Angle Regulatory News (AGL)

ANGLE plc ("the Company")

BREAKTHROUGH Research SHOWS THE POTENTIAL TO USE PARSORTIX TO ASSESS WHETHER A PATIENT WILL RESPOND TO IMMUNOTHERAPY

Researchers develop novel approach to characterise CTCs for both PD-L1 and IDO protein expression to predict patient response to immune checkpoint inhibitors in non-small cell lung cancer

Analysis of CTCs harvested using Parsortix was the only approach able to predict patient response

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce that the Laboratory of Translational Oncology, School of Medicine, University of Crete has published peer-reviewed results of new work demonstrating the potential to use Parsortix® to assess whether non-small cell lung cancer (NSCLC) patients will respond to immunotherapy drugs.

Immunotherapy drugs known as PD-L1 immune checkpoint inhibitors (ICIs), are a novel treatment increasingly being offered to patients with certain advanced cancers. Due to their high cost (c. £150,000 per patient), the small proportion of unselected patients with applicable cancers that respond to the drugs (c. 15% to 20%), the significant toxicity of the drugs, and the ensuing delay to administering other potential treatments to non-responders, there is an urgent need for a biomarker to identify which patients are likely to respond to these drugs.

Unfortunately, the current standard of care approach using solid tissue biopsy has been unsuccessful in providing a reliable biomarker as to which patients may respond to these drugs because of a combination of problems including lack of tissue availability, tumour heterogeneity (a single site tissue biopsy provides no information on other cancer sites) and the dynamic nature of immune response (the original tissue biopsy rapidly becomes out-of-date as the cancer changes over time).

The study combined, for the first time, an assessment of PD-L1 (Programmed Death-Ligand 1) with a second immune checkpoint, IDO (Indolamine-2,3-dioxygenase), on a patient's circulating tumor cells (CTCs). IDO has been shown to promote tumour evasion from the immune surveillance and is also associated with resistance to treatment with anti-PD-1 ICIs. The study demonstrates that the detection of IDO+ CTCs, and particularly of the IDO+/PD-L1- CTC subpopulation harvested using Parsortix, is significantly associated with reduced progression-free survival and overall survival in NSCLC patients treated with anti-PD-1 agents.

While a variety of CTC systems and approaches were evaluated in matched samples in this study, only CTC detection using ANGLE's Parsortix system was significantly associated with disease progression. The alternative ctDNA (fragments of dead cancer cells) liquid biopsy approach cannot be used for the analysis of PD-L1 or IDO protein expression.

The Laboratory of Translational Oncology, University of Crete's study, which has been published in the peer-reviewed journal Cancers, may be accessed via https://angleplc.com/library/publications/.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths for both men and women world-wide. NSCLC accounts for some 84% of all lung cancer cases, is often diagnosed at an advanced or metastatic stage and has dismal 5-year survival rates. Consequently, immunotherapy with ICIs has been a major focus for pharma and has revolutionised the treatment of advanced NSCLC.

Sofia Agelaki, Associate Professor in Medical Oncology at University of Crete, commented:

"In the current study we evaluated the capture efficiency of different circulating tumor cell (CTC) detection approaches in patients with non-small cell lung cancer treated with immunotherapy immune checkpoint inhibitors (ICIs) as well as the suitability of isolated CTCs for downstream analyses at the protein expression level. We have shown that, using ANGLE's Parsortix system, it is possible to assess both PD-L1 and IDO expression on the CTCs to give a prognostic indicator of whether patients will respond to immunotherapy drugs. Our findings stem from the evaluation of a small group of patients and, as such, they should be considered as preliminary, however they indicate that the assessment of immune checkpoints on CTCs may promote our understanding of the mechanisms underlying immunotherapy resistance and that the investigated approach has the potential to address a critical unmet clinical need in non-small cell lung cancer patients treated with ICIs."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"In addition to our key focus on securing FDA clearance for Parsortix, we are progressing the establishment of clinical laboratories so that we can offer laboratory developed tests. The combination of PD-L1 and IDO assessment using Parsortix opens a major market opportunity for ANGLE in the key area of cancer immunotherapy, for a test which we can offer from our clinical laboratories."

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 35 peer-reviewed publications and numerous publicly available posters, available on our website.