Efficacy and Safety of ALTB-168 in Patients With Moderate to Severe Active, Anti-TNF Alpha and/or Anti-integrin Refractory Ulcerative Colitis: a 26-week, Open-label, Multi-center, Phase II Proof of Principle Trial
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: AltruBio Inc.

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 1 of 78 
 
 
CONFIDENTIAL 
Clinical Trial Protocol 
Sponsor 
Trial No.: 
AbGenomics International, Inc. 
2017.008.01 
 
Investigational 
Product(s): 
Neihulizumab (AbGn-168H) 
Study Title: 
Efficacy and safety of AbGn-168H in patients with moderate to 
severe active, anti-TNFand/or anti-integrin refractory ulcerative 
colitis: a 26-week, open-label, multi-center, phase II proof of 
principle trial 
Clinical Phase: 
II 
Lead Investigator 
Dr. David Rubin 
 
Trial Medical 
Monitor: 
Dr. Shipra Patel 
Dr. Shih-Yao Lin 
Status: 
Official Protocol 
 
Version and Date: 
Version: Amendment 4 
Date: 2018-11-01 
 
Page 1 of 78 
Proprietary confidential information.  
 2018 AbGenomics International Inc. All rights reserved. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 2 of 78 
 
 
CONFIDENTIAL 
CLINICAL TRIAL PROTOCOL SYNOPSIS 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date (Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Title of trial: 
Efficacy and safety of AbGn-168H in patients with moderate to severe active, anti-
TNF and/or anti-integrin refractory ulcerative colitis: a 26-week, open-label, 
multi-center, phase II proof of principle trial. 
Lead Investigator: 
David Rubin 
Trial site(s): 
Multi-center trial 
Clinical phase: 
II 
Objective(s): 
Primary Objectives: 
To evaluate the efficacy of AbGn-168H administered intravenously in patients with 
moderate-to-severe active ulcerative colitis (UC) who are refractory or intolerant to 
anti-TNF and/or anti-integrin treatments. 
Secondary Objective: 
To investigate safety, tolerability, and immunogenicity of intravenous AbGn-168H 
administration. 
Methodology: 
A Phase II, single arm, open-label, multiple dose, multi-center study 
Study Design: 
Open-label 
Number of Centers: 
Around 12-18 
No. of Patients: 
A minimum of 30 patients and a maximum of 40 
Diagnosis: 
Moderate to severe active ulcerative colitis refractory or intolerant to anti-TNF 
and/or anti-integrin treatments. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 3 of 78 
 
 
CONFIDENTIAL 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date (Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Main criteria for inclusion: 1) Patients must provide written informed consent; 
2) Age 18-75 years; 
3) Diagnosis of UC ≥ 12 weeks prior to screening by full colonoscopy (i.e., ≥ 12 
weeks after first diagnosis by a physician according to American College of 
Gastroenterology guidelines); 
4) Moderate-to-severe active UC, at time of screening, defined as: 
a) Mayo Clinic Score (MCS) of 6 points or higher, AND 
b)  a centrally read MCS endoscopic subscore of grade 2 or higher, AND 
c)  MCS rectal bleeding subscore of 1 point or higher, AND 
d)  disease extending 15 cm or more from the anal verge; 
5) Stable doses of concomitant medications, including : 
a) Stable oral corticosteroids (i.e., ≤ 20 mg/day of prednisone, ≤ 9 mg/day of 
budesonide) ≥ 2 weeks before D1 dosing; Taper of oral corticosteroids per 
Investigator’s discretion during the study is allowed; 
b) Stable oral 5-amyinosalicylic acid dose ≥ 2 weeks before D1 dosing; 
c) Stable immunosuppressant including azathioprine, mercaptopurine, or 
methotrexate ≥ 8 weeks before D1 dosing. Patients taking methotrexate 
also are advised to take folic acid 1 mg/day or equivalent if there is no 
contraindication; 
d) Stable doses of probiotics ≥ 2 weeks before D1 dosing; 
e) Stable anti-diarrheas ≥ 2 weeks before D1 dosing; 
6) Patients must have previously received anti-tumor necrosis factor alpha (anti-
TNF and/or anti-integrin therapy for UC and demonstrated an inadequate 
response, loss of response, or intolerance, and must have discontinued therapy 
≥ 8 weeks before D1 dosing; 
7) Patients previously treated with cyclosporine or tacrolimus must have 
discontinued therapy ≥ 4 weeks before D1 dosing;  
8) Topical corticosteroids and topical 5-amyinosalicylic acid preparations must 
have been withdrawn ≥ 2 weeks before D1 dosing; 
9) Nonsteroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥ 
4 weeks before D1 dosing; 
10) Tofacitinib or other Janus kinase (JAK) inhibitors must have been discontinued 
≥ 2 weeks before D1 dosing; 
11) Patients previously treated with tube feeding, defined formula diets, or 
parenteral alimentation/nutrition must have discontinued treatment 3 weeks 
before D1 dosing; 
12) Females with reproductive potential must have a negative pregnancy test result 
before enrollment. Men and women with reproductive potential have to be 
willing to use a highly effective method of contraception from study start to ≥ 
3 months after the final dose of the study drug. A highly effective method of 
birth control is defined as one which results in a low failure rate (less than 1% 
per year). 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 4 of 78 
 
 
CONFIDENTIAL 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date (Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Main criteria for exclusion: GI related exclusion criteria: 
1) Indeterminate colitis (Inflammatory bowel disease unclassified, IBD-U) or 
suspected Crohn’s disease 
2) Any history of colectomy 
3) Presence of an ileostomy or colostomy 
4) A history or evidence of colonic mucosal dysplasia 
5) Short gut syndrome 
General health related exclusion criteria: 
6) Pregnant or lactating 
7) Inability to comply with study protocol in the opinion of the investigator 
8) History of dysplasia or malignancy in recent 5 years, except completely excised 
basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in 
situ of the cervix  
9) Cirrhosis or active alcohol abuse per the judgement of investigator 
10) Poorly controlled diabetes (HbA1c > 8.0%) 
11) Significant screening ECG abnormalities, including evidence of acute 
myocardial infarction, complete left bundle branch block, second-degree heart 
block, or complete heart block 
12) Impaired renal function (calculated creatinine clearance < 60 mL/min) 
13) Impaired hepatic function in the absence of diagnosis of primary sclerosing 
cholangitis, serum transaminase > 2.5x Upper Limit Normal (ULN), alkaline 
phosphatase > 2.5x ULN, or increased total bilirubin judged by the investigator 
to be clinically significant, or a diagnosis of primary sclerosing cholangitis, 
serum transaminases > 3x ULN, alkaline phosphatase > 3x ULN, or total 
bilirubin > 2.5x ULN judged by the investigator to be clinically significant 
14) Moderate to severe anemia (Hb < 8g/dL) 
15) Thrombocytopenia (platelet count < 75,000/uL) 
16) Evidence of current or previous clinically significant disease, medical condition 
or finding in the medical examination that in the opinion of the investigator, 
would compromise the safety of the patient or quality of the data 
17) Requiring parenteral corticosteroid treatment.  
18) Received any investigational product within 1 year.  
19) History of drug abuse according to the Diagnostic and Statistical Manual of 
Mental Disorders, 5th edition (DSM-V) criteria within 12 months prior to 
screening or positive drug screening tests. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 5 of 78 
 
 
CONFIDENTIAL 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date (Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Main criteria for exclusion: Infection related exclusion criteria: 
20) Human immune deficiency virus (HIV) infection or known HIV-related 
malignancy. 
21) Acute or chronic hepatitis B or C, or carrier status. Patients with anti-HBc Ab 
but with undetectable anti-HBs Ab should also be excluded. 
22) Positive IgM antibody titers in the presence of negative IgG titers to Epstein-
Barr virus 
23) Positive stool test for ova or parasites, positive stool culture for pathogens, or 
positive stool toxin assay for Clostridium difficile at screening. Patients with 
the positive stool toxin assay for C. difficile at screening could be rescreened if 
they are being treated for C. difficile and a repeat stool toxin assay at least 4 
weeks after the completion of treatment is negative with no evidence of 
recurrence. 
24) Intestinal mucosa biopsy positive for cytomegalovirus (CMV) at screening. 
25) Positive screening test for latent Mycobacterium tuberculosis (TB) infection. 
Patients with a history of latent TB infection who received an appropriate and 
documented course of therapy can be included if the screening examination 
and a chest x-ray performed ≤ 3 months before screening revealed no evidence 
of current active infection. If a Quantiferon TB test is indeterminate, the test 
should be repeated, and if the result is again indeterminate, such patient should 
be excluded. 
26) History of any opportunistic infection ≤ 12 weeks before D1 dosing. 
27) Any current or recent (≤ 4 weeks before D1 dosing) symptoms/signs of 
infection. 
28) Received oral antibiotics ≤ 4 weeks before D1 dosing or intravenous antibiotics 
≤ 8 weeks before D1 dosing. 
29) Received a live attenuated vaccine ≤ 4 weeks before D1 dosing. 
30) Neutropenia (absolute neutrophil count < 1,500/uL). 
31) Lymphocytopenia (absolute lymphocyte count < 500 /uL). 
Dose: 
9 mg/kg; Total 10 doses on Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), 
Day 22 (Week 3), Day 29 (Week 4), Day 36 (Week 5), Day43 (Week 6), Day 50 
(Week 7), Day 64 (Week 9), and Day 78 (Week 11). 
Mode of Administration: 
Intravenous infusion, infusion time approximately 1 hour 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
              Trial Protocol (Amendment 4) 
Page 6 of 78 
 
 
CONFIDENTIAL 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date (Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Duration of treatment and 
follow-up: 
Patients receive a total of 10 doses, 9 mg/kg of Neihulizumab, administered over 12 
weeks. Patients will be evaluated at the beginning of Week 0 (Day 1), Week 1 (Day 
8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 
6 (Day 43), Week 7 (Day 50), Week 9 (Day 64), Week 11 (Day 78), Week 12 (Day 
84, End of Treatment), Week 16 (Day 112), Week 20 (Day 140), and Week 26 
(Day 182, End of Study).  
Criteria for efficacy:  
Primary endpoint:  
The proportion of patients with clinical response, defined as defined as a ≥ 3-point 
reduction in MCS, a 30% or greater decrease from the baseline score, and with a 1-
point or greater decrease of the rectal bleeding subscore or an absolute rectal 
bleeding score of 0 or 1 at Week 12.  
Secondary endpoints:  
(1) The proportion of patients with clinical response at Weeks 6, 7, 9 and 11 
defined as a ≥2-point decrease in pMCS, and with a 1-point or greater decrease of 
the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.  
(2) The proportion of patients with clinical remission, defined as MCS of 2 or 
lower (or pMCS of 1 or lower) and no subscore higher than 1 at Weeks 6, 7, 9, 11 
and 12.  
(3) The proportion of responders who remain in clinical response and remission at 
Weeks 16, 20, and 26. 
(4) Flexible sigmoidoscopy subscore changes from baseline at Weeks 12 and 26. 
(5) The proportion of patients with sigmoidoscopic improvement, defined as any 
decrease in MCS endoscopic subscore, at Week 12 and 26. 
(6) The proportion of patients with mucosa healing defined as an absolute subscore 
for endoscopy of 0 or 1 at Weeks 12 and 26. 
(7) Change of histological activity grade from baseline at Weeks 12 and 26 using 
the Geboes system. 
(8) The proportion of patients with histological healing defined as histological 
grade = 0 at Weeks 12 and 26. 
(9) Change of Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline at 
Weeks 12 and 26. 
(10)The proportion of patients with IBDQ response, defined as an increase from 
baseline of at least 16 points at Weeks 12 and 26. 
Exploratory endpoints:  
Faecal calprotectin and c-reactive protein changes at Week 4, 9, 12, 16, 20, and 26. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 7 of 78 
 
 
 
CONFIDENTIAL 
Name of company: 
Tabulated 
Trial Protocol 
 
AbGenomics International, Inc. 
 
Name of finished product: 
Neihulizumab 
Name of active ingredient: 
 
AbGn-168H 
 
Protocol date 
(Original): 
Trial number: 
 
Revision date 
(Amendment 4): 
2018.11.01 
2017.09.26 
2017.008.01 
Criteria for safety: 
Physical examination, vital signs, safety laboratory tests, adverse events and 
tolerability. 
Pharmacokinetics 
parameters: 
Cmax and associated parameters 
Immunogenicity: 
The Immunogenicity (anti-drug antibody; ADA) of AbGn-168H will be evaluated by 
a qualitative bridging immunoassay with electrochemiluminescence detection.  
Statistical methods: 
Determination of sample size: Assuming placebo effects of 25% (historical data) and 
AbGn-168H responsive rate of 45%, 40 patients have > 80% power to detect an alpha 
of 0.1 (two sided). 
All patients who receive AbGn-168H treatment (modified Intent to Treat set, mITT) 
will be included in all analyses. 
Summaries of patient disposition, demographics, disease characteristics, assessments 
of physical condition and functionality. Summary statistics for the time from the first 
dosing date to the last dosing date will be provided as the extent of drug exposure. 
Descriptive statistics with appropriate plots will be employed in the analysis of all 
efficacy, PK, PD biomarkers (Fecal calprotectin and CRP), and immunogenicity 
(ADA) data. 
AEs will be listed by body system using MedDRA terms. Descriptive statistics will be 
provided for clinical laboratory test results by scheduled time of evaluation, as well as 
for the change from baseline.  
Summary statistics of continuous variables including numbers, means, standard 
deviations, median, minimum and maximum will be calculated. Categorical variables 
will be presented as number and percentages. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 8 of 78 
 
 
 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL APPROVAL/ACKNOWLEDGMENT 
APPROVAL STATEMENT OF ABGENOMICS 
On behalf of AbGenomics, only the Sponsor Medical Monitor is authorized to approve the 
Clinical Study Protocol and any subsequent amendment(s). 
The following person has approved this Clinical Study Protocol using signatures as presented 
below: 
Shih-Yao Lin, MD 
 
Sponsor Medical Monitor’s Name (Print) 
 
 
 
 
________________________________ 
Sponsor Medical Monitor’s Signature 
Date of Signature 
(DD MMM YYYY) 
 
APPROVAL STATEMENT OF THE LEAD INVESTIGATOR 
It is the responsibility of the Lead Investigator to approve the Clinical Study Protocol and any 
subsequent amendment(s). 
The following person has approved this Clinical Study Protocol using signatures as presented 
below: 
David Rubin, MD 
 
Lead Investigator’s Name (Print) 
 
 
 
 
________________________________ 
Lead Investigator’s Signature 
Date of Signature 
(DD MMM YYYY) 
 
ACKNOWLEDGE STATEMENT INVESTIGATOR(S) 
Each participating investigator must agree to the approved Clinical Study Protocol and any 
subsequent amendment(s) by signing the Investigator Clinical Study Protocol Agreement Form.
31 Oct 2018

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 9 of 78 
 
 
CONFIDENTIAL 
TABLE 1 (Scheduled Events of Treatment Period) 
 
Footnotes: 
1. Patients who completed the treatment (10 doses) should continue in the study and attend visits through EOS. Patients who 
discontinue before the completion of 10 doses will be encouraged to continue the visit until EOS. If patients are unable to 
continue the visits until EOS, the last visit should be considered as EOS and EOS assessments should be completed. 
Trial Periods 
Screenin
g V1 
V
2 
V
3 
V
4 
V
5 
V
6 
V
7 
V
8 
V
9 
V
10 
V
11 
V 
12 
V 
13 
V 
14 
V 
15 
Day   
-28 to -1 
1 
8 
15 
22 
29 
36 
43 
50 
64 
78 
84 
EOT1 
112 
14
0 
182 
EOS 
Week 
-4 to -1 
0 
1 
2 
3 
4 
5 
6 
7 
9 
11 
12 
16 
20 
26 
Time window (days) 
N.A. 
 
