Syros Pharma Reveals Discovery Of Novel Drug Targets For Triple Negative Breast Cancer

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 new data generated using its gene control platform, including the discovery of 14 new drug targets in triple negative breast cancer. These discoveries demonstrate the power of Syros’ pioneering approach for systematically analyzing regulatory regions of the genome to identify novel targets for defined subsets of patients with diseases that have eluded other genomics-based approaches. These data were presented at the IMPAKT 2017 Breast Cancer Conference in Brussels, Belgium.

“Targeted drug discovery in cancer has focused on mutations in protein-coding regions of the genome, and while some cancers have been well served by this approach, many other cancers, including triple negative breast cancer, remain unaddressed,” said Eric Olson, Ph.D., Chief Scientific Officer of Syros. “By analyzing the non-coding regulatory region of the genome of tumor cells, we have uncovered new targets in subsets of triple negative breast cancer. Our focus on the regulatory genome, coupled with our expertise in drugging transcriptional targets to control the expression of genes, positions us to develop a new wave of genomic-based medicines for patients with diseases that have remained beyond the reach of other targeted approaches.”

Using its proprietary gene control platform to analyze the regulatory genomes from 43 breast cancer patients’ tissue samples, Syros scientists identified highly specialized regions of non-coding regulatory DNA, known as super-enhancers, that drive the expression of genes critical for tumor growth and survival in defined subsets of breast cancer patients. Analysis of the super-enhancers and their associated genes revealed:

• Known cancer drivers and patient subsets, with HER2+ patients having a super-enhancer associated with the HER2 gene and ER+ patients having a super-enhancer associated with the ESR1 gene, providing validation that super-enhancer analysis can be used to identify clinically relevant disease drivers in defined patient subsets.
• Enhancer-linked genes that were validated as essential for triple negative tumor cell proliferation by CRISPR-mediated gene disruption.
  • Of those genes, 14 code for newly identified drug targets for triple negative breast cancer across a range of druggable target types, including enzymes, surface receptors, and signaling and metabolic proteins.
• A super-enhancer associated with the RARA gene that is predictive of response to SY-1425, a first-in-class selective retinoic acid receptor alpha (RARa) agonist, in multiple preclinical models of breast cancer, including those resistant to treatment with standard-of-care therapies. Notably, the RARA super-enhancer is present across known subtypes of breast cancer, and Syros estimates it is present in about 35 percent of breast cancer patients. SY-1425 is currently in a Phase 2 clinical trial for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who are positive for biomarkers for super-enhancers linked to RARA pathway-associated genes, including RARA and IRF8. Upon achieving clinical proof-of-concept in that trial, Syros plans to expand development of SY-1425 into genomically defined subsets of breast cancer patients.

Syros’ drug discovery and development platform is the first to focus solely on the regulatory genome to systematically and efficiently identify disease-causing alterations in gene expression and create medicines to selectively target transcription to control the expression of genes with the aim of treating cancer, as well as autoimmune and rare genetic diseases. Using its platform, Syros is advancing a growing pipeline of drug candidates, including SY-1425 and SY-1365, a first-in-class selective inhibitor of cyclin-dependent kinase 7 (CDK7), that is on track to begin a Phase 1 clinical trial in the second quarter of this year in patients with transcriptionally dependent solid tumors, including triple negative breast, small cell lung and ovarian cancers.

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 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.

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 clinical utility of Syros’ drug candidates, the timing for initiation of the planned Phase 1 clinical trial of SY-1365, the prevalence of the RARA super-enhancer in breast cancer patients, the clinical relevance of the targets identified by Syros and the ability to drug those targets, 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. 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 biomarkers associated with the RARA super-enhancer; 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’ Annual Report on Form 10-K for the year ended December 31, 2016, 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.