The Pill That Makes Dogs Live Longer - Episode 40 with Celine Halioua

And then if you don't mind scooching that way down a little bit, and then you can see yourself.

Make sure. Okay, my hair looks good. Okay, the hair is optimal. Nobody's gonna think I can develop dog longevity drugs if my hair looks like shit. Ashley.

And then yeah, you can be, you can be comfy with the mic. They're pretty good. So cool. Does that feel all right?

That feels great. I was doing an interview with a guy who's a rapper the other day, and he was like this on— because I guess that's how you rap. It's like the mic right there, right up.

Yeah, yeah. And I was like, oh, I thought you were talking about like a job interview. First I was like, who are you? What position are you hiring this guy for?

No, some like social media rapper dude, um, who like does freestyles. And one of our investors like brought him to an investor like portco offsite and had him like rap about our companies. It was actually the sickest thing ever. So he did a freestyle rap about Loyal.

And did he like— he did them on the fly?

Totally on the fly. Just like did a little interview and then asked me for like a couple of like technical words from developing drugs. And I was like, GMP and pathological aging. And he just like weaved it into a whole, whole narrative.

So like that part of yours would be hard. The other part was probably like a welcome change over like a SaaS software or something talking about dogs and Humans should be a little more—

well, he was a cat person, so it was a little extra tough for him.

Okay, okay. No, but I mean, at least you'd have something to hang on to as opposed to like B2B SaaS or some AI.

Oh my God, I guess AI is a new like insult now. Like, oh, some AI rapper.

I saw you tweeting about some of that stuff.

Um, shit's so stupid. I mean, look, AI is cool, but like there's more important things.

They're all right. Well, we're gonna talk about them. Um, yeah, so are you ready? Fuck yeah, let's go. All right, Celine Halioua, thank you for coming to the studio.

Ashley Vance, thank you for having me.

You have 6 names, right?

Uh, yes.

Do you wanna— you wanna do them all?

Let's do it. Celine Lia, Gerda Juliet Halioua Hobbled.

Okay. And are there hyphens in there?

Hyphens. I have 3 hyphens.

And what is— what, your dad's German, your mom's from Ethiopia?

Morocco.

Morocco. Okay. And then, I mean, where are the hyphens all? How do we figure this out?

So the, the funny story is my parents did not intend to have me at all, and I don't even know if they like thought they could still have kids. My mom had me at like 43 or 44. Oh. And I was like the only kid, and like on either side, and they were just like, oh my God, like this is our like last chance to be immortalized. And so everyone in the family wanted their name incorporated into my name, and so all the names are in my name. Leah is my grandma, Celine is one of my grandmas, Leah was I think another grandma, Gerda is a grandma on my father's side, Juliette's my uh, mom's sister. Halioua is my mom's last name. Hobbold's my dad's last name.

That feels like greedy. I guess it's nice.

I mean, no, I mean, look, I'm from the generation of Scantrons, and so having to Scantron in my name—

oh my God, yeah, that'd be horrifying. You couldn't even fit.

No, no, no, I couldn't spell my name for a long time.

So you just get as far as, as you can go.

Yeah, like all my IDs have different versions and combinations. Which gets you in trouble 'cause you always buy a ticket on one form, but then it's incorrect on the other form.

Yeah, I could see that. That's a problem.

But hey, I think it's fun.

Okay, well, I was actually always curious about that, so now I know.

I know, I know. It's first gen problems, you know?

All right, well, I'm gonna tell the audience what you do, and then we'll go explore.

That's good.

I think I wrote the first story ever.

You did? I was telling somebody that today, actually.

Yeah, what year was that?

'21.

'21. Okay.

Something like that, I would assume.

That's, that's gotta be about right. And so the premise back then was the same as the, the premise now. You guys came out of stealth mode, you, you were in the longevity arena, I guess you could say. And, and you were coming up with, with therapeutics to help dogs live longer. And this was part of a, a plan of yours to, to do dogs first and then hopefully do humans to kind of pave the way for the FDA, for people to start thinking about medications in the longevity field, increasing lifespan as a thing you could treat as opposed to just like treating an illness and to like have people wrap their heads around this. I remember when you, and before that you'd been an investor in this area, one of the first and major investors alongside Laura Deming. And I remember when you came up with this plan, I mean, I, I just knew, you know, I knew that getting drugs approved is this, this long, arduous process. And so you wanted to do it for dogs. And so you were looking for compounds that could, could help increase dogs' health and lifespan. And then here we are. So that was probably roughly 4 years ago.

Yeah.

And so this is a big task ahead of you, but you guys have, you guys have gotten quite far.

Yeah. Yeah. We are closer, closer than not. It's our ball to fumble at this point, honestly, which is, kind of crazy because there were so many existential kill points between idea formation and today that I just can't believe we've gotten through— knock on wood— gotten through all these.

I mean, it's been really impressive. So you're, you're currently, if I'm right, you're pursuing 3 different compounds?

Yeah, well, publicly we have more.

Okay, okay. And then there's one that's like this lead candidate for, for older dogs, and that just a couple months ago got this new FDA— you're not like fully, fully FDA, I could just order this, but you, you got sort of the blessing that, that it seems to be working in the studies. Is that the right way to kind of phrase it?

Yeah, the way to think about it is, you know, you can't go to your vet and get prescribed this drug today, but you know, the hardest part about, well, all parts of developing drugs are hard, but one of the hardest parts is meeting the FDA's bar for does this drug do what it says it does? And so we basically have met the efficacy bar for conditional approval, which will allow us to bring it to market once we get safety and manufacturing done too.

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Yeah. Just 1, at least 1 healthier year for the average senior dog.

Right.

Which would be pretty sick if we can deliver on that promise.

And when you guys say senior dog, it just means an older, older dog.

Yeah. Like the, the on-label criteria will be 10 years and 14 pounds and up for this drug. And then we have a couple of other drugs that are for large dog lifespan extension. And those can be started sooner because big dogs age faster. So, you know, a 10-year-old Chihuahua is in, you know, maybe a little bit over 60% of its life versus a 10-year-old Great Dane, you know, it doesn't exist. Like they've often passed away before that.

And part of doing this was setting up a clinical trial for dog aging. Oh my God.

That goddamn trial. A goddamn trial.

I mean, what, how many dogs do you have to put through a clinical trial and how do you organize a clinical trial for dogs?

Um, so we are currently running what we believe to be the largest ever, uh, animal health clinical trial, point blank period. Um, just extremely big. Uh, but also the first ever clinical trial that's FDA-enabling, double-blind, placebo-controlled, FDA-concurred, blah blah blah, for a drug for lifespan and healthspan extension. So it is a longevity a pivotal trial. And the point of this study is to hopefully definitively quantify the lifespan and healthspan benefits of our drug over a placebo. And the problem with the testing an aging and longevity drug, well, one problem is it just takes a long time. And that was, I'm sure we'll talk more about this, but this was one of the reasons we started in dogs was it takes a long time in any species, but it takes way less of a time in dogs than it does in humans, right? It's gonna be, 4 to 5 years we expect to run this study versus it would be decades to do it for you. But the other complexity is that aging is so multivariate. It's genetically driven, it's environmentally driven, it's luck-driven, it's, you know, feeding and nutrition and exercise-driven, right? And so we wanted to capture that diversity of an aging trajectory. Right? And so be able to show that for the average dog, regardless of what dog food you feed it or how often you go running with your dog or blah, blah, blah, that the average dog could expect a healthy lifespan extension from this drug. And basically the way you kind of drown out all that noise is by recruiting a crap ton of dogs all over the US across 70 clinical sites across the US. It's a totally decentralized trial, which is also crazy. To basically gather enough sample size so that you can see signal through all of that noise. And, you know, we just fully actually over-enrolled the study. So we initially went out for 1,000 dogs. We had so much interest from the public, way more interest than we could actually take in. I'm sure. We've now enrolled about 1,300 dogs in the study, and now we'll follow them for the next 5 years.

You guys, you had some mo— was it during the Oscars? Oh, when— yeah, it was, right? Wait, remind me. I remember seeing it, and then now it was—

it was, I believe it was at Oscars. It was this director of Beef, I think it's called. Yeah, the TV show or documentary, like the Golden Globes or something. Yeah, I don't know, um, I wasn't watching it, but anyhow, when he, he got his award, and during it he was like, his last thing he said is like, you know, I do this for my family, named his family. And of course my dog's name is Dog. So like, hey FDA, could you please like hurry up and get that dog longevity drug approved? Yeah, that was like the last thing he said and he walked off stage. I wasn't even watching it. I was like at a coffee shop. I just got like— my phone blew up.

I remember seeing it.

