#030: May 4th, 2021 - Longevity Marketcap Telemetry

Turn Bio funding. Unity Biotechnology and Denali Therapeutics updates. The Cost of Aging.

  1. Announcements

  2. Capital Raise Radar

  3. Last Week in Longevity

  4. Longevity Futures

  5. Longevity Jobs

  6. New Companies on Longevity List 

  7. The Cost of Aging

  8. My Links

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

Mission: To grow a wave of passionate people building, funding, and championing technologies that extend healthy human lifespan. 

If you want to be part of this mission alongside me, please consider supporting through Patreon or Longevity List Merch.


📢 Announcements 

  • The Longevity Biotech Show is officially a podcast! Check us out on Spotify. Coming soon to Apple Podcasts, pending approval.

  • forum.longevitybase.org - I’m rolling out a “StackExchange / Quora” for aging biology / longevity biotech. It is in open beta right now.Feel free to sign up and try it out. Email me if you would like to become a moderator or if you have some suggestions.

    • For academics, independent researchers, biotech founders, and scientific-minded enthusiasts.

    • Ask questions, get answers → builds a searchable longevity research knowledge base. 

  • Every Friday @ 12PM - 5PM EDT. Longevity Virtual Coworking.If you are working on longevity or thinking about getting into the longevity industry, please join me for an experimental virtual longevity coworking space using the Pluto.Video web app. (No sign-up required.) 

    • Bring something to work on.

    • Feel free to ask questions. 

    • Help out. Connect.

    • I plan on holding this weekly. It’s free. (Room Link)  

  • The 1% Bet for Longevity-- a website initiative.34 people have now signed up for the 1% Bet for Longevity Pledge. My goal is to get to 50,000 people and at least 100 companies to pledge 1% of their resources towards funding longevity companies and research by the end of the year. 


📡 Capital Raise Radar

I do not endorse or have affiliations with any of the companies listed below. This is not an offer to buy or sell securities. This is for informational purposes only. If you have intel on any other longevity companies currently raising please email me. It’s free.

  • Yuva Biosciences // Currently raised $1.75M already (Seed) // Article

    • Developing compounds that target mitochondrial dysfunction to reverse aging. Includes natural compound cosmeceutical for skin aging and hair loss. Also developing pharmaceuticals for prostate / ovarian conditions.

    • Team: Keshav Singh (University of Alabama), Greg Schmergel (Nantero)

  • Cytonics // Raised $2.8M (Series C) // SeedInvest page

    • Developing recombinant alpha-2-macroglobulin (A2M) protein to treat osteoarthritis. Also developed a diagnostic biomarker test for osteoarthritis. 

    • Team: Gaetano Scuderi, Antonio Carvalho, Joey Bose, Lewis Hanna

    • Crowdfunding on SeedInvest. Open to all investors, even retail.

  • Oncolife Therapeutics // Raising $2M - $3M // Slide deck

    • Developing drugs that modulate stem cell activity to treat cancer and aging

    • Team: Guy Barry (QIMR Berghofer Medical Research Institute, Brisbane, Australia), Paul Baldock (The Garvan Institute of Medical Research, Sydney, Australia)

  • Gerostate Alpha // Raising $500k // WeFunder page

    • High-throughput phenotypic screen platform to discover anti-aging drugs.

    • A spinout from the Buck Institute for Aging. Y Combinator-backed startup.

    • Team includes academics from the Buck Institute: Simon Melov, Mark Lucanic, Gordon Lithgow. 

    • Crowdfunding on WeFunder. Open to all investors, even retail.

    • Already raised $2.1M on a $15M valuation.

  • Oisin Biotechnologies // Raising $5M // Slide Deck

    • Senolytic gene therapy using a lipid-protein nanoparticle delivery vehicle. Kills cells that express the p16 gene -- a marker of senescent cells. Inducible apoptosis gene with a p16 promoter triggered by a chemical dimerizer.

    • Team: Matthew Scholz (Immusoft), Gary Hudson.

    • Seed round. Accredited investors only. $50K minimum check size. 

