Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

Inclusion Criteria:

- Willing and able to sign the approved informed consent.

- Age: 18-60 years old, inclusive, at Screening.

- Subjects who have received more than 20 transfusions in their lifetime and who have
transfusional iron overload requiring chronic treatment with an iron chelator. N.B.:
Sickle Cell Disease subjects receiving regular exchange transfusions and iron
overloaded subjects with thalassemia intermedia who are receiving regular
transfusions (transfusion dependent thalassemia intermedia) are eligible.

- Willing to discontinue all existing iron chelation therapies for a minimum period of
one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the
study and 1 week after last dose for a total of approximately 26 weeks.

- Willing to fast two hours prior to and one hour after each dose.

- Serum ferritin >500ng/mL at Screening.

- Baseline liver iron concentration is greater than or equal to 5mg iron per g
(equivalent dry weight, liver)determined by FerriScan® R2 MRI.

- Mean of the previous three pre-transfusion hemoglobin concentrations is greater than
or equal to 7.5g/dL.

- Adult female subjects should be:

1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or

2. Surgically sterile, or

3. Females of child-bearing potential must have a negative beta-HCG pregnancy test
at the Screening Visit and a negative urine pregnancy test at the Baseline
Visit.

Females of child-bearing potential must agree to abstain from sexual activity that could
result in pregnancy or agree to use acceptable methods of contraception.

Exclusion Criteria:

- As a result of medical review, physical examination, or Screening investigations, the
Principal Investigator (PI) considers the subject unfit for the study.

- Non-elective hospitalization within the 30 days prior to Baseline testing.

- Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic,
biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone
marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.

- Iron overload from causes other than transfusional siderosis.

- Evidence of severe renal insufficiency, eg, serum creatinine 1.5X above the upper
limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular
filtration rate <60mL/min.

- Severe iron overload including:

1. T2* MRI <10 ms

2. liver iron concentration by FerriScan R2 MRI >30mg/g liver (dw)

- Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ.

- Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at
Screening.

- Insufficient venous access that precludes prescribed blood draws for safety
laboratory assessments.

- ALT at Screening >200 IU/L.

- Use of any investigational agent within the 30 days prior to the Baseline testing.

- Pregnant or lactating females.

- Cardiac left ventricular ejection fraction

1. Below the locally determined normal range in the 12 months prior to Screening by
echocardiograph or MRI or

2. <50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI
information is not available).