Syros Presents Initial Data from Phase 1 Clinical Trial of SY-5609, Its Selective Oral CDK7 Inhibitor, at EORTC-NCI-AACR Meeting - Seite 2

• SY-5609 demonstrated dose-dependent increases in POLR2A mRNA expression, a PD marker being used in the trial to measure CDK7 biological activity.
  • Notably, increases in POLR2A in patients treated at 3 mg daily reached levels associated with tumor regressions in preclinical models, as well as with levels of CDK7 target engagement at which a clinical response and apoptosis were observed in a trial of patients treated with a first-generation IV CDK7 inhibitor.
• SY-5609 demonstrated approximately dose-proportional PK as both a single agent and in combination, minimal accumulation with repeat dosing, and a steady state half-life compatible with once-daily dosing.
• The majority of adverse events reported with SY-5609 as a single agent were low grade. The most common AEs were nausea, diarrhea, fatigue, platelet count decrease, and vomiting.
• The safety profile of SY-5609 in combination with fulvestrant was consistent with that of single-agent SY-5609.
• Five of the 13 patients treated with single-agent SY-5609 were response evaluable, and of those, three achieved stable disease and two had progressive disease; one of the four patients treated in the combination cohort was response evaluable and had progressive disease.

The Phase 1 trial continues to actively enroll patients with select solid tumors, including the recently expanded single-agent cohort in lung cancer patients and combination cohort in breast cancer patients, to further evaluate the 3 mg daily dose in focused patient populations. The trial has also been opened to patients with advanced pancreatic cancer, another tumor type that has demonstrated sensitivity to SY-5609 in preclinical models. Additional cohorts are evaluating alternate regimens, supported by preclinical data showing that intermittent regimens of SY-5609 induced tumor regressions.

Syros expects to report additional dose-escalation data, including clinical activity data, in mid-2021. Additional details about the Phase 1 trial of SY-5609 can be found using the identifier NCT04247126 at www.clinicaltrials.gov.

About Syros Pharmaceuticals

Syros is redefining the power of small molecules to control the expression of genes. Based on its unique ability to elucidate regulatory regions of the genome, Syros aims to develop medicines that provide a profound benefit for patients with diseases that have eluded other genomics-based approaches. Syros is advancing a robust pipeline, including SY-1425, a first-in-class oral selective RARα agonist in a Phase 2 trial in a genomically defined subset of acute myeloid leukemia patients, and SY-5609, a highly selective and potent oral CDK7 inhibitor in a Phase 1 trial in patients with select solid tumors. Syros also has multiple preclinical and discovery programs in oncology and monogenic diseases. For more information, visit www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.