Angle PLC Announces ctDNA and CTCs have differences in EGFR mutations
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Angle PLC Announces ctDNA and CTCs have differences in EGFR mutations

Friday, June 18, 2021 2:00 AM
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  • Study supports analysis of CTCs, together with ctDNA, from serial liquid biopsies to provide information on disease progression and drug resistance
  • CTCs found to provide prospective insight into a patient's cancer, which may not be possible with ctDNA alone

GUILDFORD, UK / ACCESSWIRE / June 18, 2021 / ANGLE plc (AIM:AGL)(OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the world-class research team led by Prof. Evi Lianidou at the National and Kapodistrian University of Athens (Greece), has published results of a new study undertaken in non-small cell lung cancer (NSCLC) which demonstrates the benefit of analysing circulating tumour cells (CTCs), in addition to circulating tumour DNA (ctDNA), to inform treatment decisions.

The aim of the study was to detect Epithelial Growth Factor Receptor (EGFR) mutations, a key target for therapy selection, in ctDNA and matched CTCs from a single blood sample. The study used the Parsortix® system to harvest CTCs in blood samples from 48 metastatic NSCLC patients, with known EGFR mutations, before treatment with a targeted therapy and again at disease progression.

Isolated CTCs were lysed and genomic DNA from the harvested CTCs was analysed using Crystal Digital PCR, a highly accurate tool for detecting and quantifying gene mutations. CTC-derived DNA was analysed in 64 samples and the EGFR mutational status assessed before treatment and at disease progression. Direct comparison of the CTC results with matched ctDNA results revealed significant differences in the patient's mutational status on which the therapy decision is based.

The differences observed are believed to be clinically important since CTCs are living cells actively involved in metastatic evolution and spread. The heterogeneity observed in CTCs is reflective of cell evolution under treatment induced selective pressure and provides insight into cancer evolution. Identifying the differences between mutations in ctDNA and CTCs in longitudinal studies could help guide therapy decisions and provide an important enhancement to monitoring patient response in cancer drug trials.

Precision medicine has transformed cancer care in NSCLC with 24 of the 34 FDA approved therapeutics targeting a specific biomarker. However, lung tissue biopsy required for biomarker assessment is associated with significant risks. Due to adverse events following the procedure, a mean cost of US$14,600 per biopsy has been estimated. Liquid biopsy offers the potential for safe, cost effective longitudinal monitoring of tumour evolution and disease progression to track mutations responsible for therapy resistance and identify biomarkers for targeted treatment selection.

In the United States, lung cancer is the second most common cause of cancer and the leading cause of cancer related mortality, responsible for 22% of all cancer related deaths. In 2021, The National Cancer Institute predicts that there will be a total of 236,000 new cases and 132,000 deaths - NSCLC accounts for 84% of all lung cancer cases. Whilst the overall 5-year survival rate for NSCLC is 25%, 60% of patients are diagnosed with metastatic (stage IV) disease for which the 5-year relative survival rate is just 5%.

The research has been published as a peer-reviewed publication in the journal Cancers and may be accessed via

Prof Evi Lianidou, Head of the Molecular Diagnostics Laboratory focused on Liquid Biopsy (ACTC lab) at the Department of Chemistry, National and Kapodistrian University of Athens, commented:

'CTCs, as living cells that are active in the metastatic process, can provide prospective insight into a patient's cancer. In comparison, ctDNA derived mainly from dead and dying cells, provides important but historical information on a patient's disease. The genetic and phenotypic diversity observed in CTCs most likely mirrors that of the patient's tumour and is reflective of cell evolution under treatment induced selective pressure.'

ANGLE Founder and Chief Executive, Andrew Newland, commented:

'This study, which analysed blood samples taken from patients during treatment, demonstrates the dynamic and heterogeneous nature of NSCLC and the need for analysis of CTCs as well as ctDNA from serial liquid biopsies to provide information on disease progression and drug resistance. Critically, this study supports the view that CTCs, rather than ctDNA, are key to gaining an insight into the future development of a patient's cancer.'

