A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis

The management of CI is a life-long endeavor, which remains largely symptomatic (i.e.,
emollients with or without keratolytics agents) and commonly focused on reducing scaling
and/or skin lubrication with both systemic and topical treatments. A first-line therapy
includes hydration and lubrication accomplished by creams and ointments containing low
concentrations of salt, urea, or glycerol, which increase the water-binding capacity of the
horny layer. Addition of keratolytics agents are used to decrease corneocyte cohesiveness, to
promote desquamation, and to dissolve keratins and lipids (e.g., α-hydroxy acids, salicylic
acid, high dose urea, propylene glycol, N-acetylcysteine, and retinoids). Systemic retinoid
treatment is reserved for those patients refractory to topical agents because of long-term
adverse effects and teratogenicity.

This is a two part, Phase 2, multicenter, proof-of-concept (POC) study of the safety and
tolerability of PAT-001 for the treatment of Congenital ichthyosis (CI) in patients ages 12
years of age and older. Part 1 will be a double-blind, randomized, vehicle controlled,
bilateral comparison of two treatments (PAT-001 [0.1% or 0.2%] vs. vehicle) for eight (8)
weeks.

Part 2 will be a double-blind, active only treatment comparison of the two PAT-001
concentrations (0.1% or 0.2%) for an additional four (4) weeks. Subjects will have the option
to participate in the PK portion of the study.

Inclusion Criteria:

- Patients of either sex aged 12 years or older.

- Females of childbearing potential should use appropriate contraception. Women of
childbearing potential must have a negative pregnancy test at screening and baseline
visits.

- Patient and legal representative(s), if applicable, has provided written informed
consent.

- Patient has congenital ichthyosis of either lamellar or X-Linked subtype.

- Patient has two contralateral comparable Treatment Areas (e.g., each arm is affected
and treatments areas can be applied equally).

- Patient is, except for their ichthyosis, in good general health.

Exclusion Criteria:

- Patient is pregnant or breast feeding, or is planning to become pregnant during the
study.

- Patient has inflammatory skin disease unrelated to ichthyosis.

- Patient is currently using concomitant retinoid therapy, within two weeks (topical) or
12 weeks (oral) of Visit 2/Baseline.

- Patient is currently taking concomitant immunosuppressive drugs, including systemic
corticosteroids, within two weeks of Visit 2/Baseline.

- Patient is currently enrolled in an investigational drug or device study.

- Patient has used an investigational drug or investigational device treatment within 30
days prior to Visit 2/Baseline.

- Patient is unable to communicate or cooperate with the investigator due to language
problems, impaired cerebral function, or physical limitations.

- Patient is known to be noncompliant or is unlikely to comply with the requirements of
the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in
the opinion of the investigator.