Forever young? Biotech's next frontier
Investments into the longevity sector is stepping up, bolstered by the pandemic
For Aubrey de Grey, the best known longevity thought leader and chief science officer of the Silicon Valley-based SENS Research Foundation, Covid-19 has made the case clear: we must make elderly people in our populations more resilient.
“It is completely unarguable that ageing is bad for you,” says Mr de Grey, a self-proclaimed provocateur and committed scientist. Almost mystical in appearance, he stands at the crossroads of the mainstream and peripheral – where the longevity sub-sector itself can also be found.
As his academic work and theories on ageing have increasingly become less fringe over the past decade, longevity has emerged as a potential ‘boom’ business. Starting in 2014, when Jason Hope asked Mr de Grey to take a project SENS was working on private, the non-profit research foundation has spun out longevity start-ups by bringing scientists together with angel investors.
Vindicated by the new streams of capital flooding into this market, Mr de Grey, who has given TED talks on the subject of ageing, purveys over a global industry that is, as he describes it, a “super cluster”.
Longevity is understood by many as the extension of average healthy lifespan — or healthspan. Short of the camp Hollywood fantasy of “living forever”, the longevity industry has its sights set on a world without age-related disease, rather than a world without mortality per se. Longevity businesses are therefore biotech companies that target specific age-related processes, enabling the eventual end-user to live an optimal life.
The pandemic has thrown a spotlight on the tremendous capabilities of biotech research combining biology with computing technology and artificial intelligence (AI), as well as the severe consequences of having an older immune system, in turn bolstering the case for the longevity industry. As we move into 2021, with vaccines and variants entering into a new race of their own, interest in disease prevention, living longer and extending one’s healthy years will only increase.
A recent McKinsey report published in January states the surge in data and analytics usage suggests that the biopharma industry has moved further digitally in the past 10 months than in the previous 10 years. According to figures compiled by the Aging Analytics Agency, Covid-19 has facilitated the development of not only the biotech capital markets, but the longevity sector in particular, resulting in more than 30% of growth of public companies compared to the previous year.
Pre-pandemic, the theme of longevity was already getting picked up by investors. In 2019, the Bank of America issued a report stating that the technology is about to bring “unprecedented increases in quality and length of human lifespans”, predicting that the market would grow six-fold to roughly $600bn by 2025.
Once more readily associated with science fiction, this multifarious sub-sector of life sciences is now “exploding”, many insiders say. From the US and Europe to east Asia, global investments have increased substantially in start-up clusters forming around research foundations, along with capital coming from holding companies and venture capital funds.
As a testament to the newness of the sector, however, there are still challenges of all kinds and investment risk remains high. It is unclear how the paradigm of age-related disease can be transposed onto the current regulatory landscape and indeed just exactly which one of the many strands of research into longevity science will stick and gain traction.
Remy Gross, vice president of business development at the Buck Institute for Research on Aging, one of the world’s foremost research centres on ageing and age-related diseases, says that the goal to reach 120 years of age is logical. Mammals typically live roughly six times the length of birth to maturity, he says; if you argue that humans mature at 20, that puts us on track for a 120-year lifespan.
Established in 1999, the institute comprises researchers-turned-companies that look at the underlying fundamental mechanisms of ageing or biochemical pathways that accelerate dysfunction, whether that be cancer, heart disease, metabolism or cellular senescence.
“In the past five years, in particular, there has been a sea change,” Mr Gross says, attributing it to the rise of Buck spin-out Unity Biotechnology, a company focused on cellular senescence, and Google’s moonshot secretive ageing company Calico.
“A lot of people looked at Calico and said ‘If these guys are buying into it, there’s got to be something here’,” he remarks, adding that in a short space of time, venture capitalists and entrepreneurs started to see potential for a tractable business model.
Fast forward to today’s pandemic, whose impact on the scientific community and the public perception of science has “emboldened” innovators and investors alike, he continues. “We should be able to get bigger answers out of better questions.”
Place your bets
Much like the rest of the biotech sector, longevity has its roots firmly in the US — specifically in San Francisco’s Bay Area. By both the number of companies and levels of capital investment, the US far outstrips fellow longevity enthusiasts, China and the UK. But other centres in Europe and Asia are forming. In Singapore, for instance, the former president of the Buck Institute, Brian Kennedy, has set up a new centre for ageing attached to the National University of Singapore.
This is still early days for greenfield foreign direct investment, but fDi Markets tracked one greenfield announcement from a longevity company: Hong Kong-based biotech company Insilico Medicine, which applies technologies such as genomics and big data to the development of new drugs and research into the reuse of aging drugs, plans to establish a research and development facility in Taiwan’s Nankang Software Park.
Mergers and acquisitions have pepped up too. In 2020, Hong Kong-based Regent Pacific, an investment firm specialising in healthcare and late-stage life sciences, acquired Insilico’s spin-out Deep Longevity. Spanish pharmaceutical company Grifols bought out its remaining stake in Stanford University start-up Alkahest for a sum total of $146m.
Jim Mellon, serial investor and co-founder of London-based Juvenescence, a shareholder in Insilico, likens these early stages of longevity investments to the “dial-up phase of the internet”.
“We are sure that something is going to work,” he says. “We, like everyone else, are not sure what’s going to work, [but] we do know that several key pathways of ageing have been identified.”
Juvenescence, also co-founded by Greg Bailey and Declan Doogan, is expected to go public this year, potentially taking the form of a Spac deal. Following some of the failures of longevity companies, such as the plummeting stock price of RestoreBio, Juvenescence has spread its bets in 20 projects across 12 companies, ranging from organ regeneration to senolytic therapies.
Sergey Young, founder of Longevity Vision Fund, with $100m of capital, likes to keep the term longevity intentionally broad and has invested in 15 such companies, four of which have gone public and three are due to go public this year.