    • Other investors include The Methuselah Fund, Kizoo Technology Capital

  • Ponce de Leon Health // Raising $15M // Article

  • Revivo Therapeutics// Raising: $5M // Slide Deck

    • Small molecule drugs that enhance cognition and reduce neuron excitability to treat neurodegenerative and CNS conditions (including anxiety and depression). 

    • Targets the nitric oxide and CREB pathways. 

    • Same team that built Cardioxyl ($2B exit to Bristol Myers Squib)

  • Equator Therapeutics// Raising: $3M - $5M // Slide Deck

    • Mitochondrial uncoupler drug to burn fat through natural body heat production.

    • Targeting obesity, type 2 diabetes, fatty liver disease, PCOS. 

    • Pro longevity: Exercise mimetic, increases mitochondrial biogenesis, etc

    • Y Combinator-backed company. 

    • Team: Jonah Sinick, Yuriy Kirichok, Michael Grabe, Liliya Gabelev, David Segura 

  • + see all (click on “Capital Raise Radar”)


📝 Last Week in Longevity

  • Turn Bio closes funding round by Khosla Ventures. Turn Bio is a preclinical longevity biotech company developing epigenetic reprogramming therapies to reverse aging. Last week the company announced the closing of a funding round by Khosla Ventures. The funding amount was not disclosed. Khosla Ventures joins other investors in Turn Bio including The Methuselah Fund, Michael Antonov’s Formic Ventures, and Kizoo Technology Capital

    Turn is planning on using mRNA technology to deliver epigenetic reprogramming factors to reverse aging --essentially resetting the epigenome to a youthful state. The company has programs in skin aging, osteoarthritis, ophthalmology, and muscle aging. Scientific co-founders of the company include Marco Quarta and Vittorio Sebastiano.

    The scientific basis of epigenetic reprogramming can be traced in part to Shinya Yamanaka’s 2007 discovery of induced pluripotency (resetting a cell back to its embryonic stem cell state) -- for which he won the Nobel Prize.

    Epigenetic reprogramming has shown some notable successes in mice. David Sinclair’s lab at Harvard recently demonstrated the regeneration of a crushed optic nerve and restoration of vision in mice by expressing OSK Yamanaka factors through an AAV gene therapy. Work by the Belmonte lab at the Salk Institute showed transient reprogramming of OSKM reprogramming factors could reverse aging phenotypes in progeroid mice and increase regenerative capacity in older wild-type mice.

    Other companies developing epigenetic reprogramming approaches for aging include AgeX Therapeutics and Iduna (David Sinclair / Life Biosciences company)

  • Denali Therapeutics DNL151 positive Phase 1a/1b for Parkinson’s disease. Denali Therapeutics is a biotech company developing drugs to treat neurodegenerative diseases. Last week the company announced positive results in their Phase 1a/1b clinical trial for DNL151, an LRRK2 inhibitor to treat Parkinson’s disease. The Phase 1a/1b trial of healthy volunteers and Parkinson’s patients showed the drug was well tolerated with no serious adverse events. Measurements of pharmacodynamic biomarkers pS935 LRRK2 and pT73 Rab10 (pRab10) suggest the drug was able to target the intended pathway. A urinary biomarker for lysosomal function also saw improvement.

    DNL151 is a small molecule drug that inhibits LRRK2 in order to restore autophagy/lysosomal function. Repeats of the LRRK2 gene are the most common cause of genetic types of Parkinson’s disease. Although the pathophysiology is still not understood, there is a strong link between LRRK2 and reduced autophagy/lysosomal function and build-up of alpha-synuclein protein. DNL151 is being developed in a partnership with Biogen. Investors in Denali Therapeutics also include Bezos Expeditions, ARCH Venture Partners, and F-Prime Capital. 

    Neurodegenerative disease represents a major gating function for healthspan extension. Alzheimer’s and Parkinson’s disease still do not have effective treatments despite a large number of attempts in the clinic. Therapeutic approaches that boost or restore the natural ability of brain cells to recycle defective misbehaving proteins are gaining popularity. Companies developing autophagy/lysosome function boosting therapies include Selphagy, Casma Therapeutics, Samsara Therapeutics, among others.

  • Capsida comes out of stealth, targeting neurodegenerative disease with gene therapy. Capsida is a newly formed company that develops AAV gene therapy vectors that selectively target cells in the brain in order to treat neurodegenerative diseases. Last week the company emerged from stealth with $140M in backing from Westlake Village BioPartners and Versant Versant in addition to a partnership with pharma giant AbbVie.

