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Zebrafish avatar as a real-time in vivo platform for personalized cancer therapeutics

Periodic Reporting for period 3 - ZEBRAONCOFISH (Zebrafish avatar as a real-time in vivo platform for personalized cancer therapeutics)

Reporting period: 2019-09-01 to 2020-05-31

Cancer is a leading cause of morbidity and mortality with approx. 35 million people affected by this disease and more than 8 million deaths per year. A major difficulty found in effective cancer treatment is the complexity of the biological mechanism underlying cancer onset and disease progression. This is because the genetic makeup and metabolic profile of each individual patient influence the effect of anticancer drugs. As such, different people respond differently to the same therapy. Therefore, the solution we propose in the ZEBRAONCOFISH project is the use of zebrafish avatars as an in vivo platform to guide therapeutic decisions in actionable cancer patient-directed interventions. These avatars will be created by xenotransplantation (interspecies transplant) of human cancer cell lines/ tumor samples in zebrafish.
In the zebraONCOfish project we seek overcoming the barriers preventing the use of zebrafish avatars in patient-directed interventions. In this way, we want becoming the first company worldwide delivering on the advantages of their use in personalized medicine to cancer patients. Our approach goes through the following objectives:
• OBJECTIVE 1: To reduce the price of the analysis, a reasonable price for a routine-use analysis in clinic.
• OBJECTIVE 2: To reduce the time required to deliver the results of the analysis to the patients from 6 weeks to a maximum of 1 week.

Conclusions: during these 2 years and 9 months we have undergone a normal evolution associated with the evolution of a tool that has a living organism as a base, such as zebrafish. The beginnings of the project, given the complexity of the organism used, were tedious and Risks appeared that were mitigated thanks to the good application of contingency plans. Subsequently we have suffered, during the course of the project, a setback such as the pandemic that has affected all kinds of sectors. However, this project has been successfully completed, with a level, in percentage, of 100%, obtaining a much more complete tool than the one initially proposed. Technology has been demonstrated and developed that is able to discern between the best treatments associated with genetic profiling and other factors associated with disease and patients. In addition, thanks to the creation of a phenotype-molecule library, controlled by its own software developed for this platform, iONCOwareTM, response times can be reduced and will be reduced over time, thanks to the association of artificial intelligence with biotechnology. Undoubtedly, a tool has been created that will help the population suffering from this technology thanks to the personalization of the treatments, helping not only to improve them and ensure their effectiveness but also to the production processes of new, more effective antimtumoral compounds, effective and fast.
The specific contributions towards the objectives per Work Package have been described below:
• WP1 for Project Management: during these 2 years and 9 months of the project, the activities in the WP have been carried out efficiently, studying the risks, applying the contingency plans and constantly updating all the information related to the project to avoid putting it at risk. This WP has been the fundamental pillar on which the following WPs have been guided in order to have absolute control of any point, deviation, improvement, etc., of the activities of the other WPs.
• WP2 for Process standardization & automation for xenotransplantation and analysis: during the course of the project, it was possible to efficiently automate the study process in a specific type of tumour, gastrointestinal tumours. During the course of it, it was necessary to apply contingency plans given the appearance of certain risks. The success of these plans was 100% allowing, as stated, to obtain a fully standardized and automated process for a type of tumour. In addition, the laboratories were certified and an ambient GLP like was implemented internally to ensure the traceability, reproducibility and certainty of all the studies carried out under the umbrella of this project.
• WP3 is devoted to Clinical Study for Technology validation & development of the phenotype-molecules library: this WP of the project was carried out during the last months of the project. Given the extrinsic problems that not only our company has suffered due to COVID-19, an amendment had to be requested to ensure the achievement of the project due to a problem associated with this pandemic, the loss of biopsies due to the legal impossibility of going to the facilities. during the state of alarm decreed in Spain. With the acceptance of the amendment and the possibility of analysing 10 stable cell lines and 5 biopsies, it was possible to verify that the technology worked in samples of clinical origin and the phenotype-molecule liberty could be performed by means of the implementation of a software, iONCOwareTM, created for this purpose and for this project. Undoubtedly, he has generated a large database that has to increase with a new number of biopsies and tumours in the coming years thanks to the continuation of the project with agreement and future investments.
• WP4 for Exploitation, IP Strategy & Commercialization Activities: in these two years of the project, a great commercialization plan was carried out, updated in recent months for two reasons: i) when implementing a new automation technology, qPCR, the studies were improving , with an appreciable increase in cost but with a higher quality, ii) until the automation and internal validation of the platform were not verified, it was not wanted to take false steps with potential stakeholders to avoid losing them due to very early contact or not having that platform fully finished. In addition, during the last 9 months a very powerful work has been generated in the world of venture capitals to show the platform, generate interest and close an investment round to continue with this platform, including new tumour types, etc. On the other hand, this marketing plan and this approach to stakeholders, allowed the company to close very powerful clinical validation agreements with public-private institutions in Spain.
• WP5 Dissemination & visibility actions:in order to publicize the platform in the specific oncology sector, in front of stakeholders, different dissemination actions were carried out using digital and non-digital channels. The actions carried out were very well received and as a result it is the next investment that the company will receive to improve the platform, perform clinical validation in a hospital environment and include new tumour types on the platform, such as lung cancer. In addition, dissemination actions were carried out in a non-professional environment through talks, webminars, etc., to raise awareness in society of the importance of having a tool in the health system such as this to improve the quality, not only of treatments, but also patients life.
The social benefits of our project are unquestionable, as it contributes to reduce the high mortality of cancer and it´s one of the most important points of convergence in developed modern societies. Considering the economic burden of cancer amounts for more than €126 billion, it is obvious that it is a major concern for the sustainability of the healthcare systems.
Logo of the project ZEBRAONCOFISH