I was like, oh my God, I know, dude. And we got a shout out on Joe Rogan yesterday, apparently. Okay. Um, which isn't as cool as the Oscars or Golden Globes, but also like we get a lot of these little like mini shout outs. It was just Joe or somebody saying There's a, there's a theme here, which is I also don't really listen to Joe Rogan's podcast. Um, and so I didn't hear it firsthand, but what I was told was said was basically like they were just talking about how much they love their dogs and how heartbreaking it is to lose their dog. But like, you know, there's this drug and there's this company developing these drugs to extend dog lifespan, and they're actually pretty close. Okay, so, so it's only us.

Well, I only— I asked that because I didn't know. I mean, were you already oversubscribed on the trial, or did —that sort of media kick off this study?

[Speaker:Celine Halioua] I mean, every time we have a media anything, it's like, my inbox is like filled with dog owners asking to be in the study. It's actually really heartbreaking because they're like, "This is my only shot." The biggest difficulty is like, they have to live, you know, there's a lot of eligibility criteria, right? They have to live within a certain distance of a veterinary site that's participating. We have a ton of sites, but does not cover all of the US, obviously. They also have to know how old their dog is, which is actually a huge challenge. And we have a lot of really creative solutions for that, like Facebook posts of like your puppy when you brought home your puppy 10 years ago from the shelter.

Yeah, like, what do you mean you have to prove it? Like, most people must have some vague idea of how— well, yeah.

So like, I don't know how old Della is. I say she's 13, but when she's seeing kind of spry, I'll say she's 11. And when she's seeming old, I might say she's 14. Like, I don't know how old she is, right? I adopted her from a shelter. Um, and so, but the problem is if you only accept it like classically, if you want to verify a dog's age, you have a birth certificate. But if we did that, then we would only have purebred or like designer-bred dogs, which is a massive, like, you know, uh, confounding variable. And so we wanted to have shelter dogs. And so what we ended up doing was figuring out a way that, for example, we can actually take— like, if somebody has a photo posted on Facebook from like whatever, 2014, being like, "Look at my cute little fluffy puppy." And it's plausible, or, you know, you can tell that the dog is like less than like a year of age or so. Or even a vet visit or something. That actually will suffice for the study of age verification. 'Cause it doesn't have to be perfect. We just have to, you know, you can't have a dog that we think is 5 actually be 10 years of age, right? It messes with the stats.

Right, okay. No, that makes sense. And then, okay, so the dogs are in the study and then they take a pill. And they take the pill how often? Daily. Daily. And then they get monitored for how long?

Rest of their lives. Okay.

And so they're just, these people are just checking in all the time. And then you're looking at metabolic indicators.

No, not even that. We are literally just looking at lifespan and quality of life, which is measured by the veterinarian and by the dog owner. Of course, we're also tracking adverse events, which in this case, an adverse event is like literally anything that happens to the dog. Dog gets, you know, dog has arthritis, dog has cataracts, right? Like, you know, in many cases that's not likely to be related to the drug, but of course you have to quantify that, you have to characterize it. The veterinarian has to do an investigation because you're trying to understand how does this drug behave over time in dogs. And then of course we're also building a really big biobank.

And then you're just, so if you're looking for this extra year of life, then across this whole study, You're looking at the breeds and what their usual lifespan is and then just seeing— No.

No. Okay. No, it's literally just placebo versus treated. Okay. And it's just, do you see a differential in the lifespan between those two? Okay.

AKA like the mortality in those two groups over time. Okay. Okay. And, and okay. And then going back to what you were talking about before, like as to why you started with dogs. I mean, I fast-forwarded pretty quick just because I knew the story, but—

but because you want to get your dog into study, is that why I'm here, Ashley? No, no, no, no, no.

I mean, I mean, just like why dogs are an interesting place to look. Because as you pointed out, I mean, we've done these studies for decades where we have mice that get some concoction and they have these incredible, you know, results that they're living twice as long as they used to. And then Every time we try to translate these to humans, it never works out quite the same way. And then nobody wants to deal with the cost and time it would take to run a study on humans because it's got to go for so long for you to be able to show some kind of results. And so I remember when we first talked, I mean, you hit on dogs because they, they had this lifespan that was in this ballpark where we could actually approach this problem, or at least that's how I remember our first chats.

Yeah, you have a good memory. Um, no, that's basically it. So I was at, um, my quick background is I did undergrad neuroscience, started a PhD at Oxford in economics of preventative medicine, dropped out to go join Laura Deming at the Longevity Fund, which was the first kind of really definitive fund investing in therapies for longevity and lifespan extension. Obviously humans, uh, was, you know, the implicit focus of that work. And I just got really frustrated that companies that would pitch us, because, you know, there was a lot of very cool companies, but they all had the same narrative of like, oh, we have this drug, extends lifespan in mice, but, you know, we can't test it for aging because of course we can't, FDA won't let us. So we're going to develop this aging drug for an acute, usually age-related disease. And, but one day we'll like also somehow magically figure out if it extends lifespan. And it just never made sense to me for a number of reasons. Like, it makes sense logistically, right? Like, to run a human lifespan extension study— so if you want to market and sell a drug for whatever is on the label, you have to run a study, many studies, that show that the drug definitively does that. And that's like, you know, pretty hard for any disease, but it's really hard for lifespan, right? Because if I give you a drug today and I'm like, okay, like, let's see if this drug extends your lifespan, A, I better be damn well sure it's not going to hurt you, right? The risk tolerance is basically zero because you're healthy, right? I can't kill you to try to extend your lifespan on the backside of your life. Um, but also, like, let's just assume everything's super safe. It just takes such a long time to show the, the remainder of the lifespan of a human being. And by the way, there's gonna be so much variance because of genetic risk, because of behavioral changes, because of environmental differences, because of whatever, where you got— study would have to be insanely huge. And just like, I mean, it's literally a billion dollars. Yeah. To run something like that. And so I was like 24 or 25 or something, and I was just like, well, that's crazy because I think somebody should develop and try to get a drug approved for lifespan extension. But like, I don't know how to get a billion dollars. Um, I have a lot of funny stories about like nearly going broke like my first year in Silicon Valley. Um, but then I realized that all these problems that were inhibiting the ability to do it in humans didn't exist in dogs, right? You can see a dog's, you know, biological aging in about 6 months. You could see lifespan extension in 4 to 5 years, which is still a long time but like much more reasonable in decades. Oh, and by the way, people absolutely adore dogs. In some ways they kind of adore dogs more than they adore themselves. Yeah. And people want it. And so if you can extend a dog's lifespan, it's a really big market. It's very like, it's super difficult, but it's like logistically feasible. And oh, by the way, we have this super unique relationship with dogs where we've co-evolved with them. We share an environment with them. They get the same age-related diseases we do. They're exposed to the same food that we are. And so if something extends the lifespan in a dog, it's not 1-to-1, right? But it's certainly a much higher probability than doing it in a mouse. Like you say, where, you know, we've cured cancer in a mouse God knows how many times and not translated that to humans. A dog's a much higher probability of success.

Why do you think nobody else had hit on this idea before? Like when you lay it out, it makes it— when you told me the first time, I was like, this makes so much sense. And there were like, there are these long-running dog aging studies from universities, but, but nobody had really zeroed in the way you did.

It's so funny. I think I literally tweeted this yesterday that loyal is the most consensus of the contrarian ideas. And I think it's— so to be clear, I did not come up with this idea that the biology of dog aging is, you know, especially relevant to human aging. The Dog Aging Project at University of Washington has been doing this. They're doing it with a drug called rapamycin. There was the One Health program at, I believe the NIH, looking at cancer in dogs. Dog cancer is extremely relevant to human cancer. But I think the pieces that we put together was the biology side, the longevity side, and the market and consumer side. And you kind of had to have all three for it to make sense. And then also bluntly, I think a lot of it's like, timing and luck, right? I mean, I've raised like $150 million. We still don't have a drug on market. Like, it's really hard to do something like this. And so it just— a lot of things had to come together for us, for this idea to have a shot. But I agree, it's like the most obvious thing ever.

Well, I mean, I didn't mean it sort of like it's just—

I think, I think it's obvious.

Yeah, you did. You did nail all the pieces. When you— what do you mean you were running out of money? Oh my God. What? This is just like in your personal life or as you were trying to start the company?

Well, no. So I, I saw— I was at Oxford and I was like, I'm going to leave Oxford, which is crazy. Yeah, it was, it was really fun. It was like probably the best 2 years of my life being there in some ways, but just so hierarchical, so old school, so linear in a way that's just extremely frustrating. Um, and so I cold emailed Laura Deming and I was like, hey, like, can I come do an internship for you? Like, I just want to like shadow you. And she was like, yeah, sounds good. Um, you know, come and fly out. Um, I don't think she realized like how much not money I had because I literally used like the last money in my bank account to buy my flight to San— and she like reimbursed me, but like 30 days is actually a lot when you don't have like, yeah, that much money in your bank account. Um, and then like the Ubers and the the hotel and whatnot. So I had like, I must have gone down into the hundreds in my bank account. And to take this risk. Yeah. Yeah. And obviously paid off. Yeah. But thinking about it now gives me anxiety.

