ANGLE plc ("the Company")

STUDY DEMONSTRATES USE OF PARSORTIX TO ASSESS PD-L1 STATUS OF CTCs IN NON-SMALL CELL LUNG CANCER PATIENTS WITH A SIMPLE BLOOD TEST

Further evidence supporting ANGLE's decision to develop a Parsortix-based PD-L1 assay to assess patient cancer PD-L1 status

ANGLE PD-L1 assay to be offered for use in cancer drug trials to pharma services customers developing new immunotherapy drugs

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that the Health Research Institute of Santiago (IDIS), Spain, has published results of a study in patients with metastatic non-small cell lung cancer (NSCLC) undergoing treatment with the immune checkpoint inhibitor (ICI), pembrolizumab.

The expression of immune checkpoint proteins is dysregulated by tumours as an immune resistance mechanism. The development of ICIs has revolutionised the treatment of NSCLC, with National Comprehensive Cancer Network guidelines recommending ICIs as first-line therapy for advanced disease. Individual patient response to PD-L1 or PD-1 inhibitors can be profound and durable. However, the proportion of patients responding is low, ranging from 13% to 50%. As such, there is a clear need for improved patient selection as non-responders do not benefit from the drug but also risk developing hyper-progressive disease and drug toxicity with immune-related adverse events. Further to this, low response rates have led to a number of PD-L1 inhibitors being withdrawn from the market or being unsuccessful in trials following a failure to demonstrate statistically significant improvement in patient population outcomes.

The current standard of care requires PD-L1 status to be established from a tumour tissue biopsy. However, lung tissue biopsy required for biomarker assessment is associated with significant risks and the evolution of the tumour after initial tissue biopsy results in this approach being a poor predictor of treatment response as the PD-L1 status can change. Liquid biopsy offers the potential for safe, cost-effective longitudinal monitoring of tumour evolution and disease progression. As PD-L1 status requires the analysis of protein expression in the cell membrane, CTCs as complete cells are the only liquid biopsy analyte able to provide this.

IDIS's study was limited to investigating epithelial CTCs in patient blood and demonstrated that the Parsortix system could be used to recover CTCs from NSCLC patient blood for investigation of their PD-L1 status prior to receiving immunotherapy targeting this pathway. All patients where the Parsortix system recovered epithelial CTCs had at least some PD-L1-expressing epithelial CTCs. Thus, the approach taken by the researchers of classifying patients as PD-L1 positive if they had any PD-L1 positive cells could not differentiate likely response to the immune checkpoint inhibitor, since all patients had some PD-L1 positive cells.

ANGLE has been working internally to develop a robust Parsortix assay for PD-L1 covering all phenotypes of CTCs including epithelial, mesenchymal and CTCs undergoing epithelial mesenchymal transition (EMT) as well as CTC clusters. This will provide a scoring mechanism by determining the proportion of CTCs with PD-L1 protein expression allowing discrimination between different patient groups. Once this assay is finalised, the aim is to use it to identify likely responders to immunotherapy drugs. ANGLE expects to collaborate with IDIS, Spain and other leading cancer centres in validation of this assay.

Early evaluation of a patient's response to immunotherapy might enable clinicians to decide if the clinical benefit is sufficient to continue treatment, or to stop treatment, thereby avoiding unnecessary toxicities and costs and allowing alternative treatment to commence sooner.

In the United States, lung cancer is the second most common cause of cancer and the leading cause of cancer related mortality, responsible for 22% of all cancer related deaths. In 2021, The National Cancer Institute predicts that there will be a total of 236,000 new cases and 132,000 deaths - NSCLC accounts for 84% of all lung cancer cases. Whilst the overall 5-year survival rate for NSCLC is 25%, 60% of patients are diagnosed with metastatic (stage IV) disease for which the 5-year relative survival rate is just 5%.

There are numerous cancer drug trials in progress or being planned in support of new immunotherapy drugs for these patients. All these drug trials could benefit from a Parsortix-based PD-L1 assay for longitudinal monitoring of patients and this will be a key focus for ANGLE's pharma services offering.

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

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"ANGLE is pleased to see continued efforts being made to better identify patients who will respond well to immune checkpoint inhibitors (ICIs). Whilst ICIs have revolutionised metastatic NSCLC patient care, they are costly and associated with significant side effects. We have made substantial progress in the development of our Parsortix-based PD-L1 assay and are offering this to our pharma services customers. In addition, we are planning to investigate its utility in guiding immunotherapy treatments with the aim of offering the assay as a laboratory developed test from our clinical laboratories for patient management."

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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 may 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 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.

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

ANGLE has established clinical services laboratories in the UK and USA to accelerate commercialisation of the Parsortix system and act as demonstrators to support product development. The laboratories offer services to pharmaceutical and biotech customers for use of the Parsortix system in cancer drug trials and, once the laboratories are accredited, and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management.