Parsortix test successful in discriminating malignant and benign abnormal pelvic masses from a simple blood draw for detection of ovarian cancer

Best in class results indicate the potential to reduce both false positives and false negatives by 50% or more

GUILDFORD, UK / ACCESSWIRE / September 29, 2022 / ANGLE plc ("the Company") (AIM:AGL)(OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce positive headline results from its ovarian cancer clinical verification study, demonstrating that a Parsortix^® blood test can be used to determine if a woman is at risk of a malignant pelvic mass. Following the recent FDA clearance and CE Marking of the Parsortix PC1 system for use in metastatic breast cancer, this achievement marks another important milestone in the Company's commercialisation strategy.

The study evaluated blood samples from patients diagnosed with a pelvic mass and was led by Dr Richard Moore at the University of Rochester Medical Centre, Wilmot Cancer Institute in New York, Unites States. 144 patients (48 of which were found to have a malignancy following surgery) had blood samples shipped to ANGLE's laboratory for processing and evaluation. The population of cells captured and harvested using the Parsortix system were evaluated using ANGLE's Landscape⁺ Ovarian assay to determine the expression levels of 164 different gene transcripts. Analysis of the data produced an algorithm for the prediction of the risk of malignancy that combines the physician's initial cancer risk assessment (benign vs. malignant), the patient's age, and the RNA expression levels of 23 different genes.

The area under the receiver operating characteristic curve (ROC-AUC) for this predictive algorithm was 95.4%, a level which is considered "Excellent"¹. Employing a threshold of ≥40% for the risk probability (a value of between 0 - 100% that is generated by the algorithm using the patient specific inputs) resulted in a sensitivity of 90%, a specificity of 93%, a positive predictive value (PPV) of 86%, a negative predictive value (NPV) of 95%, a false positive rate (FPR) of 7%, a false negative rate (FNR) of 10%, and an accuracy of 92%. Compared to the physician's initial cancer risk assessment for this patient cohort (which had a sensitivity of 75%, a specificity of 86%, a PPV of 74%, a NPV of 87%, a FPR of 14%, a FNR of 25% and an accuracy of 83%), the predictive algorithm would significantly aid the physician in their risk assessment, and in particular, reduced both the FPR and the FNR by 50% or more.

The performance of the Parsortix Landscape⁺ Ovarian assay in this study was in-line with the high level of accuracy demonstrated in an earlier 200 patient multicentre clinical study reported in 2018 (ROC-AUC 95.1%) and achieved the Company's objective of best in class results with both sensitivity and specificity of 90% or greater.

ANGLE believes the clinical data reported today provides a clear demonstration of the value of the Parsortix harvest of circulating tumour cells as the "best sample" for subsequent analysis as a liquid biopsy. This is possible because the Parsortix system recovers intact living cancer cells in the patient blood, which contrasts with other tests based on free-floating proteins that can be upregulated for reasons other than cancer.

In contrast to ANGLE's previously reported MAGIC algorithm², the new algorithm utilises more comprehensive gene expression information derived from blood samples shipped overnight to a central laboratory, uses a lysis buffer that does not require the separate extraction of RNA from the population of cells captured by the Parsortix system, and does not directly rely on the use of serum biomarkers. The clinical results therefore demonstrate the ability to undertake complex molecular analysis of the Parsortix harvest and confirms its suitability for use in both hospital laboratories and central laboratories requiring sample shipping. ANGLE believes that these key findings provide evidence of the potential for widespread use of the Parsortix system for molecular analysis in numerous different cancer applications adding greatly to the value of the FDA cleared Parsortix system.

Following these excellent results, ANGLE is finalising detailed plans for the commercialisation of Parsortix Landscape⁺ molecular assays including, but not limited to, ovarian cancer and will update the market once these are complete.

ANGLE Founder and Chief Executive, Andrew Newland, commented:
"Demonstration of clinical utility of the Parsortix system is a key strategic goal for ANGLE, so the excellent results from this study are validation of what can be achieved in a demanding clinical setting. Further, these results demonstrate the capability to undertake a complex molecular analysis of the Parsortix harvest in a real world setting. This important capability has potentially numerous, widespread alternative uses, reinforcing our belief that a Parsortix harvest of circulating tumour cells from a liquid biopsy offers the "best sample" for clinicians seeking actionable information to guide patient cancer treatment."

1. The area under the curve (AUC) for a receiver operating characteristic (ROC) plot, a plot of 1-specificity on the x-axis vs. the sensitivity on the y-axis at each possible threshold for a test's results, is a measure of the test's accuracy. The accuracy of the test depends on how well the test separates the two groups being tested into those with the outcome (sensitivity) and those without the outcome (specificity) in question. An AUC of 1 (100%) represents a perfect test while an AUC of 0.5 (50%) represents a worthless test. The traditional academic classification system for ROC-AUCs is 90% to 100% = excellent; 80% to 90% = good; 70% to 80% = fair; 60% to 70% = poor; 50% to 60% = fail. Source: University of Cambridge MRC Unit.

https://imaging.mrc-cbu.cam.ac.uk/statswiki/FAQ/roc

2. Moore RG, Khazan N, Coulter MA, Singh R, Miller MC, Sivagnanalingam U, DuBeshter B, Angel C, Liu C, Seto K, Englert D, Meachem P and Kim KK. Malignancy Assessment Using Gene Identification in Captured Cells ("MAGIC") Algorithm for the Prediction of Malignancy in Women With a Pelvic Mass. Obstet Gynecol Online ahead of print, September 08, 2022.

https://pubmed.ncbi.nlm.nih.gov/36075062/

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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 known as the Parsortix^® system and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.

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 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 70 peer-reviewed publications and numerous publicly available posters from 31 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.

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SOURCE: ANGLE plc