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Longevity and Anti-Aging Investment Opportunities

Healthspan, Life Extension and Longevity Company Investment Opportunities 

April 2021

 Question: “What’s the easiest way to make a small fortune?”  Answer: “Start with a large one!”                                                                                

[Necessary disclaimer]:  Keep Health is not an investment advisor and the content of this website is not to be used for making or refraining from investment decisions. The information provided is for general information purposes only. It may not be suitable for your situation. Although Keep Health has made every effort to ensure accuracy of the information, Keep Health makes no representation about accuracy and completeness. Keep Health does not assume and hereby disclaims any liability to any party for any loss or commercial damages, including, but not limited to special, incidental, consequential, or other damages or disruption caused by errors or omissions which result from accident, negligence or any other cause. [End disclaimer]  

How much does wealth matter for increasing healthspan? 

How much does wealth matter to enjoy living those extra healthy years? 

Does it make sense to invest in anti-aging, healthspan, life extension and longevity companies?  

Keep Health does not recommend investing in this sector unless you are an expert or getting trusted expert advice. There has been a tremendous amount of money made and lost investing in life sciences and healthcare companies. We do not want you to be on the “lost” side, especially because of anything you read here. There are plenty of people who claim to be experts in healthspan investing and want you to pay them for their expertise. There are few with verifiable track records of success.   

Emerging healthcare startups are speculative investments and are more likely to be overvalued than undervalued. It is risky to try to take advantage of over-valuations with short selling or buying put options because emerging companies may be bought by large companies for premium valuations.   Warren Buffett once said that as an investor, it is wise to be “Fearful when others are greedy and greedy when others are fearful.”  Market timing for investments is important and following sources like CNN’s Fear and Greed Index and Investor’s Business Daily’s Market Trends can provide a sense for when the market is overbought or oversold.  Market conditions and company valuations as of April 2021 are historically very high. For those wondering whether the stock market typically goes down post-Presidential elections, there is no clear trend in either direction. However, post-election year stock markets generally do not fare as well as election year stock markets. Keep Health’s investment opportunities cover notable healthspan, life extension and longevity-focused Exchange-Traded Funds (ETFs), venture capital funds and a few individual public companies. 

Research from the Stanford Center on Longevity concludes that Generation X (people born between 1965 and 1980) are expected to live 20-30 years longer than previous generations. A 45-year-old woman in excellent health has a 20% chance of living to 100. An equivalently healthy man has an 11% chance of living to 100. 

Here are some interesting emerging companies in the healthspan space attempting to be the leaders in making these longevity gains happen. We highlight their progress, strengths and weaknesses. They may or may not be successful investments. Even if they are successful, it is important to understand their fundamentals to determine whether they are valued appropriately.

Healthspan, Life Extension and Longevity ETF Investing Opportunities

There are three interesting ETFs focused on profiting from increasing number of elderly people in the world. To get a sense for the size of the rapidly growing market these companies are pursuing, see the 2019 Organization for Economic Cooperation and Development report:  Fiscal Challenges and Inclusive Growth in Ageing Societies

  1. Global X Aging Population Thematic ETF (AGNG) (previously traded as LNGR) — Optimistic View of Aging
    • Tracks an index of mostly large-cap equities from companies involved in lifespan extension and improved quality of life efforts for senior citizens.
    • Includes companies from developed countries who derive the majority of their revenue or whose stated business objective falls under the “longevity” label. 34% of investments are in companies outside the United States.
    • AGNG has an expense ratio of 0.50% and a three year average return of ~15.5% through April 2021 results.
    • In 2020, AGNG also dropped sharply because of the negative impact of COVID-19, but full recovered.
  2. The Long-Term Care ETF (OLD) — Pessimistic View of Aging
    • Tracks a market-cap-weighted index of global companies focused on long-term care services and products required by an aging population.
    • OLD is 90+% invested in specialized Real Estate Investment Trusts (REITs) and healthcare facilities of which 75% are in the United States.
    • OLD has a reasonable expense ratio of 0.35% and a three year average return of ~15.76%, through April 2021 results.
    • In March 2020, OLD dropped sharply because of the negative impact of COVID-19 on long-term care services and the elderly population. Since then, with COVID-19 vaccinations available to the elderly population, it gained 65%.  
  3. ARK Genomic Revolution ETF (ARKG)
    • Invests in companies expected to substantially benefit from extending and enhancing the quality of human and other life by incorporating technological and scientific developments and advancements in genomics into their business.
    • ARKG companies are creating advancements within CRISPR, targeted therapeutics, bioinformatics, molecular diagnostics, stem cells and agricultural biology.
    • ARKG launched in October 2014 and has an expense ratio of 0.75%. As of April, 2021, it has generated an incredible 38% average 5 year annual return. Most of these gains came from rising 129% in the last 12 months. 

