A Proposed Solution to The Longevity Industry’s Biggest Risk: Modern Tools for Safe Human Validation to De-Risk

Investment Decision Making & IPOs

By Dmitry Kaminskiy, Founder and General Partner of Deep Knowledge Group

 

In Longevity Industry 1.0: Defining the Biggest and Most Complex Industry in Human History, we distilled the complex assembly of deep market intelligence and industry knowledge that Deep Knowledge Group and its Longevity-focused subsidiaries (including Longevity.Capital and Aging Analytics Agency) has developed over the past 5 years into a full-scope documentation of the global Longevity Industry, showing the public exactly how the international consortium of commercial and non-profit entities managed to define the overwhelmingly complex and multidimensional Longevity Industry for the first time, and how they created a tangible framework for its systematization and forecasting.

 

Whereas Longevity Industry 1.0 charted the inception and rise of the industry up to 2020, and provided the methodology and framework for defining and analyzing the industry, its sequel, Longevity Industry 2.0: DeepTech Engineering the Accelerated Trajectory of Human Longevity - The Blueprint and Pathway from Longevity Industry 1.0 to 2.0, outlines Deep Knowledge Group’s recent work towards formulating the pathway to Longevity Industry 2.0, and presents the framework for safeguarding the sector’s current upward trajectory and ensuring its optimized, sustainable growth towards its next stage and the realization of its practical benefits for humanity by the year 2030.  

 

In the previous article, I outlined what Deep Knowledge Group have believed for several years (since our first investment in the Longevity Industry in 2014) to be the largest fundamental and systemic risk and source of potential market destabilization for the Longevity Industry: namely, the overwhelming reliance on results in model organism studies (e.g., in mice) rather than humans.

 

In the present article, I will outline an integrated set of modern technological and scientific approaches and the framework for a proposed solution to this problem, which can allow for safe and effective human-centered validation of Longevity therapies and technologies at the pre-clinical trial phase, and which can be used by investors to de-risk their investment decision-making in this sector, by Longevity companies to more reliably validate the safety and efficacy of their therapeutic pipelines, and by Longevity startups preparing to launch IPOs to prevent dramatic declines in their market capitalization following failures for their model organism results to translate to humans.

 

The article:

  • Begins by presenting an overview of Longevity Industry IPOs during 2020, signifying the increasing frequency with which Longevity companies are going public, and further highlighting the pressing need for more relevant, sensible and modern approaches for validation and scientific/technological due diligence;

  • Presents, describes and systematizes the full set of modern technological and scientific solutions that can (and should) be used to facilitate a shift away from 100% reliance on animal studies and towards human-centered therapeutic validation, which can be used 

    • by investors to de-risk Longevity investments, as a framework for more tangible investment decision making 

    • by companies to provide more tangible validation of their therapeutic pipelines (and, in the case of IPOs, avoid dramatic declines in market capitalization following a failure to match results from model organisms studied in clinical trials), and

    • by national governments to determine the best and most market ready technologies to support for the purpose of optimizing population health and National Healthy Longevity, as well as to track and measure the impact of their population health-focused policies and initiatives

  • Presents past and present examples of human-centered experimentation and validation, drawing from both the history of medicine and the modern scope of industrial R&D in specific sectors to demonstrate that there is nothing fundamentally misguided about the notion and desire for human validation and experimentation, provided that it can be done safely. 

 

The Rise of Longevity IPOs

 

Due to the global COVID–19 pandemic, the overall biotech and Longevity sectors are on the rise. During 2020 we have observed multiple medium and large funding rounds for biotech and Longevity companies, especially those focused on drug development. More than 500 successful Longevity companies closed large-sum late-stage venture capital rounds (B, C, and D) over 2019-2020 and several of them are now developing clinical stage drug candidates. We expect some of them to go public in 2021–2022.

And, more importantly, 2020 saw a total of 19 IPOs in the Longevity sector. The year 2020 is marked by a general
biotech IPO boom, catalyzed in part by the coronavirus pandemics – directly and indirectly – impacting the Longevity industry enormously. When some of the companies complete IPOs in the near future, it will attract a significant number of non-biotech investors to enter the Longevity sector. Despite the crisis, publicly traded companies exhibited rapid growth which reached $62.8B of cumulative capitalization or a 266.6% growth rate.

