Team:UNILausanne/Entrepreneurship
Business Plan
Problem description
Colorectal cancer (CRC) is the third most common cancer worldwide, affecting over 1 million people every year. The current therapies, surgery and chemotherapy, involve [1] substantial risk for complications and negative side-effects . We want to develop a [2] targeted therapy with high safety and specificity to help with this problem.
Our solution
Our treatment consists of a probiotic bacteria (E. coli Nissle 1917) inside of an oral pill. Our bacteria with the repressilator will colonize the area inside of the cancerous tissue in the colon and release azurin (a natural occurring peptide) directly into the tumor. This drug has proven anti-tumoral properties that will be exploited to assist in the destruction of cancerous cells, without damaging healthy intestinal tissue. The bacteria will be encapsulated to ensure their intactness in the colon. This treatment is non-invasive, and needs to be taken orally twice a month (depending on the turnover rate of the gut). Azurin will be released in an oscillatory manner every 24h without the need of external stimuli, eliminating the necessity of having doctor appointments and check ups inconveniently often.
Stakeholder Analysis
A stakeholder analysis determines people or a group of people who will be affected or involved in our project before the project begins, and can mobilize resources to influence its outcome in some type of way; grouping them according to their levels of participation, interest, and influence can give us an insight into who we will target with our marketing strategy [3].
The purpose of doing this type of analysis is to know which key players we would need to approach to help in the early stages of our product, and try to peak their interest and earn their support for our project. Knowing which types of groups will influence our project can help us avoid conflicts or issues before beginning the recruitment for help, for example the interest in our project of a private investor and of a NGO will most definitely not align and result in conflict.
For a project such as ours, where we are developing an experimental treatment for cancer, this type of disease is not of interest for public NGOs (such a WHO) so even if they could have a lot of influence their interest in our product will not be high. In the high influence, high stake, we will group the actors that will have the biggest impact on our project. As you can see in figure 1, patients will be the ultimate consumers of this treatment after B.O.T is released in the market, however, as of now their influence will not be as high as some of the other actors even if they are interested in alternative cures to CRC. We will explain in more detail below why our current target audience will be investors, biotech companies and experts. They will legitimize our project, bring resources as well as open the door to the market, but as they are high stakes, they could change their mind at any moment and pull out their support.
Intellectual Property Considerations
When working on innovative technologies, the protection of creations through the Intellectual Property system must have priority in the process. This provides the title owner the possibility to obtain an exclusivity in the use and exploitation of the product/ service. Intellectual Property (IP) refers to creations of the mind (names, images, works, inventions).
The law provides the tools to obtain the protection of these creations in the form of patents, copyrights and trademarks, which enables a recognition of the entitlement over an invention and the right to obtain an economic benefit from the same. For example, if we seek to create a startup based around our B.O.T technology, as well as obtain an exclusive right to use it, sell the final product or license the technology, we should apply and obtain a patent registration for our procedure and/or product, as well as a record trademark for the product. Our idea will then be protected from competitors trying to make an unauthorized use of the same, improving our probabilities of attracting investors as well as business partners [4].
Patent:
A patent is an exclusive right granted for an invention, as long as it offers an innovative way of resolving a problem [5].
To verify if our procedure/product could be patented, we obtained counseling from an Intellectual Property Lawyer as well as doing an extensive internet search about the state of art related to new modified microorganisms with a determined function such as B.O.T. The conditions that need to be met to obtain an invention patent are:
- The Invention should be novel in the state of art (novelty requirement): In our case, the azurin release coupled with oscillations by a microorganisms, is not known in the state of art (there are no previous patent applications/registrations, no publications or other type of disclosure that may affect its novelty)
- Complies the inventive step requirement: The invention should not be obvious for an expert in the field. We consider that we used established genetic modification techniques to create a new product that comprise a technical difficulty that is not obvious for the general expert in the field, which in our case is an oscillatory system coupled with an anti-cancer drug release.
- Industrial use requirement: The invention will be subject to its reproduction, have an industrial application/business purpose and will be manufactured as a therapeutic drug to be sold and then be used by CRC patients.
