Next Unicorns: Developing drugs to extend dog lifespans with Loyal CEO Celine Halioua | E1799

0:00there's something about being a solo act i tell people like i'm bob dylan i don't play well in a band and now i'm forced to be in a band with the all in podcast and i can tell you it is not my natural state of being like you know i am obviously the front guy i'm the lead singer i just want to play the songs and i want to play the songs the way i want to play them i want to play them correctly and then when you know somebody wants to do it somewhere different and then they want to be the lead singer it's like well there can't be two lead singers you know like you can sing a verse but like you're the guitar player you're the bass player you're the drummer like do your job like And I agree with you.

0:31I think for certain people, you got to be the solo founder and you can go faster. But it's very rare. And then at the early stage, having multiple ones, you know why actually this whole thing got started with the co-founders? That's it. You nailed it. It's in the interest of the investors. This Week in Startups is brought to you by Fount. Do you want access to the performance protocols that pro athletes and special ops use? With Fount, an elite military operator supercharges your focus, sleep, recovery, and longevity, all powered by your unique data. Want a true edge in work and life? Go to fount.bio slash twist for$500 off.

1:13LinkedIn Jobs. A business is only as strong as its people, and every hire matters. Post your first job for free at linkedin.com slash unicorn. And Catalog. Stop wasting time and money with expensive design firms and unreliable freelancers. Get fast three-day turnarounds for a flat monthly fee with catalog. Get$1 ,200 off right now at trycatalog.com slash twist. Hey everybody, welcome to This Week in Startups. We all want to live longer, right? Life extension has been the dream of technologists, alchemists, religious people, and humans since we existed. We all want to get a couple of extra years.

1:57And you might remember Altos Labs raising$3 billion from Jeff Bezos, Sherry Milner, a bunch of folks. Startups are starting to use biotech, solutions, AI, big data to look at diseases and try to fight aging. Well, today on the program, we got a slightly different take on life extension. They're working a bit backwards. Plan is to start with my favorite creatures on planet Earth, dogs. and eventually use the learnings there to develop life extension treatments for humans. And I think this makes the most sense to me because dogs are so much better than humans. So why the strategy? Well, FDA approval for life extension drugs in dogs are 50 times less expensive than for humans.

2:40And you can tell if it works much faster because dogs have such a shorter lifespan than humans do. So Celine Hollywood is the founder and CEO of Loyal. Celine, I love dogs. thanks for starting this company absolutely i'm glad you're not a cat person cat people are the worst i think we all agree on that uh and once you get to two or more cats specifically three you know something's going very very wrong in your life uh now owning multiple dogs like i do too that's completely permissible and when i retire my wife and i plan to start a bulldog rescue that is our retirement plan so in 20 years so sweet yeah um dogs uh almost by definition if you get one you're signing that contract that they're gonna you're gonna bury them and they're not gonna bury you that's just the law of big numbers right humans live to their 70s dogs live to maybe 9 to 12 years on average is that the average lifespan of a dog yeah well interestingly the bigger a dog is the shorter their lifespan is so if you really like great danes you're looking at six seven eight years if you like chihuahuas you know who knows why you're looking at 16 17 years yeah uh this is very true i looked at getting my my my dream dog is a dog de bordeaux or like a spanish mastiff an italian mastiff i love these big bull breeds but when i found out they live six or seven years that got me bummed out and my bulldogs tend to live i had one live eight and a half years one live 10 and a half 11 and then my last bulldog fondue love of my life lasted 15 plus years the longest uh you can get out of a bulldog it never happens that bulldogs live that long uh so i feel very blessed so tell me um you guys have raised 65 million for solo i'm sorry you've raised 65 million for loyal so far um what is the plan here and what's your background how did you come to this idea yeah um i'll start with the background so i actually got to college for art school but then at the very last minute i decided to switch to neuroscience because i had this um i had this realization that in my perception we don't really have free will because you can get diagnosed with many diseases often age-related diseases that if they happen there's not much anybody can do for you no matter how much money you have how much effort you put into it, how much thought you put into it.

5:06If you get certain forms of brain cancer, if you get Alzheimer's or Parkinson's, generally speaking, your life is going to be shorter and maybe much shorter than you want it to be. And to me at 18, when you kind of think adults are heroes and they can fix everything, realizing they can't was extremely scarring, candidly. So I switched from art school to neuroscience. I spent four years in the lab. I then started a PhD at Oxford in the economics of preventative medicine. And as I'm sure we'll talk about, the way I really see aging drugs is as a preventative medicine for multiple age-related diseases at the same time.

5:43I think, I was just laughing because I usually use statin, a drug to reduce risk of cardiovascular disease, but now it's looking like ozempic might actually be a better metaphor for that, right? A drug that positively impacts multiple things that might be not classically defined as the same disease. um and then i dropped out of oxford joined laura deming at the longevity fund um where i was her first employee chief of staff venture partner eir kind of every title there uh where we were investing in companies developing drugs for human aging and lifespan extension and i got kind of frustrated while i was working at longevity fund because every aging company including altos who you just mentioned that's about three billion dollars has kind of the same narrative like oh you know we want to work on aging and lifespan extension we have this drug where this mechanism that works but fda is evil aging isn't a disease so we're going to develop our aging drugs for cancer or we're going to develop our aging drugs for alzheimer's or osteoarthritis or whatever it is and it just didn't make sense to me that literally every shot on goal for an aging drug was not actually being tested for what i think the drug should be tested for which is a drug that keeps you healthier and longer that is fundamentally what we are developing these drugs to do um long story short i i'll share this because it's very silicon valley i had found that this we were talking about the big dog short lifespan that was an aha moment for me because you look at the genetics that control dog size it's actually around a very well-known aging pathway actually the og aging pathway that laura worked on when she was like 12 years old um because she's a savant and it turns out that it seems like big dogs have an accelerated aging disorder that's an unintended consequence of historical inbreeding for size so i went to a camping trip with a bunch of silicon valley founders like three weeks after i moved to the valley and didn't know anybody got drunk and was like you know telling these people i knew how to make their dogs live longer and there was a vc there who ran into another vc who ran into greg rosen at yc demo day and told him about me and he was like oh my god dogs are an amazing market so he found me and kind of helped me realize that this was not only like an interesting scientific insight but actually potentially a significant uh business and significant company and they gave me after three months of really understanding the thesis scientific consumer otherwise um gave me a term sheet it was five million dollars for me and a shitty pitch deck and literally nothing else back in 2020 um and since then we've yeah as you mentioned raised 65 we're 55 people but much more importantly we are about um a year and a half away from hopefully launching the first ever drug fda approved for lifespan extension for any species but of course our drugs will be approved if approved for dogs.

