ANGLE receives FDA clearance for Parsortix

ANGLE ACHIEVES WORLD FIRST WITH FDA CLEARANCE FOR ITS PARSORTIX SYSTEM
FDA De Novo product clearance to harvest cancer cells from blood for subsequent analysis offers the prospect of a new era of personalised cancer care
Parsortix liquid biopsy system cleared for use in metastatic breast cancer
Major validation expected to fuel commercial growth
Webcast for analysts will be held at 3pm BST today

GUILDFORD, SURREY / ACCESSWIRE / May 25, 2022 / ANGLE plc (AIM:AGL)(OTCQX:ANPCY), a world-leading liquid biopsy company, is absolutely delighted to announce that the US Food and Drug Administration (FDA) has cleared the Parsortix^® system for its intended use with metastatic breast cancer (MBC) patients.

This ground-breaking FDA clearance is the first ever FDA product clearance to harvest cancer cells from a patient blood sample for subsequent analysis and offers the prospect of a new era of personalised cancer care.

The Parsortix system's capability to harvest cancer cells for analysis from a patient blood sample has the potential to transform treatment decisions for cancer patients as it opens up the opportunity for repeat non-invasive biopsies to assess cancer status. The Company believes intact living cancer cells are the "best sample" for analysis, adding vital additional information to the current industry approach of analysing fragments of dead cancer cells (known as ctDNA).

FDA product clearance, which is the global gold standard for medical devices, gives ANGLE first mover advantage for intact cell analysis in the global liquid biopsy market, which it is estimated will grow to over US$100 billion per annum in the United States alone. Securing this clearance is the culmination of a sustained effort by the Company for over six years. The credibility associated with medical device FDA product clearance cannot be under-estimated and we anticipate that this will turbocharge all aspects of commercialisation of the Parsortix system and be a key factor in its adoption by large-scale medtech and pharma companies.

The Parsortix system approach utilises a unique technology developed, owned and patent protected by ANGLE. We believe that first mover advantage in the market is likely to be sustained for a number of years and ANGLE is not aware of any competitors even having started a similar FDA product clearance process.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"We are absolutely delighted that FDA has cleared the Parsortix system and believe this heralds a new era for personalised cancer care.

This ground-breaking first ever FDA product clearance in metastatic breast cancer provides the platform for ANGLE to work with our collaborators and customers to support further FDA submissions and the establishment of numerous specific clinical uses across different cancer types. By making the Parsortix system widely available, we intend to support the entire industry in its adoption of liquid biopsy solutions for repeat non-invasive diagnostics for personalised cancer care. Large-scale medtech and pharma companies now have an FDA cleared platform on which to develop new medical solutions.

We are most grateful to over three hundred metastatic breast cancer patients and several thousand healthy volunteer donors, who donated blood to allow us to achieve this major breakthrough in the adoption of liquid biopsy as a potential new standard in the care of cancer patients. We also thank investors for providing the considerable financial support, and patience, that has allowed us to undertake such a substantial exercise."

Dr. James M. Reuben, Professor, Department of Hematopathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center and co-PI of the trial commented:

"My lab's overarching interest is to develop assays that will serve as companion diagnostics to assist clinicians who treat cancer patients (MBC and non-small cell lung cancer) with therapies such as immune checkpoint inhibitors and targeted agents. Therefore, we have devoted considerable effort to developing multiple cellular assays utilizing CTCs which offer a minimally invasive approach to monitor a patient's cancer and their response to these therapies. Data from our trial with Parsortix showed the system was able to effectively capture a single cancer cell in a blood sample for analysis. We look forward to the further development of CTC based assays that may bring enormous benefits to patients with MBC as well as other cancers in the future."

Dr. Reuben receives research support from ANGLE, and he is compensated as a member of its Scientific Advisory Board. This financial relationship has been disclosed to MD Anderson's Conflict of Interest Committee.

