A Phase 1, First-in-Human Study of CITY-RBP4 in Healthy Volunteers and STGD1 Participants

The study consists of 3 sequential parts:

• Part A: Single-ascending doses in healthy volunteers
• Part B: Single-ascending doses in participants with Stargardt Disease Type 1 (STGD1)
• Part C: Multiple doses in participants with Stargardt Disease Type 1 (STGD1)

Key Inclusion Criteria (Part A):

• Willing and able to provide written informed consent form
• Be aged 18 to 45 years (inclusive) at the time of signing the informed consent form
• Generally healthy on medical history, exam, labs, and ECG
• BCVA 20/25 or better in each eye
• Serum retinol above protocol threshold
• Body weight ≥40 kg and BMI of 18.0 to 32.0 kg/m2
• Men and WOCBP must agree to use highly effective methods of contraception or practice abstinence from 30 days before the first dose of CITY-RBP4, throughout the study, and for at least 180 days after treatment with CITY-RBP4 or the last study visit, whichever is longer; men must refrain from donating or banking sperm during the same period
• Female participants who are not WOCBP should meet at least 1 of the following criteria: have undergone a documented hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy; have medically confirmed ovarian failure, or achieved postmenopausal status

Key Exclusion Criteria (Part A):

• Clinically significant ocular disease or prior ocular surgery that could interfere with safety assessments
• History of vitamin A deficiency, malabsorption, or chronic diarrhea
• Clinically significant cardiac, hepatic, renal, pulmonary, neurologic, or psychiatric disease
• Positive hepatitis B, hepatitis C, or HIV screening
• Prior RNAi/oligonucleotide therapy or recent investigational treatment
• Recent vitamin A-related supplements, retinoids, or medications affecting vitamin A metabolism
• Pregnancy or breastfeeding, if applicable

Key Inclusion Criteria (Parts B and C)

• Participants aged 12 to 45 years
• Clinical diagnosis of STGD1 with documented ABCA4 pathogenic/likely pathogenic variant
• Minimum BCVA is required in the study eye
• Subjects must have a defined aggregate atrophic lesion in 1 or both eyes
• Body weight ≥40 kg
• Able to complete key ophthalmic safety assessments and comply with study precautions

Key Exclusion Criteria (Parts B and C)

• Ocular conditions that could confound retinal imaging or safety evaluation
• Prior ocular gene therapy, stem cell therapy, or retinal implant
• Vitamin A deficiency or recent prohibited vitamin A-related treatments
• Recent interventional study participation
• Clinically significant non-ophthalmic disease, abnormal screening labs/ECG, or positive hepatitis B, hepatitis C, or HIV screening
• Pregnancy or breastfeeding, if applicable