Since he set up the venture capital fund two years ago, his focus has been on “bringing affordable and accessible versions of longevity” to as many people as he can. ”I’m not a fan of immortality because if you take out death from human life, you don’t have life. But I am a big fan of adding 10, 20, 25 healthy and happy years,” Mr Young says. He points to the example of the cancer treatment market, which has grown exponentially over the past decade and is now estimated to be worth more than $100bn. A similar net increase could occur with longevity drugs, he says, if there is a defined regulatory model to follow.
Regulatory rags to riches
Much of the future of longevity rests in the hands of the regulators. Should the regulatory framework bend in favour of longevity and approve the first clinical anti-ageing drug, it will be a watershed moment to help extricate the fiction from the science fiction still associated with longevity, researchers and investors say.
When that day comes, longevity — the longstanding “orphan of the investment and health worlds” — will become a “Cinderella” of the health sector, Mr Young remarks.
The US Food and Drug Administration (FDA) does not consider ageing a disease which, to an extent, has impeded longevity or ageing treatments from going into clinical trials. The Targeting Aging with Metformin (Tame) trial might shore up the case for age-based drugs.
Tame is a clinical trial looking at the anti-ageing or ‘gerotherapeutic’ properties of diabetes drug metformin, specifically to see whether those taking diabetes drug metformin experience delayed development or progression of age-related chronic diseases, such as heart disease, cancer and dementia.
Led by Nir Barzilai, director of New York-based Institute for Aging Research at the Albert Einstein College of Medicine, and funded by the American Federation for Aging Research, the trial involves 3000 people between the ages of 65 and 80, and aims to prove that an already approved drug can target ageing.
Mr Barzilai hopes that this could provide a template for other FDA-approved drugs to be repurposed and, eventually, for new drugs.
“One of the major things that we’re going to do in this trial is to see the biomarkers of ageing,” he says — biomarkers being measurements of a biological state. Mr Barzialai explains that “we have biomarkers that tell us your biological age or chronological age, but we want to see which biomarkers change when you give a patient the drug”.
San Francisco-based Bioage, a clinical stage biotech company which has built a map of different pathways related to ageing, uses biobank samples from up to 50 years ago to see what differentiates the ‘healthy agers’ and ‘unhealthy agers’ at a molecular level and investigate which existing drugs might have anti-ageing properties.
Much like the Tame trial, Bioage — which recently raised $90m in a series C funding round — has looked to repurpose two drugs, historically used for kidney disease and seasonal allergies, into anti-ageing ones.
Chief executive and co-founder Kristen Fortney notes that what distinguishes ageing science from disease-related science is that the former is defined by its relevance to many different diseases.
Statins might provide a precedent for the kind of trajectory anti-ageing drugs might take, she says. First approved for an orphan disease, hypercholesterolemia (abnormally high levels of cholesterol), it has since been expanded into a drug that is prescribed once you have passed a certain age. This is the pathway we can expect for ageing therapy drugs, she says.
Social and economic impact
Ever-increasing ageing populations have already ushered in a demographic shift, altering the dynamics of the global economy. Baby boomers, who were front and centre of the post-war rise in productivity, will now preside over an era where wealth is increasingly held by older segments of society. Those with time to kill and money to burn will soon make up the so-called “seventh continent” — the one billion people in retirement.
Jaana Remes, partner at McKinsey, whose work does not bear upon the longevity industry but rather the economic benefits of more robust health systems, says the over-60s are the new consumers. We therefore need a “more constructive way to think about ageing and longevity”, she proposes, adding that it may not necessarily all be characterised by slow growth, but rather “an opportunity for economic prosperity for everyone”.
Richard Siow, director of ageing research at King’s College London’s Ark, a cross-faculty consortium of researchers taking a multidisciplinary approach to better understand the mechanisms of ageing and longevity and its social impact, suggests that the investment and policy focus should be on extending healthspan through engaging in the societal effects on longevity as they are being experienced now.
There needs to be more investment from the “supermarket” health perspective, he says, rather than just the clinical disease perspective, by which he means that “venture capitalists should invest not only in clinical research but also in community research to see how we can make a difference at the consumer level”.
Financialisation of longevity
The interplay between living longer and healthier lives and the labour market has prompted other investors and entrepreneurs to think about what insurance policies and pension funds might look like in this brave new world.
Since 2010, longevity swaps have been a way for pension funds in the UK to hedge against their liabilities, essentially betting that their members will live longer. According to a recent estimate, the longevity swap market is worth roughly £90bn ($122bn).
As Mr Mellon points out, if a significant extension of lifespan is widely accessible to human beings, some of our social contracts will have to change. “Your whole life trajectory can change so you’re not just going to learn, earn, retire, expire. You’ll have to think of a very different way to live your life. Who’s going to pay for that?”
Dmitry Kaminskiy, general partner at Deep Knowledge Group, a consortium of commercial and non-profit organisations looking into frontier technologies, aims to create longevity exchange-traded funds, and issue longevity derivative products in a bid to provide institutional investors with exposure to this growing part of the financial market. “This can then be redeployed into additional research, creating a self-inducing cycle,” he hopes.
Mr Kaminskiy’s ultimate goal is to apply for a banking license for a longevity bank, followed by the establishment of a longevity investment bank in the UK — and further down the line, a longevity stock exchange.
An investment bank and a full-blown capital market are a world away from what Aubrey de Grey thought possible when he started campaigning for a “post-ageing world”.
Encouraged by what he describes as “all the bricks in the wall”, from regulatory advances to capital investments, Mr de Grey is determined not to rest on his laurels: “I’m not done. I’m a busy guy right now,” he says. Longevity, it seems, will remain his hill to die on — or not, as the case may be.