A Phase 2a, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and Treatment Efficacy of SAB-176 (a Quadrivalent Anti-seasonal Influenza Immunoglobulin Product) in an H1N1 Challenge Model in Healthy Adult Participants
Phase: PHASE2
Conditions: Influenza A H1N1
Sponsor: SAb Biotherapeutics, Inc.

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Protocol HVO-CS-008, Final Version 3.0 
 
hVIVO template identifier: (G_0687) v3.0 
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CLINICAL STUDY PROTOCOL 
A Phase 2a, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and 
Treatment Efficacy of SAB-176 (a Quadrivalent Anti-seasonal Influenza Immunoglobulin 
Product) in an H1N1 Challenge Model in Healthy Adult Participants 
 
Short Title: 
Phase 2a Influenza Human Challenge Study of 
SAB-176 in Healthy Adult Participants 
Version and Date of Protocol: 
Final Version 3.0. Date 13 Jul 2021 
Sponsor Protocol Number: 
SAB-176-201 
hVIVO Protocol Number: 
HVO-CS-008 
Sponsor: 
SAB Biotherapeutics, Inc. 
2301 East 60th St. North, 
Sioux Falls, SD 57104 
United States 
Compound Number (if applicable): 
SAB-176 
EudraCT Number: 
2021-001254-56 
 
Confidentiality and Protections Statement: 
This document contains confidential information of hVIVO and SAB Biotherapeutics, Inc. This document 
must not be disclosed to anyone other than the study staff and members of the Independent Ethics 
Committee/Institutional Review Board or Competent Authorities. The information in this document 
cannot be used for any purpose other than the conduct or evaluation of the clinical investigation without 
the prior written consent of hVIVO and SAB Biotherapeutics, Inc. 
Personal data included in the protocol is subject to General Data Protection Regulation 
(GDPR: EU 2016/679) considerations and protections. 
 
 
 
 

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Sponsor Statement  
This protocol was subjected to critical review. The information it contains is consistent with current 
knowledge of the risks and benefits of the study intervention, and with the moral, ethical, and scientific 
principles governing clinical research as set out in the current Declaration of Helsinki and the principles 
of International Council for Harmonisation (ICH) Good Clinical Practice (GCP). 
 
Sponsor Signatory: 
 
 
 
 
 
Rick Finnegan  
Chief Business Officer EVP, Program Management 
SAB Biotherapeutics 
 
Date 
 
 
 

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Investigator Agreement: 
I have read the protocol and agree to conduct the study in accordance with the approved protocol and 
any future amendments, the Declaration of Helsinki, the principles of ICH GCP, the current regulatory 
requirements as detailed in the Medicines for Human Use (Clinical Trial) Regulations (Statutory 
Instrument 2004/1031) and all subsequent amendments, the United Kingdom (UK) Data Protection Act 
2018, any other applicable laws and guidance. 
I agree to conduct the procedures described in this protocol according to these guidelines and to 
appropriately direct and assist the staff under my control. 
 
Principal Investigator Signatory:  
Name (typed or printed): 
Victoria Parker 
 
Institution and Address: 
hVIVO Services Limited 
 
Queen Mary BioEnterprises Innovation Centre  
 
42 New Road, London, E1 2AX, United Kingdom 
 
Signature: 
 
Date: 
 
 
 
 
(DD MMM YYYY) 
 
Note: In this protocol, the terms hVIVO and ‘Investigator’ distinguish between the Principal Investigator’s 
(PI’s) responsibility, and actions required by the organisation (hVIVO). The term ‘Investigator’ includes 
appropriately qualified persons to whom the PI has formally delegated his/her Investigator roles and 
responsibilities. 
 
