Team:Thessaloniki/Entrepreneurship

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Entrepreneurship





Overview


METIS is the diagnostic tool for Pancreatic Ductal Adenocarcinoma (PDAC) that we developed as iGEM Thessaloniki during the iGEM competition 2021. Our diagnostic tool uses urine for the detection of microRNAs that are related to pancreatic cancer. Our goal is to achieve early diagnosis of PDAC, in the 1st & 2nd stage, by making our diagnostic test a part of the annual medical exams for people over 60 years old and for high-risk groups. From the very beginning of our project, we were considering the commercial aspect of it and how to develop our idea into an entrepreneurship plan. For this reason, we took part in the Balkan entrepreneurship competition "Next Stage Challenge", which has a double role, first as a competition and secondly as a startup incubator. We started by identifying the key players and doing a Stakeholder, Market, and Competitive Analysis. With those in mind, we created our business plan, funding strategy, and future timeline plan. We continued with studying the existing regulations regarding medical devices and how to manage our intellectual property. Finally, we discussed and evaluated the interest of industries and manufacturers that are interested in making METIS come true!



Problem Description


  • | Cancer


    Cancer is a generic term for a large group of diseases that can affect any part of the body. Other terms used are malignant tumors and neoplasms. One defining feature of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs; the latter process is referred to as metastasis. Metastasis is the primary cause of death from cancer. According to the World Health Organization (WHO), cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020.

  • | PDAC


    PDAC (Pancreatic Ductal Adenocarcinoma), which is the most common subtype of pancreatic cancer estimated at around 85%, is the 7th cause of cancer deaths. According to the American Cancer Society, more than 114.000 people die every year from pancreatic cancer. The main cause for such high mortality is that most patients with early-stage PDAC are asymptomatic and they are diagnosed at advanced stages, where the treatment options are limited and associated with worse clinical outcomes because in these stages metastasis occurs. As a result, approximately 10% of patients, who are diagnosed with pancreatic cancer, survive and the rest 90% of patients die within five years. So, there is an urgent need to find a method that could potentially diagnose pancreatic cancer in very early stages leading to increased survival rates [1],[2].



Stakeholders Analysis


It is important to identify the people who are involved in a project, its stakeholders, and map their interest and power. This way crucial stakeholders’ needs are met and they can also get involved in the decision-making process and provide support for the long-term sustainability of the project. (Figure 1).




Figure 1. Stakeholders analysis






Market Analysis and Customer Discovery


A market analysis is needed for identifying the customer’s needs and demands. It will also enable us to identify the different geographic market segments and therefore the different business markets METIS will be launched in. This is important, as each market has a different regulatory system and competitors.

Pancreatic cancer is a global disease and is the seventh leading cause of cancer-related deaths worldwide. Our market size is presented through the calculation of age-standardized incidence rates (ASR) per 100,000 people. The ASR is the highest in Europe (7.7), followed by North America (7.6), Oceania (6.4), Africa (2.2). Specifically, the estimated ASR in 2018 for both sexes and all ages are displayed in the following map: [3]



Figure 2. Estimated age-standardized incidence rates, 2018

Pancreatic Ductal Adenocarcinoma (PDAC) accounts for 90 % of the cases of Pancreatic Cancer [4] and leads to great economic loss due to multiple factors. In Sweden, the cost of care for these patients is estimated at 16,066 € over the residual lifetime, while in Germany it is estimated at 31,375 €. Not only the direct costs for treatment should be considered, but also the indirect costs like productivity loss. In Sweden, the mean productivity loss per patient due to mortality was reported to be 238,843 € in men and 220,543 € in women. [5]

With METIS, these costs can be reduced, since it is more affordable than the other diagnostic methods and it can be used as part of the annual health exams of the patients, resulting in diagnosis in the first and second stages of the disease. This is very important for improving the survival rate of the patients and therefore reducing the losses, financial and non-financial, associated with PDAC.



|Competitive analysis



It is based on Porter’s Five Forces Analysis:

Figure 3. Competitive Analysis, 2018






Our Solution: METIS


METIS -> A cost-effective, non-invasive diagnostic tool for Pancreatic Ductal Adenocarcinoma.

