Vladimir Leshko of Unlimited Bio

Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Greetings and welcome to the United States Transhumanist Party Virtual
Enlightenment Salon. My name is Jannati Stolier of the Second
and I am the Chairman of the US Transhumanist Party.
Here we hold conversations with some of the world's leading
thinkers in longevity, science, technology, philosophy and politics. Like the

(00:21):
philosophers of the Age of Enlightenment, we aim to connect
every field of human endeavor and arrive at new insights
to achieve longer lives, greater rationality, and the progress of
our civilization. Greetings, ladies and gentlemen, and welcome to our
US Transhumanist Party Virtual Enlightenment Salon. Today is Sunday, June first,

(00:42):
twenty twenty five, and we have a fascinating conversation for
you about the beginnings of some combination rejuvenation therapies for longevity.
This is an exciting topic and we have a distinguished
panel joining us today, including our director of Visual Art

(01:07):
and current Vice Chairman, our Romone Garcia, and our technology
advisor and foreign Ambassador in Spain, doctor Jose Cordero. By
the way, please take a look on my YouTube channel
if you have not done so already, to see my
interview with Jose at the last Longevity sum at Dublin

(01:28):
in twenty twenty four. Jose and I will both be
at the upcoming Longevity sum at Dublin in July of
twenty twenty five. Now our special guest today is Vladimir Leshko.
He is focused on transforming healthcare toward a personalized and
preventive model, defeating age related diseases and eventually solving aging itself.

(01:53):
He has professional interests in organ on a chip technology, longevity, biotech,
and digital health. He is the chief operating officer of
Unlimited Bio, whose goal is to conduct one hundred clinical
trials of genetic preventive therapies in ten years by making
use of the regulatory flexibility of the Prospera Free economic

(02:17):
Zone in Honduras. Right now, Unlimited Bio is working to
launch its first batch of trials targeting age related hair loss,
skin quality deterioration, and sarcopenia via repurposing of an existing
safe and defective genetic therapy. And an interesting fact about Vladimir,
he is a former online pro poker player. He was

(02:38):
in the top one percent in the world, but after
graduating as a biomedical engineer, he is building a career
focused on human health and we are happy to have
him in the longevity field. So welcome, Vladimir. You have
a presentation for us about the work of Unlimited Bio,
so please feel free to begin.

Speaker 2 (03:00):
Yeah, thank you for the introg nadi and thank you
everybody for having me today. So yeah, I'm going to
tell you a bit what we do at a Limited Bio,
and that's exactly what you said. We combine therapies and
for longevity. And since I have a generous amount of

(03:23):
time today, I'm just going to say a few words
about myself, then about the approach we use it a
limited Bio, and then a bit more into the science.
So I started off like my longevity journey with buy hacking,

(03:44):
probably roughly around twenty seventeen. So I did all those
weird examinations tests protcoles and nutrition festing called plunges since
I lived in Russia at the time then really convenient
for called plunges, sauna and so on. And what it

(04:06):
led me to realize that actually the capacity to increase
lifespan with all those fancy methods, it's very limited, and
of course so they're not applicable to general population. Afterwards,
I decided to switch my career path as you mentioned, yeah,

(04:29):
and it was playing poker professionally. I also did some
entrepreneurial projects, but I thought, yeah, how can I come
close it to be an allegevity field, So I got
masters in biomedical engineering and delft in the Netherlands, where
I currently reside. Then a year later I found it

(04:52):
a limited buier together with Yvanne and Danna, who you
might have already met. So and the good thing about
unlimited biers that when you do experiment with gene therapy
is you also get such a chance to experiment on yourself.

(05:12):
So the by hacking party is still there. And the
other problem we are looking at it's a huge one,
and that aging is still the number one killer in
the world. And the problem is that aging is extremely complex.
It's hundreds, if not thousands of processes at once. And

(05:37):
what we say is that, yeah, well, you can probably
take some sort of pills like metforming or repromising, and
they may be able to attack several of those processes
at once, but not enough to make a meaningful difference
to say, make humans leave you five years long. So

(06:02):
what we say is that we need to do trials
on combinatorial therapies, So see what we have in the
field develop for diseases or close to get into the market,
and see what combinations can we make out of this
existing therapies to make a meaningful difference in the field.

(06:28):
And what we also say is that pharma pharmaceutical companies
and governments that are not trying good enough because we
still have over one hundred thousand people per day, and
with the current pace of developing drugs, when it takes
on average over a billion for a drug to market

(06:49):
and over ten years, usually it's just will take an
incredible amount of time and also will require an effort
probably higher than a pole project, So it would be
almost impossible for the economy to tackle that. And of

(07:10):
course what's also stopping that other regulations because right now
we do optimize for safety heavily, so just research that
or never reach. In the US, we have one death
two hundred thousand participants in the Phase one trials, so

(07:32):
like people during trials don't die honevers, it just doesn't happen.
And at the same time, reaching even a phase one
trials requires at least one hundred million in investment and
several years, so we sacrifice one hundred thousand people per
day to get like to and very insane safety level

(07:59):
during trials, and just a situation we want to resolve
and we try to rewrite the rules of Buyoteck. Very ambitious,
but we'll try. So what we achieved so far that
we brought our first therapy to market, not to US market,

(08:22):
of course, but to prosper Our market for only two
hundred thousand dollars even less. And we expect that a
new therapy which will require pre clinical trials, we can
bring down the costs to roughly around a million or
ten million. And also it happens way faster because you

(08:47):
don't have to redo the trials within Prosperous, so you
can just show the existing data and get the drug
to market. So compared to get into the US market,
we are greatly accelerated there. Yeah. So, as I mentioned,
we launched our first therapy in roughly the amounts and

(09:13):
we do leverage special economic zones. So we started our
company in Prospera and probably not all of you are
familiar what it is. It's like a regular Caribbean terada
As island with a small bunch of lands dedicated to
this special economic zone. It has good connections to the US,

(09:37):
it's visited by a lot of tourists, and it's considered
very safe compared to the rest of Honduras especially, And
what makes it work is like a very flexible regulatory
system inside Prospera, which allows us to ditch delays the

(10:00):
bureaucracy and too, probably the most important point to do
patient funded clinical trials because roughly maybe up to ninety
percent of the cost of getting the drug to market
clinical trials on humans. And what we say, since like

(10:22):
one hundred thousand people dies each day from aging and
they basically don't have a single chance today, then it
could be that one percent or zero point zero one
percent of them, they would be willing to experiment with
potentially life saving therapies for them and because part of

(10:47):
them will be willing to reimburse the costs. So in
twenty twenty four we launch our first therapy is called
each vascular endothelial Growth THECTAM, and what it does promotes

(11:09):
intio genesis, so formation of new capillaries in the tissue.
It's a pleasant and generally pleasant chain therapies. They are
considered extremely safe because of this pleasant it just compliments
your DNA in the cells, so it doesn't alter in

(11:29):
any way the original DNA. It also doesn't have any
sort of viral particle carrying it, so you don't get
any immune response from that. And the good thing about
this therapy we licensed it from a Russian bytech company.
The good thing about it was that it was a

(11:50):
while already in the market and it had over ten
thousand patients treated without any significant side effects registered but
with proven efficacy, and that's why we thought it's like
a great first step to try and license the therapy
and bring it to prosper On. And the facts they

(12:13):
saw in the trials were quite interesting. So the patients
that had peripheral artery disease and developed a complication called
local limp skinia, so they were having trouble walking without pain,

(12:33):
and the drug improved their pain free walking distance by
I think on average one hundred and seventy percent, and
some patients saw like seven hundred percent improvement and so on.
So for some people it had life changing and limp
saving effect because when your skinia in your legs develops,

(12:54):
you can risk imputation and in some cases it's impossible
to make a surgery, so this drug surgery, I mean
to reconstruct the vessels and to improve tissue oxygenation in
a surgical way. So for some people it was really
a life saving therapy. And of course we are also

(13:21):
interested in the original indication and we also use it
for PAD, but we thought that potentially BGF can also
be used as a preventive slash enhance an indication. So
when you injected into the muscle of healthy people that's

(13:45):
what I did on myself, you can in theory see
enhanced angulance because it get improved oxygen nutrient delivery, greater
waste removal. And you can also see offset in the
first steps of heir loss because he loss is closely

(14:09):
connected with the shrinking of hair llcles due to decreased
amount of capillaries in your scalp. So those are the
two indications we use it for apart from PAD. And yeah,
we don't work with patients ourselves, so we outsourced that

(14:35):
to the clinics and our first partner clinic his Government.
The head of the clinic is doctor Glen Terry, who
was a former physician of the US Olympic Committee and
he has a greater experience in doing trials, including trials

(14:55):
on piece. We don't want to stop there. So as
I mentioned plasmids, so they're really safe, but also they
have a questionable efficiency because they don't stay in your
cells that long. So you get a protein production for

