Angle Regulatory News (AGL)

ANGLE plc ("the Company")

ANGLE ANNOUNCES Q-SUBMISSION TO FDA CONTAINING HEADLINE DATA AND RESPONSE TO AGENCY QUESTIONS AHEAD OF FULL DE NOVO SUBMISSION

Positive results generated from analytical studies to support positive pivotal clinical study for potential FDA clearance of Parsortix liquid biopsy system

Potential FDA clearance expected in Q3 CY20

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce positive results from its Parsortix® US Food and Drug Administration (FDA) analytical studies. Headline data from these analytical studies and the successful FDA pivotal clinical study, announced on 31 May 2019, were submitted to the FDA yesterday as a "Q-Submission" ahead of a full De Novo submission seeking FDA clearance of ANGLE's Parsortix system.

The clinical and analytical studies were designed to support a De Novo submission pathway to the FDA where ANGLE is seeking Class II classification and marketing authorisation (clearance) for its Parsortix system for the intended use with metastatic breast cancer patients.

As there is no predicate device, FDA has agreed that ANGLE should follow the De Novo regulatory pathway for Parsortix. This process involves significant and iterative dialogue with the FDA regarding the extent and nature of the necessary studies to secure regulatory clearance. In the case of the Parsortix system it has required conducting additional analytical studies, as announced on 31 May 2019, to support ANGLE's positive pivotal clinical study. Although there are a few remaining samples to process from the additional studies, the analytical studies are now substantively complete with positive results demonstrating the performance of the Parsortix system in key aspects including precision and reproducibility, limits of quantification and detection, accuracy and linearity, and interferents and carryover.

Key elements of the analytical and clinical study results were submitted to the FDA yesterday in the form of a Q-Submission. The Q-Submission, which is being made at the Company's election, comprised both (i) details of the clinical and analytical studies undertaken and headline data obtained and (ii) proposed solutions to certain specific questions raised from ongoing FDA interactions, reflecting the De Novo status of the submission.

A formal review meeting has been requested with the FDA to review the Q-Submission and confirm that the headline data and proposed solutions meet FDA requirements. Assuming that the meeting is successful in addressing all the matters under discussion, a De-Novo classification request for FDA clearance will then be made to FDA, most likely in Q1 CY20. The full De Novo submission will comprise all the agreed elements required to support the FDA in granting ANGLE marketing authorisation (FDA clearance) for the Parsortix system.

The Q-Submission process that ANGLE is following, where the FDA provides formal feedback to questions submitted by a company ahead of pre-market application for regulatory clearance, is designed to de-risk the De Novo nature of the regulatory process and expedite the overall classification request procedure, in order to minimise the time needed to address questions raised by FDA prior to a classification request decision.

ANGLE now believes that a strong data package has been assembled to support both the clinical and analytical performance of the Parsortix system with the prospect of FDA clearance in Q3 CY20. The timing of the FDA regulatory decision is as always entirely dependent on the FDA's review and response to the company's submissions.

Despite the estimated addressable market potential for liquid biopsy of greater than US$100 billion per annum across all cancer types in the United States alone (Frost and Sullivan, November 2018), to date, the FDA has cleared only two liquid biopsy applications. The first clearance, for CellSearch, was for circulating tumor cell (CTC) enumeration (counting) to assess prognosis in metastatic breast, colorectal or prostate cancers. This contrasts with ANGLE's intended use to capture and harvest CTCs for subsequent analysis. The second clearance, for a liquid biopsy application on the Roche Cobas platform, was for utilising ctDNA (fragments of dead cancer cells) to investigate the presence of an EGFR gene mutation in non-small cell lung cancer. ANGLE is seeking to become the first company ever to obtain FDA clearance for a liquid biopsy platform that will capture and harvest CTCs for subsequent analysis, in the first instance for metastatic breast cancer patients.

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"We are delighted with the positive results from the FDA analytical studies to accompany the positive results from the pivotal FDA clinical study that have previously been announced. We believe there is a tremendous opportunity for ANGLE to secure the first ever FDA clearance for a platform that captures and harvests intact circulating tumour cells from patient blood for subsequent analysis, in the first instance for metastatic breast cancer. We believe that FDA regulatory clearance, considered the gold standard for approval of medical diagnostic systems globally, would further competitively differentiate our Parsortix liquid biopsy system and should lead to an acceleration in commercial adoption of the system in both research and clinical settings."

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