Goal -> Improve the poor outcome of pancreatic cancer due to the inability to diagnose the disease at a primary stage.

With the use of a non-invasive sampling method -a collection of urine-, we will be able to diagnose Pancreatic Ductal Adenocarcinoma in the 1st and 2nd stages. For our diagnostic tool, we designed our Toehold Switches, which are specific RNA sequences that can regulate the expression of a gene located downstream of the Toehold Switch. In our case, this gene is the eGFP, which once expressed produces fluorescence, which we can quantify with the use of a fluorometer. More specifically, in the presence of the biomarker in the patient’s urine, the Toehold Switch opens and the expression of the eGFP protein is allowed, the fluorescence produced is measured and the biomarker is quantified.

Our aim is for this method to become part of the annual urine tests that can be executed in every microbiological lab, globally and provide a better outcome thanks to the early diagnosis, especially in high-risk patients.



Next Stage Challenge Entrepreneurship Competition


On May 15th our team got accepted as participants in a Balkan entrepreneurship competition, the Next Stage Challenge, which is organized by the company Ideas Forward with funding from the program Interreg - IPA CBC. (https://nextstage.gr/)





For one month we attended intensive workshops with the thematology being:

  • ~Assumption Mapping & Experiment Design
  • ~Market Analysis & Competitive Landscape
  • ~Venture Funding
  • ~Financial Projections
  • ~Digital Marketing
  • ~Pitching


During this month we also had private coaching sessions with the entrepreneur Nikolaos Tsoniotis, who introduced us to the world of entrepreneurship and helped us create our business plan. On July 23th we progressed through the semifinals and advanced to the finals. We continued with the coaching sessions until the final and focused on three key points:

  • ~Learning how to manage our intellectual property
  • ~Finding out about the existing regulations regarding diagnostic devices
  • ~Learning how to create a spin-off company


At the finals on September 16th, we presented our work in front of 18 experienced evaluators, consisting of venture capitalists, angel investors, and corporate actors looking for innovative ideas. We managed to win 1st place in the Idea Stage and obtain the first place cash prize of 4,000 euros.









Intellectual Property


  • | Patentability:


    The first step we had to take was to ensure that our technology meets the conditions of the patentability criteria (novelty, inventive step, industrial applicability). We achieved that by conducting an extensive Google search, reading all the related scientific reports, and searching for related patents in many databases. After the research was over, we found out for ourselves that our technology meets all the above-mentioned criteria.

  • | Intellectual Property Strategy:


    After we checked our criteria for patentability and saw we do not risk patent infringement, we discussed with our coaches from the Next Stage Challenge and planned our IP strategy.
    We decided to file a patent through the university. The procedure will be through the ΟΒΙ. The university will have a 40% ownership of the patent and since METIS has been invented by all 11 members of the team, the patent application will be filed in the name of every single member in iGEM Thessaloniki.
    Afterward, a spin-off will be established consisting of three members of the team and as an advisor our professor Ioannis Vizirianakis, which will be under a revenue selling agreement with the university and the patent holders. The patent will be exclusively sublicensed to METIS.



Regulations


  • | European Medicines Agency


    The European Medicines Agency (EMA) is the regulatory agency responsible for evaluating, authorizing, and monitoring medicines for human and veterinary use within the European Union (EU) and the European Economic Area (EEA). The agency cooperates closely with national regulatory authorities in EU countries and companies can apply to it to grant a single marketing authorization, which enables them to market the medicine concerned throughout the EU and the EEA. Although our project is in the field of diagnostics and not therapeutics, the communication with an agency that with a single authorization gives access to the market of all European countries could be more than useful to us.
    On the 3rd of September, our team and iGEM Patras team had a zoom meeting with Dr. Iordanis Gravanis, Head of Office of the Scientific Advice, Scientific Evidence Generation Department in the EMA, to whom we presented our projects. After that, we discussed our ideas and the things we should keep in mind when applying for approval. He explained to us that EMA is not responsible for the authorization of diagnostic tools, but he informed us about Emergency Use Authorisation. For the approval of diagnostic tools for diseases associated with high mortality and no sensitive diagnostic technique or specific therapy, both EMA and WHO can accelerate the procedure in cooperation with the Notified Bodies. Pancreatic cancer falls under this category as well. Notified Bodies are the national organization authorized by the EU to evaluate diagnostic tools among other products before being placed on the market. Dr. Gravanis encouraged us to contact the National Organization for Medicines (Greek name: EOF) which is the Notified Bodies of Greece. Following his advice, we had a meeting with a presentative of EOF a few days later.