What do you like when you— for people who don't know, I mean, Laura Deming, she, she now is running her own company, but was kind of best known for a while as maybe like the major longevity investor. I think it's fair to say. And absolutely. Kind of had this crazy story as like a child prodigy of sorts, like doing a similar thing, writing letters to professors and people in life.

At a much younger age than I did.

Yeah, I think she was like 14 or 15. Literally, yeah. So what did you write in the— I mean, you made it sound so easy. What did you write in this email to get this job?

Well, so Laura, I knew about her for a while and I really admired her because the longevity field has been around for a long time. It's older than me, and in some ways it's older than any of us, right? This idea of a, you know, fountain of youth or whatever is one of the oldest pursuits of humanity. Um, but I really admired Laura because she brought to this field that everyone objectively wanted: scientific credibility and professional credibility, for a lack of a better word. Like, not over-promising, under-delivering, not just like going for the shock and awe factor, but instead really like trying to bring this crazy air quote science to the mainstream. Um, and I really admired that. And so— and she was also one of the few women in the space. Um, and so I reached out to her because I just wanted to learn from her. Um, and I was like, candidly, less intimidated in some ways. I mean, she's pretty intimidating, but I was less intimidated by her because it was like, oh, she kind of looks like me, right? She also didn't come from you know, generations of Silicon Valley elite. Yeah, or whatever, right? Like, she figured it out on her own too, albeit much earlier than me. And yeah, it was just a shot in the dark, and it really worked out.

And so you just, you just made your case really clearly in this.

I actually, I made it really badly. Okay. Um, what you told me later is like, my interview is not very good, uh, but somehow she still let me come. I think because I was really passionate Okay. It was clear that I was super passionate. Okay.

Apparently I didn't remember this, but in my first job interview ever, um, the, the person hiring me said that I asked at the end if there was going to be a drug test. And then when she, when she retired, she wrote this note and she said she had like all these tips, um, you know, things that she had learned through her career. And it was something like, if 'Your job candidate seems like— like asks if there's a drug test, but seems promising enough.

Like, take a risk on that person.' So would you have failed a drug test?

Uh, you know, it was college. I, I like— I, I don't actually remember doing that. I was kind of shocked when she put that in because I was like, man, would I really have done that?

But, but dude, I did so much stupid shit. It's like amazing that they think things that you think of as like totally normal, like social, whatever, just like non-obvious if you haven't actually been in the world. I mean, at that point, that one's pretty bad.

But, you know, I was like, it's kind of shocking because I, I, I, it's like hard for me to even put myself in the headspace where I would say something like that. That's a job interview. But I guess I was just very, um, I'm usually quite open and honest. So there you go. There you go. Um, there's, there's so many different things I want to ask you. The, I, I sort of, I want, I just want to cover a little bit just around the therapies, and then, and then I have some I have a bunch of bigger picture questions for you, but, but okay, so if everything goes well and stays on this timeline, it's kind of like 2026 when this first therapy might be available. And, and so that will be a pill that the dogs will take. And then the next one I think is an injection.

No, it's, um, it's another daily pill. It's another pill. For big dog short lifespan. Okay. Which is what you're thinking about in terms of the injectable.

Okay. And that's in a clinical trial already or—

We have done a lot of clinical work with it, but we haven't started the big, Lifespan Extension Study yet.

And then I remember this when I was first doing my story, and I think it still holds true. You guys do not say what the underlying compound is. This has always been, been sort of secret. I remember when we were talking mystery before, you know, there's things like you mentioned, rapamycin, metformin. There's a lot of people on that. So there have been these compounds that we have seen for decades that potentially could increase lifespan and have done so in mice and different things. And, and so, um, I think when we talked before, it was safe to say it's like roughly in that ballpark of things that have been tried.

I mean, I will say explicitly, it's not rapamycin or metformin or anything like directly adjacent to it, but yes, it is this idea of You know, I think we have a very different approach to longevity than some of the companies in the space in that we're not trying to reinvent the wheel, at least not yet. We're trying to clinically develop and bring to market very extremely well-validated aging biology and build a really good drug product around well-validated longevity biology. I don't think that's going to maximize efficacy or get us to immortality or anything like that. Not that's what we're trying to do. But it maximizes the probability of success. And really my thesis going in is that we can do no harm, there'd be no safety risk, and we have to have a hopeful benefit of lifespan extension, and we need to maximize the probability of success of seeing that benefit. So that means like really dying on one hill, which for us, that one hill was a label claim for lifespan extension itself, and obviously meeting the efficacy bar for that label claim, and then everything else is like boring as hell.

Okay. And so, so it's roughly like some off-label use of a compound.

Yeah. Like, think, like, it's, again, it's not rapamycin or metformin, but think similar to that. Okay. Like, you know, like metabolic fitness improvement. Okay. It's like a core driver of pathological aging in basically every species.

So then my, my one big question, I mean, like, this is amazing. Like, it makes all the sense in the world to me. People love their dogs. I'm sure they're going to flock to this. Great business, great science. This all makes sense. If you did want to push this to humans at some point, I mean, yeah, I, this is the one thing I always wondered is if you don't have some protection around this compound when you make that first switch to humans, it's like, what does that business look like? And then if you weren't doing that, but you wanted to develop your own compound, like, doesn't the second stage of this business, isn't it quite different from this stage.

It is, it is. So there's— I'd say there's 3 unlocks that dog longevity, uh, allows for human longevity. And one of them is just compound, like, direct compound data. But I would actually say that's the third in terms of importance. Uh, the first 2 is— one is just the biological data, so the actual quantitative understanding of the causative drivers of healthy versus unhealthy aging. We have so much correlation data in humans, just like ungodly amounts of correlation data in humans. We have a lot of causative data in mice and worms, but we don't have a lot of causative data in the middle, right? And so by running these giant FDA-enabling clinical trials, we can't touch any of that, you know, biobank today. But once that study is done, we'll be able to actually hopefully tease through it, right? Like, if you want our AI story, like, that's our AI story, right? Because that's going to be stupid amount of data, like 70+ million data points on the clinical and the biological side.

From these dogs' biomarkers. Mm-hmm.

Blood, saliva. Yeah. Everything like that. Clinical assessments, diagnoses, all of that, pictures. And so that's one. And I think that's gonna be absolutely crucial to understand what are, obviously validating of existing targets. Or devalidating of existing targets, but also identification of new targets. But actually even more important than that potentially is actually just going to be the revenue and the team, right? Um, like to have a team that is wholly focused and thinks every day about translational longevity biology and has the money to pursue that and doesn't have to go and tell some story to an investor of how they're going to get into a Phase 1 and then Pfizer is going to buy their drug at Phase 2, but instead it's just like, yeah, we have a billion dollars and we're, we're going to use that billion dollars to try to develop a longevity drug. And that's going to be the decision of me and a team and the, like, directors of the company. But we won't be beholden to the, the desires of Big Pharma, which I— to be clear, I think aging is going to be extremely sexy and extreme interest to Big Pharma. But I think somebody has to get there first and show— have the GLP-1 moment Yeah, you know, show that this is the next big category and then they're all going to jump in and we're going to have the opportunity to do that because we'll have the desire and the capital to do so. That is—

that's super interesting because I think if people are not in this field, maybe they don't know how much most startups come out and their whole goal is to find one molecule that the big pharma people will acquire. And so you raise enough money to develop that molecule, get through a clinical trial far enough that you're showing results. But it's, it is this sad sort of process. You're not really building a company that's meant to be like the next Genentech. You're just, you're just kind of like you're making some product for a bigger pharma company and just, just kind of being more focused and saving them the time and effort on that. So in, in this, if you have this blockbuster dog therapies, then that gives you this freedom to make these choices as you— Exactly. Moving forward. Exactly. Okay. That is exactly. That's interesting.

Yeah, it's interesting. I mean, if you think about it from a human, like, biotech side, like the human biotech drugs, they just fail at such a high rate. Like it's 90% plus all-in failure rate of, you know, initiated drugs to approval. Each stage will have somewhere between like a 30 to 50 or more percent probability of failure. If you're a, you know, a fiduciary, are you going to roll the dice on another trial or are you going to take the half a billion to a billion dollar offer in front of you? Yeah. You're probably going to take the offer in front of you.

Yeah, no, I mean, like, it makes sense why this happens. It's just, it's just not— it's sad— terribly romantic.

I know, you know, in some ways bio is like one of the most— like, trad bio is one of the most transactional. Yeah, fields, because everyone's so jaded because things fail at such a high rate.

