Update on an Investigational Agent, Voxelotor for Treatment of Sickle Cell Disease

1. Update on an Investigational Agent, Voxelotor for Treatment of Sickle Cell Disease • Dr. Ken Bridges • Global Blood Therapeutics, Inc.

2. Stroke • Renal failure • Pulmonary HTN • Priapism • Leg ulcers • Mortality • Osteonecrosis • Retinopathy Hemolytic anemia Organ damage Fatigue Organ damage HbS polymerization RBC damage Vaso-occlusion Organ damage Pain/VOC Hemolytic anemia Voxelotor Targets HbS Polymerization Voxelotor Major and growing unmet need HbS, sickle hemoglobin; HTN, hypertension; RBC, red blood cell; VOC, vaso-occlusive crisis. Adapted from Eaton WA, Bunn HF. Blood. 2017;129:2719–2726. 2

3. HOPE Trial of Voxelotor Treatment • Key Patient Eligibility Criteria • Hemoglobin • Hb between 5.5 and 10.5 g/dL • Pain Crises • Between 1 and 10 VOCs in prior 12 months • Age • Between 12 and 65 years • Concomitant hydroxyurea allowed • Confirmed SCD of any genotype

4. HOPE Trial of Voxelotor Treatment Patient Assignment • Primary Measurement after 24 weeks: • Rise in blood level- • Percent of patients with hemoglobin rise of more than 1 g/dL • Key Secondary Measurements after 24 weeks: • How fast red cells are destroyed (hemolysis) • For each patient, change in blood level from start (hemoglobin) • Key Secondary Measurement after 72 weeks: • How often pain crises (VOC) occur over one year Voxelotor Dose 1500 mg 900 mg None (placebo)

5. Published online in the New England Journal of Medicine June 14, 2019 https://www.nejm.org/doi/10.1056/NEJMoa1903212 PHASE 3 STUDY RESULT HIGHLIGHTS

6. % of Patients with a Hemoglobin Response(Rise of more than 1 g/dL) 24 Weeks of Treatment 51.1% 32.6% 6.5%

7. % of Patients with a Hemoglobin Response(Rise of more than 1 g/dL) • 24 weeks voxelotor 1500 mg treatment • Response Did Not Depend on • Age • 12 to 18 years compared to more than 18 years • Pain crises in the 12 months before treatment • 1 VOC compared to 2 to 10 VOCs • Hydroxyurea use • Hydroxyurea treatment compared to no hydroxyurea treatment • Hemoglobin level at start of treatment • Hb less than 7 g/dL compared to 7 g/dL or more

8. Average Change in Hemoglobin at 24 weeks(g/dL) 1.1 g/dL 0.6 g/dL -0.1 g/dL No Voxelotor (placebo) Voxelotor 1500 mg Voxelotor 900 mg

9. Number of Pain Crises (VOCs) During Treatment

10. Adverse Events During Treatment Not Due to Sickle Cell Disease(Occurring in ≥10% of Patients) aExcludes SCD-related adverse events (sickle cell anemia with crisis, ACS, pneumonia, priapism, and osteonecrosis). bRash is a grouped term including the following preferred terms: rash, urticaria, rash generalized, rash maculopapular, rash pruritic, rash erythematous, rash vesicular, rash macular, and rash papular. ACS, acute chest syndrome; SCD, sickle cell disease; TEAE, treatment-emergent adverse event.

11. Next Steps • GBT plans to file with the FDA for marketing approval of voxelotor later this year with potential patient availability in 2020

12. . Questions?