19 April 2018 - - Cambridge, Massachusetts-based gene control medicines specialist Syros Pharmaceuticals (NASDAQ: SYRS) has released new preclinical data showing that SY-1365, its first-in-class selective cyclin-dependent kinase 7 inhibitor currently in a Phase 1 trial in patients with advanced solid tumors, demonstrated potent anti-tumor activity in multiple models of heavily pretreated ovarian cancer, the company said.
Researchers from Syros and DCFI evaluated the anti-tumor activity of SY-1365 in a broad panel of ovarian cancer cell lines, as well as in patient-derived xenograft mouse models developed from patients treated with multiple prior therapies, including standard-of-care platinum-based therapies and a new class of targeted therapies known as PARP inhibitors.
The data show that SY-1365 induced cell death in numerous ovarian cancer cell lines; inhibited tumor growth in 10 of the 17 treatment-relapsed ovarian PDX models studied, including inducing complete regressions; and lowered expression of MCL1, a gene in the mitochondrial apoptosis pathway that is known to inhibit apoptosis, or programmed cell death.
The data also showed that sensitivity to SY-1365 was associated with low expression of BCLXL, a known apoptosis inhibitor, and RB1, a known tumor suppressor, pointing to potential biomarkers that may be predictive of response to SY-1365.
The ongoing Phase 1 trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase 2 dose and regimen.
SY-1365 is a first-in-class selective cyclin-dependent kinase 7 inhibitor with potential across a range of difficult-to-treat solid tumors and blood cancers. In preclinical studies, SY-1365 has shown significant anti-proliferative and pro-apoptotic activity in difficult-to-treat cancers, including breast and ovarian cancers and acute leukemia.
SY-1365 has also been shown to preferentially kill cancer cells over non-cancerous cells and lower the expression of cancer-driving genes, inducing significant anti-tumor activity, including complete tumor regressions, in preclinical models of these cancers.
Syros Pharmaceuticals is researching use of the non-coding region of the genome to discover medicines that control expression of disease-driving genes. The company's proprietary gene control platform has broad potential to create medicines 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.