The Longevity Revolution

At Master Investor’s Investing in the Age of Longevity event in London this week, some of the leading minds in this emerging sector mingled with the world’s most important institutional investors. Victor Hill explains why these new medical technologies are mind-blowing, yet credible.

Medical evolution

Jim Mellon thinks that the longevity sector is going to become the biggest industry ever. That’s what he told an audience of medical scientists and professional investors at an important Master Investor event (sponsored by Hill Dickinson, Axa Investment Managers and the Longevity Vision Fund) at the Science Gallery, London on Wednesday (13 November).

But, before we go into the underlying science, which, as we learnt, is moving out of the research phase towards the commercialisation phase, let’s just try to unpack this important word. Longevity is not so much about taking a pill that will give us all 50 years more life (though that is not fantastical). It’s more about regenerating and maintaining human tissue such that we can extend the period of time in which we live in good health (called the healthspan) and, as a result, live longer. It’s about developing drugs and therapies that prevent us from succumbing to the dreadful degenerative diseases of old age.

Some of these drugs and therapies are actually already undergoing in vivo medical trials – but, more importantly, there is a huge pipeline of products which will materialise over the next ten years. At the moment, regenerative medicine is hard to come by and expensive; but, in good time, there is every prospect that it will become mainstream.

This has massive implications. The focus of healthcare will shift from treatment of the principal killers (“the big four”) to which we are now prey – cancer, cardiovascular disease, dementia, diabetes (not forgetting arthritis et al) – to the prevention of these conditions. We shall be empowered to take greater responsibility for the maintenance of our own health. The education model will have to change too as we change jobs and re-train well into our ninth decade – or even longer. So the emphasis will be on lifelong learning. “Retirement” will no longer be considered the natural end-point of our working lives.

We can think of the evolution of medicine in the following way. In the first stage, we developed over-the-counter medicines which basically treated the symptoms of particular maladies. In the second stage we developed small molecule conventional drugs which addressed the consequences of complex diseases and attacked bacterial infections. In the third stage, with the emergence of “biotech” in the early 21^stcentury, we developed treatments which modify the development of diseases, for example through the use of monoclonal antibodies. (Today, eight of the top 20 drugs sold worldwide rely on monoclonal antibodies.) But only now, in the fourth stage of medical science, are we developing cell therapies which can regenerate tissue and thus cure and prevent diseases.

These cell-regenerating therapies come under the banner of longevity – but most medical scientists will tell you that increased longevity is a beneficial consequence of better healthcare. Longevity is not an end in itself: it’s what happens when humans stay healthier for longer.

Most contagious diseases have been eliminated or at least controlled by sanitation, vaccination and antibiotics. But age-related diseases have not. That is the challenge that centres of excellence in clinical research like SENS Research Foundation in California, which has fostered a number of longevity start-ups, is working on. SENS hopes to run clinical trials of rejuvenation biotechnologies by 2021. These can be of several kinds.

When cells reproduce themselves in the body, over time, the strands of DNA at the end of the cell, called telomeres, shorten. This has the effect that cells reproduce imperfectly and deteriorate in quality – imagine taking a photocopy of a photocopy on an old Xerox copying machine ad infinitum. One technology can revivify the telomeres so that cells can reproduce without ageing. Another technology relies on the use of stem cells and a third works by eliminating only damaged senescent cells. So the layman (such as this writer) should understand that bio-gerontology is not one thing but is a cluster of new medical technologies which operate at the cellular level.

Why now?

Longevity science is coming about partly, of course, because of recent breakthroughs in our understanding of how the body works and partly because of the application of artificial intelligence (AI) in research. But also, as the eminent bio-gerontologist Dr Aubrey de Grey explained, it is being impelled by the demographics of an ageing population which is driving increased demand for treatments of the diseases of old age. Last year, in the USA, a very significant demographic milestone was passed, noted Dani Saurymper of Axa Investment Managers. This was that the cohort of people aged 60 or over exceeded the number of youngsters of 15 or below for the first time. “Seniors” are now the majority.

