A Single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease

Trial status: Authorised • Incidence of AEs, SAEs, and AEs related to etavopivat (extension period) • Number of premature discontinuations, dose interruptions, and dose reductions (extension period), • Hb response rate at Weeks 12 and 24 (increase of > 1 g/dL from baseline) • Change in Hb from baseline at Weeks 12 and 24, Incidence of VOCs during the 24-week primary treatment period o Number of VOCs o Annualized Rate of VOC, Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Weeks 12 and 24 (between 5 to 18 years of age), Change from baseline in time-averaged mean of the maximum velocity (TAMMV) by transcranial Doppler ultrasonography (TCD) (> 2 years of age) • Single-dose: maximum concentration (Cmax), area under the concentration time curve (AUC)0-t, AUC0-inf • Steady-state etavopivat plasma exposure (Cmax,ss, AUCtau,ss, Cavg,ss, Cmin,ss) • Estimated using population PK • Incidence of AEs, SAEs, and AEs related to etavopivat • Number of premature discontinuations, dose interruptions, and dose reductions.

• Incidence of AEs, SAEs, and AEs related to etavopivat (extension period) • Number of premature discontinuations, dose interruptions, and dose reductions (extension period), • Hb response rate at Weeks 12 and 24 (increase of > 1 g/dL from baseline) • Change in Hb from baseline at Weeks 12 and 24, Incidence of VOCs during the 24-week primary treatment period o Number of VOCs o Annualized Rate of VOC, Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Weeks 12 and 24 (between 5 to 18 years of age), Change from baseline in time-averaged mean of the maximum velocity (TAMMV) by transcranial Doppler ultrasonography (TCD) (> 2 years of age)

Age group: 0-17 years Gender: Female, Male Target enrollment: 9 participants