Building Momentum for Global AI-driven Longevity Transformation
Today, Insilico Medicine, a leading player in artificial intelligence (AI)-driven drug discovery and longevity research, tops up its recent $60 million Series D with additional $35 million from Prosperity7 Ventures, a global VC fund by Saudi Arabia’s giant Aramco. This investment by Aramco is yet another step within Saudi Arabia’s ambitious strategy (Vision 2030) to position itself as a global technological hub and become a Mideast center of longevity research with global influence. With this investment, Aramco secures its stake in one of the most advanced research platforms on the market, capable of rapid discovery of novel targets and drug candidates for a wide range of therapeutic indications, including age-related diseases as well as biological processes underlying aging itself.
Image credit: Insilico Medicine
Why is longevity a global priority in the 21st century?
Helping people live healthier lives for longer is not only a nobel altruistic goal in its own right, but it is also a growing economical and societal necessity. For example, according to the U.S. Census Bureau, a not-so-distant 2030 will be a milestone year in which older people will actually outnumber children for the first time in history. Census Bureau data also estimates that 1 in every 5 Americans will reach retirement age by that time. The phenomenon of a rapidly aging human population is often referred to as “The Silver Tsunami”, and it will have increasingly significant impact on everyday life, the economy and society -- rapidly rising healthcare costs, infrastructural and service demands, the compounding loss of accumulated skills and competencies when people retire and become non-functional, and so on.
The only sustainable strategy to manage a rapidly aging population is to increase the “healthspan” -- a period of human life when there are little or no effects of age-related diseases and conditions, and the human beings can function efficiently, perform work duties, enjoy life, etc. In this sense, the increase of healthspan is even more important, in practical terms than the increase of the overall lifespan -- although both usually correlate.
More and more scientists, businesses, investors, non-government organizations and associations, as well as governments themselves are concerned with the increasing issue of an aging population. This led to the emergence of the Longevity industry, a fairly new notion describing intricately complex activities linking science, medicine, economy, and societal trends, all aimed at increasing the health- and lifespan of the human population.
A great deal of longevity industry includes a vast scope of companies and communities focused on various aspects of “healthy lifestyle”, such as healthy food, sports activities, stress reduction, and better sleep habits. There are apps and gadgets helping people manage their lifestyles, there are food producers prioritizing dietary products and bioactive supplements, and for a good reason -- a lot of such activities do add some value to one’s life. However, more tangible healthspan and lifespan extension is not possible without more serious and systematic interventions and therapeutic remedies. So, the more promising and impactful part of the global longevity industry is focusing on aging research and resultant therapeutic tools and therapies, as well as prophylactic therapies, some of which have serious potential to drastically extend human lifespan and healthspan, respectively.
Longevity research is getting recognition and funding
It took more than eight decades since the landmark experiments on calorie restrictions in 1930th to get to a point when the first wave of new anti-aging drugs began human testing, including senolytics, rapamycin, mitochondrial gene therapy, and WNT pathway regulators among others. Things started accelerating over the last decade, and especially after the 2013 landmark paper “The Hallmarks of Aging”, published in Cell: the area of anti-ageing research exploded in many directions, from de novo discovery of anti-aging therapeutics (e.g. senolytics), to drug repurposing, stem cells applications, genomics, discovery of biomarkers of aging (‘aging clocks’) and more. At the beginning of 2020, MIT Technology Review selected anti-aging drugs to be included in their list of 10 Breakthrough Technologies 2020.
The increasing rate of progress in aging research and technology is catalyzed not only by the improved understanding of human biology, but also by the increasing inflow of capital, and the emergence of private and public funding programs to support the longevity industry. For instance, 2021 alone was an exciting year for the longevity funding landscape, with more than $2 billion pouring into the sector, and with multiple launches of large new funds: Korify fund ($100 million), Apollo Health Ventures ($180 million), Switzerland’s Maximon ($100 million), German billionaire Michael Greve’s personal fund (€300 million), and the newly formed Longevity Science Foundation, which committed to distributing more than $1 billion over the next 10 years, to name a few. There were, also, mind-boggling Series C rounds, a series of remarkable early stage investments and the growing appeal for alternative ways to fund longevity research, such as via crowdfunding, cryptocurrencies, and DAO companies.
One of the most exciting 2022 announcements in this context, came from Saudi Arabia, where the Saudi royal family has started a not-for-profit organization called the Hevolution Foundation that plans to spend up to $1 billion a year of its wealth supporting basic research on the biology of aging and finding ways to extend healthspan.
Considering that the neighboring UAE has also been active in terms of supporting aging healthcare and the longevity ecosystem, with a longevity market sector being more than $19 billion in 2020 and growing, it seems that Mideast is rapidly emerging as a global longevity destination and technological hub.
The growing longevity ecosystem
The increasing global demand for anti-aging interventions, the rising recognition of longevity industry, a wave of scientific and technological breakthroughs, and ever increasing amount of available funding -- those are the driving factors that facilitated a rapidly growing ecosystem of drug discovery and biotech startups focused on anti-aging and rejuvenation therapeutics and therapies.
