TIDMSAR
Sareum Holdings PLC
31 October 2017
(AIM: SAR) 31 October 2017
SAREUM HOLDINGS PLC
("Sareum" or "the Company")
Sierra Oncology Reports Preclinical Data for its Chk1 Inhibitor
SRA737 Supporting its Ongoing Clinical Development Strategy
- SRA737 demonstrates synergy with replication stress-inducing
agents -
- SRA737 plus gemcitabine efficacious in gemcitabine-resistant
tumor models -
- SRA737 potentiated by novel sub-therapeutic gemcitabine dosing
-
Sareum Holdings plc (AIM: SAR), the specialist cancer drug
discovery and development business, notes that Sierra Oncology, the
licence holder advancing clinical cancer candidate Chk1 inhibitor,
SRA737, reported preclinical data supporting the ongoing clinical
development strategy. The results were presented in a poster on 29
October at the AACR-NCI-EORTC International Conference on Molecular
Targets and Cancer Therapeutics held in Philadelphia, PA, USA.
"The data generated from these experiments are consistent with
recent findings from our research and demonstrate that a potent and
selective Chk1 inhibitor such as SRA737 can effectively synergize
with sub-therapeutic doses of gemcitabine to induce replication
catastrophe and tumor cell death," said Dr. Alan R. Eastman,
Professor at the Geisel School of Medicine at Dartmouth and the
founding Director of the Molecular Therapeutics Research Program of
the Norris Cotton Cancer Center at Dartmouth-Hitchcock. "I look
forward to results from the clinical study Sierra is conducting
which translates this novel strategy for the treatment of patients
with advanced cancers."
"Chk1 is essential for managing replication stress (RS), which
is intrinsically elevated in certain oncogene-transformed tumors,
and can also be further enhanced by chemotherapeutic drugs like
gemcitabine. While gemcitabine likely causes RS by depleting
deoxynucleotide (dNTP) and damaging DNA, Chk1 protects against RS
through a variety of molecular mechanisms. Consequently, tumor
cells become highly reliant on Chk1 to manage replication stress
and its downstream consequences in order to survive and continue to
proliferate," added Dr. Christian Hassig, Senior Vice President of
Research at Sierra Oncology. "Through our research, we have
demonstrated that SRA737 has the potential to synergize with
several clinically important chemotherapeutic inducers of RS to
kill tumor cells in vitro at low concentrations. We also
demonstrated that the combination of SRA737 and gemcitabine may
prove efficacious in gemcitabine-resistant clinical settings and
that SRA737 can be potentiated by sub-therapeutic doses of
gemcitabine in animal models of cancer."
"Replication stress has been recognized as a potent driver of
genomic instability, a fundamental hallmark of cancer, and is
rapidly emerging as an area of dynamic scientific research," stated
Dr. Nick Glover, President and CEO of Sierra Oncology. "Tumors
harboring high levels of intrinsic or exogenous forms of
replication stress are potential candidates for therapeutic
intervention using SRA737. We are actively leveraging these
concepts in our ongoing monotherapy and low-dose gemcitabine
combination clinical trials."
About the Poster
Title: The Chk1 inhibitor, SRA737, demonstrates chemical
synthetic lethality with replication stress-inducing agents,
including novel low-dose gemcitabine, in preclinical models of
cancer.
Poster #181; Abstract #B181:
The Poster is available on the company's website at
www.sierraoncology.com.
Data reported in the Poster demonstrated that:
-- The combination of SRA737 with a range of RS-inducing agents
was highly synergistic in a panel of 15 cell lines of diverse
tissue lineages, with the strongest synergy observed with
gemcitabine.
-- Profound synergy between SRA737 and gemcitabine was observed
in several bladder cancer cell lines as well as in human
patient-derived bladder cancer 3D cultures, further supporting the
clinical development of this RS-inducing combination.
-- Significant anti-tumor activity and increased survival (vs.
control) were observed when SRA737 and gemcitabine were dosed in
combination in a highly aggressive gemcitabine resistant bladder
carcinoma PDX model. These findings suggest that the combination of
SRA737 and gemcitabine may be efficacious in gemcitabine-resistant
clinical settings.
-- Strikingly, anti-tumor activity was observed when SRA737 was
combined with a sub-therapeutic dose of gemcitabine in xenograft
models of colorectal adenocarcinoma and osteosarcoma. This
combination was shown to increase RS markers by three to five-fold
over the change noted with gemcitabine alone. These findings
support i) the development of SRA737 in combination with low,
sub-therapeutic doses of gemcitabine and, ii) the broader
application of this unique combination in tumor indications where
gemcitabine is not standard of care.
For further information, please contact:
Sareum Holdings plc
Tim Mitchell 01223 497 700
WH Ireland Limited (Nominated Adviser and
Co-Broker)
Chris Fielding / James Sinclair-Ford 020 7220 1666
Hybridan LLP (Co-Broker)
Claire Noyce 020 3764 2341
Citigate Dewe Rogerson (Media
enquiries)
Shabnam Bashir/ Mark Swallow/
David Dible 020 7282 9571
Notes for editors:
Sareum is a specialist drug discovery and development company
delivering targeted small molecule therapeutics, focusing on cancer
and autoimmune disease, and generating value through licensing them
to international pharmaceutical and biotechnology companies at the
preclinical or early clinical trials stage.
Its most advanced programme, SRA737, is a novel Checkpoint
kinase 1 (Chk1) inhibitor licensed to NASDAQ-listed Sierra Oncology
and in clinical trials targeting a range of advanced cancers. The
key role of Chk1 in cancer cell replication and DNA damage repair
suggests that SRA737 may have broad application as a targeted
therapy in combination with other oncology and immune-oncology
drugs in genetically defined patients.
Sareum is also advancing programmes to develop novel tyrosine
kinase 2 (TYK2) inhibitors in autoimmune diseases and cancers, and
Aurora+FLT3 inhibitors in haematological cancers, which are in the
IND-enabling preclinical and lead optimisation stages.
The Company's drug discovery technology platform (SKIL(R) -
Sareum Kinase Inhibitor Library) is being applied to generate drug
research programmes against other kinase targets.
Sareum Holdings plc is listed on the AIM market of the London
Stock Exchange, trading under the ticker SAR. For further
information, please visit www.sareum.co.uk
- Ends -
This information is provided by RNS
The company news service from the London Stock Exchange
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