8:48You see these blue light glasses I'm wearing? I'm not wearing for style, although they are very stylish. They've totally changed my life. Why? I started having headaches, right? And had eye strain. So I got these blue light blocking glasses that do a little magnification because I need readers. Yeah, I look nuts. But my eye strain's gone down, my headaches have gone away, and I'm sleeping better. Do you know how I got on this? I got on it because I now have a health coach. Who's my health coach? It's found F-O-U-N-T. It's a health company that's created custom health and performance programs that are tailored to your body, obviously, also your goals, and they take into account your lifestyle.

9:27My coach is incredible. I text with them all the time. They did a blood work for me. They check out my wearable data, and we do weekly calls to see if I'm on track and getting results I want. They also told me about some supplements I should be taking based on the blood work and they do it at a fraction of the cost. We upgraded my diet. I'm doing a little more protein. We've optimized my sleep. That's great. I got the supplement packs. I feel great. I feel like I'm in control of my destiny. If you want to be like me and you're concerned about your health and you want to just try to do better, have some experts on your team.

9:56Build your own program. Go to found.bio.twist. That's F-O-U-N-T.B-I-O.twist. Get your free consultation. Mention Twist. You get$500 off your first month and get your own personal health coach health as well and if you're running a startup you're a ceo if you're a capital allocator take it seriously i love this service found dot bio slash twist now most of the time when people do testing they use a chimpanzee right i think that's the closest living relative to a human and there are many other uh animals in the world uh that are close to humans i believe dogs uh i think are not as close to humans but they do have a number of things that they share with humans i think the primary one is environment right because they've for hundreds of years with the exception of the ones that are behind me in the mountains here coyotes domesticated dogs they live with us so they have the same exact air they get the same exact not the same exact food but similar food i think actually because they're eating scraps yeah um so tell me why dogs and not chimpanzees or another breed yeah absolutely so it's twofold if we only ever develop dog aging drugs we're going to be a multi-billion dollar business dog drugs make a ton of money heart guard which is one of the many heartworm preventatives makes about half a billion a year the leading flea and tick makes a billion a year and this is um very high margin very sticky revenue dogs are prescribed these drugs for the rest of their lives and dog owners are very loyal to the brands that they stay with.