 

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Study Personnel Contact Information 
 
CONTACT 
DETAILS 
Sponsor 
SAB Biotherapeutics, Inc. 
2301 East 60th St. North 
Sioux Falls, SD 57104 
United States 
Sponsor’s Representative  
Rick Finnegan, Chief business Officer 
EVP, Business Program Management 978-500-3354 (m) 
245 First Street, Suite 1836 
Cambridge, MA 02142 
SAB Biotherapeutics, Inc. 
2301 East 60th St. North 
Sioux Falls, SD 57104 
United States 
Email: rfinnegan@sabbiotherapeutics.com 
Principal Investigator and Clinical 
Study Site 
Victoria Parker 
hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre  
42 New Road, London, E1 2AX, United Kingdom 
Email: v.parker@hvivo.com 
Sponsor's Medical Expert 
Dr. Thomas C. Luke, MD 
SAB Biotherapeutics, Inc. 
2301 East 60th St. North 
Sioux Falls, SD 57104 
United States 
Email: Tluke@sabbiotherapeutics.com 
Medical Monitor 
Dr. Thomas C. Luke, MD 
Key Protocol Contributors 
Refer to the local study contact list document 
 
 

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DOCUMENT HISTORY 
Document 
Date of Issue  
Overall Rationale 
HVO-CS-008, V3.0 
08 July 2021 
The Protocol Amendment has been created to revise the 
below listed information. Infusion rate was amended to a 
stable rate of up to 2.0mL/min The incorrect timepoints in 
the SoA for randomisation and immune markers were 
amended from post- to pre-inoculation. Storage 
temperature of SAB-176/Placebo doses, which was 
inaccurate, was corrected. Additional information on 
blinding and randomisation process was added.  
HVO-CS-008, V2.0 
12 May 2021 
Not applicable (first approved version).  
PROTOCOL AMENDMENT SUMMARY OF CHANGES  
Protocol Amendment 01 
Section / Title  
Description of Change 
Brief Rationale  
1.2. Schedule of Activities 
(SoA): 
Randomisation  
Randomisation timepoint was 
changed from Post-
inoculation to Pre-
inoculation. 
The change was made to allow 
enough time for preparation, QP 
release and delivery of doses to 
investigational site. 
1.2. SoA: Blood -immune 
marker 
Time point for the immune 
marker was corrected from 
Post inoculation to Pre-
inoculation  
Blood immune marker time point 
was incorrect in the previous 
protocol version.  
6.1. Table 2: Study 
Intervention 
Vial concentration of SAB-
176 was corrected in the 
Packing and Labeling 
section.  
SAB-176 concentration from 
previous batch was left in the 
protocol by mistake and has been 
corrected.  
6.2., 6.2.1. Interventional 
Product / Placebo 
The infusion rate of 
interventional product was 
changed to a stable rate of 
up to 2.0mL/min.  
Infusion rate was corrected based 
on the safety and tolerability profile 
of the Phase I study, with the highest 
administered dose of 50mg/kg. Dose 
level in this study is 25mg/kg. 
6.2., 621. Interventional 
Product / Placebo 
Storage temperature of SAB-
176 / Placebo doses was 
corrected from 2°C-8°C to 
15°C-25°C. Additional 
wording was added for 
clarity.  
 Storage temperature range 2°C-8°C 
relating to SAB-176 vials (bulk 
supplies) was incorrect for SAB-176 
/ Placebo doses which must be 
stored at 15°C-25°C.  
 

