Syros Pharmaceuticals' stock experienced a significant drop after its Phase III SELECT-MDS-1 trial, evaluating tamibarotene in combination with azacitidine for newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression, failed to meet its primary endpoint. The company plans to discontinue the study and thoroughly review the results to determine the next steps.
The placebo-controlled Phase III study enrolled 190 patients. The primary endpoint, complete response rate, was 23.8% in the treatment group and 18.8% in the placebo group. Syros reported that the therapy was well-tolerated.
This news comes shortly after Syros reported that a Phase II SELECT-AML-1 trial evaluating the same combination treatment in patients with acute myeloid leukemia (AML) was unlikely to meet its primary endpoint. An interim futility analysis indicated a low probability of success based on data from the first 40 randomized patients.
According to Syros, the failure of the SELECT-MDS-1 Phase III trial to meet its endpoint constitutes a default event under its secured loan facility with Oxford Finance. The company had secured a $60 million senior secured loan facility in 2022.
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.
