FightAging
3-10-19

https://www.fightaging.org/archives/...0-summit-2019/

Jim Mellon's Juvenescence venture is at present one of the few major venture organizations focused on approaches to treat aging as a medical condition. Mellon and his colleagues outlined their take on the field in a 2017 book, also called Juvenescence. We are fortunate in that he is among the first few high net worth individuals to both agree with the SENS philosophy of damage repair, and then, much more importantly, follow through in action as well as word. He is not just seeing a massive market opportunity in treating aging, though that is certainly there, but is doing this because he wishes to achieve the goal of radical life extension - far longer, healthier lives for all.

Jim Mellon is a relentless promoter once he has entered a field. As the science progresses to clinical development, we need someone like this. He will pull in the largest, most conservative investment concerns who presently have next to no interest in treating aging, and his funds will enable the startups and development programs needed to produce therapies. This is the necessary next stage in the evolution of rejuvenation research and development: moving from the laboratory to the clinic, moving from startup with data to fully funded company with human trials underway. It is an enormous amount of work, and requires large amounts of funding. That funding doesn't just happen by magic; considerable effort goes into lining up all of the necessary moving parts.

Jim Mellon - Abundance 360 Summit 2019

Thank you ladies and gentlemen for listening at this relatively late hour in the conference. I'm absolutely delighted to be here. I'm a non-scientist, so when I do something new, which is what I'm doing in longevity at the moment with my partners, I like to write a book about the subject, so that I can organize my thoughts and get access to key opinion leaders. A year and a half or so ago, I wrote a book called Juvenesence, which is also the name of our recently formed company, and I traveled around the United States, 8,000 miles in an old Honda, which I kept in San Francisco.

The Honda has now been sold, sadly, but the information that I garnered was extraordinary, and I'm really pleased for the first time in my career - and it has been quite a long career - to have found something where I am actually able to, in a very small way, move the dial as opposed to just jump on a bandwagon, as I've done before. I started off as a fund manager, and then I got into mining, German property, and, latterly, biotech. I've been involved in the biotech business for twelve years, and what is amazing to me is that in just those short twelve years, there has been an enormous change in biotech - particularly in the last six or seven years.

So the first book I wrote on this subject was called Cracking the Code. It is available in the remainder bins of some bookshops around the world. Still available, low price. Then the second book I wrote is Juvenescence, which I mentioned earlier on. In that time frame, six or seven years, we've heard the dawn of artificial intelligence, you've heard about In Silico Medicine as an example, for the discovery of novel compounds. That didn't exist six years ago. We've had the cure for hepatitis C in the last six years. This was a terrible scourge, and now if you've got 80,000, you can be cured, and many people have been cured of it. The Gilead drug was the best selling drug in the world for a while, selling at its peak 20 billion a year. We've had cancer immunotherapy that did not exist just six years ago, and this year it is going to breach all expectations. Sales of cancer immunotherapies, which have had biblical results in some cancers, will be over 100 billion. That was just an idea six years ago. Of course everyone is familiar with CRISPR/Cas9, Cas12 and Cas13, and so forth, and its variants, and that did not exist, even in published papers, six years ago when I wrote the book Cracking the Code.

In those six years, so much has happened. New industries have been created. What is going to happen in the next six years? Well, the answer is that none of us really know. In our own company Juvenescence, which is the fourth company my partners and I have started in the biotech space in the last decade or so, we don't really know, and so we're trying to put together a load of subsidiaries that cover most of the ground of this area. Because, for sure, out of eighteen projects, which is what we have, surely something will work and produce returns for our investors, and most importantly benefit patients, and lead us all to live a healthier and longer life, which is the aspiration of most people on the planet.

It was mentioned that life expectancy has increased dramatically over the last century or so. It has stalled a bit in the United States and the UK, and that is because the environmental factors that led to the improvement in life expectancy, including such things as antibiotics and vaccinations, have run their course. Things like opioid addiction are now taking a toll on life expectancy in countries such as the United States and the UK. But it is a fact that nothing has changed biologically in the last century: you take someone out of 1900 and put them in today's environment, they will live just as long as we do. Nothing has changed in our fundamental biology. But today we're on the cusp of a major change. The biological engineering of humans, the rearrangement of our atoms and molecules to effect longer lives is with us. There are human trials going on at the moment, this is not science fiction, and one of our own products will be in humans in the first quarter of next year. We have very high hopes for that. So I say with confidence, that I believe that life expectancy at birth will reach 115 within 20 or 30 years. That will change the entire trajectory of our lives. We'll no longer just be born, learn, earn, retire, and expire. There will be a whole fundamental change to our lives, with Peter Diamandis in his various books has described admirably.