- The patentability of the use of the drug and as a medical treatment depends on the jurisdiction of the different countries we want to target.
State of Art search:
The State of Art search (applications and granted patents) puts our patent in perspective with past and present technologies of similar nature within a technical field and thus allows us to conclude if there is a possibility to patent. It can also help identify our possible competitors, the novelty of the invention, as well as prevent our product from infringing other already existing patents. To determine if the invention has [6]already been covered by a valid patent (and could mean an infringement and impossibility of patenting), or an abandoned application or expired patent (that would mean that the invention is already in the state of art, and therefore non-patentable), we need to pay attention to the claims protected by the patents. The following are some examples of patents found at the PatentScope site, which may be considered as [7] precedents to our invention, but they do not affect its novelty:
- With the keyword "Repressilator": "CN101475907 - CIRCUIT STRUCTURE FOR REALIZING SYNCHRONIZATION OF INTERCELLULAR OSCILLATORS" . Invention [8] that uses a repressilator circuit (with LacI, TetR and cI), but unlike our invention, it takes an external input to function while ours is independent.
- With the keywords "bacteria, AND oscillation, AND secretion, AND drug": WO2020018989
- PROGRAMMABLE BACTERIA FOR THE TREATMENT OF CANCER . A bacteria is modified to release an anti-cancer immunotherapeutic [9] agent (not specified which one). Then the bacteria colony performs a synchronized lysis. The novel part of our invention is that the bacteria secrete the drug and can stay alive after the secretion.
- Searching for the phrase "PROGRAMMABLE BACTERIA TREATMENT CANCER": US20190134105 - METHOD FOR PRECISE IDENTIFICATION, TARGETING AND DELIVERY OF DIRECTED THERAPIES WITH THE USE OF BACTERIA FOR THE DESTRUCTION OF CANCEROUS CELLS : One of the methods listed in the claims [10] is the bacterial proliferation within aberrant cells (cancer tumor) that selectively destroy cells. This is a pending application not granted yet. The claims filed are not clear, too broad and not yet approved.
Registration procedure:
To protect our invention, we would need to file a patent application. We could begin by filing an application in Switzerland and then in the regions that we are interested in targeting (through the PCT - the Patent Cooperation Treaty ). The modified bacteria [11] should also be deposited at the WIPO (through the Budapest System) to be evaluated by a biotechnologist to demonstrate a degree of innovation. The DNA sequence of the bacterial chromosome as well as the sequence of the two added plasmids can be registered under an invention patent.
[Here we are doing a hypothetical analysis, it needs to be disclosed that the plasmids were obtained from Addgene where we signed a material transfer agreement (MTA) that would prohibit the commercialization of the plasmids sequences. For the sake of this analysis we are considering as if we build the plasmids ourselves]
Trademarks
A trademark is a sign that allows the distinction of similar goods of services from one company to another. They are protected under IP laws. [12]
A trademark application for the name "B.O.T Bacterial Oscillation Therapy", as well as the two logos (figure 1 & 2) should be filed. We would need to apply for the trademark(s) at the Swiss Federal Institute of Intellectual Property to protect the jurisdiction of Switzerland, and consider also a Madrid Convention application to also facilitate the protection in other countries that are parties of that Convention. We also need to consider other important jurisdictions that may not be part of these conventions in where we wish to protect the invention. A company can be formed by the twelve members, and this entity may be the applicant that will obtain equal ownership of the two trademarks .
The trademarks to be filed consist of the B.O.T. logo and the B.O.T. Bacterial Oscillation Therapy (word mark).
The final product would consist of a pharmaceutical product, hence the product would be protected under International Class 5 (pharmaceutical products ).[13]
Copyright
Copyright or author’s right is the right of an author over a literary or artistic work since their creations. Computer programs, databases and technical drawings are all protected under copyrights. [14]
If we decide to create manuals or brochures with text and technical illustrations to explain how our product works, these would be protected by copyright. Its protection is born from its date of creation with no need of registration, however, they can also be deposited before the Swiss Federal Institute of Intellectual Property to obtain a deposit certificate.
