Dose-Escalation Study of SCD-101 in Sickle Cell Disease

This is single site, dose- escalation study of SCD-101 in participants with homozygous sickle
cell disease (S/S) or S/beta 0 Thalassemia. All participants will be monitored for safety,
tolerability, and dose-limiting toxicities.

The study is divided into two parts. Part A is an open-label, non-randomized,
non-placebo-controlled dose escalation study with a 28-day treatment phase and 14-day
follow-up phase with five cohorts . Part B is a randomized, placebo-controlled, confirmatory
2x2 crossover cohort with a 28 day washout between periods, and a 28-day follow-up phase.

Inclusion Criteria:

1. Male or female, 18-55 years of age

2. Homozygous sickle cell disease or S/beta 0 thalassemia

3. Hemoglobin F ≤10%

4. Hemoglobin ≥ 6.0 g/dL and ≤ 9.5 g/dL

5. Female participants of child bearing potential and male participants whose partner is
a female of child bearing potential must be willing to use approved contraception
during the trial and for 3 months following the end of treatment. Only barrier methods
or complete abstinence are acceptable for this study. Participants using hormonal
contraception (including morning-after-pill) and IUD are excluded unless willing/able
to change to an acceptable form of contraception.

6. Ability to adhere to the study visit schedule and other protocol requirements

7. Ability to understand and the willingness to sign an informed consent document

Exclusion Criteria:

1. Red blood cell transfusion within 3 months of enrollment

2. Hydroxyurea treatment within 6 months of enrollment

3. Painful or other acute sickle cell event that required a hospitalization within
4-weeks of enrollment

4. AST and/or ALT >3x upper limit of normal and/or creatinine >2x upper limit of normal
or any other significant renal or hepatic impairment

5. Estimated creatinine clearance (CrCl) < 60 mL/min (Cockcroft- Gault formula) at
screening.

6. QTc interval of >470 msec at trial entry and participant with congenital long QT
syndrome.

7. No other significant sickle cell or non-sickle cell illness that would confound the
results of the trial

8. Any condition that, in the view of the investigator, places the participant at risk
because of participation in the trial, or may influence the result of the trial or the
participant's ability to participate in the trial

9. Participant pregnant or nursing an infant or planning pregnancy during the course of
the trial

10. History of allergic reactions attributed to sorghum or compounds of similar chemical
or biologic composition (such as Nicosan, Niprisan, Jobelyn or Xickle).

11. Other investigational drug use within 3 months of enrollment

12. PROMIS Fatigue Questionnaire 8a T-score ˂ 44.3