Venture Capital Firms Focused on Healthspan, Life Extension and Longevity Investment Opportunities

  • BioVerge
    • Emerging startup company investing either individually or as part of their angel fund.
    • Portfolio companies
  • Juvenescence Ltd (UK)
    • Co-founded by British billionaire Jim Mellon.
    • Led by Dr. Greg Bailey. See his April, 2020 interview with Longevity.Tech. Sees opportunity within growth of longevity market to $600B by 2025.
    • Sought to raise $150MM C-Round in Q4, 2020, then progress to an IPO in 1H 2021. It does not appear they raised the Q4 C-Round. Unclear whether IPO is on track. They have been trying to IPO for two years. Have previously raised $165MM.
    • Investments include:
      • AgeX Therapeutics (NASDAQ: AGE). 53.7% ownership. Details on AgeX below in publicly traded company section of this article.
      • BYOMass to develop therapeutics to modulate the central control of metabolism associated with aging and age-related chronic illnesses based on work of Margaret Jackson.
      • BHB Therapeutics focuses on approaches to induce a state of ketosis, which may have protective effects against age-related disease. Have formulated an inexpensive direct-to-consumer ketone ester beverage product that is geroprotective, neuroprotective and cardioprotective, providing 8+ years of healthspan benefit. Mammals such as mice live 25% longer.
      • Fox Bio a 50/50 joint venture between Juvenescence and Antoxerene, a subsidiary of growing discovery/pre-clinical CRO Ichor Therapeutics. The company is focused on developing small molecule senolytics targeting a major survival pathway relied on by senescent cells.
      • Generait Pharmaceuticals (formerly Juvenescence AI), a 2017 joint venture with Insilico.  Generait Pharmaceuticals gets first dibs on any five compounds per year that Insilico’s AI drug discovery platform develops. Juvenescence AI was formed to investigate the therapeutic properties of specific compounds. Mellon is particularly optimistic that this venture can develop a “senolytic” drug that helps the body clear out cells that have stopped dividing and can damage other cells.
      • Insilico Medicine artificial intelligence for drug discovery, biomarker development and aging research.
      • Juvenomics — a joint venture with G3 Therapeutics for developing validated nutraceuticals and pharmaceuticals to combat aging and aging-related diseases such as those of the musculoskeletal system. Juvenomics is built on the unique combination of G3 Therapeutics ‘ proprietary, multi-omic biological dataset, consisting of trillions of proprietary data points collected in the GLOBAL Clinical Study (NCT01738838) of over 7,500 patients, and the unique machine learning platforms assembled by Juvenescence.
      • LyGenesis focuses on organ regeneration. Their Phase 2a lead clinical trial starts in June, 2021 for patients with end stage liver disease. They will initiate regeneration by injecting hepatocytes (liver cells) into the patient’s lymph nodes that drain into the liver and the bile duct. Also, LyGenesis is creating additional cell therapies using lymph nodes as bioreactors to regrow functioning organs, including pancreas, kidney, and thymus regeneration.
      • Napa Therapeutics  —  Founded by The Buck Institute, Insilico Medicine, and Juvenescence to develop drugs to impede age-related disease. Focused on NAD-type solutions. Primary target did not achieve significant results. Does not appear to still be a viable company.
      • NetraPharma is a 50/50 partnership between Juvenescence and NetraMark Corp, and is a clinical-development focused machine learning company. NetraPharma helps companies with failed clinical trials identify overlooked subpopulations of responding patients. 
      • Portage Pharmaceuticals provides a p53 suppressing senolytic as well as a potential novel drug delivery system. p53 likely will be integrated with FoxBio.
      • Souvien Therapeutics is founded on the pioneering research of Professor Li-Huei Tsai, the director of The Picower Institute for Learning and Memory at MIT, and Associate Professor Stephen Haggarty, the director of the Chemical Neurobiology Laboratory at Harvard Medical School/Massachusetts General Hospital, on the epigenetic regulation of cellular aging in neurodegeneration.
    • JuvYou Division plans to launch a web and app-based personalized healthcare recommendations in 1H 2021 based on inputs such as blood sugar and VO2 Max.
    • Juvenescence Life Division is launching products based on licensing and technology from investment companies and internal research. These include:
      • Metabolic Switch, the brand name of a new powdered beverage drink which is combining licensing and technology from:
        • BHB Therapeutics
        • Evgen‘s cruciferous vegetable extract Sulforaphane which removes toxic metabolites and markers of inflammation.
      • A product to increase autophagy. It expects to improve cognition, boost immunity and help bones, cardiac health, skin and hair.
    • Juvenescence’s RX Division plans to enter two to four drugs into human clinical trials clinic in 2021 for obesity, cachexia, immunometabolism and fibrosis, as well as combinations of those products.
  • Longevity Vision Fund
    • Founded by Sergey Young.
    • Raised $100MM and is dedicated to making longevity affordable and accessible to all.
    • Invested in Juvenescence in Oct, 2019 as well as Insilico Medicine and Lygenesis.
    • Invested in Life Biosciences, focused on becoming the leader in epigenetic reprogramming, chaperone-mediated autophagy and mitochondrial uncoupling.
    • Full portfolio is here including 4D Molecular,  Deep Longevity, Eko Health, EXO Imaging, Freenome, Sigilon, Tessera and Valo Health plus 3 stealth companies.
  • Longevity Investor Network
  • Longevity VC (USA)