Age, as most people know, is the biggest risk factor for a whole slew of diseases. A very small number of people in their twenties die of heart disease (mostly due to congenital conditions); but a relatively large number of over 65s succumb to heart disease. In fact, the statistics are rather alarming. According to AgeX Therapeutics, 80 percent of over 65s in the USA have at least one chronic condition and 68 percent have two.

As a result, the volume of healthcare spending on the over-65s is sky-rocketing. In 2010 the US spent about 18 percent of its GDP on healthcare. If present trends continue, that figure will reach 34 percent by 2040. But if people can stay healthier for longer then, far from creating an additional burden for the healthcare system, there will be what Dr Nir Barzilai calls a longevity dividend. As Liz Parrish of BioViva argues, regenerative medicine is not so much a luxury for the rich but an economic necessity.

With my economist’s hat on I might venture that if we don’t develop regenerative medicine not only will we die earlier but we’ll go broke before we go.

The clock within the cells

One recent scientific revelation is that human cells seem to be programmed to switch off after time is called – like a traditional English pub landlord chucking the customers out with “Time, gentlemen, please”. The amazing thing is that very different cells from brain cells which regenerate to tissue cells which cannot regenerate all call time together.

An evolutionary explanation goes like this. Once we pass peak fertility and are unlikely to produce any more offspring, Mother Nature has no more need of us. In fact, in her view, we just consume scarce resources without miscegenation. So she has decreed that we degenerate and die in order to make way for younger blood. This is certainly the case in mammals – though there are certain animals, like lobsters, which do not age at all and just soldier on until someone eats them for lunch.

The challenge is, therefore, to get inside the cell clocks – called epigenetic clocks – and either turn them back or turn them off. One company working on this is Repair Biotechnologies, located up-state New York. Repair is also focusing on the small lymphatic gland in our upper chest (just above the heart) – the thymus, where T-cells mature. As we age our thymus shrinks and this compromises our immune system. It turns out that a protein called FOXN1 can reverse thymus involution.

AgeX Therapeutics

On Wednesday we heard about literally dozens of start-ups operating in the longevity space but, thus far, there are less than a handful of quoted entities. One such is AgeX Therapeutics (NYSE:AGE) run by Dr Mike West who is both an eminent scientist and a businessman with a remarkable track record.

AgeX is a cell therapy company which has been working on a technique called allogenic cell therapy. This involves converting stem cells – undifferentiated cells which are capable of giving rise to cells of any kind – into cells which are deployed for a specific purpose, customised for each patient. Human embryonic stem cells and human pluripotent stem cells provide a cell source with unlimited capacity for proliferation and can potentially generate any human cell type. The main challenges here are the risk of an auto-immune response by the recipient and the high manufacturing costs of cell therapy.

AgeX’s proprietary UniverCyte technology deploys cells that can evade the patient’s immune system so that patients do not require immunosuppressant medication. It achieves this by mimicking what foetuses’ cells do in the mother’s womb to prevent triggering the mother’s immune system.

The company has over 400 patents and patent applications worldwide for therapies which use human induced pluripotent stem cells. For all that, the company has not proven to be a good investment since it was launched one year ago, with the share price well down on its initial value – but investors in this space have to take a medium-term view. Other companies operating in the stem cell space include Calico (owned by Alphabet/Google (NASDAQ:GOOGL)), Unity Biotechnology (NASDAQ:UBX), and Samumed.

BioViva

BioViva was founded by Elizabeth Parrish who is also the Washington state-based corporation’s CEO. Liz has a humanitarian vision of improving health for the human race as a whole – but she concedes that at present the cost of cell-based treatments is prohibitively expensive. For example, Novartis (SWX:NOVN)produces a drug called Zolgensma to treat spinal muscular atrophy. But right now each treatment costs between $2 million and $5 million. Liz’s vision is that the cost of treatments will plummet over the next two decades so as to make the most advanced treatments available to all.

