Angle PLC Announces Potential Treatment Strategy to Limit Metastasis

Published research using the Parsortix system to isolate CTC clusters from blood confirms the role of intra-tumour hypoxia in promoting metastatic breast cancer

Study highlights the potential for Parsortix liquid biopsy in cancer drug discovery

GUILDFORD, SURREY / ACCESSWIRE / September 23, 2020 / ANGLE plc (AIM:AGL)(OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce that the University of Basel has published breakthrough research, using ANGLE's Parsortix^® system, into the role of hypoxia (reduced oxygen levels) in promoting breast cancer metastasis.

Groups of circulating tumour cells (CTCs), known as clusters, have been reported to be 50 times more likely to generate metastasis compared to individual CTCs. The new research, led by Professor Nicola Aceto at the Cancer Metastasis Laboratory, University of Basel Switzerland, found that intra-tumour hypoxia increased CTC cluster shedding rate and metastasis formation in mice. In addition, hypoxic (compared to normoxic) CTCs formed significantly larger cell clusters, leading to the development of metastasis earlier and reducing survival time.

The new research suggests that intra-tumour hypoxia creates conditions that stimulate the formation of an increased number and size of CTC clusters, which may increase (rather than decrease) the metastatic spread of the cancer. This is critical because over 90% of patients who die of cancer die of the metastatic spread of the disease, not because of the primary tumour. In short, it is possible that some established treatments, whilst they may reduce growth of the primary tumour short-term, may actually be promoting the metastatic growth of the cancer, damaging the long-term outcome. More research will be needed to understand these impacts and the Parsortix system is the leading system to enable effective investigation of CTC clusters to facilitate this research.

The researchers also investigated alternative treatments seeking to reduce the metastatic spread of the disease in breast cancer. Hypoxia is known to occur in the central core of tumours and within regions that are poorly vascularised. By using a targeted protein, EphrinB2, the researchers could increase and normalise vascularisation in a mouse model, reducing intra-tumour hypoxia. EprinB2, or other therapies which effect a similar response, could form the basis of a new treatment strategy for metastatic breast cancer, both to prevent further metastasis by reducing tumour hypoxia and shedding of hypoxic CTC clusters, and by increasing blood flow to allow co-administered chemotherapy agents to better reach the tumour.

This study demonstrates key capabilities of the Parsortix system to support cancer drug discovery. It also exemplifies the utility of the Parsortix system in isolating metastatic breast cancer CTCs, which is the area of focus for ANGLE's FDA De Novo Submission.

The research, which has been published in the peer-reviewed journal Cell Reports, may be accessed via https://angleplc.com/library/publications/.

Breast cancer is the most frequently diagnosed cancer in women in the United States and there are an estimated 3.6 million women living with breast cancer in the United States. Despite new treatment options and advances in patient management protocols, 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent advanced or metastatic disease. Although the prognosis of patients with metastatic breast cancer has significantly improved over the last two decades, it remains largely incurable with median survival of three years.

Approximately 50% of metastatic breast cancer patients are unable to receive a successful tissue biopsy of the metastatic site due to the patient being too ill, or problems accessing the metastatic sites such as the lung, liver, brain and bone, or insufficient cells being retrieved for analysis. CTCs as a liquid biopsy, provides for non-invasive, real-time monitoring of cancer patients, giving comprehensive insight into clonal evolution during tumour metastasis and the potential to provide actionable information for targeted therapy.

Professor Nicola Aceto, Group Leader - Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Switzerland, commented:

"Our study suggests that intra-tumour hypoxia is the main trigger for the generation of hypoxic CTC clusters with a high tendency to initiate metastasis. We propose that a therapy that normalises vascularisation may suppress intra-tumour hypoxia and intravasation of clustered CTCs, leading to a reduction in metastasis. In combination with other established anti-cancer agents, Ephrin may not only prevent further metastasis to metastasis dissemination but also improve perfusion to existing cancerous lesions, thereby facilitating the uptake of the co-administered compound. Clinical studies in well-defined patient populations will be key to address this treatment approach."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"This study further exemplifies the capability of the Parsortix system to isolate viable CTCs and CTC clusters, which enable cell culture and xenograft to further our understanding of tumour cell biology and metastatic development. This seminal work, by one of ANGLE's leading customers, exemplifies how the Parsortix system can enable drug discovery by identifying mechanisms for metastatic spread which can form the basis of new treatment strategies."

For further information ANGLE:

The information communicated in this announcement is inside information for the purposes of Article 7 of Regulation 596/2015.

For Frequently Used Terms, please see the Company's website on http://www.angleplc.com/the-parsortix-system/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 a complete cell they allow DNA, RNA and protein analysis and the live cells harvested can be cultured. The Parsortix technology is the subject of 24 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 FDA clearance is in process for the United States with a 400 subject clinical study and associated analytical studies in metastatic breast cancer. ANGLE is seeking to be the first ever FDA cleared CTC harvesting system and only the third ever FDA cleared liquid biopsy test. ANGLE has already undertaken 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 (ROC-AUC) 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 (ROC-AUC) 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 36 peer-reviewed publications and numerous publicly available posters, available on our website.

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SOURCE: ANGLE PLC