Sierra Oncology Collaborator ICR Reports Preclinical Synthetic Lethality Data for Chk1 Inhibitor SRA737 at AACR

Tuesday, April 4, 2017 Cancer News
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- Research conducted by Professor Paul Workman supports the use of SRA737 in certain genetically defined tumors and in combination with chemotherapy

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VANCOUVER, April 3, 2017 /PRNewswire/ - Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response

therapeutics for the treatment of patients with cancer, today reported that preclinical results for its Chk1 inhibitor, SRA737, were presented on April 2 in a poster at the American Association of Cancer Research (AACR) Annual Meeting being held in Washington D.C. This research was conducted in the laboratory of Professor Paul Workman, Chief Executive and President of The Institute of Cancer Research (ICR), London, UK, and funded by Wellcome.

"These data demonstrate that inhibition of B-family DNA polymerases, POLA1, POLE and POLE2, combined with inhibition of Chk1, is synthetically lethal in numerous cancer cell lines," noted Professor Workman. "This supports the genetically-driven clinical development strategy Sierra intends to pursue for SRA737.  For example, subsets of colon and endometrial cancers with POLE mutations may be sensitive to CHK1 inhibitors as monotherapy.  In addition, gemcitabine is known to impair the B-family DNA polymerases, further supporting the rationale for its clinical combination with SRA737."

"The ICR is a world-class cancer research institution and we are fortunate to maintain an ongoing collaborative relationship for the development of SRA737. In particular, the data reported by Professor Workman's laboratory continues to reinforce the synthetic lethality hypothesis for SRA737, and further validates our approach to developing our lead drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "Appropriate patient selection is critical for clinical success. Fortunately, the biology underlying Chk1's role in cancer and the DNA Damage Response suggest numerous opportunities where a patient's specific tumor genetics might be linked to their predicted response to SRA737."

The poster, entitled: "Screening the druggable genome for synthetic lethal interactions with the CHK1 inhibitor PNT737" is available at www.sierraoncology.com. Additional information including full abstracts can be found at www.aacr.org.

About SRA737SRA737, is a highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), currently being evaluated in two Phase 1 clinical trials in patients with advanced cancer.

The first trial is evaluating SRA737's potential to induce synthetic lethality as monotherapy. Sierra recently proposed amendments to this trial to prospectively enroll subjects with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition. The study will employ a genetic selection algorithm targeting mutations in TP53, BRCA1, BRCA2, MYC, RAS, or other related genes associated with tumor suppression, oncogenesis, DNA damage repair, and replicative stress. Additionally, Sierra intends to modify the study to assess SRA737's clinical activity across several cancer indications that harbor these genetic mutations including, for example, cohorts of subjects with 1) previously treated metastatic colorectal cancer; 2) platinum-resistant ovarian cancer; 3) metastatic castration-resistant prostate cancer; 4) advanced non-small cell lung cancer; and 5) advanced head and neck squamous cell carcinoma.

Sierra is currently also evaluating SRA737 in combination with gemcitabine and gemcitabine plus cisplatin.  The company intends to modify the design of this clinical trial to expand enrollment in the gemcitabine combination following the completion of dose escalation.  Subjects with 1) advanced bladder cancer and 2) advanced pancreatic cancer will be enrolled into genetically-selected dose expansion cohorts, employing a genetic selection algorithm similar to that to be used in the monotherapy protocol.

About the Institute of Cancer Research, LondonThe ICR, London, is one of the world's most influential cancer research organizations. Scientists and clinicians at ICR are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organizations are rated in the top four centers for cancer research and treatment globally. The ICR's mission is to make the discoveries that defeat cancer. For more information, visit http://www.icr.ac.uk.

About Sierra OncologySierra Oncology is a clinical stage drug development company advancing next generation DNA Damage Response therapeutics for the treatment of patients with cancer. Our lead drug candidate, SRA737, is a highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key cell cycle checkpoint and central regulator of the DNA Damage Response (DDR) network. In cancer cells, replication stress induced by oncogenes (e.g., MYC and RAS) combined with loss of function in tumor suppressors (e.g., TP53 and ATM) results in persistent DNA damage and genomic instability. Targeted inhibition of the remaining components of the DDR network such as by SRA737 may be synthetically lethal to cancer cells and have utility as a monotherapy in a range of tumor indications. Chk1 is also believed to facilitate tumor cell resistance to chemotherapy or radiation-induced DNA damage and the combination of SRA737 with these standards-of-care may provide synergistic anti-tumor activity. SRA737 is currently being investigated in two Phase 1 clinical trials in patients with advanced cancer.

Sierra Oncology is also advancing SRA141, a potent, selective and orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7) undergoing preclinical development. Cdc7 is a key regulator of both DNA replication and 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 StatementsThis 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 anticipated clinical development, protocol amendments, target indications 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, SRA737 and SRA141 are at early stages of development and may not demonstrate safety and efficacy or otherwise produce positive results, Sierra Oncology may experience delays in the preclinical and anticipated clinical development of SRA737 or SRA141, 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



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