The anti-aging drug discovery startup ecosystem is still in its early days but is rapidly expanding, already having around 150 notable startups and more established companies, including strikingly well funded private companies, such as California-based biotechs Altos Lab ($3.27 billion; cell reprogramming), BioAge Labs ($124 million; AI platform for longevity drug discovery), and New Limit ($105 million; cellular reprogramming), Hong Kong-based Insilico Medicine ($366 million; AI platform for drug discovery, biomarkers of aging, cellular senescence), Massachusetts-based Elevian ($64.3 million; regenerative medicine), New York-based Elysium Health ($71 million; longevity supplements), and many others.
There are a plethora of distributed development companies, such as Juvenescence ($219.2 million), Rejuveron ($64 million), and Cambrian Biopharma ($160 million), which pursue development of multiple breakthrough programs in various aspects of aging research and longevity, bringing together leading gerontologists, and playing notable role in building longevity communities.
A list of well-established publicly traded companies in longevity space includes, for example, Geron (GERN, market cap: $713 million), a late-stage clinical biopharmaceutical company focused on developing and possibly commercializing a first-in-class telomerase inhibitor, Imetelstat, which is essentially an experimental drug targeting a hallmark of cancer. Another company, Longeveron (LGVN, market cap: $127 million) is developing cellular therapies for chronic diseases associated with aging and other additional life-threatening conditions. California-based ChromaDex (CDXC, $114 million) is dedicated to the support and development of healthy aging, via its research programs related to nicotinamide adenine dinucleotide (NAD+), which is found in every cell as we age.
The future of longevity is “tech” + “bio”
On the one hand, longevity industry is thriving to a great extent owing to a wave of biology breakthroughs over the last decades, including expanded knowledge about molecular machinery of human life and aging (e.g. “omics” research, “hallmarks of aging”), as well a better understanding of biological systems on the whole. New experimental tools such as next generation sequencing (NGS), next generation proteomics (NGP), cryo-EM, high content screening -- paired with automated labs and robotized experimental facilities -- help generate unprecedented amounts of data about biology systems.
But there is another key component for success -- equally unprecedented progress in analytical and modeling technologies, such as artificial intelligence: deep learning frameworks, natural language processing models, knowledge graphs, and so on. There is a small (but growing) number of companies -- “neo-biotechs”, or “digital biotechs” -- which adopted technology-first R&D strategies from their very foundation, and created highly automated AI-driven modeling systems, which are capable of making sense of biological big data at scale and going to uncharted depths of biological complexity. The R&D model of such neo-biotechs is strikingly different from “traditional” high-throughput trial-and-error drug discovery companies.
An illustrative example, Insilico Medicine, is uniquely positioned in this space since it pioneered the application of deep learning for drug discovery and generative chemistry back in 2014, and over the years created a powerful AI-driven end-to-end platform Pharma.AI, whose algorithm was trained on the drivers of aging and disease. The company has made a name for itself with its rapid AI-driven approach to discovering, designing and beginning trials of entirely new drug compounds, along with novel targets. Some examples included a novel drug candidate for a novel wide-indication target to treat Idiopathic Pulmonary Fibrosis (IPF), developed in under 18 months and at roughly 1/10th of the typical cost associated with similar programs. Just six months later, Insilico Medicine nominated a novel drug candidate for Kidney Fibrosis for its internal drug discovery pipeline. Further example includes a novel drug candidate for the QPCTL immuno-oncology target nominated in under 40 days since the announcement of strategic partnership with Fosun Pharmaceuticals.
Converting on its long-term focus on aging-related data for training the AI platform, Insilico Medicine announced that its system PandaOmics, a target discovery module of Pharma.AI, was able to predict molecular targets for new drugs to treat both aging and age-associated diseases like Alzheimer’s, results published in the journal Aging.
The latest major announcement from the company came out in July -- in collaboration with researchers from Answer ALS, Johns Hopkins University School of Medicine, Harvard Medical School, and Mayo Clinic, scientists from Insilico Medicine yet again applied PandaOmics to rapidly identify numerous unreported potential therapeutic targets of amyotrophic lateral sclerosis (ALS). Among the 28 proposed candidates, 18 have been validated to moderately or strongly rescue eye degeneration in c9ALS Drosophila model.
Insilico Medicine just announced it raised additional $35 million from Prosperity7 Ventures, a global VC fund by Saudi Arabia’s giant Aramco. This brings the total Series D to a lofty $95 million, opening more possibilities for the company to focus on aging-related targets and therapeutics. The new Series D capital will support the continued advancement of Insilico’s pipeline, including its lead program which is currently in a Phase 1 study in New Zealand and in China, as well as several pipeline programs in IND-enabling studies. The proceeds will also fund other key strategic initiatives, including further development of its end-to-end Pharma.AI platform, the launch of a fully automated, AI-driven robotic drug discovery laboratory and biological data factory, and the establishment of regional centers.
Insilico Medicine is not the only company in the pharmaceutical research space pursuing AI-driven platform-based approach to drug discovery -- there are also very successful and well-funded companies like Recursion Pharmaceuticals, BioAge Labs, Insitro, Relay Therapeutics to name a few -- but Insilico Medicine is certainly one of the most active players in the aging research and Longevity industry, and a catalyzing force for building global longevity ecosystem.
