Life Extension Innovations, Moonshots & Snake Oil (with Celine Halioua & James Peyer)
Newcomer PodSeptember 27, 202301:00:0555.01 MB

Life Extension Innovations, Moonshots & Snake Oil (with Celine Halioua & James Peyer)

I brought two top Silicon Valley entrepreneurs working on extending lifespans on the Newcomer podcast this week.

One of them is trying to help people live longer. The other, their dogs.

James Peyer, the CEO of Cambrian Bio, is acquiring majority stakes in drugs that could combat a particular illness while showing promise for broader use among healthy humans. Meanwhile, Celine Halioua, the CEO of Loyal, is developing drugs to make dogs live longer.

Fundamentally life extension, or longevity, is about finding drugs and treatments that can be given to healthy humans to help them live longer, healthier lives. Instead of just treating illnesses, entrepreneurs in the space want to find ways to stave off aging in already healthy people.

The space has long been a fascination of mine. In February 2022, I profiled Elad Gil’s investments in an array of companies looking to make healthy humans live longer, healthier lives.

The HBO show Silicon Valley helped popularize the idea that Silicon Valley elites were pumping their veins with younger people’s blood. (I’ve yet to get anyone to confess to me that they’re buying plasma.)

To the chagrin of this week’s guests, one tech mogul desperate to avoid death has received a lot of the attention recently. That’s Braintree founder Bryan Johnson.

Time magazine just profiled Johnson under the headline “The Man Who Thinks He Can Live Forever.”

Johnson, 46, is a centimillionaire tech entrepreneur who has spent most of the last three years in pursuit of a singular goal: don’t die. During that time, he’s spent more than $4 million developing a life-extension system called Blueprint, in which he outsources every decision involving his body to a team of doctors, who use data to develop a strict health regimen to reduce what Johnson calls his “biological age.” That system includes downing 111 pills every day, wearing a baseball cap that shoots red light into his scalp, collecting his own stool samples, and sleeping with a tiny jet pack attached to his penis to monitor his nighttime erections. Johnson thinks of any act that accelerates aging—like eating a cookie, or getting less than eight hours of sleep—as an “act of violence.” 

Even as Johnson is getting a lot of attention for his self-experimentation, there’s a growing view that there could be something credible behind Silicon Valley’s interest in life extension. The Economist just wrote that “slowing human ageing is now the subject of serious research.”

Many in mainstream science and medicine look at all this slightly askance. That is understandable. It is an area which attracts chancers and charlatans as well as those with more decent motives, and its history is littered with “breakthroughs” that have led more or less nowhere. America’s Food and Drug Administration does not recognise “old age” as a disease state, and thus as a suitable target for therapy. Nevertheless, evidence has been accumulating that such research might have something to offer.

Some established drugs really do seem to extend life, at least in mice. That offers both the possibility that they might do so in people and some insight into the processes involved. The ever-greater ease with which genes can be edited helps such investigations, as does access to large amounts of gene-sequence data. The ability to produce personalised stem cells, which stay forever young, has opened up new therapeutic options. And new diagnostic tools are now offering scientists means to calculate the “biological ages” of bodies and organs and compare them with actual calendar ages. In principle this allows longevity studies to achieve convincing results in less than a lifetime.

I dug in with Halioua and Peyer about where they saw the most opportunities, how their own companies were progressing, and why they thought Johnson’s publicity campaign was doing a disservice to companies working on longevity.

The duo helped break down the space, discussing which types of companies they think are innovators, which efforts are more speculative moonshots, and which ones are simply snake oil.

Give it a listen.



Get full access to Newcomer at www.newcomer.co/subscribe

00:00:01
Hey, it's Eric Newcomer. Welcome to the Newcomer podcast,

00:00:04
Probably my favorite episode ever.

00:00:06
This week a conversation with James Pyer, the CEO of Cambrian

00:00:11
Bio, and Celine Haliwa, the CEO of Loyal.

00:00:16
James is trying to help humans live forever, and Celine is

00:00:20
trying to help your dog live as long as possible.

00:00:23
We get into life extension and longevity, Silicon Valley's

00:00:28
chase to fight off death. You've probably read about tech

00:00:32
mogul Brian Johnson. He was just profiled in time,

00:00:36
who's desperately trying to figure out ways to optimize his

00:00:38
life to drag it out as long as possible.

00:00:42
Celine and James are skeptical of that effort.

00:00:45
Spoilers. We get into what's credible, the

00:00:49
moon shots and the snake oil in the life extension and longevity

00:00:53
space. If you're curious about Silicon

00:00:56
Valley's effort to live forever, you want to fend off death.

00:01:00
This is a great dive and with sort of serious players in this

00:01:05
space about the effort to find drugs that will keep people and

00:01:12
our pets living longer. Give it a listen.

00:01:15
Celine and James, thank you for joining the podcast.

00:01:18
Welcome. Nice being here, Eric.

00:01:20
Yeah. Thanks for having us life

00:01:22
extension longevity, like things everybody wants for themselves

00:01:26
and to know how they can live longer and it's a fun space to

00:01:30
talk about. So really, really excited for

00:01:34
this episode. I mean, I I think just start

00:01:37
off, can you each give the sort of 1st 30 seconds how you came

00:01:43
to the longevity space? Next 30 seconds, just like at

00:01:46
the high level, we'll dig into it more like what your company

00:01:49
does, so people know who we're talking to.

00:01:51
Celine, do you wanna start us off?

00:01:53
Yeah, so I got interested in aging and longevity kind of

00:01:58
indirectly. I was working, so my undergrad's

00:02:00
in neuroscience and I have an incomplete PhD in health

00:02:04
economics. And while I was doing research

00:02:06
in Neuro, we were working in a Parkinson's lab.

00:02:09
And Parkinson's, A neuro time disorder that is predominantly

00:02:13
caused by a loss of a certain type of neuron, that is.

00:02:16
Infamously difficult to treat with modern therapies.

00:02:19
And I remember sitting in this lab thinking, why are we waiting

00:02:23
until there's decades of damage and decades of neuronal loss?

00:02:26
So start trying to treat the patient instead of trying to

00:02:28
understand what led to them having this loss of brain

00:02:33
function. And so that kind of Long story

00:02:35
short, led me into the aging field, which the way I think

00:02:37
about aging drugs is preventative medicines for

00:02:39
multiple age-related diseases at the same time.

00:02:42
So not nearly as sexy as. Of 20 year lifespans,

00:02:45
immortality, saving Johnson's Johnson, things like that.

00:02:49
Sorry, I had to. We'll get into him.

00:02:52
We'll get into him. We'll get into that I'm sure.

00:02:54
And now I run a company called Loyal.

00:02:58
We're developing what we hope to be the first FDA approved drugs

00:03:02
explicitly designed to extend the lifespan and health span.

00:03:06
And we're specifically working on dogs, dogs.

00:03:09
So yeah, that's, yeah, that's the take away.

00:03:12
You're starting with dog. It's easier, we'll get into it,

00:03:15
but it's easier to extend the lifespan of dogs than humans

00:03:18
because of regulation, right. I mean, it's sort of regulatory.

00:03:22
It's honestly just a like a logistics thing or anything

00:03:24
else, right? Like a dog.

00:03:26
Well, like one of the core ideas is that big dogs live very short

00:03:29
lives. You know, a great day might live

00:03:30
678 years while Chihuahua lives 18 years.

00:03:33
You can see aging and you can see lifespan in a dog in a much

00:03:36
shorter period of time than you can or a person.

00:03:38
If I give you guys a lifespan extension drug, I'm not gonna

00:03:41
know if it works or not for a really long time.

00:03:43
Good luck like getting some VC to fund that, not the less the

00:03:46
clinical studies. My wife's family has a black lab

00:03:49
named Moon Unit that I've gotten very attached to and.

00:03:52
Well, we're working on it. Yeah, exactly.

00:03:54
Chop, chop. The realization that I, you

00:03:56
know, you're getting attached to a big dog halfway through their

00:04:00
life is sort of like, Oh no, what am I doing like?

00:04:03
Anyway, I have a senior Roddy who I'm in love with.

00:04:06
And yeah, yeah. So anyhow, that's what I'm up

00:04:09
to. All right, James, what about

00:04:11
you? How did you get into this space?

00:04:13
So my story starts in the late 90s when.

00:04:18
The the aging space was really act like academically in its

00:04:22
infancy in a lot of ways. And we had just kind of

00:04:25
discovered that there were these things inside of each of our

00:04:28
cells called telomeres that shortened every time a cell

00:04:32
divided. And a couple of books got

00:04:34
published in the late 90s when I was a student that said, hey, if

00:04:38
we can extend, like prevent the telomeres from shortening and

00:04:41
keep them long, then cells should be able to live forever.

