Angle Regulatory News (AGL)

ANGLE plc ("the Company")

TWO PARSORTIX POSTERS PRESENTED AT LEADING BREAST CANCER CONFERENCE

Studies demonstrate the utility of the Parsortix PC1 Clinical System to isolate and harvest CTCs from metastatic breast cancer patients for further downstream analysis

Harvested CTCs underwent cytological, immunofluorescent and molecular downstream evaluation

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce the presentation of two posters at the San Antonio Breast Cancer Symposium (SABCS), in San Antonio, Texas, United States, between 06-10 December 2022. The studies demonstrated the successful isolation and subsequent analysis of circulating tumour cells (CTCs) from Metastatic Breast Cancer (MBC) patient blood samples using the Parsortix® PC1 Clinical System.

The first poster, presented by ANGLE, outlines the utility of the Parsortix PC1 Clinical System in capturing and harvesting CTCs from a significantly larger proportion of MBC patients, compared to healthy donor samples. The ANG-008 study evaluated 75 MBC patient blood samples and 71 healthy volunteer blood samples. Firstly, the harvested CTCs were deposited onto glass slides for staining using cytocentrifugation, a method which has been shown to lose a significant proportion of cells. The cells retained on the cytology slides were stained using an immunofluorescence (IF) assay, and CTCs were characterized as nucleated cells that were positive for CK and/or EpCAM and negative for blood markers. The IF-stained slides were subsequently restained using Wright-Giemsa reagents and CTCs identified by a qualified pathologist. CTCs were observed in 45.3% and 42.9% of MBC patients following IF and Wright-Giemsa evaluation, respectively. Of the CTC-positive MBC patient samples, 70.6% had CK positive and EpCAM negative cells only. This high proportion of EpCAM negativity highlights the limitations of using EpCAM-based approaches to capture CTCs and the advantages of using the epitope-independent Parsortix PC1 Clinical System.

The second poster, presented by The University of Texas MD Anderson Cancer Center, showed results from the ANG-002 HOMING study, a prospective clinical trial that highlights the use of the Parsortix PC1 Clinical System for the isolation and harvest of CTCs from patients with MBC and its ability to perform multiple subsequent downstream analyses on the harvested CTCs. The research evaluated 207 MBC patients, including newly diagnosed, recurrent and progressive MBC patients, and 204 healthy volunteers. Similarly, this study identified CTCs using Wright-Giemsa staining confirmed by a qualified pathologist. Furthermore, as proof of concept, CTCs harvested from a second blood sample were evaluated using one of three additional subsequent evaluation techniques, including molecular profiling by real time quantitative reverse transcription PCR (qRT-PCR) or RNA sequencing, or analysis of HER2 amplification by fluorescence in situ hybridisation (FISH).

The cytologic evaluation, which used the same cytocentrifugation method to deposit the harvested cells onto glass slides for staining, identified CTCs in 48.5% of all evaluable MBC patient sample independent of tumour subtype. Molecular profiling demonstrated (i) a higher expression of CTC related genes in MBC patients compared to healthy volunteers, (ii) a correlation of CTC related gene expression with CTC count and (iii) genes from a specific cancer pathway (KEGG) were differentially expressed in MBC patients when compared to healthy volunteers. Furthermore, the HER2 status, analysed by FISH, of the harvested CTCs was successfully evaluated, with amplification being observed in a single CTC from an MBC patient sample.

Data generated from both studies was used to support the De Novo classification of the Parsortix PC1 Clinical System as a Class II device, which was granted by the US Food and Drug Administration (FDA) on 24th May 2022.

Overall, the research presented at the SABCS highlights the successful use of the Parsortix PC1 Clinical System for CTC enrichment in blood from patients with MBC, allowing for a variety of possible downstream analyses, including IF and Wright-Giemsa staining and molecular profiling evaluation.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"We are pleased to announce ANGLE's contributions and attendance at the San Antonio Breast Cancer Symposium this year. The two posters presented showcase the utility of the Parsortix PC1 Clinical System for the isolation and harvest of CTCs for use in multiple subsequent downstream analyses. We continue to show the valuable use of the instrument to identify EpCAM negative CTCs, which is not possible with alternative antibody-based approaches. The data from these two studies contributed to the ground-breaking success of a De Novo FDA regulatory clearance for the Parsortix PC1 Clinical System, which we believe will drive future commercial success."

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 75 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.