A Phase 1/2 Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Protocol PTR-01-001 is a saline-controlled, single and repeat dose, dose-escalation,
crossover study designed to determine the safety, tolerability, tissue kinetics,
pharmacodynamics and preliminary efficacy of PTR 01.

The study is divided into three periods: an up to 4-week Screening Period, a 10-week
Treatment Period and an 8-week Follow-up Period. During the Screening Period and Follow-up
Period there will be no study drug treatment.

During the Treatment Period a total of 3 doses of PTR-01 and 3 doses of saline control will
be administered to patients for a total of 6 doses over a 10-week period in three cohorts
dosed at 0.1, 0.3 and 1.0 mg/kg (active drug). Fourteen patients with a diagnosis of RDEB and
a history of at least one chronic wound will be enrolled. Those patients who do not have
documentation of genetic analysis and IF staining will have blood for genetic analysis and a
biopsy for IF staining prior to enrollment (both required).

Cohorts 1, 2 and 3 will consist of 2, 4 and 8 patients respectively. Each cohort will consist
of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients
will receive doses 2 weeks apart. Patients in Group 1 will receive three doses of active drug
followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline
control followed by 3 doses of active drug. This cross-over design will yield a total of 14
patients all of whom will receive active drug and saline control.

Prior to randomization, patients will complete a Screening Period to assess the extent and
impact of skin disease involvement and the chronicity of at least one wound. Only patients
who meet all of the eligibility criteria will be randomized for treatment.

Cohort 1 patients randomized to Group 1 will receive 3 doses of active treatment (PTR-01) at
a dose of 0.1 mg/kg followed by 3 doses of saline control for a total of 6 doses. Cohort 1
patients randomized to Group 2 will receive 3 doses of saline control followed by 3 doses of
active treatment (PTR-01) at a dose of 0.1 mg/kg for a total of 6 doses. After the last
patient in Cohort 1 has received their fifth dose and safety labs for all patients have been
reviewed by the Data Safety Monitoring Board (DSMB), the next cohort may be enrolled. This
same schedule and safety review process will be followed for all subsequent dosing cohorts,
with Cohort 2 and Cohort 3 receiving 0.3 and 1.0 mg/kg respectively.

Efficacy assessments will be performed prior to first dose of therapy (at the end of the
Screening Period), after the last dose of study drug in Period 1, after the last dose of
study drug in Period 2 of the Treatment Period and 2 weeks (Day 85) after the last dose of
study drug (at the end of the Follow-up Period).

Inclusion Criteria:

1. Be at least 18 years of age.

2. Has signed the current approved informed consent form.

3. Has a diagnosis of RDEB based on genetic analysis showing two confirmed RDEB type VII
collagen mutations consistent with a recessive inheritance pattern.

4. Has the presence of some but deficient C7 staining at the dermal-epidermal junction
(DEJ) by IF.

5. Has at least 1 unhealed wound ≥ 20 cm2 for at least 6 weeks at the Screening Visit.

6. Agrees to use contraception as follows:

- For women of childbearing potential (WOCBP) agrees to use highly effective
contraceptive (including abstinence) methods from Screening, through the study,
and for at least 10 weeks after the last dose of study drug. Non-childbearing
potential is defined as a female who meets either of the following criteria: age
≥50 years and no menses for at least 1 year or documented hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy (see Section 7.4.1.2 for details on the
definition of non-childbearing potential).

- For males, agrees to use a condom with any WOCBP sexual partner from Day 1 of
study treatment, through the study, and at least 10 weeks after the last dose of
study drug.

7. Be willing and able to comply with this protocol.

Exclusion Criteria:

1. Has known systemic hypersensitivity to any of the inactive ingredients in PTR-01.

2. Is pregnant or nursing.

3. Has received in the last six months any investigational product.

4. Is anticipated to receive new regimens of antibiotics or other anti-infectives during
the trial.

5. Has any other medical or personal condition that, in the opinion of the Investigator,
may potentially compromise the safety or compliance of the patient, or may preclude
the patient's successful completion of the clinical study.