00:04:45
And then sure enough, like right after that, we were able to take

00:04:48
normal human cells and let them divide an infinite number of

00:04:50
times by keeping their telomeres long.

00:04:52
And then that led to this explosion of, Oh my God, is this

00:04:55
the answer for aging. And it turned out not to be the

00:04:58
case, but it kind of sent me down this path.

00:05:01
Similar to Celine's story of like, this could be the core.

00:05:06
Not telomeres specifically, but like the study of why our cells

00:05:09
and our organs stop working as we get it.

00:05:12
Old that could be the key to keeping people healthy, the key

00:05:15
to preventing diseases from from happening in the 1st place.

00:05:20
Around the same time, my grandfather was diagnosed with

00:05:23
cancer, which kind of went from zero to 60.

00:05:27
And he was, you know, treated, failed treatment and was gone

00:05:33
within a year and a half of his diagnosis.

00:05:36
And I just saw how to Celine's point about Parkinson's.

00:05:38
Like how? Futile.

00:05:41
It was to wait for decades of molecular damage, right?

00:05:47
Decades of a disease to build up bit by bit.

00:05:49
Cancer I think, is a great example of this where it has to

00:05:52
go through one mutation, big expansion bottleneck, expansion

00:05:56
bottleneck before ever even thinking about how do we treat

00:05:59
this, how do we stop this from happening.

00:06:02
And for the past 20 years I've been either as a researcher or

00:06:06
for the last almost 10 as a kind of.

00:06:10
Investor, company, builder and now executive in this space have

00:06:13
been trying to ask the question how do we take these discoveries

00:06:17
from the academic world and understanding how our bodies age

00:06:21
and turn those into medicines with the thesis that's almost

00:06:25
100% aligned with with Celine that like this is not about.

00:06:30
You know, longevity or even health span.

00:06:32
That the the best and highest use of these breakthroughs in

00:06:35
our understanding is to create a new generation of preventative

00:06:39
medicines. That if you Fast forward 50

00:06:41
years, people are going to look at this research now and kind of

00:06:44
equate it with what happened in the first half of the 20th

00:06:47
century with vaccines and antibiotics.

00:06:50
These were the biggest killers of humanity.

00:06:53
And now we've figured out ways of understanding how they work

00:06:56
and how to get there before the disease like robs us of our

00:07:00
ability to to deal with them by becoming so complex and so, so

00:07:04
damaging. Cambrian is is kind of a unique

00:07:07
company that I run. So, so we partner with academics

00:07:10
who have made breakthroughs in aging research all over the

00:07:12
world, who have figured out ways to create a drug that can target

00:07:17
a different aspect of aging. And then we bring that into

00:07:20
Cambrian and move that forward into human clinical trials.

00:07:24
So we don't have any dog FDA stuff pending.

00:07:27
Our strategy is slightly different which is we find a

00:07:30
drug that has the potential to slow these aging processes to

00:07:34
prevent disease, to extend health span.

00:07:36
But we say, all right, well, this could be a great cancer

00:07:39
drug. It could be a great.

00:07:40
Drug for heart disease. It could be a great drug even

00:07:43
for like a rare orphan genetic disease.

00:07:45
So let's start there and after we show safety and efficacy,

00:07:49
then you can do something closer and closer to prevention.

00:07:52
The idea is you're picking drugs that you think would sort of be

00:07:56
useful to the general person or that have some reason why they

00:07:59
would be preventative. That's right.

00:08:02
And so we can get into some aspects of this, but it looks

00:08:04
actually like we're going to be able to start our first

00:08:06
preventative trial in human patients as early as the end of

00:08:10
next year. So you guys are both sort of

00:08:13
hinted at this, but just defining the space longevity,

00:08:16
life extension from what you're saying like there's a sort of

00:08:19
innocuous way to phrase it, which is just sort of

00:08:20
preventative medicine, right? Or am I wrong?

00:08:24
Is saying that like a core idea here is that most drugs are

00:08:28
meant to treat people where something's like clearly wrong

00:08:32
and there are somewhere outside of the human baseline.

00:08:35
And a key idea here is that even if you're at the human baseline

00:08:39
or over performing, are there drugs we should give you earlier

00:08:43
in your life that that give you a better outcome?

00:08:46
Is that the right way to think about it?

00:08:48
Would you quibble with anything or add anything there?

00:08:51
What I've found has been kind of the aha moment when I'm trying

00:08:55
to It's a lot of my job fundraising and also activating

00:08:58
and educating pet parents and vets is explaining what is this

00:09:02
aging thesis. And the way I think about it is

00:09:05
that as we get chronologically older, the cells that make up

00:09:12
our body accumulate damage. They, you know, accumulate

00:09:16
mistakes, etc. And these are inherently things

00:09:20
that occur overtime. And a disease that's associated

00:09:23
with this damage or decaying or loss of resiliency, a loss of

00:09:27
function, depends on where it's happening, right.

00:09:29
So if it's happening in your brain, it might lead to our

00:09:31
dementia or an urgent disorder. If it's happening in your joint,

00:09:34
it might lead to osteoarthritis, it's happening in your immune

00:09:36
system, it might lead to cancer. And these things are classically

00:09:39
thought of as completely unrelated diseases, right?

00:09:42
Having osteoarthritis considered mechanistically very different

00:09:45
from having Parkinson's and at the end stage.

00:09:48
They are. They are very mechanistically

00:09:49
different. An OA drug isn't going to most

00:09:52
likely positively impact dementia, but the underlying

00:09:55
drivers that led to a patient developing diseases, the

00:09:59
processes of aging, the processes of damage are

00:10:02
conserved or that's a piece of the field.

00:10:04
So if you develop a drug that targets the way a body breaks

00:10:07
down over time, it may have a positive impact on these

00:10:10
classical diseases that are today thought of as totally

00:10:13
separate and one like nice. You know anecdote to that is the

00:10:17
only lifespan extension study has been run to completion in

00:10:20
dogs. Was actually run by the dog food

00:10:22
company Purina in the late 1990s.

00:10:24
There was a cleric restriction study which is kind of the OG

00:10:27
way to extend lifespan is one of the reasons why tech grows

00:10:30
intermittent fast and they showed a tier lifespan extension

00:10:33
in Labradors. But more interestingly to this

00:10:36
thesis they showed A2 year delay in incidence of cancer and

00:10:40
osteoarthritis. Again, two single.

00:10:42
If they do what? Sorry, what's the?

00:10:44
Caloric restriction. So these two unrelated diseases,

00:10:49
cancer and osteoarthritis. There was a delayed incidence of

00:10:52
almost two years in these dogs who are calorically restricted

00:10:56
compared to the dogs that weren't.

00:10:59
And so that suggests that these dogs are potentially aging at a

00:11:02
slower rate or aging more healthily, which is why they

00:11:05
lived longer, but also why these unrelated age-related diseases

00:11:08
developed later. In life.

00:11:09
So that's how I think about it. And we can do this

00:11:11
pharmacologically as well. So like Celine said, like the OG

00:11:15
way of extending lifespan in animals was to just reduce their

00:11:20
number of calories. And like you go into this, your

00:11:22
body goes into this like famine preservation sort of mode.

00:11:26
Some processes run slower, but overall your lifespan is

00:11:30
extended and there's now more than 80 different.

00:11:35
Drugs or genes that you can tweak that not in dogs, which

00:11:38
are bigger and more complex and live longer.

00:11:40
My background is as a mouse geneticist, so so you know, I I

00:11:43
live in the world of mice more than dogs.

00:11:45
But in mice, you know their natural lifespan is only about 2

00:11:48
1/2 years. So you can run these studies in

00:11:51
mice really, really easily and with large numbers to get good

00:11:54
statistical confidence. And a drug like there's one

00:11:57
called rapamycin that a lot of people know about and talk about

00:12:01
which hits this this pathway called M Tor.

00:12:04
M Tor is one of the key pathways that is on when we're eating

00:12:07
three meals a day and gets kind of cranked down when we are not

00:12:12
eating three meals a day, right. When you eat once a day or you

00:12:14
know if you're reducing your number of calories and just by

00:12:18
giving small amounts of this drug to mice, you can increase

00:12:22
healthy lifespan by like close to 20%.

00:12:25
And you get exactly that same phenotype that Celine is talking

00:12:27
about where it's that the reason that the mice are living longer

00:12:30
and healthier is because they're.

00:12:33
Memory is working better, they get less cancer, their skin is

00:12:36
in better condition, their joints are in better condition.

