A Randomized, Open-Label, Multi-Dose Study of HQK-1001 in Subjects With Sickle Cell Disease

Inclusion Criteria:

- Established diagnosis of SCD

- Males and females between 12 and 60 years of age, inclusive

- At least 3 episodes of a SCD-related crisis or complication in the 3 years prior to
screening OR 1 episode of acute chest syndrome in the 5 years prior to screening

- If receiving hydroxyurea, must be receiving a stable dose for at least 6 months prior
to screening

- If hydroxyurea treatment has been discontinued, at least 3 months have elapsed since
last dose

- If transfusion in the 4 months prior to screening, then HbA level < 20% at screening

- Average of the initial two HbF levels ≥ 2.0 % within ≤ 7 days prior to the initial
dose of HQK-1001. The two must be obtained ≥ 24 hours apart

- Ability to swallow tablets

- Able and willing to give informed consent and assent (if applicable)

- If subject is a woman of child-bearing potential (WCBP), she must have a negative
serum pregnancy test within 7 days of first dose of HQK-1001

- If a subject is a WCBP, she must agree to use an effective form of contraception
within 7 days of the initial dose of HQK-1001 and for one month after HQK-1001
discontinuation

- Sexually active male subjects (with WCBP partners) must agree to use latex condoms or
ensure that their partner(s) use an effective form of contraception

- In the view of the Investigator, subject is able and willing to comply with necessary
study procedures

Exclusion Criteria:

- More than 4 hospitalizations for acute sickle cell related events in the previous 12
months prior to screening

- Pulmonary hypertension requiring oxygen therapy

- QTc > 450 msec (male) or 470 msec (female) on screening ECG (QT corrected by
Fridericia's formula)

- Assigned to a regular transfusion program

- Use of erythropoiesis stimulating agents within 90 days of screening

- ALT > 3x upper limit of normal (ULN)

- Serum creatinine > 1.2 mg/dL

- A serious, concurrent illness that would limit ability to complete or comply with the
study requirements

- An acute vaso-occlusive event within 3 weeks prior to screening

- Creatine phosphokinase (CK) > 20% above the ULN

- An acute illness (e.g., febrile, GI, respiratory) within 72 hours prior to screening

- History of syncope, clinically significant dysrhythmias or resuscitation from sudden
death

- Chronic opiate use, which, in the view of the Investigator, could confound evaluation
of an investigational drug

- Current abuse of alcohol or drugs

- Received another investigational agent within 4 weeks or 5 half-lives, whichever is
longer, prior to screening

- Currently pregnant or breast feeding a child

- Known infection with HIV-1

- Infection with hepatitis B or hepatitis C, such that patients are currently on
therapy or will be placed on therapy during the trial