Syros Announces Update on Selective CDK7 Inhibitor Portfolio

Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, today provided an update on its portfolio of selective cyclin-dependent kinase 7 (CDK7) inhibitors. The Company has decided to prioritize the development of its highly selective and potent oral CDK7 inhibitor, SY-5609, and to discontinue further development of SY-1365, its intravenous (IV) CDK7 inhibitor. Syros expects to initiate a Phase 1 clinical trial of SY-5609 in patients with select solid tumors in the first quarter of 2020.

SY-5609 inhibits CDK7 more selectively and potently than SY-1365 and has demonstrated greater anti-tumor activity than SY-1365 in multiple preclinical models. Furthermore, initial clinical activity and tolerability data from the expansion of the Phase 1 trial of SY-1365 did not support an optimal profile for patients, particularly in light of an increasing focus on oral targeted agents in cancer. As an oral molecule, Syros believes SY-5609 provides more flexibility in dosing and greater opportunity to sustain the levels of target coverage needed to improve treatment outcomes. Based on these factors, Syros has made a CDK7 portfolio decision to focus on SY-5609.

“We believe in selective CDK7 inhibition as a potentially transformative targeted approach for difficult-to-treat cancers,” said Nancy Simonian, M.D., Chief Executive Officer of Syros. “SY-1365 was the first selective CDK7 inhibitor to enter clinical development, demonstrating proof-of-mechanism for this novel therapeutic approach and showing early signs of clinical activity. We have gained important insights from our work on SY-1365 that have informed our development strategy for SY-5609, including focusing on patient populations most likely to respond to a CDK7 inhibitor. We are prioritizing SY-5609 because we believe it has best-in-class potential and that it provides the greatest opportunity to realize the promise of selective CDK7 inhibition for patients.”

SY-5609: An Oral, Highly Selective and Potent Non-Covalent CDK7 Inhibitor

SY-5609 has induced deep and sustained tumor growth inhibition, including complete regressions, in preclinical models of breast, ovarian and lung cancers at doses below the maximum tolerated dose. SY-5609 has also shown substantial anti-tumor activity in combination with fulvestrant in hormone receptor (HR)-positive breast cancer models that are resistant to CDK4/6 inhibitors. Importantly, SY-5609 showed greater tumor growth inhibition than SY-1365 in preclinical models in which they were both studied, including those that were not responsive to SY-1365.