It is clear that the implementation of machine learning (ML) and deep learning algorithms is essential for the progress of aging research, giving the unprecedented complexity or aging, and necessity for systems-level modeling of numerous cross-functional processes and pathways. Terabytes of epigenomic, transcriptomic, proteomic and metabolomic data (so-called ‘omics data’) are used to train AI systems to not only discover novel age-related targets and therapeutics, but also accurately measure the biological age and build so called ‘aging clocks’ -- universal biomarkers of aging, and crucial tools for measuring and benchmarking positive or negative effects of any longevity therapeutics, therapies, and life-style choices. Currently, more than a dozen types of ‘aging clocks’ exist, with some of them exploiting methylation profile data, such as Horvath's clocks and Hannum’s age predictor. Recent advances have been made by Deep Longevity, an aging research spinout of Insilico Medicine, which developed what they claimed to be the most accurate epigenetic clocks for today — DeepMAge. The company also released a new achievement — psychological aging clocks, both technologies are powered by deep learning-based algorithms developed by the company and inherited from Insilico Medicine’s years-long expertise.
Time to reclassify aging as a disease?
With all the progress in the aging research, there remains a conceptual bottleneck slowing down the growth of the longevity industry: a definition of aging itself, which currently essentially accepts that “aging is a normal part of life”. As long as aging is not considered a pathological abnormal process, essentially a disease, regulatory organizations, such as the Food and Drug Administration, won’t bother regulating any practices or products designed to address aging. Even the very absence of well-accepted and regulated age-related clinical endpoints makes it difficult to run clinical trials with a focus on the underlying biology of aging. Instead, the FDA requires addressing specific clinical endpoints of specific age-related diseases, which is only partially relevant for the lifespan/healthspan extension in general.
The absence of a straightforward regulatory framework for anti-aging drug discovery leads to a situation where even if someone created a drug to mitigate the cellular processes underlying aging, it is difficult to find a pathway to market. In other words, governments of various countries readily allocate money to reachearching age-related conditions such as Alzheimer’s, but getting governments to fund research into a process that is not an actual disease is an uphill battle.
The idea to classify aging as a disease has been pushed forward not only by longevity enthusiasts but also by scientists. In 1954, Robert M. Perlman introduced the term “disease complex” in his research paper “The Aging Syndrome” (the Journal of American Geriatrics Society). Later, others supported the idea, including gerontologists frustrated by a lack of funding to study the aging process itself. In 2015, a team of international researchers declared: “It is time to classify biological aging as a disease.” In 2018, the World Health Organization added an extension code in the latest version of the International Classification of Diseases for “ageing-related” diseases, which it defines as those “caused by pathological processes which persistently lead to the loss of organism’s adaptation and progress in older ages.” In other words, it included diseases that are believed to be associated with aging, like cancer and arthritis. That decision may pave the way for defining aging itself as a disease.
Together with co-authors, Dr. Alex Zhavoronkov, founder and CEO of Insilico Medicine, and a passionate supporter of the idea of classifying aging as a disease, wrote in his 2015 paper in Frontiers in Genetics: “There are definite benefits for many stakeholders in having aging classified as a disease with multiple actionable “non-garbage” disease codes that can be used to target therapeutic interventions.” In order to create a suitable and impactful platform for discussing this and other complex topics in longevity research, Alex founded the Aging Research and Drug Discovery (AADD) yearly conference in 2014 as a voice of the industry and a place to come up with actionable steps. The 8th conference, AADD 2022, is taking place on August 29 -- September 1 in Copenhagen, Denmark, with an impressive speaker list including the CEO and CSO of Hevolution along with experts from Harvard, Yale, University of Copenhagen, Shanghai University and many others:
Building momentum for the longevity industry
To summarize some of the above considerations, anti-aging drug discovery is becoming an increasingly crowded space, but the overall success will depend on many factors and players involved. For example, the increasing prioritization of longevity research by governments would stimulate a seismic shift towards a more systematic longevity strategy, with a populational and economical factors in mind. Saudi Arabia’s Vision 2030 is a good example of a program that puts forward ambitious plans to increase the country’s life expectancy at birth by 6 years, from 74 years to 80 years, an average gain of 0.43 years per annum, and achieve this over the period 2016–2030 by improving healthcare, social factors, and its activity in the longevity research space. Other regions will likely follow, inspired by this initiative.
Next, regulatory framework for aging research is critical to pave the way for more transparent and calculated routes for novel longevity therapeutics and practices to the markets. Classification of aging as a disease, or finding alternative (but actionable!) regulatory paradigms are important and should be lobbied by scientists and companies all around the world.
Finally, artificial intelligence is a key technological enabler of aging research, and much more AI-driven platform-based companies, such as Insilico Medicine, will need to emerge as soon as possible to facilitate more innovation. This is the only hope to move the longevity progress fast enough to give a chance for the existing generation to live longer than nature currently permits.
Topics: Aging & Longevity