BioViva is working on a telomerase trial targeting Alzheimer’s disease, muscle and kidney regeneration and “whole body regeneration”. Using the muscle regenerative treatment Follistatin, which has already been trialled on a little boy who suffered from muscular dystrophy very successfully (he can now climb stairs), has been used by BioViva to address ageing muscle tissue in older patients. It’s obvious that athletes will want to get some of the action here to increase muscle mass. Once the treatment is administered there would be no tell-tale signs of doping as the athlete’s genome is altered accordingly and there are no traces of doping compounds in the bloodstream. We shall no doubt be hearing more about this.

What was fascinating about Liz’s contribution is that she revealed that she has conducted a gene therapy trial on herself. It is currently not legal in the USA but Mexico is always just down the road. Liz says that she feels less tired, has more energy and overcame back ache. Her muscle mass has increased and all her health metrics have improved. She looks about 20 years younger than her actual biological age.

Before readers start emailing BioViva, bear in mind that a course of intravenous injections of Follistatin administered by a qualified clinician in a country where this is legal (Germany is one) will set you back at least $250,000. No doubt there are some readers who would be prepared to pay that.

BioViva is also building up a healthcare database for research purposes. I’ll have more to say about the rise and rise of healthcare databases (orchestrated by the usual suspects, Google and Apple (NASDAQ:AAPL)) in the December edition of the MI magazine.

Juvenescence

Jim Mellon, who is of course the Chairman of Master Investor, set up Juvenescence Ltd. in 2017 as a vehicle to direct funds into the longevity sector. Jim was the author of a very readable book on the subject of the same name (first published the same year).

If Jim is the man who has put this previously recondite sector on the investment map, it was Aubrey de Grey of SENS Research Foundation who first got Jim excited about its prospects. Aubrey is a computer scientist and geneticist by background who has spent the last 20 years pushing the boundaries in bio-gerontology. He is a visionary who communicates the underlying science with such lucidity that even non-scientists like me feel they understand what it is about. Aubrey is now on the advisory board.

In its latest funding round Juvenescence Ltd. raised over $100 million. The company’s Chief Medical Officer is Declan Doogan, who has had a long and distinguished career in the pharmaceutical industry and in medical science. Declan told us that the company is allocating to a range of entities working on a wide variety of age-related chronic conditions such as cardiovascular disease, neurodegeneration, kidney disease, osteoarthritis and sarcopenia.

One target investment is Lygenesis, which is working on liver regeneration. Lygenesis originated out of the University of Pittsburgh’s McGowan Institute of Regenerative Medicine. About 20 people die in the US every day while waiting for a liver transplant. Lygenesis’s cell therapy uses lymph nodes as bio-reactors which can grow ectopic (that is, secondary) livers in patients with end-stage liver disease.

In due course Juvenescence Limited will launch on the stock market. At that point its entire portfolio will become transparent. Watch this space. The future could happen sooner than we think.

Conclusion

This amazing event got me thinking about what has gone wrong in public healthcare policy. In the general election that is raging around us in the UK, the main contenders are in a bidding war to pledge spending hypes for the NHS – but there is very little discussion around how that spend is targeted and how to maximise health outcomes. It has become a shrill debate about numbers.

While nudging people into living healthier lifestyles in terms of taking regular exercise and watching their diet and alcohol consumption and so forth is justified, the impact of lifestyle factors on overall longevity is, according to one speaker, probably marginal. Some people who live exemplary lifestyles nonetheless fall prey to cancer; and some smokers and drinkers make it into their nineties.

Jim Mellon, backed up by some of the finest minds in medical science, thinks that there will be a cure for cancer within ten years, maybe 20 on the outside. But imagine if we could prevent people from contracting cancer in the first place. That is a vision worth investing in.

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Readers who wish to read around the longevity topic further and deeper should download our latest quarterly supplement, The Edge, from our website. My colleague Nick Sudbury surveys the universe of biotech trusts and funds (not necessarily longevity-focused); Liz Parrish provides further insights into BioViva; and Greg Bailey of Juvenescence Ltd. describes how the company went from a glint in Jim Mellon’s eye to a company knocking on the stock exchange’s door.

Enjoy!