Angle Regulatory News (AGL)

ANGLE plc ("the Company")

CTCS ISOLATED BY THE PARSORTIX SYSTEM FROM METASTATIC BREAST CANCER PATIENTS CAN BE ANALYSED BY MULTIPLE DOWNSTREAM TECHNIQUES

Publication of results from ANGLE's multi-centre clinical study in collaboration with leading US cancer centres

Data from the study contributed to the successful De Novo FDA regulatory clearance of the Parsortix system

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce the publication of results from a multi-centre clinical study undertaken with The University of Texas MD Anderson Cancer Center, TX, Wilmot Cancer Institute, University of Rochester, NY, Robert H Lurie Comprehensive Cancer Center, Northwestern University, IL, and Norris Comprehensive Cancer Center, University of Southern California, CA, US. The Parsortix® system was used to enrich circulating tumour cells (CTCs) from 207 patients with metastatic breast cancer (MBC) with each patient providing two blood tubes allowing for testing of multiple downstream analytical techniques.

This research highlights the ability to perform multiple downstream analyses on CTCs enriched using the Parsortix system. CTCs isolated from the peripheral blood of MBC patients were successfully evaluated by cytology (i.e., Wright-Giemsa staining), real time quantitative reverse transcriptome PCR (qRT-PCR), RNA sequencing and fluorescence in situ hybridisation (FISH). The analyses, demonstrated to be successfully performed on CTCs enriched by the Parsortix system, use commercially available reagents and are standard techniques used in many clinical and/or laboratory settings.

This successful study provided data to support the De Novo Class II Classification application for the Parsortix system for use in harvesting cancer cells from MBC patient blood for subsequent, user-validated analysis, which was granted by US Food and Drug Administration (FDA) on May 24th 2022.

Further details about the study

The cells captured by the Parsortix system from one of the blood tubes were subjected to Wright-Giemsa staining and a board-certified pathologist enumerated the CTCs by cytologic evaluation. The second blood tube for each patient was used to assess the proof of principle for one of three additional evaluation techniques: gene expression analysis by qRT-PCR, RNA sequencing, or analysis of HER2 amplification by FISH.

The cytologic evaluation identified CTCs in 48.5% of all evaluable MBC patient samples independent of tumour subtype. CTCs were identified in 33.3% of newly diagnosed MBC patients, and in 56.8% of recurring or progressing MBC patients. Of the MBC patients' samples assessed by qRT-PCR, 52.7% were positive for at least one of the CTC-related genes and showed a general correlation with CTC count particularly at higher burden. There were 200 differentially expressed genes in the MBC patients, compared to healthy donors, as shown through RNA sequencing, with significant enrichment of cancer signalling pathway genes. HER2 amplification, detected via FISH analysis, was observed in a single patient sample with identifiable CTCs that also had HER2 positive tissue status.

Dr. James M. Reuben, Professor, Department of Hematopathology, Division of Pathology/Lab Medicine, MD Anderson Cancer Center and co-PI of the trial commented:

"My lab's overarching interest is to develop assays that will serve as companion diagnostics to assist clinicians who treat cancer patients (MBC and non-small cell lung cancer) with therapies such as immune checkpoint inhibitors and targeted agents. Therefore, we have devoted considerable effort to developing multiple cellular and molecular assays utilizing CTCs which offer a minimally invasive approach to monitor a patient's cancer and their response to these therapies. Data from this trial showed the Parsortix system was able to effectively capture a single cancer cell in a blood sample for analysis. We look forward to the further development of CTC based assays that may bring enormous benefits to patients with MBC as well as other cancers in the future."

Dr. Reuben receives research support from ANGLE, and he is compensated as a member of its Scientific Advisory Board. This financial relationship has been disclosed to MD Anderson's Conflict of Interest Committee.

ANGLE Founder and Chief Executive, Andrew Newland, added:

"The characterisation of CTCs has the potential for clinical utility in areas such as treatment selection, longitudinal monitoring of treatment response and disease recurrence. We are delighted to share the multi-centre clinical study results that show the variety of downstream analyses possible for characterisation of CTCs enriched by the Parsortix system. The data from this clinical study contributed to the ground-breaking success of a De Novo FDA regulatory clearance for the Parsortix system, which we expect to drive the commercialisation of the system."

The research has been published as a peer-reviewed publication in the Journal Cancers and will be 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 72 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.