0 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 2 
 4 
 4 
4 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check of Eligibility 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Medical History  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Ulcerative Colitis 
History 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Therapy2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Assess for Adverse 
Events 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Demographics/Weight  
x 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
x 3 
 
 
 
Full Physical 
Examination 
x 
x 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Partial Physical 
Examination 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
 
Vital Signs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
12-Lead Resting ECG 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Flexible sigmoidoscopy4  
x5 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Administer AbGn-168H 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
Diary Instruction/review 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary collection/review 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physician Global 
Assessment 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Complete Mayo Clinic 
score4 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Partial Mayo Clinic 
score6 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
 
Histopathological 
analysis 
x7 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Inflammatory Bowel 
Disease Questionnaire 
(IBDQ) 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Stool screening8 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fecal calprotectin and 
CRP 
x 
 
 
 
 
x 
 
 
 
x 
 
x 
x 
x 
x 
PK sampling9 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
ADA 
 
x 
 
 
 
x 
 
 
 
x 
 
x 
x 
x 
x 
Safety Lab Tests 
(Hematology and 
Chemistry) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x  
x 
x 
Urinalysis10 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
HbA1c test 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON® test for 
tuberculosis 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy/Hormone 
Test11 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
x 
Drug Screening12 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral screening 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 10 of 78 
 
 
CONFIDENTIAL 
2. Any over-the-counter and/or prescription medications, including dietary supplements taken within 30 days prior to Screening, 
any ulcerative colitis medications taken 3 months prior to Screening OR any prohibited medications (as outlined in the 
protocol) that were washed out prior to Screening should be recorded in the eCRF.  
3. Weight will be reassessed before administration of AbGn-168H and at EOT. 
4. MCS endoscopic subscore will be assessed by a central reader. It is allowed if a full colonoscopy is deemed necessary at 
screening (V1) per investigator’s discretion. However, the endoscopic subscore will be determined by rectum, sigmoid and 
descending colon only. 
5. The screening sigmoidoscopy must be performed at least 14 days before Visit 2/Day 1 (or within 2 weeks after the ICF is 
signed), since it may take up to 14 days for sites to receive the results of the CMV assessment of intestinal mucosa biopsy.  
6. To be done before the infusion of AbGn-168H. 
7. CMV assessment of intestinal mucosa biopsy will be performed at screening only. 
8. Stool screening include ova and parasites, stool culture for pathogens, stool toxin assay for Clostridium difficile to be 
performed at screening 
9. PK sampling will be done at 15±10 mins predose and 2 hrs±15 mins after the end of infusion at Visits 2, 9 and 11. At Visits 3, 
4, 5, 6, 7, 8, and 10, PK sample will be done at 15±10 mins predose. 
10. If urinalysis stix assay is abnormal, a microscopic examination of urine sediment should be perform at local laboratory.  
11. Serum pregnancy test will be performed at Screening (Visit 1) for females of childbearing potential. Pregnancy test or 
confirmation of birth control should be recorded in the source document as available. Urine pregnancy test will be performed 
prior to drug administration at Visits 2~11, Visit 12 (EOT) and Visit 15 (EOS).  
12. Medical use of marijuana, benzodiazepine and amphetamine is allowed, the rest (barbiturate, cocaine, methadone, and opiate) 
is exclusionary. 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 11 of 78 
 
 
CONFIDENTIAL 
TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................2 
CLINICAL STUDY PROTOCOL 
APPROVAL/ACKNOWLEDGMENT ........................................................8 
APPROVAL STATEMENT OF ABGENOMICS ...........................................................8 
APPROVAL STATEMENT OF THE LEAD INVESTIGATOR ...................................8 
ACKNOWLEDGE STATEMENT INVESTIGATOR(S) ...............................................8 
TABLE 1 (SCHEDULED EVENTS OF TREATMENT PERIOD) ....................9 
TABLE OF CONTENTS ................................................................................... 11 
ABBREVIATIONS ........................................................................................... 15 
1. 
INTRODUCTION ...................................................................................... 18 
1.1 
MEDICAL BACKGROUND ...............................................................................18 
1.2 
DRUG PROFILE ..................................................................................................24 
2. 
RATIONALE, OBJECTIVES, AND BENEFIT-RISK 
ASSESSMENT .......................................................................................... 29 
2.1 
RATIONALE FOR PERFORMING THE TRIAL ...............................................29 
2.2 
TRIAL OBJECTIVES ..........................................................................................30 
2.3 
BENEFIT - RISK ASSESSMENT .......................................................................30 
3. 
DESCRIPTION OF DESIGN AND TRIAL POPULATION ................... 32 
3.1 
OVERALL TRIAL DESIGN AND PLAN ..........................................................32 
3.2 
DISCUSSION OF TRIAL DESIGN .....................................................................32 
3.3 
SELECTION OF TRIAL POPULATION ............................................................32 
3.3.1 
Main Diagnosis for Study Entry .............................................................33 
3.3.2 
Inclusion Criteria ....................................................................................33 
3.3.3 
Exclusion Criteria ...................................................................................34 
3.3.4 
Patient Withdrawal and Trial Discontinuation .......................................36 
3.3.4.1 Patients withdrawal from the treatment or trial ....................... 36 
3.3.4.2 Trial discontinuation by the sponsor ........................................ 37 
4. 
TREATMENTS ......................................................................................... 38 
4.1 
TREATMENTS TO BE ADMINISTERED .........................................................38 
4.1.1 
Identity of AbGenomics’ Investigational Product ..................................38 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 12 of 78 
 
 
CONFIDENTIAL 
4.1.2 
Packaging, Labeling, and Re-supply ......................................................38 
4.1.3 
Storage Conditions ..................................................................................39 
4.1.4 
Drug Accountability................................................................................39 
4.2 
TREATMENTS SCHEME, DOSING DELAY AND DISCONTINUATION ....40 
4.3 
CONCOMITANT THERAPY AND RESTRICTIONS .......................................41 
4.3.1 
Concomitant therapy ...............................................................................41 
4.3.2  
Restricted Medications............................................................................42 
4.4 
TREATMENT COMPLIANCE ...........................................................................43 
5. 
VARIABLES AND THEIR ASSESSMENT ............................................ 44 
5.1 
EFFICACY ...........................................................................................................44 
5.1.1 
Endpoint(s) of efficacy ...........................................................................44 
5.1.2 
Mayo Diary Card ....................................................................................45 
5.1.3 
Reading of MCS Endoscopic Subscore/ Flexible Sigmoidoscopy .........45 
5.2 
SAFETY ................................................................................................................45 
5.2.1  Safety Endpoints .........................................................................................45 
5.2.2. 
Adverse Events .......................................................................................46 
5.2.2.1 Definitions of adverse events ................................................... 46 
5.2.2.1.1 Adverse Events of Special Interests ......................................... 48 
5.2.2.2 Listed adverse events ............................................................... 48 
5.2.2.3 Adverse event and serious adverse event monitoring and reporting
 49 
5.2.3 
Assessment of safety laboratory parameters ...........................................50 
5.2.4 
Electrocardiogram ...................................................................................53 
5.2.4.1  ECG (12-lead) ......................................................................... 53 
5.2.5 
AE and SAE reporting ............................................................................54 
5.2.5.1 Reporting to AbGenomics ....................................................... 54 
5.2.5.2 Reporting to FDA .................................................................... 54 
5.2.5.2.1  MedWatch 3500A Reporting Guidelines................................ 55 
5.2.5.3 Expedited reporting to health authorities and IECs/IRBs ........ 55 
5.2.5.4 Other events to be reported ...................................................... 55 
5.3 
IMMUNOGENICITY (ANTI-DRUG ANTIBODY) ...........................................56 
5.4 
PHARMACOKINETICS END POINTS ..............................................................56 

AbGenomics International, Inc. 
November 2018 
Trial No.: 2017.008.01 
Trial Protocol (Amendment 4) 
Page 13 of 78 
 
 
CONFIDENTIAL 
5.5 
OTHER ASSESSMENT (S) .................................................................................57 
5.6 
APPROPRIATENESS OF ASSESSMENTS .......................................................57 
5.7 
BIOMARKERS ....................................................................................................57 
5.8 
PHARMACODYNAMICS ...................................................................................57 
5.8.1 
 Pharmacodynamic endpoints .................................................................57 
5.9 
PHARMACOKINETIC - PHARMACODYNAMIC RELATIONSHIP .............58 
6. 
INVESTIGATIONAL PLAN .................................................................... 59 
6.1 
VISIT SCHEDULE ...............................................................................................59 
6.1.1 
Screening period .....................................................................................59 
6.1.2 
Study period ............................................................................................60 
7. 
STATISTICAL CONSIDERATIONS ....................................................... 64 
7.1 
PLANNED ANALYSES ......................................................................................64 
7.1.1 
Pharmacokinetic analyses .......................................................................64 
7.1.2 
Safety analyses ........................................................................................65 
7.1.3 
Efficacy analyses ....................................................................................66 
7.1.4 
Anti-drug Antibody .................................................................................66 
7.2 
PATIENT REPLACEMENT ................................................................................66 
7.3 
DETERMINATION OF SAMPLE SIZE .............................................................67 
8. 
REGULATORY CONSIDERATIONS ..................................................... 68 
8.1 
INSTITUTIONAL REVIEW ................................................................................68 
8.2 
INFORMED CONSENT ......................................................................................68 
8.3 
DATA MONITORING PLAN .............................................................................69 
8.4 
DATA MANAGEMENT PLAN ..........................................................................69 
8.5 
DATA QUALITY ASSURANCE ........................................................................69 
8.6 
REPORTING MECHANISM ...............................................................................70 
8.7 
TRIAL RECORDS ...............................................................................................70 
8.7.1 
Source documents ...................................................................................70 

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8.7.2 
Direct access to source data and documents ...........................................70 
8.8 
STATEMENT OF CONFIDENTIALITY ............................................................71 
9. 
REFERENCES ........................................................................................... 72 
10. APPENDICES ............................................................................................ 76 
10.1 PROCEDURES FOR PREPARING NEIHULIZUMAB FOR INTRAVENOUS 
ADMINISTRATION ............................................................................................76 
11. CLINICAL STUDY PROTOCOL AGREEMENT FORM ...................... 78 

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ABBREVIATIONS 
 
AE 
Adverse Event 
ADA 
Anti-drug Antibody 
ADCC 
Antibody-dependent Cellular Cytotoxicity 
AICD 
Activation-induced Cell Death 
CDC 
Complement-dependent Cytotoxicity 
CHO 
Chinese Hamster Ovary 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
CSR 
Clinical Study Report 
DTH 
Delayed-type Hypersensitivity 
ECG 
Electrocardiograph 
eCRF 
Electronic Case Report Form 
EOS 
End of Study 
EOT 
End of Treatment 
Fas-L 
Ligand for Fas molecule 
FDA 
Food and Drug Administration 
GvHD 
Graft versus Host Disease 
GWAS 
Genome-wide Association Study 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
IBD 
Inflammatory Bowel Disease 

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IBDQ 
Inflammatory Bowel Disease Questionnaire 
IEC 
Independent Ethics Committee 
IFN 
Interferon Gamma 
IL 
Interleukin 
IL18RAP 
Interleukin 18 Receptor Accessory Protein 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
i.v. 
intravenous 
JAK 
Janus kinase 
lb 
pound 
MCS 
Mayo Clinic Score 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
NOAEL 
No Observed Adverse Effect Level 
NOD2 
Nucleotide-binding Oligomerization Domain-Containing Protein 2 
PASI 
Psoriasis Area and Severity Index 
PD 
Pharmacodynamics 
PI 
Principle Investigator 
PK 
Pharmacokinetics 
pMCS 
Partial Mayo Clinic Score 
PPS 
Per Protocol Set 
PRO 
Patient-reported Outcome 
PsA 
Psoriatic Arthritis 
PSGL-1 
P-selectin Glycoprotein Ligand-1 
SAE 
Serious Adverse Event 

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s.c. 
subcutaneous 
sr-aGvHD 
steroid-refractory acute Graft versus Host Disease 
SRD 
SUSARs 
Single Rising Dose 
Suspected Unexpected Serious Adverse Reactions  
TB 
Tuberculosis 
TLPL 
T-Lamina Propria Lymphocytes 
TNFα 
Tumor Necrosis Factor-α 
UC 
Ulcerative Colitis 
ULN 
Upper Limit of Normal 
5-ASA 
5-aminosalicylic Acid 
6-MP 
6-mercaptopurine 

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1. 
INTRODUCTION 
1.1 
MEDICAL BACKGROUND 
Ulcerative colitis (UC) is a lifelong, chronic inflammatory disease affecting colorectal mucosa. 
The hallmark clinical symptom is bloody diarrhea, rectal urgency and tenesmus. Anatomically, 
UC involves the rectum in about 95% of cases and may extend to proximally to the proximal 
portion of the large intestine. At extreme, UC may involve the entire colon. Ulcerative colitis is 
associated with significant morbidity. Typically, UC patients go through cycles of exacerbations 
and emissions, which may occur spontaneously or in response to treatment changes or concurrent 
illnesses. If poorly controlled, UC can significantly affect a person’s social and psychological 
wellbeing. An estimated 50% of people with ulcerative colitis will have at least one relapse per 
year[1]. About 80% of these are mild to moderate and about 20% are severe[2]. 
UC was estimated to affect approximately 500,000 individuals in the United States. The 
incidence of UC is about 8-12 per 100,000 population per year[3]–[7]. The direct medical costs 
alone exceed four billion dollars annually, comprising estimated hospital costs of over US$960 
million[8] and drug costs of $680 million[9]. The social economic cost associated UC is high. A 
quarter million physician visits, 30,000 hospitalizations, and loss of over a million workdays per 
year are contributed by UC[10].  
The pathogenesis of ulcerative colitis is complex and not completely known, but accumulating 
evidence suggests that environmental factors contribute to trigger in genetically predisposed 
individuals an overly aggressive T cell mediated immune-inflammatory response against 
components of the luminal flora, which eventually leads to mucosa damage [11]–[13]. From 
genome-wide association study (GWAS) data, hundreds of disease-associated loci have been 
identified. Although the molecular functions of many identified UC-related genes are not clear, 
the molecular functions of several genes (e.g., NOD2, IL23R, and IL10) are involved in 
inflammation against bacteria and T cell-mediated cytokines production[14]. Environmental 
factors and microbiota within colon also contributes significantly to colon mucosal inflammation, 
especially in genetically predisposed individuals. It is postulated that in the colon of genetically 
susceptible individual, special inflammation triggering bacteria may emerge in the presence of 
environmental factors, such as high fat diet and antibiotics use. Through an elusive mechanism, 
these bacteria activate gut mucosa homing T cells to secret an array of inflammatory cytokines: 
IL1, IL2, IL12B, IL18RAP, IL21, IFN, IL10, IL27, causing the breakdown of colorectal 
mucosa[15]. 
T cell involvement in UC has been substantiated by several observations[16]. First, UC is 
associated with a single nucleotide polymorphism on a T cell specific transcription factor T-bet 
binding site that controls the expression of IL18RAP[17]; UC is frequently associated with other 
T-cell mediated diseases such as psoriasis[16] and multiple sclerosis[18]; research has further 
shown that colitis can be induced in immune deficiency mice by native T cell transfer [18], and a 
novel helper T cell subset expressing the transcription factor PU.1 and IL9 consequently named 
Th9 cells was identified in patients with UC, and was shown to play an important role in driving 
UC by regulating the function of the intestinal epithelial barrier[19], [20]; and finally, inhibitors 

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of T cell proliferation and activation such as cyclosporine[21] and tacrolimus[22], or blocking T 
cell influx into colorectal mucosa by vedolizumab (an anti α4β7 integrin antibody)[23], [24] or 
etrolizumab (an anti-β7 integrin antibody)[25], has been proved to be effective in control disease 
activity. In line with the pathogenesis role of T cell, blocking TNF, which is secreted by 
activated T cells, among other cells, is also effective in controlling UC activities [26]–[30], so is 
Tofacitinib, an oral inhibitor of JAK pathways which modulate the signaling of IL2, IL4, IL9, 
IL21, among other cytokines and interfere with Th2 and Th17 differentiation. 
The treatment goal in ulcerative colitis is the induction and maintenance of clinical/patient-
reported outcome remission (PRO), defined as resolution of rectal bleeding and diarrhea/altered 
bowel habit, and endoscopic remission, defined as a Mayo endoscopic subscore of 0-1. 
Histological remission was considered as a adjunctive goal[31]. The primary drugs used in 
ulcerative colitis include 5-aminosalicylic acid (5-ASA), steroids, and immunomodulators such 
as azathioprine and 6-mercaptopurine (6-MP)[32]. However, most of these conventional 
medications provide symptomatic improvement but fail to stop the underlying inflammatory 
process and do not change the disease course[33]. In addition, 20-40% of UC patients do not 
respond to conventional medications[34]. The advent of biologics such as anti-TNF agents has 
dramatically changed the outcome of UC since they changed both disease course (fewer 
surgeries, less hospitalization, steroid sparing, greater clinical remission and mucosal healing 
rates) and patients’ life (quality of life and work productivity)[26], [35]. However, with all 
current available biologics, more than 50% of UC patients failed to reach remission (Table 2 and 
Table 3), with 10-20%/year the loss of response rate and withdrawal due to intolerance is 
frequent in the long term[36]. In the safety prospective, long term use of TNF inhibitors is 
associated with increased risk of opportunistic infection and even cancer[37]–[40]. All these 
clinical experiences demonstrate there are still significant unmet medical needs for ulcerative 
colitis and underscores the need for new medications which could provide therapeutic efficacy 
without compromising the protective immunity. 