00:12:38
And it's all of these things happening at once, because

00:12:40
you're fiddling with something core to how cells and tissues

00:12:45
function properly, not waiting for, like trying to untangle

00:12:49
that this very, you know, disease specific, what's the

00:12:51
name of that drug? It's called rapamycin.

00:12:54
Are people taking that? So this is.

00:12:56
A triggered. This is a whole, so rapamycin is

00:13:00
actually an FDA approved drug. And the things that it is FDA

00:13:04
approved for are and it's sort of like it's got a couple of

00:13:08
variants, but it was first approved as an immunosuppressive

00:13:12
therapy for people who are getting kidney transplants

00:13:14
because large amounts of this drug actually suppress your

00:13:17
immune system. And then it was kind of approved

00:13:20
for two other things which is treating sort of mid to late

00:13:23
stage cancer patients to prevent their tumors from growing.

00:13:26
And then finally there's a specific rare disease that where

00:13:30
this this pathway is cranked up that causes epilepsy and giving

00:13:34
this can reduce the number of seizures.

00:13:36
So those all three are like high doses of this and it's never

00:13:41
been widely experimented in low doses in humans.

00:13:44
Some people are self medicating but.

00:13:48
Man, we just don't know very much.

00:13:50
And the difference between the low dose and a high dose and

00:13:53
like when you jump into potential side effects versus

00:13:55
when your dose is too low and there's just going to be no

00:13:58
benefits. We have no idea in America am I

00:14:03
allowed as an individual to take a drug off label of my own

00:14:07
direction, or what sort of the freedom an individual has to

00:14:11
take a drug that's prescribed for one thing and mess around

00:14:14
with it for other reasons. So there's two levels here.

00:14:18
There's first what your doctor can do.

00:14:20
So a physician in the United States is allowed to prescribe a

00:14:26
drug off label with no restrictions.

00:14:29
If if your doc said hey Eric, like take this drug, it's for

00:14:33
breast cancer, but you know you have whatever and I want you to

00:14:37
take this. Like there is no authority that

00:14:40
can stop the doctor or you from making that decision.

00:14:44
There are two sort of like upstream ways that that happens

00:14:48
less. First is that your insurance

00:14:50
company may not pay for that drug and there are prohibitions

00:14:55
from, let's say I run the biotech company that created

00:14:58
that drug for breast cancer. I can never tell the doctor, oh

00:15:01
please. Also you know recommend it for,

00:15:05
I don't know cough or something like this, right?

00:15:08
So upstream, those are the protections we have in place.

00:15:11
But the doctor patient relationship is pretty open,

00:15:16
Yeah. Do you consider like Ozempic

00:15:21
wigovy to be life extension drugs you want?

00:15:25
To stop, You're the human guy. OK.

00:15:29
I can say intent put. Put that on my tombstone, the

00:15:33
human guy. I'll say this, my favorite

00:15:38
little anecdote about weight appetent suppressants is that

00:15:42
one of the bigger dog drug failures was a drug that was a

00:15:46
weight loss drug for dogs as approved years ago that worked

00:15:50
predominantly by suppressing the desire to eat and it was a huge

00:15:53
market failure despite the fact that dogs have a very high

00:15:56
incidence of obesity, just like humans.

00:15:58
The reason being is that people they perceive their dog wanting

00:16:02
dinner or wanting a treat as love.

00:16:05
And so when the dog suddenly isn't hounding you for dinner,

00:16:08
isn't hounding for a tree, and it's just kind of ignoring you,

00:16:10
they're like, God, my dog doesn't love me as much.

00:16:12
Like, oh, cheated. So one of the things we

00:16:14
explicitly look at in our studies is ensuring it doesn't

00:16:18
reduce desire to eat and doesn't reduce weight.

00:16:22
Because it would probably be a commercial failure, so I will

00:16:24
not be doing Ozempic for dogs. But James, I'm sure you have

00:16:28
more human biology expertise here.

00:16:31
So what I would say on the more critical side, jumping off from

00:16:34
what Celine was saying, is that Ozempic is not a drug that I

00:16:38
think is suitable for everybody, right?

00:16:41
We're not going to end up in a situation where really healthy

00:16:45
people who have a great diet and exercise are in relatively good

00:16:48
shape, but aging should go on Ozempic, right?

00:16:51
But it is a. Really damn good drug for

00:16:53
obesity, and it looks like the effects are just really powerful

00:16:58
for obesity and for type 2 diabetes.

00:17:00
Like this is worthy of its blockbuster status.

00:17:04
The main drawback that makes this from a risk reward

00:17:08
perspective, good for diabetics and people who are obese, but

00:17:13
not good for people who don't have those things.

00:17:16
Is that when you stop eating? Because that's the way that this

00:17:19
drug works, right? You.

00:17:20
You feel full even if you haven't eaten that much.

00:17:23
When you're not eating, you consume more fat for calories,

00:17:26
but you also consume muscle. So even for these people that

00:17:29
have a lot of extra fat, about 1/3 of the weight that they lose

00:17:33
is actually muscle mass. And if you look in people who

00:17:36
are older, right? So in your 20s and 30s, if you

00:17:39
lose a little bit of muscle mass while you're.

00:17:42
Cutting off a lot of extra adipose tissue, you can then hit

00:17:45
the gym and rebuild that muscle mass.

00:17:47
But like, once a person is about 60 or so, like, rebuilding that

00:17:52
lost muscle is really hard and it increases your risk of all

00:17:57
sorts of other things, right? It basically makes people more

00:17:59
frail, so they're more likely to fall, more likely to get

00:18:02
orthopedic or sports type injuries if they lose a bunch of

00:18:05
muscle. And so talking our own book

00:18:08
here, a little bit similar to what Celine's talking about in

00:18:10
her dogs, The drug that Cambrian has that is furthest along, it's

00:18:14
actually already treating human patients is a drug that also

00:18:19
targets. It's kind of like the flip side

00:18:20
of the Ozempic GLP, one coin where Ozempic makes you eat

00:18:25
less. But what if, instead, your body

00:18:27
thought it was exercising more? And so the same kind of group of

00:18:30
people that have been studying aging biology have known that

00:18:33
exercise is one of the best things we can do for aging since

00:18:36
forever. And the main way that our body

00:18:38
gets the positive benefits of exercise translated into

00:18:42
increased muscle mass and more calorie consumption is by

00:18:44
activating A pathway called AMPK.

00:18:47
And Cambrian has the first drug that activates AMPK safely that

00:18:53
has already started human trials.

00:18:55
And what we see is just like. In in obesity studies, you see

00:18:58
the same sort of thing where like you can put mice on a high

00:19:00
fat diet and they lose weight even if they're eating more than

00:19:06
than mice off the drug. How much?

00:19:07
That's more in that trial. So it's been in about 100 people

00:19:11
so far. And then the study that we're

00:19:13
doing will have about another 50 people treated over the next

00:19:15
year. And do you own that drug

00:19:17
outright or is it sort of a minority stake or how does that

00:19:20
actually work? So the way that Cambrian works

00:19:23
is we own a majority stake in every drug in our pipeline

00:19:28
underneath us, but we don't own 100%.

00:19:31
We kind of share that upside, usually with specific scientists

00:19:35
that have. Kind of been working on those,

00:19:38
those products, sometimes other investors as well that have been

00:19:41
working on these products since before we got involved.

00:19:44
So we're not like a private equity group that's coming in

00:19:47
and acquiring things. We're coming in and we're taking

00:19:50
a controlling stake, but leaving upside for other people that

00:19:53
aren't want to ride this train along with us.

00:19:56
It's a cool business model. While we're talking around

00:19:58
books, yeah, what's the drug that you have this farthest

00:20:00
along? For dogs.

00:20:02
Yeah. So one thing I wanted to quickly

00:20:03
note and then I'll answer your question is what James is saying

00:20:06
about safety is super key. It's like actually one of our

00:20:09
key philosophies when I started the company is the drug might

00:20:12
not work, but it shouldn't do any harm.

00:20:14
The way to think about the safety of an aging drug is, and

00:20:17
I believe there's a quote from an ex FDA individual is that it

00:20:21
needs to be basically as safe as water.

00:20:23
And the reason being is because if I'm giving you a drug today

00:20:26
to prevent something you may or may not get in the future and it

00:20:28
kills you tomorrow or maims you tomorrow.

00:20:31
That risk reward, it's not acceptable.

00:20:33
Or even having increased risk of something bad happening to you

00:20:36
like increased frailty is not acceptable.

00:20:39
So that's one of the challenges of the field and one of the

00:20:41
reasons like James and I are working on relatively simple

00:20:44
drugs, so to speak. There's a lot of companies that

00:20:46
are doing these like really sexy, you know, epigenetic

00:20:49
reprogramming, gene therapy, da, da, da.

