CAMBRIDGE, MA, USA I April 3, 2017 I Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, today announced that SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, shows significant anti-proliferative activity in multiple in vitro and in vivo models of difficult-to-treat solid tumors, including triple negative breast, small cell lung and ovarian cancers. Leveraging its expertise in transcriptional biology and chemistry, Syros also showcased its work to further elucidate the biology of cyclin-dependent kinase 12 (CDK12) and cyclin-dependent kinase 13 (CDK13), advancing its aim of designing the first highly selective CDK12 and CDK13 inhibitors suitable for clinical development. These data were presented at the American Association of Cancer Research (AACR) Annual Meeting in Washington, D.C.
“SY-1365, our first-in-class selective CDK7 inhibitor, as well as our CDK12 and CDK13 inhibitor program highlight the power of our gene control platform to selectively target transcription and potentially treat diseases that have been underserved by other genomic-based approaches,” said Nancy Simonian, M.D., Chief Executive Officer of Syros. “These new data show SY-1365 reduces proliferation and induces apoptosis in cancer cells in several difficult-to-treat tumors. The results build on earlier data demonstrating that SY-1365 preferentially kills cancer cells over non-cancerous cells and lowers the expression of disease-driving transcription factors. Our CDK12 and CDK13 inhibitor program further highlights the potential of our platform to produce drug candidates that target the transcription of unique sets of genes linked to specific tumors.”
SY-1365 in Aggressive Transcriptionally Driven Solid Tumors
Data generated and presented by Syros scientists show SY-1365 induces anti-proliferative and pro-apoptotic effects in multiple solid tumor cell lines and preclinical models of aggressive, transcriptionally driven solid tumors. Results from these studies show SY-1365:
- Induces potent anti-proliferative activity in a range of solid tumor cell lines, including triple negative breast, small cell lung and ovarian cancer cells, when profiled across a broad panel of more than 130 cancer cell lines.
- Demonstrates substantial anti-tumor activity in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of triple negative breast cancer, including regressions at a twice weekly dosing regimen consistent with the initial regimen planned for the Company’s upcoming Phase 1 clinical trial.
- Demonstrates synergistic anti-tumor activity with a BCL-2 inhibitor in cancer cells, providing a mechanistic rationale for further investigating SY-1365 in combination with inhibitors targeting apoptotic pathways.
SY-1365 has been previously shown to induce apoptosis and preferentially kill cancer cells over non-cancerous cells in preclinical models of a range of aggressive cancers, including certain solid tumors and acute leukemias. Preclinical studies have also shown that SY-1365 lowers the expression of oncogenic transcription factors, such as MYC, in these transcriptionally driven cancers.
Syros is on track to begin a Phase 1 clinical trial of SY-1365 in the second quarter, initially in patients with advanced solid tumor malignancies including the transcriptionally driven solid tumors, triple negative breast, small cell lung and ovarian cancers. Syros plans to expand future clinical development of SY-1365 into acute leukemias based on data generated in this trial.
CDK12 and CDK13 Inhibition as Promising New Approach for Treating Cancer
Syros scientists presented data on the selective inhibition of CDK12 and CDK13 in ovarian and breast cancers. Using its gene control platform, Syros is optimizing potent and selective CDK12 and CDK13 inhibitors that may be suitable for clinical development. Syros scientists presented data on a suite of proprietary assays capable of assessing selectivity and cellular target engagement of CDK12. Using breast and ovarian cancer cell lines sensitive to CDK12 inhibition, Syros scientists further showed important differences between non-selective and selective inhibition of transcriptional kinases to guide development of these inhibitors.
Selectively inhibiting CDK12 and CDK13 has previously been shown to decrease the expression of DNA damage response genes and super-enhancer associated transcription factors implicated in cancer, including breast and ovarian cancers. These findings suggest that a selective CDK12 and CDK13 inhibitor could be effective as a monotherapy in certain cancers and as a combination therapy in other cancers by increasing their susceptibility to targeted therapies involved in DNA damage repair, such as PARP1 inhibitors.
About Syros Pharmaceuticals
Syros Pharmaceuticals is pioneering the understanding of the non-coding region of the genome to advance a new wave of medicines that control expression of disease-driving genes. Syros has built a proprietary platform that is designed to systematically and efficiently analyze this unexploited region of DNA in human disease tissue to identify and drug novel targets linked to genomically defined patient populations. Because gene expression is fundamental to the function of all cells, Syros’ gene control platform has broad potential to create medicines that achieve profound and durable benefit across a range of diseases. Syros is currently focused on cancer and immune-mediated diseases and is advancing a growing pipeline of gene control medicines. Syros’ lead drug candidates are SY-1425, a selective RARα agonist in a Phase 2 clinical trial for genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome, and SY-1365, a selective CDK7 inhibitor with potential in a range of solid tumors and blood cancers. Led by a team with deep experience in drug discovery, development and commercialization, Syros is located in Cambridge, Mass.
SOURCE: Syros Pharmaceuticals
