The goal of this clinical trial is to learn about SP-420 ability to remove iron from organs in subjects with transfusion-dependent β-thalassemia or transfusion-dependent low-risk myelodysplastic syndrome.

The main questions it aims to answer are:

• How efficient is SP-420 in cleaning iron from the liver?
• How is the safety and tolerability of ascending doses of SP-420?

Participants will:

• Take medication three times weekly
• Attend up to 20 site visits
• Undergo MRI scans

Thalassemia cohorts:

Inclusion criteria:

• Women and men aged 18 years or older
• Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring iron chelation therapy (β-thalassemia with mutation and/or multiplication of α-globin is allowed)
• On a stable dose of iron chelation for at least 4 weeks prior to screening
• Weight ≥ 35kg at screening
• Transfusion iron overload
• Treated and followed for at least the past 6 months in a specialized centre

Exclusion criteria:

• β-thalassemia with the structural Hb variants HbS and HbC
• Current MDS
• Current biliary disorder
• Historic or ongoing clinically significant kidney disease
• Unable to undergo trial assessments including MRI e.g. due to claustrophobia in MRI scanner
• Pregnant or nursing women
• Men who do not agree to practice effective barrier contraception during the entire period

Myelodysplastic Syndromes Cohorts:

Inclusion criteria:

• Women and men aged 18 years or older
• Very low, low, or intermediate risk Myelodysplastic Syndrome according to IPSS-R
• Weight ≥ 35kg at screening
• Transfusion iron overload
• Treated and followed for at least the past 6 months at medical facilities experienced with MDS

Exclusion criteria:

• Therapy-related MDS or MDS with a known bone marrow fibrosis
• Diagnosis of decompensated liver cirrhosis
• Clinically significant kidney disease, either historic or ongoing
• Uncontrolled ischemic heart disease or uncontrolled arrythmia
• Uncontrolled hypertension
• Uncontrolled dyslipidaemia
• Uncontrolled Diabetes
• Major surgery within 8 weeks prior to screening
• Pregnant or nursing women
• Men who do not agree to practice effective barrier contraception during the entire period