Entrepreneurship

Overview

DIAS is a diagnostic tool for Lung Cancerthat we developed by iGEM MetaThess team during the iGEM competition 2022. Our diagnostic tool uses blood samples for the detection of microRNAs that are related to lung cancer. Our goal is to achieve early diagnosis of lung cancer, in the 1st & 2nd stage, by making our diagnostic test a part of the annual medical exams for people over 40 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 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 DIAS come true!

Problem Description

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2021. Lung cancer (both small cell and non-small cell) is the second most common type of cancer in both men and women ( (Ferlay et al., 2020). According to the World Health Organization, in 2020 more than 2.2 million new cases were reported, where more than 1.5 million people died. (Globocan, 2020) In general, about 84% of lung cancer incidents are Non-Small Cell Lung Cancer (NSCLC).

Thus, it becomes clear that while lung cancer is the second most common type, it is the first most deadly type of cancer counting approximately 10 million deaths in the last five years. This high mortality is mainly due to three main factors. First, patients in the early stages are asymptomatic and start to show symptoms from stage 3 onwards where the size of the cancerous tumor is about 7 cm which excludes the option of surgery. Therefore, late diagnosis leads to reduced treatment options which prove to be insufficient and ineffective. In addition, in the advanced stages of lung cancer, metastases are created, for example in the brain, which make it difficult to treat the cancer since vital organs are affected. Finally, this specific type of cancer shows great resistance to chemotherapy drugs, with the result that it fails as a treatment option.

In addition, there is no cheap diagnostic technique that is non-invasive and can be added to the annual check-up to detect the cancer tumor in the initial stages when the patient is asymptomatic. Specialized chest CT, MRI technique and liquid biopsy cannot be performed annually because they are expensive and invasive. This immediately creates the need to find an easy and cheap diagnostic methodology that can be supported by the Health systems of each country and offered on an annual basis to the population.

Stakeholders Analysis

Stakeholders analysis is key to assessing their needs and expectations as well as their potential project impact if the need is not met. So, from our first steps in order to complete our project design, we contacted them so that we can adapt our diagnostic tool to their own requirements and capabilities and get it to market soon. Therefore, we map the interest and power of each player (Figure 3).

Market Analysis and Customer Discovery

To identify customer's needs and demands, we should first analyze all the segments and different aspects of the market, in order to build a sound business strategy for DIAS, our diagnostic tool. Through the market analysis process, we were able to identify not only the environment and the regulatory system that DIAS is going to be launching into, but also the competition that it is going to face.

Lung Cancer is a global disease and is the first leading cause of cancer-related deaths worldwide. At the figure below, the distribution of deaths of all ages caused by lung cancer is shown. The highest mortality is observed in Europe, Asia and the United States of America. According to the United Nations, the world population in 2019 was 7.9 billion, of which 54% are people aged 40-99.

Risk factors for developing lung cancer are smoking, family history, exposure to harmful chemicals and environmental pollutants. In addition, after the age of 40 the risk of lung cancer increases sharply. Thus, an annual diagnostic examination for lung cancer is recommended in the categories of increased risk mentioned above, that is, according to the data of the UN, it will be addressed to more than 4 billion people of both sexes, worldwide. With the annual screening, which will be an inexpensive procedure using the diagnostic tool DIAS, an early diagnosis will be achieved and thus the government costs spent on cancer treatment will be reduced.

• Competitive Analysis

In order to measure competition intensity, attractiveness and profitability, our analysis was based on the Porter's Five Forces model. Porter's Five Forces is a model that identifies and analyzes five competitive forces that shape every industry and helps determine an industry's weaknesses and strengths. Five Forces analysis is frequently used to identify an industry's structure to determine corporate strategy.

Especially,

1. Threats of new entrants = LOW
• Existence of legal barries like strong Intellectual Property rights
• Provisional Patent
• R&D high budget
• Pioneering Technology and complexity of our diagnostic tool
• Expertise and validation of methodology
• Well-regulated market for in vitro diagnostics
2. Power of suppliers = LOW
• A lot of suppliers for biological reagents for CRISPR/Cas13 system
• Many suppliers for 3D-printed materials
• Economic and adaptable alternatives
3. Threats of Substitutes = MEDIUM
• No available substituted products
• New revolutionary technologies /patents have the potential to change the field
• High customer switching costs
• Expensive diagnostic techniques, requirment for specialised personnel
4. Power of Buyers = MEDIUM
• Limited number of competitors
• Price sensitivity
• Big marketplace

Our Solution: DIAS

In order to solve the problem of late diagnosis of the lung cancer to increase the survival rates we present you DIAS. DIAS is a cost-effective, quick and cheap diagnostic tool that uses blood samples to detect lung cancer in the initial stages (stage I & II). Our goal is to improve the poor outcome of lung cancer due to the inability to diagnose the disease at a primary stage. Our diagnostic method based on the detection of RNA molecules secreted in large quantities in the blood of patients with early stage lung cancer. Using CRISPR/Cas13a technology and with the help of a Microfluidic Chip that we have designed and using a simple fluorescence microscope we can accurately quantify these RNA molecules by measuring fluorescence. So when they are found in high quantities, we will know with great precision that the patient has stage I & II lung cancer and will be referred to more specialized tests so that treatment can follow. We recommend that this technique be added to the annual screening of people over the age of 40 and people who belong to high-risk groups. Thus, with a simple blood test, an early diagnosis will be made and the chances of specialized treatment will increase.