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Table 2: Response rates (2A) and Remission rates (2B) in UC patients naïve to biological treatments. 
(2A) Response Rates 
TNF naïve 
Induction 
Response rate at/within W12 
Maintenance 
Response rate at/beyond W52 
Treatment 
Placebo 
Treatment 
Placebo 
Infliximab 
ACT 1  
ACT 2 
 
69.4% (W8) 
64.5% (W8) 
 
37.2% (W8) 
29.3% (W8) 
 
45.5% (W54) 
47.1% (W30) 
 
19.8% (W54) 
26.0% (W30) 
Adalimumab 
ULTRA 1  
ULTRA 2  
 
53.8% (W8) 
59.3% 
 
43.1% (W8) 
38.6% 
 
36.7% 
 
24.1% 
Golimumab 
PURSUIT 
 
52.9% (W6) 
 
30.3% (W6) 
 
48.4% (W54) 
 
31.2% (W54) 
Vedolizumab 
GEMINI 1 
 
53.1% 
 
26.3% 
 
60.7% 
 
26.6% 
 

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 (2B) Remission rates 
TNF naïve 
Induction 
Remission rate at/within W12 
Maintenance 
Remission rate at/beyond W52 
Treatment 
Placebo 
Treatment 
Placebo 
Infliximab 
ACT 1  
ACT 2 
 
39% (W8) 
33.9% (W8) 
 
14.9% (W8) 
5.7% (W8) 
 
34.7% (W54) 
35.8% (W30) 
 
16.5% (W54) 
10.6% (W30) 
Adalimumab 
ULTRA 1 
ULTRA 2 
 
18.5% (W8) 
21.3% (W8) 
 
9.2% (W8) 
11% (W8) 
 
22% (W52) 
 
12.4% (W52) 
Golimumab 
PURSUIT 
 
17.9% (W6) 
 
6.4% (W6) 
 
33.8% (W54) 
 
22.1% (W54) 
Vedolizumab 
GEMINI 1 
 
23.1% (W6) 
 
6.6% (W6) 
 
46.9% (W52) 
 
19.0% (W52) 
Etrolizumab 
44% (W10) 
0% (W10) 
 
 
 

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Table 3: Response rates (3A) and Remission rates (3B) in UC patients refractory to TNF treatment. 
(3A) Response rates 
TNF exposed 
Induction 
Response rate at/within W12 
Maintenance 
Response rate at/beyond W52 
Treatment 
Placebo 
Treatment 
Placebo 
Adalimumab 
ULTRA 2 
 
36.7% 
 
28.7% 
 
20.4% 
 
9.9% 
Vedolizumab 
GEMINI 1 
 
39.0% 
 
20.6% 
 
44.6% 
 
15.8% 
(3B) Remission rates 
TNF exposed 
Induction 
Remission rate at/within W12 
Maintenance 
Remission rate at/beyond W52 
Treatment 
Placebo 
Treatment 
Placebo 
Adalimumab 
ULTRA 2 
 
9.2% 
 
6.9% 
 
10.2% 
 
3% 
Vedolizumab 
GEMINI 1 
 
9.8% 
 
3.2% 
 
36.1% 
 
5.3% 
Etrolizumab 
5% 
0% 
 
 
 
T cell apoptosis is a critical mechanism aimed at preserving immune homeostasis by preventing 
uncontrolled lymphocyte proliferation. Activation-induced cell death (AICD) is a specialized 
form of T cell apoptosis which follows antigen-induced T cell stimulation, and is mediated by 

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Fas (CD95) on T cells, among other molecules. AICD machinery is particularly relevant in the 
context of chronic antigenic stimulation, such as that occurring in the intestinal track, where the 
mucosal immune system is constantly exposed to luminal antigens deriving from bacterial flora 
and diet. While normal intestinal T-lamina propria lymphocytes (T-LPL) undergo apoptosis 
when stimulated in vitro with the ligand for Fas molecule (Fas-L), intestinal T-LPL of IBD 
patients are shown to be resistant to Fas-mediated cell death[41], [42].  
Neihulizumab (AbGn-168H), the development candidate, is a humanized IgG4κ monoclonal 
antibody (mAb) directed against the surface adhesion molecule, P-selectin glycoprotein ligand-1 
(PSGL-1). Binding of PSGL-1 by cross-inked Neihulizumab preferentially induces apoptosis 
(programmed cell death) of late stage activated T cells while sparing resting T cells and other 
immune cells[43]. In fact, Neihulizumab delivers apoptosis signal to late stage activated T cells, 
similar to similar to Fas/Fas-L mediated AICD in late stage activated T cells. More importantly, 
our research data also demonstrated that Neihulizumab induced apoptosis in T cells isolated from 
lamina propria of the intestinal lesion sites in Pts with Crohn’s disease, one form of IBD closely 
related to UC (data not yet published). This data suggested that Neihulizumab can deliver 
apoptosis signal and restore immune homeostasis even in cells where Fas/Fas-L mediated AICD 
are impaired, suggesting a potential therapeutic effect in IBD. 
With this novel mechanism of action Neihulizumab is anticipated to be effective in treating T-
cell mediated autoimmune diseases such as psoriasis, psoriatic arthritis, inflammatory bowel 
diseases such as Crohn’s disease and ulcerative colitis, type-1 diabetes and GvHD. Indeed 
animal model studies have demonstrated the potential therapeutic effects of Neihulizumab in 
arthritis (data not yet published), diabetes and GvHD[44], among others. Other than providing a 
potential new therapeutic effect via a new MOA, Neihulizumab also provides two possible 
additional advantages over all currently available biologics: First, while all the current available 
biologics need to be continuously used, the elimination (apoptosis induction) of activated 
antigen-specific, pathogenic T cells is anticipated to create a long-term disease-free period 
(remission); Second, equally important, since AICD could be induced only after the completion 
of protective immunity, Neihulizumab administration should have reduced risk of opportunistic 
infection and cancer compared to currently available biologics which generate a general immune 
suppression to some degree. 
Two randomized, double blind, placebo-controlled Phase II studies (Study No. 2012.005.01 and 
Study No. 2014.002.01, IND No. 115535) have demonstrated clinical proof of principle and the 
safety profile of Neihulizumab in psoriasis patients[45], [46]. Clinical proof of principle was 
also clearly demonstrated in psoriatic arthritis via a phase II open-label, multiple center trial 
(Study 2014.009.01)[47]. Neihulizumab for steroid-refractory acute graft-versus-host disease 
(sr-aGvHD) in patients undergoing allogeneic hematopoietic cell transplantation was tested in 
Study BMT-285[48], and detailed in clinical studies. A new study design (Study 2017.002.01) 

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is being prepared to address PK, PD, safety and efficacy points of view of Neihulizumab in sr-
aGvHD.  
To establish the therapeutic effect of Neihulizumab in ulcerative colitis, a Phase II, open label, 
single arm, multiple dose proof of principle study is designed in patients with moderate to severe 
active ulcerative colitis and who has failed or are intolerant to anti-TNFα and/or anti-integrin 
therapy.  
 
1.2 
DRUG PROFILE 
Drug Substance and Drug Product 
Neihulizumab (AbGn-168H) is derived from AbGn-168, a humanized monoclonal antibody of 
the IgG4 subclasses which binds to human CD162 (PSGL-1). The AbGn-168H molecule is 
composed of two heterodimers. Each of the heterodimers is composed of a heavy and a light 
polypeptide chain. The four polypeptide chains of the antibody molecule are linked together by 
disulfide bonds. In order to reduce the in vivo occurrence of half molecules (also known as 
shuffling) of wild type IgG4 antibodies such as AbGn-168, a serine to proline (S228P) mutation 
was introduced in the hinge region of AbGn-168H heavy chain by PCR mutagenesis. This 
mutation was shown to stabilize the intermolecular disulfide bonds and eliminate IgG4 shuffling 
in vivo. The heavy chains are glycosylated and there are two binding sites for CD162 per 
antibody molecule. The antibody protein has a molecular mass of approximately 148 kDa.  
 
AbGn-168H is expressed in Chinese hamster ovary (CHO) cells. It is manufactured using 
standard mammalian cell culture techniques, followed by a series of protein purification steps 
including several chromatography steps, as well as steps for removal and inactivation of potential 
viruses.  
The current formulation of the AbGn-168H drug product is a solution for injection at a 
concentration of 40 mg/mL. 
Pharmacology and Safety Pharmacology 
AbGn-168H binds to PSGL-1 and preferentially induces apoptosis of activated T cells and spares 
primary peripheral T cells, the majority of which are resting T cells. The in vivo pharmacologic 
effects have been demonstrated in a murine model of DTH (trans-vivo Delayed-type 
Hypersensitivity) and a DTH model in cynomolgus monkey, the relevant animal species, 
indicating a pharmacologically relevant effect can be achieved in vivo.  
As an IgG4 antibody, AbGn-168H does not mediate ADCC (Antibody-dependent Cellular 
Cytotoxicity) or CDC (Complement-dependent Cytotoxicity). Additional studies done with 
AbGn-168, which support the safety assessment of AbGn-168H include the demonstration that 
no apoptosis induction occurs in other PSGL-1 expressing cells, including neutrophils, B cells 
and monocytes, after AbGn-168 treatment. In vitro binding by AbGn-168 does not interfere with 

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the interaction of P-selectin with PSGL-1, a key function associated with PSGL-1 and a 
requirement for efficient localization of activated T cells and neutrophils to target tissues. In 
addition, there is no in vitro cytokine release from purified CD4+ T cells or PBMC when treated 
with AbGn-168 or AbGn-168H (see also Toxicology). Furthermore, administration of AbGn-
168H surrogate antibody in mice (cTAB4) does not have significant impact on the disease 
progression of C. difficile infection. 
Toxicology 
AbGn-168H toxicity evaluations include studies supporting the use of the cynomolgus monkey 
as the toxicologically relevant species, a study investigating the potential for cytokine release in 
humans, and 4-week intravenous and subcutaneous repeat-dose toxicity studies in cynomolgus 
monkeys. Relevant studies with AbGn-168 which support the safety assessment of AbGn-168H 
include additional cytokine release studies, intravenous repeat-dose toxicity evaluations up to 13 
weeks with a 39-week recovery period, evaluation of effects on the hematopoietic system 
(including stem cells and platelet), and local tolerance assessment. 
AbGn-168H administered over 4 weeks by twice weekly intravenous infusion or subcutaneous 
administration to cynomolgus monkeys caused no adverse effects at dose levels up to 100 mg/kg, 
and administration of AbGn-168 twice weekly at dose levels up to 100 mg/kg for 4- or 13 weeks 
likewise caused no adverse effects in monkeys. The 13-week repeat-dose study in cynomolgus 
monkeys with AbGn-168 showed no effect on a T-cell dependent antibody response or on NK 
cell cytolytic activity. Therefore, the No Observable Adverse Effect Level (NOAEL) of 
AbGn-168H was greater than 100 mg/kg, twice per week. 
There was no evidence of any treatment-related effect in vivo on circulating cytokines in the 4-
week studies with AbGn-168H or AbGn-168, or in a separate DTH monkey study with AbGn-
168 that simulated the conditions of an activated immune system. In addition, there was no 
evidence for in vitro cytokine release in whole blood from healthy donors exposed to AbGn-
168H or AbGn-168, or in whole blood from psoriatic patients exposed to AbGn-168.  Taking the 
results from all of these studies together, the weight of evidence suggests that treatment with 
AbGn-168H in humans has a low risk of inducing cytokine release.  
Studies to test the potential effects of AbGn-168 on bone marrow demonstrated that AbGn-168 
binds to human and cynomolgus monkey CD34+ stem cells but does not appear to affect 
hematopoiesis. The effect of AbGn-168 on platelet function was evaluated and data showed that 
AbGn-168 did not bind platelets that were either untreated or thrombin activated.  
AbGn-168H was well tolerated locally in cynomolgus monkeys when administered by repeated 
intravenous or subcutaneous administration twice per week over 4 weeks. AbGn-168 formulation, 
very similar to that of AbGn-168H, was well tolerated locally in cynomolgus monkeys at 
concentrations of 10 and 40 mg/mL when administered by intravenous, intramuscular, and 
subcutaneous routes. AbGn-168 did not cause hemolysis of human whole blood in vitro and was 
compatible with human plasma. 

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AbGn-168H is immunogenic in cynomolgus monkeys. Repeat dose administration of AbGn-
168H to cynomolgus monkeys resulted in an immunogenic response. However, such 
immunogenicity does not appear to have been a seriously limiting factor for other humanized 
monoclonal antibodies taken into the clinic. 
No developmental or reproductive toxicology studies have been conducted to date. No treatment-
related effects on the reproductive tissues of male and female monkeys when administered 
AbGn-168H for up to 4 weeks or AbGn-168 for up to 13 weeks were observed, with the caveat 
that many of these animals were sexually immature. Based on the biophysical nature of 
monoclonal antibodies and the demonstrated mode of action for AbGn-168H, genetic toxicology 
studies are not warranted and have not been performed. Carcinogenicity studies have not been 
conducted to date. 
Non-clinical Pharmacokinetics 
The pharmacokinetics of AbGn-168H was studied in CD57BL/6 mice and cynomolgus monkeys 
and was compared with the pharmacokinetics of AbGn-168 in those species.  Exposures for 
AbGn-168H were quite similar to those for AbGn-168 in these studies.  Whereas AbGn-168 
undergoes IgG4 shuffling in cynomolgus monkeys, AbGn-168H exhibits little if any IgG4 
shuffling.  
In the 4- and 13-week studies with AbGn-168H and AbGn-168, the highest dose level tested of 
100 mg/kg was a NOAEL. At the NOAEL, AbGn-168H mean exposures on Day 25 in the 4-
week intravenous study were approximately 5,230,000 ng/mL (Cmax) and 308,500,000 ng∙hr/mL 
(AUC0-72hr) and mean exposures on Day 22 of the 4-week subcutaneous study were 
approximately 4,450,000 ng/mL (Cmax) and 353,000,000 ng·hr/mL (AUC0-96hr). Exposure levels 
of AbGn-168H in the 4-week study were comparable to levels of total AbGn-168 (intact + 
shuffled) in 4- and 13-week studies. The results of the 4-week studies in cynomolgus monkeys 
with AbGn-168H, including exposure levels, mirror those of 4- and 13-week repeat-dose toxicity 
studies with AbGn-168. 
Clinical Studies 
AbGn-168H was first tested in a single rising dose (SRD) trial (Study 1304.1)[49] in 36 healthy 
volunteers in doses up to 2000 µg/kg i.v. and 125 and 1000 µg/kg s.c.. AbGn-168H was well 
tolerated in the SRD trial. There was no evidence of cytokine release and no critical change in 
laboratory parameters.  
The PK analysis of trial 1304.1 demonstrated that no shuffling with AbGn-168H occurred. After 
i.v. dosing, AbGn-168H Cmax or AUC0-∞ exposure increased in a close to dose-proportional 
manner. The terminal half-life of the antibody increased somewhat with dose up to the 500 μg/kg 
dose and then remained relatively constant at higher doses (40-45 h), which is relatively short 
compared to published values of endogenous IgG4 half-life. This suggests that AbGn-168H may 
be cleared by target-mediated clearance. Following s.c. dosing, bioavailability for the 125 µg/kg 