(15:18):
several weeks, which is good, but you won't get a
protein production for five or ten years. So in case
of VGF, it's important to say that we get the
effect for five years, but it's not strictly connected to
protein production because when you get a secretion of HF protein,

(15:42):
you build new capillary network around the injection sites, and
then this capillary network, according to the studies, it's a
states with the patients for three to five years and
even longer. But for some therapies we need to protein
secrete him all the way. So we partnered with bio

(16:04):
Viva so Liz Perish, and Liz arguably has like the
most experience in the world with longevity av therapists, so
we licensed for therapies from her, and what we want

(16:26):
to do next is bring all those positions here on
the slide to the market in prosper and also potentially
a few other Latin American countries, and with the first
form we want to do a combination trial because, as
I mentioned in the beginning, one protein, one gene therapy,

(16:49):
one drug, it won't get you verified in terms of aging.
So you may get increased muscle mass, which is good
like more power, more force good, but your brain will
keep aging at the same pace. We also need something
for the brain, We need something for the immune system

(17:11):
and so on. So what we want to achieve eventually
is roughly by twenty thirty four. If we move at
a high pace to assemble HUD. The therapy portfolio, hundred
is like a very not meaningful numbers, So maybe it's

(17:36):
going to be fifteen, maybe it's going to be one
hundred and twenty, no idea. But it's not only going
to be gene therapies. We also want to focus on
small molecules, antibodies, exosomes, potentially cell therapy, stem cells, plasma.
Theosis is a very interesting action for us. So also

(18:02):
including whatever else becomes available in the next decade, will
be hopefully the company which will be able to get
to humans and get destructive humans in the shortest amount
of time. Now I want to dive a bit deeper

(18:25):
for double click and AV based combination. And we go
for that combination because we experience all sourts of those
terrible processes during asing, and we think that this combination,

(18:46):
our first attempt or will indeed have pertent effect on
those processes. And that's a combination we enrolled into x
price and went to become one of the top hundred
teams still competing in the express And the first thing

(19:12):
is VGF. So that's the only therapy in the combination
that won't be in a v form. So as I mentioned,
it's a pleasant won't be delivered by a virus. That's
like a somewhat neglected factor in agent. So it's only
recently appeared on the raiders. And although for quite a

(19:37):
while Stutus already showed that all the people indeed get
less capillaries in the muscle, in the skin, in all
the organs, So it does significantly. The amount of capillaries
does go down, and so does the ability for all

(19:58):
the people to offset that loss with exercise. So exercise
indeed is a trigger for releasing VGF. But yeah, all
the people are not able to do this as good
as young and the one the potential reasons is that

(20:22):
get with h you get an increased amount of these
decoy receptors for VGF, which bind VGF and does kind
of distract the protein from binding to the signaling receptors.
But we can potentially overcome this process by increasing the

(20:44):
amount of VGF in the tissue where we need it.
And what's even more interesting that a recent study from
twenty twenty one showed that when mice have increased DJF
levels since birth, they leave for almost fifty longer than

(21:11):
regular lab mice. So quite counter intuitively, VGF had life
extension effect because VGF is also closely connected to cancer
in the body, and in this case, mice actually developed
less tumors and overall they were feeling way better in

(21:34):
all dimensions, so they had more bone mass, they had
less abdominal fat. Yeah, as I mentioned, the lifespan was improved.
The second component is Follestatin is probably the most hyped
one of the most hypetl INGVT related proteins. So full

(21:56):
stating slows down the It inhibits my stating, and my
stetting uh makes your more muscle breakdown, So fullestating kind
of stops your muscle from declining and full statting was
extensively tested not only in mice but also in primates,

(22:21):
and indeed they developed a way larger what receipts muscle
at the injection sites. And what's important, they didn't see
any safety warnings. H Further on, fulles starting improves insulin sensitivity,

(22:42):
so potentially it can also set the diabetes type two
so kind of alsen exercise mimicking effect then, and it
also improves vessel function.

Speaker 3 (22:59):
Uh.

Speaker 2 (23:00):
And in this regard, we think that full starting and
the EGF they can have like a very powerful connection
because one of them improves blood delivery to the muscle
and the other one makes muscle bigger. But it's not
enough like for the muscle size to become larger, so

(23:22):
it doesn't necessarily mean that you'll get more strength. But
I think if we combine them together, we kind of
have both the components, so blood delivery and muscle size.
And also full standing itself has a very positive effect
on blood pressure, but in this case it was shown

(23:46):
in reps I think. And yeah, also it has a
prominent effect on lifespan extension in mice. And what's even
more interesting that follestatin was already tested in humans. In

(24:08):
this case, it was tested in humans with a severe
disorders of back muscular dystrophy and these patients, what they
observed in some patients is actually the increase of the
muscle size at the injection sites. So I think this

(24:32):
was like the first trial which registed such an effect
on muscle growth in humans, and they also experienced reduced
fibrosis rates. And in this case the study is like,
it's great, it was already tried in humans and they
showed a great safety. But it's also a concern for
us because these patients developed you see some sort of

(24:55):
like bumps, so we don't want, of course people to
get that. So we strongly think that it's due to
their muscle being fibrosed. So potentially also having a combination
with eachf which will kind of allow for the static

(25:16):
spread more widely into the muscle and have like a
more systemic effect. It may prove beneficial. Then the third
thing we have is alpha CLOTHO. That's one of the
proteins of the cloth family, the one which is very
strongly connected with all sorts of positive effects in virtually

(25:42):
all organs, including brain, and it also was connected with
the extension of lifespan in mice and what we see
with often in humans, so that it has a very
prominent decline with the age. So it also gives us

(26:08):
a hint that maybe offset in this pathway, it will
have a meaningful effect on aging. Yeah, so it also
plays a role in vascular disease and all. What's even
more interesting in cognitive function. And it has also been

(26:35):
tried in humans. So in this case, several people without
only five patients, Yeah, five patients with the early onset dementia.
They got it and they written. First of all, they
found out that the safety was really incredible, so no
side effects registered, no immune reactions, nothing, and all the

(27:00):
patients got improved cognitive score according to cognitive tests. Because
such a small trial is not representative to conclude, but
we for sure think that there are some hints then
we should keep going. So cloth is also extremely popular

(27:21):
right now in the longevity community, like everybody wants it.
And the fourth thing is a bit more exotic, so BDNF.
It's a factor which promotes the formation of new connections
between neurons in the brain, but not only in the brain,

(27:42):
and also declines with age. And we think that adding
it to the cocktail will give us a shot at
stopping dimension because a big problem with the gene therapy
is and the brain is delivery to the brain. So

(28:03):
we need to experiment there with the delivery methods to
make sure it does get into the brain. That's the
tricky part. It has also been tried in humans. In
this case it was injected directly into the cortex, but
we don't want to go for that because well, most

(28:25):
of the healthy people, I guess will object from things
getting injected into their brains, So we'll try other delivery
methods like infranasal or maybe even intravenous. See so now
those for proteins once again combine I will use different

(28:47):
delivery methods, not proteins. Yeah, but gene therapy is. So
what we expect to see is very prolonged production of
those proteins within your own cells, and we want to
test it later this CM in our phase one trial.

(29:11):
So right now we have a pre clinical trial running.
It started in May on mice, and upon the results
of that pre clinical trials will make a decision if
we proceed with this phase one trial. So we already
kind of loosely looking for participants and what we'll have

(29:36):
there is not only a treatment group but also a
placible group. The design will be crossover design, so eventually
all fifteen participants will get gin therapies administered.

Speaker 3 (29:53):
But.

Speaker 2 (29:55):
It will allow us to compare side effects in the
treat group with placific group with placific control, so we'll
get a slightly high quality data there than just the
u in chetain everybody at day one. So a few

(30:17):
words about our team. Our CEO is Yvan who has
a background and building several longevity companies in the classic regulations.
One of them, for example, is trying to offset elastic degradation.
It's like a very important important protein which helps you

(30:43):
TIS should be more elastic, and they're trying to increase
spurting young humans. So far the experiment on mice, and
Ana has an amazing experience of bringing first rushing commercial
COVID vaccine to face two clinical files in just two years,

(31:06):
and she also has a great experience with avy gin therapies. Yeah,
we have less parish in partners. We have Glen Terry
runs the Calm clinic, and I should also highlight Alexander
fed himself who recently got like a rising staff longevity researcher,

(31:30):
war from or Great the Great himself. So Alexander is
a very practically oriented scientist, so he helps us look
for things that really might work in a very short
term scenario. So what we can get two humans in

(31:50):
the next two to five years. So by like kind,
they ask you to join us in our fight against aging.
And what we need is we need to buy tech partners,
we need investors. So right now we are preparing for

(32:14):
our seat round. So if you know people who might
be interested in investment, please connect us. We're also looking
for trial participants, so you're potentially interested in coming to
prosper out potentially other locations around you as now, then

(32:35):
you can come the QR quote and just feel one
question form and we'll get back to you as soon
as we have something on the radar. Yeah, there's our
website and social networks, so let's stay connected.

