Syros abandons mid-stage tamibarotene program for front-line AML

Shares of Syros Pharmaceuticals experienced a significant drop of up to 70% during after-hours trading on Monday following the company's decision to stop enrolling patients in a Phase II study of tamibarotene for newly diagnosed acute myeloid leukemia (AML) patients with RARA gene overexpression. The announcement brought disappointment, as expressed by the company's chief medical officer, David Roth.

The halted trial, known as SELECT-AML-1, was examining the efficacy of tamibarotene, an oral retinoic acid receptor alpha (RARα) agonist, in combination with venetoclax and azacitidine. Syros Pharmaceuticals conducted a prespecified analysis that included 40 participants out of 51 unfit, newly diagnosed AML patients. The study revealed that the complete response (CR) or complete response with incomplete hematologic recovery (CRi) rate for the tamibarotene-based triplet regimen was 65%, compared to a 70% rate observed in the venetoclax-azacitidine doublet regimen.

The company noted that the similar CR/CRi rates between the two treatment arms indicate a low probability that the triplet regimen would demonstrate superiority in the final analysis. Importantly, no new safety concerns were identified with the triplet therapy.

Continuing its efforts in myelodysplastic syndrome (MDS) treatment, Syros pointed out that a previous Phase II study had shown that tamibarotene combined with azacitidine achieved a 61% CR/CRi rate in newly diagnosed AML patients. This bolsters the company's commitment to exploring the doublet strategy for higher-risk MDS patients. The company's Phase III SELECT-MDS-1 study, which evaluates tamibarotene plus azacitidine in newly diagnosed higher-risk MDS patients with RARA overexpression, is anticipated to provide results in the fourth quarter. The study had previously passed a futility analysis, giving further optimism for the treatment's potential.

To better allocate its resources towards advancing tamibarotene, Syros made significant organizational changes in October. The company reduced its workforce by 35% and terminated its clinical program for SY-2101, a candidate for acute promyelocytic leukemia. Additionally, all other preclinical and discovery-stage programs were discontinued. The restructuring also included a change in leadership, with Conley Chee, the chief commercial and business officer, replacing Nancy Simonian as CEO. This strategic overhaul was partly influenced by the termination of partnerships with Incyte and Pfizer earlier in 2023.

These moves reflect Syros Pharmaceuticals' focused strategy on developing its lead asset, tamibarotene, in the face of challenging trial results and organizational changes. The company's ability to navigate these challenges while continuing to pursue promising indications for tamibarotene will be critical for its future success.