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The data that we collect from you may be transferred to, and stored at, a destination outside the European Economic Area (“EEA”). It may be processed by staff operating outside the EEA who work for us or for one of our suppliers. Such staff may be engaged in, amongst other things, the provision of support services. By submitting your personal data, you agree to this transfer, storing and processing. We will take all steps reasonably necessary, including the use of encryption, to ensure that your data is treated securely and in accordance with this privacy policy.

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Sareum Holdings PLC (SAR)

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Tuesday 17 April, 2018

Sareum Holdings PLC

AACR 2018 Update

RNS Number : 1966L
Sareum Holdings PLC
17 April 2018
 

(AIM: SAR)                                                                                                                                          17 April 2018

 

 

SAREUM HOLDINGS PLC

("Sareum" or "the Company")

Sareum Notes that Sierra Oncology will Present Late-Breaking Data Demonstrating SRA737 Preclinical Activity with PARP Inhibitors at the AACR 2018 Annual Meeting

 

Two posters reporting activity for SRA737 with PARPi (in CCNE1-driven cancers, HRR proficient cancers, and PARPi-resistant cancers) reinforce the potential broad clinical utility of this combination

 

Sareum Holdings plc (AIM: SAR), the specialist cancer drug discovery and development business, notes that Sierra Oncology, the licence holder advancing clinical cancer candidate SRA737, announced that it is reporting preclinical results in two posters, including late-breaking data being presented today, for its Checkpoint kinase 1 (Chk1) inhibitor SRA737, at the American Association of Cancer Research (AACR) Annual Meeting 2018 in Chicago, IL.

The efficacy of SRA737 monotherapy is currently being investigated in an ongoing Phase 1/2 clinical trial (NCT02797964) in replication stress-driven cancer including a patient cohort with CCNE1 amplified HGSOC.

 

Sierra is also planning to investigate SRA737 in combination with niraparib in a multicentre Phase 1b/2 study in subjects with metastatic castration-resistant prostate cancer (mCRPC), anticipated to be initiated in the fourth quarter of 2018. Janssen Research & Development, LLC will supply TESARO's ZEJULA® (niraparib) for the trial, which is to be led by Professor Johann de Bono, Regius Professor of Cancer Research, Head of the Division of Clinical Studies and Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

 

The two posters will be available on Sierra Oncology's website at www.sierraoncology.com.

 

SRA737 AACR 2018 Late-Breaker: The Novel Oral Chk1 Inhibitor, SRA737, Is Active in Both PARP Inhibitor Resistant and CCNE1 Amplified High Grade Serous Ovarian Cancers

 

Data being presented in this late-breaking poster is from research conducted in the laboratory of Dr Fiona Simpkins, Assistant Professor of Obstetrics and Gynecology at The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

 

·     Approximately 20% of HGSOCs harbour CCNE1 gene amplification. CCNE1 amplification is known to increase replication stress and genomic instability, leading to increased reliance on Chk1. These tumours show intrinsic resistance to PARPi and frequently are, or become resistant to, platinum therapy, leaving patients without effective treatment options. In this research, Chk1 inhibition by SRA737 as monotherapy in CCNE1 amplified ovarian cancer models was shown to: a) increase levels of replication stress and DNA double strand breaks, b) in turn leading to excessive genomic instability, c) resulting in subsequent tumour cell death, tumour regression and a profound survival benefit.

 

·     A distinct subgroup comprising approximately 50% of HGSOC have defective HRR genes (e.g. BRCA1/2 mutation). HRR deficient HGSOC are initially sensitive to PARPi but drug resistance ultimately emerges, frequently involving genetic reversion of BRCA mutated genes and partial restoration of HRR. HRR deficiency may also elevate sensitivity to Chk1 inhibition, given the well-established role of Chk1 in HRR, as well as other aspects of the replication stress response. In this research, SRA737 demonstrated activity as a single agent, as well as in combination with PARPi, in acquired PARPi-resistant cells. Furthermore, SRA737 in combination with PARPi demonstrated preliminary evidence of synergistic tumour growth inhibition in a HGSOC patient-derived xenograft model.

 

SRA737 AACR 2018 Poster: The Chk1 Inhibitor, SRA737, Synergizes with the PARP Inhibitor, Niraparib, to Kill Carcinoma Cells via Multiple Cell Death Pathways

 

Sierra presented a second poster at AACR with data from research conducted in the laboratory of Dr Paul Dent, Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA. The results demonstrate that the combination of SRA737 and niraparib was effective in HRR proficient ovarian and breast tumour cell lines and that both autophagic cell death and apoptotic pathways contribute to SRA737/niraparib-induced tumour cell killing. PARPi monotherapy is known to be substantially less effective in treating patients with HRR proficient tumours, making the combination with SRA737 a novel and potentially more effective treatment option. Moreover, the involvement of multiple cell death mechanisms may decrease the potential for tumours to develop resistance to these agents.

 

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

- Ends -

 


This information is provided by RNS
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