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Jim Mellon – Investing in the Age of Longevity

Interview with hugely successful investor Jim Mellon at the Undoing Aging conference in Berlin 2019!
We cover reasons why it’s a good time to invest in Anti-Aging and rejuvenation biotechnology today, the ethical reasons why we should, and effective advocacy: i.e. what one would say to a billionaire to convince them that investing in longevity medicine is a good thing to do now.
Jim raised over $150 Million for his venture Juvenescence recently!

Transcript

My name is Jim Mellon, and I’m the chairman of Juvenescence, which is a company involved in the science of longevity. It is relatively recently formed; it is about a year and a bit old, but we’ve raised a significant amount of funding – nearly $160 million now – in the last year to advance the cause of longevity science. By the end of this year, we’ll have made 18 investments. Most of them are subsidiary companies of ours, so we control those companies. We give both development and financial backing to the scientist-entrepreneurs and institutions that we collaborate with.

I am fortunate to have two partners who have broad experience in the biotech and healthcare area, in particular, Declan Doogan, who was the head of drug development at Pfizer for a long period, and then he became the CEO of Amarin, which, as you know, is a very successful biotech company with a nearly $10 billion market valuation today. About four years ago, the three of us started a company called Biohaven, which is now listed on the New York Stock Exchange and has a valuation of about $2.5 billion. The company has approval for a drug for migraine, which will be on the market in the US next year. There is a good team of veteran drug developers and business entrepreneurs who have come together to create this Juvenescence company, and we’re very, very excited about it. We’re the biggest investors in the company ourselves, on the same terms as other investors. We will take the company public in the first quarter of next year, barring market disasters, and probably on the US stock exchanges.

We’re interested in this field of longevity science and able to raise significant funding because we’ve been in biotech for quite a long period of time, together, and created a number of companies. It seemed to be a natural outgrowth of the great developments that have occurred in the last few years. The unveiling of the human genome identified aging pathways that can now be manipulated. For the first time ever, you and I are in the cohort that is able to be bioengineered to live a healthier and longer life. It is still in a very primitive stage; we’re in the internet dial-up era equivalent, but the science is advancing very quickly.

I always say that I wrote my first book on biotech seven years ago, it was called Cracking the Code, and since then, we’ve had CRISPR/Cas9, which didn’t exist seven years ago, we’ve had the cure for Hepatitis C, we’ve had artificial intelligence for the development of novel compounds. The latter of which is a key part of our strategy, as investors in In Silico Medicine, which I think you are familiar with. Then, of course, you have cancer immunotherapy, which didn’t exist seven years ago, and is now a $100 billion / year industry. So, what’s going to happen in the next seven years? We don’t know, but it’s going to be very, very good. If you want to regard it as a casino table, we’re covering all the markers that we can with the funds that we’ve raised. We hope to raise a substantial further amount on the initial public offering of the company in the first quarter of next year, and that will give us enough firepower to do five Phase 2 trials without partners so that we can get the maximum leverage on the products that we’re developing.

So far, we’ve invested in small molecules, which is the specialization of our team. For instance, we have a senolytic drug in development in that area. We’ve also invested in stem cells; we’re the largest investor in Mike West’s company, AgeX Therapeutics, which is now a public company in the US. We own about 46% of that company. Then, via Lygenesis, we’ve also got our first product going into patients in the first quarter of next year, sick patients in a phase II trial, for organ regeneration, regenerating the liver, using hepatocytes to seed lymph nodes to act as ectopic bioreactors to grow fully functioning liver tissue. The FDA has agreed to the protocol for doing that in sick patients, which is a remarkably fast path to demonstrating successful outcomes in that area. If that is successful, then we will look to regenerate other organs, in particular the thymus, which as you know is related to aging in a big way.

We’re moving very, very quickly. We’ve got great colleagues; Margaret Jackson from Pfizer is on our team. Howard Federoff, ex-Pfizer, is on our team. Annalisa Jenkins, who was head of drug development and research and development at Merck Serono, a very big drug company, is on our team. We’ve put it all together remarkably quickly, but we have experience in doing that, and so we’re full of confidence. This is a remarkable time to be alive, and I want to be alive for at least another 20 or 30 years beyond what would be considered to be my allotted life span. The same is the motivating factor for my cofounders, Declan Doogan and Greg Bailey.