11:32But as you're correctly interpreting, there is a bigger vision here. If we can show that a drug slows the rate of aging and extends lifespan in dogs, that is just about the best translational model for showing what might work in people too. And the reason being is one, exactly what you just mentioned, environment. Environment is huge in aging, both for the individual, but also generational environmental impact but also dogs about the same age-related diseases we do at approximately the same time in our lifespan dogs get cancer and they get chemo for cancer dogs get osteoarthritis dogs get dementia cognition is actually something i'm super super interested in dogs get very quantifiable forms of dementia dogs get are thought to get diseases like alzheimer's and parkinson's like we do which very few other animals do theoretically there are other animals that are genetically closer obviously chimpanzees are genetically closer even mice um are on the phylogenetic tree closer to us but dogs um because they represent the wide variety of diseases and environmental factors are actually a better model of how we age over time also functioning with chimpanzees you know one of the hacks of loyal is that we're able to gather this big data because we're gonna if this drug gets approved potentially put it in millions of dogs you've already done hundreds of dog studies right you can't do that yeah i mean that is the incredible i think insight here the same way elon did the tesla roadster for you know technological enthusiasts and only need to sell a couple of thousand of them i think they wound up selling 3 000 or so for 150k each it was an impractical car at a ridiculous price uh and was you know a gen one product and so you have this incredible uh you know place where you can land that's even bigger which is there's 65 million i think uh homes that have dogs and like you're saying the dogs have the same environment okay that's really interesting and if but 10 of people decide to give their dogs a life extension drug they're already spending like a thousand bucks a year on their dog easily i think i spend much more with bulldogs so they could afford i would you told me i could spend five hundred dollars a year to my dog to live longer and i got one more year two more years that's a no-brainer for me that's an instant purchase and now i might be the top 10 in terms of my thinking on that um but it's interesting the four horsemen of chronic disease as peter attila calls them he got the neurodegenerative i didn't know really dogs got that alzheimer's and stuff like that obviously they get cancer that happens all the time um and tragically people have to put their dogs down because i guess cancer treatments are not a lot of people can't make that decision to spend ten thousand dollars or five thousand dollars on cancer treatment then you got but what about like um cardiovascular disease i don't hear about dogs having like plaque in their hearts and stuff like that they don't get that that's that's the only one where there's a strong de-correlation between incidents of humans and incidents and dogs um that's because that disease has a lot of environmental factors to it and dogs do eat similarly to us but they don't get to go through mcdonald's drive-thrus or smoke cigarettes right didn't know a lot of yeah uh the cardiovascular stuff i think cigarettes had a big impact on that um but the insulin related stuff and diabetes do dogs get that do they have uh so actually uh so they don't they can develop diabetes but what you're hitting on metabolic fitness is actually the core mechanism um by which we're targeting aging it's one of the reasons again to go back to zempic i was so interested in all of that because it's the exact it's a very similar mechanism um so actually the only lifespan extension study that's been run to completion in dogs as far as i'm aware is a caloric restriction study um so purina in the 90s ran a clerical restriction study with labradors they showed a two-year lifespan extension and a two-year delay in osteoarthritis and cancer development in those dogs um nothing came from it purina is a dog food company that on exactly economic inside advice tell you to clarkily restrict your dog but it's a beautiful validation of what we've seen already in mice and primates and other model organisms that improving metabolic fitness which is how caloric restriction is thought to work extends lifespan it extends healthy lifespan yeah this is the great thing i just encourage everybody to get a dog and go for walks a number one killer of men i believe in the western world at least is stress and so dogs reduce stress massively found all founders should have a dog and the dog should be on their lap in their office that is that is a must yeah of course oh are you boopy is it a what is that a rottweiler what is that roddy yeah roddy they're not they're you know they look intimidating but they're big sweethearts uh they are like a toddler they think they're lap dogs those dogs are 100 pounds and they think they should be on your lap uh like a little poodle or something like that they're deranged uh that's that specific breed i'm calling out let's talk about wagovi and osempic for a second uh i had a i've been on osempic or wagovi for the last two years lost 21 pounds on it feel amazing changed my relationship with food and now uh all these reports are coming out that um it's going to help with heart disease uh it looks like so this generalized medicine that we're discovering uh could have a dramatic impact so watch it as you're working on this with dogs um what path are you going down in terms of thinking about which drugs to use and does ozampic and wagovi and what do they call these uh are they gl gp1s or something yeah what what impact does this have on your thinking and then and then what route are you taking in terms of thinking about life extension in dogs yeah so so one of the interesting things about dog drugs so actually when there was a weight loss drug that worked in a similar mechanism so appetins reduction um in dogs and it actually was a pretty big commercial failure and that's because people's food relate like food giving relationship with their dog is a kind of a proxy for love right so the dog being excited to see you when i come home like excited to see you or is he excited for dinner is he excited for a treat or is he excited for pets right it's kind of all mixed in so people would actually stop giving a drug because they felt like their dog cared about them less so one of the things we look at in our studies explicitly is making sure that the dogs on our drugs are not losing weight and that's not why we're seeing the health span benefit which is kind of non-intuitive but just one of the things i did when i started loyal is i wanted to be very i mean i'm i started loyal when i was 24 i'm 28 now uh i obviously have a very experienced team but i myself i've not brought a pharmaceutical product to market previously and so i wanted to make sure i was kind of humble and learning as much from the priors and that was a really interesting one um as far as what we're targeting so the aging field is very interesting in that there is decades of very strong research on various ways of extending lifespan but because there's no commercial path for a drug to be approved for lifespan extension there's no you know pfizer and regeneron and whatnot nobody is developing a drug for lifespan extension i'm pretty sure we're the only company perhaps there's actually there was just a loyal copycat founded there's two companies that are saying that they want to develop a drug for uh explicitly for lifespan extension and they're tiny startups relatively speaking right there's nobody else actually developing drugs for this explicit use case and so we wanted to keep everything as simple as possible except for this one idea which is that a drug can be targeted for generalized quality of life and health span extension and not for a classical disease so we went with things that we knew were very well validated biology um so our drugs are in two categories one is around big dog short lifespan so actually the very first drug i was working on uh was loi one is this big dog short lifespan drug that's what the company got funded around and it's this idea of um as i talked about earlier that big dogs when we selectively bred dogs for size we created these really awesome giant breed dogs but these big breed dogs once they're fully grown continue metabolically aging at a faster rate a big dog is literally aging at a 2x faster rate they're developing age-related diseases faster i mean great danes will often go gray at age four um or earlier start getting age-related diseases earlier and then they die sooner they have a much shorter median lifespan um and that's a our hypothesis is that that's a uh um unintended consequence of historical breeding and therefore genetic and therefore targetable with the drug um so we have two drugs that are targeting that to give big dogs a longer lifespan and then we are sorry just so i'm clear and i reflect that back to you you're talking about hey the genetic engineering we did breeding made the dogs big increased the velocity of their growth um so they get to full size but hey that growth uh has now whatever whatever is in the dna i guess that's driving that growth or in the genes the genetics um you could take a pill to reverse that maybe um or i guess you could breed them another way to do would be to breed them to not i guess get as big but that doesn't solve the problem so uh there there's some thing in the dna you could actually change or in the genetics you think so we're not doing any change to the genetics um what we're doing is a drug that compensates for the genetic changes that these dogs have i mean you you have uh you said bulldogs right english bulldogs yeah yeah so you're very aware i'm sure of you know historical inbreeding has caused genetic issues in certain breeds bulldog most of all i mean the controversy to blue bulldogs is that we shouldn't even have them they were bred to be uh first bred as warriors in arenas for bull baiting was a sport bull baiting then they were they got saved and they were bred to be kind to each other nice for humans then they were bred to look cute with smashed faces and big barrel chests and short legs which then created they call them the break goal breeds um created breathing problems that cause heart attacks all the time poor adam sandler had both meatball and matzo ball die at like three and four years old is horrific yeah no and most dog breeds have some genetic associated disease goldens are another one they develop two forms of cancer that are can be very rapidly terminal and are very hard to diagnose beforehand uh german shepherds get their hips fall out over time and so our idea is that the short lifespan of big dogs it's not inherent um if you look at a wolf wolves are massive they're larger than any dog breed and they live in captivity um into their teens easily yeah um but it's a disease like anything else and therefore it's targetable with a with a medicine and that was really kind of the drug that we first went to the fda with but also first went to the the scientific community in the world with they try to connect something that people think is inherent and say hey you know maybe it's not maybe we should question what we think is normal yeah i'm the it's really weird that the boxers and the german shepherds and all them golden retrievers i think were in there with the hip dysplasia how did that become uh you know something in the breeding that got cost it's so weird great danes in there as well term minded right so like if you think about it with the big dogs they were the people who were breeding and trying to create let's say a great dane they did this very quickly like over a period of like a couple hundred years or less and so they would breed a dog the dog would grow large in puberty then it'd be one years old and they'd probably breed it to you know a sibling or a cousin because people were inbreeding themselves back then right they didn't know anything about genetic diversity and they're doing that over and over and over again and they don't understand you know evolution only works up until the point generally speaking that that individual's genes are passed on to when they're bred so if there's some negative consequence of the gene that makes the dog grow really big, what it very effectively makes the dog grow very big, it's going to stay because the person isn't waiting to see if there's anything bad happening on the back half.

