ANGLE plc ("the Company")

ANGLE'S PARSORTIX SYSTEM KEY TO STUDY DEMONSTRATING RNA ANALYSIS OF CTCs AS A PROGNOSTIC TOOL IN NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS

Research published by world-class cancer research centre highlights critical advantages of the Parsortix system

Multi-marker transcriptomic analysis (RNA) of CTCs reveals multiple subtypes with different prognostic significance

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce the publication of new clinical research undertaken by the world-class team at the Medical University of Vienna, Austria. The study in Non-Small Cell Lung Cancer (NSCLC) patients utilised ANGLE's Parsortix^® system to isolate circulating tumour cells (CTCs) for enumeration and gene expression analysis (RNA). The Parsortix system was selected by researchers for the study due to its ability to provide unbiased CTC enrichment enabling the isolation of non-epithelial cancer cells together with exceptional depletion of white blood cells, which is key for molecular analysis.

In preliminary spiking experiments, CTC capture rates for the Parsortix system were established with two NSCLC cell lines spiked into healthy volunteer blood. Capture rates as high as 80% were observed, further confirming the high capture rates observed in previous studies. Blood was then collected either at baseline or at disease progression in 118 NSCLC patients and processed with the Parsortix system. The cells harvested by the Parsortix system were subjected to RNA molecular analysis using standard downstream analysis techniques to generate gene expression information.

The researchers report that in patients where a subset of CTCs had cancer stem cell (CSC) properties, significantly worse patient outcomes both at diagnosis and at disease progression were observed. CSCs are non-epithelial CTCs with a high degree of cell plasticity and heterogeneity making them highly adaptable and resistant to treatment and potentially representing a new avenue for drug discovery. Notably, competing antibody-based CTC systems fail to capture the clinically significant non-epithelial CTCs.

This study highlights the relevance of CTCs, harvested from a simple blood test using ANGLE's Parsortix system, as a tool for the clinical management of NSCLC. In addition to the prognostic value of certain subsets of CTCs, CTCs offer potentially useful clinical information, such as PD-L1 protein expression, as well as insight into the entire molecular profile of a tumour at the time of sampling.

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 85% 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%. One in five patients will experience an adverse event following a lung tissue biopsy. As such, the costs are significant, with a mean cost of US$14,634 rising to US$37,745 in patients with complications.

Professor Robert Zeillinger, Head of Molecular Oncology Group, Comprehensive Cancer Center, Medical University of Vienna, Austria, commented:

"This study further underlines the relevance of the molecular characterisation of CTCs. Our multi-marker analysis highlighted the prognostic value of cancer stem cell-related transcripts at primary diagnosis and disease progression. In the age of immunotherapy, CTCs may offer potentially useful clinical information at the cellular level, for example PD-L1 gene expression before treatment, at treatment and during follow-up."

ANGLE Founder and Chief Executive, Andrew Newland, added:

"Whilst ctDNA, which is derived from fragments of dead cells, has become a widely utilised tool for the stratification of NSCLC patients, it is limited to analysis of DNA alone. Intact living CTCs harvested using the Parsortix system allow for analysis of key protein targets for drug therapy, such as PD-L1 status, in addition to gene expression profiling (RNA) for any gene of interest. Gene expression analysis is becoming increasingly recognised as critical in understanding the true nature of a patient's cancer. In contrast, analysis of DNA mutations alone may fail to identify the correct patients for targeted treatment, as the genes containing these mutations may not actually be expressed.

Additionally, this research further underpins our confidence in the growth of our pharma services business, where longitudinal analysis of CTCs promises to increase the efficiency and lower the costs of clinical trials in oncology." 

The research has been published as a peer-reviewed publication in the Journal of Personalised Medicine, is available online at  https://angleplc.com/library/publications/.

For further information:

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 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 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 HyCEAD^TM 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 51 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 Parsortix in cancer drug trials and, once the laboratories are accredited and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management.