We all known of Jeanne Calment, was she a fraud or not? In my opinion she did live to 122. People can live very long lives, we're not destined to die, but there are various factors that lead to the aging process. Some people have geroprotective genes, such as Jeanne Calment, and those genes will eventually be inculcated into the broader population, and those genes - using gene editing - will be the thing that keep people alive to 115 and beyond. But for the moment, it is small molecules, stem cells, and organ regeneration that we're focusing on.

We know now that aging is largely caused by antagonistic pleiotropy and hyperfunctioning. Genes that work well in our early days work against us as we get older. That is now a converging theory, and it is very important one, and we also know that there are some creatures out there that display negligible senescence, that really don't die except from predation. We are similarly made from atoms and molecules, and when rearranged, in due course, our pattern of death will be a very different one. However, we need to stay on the bridge. We need to stay healthy, because in the next ten years there will be phenomenal stuff that will keep us alive longer, and in a healther condition, and that is a statement of the obvious. Don't smoke, floss your teeth, eat some chocolate, drink some red wine, but not in vast quantities, and exercise in moderation. The astonishing breakthroughs, the terminologies that some of you are familiar with, such as NAD+, p53, autophagy, mTOR, and so forth, will come to the fore as science accelerates and develops as rapidly as it is today.

But we are still in the primitive phase of this. We are still very early in the science, and hence the opportunity for investors such as myself, Peter Diamandis, and other collaborative colleagues in this industry. There are some things out there that we can do now. I don't recommend hooking yourself up to a young person along the Ambrosia lines. Elevian are doing great work in seeing what factors in young blood could be applied to older people. I also don't recommend caloric restriction: it might add 5% to your life span if you starve yourself, if you eat 25% fewer calories, but it will feel like a very, very, very long life. Mimetics of caloric restriction are being developed, such as by ourselves in conjunction with the Buck Institute, and they will be in wide dispersal in the relatively near future. Then of course there are things like Elysium's Basis, there is metformin, for which a trial is going on at the moment under FDA auspices and Nir Barzilai. Then there is rapamycin, which is now being applied in dogs with some stunning effects, and rapalogs will be in human beings. My own Jack Russell terrier, Horatio, who is twelve years old, is now on the rapamycin, and I can tell you he is running around like a young puppy. So if it works for him, I'll taking it myself in the relatively near future.

Coming soon, we have senolytic drugs. Many of you may be familiar with senescent cells, these cells that are somewhere between healthy functioning and apoptosis. They cause a large burden of inflammation in human beings. Unity Biotechnology has a senolytic drug in human trials at the moment. There are other people developing senolytic trials including ourselves, via our company FoxBio in conjunction with Ichor Therapeutics in New York. Senolytic drugs are going to be, in my opinion, the front line of aging technology in the relatively near future, and will be in wide dispersal within the next three to five years for specific indications, and beyond that for longevity purposes.

I think there are about twenty senolytic companies out there, of which about five are serious ones. We own 50% of something called FoxBio, and we are further back from Unity Biotechnology, but we think we've got a better compound, we just don't know. We've invested 10 million in that so far. As we grow older we develop more senescent cells, as I said earlier, and that is because the body puts these cells into a state of arrest, probably to stop cancer. The removal of those senescent cells in animals seems to reverse the process of aging, not just just halt or slow. The mouse photograph I'm showing has been very useful in our fundraising efforts. On the right hand side you see the same mouse, this is a mouse that is about equivalent to 95 years old in a human. It is treated with a senolytic drug to remove these senescent cells, which account for less than 1% of the cell population, but account for almost all the inflammation. So osteoporosis, osteoarthritis, frailty, lack of balance, all that sort of stuff. This mouse treated with this senolytic drug goes from being 95 back to being middle aged. So it is an actual reversal of aging.

Whether it works in humans or not, we don't know, but it is in human trials for osteoarthritis and also for age-related macular degeneration. We're not sure what indication we'll go for, but I'm very optimistic about this. This is a small molecule, this is our specialization in the companies that we've formed so far. I think that this is going to be a very, very large selling product category in the drug field in the relatively near future.