24:14They're like, oh, big dog, breed it. And then because they're inbreeding, it's causing all these genetic issues on top of it. All right, listen, you're listening to the next unicorns, right? That's table stakes. Well, if you want to start on the path to becoming a unicorn yourself, you're going to need to find and hire great candidates. And How do you do that? LinkedIn, of course. You're on LinkedIn. I'm on LinkedIn. Over 900 million users now. The march to a billion continues for the amazing team over at LinkedIn. Then you can attract both the passive and the active job seekers. All you have to do is put that purple hiring ring on your profile.

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That's right. linkedin.com slash unicorn to post your first job for free terms conditions apply because linkedin is so generous what are your thoughts on stem cells and therapy this keeps coming up with my rich friends and i've heard it come up with dogs uh actually i don't know if anybody's actually done it in dogs um but people i know go to like mexico costa rica and they do or germany they do this platelet spinning like Kobe Bryant did for his knees you know and then their stem cell stuff what is your general thought on this because there seems to be a huge gray market but then I hear from people who've had it done on their knees or their elbows like uh oh my god I can play tennis again oh my god I can run marathons again I can sprint this has been amazing did you look at that as a possible pathway and then what are your thoughts just generally on it so one of the things so a similar avenue to that is supplements and that's something a lot of people ask me right like why am i going you know i've been running loyal for four years almost you know we haven't made a job for revenue we just burn money a lot of money every month and that's basically it deep tech deep tech right we could have been selling supplements we could have been selling stem cell therapies since day one but fundamentally a big part of what i want to do is i want to I want to show that aging drugs are boring right that a drug can be approved for a healthy lifespan extension and even if there was a supplement that you know theoretically extended the lifespan of dogs five years I would tell somebody else that they could go work on it but I wouldn't actually feel it's in the scope of loyal because I think we need to create the regulatory path and almost be like impenetrable to controversy right and the FDA is the highest quality bar in the world and that's the only way to do it in my opinion yeah so do you think there is a stem cell therapies or a legitimate pathway uh in the world or is it i'm not super educated on this facet i so we my group at oxford actually looked at it a bit at least at the time and that was a few years ago there's a lot of issue with these kind of as you were saying being a regulatory gray area where efficacy doesn't have to be proven um i think in general when you're putting something in your body especially potentially permanently it's good to have you know understand the side effects um but also the other thing i'd caution is placebo effect is very real very very real let's talk more about this is a very interesting um discussion i was talking to somebody who's in the medical field and they said my entire life is trying to beat the placebo yeah explain what yeah the explain the the the absolutely under appreciated power of placebos so placebo is basically so when you do a scientific study you and you're trying to say like does my drug extend the quality of life and the number of years of life of a dog you um will have a placebo group so it's somebody who the vet thinks they're getting the drug the dog owner thinks they're getting the drug i guess maybe the dog thinks they're getting the drug but they're actually not it's basically like a fake sugar pill that's made to smell look exactly like the actual pill and then the other group gets the actual drug and the goal is to show that you know in the people who get the actual drug that they're having a longer healthier life or their dog's having a longer healthier life placebo will mess was everything in the weirdest ways and it's actually even harder and um it's even harder in dogs um because one of the things that we're asking dog owners to do is fill out these surveys where they tell us about how they like how active is their dog seem how comfortable does their dog seem and it's all subjective it's all perception right and so if somebody thinks like oh i'm certain my dog's on the active drug even if they're not they might subconsciously rate their dog is healthier for longer another interesting thing was dogs is that you know our ultimate endpoint unfortunately is mortality it's reduction of mortality risk and with dogs you have euthanasia and that is inevitably a human decision of when to euthanize your dog so will somebody wait to euthanize longer than they otherwise would have because they think the dog is on the drug and it's dangerous because what it can do is mask the actual real benefit of the drug and if you can't show that there's a statistical difference between the dogs on your drug and the dogs on placebo the drug fails even if it worked the drug fails oh that's a fascinating that's a fascinating point so if the placebo effect was you know 20 reduction if the actual effect was 20 reduction you get a placebo effect of 19 or 21 or whatever i think the placebo effect typically is in the low teens is my understanding for a lot of drugs and so then you don't get approved because you're like hey it's just doing as well as a sugar pill but i thought your answer was going to be placebo effect doesn't exist in dogs because they don't know they're taking medicine it turns out the human's interaction with the dogs could lead them to uh not make a different decision at end of life and so when you're going to just take end of life out of the your statistics or do two runs of your statistics ultimately ones with the euthanized uh data and then the one without it and then try to make sense of it is that is that the ultimate goal no i mean it's so predominantly what we're looking at is lifespan and then healthspan as measured by the vet and the pet parent and the way you deal with this is you just do a really large study as far as i know we are running the largest pivotal animal health study that's ever been run or one of the largest um normally there are like 50 to 100 hours is a thousand um which is going to be very operationally complex um not to mention it's long because it's a lifespan extension study um but we do that exactly for that reason you want to be able to the bigger a study is the more signal you can derive from the noise right uh where how many uh people are going to be in this study uh with it because and do we have different qualifiers for dogs like you know giving dogs medicine maybe it's like you know less of an issue this has been such an interesting question actually because so it's going to be about a thousand dogs across 55 vets um all over the u.s you have to represent you know rich new york city dogs and you know working dogs iowa and everything in between that's extremely important both for us but also to the fda um and one of the things we're trying to figure out is like where do we put these study sites because it's not us we actually work with independent veterinarians who are um enrolled in the study and then they bring dogs in it's a scientific um it's like an ethics thing right because we're biased we want the drug to get approved and we actually have been mapping the the immigration immigration paths like within the u.s like people in california moving to texas and florida and people in florida moving to new york or whatever and also where do people move over five years of their lifetime because what we don't want like a fail mode for to study is the drop works but a bunch of people drop out of the study because in year two on average people move from new york city to iowa um and that connection or maybe salt lake city would be more accurate that becomes uh challenging so we're trying to load balance having sites wherever we think people might be without also adding so much complexity but then the study is too difficult to run or i need too many employees to run the study so there's all these like that's you have to make it's so operationally complex yeah and i'm wondering if there's some core i think there should be some meta study that you could team up on where you're giving the the dogs these drugs and then you're looking at the lifespan of the human and the impact that dogs have on humans and the longer the lifespan so if you could correlate as we get into this big data pools of giant data and then ai you look at owners and then start to think like hey owners who put themselves put dogs on this drug and i wonder if the lifespan is different for younger owners versus older owners or if older owners spend more time and do more walks with the dog or what the correlations are i bet you the yeah are you tracking environmental issues around the dog or you mentioned qualitatively health span that seems like a waste of time to me because does anybody give good qualitative information on their dogs you know that um so that is a huge problem in the aging field what the hell is quality of life how do you quantify how healthy you are how do i quantify your rate of aging there is no agreed upon norm and the problem is if you go to the fda you can't be like hey here's this new drug and here's this new measure right you have to kind of keep it boring except for you know what you're trying to do but to your big data point one of the things we're working on is developing exactly that like a quantitative measure of at least quality of life and healthspan and the dog and so when we're running this study for four more years we're banking saliva samples photos of the dogs videos of the dog blood stool everything and then wait of course um and then we also just announced a collaboration with banfield pet hospital which is one of the largest pet chains uh in the u.s and they're actually very interested in working with us on these big data problems too um because they have 20 plus years of longitudinal records of people going to the vet and the dog getting diagnosed in year three with this and year five with that and what's the outcome of the dog and any control for all the other things and that's i think a huge translation right if you can understand that in a dog and if you can objectively quantify if a drug's having a rate of aging benefit in six months in a dog instead of having to wait five years that's the best screening platform you're ever going to get for human aging drugs because fundamentally humans always are going to live like decades right we can't change that so we need a better way to measure how we age to tell the drugs working yeah and just thinking about the environmental factors the positivity um versus how cynical or just negative a human being is must have an impact on a dog uh and the exercise well i mean or and it will certainly have an impact on how they would report um on how healthy their dog is positive person i'm i'm always looking for the you know silver lining i'd be like oh my dogs are so healthy they're incredible i just took them for a hike out in tahoe they were great i mean meanwhile they're walking 0.5 miles and they're panting and they're exhausted um but yeah so altitude stuff and and brachial breeds and stuff but uh you know interestingly with bulldogs there's uh a movement to make them genetically more uh like a normal or an old english bulldog where they have longer legs longer snouts and less short less big chest so you know you're like oh is that a bulldog or it's like yeah it's kind of like a ratty old bulldog not the genetic like freaks that you see in cartoons with the giant barrel chest um so when you're funding a company like this uh how many years to commercialization and how do you explain that to investors just getting to the startups part of your story yeah so that's a very interesting question so we're backed by i'd call it solid standard silicon valley funds right first round co-led our series seed was josh Josh Koppelman friend of the pod I love Josh he's the best hard ass ever is he back to working full time at first round or is he like semi-retired running some newspaper I don't got any of the hot goss I don't know he was like he was taking a break to run some newspaper for a while in Philly I don't remember I mean he's still on my board so if he shows up to those Josh Koppelman's awesome you know those guys make too much money with Uber they don't come to work anymore it's a joke here's the thing J.K.L.

