Sierra Oncology Reports Preclinical Efficacy for Immunotherapy Combination with its Chk1 inhibitor SRA737
VANCOUVER, Nov. 29, 2018
- SRA737 synergizes with immune checkpoint blockade in small cell lung cancer (SCLC) –
- Activates immune signaling STING pathway -
- Data reported at the AACR Conference on Tumor Immunology and Immunotherapy -
VANCOUVER, Nov. 29, 2018 /PRNewswire/ - Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, today reported preclinical data for its novel oral Chk1 inhibitor, SRA737, in a poster presented at the American Association for Cancer Research (AACR) Conference on Tumor Immunology and Immunotherapy in Miami Beach, Florida.
"In this study we found that the potent, selective oral Chk1 inhibitor, SRA737, activated the innate immune signaling STING pathway and demonstrated significant anti-tumor activity in an immunocompetent preclinical model of small cell lung cancer (SCLC)," said Dr. Lauren Byers, Associate Professor at the University of Texas MD Anderson Cancer Center, Houston, Texas. "Remarkably, the combination of SRA737 with an anti-PD-L1 immune checkpoint inhibitor induced tumor regression in this model, providing strong rationale for combining these agents to treat this immunotherapy refractory indication."
"SCLC remains a significant unmet need and one where immunotherapies have yielded limited efficacy. These tumors frequently harbor defects in cell cycle checkpoint and DNA damage repair (DDR) genes, with a coincident dependence on regulators of replication stress such as Checkpoint Kinase 1 (Chk1) as a compensatory mechanism," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "These encouraging preclinical results highlight an additional potential application for SRA737 that warrants further evaluation beyond our current clinical development programs for the drug as a monotherapy and in combination with replication stress-inducing low dose gemcitabine."
The poster will be presented on Thursday, November 29th from 5:00 to 7:00 pm (ET).
Title: The oral Chk1 inhibitor, SRA737, synergizes with immune checkpoint blockade in small cell lung cancer (SCLC).
Authors: Triparna Sen, Snezana Milutinovic, Robert J. Cardnell, Lixia Diao, Youhong Fan, Ryan J. Hansen, Bryan Strouse, Michael Hedrick, Christian Hassig, Jing Wang, Lauren A. Byers.
Location: Poster Session: B; Board Number: B15; Session Location: Americana 3 and 4
STING: Stimulator of Interferon Genes
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). In cancer cells, intrinsic replication stress is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g., BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic replication stress and have utility as a monotherapy in a range of tumor indications. The combination of SRA737 with other modalities, such as other agents that target the DDR network and certain chemotherapeutics, may also provide synergistic anti-tumor activity via a variety of potential biological mechanisms. Importantly, the oral bioavailability of SRA737 may afford greater dosing flexibility for both monotherapy and combination therapy settings than is possible with intravenously administered agents.
SRA737 is currently being investigated in two Phase 1/2 clinical trials primarily focused on patients with ovarian cancer: SRA737-01, a monotherapy study, and SRA737-02, a drug combination study evaluating SRA737 potentiated by low dose gemcitabine. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.
About Sierra Oncology
Sierra Oncology is a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with unmet medical needs in hematology and oncology. Our lead drug candidate, momelotinib, is a potent, selective and orally-bioavailable JAK1, JAK2 and ACVR1 inhibitor that has been investigated in two completed Phase 3 trials for the treatment of myelofibrosis and has demonstrated a potentially differentiated therapeutic profile encompassing anemia-related benefits, as well as achieving substantive spleen and constitutional symptom control.
Sierra is also advancing SRA737 and SRA141. SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). SRA737 is currently being investigated in two Phase 1/2 clinical trials primarily focused on patients with ovarian cancer: SRA737-01, a monotherapy study, and SRA737-02, a drug combination study evaluating SRA737 potentiated by low dose gemcitabine. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor. SRA141 is a Phase 1 ready, potent, selective, orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7). Cdc7 is a key regulator of DNA replication and is involved in the DDR network, making it a compelling emerging target for the potential treatment of a broad range of tumor types.
For more information, please visit www.sierraoncology.com.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Sierra Oncology's market and industry position, expectations from current data, anticipated clinical development activities and timing and potential benefits of Sierra Oncology's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that Sierra Oncology may be unable to successfully develop and commercialize product candidates, product candidates may not demonstrate safety and efficacy or otherwise produce positive results, Sierra Oncology may experience delays in the preclinical and anticipated clinical development of its product candidates, Sierra Oncology may be unable to acquire additional assets to build a pipeline of additional product candidates, Sierra Oncology's third-party manufacturers may cause its supply of materials to become limited or interrupted or fail to be of satisfactory quantity or quality, Sierra Oncology's cash resources may be insufficient to fund its current operating plans and it may be unable to raise additional capital when needed, Sierra Oncology may be unable to obtain and enforce intellectual property protection for its technologies and product candidates and the other factors described under the heading "Risk Factors" set forth in Sierra Oncology's filings with the Securities and Exchange Commission from time to time. Sierra Oncology undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.
SOURCE Sierra Oncology