TIDMAGL
Angle PLC
10 January 2022
For immediate release 10 January 2022
ANGLE plc ("the Company")
EPIGENETIC ALTERATIONS IN GENES FROM LIQUID BIOPSIES PROVIDE
INSIGHT INTO DRUG RESISTANCE IN NON-SMALL LUNG CANCER PATIENTS
Longitudinal analysis of paired samples of CTCs and ctDNA shows
important differences in epigenetic biomarkers at disease
progression
Study supports analysis of CTCs captured by Parsortix, together
with ctDNA, from serial liquid biopsies to provide information on
disease progression and drug resistance
ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy
company, is pleased to announce that the world-class research team
led by Prof. Evi Lianidou at the National and Kapodistrian
University of Athens (Greece), has published results of a further
study undertaken in non-small cell lung cancer (NSCLC) patients
with an EGFR mutation being treated with the tyrosine kinase
inhibitor (TKI), Osimertinib (AstraZeneca's Tagrisso(R) ), which
demonstrates the benefit of longitudinal analysis of epigenetic
alterations in circulating tumour cells (CTCs), in addition to
circulating tumour DNA (ctDNA), to assess possible drug resistance
mechanisms in patients.
The aim of the study was to analyse increased DNA methylation in
the promoters of six selected genes that result in loss of gene
expression and are implicated in drug resistance in lung cancer.
The analysis was performed using ctDNA and paired CTCs from a
single blood sample. The study used the Parsortix(R) system to
harvest CTCs in blood samples from 42 metastatic NSCLC patients
before treatment with Osimertinib and again at disease
progression.
After harvesting from the Parsortix system, captured CTCs were
lysed and the genomic DNA extracted. Once DNA integrity had been
evaluated, the DNA was amplified and expression levels assessed
using real-time methylation specific PCR (MSP) assays for the
targeted genes. CTC-derived DNA was analysed in 74 samples and DNA
methylation assessed before treatment and at disease progression.
For the first time, direct comparison of the CTC results with 70
paired results from 80 ctDNA samples has revealed significant
differences in DNA methylation indicating that CTCs and ctDNA give
complementary information and demonstrate a high level of
heterogeneity between patients even at the DNA methylation
level.
Moreover, the combined results from CTC and ctDNA methylation
analysis indicated that methylation rates for all genes tested were
significantly elevated at progression of disease after treatment
with Osimertinib compared to before treatment , indicating that DNA
methylation of these genes may be associated with resistance to
Osimertinib during therapy. As a result, identifying the
differences between DNA methylation in ctDNA and CTCs in
longitudinal studies could help guide therapy decisions and provide
an important enhancement to monitoring patient response in cancer
drug trials.
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%.
However, lung tissue biopsy required for biomarker assessment is
associated with significant risks. Due to adverse events following
the procedure, a mean cost of US$14,600 per biopsy has been
estimated. Liquid biopsy offers the potential for safe,
cost-effective longitudinal monitoring of tumour evolution and
disease progression to track mutations responsible for therapy
resistance and identify biomarkers for targeted treatment
selection.
Precision medicine has transformed cancer care in NSCLC. 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 variable ranging from 13%-50% but
treatment costs c. US $170,000 per patient and has significant side
effects. As such, there is a clear need for improved patient
selection to identify responders given that non-responders risk the
development of hyper-progressive disease and immune-related adverse
events, and the wasted healthcare costs are significant.
There are over 2,400 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 validating a PD-L1 assay in its clinical laboratories
which will be offered to biopharma customers for use in clinical
trials.
The research has been published as a peer-reviewed publication
in the journal Cancers and may be accessed via
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:
"Whilst the prolonged survival of patients who benefit from
targeted therapies is proven, in most cases resistance arises
inevitably and the identification of the molecular mechanisms that
lead to the progression of disease is crucial for the appropriate
sequential treatment. The identification of circulating epigenetic
biomarkers through DNA methylation studies is of utmost clinical
importance in the liquid biopsy field and can be used for the
diagnosis, prognosis and prediction of drug response".
ANGLE Founder and Chief Executive, Andrew Newland,
commented:
"This study, which analysed blood samples taken from patients
using the Parsortix system before and after treatment, further
demonstrates the dynamic nature of NSCLC and the need for analysis
of CTCs and not just ctDNA from serial liquid biopsies to provide
information on disease progression and drug resistance. In addition
to the clinical implications in guiding therapy decisions, this
information is vital for drug companies in patient selection for
clinical trials and for monitoring response to new drugs."
For further information:
ANGLE plc +44 (0) 1483 343434
Andrew Newland, Chief Executive
Ian Griffiths, Finance Director
Andrew Holder, Head of Investor Relations
Berenberg (NOMAD and Joint Broker)
Toby Flaux, Jen Clarke, Milo Bonser, Shiv Dave +44 (0) 20 3207 7800
Jefferies (Joint Broker)
Max Jones, Thomas Bective +44 (0) 20 7029 8000
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
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(R)
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(R) 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 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
53 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 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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