#029: April 26th, 2021 - Longevity Marketcap Telemetry

Rejuvenate Bio. Selphagy and autophagy. Is aging a disease?

  1. Announcements

  2. Capital Raise Radar

  3. Last Week in Longevity

  4. Longevity Futures

  5. Longevity Jobs

  6. New Companies on Longevity List 

  7. Is aging a disease?

  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 

  • forum.longevitybase.org - I’m rolling out a “StackExchange / Quora” for aging biology / longevity biotechnology. 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. 

  • Announcing LongevityBase.org - Want to earn $100 in BTC? I’m going to be posting a task on 1729.com to incentivize volunteers to get the ball rolling on an open-source database for things that modulate biological aging. 

    • Basically, I want people to read longevity intervention research papers (in mammalian models and humans) and add entries to the LongevityBase Airtable. One parameter of aging (lifespan or some phenotype of aging) per line. 

    • The goal is to get to a critical database mass at which point people will volunteer to maintain it. Interested? First, subscribe to 1729.com or sign up here. Will be rolling out instructions soon.

  • 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. 32 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”)


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📝 Last Week in Longevity

  • Rejuvenate Bio raises $10M Series A. Rejuvenate Bio is a George Church-affiliated startup that is developing gene therapies to treat aging in both dogs and humans. Last week the company announced a $10M Series A investment round led by Kendall Capital Partners. The company plans on conducting studies in dogs, which will double both as data for their veterinarian pipeline and as IND-enabling toxicity studies for later human trials.

    Rejuvenate is attempting to use a combination gene therapy to increase the expression of longevity genes —some believed to be involved in caloric restriction. In preclinical studies in mice, an AAV gene therapy delivering sTGF𝝱R2 and FGF21 was able to treat four diseases simultaneously: obesity, type II diabetes, kidney atrophy, and heart failure. Rejuvenate has an ongoing study testing their gene therapy to treat mitral heart valve disease in King Cocker Spaniels dogs.

    Rejuvenate Bio is not alone in developing the “in fido” path towards longevity therapies. Loyal, Animal Biosciences, Nugenics Research, and Genflow Biosciences are all developing longevity therapies for pet dogs. The Dog Aging Project initiated by Matt Kaeberlein at the University of Washington also seeks to study aging in dogs through big data. The project features a trial of rapamycin conducted on a small subset of dogs.

    There are many benefits to developing “woof-extension” therapies: Not only are dogs theoretically better biological models than mice, but trials can also be conducted quickly in dogs, there is a legitimate business case in extending lifespans of companion pets1, and demonstration of a proof of concept anti-aging therapy in dogs will likely catalyze significant investment in longevity. 

  • Researchers at Selphagy announce promising preclinical data for Alzheimer’s disease. Selphagy is a David Sinclair / Life Biosciences daughter company that develops drugs that stimulate autophagy -- a natural process of recycling defective components within the cell. Last week the company’s co-founder Ana Maria Cuervo, a professor at Albert Einstein College of Medicine, published promising results of their drug, CA, in mouse models of Alzheimer’s disease.

    CA is a small molecule drug that boosts chaperone-mediated autophagy (CMA)-- a process where special proteins bind to junk proteins in the cell and shuttle them inside of lysosomes to be disposed of. The drug increases the number of LAMP2A proteins on the membrane surface of lysosomes -- LAMP2A plays a role in CMA protein docking. RNA-sequencing data from post-mortem Alzheimer’s patient brain tissue suggest that chaperone-mediated autophagy activity declines 30%+ with age and likely plays a role in accelerating disease progression.

    Selphagy’s drug, CA, was given to mice of two different Alzheimer’s disease models: One that expressed defective tau proteins and one with defective tau + beta-amyloid. In both models, CA was able to improve memory and reduce protein clumping in the brain.

    Autophagy is a growing therapeutic strategy with obvious applications for neurodegenerative diseases associated with protein aggregates. However, there are also concerns about how these therapies might enhance cancer. Other autophagy-based longevity biotech companies include Samsara Therapeutics, Casma Therapeutics, and Caraway Therapeutics.  