37:52we have the aging drugs right right you can keep these vcs alive longer it's actually we'll do that i hate to go into diversions about vcs but i had a vc who's 10 years older than me and he said to me at some point a couple years ago he's like you know i just got to retire and i said why are you gonna retire it's the greatest job in the world you've done so much great work you're so supportive it's like just feels creepy to be 60 years old 62 years old and uh meeting with 20 year olds and like trying to invest in them and like i'm i'm hanging i'm like you know it just it feels like people don't want an old guy around i'm like i think quite the opposite i think they love it i think they love having your war stories he's like really i'm like the war stories are great honestly and like the the just chillness like they've seen everything and they're like five mistakes they're gonna make and here's like why you're not gonna listen to my advice and then like six months later come back and i'm like you're you're right josh i didn't listen to your advice and i went wrong and now i'm gonna listen to you and josh koppelman's really old i mean he's ancient i'm joking i'm joking josh i'm joking but you're much older than me that's true no i mean john dore michael moritz you know uh just uh your recipes don valentine that when i got to spend time with those folks and ask them questions uh man you know coastless still in the game i i'm gonna be like venoed I'm never, you have to drag me out of my firm.

39:20So sharp. That guy, I don't know how he does it. I don't know how he does it, honestly. He's like five people in one. When I see a startup that's got bad design, it's hard for me to take it seriously in today's day and age. Why? Because having great design, having world-class design, it's kind of table stakes today with consumers, with employees, with partners, and of course, with investors. But, you know, design agencies, they're very, very expensive. And there's a lot of back and forth to figure out what you want. It's not for startups. You know, you can't spend a quarter million dollars, a half million dollars getting some design agency to do your look and feel.