Okay, since day one, the Core Memory Podcast has been supported by the fine people at E1 Ventures. They are a young and ambitious VC firm in Silicon Valley investing in young and ambitious companies and people. Thank you so much to E1 Ventures for all your support. Okay. You mentioned— I saw you doing an interview and you had a couple of things that I wanted to talk about. I mean, this GLP-1 moment, this other interview, you said if the big pharma companies did get into longevity and aging, you said if they had an aging division, that would be the sickest thing ever. And, and I, you know, I was curious like how you— the GLP-1 revolution or whatever sort of happened after you and I talked for the first time. And when you and I talked for the first time, I mean, there really was beyond people experimenting with like metformin and rapamycin. I mean, you know, and that was kind of like a Silicon Valley sort of health nut kind of thing. Definitely not super mainstream. You know, there was nothing Nothing like GLP-1, which you can argue is, is a longevity. Yeah. Drug of sorts, at least for overweight people.

Yeah. Potentially for more than that.

Is it's treating these major causes of illness. And so, yeah, it was so, you know, and so clearly the pharma companies have all seen this. It's been this massive blockbuster. And so when you said if they had an aging division, it'd be the sickest thing ever. I was just kind of like surprised. Does that— that means that Big Pharma has not like turned more in this direction the last few years? And if so, why not? Because it just seems like the GLP-1 stuff would have got them maybe so excited and thinking, you know, in this— that way.

Yeah, I think it's the beginnings of it, right? Because what are the drugs that are most financially successful? In, in humans, right? It's, you know, statins, which are a daily pill to reduce risk of certain forms of cardiovascular disease. I mean, literally a trillion dollars, the drug class did. And then there's GLP-1s, which are, you know, on track by some estimates to beat statins in terms of their revenue. And of course, it's targeting, you know, multitude of things, but obesity being kind of like the really big thing. And it seems to have a bunch of downstream consequences, which actually, by the way, makes total sense that if you improve metabolic fitness of an individual, that it not only benefits their weight and their direct metabolic disease, but also tons of other downstream things because metabolic fitness is systemic and it impacts every organ system and, and plays a role in the health of every organ system. So it's really cool to see that, you know, foundational aging biology and aging thesis making it to the masses. It actually makes my job of, you know, educating much, much easier because now people get it. Um, and I, I know that there's— or if there's rumors that's like some groups are working on it, some have like kind of like kind of stated they're working on it or had like in theory aging groups, although how much of aging are they actually doing, like TBD. But realistically, it's just like, um, it's very mimetic in very— in different ways, right? Like the minute that first drug came on market and became a total, you know, craziness. Now, like, every biotech company has an obesity story. It's like, it's like, it's so similar to how AI works in the Valley, right? You know, there's a wave and then there's like the, the drivers of it, and then there's like all the straggler-ons. Yeah. And, you know, a lot of people become very wealthy and very successful by that strategy, by all means, um, but a lot of people don't, um, you know, similar to how there was the waves of crypto and whatever before it. And so I really think that somebody's gonna have to have the balls to be first and show that this is a drug class that A, can get through the FDA, which it just doesn't fit into how people think about what a drug can or can't be today. And one of the cool things is the canine FDA or the veterinary FDA is regulated by the same federal statutes as the human FDA. So in theory, our precedent should hold. I mean, we'll find out, right? We haven't gone to human FDA yet, but at least at that highest regulatory bar, it should. But I don't think— I don't think it's going to seem real until it's real.

Okay. And then I'm going to try to ask this in a semi-eloquent way. I've got a lot going on in my head, so I'll try to frame it right. But, you know, when I— okay, if I'm talking to my friends and people I know in longevity world out here in Boston or the UK, you know, I'm talking to people about transcription factors, compounds like metformin, rapamycin, kind of what you guys are doing, testing these, these molecules that we've, we've known can do interesting things for a while on the further out there end, but the thing that reasonably smart people are buying into. It's like whole organ replacement, you know. And, and, and so these are like the three giant buckets that I run into. The latter two, the transcription factors, the whole organ replacement, which for people who aren't into this stuff is like this idea of you're, you're maybe growing organs and, and swapping out your unhealthy ones. It's like changing the tire on a car.

You don't try to like regenerate the rubber. Yeah. And you change the tire.

And so when I'm in, in in those two buckets outside of like more traditional drugs. It's all startups and there is big money in the sense that like someone like Jeff Bezos or, or Yuri Milner or Sam Altman is giving hundreds of millions of dollars to one of these startups. But it's not— I don't think I've ever run across like a pharma company talking about stuff like this. So when you're saying maybe there's rumors that they're doing stuff, I mean, like what direction do you even think they would be going in. They're just going to look for some GLP-1-like compound.

Yeah, I— so I mean, I think the whole organ replacement will like definitely not be a pharma thing for a long time. That one is interesting.

Livers by Merck. Yeah. Yeah.

Can I get like the Merck logo on my liver? That'd be pretty sick, honestly. Although then it'd be bad if your liver like ended up on the black market or something. They'd be like, oh, there's that Merck liver. Um, I think it's gonna be the— I'm obviously biased, but I think the big pharma are going to get into more the vision of what, you know, I and others have, which is a cheap daily pill that reduces risk broadly of age-related diseases.

Okay, so they'd be hunting for an interesting molecule.

Yeah, because One heuristic, which is not always true, but just a heuristic, is that, you know, with the more complexity of a product comes increased safety risk, or at least safety unknowns, even if it's not necessarily risk. And again, this is like, you know, drastically simplifying something down. But, you know, I think for something new like this idea of a drug to be given to a healthy person to delay their future risk and severity of aging, You know, it's kind of like a vaccine in many ways in that like the safety tolerance or the tolerance for adverse events or the risk of adverse events is going to be almost zero. And so you're really going to want to pick things that are well characterized, that are well understood. And then once there's that foundation, then you can go higher and higher and higher and be like, okay, well this is a trade-off for efficacy. And yeah, there might be some like long-term safety risk, but you're really reducing the risk of, or eliminating the risk of neurodegeneration. Right, and maybe you only give that to patients that have like certain genetic backgrounds that increase their risk of getting Alzheimer's or Parkinson's, right? Like there's lots of different pathways this could go, but really what will be a foundational massive blockbuster drug is gonna be a statin for reducing risk of multiple age-related diseases instead of just cholesterol-associated certain cardiovascular diseases.

Okay, and since we, when we, 'cause I haven't had a chance to ask you this question even though I've run into you since I did that original story, but given these changes, Like, I was not reporting on transcription factors and partial cell reprogramming back when we first— Yeah. Whole organ replacement was a little more sci-fi and far off than it seemed. I mean, it's still far off, but there are people I know who are actually trying to do some of these things. Is there anything out of all the non-LoYAL, you know, approaches, some of this more sci-fi futures since you used to be or, you know, have invested in all these areas? Yeah. Is there anything that is particularly intriguing to you that people are trying near the fringe?

I think there's a lot of really cool things going on. I think it just depends on what are the variables that you're optimizing for. So like I started with gene therapy for Loyal, actually Loyal's first program was a gene therapy program. We immediately killed that. I think gene therapy is super sick and really interesting. Gordian, for example, is working on multimodal gene therapies. They're hitting multiple genes at the same time, which makes total sense because, you know, genetic diseases are, you know, or sorry, age-related diseases are extremely complex. Upregulating or downregulating one thing is not going to be as efficacious for complex disease as it is for a very simple genetic disease. But there's also like cogs risk and safety risk and it's you know, there's not a mass market gene therapy. So there's all those other things, right? So there's reasons I wouldn't do it and there's reasons we're not doing it at Loyal, but that's also like, again, we're optimizing for probability of success, regulatory pathway, and likelihood of safety. You know, we're not optimizing for maximal efficacy or maximal reversal or whatever, but I think that world is cool. Um, I don't know like the depths of the science, but a lot of the organ replacement stuff is interesting just because you're invariably going to have a shelf life on an organ at a certain point, or just like have a disease that might require a replacement. And of course the whole, you know, transplant system is very difficult and you lose a lot of people on it. Um, so that's obviously like massively, you know, valuable from a humanity perspective. And it kind of like— again, I'm not an expert in this space, but it like plausibly makes— like that actually feels more tractable to me versus some of the other things.

When I talk to people in that camp, I mean, I guess they've bought into the idea, but, but, you know, they, they often will argue to me that everything else is kind of pointless because you're never going to find all the root causes behind these things. There's too many things to have to manipulate.

I wouldn't go that far because you have a whole, whole portions of your body that you're never— like, your vasculature is extremely relevant. To aging. You're not gonna be able to replace, like, entire vascular system, right? But there are a lot of diseases or, like, things that can go wrong in certain organs that can become rate limiting to your lifespan. And so it's always gonna be a combinatorial, right? You want to broadly slow the rate of aging of the organism as a whole, but also, like, maybe they have some genetic predisposition to liver cirrhosis or whatever. Right? Then it doesn't matter how much of an aging drug they take or how efficacious of an aging drug, because the liver cirrhosis is still going to get them first. What are you going to do in that case? Well, maybe a replacement. And then that person can benefit from the lifespan extension that they otherwise would not have had. I'm really interested in cognitive decline personally, as a, you know, as a huge rate limiter in healthspan and lifespan, not to mention quality of life driver in the later years.