Small-Cap Publicly Traded Companies Focused on Healthspan, Life Extension and Longevity Opportunities

Although there are many large publicly traded companies focused on healthspan, life extension, longevity and anti-aging, Keep Health is only covering a few notable high risk, high reward small-cap companies at this time.

  • AgeX Therapeutics (NASDAQ: AGE)
    • Targets age-related degeneration with therapeutics that reverse aging and induce regeneration.
    • Grand ambitions, but insufficient funding and commercial progress over the past couple years.
    • As of March, 2021, plan to merge with Lygenesis to create clinical-stage cell therapy company. Lygenesis recently raised $11MM to fund its Phase 2 trial.
    • AgeX is the leader in high purity induced pluripotent stem cells (IPS) to restore organ function or grow replacement organs.
      • IPS can be re-differentiated into human tissue types. Non-pure IPS have minority of cells in undifferentiated stage or differentiated in the wrong direction. 
      • Can repair organs by eliminating cells in a damaged state and then restore using AgeX IPS in-situ (in the body).
      • 400+ patents and patent applications worldwide for pluripotency therapeutics.
    • AgeX provides two commercial platforms:
      • Immunotolerance UniverCyte™ platform for the generation of universal cells.
      • Pluripotent stem cell-based PureStem® platform for the derivation and manufacturing of allogeneic, off-the-shelf cells.
        • Partial cellular reprogramming to reverse the age of cells is set to open up a whole new field of pioneering therapeutics. We aspire to lead in this revolution using our partial cellular reprogramming technology “iTR™”.
        • Plan to execute on external licensing and collaboration cell therapy deals with third parties.
    • Market valuation: ~59MM. Has fluctuated between ~25MM to ~$200MM. Extensive patent portfolio is key to its valuation.
    • IPO’d in November 2018. Stock peaked at $5.95/share before falling to $0.67. Juvenescence has 53.7% ownership, acquired at ~$2/share and in return for investments to cover cash burn rate.
    • ~-5MM in tangible assets minus current liabilities. ~3MM quarterly burn rate. Insignificant current revenue streams.
    • Need to raise substantial cash soon and create high value partnerships for non-core applications of pluripotency such as Cytiva II adult cardiac cells for drug testing.
    • In January, 2020 signed deal with UC-Irvine to develop cellular therapies to treat neurological disorders and diseases for which there are no cures such as Huntington’s disease. Targeting a launch of clinical trial in 2H, 2021. As of April, 2020, Dr. Bailey was hopeful that they would land more licenses near-term. In 2H, 2020, Jim Mellon noted they completed 7 cell licensing agreements, however these have not produced significant revenue.
    • Long-term, have three therapies in preclinical trials, but have not secured funding to proceed. Work on most of these has been deferred because of Q2, 2020 layoffs. Plans to outsource and develop of AgeX’s iTR technology at AgeX’s subsidiary Reverse Bioengineering, Inc. were dependent on successful financing of the subsidiary.
      • AGEX-BAT1 to correct metabolic imbalances in aging including to reverse age-related changes in metabolism, especially those who suffer from obesity and Type 2 diabetes.
      • AGEX-VASC1 to restore vascular support in ischemic tissues respectively. Initial focus is on the development of young vascular cells to rebuild circulation in the context of age-related ischemic disease. Vascular progenitor therapy would deliver a youthful endothelium to rejuvenate and protect the cardiovascular system.
      • AGEX-iTR1547 is a drug-based formulation in preclinical development through Reverse Bioengineering subsidiary intended to restore regenerative potential in a wide array of aged tissues afflicted with degenerative disease using the company’s proprietary Induced Tissue Regeneration ( iTR) technology. Some animals in nature can regenerate damaged tissues after trauma; for instance an amputated leg of a Mexican salamander completely regenerates. Renelon™ is a first-generation iTR product designed to promote scarless tissue repair which the Company plans to initially develop as a topically-administered device for commercial development through a 510(k) application.
