VDP-15 Rubedo.Life assessment

Simple Summary

Our Longevity Working Group has been evaluating the Rubedo Life Science company under NDA after multiple discussions over 3 months.

Scientific reviews digest: The review team included 5 PhDs (3 of which are professor / PI level) and 2 PhD-candidates. All have expressed a vote in agreement. To quantify the level of conviction, some have provided a score on a scale of 1-5 (with 5 being the most excited), the average score was 3.8

Here we are presenting an overview of the company in front of the community to decide if this gets put on-chain for an assessment from the VITA token holders via a decentralized vote.

Longevity WG Evaluation Team

Niklas Rindtorff, Laurence Ion, Jason Colasanti, Morten Scheibye-Knudsen, David Wilson, Tim Peterson, Ariella Coler-Reily, Avi Roy

Abstract

Rubedo is building a platform for longevity medicines using “smart drugs” (prodrugs) that have the capacity to selectively be activated in target cells predicted to be pathogenic and the cause of age-related diseases

Highlights:

  • Team formed by an exceptional mix of veteran drug hunters from Pharma and Biotech, Silicon Valley tech leaders, and world-class longevity scientists (from Stanford, etc)
  • The unique discovery platform Alembic combines unparalleled computational biology and proprietary chemistry technologies
  • Raised $12M Seed round led by Khosla Ventures
  • All Intellectual Property (IP) is fully owned by Rubedo. Multiple patents filed. First patent has been issued and granted this year
  • Rubedo developed a portfolio of lead compounds for a pipeline of multiple indications of age-related diseases
  • Partnership with Cedars-Sinai Medical Center has been established to advance the first program on lung fibrosis and interstitial lung diseases
  • The company attracted the interest of several major Pharma Companies for strategic partnerships

More details

Rubedo has started developing therapeutics for idiopathic pulmonary fibrosis (IPF) and lung cancer. IPF is an orphan disease, with a potentially accelerated clearance by the FDA. They work with published and proprietary databases that they have generated in-house.

Rubedo’s proprietary ALEMBIC™ drug discovery platform is based on a synergy between sophisticated computational and chemistry strategies.

This hybrid platform enables the discovery and development of novel first-in-class engineered small molecules, such as prodrugs, designed to selectively target certain types of “bad” cells, like senescent cells, which play a key role in the progression of chronic disorders.

The first product line developed by Rubedo labs is based on engineered molecules that can selectively target a population of pro-inflammatory and pro-fibrotic cells called “Senescent Cells” (as well as other rare pathogenic cells) that arise in the body with age and diseases. Senescent cells in particular cause increased chronic inflammation, pain, and tissue decay that contribute to age-related diseases such as Pulmonary Diseases, Diabetes, Alzheimer’s, Cardio-Vascular Diseases and Cancer.

By selectively clearing the body and tissues of pathogenic cells, while preserving adjacent healthy cells, the tissues can rejuvenate again and diseases revert to improved healthy states.

Rubedo has patented technology to increase the selectivity of senolytic and rare/pathogenic-cell-targeting drugs by modifying known pharmacologically active small molecules with so-called promoeities, such as a galactose residue, to generate prodrugs that are selectively metabolized into their active form in target cells by enzymes that are specific to the target disease (e.g. SA-bGAL).

Over the past decade, a growing body of scientific evidence has demonstrated the critical role of senescent or rare (pathogenic) cells in driving aging and age-related diseases. Research has indeed shown that targeted apoptosis of senescent cells restores tissue function in response to chemotoxicity and aging in animal models (Baar et al., 2017). At Rubedo Life Sciences, they are developing a novel small molecule approach to selectively target and clear senescent or pathogenic cells from aged or pathological tissues, thereby supporting tissue regeneration and restoring organ function.

The small molecules developed from their proprietary discovery platform (ALEMBIC) are engineered to be selectively activated in target cells that emerge with age-related diseases driving the chronic degenerative pathology. Rubedo recently released in pre-print, a proof-of-concept paper where they present initial results on a tool compound that is based on a prodrug strategy. This approach takes advantage of a known enzymatic activity enriched in senescent cells, the hydrolase beta-Galactosidase, well known to be a marker of senescent cells. Their data demonstrates the strategy of converting a pan-cytotoxic drug into a selective and well tolerated senolytic prodrug capable of ameliorating age-related diseases such as frailty and the loss of cognitive and muscle function in geriatric preclinical models (Doan et al., 2020; Targeted senolytic prodrug is well tolerated and results in amelioration of frailty, muscle regeneration and cognitive functions in geriatric mice | Research Square).

Team

Marco Quarta: Serial Entrepreneur in the Longevity therapeutics space and former Stanford University Principal Investigator in full time leadership role at Rubedo. Cofounder of Turn Biotechnologies. Marco earned a Masters degree in Biotechnology, a PhD in Neuroscience, and conducted post-doctoral training in Aging, Stem Cells Biology, and Regenerative Medicine in the leading lab of his mentor Prof. Thomas Rando at Stanford University School of Medicine. He then directed a research team at Stanford/VA Hospital Palo Alto focused on translational medical research in the fields of aging and regenerative medicine.