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and 1000 µg/kg s.c. doses of AbGn-168H is 33% and 42%, respectively. These values may be 
relatively low because of the relatively rapid clearance of AbGn-168H. In trial 1304.1, Anti-
Drug Antibody (ADA) responses were only observed in 1 subject dosed at 125 µg/kg s.c. AbGn-
168H. 
Multiple doses of AbGn-168H were first tested in two randomized, double blind, placebo-
controlled Phase II studies in patients with moderate to severe chronic plaque psoriasis (Study 
No. 2012.005.01 and Study No. 2014.002.01)[45], [46]. In study 2012.005.01, six consecutive 
weekly doses of AbGn-168H at 0.5 mg/kg (19 patients) or 3 mg/kg (18 patients) were well 
tolerated. There was no evidence of cytokine release or any critical change in lab parameters, 
although a mild, clinically insignificant, transient, and reversible decreases in the mean and 
median total leukocyte counts were observed in the 3 mg/kg group. Signs of clinical efficacy 
(median PASI score over time, % of PASI50 responders, and improved TLPSS assessment) were 
observed at 3 mg/kg compared to Placebo group. Clinical proof of principle was considered 
demonstrated in psoriasis [45]. 
Analysis of the pharmacokinetic parameters for AbGn-168H revealed that increasing the 
concentration of AbGn-168H from 0.5 mg/kg to 3 mg/kg disproportionately increased both the 
plasma concentration (Cmax) and the exposure (AUC). Of the 19 patients in the AbGn-168H 0.5 
mg/kg group and the 18 patients in the AbGn-168H 3 mg/kg group, 3 (15.8%) patients in the 
AbGn-168H 0.5 mg/kg group and 7 (38.9%) patients in the AbGn-168H 3 mg/kg group were 
confirmed positive for ADA (titer ≤ 625) at one or more visits.  
In Study 2014.002.01, 4 doses of 6 mg/kg (17 patients) and 9 mg/kg (16 patients) given to 
patients with moderate to severe chronic plaque psoriasis on Day 1 (W0), Day 8 (W1), Day 29 (W4) 
and Day 36 (W5) was well tolerated. There was no evidence of cytokine release or any critical 
change in lab parameters, although a mild, clinically insignificant, transient and reversible 
decreases in the mean and median total leukocyte counts were observed in both the 6 mg/kg and 
9 mg/kg groups. Although results for the primary efficacy endpoint, the frequency of PASI75 at 
Week 10, were unremarkable, a consistently greater number of patients in the AbGn-168H 
groups achieved a PASI50 compared with the placebo group at every assessment time point 
except Week 1 (for the 9 mg/kg group compared with placebo) and Week 5 (for the 6 mg/kg 
group compared with placebo). Clinical proof of principle is considered proven once again for 
psoriasis [46]. 
Analysis of the pharmacokinetic parameters for AbGn-168H revealed that increasing the 
concentration of AbGn-168H from 6 mg/kg to 9 mg/kg increased both the plasma concentration 
and exposure (approximately 2.8 times). The steady-state T1/2 was also increased from 113.9 hr 
in the AbGn-168H 6 mg/kg group to 132.1 hr in the AbGn-168H 9 mg/kg group. Of the 17 
patients in the AbGn-168H 6 mg/kg group and the 16 patients in the AbGn-168H 9 mg/kg group, 
4 (23.5%) patients in the AbGn-168H 6 mg/kg group and 5 (31.2%) patients in the AbGn-168H 

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9 mg/kg group were confirmed ADA positive at some time during the study. The ADA titer was 
generally low (<3125) with the exception of 1 patient in the 9 mg/kg group who had an ADA 
titer of 15625 at Week 20. 
Study 2014.009.01 is a phase II open-label, multi-center, proof of principle trial for psoriatic 
arthritis in which Seven (7) doses of AbGn-168H at 9 mg/kg was administered in 20 patients 
with moderately to severely active psoriatic arthritis. AbGn-168H were well tolerated and no 
safety concerns for AbGn-168H administration at this dose. Forty percent (40%) of all patients 
treated with study agent in this open label study demonstrated meaningful responses by week 12, 
suggesting the clinical utility with AbGn-168H for the treatment of psoriatic arthritis. Clinical 
proof of principle is considered proven also for psoriatic arthritis [47]. There was only one 
positive ADA response (Ab titer is 125) detected at Week 12 from 1 patient who had received all 
7 doses of the study drug. 
Since AbGn-168H demonstrated proof of clinical principle in treating T-cell mediated diseases 
such as psoriasis and psoriatic arthritis, a dose escalation/de-escalation study using AbGn-168H 
to treat steroid-refractory acute graft-versus-host disease (sr-aGvHD) in patients undergoing 
allogeneic hematopoietic cell transplantation was initiated (Study BMT-285). Patients received 
up to 4 infusions of up to 9 mg/kg of AbGn-168H. Four (4) patients were enrolled and received 
at least one infusion of AbGn-168H.  
The AEs observed in this small group of patients were consistent with what would be expected in 
this patient population. The most frequently occurring AEs were diarrhea (n=3), elevated 
bilirubin levels (n=3), ileus (n=2), septic shock (n=2) and respiratory distress (n=2). There were 
no cytokine release reactions or infusion reactions observed with AbGn-168H and there was no 
apparent association between increasing dose of AbGn-168H and increasing incidence or 
severity of adverse events. No DLTs attributed to AbGn-168H were observed in this study. 
Three patients died during the study due to complications arising from disease progression of 
severe aGvHD.  
The mortality in this study triggered an accrual pause to conduct safety review by protocol, and 
was subsequently placed on Clinical Hold by the FDA on April 8, 2016, although the 
continuation of the study was concurred by the Institute DSMC. After a face-to-face discussion 
with FDA on Nov. 15, 2016, a newly designed study protocol (Study 2017.002.01) was 
resubmitted on May 1, 2017. May proceed letter was received on May 18, 2017 and the study is 
currently ongoing. 
This Study 2017.008.01 is a Phase II, open label, single arm, multiple dose proof of principle 
study to test the therapeutic effect of Neihulizumab in patients with moderate to severe ulcerative 
colitis and who has failed or are intolerant to anti-TNF and/or anti-integrin therapy. This study 
is to be conducted in compliance with Good Clinical Practice (GCP). For further details see 
“Investigator’s Brochure”[50]. 

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2. 
RATIONALE, OBJECTIVES, AND BENEFIT-RISK ASSESSMENT  
2.1 
RATIONALE FOR PERFORMING THE TRIAL 
Therapeutic rationale for AbGn-168H in anti-TNF and/or anti-integrin refractory ulcerative 
colitis 
As discussed previously, the pathological process that causes mucosa damage in ulcerative 
colitis is substantially involved with T cell accumulation and T cell mediated immune-
inflammatory response. The important role of T cells in the pathogenesis of ulcerative colitis has 
been suggested in the literature and therapies that target T cell mediated inflammatory response 
and T cell trafficking have demonstrated efficacy to treat UC[24]–[28]. However, with all the 
biologics available to date, more than 50% of UC patients failed to reach remission and hence a 
new therapeutic agent with a different mode of action is required for this unmet medical need. 
Anti-TNFα and/or anti-integrin agents are the major biologics available in UC treatments and 
therefore patients who are refractory to these two types of biologics are selected as the target 
population for this study. 
AbGn-168H is an agonistic mAb to PSGL-1 (CD162) which has been shown to induce apoptosis 
of late-stage activated T-cells in vitro but spare naïve T cells and other hematopoietic cells. This 
mode of action can be applied in UC to target this specific T-cell population which is driving 
pro-inflammatory reactions but spares those naive T cells which are for protective immunity, so 
without increasing the risk of infections. AbGn-168H showed in vivo efficacy in the trans-vivo 
DTH models which are models of T-cell dependent inflammatory disease. Clinical proof of 
principle is also obtained in T cell-mediated diseases such as psoriasis and psoriatic arthritis. All 
these results justify the adding on of AbGn-168H in the treatment of ulcerative colitis. 
Justification for doses  
The highest dose of AbGn-168H used in the 4-week intravenous and subcutaneous toxicity 
studies (100 mg/kg; twice weekly) was also the NOAEL. Table 4 depicts safety margins 
extrapolated from 4th doses of AbGn-168H in humans (Study 2012.005.01 and Study 
2014.002.01) versus the monkey NOAEL weekly dose and systemic exposure after 4-weeks of 
intravenous dosing. Although an adverse effect level was not reached with AbGn-168H in 
monkeys, it is clear that safety margins projected for the highest dose of 9 mg/kg based on body 
weight dose, Cmax, and AUC comparisons for patients in this Phase I trial should be 
considered adequate. Safety evaluation from Study 2014.009.01 which was only 1 dose less than 
dosing regimen proposed in study also substantiates the safety of the current 8 dose regimen. 

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Table 4  Safety Margins from 4-Week Monkey Study (IV) with AbGn-168H estimated based on 
trial 2014.002.01  
Species Route 
of Admin 
Maximum 
Dose 
Weekly 
Dose 
Dosing 
duration 
Cmax 
(ng/mL) 
AUC 
(ng·hr/mL) 
Safety Margins Vs 
Maximum Human Dose 
 
Weekly Dose Cmax AUC 
Monkey IV 
100 
mg/kg 
200 
mg/kg 
4 weeks 5,230,000 308,500,000  
 
 
Human 
Patients 
IV 
9 
mg/kg 
9 
mg/kg 
8 weeks 751,750* 151,862,500* 
>22X 
>6X >2X 
*extrapolated data from 4st doses in Phase II studies (Study 2014.002.01) in psoriatic patients at 9 mg/kg iv.  
 
2.2 
TRIAL OBJECTIVES 
The primary objective is to the evaluate efficacy of AbGn-168H administered intravenously in 
patients with moderate-to-severe active ulcerative colitis who are refractory or intolerant to anti-
TNF and/or anti-integrin treatments. 
The secondary objective of this study is to investigate safety, tolerability, and immunogenicity 
of intravenous AbGn-168H administration. 
 
2.3 
BENEFIT - RISK ASSESSMENT 
With this novel mechanism of action Neihulizumab is anticipated to be effective in treating T-
cell mediated autoimmune diseases. In both Studies 2012.005.01 and 2014.002.01, signs of 
efficacy were clearly observed for psoriasis. Study 2014.009.01 also demonstrated clinical 
efficacy for psoriatic arthritis (see Section clinical studies). Patients of UC might benefit from 
the trial because T cells play a pivotal role in the pathogenesis of UC, and based on 
Neihulizumab’s novel mechanism of action it is expected that patients with UC are going to 
benefit from the treatment of Neihulizumab. 
Risk of hematopoietic cell depletion 
In Study 1304.1, Study 2012.005.01, Study 2014.002.01 and Study 2014.009.1, Neihulizumab 
single or multiple doses were well tolerated. No cytokine release syndrome or hematopoietic cell 
depletion was observed in these four studies. A mild, clinically insignificant, transient, and 
reversible decrease in the mean and median total leukocyte counts was observed in the 3 mg/kg 
group in trial 2012.005.01 and in the 6 mg/kg and 9 mg/kg groups in trial 2014.002.01, and in 
study 2014.009.01 where 7 doses of Neihulizumab at 9 mg/kg were administered. Although the 
risk that Neihulizumab will affect stem cells is convincingly low, it is still critical that careful 
long-term monitoring of peripheral blood cells is carried out to rule out a clinically significant 
adverse effect of Neihulizumab on bone marrow stem cells in vivo. 

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Risk of impaired immune function 
Neihulizumab has been demonstrated to induce apoptosis selectively in late stage activated T-
cells. This selectivity suggests that naïve and resting memory T-cells would be spared from 
deletion by Neihulizumab, and therefore that Neihulizumab may be less immunosuppressive than 
pan-T-cell depleting mAbs or the systemic immunomodulating agent such as cyclosporine. 
However, it cannot be ruled out that depletion of activated T-cells by Neihulizumab may lead to 
a transiently increased risk of infection. This risk will be addressed by clinical monitoring for 
adverse events during the treatment and observation periods. 
Treatment of psoriasis and psoriatic arthritis with systemic immunomodulatory therapies such as 
TNFα antagonists has been associated with an increased risk of tuberculosis, and as a result, 
current guidelines recommend screening patients for latent tuberculosis infection prior to 
treatment with such agents. As it is not known if a similar risk would be posed by Neihulizumab 
administration, patients with tuberculosis, history of tuberculosis, or a positive Quantiferon test 
will be excluded (Exclusion Criterion 24).  
Risk of hypersensitivity reactions 
As with any systemically administered biologic agent, there is a risk of local or systemic 
hypersensitivity reactions. Local reactions to intravenously or subcutaneously administered 
biologic agents are uncommon, and are usually limited to redness, swelling or induration at the 
injection site. Manifestations of systemic hypersensitivity reactions include anaphylaxis, pruritus, 
hypotension, and respiratory distress, but these occur uncommonly. Both local and systemic 
hypersensitivity reactions are readily detectable, transient in nature, and manageable with 
standard medical treatment. No such events occurred in Neihulizumab related trials (trials 
1304.1, 2012.005.01, 2014.002.01, 2014.009.01 and trial BMT-285) up to date. 
Summary of benefit-risk assessment 
Patients might benefit from the trial, because it is expected that UC may improve. The risks of 
participation in the trial include the risks associated with the study procedures (e.g. blood 
drawing and i.v. infusion) which are similar to other trials of investigative agents. The specific 
risks that can be anticipated in patients receiving Neihulizumab are described above. The study 
has been designed and will be conducted in such a manner as to minimize these risks as much as 
possible. Therefore, the benefit-risk assessment is considered acceptable for the current multiple 
dose trial in human. 

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3. 
DESCRIPTION OF DESIGN AND TRIAL POPULATION 
3.1 
OVERALL TRIAL DESIGN AND PLAN 
This will be an open label, multiple dose, multi-centre study to be conducted in around 12-18 
centres in 30-40 patients with a diagnosis of moderate to severe active ulcerative colitis, 
refractory or intolerant to anti-TNFα and/or anti-integrin treatments.  
Dose of Neihulizumab will be 9 mg/kg iv. Patients will receive a total of 10 doses on Day 1 
(Week 0), Day 8 (Week 1), Day15 (Week 2), Day 22 (Week 3), Day 29 (Week 4), Day 36 (Week 
5), Day 43 (Week 6), Day 50 (Week 7), Day 64 (Week 9) and Day 78 (Week 11). Patients will 
be followed up on Day 84 (Week 12, End of Treatment, primary endpoint), Day 112 (Week 16), 
Day 140 (Week 20) and Day 182 (Week 26, End of Study) after the first dose of Neihulizumab. 
 
In some case, patient may be allowed to continue the treatment of study drug in the judgment of 
the investigator and sponsor medical monitor. 
 
Blood samples for PK determinations will be drawn approximately 15 minutes before dosing and 
2 hours post doing at Visits 2, 9 and 11, 15 minutes before doing at Visits 3, 4, 5, 6, 7, 8 and 10, 
and at Visits 12, 13 and 14. Anti-drug antibodies (ADA) will be determined in all patients before 
dosing at Visits 2, 6, 10 and at Visits 12-15. Efficacy will be assessed by Mayo Clinic Score 
(Complete and Partial), endoscopy, biopsy, Inflammatory Bowel Disease Questionnaire (IBDQ) 
and Biomarkers (faecal calprotectin and c-reactive protein). Safety will be assessed by adverse 
event (AE) monitoring, laboratory tests, vital signs, physical examinations, discontinuation of 
treatment due to AE and immunogenicity. 
 
3.2 
DISCUSSION OF TRIAL DESIGN 
The planned study design including endpoints and methodology is in compliance with regulatory 
recommendations and consistent with other recently completed phase II studies investigating the 
efficacy and safety of novel agents in the treatment of UC.  
 
3.3 
SELECTION OF TRIAL POPULATION 
It is planned that a minimum of 30 and a maximum of 40 patients with moderate to severe UC 
refractory to anti-TNF and/or anti-integrin treatments will be entered into this trial. A patient 
will be considered “enrolled” if they have signed consent and successfully passed the screening 
phase. Enrollment will be competitive. Approximately 12-18 US sites are planned for this trial.  