Intellectual Property

Intellectual Property Strategy

From our first steps we discussed about the strategy we should follow to promote DIAS tool to the market. So we decided to complete the experimental procedures to the in-vitro proof of our concept and then file a provisional patent to secure our licenses. From the moment the Project design was completed, we signed aNDA - Non Disclosure Agreement between us to be sure that the idea belongs to all of us.

Then, we had a meeting with the Representative of the Technology Transfer Office of Aristotle University of Thessaloniki Mrs. Eri Toka. We desided that the university will have a 3% ownership of the patent and since DIAS has been invented by all 8members of the team, the final patent application will be filed in the name of every single member in iGEM MetaThess team as co-inventors. Also, our PI, Dr. Ioannis Vizirianakis will have a 3% ownership of the patent. Indeed at 10.10.2022, just before the "wiki freeze" deadline, when all the information regarding our project would be published, we filed for a provisional patent at the USPTO - U.S. Patent and Trademark Office with title "A method and biomarker for early non-small cell lung cancer detection" and with No. 63/414,680.

Then we will establish a spin-off that will be under a revenue selling agreement with the university and the patent holders. The management rights of the patent will belong entirely to the spin-off which will undertake the sublicense to manufacturers, which will produce the diagnostic tool and will offer it to diagnostic centers. So, the spin-off will have revenues by the sublicensing, 5% of the manufacturer's revenues according to the royalty fees.

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.Then, we collaborated with a patent attorney in the United States where he wrote a summary of our project, did pre-research and assured us that it is free to patent. After the research was over, we found out for ourselves that our technology meets all the above-mentioned criteria.

Regulations

Very important to build an integrated diagnostic tool that can be used by diagnostic centers in the future was to investigate the regulatory framework for in vitro diagnostics tools. We were also interested in learning the process and the documents we should submit in order to have our diagnostic tool approved by the relevant organizations.

• National Organization of Medicines | 3.08.2022

National Organization for Medicines (EOF in Greek) is the regulatory organization in Greece for medicinal and pharmaceutical products for human and veterinary use, food supplements, medical aids and cosmetics. EOF in line with the regulations of the European Union evaluates and approves new safe and effective products. Among its mission is the control the production of in vitro diagnostic products before they are widely implemented. Communication with this sector was therefore imperative in order to ensure the safety and effectiveness of our diagnostic tool and to thoroughly investigate the bioethics of our project.

We performed an insightful zoom meeting with Ms. Nikokavoura Aspasia, Chemist and Employee of the Health Material Evaluation Department of the National Organization for Medicines. We found out that our diagnostic is a medical technology product and for such products, there has been new legislation established (Regulation 2017 746) that has facilitated the approval process so that it is carried out more directly, including all stages of the product. All products are classified into three categories according to their specialization and ours is subject to category C. Conducting specific experiments to ensure the effectiveness of the tool is strictly defined for each category. We were also informed that the exact completion of a technical file for our product is mandatory. This file should contain detailed information not only about the process and the production stages, but also preclinical, and clinical data and information about the stability and specificity of the product. After the file is completed with all of the above information, it has to be sent to a notified body and that is the last step of the approval process.

• European Medical Agency - EMA | 1.10.2022

On Saturday 1.10.2022 we scheduled with our partners iGEM Patras Medicne 2022 team, an online meeting with a Representative of the European Medical Agency (EMA). Firstly we described the mechanism that our diagnostic tool uses as well as the process that a microbiologist must follow to use the DIAS tool and obtain the diagnostic result. The EMA Representative informed us that in 2021 the law 2017//0746 concerning medical devices for laboratory tests considered IVDs (in-vitro Diagnostics) was amended to be classified in the category of Companion Diagnostics. In order to file and get our tool approved for this category, we would have to associate it with a chemotherapy drug for lung cancer. So we searched the literature and suggested that in cases where our diagnostic test is positive, the patient should be referred for more specialized tests and once the existence of the cancerous tumor is established, cis-platin and paclitaxel should be administered to shrink the tumor. He also told us to read the medical device legislation 2017/0746 carefully and follow the steps outlined there. Finally, he recommended us to contact the Ministry of Health and more specifically the HTA - Health Technology Assessment to inform us about the process we need to follow in order to add the DIAS diagnostic tool to the annual screening.

Business Plan

Team

The team iGEM MetaThess consists of 8 overgraduated students, from 5 different academic backgrounds and research fields, more specifically from biology, medicine, pharmacy, physics and economics. The members are divided into 6 departments: R&D, Fundraising, Communication, Business Development, and Informatics to make DIAS come true. To find more information about team members, visit our team page .

These members will create the spin-off with the help of Dr. Vizirianakis Ioannis, who will be included in spin-off as advisor.

SWOT Analysis

Since, 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.

