Parsortix: Dynamic assessment of patient response

ANGLE plc ("the Company")

USE OF PARSORTIX SYSTEM ENABLES A DYNAMIC ASSESSMENT OF PATIENT RESPONSE TO TREATMENT IN NON-SMALL CELL LUNG CANCER

CTCs harvested by the Parsortix system successfully used to measure the dynamic role of EMT and PD-L1 in patient response to therapy

Findings support ANGLE's plan for the growth of a new "pharma services" business area using the Parsortix system as a biomarker for cancer drug trials allowing longitudinal monitoring of patients

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the National and Kapodistrian University of Athens (Athens) has published results of a new study undertaken in non-small cell lung cancer (NSCLC). This study demonstrates the utility of ANGLE's Parsortix^® system for minimally invasive, longitudinal monitoring of changes in circulating tumour cell (CTC) gene expression in NSCLC patients with an EGFR mutation being treated with the tyrosine kinase inhibitor (TKI), Osimertinib (AstraZeneca's Tagrisso^®). Identifying these changes could help guide next-line therapy decisions and provide an important enhancement to monitoring patient response in cancer drug trials.

The Athens study used the Parsortix system to harvest CTCs in blood samples from 30 NSCLC patients on three occasions during the treatment cycle. The first sample was taken on enrolment in the study and before administration of the first treatment cycle of Osimertinib, the second following completion of the first cycle, and the third at progression of disease (PD). The harvested CTCs were analysed for gene expression of a broad range of biomarkers. These included epithelial, mesenchymal/epithelial to mesenchymal transition (EMT), stem cell markers and PD‑L1. The authors note that they believe this is the first study on gene expression in CTCs at three different time points in patients being treated with Osimertinib.

The study showed that Parsortix, an epitope independent liquid biopsy system, was able to isolate CTCs from patients with a mesenchymal/EMT phenotype. This is of clinical significance given that mesenchymal/EMT biomarkers were present in CTCs in 60% of patients at baseline and 80% following one cycle of Osimertinib. EMT is implicated as a key mechanism in tumour cell survival, invasion, metastasis, and drug resistance in a range of cancers. It is also implicated in resistance to TKI treatment in NSCLC.

Furthermore, a statistically significant increase in PD-L1 positive CTCs was observed at disease progression (i.e. patients who did not respond to treatment with Osimertinib). This is in accordance with previous findings that attribute upregulation of PD-L1 with TKI resistance, and suggests that this cohort of patients, as identified by their CTC status, could benefit from next line treatment with an immune checkpoint inhibitor.

This study provides further evidence that CTCs serve as an alternative biological information source, beyond ctDNA analysis, offering great potential for unveiling the tumour profile and resistance mechanisms in NSCLC. The assessment of druggable alterations in CTCs underlie their clinical utility to identify therapeutic resistance mutations and identify actionable targets to inform next line therapy.

Lung cancer is the second most common cause of cancer. The American Cancer Society predicts that there will be a total of 228,820 new cases in 2020 in the United States alone. Currently, lung cancer is the leading cause of cancer related mortality, accounting for 22% of all cancer deaths, estimated at 135,720 people in the United States in 2020.

There are 34 FDA approved therapeutics for NSCLC, 24 of these are targeted therapies including PD-L1/PD-1 inhibitors which can induce durable and long lasting antitumour immunity. Patient response to PD-L1 or PD-1 inhibitors is poor ranging from only 20-40%. As such, there is a clear need for improved patient selection given that non-responders risk the development of hyper-progressive disease and immune-related adverse events that should be addressed.

There are over 1,300 clinical studies registered at clinicaltrials.gov involving PD-L1, all of which may benefit from a CTC based biomarker to assess PD-L1 status over time. ANGLE is currently working on a PD-L1 assay to offer as part of a new "pharma services" business to be offered from ANGLE's clinical laboratories in the UK and the United States, which are due to be operational in Q1 and Q2 respectively.

The research has been published as a peer-reviewed publication in the Nature Scientific Reports and may be accessed via https://angleplc.com/library/publications/.

Prof Evi Lianidou, Head of the Molecular Diagnostics Laboratory focused on Liquid Biopsy (ACTC lab) at the Department of Chemistry, National and Kapodistrian University of Athens, commented:

"The major challenge that clinicians often face during treatment of NSCLC patients is the heterogeneous landscape of the disease. Our results demonstrated this heterogeneous pattern of gene expression of epithelial, mesenchymal/EMT and stem cell markers among patients.

The epitope independent CTC enrichment offered by the Parsortix system permitted the detection of mesenchymal CTCs at high rates at all time points indicating a potential role of EMT during Osimertinib treatment. Our observations could support further studies, including larger cohorts of patients, to clarify the potential role of PIM-1 and AXL as novel CTC biomarkers and therapeutic targets in NSCLC. The significant increase in the expression levels of the immune response marker PD-L1 in CTCs at disease progression suggests a theoretical background for immunotherapy in EGFR-mutant NSCLC patients that develop resistance to Osimertinib."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"This study, which analysed blood samples taken from patients during the course of treatment, demonstrates the dynamic and heterogeneous nature of NSCLC and the need for serial liquid biopsies to provide vital information on disease progression and drug resistance. The ability of the Parsortix system to capture mesenchymal as well as epithelial cells offers ANGLE a critical advantage over other liquid biopsy approaches in providing this information in clinical trials.

We look forward to harnessing Parsortix's unique capabilities as we continue to make strong progress with the establishment of our new laboratories to support the use of the Parsortix system for pharma services and subsequent deployment for clinical use.

As previously announced, the Parsortix system has been submitted to FDA, seeking the first ever FDA product clearance for a system that harvests cancer cells from a simple blood draw for subsequent analysis."

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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 thus 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. In addition, the live CTCs harvested can be cultured, which offers the potential for testing 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 HyCEAD^TM 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 40 peer-reviewed publications and numerous publicly available posters, available on our website.