Angle Regulatory News (AGL)

ANGLE plc ("the Company")

BREAKTHROUGH RESEARCH DEMONSTRATES PARSORTIX WORKFLOW FOR CULTURING CIRCULATING TUMOR CELLS FOR IN-VITRO DRUG TESTING

Unique capabilities of ANGLE's Parsortix system address a key aim of precision medicine to test drugs outside the patient to determine which drugs will benefit the patient

Work highlights another major opportunity for the use of ANGLE's Parsortix system in breast cancer post FDA clearance

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce that results presented by one of the leading US cancer centers at the American Association for Cancer Research conference (AACR) 2018, in Chicago have demonstrated a workflow for culturing circulating tumor cells (CTCs) using ANGLE's ParsortixTM system.

The innovative research undertaken by the Robert H Lurie Comprehensive Cancer Center and the Feinberg School of Medicine, Northwestern University, Chicago (Northwestern) has for the first time developed an optimised workflow for the recovery and culturing of CTCs from a simple blood test to produce an effective ex-vivo culture (cells growing outside the patient) of the individual patient's cancer cells. The team of investigators led by Dr. Massimo Cristofanilli focused on demonstrating the capability to interrogate and test cancer cells collected from patients with advanced breast cancer. This achievement was only possible because the epitope-independent (does not use antibodies) patented microfluidic process used by the Parsortix system for CTC enrichment harvests undamaged living CTCs, which can then be cultured.

This is the first time that an optimised workflow has been presented to culture CTCs ex-vivo. This has been a goal of many research groups for some time but has not been achievable because the methods of CTC isolation used yield low numbers of only partially purified CTCs that are fixed before isolation (hence killed), damaged during the cell purification process, or irreversibly immobilised on an adherent matrix. The Parsortix system neatly avoids all these problems providing a simple reproducible way to harvest CTCs that can be cultured. This is another example of the use of CTCs harvested using the Parsortix system, which cannot be addressed using ctDNA. Previous culturing of CTCs harvested from leukapheresis (transfusion of blood out and back into the body taking up to an hour) product using Parsortix has been reported but this is the first time it has been achieved from a simple blood test.

Northwestern tested their ex-vivo culture workflow on 16 metastatic breast cancer patients. A single 7.5ml EDTA blood tube was drawn from a simple blood test for each patient. In every patient (100%), the Parsortix system yielded viable CTCs that could be developed into an ex-vivo culture. The number of CTCs harvested using the Parsortix system was significantly higher than has been reported with other systems and ranged from 300 to 17,250 CTCs per patient.

The CTCs were then successfully cultured over a three week period at which time the DNA was isolated and purified. The CTCs in culture retained their morphology and expanded 3.5 - 5.5 fold in week one, and then 9.5 - 22.5 fold in week two yielding as many as 100,000 cancer cells within 14 days thus providing sufficient DNA for a wide range of multiple analyses to be undertaken.

Northwestern's poster presentation to AACR 2018 is entitled "A novel ex vivo culture workflow to enrich and expand circulating tumor cells (CTCs) from patients with Stage III/IV Breast Cancer (BCa) (LB-370)". A copy is available here

https://angleplc.com/library/publications/

The mutational profile of a patient's tumor evolves over time. Consequently a non-invasive method to provide a series of ex-vivo cultures of the patient's cancer cells for organoids development and in-vitro drug testing enables the changing patterns of drug susceptibility in individual patients to be monitored as their tumors acquire new mutations. This would enable the patient to receive the right drug at the right time, improving outcomes for patients and avoiding wasted resources on drugs, which are ineffective.

Professor Massimo Cristofanilli, MD Associate Director, Translational Research - Robert H Lurie Comprehensive Cancer Center, Northwestern University, commented:

"The ability to recover, culture and interrogate cancer cells expands our possibility to advance precision medicine in breast cancer patients. We believe that the optimisation of the workflow utilising the Parsortix system to produce ex-vivo cultures of CTCs is already opening up a new frontier in the management of breast cancer, by allowing the testing of treatments in a 'predictive in vitro system' truly representative of the patient's disease and improving our ability to select agents and predict efficacy. Widely adopted, this approach has the potential to transform the way we treat cancer patients."

ANGLE Founder and Chief Executive, Andrew Newland, commented:

"This is the first time that CTCs have been successfully cultured direct from a Parsortix processed whole blood sample. This work is highly encouraging for ANGLE. Firstly every metastatic breast sample analysed yielded a large number of CTCs, which is a positive sign for our FDA study. Secondly, Northwestern has achieved something that many other Centres before them have failed to do, which is to produce an optimised workflow for reproducibly growing the CTCs. This approach is potentially applicable for every metastatic breast cancer patient and provides another clear high value application for ANGLE's Parsortix system."

For further information ANGLE:

For Frequently Used Terms, please see the Company's website on http://www.angleplc.com/the-parsortix-system/glossary/

This announcement contains inside information.

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 an epitope-independent 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 ParsortixTM system and it enables a liquid biopsy (simple blood test) to be used to provide the cells of interest. Parsortix is the subject of granted patents in Europe, the United States, Canada, India, China, Japan and Australia and three extensive families of patents are being progressed worldwide. The system is based on a microfluidic device that captures live cells based on a combination of their size and compressibility. The Parsortix system has a CE Mark for Europe and FDA clearance is in process for the United States.

ANGLE's analysis technology for proteins and nucleic acids of all types is called Ziplex® and is based on a patented flow through array technology. It provides for highly multiplexed, rapid and sensitive capture of targets from a wide variety of sample types. A proprietary chemistry allows for the capture and amplification of over 100 biomarkers simultaneously in a single reaction. These technologies can be combined to provide fully automated, sample to answer results in both centralised laboratory and point of use cartridge formats. It is ideal for measuring gene expression and other markers directly from Parsortix harvests.

ANGLE has established formal collaborations with world-class cancer centres. These Key Opinion Leaders are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. Details are available here http://www.angleplc.com/the-company/collaborators/