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A log of all patients included into the study (i.e. having given informed consent) will be 
maintained in the Investigator Site File (ISF) at the investigational site irrespective of whether 
they have been treated with investigational drug or not. 
3.3.1 
Main Diagnosis for Study Entry 
Moderate to severe active ulcerative colitis refractory or intolerant to anti-TNF and/or anti-
integrin treatments 
3.3.2 
Inclusion Criteria 
1. Patients must provide written informed consent; 
2. Aged 18-75 years; 
3. Diagnosis of UC ≥ 12 weeks prior to screening by full colonoscopy (i.e., ≥ 12 weeks after first 
diagnosis by a physician according to American College of Gastroenterology guidelines); 
4. Moderate-to-severe active UC, at time of screening, defined as: 
a)  Mayo Clinic Score (MCS) of 6 points or higher, AND 
b)  a centrally read MCS endoscopic subscore of grade 2 or higher, AND 
c)  MCS rectal bleeding subscore of 1 point or higher, AND 
d)  disease extending 15 cm or more from the anal verge; 
5. Stable doses of concomitant medications, including : 
a) Stable oral corticosteroids (i.e., ≤ 20 mg/day of prednisone, ≤ 9 mg/day of budesonide) ≥ 2 
weeks before D1 dosing. Taper of oral corticosteroids per Investigator’s discretion during 
the study is allowed; 
b) Stable oral 5-amyinosalicylic acid dose ≥ 2 weeks before D1 dosing; 
c) Stable immunosuppressant including azathioprine, mercaptopurine, or methotrexate ≥ 8 
weeks before D1 dosing. Patients taking methotrexate also are advised to take folic acid 1 
mg/day or equivalent if there is no contraindication; 
d) Stable doses of probiotics ≥ 2 weeks before D1 dosing;  
e) Stable anti-diarrheas ≥ 2 weeks before D1 dosing; 
6. Patients must have previously received anti-tumor necrosis factor alpha (anti-TNF and/or 
anti-integrin therapy for UC and demonstrated an inadequate response, loss of response, or 
intolerance, and must have discontinued therapy ≥ 8 weeks before D1 dosing; 
7. Patients previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥ 
4 weeks before D1 dosing;  
8. Topical corticosteroids and topical 5-amyinosalicylic acid preparations must have been 
withdrawn ≥ 2 weeks before D1 dosing; 
9. Nonsteroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥ 4 weeks 
before D1 dosing; 

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10. Tofacitinib or other Janus kinase (JAK) inhibitors must have been discontinued ≥ 2 weeks 
before D1 dosing; 
11. Patients previously treated with tube feeding, defined formula diets, or parenteral 
alimentation/nutrition must have discontinued treatment 3 weeks before D1 dosing; 
12. Females with reproductive potential must have a negative pregnancy test result before 
enrollment. Men and women with reproductive potential have to be willing to use a highly 
effective method of contraception from study start to ≥ 3 months after the final dose of the 
study drug. A highly effective method of birth control is defined as one which results in a 
low failure rate (less than 1% per year).  
3.3.3 
Exclusion Criteria 
GI related exclusion criteria: 
1. Indeterminate colitis (IBD-U) or suspected Crohn’s disease; 
2. Any history of colectomy; 
3. Presence of an ileostomy or colostomy; 
4. A history or evidence of colonic mucosal dysplasia; 
5. Short gut syndrome. 
General health related exclusion criteria: 
6. Pregnant or lactating; 
7. Inability to comply with study protocol in the opinion of the investigator; 
8. History of dysplasia or malignancy in recent 5 years, except completely excised basal cell 
carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; 
9. Cirrhosis or active alcohol abuse per the judgement of investigator; 
10. Poorly controlled diabetes (HbA1c > 8.0%); 
11. Significant screening ECG abnormalities, including evidence of acute myocardial 
infarction, complete left bundle branch block, second-degree heart block, or complete 
heart block; 
12. Impaired renal function (calculated creatinine clearance < 60 mL/min); 
13. Impaired hepatic function in the absence of diagnosis of primary sclerosing cholangitis 
serum transaminase > 2.5x ULN, alkaline phosphatase> 2.5x ULN, or increased total 
bilirubin judged by the investigator to be clinically significant, or a diagnosis of primary 

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sclerosing cholangitis, serum transaminases > 3x ULN, alkaline phosphatase > 3x ULN, 
or total bilirubin > 2.5x ULN judged by the investigator to be clinically significant; 
 
14. Moderate to severe anemia (Hb < 8g/dL); 
15. Thrombocytopenia (platelet count < 75,000/uL); 
16. Evidence of current or previous clinically significant disease, medical condition or 
finding in the medical examination that in the opinion of the investigator, would 
compromise the safety of the patient or quality of the data; 
17. Requiring parenteral corticosteroid treatment. 
18. Received any investigational product within 1 year 
19. History of drug abuse according to the Diagnostic and Statistical Manual of Mental 
Disorders, 5th edition (DSM-V) criteria within 12 months prior to screening or positive 
drug screening tests. 
 
Infection related exclusion criteria: 
20. Human immune deficiency virus (HIV) infection or known HIV-related malignancy; 
21. Acute or chronic hepatitis B or C, or carrier status. Patients with anti-HBc Ab but with 
undetectable anti-HBs Ab should also be excluded; 
22. Positive IgM antibody titers in the presence of negative IgG titers to Epstein-Barr virus; 
23. Positive stool test for ova or parasites, positive stool culture for pathogens, or positive 
stool toxin assay for Clostridium difficile at screening. Patients with the positive stool 
toxin assay for C. difficile at screening could be rescreened if they are being treated for C. 
difficile and a repeat stool toxin assay at least 4 weeks after the completion of treatment is 
negative with no evidence of recurrence; 
24. Intestinal mucosa biopsy positive for cytomegalovirus (CMV) at screening; 
25. Positive screening test for latent Mycobacterium tuberculosis (TB) infection. Patients 
with a history of latent TB infection who received an appropriate and documented course 
of therapy can be included if the screening examination and a chest x-ray performed ≤ 3 
months before screening revealed no evidence of current active infection. If a 
Quantiferon TB test is indeterminate, the test should be repeated, and if the result is again 
indeterminate, such patient should be excluded; 
26. History of any opportunistic infection ≤ 12 weeks before D1 dosing; 
27. Any current or recent (≤ 4 weeks before D1 dosing) symptoms/signs of infection; 

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28. Received oral antibiotics ≤ 4 weeks before D1 dosing or intravenous antibiotics ≤ 8 
weeks before D1 dosing; 
29. Received a live attenuated vaccine ≤ 4 weeks before D1 dosing; 
30. Neutropenia (absolute neutrophil count < 1,500/uL); 
31. Lymphocytopenia (absolute lymphocyte count < 500 /uL); 
3.3.4 
Patient Withdrawal and Trial Discontinuation 
3.3.4.1 Patients withdrawal from the treatment or trial 
Patients should make every attempt to complete the protocol as specified. Investigators should 
encourage compliance with the dosing schedule and completion of all study visits.  
It is the right and the duty of the investigator or sub-investigator to interrupt treatment of any 
patient if they feel that study discontinuation is necessary to protect the patient, or that there are 
unmanageable factors, that may interfere significantly with the study procedures and/or the 
interpretation of results. If a patient is withdrawn from study drug, he/she will be encouraged to 
continue the rest of the visits in Table 1, without receiving study drug. 
In accordance with the Declaration of Helsinki, patients have the right to withdraw their consent 
to participate in the trial at any time, for any reason. In addition, the investigator also has the 
right to withdraw patients from the study for any legitimate reason. 
The patient must be withdrawn from treatment with the study drug in the following cases: 
- 
The patient withdraws consent 
- 
The patient has a worsening in his/her ulcerative colitis (partial Mayo Clinic Score ≥ 2 
increase compared to baseline) 
- 
The patient is no longer able to participate in the trial for any reason (e.g. surgery, 
concomitant diseases, concomitant therapies required not allowed by trial or administrative 
reasons). The patient delays dosing for more than 10 days from the previous dose, or 
noncompliance while on study  
- 
Patient lost to follow-up 
- 
Investigator’s discretion. 
- 
Female participant becomes pregnant 
Should a patient decide to withdraw from the study, or should a patient have to be withdrawn 
from the study, the date (considered End of Study) and the reason for discontinuation shall be 
recorded on the eCRF, and observation / assessment shall be recorded as thoroughly as possible. 
All patients withdrawing prior to Day 182 (End of Study) will be asked to allow follow up for 

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AEs for a minimum of 28 days after the last dose. AEs must be followed until the event has been 
resolved or no further follow-up is required in the judgment of the investigator and sponsor 
medical monitor 
Patients withdrawn from the trial due to an adverse event must be followed until the event has 
been resolved or no further follow-up is required in the judgment of the investigator and the trial 
medical monitor. 
The investigator should inform the sponsor immediately when a patient needs to be withdrawn 
from the trial. 
3.3.4.2 Trial discontinuation by the sponsor  
AbGenomics reserves the right to discontinue the trial overall or at a particular trial site at any 
time for the following reasons as long as patients’ health/welfare is not compromised: 
1. Failure to meet expected enrolment goals overall or at a particular trial site, 
2. Emergence of any efficacy/safety information that could significantly affect continuation of 
the trial. 
3. Violation of GCP, Clinical Trial Protocol, or the contract by a trial site or investigator, 
disturbing the appropriate conduct of the trial. 

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4. 
TREATMENTS 
 
4.1 
TREATMENTS TO BE ADMINISTERED 
The study medication is produced by Boehringer Ingelheim Pharma GmbH & Co. KG. 
All doses will be calculated based on mg/kg body weight. 
 
4.1.1 
Identity of AbGenomics’ Investigational Product 
The characteristics of the study medication are listed below 
Substance:  
 
 
 
 
AbGn-168H monoclonal antibody (mAb) 
Pharmaceutical form:  
Infusion concentrate 
Chemical name: 
Anti-human CD162 (P-selectin glycoprotein ligand-1; PSGL-1) 
monoclonal antibody (mAb) 
Manufacturer:  
 
 
 
Boehringer Ingelheim Pharma GmbH & Co. KG 
Unit Strength: 
 Each 2 mL vial contains approximately 1 mL of 40 mg/mL solution 
Posology:  
 
 
 
 
Multiple doses 
Route of administration: i.v. (approximately 60 minutes) 
 
4.1.2 
Packaging, Labeling, and Re-supply 
Drug supplies will be provided by Sponsor’s designated CRO. The clinical trial supplies are 
packaged in a box containing 6 vials. The required information according to the United States 
Law as well as FDA and other applicable Guideline will be on the boxes and vials. 
Each box and vial is labeled with: 
 Study number 
 Name of product and strengths 
 Pharmaceutical dosage form, quantity of dosage units 
 Term "for clinical trial use only“  
 Sponsor name and address 
 Manufacture name and address 

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 Storage conditions 
 Batch number 
Label examples are given in the Investigator Site File (ISF). 
 
4.1.3 
Storage Conditions 
Drug supplies will be kept in their original packaging under the recommended storage 
conditions, i.e. in a refrigerator with limited access, between + 2°C and + 8°C. A temperature log 
must be maintained to make certain that the drug supplies are stored at the correct temperature. 
The study medication must be stored securely, e.g. at a secure pharmacy. It may only be 
dispensed to trial patients according to the protocol by authorized personnel as documented in 
the form “Investigator’s Trial Staff”. 
All unused medication must be returned to the sponsor/sponsor designated facility or destroyed 
on-site per site's standard operation procedure. Receipt, usage and return of study medication 
must be documented on the respective forms. Account must be given for any discrepancies. 
 
4.1.4 
Drug Accountability 
The investigator is fully responsible for the investigational products at the trial site. Dispensing 
of investigational products will be delegated to delegated site staff. The person responsible for 
dispensing the investigational products will be responsible for maintaining adequate control of 
the investigational products and for documenting all transaction with them. 
The investigator and/or pharmacist and/or study medication storage manager will receive the 
study medications delivered by the sponsor or sponsor assigned CRO when the following 
requirements are fulfilled: 
 approval of the study protocol by the IRB /ethics committee,  
 availability of a signed and dated clinical trial contract between the sponsor or the 
sponsor assigned CRO and the Trial Centre, 
 approval/notification of the regulatory authority, e.g. competent authority, 
 availability of the curriculum vitae and medical license of the principal investigator, 
 availability of a signed and dated clinical trial protocol or immediately imminent signing 
of the clinical trial protocol, <in exceptional cases, medication could already be sent to 
the site, before its activation > 

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 availability of the Form 1572 and financial disclosure. 
Investigational product will be accounted for by the field CRA with the help of delegated site 
staffs for dispensing the medication. Accountability will be documented by the use of drug 
accountability forms. The investigator and/or pharmacist and/or study medication storage 
manager must maintain records (drug accountability forms) of the product’s delivery to the trial 
site, the inventory at the site, the use by each patient, and the return to the sponsor or alternative 
disposition of unused product(s).  
These records will include dates, quantities, batch/serial numbers, expiry (‘use by’) or retest 
dates, and the unique code numbers assigned to the investigational product(s) and trial patients. 
The investigator/pharmacist/study medication storage manager will maintain records that 
document adequately that the patients were provided the doses specified by the clinical trial 
protocol and reconcile all investigational product(s) received from the sponsor or sponsor 
assigned CRO.  
An inventory must be available for inspection during monitoring visits and will be checked by 
the field CRA to ensure correct dispensing of the investigational product. 
At the time of return to sponsor/sponsor assigned CRO or destruction on-site, the 
investigator/pharmacist/study medication storage manager must verify that all unused or 
partially used drug supplies have been returned or destroyed and that no remaining supplies are 
in the investigator’s possession. 
 
4.2 
TREATMENTS SCHEME, DOSING DELAY AND DISCONTINUATION 
A total of 10 doses of Neihulizumab at 9 mg/kg will be administered to patients over 12 weeks 
on Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), Day 22 (Week 3), Day 29 (Week 4), Day 
36 (Week 5), Day43 (Week 6), Day 50 (Week 7), Day 64 (Week 9), and Day 78 (Week 11). 
Neihulizumab will be administered intravenously in a total volume of approximately 100 mL 
over about 1 hour (60 minutes) at a rate of approximately 1.6 to 1.7 mL/min. See Appendix 10.1 
for the detailed procedures for preparing Neihulizumab for intravenously administration. 
 
Dosing delay 
After the initial infusion, subsequent Neihulizumab infusions can be delayed up to 10 days 
period due to reversible medical conditions or adverse events or any other reason. If a grade 3 -5 
adverse event attributable to the study drug (probably, or definitely related) is observed, 
additional doses for that patient will be held until the adverse event has returned to baseline. 
After the adverse reaction is resolved or stabilized, dosing may be restarted if continued 

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treatment is determined appropriate by the investigator. (unless the adverse reaction is a grade 3 
to 5 cytokine release or hypersensitivity reaction, see Treatment discontinuation below). 
 
Treatment discontinuation (see also 4.3 Concomitant Therapy and Restrictions and 5.2.2.3 
Adverse event and serious adverse event monitoring and reporting) 
Any patient who experiences a grade 3 to 5 cytokine release or hypersensitivity reaction will be 
permanently discontinued from Neihulizumab, and withdrawn from the treatment portion of the 
study. Patients with unambiguous evidence of progression may discontinue Neihulizumab 
treatment and receive additional therapy per standard institutional guidelines.  
 
4.3 
CONCOMITANT THERAPY AND RESTRICTIONS 
4.3.1 Concomitant therapy 
Stable doses of concomitant medications is allowed, including: 
a) Stable oral corticosteroids (i.e., ≤ 20 mg/day of prednisone, ≤ 9 mg/day of budesonide) ≥ 2 
weeks before D1 dosing; Taper of oral corticosteroids per Investigator’s discretion during 
the study is allowed 
b) Stable oral 5-amyinosalicylic acid dose ≥ 2 weeks before D1 dosing; 
c) Stable immunosuppressant including azathioprine, mercaptopurine, or methotrexate ≥ 8 
weeks before D1 dosing. Patients taking methotrexate also are advised to take folic acid 1 
mg/day or equivalent if there is no contraindication; 
d) Stable doses of probiotics ≥ 2 weeks before D1 dosing;  
e) Stable anti-diarrheas ≥ 2 weeks before D1 dosing. 
 
Any additional concomitant medication and therapy considered necessary for the patient’s 
welfare may be given at the discretion of the investigator. Stable doses of concomitant therapies 
for chronic conditions, for which neither the condition nor the treatment are judged to exclude 
the patient from participation are permissible. In case of adverse events in need of treatment, 
appropriate therapy according to the judgment of the investigator will be permitted. However, all 
concomitant medications being taken by eligible patients must be carefully evaluated, and 
questions on the use of concomitant medications should be discussed with the trial medical 
monitor. All concomitant therapies will be recorded on the appropriate pages of the eCRFs. 
 
