Syros' stock plummets after Phase II AML trial halted for inefficacy

Syros Pharmaceuticals has halted enrollment for its Phase II SELECT-AML-1 trial, which was investigating the efficacy of tamibarotene as a cancer treatment. This decision follows a futility analysis indicating that the study was unlikely to succeed.

The news of the trial halt heavily impacted Syros Pharmaceuticals' stock, which plummeted by over 62% in premarket trading on August 13, compared to the previous day's closing. This decline is a stark contrast to the company's stock performance in December when initial positive data from the same trial propelled the stock to a peak value of more than $7.79. As of the latest premarket activity, the stock is priced at $1.83, and the company's market capitalization stands at $134.3 million.

The futility analysis assessed data from the first 40 patients who had been randomly assigned within the Phase II trial (NCT04905407). This study examined a three-drug regimen involving tamibarotene, AbbVie’s Venclyxto (venetoclax), and azacitidine, compared to a two-drug regimen of Venclyxto and azacitidine. The results showed similar complete response (CR) and complete response with incomplete hematologic recovery (CRi) rates in both treatment arms—65% for the triplet therapy and 70% for the doublet therapy. Consequently, the analysis concluded that the final data from 80 randomized patients would likely not yield successful results.

In spite of the setback, Syros Pharmaceuticals remains committed to the development of tamibarotene. The company emphasized that it is not entirely abandoning the cancer drug. Instead, it will continue to explore its potential in patients with higher-risk myelodysplastic syndromes (HR-MDS).

The ongoing Phase III SELECT-MDS-1 trial (NCT04797780) is evaluating tamibarotene in combination with azacitidine for HR-MDS patients. This study has already passed a predefined futility analysis in the first quarter, and pivotal complete response data are expected in the fourth quarter of this year.

Tamibarotene is a specific agonist for retinoic acid receptor alpha/beta and may interact with retinoid X receptors (RXR), which are involved in regulating the transcription of signaling pathways that affect various cancer characteristics. These receptors play a crucial role in controlling inflammation and immune responses, thereby influencing the tumor microenvironment.

In summary, while Syros Pharmaceuticals faces a significant hurdle with the discontinuation of its Phase II SELECT-AML-1 trial due to low success prospects, the company is not giving up on tamibarotene. It continues to invest in research for HR-MDS patients, with key data from a Phase III trial anticipated by the year's end.