#020: Top 10 Things to Watch in the Longevity Industry in 2021

Juvenescence IPO. AI Renaissance. Mystery Fund. Senolytics. Woof-extension.

📡 In this Edition of Longevity Marketcap Telemetry

  1. Last Week in Longevity

  2. Longevity Futures

  3. Top 10 Things to Watch in the Longevity Industry in 2021

  4. Tweet of the Week

  5. Technical Analysis

Disclaimer: None of this should be taken as financial advice. It is for educational purposes only.

-Nathan Cheng @realNathanCheng

LongevityMarketcap.com // LongevityList.com // BiohackStack.com


📝 Last Week in Longevity

  • LyGenesis raises $11M to fund Phase 2a trial. FDA clears trial.Jim Mellon’s Juvenescence and Sergey Young’s Longevity Vision Fund participated in the convertible-debt financing. LyGenesis is developing ectopic liver regeneration through allogeneic injections of hepatocytes into lymph nodes. The company is planning to initiate their trial this year. 


📅 Longevity Futures


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Top 10 Things to Watch in the Longevity Industry in 2021

2021 is going to be a big year for the longevity industry and the growing longevity revolution. 

Others have noticed too. 

Noted biotech investor, Brad Loncar, predicts that “anti-aging” will be the most over-hyped area in biotech in 2021. Cathie Wood of ARK Invest predicted that her Genomics Revolution ETF would outperform all her other funds over the next five years. Life extension made the list for tech to watch in the 2020’s in a recent blog post by Eli Dourado. The prescient innovator-futurist Balaji Srinavasan started evangelizing longevity in 2020, too.  

From AI to IPOs, here are my top 10 things to watch in the longevity industry in 2021:

**Also be sure to check out my continuously updated Longevity Therapy Clinical Trial Tracker for a timeline of all anti-aging therapies registered on ClinicalTrials.gov

1. Juvenescence IPO

Jim Mellon, billionaire patron saint of longevity investing, announced in September 2020 that he would take his longevity portfolio company, Juvenescence, public within 6-12 months. That would mean we can expect the IPO to come as early as Q1 this year -- though the IPO has been delayed once or twice already

The Juvenescence IPO will be the biggest development in public market longevity investing since Unity Biotechnology went public in 2018. And because Juvenescence is a diversified portfolio of longevity companies it best represents the entire industry going forward. In the absence of a longevity biotech ETF this will likely be the best single longevity stock for regular people looking for exposure to the sector. (*Not investing advice!)

Juvenescence has raised $162 million in venture funding, which includes their most recent $100 million Series B. The company has a post-money valuation of $500 million, according to Craft.co

Juvenescence’s diversified portfolio of 11 assets spans the gamut of senolytics, AI companies, regenerative medicine, and nutraceutical products. Let’s take a look at their publicly disclosed portfolio companies:

JuvRx: Drug Therapeutics

  • FoxBio: A senolytics joint venture company with Ichor Therapeutics / Antoxorene. They are developing small molecule drugs that clear senescent cells via the FOXO4-p53 pathway. Their clinical pipeline includes treatments for osteoarthritis and frailty, with Phase 1 trials planned for 2021 and 2022 respectively. 

  • Souvien Therapeutics: An epigenetic therapeutics company based on the research of Li-Huei Tsai and Steve Haggarty at MIT / Harvard. They are developing modulators of epigenetic changes associated with neurodegenerative diseases. 

  • BYOMass: Founded by Margaret Jackson, this company is developing therapies that modulate central metabolism (reducing body weight and blood pressure) to treat age-related disease. 

  • Napa Therapeutics: Based on Eric Verdin’s research (Buck Institute), Napa is developing therapies that increase the levels of NAD+ in tissues. NAD+ is a crucial coenzyme found in all living cells whose levels decrease with age.

JuvDataScience: AI and Big Data

  • Insilico Medicine: Alex Zhavoronkov’s AI drug discovery company. Insilico made a splash last year with a Nature paper that demonstrated a deep learning algorithm that rapidly identified novel DDR1 kinase inhibitors. The company also has partnerships with Taisho Pharmaceuticals, Pfizer, and a number of other large pharma firms. 

  • Relation Therapeutics: Using AI and machine learning to identify existing drugs to treat age-related disease. Recently received a grant from the Gates Foundation to find potential COVID-19 treatments. 