Yeah, I think people would take that one, even if your body's a little gimpy. Yeah. You know? Yeah. Can absolutely. You can get pretty far.

Can get pretty far if your, if your brain functions. And right now it really feels like a luck of the draw. Yeah. Of who does or doesn't have cognitive function into the, into aging. Yeah. Um, although there's obviously like correlation or reason to believe that it is associated with, you know, various longevity markers too. Um, and it's also something that's never going to be replaceable. Yeah. Or I don't know, depending on Neuralink does, but You know, much rather prevent decline versus, uh, banking on, uh, uh, uploading of the complexity of your brain and not just, you know, then you have to ship a thesis or whatever. Yeah, yep, yep, yep, absolutely.

In the span that you've been doing this, we've gone through different political administrations, um, uh, if you didn't know.

And, and nah, never heard of it.

Like when you first started, I mean, one thing we talked about, which we mentioned a bit, is just that the FDA is not really— it wasn't really built to consider aging an illness. And this is a problem because they— you sort of have to have a medicine that's designed to treat an illness in order for the FDA to, to get into it. And if you don't see aging as like an illness, you know, it just, it falls into this weird regulatory, um, abyss. Have things changed? All of this technology seems so much more mainstream in some ways than it used to be. Um, is the government more open to these things? And I have no idea if this is administration dependent or not.

It's not really administration dependent. Like, a lot of these regs that, um, impede or don't impede a drug being approved for lifespan extension are actually federal regs, which are not policy-specific. It's more the funding regulations of the actual agency itself. That said, the aging field always has this as a battle cry, like, "Oh, the FDA doesn't agree that aging is a disease." We just were like, Okay, like, who gives a shit? Like, we don't need to die on that hill to have a drug approved for healthy lifespan extension. And we figure out a way to, you know, develop an efficacy package and a label claim language provisionally that, you know, achieves what we wanted to achieve without, you know, wading into a war that we didn't need to have. Yeah. And so I think there's a lot of dogmatism in the field, um, in terms of these things that— I mean, kind of bluntly, I've always felt like they're a little bit of excuses of, you know, oh, like, we would have this if it wasn't for the FDA. And it's like, figure out a way to do it. Yeah, you know, like, it's not like completely physically impossible, clearly, because we figured it out.

Yeah, and your plan's genius if it works, because not only did you tackle that problem, but it's like if people see their dogs being healthier— yeah, exactly— they're running around, is there—

oh yeah, it's a social pressure. Why can't I have that? It's exactly— it's a societal pressure, right, of the normalization of this idea. Why can I get a longevity drug for my dog and not my grandma? Yeah, right. And I think that is such a better way to quote unquote fight this battle than just like screaming and crying about the agency. And I've also had a great time with them. Like, I think they're— you just have to understand what their roles and responsibilities are. And one of the first ones, protecting the safety of the lives which they are responsible in the agency, in our case, of veterinary lives, of canine lives. And we designed our entire strategy around that to tell a really clean and data-backed story of why this won't do harm and maybe it'll have a benefit and why that benefit will actually reduce a harm in the future.

Yeah, I feel like you made a face when I said this has got more mainstream. Maybe, oh, maybe I'm too—

I'm too mid-market.

If you make a documentary about Brian Johnson, you might, you might not be like Joe Public.

Oh God, yeah, no, um, the field has definitely gotten more mainstream, um, which is good. I feel that way.

And I think people—

I mean, there's literally a documentary on Netflix now.

Yeah, and the, uh, of Brian.

Of Brian. Is it on Netflix?

Yeah, yeah, yeah, yeah, yeah. No, no, no, sorry. That was the one I worked on. Yeah. I didn't know if you were talking about some broader look at the—

No, no, not yet.

Okay, so the, and I do feel like the GLP-1 stuff has like opened people's minds up in a different way.

I think so. I think so too. Yeah, I mean, it's also consumer-driven pharma. Which is kind of our, you know, our product is obviously going to be a veterinary prescription product, but also very consumer-driven. Yeah. Similar to how we enroll these clinical trials.

Okay. Where does China fit into all this? Because, you know, are they looking at what you are doing in particular? Are they— I know that they can run clinical trials more quickly than we can. Yeah, is this— are they— do they sprint ahead of us in some of this longevity stuff?

Oh, you mean like pure longevity or like loyal specific?

Um, I mean, I was curious if you've caught the attention of somebody over there that you'd know about. And then, and then more broadly, um, I was just— I was talking to somebody today and they were telling me it's like cheaper to run a human trial than it is in China than an animal trial. Here. And then that just got me thinking, you know, that, that so you could just— you can do things that you can't— you can't.

Yeah, I mean, it doesn't mean you can use the data afterwards, but yeah. Um, I mean, so I, I haven't heard a peep from China on our stuff. Uh, I don't know how much of a dog culture there is there. Like, this kind of dog is our child is a very American thing. It's, you know, also happening more in like Singapore and Korea and Japan, anywhere that has like a declining birth rate, actually is a very strong association. Oh, that's interesting. With like dog, uh, dog love. Or like socioeconomic disparities too, because sometimes people can't afford kids but they can afford a dog. Um, man, all the like, um, American Dynasties people are gonna come after me now because they're gonna be like, Celine is promoting people not propagating the genetics of Americans. Man, I just, I just got myself canceled. Um, but no, I mean, we're mostly— I mean, we're only looking at the US right now for, for a multitude of reasons, predominantly bandwidth constraint. Yeah. Um, yeah, I mean, I know that clinical trials in non-US places have always been a thing, right? Like, I remember when I was looking at human stuff, there was a lot of talk about doing stuff in Australia or France, and I I think some sketchy people do things in like, you know, jurisdictions where there's basically no protections or regulations.

I went with Brian to Honduras, got some gene therapy.

You know, that's a choice. It's a choice that one— a human being can make. Um, I don't know if it's a choice I would make, but I think in the end, something I felt that was very important was doing everything at the highest possible bar and the kind of self-imposing maximal rigor because nobody believes in longevity, right? It sounds crazy. It sounds like billionaires trying to live forever, Fountain of Youth, like all this crap, when like my whole thing is like an aging drug is just a preventative medicine, right? It's just that it's a statin, right? It's nothing crazier than that. It's the most boring shit ever, honestly. But I think because the field has had these like overpromising, underdelivering for such a long time, and honestly like shoddy science, people have this association. And so for me, it was really important to, you know, everything we need to do from a regulatory, from a scientific, from a clinical perspective, just at the highest possible bar so nobody can question anything. And they still question it anyhow, honestly, but it's at least quite a bit more impervious than if we, you know, went into some crazy—

you brought up one point. Every time I write a longevity story, everyone says, oh, this is just a bunch of rich dudes who want to live forever. And, and you and Laura obviously stand out as, you know, not falling into that stereotype. Yeah, I mean, is this, is this, is this predominantly a field for rich dudes that want to live forever?

I think the, the, there's a correlation with the, the loudness. Um, I think Laura and I have both taken a very different approach than maybe the standard longevity dude bro. Right? We're very careful about what we claim. We're very careful about how we approach it. We're very careful about, again, not overpromising and underdelivering as much as within, you know, drugs are hard. So you kind of inevitably always end up doing that. But, and I think it's difficult because I know people will get annoyed when I talk about it. They're like, well, just tell me you're going to extend my dog's lifespan 10 years. I'm like, yeah, well, I could say that, but it's not true. Right? Um, and so it's less sexy, it's less like, you know, headliner type story. Um, but again, I think for the path we're going, it's, it's, it's the better way to do it.

Yeah. You— I'm gonna play a game with you called You Liked a Tweet, You Wrote a Tweet. Oh no.

Yes, you went through my old tweets. I did. Oh, this is horrifying.

No, it's not that bad. This is You Wrote a Tweet. About some of what we were talking about. You said Silicon Valley and many of the major VC firms have gotten so much more bro-y in the last couple of years. Is that, is that true? I saw a lot of bro, bro criticism tweets. You, you're— oh my God, not a fan of the technology brothers?

Uh, I actually love them. Like, I'm like— a lot of my good friends are like the Gundobros, like, like Chris Powers, my best friend, and all that shit. And we like started our companies together. Um, but it is a vibe, and I— it's like, I don't know, I— it's both funny and also I'm just like, I could never get away with that in a million years. Which part? Just the, uh, that, that over-voicest, over-claiming, definitive, we're saving America, saving the world, fuck Yeah, right. Like, I could never do that shit. You don't think so? No, absolutely not.

