Periodic Reporting for period 4 - ADDIA (Validation of a fast and simple peripheral blood diagnostic biomarker kit for Alzheimer’s disease) Reporting period: 2018-10-01 to 2019-07-31 Summary of the context and overall objectives of the project Validation of a fast and simple peripheral blood test for the diagnosis of Alzheimer’s disease.Alzheimer’s Disease (AD) is the most common form of dementia (60 to 70% of the overall dementia cases). Approximately 46.8 million people worldwide currently live with AD or other type of dementia. With an ageing population, this number is estimated to increase to 131.5 million by 2050 (World Alzheimer Report, 2015: http://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf). Currently, no accurate blood In-Vitro diagnostic (IVD) test to diagnose AD exists. A potential AD diagnosis is usually given by a combination of clinical examination, neuropsychological tests and neuroimaging, over several months or years. In addition, a lumbar puncture can be performed to detect biomarkers in cerebrospinal fluid, but this procedure is invasive. Consequently, AD clinical diagnosis is a real challenge for physicians! Rapid and reliable tests, based on peripheral biomarker detection, represent one of the most promising tracks to diagnose the pathology, to facilitate patient stratification and the assessment of efficacy of new AD therapeutic drug candidates under development in clinical trials. Amoneta Diagnostics SAS has developed a diagnostic kit candidate based on blood biomarkers, which allows the diagnosis of AD using only one single blood sample, in a fast, non-invasive way. In this project, a large Proof-of-Performance (PoP) clinical study in AD patients was conducted for the clinical validation of blood biomarkers, both erythrocyte cell biomarkers as primary objective and novel circulating coding and non-coding RNAs and protein biomarkers. The project is supported by the European federation of AD patients’ associations, the Alzheimer Europe. Its successful implementation and results will have a strong impact on the quality of life of patients and a significant impact on the healthcare system and economy. As a result of the present project, the validated and most accurate blood biomarker test will be available as Research-Use-Only (RUO) product for clinical applications from 4Q 2019 and is being CE-marked as approved IVD product for diagnostic applications in 2020. < See attached picture - 1 : ADDIA test as the first blood cell based IVD test approved for the Alzheimer’s diagnosis. > The 1st ADDIA test is based on blood cell biomarkers detected by flow cytometry and probes proprietary to Amoneta Diagnostics thanks to its acquired pipeline of patents from the CNRS and the 2nd ADDIA test is based on measurement of patented unique non-coding RNA panels using HTG/NGS technology. The company has recently filled two additional patents on the biomarkers and tests related to the ADDIA project. The most accurate ADDIA validated and CE registered IVD biomarker assay will be available for clinical applications, initial market introduction and further commercialization from 1Q 2020. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far "The ADDIA project was formally launched on Aug. 1, 2015. The official kickoff meeting with clinical partners took place on Oct. 2, 2015. Since the start of this project, we have made significant progress in achieving our targets. All WPs have been successfully completed.All project activities were efficiently coordinated by the ADDIA team. The two clinical studies; ADDIA chronobiological and ADDIA PoP studies received clinical qualification advice from European Medicine Agency (EMA) via a teleconference held in April 2016 and were initiated at 13 EU clinical centers after authorization from French and other EU competent authorities, as well as favorable opinions from local ethics committees. Both studies signed their 1st informed consent in Nov. 2016. The chronobiological study was successfully completed in March 2018 and the ADDIA PoP study in July 2019. The clinical and biomarkers’ data received from all clinical centers in the e-CRF are now being monitored in order to analyze them. The technical file for CE-marking, summarizing the ADDIA kits design, development, analytical and clinical validation, has been prepared. The declaration of conformity will be signed once the statistical analysis of the data is made available in 4Q 2019.As a part of the commercialization activities, ADDIA team has participated in many external meetings and congresses. The team has presented the IVD products in several business meetings with future potential clients, interested experts from the neurodegenerative field, business events such as Pitching competitions and investor specific events. Several publications and posters have been submitted in scientific congresses and workshops.ADDIA project website is also active since the beginning of the project and always updated. http://www.addia-project-h2020.eu/Progress of ADDIA clinical studies and results obtained on blood-based biomarker tests were presented at the Alzheimer's Association International Conference (AAIC) 2018, in Chicago (Abstract: https://alzheimersanddementiajournal.com/article/S1552-5260(18)31132-4/abstract). ADDIA project was also presented in the International AD/PD 2019 congress in Lisbon: https://adpd.kenes.com/2019#.XT8ezOgzY2w. For further development, initiation of large-scale production and pre-commercialization of blood IVD tests for AD diagnostics, Amoneta team has successfully raised 400K€ via Happy Capital platform and up 2 million USD award by the foundation Alzheimer’s Drug Discovery Foundation (ADDF) in the frame of the « Diagnostics Accelerator» initiative, in partnership with investors including the ADDF co-founder Leonard Lauder, Bill Gates, Jeff and Mackenzie Bezos, the family Dolby, and the foundation Charles and Helen Schwab, in support to Amoneta’ 2nd test based on blood ncRNA panel measurement (now called MemoryLinc project) on « Validation of rapid and non-invasive diagnostic test to predict mild cognitive deficits and early Alzheimer’s disease»." Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The ADDIA project aims to qualify 1st innovative non-invasive blood based in-vitro diagnostic (IVD) test for Alzheimer disease. The ADDIA’s 1st and 2nd generation of tests are based on the measurement of unique proprietary biomarker panels relevant of AD pathology. These tests will meet an urgent medical need and will impact the Alzheimer field in various ways. First, it can help physicians to diagnose AD in a fast manner, and large Pharma to succeed in drug development (in recruiting well characterized cohorts and monitoring efficacy of drug candidates in clinical trial in AD patients) which contributes in making available future new disease-modifying therapies to patients. This delays the dependency state of the patients, relieving AD patients, their families, the health care systems. Since care for dependent AD patients is very expensive, ADDIA tests will significantly reduce direct and indirect healthcare costs. In summary, this project will have a strong impact on the quality of life of patients and a significant impact on the healthcare system and economy. Thanks to the ADDIA project, additional new cellular, soluble and RNA (coding and non-coding) biomarkers have also been discovered and protected worldwide by several patents recently filed. These markers are being validated as the future blood based IVD tests for early AD diagnosis and for differential diagnosis of the AD versus other dementias. These biomarkers are also new targets for future therapies drastically missing despite several decades of huge efforts from the pharmaceutical industry. ADDIA as the first blood cell based IVD test.