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40:29It's a monthly subscription. And Catalog will never waste your time. They do three-day turnaround, okay? That's more than enough. Stop wasting time. Stop wasting money with all these expensive design firms and unreliable freelancers who disappear. here what you want is fast three-day turnarounds for a flat monthly fee with catalog and you're going to get twelve hundred dollars off right now at try catalog.com slash twist that's twelve hundred dollars off at try catalog.com slash twist well on an aging basis this is your this is your wheelhouse and your expertise and we'll get back to the funding question we've got we got to go down this path here staying intellectually curious in addition to moving around your diet calorie restriction but but really cognitively staying in the game and having purpose is this like a is it true that you there's a correlation with health and longevity or no it's so it's so hard to correlate these things right because if somebody's not intellectually curious are they getting less physical activity you know are they having depression are they less curious because they're trying to get dementia it's really like with all these things it's so hard to detangle everything changes this time that said the my favorite study we ran at loyal was a cognitive decline study in dogs so we were able to show that one of our drugs uh improved pretty objective and to your earlier point quantitative measures of cognition in dogs that had canine cognitive dysfunction and one of the tests that you do is their ability to relearn something right so they'll learn that a certain toy if they touch it like three times with their nose that it's associated with a treat they're like taught this over weeks that's like really like drilled into their heads and then they this is reversed and it turns out that a different toy um and now they have to touch three times to get the treat and the dogs that weren't on our drug would just keep on touching the original toy over and over again and then they would just abdicate from the study they just become too frustrated versus some more of the dogs on our drug relearned they learned that oh actually i'm just going to go to this toy and so there's an interesting parallel here and you know what will be the impact on society if people are able to learn new things faster or more more plastic so to speak for a longer period of time um i think it could have a massive social benefit that's why i started playing tennis i'd never done it before i started skiing again like much more actively skiing in deep powder traveling i think going around the world yeah playing chess i think just playing playing video games i started playing playing a video game again to just try to challenge my mind to be like in that flow state i think it's very important so back to the funding question you got all traditional vcs in there but traditional vc funds go for 10 years so first round is in year four five six of the investment how long does commercialization take And then, you know, is there another set of investors or a way for investors to clear their position in year 10 to get, you know, their LPs and then have other people like drug companies buy out their position?

43:29How does it all work towards that 10 year window of in which venture funds need to return capital? yeah absolutely so it's a couple of things first is that in tech startups from what i understand generally speaking the value is determined by in rational times a revenue multiple and maybe some growth factored into that too you are still creating value in a biotech company over time um but it's around your probability of success so it's kind of the risks are inverted um the there's a risk you know if i'm like building some note-taking app there is almost zero tech risk right i can do that but then the question is i am i gonna find how i'm gonna fit how big is it tam da da da da right for us you know if we get this drug to market it's um or you get a drug to market it's really deeply certain there's a very large market and one of the interesting things about drugs is that the moat is impenetrable um you don't get copycats you don't get a race to the bottom cogs are actually extremely good for drugs uh we're projecting at a very reasonable price that pet parents let's say like mid double digits um a 75 to 85 gross margin um on the product double digits per month or per year per month so somewhere 500 bucks a year maybe is what i'm thinking yeah so somewhere between like 40 to 60 a month we haven't done the final pricing uh we're trying to optimize all that right now but regardless the margins are going to be high which is great because that's how we reinvest into the company and reinvest in r &d um but the risk that you know josh underwrote and finote underwrote and the rest of my investors underwrote were could we find something that works and there's no really way to hack that like either a drug works or it doesn't work and it's kind of a bet on the team and the biology and the thesis to figure out what works so even if we're not making a drop of revenue we're still accruing value as an organization as the probability of getting that drug to market it becomes higher and higher and the other nice thing about dog drugs is it's only about four years to bring the product to market and then once it's on market that rem scale is much faster so we're projecting uh post-approval uh we think we can hit company profitability and let's call it like a year a year and a half and 100 million arr probably six months after that and that's on like very conservative estimates that are like um uh derivatives of what's standard in animal health so assuming we're significantly worse than what's standard in animal health we're still able to hit that rev acceleration that quickly but it's just a different appetence and you have to educate people because they don't have these mental models in their head because i'm i'm everybody's first dog longevity investment usually their first drug investment you wrote a blog post so that was pretty fascinating about how you hit your series a milestones with less than 500k of the original 5 million you're raising the seed and you lamented how frustrated you were about selling so much of loyal at the seed valuation you sold half the company or something uh or a third a third so you got a 15 million post and you think you could have done it for just selling five percent of the company or so or even less three four five percent of the company um so maybe talk a little bit about that because you could uh you did you make it up in the in the next couple of rounds uh by raising too much money in the beginning?

46:47So it's hard, right? The way I've always thought about loyal is there is absolutely a pharmaceutical out there that can extend a dog's lifespan. And I think we have a lot of data that people will want a drug to extend our dog's life. So then really the core question was, can we find something that works? And can we find something that works in time for what you're mentioning earlier, these venture timelines and the fundraising timelines. And so when I started off, I didn't want a false fail. And raising that amount of money ended up not being necessary because my early team was good and we found that basically the first thing we tried was great.