Funding Strategy

In order to continue our activity to make DIAS come true we will start the new fundraising cycle and we aim το raise money by 3 basic ways:

1. 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.
2. We will participate to business competitions with prices such as the 13th Innovation and Technology Competition, which organized by the Greek National Bank and you can find more information here.
3. We will get grants from the European Union such as Horizon funding programm. For more information you can visit the website.

Business Model Canvas

Industry Interest

From the first steps of the development of the DIAS diagnostic tool, our team considered it very important to get in touch with companies and industries in order to determine if the tool it proposes is feasible to manufacture in the market. We were also interested in confirming the value of our diagnostic methodology and whether industries would be willing to invest time and equipment in order to manufacture this diagnostic kit for the early diagnosis of lung cancer. The team believed that securing the support of large companies to produce our tool would bring us closer to our dream of giving the whole world the opportunity to perform this test.

• Research Genetic Cancer Center S.A. - RGCC Group | 15.04.2022

RGCC Group is a specialist medical genetics company, established in 2OO4 with headquarters in Switzerland. We are experts in developing and providing personalized cancer genetics tests for doctors and patients, and testing tumors for sensitivity and resistance to chemotherapy treatment and a range of natural substances. We are actively involved in pharmaceutical research and development. Our facilities are equipped with the most technologically advanced equipment and specialized software for data analysis. On Friday 15.04.2022 we visited the lab facilities of RGCC Group in Florina, Greece. First, we joined a tour of the labs and industry. There we saw the equipment they have and it was confirmed that the reagents used by our technology can easily be produced there.

Then, we were taken to the meeting room where we had a very interesting discussion with Dr. Papasotiriou Ioannis, an Oncologist and founder of RGCC Group. He explained to us that one of the biggest problems in treating cancer is that patients in the early stages have no symptoms. This leads to delayed diagnosis and doctors end up at a dead end because they cannot proceed with surgery nor do they have many treatment options and the progression of the disease is rapid. He also emphasized that while chemotherapy can be applied in the final stages, it actually weakens the immune system of the patient, who is susceptible to infections. In both cases the result is death. So he agreed with the idea and direction of our team as he said that he considers it particularly important to add such tests to the annual screening of the population as this would have a huge influence on the successful treatment of cancer. In addition to his advice, he offered to be a key sponsor of our effort as he believes that truly bringing such diagnostic tools to market could have an impact on public health and should be done immediately. After this discussion, he said that he can offer blood samples from patients to validate our technology and proposed a future collaboration.

• KARABINIS MEDICAL S.A. | 4.10.2022

On Tuesday 4.10.2022 our team scheduled an online meeting with Mr. Stamatiou George, Business Development Director of KARABINIS MEDICAL S.A., and Mrs. Karioti Myrsine, Executive Assistant to President and Managing Director of KARABINIS MEDICAL S.A. After the presentation of project DIAS they expressed their enthusiasm and congratulated our team for our innovative tool. They explained to us that the company they work for is active in the field of diagnostic devices and that they would definitely be interested in future collaboration. In addition, they explained to us how important it is for Public Health to have such special diagnostic techniques that make early diagnosis easy and cheap. They recognized the impact of our project in increasing survival rates. Finally, they congratulated our team for the flawless design of the project, for the cost analysis, and for the business analysis.

• ELPEN Pharmaceutical S.A. | 22.07.2022

On Friday 22.07.2022 we contacted Mr. Vakalopoulos George, Corporate Communication Associate at ELPEN Pharmaceutical S.A. After the detailed presentation of the diagnostic techniques we use, Mr. Vakalopoulos emphasized that biotechnology products are the future of Diagnostics. He told us that ELPEN Pharmaceutical S.A. aims to create medical devices that will upgrade people's standard of living. Thus, he commented that our own diagnostic tool will be very important for the prevention and diagnosis of lung cancer and will make it easier for oncologists to choose the treatment. Also, based on the cost analysis of our device and based on his experience, he said that it would definitely be able to be carried out annually and that it could easily be produced by an industry. Also, he congratulated us on our organizational skills and our professionalism. Finally, he asked us for printed material with the description of our project to study it.

After this discussion, he contacted us and told us that our project accepted the evaluation of their company with the highest rating and that they will finance us as sponsors because they believe in our innovative idea. They also expressed interest in future collaboration on the production of the DIAS diagnostic device.

Future Timeline

So far the first round of Fundraising has been carried out, R&D has started, experimental procedures and Project modeling have been completed. We proved our concept in the lab and we completed our business analysis. Finally we filled provisional patent. After the competition we will establish a spin-off which will manage our patent licenses and will be responsible for licensing to manufacturers that will produce our DIAS diagnostic tool. Furthermore, we will start the new funding cycle in order to continue the R&D and to do clinical trials. Then the market outreach to find industries all over the world thta be inderested on our technology and the promotion of our tool will follow. Our future steps were presented in a cycle not in a line. This is why after this procedures we will start the new cycle in order to find new biomarkers and create a diagnostic tool for another type of cancer and we will follow the same route. By following this steps we hope that the people will “meet” DIAS in the diagnostic centers in a few yearw.