
Three New Longevity Startups - apsec112
https://www.leafscience.org/three-groundbreaking-longevity-startups/
======
BiochemOki
Hi, I'm co-founder of Underdog and the scientist who invented the drugs we are
developing. Cool that this community has taken an interest. I agree with a lot
of the insightful comments here. If you're interested in diving deeper into
the toxic cholesterol that we're targeting I've just published a review
article all about its biology and all the aspects of aging and disease that
it's involved in:
[https://www.sciencedirect.com/science/article/pii/S221323171...](https://www.sciencedirect.com/science/article/pii/S2213231719311759)

To touch on a couple of the other points that have been raised here, no our
drugs aren't enzymes. We at SENS were working on an enzymatic approach for
many years. There is still potential to engineering enzymes for this, but I
designed our cyclodextrins to be a faster/cheaper/easier path to the clinic.
Well, not that much cheaper. It's still very expensive. And yes, we are well
aware of the hearing loss issue. It's avoidable, we believe we understand what
caused it, and we're engineering around it. We'll be able to test whether we
are successfully avoiding hearing loss in a very sensitive system in the next
9 months.

How long will we last? 16 more months with our current funding and burn rate.
By then we need to have moved into series A so if anyone has any pharma VC
contacts I'm definitely looking for warm intros :)

~~~
DrAwdeOccarim
What is your opinion of using a monoclonal antibody against 7KC instead of
cyclodextrin since mAbs are very well understood from a regulatory and PK/PD
point of view. In your review I only see that you discuss 7KC antibodies as a
method of screening for people who could benefit from your therapeutic idea.

~~~
BiochemOki
Great question. Two problems with making a therapeutic antibody against seven
KC. One is that we are not sure how good the seven KC antibodies are yet. We
are working on this. The problem there is that 7KC only differs from
cholesterol by one atom. The other problem is that the 7KC that we are worried
about is inside of cells, so our drug is designed to mechanically pull the
seven KC out, which antibodies can't really do. Also, cyclodextrins are very
well accepted by regulators, it's just that they are usually used as
excipients rather than as Active Pharmaceutical Ingredients (APIs). There are
two examples of cyclodextrin APIs already, however, one approved and one in
late stage clinical trials.

~~~
DrAwdeOccarim
Cool, thanks for the reply. Are the approved use parenteral? Have you
considered aptamers?

~~~
BiochemOki
Yes, we are looking at IV, as others have done already clinically. We aren't
looking at aptamers or other clever ways of binding small toxic biomolecules.
I hope that other groups are!

~~~
DrAwdeOccarim
This is a pretty interesting paper:
[https://stm.sciencemag.org/content/8/333/333ra50](https://stm.sciencemag.org/content/8/333/333ra50)

Is there a chance that you are developing CD that target 7KC but at the end of
the day, it dissolved chol-containing plaques inherently and that's where
you'll derive the benefit from?

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wwwtyro
More on Underdog Pharma: [https://www.fightaging.org/archives/2019/11/an-
interview-wit...](https://www.fightaging.org/archives/2019/11/an-interview-
with-matthew-oconnor-as-underdog-pharmaceuticals-secures-seed-funding/)

"We've taken a well-known and extremely safe compound, and have created novel
derivatives that can specifically target the toxic biomolecule that drives the
development of atherosclerosis, the cause of most heart attacks and strokes."

I'm excited for this one. Seems like a reasonable possibility for success
addressing a huge killer.

~~~
assadk
> The company is focused on a class of molecule known cyclodextrins, and have
> candidates capable of efficiently binding and sequestering
> 7-ketocholesterol. This form of oxidized cholesterol is of great importance
> to the progression of atherosclerosis, and possibly other age-related
> conditions as well.

The thing is cyclodextrins have been linked to causing deafness, in as little
as a week. As per
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676048/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676048/)
and [https://www.wsj.com/amp/articles/deaf-or-death-in-drug-
trial...](https://www.wsj.com/amp/articles/deaf-or-death-in-drug-trial-
parents-weigh-life-vs-hearing-loss-1425267002)

Heart disease or hearing – tough trade-offs. Here’s to hoping that they’ve
engineered a novel compound without any of the downsides.

