ANGLE plc ("the Company")

BREAKTHROUGH STUDY DEMONSTRATES FOR THE FIRST TIME CONCORDANCE OF PARSORTIX LIQUID BIOPSY BLOOD TEST WITH INVASIVE TISSUE BIOPSY OF THE METASTATIC SITE

Study explores key unmet medical need for metastatic breast cancer as over 50% of patients fail to receive successful tissue biopsies of the metastatic site preventing access to essential information to guide their treatment

Potential for Parsortix liquid biopsy blood test as an alternative to invasive surgical tissue biopsy in metastatic breast cancer

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce the publication of breakthrough research undertaken by the world-class team at the University of Southern California Norris Cancer Center. The research demonstrates the potential of circulating tumour cells (CTCs) harvested from a simple blood draw using the Company's Parsortix^® system to be used as an alternative to invasive metastatic tissue biopsy for metastatic breast cancer (MBC) patients.

In the United States, guidelines published by the National Comprehensive Cancer Network (NCCN) recommend a tissue biopsy of a secondary cancer site in MBC because of the critical need for up-to-date information on cancer progression to guide treatment decisions. However, over 50% of all MBC patients do not have a successful metastatic tissue biopsy because they are either too ill for the invasive procedure, the cancer site is inaccessible and/or insufficient tissue is available. Hence, there is nothing to guide ongoing treatment decisions in these patients. Even in those patients who can undergo a metastatic tissue biopsy, there is rarely the option for a second such biopsy, yet the cancer continues to evolve, often to multiple sites. A simple, repeatable liquid biopsy alternative using the Parsortix system could resolve the issues with metastatic tissue biopsies and, as the study finds, provide real time information on the cancer evolution to guide treatment options.

The study was the first of its kind to directly compare molecular analysis of matched patient samples from invasive metastatic tissue biopsy with Parsortix-harvested cells from a blood sample. The demonstration of a high concordance between the RNA sequencing (RNA-Seq) results of the two sample types is critical in demonstrating the potential utility of the Parsortix system for use as a routine blood test for cancer patients, which could provide a view on the spread of the disease. It is particularly important as over 90% of patients who die of their cancer die of the metastatic spread of the disease rather than their primary cancer.

The pilot study, in 19 patients with MBC, investigated whether gene expression profiling of cancer-related cells, harvested from a blood sample with the Parsortix system, using RNA-Seq technology, could provide insight into targetable mutations with the hypothesis that a Parsortix system liquid biopsy could be utilised as a surrogate biomarker to replace tissue biopsy in the analysis of metastases. Gene expression analysis (RNA) was chosen in preference to gene sequencing (DNA), because of major concerns that not all DNA mutations are expressed and therefore clinically relevant information is missed. ANGLE's Parsortix system was chosen for its efficient, unbiased marker-independent isolation method and the Parsortix system-harvested cells were characterised through RNA-Seq alongside matched metastatic tissue biopsy samples.

The authors reported a high degree of concordance between matched Parsortix system and metastatic tissue samples in clinically actionable genes, demonstrating how the Parsortix system could be utilised as a non-invasive, repeatable liquid biopsy to provide real time insight into MBC disease biology and inform targeted treatment selection. Furthermore, in three of four patients with progressive disease, the Parsortix system-enabled longitudinal analysis revealed a significant increase in the complexity and frequency of expressed mutations over time. These results indicate that the Parsortix system-enabled longitudinal monitoring could capture changes in mutational burden as the cancer evolves, including the development of resistance to anti-cancer therapies which could help guide clinical decision-making and treatment selection.

Breast cancer is the leading cause of cancer worldwide with 2.2 million new cases estimated in 2020. MBC is responsible for virtually all breast cancer deaths and for the 6% of patients diagnosed with metastatic disease or patients whose disease has progressed to stage IV, 5-year relative survival is only 29%.

The research has been published as a peer-reviewed publication in the journal Annals of Surgical Oncology and can be accessed at https://angleplc.com/library/publications/.

Dr Julie Lang, Chief of Breast Surgery and Co-Director of Comprehensive Breast Cancer Program at Cleveland Clinic Cancer Center, formerly Director, USC Breast Cancer Program, Associate Professor of Surgery, Norris Comprehensive Cancer Center, University of Southern California commented:

"Gene expression sequencing of Parsortix system-enriched CTCs could lead to minimally invasive, real time diagnostic strategies for precision therapeutic decision-making for MBC patients. Our Parsortix-based liquid biopsy approach could serve as a surrogate tissue biopsy to evaluate potentially clinically actionable drug target gene expression and mutations, allowing longitudinal assessment of the evolution of a patient's cancer for personalized care."

ANGLE Founder and Chief Executive, Andrew Newland, added:

"ANGLE is delighted to report on this breakthrough research published by Dr Julie Lang and her team, which clearly demonstrates the ability to use the Parsortix system with a simple blood test as an alternative to invasive tissue biopsy in metastatic breast cancer. The RNA-Seq technology used allows full RNA sequencing of the cancer providing information on the whole transcriptome. Analysis of CTCs using RNA-Seq was a key component of our FDA submission and we believe this form of analysis has the potential to bring great benefit to patients through access to information to guide treatment decisions as well as reducing the need for invasive procedures and associated costs."

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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 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 HyCEAD^TM 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 54 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.