Study to Assess the Effect of Long-term Treatment With GBT440 in Participants Who Have Completed Treatment in Study GBT440-031

This international open-label extension (OLE) study will be available to eligible
participants from Study GBT440-031. The study will be conducted at approximately 100 clinical
sites.

All participants in GBT440-031 who completed 72 weeks of treatment are eligible for this
study. Depending on their Group assignment in GBT440-031, participants may be eligible for
this study prior to the completion of 72 weeks of treatment; see the GBT440-031 protocol for
additional information.

All participants (approximately 435) who have received treatment in Study GBT440-031 and who
meet the eligibility criteria for this study may be enrolled.

The objective of this open-label extension (OLE) study is to assess the effect of long-term
treatment with GBT440 in participants who have completed treatment in Study GBT440-031, using
the following parameters:

1. Hemolysis markers as measured by hematological laboratory parameters (e.g. hemoglobin,
reticulocytes and unconjugated bilirubin).

2. Frequency of sickle cell-related complications

3. Safety based upon AEs, clinical laboratory tests, physical examinations (PE) and other
clinical measures.

All participants will receive daily GBT440 treatment.

If both the 900 and 1500 mg dose are maintained for the GBT440-031 study's Main Population,
then participants will continue receiving the GBT440 dose they were randomized to in the
GBT440-031 study. Participants who received placebo in GBT440-031 will be re-randomized 1:1
to receive GBT440 900 mg or 1500 mg in this study. If one dose is selected from the Main
Population analysis, this dose may be used for all participants.

Duration of Treatment:

Participants may receive study drug as long they continue to receive clinical benefit which
outweighs risk as determined by the Investigator and/or until the participant has access to
GBT440 from an alternative source (i.e., commercialization or through a managed access
program).

Inclusion Criteria:

- Male or female study participants with SCD who participated and received study
treatment in Study GBT440-031.

Note: Participants in GBT440-031 who discontinued study drug due to an AE, but who remained
on study may be eligible for treatment in this study provided the AE does not pose a risk
for treatment with GBT440.

- Females of child-bearing potential are required to have a negative urine pregnancy
test prior to dosing on Day 1.

- Female participants of child-bearing potential must use highly effective methods of
contraception to 30 days after the last dose of study drug. Male participants must
continue to use barrier methods of contraception to 30 days after the last dose of
study drug.

- Participant has provided written informed consent or assent (the ICF must be reviewed
and signed by each participant; in the case of pediatric participants, both the
consent of the participant's legal representative or legal guardian, and the
participant's assent must be obtained).

Exclusion Criteria:

- Female who is breast-feeding or pregnant.

- Participant withdrew consent from Study GBT440-031.

- Participant was lost to follow-up from Study GBT440-031.

- Participant requiring chronic dialysis.

- Any medical, psychological, safety, or behavioral conditions, which, in the opinion of
the Investigator, may confound safety interpretation, interfere with compliance, or
preclude informed consent.