Prophylaxis for hypersensitivity reactions/cytokine release syndrome  
Patients who experience a grade 2 hypersensitivity reaction/cytokine release syndrome may 
continue treatment if the event is resolved, and they may receive prophylactic pre-medications 
prior to the next infusion. Any patient who experiences a grade 3 to 4 hypersensitivity 

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reaction/cytokine release syndrome will be permanently discontinued from Neihulizumab, and 
withdrawn from the treatment portion of the study. 
In addition, enrollment will be paused pending a protocol amendment if there are 2 grade 3-5 
infusion reactions/cytokine release syndrome in the patients. In order to re-start enrollment, the 
protocol will be amended with a premedication regimen that will be based in part on the 
observed symptoms of affected patients. Until the protocol amendment, presently enrolled 
patients will be informed, but permitted to re-consent and continue treatment with 
pre-medication at the investigator’s discretion. If there are 2 or more grade 3 to 5 infusion 
reactions/cytokine release syndrome despite the use of pre-medications, the accrual will be 
stopped.  Regardless of relationship, FDA will be informed via expedited reporting of a serious 
adverse event (“IND Safety Report per 21CFR§312.32) if 2 grade 3 to 5 cytokine release / 
infusion reactions occur (see Section 5.2.2.3 Adverse event and serious adverse event monitoring 
and reporting).  
 
4.3.2 Restricted Medications 
The medications (or classes of medication) listed in Table 4.3.2: 1 must not be taken for the 
specified times before treatment and for the whole duration of the study. If patients take 
restricted medications due to experiencing an intolerable increase of UC disease activity 
according to the investigator’s judgment, patients will have to be withdrawn from the trial after 
the use of these restricted medications. 
 
Patients taking the restricted medications of biologics, Cyclosporine/Tacrolimus or 
investigational products for medical reasons other than UC will also need to be withdrawn from 
the trial. 
 
Table 4.3.2:1 Restricted medications 
- 
Any biologics, including anti-TNFα, anti-
integrin and anti-IL23 antibodies 
8 weeks before D1 dosing and during the 
whole trial duration 
- 
Tofacitinib or other JAK inhibitors 
2 weeks before D1 dosing and during the 
whole trial duration 
- 
Cyclosporine, Tacrolimus 
4 weeks before D1 dosing and during the 
whole trial duration. 

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- 
Rectal corticosteroids or  rectal 5-
amyinosalicylic acid preparations  
2 weeks before D1 dosing and during the 
whole trial duration 
- 
Antibiotics 
Oral antibiotics: 4 weeks before D1 dosing; 
intravenous antibiotics: 8 weeks before D1 
dosing; all antibiotics during the whole trial 
duration 
- 
Investigational products 
1 year prior to and during the whole trial 
duration 
- 
Nonsteroidal anti-inflammatory drugs 
(NSAIDs) 
4 weeks before D1 dosing and during the 
whole trial duration 
- 
Opiates/Methadone 
During the whole trial duration 
 
4.4 
TREATMENT COMPLIANCE 
Patients who are non-compliant, e.g., they do not appear for treatment (temporary treatment 
interruption for more than 10 days from the previous dose), must be withdrawn from the trial and 
the eCRF will be completed accordingly. Compliance will be assured by administration of all 
study medication under supervision of the investigating physician or a designee.  

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5. 
VARIABLES AND THEIR ASSESSMENT 
The primary objective of the study is to evaluate efficacy of AbGn-168H administered 
intravenously in patients with moderate-to-severe active ulcerative colitis who are refractory or 
intolerant to anti-TNF and/or anti-integrin treatments. The secondary objective is to investigate 
safety, tolerability, and immunogenicity of intravenous AbGn-168H administration. 
 
5.1 
EFFICACY  
5.1.1 
Endpoint(s) of efficacy 
The primary efficacy endpoint is the proportion of patients with clinical response, defined as 
defined as a ≥ 3-point reduction in MCS, a 30% or greater decrease from the baseline score, and 
with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding 
score of 0 or 1 at Week 12.  
Secondary efficacy endpoints are: 
(1) The proportion of patients with clinical response at Weeks 6, 7, 9 and 11 defined as a ≥2-
point decrease in pMCS, and with a 1-point or greater decrease of the rectal bleeding 
subscale or an absolute rectal bleeding score of 0 or 1. 
 
(2) The proportion of patients with clinical remission, defined as MCS of 2 or lower (or pMCS of 
1 or lower) and no subscore higher than 1 at Weeks 6, 7, 9, 11 and 12.  
(3) The proportion of responders who remain in clinical response and remission at Weeks 16, 20, 
and 26. 
(4) Flexible sigmoidoscopy subscore changes from baseline at Weeks 12 and 26. 
(5) The proportion of patients with sigmoidoscopic improvement, defined as any decrease in 
MCS endoscopic subscore, at Weeks 12 and 26. 
(6) The proportion of patients with mucosa healing defined as an absolute subscore for 
endoscopy of 0 or 1 at Weeks 12 and 26. 
(7) Change of histological activity grade from baseline at Weeks 12 and 26 using the Geboes 
system. 
(8) The proportion of patients with histological healing defined as histological grade = 0 at 
Weeks 12 and 26. 
(9) Change of Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline at Weeks 12 
and 26. 

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(10)The proportion of patients with IBDQ response, defined as an increase from baseline of at 
least 16 points at Weeks 12 and 26. 
Exploratory efficacy endpoints are faecal calprotectin and c-reactive protein changes at Week 
4, 9, 12, 16, 20, and 26. 
5.1.2 
Mayo Diary Card 
During Screening Visit, subjects will be provided the Mayo diary card and an instruction to fill 
the card. In brief, patient should record in the Mayo diary card with information including the 
day(s) having a clear liquid diet, the total number of stool in 24 hours per day and the amount of 
blood having in the stools each day for 7 consecutive days prior to a visit with the exception of 
the preparation day of endoscopic examination. Study Coordinator will collect the Mayo diary 
card from subjects at each visit to calculate Mayo Clinic Score according to the subscores of 
stool frequency and rectal bleedings from the 3 consecutive days closest to the visiting day. 
5.1.3 
Reading of MCS Endoscopic Subscore/ Flexible Sigmoidoscopy  
MCS endoscopic subscore will be assessed by a central reader. At Screening Visit, if there is 
difference in confirmation of study inclusion criteria of MCS endoscopic subscore of grade 2 or 
higher, an adjudication review will be triggered. At Visit 10 (EOT, Week 12) and Visit 13 (EOS, 
Week 26), if there is a discrepancy of the change in overall MCS endoscopic subscore, an 
adjudication review will be triggered. The central adjudicating reviewer will be blinded to which 
overall Mayo endoscopy subscore was provided by the site gastroenterologist or by the central 
reviewer. The adjudication will be considered as final. If a full colonoscopy is deemed necessary 
at Screening Visit per investigator’s discretion, it is allowed, however, the endoscopic subscore 
will be determined by rectum, sigmoid and descending colon only. 
5.2 
SAFETY 
5.2.1  Safety Endpoints 
Safety assessments will consist of evaluating physical examination, vital signs, safety laboratory 
tests, adverse events, immunogenicity and tolerability. 
Safety endpoints include: 
- 
Adverse events (AEs) graded according to CTCAE v4.03. 
- 
Discontinuation of therapy due to AEs 
- 
Changes in safety laboratory analysis  
- 
Changes in vital signs and physical examination 
- 
Immunogenicity 
- 
Tolerability  

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5.2.2. 
Adverse Events 
5.2.2.1 Definitions of adverse events 
Adverse event 
Adverse event (AE) means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a drug, and does not imply any judgment about causality. An adverse event can arise with 
any use of the drug (e.g., off-label use, use in combination with another drug) and with any route 
of administration, formulation, or dose, including an overdose. 
 
Serious adverse event 
An AE is considered “serious” if, in the view of either the investigator or sponsor, it results in 
any of the following outcomes: Death, a life-threatening adverse event, inpatient hospitalization 
or prolongation of existing hospitalization, a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse 
Events reported by the patient or observed by the (sub) investigator and that fall into any of the 
above definitions must be recorded on the adverse event page of the eCRF and should be 
described in the following manner: 
 
Nature of adverse event 
The nature of the event will be described in precise English medical terminology (i.e. not 
necessarily the exact words used by the patients). Whenever possible, a specific diagnosis should 
be stated (e.g. allergic contact dermatitis). 
 
Intensity of adverse event 
The intensity of the AE should be judged based on the following: 

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Mild:  
 
 
Awareness of sign(s) or symptom(s) which is/are easily tolerated 
Moderate: 
Enough discomfort to cause interference with usual activity, and may warrant 
intervention. 
Severe:  
Incapacitating or causing inability to work or to perform usual activities, or 
significantly affects clinical status, and warrants intervention. 
 
Duration of adverse event 
The duration of the event will be reported as the start date and stop date of the event. 
 
Causal relationship of adverse event 
The relationship between an AE and the use of the investigational product will be determined by 
a medically qualified Investigator on the basis of his/her clinical judgment, considering all 
relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-
challenge, confounding factors such as concomitant medication, concomitant diseases and 
relevant history, with the following definitions and causality rating scale (1-3 related; 4-5 not 
related):  
1. Definitely Related: There is evidence of exposure to the test drug. The temporal sequence of 
the AE onset relative to administration of the test drug is reasonable. The AE is more likely 
explained by the test drug than by another cause. De-challenge is positive. Re-challenge (if 
feasible) is positive. The AE shows a pattern consistent with previous knowledge of the test 
drug or test drug class. 
2. Probably related: There is evidence of exposure to the test drug. The temporal sequence of the 
AE onset relative to administration of the test drug is reasonable. The AE is more likely 
explained by the test drug than by another cause. De-challenge (if performed) is positive. 
3. Possibly related: There is evidence of exposure to the test drug. The temporal sequence of the 
AE onset relative to administration of the test drug is reasonable. The AE could have been due 
to another equally likely cause. De-challenge (if performed) is positive. 
4. Probably not related: There is evidence of exposure to the test drug. There is another more 
likely cause of the AE. De-challenge (if performed) is negative or ambiguous. Re-challenge 
(if performed) is negative or ambiguous. 
5. Definitely not related: The patient did not receive the test drug, or temporal sequence of the 
AE onset relative to administration of the test drug is not reasonable, or there is another 
obvious cause of the AE. 

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Assessment of causal relationship should be recorded in the case report forms.  
 
Outcome of adverse event 
The outcome of the event will be classified and handled as follows: 
Recovered/resolved 
The event has stopped. The stop date of the event 
must be recorded. 
Recovering/resolving 
The patient is clearly recovering from an event. The 
event is, however, not yet completely resolved. 
Follow-up on the event is required until final 
outcome is established. 
Not recovered/not resolved 
Event is still ongoing.  
Follow-up on the event is required until final 
outcome is established. 
Recovered with sequelae 
The event has reached a state where no further 
changes are expected and the residual symptoms are 
assumed to persist. An example is hemiparesis after 
stroke. The stop date of the event must be recorded. 
Fatal 
The patient has died as a consequence of the event.  
Date of death is recorded as stop date for the 
adverse event. 
Unknown 
Unknown to investigator, e.g. patients lost to 
follow-up. 
 
5.2.2.1.1 Adverse Events of Special Interests 
Potential significant risks from infusion of Neihulizumab that are described in the informed 
consent:  
1) Infusional toxicities.  
2) Infection: Related to immunosuppression. 
 
5.2.2.2 Listed adverse events 
No AEs are classified as listed for Neihulizumab and the current study. 

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5.2.2.3 Adverse event and serious adverse event monitoring and reporting 
All adverse events occurring from the administration of study medication and all serious adverse 
events occurring during the course of the clinical trial from signing the informed consent 
onwards through Day 182 will be collected, documented and reported to the sponsor via the 
clinical trial CRO by the investigator on the appropriate CRF(s)/eCRFs/SAE reporting forms. 
Reporting will be done according to the specific definitions and instructions detailed in the 
‘Adverse Event Reporting’ section of the ISF.  
For each adverse event, the investigator will provide the onset date, end date, severity, treatment 
required, outcome, seriousness, and action taken with the study medication. The investigator will 
determine whether it is unexpected according to the Informed Consent, Protocol, or 
Investigator’s Brochure, the underlying disease and concomitant treatment and the relationship 
of the study medication to all AEs as defined in Section 5.2.2.1. 
 
Adverse event grading 
Adverse event will be graded according to CTCAE v4.03. 
 
Development of Infusion-Related Reactions 
The incidence of infusion-related reactions will be assessed as the combined incidence for acute 
cytokine release syndrome, infusion reactions, and hypersensitivity related to Neihulizumab. The 
following Stopping Rule will apply: enrolment will be paused pending a protocol amendment if 
there are 2 or more grade 3-5 infusion reactions/cytokine release syndrome observed during the 
study period. In order to re-start enrolment, the protocol will be amended with a premedication 
regimen that will be based in part on the observed symptoms of affected patients. If there are 2 or 
more grade 3 to 5 infusion reactions/cytokine release syndrome despite the use of pre-
medications, the accrual will be stopped.  
Observed cases of Grade 3 to 5 Infusion 
Reactions in Safety Analysis Cohort 
Action 
2 or more Grade 3-5 on an ongoing basis 
Pause accrual;  
Conduct Safety Review;  
Amend protocol to add premedication 
regimen  
2 or more events on an ongoing basis,  
despite the use of pre-medications 
Stop accrual 
 

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5.2.3 
Assessment of safety laboratory parameters 
The safety laboratory tests will be performed at the visits as indicated in the Table 1 and as listed 
in Tables 5.2.3: 1 and 5.2.3: 2.  

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Table 5.2.3: 1 
Routine laboratory tests 
Category 
Test name  
Haematology 
Haematocrit (Hct) 
Haemoglobin (Hb) 
Red Blood Cell / Erythrocytes Count 
White Blood Cells / Leucocytes Count 
Platelet / Thrombocytes  Count 
Diff Automatic 
Neutrophils (Relative and absolute Count) 
Eosinophils (Relative and absolute Count) 
Basophils (Relative and absolute Count) 
Monocytes (Relative and absolute Count) 
Lymphocytes (Relative and absolute Count) 
Diff Manual 
(if Diff Automatic is 
abnormal) 
Neutrophils, Bands (Stabs)  
Neutrophils, Polymorphonuclear (PMN) 
Eosinophils  
Basophils  
Monocytes  
Lymphocytes  
Enzymes 
AST/GOT, SGOT 
ALT/GPT, SGPT 
Alkaline Phosphatase (AP/ALP) 
Lactic Dehydrogenase (LDH) 
Hormones 
Serum ß-Human Chorionic Gonadotrophin (pregnancy 
test) (only female patients of childbearing potential, only 
as indicated in Table 1) 
Substrates 
Glucose  
Creatinine 
Blood urea nitrogen 
Bilirubin Total  
Bilirubin Direct 
Protein, Total 
Electrolytes 
Calcium 
Sodium 

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Potassium 
Urinalysis (Stix) 
Urine Nitrite 
Urine Protein 
Urine Glucose 
Urine Ketone 
Urobilinogen 
Urine Bilirubin 
Urine Hemoglobin (RBC) 
Urine Leukocyte Esterase (WBC) 
Urine pH 
Urin-Sediment 
(microscopic examination) 
(if urine analysis 
abnormal) 
 
Urine Sediment Bacteria  
Urine Cast (hyaline, WBC, RBC, waxy and granular) in 
Sediment  
Urine Squamous Epithelial Cells 
Urine Sediment Crystals (calcium oxalate, uric acid and 
triphosphate) 
Urine Sediment RBC/Erythrocytes   
Urine Sediment WBC/Leucocytes 
 
The tests shown in Tables 5.2.3: 1 and 5.2.3: 2 will be done at screening. The tests shown in 
Table 5.2.3: 1 will also be performed at the other visits as indicated in Table 1. The tests listed in 
Table 5.2.3: 2 constitute exclusionary laboratory tests that will be done only at screening. These 
tests may be repeated as required. The results will not be included into the CSR. 
Urine sediment will only be done if there is a positive finding on the urinalysis (stix).  

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Table 5.2.3: 2 Exclusionary testing 
 
 
5.2.4 
Electrocardiogram 
5.2.4.1  ECG (12-lead) 
12 lead resting ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be recorded using a standard 12 
lead ECG machine. 
Electrode placement will be performed according to the method of Wilson, Einthoven and 
Goldberg. 
The site personnel will be instructed to assure a relaxed and quiet environment and that all 
patients are at complete rest during the recordings. 
ECG recordings may be repeated for quality reasons like alternating current artifacts, muscle 
movements and electrode dislocation.  
Category 
Test name  
Drug Screening (Urine) 
 
Amphetamines  
Barbiturates  
Benzodiazepine 
Cannabis  
Cocaine  
Methadone  
Opiates  
Viral screening 
Hepatitis B HBc Antibody (qualitative) 
Hepatitis B HBs Antibody (qualitative) 
Hepatitis C Antibodies (qualitative) 
HIV-1 and HIV -2 Antibody (qualitative) 
Epstein-Barr virus IgM and IgG Antibody (qualitative) 
Cytomegalovirus (CMV) assessment of intestinal mucosa 
biopsy 
Stool screening 
Ova 
Parasite 
Pathogen (stool culture) 
Clostridium difficile toxin 
Diabetes screening  
HbA1c test 
Tuberculosis screening 
QuantiFERON® test for Mycobacterium tuberculosis 

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All locally printed ECGs will be evaluated by the site investigator or a designee. Additional 
(unscheduled) ECGs can be recorded for safety reasons at any time based on the judgment of the 
investigator.  
Clinically relevant abnormal findings will be reported as medical history if detected at visit 1.  
 
