A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)

Inclusion Criteria

• •1. Aged 18 years or older at the time of signing the informed consent form (ICF).
• •2. Male or female study participants with SCD HbSC or HbSS.
• •3. Participants who have been diagnosed with any of the following SCD-related complications: between 1-10 episodes of VOC in the past 12 months, any history of sickle cell related retinopathy, silent cerebral infarct, avascular necrosis, sensorineural hearing loss; or at least 1 episode of priapism, hepatic sequestration, splenic sequestration, or splenic infarct within the last 12 months as assessed locally.
• •4. Hgb ≥7.0 g/dL during Screening. The first 2 participants must have an Hgb ≥9 g/dL.
• •5. Normal alpha globin gene screen.
• •6. Absolute reticulocyte count or % reticulocyte count \>1.5 × upper limit of normal (ULN) during Screening.
• •7. TSAT ≥15% at Screening.
• •8. Ferritin ≥50 ng/mL for HbSC or ≥100 ng/mL for HbSS (ferritin must be \<1000 ng/mL at Screening).
• •9. For participants taking hydroxyurea, L-glutamine, or crizanlizumab, stable dose for at least 2 months prior to Screening and with no anticipated need for dose adjustments during the study.
• •10. If male, not vasectomized for at least 6 months, with female sexual partner(s) of childbearing potential, agrees he and partner will use double methods of the following highly effective methods of birth control (described below) from the first dose of randomized study drug until 120 days after the last administration of study drug and must not donate sperm during their study participation:
• •1. Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •2. Intrauterine device, in place for at least 3 months (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •3. Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •11. If female, then EITHER postmenopausal, defined as at least 12 months natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agree to use 1 of the following highly effective methods of birth control on Day 1 (or earlier) and for at least 120 days after the last administration of study drug:
• •1. Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •2. Intrauterine device, in place for at least 3 months in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •3. Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• •12. Negative pregnancy test (females of childbearing potential) prior to dosing.
• •13. Able to understand the study aims, procedures, and requirements, and provide written informed consent.
• •14. Able to comply with all study procedures.