the things that weighs most heavily on my shoulders.

What aspects of drug development can't be learned from papers or textbooks? And what did you learn by doing? Literally all of it.

You're fucked if you're trying to learn how to develop a drug from papers and a textbook.

I just bought a lot of textbooks. I got to throw them out.

Yeah, we got to burn those afterwards, Daniel.

But I've read literally everything that there is out there and the knowledge doesn't exist. Or maybe there's like a foundational, like a scaffolding you can get from those resources. But honestly, the knowledge mostly lies within— it's like an apprenticeship industry. It's why you have to hire expertise. And also a lot of it's not first principles, which people get wrong, right? Like there's a lot, especially like a lot of context is just not intuitable from first principles because often there's a chaos variable that like is not obvious if you haven't worked in that space before. So basically hire great people and ask really good questions and be very humble. And that's like, that's how you learn about drug development. And then you'll make really painful mistakes that hopefully don't kill your company.

Yeah. And I think like for that reason, like biotech can obviously be extremely intimidating, right? Like my goal, I would like one day to build, you know, a startup that contributes meaningfully to longevity. But of course it's extremely hard to develop like an earned insight in science, right? Like, how do you, how do you figure out something that nobody else knows or something that can really meaningfully move the needle? I mean, what do you think are the quickest paths for people to gain like genuine insight, both about market and I think biology in order to build something meaningful?

So I'm really on the quote game today and I'm not normally like this. I'm sorry. I don't know what's wrong with me, but Michael Nielsen has this really interesting framework where We codified it as a value at Loyal, this idea of opportunities at the intersection where maybe there's two ways where you can find earned insight. One is diving deeper and deeper and deeper into one technical area until you learn something about the biology of breast cancer or whatever it is. It's a new insight that nobody ever understood before, and then you can go and develop a drug for that. And to your point, it is extremely difficult to do that. You certainly almost— it's extremely difficult to do it intentionally. And you probably shouldn't go and be a researcher for 20 years with the intention of maybe finding something like, you know, biology is not that cooperative most of the time. And I certainly didn't have the depth of skill set to do that. But the other way, and the way that I kind of happened across Loyal, is the opportunity is that the— there are opportunities at the intersection of fields that don't normally touch. And so if you don't often have— if an individual doesn't often have competency for field 1 and field 2, there might be intersections of field 1 and field 2 that are actually relatively obvious if you have context for both, but you have to spend the time to get context for both. And so the thing that Michael Nielsen would say is when you go and find these inflection points or these new foundational discoveries, so gene therapy becoming a thing or whatever, that then opens up a field of a whole number of low-hanging fruits that didn't exist before. Now, again, pretend that gene therapy isn't having all its issues that are having, right? If you were a gene therapy expert and an ocular disease expert, it is then a very low-hanging fruit to go against and try to target these monogenic blindness disorders that kids get, right? Because the eye is immune privileged and all these reasons. But it might not be obvious if you're a gene therapy expert who doesn't know anything about the ocular field, and it might not be obvious if you're in the ocular field, and I don't know anything about gene therapy. And so for Loyal, that was the combination of canine biology, longevity biology, and consumer go-to-market that really, that I had the context for all three that made Loyal extremely obvious, but wouldn't have been obvious if I was missing the context for one. I was actually missing a lot of the consumer context. It was an outside party, an investor who came to me because I'd been working on the first two, and he was like, Celine, this is like the biggest consumer market ever. And then that was kind of like the click that made it all fall into place.

And on this point of, you know, how to find a good opportunity, do you have a view on what is the highest value sort of longevity idea that nobody is developing? And if it's something that I think I can work on, we're going to edit it out.

We won't share it with everyone else. Honestly, I think there just needs to be more companies working on longevity drugs for longevity, fundamentally. I don't think we need more discovery. Like, obviously we're going to need discovery eventually, right? But I don't think we need more discovery. I don't think we need more, you know, this super explicit, technically difficult mechanism in its application. I think the thing the field needs is a clinical path for a longevity drug.

So by clinical path for longevity drug, you mean focusing on the nuts and bolts, less of the science and more the commercialization of existing science and clinical development, FDA regulation, you know, payer reimbursement, that sort of thing?

I think there is enough science out there. There is enough science out there for a first-generation longevity drug. You're not going to go and make people live to 200 with anything that's out there right now. But I think you can get statistically increased lifespan and healthspan with drugs, with mechanisms that are well validated today. And then the question is, I mean, there's a huge question of reimbursement, there's a huge question of ROI, there's a huge question of a lot of things that again, the dog go-to-market avoids a lot of that. And maybe it's not possible going straight to human, but I think that is what the field needs. It kind of needs its Ozempic moment. Like what's this drug that's going to show that this category is a massive gold mine? And in the minute you show that, you're going to economically incentivize all these people to work on longevity R&D and development. And that's where the next generation and next generation and next generation drugs are going to come from. The first drug doesn't need to be insane. It just needs to be sufficient for approval and safe. It's not safe. It'll burn everything.

