TIDMAGL
RNS Number : 7590M
Angle PLC
10 January 2019
For immediate release 10 January 2019
ANGLE plc ("the Company")
BREAKTHROUGH RESEARCH USING THE PARSORTIX SYSTEM HIGHLIGHTS
POTENTIAL TO TRANSFORM CANCER TREATMENT BY SUPPRESSING CANCER
METASTASIS
Research using Parsortix to isolate CTC clusters from blood
identifies drugs which dissociate highly metastatic CTC clusters
resulting in a near total elimination of metastasis in animal
models
Opportunity for Parsortix liquid biopsy to be routinely used to
identify patients who may benefit from the new approach to suppress
cancer metastasis
University of Basel planning to commence clinical trial in
breast cancer in 2019
ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy
company, is delighted to announce that its Parsortix(TM) system has
been utilised in ground-breaking new cancer research, which may
provide a novel way to treat cancer through the suppression of
cancer metastasis.
The research, led by Professor Nicola Aceto at the Cancer
Metastasis Laboratory, University of Basel (Basel, Switzerland) has
been published today as a peer-reviewed publication in the
prestigious journal Cell.
The research demonstrated the ability to harvest intact
metastatic circulating tumor cell clusters (CTC clusters, a group
of cancer and other cells tethered together as a single mass) using
Parsortix and highlights the potential to treat cancer patients
identified with Parsortix to have CTC clusters with repurposed FDA
approved medications, which have been shown in mouse models to
break up these CTC clusters and suppress metastasis. Basel's
research indicated that treated animals showed 80x less metastasis
compared with untreated animals, with the metastatic spread of
cancer virtually eliminated in the treated animals.
The development of metastasis, the spread of cancer to distant
sites primarily via the blood, is responsible for more than 90% of
all cancer-related deaths. Previous work has shown that CTC
clusters in the blood are highly metastatic causing greatly
increased spread of the disease. If metastasis could be suppressed
by disrupting CTC clusters then patient outcomes could be
dramatically improved.
There are a variety of technical challenges to capturing intact
CTC clusters from patient blood, which has historically led to
problems with other CTC systems and an inability to effectively
research CTC clusters. In controlled tests with spiked samples,
Basel demonstrated that the Parsortix system used with a
specialised protocol performed exceptionally well to overcome these
technical challenges and was able to successfully isolate >99%
of CTC clusters from a simple blood test.
Using the Parsortix system, Basel was able to investigate CTC
clusters both from patient blood and from animal models. The
analysis of the CTC clusters led to Basel discovering key,
previously unknown, epigenetic changes present in the CTC clusters
making them highly effective at spreading the cancer.
Following this discovery, the researchers investigated the
potential for 2,486 compounds already approved by the FDA for a
number of different indications, to cause the CTC clusters to
dissociate (break up into individual cells). They found a small
number of drugs with the capability to do this. Once dissociated,
they found that CTC clusters (now single cells) lost their high
metastatic potential.
The directors believe that the results show exceptional promise
for use in human cancer. The mechanism of action of the drugs was
to effectively weaken the cell-cell connections in the CTC cluster
rather than to kill the cancer cells. Conventional chemotherapy
seeks to kill the cancer cell and is consequently inherently toxic,
which is why patients can suffer serious side effects from the
treatment as non-cancer cells may also be adversely affected.
Further, conventional therapies aimed at killing cancer cells are
prone to give rise to drug-resistant cell populations, which can
ultimately lead to disease relapse. In contrast, the drugs used for
the CTC cluster dissociation are already approved by the FDA for
different non-cancer indications and do not have the typical side
effects of chemotherapy or immunotherapy.
Basel have applied for ethics approval to undertake a clinical
trial in 2019 utilising the Parsortix system as a companion
diagnostic to identify which patients have CTC clusters and may
respond to the identified drugs. The first area of focus is in
breast cancer, which complements ANGLE's ongoing FDA studies in
metastatic breast cancer.
Professor Nicola Aceto, Group Leader - Cancer Metastasis
Laboratory, University of Basel and University Hospital Basel,
Switzerland, commented:
"CTC clusters are extraordinarily important mediators of breast
cancer metastasis, and discovering the first anti-cluster therapy
may provide a new powerful tool to help treat millions of women
currently living with this potentially fatal disease. The Parsortix
state-of-the-art technology platform has played a key role in
enabling us to isolate CTC clusters for investigation. We are now
working on proof-of-concept clinical studies using Parsortix as a
companion diagnostic."
ANGLE Founder and Chief Executive, Andrew Newland,
commented:
"The ground-breaking CTC cluster work undertaken over the last
three years by the University of Basel, one of ANGLE's leading
customers, highlights completely new clinical uses for the
Parsortix system with the potential to play a central role in
dramatically improving patient outcomes. This is a key potential
application for Parsortix liquid biopsy once we receive FDA
clearance. Our ultimate aim is for the Parsortix system to be
routinely used for all cancer patients in the future."
The study published in the journal Cell today can be accessed
here:
https://www.cell.com/cell/home and is described in the
University of Basel's press release, which is reproduced in full
below. An image of CTC clusters in a Parsortix cassette is featured
on the front cover of the journal.
-----------------
Basel researchers identify drug against the formation of
metastasis
The most deadly aspect of breast cancer is metastasis. It
spreads cancer cells throughout the body. Researchers at the
University and the University Hospital of Basel have now discovered
a substance that suppresses the formation of metastases. In the
journal Cell, the team of molecular biologists, computational
biologists, and clinicians reports on their interdisciplinary
approach.
