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Sierra Oncology reports preclinical efficacy for SRA737.

Sierra Oncology reported preclinical data for its novel oral Chk1 inhibitor, SRA737, in a poster presented at the 30th EORTC-NCI-AACR Symposium held in Dublin, Ireland. "Oncogene-driven high-grade serous ovarian cancers, or HGSOC, with CCNE1 and MYCN pathway activation exhibit defective cell cycle checkpoint control and replicative stress. The DNA damage response effector kinase, Chk1, modulates the cellular response to replicative stress and has been shown to be upregulated in these subtypes of HGSOC," said Dr. Clare Scott, Professor at The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. "Our pre-clinical results show that the Chk1 inhibitor SRA737 has impressive efficacy in our most aggressive models of ovarian cancer." As detailed in the poster, the efficacy of single agent SRA737 was explored in two cyclin E overexpressing HGSOC patient-derived xenografts, or PDX, and also compared to olaparib, a PARP inhibitor recently approved for HGSOC. Both PDX models had pronounced amplification of CCNE1; one also harbored a MYCN amplification. Both PDX models were insensitive to standard platinum-based therapy and did not harbor BRCA1/2 or related gene mutations. Treatment with SRA737 resulted in significant and differentiated anti-cancer activity, including dose dependent tumor regression. As anticipated, the PARP inhibitor olaparib was inactive. "Sierra's ongoing SRA737-01 monotherapy and SRA737-02 low dose gemcitabine combination studies were recently prioritized for CCNE1-enriched HGSOC, a promising potential indication for Chk1 inhibition," stated Dr. Barbara Klencke, Chief Development Officer, Sierra Oncology. "We look forward to reporting clinical data from these studies in the first half of 2019."

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Publication:The Fly
Date:Nov 15, 2018
Words:250
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