Life of man, living forever

If there was a red button on the table in front of you now that would stop the clock on your body’s ageing for the next 20 years, would you push it?

How about 50 years – 50 years without ageing whatsoever? Or what about forever?

Offering you an infinite lifespan of good health is beyond the power of our humble e-letter. And perhaps it’s a daft question. Who wouldn’t want to stop their body ageing, to freeze time and expand their lifespan? Maybe you consider yourself too old to want to stop the clock on your ageing. In which case, think about how you would have answered that question 30 years ago.

I think most people would push the button. But will the button ever exist?

We may be getting there.

Nobel Prize winner figures out how to stop your body “eating itself”

Earlier this month the Nobel Prize committee awarded the 2016 prize for Physiology or Medicine to the Japanese professor Yoshinori Ohsumi. Ohsumi’s work centred around the process of autophagy – the means by which a cell’s unnecessary components are destroyed and recycled (when parts of the cell that aren’t needed are “eaten” and reused by autophagosomes).

Research suggests it’s vital to everything from dealing with starvation and infection, to the process of cell death itself.

As the Nobel committee put it in its announcement (added emphasis mine):

We now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled.

Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses.

Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality-control mechanism that is critical for counteracting the negative consequences of ageing.

The awarding of the prize is recognition of another step towards understanding how and why our bodies age. The step after understanding is action: figuring out how to use that knowledge to reverse or freeze the ageing process. It won’t happen overnight. But as Bill Gates famously said, we often overestimate the amount of change we’ll see in the next two years, while dramatically underestimating the change over ten.

The idea of dramatically increasing the average human’s lifespan, perhaps even figuring out the secret to immortality itself, doesn’t seem quite so far fetched today as it once did.

The best way to get there, though, is to try and eliminate the diseases and ailments that kill people young. Knowing you’ll get 80 or 90-odd good, disease-free years on this planet would be enough for most people today.

The road to dramatic life extension starts with figuring out how to keep more people alive and well for longer. Autophagy research could play a key role there: Oshumi’s work is particularly applicable to cancer and Alzheimer’s disease. But it’s not alone. Gene editing, immunotherapy, nanotechnology and personalised medicine will all play their part in fighting disease and extending the human lifespan.

But in time ageing itself will come to be treated as another disease to be understood, taken on and overcome. In fact you could argue that immortality is the logical final outcome to capitalism.

Inherent to the idea of capitalism is that human innovation and ingenuity can overcome any limit. The ceaseless growth of capital requires us to constantly push the limits of possibility and find new markets, new ideas, and new ways of creating wealth and adding value.

That means the very idea of capitalism requires constant, ever-growing innovation and expansion. It requires ambition and human ingenuity to constantly push at the frontier of the possible. Often that’s literally the opening up of a new market – a new nation added to the global economy, a new source of labour, a new product.

What is death but another limit to be overcome?

This may sound far fetched, but there’s a very real – and commercial – effort under way by a series of companies whose goal is nothing less than radical life extension. With that in mind, I wanted to share an interview with a man who is actually trying to make this happen.

His name is Ira Pastor. He’s CEO of Bioquark. His insights on the issue are fascinating. I’ve reproduced Andrew Lockley’s interview with him below.

Before we do that – if you’ve missed any of my special issues this week, it’s not too late to read them.

We’ve looked at “the wrath of man” – how humanity is fighting back against diseases that have killed millions using new high-tech weapons.

We’ve studied “neoevolution” – how we’re able to guide evolution and create an “intelligent designer” of the universe (not a god, but a man).

And tomorrow we’ll be taking another step forward. I want to show you how these technologies are translating into real financial returns – at eye-watering speed. Look out for my email tomorrow.

Right, let’s get a report from the frontline of the battle against ageing…

Until tomorrow,
Nick O’Connor
Publisher, Exponential Investor


Who wants to live forever?

by Andrew Lockley

One of the more memorable films I saw growing up was Highlander, which involved a battle between immortal warriors. I was a big Queen fan at the time, so I liked the soundtrack – which included the famous line “Who wants to live forever”.

The idea that we’ll never die is pure fiction. If nothing else, we’ll all end up having accidents at some point. However, in one way, the idea in the film isn’t so crazy – and I think that’s why it has stuck in my mind. There’s nothing we know of to suggest that human lifespans can’t be extended dramatically. Most animals age, but not all do – and particular ones can even return to a juvenile state. If we could hack the biological clock of ageing, we could live much longer – and not as elderly men and women, but as healthy adults.

Firms in this space are at the forefront of a true transformation in the way we will address the most dreaded ailments responsible for human degeneration, suffering and death, in the future. Today, I’m interviewing Ira Pastor, the CEO of Bioquark. Like all the firms we interview for Exponential Investor, it’s not paid for this exposure.