Speaker 1 (32:54):
Thank you all right, Thank you very much, Lajimir for
an excellent presentation, and we have a lot of our
viewers expressing agreement with that. Rudy Hoffman says that you
are a great guest for Freedom says, this is a
very nice presentation, and we have a number of other

(33:18):
compliments for you. Right now, let's go to questions, and
there have been many questions in the chat. There are
some questions for me as well, but let us start
with doctor Jose Cordero.

Speaker 4 (33:35):
Yes, thank you so much. It was a fantastic presentation,
very comprehensive. And first of all, let me congratulate you
and the team because you achieved to become one of
the one hundred first finalists of the Healthspan X Prize.

Speaker 5 (33:54):
In fact, I think you should have mentioned that.

Speaker 4 (33:56):
I mean this is important, very important to be among
the top ten teams competing for the Healthspan X Prize,
which was announced a couple of weeks ago.

Speaker 5 (34:09):
So first of all, congratulations.

Speaker 4 (34:12):
I know very well and Evan, in fact, we work
together in Prospera when they were beginning to do many
of these ideas and making them reality. Also, the picture
that you shared with Liz Parish, I took that picture.
I don't know if you know I took that picture

(34:33):
with Liz Parish because she presented that in a congress
in Germany where we both were in Leipzig, Germany, and
I send it to Ivan Atuana.

Speaker 5 (34:45):
So I'm so happy to see that picture.

Speaker 4 (34:47):
Also in your presentation, So congratulations for that too. I
have two questions. One, it's about funding. You didn't mention
any of that. This is the most important thing. What
kind of funding are you looking for? And also when

(35:08):
and which human clinical trials would you do first? And
if they will be in Prospera or in other places?
Have you considered other places because there are different initiatives.
Prospera is not the only one right now, there will
be and there are other places trying to open up
for these clinical trials. So those are my questions funding

(35:31):
and clinical trials and where.

Speaker 2 (35:34):
Yeah, thank you say it's nice to see you here
today and at least a picture without knowing that you'll
be around, so it's good you witnessed your work on
the screen, so thanks for that. Yeah. And regarding yeah,
and in the top hundred health pend teams, I personally

(35:59):
was really really disappointed, was like almost crying for today's
that we didn't get in the top forty. But we
did had some improvements to make to our trial plan
there to make it. Maybe they thought it's a bit unrealistic,
a bit too fast. Whatever, we are past that. So

(36:24):
regarding funding, yeah, we are. We want to raise two
million right now, and we have a few small commitments,
not enough to proceed with the round. So we're looking
for like longevity minded, rebellious venture capitalists that will back
us up. And the hardest part is there for us

(36:49):
is to show our business model. They say like, how
are we going to make money on this? And we
are very radical in that regard, So we want to
go to treating aging as fast as possible right now,
and indeed it may raise questions for them with them

(37:13):
like how we got to patent all those combinations? Will
the pharmaceutical companies be interested in getting our data if
it wasn't prosper like whatnot? So yeah, but we are
open to those conversations. So indeed we wanted to talk
to more vcs and to angel investors work as well.
So these connect us and the second question, Yeah, we're

(37:38):
also looking at other locations, so we just signed with them.
Clinic in Mexico, clinic in Dubai. So Dubai has right
now very interesting regulations which will allow even paragin therapy
hopefully to get to the market very quickly there and
to get to human trials. And we're also looking at

(38:02):
the hamas. So we also have a part in the
hamas they opening and clinic the White Stone, I think,
so it's not set in stone that will do our
trials only in prosper So we indeed want to protect

(38:23):
us from any sort of political instability and also have
other allocations than that.

Speaker 1 (38:33):
Yes, thank you very much for those answers, Vladimir, and
our friend Rudy Hoffman does have a question along these
lines as well, in terms of the legal stability of
prosper and what your assessment of that is, as well
as the future of that jurisdiction and what alternatives you're
looking at in terms of contingency planning.

Speaker 2 (39:00):
Yeah, so there was a lot of turmoil in Prospero
when the current government's current president, they tried just to
completely destroyed it, left on paper. So there was a
statement released from their like water that prosper was declared

(39:25):
not constitutional and it actually didn't have any sort of
circumstances on people living or making business in prosper So
all the companies there, they're just business as usual. They
tried to shut down one building they but it was

(39:48):
some sort of a small office, I know, or even
a storage room or something, and then they just let
it go and so patients are still coming to gal
clinic getting treated. Nobody faces problems with on the border anything,
So we didn't see any any circumstances, any consequences so

(40:12):
that like how banker operates and so on. And but
they also have elections later this year, and I think
the current socialist government they are so fight seems they're
losing the elections. And also because of Trump influence, I

(40:35):
think US will be fighting to protect the investments in Prospero.
It has a lot of backing from like a billionaires,
and so it seems to to be able to survive.
And I also talked a bit with locals when I

(40:57):
was there, and I didn't really see any serious counter
arguments to prosper existing because they do employ local people.
That's effect they do pay high salaries and Honduras average.
That's also the fact they don't occupy a significant portion

(41:20):
of lands, so they don't disrupt like the local communities.
And the main argument I've heard from local so that
let prosper is a legal paradise and everything is allowed there,
so you can do drugs there, you can like a
noble committed crime, and Honduras kills someone and hide and

(41:41):
prosper because Honduran police is not active in prosper and
the fact that's certainly fake because Prospero follows the criminal
code of Honduras, so you cannot do drugs or commit
crimes within prosper same as mainland Honduras. That's why from

(42:02):
something Prospera doesn't see any sort of company switched to
psychedelic research, not a single one. So I hope it survives.
I sincerely hope it survives. But in case thousands, we
also have some back up.

Speaker 1 (42:21):
Yes, thank you for that answer, and I share your hope.
I do think a lot will hinge on the upcoming
presidential election in Honduras, because it really is the socialist
government of Cmara Costro that has endangered Prospera. The prior

(42:41):
government was in support of it, and perhaps if a
different party comes to power again, prosper will be more
secure from a legal standpoint. We do have a question
from Dave Ringelberg, who wonders what are your plans for
data that you would collect from the gene therapy is,

(43:02):
particularly the combination gene therapies, which would be quite innovative
since you would be essentially targeting for genes. At the
same time, will any of the findings be openly published
so that others in the field can build on them.

Speaker 2 (43:20):
Yeah, that's a plan. So since we don't like regular
bi techs, we don't attach ourselves to certain like single pathway,
a single molecule. So if BGP doesn't work or healthy humans,
we say, like guys that we didn't see an effect,
so we discovered that, we remove it. We move on.

(43:44):
So if we see side effects with full statting, we
also iterate on that. So we are not so we
don't have any like sentimental ties to any of this.
Gene therapy is approved things. So the goal is really fine,
what works and keep it and for the rest publish

(44:08):
data that it doesn't work, like, let's work on something else.
We need new stuff. So yeah, that that allows us
to be really open with the data. So and actually
one of the key points of X price is that
you have to publish everything. You have to disclose all

(44:29):
the data you've got. You got otherwise yeah, you're not
you're not competing. And I imagine if you if you
don't disclose that it means it didn't work or you
didn't do the trial and just a it's a bit
of off topic, but it would be really interesting to
see regarding X price that they have a lot of

(44:52):
like health nutrition, I know, Japanese tea or exercise, some
sort of nutraceutical companies and so on. So what we
potentially may see as a result of X price that
will actually observe how many things have no effect on agent.

(45:17):
Maybe during that price we won't find a thing that works,
So that's offsets human agent by twenty years. So everybody
doubts that, but we'll be able to see how many
things don't work. That could be a good result there.

Speaker 1 (45:34):
Yes, And of course publishing negative results is quite important
for scientific progress. It is not done as often as
it should be, but it does give a lot of
information to future researchers or even the same researchers about
what paths not to follow, what paths have been followed

(45:56):
already without the desired results. So we have a number
of questions. Now, I did want to ask one about
the EGF and the angiogenesis effects of it. And I'm
curious from a safety standpoint, what you know about the

(46:21):
effects if there are new small blood vessels that are
formed clearly that can improve blood flow but small blood vessels.
New blood vessels can also be pretty delicate, and I
wonder if there's an increased risk of rupture of those
blood vessels and whether that is an important safety concern

(46:44):
for the patients, or if you haven't observed that either
in the literature or any trials preliminary trials that you've done,
let me know as well.