Market Analysis
A market analysis assesses the size of the market that our product could reach as well as the monetary value that would be available. It analyses the different segments that will be targeted to take into account the buying pattern of customers as well as existing competitors that could limit our reach.
Our product is still in the development phase and we are looking to develop it further with animal and pre-clinical trials focused on CRC. This technology has an easy application (just has to be taken orally like a normal pill), and is non-tissue specific (once ingested the bacteria is attracted to the tumoral area after being released in the colon). It has a cheap production price and the treatment administration has to be taken twice a month, not quite as often as normal chemotherapies for cancer treatments, and once in place the system is independent without the need of external manipulation.
Market Segmentation
Market segmentation is the process that divides potential customers into segments or groups with similar characteristics amongst them. The segments will be targeted with similar marketing strategies, therefore expecting that the customers in the same segment will react similarly. [15]
We have to target different segments in the market:
- Biotechnology companies on the biomedical or oncology domain - Researchers (private and public)
- Specialists: Oncologists, gastroenterologists
- Potential investors outside of the scientific field (Business angels, financial advisors, venture capitalists, etc)
We are basing our analysis on socio-economical criteria, targeting the segments of groups of people (or companies) with high scientific expertise and/or a somewhat high financial power.
We want to start developing our business in Switzerland where funds for cancer research are more readily accessible. However, since our production cost is not high, the price will be relatively accessible (in comparison to other therapies) which will allow us to expand to an international market, more specifically the market of developing countries (such as Latin America and Southeast Asia).
The reason why we are focusing on those regions is that a product that would not need regular doctor visits would be interesting where constant access to hospitals or specialists would not be practical or possible. Also, as it is not a stand-alone treatment it would not be as interesting in countries with a more robust health system where stronger treatments are available.
Target analysis & Expectations
Because we have not conducted our animal or human trials as of yet, our product cannot be on the market or be legally marketed towards patients/users. Thus our target demographic will be experts in the oncology field, biomedical microbiology researchers as well as big biotechnology companies.
We will aim to obtain funding to progress in the development of our product and conduct our animal and pre-clinical trials. With our product, we are giving oncologists an alternative after surgery treatment for their patients with less intensive follow-ups, while the companies would look for a functional and promising product that would allow a return on investment in the future.
Competitors
The current cancer treatment market is constituted mostly of chemotherapy treatment and pharmaceutical drugs. To prevent tumor recurrence and metastasis in CRC stage II and III, after surgery drugs are given as treatment [16]. These treatments need to be administered often and have a lot of side effects, as they are quite aggressive against healthy cells as well as cancer cells.
Our main competitors will be drugs or treatments that treat mainly (or exclusively) CRC. Therefore, we would be competing with chemotherapies such as:
- Adrucil (or 5-fluorouracil) known for its use in chronotherapies for CRC by injection into a vein (around $38 for a supply of 100 mL)[17]
- Leucovorin (or Folinic acid ) used in combination with 5-fluorouracil for CRC taken [18] orally, injection into the muscles, or injection into a vein ($13 for a supply of 1 powder for injection)
- Xeloda (Capecitabine ) in the form of an oral tablet taken twice a day. The cost for a [19] Xeloda oral tablet 150 mg is around $859 for a supply of 60 tablets
- Eloxatin (Oxaliplatin ) used together with Adrucil and Leucovorin or with Xeloda, [20] given by injection into a vein. The cost for Eloxatin intravenous solution (5 mg/mL) is around $1,395 for a supply of 10 mL
All of these drugs have to be taken in high dosage to affect the tumor (compensating for the diffusion in the body) and cause very harsh side effects as a consequence. [21]
Other companies with similar projects/products to ours such as Redbiotec AG (bacteria to treat pancreatic cancer), T3 Pharmaceutics AG (bacteria that target tumors in general) and PharmaBiome (non modified bacteria strains that target pathologies) are starting to develop treatments that use bacteria to release drugs in the body and could become potential competitors, however their research area is not targeting CRC.
Market Need
"Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. There were over 1.8 million new cases in 2018 […] Colorectal cancer is considered one of the clearest markers of epidemiological and nutritional transition, with incidence rates of this cancer – together with other cancers linked to Western lifestyles” [22]
- World Cancer Research Fund.
