On October 29, 2019 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported new preclinical data for SY-5609, its highly-selective and potent oral inhibitor of cyclin-dependent kinase 7 (CDK7) (Press release, Syros Pharmaceuticals, OCT 29, 2019, View Source [SID1234549991]). The data demonstrate that SY-5609 induces deep and sustained anti-tumor activity, including complete regressions, in multiple preclinical models of solid tumors at doses below the maximum tolerated dose (MTD). These data were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston.

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"We are excited to share these new preclinical data for SY-5609, which speak to its potential as a best-in-class oral CDK7 inhibitor and reinforce our conviction in CDK7 inhibition as a potentially transformative approach for difficult-to-treat cancers," said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. "We are particularly encouraged that SY-5609 as a single agent induced rapid and dose-dependent tumor growth inhibition in preclinical models of lung, breast and ovarian cancers, and by the observation that sustained regressions are associated with RB pathway alterations. These data support the focus of our planned Phase 1 trial on those patient populations, which we believe are most likely to benefit from treatment with SY-5609, and we look forward to initiating the study early next year."

New Preclinical Data on SY-5609 Highlight Broad Potential Across Solid Tumor Types

Researchers from Syros conducted a series of preclinical studies to characterize the in vitro and in vivo profile of SY-5609. The data show that SY-5609 induced:

Dose-dependent tumor growth inhibition in ovarian and breast cancer models, with tumor regressions observed at doses as low as one-fifth of the MTD.
Rapid, sustained and dose-dependent transcriptional pharmacodynamic responses in xenograft tumor tissue that correlated with tumor growth inhibition.
Substantial tumor growth inhibition in 100% (12/12) of triple negative breast cancer, small cell lung cancer and high grade serous ovarian cancer models tested, including deep and sustained regressions in 58% (7/12) of these models, at well-tolerated doses.
RB pathway alterations were associated with deeper and more sustained responses.
Robust anti-tumor activity in combination with fulvestrant in treatment-resistant models of estrogen receptor-positive breast cancer, including models that were resistant to both fulvestrant and a CDK4/6 inhibitor.
Additionally, the data suggest that SY-5609 plasma exposures are dose proportional and do not accumulate with repeated daily dosing at therapeutic doses and that the overall pharmacokinetic profile supports a daily dosing regimen.

Syros expects to complete investigational new drug application-enabling studies for SY-5609 by year-end. The Company plans to initiate a Phase 1 trial in patients with select solid tumors, including breast, lung and ovarian cancers, and in solid tumors of any histology harboring RB pathway alterations, in the first quarter of 2020.

The poster presented at AACR (Free AACR Whitepaper)-NCI-EORTC is now available on the Publications and Abstracts section of the Syros website at www.syros.com.