00:20:51
And like my work might not work. We'll see.

00:20:53
But at least I can't speak for James.

00:20:55
I'm pretty sure you're mostly doing boring molecules.

00:20:57
I'm only doing boring molecules. And that's because safety is so

00:21:02
important and you just don't want to introduce variables when

00:21:05
you don't know how something will behave in the body.

00:21:08
I think that's also been key and this is an interpretation.

00:21:11
They haven't hit this to me explicitly, but I think that's

00:21:13
been key to a lot of our success with the regulatory bodies is

00:21:17
demonstrating safety far and beyond what is required of us

00:21:22
legally. To answer your question on talk

00:21:25
in our talk in our book, I was trying to think.

00:21:27
Have like a metaphor. Like a dog.

00:21:29
Our furthest along drug is a daily drug for old dog lifespan

00:21:33
extension. So for dogs of almost any size,

00:21:36
any breed, for already showing signs of aging and you know, if

00:21:40
everything goes well, we're running towards it being on the

00:21:43
market in 2025. Really 2025.

00:21:46
So lots of work. I know, I know.

00:21:48
It's so cool. Lots of work.

00:21:50
You you've passed some trial or is it the same with dogs we have

00:21:54
trials or? Yeah.

00:21:57
So we've completed the safety studies awaiting FDA feedback,

00:22:00
but it looked really nice. We've completed the efficacy

00:22:04
work, awaiting feedback from the FDA.

00:22:06
And then the thing that kind of determines our go to market

00:22:08
timeline is actually manufacturing.

00:22:11
And manufacturing is like a pain in the ass.

00:22:12
It's hard, don't get me wrong, but it's a great problem to have

00:22:17
because it's completely physically possible to

00:22:19
manufacture a beef flavored pill at scale.

00:22:22
It's really just like how operationally competent are we

00:22:24
ever gonna pick the right supply chain partners, We're gonna

00:22:27
manage them correctly or we're gonna see around corners.

00:22:29
So you know if we're wrong and like we're quarter delayed or

00:22:32
something. It's not a binary existential

00:22:34
thing. Assuming the FDA agrees was the

00:22:36
technical packages that we believe are very strong showing

00:22:39
that the drug does what we think it does, what's the mechanism

00:22:43
for this drug? Yeah.

00:22:44
So kind of what James was talking about earlier with

00:22:46
caloric restriction when we started the company, we wanted

00:22:49
to take his little biological risk.

00:22:51
As possible, right? Like it is almost certainly true

00:22:53
that you can extend a dog's lifespan with a drug because

00:22:56
we've done it and everything from you know yeast to mice all

00:22:59
the way up and there's correlation data and people.

00:23:01
So it'd be weird if that wasn't possible also in dogs.

00:23:05
The question then what is the highest probability and also

00:23:07
safest thing that we could use in dogs to show that a drug can

00:23:10
be approved for lifespan extension.

00:23:12
And so as I mentioned earlier, the only lifespan extension

00:23:15
study that I'm aware of that's been run to completion and dogs

00:23:17
is at Purina lifespan extension study, which is using chlor

00:23:20
restriction. And so the drug emulates the

00:23:23
benefit or the molecular impact that has had on the dogs when

00:23:27
they chlorically restrict specifically working on

00:23:30
metabolic fitness and also fat tissue function and the

00:23:33
age-related decline of fat tissue function.

00:23:37
Cool. I mean we've sort of touched on

00:23:39
sort of different parts of life extension you both have invested

00:23:43
also and sort of see the space just sort of like a framework of

00:23:46
sort of the different categories of longevity that we're sort of

00:23:51
seen from what you're saying you're like okay, we're like

00:23:54
simple molecule to sort of the most like far out there which

00:23:58
you said like epigenetic or just give me this sort of roadmap of

00:24:02
the different buckets of this that are happening right now.

00:24:06
I can take a shot at that one. Yeah, I know that's like the

00:24:09
bucketing the world. That's like frameworks.

00:24:11
Yeah, yeah. And he's the real investor.

00:24:13
I just late investor. I did, I was at Longevity Fund

00:24:17
and I like invest a little bit personally, but I'm a much

00:24:20
better founder than I am investor.

00:24:22
So the way that I look at this space, I'm gonna give a title to

00:24:28
three different buckets. I'm gonna call them innovations,

00:24:32
Moon Shots, and Snake Oil. And I think spicy.

00:24:37
I love it. Come with the spice, James.

00:24:39
Like innovations, Moon shot? Reading on this podcast and

00:24:42
snake oil. Yeah, hell yeah.

00:24:44
Who's gonna be in the snake hole, loyal?

00:24:47
So, so I would describe innovations as anything that

00:24:53
looks an awful lot like other preventative medicines that we

00:24:58
can like draw a Direct Line from that work to us.

00:25:02
Right. And there's a series of

00:25:04
preventative medicines that I think are really going to be

00:25:06
useful comparators to the first true drugs that we think of as

00:25:11
coming out of the longevity or aging biology space that like

00:25:13
everyone's going to draw comparisons to like statins,

00:25:16
right. So we already talked about

00:25:17
Ozempic, which I think is going to have a lot of comparators

00:25:20
because a lot of these drugs are going to come in for cardio

00:25:22
metabolic disease. Statins is the other fantastic

00:25:24
example where like you have a risk factor and you.

00:25:28
They start giving people a drug based on their risk factor to

00:25:31
prevent heart attacks and strokes and so.

00:25:33
So I think those parallels which like Selena already touched

00:25:36
upon, they are every single one of them small molecules that

00:25:41
have a really good safety profile that target well

00:25:45
understood molecular mechanisms mostly having to do with

00:25:49
treating metabolic health. There's this big mess of cardio

00:25:53
metabolic, like how our heart works and how our our metabolism

00:25:56
work. That's sort of where the first

00:25:59
wave of innovation, I call it the first dominoes to fall, are

00:26:03
going to be in that innovation bucket.

00:26:05
My second bucket is moonshots, which is like we have some

00:26:09
really powerful, interesting ideas, many of which are getting

00:26:13
funded, that are sort of like a next layer of where this space

00:26:18
could go. And things like, you know,

00:26:20
probably the interface between innovations and moonshots is

00:26:23
like biologics that we have. For example, there's a protein

00:26:26
that's naturally produced in people that when it's present

00:26:31
prevents a woman from going into folliculogenesis, prevents

00:26:36
someone from ovulating so. So with an injection of this

00:26:39
protein, one could potentially completely control ovulation,

00:26:43
which we think if you then maintain the ovarian reserve,

00:26:47
could prevent menopause. Like, that's a cool ass idea,

00:26:51
right? It's more complicated than a

00:26:53
small molecule daily pill that's affecting metabolic disease.

00:26:57
But like, that's the kind of cool moon shot type approach

00:27:02
that one of the ones that we're taking.

00:27:04
There's also stuff like reprogramming.

00:27:07
The epigenetics of a cell is one that's talked about a lot to

00:27:10
like a more immature state. So that then it can become kind

00:27:13
of repair damaged tissues. It's another moon shot that has

00:27:16
like some really promising data coming out.

00:27:19
Especially there's a company called Life Biosciences that has

00:27:22
reversed like eye diseases or optic nerve damage in monkeys

00:27:27
already and like so that will be probably used for more specific

00:27:32
functions, right? Like in the.

00:27:35
Menopause case, it'll probably be used in IVF first.

00:27:38
The epigenetic reprogramming will probably come out in like

00:27:41
nerve degeneration in the eye 1st.

00:27:43
And then if it's safe, if it's really, really safe, then it can

00:27:48
expand, especially if it can walk in the sort of footprints

00:27:53
in the snow made by the innovative drugs, right.

00:27:56
And one of the reasons I'm so excited about the work that

00:27:58
Selena's doing is because of the strategy that she's taken in

00:28:01
Dogs Like She's. Jumped ahead of the rest of us,

00:28:06
you know just human people in terms of talking about this

00:28:09
multi disease prevention, correcting metabolic dysfunction

00:28:13
to prolong health span and like hopefully that will allow us to

00:28:18
walk in loyal's footsteps a little bit as we talk about

00:28:20
doing this in people. Yeah, you guys are welcome.

00:28:24
I think it should take a tax on all the longevity companies.

00:28:27
Like you guys need to give me like 5% of your fund.

00:28:32
Especially the epigenetic companies that raise like a

00:28:34
billion dollars. I mean, and to be honest, I

00:28:37
wanna say like this, this moon shot category, I don't wanna

00:28:41
throw any shade at that because I think that those techniques

00:28:45
and technology and the biology underlying a lot of this is

00:28:48
really damn exciting. It's.