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TheUndead96
I think longevity is vastly underestimated. Besides the natural innate desire
to live longer, every extra year of healthspan is an opportunity to reap
benefits on long term investment in friends, family and financial instruments.
Knowing that you may live to 150 changes how you might approach investing and
spending your time in money and skills development. People with the
conscientiousness and forethought to apply themselves to important but not
urgent tasks might experience compound interest the likes of which we have
never seen before. Imagine if Warren Buffet was only half way through his
healthspan.

~~~
speedplane
> I think longevity is vastly underestimated.

Many people would give up their entire life fortune, any inheritance to their
children, just to live for a few more years. People have been killing and
dying searching for the fountain of youth for centuries.

Everyone is going to die eventually, yet the extremes people go to extend life
is unlike any normal supply and demand curve.

I'm not sure there's anything more overestimated and over-hyped than
longevity.

~~~
luspr
There is not enough funding or investment in longevity to consider it over-
hyped. Compare it to, say, AI and VR. Or even meat substitutes.

~~~
speedplane
> There is not enough funding or investment in longevity to consider it over-
> hyped. Compare it to, say, AI and VR. Or even meat substitutes.

You're very much mistaken.

The National Institute of Health gets $31B of government funds every year for
research. The NSF gets $8B, NASA gets $20B, and DARPA gets around $3B. So
healthcare research gets roughly 50% of the entire U.S. public research
budget, and that's not including private investment.

It's difficult to pull accurate numbers, but meat substitutes, VR, and even
super-hot AI get far less every year, it's nowhere near healthcare research.

Extending life has been a priority of the US government for many years,
largely because it's politically popular. Everyone rich or poor wants to live
longer.

~~~
hobofan
That is "traditonal" healthcare, where the target age is 70-80ish, with
basically no means to get past that.

This is very different from what longevity research (like in the article) is
tackling, and almost non of that money (public or private) is invested there.

~~~
speedplane
> That is "traditonal" healthcare, where the target age is 70-80ish, with
> basically no means to get past that. This is very different from what
> longevity research (like in the article) is tackling...

If you're searching for a cure for cancer, heart failure, or any of fatal
health ailment, you are by definition trying to extend people's lives. The
entire purpose of healthcare is to extend both the length and quality of
people's lives.

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jv22222
Reading this article makes me very glad that I've been donating to SENS for
some time now. They are doing awesome work:

[https://www.sens.org/get-involved/donate/](https://www.sens.org/get-
involved/donate/)

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khaledkteily
I learned a lot through this, thank you for sharing.

I run a sperm freezing company (YC S19) incubated at Harvard and we've always
thought about freezing sperm as an extremely logical pairing with any life
extension technology; sperm can be frozen indefinitely with no loss in quality
(as far as we know), you could have 30-year old sperm frozen for us when
you're 130.

Since sperm develops mutations over time (~1 every 8 months) and DNA
fragmentation is associated with all manner of congenital conditions like
autism, younger sperm is generally speaking healthier.

Just wanted to share since it's something we talk about internally quite a
bit. What does it mean to live forever if you lose all your family members
along the way? How will society change to accommodate?

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tempsy
Longevity is a interesting one because there are so many studies out there
that have looked into calorie restriction as having a large positive influence
on healthy aging...

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deegles
At what age would these treatments be applied? How often?

~~~
rantwasp
this is mostly research. there are a lot of things you can do to slow down
aging right now - almost orthogonal to your age: sleep 7+ hours per night, hit
the gym (mix of cardio+strength), eat high quality food - the less processed
the better - also try to eat a plant based diet, reduce the level of stress in
your life, properly hydrate yourself, hang out with people you like, get a
pet, get a side project that is a work of love, learn something every day,
read books, reduce your social media (and media in general) consumption.

~~~
nostromo
> eat a plant based diet

I agree with everything else you've said, but the jury is definitely out on
this one.

