Syros Pharmaceuticals’ stock has declined sharply for the second time in the past three months as a Phase III trial with its lead cancer therapy, tamibarotene, failed to meet its primary endpoint.
The SELECT-MDS-1 Phase III trial (NCT04797780) evaluating the combination therapy of tamibarotene and azacitidine, a chemotherapy, was focused on newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression. The Massachusetts-based company’s CEO Conley Chee noted that the company plans to discontinue the study with plans to review the results “thoroughly” and evaluate next steps.
The news comes three months after the company reported that a Phase II SELECT-AML-1 trial (NCT04905407) evaluating the combination treatment in patients with acute myeloid leukaemia (AML) was unlikely to meet primary endpoint. The futility analysis concluded that the study had “low probability of success”, based on the data analysis of first 40 randomised patients enrolled in the trial.
Following the news, the company’s stock was down by over 76% in premarket trading today (13 November). Syros’s stock was showing an upward trend after the value drastically declined in August after the news of a potential Phase II SELECT-AML-1 trial failure broke.
Syros also noted that the SELECT-MDS-1 Phase III trial’s failure to meet its endpoint constituted a default event under its secured loan facility with Oxford Finance. The company secured a $60m senior secure loan facility from Oxford Finance in 2022. Syros made monthly interest-only payments on each tranche prior to the amortization date of 1 March 2023, with the debt facility expected to mature on 1 February 2025.
The placebo-controlled Phase III study enrolled 190 patients. The complete response rate, the study’s primary endpoint, was similar in both treatment and placebo groups, 23.8% and 18.8% respectively. The company noted that therapy was well tolerated.
Tamibarotene is a specific agonist of retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR). The RXR receptors regulate the transcription of signalling pathways that impact numerous hallmarks of cancer by controlling both inflammation and immune responses that modulate the tumour microenvironment.
