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...
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 :)
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.
"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.
> 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.
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.
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.
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?
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...
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.
Complete guess: Every 5-10 years (as it looks none of them are gene thereapies), depending of lifestyle and specific rate of damage of the individual starting around ~30.
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.
Would you rather billionaires place their money in a big trust fund so their giant tree of descendents don’t have to work for a living or would you rather them spend their entire fortune on longevity research in a desperate plea to stay alive? Which one would be better for society? I would argue the latter.
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).
But, to take your line of thinking further, what are the odds that we are currently at just the right lifespan for humans? If you are against increasing human lifespan, you should also probably be in favor of decreasing it, unless you think we are at very special point in time in entire human history.
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.
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.
[+] [-] BiochemOki|6 years ago|reply
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|6 years ago|reply
[+] [-] wwwtyro|6 years ago|reply
"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|6 years ago|reply
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/ and https://www.wsj.com/amp/articles/deaf-or-death-in-drug-trial...
Heart disease or hearing – tough trade-offs. Here’s to hoping that they’ve engineered a novel compound without any of the downsides.
[+] [-] mjfl|6 years ago|reply
[+] [-] TheUndead96|6 years ago|reply
[+] [-] speedplane|6 years ago|reply
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.
[+] [-] jv22222|6 years ago|reply
https://www.sens.org/get-involved/donate/
[+] [-] khaledkteily|6 years ago|reply
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?
[+] [-] tempsy|6 years ago|reply
[+] [-] deegles|6 years ago|reply
[+] [-] rantwasp|6 years ago|reply
[+] [-] hobofan|6 years ago|reply
[+] [-] AnimalMuppet|6 years ago|reply
[+] [-] rantwasp|6 years ago|reply
[+] [-] kresten|6 years ago|reply
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[+] [-] mjfl|6 years ago|reply
[+] [-] SubiculumCode|6 years ago|reply
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[+] [-] scandox|6 years ago|reply
Am I quite alone in this?
[+] [-] TeMPOraL|6 years ago|reply
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).
[+] [-] balfirevic|6 years ago|reply
I sure hope so.
But, to take your line of thinking further, what are the odds that we are currently at just the right lifespan for humans? If you are against increasing human lifespan, you should also probably be in favor of decreasing it, unless you think we are at very special point in time in entire human history.
[+] [-] thrwaway69|6 years ago|reply
[+] [-] macrolime|6 years ago|reply
[+] [-] placebo|6 years ago|reply
[+] [-] waterhouse|6 years ago|reply
So, it's less a question of what drives the search for longevity than what we'll do with it once it arrives.