47:26But if it hadn't, and we only had that 500k, then we would have been, I mean, nobody would give us another 500k or another million. the other interesting difference with building deep tech and biotech companies is that the the talent you hire is much different um you know my second employee was a father of two kids um he had a mortgage he was saving for college they you know they are coming from these companies where a equity is not that valued i still gave them a lot of equity but equity was not that valued and cash comp is extremely important um and in the executive levels it's very high in biotech and so you're not going to be able to convince somebody's family to let him take a swing on this weird dog longevity company run by a 24 year old if you're also offering him 100k a year salary like you have to give you have to show the runway so that was actually quite important in the end it makes total sense because you have a family you got kids in private school you got a mortgage payment you know they're going to need to make 250 300 400 whatever and they got an offer from pfizer or somebody or merc for that amount so you're not operating in a vacuum and these folks uh they need to have a couple of decades experience in order to qualify to work for you it's different than making an app or in fact some people say it's a young person's game um to do software and stuff like that because you know you you're putting in 60 hours a week 70 hours a week having a family all that stuff listen i want to get into it it makes people very uncomfortable but but that's the thing it's in it's in different disciplines right for us having the right brain will save literally six months of time right it's just the right context but it's almost an apprenticeship model where you have to have been there to see that there's a book you can read nope that will teach you how to build a drug it's just it's experience it's actually very artisanal uh which i think freaks people out but it is and so we invest in good people um but it does change the scope of how you build the company yeah you're a solo founder a lot of talk about solo founders being a huge risk factor yada yada you and i saw esther were getting into it back and forth on the twitter or the x uh you were posting on x about it it's gonna take me a right there you're you know there's upside and downside to each are you lonely as a solo founder is it harder do you wish you had a co-founder um or are you glad you're a solo founder i'm definitely glad i'm a solo founder i think one of the things i've learned over the last four years of running this company is the growth rate necessary to build and scale the startup is absolutely insane and you can't underwrite anybody's growth rate but yourself i've had amazing team members who just hit a wall um and i don't know how you would predict that honestly and honestly to put somebody in a position where you're either forced out you have to grow it's distracting to the business i always say loyal is a benevolent matriarchy right like there's no place where decisions get stuck i come in and i just cut it and i'm like let's do it and to be clear the majority of decisions that loyal are made by my executive team right i'm not a manufacturing exec i'm not an r &d exec i'm not a supply team exact but i'm there to drive the clarity and kind of keep them all working together for us it's been extremely efficient i am however also like an only child and kind of like a solo you lose to being yeah i mean yeah i tell i i think you have to know yourself you know i had a great co-founder brian alvey we had a wonderful relationship my best friend for many years still considered my best friend uh and i would immediately jump at the chance to co-found another company with him however you know he's got other things he wants to do i have things i'm doing and there's something about being a solo act i tell people like i'm bob dylan i don't play well in a band and now i'm forced to be in a band with the all in podcast and i can tell you it is not my natural state of being like you know i am obviously the front guy i'm the lead singer like i i just want to play the songs and i want to play the songs the way i want to play them i want to play them correctly and then when you know somebody wants to do it someone different and then they want to be the lead singer it's like well there can't be two lead singers you know like you can sing a verse but like you're the guitar player you're the bass player you're the drummer like do your job like and and i agree with you like i think for certain people you got to be the solo founder and you can go faster but it's very rare and then at the early stage having multiple ones you know why actually this whole thing got started with the co-founders it's that's it you nailed it it's in the interest of the investors so y combinator realized having three founders meant you didn't need as much money because yet and they only hired developers which is why it was very predominantly male at the start it's since they've corrected that but it was three dudes two dudes making reddit drop whatever you know uh you know airbnb no no just any of those companies i'm friends with everybody they've all been on the pod they're amazing but they went all developers all product designers because they were only giving them 16k or 25k in those early days yeah that meant the company was de-risked you lose one and they did lose one at a lot of these companies you lose one they lost one at youtube i think um you still have the other two so it's just de-risking i i think one of the most important things founders have to learn is that you should be humble and listen to advice and understand why people have certain positions but you also are responsible for the outcome in the end and you have to make a decision off of the data that you have independently right if i had gone and gotten a co-founder because yc and twitter whatever says i should have a co-founder i maybe loyal would have made it but i don't think so right i think it would have been much more difficult for us to have succeeded um you just got to do what you think is right and you have to be comfortable with that understanding when people are talking their book is i think one of the hardest things for startup founders to understand And every year at this time, when YC has a demo day, a bunch of investors come out and say, why are people raising a 20 to 30 million?

53:36They have a product in market for three weeks. This makes no sense. And it's like, well, they went to Y Combinator because Y Combinator creates a demo day with a bunch of dentists and newbie investors. And they just create this FOMO. And you got to invest in the next two days or else you're going to lose your spot. And the valuation is going up 1 million every week. All these tricks to create FOMO. And you think about YC's position. they're like well we have the best companies that could be true they they very well might have the best selection of companies of any accelerator i would say ours was just as good but putting that aside um they're investing at 1.7 million so of course you know 12 weeks after their program if somebody's raising at 25 million they're thrilled with that talk about de-risking they de-risk by having three people as co-founders but then they de-risk by having the valuation go 20 times or 10 times or 15 times what they invested at of course they love this situation and less dilution at the most round you got it and so everybody's talking their own book everybody i'm talking my own book right now uh everybody's talking about a competing accelerator right a competing accelerator and so as a founder always ask people like can you can you steal me on the other side of that and and i would just ask people blatantly like are you talking your book and what is your incentive to give me this advice and you know people will be honest about it i think um and people always advise you to do what they did i mean even i am right i'm saying solo founder is great you know if you talk to somebody's good co-founding relationship they're saying gonna say being a co-founder is great it's like that's i think the hardest thing to realize is you'll have to hit really challenging questions and problems and nobody out there knows the answer because you're at the forefront and you just got to figure it out um confirmation bias is real um you know hey this this plane made it back gotta be something about this pilot or this plane or something with the design or the mission something and this must be the greatest pilot ever matching founders that's another example matching founders i mean you experienced that as a female founder uh i'm sure people brought up elizabeth holmes 10 times to you and if they didn't they must yeah good i uh one time uh perhaps not as wisely given the marketing conditions now but a few years ago there was an investor wanted to invest five million in the company and then they made some like extremely offensive elizabeth holmes joke at me and i just nuked it i was like i can't i can't with this because it's actually really dangerous right to have people who like think that even if they don't think that on your cap table because inevitably somebody's going to come for me at that what was the joke what was the joke i don't even remember now it was just basically like basically are you going to start wearing turtlenecks you should start wearing turtlenecks you shouldn't deepen it's like you can tell when people jokingly ask you but they actually are like worried that you are um and it's like it's very common and it's i understand why right especially now with like ftx all these things that have happened people are very worried about being embarrassed it's very hard to diligence loyal even if you understand one aspect you can't understand all the aspects of the company and a lot of my fundraising strategies around like giving people chump insurance without realizing that they're getting chump insurance right and like helping them with the diligence but you still gotta you know not be sexist even if you're feeling insecure about your bio skills i mean yeah i mean pattern matching's a thing there could in fact be patterns the pattern of like people going to stanford are great entrepreneurs are we going to really actually argue that i mean it's one of the hardest schools to get into yeah and they specifically are across the street from sand they're on sandhill road it's literally on sandhill road if you're an entrepreneur proximity to sandhill road is going to be like a virtuous circle they put the they put their offices there they invested in folks and now folks go to stanford because they know the chances of getting funding go up and if you wanted to go for business you would have went to harvard or penn or wharton and or maybe wharton sits between the two in terms of entrepreneurship versus going to work at a big company so you do have to understand signaling but yeah signaling like you're a woman in health biotech broadly and she was a woman in biotech broadly but she was a scam so are you a scammer and it's like diligence is your job like by all yeah yeah biotech moonshot in common one was a sociopath doesn't mean everybody's a sociopath Well, that's probably one of the things I actually take really seriously, you know, succeeding in loyal, because I think that the only way to change a pattern match is to have positive examples, to have positive patterns and create positive patterns.