    Capsida is based on the work of Viviana Gradinaru, a neuroscientist researcher at Caltech. The company leverages machine learning, high-throughput approaches, non-human primate models, with computational/structural biology techniques to develop AAV vectors that selectively target specific tissues.

    Current AAV vectors used in gene therapies largely end up in the liver. This makes it difficult to selectively target specific tissues without increasing dosage -- which could elicit an immune response. Development of gene therapy platforms that “just work” and can be delivered in specific tissues and at controlled times will be a useful tool for longevity therapeutics.   

  • Unity Biotechnology announces positive preclinical UBX1325 data. Unity Biotechnology is the oldest and most visible senolytics company in longevity biotech. Last week at the ARVO 2021 conference the company announced preclinical data for UBX1325, their drug for diabetic macular edema. Unity’s data showed that UBX1325 was able to reduce retinal vasculature in two preclinical models of retinopathy. Diabetic edema is a disease that causes blindness. It is characterized by the growth and leakage of blood inflamed blood vessels in the retina and is linked to the presence of senescent cells

    UBX1325 is a locally injected small molecule drug that targets senescent cells by inhibiting Bcl-xL, an anti-apoptotic protein. The drug induces cell apoptosis in senescent cells and thus reduces the production of inflammatory SASP factors.

    UBX1325 is currently undergoing Phase 1 clinical trials with data readouts expected sometime this year. This trial represents another chance for Unity to validate the senolytics hypothesis. In August 2020, Unity’s knee osteoarthritis trial with UBX0101 failed in Phase 2, sending the company’s stock tumbling ~60%.

    Unity Biotechnology is the biggest and most well-known senolytics company -- investors include Peter Thiel, Jeff Bezos, ARCH Venture Partners, and the Longevity Fund. However, their current senolytic drugs represent a first-generation approach, whereas more targeted 2nd generation senolytics are being developed at Unity and other companies. Unity also appears to be advancing their neurology program with alpha-klotho (UBX2089)-- an anti-aging protein (not a senolytic) licensed from UCSF. 

  • Muhdo partnership with the National University of Singapore. Muhdo is a DNA and epigenetic (DNA methylation) testing company based in the United Kingdom. The company recently announced a partnership with the National University of Singapore (NUS) to undertake a large-scale global study of how epigenetics changes with age. 

    Singapore is one of the nations at the forefront of accelerating progress in longevity. And with good reason: Their population is one of the fastest aging populations in the world. The government of Singapore has taken a number of steps to prioritize aging research and policy, including recruiting Brian Kennedy from the Buck Institute to spearhead longevity initiatives at NUS. 


📅 Longevity Futures

Know of any interesting longevity talks, meetings, or events? Please email me.


Featured Longevity Jobs

Looking for jobs, companies, or investors in the longevity biotechnology industry? Check out my website LongevityList.com.

If you are hiring, email me a link to your job postings and I will post them on longevitylist.com (it’s free).


➕ New Companies on Longevity List

Some interesting longevity companies I have stumbled upon and added to the Longevity List database in the past week. Have any longevity company tips? Please email me. 

  • Gero.ai: A Singapore-based company that leverages AI and whole-exome DNA sequencing to discover anti-aging drugs. Their approach leverages genomics to find rare mutations that can lead to general druggable pathways. Gero also offers their drug discovery platform as a service to pharma companies. The company was founded by Peter Fedichev (physicist) and Maxim Kholin.  

  • Khondrion: A clinical-stage biotech company developing mitochondrial-targeted therapeutics for rare diseases. The company’s main program is KH176, a redox modulator that is also believed to inhibit PGE2, a prostaglandin involved in inflammation. Khondrion is currently conducting Phase 2 clinical trials for MELAS, Leigh syndrome, and other rare mitochondrial diseases. 

  • Mitobridge: A clinical-stage mitochondrial therapeutics company acquired by Astellas. Mitobridge develops small molecule drugs that modulate PPAR-delta, a key protein involved in muscle endurance and mitochondrial fatty acid utilization. The company has two clinical trials: A Phase 2 trial for acute kidney injury and a Phase 1 trial for Duchenne muscular dystrophy. 