  • Juvenomics: A joint venture with G3 Therapeutics to develop anti-aging nutraceuticals and pharmaceuticals guided by proprietary multi-omics datasets. 

JuvRegeneration: Regenerative Medicine

  • LyGenesis: A regenerative medicine company spun out of research from the University of Pittsburgh. They are developing a therapy to regenerate livers by injecting allogeneic hepatocytes into patient lymph nodes. Their Phase 2a trials are scheduled for 2021.

  • AgeX Therapeutics (NYSE:AGE): Mike West’s preclinical stem cell regenerative medicine company. They are developing an off-the-shelf embryonic-derived cellular transplant therapy and also have a pipeline for induced tissue regeneration using epigenetic reprogramming.

  • Morphoceuticals Inc: Early stage company based on Michael Levin’s (Tuft’s) research on bioelectric control of regeneration. I love Levin’s work. If you are not familiar with his work I highly recommend you watch this talk.

JuvLife: Nutraceuticals 

  • BHB Therapeutics: A joint venture with the Buck Institute to develop a ketone body (beta hydroxybutyrate) to induce ketosis

  • Metabolic Switch: Direct to consumer ketone ester drink. I’m not sure if this is the same product as the one above. At any rate it seems like a competitor to HVMN’s drinkable ketone ester, a popular product in the rapidly growing keto space. 

Not only is Juvenescence’s portfolio excellent, the management team is also extremely competent. CEO Gregory Bailey was an early backer of Medivation and also recently brought Biohaven to IPO. CMO Declan Doogan was a head of research at Pfizer. Jim Mellon is an accomplished investor, businessman. He also wrote the book on investing in longevity

I will definitely be investing in Juvenescence. The attention the IPO will bring to the longevity industry could also trigger some notable hype. Keep your eyes peeled.  

2. BioAge Heads to the Clinic

Kristen Fortney’s AI / computational drug discovery company BioAge recently closed a $90 million Series C round led by Andreesen Horowitz (a16z) and will use the funds to initiate Phase 2 clinical trials this year. 

BioAge uses AI/ML and systems biology models to mine multi-omics patient datasets and identify existing drugs that are likely to treat age-related disease. The company has two candidate drugs in their clinical pipeline: BGE-117 is an inhibitor of HIF-PH (hypoxia-inducible-factor prolyl-hydroxylase) that is linked to multiple age-related diseases. BGE-175 is an inhibitor of the PGP2-DP1 prostaglandin receptor, which BioAge believes can treat immunosenescence. 

Since BioAge’s strategy is to repurpose existing drugs they are able to go straight to Phase 2 trials. Their platform has the potential to significantly increase the rate of anti-aging drug discovery. I’m excited to see what BioAge chooses for their initial clinical trial indications. 

3. Mystery Foundation to Fund $1 Billion into Aging per year  

Nir Barzilai, Professor of Genetics at Albert Einstein College of Medicine and organizer of the TAME metformin-longevity trial, recently gave an online talk with the Foresight Institute. In the talk he mentioned that an unnamed wealthy individual was in the process of setting up a longevity foundation that would invest $1 billion into anti-aging research and companies per year. Barzilai said the foundation would be announced in January of this year. 

This of course is a big deal, not just from a funding standpoint but also from the publicity and change in social zeitgeist it will cause. 

But who could be the mysterious donor? Nir Barzilai indicated it is the same mysterious person that is funding the TAME trial and is a well known tech billionaire. 

My guess: It’s Larry Ellison, founder of Oracle. He has a net worth of $88 B and is 76 years old. Ellison has also donated to longevity causes in the past through the Ellison Medical Foundation. My second guess is Sergey Brin of Google.  

4. Celevity / Loyal comes out of Stealth with Dog Healthspan Study

Celine Halioua’s dog rejuvenation startup, Loyal (formerly Celevity), broke out of stealth late last year / early this year. They are currently recruiting 500 dog-patients for a blood-based aging biomarker study that will last roughly 6 months. This will be enormously useful for development of anti-aging therapies for our furry friends -- with the hope they might one day be translated for humans too.

Loyal is just one company / organization developing anti-aging therapies for pets. George Church’s Rejuvenate Bio and David Sinclair’s Animal Biosciences are examples of others. Matt Kaeberlein at the University of Washington is conducting a trial to see whether rapamycin will extend the lives of dogs like it does in mice. 

