Syros Pharmaceuticals (SYRS) Status Update summary

Tamibarotene clinical development and mechanism

• Tamibarotene is being advanced as a targeted therapy for higher-risk MDS and AML patients with RARA gene overexpression, aiming to become a new standard of care, supported by robust clinical evidence and favorable safety profile.

• The drug acts as a selective RAR alpha agonist, restoring normal myeloid maturation and showing high complete response rates in RARA-overexpressing patients.

• Clinical data demonstrate rapid, durable responses and favorable safety, with no additive myelosuppression when combined with standard agents like azacitidine or venetoclax.

• Tamibarotene has been well-tolerated in over 1,000 patients, with most adverse events being low grade and reversible.

SELECT-MDS-1 phase III trial design and regulatory status

• SELECT-MDS-1 is a global, double-blind, placebo-controlled phase III trial in newly diagnosed higher-risk MDS patients with RARA overexpression, using a 2:1 randomization to tamibarotene plus azacitidine versus placebo plus azacitidine.

• The primary endpoint is complete response rate, with overall survival as a key secondary endpoint; the trial is powered to detect significant differences and supports potential accelerated or full approval.

• The trial passed a futility analysis and expects pivotal data readout by mid-Q4 2024.

• Fast Track designation has been granted by the FDA for tamibarotene in this setting.

Disease context and unmet need

• Higher-risk MDS is a biologically heterogeneous disease with poor outcomes and limited effective therapies; most patients do not proceed to transplant.

• Current standard of care, hypomethylating agents, offer low complete response rates and limited durability, highlighting the need for novel, biomarker-driven therapies.

• Biomarker-driven approaches, such as targeting RARA overexpression, are seen as promising for improving outcomes and personalizing therapy.