Dr. Naoto T. Ueno, Professor, Department of Breast Medical Oncology, Chief of Section of Translational Breast Cancer Research, The University of Texas MD Anderson Cancer Centre and co-PI of the trial added:

"Liquid biopsy to collect circulating live cancer cells is an essential tool that we need to make advancements in understanding the biology of metastatic breast cancer. We anticipate that this announcement may help to develop novel biomarkers, therapeutic approaches and contribute to selecting the best treatment for metastatic breast cancer patients."

Dr. Julie Lang, Chief of Breast Surgery and Co-Director of Comprehensive Breast Cancer Program at Cleveland Clinic Cancer Center, and formerly Director, USC Breast Cancer Program, Associate Professor of Surgery, Norris Comprehensive Cancer Center, University of Southern California commented:

"In my team's research, we have demonstrated how circulating tumor cells harvested by this system are a good surrogate for tissue biopsies of the metastatic site. With this regulatory clearance we can now obtain repeat biopsies periodically to provide up-to-date information to guide treatment decisions, improving care and minimising invasive procedures for these patients."

Dr. Massimo Cristofanilli, a pioneer and recognized leader in the field of liquid biopsy commented:

"Circulating tumor cells (CTCs) have long been recognized as a robust prognostic marker in metastatic breast cancer but its clinical application has been limited by the lack of predictive molecular information. MBC is a heterogenous disease that requires targeted and biological therapies and diagnostic monitoring of the natural molecular evolution of the disease to be able to longitudinally identify and implement the most effective treatment and measure its benefit. I believe that the Parsortix^® PC1 system provides the ideal technology for such purpose allowing point of care diagnostic capabilities that capture the complexity of the ever-changing molecular landscape of MBC. In fact, I envision that the clinical application of the Parsortix^® PC1 system can result in an unprecedented opportunity to perform a real-time molecular diagnostic assessment of enriched CTCs with comprehensive molecular information on both protein expression and genomic abnormalities driving the disease."

Dr Richard Moore, Director of the Gynecologic Oncology Division, University of Rochester Medical Center, Wilmot Cancer Institute commented:

"As a leading translational research team, we have a long association with the team at ANGLE and are delighted to have played a key role in their clinical studies in an effort to bring the Parsortix system into clinical use. Real-time analysis of live circulating tumour cells offers the potential to transform patient care by enabling actionable information that can guide treatment decisions in heterogeneous and dynamic cancers such as MBC. FDA clearance is a major advance in cancer care and we look forward to bringing this benefit to MBC patients as well as continuing to support further research into the advantages of CTC analysis using the Parsortix system"

Further detail on the FDA Clearance and market potential

The FDA has granted a De Novo Class II classification for the Parsortix system for use in harvesting cancer cells from metastatic breast cancer (MBC) patient blood for subsequent analysis. This means that an entirely new medical device classification has been granted by FDA for the Parsortix system. De Novo clearance is rare and this is the first such medical device classification for a new instrument in oncology for many years.

This FDA regulatory clearance is the culmination of a sustained effort by the Company for over six years including extensive dialogue and formal pre-submissions with FDA, and the submission of over 400 technical reports and documents and processing of over 16,000 samples to demonstrate system performance. The process has been extremely demanding and technically challenging involving the development of many new innovative processes, which now form part of ANGLE's proprietary know-how, and the De Novo classification represents the uniqueness of the Parsortix system as there is no comparable predicate device.

The characterisation of the Parsortix system for FDA clearance included the assessment of performance with clinical samples, recovery, linearity, limit of detection, reproducibility, repeatability, blood volume, blood stability and interfering substances both exogenous and endogenous, requiring samples to be run on the Parsortix system in the UK and at multiple clinical sites in the United States. This process, combined with the manufacture of the Parsortix system and associated consumables, was completed and fully documented under ANGLE's ISO 13485:2016 quality management system and in compliance with numerous other technical and quality standards active in the United States and Europe. The work was also designed to meet the requirements for European CE Mark and ANGLE has registered the same device in the European market allowing clinical sales in both the United States and Europe for the intended use.