For further information:


+44 (0) 1483 343434

Andrew Newland, Chief Executive

Ian Griffiths, Finance Director

Andrew Holder, Head of Investor Relations


finnCap Ltd (NOMAD and Joint Broker)

Corporate Finance - Carl Holmes, Simon Hicks, Teddy Whiley
ECM - Alice Lane, Sunila de Silva

+44 (0)20 7220 0500

WG Partners (Joint Broker)
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+44 (0) 203 705 9330

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Notes for editors

About ANGLE plc

ANGLE is a world leading liquid biopsy company with sample-to-answer solutions. ANGLE's proven patent protected platforms include a circulating tumor cell (CTC) harvesting technology and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.

ANGLE's cell separation technology is called the Parsortix® system, and it enables a liquid biopsy (a simple blood test) to be used to provide the cells of interest to the user in a format suitable for multiple types of downstream analyses. The system is based on a microfluidic device that captures cells based on a combination of their size and compressibility. The system is epitope independent and can capture all types of CTCs as well as CTC clusters in a viable form (alive). CTCs enable the complete picture of a cancer to be seen as being an intact cell they allow DNA, RNA and protein analysis and may provide comparable analysis to a tissue biopsy. Because CTC analysis is a non-invasive process, unlike tissue biopsy, it can be repeated as often as needed. This is important because cancer develops and changes over time and there is a clear medical need for up-to-date information on the status of a patient's tumor. In addition, the live CTCs harvested by the Parsortix system can be cultured, which offers the potential for testing tumor response to drugs outside the patient.

The Parsortix technology is the subject of 26 granted patents in Europe, the United States, China, Australia, Canada, India, Japan and Mexico with three extensive families of patents are being progressed worldwide.

The Parsortix system has a CE Mark in Europe for the indicated use and, in the United States, a De Novo Submission has been made to FDA for the Parsortix® PC1 system seeking FDA clearance with Class II Classification for use with metastatic breast cancer patients. FDA clearance is seen as the global standard. ANGLE is seeking to be the first ever FDA cleared system for harvesting CTCs for subsequent analysis.

ANGLE has also completed two separate 200 subject clinical studies under a program designed to develop an ovarian cancer pelvic mass triage test, with the results showing best in class accuracy (AUC-ROC) of 95.1%. The pelvic mass triage assay has undergone further refinement and optimisation and is currently in the process of a 200-patient clinical verification study.

ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM Ziplex® platform and is based on a patented flow through array technology. It provides for low cost, highly multiplexed, rapid and sensitive capture of targets from a wide variety of sample types. A proprietary chemistry approach (the HyCEAD method) allows for the capture and amplification of over 100 biomarkers simultaneously in a single reaction. The HyCEAD Ziplex system is extremely sensitive and is ideal for measuring gene expression and other markers directly from Parsortix harvests and was used in the ovarian cancer pelvic mass triage test to achieve best in class accuracy (AUC-ROC) of 95.1%.

ANGLE's proprietary technologies can be combined to provide automated, sample-to-answer results in both centralised laboratory and point-of-use cartridge formats.

ANGLE has established formal collaborations with world-class cancer centres and major corporates such as Abbott, Philips and QIAGEN, and works closely with leading CTC translational research customers. These Key Opinion Leaders (KOLs) are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. The body of evidence as to the benefits of the Parsortix system is growing rapidly from our own clinical studies in metastatic breast cancer and ovarian cancer and also from KOLs with 45 peer-reviewed publications and numerous publicly available posters, available on our website.

ANGLE has established clinical services laboratories in the UK and USA to accelerate commercialisation of the Parsortix system and act as demonstrators to support product development. The laboratories offer services to pharmaceutical and biotech customers for use of the Parsortix system in cancer drug trials and, once the laboratories are accredited, and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management.

This information is provided by Reach, the non-regulatory press release distribution service of RNS, part of the London Stock Exchange. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact [email protected] or visit


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