At present, VC funds categorize Longevity companies according to seed, series A, series B, etc.; the stage of a company's development moving forward will become less important while TRL levels and the level of the technology according to other tangible metrics will become much more important, because they will provide data-driven analysis allowing the performance of certain mathematical calculations of how valuable a portfolio company is.

The increasing frequency and size of Longevity IPOs, combined with the destabilizing threat posed by overwhelming industry reliance on model organism (non-human) validation, is intensified and further complicated by the fact that the majority of funding is being poured into biomedical sectors (predominantly geroscience and P4 medicine), which are the exact sectors that are most in need of human-centered approaches to experimental validation.

 

By 2020, total investments into Longevity companies globally had crossed the $156 billion mark, of which $60B were raised during the last year. Some of the major deals included:

  • Sana Biotechnology – $700M in initial financing to advance the company’s discovery and development programs that create and deliver engineered cells as a treatment for different disease types (Series A round);

 

  • Cue – $481M (grant from US government);

 

  • Freenome – $270M to advance novel multiomics blood resting platform for early cancer detection (Series C Round);

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  • Recursion Pharmaceuticals – $239M (Series D Round led by Bayer);

  • ElevateBio $170M which will be directed toward manufacturing cell and gene therapies, enabling new technology platforms, and pursuing therapeutics (Series B Round).

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P4 Medicine (Precision, Preventive, Personalized, Participatory) is the largest sector within the Longevity Industry in terms of both total funding raised and the number of companies. The most active capital-raising P4 Medicine subsectors are Diagnostics and Mobile Health. 

 

The distribution of investments across different Longevity sectors demonstrates that drugs and gene therapies are more attractive for investors than devices (e.g. AgeTech).

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The Solution: Modern Tools for Human-Centered Validation and Experimentation Platforms for Tangible Investment Decision Making 

 

Given the enormous differences between the biology of humans and the biology of common model organisms like mice, combined with the higher degree of biological complexity as it pertains to ageing vs. single diseases, we can expect the clinical translation failure rate in the Longevity Industry to be much higher than the already-enormous failure rate in traditional BioTech.

 

At this point, we have defined the major problem threatening the stability of the Global Longevity Industry, and described why a fundamental shift in the ways that Longevity therapies and technologies are tested and validated (in terms of both safety and efficacy) is needed to safeguard the industry’s potential to become the biggest, most stable and most ethical industry in human history.

 

Having stated the problem, we now turn to modern approaches and tools that can be used to formulate the solution – namely, a safe and effective platform for validation of Longevity therapies and technologies in humans, which is the only relevant approach considering the huge differences between the biology of aging in humans and in mice. New approaches to scientific due diligence and the validation of results for Longevity companies are needed to protect against company and industry devaluation. Fortunately, there are a number of existing approaches that can be used by investors to de-risk Longevity investments.

 

The use of biomarkers of aging and Longevity constitutes the most market-ready and validated means of proving efficacy in humans, and can serve as the basis for demonstrating human-validated results by Longevity companies and startups. A wide array of single biomarkers and panels of biomarkers of Longevity exist in market-ready form, and should be adopted into due-diligence practice by Longevity investors in order to create a more modern, sophisticated and robust method of preliminary validation of therapeutic safety and efficacy.

 

Besides biomarkers, there are a number of other modern approaches, capable of providing preliminary indications of human validation, which can be used to create a coordinated framework to provide investors with greater confidence in the likelihood of clinical translatability. These include:

 

  • In silico human modelling
     

  • In vitro tests using human cells and tissues
     

  • Human-animal chimeras (e.g., human-mouse chimeras) for safety, toxicity and efficacy testing. This approach is already common in immuno-oncology research, and a wide array of validated approaches can be applied for testing of ageing-focused interventions
     

  • In vivo administration of sub-therapeutic doses using microfluidic chips (i.e.,  in vitro “skin-on-a-chip” testing)

 

Modern and Historical Precedents for Human Validation

 

While the notion of human validation may seem controversial to many readers, the truth is that we now have a full set of modern tools and approaches for safely demonstrating varying levels of human validation of Longevity therapies and technologies. Furthermore, the notion of human validation is itself not modern but very ancient, and pre-dates the present-day system of model organism studies.