5. Samumed Lorecivivint Osteoarthritis Phase 3 Readouts

Samumed is a $12 billion dollar regenerative medicine company founded by Osman Kibar in 2008. They develop therapies based on modulating the Wnt signalling pathway to control stem cell renewal and differentiation.

Currently they have two late stage clinical assets: Lorecivivint (SM04690) is an injected drug that treats osteoarthritis of the knee. SM04554 is a topical drug that treats androgenic alopecia (male pattern hair loss)  

Lorecivivint is currently in Phase 3 trials (STRIDES-X-RAY, STRIDES-1), both of which will conclude sometime in the later half of this year. The drug has shown promise in earlier studies to reduce patient-reported pain and also reduce intra-articular joint space -- suggesting cartilage regeneration. 

Samumed is the highest valued anti-aging startup -- even likely higher than Google’s Calico. Because of the generality of their anti-aging and regenerative technology Samumed has the potential to treat many different age-related diseases. 2021 will be the year that we will see a proper first test of this promise of the “Grand Unified Theory of Anti-Aging Medicine”. 

6. Unity Biotechnology’s UBX1325 DME Trial

2020 was a disastrous year for Unity Biotechnology. 

The high profile senolytics company funded by Peter Thiel, Jeff Bezos, The Longevity Fund, and ARCH Venture partners suffered a major defeat when UBX0101, a MDM2-p53 inhibitor to treat osteoarthritis of the knee, failed in a Phase 2 trial. Unity’s stock crashed over 60% on the news.

But 2021 could be a year of redemption for Unity. Their new Phase 1 trial for UBX1325, a Bcl-xL inhibitor to treat Diabetic Macular Edema (DME), will be completed in the first half of this year, with a proof of concept trial to follow shortly afterwards.

Unity Biotechnology was founded in 2011, raised over $210 million in venture funding, and IPO’d in 2018 -- the first senolytics company to do so. As the flag bearer for the senolytics industry (the largest sub sector of anti-aging pharma by # of companies) their osteoarthritis failure was a big disappointment. And unfortunately their data was unable to answer whether the failure was due to the drug failing to clear senescent cells or that senescent cell clearance does not have therapeutic benefits in humans. 

The clearance of senescent cells (i.e damaged cells that lose the ability to divide) has shown to rejuvenate aged mice and increase median lifespan in many studies. There are hints this approach may work in humans as well (see James Kirkland’s work on Dasatinib + Quercetin in humans).

I am cautiously optimistic for Unity Biotechnology. But I am also totally unworried if they fail, as there are many many other senolytics companies preparing for clinical trials -- many with 2nd generation targeted approaches that may prove superior to Unity’s.

7. More Senolytics in the Clinic

2021 will be the year that more senolytics companies finally join Unity in the clinical race. And many of these companies are using 2nd gen targeted approaches to clear senescent cells. 

Marco Quarta’s Rubedo Life Sciences closed $11 million in seed financing by Khosla Ventures, Longevity Fund, Elad Gil, and others. They intend to begin Phase 1 trials for a therapy to treat pulmonary fibrosis in 2021. Although the company is still tight-lipped about their assets, their published work suggests they are developing prodrugs that selectively kill senescent cells in the presence of SA-beta-galactosidase -- a biomarker of cellular senescence. 

FoxBio, a Juvenescence and Ichor Therapeutics senolytics joint venture, is planning Phase 1 trials for an osteoarthritis drug this year as well. They are developing small molecule drugs that target the FOXO4-p53 pathway discovered by Peter de Keizer in 2017.

Numeric Biotech, a spin out from Erasmus Medical Center in the Netherlands, is planning to test the FOXO4-DRI peptide (discovered by Peter de Keizer) to treat neuro-inflammatory or autoimmune diseases in 2021.

Senolytic Therapeutics, one of David Sinclair’s Life Biosciences daughter companies, has two mature assets that should be close to ready for clinical trials -- although there is no set date. STX519 and STX 434 are senomorphic and senolytic drugs developed to treat fibrotic disease of the lung and kidney. 

If you are interested in learning more about the senolytics industry check out Newsletter #018: A Tour of All Senolytics Companies.

8. LyGenesis Liver Regeneration Trials

LyGenesis recently secured $11 million dollars of financing and FDA approval to go ahead with their ectopic liver regeneration therapy for end stage liver disease patients. Their Phase 2a trial will start this year. The Juvenescence-backed spin out from the University of Pittsburgh previously demonstrated that injection of hepatocytes into the lymph nodes of pigs was able to regenerate functional livers. 