~~~
chrisco255
The current life expectancy for Iceland in 2020 is 83.07 years, a 0.18%
increase from 2019. [1]

Life expectancy for Hong Kong is 84.7 years. [2]

Based on a comparison of 158 countries in 2013, Maldives ranked the highest in
fish consumption per capita with 166 kg followed by Iceland and Hong Kong [3]

Hong Kong also beats most countries in beef consumption, out-eating Americans
by nearly 50% per capita. [4]

So of the countries in the top 10 for life expectancy, we see a lot of meat in
the diet. India has the most vegetarians of any country (at 38%). And their
life expectancy ranks 133rd at 69.4 years.

[1] [https://www.macrotrends.net/countries/ISL/iceland/life-
expec...](https://www.macrotrends.net/countries/ISL/iceland/life-expectancy)
[2]
[https://en.wikipedia.org/wiki/List_of_countries_by_life_expe...](https://en.wikipedia.org/wiki/List_of_countries_by_life_expectancy)
[3] [https://www.helgilibrary.com/indicators/fish-consumption-
per...](https://www.helgilibrary.com/indicators/fish-consumption-per-capita/)
[4] [https://beef2live.com/story-world-beef-consumption-per-
capit...](https://beef2live.com/story-world-beef-consumption-per-capita-
ranking-countries-0-111634)

~~~
Rotten194
Some big confounding factors there. Hong Kong and Iceland are also very
wealthy compared to India.

~~~
scarejunba
There is a fortunate coincidence here. There are wealthy vegetarian castes in
India, and India tracks demographics by caste, so it's likely that the data is
out there for us to figure this part out.

An alternative is to do something like follow second-generation Western people
of Indian origin. I know at least one study of Tuberculosis in the UK tested
the effect of vegetarianism there and used the British Asian sub-population to
do so, so there's probably some info there too.

I don't know of any other large vegetarian groups.

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AnimalMuppet
Wonder how long they'll last...

~~~
rantwasp
the whole point of these spin-offs is that the majority of them will not
survive. there are a lot of ideas around aging and it’s really easy to get
carried away to the point we throw everything against a wall and see what
sticks.

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scandox
I'm interested if there is much anti-longevity sentiment here. I admit I'm
very much against further moves to artificially increase human lifespan.

Am I quite alone in this?

~~~
TeMPOraL
You're definitely not alone - though I disagree with your view, I've been in
enough back-and-forths about it on HN to know that plenty of thoughtful people
here are against life extension, for various reasons (that can't all be just
reduced to Stockholm syndrome).

For instance, there's worry that life extension will vastly worsen economic
inequality. Another problem is that a lot systems in society (e.g. retirement,
insurance) is implicitly based on current average lifespan, and a sudden
extension of it could cause such shockwaves in the economy that it would
create more suffering than it would save.

I mention these two because I acknowledge them as real risks, but despite
them, I'm 100% in support of life extension. I sincerely hope that one day
humans will be able to extends life indefinitely, while retaining full
capacity (i.e. no everlasting life in a body of a 90-years-old).

~~~
scandox
Interesting. I'm also interested in how you imagine your indefinite life. Do
you suspect that whole new avenues of existence and thought will open up? Or
do you view it as essentially more and better of the same?

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placebo
Love of life is not the same as fear of death. If the latter is what drives
the search for longevity then it will never be enough. So long as longevity
isn't used to find peace with life and death, and transcend our limited
perspective on life then I see it as just a frantic attempt to delay the
inevitable. Resisting death at 150 will be just as painful as resisting it at
any other age. If on the other hand it will give people more time to gain
wisdom and perspective on what life is about then that's a whole different
story.

~~~
waterhouse
Assuming it's like any other product or service, the people that implement
longevity (if they do) will be a tiny fraction of the general population, and
certainly not a random sampling thereof. Most people who end up being able to
make use of longevity treatments will have had nothing to do with those who
implemented them (except by working for company A which made product X which
was used by company B to make ... which was one of the components the
longevity researchers used); I think it'll happen regardless of their opinion
about it (well, I guess if they violently opposed it, maybe they could stop
it).

So, it's less a question of what drives the search for longevity than what
we'll do with it once it arrives.

