VDP-143 [Funding] Fission Pharma - Revised

One-liner : Fission Pharma is developing a protein-protein interaction inhibitor that cuts the link between chronic inflammation and mitochondrial dysfunction to treat multiple age-related diseases and extend human lifespan.

Revision Notes:

• This project was originally proposed as funding an external company with VDP-123 and rejected.

• It was then revised as a VitaDAO company building project worth $250k and proposed as VDP-143 on March 15th 2024, taking into account the feedback received on VDP-123. The Discourse poll had a positive outcome, with 16 votes in favor and 1 vote against

• The current update of the revision, dated April 5th 2024, includes a research plan expansion to be covered with $83 333 co-funding from Cerebrum DAO in exchange for a share of the resulting IP-NFT. It is motivated by the opportunity to significantly increase the probability of success at marginal cost as well as the interest of Cerebrum DAO to support this project

• Due to Snapshot’s character number limitation, the current proposal is an abridged version of the full proposal available on Discourse.

Longevity Dealflow WG Team

• Senior reviewers: the same reviewers as the previous proposal, including two entrepreneurs, an executive, a VC, and a professor, provided a review update.

• Shepherd: Paolo Binetti, Ryan Spangler

• Squad members: Eleanor Davies

• Sourced by: Paolo Binetti, Ryan Spangler

Project Team

• Principal Investigator: Luis Rios, PhD

• VitaDAO Entrepreneur In Residence/Project Manager: Anthony Schwartz, Ph.D.

Simple Summary

Fission Pharma is creating the first drug-like small molecule P110 mimetics. P110 is a mito-protective peptide originating from Stanford University [1]. The efficacy of P110 in treating neurodegenerative and cardiac disease is supported by 13 years of research, resulting in 20 scientific publications across 11 disease models and collaboration with 15 independent labs globally. P110 has highly generalized anti-degenerative activity, increasing lifespan in mouse models of neurodegeneration (HD [2-5], ALS [5-6], AD [5, 7, 8], PD [1], MS, stroke, and scrapie) and also a model of ischemic heart disease [9]. Dr. Luis Rios published the first small molecule P110 mimetics in 2023 [10] and showed comparable efficacy to P110 in mouse models of ALS and sepsis. These inhibitors have a unique property, they inhibit the downstream pathological consequences of inflammation without inhibiting immune signals. These compounds aim to be the first effective and generalized orally available and brain penetrant treatments for chronic inflammation and mitochondrial dysfunction, critical hallmarks of aging, and may do so without causing immunosuppression, the limiting factor in chronic inflammation treatment. The most tractable go-to-market strategy will be in a rare neurodegenerative disease (ALS) and they will expand to age-related degenerative indications such as AD and ischemic heart disease, the major limiting factors in human lifespan.

Problem

Please see the full proposal on Discourse.

Solution

Please see the full proposal on Discourse.

Opportunity

Please see the full proposal on Discourse.

Relevance to Longevity

Please see the full proposal on Discourse.

IP Roadmap

Please see the full proposal on Discourse.

Experimental Plan

Below is the draft plan proposed for this project divided in four phases with go / no go milestone to trigger funding tranches (also shown) for each one of them:

December is considered a contingency buffer in case the project or the funding campaign for the follow-up take longer than expected.

Below is the draft plan for the follow-up until phase 1 clinical trial (not covered by this project, but provided for visibility into the next steps), including preliminary budget and milestones.:

For more details, please see the full proposal on Discourse.

IP Building Round Budget Breakdown

The total budget requested for this proposal is $333k, broken down as follows:

Financing and VitaDAO funding terms

IP Building Round: This phase focuses on identifying promising leads and filing provisional patents for NCEs (New Chemical Entities). The proposed amount is $333 333, consistent with the budget above, to be funded by:

• VitaDAO for $250 000

• Cerebrum DAO for $83 333.

The IP built by the team becomes an IP-NFT, whose ownership is split:

• 60% VitaDAO

• 20% Cerebrum DAO

• 5% PI, Luis Rios

• 5% Employee Option Pool

• 5% EIR, Anthony Schwartz

• 5% Deal squad

Pre-Seed Round (not included in this proposal): If milestones met for phase 1, would proceed to raise approximately $500k community-funded via an IPT mechanism. The objective is to progress from initial hits to lead compounds, positioning Fission for a subsequent seed round. Details would be determined in a future VDP proposal.

Team

Please see the full proposal on Discourse.

Slide deck

VitaDAO-Fission Pharma Deck.pdf

Highlights

• P110 , a proof of concept peptide inhibitor for DRP1-FIS1 interaction, shows efficacy and no toxicity in many age-related disease models. 13 years of research, 11 disease models, and 20 publications on P110.

• The founder has developed SC9 , a P110-mimetic small molecule showing efficacy in vitro and in vivo.

• These compounds act via a novel mechanism of action and target site.

• VitaDAO will own composition of matter patents on compounds discovered.

• Pre-seed program with substantial scientific validation and IP-NFT offer.

• “Pipeline in a pill” with 3 major classes of compounds targeting different tissues.

Risks

• Novel mechanism of action that hasn’t been tested in humans (on-target tox)

• Poor models for brain aging (but good models of Huntington’s).

• Relevance for life extension not tested

• Competition

Bibliography

Please see the full proposal on Discourse.*

Senior Review Digest - Quantitative

Below is the average scores out of 5 per category from 5 reviewers, who all recommended that the project should be advanced for token-holders vote.

Average Scores

• Team Expertise: 4.4

• Feasibility & Data: 4.2

• Commercial Potential & Impact: 4.2

• Novelty & Market Advantage: 4.2

• IP Defensibility: 4.2

• Relevance to Longevity: 4.2

• Deal Terms: 4.8

• General Conviction Score 4.2 (for reference, the average score of past funded projects is 3.7)

Note: while these scores refer to the original version of this proposal (VDP-143), we believe that they are mostly still applicable to the current revision.

Senior Review Digest - Qualitative

Each reviewer was asked whether they would endorse the project, below are their answers.

Reviewer 1 I would endorse the project because of its applications in several age-related diseases. Nevertheless, VitaDAO should take an active role in tracking the progress of the company and help in reaching the next milestones. With the new updates in company team and focused strategy for drug development convinced me more in a positive way. I have updated my scores and would be happy to endorse the company.

Reviewer 2 Yes, I would endorse it. Very feasible. The background science is solid and validated in mice disease models. The question is whether it will work in humans. They focus on a rare disease approach. Looks like a good first step.

Reviewer 3 Given the new additions to the team, the more straightforward path to IP, and the clear unmet need for ALS, I am more than happy to endorse this project. I am personally excited to see how the science plays out. The science is interesting. There could be applications to Longevity. The ask is reasonable.

Reviewer 4 Yes. Despite adding Anthony, this is still a risky project as it uses computational chemistry to screen for a new compound. However the risk/reward is worth it. Good survival data. Market is big for ALS, neurodegenerative diseases, etc. The terms are better now.

Reviewer 5 The project is in its infancy stage. If the company does not claim its relevance to longevity, I am more than happy to support the project once the team has clinical & commercial experts; if it is related to longevity, I would not support but will actively participate in it until data on longevity related conditions/diseases come out (i.e. premature ovarian failure, dementia, AD, etc.).

Note: while these endorsements refer to the original version of this proposal (VDP-143, not VDP-123), we believe that they are mostly still applicable to the current revision.

Vote

Here, you, the VITA token holders, are voting to agree or disagree with VitaDAO funding this venture.