A Randomized, Placebo-controlled, Phase 2 Study of HQK-1001 in Sickle Cell Disease

Inclusion Criteria:

- Males and females between 12 and 60 years of age

- Diagnosis of SCD, type Hb SS or Hb S-B0 Thalassemia

- At least 1 episode of SCD pain crisis, acute chest syndrome, other acute SCD
complications, or leg ulcers in the 12 months prior to screening

- Not being treated with Hydroxyurea (HU); if HU treatment has been previously
administered and then discontinued, at least 3 months must have elapsed since last
dose of HU

- If subject has been transfused in the 3 months prior to screening, then Hb A level <
20% at screening

- Baseline Hb F level obtained within 14 days prior to randomization

- Able to swallow tablets

- Able and willing to give informed consent and/or assent

- If subject is a woman of child-bearing potential (WCBP), she must have a negative
serum pregnancy test within 14 days of first dose of HQK-1001 and a negative urine
pregnancy test prior to dosing on Day 1

- If a subject is a WCBP, she must agree to use an effective form of contraception
starting at screening and for one month after HQK-1001 discontinuation

- Sexually active male subjects who have not had a vasectomy must agree to use latex
condoms with WCBP partners or ensure that their partner(s) use an effective form of
contraception starting at screening and for one month after HQK-1001 discontinuation.

Exclusion Criteria:

- Assigned to a regular transfusion program

- Use of erythropoiesis stimulating agents within 90 days prior to screening

- An SCD pain crisis or SCD-related acute complication within 3 weeks prior to
randomization

- More than 5 SCD pain crisis or SCD-related acute complications within 12 months prior
to screening

- Pulmonary hypertension requiring therapy

- ALT or AST > 3x ULN

- Serum creatinine > 1.5x ULN

- Serum amylase levels > 1.5x ULN

- Serum lipase level > 1.5x ULN

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

- 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 due to SCD-related complication

- Symptomatic peptic ulcer, hiatus hernia, or gastroesophageal reflux disease (GERD)

- History of pancreatitis

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

- Current abuse of alcohol or drugs

- Use of 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 subjects are currently on
anti-viral therapy or will be placed on therapy