  • Andrew Brack’s longevity startup exits stealth. Last week during an event on Clubhouse, Andrew Brack (professor at UCSF) unveiled his new longevity startup, Arrive Bio. Although many details were not disclosed, he revealed that his company’s approach leverages AI/ML and that pharma giant, Roche, are customers of the technology Arrive has developed. Given Brack’s research background in stem cell biology and muscle regeneration, it is likely the company will also be related to these areas.

    Andrew Brack made waves on Twitter earlier this year when he announced that he would be transitioning away from his tenured position at UCSF in order to pursue his anti-aging startup. Brack cited the time afforded to him for self-reflection during the pandemic as playing a part in his bold decision.  

  • SiPhox biosensor aging blood biomarker open beta study. SiPhox is a Y Combinator-backed handheld, at-home, photonic biosensor company. They are currently running a 6-month aging biomarker open beta program for early adopters.

    Users will take weekly microliter blood samples and analyze them at home with SiPhox’s OneLab handheld photonic device. The device will measure markers of aging and inflammation: CRP, GDF-15, NT-proBNP, NfL, alpha Klotho, IGF-1, CCL2, CST3, MCP-1, & LBP, and upload the measurements to your mobile device. Anonymized data will be used to help advance longevity research. The cost is $200 for the device and $100 / month for the blood draw cartridges. Interested? Sign up here.

    SiPhox’s OneLab approach looks very promising. The characterization of how the blood proteome changes with age has been studied extensively and provides the basis behind longevity companies such as Alkahest, BioAge Labs, and Elevian. A photonic device platform theoretically allows for easy interchangeability of measurement of many different kinds of proteins as scientific understanding of their relevance changes. The at-home device also allows for more frequent measurement, which could be useful when designing interventions or monitoring changes in relation to various factors. 

  • Alchemab Therapeutics raises $82M in Series A round to develop antibody therapies. Alchemab is a London, UK-based biotech company developing antibody therapies based on the naturally occurring personal antibody profiles of exceptional individuals that are resistant or resilient to diseases like cancer and neurodegeneration. The company leverages high-throughput antibody sequencing of patients combined with deep learning and computational biology in their discovery platform.

    The round was led by RA Capital Management with Lightstone Ventures and DHVC.


📅 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

  • Casma Therapeutics:  An early-stage biotech company developing drugs to stimulate autophagy in order to treat neurodegenerative disease, metabolic disorders, inflammation, and muscle degeneration. Casma focuses on small molecules that boost macroautophagy (mediated by autophagosomes) in a targeted manner, able to selectively remove specific structures or proteins. The company was incubated at Third Rock Ventures and was co-founded by the late Beth Levine, a pioneer in mammalian autophagy research.

  • Caraway Therapeutics: Formerly Rheostat Therapeutics. Caraway is developing autophagy enhancing small molecule drugs to preserve neurons in two programs: TRPML1 modulators and TMEM175 modulators. TRPML1 is an ion channel protein found in the lysosomal membrane that plays a role in regulating autophagy. TMEM175 is a lysosomal potassium channel whose genetic dysfunction is linked to Parkinson’s disease and Lewy Body Dementia. Investors in Caraway include pharma giants AbbVie, Merck, and Amgen.  

In 2016, the Nobel Prize in Medicine was awarded to Yoshinori Ohsumi for his work on elucidating the underlying mechanism behind autophagy. Ohsumi’s discoveries were made in the 1990s and early attempts to drug autophagy were centered around inhibition to treat cancer. It wasn’t until recently that serious efforts were made to try activating autophagy with pharmaceuticals to treat diseases.

Autophagy is growing in popularity. Some other companies pursuing autophagy therapies include Selphagy, a David Sinclair / Life Biosciences company and Samsara Therapeutics, an Apollo Health Ventures company. Mitokinin is also leveraging an autophagy mechanism specific to mitochondria (mitophagy) to treat Parkinson’s disease.


