Periodic Reporting for period 1 - MY FISH CURE (Zebrafish avatar as a real-time in vivo platform for personalized cancer therapeutics)
Okres sprawozdawczy: 2016-08-01 do 2017-01-31
Podsumowanie kontekstu i ogólnych celów projektu
The Zebrafish Lab (http://thezebrafishlab.com/(odnośnik otworzy się w nowym oknie)) a biotechnological company leader in the development and commercialization of novel, tailor-made solutions based on in vivo zebrafish assays. Our mission is to offer our innovative solutions to a wide range of industry sectors, with a major focus on the healthcare and pharmaceutical industries. Thanks to the extensive knowledge acquired by the R&D projects performed in the field by our team for many years and a close collaboration with Hospitals and Cancer Research Institutions, we have identified a substantial clinical and commercial opportunity in bringing to the healthcare market a novel real time in vivo platform for personalized cancer treatment. This business opportunity is the one presented as MY FISH CURE project and it is based on the use of zebrafish “avatars” as personalized-living test tubes. The explanation of MY FISH CURE project concept it is summarized herein.
MY FISH CURE PROJECT CONCEPT:
The main objective of MY FISH CURE project is to bring to the healthcare market a simple, cost-effective, and faithful in vivo model based on the use of zebrafish “avatars” to guide therapeutic decisions in actionable cancer patient-directed interventions (personalized medicine).
Nowadays and specially when referring to cancer treatment, doctors and drug developers are increasingly focused on treatments based on a personalized medicine approach. This approach is fundamentally based on studying the genetic profile of each patient, understanding their genetic makeup and how the tumor develops and grows. This innovative approach enables them to customize treatment to each patient’s needs for an increased efficiency and with fewer side and toxic effects.
Before the appearance of Personalized Medicine, most patients with a specific type and stage of cancer received the same treatment and the results show that some treatments worked better for some patients than for others, being in fact some patients who do not even respond to the prescribed treatments whatsoever.
This can be explained due to different challenges associated to cancer therapies: a) one of them is to the difficulty in identifying group of patients with the same diagnosis so to correctly stratifying them according to the toxicity responses and benefits associated to the drug administration (See figure 1), b) another important challenge is to define the best drug combinations to eradicate and combat carcinogenic cells after diagnosis and in case of cancer recurrence.
How to combat cancer using personalized medicine?
The idea is to analyze individually the patient tumor to determine what combination of drugs will work best.
Many different approaches have been developed so far and currently the most extended approach is the use of molecular profiling of biopsied tissue using in vitro cell culture assays. This approach is founded upon the idea that tumor biomarkers are associated with patient prognosis and tumor cells response to therapy. Although this approach has demonstrated effectiveness in certain cases, it founds limitations when it comes to predict how cancer will actually progress in a living organism.
The in vitro characterization is only made after the tumor is biopsied, so it only provides information of the tumor at a certain point in time, limiting the prediction of cancer proliferation, migration, metastasis, recurrence, and resistance to treatment. The major challenge in prediction of cancer progress in a living organism is that the study of the tumor by itself, do not seem an effective approach without knowing more about the interactions that take place between tumor and normal cell populations. These interactions are indispensable to understand cancer progression. Therefore, despite all the promises of molecular profiling for cancer treatment personalization, the in vitro models will hardly provide an effective solution, because it is extremely difficult to simulate the tumor microenvironment of a living organism in an in vitro cell culture assay .
Conversely, in vivo models (also known as “Avatars”), allow studying cancer progression with different treatments in a living environment, so they open the door to a more effective personalized approach. However, although in vivo models have been widely used un pre-clinical drug development and, to a less extent, as tools for personalized anticancer therapy, their widespread use in clinic is currently prevented mostly because of the completely unfordable cost (for example mouse avatars are being offered to patients at about 12.000€).
The solution proposed in MY FISH CURE project is to use zebrafish avatars as a cost effective (costs lower than 500€/patient) in vivo platform to guide oncologist finding the best therapeutic option for each patient. These zebrafish avatars will be generated by xenotransplantation of human cancer cell lines and primary tumor samples in zebrafish and these avatars will serve as living test tubes to evaluate the efficiency and toxicity of different drug combinations, so to find the best treatment for each patient: the best survival rates and the lowest toxicity (side effects) results founded in ZB avatars will serve to identify the best drug combination for each patient.