00:28:51
Throw some shade, I can throw your well, yeah, we're all

00:28:54
waiting for the snake oil category.

00:28:56
Come on. Okay.

00:28:57
And then the third. 1 can be thrown here too though.

00:28:59
Right. The third one for me is then the

00:29:01
snake oil category, which is basically everybody who is

00:29:05
taking advantage of the fact that longevity has become one of

00:29:08
the biggest, let's call it mega trends of like fascinations of

00:29:12
people, especially in the developed world over the last

00:29:15
three or four years. And realize that even without

00:29:20
validating any new technologies, we can just like sell stuff to

00:29:24
people who are scared of their own mortality and scared of

00:29:27
their own decline the way that humans are.

00:29:30
If you're super rich post post wealth, what do you wanna spend

00:29:33
your money on Like living longer?

00:29:35
Higher quality of life? And especially if you control a

00:29:38
venture fund, not even your money.

00:29:40
What do you wanna throw it at? Things that could.

00:29:42
Yeah, it's interesting, I think that.

00:29:46
Where the bigger bucket of snake oily things are living is

00:29:50
outside of the venture backed company space.

00:29:52
It's more in the direct to consumer space stuff that's like

00:29:55
we want to sell stuff to people. Now what can we sell?

00:29:57
What can we make profit on today?

00:29:59
That's the biggest snake oil bucket.

00:30:01
We're like the red flag that jumps in my mind is like, OK, is

00:30:05
your R&D and clinical trials, is that coming out of an actual R&D

00:30:09
budget or is it coming out of your marketing budget so that

00:30:11
you can run ads on Facebook and Instagram saying?

00:30:15
Clinical trials suggest this. And if it's the latter category,

00:30:18
it's probably in the snake oil bucket.

00:30:20
I think there's been a bunch of efforts over the past three or

00:30:25
four years to try to establish some kind of standard around

00:30:28
what good looks like and it all kind of funnels down to are you

00:30:33
going to run clinical trials to test whether this thing actually

00:30:39
works before you start selling it?

00:30:41
And if the answer is yes, you're probably in bucket one or two.

00:30:44
If you're serious and the answer is no, or you say you are, but

00:30:48
you've really got no shot at it and there's no real plan there,

00:30:51
you're probably in bucket 3. The snake oil companies are, you

00:30:55
know, you could argue that they're like trying to get

00:30:57
things to consumers immediately. Drugs take years to get approved

00:31:00
da da da da. But I think that they don't

00:31:02
realize, like the biggest hurdle I have to overcome when I'm

00:31:04
educating veterinarians and regulators, what we're doing is

00:31:07
that it's legit, right? Like the number one pushback we

00:31:11
get is It sounds too good to be true or.

00:31:14
Is this, is this really real? Is this just like, you know

00:31:16
fountain of youth stuff And that's dangerous.

00:31:19
It's dangerous for a field because it means legitimate,

00:31:21
skeptical people are not going to engage in it or much more

00:31:24
difficult to engage in it. So all the kind of, you know,

00:31:28
we're here to make thousand year lifespans, even 120 year

00:31:31
lifespans. Like, maybe it's possible, but

00:31:33
leading with that is was so unnecessarily controversial was

00:31:36
often just an attempt to get, you know, earned media so more

00:31:39
people will buy their thing versus leading with, you know?

00:31:44
Good science and that these are preventative medicines to reduce

00:31:46
risk of future disease, which is the most consensus thing on the

00:31:49
planet, right? To reduce the risk of developing

00:31:52
a future disease cheaply and safely.

00:31:54
So yeah, these people piss me off.

00:31:56
What are people shit every day? You know this?

00:31:59
I mean, it's like they're sort of like vitamin type pitches or

00:32:02
what? Vitamins are common, yeah.

00:32:06
So I think there's also a bunch of like.

00:32:09
Interventional stuff that can be done without regulation.

00:32:12
So there's a big push in stuff that.

00:32:15
And like, the big tragedy for me is some of these things may

00:32:17
actually be helpful. We just don't know because no

00:32:19
one's really like the worst. People are so busy selling this

00:32:23
that no one's really asking the scientific questions, right.

00:32:25
So there's like people out there, you know, offering 10s of

00:32:30
$1000 for your daily hyperbaric oxygen containment and like.

00:32:36
You know, you got to do these ice baths and you got to do

00:32:38
these skin treatments and you got to do this, you know,

00:32:42
plastic transfusion. Yeah, OK.

00:32:44
That like. Like those things do exist.

00:32:46
Blood transfusion in the room. Like do you where is that fit in

00:32:51
in this because I mean blood boys, I feel like that's what

00:32:54
sort of the regular persons taken from Silicon Valley or the

00:32:57
show or whatever, you know? So I think it's a perfect like

00:33:00
microcosm of. Both the scientific potential

00:33:04
and the hucksterism and snake oil possibilities of this.

00:33:08
Cuz like if you go down to what got people excited, there are

00:33:11
some mouse experiments where you took young plasma, put it into

00:33:15
an old mouse, and the old mouse just got better in a lot of

00:33:19
ways, right? And you take the old plasma, put

00:33:21
it into the young mouse, the young mouse behaves worse.

00:33:24
Figuring out why exactly has been.

00:33:28
Actually kind of a fraught scientific odyssey where we

00:33:30
still don't have good answers as to why after almost 15 years of

00:33:34
looking at it. And there have been some

00:33:37
companies. The one that I'm most admiring

00:33:40
of is called Alkahest, which spun out of Tony Whiskerrey's

00:33:43
lab at Stanford and actually created what they called drugs

00:33:47
based on chrono kinds. So things that either go up as

00:33:52
you age and therefore you want to remove, or go down as you age

00:33:55
and therefore you want to replace.

00:33:56
And they were able to use this to say like, oh, well, these

00:33:58
could be good drug targets. And they were actually bought by

00:34:02
the biggest plasma company in the world called Grifols, which

00:34:06
is a Spanish pharma company. And they were as like a positive

00:34:09
story both from a pharma perspective and from a venture

00:34:13
kind of like investment perspective.

00:34:15
So like, that's a nice little story that I can get behind and

00:34:18
I have a lot of respect for the people of Alca Hest doing

00:34:20
something hard and pioneering and then on the other side you

00:34:23
have like. Whether it's people trying to

00:34:25
open individual clinics or or physicians or non physicians who

00:34:30
are like OOH, I'll bet we can sell plasma for whatever $4000 a

00:34:36
pint to people who heard about these mouse experiments and for

00:34:40
whom we have really no evidence that this will help them.

00:34:42
But you know, there was a piece in the Guardian or whatever

00:34:46
saying that it worked parentheses in mice.

00:34:50
And like that's that snake oil bucket.

00:34:52
And like I would say 98% of the conversation that we hear in the

00:34:56
media or out in the lay press is about that second bucket and 10%

00:35:01
is about the actual science that has been making some positive

00:35:05
steps. And there's a couple of other

00:35:06
companies that are trying quietly to do some hard but

00:35:09
interesting work in that space. We're not one of them.

00:35:12
But I have a ton of respect for those people and I think that

00:35:15
the core scientific insight, like there's probably something

00:35:17
there that could be important. We just don't know exactly what

00:35:20
it is. Yeah.

00:35:21
All right. I feel like this is the time to

00:35:23
bring up Brian Johnson, which I have generously not led this

00:35:26
conversation with. But, you know, he's the rich guy

00:35:30
who's, you know, doing a bazillion different things to

00:35:33
extend his life, recaptures youth.

00:35:35
The media is, like, fascinated by it, you know.

00:35:39
Yeah. As serious people in the space,

00:35:41
what do you make of what he's trying to do?

00:35:46
My short answer is I think the best thing Brian Johnson could

00:35:49
do to extend his lifespan would be investing in loyal or

00:35:53
Cambrian or another legitimate aging company.

00:35:57
Does it have to be us? I understand the grift, but I

00:36:02
think he doesn't understand pharma and drugs and the reality

00:36:07
of actually getting something approved.

00:36:09
I don't think he's ever going to work getting something approved

00:36:12
or statistics, you know, science.

00:36:14
Physics, you know, all these things, which is fine.

00:36:18
You don't have to. I mean, I I can't code right,

00:36:21
but it actually slows down the progress of the field.

00:36:26
Like the biggest issue I have to worry about when I'm fundraising

00:36:31
is making sure people don't feel like we're the next serrano's or

00:36:34
like other illegitimate thing that's going to embarrass them.

