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

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.