Who's the closest woman? Lucy Cao. That's right. Oh yeah, I don't know a ton about Lucy, but she's in AI, right?

She was the co-founder of Scale AI. She's a loyal investor, um, and now is doing Passes. Um, and she's like very like famous for like being, uh, you know, one of the youngest female billionaires.

That part I know, but what is she— what is she kind of like champion?

You should follow her on Instagram next. Yeah, dude, she's way more interesting than me on Insta. Yeah, she like is just, um, very like— she's like— she's been described as like the female Keith Raboy. Okay. She's like very loud and declarative, but people honestly give her a lot more crap for it than they do any of the dude bros who do it. She gets punched back. Oh yeah, yeah. Oh yeah, she gets like roasted. You gotta look this up. Well, because—

and there is a thing, because I like the Gundo guys too, although I, you know, I feel like I like their mullets. But it goes— it has to be off-putting to women who might— I mean, it would— I would think so. It would just—

it's just a very specific pattern match. Yeah, that is like pattern matched with competency in like deep tech spaces that like you just— like, I'm all about adapting a space. Like, pick your hills, die on, you know, don't die on hills that don't matter, right? Pick your battles, blah blah blah. But like sometimes there are pattern matches that if you don't hit them or it goes against you, but you also cannot physically hit them because that would also go against you, right? Like I just like, I'm always gonna have this different style. Laura's always gonna have a different style, and that's fine. But like it, it just like, I think we've had like this overcorrection from woke, which I agree was also annoying to now we've gone all the other way to like Americana, da da da da crap. And it's like, can we just be fucking normal? Yeah.

So too—

and just like talk about our— like talk about our tech and our science. Like, come on, guys. Um, my favorite Silicon Valley bros are like the autist tech bros. Okay, those— we got some— we got some in common, right? I can— I can do that pattern match.

All right, you did— you do have a website where you list your vanity goals. Oh no. Yeah, I've done it. I've done it. Shit. I need to go through all that. Number 2, I think quite along the lines of what we were talking about, your number 2 vanity goal. Okay, let's do your number 1 first, but I'm gonna ask you about number 2.

I don't even remember what's on here, so this is gonna be live reaction.

Number 1 is that you would like to be the youngest woman to IPO a company. I missed that. You missed that 'cause you were turning 27 that year.

And I think the youngest was Whitney Wolfe Herd at 30. At 30. Okay. She just turned 31. Okay, okay. I know I've gotten old.

Do you have any idea what your number 2 vanity goal was?

I know one of them.

I can't tell if this is going to be shocking or if you're just going to stand by it.

One of them was to be on the COVID of a, like, a cool magazine.

It was. And you said, you said that was number 7. You said be on the COVID of a magazine, but a cool one, not a business one. And I saw you were just on the COVID of Forbes, although they did something quite strange looking to you. Photo.

I know, it was a bit weird. It was a very zoomed in— well, I tried to convince them to do a photo of me and Della because I had a sneaking suspicion this is what they were going to use the photo for. And I was like, okay guys, wait, stop, dog. Yeah, they didn't let me.

So what's a cool— what's a cool one?

Cool is like Vogue. Okay, right. It's like checking. It's not checking. It's not, you know.

All right, number 2. Oh no, invited to Elon's house to talk aging.

I did not remember this. That has not happened yet.

Is that, is that still a vanity goal?

Where are you? I still admire him a lot. I mean, obviously it's a lot more controversial now, and you know, there's things I admire less, but holy shit, like, to have that degree of impact on the world and create all these futures that like probably wouldn't exist if he hadn't done them Oh my God, like hands down epic. I'm a stan.

He's weird though, he's kind of like have more babies but he's kind of anti-aging stuff.

Yeah, he is, I guess.

Um, yeah, he like wants you to live but just enough.

Yeah, maybe he's gotten old enough yet, back hasn't started hurting enough yet. Invited to the Met Gala, that one has not happened yet.

It's not happened. So is that still, still a goal?

Um, I don't know. I don't know. Probably. I think it'd be cool. I think I would now find it probably stressful because like the outfits are such a thing, and I find it stressful even to get dressed for something like this. I'm like, oh fuck, I can't wear my Gymshark. Like, what am I gonna do? This is gonna live forever.

All right, we did— you wrote a tweet. Now this is— you like the tweet. Wait, you can see what tweets I like?

I thought they blocked that.

I cheated on this a little bit. You reposted it, which I'm gonna take as a tacit—

oh God, I got nervous there.

San Francisco men are afraid of mRNA but would happily inject themselves with something called checks notes Chinese peptides. Exploring.

Oh God. Uh, yeah, I mean, I'm sure you've seen the whole peptides.

I have friends making their own GLP-1. Is that— that's what you're talking about, right?

There's that. There's like tons of random peptides that are derived or synthetic emulates of whatever peptide is in your body that like goes down with aging that you need to crank up. Um, and it is funny because, you know, one of the things about building a drug is you become very cognizant of all the ways a drug can fuck you up, but also all the way manufacturing can go wrong and that can fuck you up. And so when I think about people taking random-ass Chinese peptides, I'm just like What's the quality control on that? Have they tested it for infectious agents? Was it temperature controlled when it was shipped across the ocean? Like, I just think about all the things that could go wrong. I would never in a million fucking years inject myself with that shit. Now, GMP stuff is actually manufactured by somebody legit. Like, yeah, I would maybe do something like that, but like, yeah, Chinese peptides, way scarier than, uh, the COVID vaccine.

I have people asking me though, you think this is like a big thing? Like, the dudes, the dudes are doing this.

I mean, it was like I was at some tech thingy conference and there was a lot of, a lot of questions. Like there's always like the topic du jour that I end up getting asked a ton of questions about. And like peptides is definitely it right now. Compounded GLP-1s were a thing for a while. It's a little bit chiller now. Everybody kind of has an opinion on it now.

Do people say GLP-1? Am I—

I'm like out of the— I think it's— no, I think it's It's so funny. Somebody else asked me this too, and I actually texted one of our scientists who used to work at Pfizer, and he said that the way scientists do it is GLP-1. Okay. But that's just like so many syllables. Like, GLP-1 is like, GLP-1. Yeah.

I saw Trump today. He said he calls it the fat pill. Subtle, subtle. He said it doesn't work. All his friends—

Well, he shouldn't. If he's taking it as a pill, that's probably why it doesn't work.

No, no, no. Well, he said his friends, it doesn't work on them.

Um, well, you know, when you take peptides by the mouth, generally speaking, they get eaten up by your stomach acid. That is how, in fact, your stomach acid is designed to break down peptides and proteins.

You, you had to, you know, pharmacodynamics.

What's that? Never heard of her.

You've got another section on your website. Oh no, this isn't even bad, and I— this is the last thing I'm going to torture you with. Um, but you—

I've been telling my team we need to clean up all this shit. You We're gonna go through my Instagram next.

No, because I only— I just got— I just got permission, so I haven't had time to—

you know, I have literally thousands and thousands and thousands of Instagram follow requests, and it's all from dudes.

Every single time we have an article, I do my research.

Look, Ashley, you made it through. You made it through the filter. You have been accepted into the fold. You will now get to see all my dog photos. And horse photos and just get ready. I'm here. I love coffee shop photos. My life is actually very boring. I like the animals.

You said I— and I shamefully did not, because you write update on this. And so I forget the exact wording of the thing that this is updating. But you wrote, I've become pretty bearish on academic scientific founders. I'm more interested now in the idea of non-scientific founders building biocompanies. And I I brought this up because this is a theme I hear from people I tend to gravitate towards, which is that the traditional kind of bio thing is too conservative. But there's like this massive dilemma, you know, because you, at least when you're in my shoes as a reporter type, which is you, you want, you, it's not like I want to see the PhD or the MD or the experience, like you kind of do a little bit, but hopefully you know well enough that I'm quite open-minded. You're an independent thinker. Yes. But, you know, it is that field where, like, when I do have other people coming to me who are like 24 and they're like, I'm growing organs in, uh, you know, my, my lab, and then I'm kind of like, well, are you? I don't know. I mean, like, yeah, I remember I went with, uh, when I went with Brian to Honduras and the two dudes from Mini Circle who made the gene therapy, you know, they I think one had kind of done either an undergrad or like maybe a master's from Duke. And anyway, it was not like your traditional academic pedigree. When you talk to them, they're clearly super bright guys and they could definitely walk through the science. But yeah, it gets very hard to tell like who's real, who's not. Yeah. So like, I kind of get this desire that you have and why it would make sense. And then when I go to— I don't mean to wholly disparage Boston and Cambridge because there's so many smart people there. But when I go there, it's just like, it feels so traditional and everybody's kind of doing the same thing.

Yeah.

And, and like, you can, you don't have to be like super in tune with the world to just know that it's, it feels very conservative. So I get, I get where this is coming from. But, um, isn't this like, this seems like an impossible problem to solve.

Oh my God. I could talk about this for hours because it's also a problem when you're thinking about building a biotech company. Of like anything I think about in building an executive team. How much of it is like first principles generalists who, you know, you need to have enough bio context to be dangerous, but you certainly don't need to be a, you know, multi-decade biotech executive. And then how much of it is just like inject as much experience as possible. And, you know, with bio founding, it's, you know, it's hard. Like, I think knowing what I know today, I never would have started Loyal. Because I could have told myself 100 reasons why this company didn't work. And I just had no idea what I didn't know. I was super naive and super optimistic, and I was wrong about a lot of shit. But like, being wrong actually— I mean, it's— it, it, it, it in some ways was like better, right? Um, because I was like, ah, let's just go for it, let's see what happens. Yeah, gene therapy makes total sense. It didn't make any sense, right? But like, the broad overtures were correct. And, you know, actually all the biotech investors passed on our seed round because they're like, gene therapy for, uh, dog longevity doesn't make sense. And like, also, what the fuck, dog drugs? Why would you do that? And then the tech guys invested because they didn't understand that the gene therapy idea didn't make sense, but they thought I was cool and they thought the thesis made sense. And they, like, at least so far have, like, at least plausibly made a good investment, right? And so it's, it's really difficult because, like, like, the reality is that there's certain portions of building a drug where you absolutely need expertise in the room. And, you know, you just don't know what you don't know. And you can first principles till the end of the earth, but then you just, you just can't always get there, right? Um, and there's certain aspects where the, the super trad Boston Cambridge, you know, transactional whatever, are just never going to do something like crazy or something that like violates the priors that they've had previously. And so I think that there needs to be a middle ground. This is like the thing I'm always lobbying for is we need kind of like, you know, there was a whole like swath of like the Silicon Valley firms getting into bio, but then they're like, I think they didn't know how to handle this problem. And then now they're kind of like kind of doing East Coast biotech, but just like they happen to be in Silicon Valley and like they did some weird things and the weird things didn't work out and then they kind of got like gun-shy. Now they don't do weird shit and they just do the deals that like like, you know, Venrock or whatever follows on in, and/or Arch or whatever. And that's fine. Um, but I think we kind of need the middle ground of like technically competent enough to be like, okay, here's where you need an adult in a room, here's what makes sense, here's where this is completely fucking idiotic. And, you know, first principle stinky and open-minded enough to not just be like, well, this is how I've done it for the last 50 years and You know, you're not proposing to do something like how I've done it, and I— you don't have white hair and you don't have enough wrinkles, so like you can't be CEO. And also give me my 5x lick prep, right? Um, and I— somebody needs to build this. Um, there's some like— there's some contenders for who are like trying to build this, but yeah, it needs to happen.

Would you have to build it in a different location? Like we've tried San Diego, Silicon Valley, Miami.

Bring back Miami.

No, I think Silicon Valley is the best place in the world.

Miami, I know, thank God. I actually kind of liked Miami. I like the cortados, very good. But I always like, I was like, man, I'm neither hot nor rich enough to be in Miami. Really stresses me out every time I'm there. Interesting doesn't get you very far in Miami. Um, having really big boobs does. So, but, um, I think Silicon Valley is actually a really good spot for it. It's just, um Yeah, it's just, I think bio and deep tech is like still pretty incipient, so we probably need to have this generation of founders, some portion of them, and succeed or be successful enough, and then I'll go and start funds, and then they can bring along the next generation of founders. And maybe like AI and whatnot, it does make information discovery much easier. Yeah, right. So maybe people can get to a degree of competency in an amount of time that doesn't require 6 years like a PhD. I don't know, we'll see what happens. Um, I don't like VC, so I'm not going to do that.

But you don't like VCs?

I don't like VC for myself. I see. Because it's very, um, I like operating. Okay. But maybe I'll like, if Loa is successful, I'll like be the LP for whoever does this, or LP for whoever does this.

Yeah, I mean, it's, uh, it's funny because people keep telling me biotech is really, um, you know, low, or is, is like VCs have turned. Yeah, I tried biotechs on it.

Like nothing is happening right now.

That's, I guess my worldview is so tilted because I have people pitching me all the time on these sorts of things because I just, I just look at like Retro and New Limit and all these other companies I'm interested in raising just enormous amounts of money. But then people keep telling me that bio, this is a problem. People aren't funding interesting Big Ideas.

Yeah, I mean, those are a little bit different too, right? Because they're, they're really backed by like the— like they all have like a sponsoring billionaire. Yeah, right. Like New Limit has Brian. Yeah. Retro has Sam. Yeah. And it's, you know, that's not a model that a lot of these companies have. Like we, we have obviously, you know, individuals and high net worth and family offices, but we don't have a, we don't have a quote unquote sponsoring billionaire. Yeah, right. We raise from funds. And so, um, there's lots of different ways to do these things. But if, if the traditional infrastructure, you know, isn't going to fund stuff like this, then the only people or only companies that will get funded are those that are connected to the individuals who can make individual decisions. And that is just— it's another slice of Swiss cheese that, like, a good idea has to get through. To become viable. So it's hard. Yeah, it's hard. But I'm glad those people are investing in that stuff because otherwise, you know, these companies might not exist and it's better they exist and then we can build the infrastructure later.

I'm going to let you go in a second and then I'm going to ask one last question, which now I'm realizing I don't know how touchy this question is. Oh no. Well, along the lines of what we're talking about, you know, Are you gonna make me cry, Ashley?

No, no, definitely not.

Um, I mean, this would be in 3D, 3D crying. I've done it to people, but I'm not going to do it to you, definitely not with this question. Um, you'll laugh when you hear this one now. Uh, no, I mean, of all the big tech companies that have made a ton of money who really took a massive swing at this, it was, it was Google with, with Calico and what is it, Verily. Barely. Yeah, yeah, you know, sort of going after— I mean, they were always kind of a little clandestine about exactly what they were working on, but it was like, we're gonna cure death, kind of somewhere in that, that ballpark. And then, you know, I think they're— if I remember, one of them shut down, or they're both like going along, but you don't hear a lot. Um, they've always been kind of secretive. You had Arthur Levinson at Calico, who's, you know, he, he— what, he started Genentech and and is like a god in this field. And so, you know, is— does that— maybe it's too soon to sort of write them off, but it feels like that has also kind of cast something of a pall, which was, oh, if this company with like infinite resources and, and Larry and Sergey behind these projects can't do it either— I don't know, does that make sense?

Yeah, you know, it's funny, I always— it's always interesting to me that you'll have these like companies or individuals that were started by like young you know, disruptors. Um, and then when they become successful, instead of investing or facilitating other young disruptors, they sometimes will go to like the canon, right? And they're like, oh well, in this place it needs to be the canon. And I think you're just seeing the difference of like— think about like a— maybe a good example is like a SpaceX, right? If you listen to, obviously, to your book or um, the Isaacson book about SpaceX. Like, we don't talk about it. Oh, I'm sorry, I'm sorry. There's only one biography on Elon, um, and you have to read it. Um, but if, if you, if you read it, right, like, you look at like the trials and tribulations that SpaceX went through, like, the only person who could have pulled that through is a founder, right, who is so emotionally and personally intergrained with the organization and the mission, and who— it's who they are. Like, otherwise any sane person would have stopped 100 times before, right? It's way too painful, especially if you're super wealthy like, like Elon was even at that time. Obviously not relative to how he is today, but like, yeah, way more money than vast majority of people. And so I think a lot of these initiatives and You know, you need to have someone who has an unreasonable view into the future, and that doesn't have to be correlated with experience. But like, I think I've seen that like experience goes two ways. It either is like, I don't give a fuck, like I've already done it, I'm just going to go for it and like go big or go home because whatever, I still got my mansion out back. And I love it when people go that way. A lot of our executives are that way, actually. Um, or it's, I can't taint my reputation. This can't be like the thing that, you know, this can't ruin who and what I did previously.

So I can't fail. You can't fail.

Yeah. And, you know, I think sometimes biotech talent on average falls more into that ladder, right? Um, and can't— again, has this like desire and this kind predisposition to be more conservative. Um, also you just get really jaded working in bio because you just see a thousand ways something can fail and then one way something can succeed. And it's just like, I have to remind myself constantly to stay super optimistic when like young idiot founders come to me pitching me their crazy idea. I have to be like, Celine, you were once a young idiot founder too. Listen to them. It's okay. I know everything is wrong, but it doesn't— like, what matters, right? It's like, but like, I was that person and I still struggle with it. It's like bio just it's really difficult to keep an open mind, um, because you just become so cognizant of how hard everything is. Yeah. And so I don't know, I think— I mean, this kind of goes back to what you were previously saying, but how you kind of need that naivety, but you can't be too naive or you're gonna fail. And I think this is something the bio field really, really, really, really struggles with. And my hope is that there'll be some, like, some company like SpaceX like the equivalent of what SpaceX did and, you know, normalize these like young, crazy founders and like spun out these people who then started like all these companies around this like aerospace industries, right? This next gen, like I hope that occurs for bio too.

