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Syros (SYRS) Falls 62% on Phase II Leukemia Study Termination

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Syros Pharmaceuticals’ (SYRS - Free Report) shares plunged 61.7% on Aug 13, after the company discontinued enrollment in the mid-stage acute myeloid leukemia (AML) study of its investigational candidate, tamibarotene, based on poor results from a prespecified interim analysis of the study. Tamibarotene is an oral selective RARα agonist.

The phase II SELECT-AML-1 study is evaluating the triple therapy of tamibarotene in combination with AbbVie’s (ABBV - Free Report) Venclexta (venetoclax) and azacitidine compared with the doublet regimen of Venclexta and azacitidine in newly diagnosed, unfit AML patients with RARα gene overexpression.

Per Syros, on Aug 9, 2024, data from 51 patients in the SELECT-AML-1 study were analyzed, including a planned futility analysis of the first 40 randomized patients, who had received approximately three months of treatment or had discontinued it.

The study observed similar complete response (CR)/complete response with incomplete hematologic recovery rates of 65% and 70% between the triplet and doublet arms, respectively. Based on such findings, Syros concluded that the likelihood of the study demonstrating superiority at the final analysis in 80 patients is low, leading to the decision to halt enrollment.

Year to date, shares of SYRS have plunged 75.4% compared with the industry’s 2.4% decline.

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However, Syros stated that tamibarotene, combined with AbbVie’s Venclexta and azacitidine, was overall well-tolerated and no new safety signals were identified. Patients who are already enrolled in the phase II SELECT-AML-1 study can opt to remain on the study at the discretion of study investigators. 

Please note that Syros is also evaluating tamibarotene in combination with azacitidine compared with azacitidine monotherapy in a pivotal phase III SELECT-MDS-1 study to treat newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression.

In the press release, the company stated that considering the discontinuation of the AML study of tamibarotene, it will focus its efforts on the HR-MDS study.

The SELECT-MDS-1 study has already passed a prespecified futility analysis which was conducted in the first quarter of 2024. Syros expects to share pivotal CR data from phase III SELECT-MDS-1 by the middle of the fourth quarter of 2024.

AbbVie’s Venclexta is currently approved in the United States to treat adult patients with chronic lymphocytic leukemia (CLL) and AML. The drug is also approved in the EU for the same indications under the brand name, Venclyxto.

AbbVie is currently studying Venclyxto/Venclexta to expand the label for approved indications and broaden into other hematologic malignancies like acute lymphocytic leukemia and myelodysplastic syndrome. Label expansion approvals in the past couple of years have expanded the eligible patient population of Venclexta significantly, which is boosting sales of the drug.

In the first half of 2024, Venclexta generated revenues of $1.25 billion, reflecting 16% growth, driven by strong demand in both AML and CLL indications. AbbVie expects Venclexta's peak revenues to approach $5 billion.

Zacks Rank & Other Stocks to Consider

Syros currently carries a Zacks Rank #2 (Buy). 

Some other top-ranked stocks in the overall healthcare sector include Entrada Therapeutics (TRDA - Free Report) and Immatics (IMTX - Free Report) . While TRDA sports a Zacks Rank #1 (Strong Buy), IMTX carries a Zacks Rank #2 at present. You can see the complete list of today’s Zacks #1 Rank stocks here.

In the past 60 days, the Zacks Consensus Estimate for Entrada Therapeutics’ 2024 loss per share has narrowed from 34 cents to 13 cents. The consensus estimate for 2025 loss per share has narrowed from $4.06 to $3.21 during the same period. Year to date, shares of TRDA have gained 4.8%.

Entrada Therapeutics beat earnings estimates in three of the last four quarters and missed once, delivering an average earnings surprise of 97.14%.

In the past 60 days, the consensus mark for Immatics’ loss per share has narrowed from $1.26 to $1.25 for 2024. During the same period, the Zacks Consensus Estimate for 2025 loss per share has narrowed from $1.49 to $1.41. Year to date, shares of IMTX have gained 9.3%.

Immatics beat earnings estimates in three of the last four quarters and met once, delivering an average earnings surprise of 32.57%.


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