Angle Regulatory News (AGL)

ANGLE plc ("the Company")

BREAKTHROUGH RESEARCH DEMONSTRATES A PARSORTIX TEST COULD AVOID UNNECESSARY PROSTATE BIOPSIES

 Barts Cancer Institute demonstrates capability of Parsortix system to detect clinically significant prostate cancer to reduce over-diagnosis and over-treatment

Results published in peer-reviewed Journal of Urology offer major market opportunity for ANGLE

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce that Queen Mary University of London's Barts Cancer Institute has published results of new work undertaken in early stage prostate cancer utilising ANGLE's Parsortix® system demonstrating the potential to out-perform current standard of care in the detection and assessment of prostate cancer. This builds on Barts Cancer Institute's previous work with the Parsortix system in later stage prostate cancer and assessment of aggressiveness.

The work investigated 98 pre-biopsy patients and 155 newly diagnosed but as yet untreated prostate cancer patients over a two year period. Results have been published as a peer-reviewed publication in the Journal of Urology and may be accessed via https://angleplc.com/library/publications/.

Under the current standard of care, investigation of symptoms for prostate cancer is typically made via a blood test measuring PSA (prostate specific antigen) protein levels in the blood. If the PSA level is above a threshold level, then the patient will be subjected to a tissue biopsy of the prostate gland. The tissue biopsy is invasive and carries a risk of infection (between 2% and 4% of patients having a prostate tissue biopsy suffer sepsis, a potentially fatal infection, as a direct result of the procedure). It can also be inaccurate and misses the presence of cancer in around 20% of cases as it only samples a small fraction of the prostate gland; consequently men with ongoing high PSA readings may end up having multiple tissue biopsies and potentially a delayed diagnosis.

The PSA blood test has a notoriously low specificity (high false positives) with about 75% of all PSA positive results ending up with negative biopsies that do not find cancer. Consequently the majority of prostate tissue biopsies undertaken are unnecessary, resulting in needless invasive intervention for the patient and a waste of healthcare resources.

In contrast, because it is investigating a biologically specific analyte of living cancer cells in the blood stream, the Parsortix based test in this study showed a dramatically higher performance with 93% (38/41) of Parsortix positive results yielding a malignant tissue biopsy, which is extremely high bearing in mind the tissue biopsy has its own limitations in missing cancers.

The data suggest that, if a combined Parsortix and PSA approach was adopted to determine which patients should have tissue biopsies, a substantial proportion of unnecessary biopsies could be eliminated without missing any clinically significant prostate cancer cases. This would reduce the problems of injury to patients from the tissue biopsy and over-treatment as well as save substantial healthcare expenditure.

Prostate cancer is the most prevalent cancer for men with an estimated 3.7 million men living with the disease and 1.3 million new cases being diagnosed each year worldwide. Because the Parsortix system measures intact living cancer cells in the patient blood (not just a protein than may be over-expressed for reasons other than cancer), it offers the potential for a high specificity test (low false positives) to detect clinically significant prostate cancer.

Further studies will be needed to develop and validate a Parsortix test in this area, which offers a market potential for ANGLE estimated to be in excess of US $3 billion per annum globally.

Dr Yong-Jie Lu, Professor in Molecular Oncology at Barts Cancer Institute, Queen Mary University of London, commented:

 "In this work, we have developed protocols using the Parsortix liquid biopsy system to detect CTCs in early stage prostate cancer and have shown its potential in avoiding unnecessary prostate biopsies, allowing resources to be focused on men with clinically significant prostate cancer. This would improve the diagnostic pathways/procedures for patients as well as reducing healthcare costs."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"This is a major new study from Barts Cancer Institute demonstrating potential for ANGLE's Parsortix system to transform care in early stage diagnosis for the most prevalent cancer type in men. Prostate cancer is a high priority for the Company's development once we have concluded our current FDA and verification studies in breast cancer and ovarian cancer."

The study published in the Journal of Urology is described in Queen Mary University of London's press release, which is reproduced in full below.

*** Queen Mary University of London IMMEDIATE RELEASE ***

New blood test for prostate cancer is highly-accurate and avoids invasive biopsies

A new and simple blood test has been found to efficiently and accurately detect the presence of aggressive prostate cancer, according to research by Queen Mary University of London.

