ANGLE plc ("the Company")

STUDY USING PARSORTIX DEMONSTRATES IMPORTANCE OF BIOMARKER-INDEPENDENT CTC ISOLATION IN HEAD AND NECK CANCER

EMT status of CTCs found to provide additional insight to tumour tissue biopsy

Potential role of CTC EMT biomarkers as therapeutic targets

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the University of Birmingham has published the results of a study undertaken in head and neck squamous cell carcinoma (HNSCC) which characterised the epithelial-mesenchymal transition (EMT) status of circulating tumour cells (CTCs). EMT is clinically significant due to its role in tumour progression and invasion, the development of metastasis, metabolic reprogramming, immune evasion, and resistance of cancer cells to therapy.

The study used the Parsortix^® system to harvest CTCs from peripheral blood samples from 20 treatment-naïve HNSCC patients at baseline prior to surgery. The researchers performed flow-cytometry EMT characterisation of CTCs as compared to EMT gene expression in tumour tissue and investigated expression correlation with respect to clinical outcomes. The expression of EpCAM and N-cadherin were utilised to characterise CTC status as epithelial or EMT. CTCs were detected in 65% of patients and 77% of positive samples included CTCs undergoing EMT.

The research demonstrated that EMT status of CTCs was almost exclusively associated with advanced stage (III-IV) disease. In this small patient cohort CTC enumeration alone was not reported to be prognostic with respect to overall survival and progression free survival. However, CTC EMT status was found to be independent to that of tumour tissue, highlighting the potential clinical utility of CTC EMT biomarkers as a complementary analyte to tumour tissue biopsy or as therapeutic targets.

Head and Neck Cancer (HNC) is a broad term used to group oral cavity, pharynx, larynx, salivary gland and nose and sinus cancer, with 90-95% of HNCs being squamous cell cancers. Globally, HNC accounted for over 930,000 new cases and over 460,000 deaths in 2020. In head and neck squamous cell carcinoma, 5-year survival rates are in the region of 50%, depending on cancer type and stage, but largely static for several decades. Common risk factors of this cancer include gender, ethnicity, age, poor oral hygiene, tobacco and alcohol use. The toxicity associated with current treatment regimens for this cancer results in a significant impact upon quality of life. Therefore, early diagnosis and effective targeted treatment options are urgently required to improve patient outcomes. A liquid biopsy, in particular analysing CTCs, is one potential avenue to define such therapeutic biomarkers.

Professor Hisham Mehanna, the Chair of Head and Neck Surgery, and Director of the Institute of Head and Neck Studies and Education (InHANSE) at the Institute of Cancer and Genomic Sciences, University of Birmingham, commented:

"The successful characterisation of EMT CTCs in HNSCC sheds light on the potential adaptive EMT response to stimuli within the circulation of blood, providing an important and unique insight into metastasis. Prospective clinical trials are needed to answer the question regarding the predictive utility of a CTC liquid biopsy (for example CTC immune checkpoint expression directing personalised treatment), especially in recurrent/metastatic patients not amenable to repeat tissue biopsies."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"ANGLE is pleased to report on the use of the Parsortix system as a tool for HNSCC EMT classification. Evidence continues to grow supporting the potential clinical utility of CTC enrichment to provide clinical information beyond the scope of tissue biopsy. This research provides further evidence for the role that EMT CTCs play in the metastatic cascade and the clinical importance of biomarker independent CTC isolation methods which capture all subsets of CTCs. In drug discovery, this may enable the identification of drugs that are better able to target cancer cells known to be the precursors of metastasis. As metastasis is responsible for 90% of cancer deaths, this could be transformative for cancer care and patient outlook."

The research has been published as a peer-reviewed publication in the Journal Head and Neck and 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 platforms include a circulating tumor cell (CTC) harvesting technology known as the Parsortix^® system and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.

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 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 69 peer-reviewed publications and numerous publicly available posters from 31 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.