Is aging a disease?


The average person does not consider aging to be a disease. Most have not even considered the possibility that aging is treatable or curable. A paradigm shift here would be massively beneficial in terms of funding and political will. So please, spread the word.

From a regulatory standpoint, the FDA does not consider aging to be a disease. However, what the FDA considers to be a disease can change -- though often with great difficulty. A case in point is sarcopenia (muscle loss with age), which was not recognized by the FDA as a disease until 2016

Even without the blessing of an official aging-is-a-disease classification by the FDA, the growing number of longevity biotech companies can and do develop anti-aging therapies. Companies choose a disease indication (often age-related) that is downstream or related to the aging mechanism target. 

An FDA classification, however, would be immensely beneficial in unlocking funding for anti-aging therapies. And not just because it clears paths for longevity therapy commercialization and health insurance reimbursement. A declaration of a new disease that kills 100,000+ people every day (more than 5x peak global COVID19, which itself can be considered an age-related disease) would necessitate a commensurate response from governments, industry, and society. 

But how would we measure aging in clinical trials if aging was recognized by the FDA as a disease tomorrow? Developing a surrogate biomarker for aging still needs to be worked out. In the meantime, Nir Barzilai’s TAME trial provides a usable example of a composite clinical measurement of aging (by measuring the time to onset of age-related disease).

We have all the basic pieces in place for a fully-fledged longevity biotechnology revolution, save for the approval of perhaps 500 - 1000 FDA employees (all of whom are unelected). All they need to do is say four little words: Aging is a disease.

What others are saying

What do prominent voices in longevity believe? Is aging a disease? Here are some responses, which vary in nuanced ways.

Aubrey de Grey (SENS Research Foundation, “Ending Aging”)

Stance: Aging = diseases.

“All gerontologists know full well that it’s no accident that age-related diseases are age-related: they appear at advanced ages because they are consequences of aging, or (to put it another way) because aging is no more and no less than the collective early stages of the various age-related diseases.”

Source: Ending Aging (2007)

David Sinclair (Harvard Medical School, “Lifespan: Why We Age -- And Why We Don’t Have To”)

Stance: Aging is a disease. And we can treat it in our lifetimes.

“Why would we choose to focus on problems that impact small groups of people if we could address the problem that impacts everyone—especially if, in doing so, we could significantly impact all those other, smaller problems? We can. I believe that aging is a disease. I believe it is treatable. I believe we can treat it within our lifetimes.” 

Source: Lifespan: Why We Age — And Why We Don’t Have to

Vadim Gladyshev (Harvard Medical School)

Stance: Not a disease. But not a non-disease.

“The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes...

However, aging is as natural as age-related diseases, which both essentially comprise pathological changes. The recognition of aging as a combination of diseases (together with other deleterious changes) should expose the fundamental role of aging in chronic diseases; and to target aging, it may also invite various strategies normally aimed at treating such diseases.”

Source: A Disease or Not a Disease? Aging as a Pathology. Cell Press. (Gladyshev et al. 2016)

Jean Hebert (Albert Einstein College of Medicine, “Replacing Aging”) 

Stance: Doesn’t matter. We can beat it anyway (through replacement — in the brain too!)

“On the other hand, it has been argued that referring to aging as a disease may unnecessarily stigmatize the elderly as inherently sick. The latter point of view appears to currently predominate. Regardless of the semantics surrounding the word “disease”, the process of aging doesn’t change: damage accumulates, diminishing health and weakening the body until it either succumbs to a bona fide disease or is no longer able to sustain a heartbeat or a breath. In the end, whether we call aging a disease or a natural process, there is a growing consensus among scientists who study aging that we should be able to beat it.”

Source: Replacing Aging

Nir Barzilai (Albert Einstein College of Medicine, Cohbar, “Age Later: Health Span, Life Span, and the New Science of Longevity”)

Stance: Aging can be cured as if it were a disease and I’m spending $70M in a clinical trial to prove it (TAME).