MY FISH CURE: Objectives of the action
The ultimate objective we sought for MY FISH CURE project during Phase 1 was to anticipate the possible potential risk that could appear during the project development to ensure that our business innovation project will be efficient and productive. Having this objective in mind, the Phase 1 was developed as a feasibility study with the ultimate objective of determining the key aspects for the prosperous implementation of our ZB in vivo platform as a companion diagnostic test, useful for oncologists to determine which drug combination will be the best option for each patient. The specifics objectives for the action were as follows:
To target Key Opinion Leaders within the Oncology, Pharmaceutical and Cancer Research Communities, to validate the potential of the proposed solution in the market.
To enlarge our network of collaborators by putting in place new collaboration agreements with the Research Institutions and Biobanks that are needed to complete the R&D activities essential to bring MY FISH CURE to the market.
To define the regulatory pathway for us to follow in order to achieve the clinical trial approval by the pertinent ethic committees for clinical experimentation with human samples and by the regulatory bodies (EMA/FDA) to commercialize our solution as a clinical tool for cancer patients’ management.
To perform an in-depth market analysis, that includes the analysis of main market features, drivers and barriers, geographic markets of major interest and the requirements to access them.
To carry out a comprehensive financial analysis (5 years business plan): investment needs, financial projections (P&L, cash flow projections) and sensitive analysis.
To perform an in-depth risk analysis and define a contingency plan.
MY FISH CURE PROJECT CONCEPT:
The main objective of MY FISH CURE project is to bring to the healthcare market a simple, cost-effective, and faithful in vivo model based on the use of zebrafish “avatars” to guide therapeutic decisions in actionable cancer patient-directed interventions (personalized medicine).
Nowadays and specially when referring to cancer treatment, doctors and drug developers are increasingly focused on treatments based on a personalized medicine approach. This approach is fundamentally based on studying the genetic profile of each patient, understanding their genetic makeup and how the tumor develops and grows. This innovative approach enables them to customize treatment to each patient’s needs for an increased efficiency and with fewer side and toxic effects.
Before the appearance of Personalized Medicine, most patients with a specific type and stage of cancer received the same treatment and the results show that some treatments worked better for some patients than for others, being in fact some patients who do not even respond to the prescribed treatments whatsoever.
This can be explained due to different challenges associated to cancer therapies: a) one of them is to the difficulty in identifying group of patients with the same diagnosis so to correctly stratifying them according to the toxicity responses and benefits associated to the drug administration (See figure 1), b) another important challenge is to define the best drug combinations to eradicate and combat carcinogenic cells after diagnosis and in case of cancer recurrence.
How to combat cancer using personalized medicine?
The idea is to analyze individually the patient tumor to determine what combination of drugs will work best.
Many different approaches have been developed so far and currently the most extended approach is the use of molecular profiling of biopsied tissue using in vitro cell culture assays. This approach is founded upon the idea that tumor biomarkers are associated with patient prognosis and tumor cells response to therapy. Although this approach has demonstrated effectiveness in certain cases, it founds limitations when it comes to predict how cancer will actually progress in a living organism.
The in vitro characterization is only made after the tumor is biopsied, so it only provides information of the tumor at a certain point in time, limiting the prediction of cancer proliferation, migration, metastasis, recurrence, and resistance to treatment. The major challenge in prediction of cancer progress in a living organism is that the study of the tumor by itself, do not seem an effective approach without knowing more about the interactions that take place between tumor and normal cell populations. These interactions are indispensable to understand cancer progression. Therefore, despite all the promises of molecular profiling for cancer treatment personalization, the in vitro models will hardly provide an effective solution, because it is extremely difficult to simulate the tumor microenvironment of a living organism in an in vitro cell culture assay .
Conversely, in vivo models (also known as “Avatars”), allow studying cancer progression with different treatments in a living environment, so they open the door to a more effective personalized approach. However, although in vivo models have been widely used un pre-clinical drug development and, to a less extent, as tools for personalized anticancer therapy, their widespread use in clinic is currently prevented mostly because of the completely unfordable cost (for example mouse avatars are being offered to patients at about 12.000€).
The solution proposed in MY FISH CURE project is to use zebrafish avatars as a cost effective (costs lower than 500€/patient) in vivo platform to guide oncologist finding the best therapeutic option for each patient. These zebrafish avatars will be generated by xenotransplantation of human cancer cell lines and primary tumor samples in zebrafish and these avatars will serve as living test tubes to evaluate the efficiency and toxicity of different drug combinations, so to find the best treatment for each patient: the best survival rates and the lowest toxicity (side effects) results founded in ZB avatars will serve to identify the best drug combination for each patient.