AL: Hi Ira. Can you start off by giving us a little bit about your background?

IP: I spent the last 30 years of my career in various sectors of the pharmaceutical industry – including pharmaceutical commercialisation, biotech drug development, managed care, distribution, over-the-counter, and retail. Hence, I am a bit of an industry generalist.

AL: So, what’s novel about Bioquark?

IP: Bioquark is an innovative life sciences company focused on the development of novel products focused on complex organ regeneration, disease reversion, and age reversal in humans.

AL: Wow – that’s quite a wide basket. What prompted you to explore such a broad space?

IP: We took some clues from how the modern pharmaceutical industry got started 100+ years ago – in essence, “going back to nature”.

Today, if a person loses their leg, it’s forever. However, some animals can replace lost or damaged organs and tissues. These are identical in structure and function to the original. To do this, the body has to regenerate a wide variety of tissues, and make them work as a proper organ. We can see examples of animals regrowing many body parts – including spinal cords, limbs, hearts, eyes, and even parts of their brains.

Many of the species that can do this regrowth trick also have the ability to repair and reverse disease-causing cellular and genetic damage. Cancer, as an example, is found to be extremely rare in species displaying an efficient regenerative mechanism. This holds true even under the action of potent carcinogens. In many cases, when cancer does occur, tumours have been found to spontaneously remodel and integrate into their surroundings as normal, healthy tissue.

Some of these organisms can even age, and then return to a youthful state later on in life.

AL: That would be an amazing set of abilities to add to modern medicine. What was the “eureka moment” that came from this initial work?

IP: We focused on the three “Rs”: regeneration, reversion, and rejuvenation. What we ultimately discovered was that these were connected by an underlying capability in such organisms to turn back biological time in targeted tissues, and start the development process over again.

In essence, we found that disease, degeneration, and ageing were all intimately connected by this single underlying biological regulation process.

This realisation led us to develop an integrated platform, which could eventually help humans to reawaken and mimic these abilities for purposes of health, wellness and longevity. This is a platform which the company believes can change the paradigm, and the way we think about healthcare and disease.

AL: Very interesting. Tell us a bit about the market potential for such technologies.

IP: Setting aside infectious diseases, the majority of the $7 trillion we spend globally on healthcare goes either to diseases of cellular degeneration (Alzheimer’s, congestive heart failure, Parkinson’s, type 1 diabetes, etc) or cellular damage (autoimmune diseases, cancer, chronic inflammation and pain, fibrotic disorders, etc). So it is a fairly lucrative segment!

AL: I see. How does this area of regenerative medicine compare to what currently goes on in the pharmaceutical industry in regard to traditional drug development?

IP: This is a very different approach. The current model is based primarily on treating disease, while regenerative medicine offers the promise of actual cures for these ailments.

For the last century, the pharmaceutical industry has attempted to reduce and study human health and disease at the level of their most basic components – proteins, genes, cells, etc. They’re continually looking for new drug targets, so that they can interfere in some fashion with specific biological processes.

This approach has allowed the pharmaceutical industry to grow in size to around $1 trillion in annual sales. However, with exceptions such as antibiotics, we still have very few real cures for disease.

From the perspective of drug development, these targets are often no more than the late-appearing indications of dysfunctional tissue/organ systems. Therefore, instead of curing diseases, we end up treating symptoms – inflammation, immunity, fibrosis, thrombosis, haemorrhage, cell proliferation, apoptosis, and necrosis. Most drugs are developed without regard for, or knowledge of, any of the biological factors that precede these abnormalities. In short, the current healthcare model usually ignores the actual causes of disease.

Additionally, this reductionist approach used to identify therapeutic targets continues to ignore the fact disease is not usually a result of an abnormality in a single gene product. Instead, it is an emergent state – involving multiple biological processes that interact in complex ways.

Regenerative medicine offers to completely change the status quo, by finally allowing us to alter the underlying causes of disease. This gives us the hope of developing actual cures.

AL: Tell us a bit about the competitive landscape, both current and future.

IP: Frankly, the “state-of-the-art” is pretty woeful in this field – both for therapeutic regeneration and repair.

From the perspective of therapeutic regeneration, it’s an alternative to organ transplantation. Transplants are only seeing limited application – due to the number of donors, and host-versus-graft immune reactions. Pharmaceutical growth factors are currently constrained mechanistically and dimensionally to single cell types, meaning it’s impossible to regrow complex organs. Finally, stem cell technology suffers from an endless array of both technical and efficacy hurdles, as it pertains to complete regeneration possibilities.