Speaker 6 (47:01):
Yeah, for sure, they're very delicate, So they're mostly kepitlars,
so it's the thinnest type of vessels you can imagine.

Speaker 2 (47:11):
And yeah, what you mentioned having kind of I'm not
familiar with the except medical term, but you indeed can
get like an unappropriate formation of capillarists, which don't supply
the muscle but just kind of lead blood. It's one
of the potential side effects of VGF, but it wasn't

(47:33):
observed in clinical files of what they did in Russia,
and it was quite extensively started. So like the main
thing why we went for VGF is like it was
very very safe that so, as I mentioned, over ten
thousand patients got that and we didn't see that effect,

(47:57):
so part with the people we administered to, we also
didn't observe that effect in healthy people. Most of people
raise the more significant concern regarded VGF, which is cancer,
because you might have heard that there are some chemotherapies

(48:20):
which target VGF which block this pathway and slow down
the growth of tumors, and it's a more major concern,
but once again we didn't see it in the clinical trials.
We didn't see it on animals. In fact, the animals
got less cancer with the VGF And then now we

(48:43):
also protect ourselves from that because the plasmid effect is
strictly local, so it cannot be distributed in the bloodstream
because it gets chopped in the blood stream with nucleases,
so it's only gets into the cells which are in

(49:05):
proximity to the injection site. So the downside is that
you need to do a lot of injections so at
least tend per lag for example, but you don't get
an effect on the brain or even if you have
tumor somewhere in the lung for example, it wants to

(49:27):
want to affect that tumor, so the only thing you
have to avoid is like injecting around the tumor and
the tumor itself. That's why we also referred as for
additional safety, not to work with patients which have oncology history.

Speaker 1 (49:47):
Yes, thank you for that explanation. And I take it
if one were to get a VEGF therapy for say,
hair regrowth, one would have to get injections in the
out or close to the scalp. Yes, And I'm curious
also what stages of hair loss does the therapy work on.

(50:11):
So of course some people have lost almost all or
all of their hair. Others may just get some minor
hair thinning. Where is that delineation between where the therapy
could work or where the hair loss is just too significant?

Speaker 2 (50:31):
Yeah, we think that like the correct answer. We don't know.
We don't know what stage of hair loss it will
work on. So we just know that the mechanism is
there that it might work on certain stages. We don't know. Yep,
we would have the data to say, yeah, it works

(50:52):
for this stage.

Speaker 1 (50:56):
Right now.

Speaker 2 (50:56):
The owner of for the rights for the therapy, they
have a trial running for male pattern alipisia, so for
hair loss related to hormone levels in the body, and
we are you know, maybe it will work, but yeah,

(51:21):
I'm not sure. We think that it might work for
h related heaping and hair loss. When you know all
the people, they get the sort of thing hairs and
then kind of less hairs, but they are still evenly
spread around the scalp. So that's the condition we want

(51:43):
to primarily target. And because they still have follicles all
over the scalp, and if we improve the blood supply
will at least make those follicles stronger and larger. So
that's where we want to experiment. For example, Michael Fontdevan,

(52:04):
he has like a very severe stage of hair loss
that he cannot even make a hair transplant. So for him,
we don't expect it will work because he does have
any follicles left. Maybe after he makes a transplant, it
can be like an additional support of therapy to improve

(52:25):
for blood flow to the place where he made the transplant.
But it's also hypothesis. So what we have that for
hair loss is the mechanism we have the results yet unfortunately.

Speaker 1 (52:39):
Yes, thank you for that explanation. And I will note,
by the way, for anybody who is curious about this,
there is no correlation between hair loss and longevity as
far as we know, so even people who lose all
of their hair can have the same life expectancy as
people who don't. However, this therapy is interesting from an

(53:04):
angiogenesis standpoint because the ability to regrow blood vessels and
improve circulation, if that can be done to reverse hair loss,
could potentially also be done to reverse other aspects of
biological aging. So now Jose has another question, so please

(53:24):
go ahead.

Speaker 5 (53:26):
Yes, thank you, and I agree with you.

Speaker 4 (53:28):
First of all, Gennadi as well hair loss, even though
I'm also beginning to suffer hair loss like most men do.
It's not a critical condition, it's not death or life.
I am more interested in cloto and foliestatin. In fact,
I would love to inject myself with those two as

(53:50):
soon as we know how, when, and all of those details.
So yeah, my question is a bit about that about
Clotho band, I have other things to mention. Maybe since
you are in the Netherlands, you should go to the
International Longevity Summit ed Madrid. This is the biggest conference

(54:11):
in Spain about longevity. We have top scientists like people
from from Harvard George George, the CEO of Evolution Foundation,
Mahmud Khan, one of the top Alto Slabs researchers, Steve
Horvard who created the epigenetic clocks, and many other people,
So it gotta be fantastic to have you with us.

(54:33):
And then besides the clot of Hollistatin question when when
are they coming up? Have you also read my book
which is in Russian. I'm so happy. My book is
soon in twenty languages, including Russian. But they changed the title,
so can you read at.

Speaker 5 (54:50):
The title because it is not the death of death,
it is.

Speaker 2 (54:53):
Something that death could die.

Speaker 5 (54:58):
Russian estyle death die.

Speaker 1 (55:01):
That's good though, yes, absolutely death should die, and hopefully
are various forms of advocacy and research and advances and
gene therapies will help to kill death within our lifetimes now. Also, Vladimir,

(55:25):
you were issuing a call for volunteers and art Ramone
said that he would like to volunteer. So Artur, would
you like to say any more about this or have
any questions and connection to your desire to volunteer, anything
that perhaps could be answered during the salon.

Speaker 7 (55:47):
Yeah, it's I've had long COVID for quite some time.
Hit me the hardest towards the end of twenty twenty,
and I've tried numerous therapies and somewhat for a while
to be quit working. Some do work, but their effects
diminish over time. And right now, I'm actually experimenting with TRT.

(56:10):
Right now, I'm a month and a half in and
I'm gonna do like a six month experiment with TRT.
I had to get off the hyperbaric oxygen therapy to
just you know, to feel how it's really working. And
I feel like getting off the hyperbaric oxygen therapy, even
though the effects had diminished, it was still doing a

(56:33):
bit to give me a lot of energy.

Speaker 3 (56:36):
So I'll probably eventually.

Speaker 7 (56:38):
Get back on the hyperbaric oxygen therapy. But yeah, I'll
be happy to volunteer. Right now, I really hate my
quality of life the way it is without any sort
of therapy. If I didn't have any therapy, I mean,
life really sucks because I have to drink so much
coffee to make it through the work day, and then
I'm just dead tired. After words, I have to sleep

(57:01):
four hours and then I have to you know, wake
up and do a little bit of whatever and then
go back to sleep and repeat. And quality of black
fly sucks, you know, when you don't have that energy.
And yeah, I'll be happy to volunteer. I'll I go
to the site and register. Uh, I got to get
my passport in order start in order. My dad said

(57:25):
he would help me out financially. So that was one
of the sticking points to try and any this experimental
type therapies to try and help with long COVID. So
you know, after this six month, might even uh go
back to odor the stem cells and try to stem cells.
And I can do that here in this country without

(57:46):
having my passport in order. But one of the things
I used to do even before COVID was do inversion
therapy and hang upside down and that would that would help,
uh picked a lot of more vascularity in the upper chest.
And I did that as sort of as an anti

(58:07):
cognitive client therapy because I did have a cognitive decline
I think twenty sometime after it was even before twenty twelve,
I was having some COGNITIVI client issues, which is why
I started to learn sign language and do other things
to get my mind working.

Speaker 3 (58:28):
I did have a rare.

Speaker 7 (58:30):
End incident and a few jiu jitsu injuries where I
banged my head, which probably didn't help. So inversion therapy
was one thing I tried. I think it did help,
but again with a lot of therapies, it's just diminishing returns.

Speaker 3 (58:49):
It sucks. I mean, you do with therapy. It takes
a lot of time, it takes a lot of.

Speaker 7 (58:53):
Effort, and then you end up with diminishing returns, which
is one of the thing I absolutely hate that. You know,
I have found certain therapies that work, like hepot that.

Speaker 3 (59:08):
That is expensive long term.

Speaker 7 (59:11):
If I could do it weekly, it would be the best,
but you know, at one hundred dollars pop.

Speaker 3 (59:16):
It does get expensive. So I was doing it.

Speaker 7 (59:18):
Bi weekly and it seemed to be okay until I
did a full stop when I got some nasal surgery
and I couldn't do HPOT for two months, and then
since when I restarted, it wasn't as effective because maybe
somehow I need to get on a caviar dose and
then to a maintenance dose, and I haven't done that.

(59:43):
But said, I've also been experimenting with other therapies for
long COVID, and you know, a lot of the long
COVID symptoms are very similar to aging.

Speaker 3 (59:52):
Whether long COVID.