  • | National Organization for Medicines


    National Organization for Medicines (Greek name: EOF) is Greece’s regulatory organization for medicinal products for human and veterinary use, special nutrition foods and nutritional supplements, biocides, medical devices, and cosmetics. Its mission is the protection of Public Health and, by the European Union’s regulation, all medical devices, and therefore in vitro diagnostic (IVD), too, are evaluated and approved by EOF before they become available to the public as products. Thus, we took the initiative to contact EOF because, for our project to have a big impact on human lives, it should first be available to the general public as a product.
    On the 10th of September, our team contacted EOF through zoom and discussed our project “METIS” with the Deputy Head of the Medical Devices Assessment Department, Dr. Virginia Safra. Dr. Safra informed us about in vitro diagnostic current regulation (Regulation 746) to which our kit is subjected to and generally about medical devices regulation (Regulation 745) to which our device is submitted to. Through this presentation, we were given guidelines and advice for the further utilization of our project and the steps necessary for approval by EOF. In addition, we discussed the course of action we should follow through clinical trials and how they must be conducted so that our project can become a product and be put into production. Finally, we received information about the utilization framework of in vitro diagnostics for “Orphan Diseases”. Pancreatic Ductal Adenocarcinoma (PDAC) is a rare type of cancer and due to that approval and clinical trials could be difficult. Dr. Safra informed us about the Emergency Use Listing procedure both by WHO and EOF, for IVD referred to diseases with high mortality and inadequate diagnostic methods. This information affected the final form of our business model and strategy and we hope that it will make our project easily available to the public.




You can check out our Human Practices page:

Human Practices



Business Plan



|Team



The team iGEM Thessaloniki 2021 consists of 11 members, from 7 different academic backgrounds and research fields, more specifically from biology, molecular biology, and genetics, chemistry, pharmacy, physics, informatics, and engineering. The members are divided into 6 departments: R&D, Fundraising, Communication, Business Development, and Informatics to make METIS come true. To find more information about team members, visit:

Members






Figure 4. iGEM Thessaloniki organogram





|SWOT Analysis



Because we are providing an already existing market with a new product, it is important to carefully construct the product development strategy and develop a sound business plan. The first step to that is to perfectly understand the characteristics of our product, which we tried to achieve by doing a SWOT Analysis.




Figure 5. SWOT Analysis





|Funding Strategy



Throughout our journey in iGEM, we were in fundraising mode to obtain lab equipment and reagents for the experimental procedures for our project implementation and additionally to ensure our team registration and pay the Jamboree fee. From our first steps, we calculate our budget for the experimental procedures, our registration, and our activities. Our total budget was about 47.880 €.




Figure 6. Budget Analysis



To achieve our goal, firstly, we sent emails to approximately 207 medical and pharmaceutical companies, and then we scheduled phone calls to give them more information about our team’s mission. At our first online communication via email, we attached a sponsorship booklet, which includes information about iGEM Competition, our team members, our project description, our budget analysis, and finally specific sponsorship packages for our potential sponsors. The selling points for our sponsorship packages are presented below.

Sponsorship Booklet




Supporter 200€ Bronze 500€ Silver 1000€ Gold 5000€ Platinum >10000€
Your company’s logo will be displayed at the official iGEM wiki page of our team.
Your company’s logo will be displayed at the printed advertising material of our team.
Your company logo will be printed at the advertising material that will be shared at the International Fair of Thessaloniki.
Your company will be promoted through our social media (Facebook, Instagram, Linkedin).
You will have the chance to promote your company with your printed material at our social events (workshops/speeches).
You will have the chance to promote your company with a banner at our social events.
Your company will be mentioned as a sponsor (silver or golden) at advertising articles, scientific magazines and publications.
Your company’s logo will be displayed at our advertising videos.
Your logo will be displayed at the official team clothing.
Your company's logo will be included to our presentation Video.
Your company will have the ability to be advertised by its contribution in our team through your own advertising sites and social media.
After this communication, we scheduled project presentations to the companies, who were interested to learn more about our project. For this reason, we prepare a presentation about iGEM Competition, team creation, our project description and timeline, and finally the budget analysis.

