ADP-002: Funding AthenaDAO’s First 2 IP-NFTs

Summary:

In this proposal, we provide additional details about the two IP-NFTs that have already been minted.

Overview:

AthenaCore made the strategic decision to focus on proof-of-concept and start building the science and deal-flow working group first. In December 2022, AthenaDAO initiated its inaugural call for submissions, focused on Ovarian Aging. We received a total of 50 submissions from research labs worldwide.

After careful evaluation, we shortlisted six exceptional projects for senior review. Out of these six, three have progressed to the subsequent stage, and two have already been funded. AthenaDAO is currently negotiating the last one with the research lab.

The senior review committee was composed by:

• Two entrepreneur scientists and investors with more than 30 years of combined managerial experience in the biopharmaceutical industry.
• A recognized academic scientist and lab leader in the field of aging and women's health with more than 50 publications in high-impact scientific journals.

The decision was made to fund these 2 projects before the formal kick-off of the DAO’s governance. We wanted to showcase our commitment to driving tangible impact in the field of women’s health and give an opportunity for both the AthenaDAO’s community and the web3 community to see a BioDAO take action and set clear expectations for the future.

In the recently concluded Second Call for Submissions on Endometriosis and PCOS, projects are set to adhere to the governance process, whereby they will undergo comprehensive evaluation and scrutiny. Subsequently, they will be subjected to a community-wide vote on the Snapshot platform before any allocation of funding takes place. This approach underscores our commitment to transparent decision-making and ensures that the AthenaDAO community plays an integral role in determining the projects that receive support.

Research Project 1: Understanding the role of the cGAS-STING pathway and senescence in ovarian aging

On August 1, 2023, AthenaDAO funded its first IP-NFT with $120,200, split into two tranches.

Dr. Mario Cordero, Principal Investigator at Universidad Pablo de Olavide, Sevilla (UPO) is working on the Diminished ovarian reserve (DOR), an overlooked issue that currently lacks effective treatment. Mario's project aims to address this problem by targeting inflammation by inhibiting the cGAS-STING pathway, offering a novel approach. The project has the following aims:

• Identification of the specific cells associated with the cGAS-STING pathway activation in aging, and validation of cGAS-STING pathway activation as a target for early Diminished Ovarian Reserve (DOR) in human samples.
• Validation of cGAS-STING pathway activation as a target for chemotherapy-induced DOR in both animal models and human patients.
• Development and in vitro evaluation of the pharmacological efficacy of novel cGAS-STING pathway inhibitors.
• Evaluation of the efficacy of cGAS-STING pathway inhibition in animal models of age-induced and chemotherapy-induced DOR.

The first tranche of funding will cover aims 1 and 2, as well as the design and synthesis of the novel inhibitors from aim 3. The second tranche will cover the in vitro evaluation of the novel compounds in aim 3 and aim 4. To increase the likelihood of success of the project, the agreement stipulates funding milestones.

The chosen target seems to be promising and has some genetic validation. Certain autoimmune diseases, resulting from rare mutations that cause an overactive cGAS-STING pathway, have been associated with fertility issues and early DOR.

We have confidence that, by its conclusion, the project will produce proof of concept data and strong IP that will leave it in a good position to attract further funding. This progress will pave the way for a spin-out company and ultimately make a positive impact on patients.

About Mario Cordero

Dr. Mario D. Cordero is a passionate and accomplished researcher with a strong focus on inflammation and metabolism during aging. Holding a Ph.D. in health science and a Bachelor's degree in Human Nutrition, he currently serves as a Principal Investigator at Universidad Pablo de Olavide, Sevilla (UPO), leading the "Inflammation and Metabolism during Ageing Research Group."

Dr. Cordero brings with him a history of excellence; he has published 90 articles, 8 book chapters, 2 books, and 5 patents, being cited more than 8993 times.

You can watch the IP-NFT Minting Ceremony here. You can see here the IP-NFT.

Research Project 2: Targeting the Integrated Stress Response to Enhance Ovarian Follicle Survival and Growth

On October 19, 2023, AthenaDAO funded its second IP-NFT, a project led by Dr. Joshua Johnson at the University of Colorado. The total budget for the project is $102,495.

The project's premise is that improved biomarkers of ovarian aging are leading to greater awareness of the risks associated with Primary Ovarian Insufficiency (POI), and there's a growing need to develop interventions that can extend ovarian function and delay health-related complications.

The scientific basis of this endeavor is the identification of the Integrated Stress Response (ISR) pathway as a central regulator of ovarian aging. The ISR pathway is a complex network of molecular processes that respond to various stresses and threats within the cell. One of its key components is eukaryotic initiation factor 2 subunit alpha (eIF2α), which plays a crucial role in controlling protein synthesis. Activation of the ISR pathway, through the phosphorylation of eIF2α, leads to the translation of pro-survival genes that are essential for cell survival under stress.

The aims of Dr. Joshua Johnson's project are:

• Understand the role of the ISR pathway in ovarian aging.
• Validate phosphorylated eIF2α as a biomarker for ovarian health.
• Develop interventions to prolong ovarian function and mitigate risks associated with POI.
• Compare P-eIF2α levels in normal vs. accelerated ovarian aging models.
• Bridge the gap between research findings and clinical applications.
• Explore ways to enhance cell survival in the ovaries.

In essence, the project aims to understand and address the challenges of ovarian aging through the lens of the ISR pathway. To increase the likelihood of success of the project, the agreement stipulates funding milestones.

The research team, led by Dr. Joshua Johnson, has pioneered the investigation of how the ISR pathway influences ovarian aging. They've demonstrated the presence of phosphorylated eIF2α in human and murine granulosa cells and oocytes, suggesting its importance in regulating ovarian health. The above points will be tackled by first mouse studies (first tranche of funding) and then human tissue sample experiments to validate the mechanisms (second tranche of funding).

About Joshua Johnson:

Dr. Joshua Johnson, an Assistant Professor in the Divisions of Reproductive Sciences & Reproductive Endocrinology and Infertility at the Department of Obstetrics and Gynecology, earned his PhD in Biology from Arizona State University and furthered his expertise with a postdoctoral fellowship at Harvard Medical School and practical experience as an embyologist from the Yale IVF Center. Over the years, he has focused on unraveling the genetic and environmental factors that influence this process, with the ultimate goal of understanding how the mammalian ovary sustains years of function. This has made him a well-known and respected figure in the field of reproductive longevity with over 4000 citations.

You can watch the IP-NFT Minting Ceremony here. You can see here the IP-NFT.