Introduction
Academia today is funded exclusively from national bodies and, increasingly, the industry. Climbing the ladder means shying away from basic, groundbreaking research and focusing on headline, pop-culture friendly, industry-wooing results. This is incentivized by governments looking to the next election cycle and corporations looking to next quarter’s results. In short, science today is structured and funded to serve short term interests. We think this is unsustainable, ethically questionable and, most worryingly, promotes bad science. We believe that we should never look at the next victim, of an unprofitable drug, killed before it ever reached the shelves and claim that our “commercial realities lied elsewhere”. We believe that science should be about the pursuit of truth for the betterment of humanity; we want to empower the people to have a larger say into the future of science and to incentivize research funded and supported from the people for the people.
What follows is an innovative suggestion of iGEM Thessaloniki team, collectively supported by 6 other iGEM teams; iGEM ELTE, iGEM IISER-Tirupati India, iGEM Heidelberg, iGEM Toulouse, iGEM Stockholm, iGEM Colourectal that came together even under the scope of a winner-takes-all competition to bring forward an idea we believe is bigger than a prize – bigger than any single team. This is our answer to democratizing science.
Bringing THERIAC to market
Having a frequency of 3 to 4 cases per 100,000 people worldwide, glioblastoma is still a rare disease even though it accounts for almost 50% of primary malignant brain tumors. It is also the most aggressive brain tumor, with a median survival of less than 2 years and a five-year overall survival rate of less than 6% with the current standard of therapy. Over 200,000 people globally, including nearly 15,000 in Europe, lose their lives to glioblastoma each year. Also, it is justifiable to anticipate that about 250,000 new cases of glioblastoma each year, with an over-incidence in the Caucasian populations and a slight increase accounted to population aging (Hanif et al. 2017; National Brain Tumor Society. 2022 Oct 9).
However, glioblastoma remains a rare type of cancer and biopharmaceutical research and development in this scientific topic remains limited and challenging. Time and resources are crucial for new cancer drugs’ development while the market is mainly interested in benefiting of the most cost-effective and accelerated fast-track procedures.
New drug development that actually “makes it to market” takes approximately 10 to 17 years and costs from $314 million to $2.8 billion (Braintumourresearch.org. 2022; Wouters et al. 2020; Mandel et al. 2018). The costs included funding of failed clinical trials and had various analyses with different estimates of trial success, preclinical expenditures, and cost of capital.
According to Wouters et al, “Estimates differed across therapeutic areas, with costs of developing cancer drugs the highest.”
Understanding our positioning and steps forward
What follows is an estimate of where we would have to go in order for THERIAC to reach the market; Figure 1 is hugely helpful in illustrating this.
Figure 1: New drug development pipeline
Sun, D., Gao, W., Hu, H., & Zhou, S. (2022). Why 90% of clinical drug development fails and how to improve it?. Acta pharmaceutica Sinica. B, 12(7), 3049–3062. https://doi.org/10.1016/j.apsb.2022.02.002
The stages of a rare disease drug development are:
- Basic Research – Target validation, screening and optimization (current stage of THERIAC: before target validation)
- Preclinical development: in vitro efficacy using representative model systems, in vivo studies for drug toxicity, efficacy and drug delivery (animal studies).
- Phase 1: Safety profile, toxicity, and side effects in healthy individuals
- Phase 2: Safety and effectiveness tested in patients - volunteers (hundreds or thousands).
- FDA/EMA Review and approval.
- Phase 3: Confirmation of effectiveness and safety against golden standards treatments in patients
- FDA/EMA Post-Market Safety Monitoring.
Our problem
The failure of most clinical studies shows how difficult it is to develop new, efficient therapies for glioblastoma (GBM), considering that the last approved therapy for GBM has been before year 2000 (Mandel et al. 2018). Major barriers to this procedure include the blood-brain barrier and enormous intra- and inter-tumoral heterogeneity of GBM.
As any novel cancer therapy, THERIAC must undergo clinical trials before being generally accessible, and clinical trials need a set number of people to test new therapies for efficacy and safety. In order to advance research, clinical trials for GBM cancer require collaboration, data sharing, and good communication among experts nationally and world-wide.
