Study of Human Placenta-derived Cells (PDA002) to Evaluate the Safety and Effectiveness in Subjects With PAD and DFU

The goal of this study is to determine a safe dose of PDA-002 [human placenta-derived cells]
for further study. This is a dose-escalation study where each of four dose levels will enroll
three to six subjects. Doses will be range from 3 million up to 100 million cells. If one
dose is considered safe after all treated subjects have been evaluated and reviewed, then the
next group of subjects will be enrolled to receive the next higher dose. This will continue
until either the highest dose is reached, until at least 2 subjects at a dose level have ≥
Grade 2 allergic reaction that is suspected to be related to PDA-002 or 2 or more subjects at
a dose level experience an unexpected, treatment-related serious adverse event or dose
limiting toxicity within 14 days following the initial dose of PDA-002. This is an open-label
study where all subjects will be taking the study drug and all study personnel will know the
dose each subject receives.

Inclusion Criteria:

- Subjects must satisfy the following criteria to be enrolled in the study:

1. Males and females, 18 to 80 years of age at the time of signing the informed
consent document.

2. Understand and voluntarily sign an informed consent document prior to any study
related assessments/procedures are conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Diabetes mellitus type 2

5. Ischemic or neuro-ischemic diabetic foot ulcer with severity of Grade 1 (full
thickness only) or Grade 2 on the Wagner Grading Scale (Appendix A) of greater
than one month duration which has not adequately responded to conventional ulcer
therapy.

6. Peripheral arterial disease with ankle-brachial index > 0.6 and ≤ 0.9 or
toe-brachial index > 0.35 and ≤ 0.7.

7. No planned revascularization or amputation over the next 3 months after Screening
visit, in the opinion of the Investigator.

8. Not a candidate for peripheral artery percutaneous or surgical revascularization.

9. Screening should not begin until at least 2 weeks after a failed reperfusion
intervention and at least 2 months after a successful mechanical intervention.

10. Subject can have stable angina, (Canadian Cardiovascular Society (CCS) Class I-II
angina (Appendix H).

11. Subjects should be receiving appropriate medical therapy for hypertension and
diabetes.

12. Subject must be a non-tobacco user defined as someone who has not used
tobacco/nicotine patch for ≥ 3 months and must agree to remain tobacco/nicotine
free for the duration of the study.

13. A female of childbearing potential [FCBP] must have a negative serum pregnancy
test at Screening and a negative urine pregnancy test prior to treatment with
study therapy. In addition, sexually active FCBP must agree to use 2 of the
following adequate forms of contraception methods simultaneously such as: oral,
injectable, or implantable hormonal contraception; tubal ligation; intrauterine
device [IUD]; barrier contraceptive with spermicide or vasectomized partner for
the duration of the study and the follow-up period.

14. Males (including those who have had a vasectomy) must agree to use barrier
contraception (latex condoms) when engaging in reproductive sexual activity with
FCBP for the duration of the study and the follow-up period.

Exclusion Criteria:

- The presence of any of the following will exclude a subject from enrollment:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness
that would prevent the subject from participating in the study.

2. Any condition including the presence of laboratory abnormalities, which places
the subject at unacceptable risk if he or she were to participate in the study.

3. Any condition that confounds the ability to interpret data from the study.

4. Subjects whom, in the judgment of the Investigator, are at elevated risk for the
development of a malignancy. This judgment may be based on family history,
history of industrial exposures, smoking history or other cancer risk factors.

5. Known to be positive for human immunodeficiency virus.

6. Pregnant or lactating females.

7. Subjects with a body mass index > 35 at Screening.

8. Aspartate transaminase (AST) or Alanine transaminase (ALT) > 2.5 x the upper
limit of normal (ULN) at Screening.

9. Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2 at Screening
calculated using the Modification of Diet in Renal Disease Study equation (Levey,
2006) or history of eGFR decline > 15 mL/min/1.73 m2 in the past year.

10. Alkaline phosphatase > 2.5 x the ULN at Screening.

11. Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at
Screening.

12. Untreated chronic infection or treatment of any infection with systemic
antibiotics, including the ulcer site, within 4 weeks prior to dosing with
investigational product [IP].

13. Known osteomyelitis.

14. History of Methicillin-resistant Staphylococcus aureus (MRSA).

15. Ulcer that has decreased or increased in size by ≥ 50% during the screening
period.

16. Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or
systolic blood pressure > 180 mmHg during Screening at 2 independent measurements
taken while subject is sitting and resting for at least 5 minutes).

17. Poorly controlled diabetes mellitus (hemoglobin A1c > 9%).

18. Untreated proliferative retinopathy.

19. History of malignant ventricular arrhythmia, CCS Class III-IV angina pectoris,
myocardial infarction/PCI (percutaneous coronary intervention)/CABG (coronary
artery bypass graft) in the preceding 6 months, pending coronary
revascularization in the following 2 months, transient ischemic
attack/cerebrovascular accident in the preceding 6 months, and/or New York Heart
Association [NYHA] Stage III or IV congestive heart failure, (Appendix C).

20. Abnormal ECG: new bundle branch block (BBB) ≥ 120 msec in the preceding 3 months;
QTcB and/or QTcF > 480 msec or QTcB and/or QTcF ≥ 500 msec with old BBB. Patients
with a potential risk for Torsades des Pointes should not be enrolled.

21. Uncontrolled hypercoagulation.

22. Life expectancy less than 2 years due to concomitant illnesses.

23. In the opinion of the Investigator, the subject is unsuitable for cellular
therapy.

24. History of malignancy within 5 years except basal cell or squamous cell carcinoma
of the skin or remote history of cancer now considered cured or positive Pap
smear with subsequent negative follow-up.

25. History of hypersensitivity to any of the components of the product formulation
(including bovine or porcine products, dextran 40, and dimethyl sulfoxide
[DMSO]).

26. Disorders or allergies precluding the use of radiographic contrast or renal
insufficiency severe enough to contraindicate the use of radiographic contrast.

27. Subject has received an investigational agent —an agent or device not approved by
the US Food and Drug Administration (FDA) for marketed use in any indication—
within 90 days (or 5 half-lives, whichever is longer) prior to treatment with
study therapy or planned participation in another therapeutic study prior to the
completion of this study.

28. Subject has received previous gene or cell therapy.