Yeah. Yeah, that's funny. It reminds me when young people come to me asking for advice on writing a book and you're just like, you should not do this because you will spend a lot of time, you will sell no books and you'll make no money, you know? And yeah, that is like 99.5%, probably even higher chance of what is, is gonna happen, you know? So I just always tell them, I'm like, you have— the only reason you should do this is because you feel compelled to do this.

Oh my God, this is what I tell founders all the time.

You just cannot live unless you write this thing and you're happy just going through the exercise, you know? Like, if you're— if you and your parents are the only people who read this, it's like, you just have to have this out in the world. And yeah, you should expect nothing else from this.

No, as I tell founders all the time, it's like if you can't imagine the world without this and like you're obsessed with it, then maybe you should consider starting a company. Everything less, in my opinion, I don't know how you have the discipline or the desire. I mean, it's like, I mean, it really is like eating glass. Like there's good moments too, but it's also like eating glass. Like it is a— I'm pretty like stable. And even for me, it's a roller coaster, right? Yeah, it's, um, it's interesting. It's an interesting thing. Um, it's an interesting space to be in.

All right, promised I would not keep you forever. Can I sneak one last question? Yes. I mean, I saw you kind of— you, you were dismissive of AI a couple times. Um, is it mostly you're just tired of people slapping AI on everything, or do you have a deeper—

I don't There's nothing particularly like— I would— well, let's say there's a couple of things. I think particularly insightful, um, but I think one is just like the, um, when you— I, I feel like it's just me being a, a bio deep tech douche a little bit. I'm like, oh, I'm trying to save you from disease and you're figuring out how to write sales emails. With AI so I can get 100 more spam emails per day that, you know, my spam filter can differentiate. Like, fuck you, man. Like, go spend your life on something about— again, douchey. I'm not saying it's the right way. LPs need to make money. Lots of LPs are like hospital systems and schools and shit. Like, blah blah blah, whatever, right? But like, I'm just— I'm a dickhead about this stuff. I'm sorry, I'm never gonna respect it. Um, There's also a lot of like interest of like AI and bio, which like is gonna be interesting.

That's what I was like, I didn't know if you were so underwhelmed that when you hear about the AI— like I was reading, what was it, that Chai 2, where the AI is, is developing, um, I think it's actually a smart application of it, medicines, you know. Yeah, they're doing antibody, antibody development. And I, so I was just curious if you thought that stuff is if there's anything real or if you thought it was—

there's definitely real things. And it's like, um, the fundamental problem with bio is not actually the AI. Like, I'm not an AI expert, but like, obviously, you know, AI is pretty damn epic. Like, I'd be an idiot not to like acknowledge and see that. But that— the problem isn't the models. The— for most AI problems in bio, the problem is the datasets. You know, we just just can't model a human being, right? If I'm like, oh, I have this small molecule and I put it into Ashley, is it going to extend his lifespan? And like, what is it going to do, right? Like, there's just so many, like, infinite, infinite interactions. And you can like boil it down to like, okay, well, these are the top 5 like adverse events, or these like, you know, moieties on a small molecule are associated with X, or You know, that's why I think the antibody thing is smart, because like a classical challenge with antibodies is just optimizing— basically, antibody is like a, a designed protein. It's like a Y shape usually, and it's designed to like float around your blood and bind to other protein targets. And it's designed in a way to like last a longer time, because peptides normally only last like 30 minutes, even your fancy Chinese peptides. These can last like a month or so. And like some of the most successful drugs in the world are antibodies, but like the way they like optimize the binding of that antibody to whatever you're trying to block, whether it's like a receptor or something, is like actually very archaic. And so it makes sense that like, okay, you know, this protein structure of the receptor and then you have an amino acid profile, like how can you design the best mapper? Like that is a perfect problem for AI, right? Predicting, you know, protein folding off of genome sequences. Perfect problem for AI. But there's a whole other category of things like curing cancer. Yeah. Or understanding how a drug will behave in a body or how a cancer will react to something. It's, we just don't have the datasets or the quantification. Like this is one of the challenges we have is how the hell do you actually quantify quality of life? It's actually really hard. Yeah. It's really, really hard. And so.

Especially when the dog can't talk.

No. Yeah, I mean, your cells can't talk either, right? And like, you know, things are like, oh, things go up, things go down, it's associated with X, but it's actually very hard to detangle what's going up because a bad thing is going down and it's causing that— this thing to go up. What is like this thing going up is actually positively driving X? Like, detangling— like, you know what, you should just like flash a picture of like those posters of like the inside of a cell and like the chemical reactions and signaling cascades, because that's just like literally in one cell, and there's God knows how many in a human, right? It's just ridiculously complex. So I obviously think it's interesting. I'd be an idiot not to think it's interesting. And it's not like— there's so much foundational work that needs to be done in like actually quantifying the human body. Um, I hope we get to do some of that work. I'm sure others will do that work too. This will be a great problem for pharma to work on. And I think that's actually the rate limiter to AI doing cool things in bio and directly in drug development. There's a ton of other augmentative stuff that will be valuable, I'm sure, like reg writing and whatnot. But like, that's a— yeah, we need better data. Okay. Okay. So I'm sorry, I'm not going to be able to make you immortal with AI, Ashley. I tried. Somebody will. Yeah, I called Sam. I said he can't do it. I'm out of credits.

Uh, well, thank you so much. If so, if— and I don't want to get you in trouble with the FDA, so if we can't say things, let me know. But if all goes well and according to plan, then people— and people have an older— which plan? Which version of the Gantt chart? People could perhaps go to—

in next year, if they have an older dog, year 27. Yeah. As fast as we're working, as fast as we can. It's just hard.

So, but it could be within the next year or two. If you have an older dog, you might be able to have an even older dog.

Yes. And healthier dog. And healthier.

Okay. And what, people should go to Loyal to get the updates on all this? Can I— you can't get in a trial still, can you?

The trial I was talking about is fully enrolled. Yeah. But we're going to be recruiting other studies. We're going to run a lot of these big lifespan extension studies. So if you'd like to, you know, be on the list or potentially enroll, you can register interest. We have a newsletter where we update people at loyal.com. At loyal.com. You can follow me on Twitter for some hot bro takes. I need to stop tweeting about bros. I'm getting outed here. Um, uh, you know, lots of bro takes. Also posted a picture of our, uh, some drug today, some beefy drugs.

I saw that. Beefy? They're beefy, meaning they're just big, or they're beefy?

No, they're like literally beefy flavor for the—

they're beef flavor. They smell like beef ramen.

Yeah, they're really cute. I was going to bring some, but I was like, he's going to have cameras and can't have it on camera.

I was going to bring that. I was going to bring that photo up, but I didn't.

Well, you can bring the photo up. I was just— I was going to bring you like a— I'm going to get myself in trouble. I'm going to stop talking now.

Okay. Well, thank you so much for coming in. I really— we really appreciate it. And it's just some of the most like I don't know, sometimes you just run across a person and a company that just goes about things very smartly and interestingly. And I remember meeting you for the first time and just being like, that's really clever, right? And kind of like we were talking about, I was like, why hasn't somebody done this? And then, you know, it's just, it takes, um, so much effort and will and everything to pull something like this off. And I think you guys, I was always into the idea. I, in my head, you got here faster and farther than than I would have predicted. So, uh, oh yeah.

I mean, we've, I think I've always, I remember fighting with some investor about this where I was like, they had like written me off and I was like, you don't understand, like this company's gonna be successful. Like you're wrong. And I said this like 6 or 12 months into starting Loyal. Um, and I, I, I think the idea is inevitable. Um, you know, even if we don't pull it off, which I will literally be heartbroken forever if we don't, I will never recover from that. But even if we don't pull it off, we've blazed a path for somebody else too. And that already is, you know, the honor of my life to have, you know, created and normalized this idea that just was, you know, very niche. Yeah. 5 years ago. And yeah, we've done more than I think literally anybody thought we would. And we could have done a lot of things better, but honestly, we did a lot of things better than many other people who have tried too. So I'm pretty proud.

100%. Well, thank you so much for coming in.

Thank you.

The Core Memory Podcast is hosted by me, Ashley Vance. It is produced by David Nicholson and me. Our theme song is by James Mercer and Jon Sortland, and the show is edited by the Jon Sortland. Sortland. Thanks as always to Brex and A1 Ventures for making this possible. Please visit our Substack, YouTube, and podcast channels to get more of what Core Memory makes. Thanks, y'all.