In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years/ [23]
With millions of cases every year, our treatments against colorectal cancer would always be in demand everywhere in the world. However, in North and South America, CRC is the fourth most common form of cancer with 240.000 new cases and approximately 112.000 deaths in 2014 (and expected to increase by 60% in cases by 2030 according to the Pan American Health Organization). Focusing on developing economies going through socio-economic transition would be interesting for this type of cancer as the demand for treatment would be expected to increase with time with the transition into a more western type lifestyle, having as a consequence an increase of cases with the passage of time. Our technology would also not be in competition with other alternative treatments either, as their high price makes them inaccessible for people with lower income. [24]
SWOT Analysis
SWOT stands for Strengths, Weaknesses, Opportunities and Threats. A SWOT analysis allows the assessment of these four aspects in our project, to predict failures by being aware of what our product lacks as well as to know what are our advantages.[25]
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| Opportunities | Threats |
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Marketing Strategy
A marketing strategy is a long term plan that aims to give a business a competitive and strategic advantage by analyzing and understanding the needs and expectations of customers. [26]
Because we have not done all the necessary tests and trials to put our product on the market, we will be aiming out marketing towards academia, medical experts and biomedical companies with a B2B strategy that does not target users or patients. This strategy targets the interests and needs of individuals who are making purchases on behalf of an organization or someone other than themselves. The reason why we are choosing this strategy is that we are not legally allowed to market to patients as our product is still in the experimental phase, and can therefore only be marketed toward experts.
Marketing Strategy Proposition
We want to improve our scientific dossier to make it more robust by continuing of lab work to have a proof of concept, as well as getting our papers peer-reviewed to legitimize our findings. This will prove the efficiency and safety of our product, reassuring possible investors or clients to obtain sufficient funding to start our animal trials.
To obtain our objectives we will have two strategies. First, we want to raise awareness of our product in academia to reinforce our scientific credibility, and at the same time raise awareness of our product with biotechnology companies to obtain investors to be able to continue with our research. If this strategy fails, and we do not feel confident in continuing with our private company we will either give a temporal license to use our patent to a bigger company or we will sell off our patent completely ( this strategy is known as an "Exit Strategy" ).[27]
We will focus on the market of developing countries (Latin America or South East Asia) but look for funding in Switzerland where cancer research is heavily invested with public and private investors (big biotech companies or family financial advisors for example). We will also target oncologists as well as researchers in the developing regions, they will be the ones recommending our product to possible patients.
Our product is based on the concept of chronotherapy, a new raising type of treatment that takes into account the administration time of a drug to obtain the optimal effect, and medical microbiology, that takes microbiology knowledge and applies it to medical treatments. We want our product to be associated with innovative technologies that pushes the envelope on how cancer should be treated beyond the usual treatments.
Target Key Messages
There are different messages that we want to relay to each segment of the market; they are the core messages you want your target audiences to hear and remember. [28] First, when targeting oncologists, we want to offer an efficient treatment for patients, which would reduce the amount of side-effects as a consequence of prescribing multiple aggressive treatments at once. Our treatment would also reduce the number of follow-up treatments as our system can work quite independently.
For the biotechnology companies, we want to produce a safe and efficient product that will allow a return on investment if they want to become investors or if they want to buy our patent.
Marketing/Com Tactics & Priorities/Planning
To raise awareness in the private sector we will participate in oncology and scientific congresses in Latin America and Asia, for example those organized by the Latin American School of Oncology: "Escuela Latinoamericana de Oncología" (ELO) or ESMO Asia Virtual Congress 2020 the leading scientific platform in the Asia-Pacific region. As well as in Switzerland, in the congress organized by the organization "Soins
en Oncologie Suisse", to make ourselves known with Swiss investors. We will create brochures to present our product to company representatives as well as oncologists.
To reinforce our scientific credibility we will create clinical and scientific advisory boards that would include members with in-depth experience in the fields of oncology, medicine and clinical research. We want to continue with our animal and pre-clinical trials, and publish our findings to solidify our scientific dossier.