The Cost of Aging

Aging has a cost on all levels: Personal, familial, societal, and economic. It does not merely rob life through mortality/premature death. It also robs life free of debilitating chronic age-related conditions -- i.e reduction in healthspan.

While the true human cost of aging may well be incalculable, we can determine some estimates of the lower bounds to make the moral, economic, and financial case for developing technologies that target aging. 

One way to estimate the lower bound cost of aging is to first find the total DALYs (Disability-Adjusted Life Years) incurred by age-related disease. 

DALY =  Years of Life Lost (YLL) + Years of Lost due to Disability (YLD).  

Years of Life Lost (YLL) is measured relative to life expectancy at age of death. 

Years Lost due to Disability (YLD) is measured using disability weightings for each disease or condition. For instance, blindness and Alzheimer’s disease have high disability weightings (~ 0.6 ), whereas a condition like lower back pain has a disability weighting of ~0.03.

How many diseases of aging are there? 

In a report in the Lancet (Chang et al. 2019), authors defined age-related diseases as those that quadratically increase in incidence with age -- i.e incidence rate accelerates with age. They found that 92 of the 293 diseases in the WHO Global Burden of Disease dataset fit this criterion, listed here:

92 age-related diseases, by broader disease categories

Cardiovascular diseases

Atrial fibrillation and flutter; endocarditis; hypertensive heart disease; intracerebral haemorrhage; ischaemic heart disease; ischaemic stroke; myocarditis; non-rheumatic calcific aortic valve disease; non-rheumatic degenerative mitral valve disease; other cardiomyopathy; other cardiovascular and circulatory diseases; other non-rheumatic valve diseases; peripheral artery disease

Chronic respiratory diseases

Asbestosis; chronic obstructive pulmonary disease; coal worker pneumoconiosis; interstitial lung disease and pulmonary sarcoidosis; other pneumoconiosis; silicosis

Communicable, maternal, neonatal, and nutritional diseases

Diarrhoeal diseases; encephalitis; lower respiratory infections; pneumococcal meningitis; trachoma

Diabetes and kidney diseases

Chronic kidney disease due to type 2 diabetes mellitus; chronic kidney disease due to glomerulonephritis; chronic kidney disease due to other and unspecified causes

Digestive diseases

Cirrhosis due to NASH; pancreatitis; paralytic ileus and intestinal obstruction; peptic ulcer disease; vascular intestinal disorders

Injuries

Drowning; environmental heat and cold exposure; falls; foreign body in other body part; other transport injuries; other unintentional injuries

Neoplasms (cancer)

Acute lymphoid leukaemia; acute myeloid leukaemia; benign and in-situ intestinal neoplasms; bladder cancer; brain and nervous system cancer; breast cancer; chronic lymphoid leukaemia; chronic myeloid leukaemia; colon and rectum cancer; gallbladder and biliary tract cancer; Hodgkin lymphoma; kidney cancer; larynx cancer; lip and oral cavity cancer; liver cancer due to NASH; liver cancer due to alcohol use; liver cancer due to hepatitis C; malignant skin melanoma; mesothelioma; multiple myeloma; myelodysplastic, myeloproliferative, and other hematopoietic neoplasms; non-Hodgkin lymphoma; non-melanoma skin cancer (basal-cell carcinoma); non-melanoma skin cancer (squamous-cell carcinoma); oesophageal cancer; other benign and in-situ neoplasms; other leukaemia; other malignant neoplasms; ovarian cancer; pancreatic cancer; prostate cancer; stomach cancer; thyroid cancer; tracheal, bronchus, and lung cancer; uterine cancer

Neurological disorders

Alzheimer's disease and other dementias; motor neuron disease; Parkinson's disease

Other non-communicable diseases

Congenital musculoskeletal and limb anomalies; digestive congenital anomalies; endocrine, metabolic, blood, and immune disorders; other haemoglobinopathies and haemolytic anaemias

Sense organ diseases

Age-related and other hearing loss; age-related macular degeneration; cataract; glaucoma; other sense organ diseases; other vision loss; refraction disorders

Skin and subcutaneous diseases

Cellulitis; decubitus ulcer; fungal skin diseases; other skin and subcutaneous diseases; pyoderma

Source: Chang et al. 2019

******

Interestingly, type 2 diabetes and osteoarthritis were not considered age-related diseases by Chang et al. because, while these diseases increased in incidence with age, they were not convex with age.1

Chang et al 2017 determined that 51.3% of all disease burden was attributable to age-related disease.2 The total global disease burden (aging and non-aging) in 2017 was 2.5 billion life years lost to premature death or disability.