00:36:36
Embarrassment insurance. Trump Insurance is a huge thing

00:36:39
that I have to build into everything I do when I'm

00:36:42
fundraising for this company. And I'm a really fucking good

00:36:45
fundraiser, right? So think about like, how many

00:36:47
people who have, like, interesting scientific concepts,

00:36:50
new drugs that should get piloted.

00:36:51
I just aren't happening because there's such a negative bias

00:36:54
when you're coming in with this field.

00:36:56
It's not just because of him. But he sure as hell isn't

00:36:58
helping, and I wish you'd use his platform to educate in a way

00:37:04
that would promote the entire field and not become a problem

00:37:06
that I I literally have to explain away probably once or

00:37:10
twice a week. Are there things that he's doing

00:37:14
that make sense or don't, or I don't actually know all the

00:37:16
different? Do you have a sense of what he's

00:37:18
actually doing? People are constantly

00:37:21
experimenting with their own sort of personal fitness to try

00:37:26
to make themselves healthier. This is something that at

00:37:29
different scales, we're all doing right.

00:37:31
Many of us are taking some supplements, whether it's just a

00:37:33
multivitamin or fish oil or more exploratory things.

00:37:37
Beyond that, we change our diets, right people go keto

00:37:40
people, do paleo people. Get breakfast right?

00:37:44
So, like that kind of playing around with diet and exercise

00:37:50
and supplements is something that so many people are doing

00:37:54
day-to-day by themselves. And this is just sort of like a,

00:37:57
you know, twenty 20s. Internet like look at the far

00:38:01
extreme and trying to spotlight on that version of what people

00:38:04
have been doing forever. But as far as scientific value

00:38:07
like what this could give to the community of like understanding

00:38:10
something, there is 0 value in any of the stuff that he is

00:38:14
doing. Like anyone who has thought

00:38:16
about like how we move from theory to truth in medicine

00:38:22
knows that you have to change one variable at a time.

00:38:25
You have to do it in a large number of people and.

00:38:29
Then you can Start learning little things and it would takes

00:38:33
years to learn little things. So saying like, hey, I'm gonna

00:38:37
change this and that and I'm gonna combine 20 different

00:38:40
things into my protocol and like what's gonna come out of it is

00:38:43
like I feel a little better. I feel a little worse for one

00:38:46
person. There's no scientific value in

00:38:48
that. There's only media value in it.

00:38:50
Yeah, this is such a meme with Silicon Valley tech people, I

00:38:54
cannot tell you the amount of tech what for to talk out is.

00:38:57
Massive combo studies. So like, Wow Pharma is so dumb.

00:39:01
They only use one drug at a time, but aging is complex and

00:39:05
they should use multiple drugs at a time.

00:39:07
And we're going to do these combo studies and I'm like 1.

00:39:10
Like the path of getting that approved is like, good fucking

00:39:12
luck. But two, you can't actually

00:39:15
attribute and tell like aging is such a complex thing.

00:39:17
We haven't even gotten one thing through.

00:39:20
You're not going to be able to then like, start.

00:39:23
Like all the all the other way and have like multiple things

00:39:25
that you're permitting over a long period of time.

00:39:28
Like these studies take even for us and dogs, we're running a

00:39:30
pivotal lifespan extension study.

00:39:32
It's going to be at least four to five years and that's in

00:39:35
dogs. Like in people it's going to be

00:39:37
way longer. So like usually with somebody

00:39:39
saying, oh, pharma is so dumb, why didn't they just realize

00:39:42
XYZ? The answer is they have realized

00:39:45
and there's probably a reason they're not doing it.

00:39:46
And there's a lot of other things wrong with pharma to be

00:39:48
clear that like, you know, me and James are like, you know,

00:39:51
working on countering. But they're not done.

00:39:54
That was exactly my question. I mean, yeah, it seems like a

00:39:57
premise of some of the longevity spaces, that there's something

00:40:00
wrong with Pharmaceutical industry, sort of traditional

00:40:05
medical investing, drug development.

00:40:07
Like. Another way of asking that is

00:40:09
why should venture capitalists who aren't experts in this be

00:40:12
the ones asked to fund something?

00:40:14
It sort of suggests that there's something broken about the

00:40:17
traditional model, or that this is fundamentally different in

00:40:20
approach. I see that on you know some of

00:40:23
the moon shot ones you guys are talking about, but if you're

00:40:25
positioning yourself as more as we believe in standard clinical

00:40:28
trials, we want to be you know incrementalist to the extent

00:40:31
that's that's possible. Yeah.

00:40:33
So I I would say this is probably the stake around which

00:40:37
I've built my whole career and something that I've brought to

00:40:42
what attribution I can claim for it myself versus all of the

00:40:45
other people who have been. Kind of touting a similar idea.

00:40:49
But the fund that I built before Cambrian and now Cambrian as one

00:40:54
of the larger sort of drug developers in this space was

00:40:57
premised around the idea that it's not that the FDA is broken,

00:41:01
it's not that pharma is dumb and ignoring this, It is in fact

00:41:04
that we are at the precipice of a brand new revolution in

00:41:09
science that is just now ready and mature enough for drug

00:41:12
development. And it is this.

00:41:14
Fertile ground of new science that is going to make the great

00:41:18
drugs of the next 10 or 20 years.

00:41:21
In the same way that, like, you know, 20 years ago you'd want to

00:41:24
be studying basic mechanisms in cancer, which made the best

00:41:28
drugs of the 20 Tens and the and the 2000s.

00:41:33
And like 15 years ago, you might have been wanting to study basic

00:41:36
mechanisms of metabolism and obesity, which led to like the

00:41:39
GLIP ones and these sorts of things now.

00:41:42
This is not different than the rest of pharma innovation, and

00:41:45
it's going to create drugs that are going to be the most

00:41:48
important drugs of the next 10 or 20 years.

00:41:50
That's the investor pitch and the pitch to pharma and to the

00:41:55
FDA that is both most rooted in what the actual scientific

00:41:59
reality is and gives the most upside for people spending their

00:42:04
time and money making this space happen.

00:42:07
So I think that's like the stake.

00:42:09
I, I always called it the stepping stone approach to kind

00:42:13
of bringing these aging drugs to their best and highest use,

00:42:16
which is try to find whichever way makes sense to make those

00:42:19
discoveries coming from the basic biology of aging, show

00:42:23
that they're safe, effective and ultimately profitable right as

00:42:27
quickly as possible. And then you can start doing

00:42:31
what me and Celine are most excited about, which is what

00:42:34
happens when you start giving this sort of tool.

00:42:37
Into the hands of someone where they can use it for prevention

00:42:40
before they get sick. And that's not an easy thing to

00:42:42
do first, because you need to know in humans that something is

00:42:45
really safe and really effective before you can start doing that,

00:42:49
generally speaking. Yeah, one thing I will say here

00:42:52
that was that I think loyal is a really good example.

00:42:55
So I agree with everything in jail said.

00:42:57
Like one of the things we've done is like, we try to be like

00:43:00
the hill we die on, the hill that we're radical on as a drug

00:43:02
approved for lifespan and healthspan, extension and

00:43:04
everything else, we are extremely.

00:43:07
Traditionally competent on right.

00:43:10
It's like I'm you know the the young techie founder, da, da,

00:43:15
da, whatever of the company. But like my executive team are

00:43:17
experienced pharma executives right?

00:43:20
Like they're the best possible people for a job.

00:43:22
One thing I will give tech a lot of credit for is loyal never

00:43:24
would have been funded by traditional biotech investors of

00:43:27
biotech funders, right. I was 24 years old when I

00:43:30
started the company. It was basically my first job,

00:43:32
like I worked for Laura, but it was a two person fund.

00:43:36
We were working on dogs, we were working on lifespan extension

00:43:39
and we didn't have anything right.

00:43:41
It was an idea and an insight, and this side ended up being

00:43:44
correct but nothing else. Who took the first bet?

00:43:47
Laura and Greg Rosen, Greg's A Box Group and Laura's at

00:43:51
Longevity Fund and then First Round and Collaborative Fund.

00:43:54
We're also big investors in the seed round and I mean we'll see,

00:43:57
but so far so good but. This is definitely something

00:44:01
that, like, I don't think I could have walked into the

00:44:03
traditional East Coast biotechs. They would have laughed me out

00:44:05
of the room. They would have said, like,

00:44:06
apply for our associate program. Like, we'll consider you maybe

00:44:10
actually, just kidding, you didn't even like finish your

00:44:12
PhD, go home. And so I think there's a line

00:44:15
where I take that very seriously that I've brought.

00:44:19
Like most of my investors, I'm one of the first times they've

00:44:22
invested in a biotech or company like this.

00:44:25
I have got responsibility. Super.