In combination with the current prostate specific antigen (PSA) test, the new test could help men avoid unnecessary and invasive biopsies, over-diagnosis and over-treatment.

Prostate cancer is the most common cancer in Western men, with 1.3 million new cases being diagnosed each year worldwide. It is currently detected using a blood test that measures PSA levels. Although it provides early diagnosis, the PSA blood test has a low specificity (high false positives) with about 75 per cent of all PSA positive results ending up with negative biopsies that do not find cancer.

When a high PSA level in the blood is detected, the patient undergoes a tissue biopsy of the prostate gland, which is invasive and carries a significant risk of bleeding and infection. On biopsy, the majority of patients with elevated PSA levels are found not to have cancer.

Additionally, most diagnosed early-stage prostate cancers are not fatal if left untreated. The current practice of the combined PSA test and biopsy for prostate cancer therefore results in unnecessary biopsies and over-diagnosis and overtreatment of many men.

The new prostate cancer test (the Parsortix® system from ANGLE plc) detects early cancer cells, or circulating tumor cells (CTCs), that have left the original tumour and entered the bloodstream prior to spreading around the body. By measuring intact living cancer cells in the patient's blood, rather than the PSA protein which may be present in the blood for reasons other than cancer, it potentially provides a more accurate test for prostate cancer.

The study, published in the Journal of Urology, looked at the use of the CTC test in 98 pre-biopsy patients and 155 newly diagnosed prostate cancer patients enrolled at St Bartholomew's Hospital in London.

The research team found that the presence of CTCs in pre-biopsy blood samples were indicative of the presence of aggressive prostate cancer, and efficiently and non-invasively predicted the later outcome of biopsy results.

When the CTC tests were used in combination with the current PSA test, it was able to predict the presence of aggressive prostate cancer in subsequent biopsies with over 90 per cent accuracy, better than any previously reported biomarkers.

Additionally, the number and type of CTCs present in the blood was also indicative of the aggressiveness of the cancer. Focusing on more aggressive prostate cancer may reduce over-treatment and unnecessary biopsies for benign and non-aggressive conditions.

Lead researcher Professor Yong-Jie Lu from Queen Mary University of London said: "The current prostate cancer test often leads to unnecessary invasive biopsies and over-diagnosis and overtreatment of many men, causing significant harm to patients and a waste of valuable healthcare resources. There is clearly a need for better selection of patients to undergo the biopsy procedure.

"Testing for circulating tumour cells is efficient, non-invasive and potentially accurate, and we've now demonstrated its potential to improve the current standard of care. By combining the new CTC analysis with the current PSA test, we were able to detect prostate cancer with the highest level of accuracy ever seen in any biomarker test, which could spare many patients unnecessary biopsies. This could lead to a paradigm shift in the way we diagnose prostate cancer."

As this is a single centre study, the results need to be further validated in other independent research centres before the CTC test is available either privately or on the NHS in the UK, which could take a further 3-5 years. Clearance by the US Food and Drug Administration could also take 3-5 years.

This work was funded by Orchid Cancer Appeal, Cancer Research UK and ANGLE plc (which manufactures the Parsortix system). The funding sources had no role in the design of the study; the collection, analysis, or interpretation of the data; or the writing of the research paper.

More information

Research paper: Non-invasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells. Lei Xu , Xueying Mao , Alistair Grey , Glenda Scandura , Tianyu Guo , Edwina Burke , Jacek Marzec , Semah Abdu , Elzbieta Stankiewicz , Caitlin R Davies , Prabhakar Rajan , Karen Tipples , John Hines , Pui Ying Chan , Diane Campbell , Karen Wilkinson , Sakunthala Kudahetti , Jonathan Shamash , Tim Oliver , Daniel Berney , Greg Shaw , and Yong-Jie Lu. Journal of Urology. Doi 10.1097/JU.0000000000000475

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 an epitope-independent 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 downstream subsequent analyses. CTCs enable the complete picture of a cancer to be seen as 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 system is based on a microfluidic device that captures cells based on a combination of their size and compressibility. 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 study 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 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 24 peer-reviewed publications and numerous publicly available posters, available on our website.