Speaker 7 (59:53):
Is aging me, I don't know, or it's some other
mechanism at work. I just know when I exercise. I've
been trying to exercise get finigan, and it seems like
whatever mechanism that exercise is supposed to do to make
your body fit and state it is broken.

Speaker 3 (01:00:10):
It's like I exercise and.

Speaker 7 (01:00:11):
Exercise and the games are very hard and they're quick
to lose. And I with a TRT, I hope that
would give me more energy to do more exercise. And
the first injection was great. I had a lot of
energy after that first injection, but then I increased my
activity levels my walking, and then the second and third injection.

Speaker 3 (01:00:35):
So far I'm not impressed.

Speaker 7 (01:00:38):
So I was talking to chat GVT and I said, well,
maybe I'm just kind of overdoing it with the exercise.
But I'm like, this is the way I've always exercised.
You know, I exercise hard, but the body gets stronger.
Now I exercise hard and I spend days in bed
because it doesn't make me stronger after this or the

(01:01:01):
goat walk. Before the TRT therapy, I had a sticking
point where a go walk in this canyon, which is
a paved road in the canyon.

Speaker 3 (01:01:11):
I had a sticking point about a mile and a
half in That was my sticking point. I could not
get past that.

Speaker 7 (01:01:17):
The TRT helped me break through that and I was
able to get to two miles, but then to get
a quarter of a mile past that was extremely painful.
I'm literally walking as slow as possible, taking half steps.
My heart rate is like high one hundred and fifties.
I've got people who are older than me, like twenty

(01:01:39):
years old, passing me up, and I feel like I
died because my muscles are burning. The good thing is
it doesn't feel like my heart is giving out. My
heart is definitely popping hard, but it seems.

Speaker 5 (01:01:51):
To lesten I muscles.

Speaker 7 (01:01:53):
My muscles is like that if I'm doing ten squats,
you know, and then I take a step doing ten
swaps and take another step.

Speaker 3 (01:02:02):
My muscles are just burning.

Speaker 7 (01:02:05):
So that's what I'll subject myself to after this because I'm.

Speaker 3 (01:02:09):
Trying to break past the two and a half miles.

Speaker 7 (01:02:13):
But it's very painful, very very painful to exercise in
this fashion, and I don't see any other way of
getting fent. I've tried other things, and the gradual I
lose my games. It doesn't matter if I if I
take it easy and get those fitness gains, I'm gonna

(01:02:35):
lose them the moment I can't exercise two weeks of
the row, so and that's just ridiculous. In the past,
before COVID, I could take two months off and be
perfectly fine, you know, getting back into exercises. Now I
can't take two weeks off it without losing in a gang.
So yeah, so yeah, my point, life sucks. I'm willing

(01:02:57):
to be that guinea pig.

Speaker 2 (01:03:00):
So any dos well, I've never seen anyone complain about
not having enough energy with so much energy in the voice,
So with that kind of motivation, you'll make a great

(01:03:22):
participant for experiments. Actually, we are planning a more even
a more comprehensive protocols for X price because you need
to show fifteen to twenty year EAH decrease like a
buymarket decrease, So you have to make Ramona bring him

(01:03:46):
back to age thirty three technically, which is or at
least like two thirty eight. So we also want to
add of course lifestyle and nutrition and all that because
it's if somebody is not already doing that. We can
also get some edit effect there to do a good

(01:04:10):
job in this competition, because like it's not very scientific
because you know, combining one hundred things you want really
know what makes the effect, but for ex prising it
might work. So we'll also add Yeah, potentially TRT or

(01:04:34):
stem cells there, so we'll see. But this trial a
more comprehensive one. It will happen, probably not eleven twenty
twenty seven, but yeah, we'll keep you in the loop.

Speaker 7 (01:04:50):
Yeah, it's looking at my biomarkers are not very good
from what I've got a very high BMI. That's one
of the things of not being able to exercise well,
he said, it's very difficult to keep my body weight
down and keep my appetite down. I did get an
HRV monitor. My HRV is terrible. I'm like, it's average

(01:05:13):
is like eight, but it weren't supposed to be like
in the thirties. And I did go to a COVID
therapist and she said about meditating to get either of
the sympathetic mode. But frankly, it just doesn't work. I
could meditate, maybe I'll work for fifteen thirty minutes, and
I'm just back to my crappy HRV. So it's not

(01:05:35):
really a cure. It's just a very short term therapy
of meditating. I've tried even the postsetto it might help,
but it's very temporary effect. So yeah, I'm definitely looking
for something.

Speaker 3 (01:05:51):
Harder, hitting.

Speaker 7 (01:05:53):
Along a ture, not just a therapy that gets me by.
Thank you, thanks for coming on.

Speaker 1 (01:06:00):
Indeed, and long COVID, of course, is a very difficult
condition to treat because it manifests differently in different patients,
so therapies that might work for some don't necessarily work
for others. I had long COVID for a year myself,
and I essentially exercised my way out of it through

(01:06:23):
graded exercise therapy where I would target particular heart rate zones.
And initially I didn't care so much about the pace
of my running as long as I was hitting those
heart rate zones. But over time my speed improved and
I essentially became reconditioned. My response to stress became normalized.

(01:06:48):
But I most likely had a lighter case of long
COVID than art ramone does. So Jose did have another
part to his question about moving faster with fuller stet
and cloth though, So if you could address that, I
think that would be of interest to our audience.

Speaker 5 (01:07:09):
Thank you.

Speaker 2 (01:07:10):
Yes, yeah, So, first off, start with hair loss here. Indeed,
the hair loss your correct process is not that important,
but we in the team, we think it's like how
you look, it shows also your age, So if you'll
be able to improve your looks to a younger state,

(01:07:31):
you're kind of also offset aging. So we think it
People really care about how they look, at least a
lot of people. And what's counterintuitive, and what's been told
to us also by our clinical partners, is that generally
from a financial standpoint, people are willing to pay more

(01:07:53):
to improve how they look. And they already do, like
invest I know, tens of thousands per year into improving
how they look, and not so many people invest that
much into preventive help. So it's it's kind of becoming
in trend right now, but it's not that big compared
to this huge aesthetic industry so far. It's also a

(01:08:20):
way to be more interesting to investors or to people
who don't care that much about aging at this point.
But I want to do like experiment with the halos
and it's surprising. It's all surprising for me maybe because
I don't have halos, but a lot of people do

(01:08:40):
care about that. And yeah, regarding to for all the
statting cloth, yeah, we see a lot of demand for
that in the market, and we want to get there
as fast as possible. As soon as we solve for

(01:09:02):
like all the issues, we plan the trials, so right
now we are we'll probably do trials with a full
standard as well. So we need to map out, like
how to test patients for some applicability of A V
therapies because, for example, some people have elevated antibiodies for

(01:09:28):
A V's and they for them the therapy won't be
effective or will have a larger side effects in terms
of immune reactions. So one of the screenings we need
to do is testing for AV antibiodies and even be

(01:09:48):
specific for the AV serotype we use, because there are
different types of A V. Also, there are also ways
to suppress immunity before the injection, so we are also
developing immuni suppressed protocols and we learn a lot from
lis Parish there of course, So there are various approaches

(01:10:10):
to that and we need to get them straight yeah,
before we go to humans, but we expect it to
happen this year, so that's the target.

Speaker 1 (01:10:23):
All right. Thank you very much for those answers, and
we have a number of additional questions. Mike Lausine wonders
whether these gene therapies might be less effective the older
a patient is. To him, it seems the gene therapies
might work best in younger people, and I wonder if

(01:10:47):
that has been your observation, or whether the efficacy is
largely uncorrelated with the age of the patient. And we
could have, say, even extreme situation, somebody who's twenty years
old receiving the gene therapy versus someone who is ninety
years old, But clearly the ninety year old would be

(01:11:08):
in a position to benefit more as compared to a
twenty year old who is healthy.

Speaker 2 (01:11:17):
Well, in our case, we'll be targeting slightly older people,
so I would say roughly about fifteen years old and
older I think up to seventy or eighty, because also,
of course, after a certain threshold you do get a

(01:11:38):
lot of risk. For example, if you get eighty year
old patients which already have like home abilities and inject
them with like therapies which do affect the immune system,
so they produce a strong immune reaction that potentially can
be dangerous. Although those patients are the ones who might

(01:12:00):
benefit a lot from them, of course, because they're just
going to die from old age. So they should be
a certain like best guge to do gene therapy. We
just don't know what that number is because, for example,
if you look like prevention is amazing, of course that

(01:12:24):
you don't wait for your car to break down. You
just do maintenance and it's always in a good working,
stable condition, let's go. But also people who are in
great shape, who are young, and who exercise, and so
it would be for sure harder to see in effect.
So for us, I think like the best possible person

(01:12:48):
to see in effect would be someone in like late
fifties or sixties who doesn't do much about longevity. I
think in this case we'll see the biggest effect. Yeah,

(01:13:08):
we need to, we need to, we need to show
the team trials. So it's just the idem.

