Neihulizumab (AbGn-168H) in Patients With Steroid-refractory Acute Graft-versus-host Disease

This study is a Phase I, single dose, dose-escalation study to study the pharmacokinetics,
safety, signs of efficacy, receptor occupancy and pharmacodynamics biomarkers (REG3-alpha and
ST2 of Neihulizumab in patients with steroid-refractory acute GvHD. Up to 24 patients will be
recruited in 4-9 clinical centers in US.

Inclusion Criteria:

1. Patients must have clinical aGvHD and pathologic findings consistent with the
diagnosis by biopsy of at least 1 involved site and treated initially with steroids at
prednisone-equivalent doses ≥1 mg/kg/day, and i) worsening of GvHD manifestations
across any interval of at least 2 days before tapering of steroid doses has begun, or

ii) persistence of grade II to IV aGvHD across any interval of at least 7 days without
improvement during steroid treatment at any prednisone-equivalent dose >0.4 mg/kg/day
or at any lower dose in patients with contraindication to continued treatment at
higher steroid doses because of severe steroid-related toxicity (e.g., myopathy), or

iii) initial response of GvHD manifestations followed by exacerbation of aGvHD across
any interval of at least 3 days while tapering glucocorticoid treatment at any
prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with
contraindication to continued treatment at higher steroid doses because of severe
steroid-related toxicity (e.g., myopathy).

2. Patients must have erythematous manifestations of cutaneous aGvHD. Characteristics of
the rash must indicate active inflammation (red coloration) as distinct from resolving
inflammation (brown coloration).

3. Providers and patients must be willing to defer new systemic or cutaneous topical
treatment of aGvHD for at least 36 hours after administration of Neihulizumab.

4. Patient must give informed consent and sign an approved consent form prior to any
study procedures.

5. Females of childbearing potential must have a negative pregnancy test result before
enrollment. Males and females of childbearing potential must agree to use a highly
effective method of birth control during the study for at least 30 days after
enrollment in the study.

Exclusion Criteria:

1. Uncontrolled infections not responding to antimicrobial therapy or requiring intensive
critical care or vasopressors

2. Evidence of end-organ Cytomegalovirus (CMV) infection

3. Patients known to have CMV, adenovirus, human herpes virus 6 (HHV6), Epstein Barr
virus (EBV) or any hepatitis viremia from screening according to institutional
standard practice

4. HIV infection or a known HIV-related malignancy.

5. Tuberculosis, history of tuberculosis or a known positive Quantiferon test for
tuberculosis

6. Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed
chimerism. DLI as part of the planned HCT protocol is allowed.

7. Known relapsed or progressive malignancy after transplant, post-transplant
lymphoproliferative disease or any secondary malignancy diagnosed after HCT

8. Absolute neutrophil count (ANC) <1000/mm3

9. Total serum bilirubin concentration >3.0 mg/dL UNLESS attributed to GvHD

10. Creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.

11. Ileus, abdominal pain, extensive denudation of intestinal mucosa or stage 4 GI GvHD.

12. Karnofsky Performance Status (KPS) <50%

13. Intensive care unit (ICU) care, life expectancy of less than 28 days, ongoing or
unresolved hepatic sinusoidal obstruction syndrome, unstable hemodynamics, or evidence
of current or previous clinically significant disease, medical condition or finding
(including vital signs and ECG) that in the opinion of the Investigator, would
compromise the safety of the patient or the quality of the data

14. History of allergy or hypersensitivity to any systemically administered antibody agent
or its excipients

15. Pregnancy or nursing

16. Prior treatment with anti-lymphocyte globulin or anti-thymocyte globulin

17. Patients <18 years of age