So there are lots of things going on. You are familiar, this audience, with Samumed, which I visited last year in San Diego. I think it is a fabulous company. That is an indication of how much money is coming in to the space. They have raised 685 million and a 12 billion rumored pre-money valuation. The FOXO family is being interfered with, so our company FoxBio is an indication of that. Then of course you've got stem cells. We have our own company AgeX Therapeutics, which is now public here in the United States, we own about half of that company. I think stem cells are going to be the second major factor in the armatorium of fighting aging. Then down the pipe there is gene therapy, which undoubtably will be the way in which some of us will live to over 115 and beyond.

My partners and I have done several biotech companies, the most recent one is listed on the New York Stock Exchange. It is called Biohaven, and we started it four years ago. It has an approvable drug for migraine. Chairman Declan Doogan was formally the head of R&D at Pfizer, and latterly the CEO of Amarin, which was a huge success as some of you will know, with a drug for heart health. So we have a great seasoned team, and we have a personal motivation, because we are all of a certain age, to accelerate this process. So the aging acceleration of course includes artificial intelligence, which is one of Peter Diamandis' specializations, and we, Juvenescence, are the largest outside investor in In Silico Medicine, which has been mentioned a couple of times here today. This is a very exciting thing.

In the last few minutes I wanted to talk about Lygenesis. This is the first company that will be in humans, in the first quarter of next year. One year away - it is not very far. It will be in sick patients, so we can see immediately in a phase 2 trial whether it works or not. The idea is to take a cadaver liver, donated by someone, probably someone who fell off a motorbike, unfortunately, and divide it into 75 pieces. Those 75 pieces are implanted into 75 patients, and put it into a lymph node, and hope that the liver fully vascularizes and works and takes over from the patient's failing liver. There are plenty of people in the work who have failing livers. It costs 700,000 for a liver transplant here in the United States. It takes fifteen hours, and has a high mortality rate associated with it. Lygenesis has a twenty minute outpatient procedure, and it will cost less than 100,000 to do. It expands the number of potential liver transplants, and there are seven million people in the US and Europe who have failing livers to the point at which it is going to kill them.

Now it hasn't been done in patients yet, but the FDA has accepted that this will be in patients in the first quarter of next year. In animal models, that is dogs, pigs, and mice, 450 plus trials have been done, and there has been a 100% success rate, which is absolutely remarkable in the context of scientific research. So I'm super excited about this company, which we own half of, because very importantly, this could be done not just in the liver, it could also be done for the thymus. The thymus is where your T cells are grown or matured, so your T cells come out of the thymus. As you get older the thymus involutes to nothing, it becomes very small, and that is why very old people have impaired immune systems. This could be a way of restoring immune systems in human beings.

We are at the dawn of the internet equivalent in this industry. As I said earlier, it is primitive, but it is accelerating, largely as a result of the efforts of people such as Peter Diamandis and other proselytizers, and you will remember, vaguely, in the 1980s and the 1990s, the geeky Bill Gates and others of this world, and none us thought that they would be as successful as they have been. We're at that stage in the longevity industry at the moment. Markets develop very quickly; I mentioned cancer immunotherapy taking over in cancer therapy as a gold standard, while biologics were nothing in 1995 and now are a third of all drug sales around the world. So this could be the same for longevity products. Of course, people are willing to spend money to gain extra years of healthy life. Eventually this will be available to everyone, even if at the beginning it will be available only at an expensive level, for the people who have money. But therapies come off patent, and will be widely available to everyone around the world. That is why I say with confidence that we are going to live a much longer life, and in good health.

The last thing I wanted to say is that if you take a stadium like this, and you dribble 1ml of water into it, and then you double that amount every minute, then it will take just 40 minutes for the whole stadium to be covered by 10cm of water. If you then wait for another four minutes, you will fill the entire stadium. This is equivalent to this science; at moment it is not widely known, it is only very nascent, it is in its early days. We are so lucky to be the first cohort on the planet to experience this science, but it is going to hit us very hard in the face if we are not prepared for it, because everything in the world is going to change as a result of changes due to biologically engineered life expectancy. It is going to happen very fast.

No-one, if I ask them, really knows how long it is going to take for the stadium to fill. Most people would say five days or ten days. It actually only takes 44 minutes, because you are doubling all the time, and this is where we are at in the science of longevity. At the moment longevity drugs and products are all snake oil, and sell about 140 billion around the world on an annual basis. None of them work. Imagine how big this market will be when the products start to work - and they are starting to work, they are in human trials, and I am super excited to be part of this.