Presentation




In this way, we found our sponsors. To find more information about our sponsors please visit:

Sponsors




For our future business plans, we will continue fundraising. To raise the money we will schedule meetings with potential investors and through our pitch deck presentation, we will give to the investors an overview of our business plan and our diagnostic tool. To find our pitch deck presentation you can click here:

Pitch Deck Presentation






You can watch our pitch deck presentation here:


In this way, we have already presented our project to approximately 27 investors and mentors from all over the world, at the finals of the Next Stage Challenge Competition and 8 of them were interested in scheduling a meeting to learn more information about our technology and our business plan.

In addition, we will ask to receive government grants and scientific grants from the European Union to continue our Research for the diagnostic tool and to build our prototype.

So, by January 2022 we will be in fundraising mode in order to ensure the funds for:
  • ~Filing our patent
  • ~Establishment of spin-off
  • ~R&D and private lab to continue
  • ~Market outreach for IP licensing


Finally, our future needs for our next business steps are detailed below:



Figure 7. Funding Analysis






|Business Model Canvas






Figure 8. Business model Canvas



~Customer Segments

Our team is targeting companies and industries specializing in the field of diagnostics interested in investing and licensing the patent we are developing. These are either companies in the pharmaceutical sector that specialize in the manufacturing of diagnostic tools or companies in general that manufacture diagnostic tools that can be utilized in microbiology labs. Such companies not only have their industrial infrastructures, labs, and Research & Development teams but also possess the knowledge and experience for the manufacture and scale-up of the METIS kit. They need to have experience with how clinical trials are conducted and the licensing standards required for such a device to be approved to be brought to the market. Since PDAC (Pancreatic Ductal Adenocarcinoma) is a global disease, a device used for its diagnosis can be an important piece of equipment of every microbiology lab or hospital so our primary focus is international companies that will promote the supply of the METIS kit around the globe.



~Value Proposition

METIS (miRNA Expression Toehold Investigation System) is a new, innovative molecular diagnostic device capable of performing fast, cheap, and non-invasive diagnosis of pancreatic adenocarcinoma in the first and second stages. Pancreatic adenocarcinoma accounts for 85% of pancreatic tumors, a type of cancer that leads to high mortality due to inadequate, difficult, and untimely diagnosis that makes treatment even more difficult and ineffective with the methods which are used until today in medicine. This device with urine treatment can detect with great accuracy and specialization the presence of adenocarcinoma in the pancreas very quickly and at low cost as the technology it uses is based on the quantification of urine biomarkers and methodology performed with inexpensive laboratory techniques without requiring expensive chemical and biological reagents. In addition, this automated diagnostic device provides the possibility of easy transport and installation so that it can be used by any small or large microbiological laboratory worldwide. Thus, with frequent urologic tests of individuals of vulnerable groups for this type of cancer, a fact this inexpensive method allows, it will be possible to detect the tumor in the first and second stage of its development when patients are asymptomatic, which makes it difficult to diagnose so far with the imaging and the invasive biochemical methods that are being used. Early diagnosis in the early stages excludes the metastatic development of cancer while making any therapeutic approach more effective by increasing the survival rates of the patients with this type of cancer.



~Channels

A channel we will utilize for the initial awareness and customer acquisition will be presentations of our technology at scientific and medical conferences. The project has already been presented at conferences like the Electrical and Computer Engineering Student’s Conference (SFHMMY 2021). It will also be presented in the iGEM 2021 competition organized by the global iGEM Foundation and is attended by many investors, academics, and manufacturers from the healthcare sector. Our team will also organize promotional workshops and seminars, targeting as guests people working in the manufacturing industry, where the function of our prototype will be demonstrated to the public.
Moreover, we have had free media coverage, in the form of TV and Radio interviews and articles, due to the novelty factor of our technology and the support of our university. Since our technology will have proof of concept coming from our laboratory research, the results from this research will be made public by a scientific publication and in this form reach innovation leaders in the healthcare sector. Customers can find us through our website and social media (Facebook, Instagram, LinkedIn). Last but not least, we will do direct sales by utilizing the results of our market research, which was targeting to find companies and manufacturers in the field of diagnostics interested in our technology, and then we will directly approach the companies we believe will be interested in our technology.



