RCS - Angle PLC - Parsortix: Dynamic assessment of patient response

AngleAnnouncement

08/02/2021 07:00

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RNS Number : 2259O  Angle PLC  08 February 2021

 For immediate release  8 February 2021

 

ANGLE plc ("the Company")

 

USE OF PARSORTIX SYSTEM ENABLES A DYNAMIC ASSESSMENT OF PATIENT RESPONSE TO
TREATMENT IN NON-SMALL CELL LUNG CANCER

 

CTCs harvested by the Parsortix system successfully used to measure the
dynamic role of EMT and PD-L1 in patient response to therapy

 

Findings support ANGLE's plan for the growth of a new "pharma services"
business area using the Parsortix system as a biomarker for cancer drug trials
allowing longitudinal monitoring of patients

 

ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is
pleased to announce that the National and Kapodistrian University of Athens
(Athens) has published results of a new study undertaken in non-small cell
lung cancer (NSCLC). This study demonstrates the utility of ANGLE's
Parsortix(®) system for minimally invasive, longitudinal monitoring of
changes in circulating tumour cell (CTC) gene expression in NSCLC patients
with an EGFR mutation being treated with the tyrosine kinase inhibitor (TKI),
Osimertinib (AstraZeneca's Tagrisso(®)). Identifying these changes could help
guide next-line therapy decisions and provide an important enhancement to
monitoring patient response in cancer drug trials.

 

The Athens study used the Parsortix system to harvest CTCs in blood samples
from 30 NSCLC patients on three occasions during the treatment cycle. The
first sample was taken on enrolment in the study and before administration of
the first treatment cycle of Osimertinib, the second following completion of
the first cycle, and the third at progression of disease (PD). The harvested
CTCs were analysed for gene expression of a broad range of biomarkers. These
included epithelial, mesenchymal/epithelial to mesenchymal transition (EMT),
stem cell markers and PD‑L1. The authors note that they believe this is the
first study on gene expression in CTCs at three different time points in
patients being treated with Osimertinib.

 

The study showed that Parsortix, an epitope independent liquid biopsy system,
was able to isolate CTCs from patients with a mesenchymal/EMT phenotype. This
is of clinical significance given that mesenchymal/EMT biomarkers were present
in CTCs in 60% of patients at baseline and 80% following one cycle of
Osimertinib. EMT is implicated as a key mechanism in tumour cell survival,
invasion, metastasis, and drug resistance in a range of cancers. It is also
implicated in resistance to TKI treatment in NSCLC.

 

Furthermore, a statistically significant increase in PD-L1 positive CTCs was
observed at disease progression (i.e. patients who did not respond to
treatment with Osimertinib). This is in accordance with previous findings that
attribute upregulation of PD-L1 with TKI resistance, and suggests that this
cohort of patients, as identified by their CTC status, could benefit from next
line treatment with an immune checkpoint inhibitor.

 

This study provides further evidence that CTCs serve as an alternative
biological information source, beyond ctDNA analysis, offering great potential
for unveiling the tumour profile and resistance mechanisms in NSCLC. The
assessment of druggable alterations in CTCs underlie their clinical utility to
identify therapeutic resistance mutations and identify actionable targets to
inform next line therapy.

 

Lung cancer is the second most common cause of cancer. The American Cancer
Society predicts that there will be a total of 228,820 new cases in 2020 in
the United States alone. Currently, lung cancer is the leading cause of cancer
related mortality, accounting for 22% of all cancer deaths, estimated at
135,720 people in the United States in 2020.

 

There are 34 FDA approved therapeutics for NSCLC, 24 of these are targeted
therapies including PD-L1/PD-1 inhibitors which can induce durable and long
lasting antitumour immunity. Patient response to PD-L1 or PD-1 inhibitors is
poor ranging from only 20-40%. As such, there is a clear need for improved
patient selection given that non-responders risk the development of
hyper-progressive disease and immune-related adverse events that should be
addressed.

 

There are over 1,300 clinical studies registered at clinicaltrials.gov
involving PD-L1, all of which may benefit from a CTC based biomarker to assess
PD-L1 status over time. ANGLE is currently working on a PD-L1 assay to offer
as part of a new "pharma services" business to be offered from ANGLE's
clinical laboratories in the UK and the United States, which are due to be
operational in Q1 and Q2 respectively.

 

The research has been published as a peer-reviewed publication in the Nature
Scientific Reports and may be accessed via
https://angleplc.com/library/publications/
(https://angleplc.com/library/publications/) .

 

Prof Evi Lianidou, Head of the Molecular Diagnostics Laboratory focused on
Liquid Biopsy (ACTC lab) at the Department of Chemistry, National and
Kapodistrian University of Athens, commented:

 

"The major challenge that clinicians often face during treatment of NSCLC
patients is the heterogeneous landscape of the disease. Our results
demonstrated this heterogeneous pattern of gene expression of epithelial,
mesenchymal/EMT and stem cell markers among patients.

 

The epitope independent CTC enrichment offered by the Parsortix system
permitted the detection of mesenchymal CTCs at high rates at all time points
indicating a potential role of EMT during Osimertinib treatment. Our
observations could support further studies, including larger cohorts of
patients, to clarify the potential role of PIM-1 and AXL as novel CTC
biomarkers and therapeutic targets in NSCLC. The significant increase in the
expression levels of the immune response marker PD-L1 in CTCs at disease
progression suggests a theoretical background for immunotherapy in EGFR-mutant
NSCLC patients that develop resistance to Osimertinib."

 

ANGLE Founder and Chief Executive, Andrew Newland, commented:

 

"This study, which analysed blood samples taken from patients during the
course of treatment, demonstrates the dynamic and heterogeneous nature of
NSCLC and the need for serial liquid biopsies to provide vital information on
disease progression and drug resistance. The ability of the Parsortix system
to capture mesenchymal as well as epithelial cells offers ANGLE a critical
advantage over other liquid biopsy approaches in providing this information in
clinical trials.

 

We look forward to harnessing Parsortix's unique capabilities as we continue
to make strong progress with the establishment of our new laboratories to
support the use of the Parsortix system for pharma services and subsequent
deployment for clinical use.

 

As previously announced, the Parsortix system has been submitted to FDA,
seeking the first ever FDA product clearance for a system that harvests cancer
cells from a simple blood draw for subsequent analysis."

 

For further information ANGLE:

 

 ANGLE plc                                                    +44 (0) 1483 343434
 Andrew Newland, Chief Executive

 Ian Griffiths, Finance Director

 Andrew Holder, Head of Investor Relations

 finnCap Ltd (NOMAD and Joint Broker)                         +44 (0)20 7220 0500

 Corporate Finance - Carl Holmes, Simon Hicks, Teddy Whiley

 ECM - Alice Lane, Sunila de Silva

 WG Partners (Joint Broker)                                   +44 (0) 203 705 9330

 Nigel Barnes, Nigel Birks, Andrew Craig, Chris Lee

 FTI Consulting

 Simon Conway, Ciara Martin                                   +44 (0) 203 727 1000

 Matthew Ventimiglia (US)                                     +1 (212) 850 5624

 

For Frequently Used Terms, please see the Company's website on
https://angleplc.com/investor-relations/glossary/

 

Notes for editors

 

About ANGLE plc www.angleplc.com (http://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 thus
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. In
addition, the live CTCs harvested can be cultured, which offers the potential
for testing 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 40
peer-reviewed publications and numerous publicly available posters, available
on our website.

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