Syros Pharmaceuticals (SYRS) Announces Agreement with Roche to Evaluate SY-5609 as Part of a Novel Combination for Treatment of Colorectal Cancer

Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, today announced that it has entered into a clinical supply agreement with Roche. Under the agreement, Syros will supply SY-5609, its highly selective and potent oral inhibitor of cyclin-dependent kinase 7 (CDK7), for a combination dosing cohort in Roche’s ongoing Phase 1/1b INTRINSIC trial, which is evaluating multiple targeted therapies or immunotherapy, including atezolizumab, as single agents or in rational specified combinations in molecularly defined subsets of colorectal cancer (CRC) patients.

“We are pleased that Roche has chosen to study SY-5609 as part of its broader strategy to explore atezolizumab in combination with other targeted agents in defined colorectal cancer patient populations,” said Nancy Simonian, M.D., Chief Executive Officer of Syros, “We believe SY-5609 is a potentially transformative targeted approach for difficult-to-treat cancers. Preclinical data has shown that CDK7 inhibition enhances the anti-tumor activity of PD-L1 inhibition, providing a strong rationale for combining SY-5609 and atezolizumab. Notably, this trial marks the first clinical investigation of a CDK7 inhibitor with an immunotherapy, and we look forward to working with Roche to evaluate the potential of this novel combination in patients with BRAF-mutant colorectal cancer.”

Under the terms of the agreement, Roche will sponsor and conduct the Phase 1/1b study to evaluate the safety, tolerability and preliminary efficacy of the combination and will assume all costs associated with the study. In exchange for providing SY-5609, Syros will receive access to the data on SY-5609 in combination with atezolizumab. Syros retains all rights to SY-5609.

Selective CDK7 inhibition has been shown to target two fundamental processes in cancer: transcription and cell cycle control. Additionally, published peer-reviewed research has shown that CDK7 inhibition induces DNA replication stress and genome instability in preclinical cancer models, triggering immune-response signaling, which is further enhanced by the addition of immune-checkpoint blockade.1

In May 2020, Syros presented preclinical data at the American Society of Clinical Oncology Virtual Scientific Program demonstrating that SY-5609 inhibited tumor growth, including inducing sustained regressions at well-tolerated doses in CRC models. In preclinical studies, SY-5609 resulted in ≥ 50 percent tumor growth inhibition in 67 percent (20/30) of patient-derived xenograft models of CRC, and ≥ 90 percent tumor growth inhibition in 23 percent (7/30) of models. Deeper responses were observed more frequently in models with BRAF mutations (50 percent, 5/10) relative to wild-type models (10 percent, 1/10).

Syros is evaluating SY-5609 in an ongoing, multi-center, open-label Phase 1 dose-escalation study in patients with advanced breast, colorectal, lung, ovarian or pancreatic cancers, or with solid tumors of any histology that harbor Rb pathway alterations. Initial data from the dose escalation showed proof of mechanism at tolerable doses. Syros expects to report additional dose-escalation data, including clinical activity data, at the ESMO Congress in September and initiate the expansion portion of the trial in the second half of 2021.

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