SY-2101 is a novel oral form of arsenic trioxide (ATO) previously in development for acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML) that is caused by a fusion of the RARA and PML genes. An intravenously administered formulation of ATO is part of a combination regimen that cures more than 80% of APL patients, but it is extremely burdensome on patients. The regimen requires up to 140 lengthy infusions over the course of a year. We believe that an oral form of ATO that offers similar efficacy to IV ATO would dramatically reduce the treatment burden on patients and improve access
SY-5609 is a highly selective and potent oral inhibitor of the cyclin-dependent kinase 7 (CDK7) previously in development for select solid tumors. We have completed enrollment in the safety lead-in portion of the Phase 1 SY-5609 trial in combination with chemotherapy in pancreatic cancer. SY-5609 represents a novel targeted approach that we believe has potential in a range of difficult-to-treat cancers. Data from a dose-escalation study demonstrated single-agent activity, including prolonged stable disease, tumor shrinkage, and tumor marker decreases, across multiple tumor types. Notably, the prolonged stable disease and tumor shrinkage observed in metastatic pancreatic cancer patients is distinct from what one would expect to see in this highly refractory patient population. Data evaluating SY-5609 in combination with chemotherapy demonstrated that the combination was well-tolerated with evidence of clinical activity, including a confirmed partial response in a pancreatic cancer patient who was unresponsive to frontline therapy. We believe SY-5609 has the potential to provide a profound benefit for patients with cancers that have largely eluded treatment to date, based on these clinical data as well as preclinical data and mechanistic rationale that support the potential of CDK7 inhibition in solid tumors. Syros is seeking out-license opportunities for further development of SY-5609.
