A Trial Testing SP-420 in Subjects With Transfusion-dependent β-thalassemia or Low-risk Myelodysplastic Syndromes

Thalassemia cohorts:

Inclusion criteria:

• Women and men aged 18 years or older

• Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring ironchelation therapy (β-thalassemia with mutation and/or multiplication of α-globin isallowed)

• 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 MRIscanner

• Pregnant or nursing women

• Men who do not agree to practice effective barrier contraception during the entireperiod

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 facilitiesexperienced 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 entireperiod