A Safety, Tolerability and Efficacy Study of Sernova's Cell Pouch™ for Clinical Islet Transplantation

The Sernova Cell Pouch™ will be implanted under the skin. A minimum of three weeks after Cell
Pouch™ implantation, immunosuppression will be initiated and optimized for another 3 weeks.
This will allow for proper vascularization of the Cell Pouch™ chambers and the patient to be
stabilized on immunosuppression prior to transplantation. A mass, >3,000 islet equivalent
(IEQ) numbers per kg of patient body weight (IEQ/kg), of highly purified islets will be
transplanted in the Cell Pouch™. The Cell Pouch™ will be assessed for safety and tolerability
for up to one year following transplant. Data for the primary and secondary endpoints will be
summarized using descriptive statistics (such as counts and percentages).

Inclusion Criteria:

1. Male and female patients 18 to 65 years of age.

2. Ability to provide written informed consent.

3. Mentally stable and able to comply with the procedures of the study protocol.

4. Clinical history compatible with Type 1 Diabetes Mellitus (T1DM) with onset of disease
at <40 years of age, insulin-dependence for ≥5 years at the time of enrollment, and a
sum of patient age and insulin dependent diabetes duration of ≥28.

5. Absent stimulated c-peptide (<0.3 ng/mL) in response to a mixed meal tolerance test
(MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with
equivalent caloric and nutrient content may be substituted for Boost) measured during
the 4 hour test.

6. Involvement in intensive diabetes management defined as self-monitoring of glucose
values no less than a mean of three times each day averaged over each week and by the
administration of three or more insulin injections each day or insulin pump therapy.
Such management must be under the direction of an endocrinologist, diabetologist, or
diabetes specialist with at least 3 clinical evaluations during the 12 months prior to
study enrollment.

7. At least one episode of severe hypoglycemia in the 12 months prior to study
enrollment.

8. Reduced awareness of hypoglycemia. More information about this criterion, including
specific definitions of hypoglycemia unawareness, is in the protocol.

Exclusion Criteria:

1. Body mass index (BMI) >30 kg/m2

2. Insulin requirement >1.0 IU/kg/day

3. Glycated Haemoglobin (HbAlc) >11%.

4. Untreated proliferative diabetic retinopathy.

5. Blood Pressure: Systolic blood pressure (SBP) >160 mmHg or Diastolic Blood Pressure
(DBP) >100 mmHg.

6. Measured glomerular filtration rate <70 mL/min/1.73m2 (More information about this
criterion is in the protocol

7. Presence or history of macroalbuminuria (>300 mg/g creatinine).

8. Presence or history of panel-reactive anti-HLA antibodies >30%

9. For female subjects of child bearing potential: Positive pregnancy test, presently
breast-feeding, or unwillingness to use effective contraceptive measures for the
duration of the study and 4 months after discontinuation. For male subjects: intent to
procreate during the duration of the study or within 4 months after discontinuation or
unwillingness to use effective measures of contraception. More information about this
criterion is in the protocol.

10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or
tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded
even in the absence of clinical evidence of active infection.

11. Patients with negative screen for Epstein Barr Virus by Immunoglobulin G (IgG)
determination. More information about this criterion is in the protocol,

12. Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year
prior to study enrollment.

13. Any history of malignancy except for completely resected squamous or basal cell
carcinoma of the skin.

14. Known active alcohol or substance abuse.

15. Baseline Hb below the lower limits of normal at the local laboratory for patients
initially being enrolled into study.

16. Severe co-existing cardiac disease, characterized by any one of these conditions:

- Recent myocardial infarction (within past 6 months).

- Left ventricular ejection fraction <30%.

- Uncontrolled coronary artery disease.

- Known hypercoagulative state or

- International Normalized Ratio > 1.8

17. Uncontrolled hyperlipidemia (fasting LDL cholesterol >130mg/dL and/or fasting
triglycerides >200mg/dL) at the time of enrollment.

18. Persistent elevation of liver function tests at the time of enrollment. More
information on this criterion is in the protocol

19. Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially
interfering with the ability to absorb oral medications (for example untreated celiac
disease).

20. Untreated Graves' disease

21. Portal hypertension

22. Receiving treatment at the time of enrollment for a medical condition requiring
chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an
equivalent dose of hydrocortisone, for physiological replacement only.

23. Treatment with any anti-diabetic medication other than insulin within 4 weeks of
transplant, More information on this criterion is in the protocol

24. Use of any investigational agents within 4 weeks of enrollment.

25. Administration of live attenuated vaccine(s) within 2 months of enrollment.

26. Any medical condition that, in the opinion of the study investigator, will interfere
with safe participation in the trial.

27. Treatment with any immunosuppressive regimen at the time of enrollment.

28. A previous islet transplant.

29. A previous pancreas transplant. More information on this criterion is in the protocol

30. Known allergy or hypersensitivity to polymers More information on this criterion is in
the protocol

31. Presence of colostomy/ileostomy, incisional hernia or other deformity of the abdominal
wall precluding implantation of the Cell Pouch ™.

32. History of malignant hypertension or other conditions precluding general anesthesia.
Use of coumadin or other anticoagulant therapy (except aspirin) or subject with
prothrombin time (PT-INR) > 1.5.