Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of FTX-6058

Open to people ages 18-65

• Participant is 18 to 65 years of age, inclusive at the time informed consent is obtained.
• Participants who meet at least one the following criteria:
  1. ≥4 episodes of SCD pain crisis over 12 months, or ≥2 over 6 months prior to screening
  2. ≥2 episodes of SCD pain crisis plus at least one of the following over previous 12 months:
  3. Acute chest syndrome (ACS) ii. Hepatic or splenic sequestration iii. Priapism c. ≥2 of the following events over the previous 12 months: i. ACS ii. Hepatic or splenic sequestration iii. Priapism d. SCD-related pulmonary arterial hypertension
  4. SCD-related chronic kidney disease (CKD) f. Meet medical criteria to receive (e.g., post-cerebrovascular accident) but are contraindicated for chronic transfusions (e.g., alloimmunization, transfusion reactions)
• Previous experience with Hydroxyurea (HU) use for at least 6 months at the maximum tolerated dose but have shown to be unresponsive and/or intolerant or ineligible AND
• Previous experience with a stable dose of voxelotor, crizanlizumab, or L-glutamine for at least 6 months but have shown to be unresponsive and/or intolerant or ineligible
• Documented SCD at the time of screening (S/S, S/β0 and S/β+ genotypes only).
• Documented HbF ≤ 20% of total Hb.
• Total Hb ≥ 5.5 g/dL and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening.
• Participant must meet both of the following laboratory values at screening:
  • Absolute neutrophil count ≥ 1.5 × 10⁹ per liter (/L)
  • Platelets ≥ 80 × 10⁹/L
• Absolute reticulocyte count at screening ≥ 100 x 10⁹/L.

• Sickle cell complication requiring care from a medical provider in the 14 days prior to starting study drug.
• History of bone marrow transplant or human stem cell transplant or gene therapies.
• Participants with a history of severe renal disease defined as estimated glomerular filtration rate < 30 mL/min/1.73m². Participants on dialysis of any kind are excluded.
• Participants receiving regularly scheduled transfusions or any participant who has been transfused within 60 days prior to initiating study drug.
• Participant with active malignancy, or history of cancer (except for squamous cell skin cancer, basal cell skin cancer, and stage 0 cervical carcinoma in situ, with no recurrence for the last 5 years), or with an immediate family member with known or suspected familial cancer syndrome. Known presence of a chromosomal abnormality or genetic mutation that may put the participant at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Participant currently on HU, voxelotor, crizanlizumab, and/ or L-glutamine or have received HU, voxelotor, crizanlizumab, and/ or L-glutamine within 60 days prior to initiating study drug.