RCS - Angle PLC - Insight into drug resistance in NSCLC

AngleAnnouncement

10/01/2022 07:05

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RNS Number : 8278X  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(®)), 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(®) 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/
(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)               +44 (0) 20 3207 7800

 Toby Flaux, Jen Clarke, Milo Bonser, Shiv Dave

 Jefferies (Joint Broker)                         +44 (0) 20 7029 8000

 Max Jones, Thomas Bective

 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/
(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 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(®)
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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