Marc Gallop: Chemist, drug hunter, serial entrepreneur and executive (in companies including Affimax [Nasdaq: AFFY], Xenoport [acquired] and Nurix with track records of FDA approved medicines including prodrugs) and former executive in residence at 5AM ventures. Key inventor of cell type specific promoiety chemistry.

Alex Laslavic: Computer Scientist and former Facebook lead engineer. Developer of target identification platform with a focus on differential gene expression analysis in senescent cells for neo moiety design. He is the CTO.

Technology

The team has identified a portfolio of small molecules that target signature metabolism features of rare (presumably pathogenic) cells and are currently working to test and optimize these compounds in preclinical models.

The team has filed 3 patents for its pro-moieties platform. One patent, focused on glycosidic modifications of small molecules, was granted recently.

Maturity of opportunity

The company is currently raising a Series A. It has plans to bring in a chief business officer to aid the team in negotiating licensing deals for assets within its IPF, oncology pipeline and in other undisclosed indication programs.

Additional reading

Long-form presentation: ‎The Longevity Biotech Show: #013: Marco Quarta

Press:

Publications:

You can read here a couple of publications, including one early POC in pre-print (but take into account that the work described in this preprint is a simple proof of concept exercise. With the current Alembic platform, the company is pursuing and developing more sophisticated molecules or prodrugs for selective targeting of pathogenic cells): The Science | Rubedo Life Science

  • Strongly Agree
  • Agree(with revisions)
  • Disagree

0 voters

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The Longevity WG has also voted on a level of funding they believe would be appropriate. All voted in favor of funding, at an avg level of $540,000. However, this is not up for a vote here, it’s not a recommendation to invest or any other action. It is just a vote asking for agreement or disagreement with the Longevity WG’s assessment. Further action will depend on the vote outcome.

The conviction level of the 7 scientists has increased to an average of 4.17/5

VDP-7 allocated $1.5M for investing in a fund, out of which ~$1.05M has been allocated and a range of 200-400k would be appropriate

Addressing the vagueness here:

It is an assessment from the Longevity/Dealflow Working Group. It isn’t asking for any funds to be invested.

This is similar to VDP-8 where we had an evaluation of Turn.bio
In VDP-7, a $1.5M budget was allocated for VitaDAO to get exposure to equity deals.

VitaDAO, for legal reasons, cannot/must not give investment recommendations, but it can provide a service, assessing research projects, either in academic labs or companies.

This is unique. This collective has a Longevity/Dealflow WG with domain experts and they are able to source and evaluate projects. They summarize the project details and their assessment/conviction about the merits of the project and put a report in front of the community for review and commentary. Then it goes to a decentralized vote by VITA token holders.

This is especially cool because the internet provides reach and anonymity, someone can dig up dirt (or positive things) and augment the Working Group’s assessment, without being afraid of retaliation.

Vitality Healthspan Foundation, a Canadian not-for-profit that’s aligned with VitaDAO’s mission, is a legal entity that can actually hold equity in companies.

VitaDAO has previously sent $1.15M to this Foundation and might send more than $1.5M but that would need a separate vote.

Ultimately, the Foundation or anyone can use this information for any purpose they want. There is and, for now, legally needs to be a separation. As long as VitaDAO doesn’t make investment recommendations and only assesses the science, and sometimes the business aspects, we’re good.

This is pretty standard. Even if VitaDAO was an LP (Limited Partner) in a VC fund, it couldn’t decide if and how much to invest in any specific deal, otherwise the “limited liability” protection would be lost.

Qualitative summaries from the review team:

  1. This platform has a high potential for impact since it can be applied to a wide variety of cellular phenomena ranging from eliminating pathogenic cells, regenerating stem cells, removing ECM debris, repairing mitochondria, etc.
    Focusing on prodrugs is a valuable approach since it allows for the delivery of drugs to be highly cell-specific and avoid off-target effects
    Their successful proof-of-concept for targeting cellular senescence is a great example of this and shows strong in vivo results with virtually no off-target effects
    However, it has yet to be seen if they will be as successful in targeting other cellular phenomena as they are with cellular senescence. Also, it is still unclear how these prodrugs will be delivered in vivo and what their plan is to address this, but I don’t see this as a major hindrance to the company’s success at this stage. Overall, Rubedo’s workflow is logical and feasible - from target discovery in silico, moving to in vitro testing, and finally in vivo - and the ALEMBIC platform is very promising for the longevity field, and possibly other fields as well.

  2. Creative proposal but the platform seems too nascent

  3. I like their platform and concept. There’s nothing extremely novel about their platform, but it does contain proprietary data sets. I like the focus and strategy, i.e., identifying rare, disease-specific cell signatures and targeting metabolic defects in those cells. The idea of removing pathogenic cells (e.g., senescent cells) is a nice one, and they have reasonable POC data. Prodrugs are gaining some steam, so that’s attractive, particularly from the perspective of building in treatment specificity. There were some questions about their chemical compounds, and I think that’s the part that knocks their position down. We are really relying on them being “truthful”. That in and of itself is not a problem, but without being able to gauge the strength of the chemical entities on our own, there’s a bit of unknown here. That part I don’t like. I was impressed with Marco and his team, particularly their depth of responses. The team has collaborated with and involved several high profile scientists in past work, so that adds further legitimacy to their credentials. I hope it works out in the end!

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