ANGLE plc ("the Company")

Parsortix system demonstrates ability to isolate CTCs for downstream gene analysis revealing multiple prognostic biomarkers

Leading European study centre presents results of three studies in ovarian and lung cancer at 5^th ACTC Conference

Novel CTC biomarkers found to predict progression free survival and treatment response for longitudinal patient monitoring in ovarian cancer

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the Molecular Oncology Group at the Medical University of Vienna, presented results of three studies at the 5^th Advances in Circulating Tumour Cells (ACTC) conference, held 22-25 September in Kalamata, Greece.

The studies in ovarian cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients, all utilised ANGLE's biomarker-independent Parsortix^® system to isolate circulating tumour cells (CTCs) from a simple blood draw.

The largest study, a Phase II drug trial including 133 ovarian cancer patients, explored longitudinal gene expression of CTCs isolated using the Parsortix system in platinum-resistant patients enrolled on the GANNET53 trial over a five year period with an average four time points for each patient. Gene expression analysis of genes expressed on CTCs isolated from successive blood draws correlated closely with significantly improved progression free survival and response to therapy. For example, at cycle 1, gene expression analysis of CTCs isolated by the Parsortix system could predict responders (with a survival rate of 85% at 120 days) compared to non-responders (with a survival rate of 30% at 120 days). This pattern was repeated at all the cycle points. In the conference poster, the researchers described this as a "landmark analysis". This study demonstrates how gene expression analysis of CTCs, isolated by the Parsortix system, can be used in pharma drug trials for longitudinal patient monitoring and to guide treatment selection.

In the second study, researchers evaluated the detection of tumour protein p53 as a new marker for CTC detection in SCLC. p53 is coded for by the tumour suppressor gene TP53, which is mutated in 75-90% of SCLC patients and is the target of several novel drugs in clinical development. For the first time, the presence of p53 in CTCs was demonstrated, suggesting that they are a unique new marker for CTC detection. Furthermore, the presence of p53 aggregates is likely to be a valuable biomarker for targeted treatment selection, and of interest to pharma companies developing drugs targeting p53.

In the third study in NSCLC, the researchers performed qPCR molecular analysis on the CTCs captured by the Parsortix system in samples from 118 NSCLC patients and 30 healthy volunteers. The research demonstrated that the CTCs expressing EMT (epithelial mesenchymal transition) and/or cancer stem cell markers were the most clinically relevant for prognosis rather than CTCs expressing epithelial markers. This is significant because competing antibody-based CTC systems utilise epithelial markers for CTC capture and miss the CTCs that do not express these markers.

In addition, in matched samples, the gene expression analysed by qPCR of CTCs harvested by the Parsortix system was found to be more effective at prognostic analysis (predicting overall patient survival) than assessing the presence of epithelial CTCs.

These studies demonstrate that CTC analysis before and during treatment can provide non-invasive monitoring of cancer patients throughout their treatment pathway and that CTC gene expression profiles can determine progression free survival and response to therapy.

Ovarian cancer accounts for an estimated 21,400 cases in the United States in 2021 and is associated with poor patient outcomes. 57% of cases are diagnosed when the cancer has already metastasised and in these patients 5-year survival rates are just 30%. As such a clear need exists for biomarkers which can support personalised medicine and track patient response to optimise the care pathway.

Lung cancer is the second most common cause of cancer in the United States and the leading cause of cancer related mortality, responsible for 22% of all cancer related deaths. In 2021, The National Cancer Institute predicts that there will be a total of 236,000 new cases and 132,000 deaths - NSCLC accounts for 84% of all lung cancer cases. Whilst the overall 5-year survival rate for NSCLC is 25%, 60% of patients are diagnosed with metastatic (stage IV) disease for which the 5-year relative survival rate is just 5%. SCLC accounts for 13% of all lung cancer cases with a 5- year survival rate of just 7%.

These studies were presented at the 5^th ACTC conference, which took place on 22-25 September, and may be accessed via https://angleplc.com/library/publications/.

Associate Professor Robert Zeillinger, Founder and Head, Molecular Oncology Group, Dep. of Obstetrics and Gynaecology, Medical University of Vienna commented:

"These studies further demonstrate the relevance of the molecular characterisation of CTCs by qPCR. Our multi-marker analysis highlights the value of gene expression analysis for patient monitoring and determining response to therapy."

ANGLE Founder and Chief Executive, Andrew Newland, said:

"The Advances in Circulating Tumour Cells (ACTC) conference is the pre-eminent event focused on exploring the promise of CTCs in cancer research and patient management. ANGLE is pleased to see further world-class research being presented by Prof. Zeillinger and his team, which has been enabled by the Parsortix system. These studies, including data from a large multicentre European clinical trial, build on the growing body of evidence supporting the use of the Parsortix system to provide cancer cells for analysis from a simple blood test and to uncover potentially valuable new cancer biomarkers, with the potential to guide drug development and inform treatment decisions."

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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 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 49 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.