Angle Regulatory News (AGL)

ANGLE plc ("the Company")

PARSORTIX POSTER PRESENTED AT INTERNATIONAL SOCIETY OF LIQUID BIOPSY MEETING

Study demonstrates ability to analyse both CTCs and ctDNA from the same sample

Value of multimodal analyte analysis in liquid biopsy gaining recognition and momentum

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce it presented results from a proof of concept study at the International Society of Liquid Biopsy meeting in Miami, Florida on 20-22 October 2022. The study demonstrated that both circulating tumour cells (CTCs) and cell-free circulating tumour DNA (ctDNA) can be analysed from a single blood sample. The results show that removal of plasma from blood samples for circulating tumour DNA (ctDNA) analysis does not impact on the number or quality of circulating tumour cells (CTCs) which can be successfully isolated from the same sample using the Parsortix® system.

Liquid biopsy, utilising CTCs and ctDNA, has the potential to characterise cancer at genetic, transcriptional, and protein levels simultaneously. This is not achievable with a single-timepoint tissue biopsy or with ctDNA alone since ctDNA does not allow for RNA sequencing or protein analysis. Several studies have assessed the value of combining multiple blood-based analytes for informing on a variety of oncological conditions including, but not limited to, lung cancer and metastatic breast cancer. These studies conclude that multimodal assessment, including dual analyte analysis of CTCs and ctDNA, can provide complementary information valuable for prognostic, therapy selection and patient monitoring purposes.

This study aimed to establish a workflow to allow the isolation of both ctDNA and CTCs from a single blood sample. Both spiked cell samples (blood samples collected from eight healthy volunteers spiked with cultured cancer cells) and 13 metastatic breast cancer (MBC) patient samples were included in the study. Two blood samples were taken from each donor or patient and samples were run in parallel down each workflow; plasma was removed by centrifugation of one sample per donor (for ctDNA analysis), whilst the other sample was not centrifuged (plasma remained in the sample). The cellular component left in each centrifuged tube was resuspended in solution and then processed using the Parsortix system and CTCs detected via immunofluorescence.

In the spiked healthy volunteer samples, the percentage of CTCs detected was comparable between samples processed with and without plasma. This finding was confirmed in the MBC samples; CTCs were identified in 39% of patient samples with matched findings for both workflows. Similarly, the number and size of CTC clusters were equivalent in both samples with and without plasma.

This study demonstrates the feasibility of combining CTC isolation using the Parsortix system with plasma removal for subsequent ctDNA analysis from a single tube of blood with minimal additional sample handling. This opens the possibility for clinical laboratories to broaden the clinical utility of their assays and maximise the value of each patient's sample. Despite the emerging realisation of the benefit of a combinatorial approach to blood analysis, the logistics revolving around access to both a CTC enrichment platform and a ctDNA sequencing platform at the same site has so far limited such analysis. ANGLE believes there will be significant demand from biopharma companies for an assay that combines ctDNA and CTCs. The workflow presented, demonstrating effective CTC isolation utilising the Parsortix system with concurrent removal of plasma for ctDNA analysis, puts ANGLE in a highly competitive position in this emerging arena.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"We are pleased to share the results of our own in-house research which further showcases the utility of the Parsortix system for the unbiased isolation of CTCs which, in combination with plasma removal, allows for the additional analysis of ctDNA. Although ctDNA is established in the US market for targeted treatment selection, CTCs provide information that is both complementary and additional to that which can be provided using ctDNA alone. This is recognised by the National Cancer Institute, who highlight the unmet need for transcriptional and protein analysis to truly enable precision medicine."

The research is available online at https://angleplc.com/library/publications/.

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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 circulating tumor cell (CTC) harvesting technology is known as the Parsortix® system.

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 three separate 200 subject clinical studies under a programme designed to develop an ovarian cancer pelvic mass triage test, with the results showing best in class accuracy (AUC-ROC) of 95.4% with sensitivity of 90% and specificity of 93%. This excellent clinical result demonstrates the utility of cells harvested by the Parsortix system, which the Company believes is the "best sample" for liquid biopsy analysis as it recovers intact, living cancer cells that are involved in the progression of the disease providing prospective information.

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 70 peer-reviewed publications and numerous publicly available posters from 33 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.