Our team’s project has a detailed basic science backbone to support the development of a drug that is widely available, inexpensive and effective. However, it is not likely that with the existing system of drug development, it will never be readily incorporated into clinical care. Once a promising breakthrough is discovered in a lab, it must undergo a protracted and costly process of translation into a potential new therapy. The next phase in this process is drug development which is expensive and risky because of pharmaceutical companies leaning to the most accelerated processes and being our clients, and the high competition of the vast number of drugs being tested each year. The costs and time needed to develop our product, based on today’s standards in academia, is unsustainable and by-and-large makes it un-fundable.
Figure 2: Submissions for orphan diseases drugs submitted in contrast to drugs for common disease (EMA Orphan Medicinal Product Designation Overview 2020-2021)
Thus our major concern is how to address these issues without compromising the status quo of the biopharmaceutical market, but rather, changing the rules of the marketing game; how we can empower Sustainable Development Goals (SDGs) through medical technology development.
For glioblastoma patients, THERIAC will provide a more accessible treatment, reaching SDG3 ‘Good health and well-being’ in equal terms. For other unfundable ideas other SDGs are sacrificed.
We believe that medical research must be more inclusive when it comes to rare diseases to support knowledge translation and implementation if it is to be effective. A clear vision and plan for health research that links to improving health is required and will have co-benefits for health since better health is closely linked to several of SDGs, including climate, and environment, economic expansion, and inequality will be aided by improved health. Frequency should not play the main role in funding research, as
“no disease is too rare to deserve research funding”.
Today’s funding pipeline
It is a fact that academic Research and Development (R&D) requires sponsors and funds in order to achieve its goals. But who funds the R&D and what is the funding pipelines?
There are no specific requirement for someone to be a R&D sponsor, even though in the U.S. , the vast majority of them are businesses (73%), higher education (13%) and the federal government (10%) (Beethika Khan et al. 2022).
The way the academic funding pipeline works is simple and divided in 3 stages. The frist stage of funding applies to” basic research”. That includes a concept with IP protection, proof of concept (containing scientific validation, regulatory requirements possible scale up issues) as well as preclinical development (having appropriate models and prototype development). The next level of funding is called “product development” requires additional information, such us human clinical trials and commercialize of the concept (manufacturing and marketing). The third and final step is called commercialization requires impact practice and policy (Rafiq et al. 2015).
iGEM team ideas meta-analysis
We undertook a process of thoroughly scrutinizing old iGEM groups and their need for clinical trials. Specifically, we contacted other iGEM teams that were respectively on a therapeutic and diagnostic track and asked the following questions:
- For the implementation aspect of your project, have you included clinical trials?
- If so, have you also developed the enterpreurship aspect of your project?
- Have you included the potential cost range?
After a statistical analysis of the data, we observed that 80.5% of the groups, although they are on a therapeutic-diagnostic track, do not mention clinical trials as part of the implementation. However, it is worth mentioning the 5% figure that includes the iGEM teams that has both taken into account the clinical trials and at the same time considered the business side of the project. This realization shows the difficulty of commercializing an innovative therapeutic or diagnostic idea that has not yet moved the market (Figure 3 & 4).
Figure 3. Measurement of clinical trials in iGEM teams
Figure 4. Measurement of the Entrepreneurship in iGEM teams that inclluded clinical trials
The THERIAC platform
The problem
The conduction of a research project requires manpower and material resources, and funding is of cardinal importance to meet these requirements. When studies are multi-centric, observational with large sample size or experimental, including clinical trials, the need for external funding is even greater.
Today’s main sources of funding in academia are national bodies and industry grants. However, the criteria on which these grants are awarded pose significant issues for the scientific community and its progress. Scientists are forced to do research that is profitable and marketable instead of asking the questions that matter, while they are encouraged to overpromise, which leads them to engage in questionable practices when faced with the danger of underdelivering. Moreover, researchers have to be well connected, spend a significant amount of time applying for grants, and be in a constant struggle of publish in the top journals, discouraging them from reproducing existing work and stifling creativity and intellectual risk-taking.
