On May 19, 2016 Syros Pharmaceuticals reported that preclinical data on its lead program, SY-1425, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) will be highlighted in an oral presentation at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 9-12 in Copenhagen, Denmark (Press release, Syros Pharmaceuticals, MAY 19, 2016, View Source [SID:1234512614]). The Company will also present new preclinical data on its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, SY-1365, in acute leukemia.
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SY-1425 in Novel Genomically Defined Subset of AML and MDS Patients Using its gene control platform, Syros identified a subset of AML and MDS patients whose tumors have a highly specialized regulatory region of non-coding DNA, known as a superenhancer, associated with the RARA gene. The super-enhancer associated with RARA is believed to lead to over-production of the RARα transcription factor, locking cells in an immature, undifferentiated and proliferative state. Treatment with SY-1425, an oral, potent and selective agonist of RARα, appears to promote differentiation of cancer cells with the RARA-associated super-enhancer, inhibiting the cancer’s growth. The oral presentation at EHA (Free EHA Whitepaper) will detail SY-1425’s mechanism of action as well as in vitro and in vivo data showing that a biomarker for the RARA super-enhancer discovered by Syros is predictive of response to treatment with SY-1425 in models of AML, including a survival benefit observed in the mice with the RARA biomarker when treated with SY-1425. Syros is on track to advance SY-1425 into a Phase 2 trial in mid-2016 in subsets of AML and MDS patients whose tumors are positive for the RARA biomarker.
Date & Time: Sunday, June 12, from 9-9:15 a.m. CEST Presentation Title: Super-Enhancer Analysis Defines Novel AML and MDS Sub-Types Sensitive to SY-1425, a Potent and Selective RARα Agonist Session Title: AML Biology – Novel Targeted Therapies Presenter: Michael R. McKeown, Ph.D., Senior Scientist, Syros Pharmaceuticals Abstract Number: S807 Location: Bella Center, Auditorium 2
CDK7 Inhibition as a Novel Treatment Strategy for Acute Leukemia
Certain cancers, including AML and acute lymphoblastic leukemia (ALL), are dependent on high and constant expression of transcription factors for their growth and survival and have been shown to be particularly responsive to selective inhibition of the transcriptional kinase CDK7. The poster presentation at EHA (Free EHA Whitepaper) details preclinical data demonstrating that SY-1365, the Company’s first-in-class selective and potent CDK7 inhibitor, preferentially kills cancer cells by inducing robust and dose-dependent apoptosis in acute leukemia cell lines while not inducing apoptosis in non-cancerous cells. The data also show that SY-1365 produces a significant survival benefit in patient-derived xenograft models of AML. Syros expects to advance SY-1365 into a Phase 1/2 trial in the first half of 2017 in patients with acute leukemia, including AML and ALL.
Date & Time: Saturday, June 11, from 5:30-7 p.m. CEST Presentation Title: First-in-Class CDK7 Inhibitor Induces Robust Apoptosis in Acute Myeloid Leukemia and Demonstrates Durable In Vivo Efficacy Session Title: Acute Myeloid Leukemia – Biology 3 Presenter: Yoon J. Choi, Ph.D., Senior Scientist, Syros Pharmaceuticals Abstract Number: P558 Location: Bella Center, Hall H, Poster Area