The importance of CTCs

The Directors believe that harvesting intact cancer cells from blood (CTCs) provides the best sample of a patient's metastatic breast cancer for assessment of ongoing patient care. CTCs offer the potential for a wide range of downstream analyses using established laboratory techniques, which may transform the treatment of metastatic breast cancer, providing patients with personalised cancer care through a non-invasive, repeat biopsy based on a simple blood draw (a "liquid biopsy").

The analysis of CTCs may provide a "prospective view" on how the cancer is developing and spreading whereas ctDNA is inherently "retrospective" in nature as it comes from fragments of dead cells and may not be representative of how the cancer is progressing. ctDNA is a useful but more limited analyte providing only DNA information and many patients who are matched to therapy based on their DNA do not respond as key information about the biology of the tumor is missing from looking at the genome alone. CTCs provide a more complete picture on the cancer development including DNA, RNA, and protein expression (multi-omics) as well as the potential to undertake cytological and morphological examination of the actual cancer cell, making it the closest potential proxy to information that can be obtained from a metastatic tissue biopsy.

Market potential

ANGLE anticipates that the Parsortix system will be adopted worldwide. Market research estimates the market opportunity for liquid biopsy in the United States alone could grow to more than US$100 billion per annum. Despite this, ANGLE believes this FDA classification is only the third liquid biopsy product clearance ever granted, with the other two being limited to a single gene in a single cancer using ctDNA (fragments of dead cells) and a system for counting cells that does not allow downstream analysis of the cells. ANGLE's clearance is the first and only FDA product clearance, considered the gold standard regulatory clearance worldwide, for a liquid biopsy solution to harvest intact cancer cells for subsequent analysis.

Because of the critical medical need to understand how a cancer changes over time, the current National Comprehensive Cancer Network (NCCN) Guidelines in the United States for the treatment of MBC patients require a tissue biopsy of the metastatic site at the first available time point to support clinical decision-making. Despite being recommended in the Guidelines, only around 50% of MBC patients receive a successful biopsy as a result of patients being too sick for the invasive procedure, the inaccessibility of the metastatic site or insufficient tissue being available. For the same reasons, virtually no MBC patients will have a further biopsy of another metastatic site, despite it being well-established that cancer develops and changes over time and there is a clear medical need for up-to-date information on their disease status.

For those patients not able to have a successful metastatic tissue biopsy, there is no information available to guide treatment decisions and doctors are essentially "flying blind" in their treatment. The Parsortix system offers an alternative method for obtaining MBC cells for analysis, which is non-invasive and can be repeated as often as needed. Furthermore, unlike ctDNA (fragments of dead cells) which is limited to DNA analysis and is the focus for most of the liquid biopsy industry, a full range of analyses can be undertaken with circulating tumor cells (CTCs) harvested from MBC patients by the Parsortix system including DNA, RNA and protein analysis, as well as cytological and morphological analysis, making it the closest potential proxy to a metastatic tissue biopsy.

Globally, breast cancer is the most frequently diagnosed cancer with 2.3 million new cases per year. In the United States, there are an estimated 3.7 million women living with or after breast cancer and a further 290,000 cases are predicted in 2022. Globally the incidence of breast cancer is growing with cases expected to increase by 80% between 2020 and 2040. Despite new treatment options and advances in patient management protocols, an estimated 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent advanced or metastatic disease. Although the prognosis of patients with metastatic breast cancer has significantly improved over the last two decades, it remains largely incurable with a five-year survival rate of just 29%. ANGLE estimates that the addressable market for the Parsortix system used with metastatic breast cancer patients is in excess of US$500m per annum in the United States alone.

ANGLE is proud to be playing a leading role in the development of new approaches to assist the care of cancer patients and today's announcement is testament to the passion, commitment and resilience of our team over many years.

Webcast for analysts

A virtual meeting and webcast for analysts will be held at 3pm BST today. If you wish to attend, please register in advance and log on to the webcast approximately 5 minutes before 3pm. Details of how to attend can be accessed via https://angleplc.com/investor-relations/corporate-presentations/. A replay will be available shortly afterwards at the same weblink.

For further information:

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 https://angleplc.com/investor-relations/glossary/

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 59 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