A Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome

Inclusion Criteria:

• Male or female participants aged 18 to 65 years with clinical diagnosis of NSincluding at least 3 out of the 4 following clinical criteria:

• Neonatal erythroderma

• Bamboo hair and/or alopecia

• Chronic atopy specified as food allergy and/or asthma and/orrhino-conjunctivitis and/or eczema for at least 2 years

• Ichthyosis linearis circumflexa or scaling erythroderma or equivalent

• Immunohistochemistry documentation of absence of LEKTI in the skin or confirmedSPINK5 gene mutations

• NS involvement of ≥20% of Body Surface Area (BSA)

• Patients must give written informed consent to participation in the study prior toScreening

• Participants must be willing and able to understand and comply with studyrequirements

• Participants must be willing to have skin tape harvests collected from lesional andnonlesional skin areas

Exclusion Criteria:

• Any skin disease that may interfere with the diagnosis or evaluation of NS

• Any infection requiring treatment with systemic antibiotics, antivirals,antiparasitics, or antifungals within 2 weeks before Screening visit

• Concomitant systemic disease not controlled by treatment. Stability for 3 monthsprior to Screening is required

• Kidney or liver disease with significant impairment of organ function (creatinineclearance <30 mL/min, calculated using the Cockcroft-Gault Equation, and Child-PughClass C; ALT and AST >2 × ULN range; total bilirubin >1 × ULN).

• Concomitant disease or condition that may interfere with, or treatment of which mayinterfere with, the conduct of the study or that would, in the opinion of theInvestigator, pose an unacceptable risk to the patient in this study

• Any significant condition (eg, medical, psychiatric, or social) that according toInvestigator's judgment would prevent compliance with study protocol and full studyparticipation

• Known hypersensitivity to any ingredient of the study drug product

• Anticipation of the need for surgery or hospitalization during the study

• History of suicide attempt or suicidal ideation within 1 year prior to Screening

• History of substance abuse within 6 months prior to Screening or a positive urinedrug test at Screening. Medical marijuana may be used per discretion of theInvestigator

• History or positive test result for human immunodeficiency virus (HIV) at Screening

• Active hepatitis B virus (HBV) infection, determined by positive test result forhepatitis B surface antigen, at Screening

• Active hepatitis C virus (HCV) infection, determined as HCV ribonucleic acid (RNA)above the limit of detection in patients with positive HCV antibody titer, atScreening

• Use of topical drugs that may alter the course of NS (eg, topical corticosteroidsand topical calcineurin inhibitors) within 2 weeks before Screening or anticipationof need to use these drugs during study drug

• Systemic treatment with corticosteroids, immunosuppressants, targeted therapeutics,biologics, and IV Ig within 8 weeks before Screening

• Participation in any other clinical study or expanded access program with aninvestigational drug or device within 4 weeks before Screening

• Suspected or confirmed COVID-19 within 4 weeks before or ongoing at Screening andplanned vaccination against COVID-19 during study drug