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Syros Presents Biomarker Data from its Mid-Stage Trial in Genomically Defined AML and MDS Patients

CAMBRIDGE, Mass.–(BUSINESS WIRE)–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 the biomarker status of patients screened for the ongoing Phase 2 clinical trial of SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), was predictive of myeloid cell differentiation in the patients’ blood samples treated ex vivo with SY-1425. These data will be presented tomorrow at the European School of Haematology’s 4th International Conference on Acute Myeloid Leukemia “Molecular and Translational” Advances in Biology and Treatment in Estoril, Portugal.

“We are encouraged that the RARA and IRF8 biomarkers predicted the differentiation of patient blood samples treated ex vivo with SY-1425,” said David A. Roth, M.D., Chief Medical Officer of Syros. “These findings validate our platform’s ability to select patients we believe may be most likely to respond to gene control therapies such as SY-1425. We found the RARA or IRF8biomarkers in a significant portion of patients screened to date for the Phase 2 clinical trial and believe there remains a high unmet need for better treatment options for these AML and MDS patients.”

Syros announced that the biomarker test being used to screen patients for the clinical trial is a qPCR-based clinical assay measuring RARA and IRF8 mRNA expression with a turnaround time of less than three days on average. RARA and IRF8 mRNA serve as biomarkers for super-enhancers, which are highly specialized regulatory regions of DNA, associated with the RARA and IRF8 genes. Syros discovered these super-enhancers in subsets of AML and MDS patients and showed in preclinical studies that the super-enhancers were predictive of response to SY-1425. The data being presented at ESH demonstrate that:

  • Approximately 40% of 201 evaluable patients screened for the clinical trial through August were biomarker-positive, including approximately one-third of relapsed or refractory AML and higher-risk MDS patients tested.
  • Induction of myeloid cell differentiation following ex vivo treatment of patient blood samples with SY-1425 was significantly correlated with a positive biomarker test result. Importantly, this finding supports the potential clinical utility of the biomarker test for patient selection.
  • SY-1425 robustly induced CD38, a differentiation marker, in an in vivo model of biomarker-positive AML. By contrast, there was minimal or no CD38 expression induced in the same in vivo model of biomarker-positive AML treated with ATRA, a non-selective retoinic acid receptor agonist, and an untreated control, respectively.
    • Syros plans to expand the ongoing Phase 2 clinical trial to assess the safety and efficacy of SY-1425 in combination with an anti-CD38 therapy in RARA or IRF8 biomarker-positive AML and MDS patients.

The Phase 2 clinical trial is assessing the safety and efficacy of SY-1425 as a monotherapy and in combination with azacitidine in AML and MDS patient populations. All patients enrolled in the trial are prospectively selected using the RARA and IRF8 biomarkers. Additional details about the trial can be found using the identifier NCT02807558 at www.clinicaltrials.gov. Syros plans to present initial clinical data from the trial at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition taking place Dec. 9-12 in Atlanta.

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 in a Phase 1 clinical trial for patients with advanced solid tumors, including transcriptionally dependent cancers such as triple negative breast, small cell lung and ovarian cancers. Led by a team with deep experience in drug discovery, development and commercialization, Syros is located in Cambridge, Mass.

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