  • Amarin (NASDAQ:AMRN)
    • Provide Vascepa (USA) / Vaskepa (EU brand name) for icosapent ethyl, the active ingredient in fish oil. They have no other products.
    • Clinically proven to reduce triglycerides and cardiovascular risks such as heart attacks and strokes.
    • Amarin’s Reduce-IT trial showed it substantially cut major adverse CV events by 25% over about 4.9 years in statin takers with blood fat levels of 150 mg/dL or higher.
    • Market Cap of $2B down from $7.5B as of Jan 1, 2020.
    • $600MM+ in assets – liabilities.
    • 2020 revenue of $615MM. 2019 revenue of ~$430MM. 
    • 2020 $19MM corporate loss. Approaching profitability.
    • Believe they have regulatory exclusivity in major global markets through 2028-2033.
      • However, in March, 2020, lost patent protection in the United States where analysts expected a $3-4B market opportunity. Their appeal of the decision failed in September 2020. They will face competition from generics, although because of manufacturing complexity, it will take a major investment to compete. Will that happen? Teva, Hikma Pharmaceuticals and Dr. Reddy’s are among potential market entrants.
      • Received EU approval in March 2021 for what analysts estimate is a $650MM annual revenue market opportunity. Received Canadian approval as well.
      • Planning launches into Asia and the Middle East as well.
    • Alternative proprietary competitive solutions such as Epanova have been discontinued.
    • Vascepa contains only purified EPA, whereas Epanova included both EPA and DHA. As FiercePharma writes, “Evidence suggests that DHA may raise the level of bad LDL cholesterol, which is itself a risk factor for heart disease and stroke. So, it’s possible that DHA’s presence has compromised Epanova’s CV disease reduction ability.” This impurity is rather ironic given EPAnova’s name.
  • Chromadex (NASDAQ: CDXC)
    • Leader in product sales and IP for anti-aging dietary supplement  Nicotinamide Riboside (NR).
    • NR is proven in animals to promote proper mitochondrial function and thus enhance the immune system. NR has been validated for safety and efficiency, although this January, 2021 Nature study indicated that an excessive increase in NR can contribute to cancer progression.
    • Market cap of ~$500MM, up from $300MM in October 2020.
    • 2020 revenue of nearly $60MM from Tru-Niagen brand NR sales. > 100% YoY sales growth. Tru-Niagen is available directly from Chromadex and on Amazon.
    • ~20MM loss in 2020. Need to get to ~80MM in annual sales for break-even. On pace for that.
    • ~$15MM liquid assets less total liabilities. May need to raise capital in 2021.
    • Won initial lawsuit against competitor Elysium Health. October 2019 legal discovery found egregious behavior by Elysium related to the theft of trade secrets and confidential information including text messages revealing unethical conduct and a stated intention to “destroy” ChromaDex. The legal battle between them is covered here with more of the history behind the dispute here. The next trial is set for August 9, 2021, although there may be continued delays.
    • 60+ registered clinical studies are in progress on NR focused on various human health benefits, including treatment of cardiovascular, neurodegenerative, and metabolic disorders. There is not conclusive evidence of benefit in humans for these disorders yet.
    • Partnerships with Nestlé and Watsons, the largest healthcare chain store in Asia. Pursuing markets in Hong Kong, Macau, China and Turkey. Approved in the European Union (EU), Australia, Canada and New Zealand. In the EU, received market exclusivity through February, 2025.
    • Competition from new market entrants including Juvenescence’s Napa Therapeutics and David Sinclair’s MetroBiotech seems to have failed as they were based on the biosimilar Nicotinamide Mononucleotide (NMN) which was not proven effective.
  • CohBar (NASDAQ: CWBR)
    • Founded in 2007, CohBar discovered hundreds of genes in the mitochondrial genome that encode peptides (small proteins), and identified the first mitochondrial derived peptide (MDP) associated with age related diseases in human centenarians and their offspring. Studies in animal models demonstrated metabolic regulation and protection, cytoprotection and anti-inflammatory effects across multiple age-related diseases.