5.2.5 
AE and SAE reporting 
5.2.5.1 Reporting to AbGenomics  
The site PI is responsible for adhering to the timelines for reporting SAEs and clinical outcomes 
to the sponsor. Any AEs reported to the sponsor during this phase must be documented in the 
electrical database system. 
If not stipulated differently in the Investigator Site File (ISF), Pursuant to 21CFR§312.64, the 
investigator must report the following events using paper process SAE form via fax or email to 
sponsor appointed CRO immediately (within 24 hours or the next business day): SAE, grade 3-5 
cytokine release/infusion reactions, and AE of special interest (see 5.2.2.1.1). This immediate 
report is required irrespective of whether the investigational product has been administered or 
not and irrespective of causal relationship.  
With receipt of any further information to these events, a follow-up SAE report has to be 
provided. SAEs and non-serious AEs must include a causal relationship assessment made by the 
investigator. 
 
5.2.5.2 Reporting to FDA 
1. Events that are serious, related and unexpected as assessed by the site investigator should be 
reported to the sponsor appointed CRO and sponsor's medical monitor within 24 hours after 
the site investigator has become aware of the event.  The sponsor's medical monitor will 
review these events to determine whether expedited reporting to all sites and the FDA is 
required. Sponsor appointed regulatory CRO will submit each SAEs to FDA pursuant to IND 
Safety Report per 21CFR§312.32.  
2. FDA will be informed via expedited reporting (IND Safety Report per 21CFR§312.32) if, 
regardless of relationship, two grade 3 to 5 cytokine release / infusion reactions occur, and 
for each additional such reaction, if any.  
3. In the event the “Grade 3 to 5 Infusion Reaction stopping rule” is invoked or if 2 grade 3-5 
grade 3 to 5 cytokine release / infusion reactions occur despite the use of pre-medication , 
FDA will be informed via an expedited safety report (IND Safety Report per 21CFR§312.32).   
 

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5.2.5.2.1  MedWatch 3500A Reporting Guidelines 
In addition to completing appropriate patient demographic and suspect medication information, 
the MedWatch 3500A report will include the following information. 
 Protocol number 
 Description of event, severity, treatment, and outcome, if known 
 Supportive laboratory results and diagnostics, if known 
 Investigator’s assessment of the relationship of the adverse event to each investigational 
product and suspect medication 
Additional information may be added to a previously submitted report by any of the following 
methods: 
 Adding to the original MedWatch 3500A report and submitting it as follow-up 
 Adding supplemental summary information and submitting it as follow-up with the 
original MedWatch 3500A form  
 
MedWatch 3500A (Mandatory Reporting) form is available at: 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM048334.pdf.   
 
5.2.5.3 Expedited reporting to health authorities and IECs/IRBs 
Expedited reporting of serious adverse events, e.g. suspected unexpected serious adverse 
reactions (SUSARs) to health authorities and IECs/IRBs, will be done according to local 
regulatory requirements. Further details regarding this reporting procedure are provided in the 
ISF. 
 
5.2.5.4 Other events to be reported 
Changes in vital signs, physical examination, and laboratory test results 
Changes in vital signs, physical examination and laboratory test results will be recorded as an AE 
or SAE in the (e)CRF , if they are judged clinically relevant by the investigator. 
 
Worsening of the underlying disease or other pre-existing conditions 
Worsening of the underlying disease or of other pre-existing conditions will be recorded as an 
AE or SAE in the (e)CRF through the Follow-Up period. 
 

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Overdose 
Any overdose defined as any higher dose than prescribed for the individual patient must be 
reported on the adverse event form of the eCRF book. AEs originating in the overdose must be 
documented on a separate line. 
 
Pregnancy 
Pregnancy Test or Confirmation of Birth Control: Performed at indicated study visits (Table 1). 
Record of a pregnancy test or confirmation of birth control will be recorded as available at each 
study visit. This information will be kept in the source documents and not recorded in the eCRF. 
Once a female patient has been enrolled into the clinical trial and has received study medication, 
the investigator must report immediately any drug exposure during pregnancy to the sponsor 
appointed CRO. Drug exposure during pregnancy has to be reported immediately (within 24 
hours or next business day whichever is shorter) by the treating physician or designee to the 
sponsor appointed CRO when the treating physician or designee first becoming aware of the 
occurrence. The outcome of the pregnancy associated with the drug exposure during pregnancy 
must be followed up through to resolution. In the absence of an AE or SAE, only the Pregnancy 
Monitoring Form for Clinical Trials must be completed.  
If an SAE occurs in conjunction with the pregnancy, then the reporting time frame for an SAE 
(within 24 hours or next business day whichever is shorter) must be met. The SAE form is to be 
completed. The sponsor or designee will provide instructions on how to collect pregnancy 
information. Follow-up, information on the outcome of the pregnancy is also required be 
forwarded to the sponsor’s designee. The ISF will contain the Pregnancy Monitoring Form for 
Clinical Trials. 
 
5.3 
IMMUNOGENICITY (ANTI-DRUG ANTIBODY) 
ADA samples will be collected at approximately 15 min. before Neihulizumab administration on 
Day 1, Day 29, Day 57 and also at EOT (Day 84), 28, 56 and 98 days after EOT (Days 112, 140 
and 182) for each patient in a non-anticoagulant serum drawing tube to produce about 1.0 mL of 
serum. Instructions for handling and shipping specimens will be provided in detail in the 
Laboratory Manual.  
 
5.4 
PHARMACOKINETICS END POINTS 
If feasible, the following PK parameters will be calculated:  

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Day 1, Day 50 and Day 78: Cmax and associated parameters 
For quantification of analyte plasma concentrations, PK blood samples will be taken from a 
forearm vein in an EDTA (ethylendiaminetetraacetic acid)-anticoagulant blood drawing tube at 
the time points specified in Table 1. 
Instructions for handling and shipping specimens will be provided in detail in the Laboratory 
Manual. 
5.5 
OTHER ASSESSMENT (S) 
A medical examination will be carried out within 28 days before visit 2 (i.e., during the 
screening period before the infusion of Neihulizumab). Screening activities will include 
documentation of information provided to patients, informed consent, review of demographics 
including weight, relevant medical history, ulcerative colitis history, concomitant medication, 
inclusion/exclusion criteria, vital signs (BT, BP, PR, RR, and oxygen saturation), 12-lead ECG 
and laboratory (including safety, drug and viral screening, stool screening, QuantiFERON® test 
and pregnancy), physical examination, flexible sigmoidoscopy, complete Mayo Clinical Score, 
IBDQ, biomarkers (fecal calprotectin and CRP), and histopathological analysis. The weight will 
be reassessed before administration of Neihulizumab in order to confirm the dosage. The EOS 
examination will include physical examination, vital signs, flexible sigmoidoscopy, complete 
Mayo Clinic Score, IBDQ, biomarkers (fecal calprotectin and CRP), histopathological analysis, 
safety lab, ADA test and pregnancy.  
 
5.6 
APPROPRIATENESS OF ASSESSMENTS 
All assessments performed during this trial are standard and will be performed in order to 
monitor efficacy and safety aspects relevant to Neihulizumab administration in an appropriate 
way. The scheduled assessments are appropriate to observe drug related changes over time. 
Therefore, all assessments taken in this trial are appropriate. 
 
5.7 
BIOMARKERS  
Biomarker studies for faecal calprotectin and c-reactive protein (CRP) will be performed to 
monitor ulcerative colitis activities. 
 
5.8 
PHARMACODYNAMICS 
5.8.1  
Pharmacodynamic endpoints 
None. 

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5.9 
PHARMACOKINETIC - PHARMACODYNAMIC RELATIONSHIP 
Not applicable. 

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6. 
INVESTIGATIONAL PLAN 
All patients must provide written informed consent before any study-specific procedures or 
assessments are performed. Day 1 (Visit 2) will occur as soon as possible and within 28 days 
after the initial screening visit (Visit 1) has verified eligibility and documented informed consent.  
 
6.1 
VISIT SCHEDULE 
6.1.1 
Screening period 
After the patients have been informed about the trial, all patients will have given their written 
informed consent in accordance with GCP and the local legislation prior to enrolment to the 
study. The following Screening laboratory tests/evaluations will be performed within 4 weeks 
(28 days) prior to the infusion of Neihulizumab (Week 0). A single retest for screening 
laboratory retest is allowed per investigator’s discretion. 
 Assignment of patients number 
 Review of inclusion and exclusion criteria 
 Demographic data (e.g., sex, age, race/ethnicity) 
 Complete medical history  
 Patient ulcerative colitis history 
 Concomitant medications  
 Complete physical examination-including weight and vital signs. 
 12-lead ECG 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 Drug and viral screening 
 Serum pregnancy test, if applicable 
 Provide and review the diary instruction and diary sheet to patients 
 Flexible sigmoidoscopy 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Complete Mayo Clinic Score assessment 
 Histopathological analysis 
 IBDQ assessment 
 Stool screening 
 Fecal calprotectin and CRP tests 

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 HbA1c test 
 QuantiFERON® test for Tuberculosis 
 
6.1.2 
Study period 
Patients who meet the inclusion/exclusion criteria will receive one dose of Neihulizumab 
intravenously starting from Day 1 (Week 0). It is preferred but not required that the drug 
administration should occur at the similar time of each visit day. See Appendix 10.1 for the 
detailed procedures for preparing Neihulizumab for intravenously administration. Administration 
of the study drug will be repeated on Day 8 (Week1), Day 15 (Week 2), Day 22 (Week 3), Day 
29 (Week 4), Day 36 (Week 5), Day 43 (Week 6), Day 50 (Week 7), Day 64 (Week 9), and Day 
78 (Week 11). 
The measurements performed during the study period are specified in Section 5 of this protocol 
and Table 1. 
All assessments should be performed prior to drug administration unless it is specified. 
 
Visit 2/Day 1 
Procedures at Visit 2/Day 1 should preferably be done in the sequence specified. Drug 
administration and blood sampling should adhere as closely as possible to the time schedule 
given in Table 1 
 Urine pregnancy test, if applicable 
 Review of inclusion and exclusion criteria 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Partial Mayo Clinic Score assessment 
 Concomitant medications 
 Adverse events 
 Full physical examination including weight and vitals 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 Blood sampling for anti-drug antibody (ADA) test at -15 min (prior to Neihulizumab 
infusion) 
 PK sampling: -15min (prior to Neihulizumab infusion), and 2 hrs after the end of 
Neihulizumab infusion 

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 Administration of Neihulizumab: Study drug will be administered by approximately 1hr 
(60-minute) i.v. infusion. Patients should remain at the clinical site for at least 1 hour 
after the infusion for observation. 
 
Visit 3/Day 8, Visit 4/Day 15, Visit 5/Day 22, Visit 7/Day 36, Visit 8/Day 43,  Visit 9/Day 50, 
and Visit 11/Day 78 
 Urine pregnancy test, if applicable 
 Concomitant medications 
 Adverse events 
 Partial physical examination including, weight and vitals 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Partial Mayo Clinic Score assessment 
 Safety lab tests (Hematology and Chemistry)  
 PK sampling: -15min (prior to Neihulizumab infusion) and 2 hrs after the end of 
Neihulizumab infusion for Visit 9 and 11. Fifteen (15) minutes prior to Neihulizumab 
infusion for Visits 3, 4, 5, 7 and 8 
 Administration of Neihulizumab: Study drug will be administered by approximately 1hr 
(60-minute) i.v. infusion. Patients should remain at the clinical site for at least 1 hour 
after the infusion for observation. 
 
Visit 6/Day 29 and Visit 10/Day 64  
 Urine pregnancy test, if applicable 
 Concomitant medications 
 Adverse events 
 Partial physical examination including weight and vitals 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Partial Mayo Clinic Score assessment 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 Fecal calprotectin and CRP tests 
 Blood sampling for anti-drug antibody (ADA) test at -15min (prior to Neihulizumab 
infusion) 

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 PK sampling: Fifteen minutes prior to Neihulizumab infusion (-15 min). 
 Administration of Neihulizumab: Study drug will be administered by approximately 1hr 
(60-minute) i.v. infusion. Patients should remain at the clinical site for at least 1 hour 
after the infusion for observation. 
 
Visit 12/Day 84 (End of Treatment) 
 Urine pregnancy test, if applicable 
 Concomitant medications 
 Adverse events 
 Full physical examination including weight and vitals 
 Flexible sigmoidoscopy 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Complete Mayo Clinic Score assessment 
 Histopathological analysis 
 IBDQ assessment 
 Fecal calprotectin and CRP assessments 
 PK sampling 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 Blood sampling for anti-drug antibody (ADA) test 
 
Visit 13/ Day 112 and Visit 14/Day 140 
 Concomitant medications 
 Adverse events 
 Partial physical examination including vitals  
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Partial Mayo Clinic Score assessment 
 Fecal calprotectin and CRP tests 
 Blood sampling for anti-drug antibody (ADA) test. 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 PK sampling 

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Visit 15/Day 182 (End of Study) 
 Urine pregnancy test, if applicable 
 Concomitant medications 
 Adverse events 
 Full physical examination including vitals 
 Flexible sigmoidoscopy 
 Collect the filled diary card from patient 
 Physician Global Assessment 
 Complete Mayo Clinic Score assessment 
 Histopathological analysis 
 IBDQ assessment 
 Fecal calprotectin and CRP tests 
 Safety lab tests (Hematology and Chemistry) 
 Urinalysis 
 Blood sampling for anti-drug antibody (ADA) test 
 

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7. 
STATISTICAL CONSIDERATIONS 
This is a phase II, open labelled, multiple dose study to be held at multiple study centers. The 
trial was designed to assess the efficacy and safety of Neihulizumab treatment in moderate-
severe ulcerative colitis patients. Due to the small number of patients expected to be enrolled at 
each center, all summaries and analyses will be performed using data pooled across centers.  
Unless otherwise specified, continuous variables will be summarized with the number of non-
missing observations, mean, standard deviation, median, maximum and minimum displayed.  
Categorical data will be summarized as counts and percentages. Missing data will not be 
estimated or carried forward in any of the analyses. 
Patient data will be listed, sorted by investigative center and patient number. Deviations from the 
statistical analysis plan will be documented in the clinical trial report. 
Except where other software may be deemed more appropriate (e.g., S-Plus or R), all analyses 
will be performed using SAS Version 9.2 statistical software (SAS Institute, Cary, NC). Details 
of the statistical analysis (beyond those specified below) will be defined in the TSAP. 
 
7.1 
PLANNED ANALYSES 
Intent to Treated Set 
The ITT set is defined as all patients who are enrolled irrespective of treatment received or not.  
 
Modified ITT (or Analyzable Set) 
The mITT set is defined as all patients who are enrolled and have received at least one dose of 
Neihulizumab treatment.  
The statistical analysis will be based on the modified ITT set. Summaries of patient disposition, 
demographics, disease characteristics, assessments of physical condition and functionality, and 
dosing of study drug will be provided.  
 
7.1.1 
Pharmacokinetic analyses 
The following PK parameters will be assessed:  
1. Cmax,  
2. Any additional parameters as relevant 
The PK profile will be monitored as specified in Table 1 till Day 140 so that the profile of Cmax 
and associated parameters can be determined. 

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All evaluable patients who received Neihulizumab will be included in the pharmacokinetic 
analysis. Patients who are considered as not evaluable will be listed with their individual plasma 
concentrations and individual pharmacokinetic parameters, however, will not be included in 
descriptive statistics for plasma concentrations, pharmacokinetic parameters or other statistical 
assessment. 
A patient is considered to be not evaluable if the patient has a protocol violation relevant to the 
evaluation of pharmacokinetics. 
 
