On December 10, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that new preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase 1 clinical trial in advanced solid tumors, show anti-tumor activity in in vitro and in vivo models of blood cancers (Press release, Syros Pharmaceuticals, DEC 10, 2017, View Source [SID1234522498]). Additionally, the data point to a potential biomarker of response to SY-1365 and synergistic activity with a BCL2 inhibitor in preclinical models of acute myeloid leukemia (AML). These data are being presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"We believe SY-1365 represents a promising therapeutic approach across a number of solid tumors and blood cancers," said Eric R. Olson, Ph.D., Chief Scientific Officer of Syros. "These new preclinical data underscore the power of our gene control platform to elucidate the underlying biology and mechanism of action of SY-1365, furthering our ability to identify biomarkers to select the patients most likely to respond and to identify rational combination approaches with the potential to provide a profound benefit for patients."

Syros scientists analyzed the anti-tumor activity of SY-1365 in a broad panel of leukemia and lymphoma cell lines, as well as in primary cell cultures from leukemia patients. They then grouped the cell lines according to sensitivity to SY-1365 and looked for markers of response using Syros’ gene control platform. Based on the findings, Syros evaluated SY-1365 in combination with venetoclax, a BCL2 inhibitor, in preclinical studies. The data showed that:

SY-1365 inhibited proliferation in vitro in leukemia and lymphoma cells, as well as in leukemia cells from primary patient cultures.
SY-1365 induced cell death in the majority of AML, leukemia and lymphoma cell lines tested.
SY-1365 inhibited tumor growth, including inducing tumor regression, using biweekly dosing in preclinical mouse models of AML.
Sensitivity to SY-1365 was associated with low expression of the mitochondrial apoptosis antagonist BCL2L1 in AML and other leukemia cell lines.
SY-1365 lowered expression of MCL1, a gene in the mitochondrial apoptosis pathway that is known to inhibit apoptosis.
SY-1365 synergized with venetoclax in AML cell lines in vitro and increased tumor growth inhibition when combined with venetoclax, compared to either SY-1365 or venetoclax alone.
The Phase 1 trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase 2 dose and regimen. The dose-escalation phase is open and expected to enroll approximately 35 solid tumor patients for whom standard curative or palliative measures do not exist or are no longer effective. Following the dose-escalation phase, expansion cohorts are planned to further evaluate the safety and anti-tumor activity of SY-1365 in patients with transcriptionally driven tumors and to enroll patients with tumors of any histology in a cohort focused on analyzing biopsied tumor tissue. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov. Syros expects to present initial clinical data from this study in 2018.