Periodic Reporting for period 1 - ONCOTECT (Early detection of tumor DNA in liquid biopsies as a biomarker of cancer recurrence) Reporting period: 2019-06-01 to 2019-11-30 Summary of the context and overall objectives of the project Cyclomics BV is a Dutch start-up company with the ambition to disrupt the cancer diagnostics market with its proprietary circulating tumor (ct) DNA detection technology. Cyclomics has developed a ground-breaking sequencing methodology that enables reliable, fast and ultrasensitive detection of cancer recurrence from blood samples (liquid biopsies). The first product, ONCOTECT, detects oncogenic mutations in the TP53 gene, and is developed for accurate and early detection of head and neck cancer (HNC) recurrence. Recurrent disease after initial remission is a main cause of cancer-related death. In HNC, radiological examination is the current standard in detecting cancer lesions, but is unable to reliably detect recurrence early on, leading to treatment delays and low survival rates. Integration of the ONCOTECT assay into routine clinical workflow is inexpensive and will provide faster time-to-results relative to competing sequencing methods. The main objectives of this feasibility study were to obtain critical insight in Cyclomics’ commercialization strategy, including freedom to operate (FTO), user needs and regulatory requirements. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far To assess if Cyclomics can commercially roll-out ONCOTECT in Europe and in the US, a preliminary FTO analysis has been performed. Furthermore, interviews with Key Opinion Leaders in the field have been conducted to define user needs for the ONCOTECT technology. These user needs allowed the identification of critical product optimization requirements, which in part have been carried in parallel to this feasibility study and will be completed before 2021. Lastly, the regulatory strategy for ONCOTECT has been defined and finetuned for the most effective route to market. In conclusion, the overall strategy of Cyclomics for the development and commercialization of ONCOTECT seems very feasible. In the short term, Cyclomics should aim to generate promising clinical data on the efficacy and safety of ONCOTECT, perform the specified optimization steps in line with the identified user needs, and ideally also provide data on the cost-effectiveness of ONCOTECT in parallel to the clinical trials. Furthermore, additional support regarding the regulatory pathway of ONCOTECT will be secured by expansion of the Cyclomics team. 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) Recurrent disease after initial remission is a main cause of cancer death, warranting early detection as key to improving patient outcomes and quality of life. This need is particularly strong in HNC, where over 100,000 new cases arise every year in the EU. Radiological imaging is the current standard in detecting HNC recurrence, but suffers from low sensitivity and specificity, revealing relapsed tumor lesions only when they have progressed too far for curative treatment strategies. Since 90% of HNC patients carry specific oncogenic DNA mutations in the TP53 gene, the first application of this novel technology in recurrent HNC presents a considerable market opportunity for ONCOTECT. After achieving clinical proof-of-concept in a cohort of 20 patients, Cyclomics will offer its technology for licensing to a diagnostics company to further develop ONCOTECT as an in vitro diagnostic kit. This kit will be brought to the market with the aim of enabling superior quality in diagnostic and clinical decision making. Future applications include monitoring of cancer treatment response and early screening programs, encompassing various genes and cancer types, with the potential to impact the full spectrum of cancer diagnostics.