Parsortix-harvested CTCs uncover novel biomarker

ANGLE plc ("the Company")

CTCS HARVESTED BY PARSORTIX UNCOVER NOVEL METASTATIC BIOMARKER

Parsortix system able to harvest difficult-to-detect mesenchymal CTCs

Metastatic biomarker Cyr61 found by researchers in 40% of breast cancer CTCs may be a novel therapeutic target in treating drug-resistant breast cancers

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the University Medical Centre Hamburg-Eppendorf, Germany, has published new research in the peer reviewed journal Cancers, that demonstrates the ability of the Parsortix^® system to harvest circulating tumour cells (CTCs) with a mesenchymal phenotype, which can be used to detect the metastatic biomarker cysteine-rich angiogenetic inducer 61 (Cyr61) in breast cancer patients.

The Cyr61 protein is a potent regulator of many cellular functions important in cancer development, including cell proliferation, survival/apoptosis, senescence, motility/chemotaxis, invasion into the extracellular matrix, gene expression, differentiation, and angiogenesis. Cyr61 is expressed in most forms of solid tumours and in breast cancer, potentially playing a role in tumour progression, metastatic expansion, and the development of resistance to anti-cancer drugs including endocrine therapies.

In this study, researchers found that Cyr61 was over-expressed in 43% of CTCs isolated from 35 breast cancer patients. In addition, they were able to demonstrate in breast cancer cell-lines that the loss of Cyr61 reduced the viability of tumour cells by decreasing cancer cell proliferation and cell survival. As such, Cyr61 might serve as a novel marker for CTCs and disseminated tumour cells (DTCs) similar to those found in the bone marrow and help identify cells with a more aggressive phenotype. Furthermore, Cyr61 could represent a target for the development of novel anti-metastatic drugs.

In the US, breast cancer is the most frequently diagnosed cancer in women with an estimated 276,480 new cases recorded in 2020. Despite new treatment options and advances in patient management protocols, some 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent advanced or metastatic disease. Although the prognosis of patients with metastatic breast cancer (MBC) has significantly improved, metastatic disease remains largely incurable with median survival of three years.

CTCs, as a liquid biopsy, have significant potential as a complementary prognostic and diagnostic tool for clinicians. Access to tumour cells from a peripheral blood sample provides non-invasive, real-time monitoring of cancer patients, giving insight into clonal evolution during tumour metastasis. Critically, the analysis of CTCs from a blood sample has the potential to provide actionable information for the approximately 50% of all MBC patients who are unable to have a solid tissue biopsy of the metastatic site.

This study demonstrates how CTCs can provide insight into molecular mechanisms of cancer cell resistance and metastatic spread, which may have potential as a novel therapeutic target in treating drug-resistant breast cancers.

This research has been published in the peer-reviewed publication Cancers and may be accessed via https://angleplc.com/library/publications/.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"This new study observed that mesenchymal DTCs are strongly positive for PD-L1 and Cyr61 and that Cyr61/PD-L1 double-positive DTCs may escape the immune system and establish distant metastasis. Cyr61 might therefore serve as a novel biomarker for a subset of CTCs and DTCs with high plasticity in breast cancer. In addition, Cyr61 might represent an interesting anti-metastatic target that could be explored in future studies.

Use of the Parsortix system in uncovering potential new therapeutic targets through its ability to harvest mesenchymal as well as epithelial CTCs for analysis provides yet further evidence of its advantages over other liquid biopsy approaches. ANGLE's ability to provide this actionable information should prove highly attractive to drug developers looking for new approaches for hard-to-treat cancers and bodes well for the forthcoming launch of our new pharmaceutical services business."

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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 thus 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. In addition, the live CTCs harvested can be cultured, which offers the potential for testing 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 41 peer-reviewed publications and numerous publicly available posters, available on our website.