MY FISH CURE: Objectives of the action
The ultimate objective we sought for MY FISH CURE project during Phase 1 was to anticipate the possible potential risk that could appear during the project development to ensure that our business innovation project will be efficient and productive. Having this objective in mind, the Phase 1 was developed as a feasibility study with the ultimate objective of determining the key aspects for the prosperous implementation of our ZB in vivo platform as a companion diagnostic test, useful for oncologists to determine which drug combination will be the best option for each patient. The specifics objectives for the action were as follows:
To target Key Opinion Leaders within the Oncology, Pharmaceutical and Cancer Research Communities, to validate the potential of the proposed solution in the market.
To enlarge our network of collaborators by putting in place new collaboration agreements with the Research Institutions and Biobanks that are needed to complete the R&D activities essential to bring MY FISH CURE to the market.
To define the regulatory pathway for us to follow in order to achieve the clinical trial approval by the pertinent ethic committees for clinical experimentation with human samples and by the regulatory bodies (EMA/FDA) to commercialize our solution as a clinical tool for cancer patients’ management.
To perform an in-depth market analysis, that includes the analysis of main market features, drivers and barriers, geographic markets of major interest and the requirements to access them.
To carry out a comprehensive financial analysis (5 years business plan): investment needs, financial projections (P&L, cash flow projections) and sensitive analysis.
To perform an in-depth risk analysis and define a contingency plan.
Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty
During Phase 1, we have performed an in-depth assessment of the feasibility of the MY FISH CURE project. The work performed and main achievements are as follows:
COMMERCIAL FEASIBILITY ASSESSMENT: The Commercial feasibility study was planned for this Phase 1 as a way to understand better the market we aim to enter, so this will help us to define the best strategy for the commercialization success. The work performed during the action has been the following:
Market research study to identify: our target clients, the Unique Selling Points, the commercialization channels, geographic areas of interest, the commercial barriers and the dissemination strategy. We have also carefully analyzed and studied our main competitors in different areas, including companies that perform genetic tests for personalized cancer treatment and companies that offer in vivo models, also including ZB Avatars, for drug development (Pharma industry). It is worth to highlight that after this in-depth study of our competitors, it was not possible to identify a single company that offers the ZB as clinical tool for personalize medicine in cancer. This gave us a very positive idea about the innovation of the proposed concept and the strong impact that MY FISH CURE project will have in the market.
Update our commercialization plan: go-to-market strategy, timeline to reach this market and the commercial goals for the first 5 selling years and the necessary resources to achieve these commercial goals.
TECHNICAL/SCIENTIFIC FEASIBILITY ASSESSMENT: From a technical/scientific perspective, MY FISH CURE project is aimed at the full optimization of our technology for the generation of zebrafish avatars using real and different tumor samples (including hematological malignancies and solid tumors) retrieved from cancer patients and at the clinical validation for their use as tools to support a personalized cancer treatment. Therefore, the objectives of this Phase 1 project regarding the technical /scientific feasibility study were aimed at planning and designing the design the scientific/technical roadmap for the next 2 years. The following activities have been performed to this regard:
Partner engagement. We have developed alliances with clinical research institutions and biobanks to develop the second phase of MY FISH CURE project. While forging these new collaborations, our team has acquired a better understanding of the potential of MY FISH CURE test as a companion diagnostic tool for personalized medicine in cancer treatment, as most of the targeted institutions have expressed their interest in play an active role during the project development.
Definition of the regulatory pathway we must follow to bring MY FISH CURE to the market and design of the clinical study based on it.
Design of 2-years scientific/technical roadmap. The next 3 activities will be essential before we are able to bring MY FISH CURE to the market:
1) Standardization & Automation of the xenotransplantation process for different cancer including haematological malignancies and solid tumours.
2) Clinical study for technology validation and development of the phenotype-molecules library (software).
3) Implementation of a quality process to achieve our laboratories Certification under the ISO15189 standard for clinical diagnosis laboratories.
FINANCIAL FEASIBILITY ASSESMENT: The financial feasibility study was planned for this Phase 1 as a way to carefully analyze the funding requirements for the right development of MY FISH CURE project and to determine the project profitability (Return of Investment, R.O.I.) The work performed during the action has been the following:
Calculation of the total financing needs for MY FISH CURE project: funding requirements to reach the go to market stage.
Update of our financial and cash flow projections for the following 5 years of the MY FISH CURE commercialization.