"Science, I had come to learn, is as political, competitive, and fierce a career as you can find, full of the temptation to find easy paths." — Paul Kalanithi, neurosurgeon and writer (1977–2015)
In the pharmaceutical field all the above mean that many drug research products are held “hostages” of economic interests, and many of them never reach the market, because the disease in not “common” one and or the cost of the research/ clinical trials deem the drug unprofitable.
Thus, life-saving products, breakthrough discoveries and social initiatives that are not commercials enough are forced to find new innovative ways to acquire the necessary funding.
This is the main problem THERIAC and the other iGEM teams, as data shows. Teams avoid taking up diagnostic - therapeutic projects, especially involving clinical trials, and one step further they avoid supporting entepreneurship.
The solution
Even with the uptake of digital retail, the world has struggled to find ways to reward scientists and researchers for not immediately marketable work. Non-fungible tokens (NFTs) are one proposed solution.
We propose the creation of the THERIAC Platform – a crowdfunding platform that enables the public to actively support breakthrough research projects and be rewarded for it by sharing in the profits of world-shifting results.
The THERIAC platform will:
- Provide a novel funding stream for groundbreaking research
- Provide actual, tradable proof of project support for backers while ensuring transparency through a dedicated blockchain
- Set the foundations of a decentralized market for and of science.
How it works:
Researchers create their project in the form of an NFT and then sell it online, with ownership tracked on the blockchain to determine who owns every unique copy of the IP associated with the project. While NFTs offer a model for researchers to fund their work, they do not intrinsically offer a way for researchers to raise funds for their projects in the first place. In our design, inspired by (Basu, Basu, & Austin, 2022), a researcher posts a transaction to the blockchain promoting their research endevour. Other backers may then contribute to the project, in exchange for a percentage of the future potential earnings related to the IP of the project (e.g., a patent sale). Once the researcher then publishes their work (NFT) on the blockchain, the funding campaign is tied to the NFT itself. The researcher may then sell the NFT as they see fit, and the researcher’s backers are compensated automatically. For a successful researcher, a history of successful projects can be an excellent form of marketing; backers can see the researcher’s history on the blockchain and thereby be encouraged to invest in the researcher’s next fundraising campaign.
Figure 5. Research Funding
In a wider sense this creates the opportunities for researchers to fund their work through means that do not tie them to the institutional gatekeepers ever present in academia. As an economic model, the THERIAC Platform can act as an equalizer of scientific funding, generating “indie” researchers and reducing the geopolitical aspect of science. It also creates the opportunities for the creation of a research stock market, with institutional investors trusting the work of labs that consistently deliver results while small, “penny stock”, upstarts can yield great returns for the more risk-oriented.
Figure 6. A sale of a project’s IP
Our vision is a liberated scientific sector that promotes equal opportunities for all and delivers results the offer great value to society.
The market/traction
NFT market is a booming one. In 2020 it was estimated at $ 232 Million, in only one year it valued at $15.53 Billion, and based on Business Research Insights is projected to touch $ 73.90 Billion by 2028, with an estimated compound annual growth rate (GAGR) of 24.4%. NFT technology is being adopted day by day in new fields (art, sports, entertainment, etc), as influence of Blockchain and globalization, fueled by increasing adoption of internet and technological breakthroughs.
Scientific community is embracing NFTs. Tim Berners-Lee, the creator of the world wide web has sold an NFT of the origan source code for a staggering $ 5.4 Million on June 30th 2021, and that is just one example. Many scientists and scientific institutes understand the benefits of making science open, popular, and accessible at the public, and at the mean time an innovative method of fundraising.
Another popular way of fundraising, especially among startups, is crowdfunding. It is the use of small amounts of capital donated from a large group of individuals to finance a project, business venture, etc. The individuals can receive some kind of reward, like an early product, discount or other, but it is not necessary. Crowdfunding market is expected to increase by $239.78 Billion from 2021 to 2026, at a GAGR id 16.81%.
The number of researchers engaging in crowdfunding is growing and the reasons are especially junior scientists face difficulties in getting funding through traditional channels, and people will be more willing to donate new scientists, with more innovative, breakthrough and sometimes “riskier” projects. Moreover, it is a faster way to collect money in contrast to grant-based system, and it can help researchers to develop important skills, like communicating science to the general public, receive feedback on their research, achieve greater visibility and gain confidence in their work by realizing that others care for their work (Sauermann et al. 2019).
