Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124

Phase 1b Single Ascending and Multiple Dose First-in-man Study in Adult Patients With Non-transfusion-dependent Beta-thalassaemia or Low Risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN124

The primary purpose of this study is to determine the safety and tolerability of SLN124 for the treatment of non-transfusion-dependent (NTD) β-thalassaemia and low risk myelodysplastic syndrome.

Inclusion Criteria:

• Age ≥ 18yrs; BMI 18-35 kg/m2
• β-thalassaemia intermedia or compound heterozygous HbE/β-thalassaemia
• Non-transfusion dependent: ≤ 5 units red cells in last 6 months and transfusion-free for ≥8 weeks
• Hb between 5 & 11 g/dL
• Ferritin > 250 µg/L and /or liver iron ≥ 3mg Fe/g dry weight and TSAT >40%

Exclusion Criteria:

• Haemoglobin S/β-thalassaemia, homozygous β-0 thalassaemia or α thalassaemia
• ALT/AST > 1.5 x upper limit normal or cirrhosis
• eGFR < 60 mL/min/1.73m2
• Platelets <100 or > 1000 x 109/L
• Untreated B12/folate deficiency
• Iron chelation therapy unless stable for ≥8 weeks
• Daily NSAID, therapeutic dose anticoagulant, ESA ≤12 weeks or stable dosing of hydroxyurea ≤ 6 months
• Significant cardiac disease (MI in 6 months, NYHA class III-IV heart failure, long QT)
• HIV or active hepatitis B/C or malignancy within 5 year