[Highlight] Why Dog Longevity Drugs Are the Fastest Path to Human Longevity with Celine Halioua

0:00Hey, Ben Kesinoka here, co-founder and general partner at Village Global Global, a network-native venture firm. What you're about to hear is a clip from a longer conversation. If you'd like to listen to the full-length version, find the link in the description. And, of course, subscribe so you don't miss the next one. Enjoy.

0:20When you think about the company 10 years out, what do you imagine Loyal looking like? I think we'll be a multi-subsidory company that's developing numerous products for dog longevity, probably for cat longevity by that time, and also human drugs. I think we'll also be working on early discovery and R &D. So right now I'd consider us more of like a clinical company. We take existing biological hypotheses and ideas and we turn those into drug products and then prove hopefully that they are efficacious and safe for lifespan extension. But we're not like de novo discovering biology of aging, right?

1:05In 10 years, I think we're going to have an extremely robust pipeline and discovery unit that's ideating new mechanisms and new ways to intervene in the aging process to hopefully slow it, but potentially even reverse it one day too, which is the holy grail. And I also think in 10 years, aging will be a lot more consensus and most pharma companies will have an explicit aging division within their organizations. Why do you think pharma companies have been so slow to adopt this? Because it's not canonically considered something you develop a drug for. One of the biggest risks when you guys invested, besides random chick, never done anything, besides being an associate at a two-person venture fund, didn't finish her PhD, and very disagreeable, which adds a lot of other risks.

1:57Besides all of that risk that you guys took. Oh, by the way, it's just an idea and literally nothing else. and a like mediocrely designed slide deck. Sounds like a great founder to me. Could have gone worse. It also was, you know, I had this idea that the FDA would accept that a drug could be approved for lifespan extension and healthspan extension itself, even though it had never been done before and was canonically considered impossible. And that was the case, right? This was not considered like a pharmaceutical is developed for a disease. like Alzheimer's, like cancer, like the flu. It is not developed for, hey, you're aging.

2:39Oh, you're still aging. Oh, you're aging at a little bit of a faster rate now. You're aging better or you're aging worse, right? That isn't something that you develop a pharmaceutical for. And so I didn't think that had to be the case. I didn't think that was true. I didn't think it was inherent. I thought it was a self-limitation of the field. But nobody had shown before that that was possible. So I think that it's just – I think we'll really definitively show it's possible if and when the drug gets approved. I think that's a catalyst moment for everyone. When you think about taking what you've learned and bringing it to humans, you've talked about this vision of essentially going from this pathway for dogs to using this on humans, which is kind of the holy grail, right?

3:21Save the dogs, save the world, right? Exactly. Yeah, that's the thesis. But I've never heard you actually go in depth on that idea of like what would it look like to create a human drug. Do you have like some conception of what that part of the business will look like in the future? Yeah. I mean we don't have like a drug candidate yet because I think some of the challenges was doing – the original insight of the company was that you cannot develop a human longevity drug today. And everybody thinks that's because of the biology. But it's actually not because of the biology. It's because of logistics and like financial norms.

3:54It's because running a lifespan extension study in humans would take forever. It would cost a billion plus dollars. By the time you're done running it, your patent would be expired. So you're not going to get any of the ROI of the drug that you just invested billions of dollars in developing. Oh, by the way, most human drugs fail. So multiply that number out by the failure rate before you actually get a drug approved. It's difficult in certain health care systems to do something like that, right? The ROI is usually higher for acute medicine drugs versus preventative drugs. And so all of those issues were preventing – the thesis was that these were the reasons, the real reasons why we don't have longevity drugs for humans today.

4:34But luckily those reasons don't exist in dogs because they have a shorter life. It's a cash-paced system. You're economically incentivized for your dog to be healthy today and five years from now. So you'll invest in preventative care much more easily and much more quickly. And so A, it was that you can go dogs first. and then while you can't go for humans and then b that actually by doing it in dogs it accelerates and i believe is the fastest way to a human longevity drug and there's two reasons for this one is the biological right so okay if like one of the reasons why we can't develop human drugs for longevity is because the failure rate you know the success rate of a dog of a new human drug is about nine percent and for a number of reasons but one of the big reasons is that we you know, prove and test and ideate new drugs in like mice, which don't really age in the way we do and mechanisms, right, that don't really exist in the way we do.

5:28And we translate over to humans and everything breaks, right? We've cured most diseases in mice or like versions of these diseases in mice. We haven't done that in humans versus in a dog, like a dog naturally ages over time. A dog naturally develops dementia. So they develop Parkinson's, they develop cancer like we do. They develop osteoarthritis like we do. So if our drug can successfully slow the rate of unhealthy aging in these dogs, it's not one-to-one that it's going to work in a human, but it's certainly much more compelling than it working in a mouse, right? So then that makes the ROI more compelling, right?