Nfts and crowdfunding are both great ways of funding research, which both individually are presenting a rising tendency in the years forward. Our idea, Theriac platform, combines these two variations, into a new innovative way to make scientific research funding accessible to anyone.
The technology
What is an NFT: A non-fungible token (NFT) is a unique digital identifier that cannot be copied, substituted, or subdivided, that is recorded in a blockchain, and that is used to certify authenticity and ownership. The ownership of an NFT is recorded in the blockchain, and can be transferred by the owner, allowing NFTs to be sold and traded. NFTs can be created by anybody, and require few or no coding skills to create. NFTs typically contain references to digital files such as photos, videos, and audio. Because NFTs are uniquely identifiable assets, they differ from cryptocurrencies, which are fungible. – Definition by Merriam Webster Dictionary
The implementation of the THERIAC Platform will be based upon already existing solutions, frameworks and principles. We consider the existing Technology Readiness Level of the solution based on products on the market to be 5 or 6. While developing a blockchain – Ethereum was selected due to its widespread adoption – is something that has been proved many times over, the main challenge lies in translating scientific work to NFTs. Nevertheless, given that much more complex works have been achieved, that is also considered easily implementable.
Revenue model
Our revenue model is based on receiving a percentage fee, estimated around 5% from any money raised on our platform, that is going to be paid by the creator, along with the payment processing fees. This model is user friendly, it doesn’t require from researchers any initial capital, and it is only going to keep a small percentage of their raised amount.
As we are still in the business development phase, there are three more revenue models under consideration, that may be implemented individually or combined.
1. This model is similar to the chosen one, with the difference that the fee is going to be charged to the donator. This way the scientists receive the full amount of the donations, and backers will be possible to accept to cover the charging fee, as it is for good cause.
2. Another revenue model is offering crowdfunding services, like marketing, campaign management, content creation etc, and be paid as a service. The advantage of this model is that in case the crowdfunding campaign goes well, we will gain brand exposure.
3. Last option is to create a software subscription services. We will “rent out” the software for researchers to use in their website, with their branding. This way revenue will be raised in the form of a subscription or license, gaining more stability in finance, as we will not be depending solely of fees from donations.
Next steps
Go-to-market
We estimate that the time required to reach the alpha version of the THERIAC platform is 8 months, given the combined manpower of 7 teams. The software development necessary will be managed through agile sprints focused on continuous engagement will all relevant stakeholders. We aim to commence investor relations when near the launch of the MVP.
Figure7. Timeline of basic procedures in developing Theriac Platform
5-year projections
Our goal is to fund 12.000 research projects by 2027. To do this, the THERIAC platform will have to pursue an aggressive growth strategy that burns through investors cash to optimize for critical mass adoption. Costs will be driven mainly from marketing and sales efforts along with personnel. Of course, the capital necessary to deliver a MVP Platform will be leveraged from our favorite three “f”s – friends, fools, and family willing to support us.
Key Performance Indicators
- Month users
- Funding invested through the platform
- Research projects funded
Figure 8. Reseach projects funded
Figure 9. Funding invested through the platform
Team
Our team is characterised by interdisciplinarity as it consists of people with different backgrounds and expertise. Specifically, due to this composition we have people capable of approaching the web development aspect, the marketing, sales part and branding part. This aside from the scientific development of the project, approaches the business model methodically.
In this effort the stakeholders of the team rushed to help in the implementation of this idea with a letter of support.
Dr. Nikolaos Foroglou is a member of the Education Committee of the Hellenic Neurosurgical Society, a member of the Administrative Council and a former President of the National Neurosurgical Society. He collaborated with the team from the beginning and supported our project from both a scientific and financial background. Seeing the potential of this project, and the commercialization aspects decided to support the effort of creating this business model.
Dr. Theodoros Dardaversis is a professor of the Laboratory of Hygiene, Social-Preventive Medicine and Medical Statistics and Dean of the School of Health Sciences of Aristotle University of Thessaloniki. The support of the Deanery strengthens the dynamic of this project.
