Periodic Reporting for period 3 - Colodetect (Development of a novel blood-based diagnostic test for colorectal cancer) Periodo di rendicontazione: 2017-10-01 al 2019-03-31 Sintesi del contesto e degli obiettivi generali del progetto Recent colorectal cancer (CRC) epidemiology reports (GLOBOCAM 2018) demonstrated that CRC is still a burden in European countries, having very high incidence (499,667 cases in 2018) and mortality rates (242,483 cases in 2018; 48%). The overall objective of COLODETECT® project was the development and future commercialization of a minimally invasive blood-based test for the early detection of CRC in population at risk (men and woman from 50 to 75 years old). The test is based on the detection and measurement of a reduced number of cancer-specific autoantibodies (AAbs) that are present in the blood of patients, which were generated by the own body in response to proteins from the tumor. COLODETECT® will allow surpassing the obvious limitations of the invasive detection techniques extensively used, as the colonoscopy, while retaining a good detection capacity. The test offers additional advantages compared to traditional CRC screening methods (Fecal immunochemical test - FIT), such its simplicity in use, good detection capacity and an affordable cost. Since the test only requires one conventional blood extraction and does not entail any previous patient preparation or diet, it is expected to improve the current adhesion rates of risk population thus improving early detection and patient’s survival. The expected outcome of COLODETECT® project will be a non-invasive and easy to use CRC diagnostic test, a high profit product, aimed for the screening of large populations at risk. Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti During the whole project implementation period, two blood-based colorectal cancer detection tests were developed using two different affordable technologies, ELISA and Luminex. Both tests were clinically validated. For that purpose, a clinical trial was carefully designed and all associated procedures for recruitment of samples (serum/plasma) from selected patients’ were defined and implemented. By the end of the project, a total of 4,213 samples belonging to 3,339 patients has been collected. In all cases, sample-associated information was obtained and most critical information was harmonized in a database (DB) constructed by the company. Subcontractors made a great contribution to reach this ambitious milestone. Standard operation procedures (SOPs) were followed for sample collection and management. All samples incorporated to the study had the Patient’s informed consent and the approval of the Ethical and Scientific Committees of each Center. All biomarkers in study that were used in the different technological platforms of COLODETECT® project (ELISA and Luminex®) were continuously produced, improved and tested by their ability to bind the autoantibodies (AAbs) present in samples from a patients. Scale-up procedures were also implemented for the manufacturing of kits, and a quality control system was implemented under ISO13485 standards. ELISA-based studies initially involved 14 different antigens (lead antigens) and later another 10 antigens (antigens in back up). A pre-selected validation group of serum/plasma samples from patients (N=576; validation cohort: CRC patients vs. ‘healthy’ donors) was used for prototypes validation. ELISA plates were manufactured and used to analyze 576 patients’ samples. A total of 16,128 tests were performed in years-1 and -2. By the end of year-2, ProAlt started with the large-scale manufacturing of (i) the ELISA-based test and in parallel (ii) the multiplexed assay in Luminex®, both aimed for early detection of colorectal cancer in patient’s blood. During year-3, the company conducted the full clinical validation of the diagnostic tests developed (ELISA and Luminex) using a large number of patients’ blood samples from the collection constructed during the project (multicentric and diverse). The cohort assayed consisted of serum/plasma specimens from 1,361 selected CRC and ‘healthy’ individuals covering all tumoral stages. A great volume of data, up to 610,368 tests, was generated. The diagnostic capacity and performance of each antigen in study led to the establishment of an autoantibodies signature for each platform assayed. At the end of the project, two different diagnostic tests for CRC were developed: a multiplex test based on the Luminex platform and an ELISA singleplex test. The regulatory procedure for IVD (CE marking) obtaining was initiated as well. Complimentary and strategic activities were also developed as part of the business and exploitation plan, which were supported by the maintenance and extension of the intellectual property related to the use of autoantibodies as diagnostic tools. New patents were filled. COLODETECT® trademark registration was also performed. Competitors have been monitored systematically, and Technology Surveillance reports were generated twice a year. The commercialization strategy was continuously adapted to the product performance and limitations. Dissemination and communication activities were periodic and substantial,B ilateral meetings with potential partners and investors (Medica, BIO Convention, BioEurope Spring, Anglonordic, others), potential clients (Olympus, Roche Diagnostics, Johnson & Johnson, others) and personalized follow up presentation to investors who showed special interest. Meetings with CRC patient associations also were celebrated. A project webpage, graphic and visual materials were produced, among others. Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora) The main outcomes of this project are two tests in ELISA and Luminex® formats. Those high profit products are easy to use and affordable, making them a useful tool for screening of large populations at risk when compared with high complexity tools competing technologies (colonoscopy/sigmoidoscopy). Their good detection capacity at early stages will represent better treatment options and will improve patient’s survival. The multiplexed assay version offer some additional characteristics (fast and more amenable to automation) compared to the ELISA singleplex assay. Along the year-3 of the project, an exhaustive clinical validation was performed to determine the potential of the multiplex and singleplex assays. COLODETECT is the first diagnostic test based on the novel auto-immunity strategy applied to colorectal cancer (CRC) early diagnosis, a strategic and high impact area of the human healthcare system worldwide, being the early identification of CRC the main therapeutic area where the company expect to become a reference company during next years. Additionally, and after completing the CE marking procedure and launching COLODETECT®, the company will increase significantly its personnel in all business areas, consolidating the R&D department as well and increasing the investments in current and future research projects following the same auto-antibodies strategy. Other benefits will be the creation of a complete management structure within the company, including manufacturing, quality control, customer service, technical assistance, sales, marketing, business development, intellectual property, accounting, financial and administrative departments, employing qualified professionals according to each specific necessity.