The study will not be officially finished until 2024 but hopefully some interim data will shed some light on efficacy before then. If LyGenesis’ technique is successful for the liver they plan to extend their approach to regenerate the pancreas, kidney, and thymus as well.

LyGenesis is a promising company and once Juvenescence goes public later this year it will be possible for public market investors to gain exposure to it. 

9. Frequency Therapeutics FX-322 Phase 2 Readout

“..the blind receive sight and the lame walk, the lepers are cleansed and the deaf hear, the dead are raised up, and the poor have the gospel preached to them.”

Matthew 11:5

Jesus Christ had an incredible clinical pipeline -- I certainly would have invested. Unfortunately that opportunity is long gone. 

However, regenerative medicine approaches from companies like Frequency Therapeutics and Lineage Cell Therapeutics have the potential to realize the miracles of old by stimulation or transplantation of stem cells.

Frequency Therapeutics will be giving an update on their Phase 2a trial of FX-322 to treat age-related (sensorineural) hearing loss in late Q1 2021. Their early data demonstrated the first ever sustained clinical improvement in age-related hearing loss.

Frequency Therapeutics was spun out of research from Robert Langer’s lab at MIT in 2014. The company is developing small molecule drugs that stimulate inner ear progenitor stem cells (“hair cell” progenitors) to divide and differentiate thereby restoring hearing function. Currently there are no FDA approved treatments for age-related hearing loss. The company also has early development work in translating their approach to regenerate myelin in order to treat Multiple Sclerosis.

As an investor in Frequency Therapeutics -- and a guy who played in bands throughout high school and college-- I sincerely hope the FX-322 trials are successful. 

10. AI Drug Discovery 

Vijay Pande, Partner at Andreesen Horowitz, believes that AI and machine learning are presently transforming drug development into an engineering discipline. Recent AI-powered demonstrations by Deepmind’s AlphaFold (AI protein folding) and Insilico Medicine (Deep Learning rapid identification of novel kinase inhibitors) and all the funding pouring into dozens of AI drug discovery startups all point towards the coming renaissance. 

And we could be seeing the first tangible results very soon. 

Exscientia was the first to bring a completely AI-derived drug to the clinic in 2020. Google’s Calico followed suit later that year and this year BioAge will enter the clinic as well. As more of these AI-derived drug trials succeed and fail we will get a better picture of how much of an improvement AI gives over our current pathetic 10% win rate. 

This decade will be an era of tremendous progress in biomedicine.   

Some companies to watch in the AI drug discovery / AI biology space:

  • Insilico Medicine

  • BioAge

  • Recursion Pharma

  • Exscientia

  • Blackthorn

  • Insitro 

  • Atomwise

  • Postera

  • Deep Genomics

  • DeepCell

  • Calico

  • Spring Discovery


Tweet of the Week

The conspicuous overlap between the cryptosphere and the longevity movement is more than just about futurism: BTC and Longevity are both survivalist religions. I imagine we will see many of the nouveau-crypto-riche to begin investing in longevity biotechnology in the coming years.


Technical Analysis

Interesting buy or sell opportunities based on momentum and charts of longevity / biotech stocks. Not investing advice.

Lineage Cell Therapeutics (NYSE:LCTX)

This regenerative medicine / stem cell therapy stock has been slowly rising since July 2020. Currently, it is breaking out to new swing highs and looks decent on a daily scale. However on the weekly scale a TD Sequential 9 sell indicator coming next week suggests momentum is exhausted.  

Moderna (NASDAQ:MRNA)

The frothy vaccine stock was recently down ~42% from its most recent high, filling all of the gap ups from November - December 2020. mRNA has tremendous therapeutic potential aside from vaccines so buying now after a massive beat down could be a decent long term play.

Sigilon Therapeutics (NASDAQ:SGTX)

Not technical analysis, however this recently IPO’d company spun out from the lab of the legendary Robert Langer is worth investigating. They are developing a platform technology to treat chronic disease using engineered human cells that produce proteins, enzymes, or factors in vivo. A biomatrix material shields the engineered cells from immune rejection. Very interesting -- as is the case with all of Langer’s companies. If I had discovered this company earlier I would have gotten in on the opening day. Presently I may consider adding a small position.