Speaker 1 (01:13:15):
Yes, thank you. And that makes sense essentially to attempt
rejuvenation therapies in people who already need some significant rejuvenation,
but who are also young enough to be able to
benefit significantly from the therapies. So that's definitely a sensible approach.

(01:13:42):
Now in terms of how long these therapies last, Rudy
Hoffman wonders in regard to a time frame that he
saw recently that some gene therapies may only last a
few months, and if I recall correctly, five months was
a timeframe mentioned earlier on in this stream, but he

(01:14:03):
notes it probably depends on the vector and the level
of the effect itself. So what could you tell us
about the effective time frames of any of the gene
therapies that Unlimited Bio plans to administer if that period
of effect is known? And if it is known, what
would be the plan for these patients, especially if they

(01:14:25):
receive significant benefits? Would they be coming back for periodic
administrations of the gene therapies every few months or every
few years, whatever is convenient for them and whatever would
maximize the effects. What are your thoughts on this?

Speaker 2 (01:14:46):
Yeah, thank you, it's a great question. Yeah, there is
this concern, of course, because for now quite pricing, So
you don't want to spend a lot of something which
just works a few months. In case a pleas mets,
we expect that's the case. Pleasmet is just DNA and

(01:15:07):
it's unprotected. It's and inside the cell, say, it also
has to go through the cell membrane and travel to
the nucleus to actually start working. So the first problem
is you need like a very large density of those
pleasmids injected for some of them to actually ask the

(01:15:27):
cell membrane and get to the nucleus, and there will
be few of them and they will degrede. I think
what the science shows so far that in a few weeks,
so not even months, but what we rely upon one
day is clinical data and also how VGF works that

(01:15:52):
if it gets increased production for a couple of weeks
or even like one month, if you do two rounds
of inject for VGF, we recommend two rounds of injections
two weeks apart. That's what he was found out who
works best in clinical trials. And when you get this
protein secretion for one month in this site, it'll get

(01:16:15):
the capillary bad formed. Then the pleasants will degrade and
kind of the therapy will stop working, but the capillaries
will keep functioning. So if you'll use those muscles afterwards,
so you'll keep walking. Of course, if you'll sit on
a couch, probably it won't be as good, but if
you keep moving and keep using those muscles, then the

(01:16:42):
capillary network will persist. And there were five years follow
up whiles with the VGF plasmid and they show that
the effect grows up to three years, then it kind
of starts going down, but still even after five years
is above the baseline. So with the VJF pleasant specifically

(01:17:05):
we need to reject reinject every three to five years.
But an important point is that it is for VGF
because it does form our caplorists for other proteins which
you need like all the time for example, fall the
stat and you need it in your body all the time. Wise,

(01:17:26):
if the levels go down, your muscle mass will go
down to the baseline. Right, So in this case we
want a longer a way longer effect, and that's why
we go for a v therapist in this case. And
it is I think the lasts so we say like

(01:17:46):
roughly ten years or something like maybe longer. I'm not
even sure there are studies to to make like a
good opinion there, but certainly way longer than pleasants. So
we hope to see a really long lesson effective babies.

Speaker 1 (01:18:12):
Yes, thank you for that answer. And it does make
sense that the effective timeframe would vary by the therapy
and the delivery mechanism.

Speaker 5 (01:18:23):
For VGF.

Speaker 1 (01:18:25):
I assume somebody would go to prosper and stay there
for the multiple administrations space several weeks apart, and then
when the blood vessels do grow, then they won't need
the treatment for a while and they could depart and
live their lives. So interesting answer and good to get

(01:18:47):
some insight into the patient experience. Now another aspect is,
of course the cost, and Rudy Hoffman does wonder about
whether there's a cost estimate for the gene therapy clinical
trials themselves, and then a follow up question would be
what would be the cost for the patient. Some gene

(01:19:10):
therapies are expensive. I remember Bill Andrews was working on
a gene therapy for telomerase activation for Alzheimer's disease patients
back in twenty eighteen twenty nineteen, and he said essentially
the only way to administer his gene therapy would be

(01:19:33):
for a patient to pay a cost of about a
million dollars. So he was seeking essentially celebrities with Alzheimer's disease,
but to my knowledge, he wasn't able to find any,
even though they existed, But maybe their caretakers weren't as
eager to have them undergo an experimental gene therapy, so

(01:19:54):
that was unfortunate. But what is essentially your cost ex
and would you have the patients fund most of the
cost or would you have your investors fund most of
the cost in order to show the results that you
are looking to achieve.

Speaker 2 (01:20:16):
Yeah, so for therapies which were already proven safe and
effective in case of PD, for VGF pleasment, we do
charge for participation in the trials, and the prices from
ten to thirty thousand or VGF pleasment depending on the
amount of wiles and on the injection sites you want

(01:20:38):
to get administered in and for the trial I was
talking about a lot. For GIN therapies, it will be
free for the patients because we need to show that
this combination is safe, so we'll know that each of
them is safe separately, will know that they're safe in

(01:21:01):
a combination within animals, and then we'll need to show
that they're safe in a combination within humans. And that
will be free of charge for the participants. But of
course you'll need to reimburse the travel costs and it
will require several visits to the clinic, so you'll still

(01:21:25):
need to spend some money for travel and potentially for
tests not so much. And yeah, what you mentioned so
right now we have gene therapies on the market av
gene therapists which are like two million or one million
and so on, extremely expensive, and right now there are

(01:21:47):
people traveling to Latin American countries getting those gene therapies
like follestating or each thirty for telemerase extension for hundreds
of thousands the single therapy, So people to trail there,

(01:22:07):
they get those injections, they pay a lot of money,
and then we don't get any knowledge and what happens there,
like what are the results. It's like just disappear somewhere
in the grade. And what we want to do is
actually bring that data out. So we want to see

(01:22:31):
what works. And with those therapies we expect if they
were we should really see impressive results. For example, if
you do get high dose for the starting therapy, we
expect that you really get an increase muscle mass. So
it won't be just I might see something on the scale.

(01:22:51):
I'm sure if it's like plus one killer, you know,
it should be like a really significant effect. So should
help us also to see the efficiency in the trials
with a few participants. So if we really see before
and after pitches then yeah, it would be amazing. M

(01:23:14):
that's where we need people at least rembers in the
or cost of travel coming to the clinic taking the therapies.
And then.

Speaker 1 (01:23:27):
Yes, indeed, thank you for that answer. And ten to
thirty thousand dollars is of course a much more affordable
price point for many more people than the hundreds of
thousands or the millions of dollars that prior gene therapies

(01:23:48):
have costs. So even if people do need to fund
their own transportation, hopefully this will be a significant improvement
to the accessibility of these treatments. And that is the
pattern that we hope will manifest itself to a greater
extent over time as these therapies become more developed, as

(01:24:13):
companies like Unlimited Bio enter the market. Essentially, the innovation
the research will help to drive down the cost and
make the therapies increasingly available. And Rudy Hoffman along these lines,
compliments you on the aspirational goal of being a thousand

(01:24:35):
times cheaper to market, So thank you to Rudy for
those good words. And Rudy does wonder though, if the
optimal gene therapy would need to have hundreds of impacts
on the genome. Given that aging is multifactorial, could each

(01:24:56):
one of these impacts possibly have its own unintended console
quensis And what would you do to essentially reduce those
unintended consequences and monitor for them to understand if you're
giving a combination gene therapy, which aspect of that treatment
actually led to any undesirable side effects? And hopefully there

(01:25:20):
won't be many side effects, But if you do see one,
how would you associate it with a particular part of
the combination gene therapy.

Speaker 2 (01:25:34):
Yeah, So the good thing about gene therapy is that
you get an increased secretion of protein which is already
present in your body. But if you do it right,
you just bring this secretion to like a younger state.
So for example, as I showed with CLOTHO, it's declients

(01:25:54):
with age. So if we make it like this, maybe
we shouldn't go like this, like to get the super
over expressed in humans. It's potentially can have some weird consequences.
But if we go to a level which young people
show them, we have safe to go there because it's

(01:26:18):
just a protein. You didn't get anything else with it, Like,
it doesn't it affect the same pathways as the original
protein and it's absolutely the same molecule. So that's the
good part about gene therapy that well natural is probably
a bad word, but it's like really natural to your
body comparedity to small molecules which have like a hundred

(01:26:42):
effects all over your body and we know a few
of them and maybe the rest of them we don't
even imagine, and then they will show up unexpectedly in
the trials and that sounds gene therapy is they are
way way more predictable. So the major concern with them is,

(01:27:02):
as I mentioned, the immune response. Because you get a
lot of virus in your body, then you do get
an immune response, So tackling that is the most important concern.
And regarding the combination, yeah, for sure, we need to
test every combination before we go to humans, and we

(01:27:24):
also need to have a safety data on each component
of the combination. And that's why it's important to do
for clinical trials also in a cost efficient manner, and
in this case, we do our trials and mice. So
right now we do trial on old mice and we

(01:27:46):
do it in Russia just because it's like five to
ten times cheaper that than doing it in the US
or Europe. I think the mice itself, they're like old mice,
extremely expensive in US and Europe, so that's how we
cut down the cost. But of course, well we'll check

(01:28:09):
the safety before going to humans.