The development of metastasis is responsible for more than 90%
of cancer-related deaths, and patients with a metastatic disease
are considered incurable. The interdisciplinary team led by Prof.
Nicola Aceto from the Department of Biomedicine at the University
of Basel has identified a drug that suppresses the spread of
malignant cancer cells and their metastasis-seeding ability.
Precursors of metastases: Circulating tumor cell clusters
Circulating tumor cells (CTCs) are cancer cells that leave a
primary tumor and enter the bloodstream, on their way to seeding
distant metastases. These so-called CTCs can be found in the blood
of patients as single cells or cell clusters. CTC clusters are the
precursors of metastases. The Basel research team has discovered
that CTC cluster formation leads to key epigenetic changes that
facilitate metastasis seeding. These changes enable CTC clusters to
mimic some properties of embryonic stem cells, including their
ability to proliferate while retaining tissue-forming capabilities.
The scientists have also shown that these epigenetic changes are
fully reversible upon the dissociation of CTC clusters.
In their search for a substance that suppresses metastasis
development, the research team tested 2486 FDA-approved compounds
used for a number of different indications. They found inhibitors
with the unexpected ability to dissociate patient-derived CTC
clusters. This drug-based dissociation of CTC clusters into
individual cells also resulted into epigenetic remodeling and
prevented the formation of new metastases.
Preventing metastasis versus killing cancer cells
"We thought of acting differently from standard approaches, and
sought to identify drugs that do not kill cancer cells, but simply
dissociate them," states Nicola Aceto, holder of an ERC starting
grant and SNSF professorship.
In the fight against breast cancer, metastases remain the
greatest danger. These new findings on the mechanisms of metastasis
formation are the result of a large collaborative effort across
various disciplines. "Our ambitious approach would not have been
possible without collaboration with outstanding clinicians,
molecular and computational biologists, with the support of
state-of-the-art technology platforms," says Aceto and adds: "Our
methodology is positioned directly at the interface between these
different disciplines. We are already working on the next step,
which is to conduct a clinical trial with breast cancer
patients."
Original source
Sofia Gkountela, Francesc Castro-Giner, Barbara Maria Szczerba,
Marcus Vetter, Julia Landin, Ramona Scherrer, Ilona Krol, Manuel C.
Scheidmann, Christian Beisel, Christian U. Stirnimann, Christian
Kurzeder, Viola Heinzelmann-Schwarz, Christoph Rochlitz, Walter
Paul Weber, Nicola Aceto
Circulating Tumor Cell Clustering Shapes DNA Methylation to
Enable Metastasis Seeding
Cell (2018), doi: 10.1016/j.cell.2018.11.046
Links
Research group of Prof. Dr. Nicola Aceto
(https://biomedizin.unibas.ch/en/research/research-groups/aceto-lab/)
Additional information on the research group of Prof. Dr. Nicola
Aceto (http://www.cancermetastasislab.com/)
Scientific Contact
Prof. Dr. Nicola Aceto, University of Basel and University
Hospital Basel, Department of Biomedicine, phone: +41 61 207 0773,
email: Nicola.Aceto@unibas.ch
Further information
The accompanying image was chosen as cover story for the current
issue of "Cell". A workshop report on the production of the picture
is available under this link once the embargo has expired:
https://medium.com/sci-five-university-of-basel
Caption and credit:
The image represents an artistic coloration of a cluster of
circulating tumor cells (CTCs), isolated from the blood of a
patient with breast cancer, trapped on a microfluidic device.
Image: (c) M Oeggerli / Micronaut 2018, supported by Pathology-,
C-CINA / Biozentrum-, and I Krol, and N Aceto, Faculty of
Medicine-, University Hospital and University Basel
-----------------
For further information ANGLE:
ANGLE plc +44 (0) 1483 343434
Andrew Newland, Chief Executive
Ian Griffiths, Finance Director
finnCap Ltd (NOMAD and Joint Broker)
Corporate Finance - Carl Holmes, Simon
Hicks, Max Bullen-Smith
ECM - Alice Lane +44 (0)20 7220 0500
WG Partners (Joint Broker)
Nigel Barnes, Nigel Birks, Andrew Craig,
Chris Lee +44 (0) 203 705 9330
FTI Consulting
Simon Conway, Stephanie Cuthbert, Ciara +44 (0) 203 727 1000
Martin +1.212.850.5624
Matthew Ventimiglia (US)
This announcement contains inside information.
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
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 Parsortix(TM)
system and it enables a liquid biopsy (simple blood test) to be
used to provide the cells of interest. CTCs enable the complete
picture of a cancer to be seen as they allow DNA, RNA and protein
analysis and the live cells harvested can be cultured. Parsortix is
the subject of 21 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 in Europe for the indicated use and FDA clearance is
in process for the United States with a 400 subject study 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 undertaken 400 subject clinical
studies in an ovarian cancer pelvic mass triage test that achieved
best in class accuracy (ROC-AUC) of 95.1% and is being
optimised.
ANGLE's analysis technology for proteins and nucleic acids of
all types is called the HyCEAD Ziplex(R) 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
allows for the capture and amplification of over 100 biomarkers
simultaneously in a single reaction. The HyCEAD Ziplex system 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 the 95.1% accuracy.
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 QIAGEN, Abbott and
Philips, 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
13 peer-reviewed publications and 23 publicly available posters,
available on our website.
This information is provided by RNS, the news service of the
London Stock Exchange. RNS is approved by the Financial Conduct
Authority to act as a Primary Information Provider in the United
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of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
END
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