Syros Pharmaceuticals (SYRS) Corporate Presentation summary

Advancing tamibarotene for hematologic malignancies

• Tamibarotene is being developed as a potential new standard of care for high-risk myelodysplastic syndrome (HR-MDS) patients with RARA overexpression, targeting a large, underserved population.

• Phase 3 SELECT-MDS-1 trial completed enrollment in Q1 2024, with pivotal data expected by mid-fourth quarter 2024; FDA supports complete response (CR) as the primary endpoint for approval.

• HR-MDS has limited treatment options, with current standard azacitidine offering only a 17% CR rate and median overall survival of 18.6 months; no new frontline therapies approved since 2006.

• Tamibarotene, a selective RARα agonist, has shown high CR/CRi rates and durable responses in Phase 2 AML studies, with a well-tolerated safety profile and minimal added toxicity when combined with azacitidine.

• Commercial launch preparations are underway, including building a specialized field force, logistics for manufacturing and distribution, and establishing patient identification and RARA testing infrastructure.

Market opportunity and clinical rationale

• Approximately 18,500 newly diagnosed HR-MDS patients in the US and EU annually, with about 50% positive for RARA overexpression, representing a significant market.

• Tamibarotene aims to be the first new frontline therapy in over a decade for this population, addressing a major unmet need for more effective and convenient treatments.

• SELECT-MDS-1 is a robust, double-blind, placebo-controlled global study with fast track designation, focusing on CR as the primary endpoint and overall survival as a key secondary endpoint.

• Prior clinical data show tamibarotene plus azacitidine achieves higher response rates than azacitidine alone, with deep molecular responses and high rates of transfusion independence.

• The company has sufficient capital to fund operations into Q3 2025, supporting ongoing development and commercialization plans.

Leadership and vision

• Leadership team has extensive experience in clinical development and commercialization of targeted oncology therapies.

• Vision is to establish tamibarotene as a new standard of care for frontline treatment of hematologic malignancies, starting with HR-MDS.

• Pre-launch activities include defining field force requirements, commercial logistics, and patient identification strategies.

• The company is preparing for a US launch, with infrastructure to support targeted patient access and RARA testing.

• Pivotal data readout and launch preparations position the company for transition to a commercial-stage organization.