~Customer Relationships

The relationships between us and our customers will have many levels. Our direct interaction will be through physical contact after a scheduled appointment and will be reserved for important decisions. Indirect contact will be achieved by email and phone contact with a dedicated personal contact that will be used for everyday issues that come up. Moreover, we will provide technical support by experienced personnel for any issues that may come up with our technology or with the scale-up process. Our relationship will continue to evolve as we will gradually offer the customer more deals for new biomarkers, aiming at different types of cancer that can be detected with the use of our technology.
Further support will be given to our customers in the form of workshops and seminars, where the use of our kit will be demonstrated and its basic principles will be explained. The research and development team of our client will be trained so that they will be able to work with the biological materials needed for the kit and make copies of the prototype that reproduce the same results.



~Key Activities

The key activities that are required for the successful construction of the METIS diagnostic device include, at an early stage, the literature search for the appropriate biomarkers excreted in the urine of the patients during the early stages of pancreatic adenocarcinoma, as well as the techniques required for their detection. Then, with the use of programming tools (software development) the design and production of specific sequences will follow. These specific sequences will be able to accurately detect and quantify specific biomarkers in patients' urine. Once the effectiveness of the diagnostic tools is certified at a laboratory level by conducting a series of experiments that will certify the sensitivity and specificity of the diagnostic method for this type of cancer, the automation of the methodology and the construction of the diagnostic machine using a microchip called Arduino will follow. Our machine will process the biological materials and will display the quantity of the three microRNAs in each sample.
With the completion of the above processes, the goal is to obtain a patent in Greece and abroad that will describe in detail the technology on which the device was based, how it works and the methodology to be followed for early diagnosis of PDAC using the METIS device. Finally, marketing and advertising campaigns will be carried out where the product, its development technology, and the way of its use will be presented to be announced in the field of Medical and Pharmaceutical companies that specialize in the production of diagnostic tools. Following the grant of the patent rights, companies will be able to undertake the manufacture and production of the diagnostic machine on an industrial scale to be available to the public.



~Key Resources

The supplies available to our team that will contribute to the achievement of the goal are patenting, which secures the property and copyright around the effective methodology for detecting pancreatic adenocarcinoma in the first and second stage using METIS device. For the development of the diagnostic tool that will lead to the submission of the patent, the expertise of the inventors will contribute both at the level of molecular biology and synthetic biology and also at the level of development of programming algorithms for the construction of sequences for diagnostic use in biological samples. An additional crucial role in the development of the diagnostic device is played by scientific knowledge, laboratory experience, and specialization in the design of molecular diagnostics that was acquired during its implementation. The laboratory development and certification of this tool are highlighted by the design of a suitable processing microchip capable of easily giving the user the amount of each microRNA in the urine sample (hardware development). Also, access to the university laboratory space, fully equipped with the appropriate equipment as well as the supply of biological materials make it possible to conduct the research laboratory process and test the diagnostic tool in vitro before conducting clinical trials. Finally, the critical factor for the successful development of the diagnostic tool is the human resources consisting of students in the fields of Health, Exact Sciences, and Polytechnic Science. The interdisciplinarity and specialization that characterizes the composition of the research team gather the necessary supplies both for in silico design of the diagnostic tool and in vitro control of its use as well as for the final, integrated, and certified development of the METIS diagnostic machine.



~Key Partners

Among the main partners that contribute to the creation and promotion of the METIS tool is the Aristotle University of Thessaloniki both by providing the laboratory facilities with the appropriate equipment for conducting experiments and by the scientific and advisory support of the university staff i.e., professors and researchers working on campus. Advising on the proper scientific development and laboratory design for the creation of the METIS diagnostic tool is also provided by non-university partners such as health scientists, researchers, professors from other universities, and business executives on diagnostics. In securing the financial resources for the supply of raw materials for the research and development of the tool as well as for any activity, the assistants of our team are sponsors from the Medical-Pharmaceutical and research field. In addition, for the conduct of laboratory experiments, it is important the contribution of relevant suppliers, who give us the necessary biological materials and equipment for the experimental procedures required by the development of the diagnostic machine. Furthermore, to obtain a patent in which the methodology and technology of the METIS will be precisely analyzed, it is necessary to cooperate with specialized legal staff that will research possible patents in the same subject as well as the bureaucratic procedure for writing and copywriting of the patent in each country.



