VDP-5 Scheibye-Knudsen Lab Funding Proposal

Summary

What if therapeutics to slow down the aging process and prevent age-related disease already existed? Recently, in an unprecedented effort, a large-scale study employing advanced machine learning methods analyzed medical records from over 4 million individuals in the Danish Health System’s medical and prescription records. The study, consisting of over 1.4 billion prescriptions, found that a number of prescription drugs were highly associated with longer life- and health-span in long-live populations. Here, we present a unique investment opportunity. We seek to validate these observations through a series of carefully conducted wet lab experiments. If successful, this work could result in the repurposing of several FDA-approved therapeutics for the purpose of extending human lifespan, at a lower cost and over faster timelines than conceivably possible with de novo drug discovery. This unique investment opportunity allows savvy longevity investors the chance to own a share of the potential intellectual property generated from these studies, and in turn, a potential share in the future of life extension.

Justification

The global elderly population is projected to substantially increase throughout the 21st century. By the year 2100 a fifth of the total world population will be aged 65 or older posing a serious socioeconomic challenge to societies world-wide. Interventions that ensure healthy aging are therefore of critical importance.

Next Steps

This program focuses on testing and developing three of these small molecules as possible interventions in aging. Specifically, we will test the drugs on human cell cultures and in fruit flies, before moving to mice in the future. Importantly, the current market for longevity stands at 200 billion USD, even without a single scientifically proven treatment. Our molecules targets this specific market with the aim of letting everyone live healthier, happier and longer lives.

Research Background

To date, more than a hundred compounds have been shown to extend the lifespan of model organisms. In humans, no drug is currently recognized to extend lifespan. Given the large diversity of drugs able to extend the lifespan of model organisms it is likely that multiple drugs are able to extend the healthspan of humans. But how do we find these compounds?

The Scheibye-Knudsen lab has analyzed 1.5 billion prescriptions from 4.8 million individuals over 40 years in The Danish National Health Service Prescription Database and correlated this with the survival of individuals prescribed certain drugs. They received exclusive access to carry out this work. The Scheibye-Knudsen Lab has identified 10+ FDA approved medications that appear to have a strong effect on lifespan following analysis. This project will focus on optimising, repurposing, and re-formulating the 3 drugs with the strongest effect on human lifespan. Additionally, there is a database of compounds that could be pursued. The identities of the molecules are not disclosed in this presentation to protect the full viability of the intellectual property. They are referred to as X, Y, and Z.

Project Significance

Since aging is the largest risk factor for most diseases, discovering compounds able to extend the healthy lifespan could have profound implications not only on disease progression but on the society as a whole. We now have an unprecedented possibility to find interventions that may work in humans allowing us a leap forward in how we perform healthcare. Indeed, this proposal may allow everyone the possibility of living a longer and healthier life.

Scientific Approach

To confirm findings from the database, it will be necessary to test how the compounds impact aging in controlled model organisms. We will apply a two-pronged approach by investigating the effect of the drugs on human cells in culture and the well-used aging model drosophila melanogaster. If these tests are positive we can proceed to test the compounds in mice and later transition to trials targeting aging in humans.

Research Task

To confirm findings from the database, it will be necessary to test how the compounds impact aging in controlled model organisms. We will apply a two-pronged approach by investigating the effect of the drugs on human cells in culture and the well-used aging model drosophila melanogaster. If these tests are positive we can proceed to test the compounds in mice and later transition to trials targeting aging in humans.

For cells: we will use DNA damage induced senescent human cells as well as replicative senescent cells as models for aging. We will investigate the ability of the compounds to affect the senescence markers β-galactosidase staining, interleukin-6 secretion and lamin b1 levels. Another hallmark of aging and senescent cells is the accumulation of DNA damage foci, and we will investigate this by measuring the number of 53BP1 and gammaH2AX foci present in the cells by high content microscopy at the Biotech Research and Innovation Center.

For drosophila we will investigate how the drugs impact lifespan and motor function. Specifically, we will test log-scale concentration curves in a high-throughput lifespan machine that we have invented. We will further investigate how the compounds impact the motor function of flies.

Phase I Duration: 12 months

Phase I Budget: $250,000

Phase II Duration: 12 months

Phase II Budget: $250,000 pending successful completion of Phase I and community vote.

