ANGLE plc ("the Company")

PARSORTIX SYSTEM DEMONSTRATES POTENTIAL IN PREDICTING IMMUNOTHERAPY RESPONSE IN SMALL CELL LUNG CANCER

CTCs isolated by the Parsortix system can be used to evaluate PD-L1 expression

Marker independent isolation of CTCs enables isolation of both EpCAM-negative and positive CTCs from small cell lung cancer patients

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 small cell lung cancer (SCLC) patients using the Parsortix^® system. The primary aim of this study was to demonstrate the ability to evaluate the PD-L1 status of isolated circulating tumour cells (CTCs), providing an alternative sample than solid tissue in SCLC, which may help to predict response to immunotherapy.

The Parsortix system was selected by researchers for the study due to its ability for unbiased CTC enrichment enabling the isolation of both EpCAM-positive and EpCAM-negative cancer cells. This is clinically relevant because, although there is an abundance of high EpCAM expressing CTCs in the SCLC population, EpCAM expression can be lost or downregulated during cancer progression. This progression is associated with increased metastatic potential and worse prognosis, but still many CTC isolation methods, including the leading antibody-based system, only isolate and identify cells expressing the EpCAM marker.

Blood collected from 18 SCLC patients was processed using the Parsortix system (20 samples; 18 samples collected prior to treatment for all patients, with two patients also providing samples at relapse). CTCs were identified in 50% of the samples, from ten of the 18 SCLC patients. The researchers found EpCAM-negative CTCs in three patients, with a small proportion of the CTCs identified also positive for PD-L1 expression. Of the ten CTC-positive patient samples, four samples (40%) had PD-L1-positive CTCs.

This study demonstrates both the ability of the Parsortix system to isolate EpCAM-negative and positive CTCs from SCLC patient samples and how isolated CTCs can be used to quantify PD-L1 expression. This shows the potential of CTCs harvested from a simple blood sample as an alternative to a tissue sample for PD-L1 evaluation in the SCLC population, with the possibility to provide an indication on the likelihood of a patient response to immunotherapy. Currently the proportion of cancer patients that respond to PD-L1 or PD-1 inhibitors is low, ranging from 13% to 50%, yet the cost of treatment is c.$170,000. This highlights a clear need for improved patient selection as non-responders risk developing hyper-progressive disease and suffering from drug toxicity with immune-related adverse events.

Lung cancer is the second most common cancer in the United States. The National Institutes of Health predicts that there will be a total of 235,000 new cases in 2022 with a similar incidence in men and women. Lung cancer is the leading cause of cancer related mortality, accounting for 21% of all cancer deaths, estimated at 130,000 people in 2022. SCLC accounts for approximately 14% of lung cancer cases. Prognosis for SCLC patients is extremely poor with a 5-year survival rate of only 7% and a median overall survival of just 8.5 months. Improved patient selection for targeted treatment and immunotherapy is urgently needed to improve outcomes.

Associate Professor Elin Gray, School of Medical and Health Sciences, Edith Cowan University, commented:

"The current findings extend our knowledge of the ability of epitope-independent technologies to detect subsets of CTCs. The study demonstrates that PD-L1 expression can be quantified on CTCs detected in SCLC patients. This could potentially serve as a marker to evaluate the likelihood of anti-PD-1 therapy response."

ANGLE Founder and Chief Executive, Andrew Newland, added:

"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 SCLC patients and in doing so providing a sample that allows quantification of PD-L1 expression in this population. This publication is well-timed given that ANGLE is currently in the process of developing 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 Translational Lung Cancer Research 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 62 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.