“In a very short period of time, geroscientists have revolutionized the discipline: to think of aging not as a certainty but as a phenomenon—like many other difficult conditions—that can be targeted, improved, and even cured as if it were a disease.”

Source: Age Later: Health Span, Life Span, and the New Science of Longevity

Reason (Repair Biotechnologies / FightAging.org)

Stance: Aging is a medical condition. Also: The FDA is bad.

“Disease is a much abused word, and the boundaries of its varied meanings to different groups shift over time. Most of the well-known failures that occur in organs and other biological systems over the later stages of aging are referred to as diseases, but are in fact better designated as medical conditions. Medical condition is much broader term that clearly covers unpleasant things that happen to everyone, and are thus not abnormal in a given age group.”

Source: FightAging.org

As you might already know, whether or not aging is called a disease has very little to do with words and definitions, and a great deal to do with money and regulation. Unelected officials of organizations like the FDA in the United States cause untold harm to progress in medical science by (a) placing huge and unnecessary burdens upon research and development, and (b) forbidding outright commercial application for any purpose or disease that is not in their list. It can take a decade - and millions of dollars in the formalized bribery known as lobbying - for a new discovery, new classification, or new form of therapy to be recognized by regulators. Or even longer, as is the case for aging.

A world without the FDA would be a far better place, in which progress was faster and the breadth of medical development far greater. The death toll of those who wait in vain for new and more effective therapies would be greatly reduced, and the engines of free market competition turned to building new medical miracles. But sadly we do not live in that world - it lies somewhere beyond the next revolution, or perhaps beyond the next great open frontier.

Source: FightAging.org

Laura Deming (Longevity Fund)

Stance: Aging is a disease -- a spectrum of diseases. 

“Oh definitely, definitely [responding to the question “Is aging a disease?”]... When I was a kid it was interesting because books would talk about ‘Let's try to cure cancer, let's try to cure Alzheimer’s disease’ as specific diseases. And the question is why are we calling that a disease and not the underlying cause that is really the problem. To study aging is to look for pathologies or damages or types of bad things that happen as you get old that cause a spectrum of disorders. So you'll have one thing -- call them a spectrum of diseases. And so you can target that one thing as kind of the causal agent as opposed to going after each of the individual diseases on their own.”

Source:  https://hartmanmedia.com/ls45/

James Peyer - Cambrian Biopharma

Stance: The question is a distraction. It doesn’t matter.

“I have a somewhat controversial view on this amongst folks in our field. I believe that the entire discussion about whether aging should be considered a disease is actually little more than a distraction from the real, more technical issues standing in the way of getting a medicine that enhances healthspan from being approved for that use. Many of my colleagues advocate in good faith that this would be a key inflection point for the field, and I used to believe the same. However, the more I have come to understand about the way that these drugs would be regulated in the future, the less concerned that I am with worrying about categorizing aging as a disease."

"I do absolutely think that it is appropriate and proper to classify the build-up of damage that accumulates during aging as a disease. There is already a gray area about when other conditions are labeled a pathology vs not a pathology. We have categorizations for pre-diabetes, mild cognitive impairment, benign tumors, and high cholesterol. Are these conditions diseases? I would argue that it's not important what we call it. What is important is the following: (A) Can we run a clinical trial to address the condition and (B) would health insurance companies provide such a medicine to its patients?

Source: Longevity.Technology

Alan Cohen (University of Sherbrooke) 

Stance: Aging doesn’t exist.

“There is substantial disagreement within the field of aging biology and among the public as to whether aging is a disease and whether it should be treated as such (Calimport et al., 2019; Cohen et al., 2020; Fulop et al., 2019; Rattan, 2014). Our argument at least superficially appears to render the discussion moot – if there is no unitary phenomenon, it is not possible to intervene in “aging,” and there is nothing to treat or classify as a disease.”

Source: Cohen et al. 2020


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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 / 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.

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Do owners of pet mice buy rapamycin for them?