Research Lead

Morten Scheibye-Knudsen, Associate Professor

Morten Scheibye-Knudsen is Associate Professor and group leader at the Center for Healthy Aging, University of Copenhagen, Denmark. Besides his research activity, he has been committed to educational programs and his online companies Mitodb.com and Forsøgsperson.dk. The latter has grown to become the largest single provider of study participants in Denmark. Morten Scheibye-Knudsen also acts as an advisor or committee member for organisations such as the Longevity Vision Fund, the Lifeboat Foundation, the NNF Big Data in Biomedicine project and others. Morten Scheibye-Knudsen earned his MD in 2007 and his DMSc (PhD) in 2016 from the University of Copenhagen. After graduation, he worked as physician at Slagelse Hospital and at Nuuk Medical Clinic in Greenland. In 2008, he became a Postdoctoral Fellow at the National Institute on Aging at the NIH in Baltimore, Maryland. His work focused on the cross-talk between DNA repair and mitochondrial function in aging and has been honored by a number of competitive awards. In 2015 he was recruited to start his own research group at the University of Copenhagen, where his research group aims to understand the cellular and organismal consequences of DNA damage in the context of aging. He now runs one of the largest research programmes in Europe focusing on aging. His ultimate goal is to modulate and perhaps treat aging and age-related diseases, allowing everyone to live healthier and longer lives.

Research Institution

The Center for Healthy Aging at the University of Copenhagen studies how more people can have a healthy life and healthy aging. Their approach to research is interdisciplinary and the center studies aging and aging processes from cell to society.

IP

All intellectual property resulting from the project will be fully owned by VitaDAO.

Learn more and see the deck on Molecule

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  • Agree with revisions (please comment)
  • Disagree

0 voters

8 Likes

@tylergolato I’m having some issues downloading the PDFs from Molecule, they appear blank for the IP assessment and the deck

3 Likes

The slide presentation is embedded on the first page - the others are not available at the moment. Please make an account to view the additional tabs.

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Ok thank you. I have a few questions based on this proposal and deck combined, please forgive me if this is premature, I’m trying to find my footing with this process.

So this proposal covers partly this section (“Pre-clinical Studies I”) from the deck and is only concerned with 1 year of funding of $250,000 and there will be an additional proposal in in the future (~9-12mo from now?) covering the remaining $250,000, that will likely contain a summarization of the outcomes from this proposal.

Is this proposal solely focused on 12months of $250,000?

From the deck it indicates that patent filing will like take place after the 2 year duration, will we expect to see any IP filing within 12 months of this proposal being adopted?

Please could you provide more information to how the virtual spin off, University of Copenhagen and VitaDAO are related. For example, does VitaDAO own the IP? Does the virtual NewCo own the IP and VitaDAO owns equity in NewCo?

What are the risks and mitigations here, I didn’t see too much in the deck? For example do we expect that the 3 compounds from the population study will need modification? Obviously modification would entail broader ADMET and medicinal chemistry work increasing the budget requirements

3 Likes

Hey Ben,

Sorry - this deck is quite dated. It originates from last year when the project was exploring routes for possible funding and we were evaluating doing a virtual spin-off company to raise for the project. Currently, there is no virtual spin-out, and no plans for one. It could be a way to allow the asset to be exited in the future. In the interim, Molecule has out-licensed this project to allow for the smooth transitioning of the IP into VitaDAO. I will update the presentation.

I suggest we host a small discussion with Morten, the PI (have had several already, but might be useful) for him to explain the possible routes to IP. These include identifying a new method of use (repurposing) or employing medicinal chemistry techniques to create analogs (a bit longer term).

I think it would likely be more than 12 months before we would see a patent filing.

VitaDAO will own exclusive rights to all of the IP resulting from the project.

5 Likes

I agree with VDP-5 and think this is an exciting project.
In addition, I have a set of questions for the team, that might be important to address at some point within the project:

  • what is the FDA’s current (official or implicit) attitude when it comes to approving drugs for the “ageing” label?
  • are the FDA approved compounds X, Y, Z currently still on patent? If so, will chemical modification or an additional method of use patent still require payments of licensing fees to the current manufacturer?
  • based on the brochure provided, the team is planning to run clinical trials with their candidate compounds eventually. What is the planned primary endpoint? The way I understand these plans, this will either result in a large phase 2/3 label-extension trial or a phase 1 first in-human trial, depending on whether the lead compound was chemically modified or not. How does the team at this early timepoint think about the risk-reward tradeoff for both of these possible ways forward?
2 Likes

I share @Ben and @NiklasTR views that the IP and commercialization plan as well as clinical plan needs to be more thoroughly explained.

3 Likes

From my side the proposal and project as described herein are sufficient to go on-chain for vote. @NiklasTR and @Ben questions are valid but I would propose to address them in a collaborative call with Morten.

We want to be seen as an agile organisation. The DAO, longevity WG and community have had 4 weeks to review the project, ask questions and Morten and his lab have already provided several community calls to answer questions. They’re also on the Discord.

I currently see 16 Agree votes, which meets the 10 quorum threshold to go on-chain. Let’s put it up to vote and prove our first successful proof of concept if accepted!

7 Likes