ANGLE plc ("the Company")

PEER-REVIEWED PUBLICATION HIGHLIGHTS POTENTIAL FOR PARSORTIX SYSTEM IN IMMUNOTHERAPY TREATMENT SELECTION

Parsortix isolation of CTCs highlights relationship between PD-L1 expression and epithelial to mesenchymal transition (EMT)

CTCs in the process of epithelial mesenchymal transition (EMTing CTCs) found to be most closely associated with PD-L1 expression

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the Edith Cowan University, Perth, Australia, has published results from a study in ovarian cancer patients using the Parsortix^® system. The primary aim of this study was to demonstrate the ability to evaluate the expression of both epithelial and mesenchymal markers, as well as PD-L1 status, of circulating tumour cells (CTCs) isolated using the Parsortix system, which may help to predict whether patients will respond to immunotherapy drugs. 

The Parsortix system was selected by researchers for the study due to its ability for unbiased CTC enrichment, enabling the isolation of both epithelial and mesenchymal cancer cells and those in transition (EMTing-CTCs). This is clinically relevant because, although the transition to a mesenchymal phenotype is associated with increased metastatic potential and worse prognosis, many CTC isolation methods, including the leading antibody-based system, only capture epithelial cells and miss mesenchymal and EMTing cells.   

Blood from 16 ovarian cancer patients was collected and processed using the Parsortix system. Isolated CTCs were stained with multiple markers to determine their phenotype (epithelial, EMTing or mesenchymal) and their PD-L1 status. CTCs were identified in 63% of patients and, of these CTCs, 61% were exclusively epithelial, 26% exclusively mesenchymal and 11% were positive for both epithelial and mesenchymal markers (EMTing-CTCs). The remaining 2% expressed the ovarian-specific marker only. Half of the patients with detectable CTCs were PD-L1 positive. PD-L1 positive CTCs were more common amongst EMTing-CTCs, accounting for 76% of the EMTing-CTCs observed, with a significant association between the two when compared to epithelial and mesenchymal CTCs.

This study highlights the potential for this multi-marker staining procedure to be useful in PD-L1 status investigation, evaluating its utility as a biomarker to select patients for inclusion in clinical trials that are likely to respond better to immunotherapy treatments. Currently the proportion of patients that respond to PD-L1 or PD-1 inhibitors is low, at around 13% to 50%, indicating a clear need for improved patient selection as non-responders do not benefit from treatment but risk developing hyper-progressive disease and drug toxicity with immune-related adverse events.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"We are pleased to report on this promising pilot data showcasing the utility of the Parsortix system for the unbiased isolation of multiple subsets of CTCs in ovarian cancer patients. Whilst ctDNA is increasingly used for the stratification of cancer patients, it is unable to provide insight into PD-L1 status. In contrast, CTCs can provide PD-L1 status. ANGLE is currently in the process of validating a PD-L1 assay in its clinical laboratories as a key part of its pharma services offering for clinical trials." 

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

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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 55 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.