(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® - 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
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