Syros tanks on single-digit response rate in AML, MDS trial 

If Syros' SY-1425 has a future, it will be in combinations.

Syros Pharmaceuticals has emerged from the weekend of data drops at the American Society of Hematology (ASH) annual meeting in a battered state after it was unable to put a positive spin on an initial look at phase 2 data. The clinical trial recorded one partial or complete response among the 48 evaluable patients, wiping 50% off Syros’ stock.

Cambridge, Massachusetts-based Syros led on the fact that investigators saw “clinical activity” in 43% of the acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients enrolled in the study. But, to the detriment of Syros’ stock price, investors zeroed in on the responses, or lack thereof, seen in either cohort of subjects.

The trial linked single-agent use of SY-1425 to one complete response among the 23 evaluable AML and higher-risk MDS patients. SY-1425 failed to clear even that low bar in lower-risk MDS patients. No responses were seen in that population. That near-total lack of efficacy raises major doubts about the future of SY-1425, particularly as a monotherapy, while also casting Syros’ broader R&D strategy in an unfavorable light. 

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Syros pulled in VC funding from Flagship Ventures, Arch Venture Partners and other well-regarded investors—and picked up a Fierce 15 award—on the strength of its work to understand superenhancers. These stretches of the genome play a central role in cell identity, leading Syros to speculate it could use them to identify targets and the patients most likely to respond to therapies.      

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The potential of the idea saw Syros through multiple rounds of private financing and a 2016 IPO. But it now finds itself at a low ebb. 

If SY-1425 has a future, it will be in combinations. And, despite the lack of responses, Syros and its supporters found reasons for optimism about this future in parts of the monotherapy data. 

“These data, along with the mechanistic and preclinical data supporting combinations with azacitidine and with daratumumab, suggest SY-1425 could be a meaningful combination agent with the potential to address a substantial unmet need for patients with AML and MDS,” Columbia University Medical Center’s Joseph Jurcic, M.D., said in a statement.