    • Peptides encoded in the mitochondrial genome are messengers regulating multiple organs and systems in the body. CohBar discovered 100 peptides and >1,000 analogs. 12 issued patents, 65+ CohBar patent filings.
    • CohBar’s peptide therapeutics target chronic and age-related diseases with underlying mitochondrial dysfunction, such as NASH, obesity, cancer, fibrotic diseases, acute respiratory distress syndrome (ARDS), type 2 diabetes, and cardiovascular and neurodegenerative diseases. US healthcare spending for these diseases tops $500 billion annually.
    • Market Cap: $66MM, up from $57MM in October 2020.
    • $18MM in cash at year-end 2020. Quarterly burn rate of $2.5MM.
    • Lead compound, CB4211, is in Phase 1b clinical trial of 20 fully-enrolled people for an advanced form of Non-Alcoholic Fatty Liver Disease and impact on weight loss. Results are expected in early Q3, 2021.
    • In Q1, 2021, initiated IND work for CB5138-3 as clinical candidate for Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases.
    • On April 27, 2021, CohBar replaced their CEO and Chair of the Board.
  • Unity Biotechnology (NASDAQ: UBX)
    • Initial leader in senolytics, the selective removal of senescent (old, poorly functioning) cells from the body to halt, slow or reverse age-associated disease and restore tissue to a more functionally healthy state.
    • Senescent cells secrete large quantities of harmful proteins, which cause inflammation, tissue degradation and the production of unwanted growth factors.
    • Unity’s injectable therapies disrupt proteins that senescent cells need for survival.
    • Pipeline of targeted therapies
      • In Q4, 2020, initiated Phase 1 study of UBX1325 in patients with diabetic macular edema or age-related macular degeneration. There are many more-advanced competitors in this space. In April 2021, UNITY published a study in Cell Metabolism featuring a novel mechanism – Bcl-xL inhibition – for treating age-related eye diseases by restoring vascular health in the retina. By selectively eliminating the senescent cells accumulating in diseased blood vessels of the eye, researchers identified a way to target diseased vasculature while leaving healthy blood vessels intact, thus enabling the retina to repair itself. 
      • Liver, kidney and neurodegenerative diseases (Preclinical). They seek to remove abnormal Tau from the brain to slow or prevent Alzheimer’s. There are many more-advanced competitors in this space.
    • Failed therapy — Osteoarthritis in the knee
      • Phase 1 completed.  Achieved some pain reduction and improved functionality.
      • Failed Phase 2 in August 2020. Discontinued.
    • Market cap valuation is ~280MM down from ~340MM at the beginning of 2020.
    • Tangible assets – liabilities of ~120MM as of Dec 31, 2020.
    • Quarterly burn rate of $17MM, mostly from research and development. Forecasting sufficient cash to fund operations through 2022. Will need to raise additional capital to bring therapies through clinical trials and potential FDA approval.
    • Co-founded by Judy Campisi, a member of the faculty at the Buck Institute for Aging Research, Jan van Deursen of the Mayo Clinic College of Medicine and Dr. Daohong Zhou. In 2008, Campisi showed that senescent cells produce damaging proteins, the same year that van Deursen showed that mice engineered to produce large amounts of senescent cells aged rapidly. In 2015,  Zhou showed at the University of Arkansas for Medical Sciences that a single drug-like molecule could eliminate senescent cells.
    • Investments from Jeff Bezos and Amazon provided beneficial early publicity.

Thanks for reading this article. As your reward for continuing to focus on your health and wealth, treat yourself to 50 billion-dollar bills.  

[Disclosure]: Keep Health wrote this article and it expresses our own opinions. We are not receiving compensation for it. We have no business relationship with any company whose stock is mentioned in this article. We have no positions in the ETFs or venture capital funds mentioned. We may at times take either long or short positions in the individual public stocks mentioned.

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