WEP is an international non-profit organisation based in Brussels, Belgium, which promotes, supports and advocates on behalf of women entrepreneurs. Having this support from such an organization in this business move enhances the sustainability of our business model.
The iGEM groups, recognizing also the gap that exists in the realization of such a project, show their practical support and participate in this initiative.
Funding
Having completed the Theriac Platform MVP, the project will pursue 750K euros in seed-funding to support the necessary marketing efforts to achieve critical mass. Personnel costs will be focused on integrating the platform with existing NFT marketplaces, while marketing will focus on key client channels – social media, SEO & Google ads.
Figure10. Funding required profile
Coworkers in our future vision are the people that believed in our idea. At the end of our page we cite the letters of support provided to us by: Novartis, WEP, Dr. Dardavesis, Dr. Foroglou, Anadrasis Med!
Honourable Mentions
Falling Walls Lab Greece
Our team participated in the Falling Walls Lab Greece Competition where we won the first place. Thus, we will represent Greece in the semifinals "Falling walls international" which will be held in Berlin in November. The focus is entrepreneurship and is mainly addressed to young innovative students, researchers and professionals in their first steps. The competition requires you to present your idea and develop your business plan in 3 minutes. In this way, we proved that our business idea is viable and interesting to the market by strengthening our innovative idea. We also understood the potential of our project as we explored the possibility for our first potential clients.
WEP
WEP is an international non-profit organisation based in Brussels, Belgium, which promotes, supports and advocates on behalf of women entrepreneurs as an official European body. During the meeting we presented our business model canva and we were given feedback by Mrs. Lina Tsaltampasi which we incorporated into our project. The prospects of our project and the prospect of commercializing such a drug in the market were acknowledged and we were informed about the posible future funding of such a project.
Beetroot
Beetroot is a graphic design company which prioritise the communication design. During this meeting we explored the identity and general branding that our project could have in the market and analysed the potential dynamic that it could have. They gave us feedback about the presentations of the team and the idea and incorporated in our project.
Novartis
Novartis characterised our project as innovative and we explored the applicability of it. They recognized the many potentials of our innovation and agreed to support us.
References
Basu, S., Basu, K., & Austin, T. H. (2022). Communications in Computer and Information Science. San Francisco: Springer Link.
Beethika Khan, C. R. (n.d.). Science & Engineering Indicators. NSF. Retrieved October 12, 2022, from https://ncses.nsf.gov/pubs/nsb20201/u-s-r-d-performance-and-funding
Braintumourresearch.org. 2022. The cost of developing new treatments and the case for front-loading discovery science funding. [online] Available at:
Hanif, F., Muzaffar, K., Perveen, K., Malhi, S. M., & Simjee, S. (2017). Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pacific journal of cancer prevention : APJCP, 18(1), 3–9. https://doi.org/10.22034/APJCP.2017.18.1.3
National Brain Tumor Society. 2022. About Glioblastoma - National Brain Tumor Society. [online] Available at:
Mandel, J. J., Yust-Katz, S., Patel, A. J., Cachia, D., Liu, D., Park, M., Yuan, Y., Kent, T. A., & de Groot, J. F. (2018). Inability of positive phase II clinical trials of investigational treatments to subsequently predict positive phase III clinical trials in glioblastoma. Neuro-oncology, 20(1), 113–122. https://doi.org/10.1093/neuonc/nox144
Rafiq, Q. A., Ortega, I., Jenkins, S. I., Wilson, S. L., Patel, A. K., Barnes, A. L., Adams, C. F., Delcassian, D., & Smith, D. (2015). The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products. Regenerative medicine, 10(8), 989–1003. https://doi.org/10.2217/rme.15.56
Sauermann H, Franzoni C, Shafi K (2019) Crowdfunding scientific research: Descriptive insights and correlates of funding success.PLoS ONE 14(1): e0208384. https://doi.org/10.1371/journal.pone.0208384
Wouters, O. J., McKee, M., & Luyten, J. (2020). Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA, 323(9), 844–853. https://doi.org/10.1001/jama.2020.1166