Working to extend life is an ethical cause. No one can argue, successfully at least, that this isn’t a good thing to do. There are some people who say “well, it is for the haves and not for the have-nots” but that is rubbish, because, ultimately, all these drugs will become generally available, and some of them already are. Metformin, which, as you are aware, is a drug that has some anti-aging properties, costs essentially nothing. It is a generic drug. As antibiotics, ulcer drugs, and so forth were once expensive and are now very cheap, the same thing will happen to drugs for longevity. Gene therapy and stem cells are another matter, though, and they will probably be expensive things for some time to come. But, undoubtedly, the cost will come down for those as well.

The other people who argue against work on aging talk about overpopulation; if there are all these old people, will there be enough room on the planet. Well, the answer is, we’re already alive, so we’re not going to be adding to the population. You and I are already here. The big issue on population is how many children does each woman have around the world, and that figure is falling dramatically, to the point where we can see populations actually shrinking. Just as an example, if Japan doesn’t allow immigration, or doesn’t have a baby boom, its population will fall from 126 million today to 50 million by the year 2100. So both those arguments, the haves versus the have-nots, and the overpopulation concern, are nonsensical arguments. In my view, there is absolutely no reason why governments, institutions, the general population, and the voting population shouldn’t be pushing really hard to make this happen.

Regarding the aging of the existing population and how to cope with it, the main point made by Aubrey de Grey, and other eminent scientists as well, is that if you treat the top of the cascade of damage in aging, then you are going to treat the underlying diseases of aging that pharmaceutical companies are trying to address. But for those pharmaceutical companies, it is a whack-a-mole exercise, so if you get one disease and that is cured, then you’ll get another one, and they’ll have to cure that one. Ultimately, we become destabilized and we die, all of us. So, let’s try and treat aging as the central disease, and from that as the unitary disease, we’ll be treating the cascade that follows from that.

Some people say it is hubris to target aging, but I think that this is because until relatively recently, nothing worked. It has been an aspiration of human beings for millennia to find the fountain or elixir of youth, and nothing has worked. So, people are skeptical about the fact that it might be working now: why now rather than 20 years ago or 20 years in the future? But the fact is that it is now, and we need to seize the moment and rise to the challenge. We need much more funding to come into this area, and that funding will drive the science. We need many more advocates for this cause to come to the fore and tp spread the word, that this is going to be monumentally great for human beings.

In my own case, I’ve set up a charity with Andrew Scott, who wrote The 100 Year Life, and we do a Longevity Week in London. We did the first one last year, and we’re doing the next one in November of this year, to spread the word. This will have a big societal impact, on consumption, on the way in which we look at the trajectory of life, but it is also going to have a major impact on us as human beings. In the past, you’d have expected to live to about 85 or 90, the same with me, and now we’re very likely to live to 110 or 120, so let’s do it. Let’s make it happen. I think that all of us, yourself, myself, have relatives, dear friends, and acquaintances who are suffering the indignities of aging as it currently exists. We’d like to relieve that burden of suffering by extending the healthy span of life. The personal motivation is a very big factor. Here in Berlin, there are 300 or 400 people at this conference, and I imagine that all of them, beyond just the business or scientific side of things, have an altruistic motivation for this as well. More people need to do it, so get on to it!

The elevator pitch for high net worth people thinking about investing in this space is that, first of all, we’re at the front end of a huge upward curve. I said earlier on that this was like the internet dial-up phase of longevity biotech. If you’d invested in the internet in the very early days, you’d be more than a billionaire now; you’d be one of the richest people on the planet. We’re at that stage now, so the opportunity for investors is huge, but you could do both. You could invest in something like the SENS Research Foundation or the Buck Institute or one of those wonderful organizations that is trying to advance the cause, and at the same time invest in some of the companies that come out of those institutions. We’ve undertaken two joint ventures with the Buck Institute, and we’ve made a couple of investments as a result of introductions by the SENS Research Foundation, including the organ regeneration program. If you’re a sensible billionaire, you will be putting some of your funds to work in a combination of a charitable enterprise that drives the science and the businesses themselves that come out of those enterprises.

Many thanks to Leaf Science for doing the transcript!

Perhaps one of the most interesting companies in which Juvenescence has invested is Lygenesis, which is developing an approach to address liver failure by creating miniature livers to pick up the slack. Lygenesis is using a technique in which liver cells are delivered to lymph nodes, where they develop and grow into fully working liver tissue, albeit smaller than the organ they replace. If these organs are shown to perform all the functions of a working liver, they could potentially remove the need to replace damaged livers through transplants. Initial work in mice and pigs has been promising, and Lygenesis plans to move to phase 2 clinical trials in early 2020.