~Cost Structure

Our team will have initial costs, including the costs of biological materials and lab maintenance. After the development of our prototype, our research costs will continue to increase, since we will not stop after the creation of a diagnostic tool for PDAC. We aim to create diagnostic tools for different types of cancer by detecting different biomarkers, with the use of the same technology. We are also considering marketing costs such as market research to find companies and manufacturers in the field of diagnostics interested in our technology, not only in Greece but worldwide as well. After our target group is identified, we will need to promote our product to the right circles, to attract interest and get approached by companies or investors. Also, regarding marketing costs, an upgrade of our social media is needed. We will need to cover the cost of our legal partners, too. They are needed for doing all the necessary paperwork for the filing of the patent and for the non-disclosure agreements our team will sign with other external partners and create our statute. The cost of a patent attorney will also be included in legal costs, as well as the cost of filing the patent itself. Lastly, necessary investment in human capital will be needed.



~Revenue Streams

Our largest expected revenue stream will be the profits gained by sublicensing the patent. There will be exclusive sublicense categories regarding different geographic regions. Moreover, we will offer professional services in the form of creating diagnostic tools for custom biomarkers and therefore enabling the detection of different types of cancer. Since we are a team affiliated with the university, we will also apply for research grants and other funding opportunities that will enable us to continue our research work and improve our diagnostic device.






Industry Interest






Research Genetic Cancer Centre (R.G.C.C.) - According to our business model, after filing our patent we will get in touch with pharmaceutical companies and manufacturers of medical devices to sublicense our technology to build our diagnostic tool. To achieve this, on Wednesday 14/07/2021 we visited the Research Genetic Cancer Centre (R.G.C.C.), which specializes in the development of diagnostic and therapeutic tools for cancer. After a tour of the company premises to see the workflow of the production of diagnostic devices such as our tool “METIS”, we met Dr. Ioannis Papasotiriou, oncologist and Founder of the Company. Throughout this meeting, we presented once again our project and our first experimental results, which provide a proof of concept for our project and we received feedback for how we can continue with our experimental procedures. In this discussion, Dr. Papasotiriou validated the value of our tool, which could lead to saving people’s lives, and expressed his interest to license a patent on our project and produce the diagnostic device for PDAC. Moreover, he informed us that he could help our team with the clinical trials, which will follow after the iGEM Competition. This could be achieved since his company cooperates with companies and agencies in Europe that take over to execute clinical trials through urine samples processing.



Pfizer - Another important pillar of our human practices plan of action, concerned the companies that could offer their experience and feedback. So we considered that it was very important to understand if our diagnostic tool could be practically materialized for people to be tested. For that reason, we contacted industries of medicine like Pfizer, one of the biggest industries of medicines and molecular diagnostics. Our meeting happened on 24/09/2021 with Ms. Karamanou Vasso, the head of the corporate social responsibility team of Pfizer Hellas, and Mr. Aggeloudis Nikolaos, Public Affairs Manager in Pfizer Hellas to present our project and take feedback so that we could improve our idea. Apart from their warm support of our research goal, they pointed out the importance of multidisciplinarity for the development of innovative ideas and they confirmed the importance of early diagnosis of all types of cancer and especially for aggressive types like PDAC.







Time Plan




The timeline of the first two years of METIS is presented in the following diagram:


Figure 9. Future Timeline for our team






Summary




Our goal for our entrepreneurship efforts was to discover the steps that should be done to release our tool to the market. In conclusion, our Entrepreneurship study consists of the following:

  • 1.Stakeholders analysis
  • 2.Intellectual Property study
  • 3.Business Model Canvas
  • 4.Fundraising Strategy
  • 5.Customer segments analysis
  • 6.SWOT analysis
  • 7.Regulations for molecular diagnostic tools study
  • 8.Future timeline
  • 9.First prize in Next Stage Challenge Competition







References