Novel insight into metastasis in NSCLC patients

RNS Number : 9947T
Angle PLC
28 July 2022
 

For immediate release

28 July 2022

 

ANGLE plc ("the Company")

 

CTCS HARVESTED USING THE PARSORTIX SYSTEM PROVIDE NOVEL INSIGHT INTO METASTASIS IN EARLY-STAGE NON-SMALL CELL LUNG CANCER PATIENTS

 

Metabolism-Related Genes are overexpressed in the CTCs of early-stage NSCLC patients harvested using Parsortix and are associated with mesenchymal markers

 

Identifying the overexpression of metabolic function markers in CTCs may provide new prospective biomarkers to aid diagnosis

 

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce details of a new separate study from the world-class research team led by Prof. Evi Lianidou at the National and Kapodistrian University of Athens, Greece. The study used the Parsortix® system to harvest CTCs from whole blood samples from 46 early-stage non-small cell lung cancer (NSCLC) patients, to analyse the expression of Metabolism-Related Genes (MRGs). Use of the biomarker-independent Parsortix system also allowed the researchers to investigate the association of MRG expression with epithelial and epithelial to mesenchymal transition (EMT) markers.

 

Using the Parsortix system, followed by quantitative PCR (RT-qPCR) analysis, the authors examined the molecular expression of three MRGs in CTCs from early-stage NSCLC patients prior to surgery (baseline), one month following surgery and at relapse. Overexpression of at least one of the three MRGs was detected in 47.8% patients prior to surgery. Analysis of CTCs in patients one month after surgery showed a reduction in the expression of two of the MRGs compared to baseline levels. Subsequently, expression of two of the three MRGs analysed increased in CTCs at relapse.

 

The researchers also demonstrated that overexpression of two MRGs were associated with the overexpression of mesenchymal markers in a subpopulation of CTCs from these early-stage NSCLC patients. The EMT of CTCs is a hallmark of NSCLC and has limited the ability to accurately identify and enumerate CTCs using EpCAM dependent approaches. The use of the biomarker-independent Parsortix system in this study, which instead relies on cell size and deformability to isolate CTCs, allowed the researchers to capture and analyse epithelial, mesenchymal and transitioning CTCs. EpCAM-dependent systems would have been unable to detect mesenchymal CTCs and consequently would have missed the crucial association between the MRGs analysed and mesenchymal markers.

 

This new research supports the importance of MRGs in metastasis and shows that MRG overexpression can be assessed in CTCs isolated from early-stage NSCLC patients. The overexpression of the MRGs analysed in this study points to their utility as potential biomarkers in NSCLC. Globally, lung cancer remains the leading cause of cancer death with NSCLC accounting for over 80% of all lung cancers. Whilst the overall 5-year survival rate for lung cancer is 23%, 55% of patients are diagnosed with metastatic (stage IV) disease for which the 5-year relative survival rate is just 7%. Thus, there is an urgent need for early diagnosis and effective targeted treatment options to improve both the quality and longevity of those patients whose lives are affected by this disease.

 

Professor 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:

"MRG overexpression was observed at a high frequency in the CTCs of early-stage NSCLC patients, supporting its role in metastatic processes. The glycolytic and mesenchymal subpopulation of CTCs was significantly predominant compared to CTCs that were glycolytic and not mesenchymal-like. Our data indicate that MRGs merit further evaluation through large and well-defined cohort studies."

 

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"ANGLE is pleased to announce further world-class research published by Prof. Lianidou and her team, providing novel insight into the role of MRGs as biomarkers for disease remission or relapse in NSCLC.

 

"The high proportion of mesenchymal CTCs observed in patients who had relapsed demonstrates the importance of isolating this subset of CTCs which is enabled by the Parsortix system. Not only could MRGs be utilised as a biomarker for cancer relapse and disease progression but could also have potential as a target for drug discovery."

 

For further information:

 

ANGLE plc

+44 (0) 1483 343434

Andrew Newland, Chief Executive

Ian Griffiths, Finance Director

Andrew Holder, Head of Investor Relations

 

 

 

 

 

Berenberg (NOMAD and Joint Broker)

Toby Flaux, Ciaran Walsh, Milo Bonser

+44 (0) 20 3207 7800

 

Jefferies (Joint Broker)

Max Jones, Thomas Bective

 

+44 (0) 20 7029 8000

 

 

FTI Consulting

Simon Conway, Ciara Martin

Matthew Ventimiglia (US)

 

 

+44 (0) 203 727 1000

+1 (212) 850 5624

 

For Frequently Used Terms, please see the Company's website on https://angleplc.com/investor-relations/glossary/

 

Notes for editors

 

About ANGLE plc www.angleplc.com  

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 known as the Parsortix® system and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.

 

ANGLE's Parsortix® system is FDA cleared for its intended use in metastatic breast cancer and is currently the first and only FDA cleared medical device to harvest intact circulating cancer cells from blood.

 

Intended use

The Parsortix® PC1 system is an in vitro diagnostic device intended to enrich circulating tumor cells (CTCs) from peripheral blood collected in K2EDTA tubes from patients diagnosed with metastatic breast cancer.  The system employs a microfluidic chamber (a Parsortix cell separation cassette) to capture cells of a certain size and deformability from the population of cells present in blood.  The cells retained in the cassette are harvested by the Parsortix PC1 system for use in subsequent downstream assays.  The end user is responsible for the validation of any downstream assay.  The standalone device, as indicated, does not identify, enumerate or characterize CTCs and cannot be used to make any diagnostic/prognostic claims for CTCs, including monitoring indications or as an aid in any disease management and/or treatment decisions.

 

The Parsortix system enables a liquid biopsy (a simple blood test) to be used to provide the circulating metastatic breast cancer cells 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 phenotypes of CTCs (epithelial, mesenchymal and EMTing CTCs) as well as CTC clusters in a viable form (alive).  CTCs harvested from the system enable a complete picture of a cancer to be seen; as being an intact cell they allow DNA, RNA and protein analysis as well as cytological and morphological examination and may provide comparable analysis to a tissue biopsy in metastatic breast cancer. 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.

 

In the United States, the Parsortix® PC1 system has received a Class II Classification from FDA for use with metastatic breast cancer patients. FDA clearance is seen as the global gold standard. ANGLE's Parsortix system is the first ever FDA cleared system for harvesting CTCs for subsequent analysis. ANGLE has applied the IVD CE Mark to the same system for the same intended use in Europe.

 

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 a 200 patient clinical verification study has now completed enrolment.

 

ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM 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 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 65 peer-reviewed publications and numerous publicly available posters from 31 independent cancer centres, available on our website.

 

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

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