Parsortix study uncovers targets in TNBC patients

ANGLE plc ("the Company")

NEW PARSORTIX STUDY UNCOVERS THERAPEUTIC TARGETS IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

Parsortix system harvests intact CTCs for whole genomic sequencing identifying multiple druggable targets

Study demonstrates ctDNA and CTCs can both be analysed using the same blood sample

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that a leading cancer research institute, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, has published results of new work undertaken in triple negative breast cancer (TNBC) patients. Researchers used ANGLE's Parsortix^® system to isolate circulating tumour cells (CTCs) in patients with recurrent disease and analysed these concurrently with circulating tumour DNA (ctDNA, fragments of tumor derived DNA) in the blood.

Neoadjuvant chemotherapy (chemotherapy administered before surgery) is increasingly used in TNBC. In this study, researchers investigated the value of ctDNA for patient monitoring and CTCs for disease characterisation at progression or recurrence, from a single blood sample.

Using ANGLE's marker-independent Parsortix system for CTC-enrichment, coupled with the DEPArray™ system for automated single-CTC retrieval following harvest by Parsortix, the authors showed that, in the vast majority of recurrent cancer cases, CTCs identified were non-epithelial and would not have been detected by any of the commercially available epithelial antibody-based approaches, including the market leader.

The inclusion of CTC harvest and subsequent analysis at disease recurrence enabled multiple druggable targets to be identified. This included PI3K, HER2, BRAF, platinum-resistance signalling, and regulation of immune response correlating to at least 12 FDA approved drug treatment options. This is of particular significance in patients with TNBC where endocrine therapy or anti-HER2 agents are ineffective and therefore treatment options are limited.

Breast cancer is the most frequently diagnosed cancer in women in the United States with 280,000 new cases anticipated in 2021, accounting for 15% of all new cancer cases. The American Cancer Society estimates that TNBC accounts for about 10-15% of all breast cancers. TNBC differs from other types of invasive breast cancer in that it grows and spreads faster, has limited treatment options, and a worse prognosis.

This study demonstrates how analysis of CTCs harvested by the Parsortix system, as a liquid biopsy, have significant potential for non-invasive, real-time monitoring of cancer patients, giving insight into druggable targets for next line therapy at disease recurrence.

The research has been published as a peer-reviewed publication ESMO Open and may be accessed via https://angleplc.com/library/publications/.

Dr Serena Di Cosimo, Senior Clinical Researcher at the Department of Applied Research and Technological Development of the National Cancer Institute of Milan commented:

"We designed this observational prospective study to explore ctDNA for earlier detection of relapse in TNBC patients with CTC analysis from blood drawn as a means to identify druggable molecular features in relapsed cases.

Of the CTCs isolated by the Parsortix system, only ~5% had epithelial markers. This highlights the importance of marker independent CTC enrichment to provide insight in patients with recurrent disease. Our findings support blood-based genomic analyses as complementary tools to optimize monitoring and to guide therapy in TNBC patients. Prospective trials are ongoing and will address the clinical utility of incorporating such strategies into routine clinical practice."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"The use of the Parsortix system in uncovering potential new therapeutic targets through its ability to harvest mesenchymal as well as epithelial CTCs for analysis showcases further evidence of the advantages of using the Parsortix system over antibody-based CTC systems. ANGLE's ability to provide this actionable information could help patients who have limited treatment options and should prove highly attractive to drug developers looking for new approaches for hard-to-treat cancers, such as TNBC.

Harnessing these unique capabilities in our clinical services laboratories is allowing ANGLE to accelerate the commercial deployment of the Parsortix system by offering services to pharmaceutical and biotech customers for use in cancer drug clinical trials, a market where we are already gaining traction."

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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 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 HyCEADTM 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 42 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.