Aubrey de Grey – Artificial Organs as Replacement Parts to aid in Defeating Aging

Aubrey de Grey discusses using artificial organs and synthetic devices as replacement parts to aid in defeating aging. (Also see this interview where Aubrey discusses some of the various approaches that SENS therapy will likely be delivered.)


Replacing a failing organ with a healthy one can sidestep the need for the various SENS therapies for that organ only – however there are two limitations – 1) much of the body is made up of non-transplantable organs, 2) transplanting organs or tissue engineering involves invasive surgery, something that involves risks if it is done too much.
Organ transplantation/Tissue engineering is useful today and will be useful when early forms of SENS delivery become available – however there will continue to be a very high priority in approaches that mitigate the need for invasive organ transplantation.
Non-biological organs are useful today – for instance the cochlear implant – and there will continue to be a place for them. Though in the long run biological organs will likely work more effectively because they are ‘evolved’ for that purpose.


Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections:

Aubrey de Grey – SENS Therapy Delivery

In this interview Aubrey discusses some of the various approaches that SENS therapy will likely be delivered. Mostly covering gene therapy. Also see this interview where Aubrey de Grey discusses using artificial organs and synthetic devices as replacement parts to aid in defeating aging.

Ex-Vivo Gene Therapy

Ex Vivo Gene Therapy

ref: yolasite.com (click for larger image)

Some things that people are already looking at, for instance introducing new blood stem cells into AIDS patients that contain an AIDS resistant gene named CCR5. A very small portion of people have a natural variant of that gene, called Delta32, which confers very strong resistance to HIV. If you could give this variant of CCR5 this could be a very powerful therapy – luckily the cells that need to have that variant are blood cells – blood cells come from stem cells – so bone marrow transplants with this appropriately modified version of this gene would be very powerful, and that is already being worked on.
There may be very many other cases of inherited diseases (especially) which could be modified and indeed perhaps cured by using genetic modification of stem cells for stem cell therapy.
Now in the case of ageing, this may also be a good way of delivering certain of the SENS therapies – the one that’s most obvious is LysoSENS – the Lyso Enhancement idea for getting rid of the molecular garbage inside of cells – because here we have to introduce new enzymes into these cells (enzymes that are not encoded into the normal human genome) and in some cases it may make sense to actually introduce the enzymes by injecting the enzymes into the circulation in the same way we already treat certain inherited diseases of Lysosomal function (called Lysosomal storage diseases). But in other cases it may be actually be preferable to make genetic modifications to stem cells so that the blood cells or the other cells that are created from those stem cells are able to have that genetic modification and thereby not to accumulate the molecular garbage that we are talking about – perhaps even to eliminate the molecular garbage that had already accumulated.

Somatic Gene Therapy

In_vivo_gene_therapy

ref: yolasite.com (click for larger image)

Some of what were going to need to do in genetic modification of people so as to implement SENS will not, or almost certain not be able to be implemented using ex-vivo gene therapy – the genetic modification of cells outside the body that are then introduced into the body. Some of it is going to have to be done by genetically modifying cells in the body itself. That is what is called ‘Somatic Gene Therapy’ – the way it’s normally done is by engineering a virus contain the engineered DNA that we are interested in and not to contain the DNA that the virus naturally has that makes it bad for us*. And of course gene therapy as an idea has been around for quite a long time – and in fact the first clinical trials of gene therapy happened about 20 years ago. But it’s had a pretty rocky ride because in fact there is an awful lot of risks involved in gene therapy and it doesn’t really work very well yet.
There are certain diseases with a very low hit rate – that is getting a suitable genetic modification to a very small number of cells is enough to be able to actually cure the disease. But in most cases you have to hit quite a lot of cells and we really just don’t know how to do that yet. We at SENS foundation are very interested in helping to address that problem and there is one particular approach to improving very substantially the ability to very safely introduce new DNA into a lot of cells into the body which we are just starting a project to explore. **

* Note this interview was done shortly before CRISPR was discovered.
** This project is called?? Note I will follow up with Aubrey de Grey on this point – but my feeling is that CRISPR may have solved the problem, at least partially