 

In the early centuries and decades of biomedical research, it was common for doctors to engage in self-experimentation and to test their therapies on their own bodies. The most famous example is Edward Jenner (inventor of the vaccine), who inoculated himself with his smallpox vaccine in the late 1700s. This practice is more common among doctors and biomedical researchers leading up to the 20th century than many people realize. This is not to say that the same simplistic approaches should be revived, but that the mindset of practical self-experimentation and human validation is itself more ancient than its opposite.

 

These practices were rightly replaced by paradigms and systems of model organism experimentation and validation in the 19th and 20th centuries which secured the safety of doctors and scientists and which proved effective for many decades when the complexity of biomedical treatments was low enough not to become fundamentally stalled by differences in the biology of humans and model organisms. However, today this entire mindset serves as a major bottleneck for scientific and industry progress, posing massive bureaucratic hurdles that prevent us from adopting and developing to scale modern technologies that can ensure safe human validation, and that are equipped to handle the increasing complexity of biomedical research and translation.

 

Another historical example is warfare medicine, which by necessity has historically been focused on human validation rather than model organism experiments precisely because of its urgency – i.e., the recipients of these techniques need immediate care, and would be likely to die anyway if they were not treated, while the sheer scale of those needing care (especially in the cases of World Wars I and II) was enormous. While this seems like an isolated and unrelated example, in many ways we are in a similarly urgent war with aging, and each of us has been assigned a death sentence if we do not get treatment. Likewise, the scale of the need is even more pressing, affecting all of humanity. 

 

There are also modern-day examples, the most well-known of which are the biohacking and Quantified Self movements, where individuals attempt to push the limits of the preventive medicine methods and technologies available to them to the extreme, utilizing the full arsenal of tools at their disposal (including those outside the scope of FDA-approved treatments) in order to optimize their state of physical, biological and cognitive health and performance. California is home to a community of scientists practicing self-experimentation and so-called “Quantified Self” methods by using advanced approaches and techniques related to precise diagnostic and monitoring, as well as implementing safe applications of geroprotectors. Such an approach can be viewed as a more balanced and pragmatic alternative to biohacking as the latter is perceived as a more radical option.

 

Meanwhile, I personally know several medical doctors who pride themselves on the development, refinement and validation of their Longevity-focused lifestyle practices, and even technologies, on their own bodies. And while I am not in a position to reveal specifics at this time, I can attest to several technologies (not just lifestyle and behavioural practices, diets and supplements, but actual technologies) that I am personally using to optimize my Healthy Longevity and performance.

 

It is important that the modern set of tools, technologies and approaches that make up the proposed framework for safe human experimentation and validation described earlier in this article be adopted not only by the Longevity Industry, but also the underlying drivers: Longevity scientists, doctors, and practitioners. 

 

While the real number of scientists and practitioners actually experimenting on themselves is increasing, it remains a core taboo of the scientific community. More work is needed to create institutional and infrastructural frameworks which normalize these activities, such as the establishment of a peer-reviewed journal dedicated to exactly this – publishing the results of personal Longevity experimentation in scientists, doctors and practitioners.

 

We also have industry examples of biomedical sectors that place greater emphasis on human validation than model organism studies; this serves to strengthen the notion that there is nothing fundamentally wrong or misguided in human validation if it is done safely. One of the most immediately obvious sectors is the NeuroTech industry, which focuses on human validation primarily out of necessity – the  size and functionality of mouse brains is so vastly different to that of human brains that there would be no useful extrapolation to be made from experimental results in mice. And, indeed, while the difference between the genomes, physiological complexity and the nature of the biology of aging in mice vs. humans is arguably just as large, if not larger, than the difference in the size and capacity of brains between mice and humans, it is less recognised by conservative scientists and regulators because the difference is not as immediately understandable.

 

Finally, the domains of SpaceTech and Space Medicine in particular are areas which are not only overwhelmingly focused on human-centered validation, but,  interestingly, have many technical and scientific convergences with Longevity research and clinical translation as well, so much so that they warrant being analyzed and discussed as exemplary case studies of this larger phenomenon. As such, we will cover them in depth in the next article in this series.

