Syros Presents New Preclinical Combination Data on SY-1365 and First Preclinical Data from Oral CDK7 Inhibitor Program at EORTC-NCI-AACR Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, today announced preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, showing synergistic anti-tumor activity in combination with carboplatin, a standard-of-care therapy, in models of ovarian cancer and providing a mechanistic rationale for the ongoing investigation of the combination in the Phase 1 clinical trial of SY-1365. The Company also announced the first preclinical data on its class of highly selective oral CDK7 inhibitors, which showed significant anti-proliferative activity in preclinical models of breast and ovarian cancers. These data were presented at the 30^th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Dublin.

“Selective CDK7 inhibition represents a potentially transformative approach for treating a range of cancers that have eluded effective treatment,” said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. “Our presentations at the EORTC-NCI-AACR meeting highlight our leadership in the field and support the ongoing clinical development of SY-1365 as well as the selection of SY-5609, a highly selective oral CDK7 inhibitor, as our next development candidate. Given the broad potential of CDK7 inhibitors as a new class of medicines, we believe physicians and patients will seek options across multiple modalities and believe an oral molecule could serve as an important complement to SY-1365. We are committed to maximizing the potential of CDK7 inhibition for patients, as we work to achieve our vision of developing new medicines that provide profound benefit for patients.”

SY-1365 Preclinical Combination Data
The preclinical data presented at EORTC-NCI-AACR provide a strong mechanistic rationale for the ongoing clinical investigation of SY-1365 in combination with carboplatin in ovarian cancer patients. Homologous recombination deficiency (HRD), a cellular defect caused by the disruption of normal DNA damage repair processes, sensitizes cells to treatment with DNA repair inhibitors, including PARP inhibitors and DNA-damaging agents such as carboplatin. In preclinical models of ovarian cancer, SY-1365 was shown to inhibit DNA repair and decrease the expression of homologous recombination repair (HRR) genes, which are important for repairing harmful breaks in DNA. These data suggest that SY-1365 induces an HRD-like state, which may result in enhanced sensitivity to DNA-damaging agents and DNA repair inhibitors.

Consistent with the proposed mechanism-of-action, SY-1365 demonstrated synergy with carboplatin in ovarian cancer cell lines and demonstrated greater anti-tumor activity in combination with carboplatin in xenograft models of ovarian cancer than either agent alone.

Syros is currently conducting a Phase 1 clinical trial assessing the safety and efficacy of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations. The ongoing trial includes a study cohort evaluating SY-1365 in combination with carboplatin in ovarian cancer patients who have relapsed after one or more prior therapies. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.

Preclinical Data from Oral CDK7 Inhibitor Program
Syros created a suite of highly selective and potent orally available CDK7 inhibitors. The preclinical data at EORTC-NCI-AACR detail for the first time the selectivity, potency and anti-tumor activity of these inhibitors. Using a representative member of Syros’ suite of oral CDK7 inhibitors, these data show:

• 200- to 1,200-fold greater selectivity for CDK7 over other members of the CDK family, including CDK2, CDK9 and CDK12.
• Robust anti-proliferative activity in triple negative breast cancer and ovarian cancer cell lines, which was associated with the induction of apoptosis and cell cycle arrest.
• Strong correlation between biochemical potency, CDK7 target engagement and tumor growth inhibition.
• Substantial anti-tumor effects in multiple cell-line and patient-derived xenograft models of triple negative breast and ovarian cancers.

These data helped support the selection of SY-5609 as the Company’s next development candidate. Syros is currently advancing SY-5609 into Investigational New Drug (IND) application-enabling preclinical studies.

The poster presentations on the SY-1365 preclinical combination data and on the oral CDK7 inhibitor program are now available on the Publications and Abstracts section of the Syros website at www.syros.com.

About Syros Pharmaceuticals
Syros is pioneering the understanding of the non-coding regulatory region of the genome to advance a new wave of medicines that control the expression of genes. Syros has built a proprietary platform that is designed to systematically and efficiently analyze this unexploited region of DNA 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 monogenic 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 ovarian and breast cancers. Syros is also developing a deep preclinical and discovery pipeline, including SY-5609, an oral CDK7 inhibitor, as well as programs in immuno-oncology and sickle cell disease. 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 potential benefits of CDK7 inhibition and of SY-1365, alone or in combination with carboplatin, and of SY-5609; the commercial potential of Syros’ CDK7 inhibitors; the ability to successfully enroll the ongoing Phase 1 clinical trial of SY-1365 and complete preclinical studies and file an IND for SY-5609; and the benefits of Syros’ gene control platform. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ “hope,” ‘‘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-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; 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, 2017, as updated in its Quarterly Reports on Form 10-Q for the quarters ended March 31, June 30 and September 30, 2018, each of 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.

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