Risks & Stakes of our Strategy
Our product is still in development as an experimental treatment that has not been tested on animals. It could be an effective treatment for CRC in stages 0 and 1, however, in later stages, it will most probably not be used as a stand-alone treatment for the cancer tumors and will only be a complement for surgery. There are also treatments with a sturdier scientific dossier than ours that will be prioritized when choosing a treatment for a cancer patient, as they have been used for years with a lot more studies that prove their effectiveness, while our product will be quite new on the market not many specialists or patients will trust it right away. If the experts decide that our product is not convincing enough, they will not recommend it at all to their patients.
As we are a group of young entrepreneurs with almost no experience managing a company, we still have a long way to go to be able to develop B.O.T into a full fledged product. However we truly believe there is potential in our device, and it could help a lot of people with a problem that is so prevalent today. We will need to bring other scientists with more expertise than us into the team, as well as hiring people with business/marketing background to improve on that aspect of the project.
Timeline for Market Access:
We can assume that it will be between 8 and 11 years until our product will be approved to go into the market as it still needs to go through multiple tests to be deemed safe for human use. For now, our goals will be to finish our proof of concept for our product, as well as start talking with investors to obtain funding to start the next stages of the process.
Cost Analysis:
To know how much our product would cost on the market we need to first know how much it would cost to produce and develop to make sure we attract sufficient funding. As it is a product that needs special handling for its storage it will be sold per unit and not multiple pills at once.
To know how much each pill will cost to produce we need to know the parts that constitute it: media to grow the bacteria as well as the drug capsule. If we were to use a reactor of 1000L we would need 10 kg of Tryptone ($924.3 USD), 5kg of yeast ($393.65) and 10kg of NaCl ($405.9 USD) to make the LB bacterial growth medium.[29] Current empty drug capsules (size 00) cost between $0.0023 - $0.0045 USD/piece, [30] so we could assume that if we made them they would cost similarly. After that, we would need to factor the costs of manufacturing such as transport, electricity, machinery (industrial reactors) as well as the salaries of all the employees, so estimating a price at this point of the project is quite difficult. Also, there is a trend in the pharmaceutical industry on marking up the prices to extreme extents (up to 5000% sometimes ), but as that goes against our company values our mark up wouldn’t be [31] anywhere as high and as consequence our profits wouldn’t be as high either.
Expert Advice
Industry Perspectives
We interviewed multiple people who are experienced in the start-up domain, from having started their own company to directing a program that helps guide people wanting to start one.
Prof. Städler helped us realize what the market of biotechnology looks like right now and where a product like ours could fit. He also reminded us of the importance of making sure that a product similar to ours has not been already invented to avoid legal complications. He highlighted how we needed to make clear how we saw our company’s future. This would be a question that investors would make, considering that they would be difficult to convince on our credibility as a group of young (and mostly inexperienced) Biology Students. He would advise us to develop the bacteria until the preclinical or clinical stage I, as to maximize the value of our company and then sell it off. He finally told us how it could be a product that would be interesting in developing nations, as a start-up with a more "social" emphasis, which would also change the type of investors it would attract. In general he thought it was quite an interesting and ambitious project that would come with a lot of challenges.
Mrs. Headon explained how the HUB helps start-ups like ours with coaches and guidance. She explained how there are different programs for ideas at different stages of development (from undefined ideas to mostly developed projects) and told us our project would be an interesting candidate for the HUB’s program. She advised us to get in contact with some of the start-ups that were in the HUB program at the moment.
source some part of the production process to third parties, how important team work (and good communication) is in a project. He gave us important questions that would shape this business plan: Who are the clients? Who are our competitors? How is our product different? And finally he left us with some important advice: "Listen to others around you, but don’t listen too much"
Legal Counsel
Morena Zavaleta, reviewed our legal analysis for our hypothetical patent and trademark. She is a regional partner at Arias Law Firm in El Salvador and head of the Intellectual Property and Lifesciences Law Department and manages over seven fully-integrated offices in six countries of Central America.
Mrs. Zavaleta helped us define the important steps in how to protect the IP of a biotech product such as B.O.T, as well as some of the limitations that are inherent with a patenting of a living organism.
Percy Zavaleta, canine associate.
