Phase 2 Study to Evaluate Safety, Pharmacokinetics, Immunogenicity and Pharmacodynamics/Efficacy of EDI200 in Male Infants With X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

This Phase 2 first-in-neonate EDI200 study will enroll treatment-naïve, XLHED-affected male
newborns in the first two weeks of life. All subjects will meet entry criteria including
documentation of an EDA mutation associated with XLHED. Following Baseline evaluations,
EDI200 dosing will be initiated between day-of-life 2 and 14, with each study subject
receiving 2 doses/week for a total of 5 doses. This dosing regimen mirrors that used to
enhance efficacy in the dog XLHED model, considered to be most relevant to the clinical study
design. The study will enroll subjects in two cohorts with subjects in cohort 1 dosed at 3
mg/kg/dose, associated with partial efficacy, and cohort 2 dosed at 10 mg/kg/dose where
enhanced efficacy was demonstrated in the most relevant preclinical model. Given the
challenge of identifying families where the subject is yet to be born, it is expected that
cohort size and time for recruitment will be variable. The sponsor anticipates enrollment and
dosing of 6-10 subjects over a 12-18 month period, 3-5 subjects per cohort.

Inclusion Criteria:

Subjects for study drug administration must meet all of the following criteria to be
enrolled:

1. Male with genetic confirmation of an XLHED diagnosis.

2. Subject must be at least 48 hours age and no older than 14 days.

3. Subject will have reached term (defined as 37 weeks gestation or older) prior to
receiving first dose study drug.

4. Written informed consent of both parents (if reasonably available) must be obtained
for treatment of their XLHED-affected male infant.

5. Neither mother nor the XLHED-affected male infant known to have received an
investigational study drug in the 9 months prior to study subject enrollment in this
study.

6. No major medical issues that the PI considers a contraindication to participation.

Siblings of subjects receiving study drug must meet all of the following criteria to be
enrolled in the natural history sub-study (no age limit involved):

1. Provide written informed consent/assent.

2. A full or half-sibling of a study subject where the study subject has received at
least one dose of study drug in the Phase 2 XLHED Neonate Study and has not yet
completed the study.

3. No major medical issues that the investigator considers contraindications to
participation.

Exclusion Criteria:

Subjects for study drug administration who meet any of the following criteria cannot be
enrolled in this study:

1. Medically significant postnatal complications or congenital anomalies outside of those
considered to be associated with the diagnosis of XLHED.

Siblings of subjects receiving study drug who meet any of the following criteria cannot be
enrolled in the natural history sub-study:

1. Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists.

2. Known hypersensitivity to lidocaine or lidocaine-like agents.

3. Presence of pacemaker.

4. Subjects who are not able or are not willing to comply with the procedures of this
protocol.

5. Subject has a condition, which in the opinion of the investigator would not allow for
safe conduct of the study.