In 2021, you wrote that part of Loyal's mission is to socialize the aging thesis and quote unquote, make biotech sexy again. Like what has happened with space tech with SpaceX. Yeah. So Celine, why has aging research struggled to do this?

Oh God, man, I'm going to get fucking canceled. You guys are going to get canceled by the aging field.

We got to answer this now.

I just think the aging field is full of charlatans. It's full of low scientific rigor, high dogmatism. Individuals who are just petrified of their own mortality and like overpromising, underdelivering. And I think the field has been that way for a really long time. There's obviously a few notable bright spots and it's getting more rigorous over time and it's getting real funding now. And there's real companies with like really good founders actually going and doing ambitious shit. But like, man, still the public perception of longevity is Billionaires Trying to Live Forever. And I get why. It's a great headline. And it's really delegitimizing— legitimizing— legitimizing— I can't pronounce English. It's not good for the field.

Do you think that's a problem that's gotten worse over time, or is the narrative changing for the better?

No, it's gotten worse. It's gotten worse. It's gotten worse. Yeah. I mean, I think it's— I think maybe it was always, maybe I would say they have gotten, both have gotten louder together. So in general, like the magnitude of good work happening in longevity is so much bigger now than it even was 5 years ago when I started working on this. And I would say the like charlatany voices have gotten so much more airtime and energy in the last 5 years from a magnitude perspective than they ever were getting previously. So there was more charlatan than legitimate work happening in the '90s, but it was still just a small fraction of a small fraction versus now it's actually— it's in major media, right? It's a very consensus thing to talk about now, which is unfortunate. Do you think—

something I try to think about with this, right, is I guess you have like industries go through like bubbles, right, where sometimes there is like a lot of hype, but sometimes like the hype makes it come true, right, because it attracts investing. Like, I guess, do you see any balance there of, I don't know if, you know, non-charlatans, but saying like, hey, look, we are working on immortality, or like, is that needed to some extent to like drive the sort of Manhattan Project level investment? Into the space?

That would certainly be their argument if they were on this podcast. I mean, I hope, yes. I really hope so. I think my concern is that with the field so loosely validated and with— it hasn't had its objective Ozempic moment or true validation moment yet. That if the— yes, there's going to be more shots on goal and more money put into those shots. But if those shots are bad, it actually, it's gonna turn back the field, um, because they're just like, this field is full of shit, there's nothing good here, it's just all overhyped, overpromising, underdelivering, um. And so there's kind of a subtlety of, I think, yes, more shots on goal are good, but if 90% of that money is going— not that I'm saying it is, but if in theory 90% of that money was going places that aren't actually like real shots on goal, it could actually make things a lot worse. Like we all know there's like categories that VC just like will not invest in because they lost money in some like big company. Like longevity is like very prone for that to occur too.

What advice do you have for our listeners in identifying, 'cause there's so much signal, there's so little signal out there and so much noise out there for fields like longevity. What advice would you give to your team, to our audience members on how to identify the signal from the noise and the true innovators versus the charlatans?

I think one is just like talking a book or like being very dogmatic about any one pathway mechanism. There is no magic mechanism, right? Like there is no one thing that has been shown to definitively, you know, extend human lifespan. I think a lot of people tend to get very anchored around a mechanism and maybe they're right, maybe they're not, but it's difficult to— you have to be open to being wrong to find and kill an idea so you can go and find that right idea. And I think a lot of the field often like avoids disproving themselves. And there's some like interesting antibodies that are being built now around that. But it's also difficult because the studies are so long, even in mice. That things like theories can go floating around for a really long time. So that's one. Two is just like, you know, overhyped claims or anything that feels like very consumer-y. So like biological age, this thing reversed my aging 5 years. Like anything that's like unsubtle like that usually does not stand up to a ton of scrutiny. Like, it might be interesting, it's anecdotal, but it's not— it's often a few degrees overstated relative to what you could actually learn or extrapolate from that. There's always this difficulty though with science, right? Because then you have like the average scientist who communicates everything with so much caveating and doubting and uncertainty and technical accuracy that then you just lose everyone. Right? Like traditional sitcom is also bad. So I'm not saying we should go with the— there needs to be some middle ground. We try to hit that at Loyal. It's really difficult. But I think that's really— the field needs more people talking about science in a rational but accessible way.