58:16And I think Silicon Valley could build 10x the number of deep tech companies than it does today. um i think you know i've built a company and we've done real very valid science that never would have been funded by traditional biotech and never would have happened and it only happened because of this pool of investors and the the mindset and that being applied to a problem uniquely and god knows how many more companies are like that that just aren't being started um so i i hope this is a big conversation and that's one of the reasons i write right because there's like no resources for building biotech and deep tech in this way because that culture of sharing doesn't exist in biotech as much yeah and deep tech is hard it's got longer windows it's actually a big discussion in the capital allocator community steve jervison's doing it his new fund is 15 years in terms of the life cycle so he's structuring it that way and i think you know what elon do with spacex has inspired a lot of people that like hard things are moats and so you know in palmer lucky and um i've got his co-founder's name nice guy from a founder's fund trey stevens um much nicer than palmer lucky actually in fact just a much much better human being than i'm joking palmer i'm joking that dude hates me so much um but i'm not joking but i don't think that's a drug there's here but i think andrew is you know standing on the shoulders Those are SpaceX, government contracts, you know, hard science, you know, and then now you, they, they basically proved it.

59:50And Founders Fund was in SpaceX, friend of Elon's. So Founders Fund gets more bold. And then you look at Dalian, who's just been on the program from Varda, like, you know, space labs and stuff like that. And all this getting government contracts, they're, they're all part of this little thread of people with some common investors, some common employees, who all know how to work with the government. Boom, you know how to work in pharma. so there'll be all these great new companies uh elizabeth homes notwithstanding all right listen you've been an incredible guest you got to come on again uh and just even to talk about startups is great so you got to promise me to come on in a year can we put it on the calendar uh for uh third quarter next year we get the update and we talk startups uh you got some great insights uh where can people find you and follow you and keep track of the company um i write on selenehh.com I'm on Twitter, Celine Hollywood.

1:00:39And yeah, I mean, in a year, we're going to know if this thing is going to make it or not. So it'll be an interesting conversation. If it doesn't make it, I'm going to be scarred for life. So I literally have a tattoo of the thesis on my arm. So I'm going to cut off his arm. Let me see the arm. Let me see the arm. You did not need to cut it off. So it's C. Elegant, the black six mouse and the black Labrador. This is the dog that they showed the lifespan extension in the first time the study I told you about. and then in the worm it's where they they made the genetic mutation that's the same one that we want to support dogs with so they live a longer life the larger dogs um founder i love it alexis was just talking about he knew reddit was going to be a phenomenon when somebody got the alien tattoo if you if you got tattoos of the logo and a lot of people get the apple logo that that's an easy one people doing that for a long time i bet you there's tesla tattoos out there in the wild as well i'm sure there are people are fanboys of tesla yeah listen you've been a great guest and uh yeah whenever you know if this is going to work or not let's have let's pop a bottle of champagne uh or we'll sit here and we'll amputate your arm or just you know we'll do we'll do laser removal you'll go through painful laser removal and then i'll ask you questions about why you failed and it'll just be this great post-mortem be the most exciting episode of this week it's ever you're getting laser remover you ever see somebody get that yeah it's It's like a light or something, and it's going, bop, bop, bop, bop, bop.

1:02:04This is retribution for you making stupid decisions in your youth to get tattoos that you had no intention of keeping. I hope you had a great time in Cancun. You should not have gotten this tattoo. Bop, bop, bop, bop, bop, bop, bop, bop, bop, bop, bop. And the people are crying. It's so painful. I love it. They should show those videos of how painful tattoo removal is to everybody before they get their tattoo. it should be like a requirement i'm a but it's a but terminal bias to action right it's like really good in startups really bad and like most other life things have you listened to the second time founders podcasts i have not shout out second time founders i'll check that out they have a really i bring it up because you're talking about postmortems they have a really interesting postmortem of clout um and oh yes klout store yeah um and it's i'd see only podcast i have found it really talks about a company that failed and what happened and why um so we've done those episodes here but you know what i want to formalize post-mortem let's do post-mortems once a month nick i think it'd be great in the rotation we do them in total at loyal what do you make mistakes yeah no i've been we've been doing it on our investment team and looking at hey what do we screw up and then after when we do like in-person events we do um what do we learn and so i have everybody the day after we go out to brunch or a lunch after an event hey what do we learn what's top of mind um you know and uh i call it lessons learned so people can be honest with you know language matters so i've gotten very soft doing oh yeah it's a big one right it's like okay what what did you learn and like a bad thing happening is still um it's still a learning so it's a good yeah see the original thing i wrote was a shared document that says what did you up and then somebody on my team said this is kind of negative jake how can you make it a little softer and i said lessons learned yeah i got in trouble for that too i'm known to have a body now this is why we're solo founders this is why solo founders because how we treat ourselves is not how human beings want to be treated but it's very efficient for building big things yes i was talking to a very high profile founder i won't say who and he was lamenting to me how he wants negative feedback people don't give it to him historically and then when he gives negative feedback everybody gets crushed and he's like please tell me how i could be better and then i feel like i'm talking to myself i feel like uh you're the more successful female biotech version of me you're are you brutal to people i think so i may be higher profile but i think you're going to be more successful although i did have a really good joke that i didn't drop when you said like i have never taken a drug uh you know i've never got a drug approved before and i was like not in high school in college like give yourself a break you're 28 kid you got time i think you'll be okay i'm old for tech and uh a child for biotech so fair point fair point uh all right listen we'll see you all next time on this week's hours bye-bye