00:44:26
Seriously. Because I want them to invest in

00:44:28
more companies after us and more weird companies.

00:44:31
But again, it's like I don't take advantage of that situation

00:44:34
by being radical and like doing shit that like reduces

00:44:37
probability of success. Like we still are very

00:44:39
conservative and everything else except for the radical core

00:44:42
ideas of you know a young solo founder woman can build a dog

00:44:46
longevity company and a consumer brand around these

00:44:48
pharmaceutical products and like hopefully get it approved for

00:44:50
lifespan extension. So it's a balance, right?

00:44:53
But I think like a lot of these snake oil people really take

00:44:56
advantage of the fact that the average Silicon Valley person

00:44:59
doesn't understand science or how a drug is approved at all.

00:45:02
Yeah, you know, there's this sort of meme that Silicon

00:45:05
Valley, you know, hasn't been friendly enough to women.

00:45:08
I mean, certainly there aren't sort of as many women founders

00:45:11
as you would like. But it's interesting that you're

00:45:13
saying in some ways that you found VC sort of more open to

00:45:18
the idea of sort of young founder type at least then and

00:45:22
you think would. Have been totally.

00:45:24
I mean, there's a ton of sexism in Nessa.

00:45:27
Like, don't get me wrong. Like the way I would explain it

00:45:30
is like when I walk into a room, the assumption of my competency

00:45:33
is not zero or positive. Like it might be of a much

00:45:36
traditional like bro founder. It's usually negative and then I

00:45:39
have to work within that conversation to get them to zero

00:45:42
and positive. We're just frustrating because

00:45:43
I'm like, I have a lot to learn, etc.

00:45:47
But I am a really good operator. Like, we've gotten this company

00:45:49
really far in four years with a lot less money than a lot of the

00:45:52
other groups have had. And again, starting from zero.

00:45:55
But I've kind of gotten like, I used to just get so pissed.

00:45:58
Like, I remember I pitched one fund and afterwards I called the

00:46:00
partner. I was like, do you not realize

00:46:02
your stupid GP was mansplaining longevity to me the entire time?

00:46:05
Like, I got so, so irritated, and now I'm just like, whatever,

00:46:10
it's fine. I'm gonna be richer anyhow than

00:46:12
these guys. And like, I'll create my own

00:46:14
fund and support. People building interesting

00:46:18
stuff, but you just gotta play the game to win the game.

00:46:20
And the game has the rules it has.

00:46:21
So I've just been wondering, this whole time, is loyal only

00:46:25
about dogs, or is this like a road map to humans?

00:46:28
I'm sure there's a world where it's like you get the perfect

00:46:30
drug, you're ready to go. But like, how do you think about

00:46:33
it in terms of your focus? So it's both loyal has I believe

00:46:39
a relatively like. Hard but straightforward path to

00:46:43
a multi billion dollar company just off the dog aging drugs.

00:46:46
Just if you look at comparable market size dog drugs like

00:46:49
heartworm, preventative heart guard makes half a billion a

00:46:52
year flea and tick next guard made $1.2 billion last year of

00:46:56
revenue, high margin revenue. So there's a clear path there

00:46:59
and if we only do that that's really awesome.

00:47:02
But dogs are also the best or one of the best biological

00:47:06
models of human aging because it Co evolved with us a shared

00:47:08
environment for 10s of thousands of years.

00:47:11
And most importantly to develop age-related diseases over time.

00:47:15
So a dog gets cancer not due to you know it should ton of

00:47:18
inbreeding like a mouse has but just environmental factors.

00:47:21
A dog gets never thought to get nerve disorders.

00:47:24
Dog gets dementia that we've looked at cognitive decline in

00:47:27
dogs. My favorite study we ever ran

00:47:30
was a cognitive decline study in dogs.

00:47:32
They get osteoarthritis. And so if something works in

00:47:35
reducing the onset of cognitive decline or cancer or whatever in

00:47:39
a dog, which will learn in this thousand dog companion dog study

00:47:43
we're running later this year, starting later this year, it's

00:47:46
not 1 to 1 to work at a human, but it's as sure as hell really

00:47:49
awesome biological insight that might translate over.

00:47:53
So yeah, I mean my goal is to build an aging pharmaceutical

00:47:56
company. I think agings need larger than

00:47:58
oncology. There's no one oncology company.

00:48:00
There's no one Parkinson's company.

00:48:02
There's gonna be many, but I wanna build one of the defining

00:48:05
ones. And hopefully James does too,

00:48:08
and we'll be able to talk about the good old days.

00:48:10
James, you can go after a bunch of drugs at once, I guess, so

00:48:13
you sort of get to hedge your bets.

00:48:14
Yeah, I think I know where you're going, which is something

00:48:17
along the lines of like we get asked a fair amount, What does

00:48:22
like are all of these people who are trying to do real drug

00:48:25
development within this? Broad aging biology.

00:48:28
Space. Aren't they all competing with

00:48:30
each other? Isn't everyone like trying to

00:48:32
get the first drug to increase health span and that will be

00:48:36
like the pot of gold at the end of the rainbow that one person

00:48:39
wins? And it's really fascinating

00:48:41
because this ecosystem, this kind of community is uniquely

00:48:49
collaborative within any tech or biotech or pharma.

00:48:54
Kind of competitive landscape that I've ever seen because so

00:48:59
many of the drugs are targeting completely different things,

00:49:03
right. So like you have Ozempic and and

00:49:05
like Novo Nordisk has their GL P1, right.

00:49:08
And then Lily has their GL P1 and it's you're going to take

00:49:11
one or the other, right. And and like they both wanted to

00:49:14
go and they're like Headtohead competing with each other.

00:49:17
Celine's drug and all of our drugs, they don't even target

00:49:19
the same molecular pathways. They're just kind of coming from

00:49:23
the same broad field of how we studied cellular biology.

00:49:27
So Cameron has 15 different drugs and development and none

00:49:30
of them are targeting the same two things.

00:49:33
This is something so much broader than just like, oh, we

00:49:37
found a new way to treat obesity like and it's this pathway which

00:49:41
is how you get real head to head competition.

00:49:43
This is instead like we've just opened the doors to hundreds of

00:49:48
new ways of approaching cellular dysfunction, at its core, of

00:49:52
which some will be right and some will be wrong.

00:49:55
And they're even going to be approved for different things

00:49:58
first and then once they're approved, when you get the first

00:50:01
one. That is approved for a healthy

00:50:03
lifespan extension, then that will be a tide that raises all

00:50:06
ships. Cuz now there are footprints to

00:50:09
follow towards a prevention study in the way that the most

00:50:12
successful Staten was like the third Staten that was approved,

00:50:16
not the first one I. Was just gonna add quickly on

00:50:19
here. So loyal is kind of like mini

00:50:22
came written in that way. So we have three programs that

00:50:24
we're developing concurrently. And the way I thought about it

00:50:28
and this is actually like a pretty big fight we had in the

00:50:30
early days on the board because like the traditional tech

00:50:33
company only develops one product, right, And you focus

00:50:36
all your energy on that one product.

00:50:37
But the big difference between tech and biotech is that your

00:50:40
product is locked in, right? And once you start doing your

00:50:44
studies, that is your final product.

00:50:45
And you might do like different formulations that are the right,

00:50:47
but the active ingredient that's driving the lifespan extension

00:50:50
is locked in. And so there is nothing you can

00:50:53
do. There's no iteration.

00:50:54
There's a product market fit finding you can do to make a

00:50:57
drug work if it doesn't work. I always say there's a God in

00:51:00
biology, even if you're not religious, because it is

00:51:02
predetermined whether our drug will work or not.

00:51:05
It's about us finding the truth as effectively as possible.

00:51:08
And there's other execution bits we can do to increase

00:51:10
probability of success post that binary truth, but that's core

00:51:14
importance. So what we did is we have three

00:51:17
programs, two around large dog lifespan extension, 1 around old

00:51:20
dog lifespan extension that share a really concrete core.

00:51:24
That is how do we prove the FDA of the drug works?

00:51:27
What does the pivotal lifespan extension study look like?

00:51:30
There's a regulatory strategy, but like all these different

00:51:32
things and it's an idea that a drug could be developed to

00:51:35
extend lifespan extension. And then it's slightly different

00:51:38
mechanisms or active ingredients on that.

00:51:41
So almost everything is shared that is able to be held true and

00:51:45
then we're able to externalize out the risk that we can't

00:51:48
control, which is the binary, yes, no, whether the drug works,

00:51:51
we're now beyond that like we we have positive data for our drug

00:51:55
programs, which is great. But that's how I designed the

00:51:57
company early on because I was also very cognizant of the fact

00:52:01
that if our first drug failed. It would just blow out in

00:52:04
general the opportunity of me or anybody else to build a dog

00:52:07
longevity company, even though our first drug failing would

00:52:10
have not been at all reflective of the validity of the thesis,

00:52:13
right? There's an expected amount.