6:05Maybe you are willing to run that billion-dollar lifespan extension study if the probability of success is 40 % instead of 9%, right? So that's the first one. But the second, and I think actually the thing I didn't appreciate when I started the company, but I appreciate much more now, is actually just the economic model of biotech. Most biotech companies never make money. Most biotech companies exist to be externalized R &D for big pharma to take an idea or an asset, bring it to a value inflection point, you see some efficacy, you show it's safe, you have a compound, a compound seems like it makes sense, and then sell it to big pharma.

6:45They're not actually, biotech isn't a commercialization engine in most cases. There are notable exceptions, right? But in most cases, you're exiting long before you bring that product to market versus for us. And so you're always having to think about your investment in the scope of what would have an ROI for a pharma company, right? And this is partially also because, again, developing a human drug is just so stupid expensive and it's so risky. For a dog drug, it's like 50 mil-ish all in to bring a dog drug from idea to approval, not including a team. And so it is much more reasonable to raise that money on the private markets.

7:19It's much more reasonable to fund the entire life cycle. And in the commercialization, we believe, and I guess we'll find out, that you can do it yourself because there isn't all that insurance payer, PBM crap that makes it so difficult to commercialize on the human side. So actually a small company can commercialize. And so I actually think the fact that we have the potential of being a revenue generating biotech, biopharma company means that then we have hopefully a bolus of cash that we can do whatever the fuck we want. We can go invest it in crazy incinerator uses of capital like human longevity.

7:54And that's fine because we have a cash engine. And so I think that plus the mission motivation, plus the team, plus the dog data set, I think is how we're going to be able to do that. Yeah. It makes a ton of sense, especially on the revenue generation side. It's like you now have a core business model that can help fuel these bigger and bigger moonshots that can be a part of the business. Yeah. And I mean, and it's not like I'm the first one to come up with, like that was the Tesla moonshot, right? Like a lot of these deep tech companies, like you You bring something to market. Whew, great. OK, now you bring the next thing.

8:22Now you bring the next thing. Each, the previous one's success funds the next most audacious, most audacious, most audacious next step. Yeah, to your point on Tesla, Tesla, I mean, the speed at which you can get cars to market, though, is more regular, right? Whereas, like, because of these clinical studies, you actually could be 10 years for a human, 20 years for a human. How are you thinking about timeline for these? So what do you expect the timeline to be in terms of like drugs are starting to fall into consumers' hands on the dog side and how long do you think the clinical studies could take for humans if you were to run something like that?

8:56On the dog side, we'll hopefully have a drug approved in a year, year and a half. It really just depends on the manufacturing timeline. Got it. That's the problem, right? That's a determinant. If we're going to resummit manufacturing this year, hopefully we get it. If we don't pull it off, which is entirely possible, then it adds another at least six months to that cycle. So that's really the biggest determinant. That's where I'm spending all my time right now and working on it. Sorry. If anybody's listening to this and like really good drug manufacturing, hit us up because that shit is complicated.

9:27I really underestimated it. So that's on the dog side. Then we'll have a couple of products. Hopefully we want to have five approvals by 2030 is the vision. So five dog approvals by 2030. um human i mean we haven't even begun to design this clinical trial um and i think there's a lot of questions right like do we explicitly look at mortality risk reduction right so like your reduced the risk of you dying in any one year and the ability of a drug to reduce that do we look at what we think are leading indicators of mortality risk reduction but still more general than disease like all of these things are going to determine so i can't really give you a timeline for a human longevity trial right now.

10:09I think actually the biggest issue is I think we have a little bit of a catch-22 with what kind of drug you develop for human longevity because, again, of this patent issue. And you need something – like the bar is going to be so high for safety. You're really going to want to hit a mechanism that is like well understood and established. But if the mechanism and the API, the drug, are well understood and established, it probably doesn't have enough patent life left on it to be protected post-approval. And how long do you think a human study would be? Is that like a 10-year study? I mean, again, it depends what you're looking at, right?

10:41So it's like you have this tension between probability of success and ability to see a readout in a period of time. So you could run a 10-year lifespan extension study, but it's going to be in relatively older or high-risk individuals. If you're in older or high-risk individuals, the probability of success of that study in general is going to go down because those individuals might be too, quote-unquote, far gone down the aging process to be intervenable or to be intervenable with that type of mechanism. So then you can go earlier, right? Like I could start you in a longevity drug today. I feel pretty confident there are things I can give you today that would extend your lifespan significantly.

11:16But it's going to take us hopefully 50, 60 more years to see if it extends your lifespan and see how much it extends your lifespan relative to somebody on a placebo. And so that's the tension. It's like what's that right intervention point where you're intervening early enough that you actually do see biological efficacy but not so early that by the time the study reads out, the company is dead. Hey, this is Ben Kaznoka, co-founder of Village Global. Thanks so much for tuning in to the Village Global podcast, where we go deep on all of the biggest topics of tech. If you enjoyed this conversation, please subscribe to our YouTube channel.

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