Safety Study to Examine the Systemic Exposure of Granexin® Gel After Topical Application to Diabetic Foot Ulcers

The objective of this study is to ascertain the systemic exposure of the active ingredient in
Granexin® gel (aCT1 peptide) after topical application to diabetic foot ulcers using
pharmacokinetic analysis. It is planned that a total of 16 patients with diabetic foot ulcers
will receive Granexin® gel treatment plus standard of care in this one arm study. The study
includes a screening period (1 week) and a treatment period (1 week) which occur sequentially
for a given patient. The baseline day, which demarcates the beginning of the treatment
period, is the designated as Day 0. Screening procedures are initially conducted on Day -7.

A target foot ulcer is identified at screening and patient eligibility is confirmed at
screening and then again at the beginning of the Day 0 (baseline) visit. A patient enrolled
in the study may have multiple ulcers on the same or either foot; in this case, all ulcers
will be treated with Granexin® gel, but only ulcer(s) meeting the following criteria will be
designated as the target ulcer(s) and will determine eligibility: >4cm2 in post debridement
of at least 4 weeks duration.

The treatment period for a given patient begins on Day 0 and ends one week later; the last
scheduled day of the treatment period is designated as Day 7. During the treatment period,
each patient is scheduled to receive topical treatment with study drug gel (3 applications
total) administered by study staff at scheduled study site visits at each of the following
time points: Day 0, Day 3, and Day 7. All patients, regardless of treatment assignment, also
receive standard-of-care treatment at scheduled study visits during the treatment period.

Study drug pre-application blood samples will be collected from each patient at Day 0, Day 3,
and Day 7. Study drug post-application blood samples will be collected at Day 0 and Day 7 at
time points specified in the protocol. These blood samples will be shipped to a designated
laboratory for pharmacokinetic analysis.

Safety will be assessed during the treatment period by monitoring adverse events, measuring
vital signs at each visit, performing physical examinations, electrocardiograms (ECG), as
well as pharmacokinetic (PK) blood analysis.

Inclusion Criteria:

1. Age 18 or older

2. Established diagnosis of diabetes mellitus (type I or II)

3. Glycosylated hemoglobin (HbA1c) value < 10.0% at the screening visit

4. Diagnosis of neuropathic foot ulcer(s)

5. Designated foot ulcer meets the following criteria at both the screening an baseline
visits. If the patient has multiple ulcers, at least one ulcer must meet the following
criteria at both the screening and baseline visits: a) Present for at least 4 weeks;
b) Full-thickness cutaneous ulcer below the ankle surface; c) University of Texas
grade A1; d) Area (after debridement) > 4 square cm; e) Viable, granulating wound
(investigator discretion)

6. Ankle brachial index 0.7 to 1.3 at both the screening and baseline visits

7. Signed informed consent

8. Female patients of childbearing potential must have a negative pregnancy test at
screening and must agree to use hormonal contraceptive, intrauterine device, diaphragm
with spermicide, condom with spermicide, or abstinence throughout until 2 weeks after
the last administration of study drug.

Exclusion Criteria:

1. Decrease in size of the designated target ulcer(s) by ≥ 30% during the 7-day screening
period.

2. Impaired cognition determined by clinical investigator

3. Cannot tolerate the off-loading method or cannot comply with study-defined
standard-of-care treatment.

4. Has an ulcer that meets any of the following criteria: a) Shows signs of severe
clinical infection, defined as pus oozing from the ulcer site; b) Is positive for
β-hemolytic streptococci upon culture; c) Has > 50% slough, significant necrotic
tissue, bone, tendon, or capsule exposure; d) Is highly exuding (i.e., requires daily
change of dressing)

5. Requires total contact cast

6. Ankle brachial pressure index <0.7 or > 1.3 or ankle systolic pressure <70 mmHg.

7. Has a systemic infection

8. Has any 1 of the following (only 1 of the 3 tests is required): a) On Doppler waveform
analysis of the dorsalis pedis and posterior tibial arteries, a monophasic or biphasic
flow (with loss of reverse flow) in either the artery of either foot; b) Toe: bracial
index < 0.7 or > 1.3; c) Transcutaneous oxygen pressure < 40 mmHg

9. Presence of active systemic or local cancer or tumor of any king (exception:
nonmelanoma skin cancer allowable at investigator discretion)

10. Congestive heart failure (New York Heart Association class II-IV) or coronary heart
disease with ST segment elevation, myocardial infarction or coronary artery bypass
graft, or percutaneous transluminal coronary angioplasty within the last 6 months.

11. Active osteomyelitis of the foot with the target ulcer(s)

12. Active connctive tissue disease

13. Acute Charcot's neuro-arthropathy as determined by clinical and/or radiographic
examination.

14. Active treatment with systemic corticosteroids.

15. Previous or current radiation therapy to the distal lower extremity or likelihood to
receive this therapy during study participation.

16. Pregnant or nursing.

17. Uncontrolled anemia (hemoglobin < 10 g/dL in females and < 12 g/dL in males).

18. Estimated glomerular filtration rate < 25 g/L.

19. Poor nutritional status, defined as an albumin < 25 g/L.

20. Significant peripheral edema as per investigator's discretion

21. Known inability or unavailability to complete required study visits during study
participation.

22. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse
problem, determined from the patient's medical history, which in the opinion of the
investigator, may pose a threat to patient compliance.

23. Use of a platelet-derived growth factor within 28 days before screening.

24. Use of any investigational drug or therapy within 28 days before screening.

25. Has any other factor which may, in the opinion of the investigator, compromise
participation and/or follow-up in the study.