Sierra Oncology is a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with cancer. We are an ambitious oncology-focused company, oriented towards achieving the successful registration and commercialization of our product candidates. We have a highly experienced management team with a proven track record of success in oncology drug development and we are advancing an emerging pipeline of next generation therapies that target the DNA Damage Response (DDR) network.
Our lead product candidate, SRA737, is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1). Chk1 is a key regulator of important cell cycle checkpoints and central mediator of the DNA Damage Response network. In cancer cells, replication stress induced by oncogenic drivers (e.g., MYC or RAS) or genetic mutations in DNA repair machinery (e.g., BRCA1 or FA) combined with loss of function in tumor suppressors (e.g., TP53 or ATM) 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 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, as such, the combination of SRA737 with these standards-of-care may provide synergistic anti-tumor activity. 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.
We are pursuing an innovative development plan for SRA737, which is currently being evaluated in two Phase 1 clinical trials in patients with advanced cancer. The first trial is intended to evaluate SRA737’s potential to induce synthetic lethality as monotherapy, while the second trial is intended to explore the potentiating effects of low-dose DNA-damaging chemotherapy in combination with SRA737. We successfully transferred sponsorship of these two trials in January 2017 and, in May 2017, we reported having received clearance from regulators to amend the protocols for these trials. In particular, these amendments allow us to prospectively enrolling patients with genetically-defined tumors, determined using Next-Generation Sequencing, that harbor specific genetic alterations that are hypothesized to confer potential sensitivity to SRA737 therapy via synthetic lethality. A preliminary update of the SRA737 clinical trials is anticipated to be available in early 2018.
Concurrently, we are conducting preclinical research evaluating SRA737 in combination with other DDR-targeted agents, including poly ADP ribose polymerase (PARP) inhibitors, as well as with immuno-oncology therapeutics, that may guide a potential next wave of clinical development for our asset, possibly further broadening its therapeutic utility.
We are 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 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.
Sierra Oncology retains the global commercialization rights to both SRA737 and SRA141.