Speaker 1 (01:28:12):
Yes, and I would encourage you to publish the lifespan
data for those old mice, because, as you know from
Aubrey de Grey's comments, it is absolutely essential to show
major rejuvenation and mice that are already fairly advanced in
age and the longevity Escape Velocity Foundation recently concluded its

(01:28:36):
first robust mouse rejuvenation study with a thousand mice that
were in middle age, so around a year and a
half old when the study started, and the oldest mouse
died at a bit over three and a half years old.
So that was significant life extension, but comparable to what

(01:28:57):
various other studies have shown at the outer limit. But
if the study you mentioned starts with already quite old
mice and is able to achieve significant life extension in them,
that would be remarkable, definitely worth publishing and sharing with

(01:29:17):
the world. So I would strongly recommend that this be
done now. I also see a question here from Daniel
Tweed which is an interesting one, perhaps a bit unconventional,
but maybe helpful to some potential trial volunteers. Does Prospera

(01:29:43):
recognize the World Citizen Passport? There are some countries that do,
apparently Burkina, Fasso, Ecuador, Mauritania, Tanzania, Togo, and Zambia. And
it seems that Prospera is fairly open in terms of
the people it welcomes. So you presumably didn't have any

(01:30:07):
issues getting into prosper even though a visa from Russia
may be scrutinized in other parts of the world. So
what about this World Citizen passport and what else can
you tell us about how easy it is for people
from various countries to get into prosper and if there

(01:30:29):
are any barriers or processes that need to be followed.
I think it would be helpful for people to know
about those as well.

Speaker 2 (01:30:40):
Yeah, to be honest, I never heard about that kind
of passport, and I'll try to find out if Prospera
recognizes that well. Part of that. Yeah, they seem to
be really open to all the nationalities, so it might
have some restrictions, maybe for North Korea, I'm sure lot.

(01:31:03):
So I don't want to say anything there that I'm
not sure of. So they're quite open, but no idea
if they recognize it. Sorry about that. I also wanted
to say a word about what you said regtting mice lifespan. Yeah,

(01:31:25):
we did have some groups planned a small ones unfortunately
for lifespan file, so we'll see how long they live
with that combination. Unfortunately. Yeah, we couldn't allocate minimize into
them because as I said, the old mice really rare,

(01:31:46):
and we got all the mice we could get, Uh,
it wasn't enough. So we have I think one hundred
and six mice in the trial. And also that being said,
I mean and it's very important for competition, and it's
it makes a good headline if you make a mice
live one hundred percent longer. But even if it does

(01:32:10):
make mi s live that long, it won't necessarily have
any effect in humans. So the most important thing in
mice for us is to see the safety effects on
the liver, on the brain, and so on. And that's
the most important finding that we can go into humans
and to actually meaningfully say that yet will have an

(01:32:34):
effect on humans. We need to check that in humans.
And I think that's the problem in the longevity science
right now that everybody has a lot of things to
say about mice lifespan and what works on mice doesn't,
but it doesn't really translate to humans because even mice

(01:32:55):
in humans, they have really different aging patterns, different consequences
of death. Mice get way more cancer and they don't
get to Alzheimer's and so so yeah, we'll see, will
still check it, but it's not the most important thing
for us.

Speaker 1 (01:33:16):
Yes, thank you for that answer. And indeed, just yesterday
I had an online message exchange with someone who asked
me after I shared the final survival curves for the
Robust Mouse rejuvenation study, which showed that the treated mice
by and large lived significantly longer than the untreated mice,

(01:33:39):
and RAP a micein was the most effective of the interventions.
The mouse that lived the longest was actually a mouse
that received just the rap of mice. And so this
person asked me, well, do you personally plan to take
any of the interventions that were administered, and I said, no,

(01:33:59):
not this time, because mice are not humans, and what
extends lifespan and mice may not necessarily extend lifespan and
humans so rap a micein has been demonstrated by numerous
studies now to significantly extend lifespan and mice by thirty
to forty percent, and yet that demonstration in humans has

(01:34:19):
not yet been achieved. Some people do take rapamcein, but
others who have taken it have discontinued it because of
some of the side effects. Brian Johnson is a prominent
example of such an individual. And in terms of say
caloric restriction, which has also worked to significantly extend the

(01:34:41):
lifespans of mice, the larger an animal is, the less
the benefits are of the caloric restriction. So in primates
there has been shown to be a very modest benefit.
In humans, it's not certain whether there's much of a
benefit at all. Maybe there is benefit of one to
two years or so, but that's still an open question

(01:35:05):
because there's not really a huge longitudinal lifespan study on
caloric restriction in humans. But clearly it doesn't achieve the
kind of rejuvenation that we would need to truly reverse
biological aging. Now, on Prospera and the ease of admission,

(01:35:28):
Josh Universe does note that Prospera requires an application for residency,
so that is something that any tourists would need to
fill out. But presumably those applications are granted fairly easily,
so people aren't scrutinized heavily, but they do need to
complete the paperwork and fill out all the fields correctly,
so that's important to note. And Jose has a question,

(01:35:51):
so please go ahead.

Speaker 5 (01:35:52):
Yeah, sure, I was in Prospera.

Speaker 4 (01:35:54):
Also, actually Prospera is within Honduras, so you need to
go through immigration in Honduras. There is no separated immigration.
You have to go through Honduras immigration. Honduras, though, is
a fairly open country, so there shouldn't be many problems
getting in. But yes, there is no separate immigration. It

(01:36:16):
is the big government, Honduras government.

Speaker 1 (01:36:22):
Yes, thank you for clarifying, Jose, And yes, it seems
like the Honduras government is one of the more open
governments when it comes to immigration policy. Mike Lasine wonders,
so is it easier to become a citizen of prosper
than of Mexico and some EU countries. So I would
say there's a difference between being able to travel there

(01:36:45):
and becoming a citizen. I don't know what the policies
are of becoming a citizen of Honduras, because that's what
this would entail. But presumably traveling there spending a few
months there is a lot easier than citizenship application would be.

Speaker 2 (01:37:03):
So that, yeah, like becoming a resident is extremely easy,
So you do it online and I think it costs
like a hundred us D roughly for a years something
like that. And in fact, all our trials will require
for the participants to get Prosper residents because we are
a company based on Prosper and our insurance company obliges

(01:37:28):
us to only work with Prosper residents. Luckily that the
residency is very easy to get. And yeah, I know
some people who live for a prolonged time in Prosper
and in this case they either need to get also
residency in Honduras to not get any problem on the border,

(01:37:48):
or you can just forget about it and just pay
a small fine when you leave, and you can even
stay for a few years in Honduras and then just
pay a few hundred dollars fine quite small and they
will let you out. So it's hard work to know.

Speaker 1 (01:38:09):
Yes, thank you, and you mentioned your insurance company. Now
I am in actuary. So I have considerable knowledge about
insurance and I am curious for a company like Unlimited
Bio that works in Prosper what kinds of insurance do
you have or are you required to have or do

(01:38:30):
you feel that you need? What do they cover and
what are the requirements?

Speaker 2 (01:38:37):
Yeah, insurance is the obligatory for all residents a Prosper
and for companies as well, especially if you operate in
health or some regulated spheres so to say, so where
in all the spheres where you can potentially endanger humans,

(01:38:58):
you do need to get extra coverage. And yeah, it's
obligatory tork rates and we have that although we don't
directly work with patients, but we are responsible for delivering
they drug to the clinic. So the clinic of course
is also insured. So there's this double layer for protection.

(01:39:21):
It's not very hard to get likely. You just need
to show what you'll be willing to do, what kind
of data do you have, who you will work with like,
then they will evaluate and your risk profile and you
just have to pay it every year. And yeah, that's it.

Speaker 1 (01:39:46):
Yes, thank you for that answer. And I actually spoke
at the last Longevity Summitt Dublin in twenty twenty four
with trake Off from Prosper who was there as a
represent and I had an extensive conversation with him about
the insurance aspects as well, and he said at that

(01:40:08):
time that essentially the entity behind prosper was itself providing
the insurance at that point in time, but they were
open to other insurance companies participating in essentially offering these
insurance policies as options for businesses that seek to set

(01:40:31):
up on Prosper. Is it still the case that you're
getting your insurance from prosper it directly or are you
getting it from another company?