 

Deep Knowledge Group Holds Human Validation as a Fundamental Due Diligence Requirement

 

Deep Knowledge Group and its venture investment arms, including both Deep Knowledge Ventures and Longevity.Capital, have been warning of the fundamental false assumption at the very base and foundation of the Longevity Industry for several years now, and have been working to develop modern approaches to combat this systemic problem, both in order to optimize their own internal investment strategies, and to promote the adoption of similar approaches by other investors to help secure the long-term stability of the Longevity Industry more generally, which, as I have explained in detail in my recent book, Longevity Industry 1.0: Defining the Biggest and Most Complex Industry in Human History, has the potential to become the largest and most ethical area of business to date.

 

On the one hand, Deep Knowledge Group has been hedging against this fundamental and paradigmatic risk by strategically prioritizing other sectors with high degrees of market-readiness which are not exclusively focused on biomedicine – such as AI for Longevity, AgeTech and Longevity FinTech – while also developing and deploying sophisticated and modern approaches to investment analytics, due diligence, and company valuation that are equal to the complexity, intersectionality and multidimensionality of the Longevity Industry itself. These approaches have been developed over the period of 2013-2021 by Deep Knowledge Group’s Longevity-focused analytical subsidiary, Aging Analytics Agency.

 

However, Deep Knowledge Group has also been working to combat this insidious threat to the stability of the global Longevity Industry in a more direct and tactical manner which has not yet been publicly disclosed. It is a strict internal mandate that Deep Knowledge Group’s venture arms do not make any investments into biomedical Longevity companies without some form of human validation. 

 

What is more, in many cases Deep Knowledge Group uses as a component of its scientific due diligence process something that at first glance may seem controversial, but which in my belief will come to be recognized as an increasingly common, pertinent and sensible approach within the Longevity investment community: namely, by having Deep Knowledge Group partners validate the safety and efficacy of the Longevity technology or therapy offered by a given investment prospect through their own bodies. 

 

I am the foremost practitioner of this mandate, in that I am the Deep Knowledge Group partner who most frequently partakes in the practical, real-world use of Longevity technologies as a component of our internal due diligence process (though I am certainly not the only partner to do this). Having pushed the consortium to make its first investments in the Longevity space in 2014 – and having founded its Longevity-focused analytical subsidiary in 2013 precisely as a conveyor-belt and gigafactory of analytics, research, market intelligence and industry understanding of Longevity science, business, finance and policy – I consider this quite natural. I have been developing and refining my own personal, practical Longevity regime for almost a decade, and I am very well equipped both psychologically and physiologically to understand what has a high likelihood of being safe before applying it, and to assess its effects on my own body.

 

I believe that as approaches for varying levels of safe human validation in the Longevity Industry become more common, accepted, and demanded as industry-standard components of scientific and technological due diligence by investors, an increasing number of Longevity entrepreneurs, investors and even scientists will begin to adopt the mindset that the only reliable form of validation – and the most definitive proof of safety – is in their own bodies. 

 

About the Next Article

 

In this article, we build upon the background and context provided by the previous article in this series, which identified the largest and most fundamental source of risk threatening the continued stability of the Longevity industry (the assumption that positive results in model organisms will translate to humans successfully) by outlining an integrated set of modern technological and scientific approaches and the framework for a proposed solution to this problem, which can allow for safe and effective human-centered validation of Longevity therapies and technologies at the pre-clinical trial phase, and can be used by investors to de-risk their investment decision-making in this sector; by Longevity companies to more reliably validate the safety and efficacy of their therapeutic pipelines; and by Longevity startups preparing to launch IPOs to prevent dramatic declines in their market capitalization following the failure of their model organism results to translate to humans.

 

In the next article in this series, we will turn to a specific modern precedent of safe and effective human experimentation and validation within the realm of SpaceTech and Space Medicine, exploring the lessons that can be learned, and taken on board, by the Longevity Industry to facilitate a paradigm shift away from almost complete reliance on the results of model organism studies for due diligence, company valuation and investment decision making; and towards a more realistic, relevant and modern human-centered approach. We will also look at some interesting scientific and technological convergences between aging and the negative effects of spaceflight; and the ways in which the specific therapeutic approaches used to protect and preserve the health of astronauts intersect with Practical Healthy Human Longevity.