COMMERCIAL FEASIBILITY ASSESSMENT: The Commercial feasibility study was planned for this Phase 1 as a way to understand better the market we aim to enter, so this will help us to define the best strategy for the commercialization success. The work performed during the action has been the following:
Market research study to identify: our target clients, the Unique Selling Points, the commercialization channels, geographic areas of interest, the commercial barriers and the dissemination strategy. We have also carefully analyzed and studied our main competitors in different areas, including companies that perform genetic tests for personalized cancer treatment and companies that offer in vivo models, also including ZB Avatars, for drug development (Pharma industry). It is worth to highlight that after this in-depth study of our competitors, it was not possible to identify a single company that offers the ZB as clinical tool for personalize medicine in cancer. This gave us a very positive idea about the innovation of the proposed concept and the strong impact that MY FISH CURE project will have in the market.
Update our commercialization plan: go-to-market strategy, timeline to reach this market and the commercial goals for the first 5 selling years and the necessary resources to achieve these commercial goals.
TECHNICAL/SCIENTIFIC FEASIBILITY ASSESSMENT: From a technical/scientific perspective, MY FISH CURE project is aimed at the full optimization of our technology for the generation of zebrafish avatars using real and different tumor samples (including hematological malignancies and solid tumors) retrieved from cancer patients and at the clinical validation for their use as tools to support a personalized cancer treatment. Therefore, the objectives of this Phase 1 project regarding the technical /scientific feasibility study were aimed at planning and designing the design the scientific/technical roadmap for the next 2 years. The following activities have been performed to this regard:
Partner engagement. We have developed alliances with clinical research institutions and biobanks to develop the second phase of MY FISH CURE project. While forging these new collaborations, our team has acquired a better understanding of the potential of MY FISH CURE test as a companion diagnostic tool for personalized medicine in cancer treatment, as most of the targeted institutions have expressed their interest in play an active role during the project development.
Definition of the regulatory pathway we must follow to bring MY FISH CURE to the market and design of the clinical study based on it.
Design of 2-years scientific/technical roadmap. The next 3 activities will be essential before we are able to bring MY FISH CURE to the market:
1) Standardization & Automation of the xenotransplantation process for different cancer including haematological malignancies and solid tumours.
2) Clinical study for technology validation and development of the phenotype-molecules library (software).
3) Implementation of a quality process to achieve our laboratories Certification under the ISO15189 standard for clinical diagnosis laboratories.
FINANCIAL FEASIBILITY ASSESMENT: The financial feasibility study was planned for this Phase 1 as a way to carefully analyze the funding requirements for the right development of MY FISH CURE project and to determine the project profitability (Return of Investment, R.O.I.) The work performed during the action has been the following:
Calculation of the total financing needs for MY FISH CURE project: funding requirements to reach the go to market stage.
Update of our financial and cash flow projections for the following 5 years of the MY FISH CURE commercialization.
Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)
Cancer is a leading cause of morbidity and mortality with approx. 35 million people affected by this disease and more than 7 million deaths per year. Within the European Union, more than 2 million patients are diagnosed at cancer and 1 Million die annually. The economic burden of cancer is another huge problem for the national health systems. As an example, direct costs from cancer in 2014 reached 126 billion euros, which represented a 40% of the global expenditure in Europe.
Through the MY FISH CURE project, we aim to position our company as leader in the Companion Diagnostic (CDx) Market, which is estimated to reach €12 million by 2021, at a compound annual growth rate (CARG) of 22.7% during this period. The main market drivers are that CDx tests are playing an important role as a “decisive” patient stratification factor, avoiding that patients with a genetic profile that would not respond properly to certain medication will be exposed to it. Most of the CDx tests already in the market have helped to improve treatment effectiveness, resulting in cost reductions due to the avoidance of ineffective treatment prescriptions based on traditional methods. Under these positive perspectives, MY FISH CURE project will contribute to the sustainability of the healthcare system by helping to reduce cost associated with cancer management.
Through the MY FISH CURE project, we aim to position our company as leader in the Companion Diagnostic (CDx) Market, which is estimated to reach €12 million by 2021, at a compound annual growth rate (CARG) of 22.7% during this period. The main market drivers are that CDx tests are playing an important role as a “decisive” patient stratification factor, avoiding that patients with a genetic profile that would not respond properly to certain medication will be exposed to it. Most of the CDx tests already in the market have helped to improve treatment effectiveness, resulting in cost reductions due to the avoidance of ineffective treatment prescriptions based on traditional methods. Under these positive perspectives, MY FISH CURE project will contribute to the sustainability of the healthcare system by helping to reduce cost associated with cancer management.