Speaker 2 (01:40:40):
Yeah, we're getting for now, we're getting from prosper directly
from a company directly affiliated with prosper. But yeah, I
know they have a plan that should be competitive, so
kind of on one hand they evaluate the risks. On
the up hand, they don't want to charge you that
much because I can get insurance in another application to

(01:41:01):
keep it like the market to open. But yeah, it's
right now. It's a very small place, so I think
they only have like a little over one thousand residents,
so it's very small and they don't get that many
businesses there. But they did get a lot of promotion recently,

(01:41:24):
so they got visited by The Drapers and they did
an episode of the show for mid the Drapers Show,
so the start up show. They had a large crew
coming in. Both Adam and Team Draper were there and
actually we competeed and we went on to the finals
or I probably cannot disclose that. You should tell a

(01:41:47):
sense of that. But the finals will be in October
this year, and he asked us to not to say
one the result because they will be releasing the show
later in the year, so sorry about that. And they
also got visited by quite a popular YouTube channel recently

(01:42:09):
called Yes Theory, and that was a curious episode. So
if you want to see a bit inter Prosper, you
should watch this episode. Yeah, it's fun. And unfortunately we
were not there because my teammates already left Prosper. But

(01:42:33):
I'll drop the link in the chat.

Speaker 1 (01:42:36):
Yes, we will share that link once you make it available.
And in the meantime, I would encourage everyone to watch
my interview with Trey Goff of Prosper. We had a
conversation for about half an hour on the legal, jurisdictional, logistical,

(01:42:56):
reputational aspects of Prosper, and he gave some quite thorough answers.
John H. Wonders, what is the entity behind Prosper. The
name of that corporation is Honduras Prospera, Inc. And that's
the entity that offers the insurance. And then the link

(01:43:19):
to the documentary that Vladimir shared is posting right now
and I will elevate it to the screen here. It
is for anybody who is interested. And now we have

(01:43:39):
another question with regard to essentially the jurisdictional aspect. So
I asked, well, what are some contingency plans, if anything
should happen to the stability of prosper. Daniel Tweet wonders
about a company nation of a cruise ship in longevity

(01:44:03):
laboratory cruise ships are in international waters. I know there
are some cruise ships that do administer medical procedures. I
recall being on a cruise once in the Caribbean where
they had a medical clinic as well, and I don't
recall what treatments were being offered there, but it seems
that there's more flexibility in international waters. Have you considered

(01:44:27):
something like that.

Speaker 2 (01:44:31):
Yeah, we didn't actually consider that, but yeah, but potentially
it might be interesting because also Prospero does get not
prosperably rot on islands, but Prospero is based does get
visited by a lot of cruise ships. So I think
like two million tourists a year visit rout because of

(01:44:53):
cruise ships, and maybe some of them visit the clinic.
But yeah, if somebody can provide us with a cruise
ships where we can set up a lab in a clinic,
then yeah, we can consider that. But so fine, it
seems like a nice ski fi perspective that you know,

(01:45:15):
people get rejuvenation treatments in the securitive ship and unusual waters.
Sounds fun but probably not very realistic. And it's good
to be in a place where you also have an
emergency care and the ease of transportation and so on.

(01:45:40):
So we want to stay on the land now. Yes.

Speaker 1 (01:45:47):
Actually, a discussion that I recently had about Prospera pointed
out that the prosper jurisdiction itself, so Honduras pross for
a ink, does impose certain restrictions on the kinds of
treatments that may be administered there, particularly from a standpoint

(01:46:10):
of what would happen if the patient needs emergency hospital
care because there's not an emergency hospital on the Prospera grounds,
so to speak. Somebody would need to travel farther away
to get true intense, life saving emergency treatments. So perhaps

(01:46:32):
you could talk a bit more about that and what
limitations there are on the kinds of treatments that could
be administered in prosper and where someone would go if
they needed emergency care.

Speaker 2 (01:46:50):
Yeah, there isn't a problem in Rawtant. They had a
hospital there, but I think it got burned down recently,
so yeah, the situation with the regular healthcare is far
from good.

Speaker 1 (01:47:02):
Then.

Speaker 2 (01:47:03):
I think our clinic, I think we partnered with it
has all the facilities to help patients in case of emergency.
But as an additional precaution, of course, we don't go
for ultra high dose av therapies, which can have a
severe effects on the immune system, so we want to

(01:47:26):
start safe with relatively low doses which were already shown
very safe in humans. And also I think they had
contract with helicopter company to evacuate patients in case of
a real emergency, so they had that plant. I think

(01:47:49):
it kind of got slowed down because of the political situation.
Probably you could have help just flying without using the
Honduran customs or whatever. But maybe they'll get it later on.

(01:48:11):
We'll see.

Speaker 1 (01:48:13):
Yes, thank you for that answer. And as you can see,
we have a lot of questions about Prospera as a jurisdiction.
There's another one from Rudy Hoffman. He wonders, is there
a strong culture in Prospera that emphasizes rigorous, scientific and

(01:48:34):
replicable protocols to take the place of overreaching regulations. So
clearly Prospera does not want governments to regulate the treatments
that are administered there, but it does have some of
its own parameters in terms of what it permits what
it doesn't permit. We mentioned essentially that some gene therapies

(01:48:56):
may be outside the scope of what's permitted there, or
psychedelic experiments are not permitted there. So it does seem
like there is an emphasis on scientific rigoran making sure
that these trials are conducted safely. But what are your
thoughts on this?

Speaker 2 (01:49:16):
Yeah, I think in case of prosper actually we need
to put a lot of emphasis on safety because if
something goes wrong within prosper it will not only damage
the company that led to that, but also the whole
So to say a country, the whole regime maybe under

(01:49:39):
under fire. In case something happens, your own authorities might
take a far more serious approach to technic prosper of course,
like we cannot speak for everybody, but in our case,
we do realize that significant risk and we want to

(01:50:05):
approach safely. So we want to work with therapies that
were proven safe but which are still not allowed in
the US because for example, they don't have a diase
indication or they didn't pass phase three trials yet. So

(01:50:28):
if they were filling safe in humans, I think we
are good to go there, provided that takes place in
a high quality medical facility.

Speaker 1 (01:50:41):
Yes, and that's a very important point. A lot of
people do not realize that the US FDA is much
more restrictive than is needed to simply validate the safety
of a treatment because of Phase two and Phase three
clinical trial requirements, which are the most expensive, especially phase

(01:51:01):
three to demonstrate efficacy with specific disease indications. But of course,
a big obstacle to research in the US getting funded
or approved is that aging is not officially recognized as
either a disease or a targetable medical indication, whatever name
you want to call it, for the purpose of actually

(01:51:24):
developing and testing treatments for those conditions. And that's why
it's essential to have other jurisdictions that do allow such trials,
such as Prosper and it's essential for those trials to
get underway as quickly as possible, which is why we
applaud Unlimited Bio for rolling out these combination gene therapy

(01:51:46):
trials very soon, and we thank you for being here, Vladimir.
We have about two minutes left in our virtual Enlightenment, Salonso,
I would invite you to make any concluding remarks, anything
else you want to share with our audience before we conclude.

Speaker 2 (01:52:06):
Yeah, one last thing. You mentioned Aubrey de Gray and
his combination trials on mice, and I maybe it felt
for the audience that I disregarded the mice trials, but
I just wanted to say that Aubrey does support us
greatly and he thinks it's great. Finally somebody is bringing

(01:52:27):
the gen therapy combinations, say into humans, so I very
much thank him for all his support and what he's
done in the field and his work on combination gene
therapy or on mice is incredible and nobody did that before.
So I applaud to him and thank him for the
support he has given us. So and I also thank

(01:52:54):
you guys for having me this afternoon or evening. Was
a great to ours with you. So thank you very
much for the questions and all the decency interest and
what we're doing. So I hope to see you around
at events or gene therapy trials whatever. Stay alive and

(01:53:16):
stay healthy.

Speaker 4 (01:53:17):
And welcome to Madrid in October. Yes, thank you, Transvision.

Speaker 1 (01:53:24):
Madrid will happen in October of this year. And thank
you Vladimir for mentioning the robust mouse rejuvenation trials which
have been conducted by the Longevity Escape Velocity Foundation. Visit
their website at LVF dot org. I am on the
board of directors of LVF, so I would highly recommend

(01:53:45):
their work and supporting their work. Also, visit the website
of Unlimited Bio at Unlimited dot bio. Find out more
about the team about the clinical trials that will be underway.
And indeed, as Brian Johnson would say, don't die, as
we would say, live long.

Speaker 5 (01:54:06):
Prospers word

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