4D-710 in Adult Patients With Cystic Fibrosis

Prior treatment

• Any prior gene therapy for any indication (Exception: mRNA-based or antisense oligonucleotide therapies are not exclusionary)
• Smoking (e.g. cigarettes, cigars, cannabis) or use of a vaping product during the 2 months prior to screening; must agree to not smoke or use vaping products during Screening and initial 24-month observation period.
• Contraindication to systemic corticosteroid therapy

Other illness

• Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
• Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
• Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
• Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
• Known CF liver disease with evidence of multilobular cirrhosis
• History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

Lab values

• If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
• If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C \> 7.5% at Screening
• Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
• Laboratory abnormalities at screening:
  • ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
  • Total bilirubin ≥ 2 × ULN
  • Hemoglobin \< 10 g/dL

Other

• Body Mass Index (BMI) \< 16
• Requirement for continuous or night-time oxygen supplementation

• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
  • Sweat chloride ≥ 60 mmol/L
  • Mutation Status
  • Bi-allelic mutations in the CFTR gene, or
  • Single mutation in the CFTR gene and clinical manifestations of CF lung disease
  • Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
• Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
• Resting oxygen saturation ≥ 92% on room air at Screening
• 18 years and older
• Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
  • Sweat chloride ≥ 60 mmol/L
  • Mutation Status
  • Bi-allelic mutations in the CFTR gene, or
  • Single mutation in the CFTR gene and clinical manifestations of CF lung disease
• Currently on a stable dose of CFTR modulator therapy for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 24-month Observation Period
• FEV1 ≥ 40% and \< 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics