Syros Pharma Presents Biomarker Data From Its Ongoing Phase II Clinical Trial Of SY-1425 In Genomically Defined AML And MDS Patients At ESH Conference On AML

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 (RARa) 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 IRF8 biomarkers 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 RARa 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.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the therapeutic benefit of SY-1425 as a single agent and in combination with azacitidine; the reporting of initial clinical data from the ongoing Phase 2 clinical trial of SY-1425 at the ASH Annual Meeting; plans to amend the Phase 2 protocol to assess the safety and efficacy of SY-1425 in combination with an anti-CD38 therapy; the percentage of AML and MDS patients who have the RARA or IRF8 biomarker; and the benefits of Syros’ gene control platform. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Moreover, there can be no assurance that PK and PD data and ex vivo differentiation data generated to date in the ongoing Phase 2 clinical trial of SY-1425 are predictive of the ability of such trial to meet any of its endpoints. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros’ ability to: advance the development of its programs, including SY-1425 and SY-1365, under the timelines it projects in current and future clinical trials; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; replicate scientific and non-clinical data in clinical trials; successfully develop a companion diagnostic test to identify patients with the RARA and IRF8 biomarkers; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption “Risk Factors” in Syros’ Quarterly Report on Form 10-Q for the quarter ended June 30, 2017, which is on file with the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Syros expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.