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proLungPlasma Report Summary

Project ID: 672680

Periodic Reporting for period 1 - proLungPlasma (Validation of a Lung Cancer Plasma Reflex Test Using Epigenetic Biomarker for Cancer Detection)

Reporting period: 2015-07-01 to 2016-06-30

Summary of the context and overall objectives of the project

The objective of “proLungPlasma” is the clinical validation of a lung cancer test for the assessment of methylated DNA biomarkers prepared from DNA extracted from plasma.
The Epi proLung test provides an aid in the diagnosis of lung cancer in patients at increased risk for the disease. Lung cancer risk factors include patient life history, and/or presentation with symptoms, and/or radiological findings in the lung.
Methylation of DNA is an important epigenetic process involved in fundamental biological processes as development and cell differentiation. Aberrant DNA methylation plays a major role in cancer development.

Lung cancer remains one of the world’s most common and deadliest forms of cancer. While early detection is clearly beneficial for survival, there are no recommended screening methods in many parts of the world and lung cancer patients are usually diagnosed by the appearance of suspicious symptoms or accidentally by clinical imaging performed for other indications.
Recently, based on the evidence of a 20% mortality reduction in the National Lung Screening Trial (USA), a recommendation to screen patients with an elevated risk for lung cancer based on a smoking history and age was issued in the USA, using Low-Dose Computed Tomography (LDCT). To date, similar recommendations have not been made in Europe or the rest of the world, in part because LDCT is burdened by a high positive rate. As a consequence, as screening is implemented there will be a significant need for additional methods to distinguish between true and false positives and to clarify the clinical status of indeterminate positives.
Furthermore, regardless of the method of identification, clinical evaluation of patients with suspected lung cancer usually includes a Computed Tomography scan (CT-scan) of the chest and a bronchoscopy for definitive diagnosis. The latter is often used to confirm a lung tumour by pathological assessment of a cytological specimen obtained by rinsing the affected lung area. However, definitive diagnosis following an initial bronchoscopy is often not possible because either the tissue could not be collected or the cytological assessment is inconclusive and additional invasive diagnostic procedures are necessary. In this instance, a diagnostic test with a low false positive rate could reduce the need for risky, invasive and costly follow-up procedures and dramatically facilitate early treatment.
The newly developed Epi proLung Assay may serve as a tool for reducing false positive rates.
The objective of the business innovation project is to validate an epigenetic biomarker test for lung cancer detection in plasma samples. Development and clinical validation will follow the upcoming new European IVD regulation. This business innovation project will prepare a valid instrument for lung cancer detection. It will deliver a molecular diagnostic instrument (IVD) for complementing systematic lung cancer screening for the very first time.

The resulting standard process for validation of all further test kits of Epigenomics’ Epigenetic Biomarker Test Platform will enable Epigenomics to grow its MDx business for the detection of relevant cancers including colorectal, lung cancer, and others based on its outstanding portfolio of proven biomarkers.

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 project started with set-up of the project with regard to project management, product risk and manufacturing risk management, management of regulatory issues, as well as quality managment.
Epigenomics operates under a quality management system which is ISO 13485 certified for the design, development, manufacturing and distribution of in vitro diagnostic (IVD) products.
This project is run under this quality management system which is essential to the success of the project.
With the Proposal for a Regulation of the European Parliament and of the Council on in vitro diagnostic medical devices submitted by the General Secretariat of the Council of the EU to the Delegations, the assessment of the impact of the changes proposed on the registration requirements for Epi proLung is ongoing, as is the study of relevant documents and standards published by GHTF, IMDRF or CRF.
Since development and clinical validation of the Epi proLung is the central part of this project, the actual validation requirements were identified, and implemented via the respective analytical and clinical validation plans.
These plans were implemented via verification and validation protocols. After preparation for the analytical (non-clinical) validation activities was completed experimental testing and analysis has been started during the reporting period and is ongoing.
The clinical validation activities were planned and prepared with feedback of the built scientific network. Clinical validation via conduct of respective clinical studies will occur during the second year of the project.
Manufacturing of the Epi proLung product was set-up such that the scale of the production meets technical requirements as well as economic needs. Respective equipment qualification, manufacturing process and quality control method validation has been planned, partly executed and is ongoing. Kit lot production is currently ongoing, too.
Results of the project were presented at major international scientific cancer conferences and a scientific manuscript summarizing these results has been accepted for publication (see below).

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)

Development of the Epi proLung test was conducted obeying scientific principles and regulatory rules. Research work conducted as pre-requisite to the final project goal has been summarized in scientific abstracts and were presented in scientific poster sessions at international cancer conferences in Europe (ELCC 2016, Geneva, CH) and USA (AACR-IASLC 2016, San Diego; AACR Annual Meeting 2016, New Orleans, US). These results were furthermore described in a scientific manuscript that was recently accepted for publication in the Journal of Thoracic Oncology (Weiss, G. et al. (2016) Validation of the SHOX2 / PTGER4 DNA methylation marker panel for plasma-based discrimination between malignant and non-malignant lung disease patients, JTO in print).

Epigenomics proposes the Epi proLung as a necessary and suitable tool for clarifying these indeterminate radiological findings. Successful deployment will lower false positive rates, reduce unnecessary procedures and associated psychological burdens, and would result in detection at earlier stages with better prognosis. In this regard, the Epi proLung is a highly anticipated prerequisite for successful implementation of lung cancer screening by LDCT in Europe.

The Epi proLung test will be Epigenomics' second major product in the context of cancer screening after Epi proColon.
After premarket approval by US FDA in April 2016 the Epi proColon product is available in U.S.A. (as US FDA approved IVD), in Europe (as CE-marked product), as well as in China (approved by the CFDA).
Therefore, three major markets are addressed with this product. With the Epi proLung test Epigenomics will offer a second high impact product to these markets and potentially additional markets (Japan) supporting the ambition of the firm to become a market leader in molecular diagnostics.

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