8-K: Syros Pharmaceuticals Halts Enrollment in Phase 2 AML Trial After Interim Analysis

Syros Pharmaceuticals has discontinued enrollment in its SELECT-AML-1 Phase 2 clinical trial due to a low probability of demonstrating superiority of the triplet regimen over the doublet regimen based on an interim analysis.

Summary

• Syros Pharmaceuticals has stopped enrolling new patients in the SELECT-AML-1 Phase 2 clinical trial.
• The trial was evaluating a triplet therapy of tamibarotene, venetoclax, and azacitidine against a doublet therapy of venetoclax and azacitidine in newly diagnosed AML patients with RARA gene overexpression.
• An interim analysis of data from 51 patients, including a futility analysis on the first 40 patients, showed similar complete response rates in both the triplet (65%) and doublet (70%) arms.
• The company concluded that the trial had a low probability of demonstrating the superiority of the triplet regimen at the final analysis with 80 patients.
• Syros will present the data from the SELECT-AML-1 trial at the SOHO annual meeting in September 2024.
• The company remains focused on the SELECT-MDS-1 trial, which is evaluating tamibarotene and azacitidine in higher-risk MDS patients, with pivotal data expected by mid-fourth quarter 2024.

Sentiment

Score: 4

Explanation: The document reports a negative outcome with the discontinuation of a clinical trial, but the company is pivoting to another trial and remains committed to its goals. The sentiment is therefore negative but not catastrophic.

Positives

• No new safety signals were identified with the use of tamibarotene in combination with venetoclax and azacitidine.
• Patients currently enrolled in the SELECT-AML-1 trial can remain on the study at the discretion of the investigators.
• The SELECT-MDS-1 trial is progressing as planned and has passed a futility analysis.
• Syros remains committed to developing tamibarotene for the treatment of higher-risk MDS.

Negatives

• The SELECT-AML-1 trial failed to show a clear benefit of the triplet regimen over the doublet regimen.
• The company has discontinued enrollment in the SELECT-AML-1 trial due to low probability of success.
• The results were described as an 'unexpected outcome' by the Chief Medical Officer.

Risks

• The company faces risks related to the development of its programs, including the ability to demonstrate safety and efficacy in clinical trials.
• There are risks associated with sustaining response rates and durability of response seen to date.
• The company needs to successfully develop a diagnostic test to identify patients with the RARA biomarker.
• Syros needs to obtain and maintain patent protection and regulatory approvals.
• The company faces risks related to competition, managing expenses, and raising additional capital.
• There are risks associated with attracting and retaining qualified personnel and executing business strategies.

Future Outlook

Syros is focused on the SELECT-MDS-1 trial and expects to share pivotal data by mid-fourth quarter 2024. The company remains committed to developing tamibarotene for the treatment of higher-risk MDS.

Management Comments

• We are disappointed by this unexpected outcome, especially for people living with AML, said David A. Roth, M.D., Chief Medical Officer of Syros.
• This supports our conviction in pursuing a doublet strategy in higher-risk MDS, where we are comparing tamibarotene and azacitidine to azacitidine alone.

Industry Context

The discontinuation of the SELECT-AML-1 trial highlights the challenges in developing effective treatments for AML. The focus on the doublet strategy in MDS reflects a shift in approach based on the observed data. The company is still pursuing a similar drug in a different indication.

Comparison to Industry Standards

• The reported CR/CRi rates of 65% in the triplet arm and 70% in the doublet arm are within the range of other AML treatments, but the lack of superiority of the triplet regimen is a setback.
• The previous Phase 2 trial of tamibarotene and azacitidine showed a 61% CR/CRi rate, which is comparable to the results in the doublet arm of the SELECT-AML-1 trial.
• Other companies are also exploring combination therapies for AML, and the results of this trial will be closely watched by the industry.
• The focus on RARA gene overexpression as a biomarker is a targeted approach, which is becoming more common in cancer drug development.

Stakeholder Impact

• Shareholders may react negatively to the news of the discontinued trial.
• Patients with AML may be disappointed by the lack of progress in this specific treatment approach.
• Employees may be affected by the shift in focus and potential resource reallocation.
• The company's reputation may be slightly impacted by the trial's outcome.

Next Steps

• Syros will present data from the SELECT-AML-1 trial at the SOHO annual meeting in September 2024.
• The company will continue the SELECT-MDS-1 trial, with pivotal data expected by mid-fourth quarter 2024.

Key Dates

Keywords

Syros Pharmaceuticals, tamibarotene, acute myeloid leukemia, AML, myelodysplastic syndrome, MDS, clinical trial, RARA gene, venetoclax, azacitidine, hematologic malignancies, SELECT-AML-1, SELECT-MDS-1