Therefore, a 2017 estimate of the cost of aging would be ~ 1.28 billion life years lost. That’s the equivalent of 300 million Ph.D. degrees!3

For context, the global disease burden of malaria in 2017 was ~46M disability-adjusted life years.

How much is one DALY averted worth?

To generate a dollar value to shock governments and investors into investing in longevity research and anti-aging biotechnology we need to first determine a dollar value cost of 1 DALY. 

This is a bit tricky. 

In one study (Daroudi et al 2021), regression analysis between DALY and healthcare expenditure was performed to obtain a dollar value of 1 DALY in different countries. Naturally, the value was different depending on the socioeconomic development (sometimes measured by the Human Development Index - HDI) of each country. 

Daroudi et al calculated that “the estimated cost per DALY averted was $998, $6522, $23,782, and $69,499 in low HDI, medium HDI, high HDI, and very high HDI countries, respectively”. The average was $25,200. 

Thus we can crudely estimate that the total global cost of aging in 2017 was ~$32 trillion when factoring in loss from premature death and loss due to disability. For context, global GDP in 2017 was ~ $80 trillion. 

Many assumptions have been made in these estimations -- some dodgier than others -- but at least it gives a rough idea of the scope of the problem of aging and the rewards if we can solve it. 

From a moral standpoint, 1.28 BILLION years of healthy life lost is an outrage4. And yes, there are other non-age-related diseases that deserve attention too. But in terms of pure effective-altruism-bang-for-your-buck, you really cannot beat a strategy of targeting a single root cause -- aging --to reduce suffering and increase quality of life universally.

And if I have managed to convince you of the gravity of the situation of aging, please start doing something about it today. If you can’t build a longevity company or project, then fund it. If you can’t fund a longevity company, then champion one. 

Here are some longevity entities anyone can fund / advocate for:

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-NATHAN


My Links

Some of my projects, resources, and ways to support my mission. More projects coming…

Projects

  • Longevity List  - Find jobs, companies, and investors in the longevity industry. Email me if you want to add your job or company to the list. It’s free.

  • Longevity List Database- A handy Airtable base covering people, companies, trials, academic labs, and a list of longevity companies that are presently raising capital.

  • LMC Clinical Trial Tracker- Longevity therapeutics in clinical trials. Completion calendar useful for investors who want to time data readout catalysts.

  • LongevityMarketcap.com- The main page tracks prices of publicly traded longevity stocks.

  • Longevity Biotech Show - Official website of the Clubhouse show / podcast. We interview the people building, funding, and championing technologies that extend healthy human lifespan. On Clubhouse / Spotify podcasts. 

  • The One Percent Bet for Longevity Pledge - An initiative to get individuals and corporations to pledge at least 1% of their resources to fund longevity companies and research.

  • LongevityBase.org -  An open-source volunteer initiative to itemize every instance of modulation of biological aging in the scientific literature.

  • forum.longevitybase.org - An open question and answer system for aging biology and longevity biotechnology. 

Support

A special thanks to my Patreon supporters who have joined forces with me to undertake this mission.

1

My guess is the authors are looking for age-related diseases that cause loss of function that accelerates dysfunction in a feedback loop. Gompertz Law etc.

2

I ran the numbers using the WHO GBD dataset for 2017 and Chang et al’s 92 age-related diseases. I found age-related disease burden to be 44% of total burden. Not sure where the discrepancy is, but the figures are close.

3

Or 150 million really long ones.

4

DALYs are calculated using the life lost relative to average life expectancy at age of death. If one were to (provocatively) measure life lost relative to a theoretical average life expectancy of ~500 years (which could happen if aging is solved, death only from accidents, etc) then the cost of aging may be much much higher.