00:52:15
Not every drug works, even if you're operating perfectly.

00:52:20
This is the hardest part of pharma that only statistically

00:52:23
only about 12% of drugs that start clinical trials get

00:52:28
approved and. Within biotech companies, it's

00:52:31
slightly better. They do better than pharma or we

00:52:33
do better than pharma. It's but still like nearly 20%

00:52:37
and that's the highest that you get from the statistical

00:52:40
operators. The Brian Johnson idea, I think,

00:52:42
you know, people are so excited about it, partially you know,

00:52:45
because people want to know what to do with their own health.

00:52:48
I mean it's like you know like you sort of said we've had

00:52:51
Atkins, we've had so you know intermittent fasting.

00:52:53
You know there's so many, so many things.

00:52:56
And certainly I obviously like what what you should do in a

00:52:59
societal level to prove a drug versus what an individual who is

00:53:03
actually aging right now and not cannot wait for for things you

00:53:07
know for drugs to get approved. Those are sort of very different

00:53:11
considerations and you know you you both are sort of measured in

00:53:16
science based. So probably the the last people

00:53:18
to sort of like push on everybody what what you think

00:53:22
they should do. But I am curious what you would

00:53:24
recommend for people now that's sort of available to them or

00:53:28
like are yeah, are you taking anything sort of strange

00:53:32
yourself? Like, I'm curious in terms of

00:53:34
just like an individual like who've looked at this space, how

00:53:37
you approach and what you recommend to your family and

00:53:40
friends? So I think one of the best

00:53:43
predictors slash like rough categorizers of whether somebody

00:53:46
you have charlatan or not. Is like how much they work on

00:53:49
their own personal longevity. Like all of the people who are

00:53:52
like super legit in the field, like Laura Deming, the Longevity

00:53:56
Fund founder is like a very famous example of this.

00:53:59
They often do things that are like negatively selected for a

00:54:03
lifespan extension, right? So, like when I was working at

00:54:05
Longevity Fund, all we ate at the fund was like chocolate,

00:54:08
Cheerios and dandelion chocolate, and I was like the

00:54:11
meals we had at the fund. You know, having pumping up your

00:54:16
blood glucose levels that high, not good for longevity.

00:54:19
I don't do anything like I work out I guess, but hey, I'm like

00:54:24
not doing longevity drugs for myself and I think that's

00:54:26
actually a really important thing to like keep cognitively.

00:54:29
Like. I think people who intertwine

00:54:31
their fear of mortality into their pursuit of aging drugs

00:54:35
become dumb, right? Because it's a fear based way of

00:54:38
approaching the field. Versus a logical way, they're

00:54:41
like, God, I have to find something because it's my

00:54:42
mortality on the line. Versus I see this as like my

00:54:48
thing to help other people. And like, I try to think about

00:54:50
it as other people and try not to focus on myself.

00:54:53
Maybe that'll get harder as I get older, I don't know.

00:54:55
But I think it's a pretty good predictor.

00:54:57
You don't take vitamins or anything.

00:55:00
I think literally nothing. Like I'm trying to eat more

00:55:02
vegetables. I'm vegetarian, but like, I love

00:55:05
on frozen and canned vegetables, OK, like I am.

00:55:09
Don't do anything. I do.

00:55:11
Just maybe if the drug is approved and your vet says so

00:55:14
prescribed her drug, I don't steal it.

00:55:18
But no, otherwise not. I don't do anything, James.

00:55:20
What's your approach? So I'm like a decade older than

00:55:22
Selena's and and I still get called like the young kid on the

00:55:28
on the biotech block most of the time.

00:55:30
And I take a little bit more of an experimental approach like we

00:55:33
were talking about before. I think almost everybody that I

00:55:37
know is thinking about. Especially like, so for example,

00:55:40
in my my family, we've had two people die of Alzheimer's in the

00:55:46
last, you know, in the last five years.

00:55:49
My boyfriend's mom is starting to show signs of this.

00:55:53
And so we're thinking, okay, well, what can we do to maximize

00:55:56
the time that we have healthy to be around and to be with each

00:56:02
other. And so there are things that I'm

00:56:04
doing, I think. The best, like validated things

00:56:07
that we really know will work is don't get diabetes regularly

00:56:13
exercise, eat fruits and vegetables.

00:56:16
Get enough sleep, don't change time zones every week or two.

00:56:21
This is 1. This is one that, like I was I

00:56:24
was in Europe last week, I'm in Europe next week.

00:56:26
Like it fucks with you for, like, a while.

00:56:31
I get sick every time I come back from a big time zone

00:56:33
change. Every single time without fail.

00:56:36
So, you know, I do play with some supplements, but like,

00:56:40
there's some that have real evidence behind them, the best

00:56:42
of which is fish oil for the prevention of heart disease.

00:56:45
I have two grandparents who died of heart attacks in their 50s.

00:56:49
And so, like, I care a lot about my heart health, you know,

00:56:52
beyond that, we just don't have a lot of evidence.

00:56:55
And so whatever, you know, people are doing, like they can

00:56:58
play with this or that, but it's just like it's.

00:57:03
Not backed by facts until it is and and the big part of I think

00:57:08
this whole field and if if there's one message that I would

00:57:11
love someone listening to this to walk away from is like

00:57:14
ultimately we need to create new truth in order to know new

00:57:17
things. And the only tool in medicine

00:57:20
that we have for creating new truth is running randomized

00:57:23
placebo-controlled clinical trials which will create one

00:57:27
little new piece of knowledge at a time and like that just takes

00:57:30
a long ass time. And this is all brand new

00:57:33
science where we have a pretty good idea that, like it might

00:57:36
work in mice, but before we know that it will work in humans and

00:57:40
especially with the diversity of humans that exist, which is way

00:57:43
more than the diversity of mice. Like it's just going to be a

00:57:46
while before we can think about how this longevity science is

00:57:50
going to impact everybody's day-to-day life.

00:57:52
There's just not that much outside of the the stuff that we

00:57:56
knew before. You know 10 years ago that we've

00:57:59
just gotten more and more evidence the placebo effect is

00:58:02
so fucking strong that it would outperform almost any drug on

00:58:06
the market today. So until you can disentangle

00:58:10
what scientifically is going on at their mechanistic level

00:58:14
versus what's kind of happening at the psychosomatic or the the

00:58:17
placebo level, like we just don't know.

00:58:20
So what I advise people is like get excited, do things like try

00:58:25
stuff. Right.

00:58:27
Be healthy, be active, enjoy life, think that you're going to

00:58:30
live a really long time, and then also try to do these basic

00:58:33
things that we know are supported by, like the

00:58:36
Physiology underlying your body. If you have high cholesterol,

00:58:38
take a statin. If you're overweight, like

00:58:42
exercise, have a good diet, maybe end up on one of these

00:58:46
obesity or metabolic drugs that are pretty good if your doctor

00:58:50
recommends but like apart from that.

00:58:53
Wait until the science comes out and see if we have like novel M

00:58:57
Tor inhibitors or caloric restriction mimetics or AMPK

00:59:00
activators that will be coming not that far in the future.

00:59:04
If they show to be safe and effective, that could be used

00:59:07
for people. But that's really like the next

00:59:10
frontier. This is why this whole longevity

00:59:11
space it's going to create a world that is so different than

00:59:14
the one that we have now, because it will be grounded in

00:59:16
truth instead of in speculation. Great.

00:59:22
I think that's a great end point for the show.

00:59:23
Thank you both for coming out this.

00:59:26
Is fun, Celine. I always love doing podcasts

00:59:28
with you. Yeah.

00:59:29
This was sincerely one of my favorite episodes.

00:59:32
I mean, it's such a great topic. So thanks so much.

00:59:37
My pleasure. Yeah.

00:59:38
Thanks for inviting me. That's our episode.

00:59:40
Thanks to James and Celine. Shout out to Tommy Herron, our

00:59:43
audio editor, Riley Kinsella, my chief of staff, Young Chomsky

00:59:48
for the theme music. Annie Wen for booking the

00:59:50
guests, please like comments, subscribe on YouTube and

00:59:54
subscribe to the subsetnewcomer.co Thanks so

00:59:57
much. Goodbye.

00:59:58
Goodbye. Goodbye.

01:00:00
Goodbye. Goodbye.

01:00:01
Goodbye. Goodbye, Goodbye, Goodbye.