Adeno-Associated Virus

Adeno-associated_virus_serotype_AAV2One of the biggest dangers in somatic gene therapy and also it’s a danger for ex-vivo gene therapy (where you genetically modify stem cells and then you introduce them) is that on occasion the engineered gene may go into the genome in the wrong place – into a place that causes damage in the form of disrupting the DNA that was already there – in a way that you don’t want.  In general that disruption is harmless, but very occasionally it may not be harmless – it may actually make the cell cancerous (and there have been genuine cases of this in clinical trials for particular gene therapies).  So, people are very interested in ways to stop that from happening.  The most obvious way to stop that from happening is to develop a gene therapy vector (a type of virus) that preferentially goes into a particular harmless place in the genome and not go into any of the potentially harmful places – now it turns out that there are some viruses that naturally do this – there is something called AAV (Adeno-Associated Virus) which preferentially go into one particular site of chromosome 19 and people have been very interested in that virus for quite a long time for exactly that reason.  However it turns out that its quite complicated to make that really work and the hit-rate is not good enough – it still has random integration at an unacceptably high level.   So people will want to find other ways to go about this – and there really are lot’s of very creative technologies out there that are being explored to do exactly that.  I’m very optimistic that quite soon we will have gene therapy that very robustly does not disrupt DNA that it would be dangerous to disrupt.

RNA Interference

I believe there are other types of manipulation of gene expression other than gene therapy are also potentially valuable in treatment of ageing and of course medicine in general.  A lot of interest these days is in RNA Interference (RNAi) which is a method for inhibiting expression of particular proteins by introducing short RNA molecules that interfere with that process.  And that’s got a lot of potential – people are looking into it in a variety of different applications – one area that people have been trying to look into it for is cancer.  So see if one can close down cells that are over -expressing when they shouldn’t be over-expressing (for example).  Personally I’m not very optimistic about this application for cancer because it’s just too easy for cancers to mutate into a form that makes the RNAi in-effective – so the short RNA does not work anymore.  But in other applications it might be useful.

Neuro-Regeneration

So the brain is of course arguably the most essential to repair from the damage of ageing – there’s not much point in rebuilding the rest of the body if you are demented – how hard is that?  In particular is it significantly harder (to repair) than the rest of the body?  I believe it’s not significantly harder than the rest of the body – ultimately the brain is certainly vastly more complicated than any other organ, and we are vastly more ignorant about how it works than we are about any other organ – but the thing about SENS, the thing about the whole preventative maintenance approach to combating ageing is that we don’t need to understand how the organ works in order to restore its function or we need to do is understand what its made of, and more specifically how what it’s made of changes throughout life so that we can reverse these changes – repair those changes – and put structure and composition of the organ back to how it was at an earlier stage in early adulthood and thereby restore its function irrespective of our ignorance of how that function arises from that structure – that’s just as true for the brain and any other organ.  So one example of this is the fact that brain cells (neurons) don’t divide, and in most cases don’t have per-cursor cells that don’t divide either – there are a couple of areas of the brain that do exhibit the creation of new neurons throughout adulthood – the rest of the brain doesn’t luckily the rest of the brain exhibits a very very very slow rate of cell death – so it’s not really a problem – and the problems we need to fix are the problems of accumulation of garbage inside neurons for example, or outside of neurons that make those neurons not work so well even while those neurons are still alive.

 

Aubrey-de-Grey---SNES-Therapy-Delivery


Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections:

Maria Entraigues on Anti-Aging and the SENS Research Foundation

Interview conducted in 2012 with Maria Entraigues at the eXtreme Futurist Festival in Los Angeles 2012.
Maria Entraigues is the Global Outreach Coordinator for SENS Research Foundation. As the outreach coordinator for the SENS Research Foundation, Entraigues has represented the Foundation internationally at conferences and in the media, and has explained and promoted the Foundation’s goals of eradicating the diseases and disabilities of aging through innovative biotechnologies, including presentations at conferences internationally. Entraigues is also one of “The 300 Members of Methuselah Foundation”, a group of people committed to help the advancement of technologies to eradicate the needless suffering of age-related disease and extend healthy human life.

The SENS Foundation (Strategies for Engineered Negligible Senescence Foundation) is a 501(c)(3) non-profit organization co-founded by Michael Kope, Aubrey de Grey, Jeff Hall, Sarah Marr and Kevin Perrott, which is based in Mountain View, California, United States. Its activities include SENS-based research programs and public relations work for the acceptance of and interest in scientific rejuvenation research. Before the Foundation was launched in March 2009, the SENS research program was mainly pursued by the Methuselah Foundation, co-founded by Aubrey de Grey and David Gobel.