From the perspective of therapeutic repair, the majority of all chronic diseases have an underlying cellular and genetic damage component. However, pharmaceuticals are incapable of repairing this damage once it has occurred. Meanwhile, stem cells are only capable of providing transient treatment. By themselves, they don’t ordinarily allow the body to fully maintain the improved level of health, once treatment has stopped.

Bioquark does not consider companies engaged in ex vivo stem cell or tissue engineering approaches to be direct competitors. Our endogenous regeneration and repair approach is different. However, there are a handful of pharmaceutical and biotechnology companies that are trying to develop small molecules, proteins, or gene therapies that could be used to activate various components of patients’ own regenerative processes.

While some of our competitors’ substances represent creative drug candidates, none has the ability to do what Bioquark is aiming to do. We are working to reverse cellular damage, repair a broad array of tissues, or perform heterogenic cell remodelling. Additionally, many of these competing drugs have transient activity profiles, so they must be re-administered long term for a lasting effect.

AL: How does ageing and longevity relate to regeneration?

IP: Ageing and longevity, like all of the chronic diseases mentioned above, are purely a function of your cell’s regulatory states.

If that regulatory state can be altered from point B back to point A, a human can technically become biologically younger. Some animals can do this already. This is how several species of jellyfish accomplish real time, whole body “age reversal”. This is the ultimate path humans will follow, in order to achieve the same results.

This is similar to the way new babies are born “age 0” despite their parents contributing much older “starting materials”. As a result, life extension is a very likely “side effect” of our core therapeutic programs.

AL: How widely accepted are the claims you’re making?

IP: Actually, quite widely. The concept of using combinations of biologic materials derived from eggs (ooplasms) for age reversal has its beginning in the original cloning experiments of the 1950s. The study of regenerative biology, and dynamics such as tumour reversion, began prior to that – in the 1940s.

Hence, we are just revisiting and recombining an old body of knowledge for a new and beneficial purpose.

AL: That’s reassuring. Tell us a little about your specific business model.

IP: Our core business model is to develop our biologics through later-stage clinical trials. We anticipate large licensing events occurring in deals with various speciality pharma partners. We expect to team up with firms who have “organ specific” business units in their model (ie, kidney care, spinal cord injury, etc).

Additionally, due to the unique nature of our biomaterials and potential application in the area of wellness and aesthetic products, we will also be taking advantage of lower-hanging fruit.

AL: How will you create long-term revenues, if your treatments don’t require continuous application?

IP: Our therapies may not have to be taken for the rest of a patient’s life, unlike a traditional drug treatment. However, we will be able to price curative interventions at a much higher price point – as long as they yield an economic benefit, versus maintaining the same patient with that disease for a lifetime.

Nature, and time, will always be delivering a wide base of new patients for us.

AL: Can you tell me about the firm itself – your future plans, fundraising, that sort of thing?

IP: We are a privately held Delaware C-corp. We have raised its angel and seed money of a little over $1 million from private accredited investors on the US East Coast. We are now in the process of raising a total of $25 million to scale up our biologic production systems and conduct a series of registrational clinical studies for medical conditions of substantial unmet medical need. These include kidney failure, cancer, and traumatic brain injuries.

AL: What is your strategy for performing late-stage clinical trials, with a relatively small pot of money?

IP: Initially, we will be focusing on disease indications that could qualify for accelerated approval of products for life-threatening illnesses, as well as orphan disease classification benefits.

An example would be our target indication of focal segmental glomerulosclerosis (FSGS), an untreatable degenerative kidney disease that leads to dialysis or transplant in a majority of patients.

Such an indication, which will allow us to rapidly demonstrate complex regeneration in the human kidney, represents a total market value of over $60 billion annually – and that’s only taking into account the population of patients with diagnosed end-stage renal disease.

AL: What do you see as being the key challenges for your firm, other than the usual trials process?

IP: One of the key challenges for us is in getting combination therapies (drug cocktails) more widely accepted by the regulators and medical community. For the last few decades, the “single magic bullet” philosophy has dominated the drug development industry.

The concept of “combination therapy” has become more popular in recent years. You may be familiar with this approach to chemotherapy, and to treating HIV. However, combinations generally take more time to be accepted and employed than “single magic bullet” drugs. But, as mentioned above, that is not the way biology or disease works – hence why the established concept has given us few cures.

Well, that was one of the most jaw-dropping interviews we’ve ever featured in Exponential Investor – and it’s got some serious competition. Can you imagine what life would be like, if you could live for many decades longer, reverse the onset of ageing, or regrow organs?

Until next time,

Andrey Lockley, Exponential Investor

PS We’d love to hear your views on the investment opportunity offered by these technologies – and of course the social impact they’d have. Please send feedback to [email protected].

Category: Genetics and Biotechnology

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