VitaDAO Project Submission
One-liner: Optimizing RNA Delivery for Longevity Therapeutics
Project Name: ExcepGen Inc
Project lead name: Thomas Folliard
Project lead email address: Thomas.firstname.lastname@example.org
Lead organization website: Excepgen.com
Thomas Folliard (Chief Executive Officer)
Barbara Mertins (Chief Technology Officer)
Katherine Barcay (Chief Operating Officer)
Imre Mager (Head of R&D)
Jason Wojcechowskyj (Director of Vaccines)
Pragya Mukherjee (Scientist)
Describe what you’ll produce in 50 characters or less:
RNA therapeutics for longevity/age-related disease
Please provide a fuller description of what you are doing and how it will impact longevity/healthspan/lifespan
Next-generation vaccines with better efficacy and broader protection are critical for increasing longevity. Severe viral infections have been associated immune dysfunction and chronic inflammation that match signatures of premature aging, an effect that can persist even after the pathogen has been cleared. Moreover, seasonal infections are a common cause of life shortening, frequently even in otherwise healthy individuals. The NIH’s National Institute on Aging has categorized flu as a very serious and life-threatening disease for elderly adults. The respiratory illness caused by viral influenza infection caused more than 12,000 deaths in older Americans over age 65 in 2018. Now in the endemic phase of Covid-19, the risk that aging populations face from viral infections has never been greater.
ExcepGen is developing a new generation of vaccines and therapeutics with its RNAx platform. ExcepGen’s RNAx is delivered alongside primary RNA cargo. RNAx is translated by the cell to produce a regulator protein that modulates signals between the nucleus and the cytoplasm of cells in a tunable manner. By doing this, we keep cells in a low-stress state improving the effectiveness of the RNA cargo to produce significantly more protein leading to increased protection.
We are applying this technology to produce RNA vaccines for challenging antigens, such as universal flu antigens.
While industry-standard messenger (mRNA) was successful in producing a COVID-19 vaccine, this was partly possible because the Spike antigen is highly immunogenic. Other RNA vaccines that target more challenging viral antigens may require longer antigen expression and better immune engagement to be effective.
Self-amplifying RNA (saRNA) is a promising modality for eliciting broader immunogenicity and making better RNA-based vaccines, but it comes with a catch-22. On one hand: saRNA allows for greatly increased antigen expression, potentially requiring lower doses, increasing valences (number of encoded antigens), and providing better adaptive immune responses. On the other hand: its delivery and replication cause inflammatory intermediates and harmful innate signaling that counteract the potential benefits.
With ExcepGen technology, saRNA translation is protected from these cellular triggers. We have demonstrated that
I. saRNAx produces a 400% boost in cargo expression in vivo in mice compared to standard saRNA
II. saRNAx produces up to 2600% improvement in cargo expression in innate-immune-competent human BJ cells
III. saRNAx majorly reduces, and in some cases completely prevents, deleterious inflammatory cytokine release
Based on these exciting platform data, we are pursuing the holy grail of vaccines - a fully differentiated universal pan-flu vaccine that we believe can only be unlocked by saRNAx technology. This product is our primary focus for the vaccine space with additional pipeline products planned for vaccines, protein replacement, and gene-editing.
How far along are you? How close to having intellectual property are you? For projects that you don’t think require IP, please explain.
We expect that we have already generated significant IP and we expect that we have strong IP coverage. We have a portfolio of patent applications submitted by Cooley LLP to protect our core technology and its applications.
What are your competitive advantages over other research and people in your space?
Core technology mechanism: We identified a counterintuitive, holistic way to make RNA perform better. Because our mechanism is counterintuitive, others in the space have not already been exploiting it.
Synergistic technology: Our technology works across many RNA types so we can work with our own RNA modalities or those generated by Pharma partners (including linear and self-amplifying, modified and unmodified, etc.)
IP Strategy: We have applied our technology broadly across RNA types and other nucleic acids to demonstrate our key benefits. We kept the company in stealth mode while developing our strong IP portfolio, which now gives us a strong foundation for technology partnerships in the RNA space.
Nimbleness: We are a small team and we can iterate quickly. Our research process enables rapid in vitro and in vivo testing and refinement.
Why did you pick this area to work on? Briefly discuss your domain expertise. How do you know people need specifically what you’re making?
Severe viral infections have been associated immune dysfunction and chronic inflammation that match signatures of premature aging, an effect that can persist even after the pathogen has been cleared.
The company founding team has deep technical expertise engineering reliability into biology for use in unreliable environments such as in microgravity and the rhizosphere. Educated at top universities, the co-founding team met at Oxford university and founded ExcepGen to engineer reliability into genetic medicines.
We know people need specifically what we are making because of the number of major mRNA companies looking to evaluate our technology for licensing.
What is it about your approach or your findings that you think others don’t understand? What’s new about it and/or surprises people the most when they hear about it?
We encode RNA to produce a regulator protein that makes cells amenable to RNA instructions, resulting in majorly increased cargo expression and prevention of unwanted innate signaling and inflammatory responses. The regulator works by dampening transport of signals between the nucleus and the cytoplasm. Others think this sounds like it would be detrimental to RNA translation and cell function. Counterintuitively, by dampening that “information highway” for the cell, we actually prevent stress signaling and innate immune signaling. The expected MOA is that stress signals are activated when certain cell signaling pathways rise above “normal” signal thresholds. By slowing down the flow of information, ExcepGen technology makes cells amenable to executing the instructions they have been given. We believe that this technology will open up a whole new world of RNA drugs across vaccines and oncology.
Briefly explain how you will spend the money we would give you. This can be as simple as an itemized list of your costs.
ExcepGen is currently applying its technology to vaccines. An assessment from VitaDAO would fund in vitro research, scientific operations, and an in vivo immunogenicity study.
Any other project ideas or IP you’d like us to consider?
How did you hear about VitaDAO?
Pfizer - Mike Baran
- Needs Revision