Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD

This is a Phase IIa single arm open-label study to investigate the safety, tolerability, and
PK of F-652 in combination with systemic corticosteroids in subjects who have undergone HSCT
and have newly diagnosed grade II-IV lower GI aGVHD. The HSCT may be derived from bone
marrow, peripheral blood stem cells, or cord blood. The PK of F-652 in this subject
population will be investigated. Subjects may be replaced if subject withdrawal is not
related to safety or treatment response.

F-652 will be administered in conjunction with prednisone (or equivalent) at the time of the
onset of clinical symptoms consistent with GI and/or liver aGVHD. Prednisone (or equivalent)
will be given at a dose of 2 mg/kg/day and tapered as per protocol.

F-652 will be administered intravenously at a rate of 100 mL/hour for one hour once per week
for four weeks. A total of 4 doses will be administered at a dose of 45 μg/kg each. Subjects
will be followed for safety and efficacy through Day 180, and subject survival status will be
collected at Day 365.

In the first stage of the trial, a total of 16 subjects will be enrolled. If six or fewer
have a Day 28 treatment response, the trial will close due to a lack of efficacy. If seven or
more have a response, an additional 11 subjects will be enrolled into study for a total
sample size of 27. During the course of a subject's therapy, dose reduction may occur on an
individual basis as per protocol.

Inclusion Criteria:

1. Age ≥18 years and ≤80.

2. Newly diagnosed lower GI grade II-IV aGVHD with clinical diagnosis based on modified
Keystone criteria1 following allogeneic HSCT using bone marrow, peripheral blood stem
cells, or cord blood. Grading of aGVHD will be based on International Bone Marrow
Transplant Registry (IBMTR) criteria.

3. Subjects are willing to undergo a biopsy to confirm lower GI aGVHD. Biopsy results are
not needed to initiate treatment. However, if aGVHD is not confirmed histologically,
treatment with F-652 will be discontinued.

4. Female subjects of childbearing potential who agree to practice 2 effective methods of
contraception.

5. Male subjects, even if surgically sterilized (i.e. Status post-vasectomy) must agree
to agree to practice contraception.

6. Have adequate renal function (Serum creatinine <3 mg/dL).

7. ANC >500/mm3.

8. Show evidence of a personally signed and dated informed consent document indicating
that the subject (or legally acceptable representative) has been informed of all
pertinent aspects of the trial.

Exclusion Criteria:

1. Evidence of relapse or progression of hematologic malignancy at the time of study
enrollment.

2. Active uncontrolled infection.

3. Subjects requiring vasopressor or mechanical ventilation.

4. Subjects, who have received previous systemic corticosteroids treatment or poorly
absorbable corticosteroids for the treatment of aGVHD, for longer than 3 days (72
hours).

5. Subjects who received any corticosteroid therapy (for non-GVHD) at doses >0.5
mg/kg/day prednisone (or equivalent) within 7 days prior to the onset of GVHD therapy.

6. Subjects who developed aGVHD after unplanned donor lymphocyte infusion.

7. Subject with chronic GVHD features (acute/chronic GVHD overlap syndrome or classical
chronic GVHD).

8. History of personal psoriasis.

9. History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.

10. Subject is pregnant or breast-feeding.

11. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
unstable angina, or myocardial infarction within the past 6 months.

12. The subject or guardian is unable to give informed consent or unable to comply with
the treatment protocol including appropriate supportive care, follow-up and research
tests.

13. The subject has tested positive for the Clostridium difficile toxin within 7 days of
study entry.

14. Receiving other investigational drugs or biologics within 1 month or five half-lives.
Cytotoxic or biologic are not permitted throughout the study.

15. ALT (alanine aminotransferase; SGPT), AST (aspartate aminotransferase; SGPT), alkaline
phosphatase (ALP) >2.5 upper limit of normal (ULN), unless attributed to GVHD.

16. Chronic active Hepatitis B or C.

17. Subjects with a history of tuberculosis or a history of a chest X-ray suspicious for
tuberculosis, unless confirmed to be purified protein derivative (PPD) negative or
latent tuberculosis that has been previously treated.

18. Any serious medical or psychiatric illness that could, in the Investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.