You bring up like biology has an interesting problem, right? Where it's just, it's so empirical and it's so detailed, right? Like there's just so many mechanisms and we don't know all of it. Like you can't really do it from first principles. And, you know, that's why, of course, like, theory is attractive, right? Like, in physics, we can come up with theories that explain everything, right? Like, it's very attractive to come up with theory for biology, but that's how you could end up being dogmatic and wrong. Mm-hmm. But it, you know, it's something I'm always chasing. Like, I'm always hoping, hey, is there some theory we're gonna find, right, that's gonna help us understand things, and then we can predict the right interventions? Like, in your free time, when you're, like, entertaining some of these notions, like, are there any, like, sort of theories of biology, any sort of more radical ideas that you do hope get developed? Maybe there is something, some unifying theory we're going to crack in the future.

I don't think so. I think biology is fundamentally entropy. That's why I'm really skeptical of a lot of the AI companies. I think obviously there's going to be interesting AI work done in bio, just like in every other field. And I don't know if we will see— we don't have the datasets. We don't have even the basic quantification or understanding of what's happening in my body literally right now and what's variance in me and what's variance in me because of my genetic changes or my epigenetic changes versus my cells turning over and having mutations in certain areas. And I got a mono 10 years ago and it caused X, Y, and Z. All of these things directly influence how efficacious or not a drug's going to be, or safe or not a drug's going to be, or what diseases I may or may not get in the future. And that's just one person is so like fractally complex. And maybe there's going to be levers in biology to your point that there are in, in, you know, in other areas like one of the theses of what we target right now for longevity are things that we think are evolutionarily served. So they're as relevant to a worm as they are to a dog as they are to a human. Maybe as I'm talking, there is going to be versions of that that allow a similar kind of step-in or V1. But I don't know if there's one thing I've just learned building Loyal for the last 5 years is like, as complicated as you think everything is, it's 10x worse. And it's just, I don't know how you build a model. I don't know how you build an ability to get that quantification of those states to allow an AI to do what it can do. If you could magically have all that data, obviously it would do amazing things, but we can barely even quantify quality of life.

Just crushing my dreams, but it makes sense. Yeah.

Hey, look, I know nothing about AI, so like maybe I'm totally wrong. I'd love to be wrong. And I think that it does make sense that there would be like a step in somewhere. Um, there certainly is in like the pre, like drug development stuff, like stuff like you know, how well does this antibody bind to this receptor or how well does this small molecule block this protein or modeling folding like that all makes sense. If you're anchoring for something like that specific. But then that, that to human, that jump feels much harder.

Yes, I 100% agree with that.

I have a question I'd like to end on. So you wrote back in 2018 in an article on your blog, Why I Care About Longevity. and in it you ended it with this quote, which I loved. Uh, I am definitely naive and certainly overenthusiastic, but that will just make for a more interesting journey and maybe, and ample content. Uh, can you say a bit about like, where do you feel like you are in your like development now having worked in the space? And I don't know, any commentary on like the role of naïveté, like when building something?

Oh man, it's so funny. I actually tell people this a lot. That I would not start Loyal knowing what I know today. And not because Loyal is wrong. Loyal is right, our thesis is correct. And if I had known how hard everything we were trying to do is and how small of a gap we were trying to traverse through, like I thought the gap was this big, the gap was actually this big, right? If I had known that at the time, I mean, the logical choice would've been not to do it. I think candidly, this is a lot, it is another reason why a lot of biotech VCs didn't invest in us, 'cause they're like, here are the 10 ways you fail. And yeah, like, yeah, like it was, they were right. And we still figured it out. So I think being naive is really, really helpful because man, like if I actually knew anything about FDA, if I had known anything about getting manufacturing approval or running a clinical trial or, recruiting 1,000 dogs or hiring and managing and building an executive team and all this crap that I do all the time. It would have been so intimidating. It would have been so intimidating. That's why you, if you actually want to start a company, you should just go do it because you're going to convince yourself out of it, not into it, with more experience.

That's great. Celine Halioua, I think this is around time for us to wrap up, but Um, hopefully this is a fun conversation for you. I had a blast. I really enjoyed this, and I want to thank you again for taking time out of your day to chat with us. And we're looking forward to publishing this at some point soon.

Thanks, guys. I also love the name, by the way, Free Radicals.

Yes, thank you. Thank you so much. We've been consternated about that for a long time.

It's really good.

Great. Awesome, we have an endorsement. Thank you for listening to the Free Radicals podcast. If you enjoyed this episode, please share it with someone else that might enjoy it too. If you're on YouTube, please like, comment, and hit the subscribe button. And please leave a 5-star review on Apple Podcasts and Spotify. It would really help us a lot. I'm Daniel Scher, and my co-host is Eric Dye. Thank you so much, and we'll see you next time.