Syntara (SNT) Study Result summary

Study background and rationale

• SNT-5505 is a pan-lysyl oxidase inhibitor developed for myelofibrosis, targeting fibrosis and PDGF signaling, with FDA Orphan Drug Designation and prior positive monotherapy data.

• The drug is being tested in combination with ruxolitinib, the most common JAK inhibitor for myelofibrosis.

• Patients enrolled had significant disease burden, with a median symptom score of 23, median MF duration of 60 months, and long prior ruxolitinib exposure.

• The study aims to address unmet needs in myelofibrosis, where current therapies have limited impact on disease progression.

• Interim results were presented at the American Society of Hematology annual meeting in 2024.

Study design and endpoints

• Phase 2a open-label study evaluated SNT-5505 (200 mg BID) with ruxolitinib over 52 weeks, focusing on safety, PK/PD, and efficacy endpoints.

• Patients had to be on stable ruxolitinib for at least three months and have a symptom score of at least 10.

• Key endpoints include 50% reduction in symptom score (TSS50), 35% reduction in spleen volume (SVR35), platelet response, and bone marrow fibrosis grade.

• 16 patients enrolled; 13 reached 12 weeks, 8 reached 24 weeks, and 5 reached 38 weeks at data cut-off.

• Bone marrow biopsies were taken at 3, 6, and 12 months to assess fibrosis.

Patient population and baseline characteristics

• 16 patients enrolled; median age 71, 44% male, median MF duration 60 months.

• 75% had intermediate-2 risk, 25% high-risk; 44% had high molecular risk mutations.

• All had prior ruxolitinib exposure and high disease burden.

• Median prior ruxolitinib therapy was 38 months; median daily dose 20 mg.

• The trial is being conducted across 19 sites in Australia, South Korea, Taiwan, and the USA.