PhI fizzle forces Syros to spike its lead drug, triggering another rout on shares
Less than stellar Phase I results have triggered a pipeline cleanup at Syros Pharma, where one of its two lead drugs — a CDK7 inhibitor administered intravenously — is getting swapped out with an oral version.
The biotech said it maintains its belief in the CDK7 pathway for cancer, but thinks prioritizing SY-5609, which appears more selective and potent in preclinical models, is a wiser choice than holding onto an IV drug that didn’t quite embody the optimal balance between efficacy and tolerability. A human trial for SY-5609 is planned for early next year.
Syros had positioned SY-1365 in a number of solid tumors marked by specific genetic mutations, including ovarian and breast cancers. Having treated 68 patients in an expansion portion of the trial with both single-agent and combination therapies — targeting some patients who are resistant to CDK4/6 inhibitors — investigators concluded they would need more frequent dosing to sustain the level of CDK7 they need.
Notably, only 24 patients were evaluable at the data cutoff, and none had better response than stable disease. Of those treated with single-agent SY-1365, 42% had stable disease as defined by RECIST criteria, and the percentage was 64% in the combo group (who were also given fulvestrant or carboplatin).
“We have gained important insights from our work on SY-1365 that have informed our development strategy for SY-5609, including focusing on patient populations most likely to respond to a CDK7 inhibitor,” CEO Nancy Simonian said in a statement. “We are prioritizing SY-5609 because we believe it has best-in-class potential and that it provides the greatest opportunity to realize the promise of selective CDK7 inhibition for patients.”
Investors, though, saw the glass half empty. Shares $SYRS are down 33.32% to $6.74.
This is not the first time Syros’ lead drugs have disappointed. SY-1425, their RARα agonist deployed against acute myeloid leukemia, flopped in a Phase II two years ago. Syros is conducting another trial pairing the drug with azacitidine, the standard of care, that they say is turning up higher response rates. They will need some solid, hard data to win skeptics back.