Drug plasma concentrations 
Concentrations will be used for graphs and calculations in the format that is reported in the 
bioanalytical report. Only concentrations within the validated concentration range will be used 
for the calculation of pharmacokinetic parameters. 
Plasma concentrations will be plotted graphically versus time for all patients as listed in the drug 
plasma concentration-time tables. For the presentation of the mean profiles, the arithmetic mean, 
geometric mean and the planned blood sampling times will be used. 
 
Drug plasma concentrations and pharmacokinetic parameters 
The following descriptive statistics will be calculated for analyte concentrations as well as for all 
pharmacokinetic parameters: N, arithmetic mean, standard deviation, minimum, median, 
maximum, arithmetic coefficient of variation, geometric mean, geometric coefficient of 
variation.  
The data format for descriptive statistics of concentrations will be identical with the data format 
of the respective concentrations. The descriptive statistics of pharmacokinetic parameters will be 
calculated using the individual values with the number of decimal places as provided by the 
evaluation program. Then the individual values as well as the descriptive statistics will be 
reported with three significant digits in the clinical trial report. 
 
7.1.2 
Safety analyses 
Safety analyses will be performed based on the mITT set. No hypothesis testing is planned 
prospectively. 
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Affairs 
(MedDRA). Adverse events occurring prior to drug administration will be assigned to the 
screening period. All other adverse events will be assigned to the treatment periods for 
evaluation. 

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Independent of this rule, the relationship of an adverse event to the study drug treatment will be 
assessed by the investigator. The evaluation of adverse events will comprise various frequency 
tabulations. 
Descriptive statistics of demographic data, of time-courses and of changes from baseline of vital 
signs and physical examination will be provided. 
Descriptive statistics of laboratory values over time and for the difference from baseline will be 
provided. Frequency tables of changes with respect to the reference range between baseline and 
last value on treatment will also be presented. 
Relevant findings in ECG measurements will be reported under “Relevant Medical History 
/Baseline Conditions” (at screening). 
 
7.1.3 
Efficacy analyses 
Efficacy analyses will be performed based on the mITT set. 
Summary statistics for efficacy endpoints will be provided. 
 
7.1.4 
Anti-drug Antibody 
Human ADA concentrations will be determined by an ADA ELISA. The plate-specific, 
screening assay cut point will be set by a statistician to achieve a 5% false positive rate and was 
derived from assays using samples from naïve human donors. Study samples screened with 
signals below the cut point will be deemed negative for the presence of ADA, while samples at 
or above the cut point will be deemed putative positive for the presence of ADA.  
All putative positive samples will be analyzed in a confirmation assay which is designed to test 
whether an excess of Neihulizumab added to the putative positive sample can inhibit the 
Neihulizumab response by a percentage greater than or equal to the confirmation cut point, thus 
confirming the presence of specific Neihulizumab antibodies. In addition, a titer, defined as the 
reciprocal of the lowest dilution of the sample whose signal fell below the cut point, will be 
determined for those samples that were confirmed to be positive for ADA.  
A listing will be made of all patients with ADA values above the established cutoff level, along 
with their titers. 
 
7.2 
PATIENT REPLACEMENT 
Patients receiving less than 6 doses (60% planned dosing) will be replaced.  

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7.3 
DETERMINATION OF SAMPLE SIZE 
The primary endpoint is overall responsive rate at Day 84. Assuming Neihulizumab has a 
responsive rate of 44.6% (6.8 % higher than conventional treatment and 20% higher than control 
rate), 40 patients in Neihulizumab treatment is estimated to have > 80% power to detect the 
difference with a 1 sided significance level of  = 0.1 

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8. 
REGULATORY CONSIDERATIONS 
The trial will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, in accordance with the ICH Harmonized Tripartite Guideline for Good 
Clinical Practice (GCP). Standard medical care (prophylactic, diagnostic and therapeutic 
procedures) remains in the responsibility of the treating physician of the patient. 
The investigator should inform the sponsor immediately of any urgent safety measures taken to 
protect the study patients against any immediate hazard, and also of any serious breaches of the 
protocol/ICH GCP. 
The rights of the investigator and of the sponsor with regard to publication of the results of this 
trial are described in the clinical trial contract with the trial institute and/or investigator. As a 
general rule, no trial results should be published prior to finalization of the Clinical Trial Report. 
Insurance Cover: The terms and conditions of the insurance cover are made available to the 
investigator and the patients via documentation in the ISF or upon request. 
 
8.1 
INSTITUTIONAL REVIEW 
The protocol, the proposed informed consent and all forms of participant information related to 
the study (e.g., advertisements used to recruit participants) will be reviewed and approved by the 
IRB.  Any changes made to the protocol will be submitted as a modification and will be 
approved by the IRB prior to implementation. The site PI will disseminate the protocol 
amendment information to all participating investigators. 
 
8.2 
INFORMED CONSENT 
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments. 
Prior to patient participation in the trial, written informed consent must be obtained from each 
patient (or the patient’s legally accepted representative) according to ICH GCP and to the 
regulatory and legal requirements of the participating country.  
Informed consent will be obtained from the HCT patient patients by the investigator or his 
representative.  The rationale, risks and benefits, and study procedures will be reviewed with the 
patient. Alternative therapies will be discussed. Patients will be given ample time to ask 
questions and do not need to sign the consent form until they are ready to proceed. Patients will 
be notified that they may withdraw their consent any time during the study. 

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The patient must be informed that his/her personal trial-related data will be used by AbGenomics 
in accordance with the local data protection law. The level of disclosure must also be explained 
to the patient. 
The patient must be informed that his/her medical records may be examined by authorized 
monitors (CRA) or Clinical Quality Assurance auditors appointed by AbGenomics, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
During the consent process, the investigator or his representative will ask the patient questions to 
assess their understanding of the study and consent.  Each signature must be personally dated by 
each signatory and the informed consent and any additional patient-information form retained by 
the investigator as part of the trial records. The investigator will store the original, signed 
informed consent form and any additional patient-information form per institutional policy. A 
signed copy of the informed consent and any additional patient information must be given to 
each patient or the patient’s legally accepted representative.  This process will be documented in 
the patient’s record. 
For patients who are not fluent in English, the consent procedure will be performed with an 
interpreter present (or via telephone), or a sign language-capable interpreter for those that are 
hearing-impaired.   
 
8.3 
DATA MONITORING PLAN 
Primary internal data monitoring will be performed continuously over the accrual and follow-up 
periods by the site PI and the Study Coordinator. The site PI will review data to assure the 
validity of data, as well as the safety of the patients. The site PI will also monitor the progress of 
the trial. The site PI will be responsible for maintaining the clinical protocol, reporting adverse 
event, assuring the consent is obtained and documented, reporting of unexpected outcomes and 
reporting the status of the trial in the continuing renewal report submitted annually to the IRB 
and SRC if applicable. 
 
8.4 
DATA MANAGEMENT PLAN 
This study will use Case Report Forms (CRFs) to record all protocol-related and study specific 
information on each trial participant, for data analysis.   
 
8.5 
DATA QUALITY ASSURANCE 
A quality assurance audit/inspection of this trial may be conducted by the sponsor or sponsor’s 
designees or by IRBs/IECs or by regulatory authorities. The quality assurance auditor will have 

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access to all medical records, the investigator’s trial-related files and correspondence, and the 
informed consent documentation of this clinical trial. 
 
8.6 
REPORTING MECHANISM 
The site PI (or designee) will be responsible for the coordination of all protocol amendments.  
Any changes to the protocol or consent will be approved by IRB prior to implementation.  This 
process will be included in the monitoring plan. Changes or amendments to the protocol or 
consent will be reported to the IRB and FDA. All IRB actions will be reported to FDA. 
 
8.7 
TRIAL RECORDS 
Case Report Forms (CRFs) for individual patients will be provided by the sponsor, either on 
paper or via remote data capture. For drug accountability, refer to Section 4.1.4. Research 
records will be maintained in a secure office, and electronic data will be maintained in a 
study-specific, secure database.  
 
8.7.1 
Source documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. Source documents are filed at the investigator’s site. 
For eCRFs, all data must be derived from source documents. Data entered in the eCRFs must be 
consistent with the source documents or the discrepancies must be explained. The investigator 
needs to request previous medical records or transfer records, depending on the trial; also current 
medical records must be available. 
8.7.2 
Direct access to source data and documents 
The investigator/institution will permit trial-related monitoring, audits, IRB/IEC review and 
regulatory inspection, providing direct access to all related source data/documents. CRFs/eCRFs 
and all source documents, including related medical records, progress notes and copies of 
laboratory and medical test results must be available at all times for review by the sponsor’s 
clinical trial monitor, auditor and inspection by health authorities (e.g. FDA). The Clinical 
Research Associate (CRA)/on site monitor and auditor may review all CRFs/eCRFs, and written 
informed consents. The accuracy of the data will be verified by reviewing the documents 
described in Section 8.7.1. 

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8.8 
STATEMENT OF CONFIDENTIALITY 
Individual patient medical information obtained as a result of this trial is considered confidential 
and disclosure to third parties is prohibited with the exceptions noted below. Patient 
confidentiality will be ensured by using patient identification code numbers. 
Treatment data may be given to the patient’s personal physician or to other appropriate medical 
personnel responsible for the patient’s welfare. Data generated as a result of the trial must be 
available for inspection on request by the participating physicians, the sponsor’s representatives, 
by the IRB/IEC and the regulatory authorities.  

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9. 
REFERENCES 
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[32] E. F. Stange and S. P. L. Travis, “The European consensus on ulcerative colitis: new 
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[34] S. C. Park and Y. T. Jeen, “Current and emerging biologics for ulcerative colitis,” Gut 
Liver, vol. 9, no. 1, pp. 18–27, Jan. 2015. 

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[35] B. G. Feagan et al., “Effects of adalimumab therapy on incidence of hospitalization and 
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[39] P. Raaschou, J. F. Simard, M. Holmqvist, J. Askling, and ARTIS Study Group, 
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[40] J. A. Smith and C. A. Kauffman, “Endemic fungal infections in patients receiving tumour 
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[45] “Efficacy, safety, tolerability, and pharmacokinetics of multiple doses of AbGn-168H 
administered by intravenous infusion to patients with moderate to severe chronic plaque 
psoriasis (randomized, double-blind, placebo-controlled),” AbGenomics, Clinical Study 
Report Study 2012.005.01, 2012. 
[46] “Efficacy, safety, tolerability, and pharmacokinetics of multiple doses of AbGn-168H 
administered by intravenous infusion to patients with moderate to severe chronic plaque 
psoriasis (randomized, double-blind, placebo-controlled),” AbGenomics, Clinical Study 
Report Study 2014.002.01, 2014. 
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open-label, multi-center, phase II proof of principle trial,” AbGenomics, Clinical Study 
Report, Study 2014.009.01. 
[48] “A Phase 1b Treatment Trial using AbGn-168H to Treat Steroid-Refractory Acute Graft-vs-
Host Disease (aGvHD) in Patients undergoing Allogeneic Hematopoietic Cell 
Transplantation,” Clinical Study Report BMT-285, 2017. 
[49] “Safety, tolerability and pharmacokinetics study of single rising doses of AbGn-168H 
administered by intravenous infusion (125 μg/kg, 500 μg/kg, 1 mg/kg, 2 mg/kg) or 
subcutaneous injection (125 μg/kg, 1 mg/kg) to healthy male volunteers (randomised, 

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CONFIDENTIAL 
double-blind, placebo-controlled within dose groups),” AbGenomics, Clinical Study Report 
Study 1304.1. 
[50] “Investigator’s brochure.” 

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CONFIDENTIAL 
10. 
APPENDICES 
10.1 PROCEDURES FOR PREPARING NEIHULIZUMAB FOR INTRAVENOUS 
ADMINISTRATION  
All steps will be done at room temperature. 
Have IV infusion set ready: IV tubing must be able to be used with appropriate infusion pump to 
precisely control flow rate (NOTE: flow rate for all groups will be fixed at 1.67 mL/min). 
Proximal end of IV infusion tubing is inserted into appropriate portion of 100 mL IV infusion 
bag of normal saline (0.9% NaCl). Distal end of IV infusion set is inserted into the tubing end of 
a 25G x ¾ inch butterfly infusion set.  An infusion set of similar size can be used as long as the 
infusion rate can be controlled at 1.67 mL/min. 
Note that throughout the following preparation procedures the maximum holding time at each 
step should not exceed 10 min except the time between preparation and administration to the 
patient which should not exceed 90 min.  Preparation will be done under aseptic conditions. 
Required items for preparation (refer to the respective dosing sections below for quantities): 
- Vial(s) of AbGn-168H (concentration of antibody in stock solution is 40 mg/mL) 
- Standard 10 mL syringe (BD 300912 or equivalent) 
- #20 gauge needle (Braun 4657500 or equivalent) 
- IV tubing (non-DEHP, 0.2 micron filter i.e Paclitaxel 2C7558 or equivalent) 
- IV infusion bag of 100 mL normal saline (Braun S8004-5264 non-DEHP or equivalent). 
- 25G x 3/4 inch butterfly infusion set  (Exel International 26708 or equivalent/similar) 
1. Use a 10 ml syringe with #20 gauge needle attached to remove appropriate amount of saline 
solution from the 100 mL 0.9% NaCl (normal saline) bag according in the patient’s weight in 
kg, as shown in the following table. Discard the removed saline.  
2. Inject the required volume of AbGn-168H, as shown in the table above into the reduced 100 
mL saline bag and mix gently. Syringes to be used here are the same type as those for 
removing saline solution from the 0.9% saline.  
3. Within 90 minutes of starting the preparation, start the infusion of the saline solution at 1.6-
1.7 mL/min, for a total of approximately 100 mL over about 1 hr (60 minutes).

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CONFIDENTIAL 
9 mg/kg Neihulizumab dosing table 
Weight (Kg/lb) 
Volume of 
saline to be 
withdrawn out 
of saline bag 
Volume of 
Neihulizumab 
to be injected 
into saline bag 
 
Weight (Kg/lb) 
Volume of 
saline to be 
withdrawn out 
of saline bag 
Volume of 
Neihulizumab 
to be injected 
into saline bag 
at least 
and less than 
at least 
and less than 
Kg 
lb 
Kg 
lb 
(mL) 
(mL) 
 
Kg 
lb 
Kg 
lb 
(mL) 
(mL) 
40 
88.2 
45 
99.2 
9 
9 
 
90 
198.4 
95 
209.4 
20.3 
20.3 
45 
99.2 
50 
110.2 
10.1 
10.1 
 
95 
209.4 
100 
220.5 
21.4 
21.4 
50 
110.2 
55 
121.3 
11.3 
11.3 
 
100 
220.5 
105 
231.5 
22.5 
22.5 
55 
121.3 
60 
132.3 
12.4 
12.4 
 
105 
231.5 
110 
242.5 
23.6 
23.6 
60 
132.3 
65 
143.3 
13.5 
13.5 
 
110 
242.5 
115 
253.5 
24.8 
24.8 
65 
143.3 
70 
154.3 
14.6 
14.6 
 
115 
253.5 
120 
264.6 
25.9 
25.9 
70 
154.3 
75 
165.3 
15.8 
15.8 
 
120 
264.6 
125 
275.6 
27 
27 
75 
165.3 
80 
176.4 
16.9 
16.9 
 
125 
275.6 
130 
286.6 
28.1 
28.1 
80 
176.4 
85 
187.4 
18 
18 
 
130 
286.6 
135 
297.6 
29.3 
29.3 
85 
187.4 
90 
198.4 
19.1 
19.1 
 
135 
297.6 
140 
308.6 
30.4 
30.4 
 
 

 
 
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CONFIDENTIAL 
11. CLINICAL STUDY PROTOCOL AGREEMENT FORM 
 
PROTOCOL NUMBER: 2017.008.01 
 
CLINICAL STUDY PROTOCOL DATE (NOVEMBER 2018) AND VERSION NO.: 
AMENDMENT 4 
 
 
Each participating investigator must agree to the approved Clinical Study Protocol and any 
subsequent amendment(s). By signing this form, I acknowledge receipt of and confirm to have 
read the above clinical study protocol. 
 
I shall implement all requirements specified in the clinical study protocol after 
approval/authorization by the regulatory authority and/or IRB (as appropriate) has been obtained. 
 
I shall ensure to inform all my staff involved in the trial about the Clinical Study Protocol and 
any changes it may lead to for staff’s trial related duties/responsibilities. 
  
 
________________________________ 
Investigator’s Signature 
Date of Signature 
(DD MMM YYYY)