Identifying drug targets in cancer metastasis

RNS Number : 8579G

Angle PLC

01 April 2022

 

For immediate release

01 April 2022

ANGLE plc ("the Company")

PARSORTIX SYSTEM DEMONSTRATES ABILITY TO ISOLATE CTCs FOR DOWNSTREAM MOLECULAR ANALYSIS, IDENTIFYING KEY DRUG TARGETS INVOLVED IN CANCER METASTASIS

World-class research identifies specific genetic steps in the metastatic process, paving the way to test targeted treatment approaches

Metastatic process driven by invasion of CTCs and CTC clusters found to be dependent on druggable gene targets

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the Molecular Oncology Laboratory at the Swiss Federal Institute of Technology (ETH) Zurich, Switzerland, has published results of work undertaken in preclinical models of metastatic breast cancer (MBC), where they have identified specific genes involved in various steps of the metastatic process. This included actionable targets found to be required for the formation of circulating tumour cells (CTCs) and their seeding at secondary metastatic tumour site. In a preclinical model, targeted therapy was found to reduce metastasis and has the potential to improve patient outcomes.

Researchers used ANGLE's Parsortix^® system to isolate single CTCs and CTC clusters from preclinical MBC models engineered with CRISPR technology, and the CTCs were analysed using DNA sequencing. The team identified metastasis-relevant genes, where loss-of-function of the genes resulted in decreased CTC cluster generation and reduced metastatic burden. This has clinical relevance as it has been estimated that CTC clusters have 23-50-fold increased metastatic potential compared to single CTCs and confer a higher risk of death in MBC patients. The authors also identified actionable gene targets, such as PLK1, that are required for the formation of both single CTCs and CTC clusters. Treatment with approved targeted therapy reduced CTC shedding and metastasis formation in the preclinical model. This is particularly relevant to patient outcomes given that ~90% of cancer deaths are a result of metastasis.

This study adds to the growing body of evidence demonstrating the ability of the Parsortix system to isolate single CTCs and CTC clusters, enabling the identification of actionable targets involved in the metastatic spread of cancer. This research has potential clinical applicability in discovering and testing, new and existing, targeted therapies.

In the United States, breast cancer is the most frequently diagnosed cancer in women with 287,000 new cases expected in 2022, accounting for 31% of all new cancer cases. It is estimated that 6% of patients have metastatic disease at diagnosis and approximately 20-30% of all breast cancer patients will eventually develop metastatic disease. Identification of appropriate targets will be essential to enable the development of targeted therapies for MBC.

Prof Nicola Aceto, ETH Zurich, commented:

"Our study provides a novel CTC-based tool to study spontaneous breast cancer metastasis in a highly clinically relevant fashion. Using this model in combination with a CRISPR-based approach, we demonstrate the involvement of targetable players in the metastatic spread of cancer, with potential clinical applicability."

ANGLE Founder and Chief Executive, Andrew Newland, added:

"We are pleased to report on the use of the Parsortix system for the isolation of single CTCs and CTC clusters in preclinical MBC models, allowing the identification of actionable targets involved in cancer metastasis. ANGLE's ability to provide such actionable insight shows potential to guide targeted drug development, which can be achieved through our growing pharma services business."

The research has been published as a peer-reviewed publication in the Journal Cancer Research and is available online at https://angleplc.com/library/publications/ .

For further information:

ANGLE plc	[phone]
Andrew Newland, Chief Executive Ian Griffiths, Finance Director Andrew Holder, Head of Investor Relations
Berenberg (NOMAD and Joint Broker) Toby Flaux, Ciaran Walsh, Milo Bonser	[phone]
Jefferies (Joint Broker) Max Jones, Thomas Bective	[phone]
FTI Consulting Simon Conway, Ciara Martin Matthew Ventimiglia (US)	[phone] [phone]

For Frequently Used Terms, please see the Company's website on https://angleplc.com/investor-relations/glossary/

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 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 59 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 Parsortix in cancer drug trials and, once the laboratories are accredited and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management.

 

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