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Table of Contents 
Table of Contents .................................................................................................................................. 6 
1. 
Protocol Synopsis .................................................................................................................... 10 
1.1. 
Study Schematic: On-study Participant Progression ............................................................. 16 
1.2. 
Schedule of Activities (SoA) .................................................................................................. 17 
2. 
Introduction ............................................................................................................................... 22 
2.1. 
Background ............................................................................................................................ 22 
2.2. 
Study Rationale ..................................................................................................................... 23 
2.3. 
Benefit/Risk Assessment ....................................................................................................... 23 
2.3.1. 
Risk Assessment .............................................................................................................. 23 
2.3.2. 
Benefit Assessment .......................................................................................................... 29 
2.3.3. 
Overall Benefit: Risk Conclusion ...................................................................................... 30 
3. 
Objectives and Endpoints ........................................................................................................ 31 
4. 
Study Design ............................................................................................................................. 34 
4.1. 
Overall Design ....................................................................................................................... 34 
4.2. 
Scientific Rationale for Study Design .................................................................................... 34 
4.2.1. 
Rationale for Study Design ............................................................................................... 34 
4.2.2. 
Justification for Dose ........................................................................................................ 35 
4.3. 
End of Study Definition .......................................................................................................... 35 
5. 
Study Population ...................................................................................................................... 36 
5.1. 
Inclusion Criteria .................................................................................................................... 36 
5.2. 
Exclusion Criteria ................................................................................................................... 38 
5.3. 
Lifestyle Considerations......................................................................................................... 40 
5.3.1. 
Meals and Dietary Restrictions ......................................................................................... 40 
5.3.2. 
Caffeine, Alcohol, and Tobacco ........................................................................................ 40 
5.3.3. 
Activity .............................................................................................................................. 40 
5.3.4. 
Other Restrictions ............................................................................................................. 41 
5.4. 
Screen Failures ...................................................................................................................... 41 
6. 
Study Intervention .................................................................................................................... 42 
6.1. 
Study Interventions Administered .......................................................................................... 42 
6.2. 
Preparation/Handling/Storage/Accountability ........................................................................ 43 
6.2.1. 
Interventional Product / Placebo....................................................................................... 43 
6.2.2. 
Challenge Virus ................................................................................................................ 44 
6.2.3. 
All Study Interventions ...................................................................................................... 44 
6.3. 
Randomisation and Blinding .................................................................................................. 44 
6.4. 
Study Intervention Compliance .............................................................................................. 45 
6.5. 
Concomitant Therapy ............................................................................................................ 46 
6.6. 
Dose Modification .................................................................................................................. 47 
7. 
Discontinuation of Study Intervention/Withdrawal ............................................................... 48 
7.1. 
Participant Withdrawal ........................................................................................................... 48 
7.2. 
Participant Discontinuation .................................................................................................... 48 
7.2.1. 
Temporary Discontinuation / Temporary Delay in Enrolment .......................................... 49 
7.3. 
Lost to Follow up .................................................................................................................... 49 
7.4. 
Participant Replacement Strategy ......................................................................................... 49 
7.5. 
Stopping Rules ...................................................................................................................... 49 
8. 
Study Assessments and Procedures ..................................................................................... 51 
8.1. 
Medical and Medication History ............................................................................................. 51 
8.2. 
Demographics ........................................................................................................................ 51 

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8.3. 
Height, Weight and Body Mass Index ................................................................................... 51 
8.4. 
Alcohol Breath Testing ........................................................................................................... 51 
8.5. 
Urine Samples and Assessments .......................................................................................... 52 
8.5.1. 
Urinalysis .......................................................................................................................... 52 
8.5.2. 
Drugs of Abuse ................................................................................................................. 52 
8.5.3. 
Pregnancy Test................................................................................................................. 52 
8.6. 
Complete Physical Examination ............................................................................................ 52 
8.7. 
Directed Physical Examination .............................................................................................. 52 
8.8. 
Vital Signs .............................................................................................................................. 53 
8.9. 
Tympanic Temperature .......................................................................................................... 53 
8.10. 
Exploratory Wearables and Continuous Monitoring .............................................................. 54 
8.11. 
Participant Diary Cards .......................................................................................................... 54 
8.12. 
Nasal Discharge Collection from Paper Tissues ................................................................... 55 
8.13. 
Electrocardiogram .................................................................................................................. 55 
8.14. 
Spirometry ............................................................................................................................. 55 
8.15. 
Questionnaires ....................................................................................................................... 56 
8.16. 
Blood Samples ....................................................................................................................... 56 
8.16.1. 
Safety Blood Analysis and Assessments ......................................................................... 56 
8.16.2. 
Challenge Virus Serology Samples .................................................................................. 56 
8.16.3. 
Pharmacokinetic Blood Samples ...................................................................................... 56 
8.16.4. 
Anti-drug Antibodies ......................................................................................................... 57 
8.16.5. 
Blood for Immunology Biomarker Evaluations ................................................................. 57 
8.17. 
Nasal Samples ....................................................................................................................... 57 
8.17.1. 
Respiratory Pathogen Screen .......................................................................................... 58 
8.17.2. 
Rapid Influenza Discharge Test ....................................................................................... 58 
8.17.3. 
Viral Load .......................................................................................................................... 58 
8.17.4. 
Exploratory Analyses ........................................................................................................ 58 
8.18. 
Recording of Adverse Events and Serious Adverse Events ................................................. 59 
8.18.1. 
Time Period and Frequency for Collecting AE and SAE Information ............................... 59 
8.18.2. 
Method of Detecting AEs and SAEs ................................................................................. 59 
8.18.3. 
Follow-up of AEs and SAEs ............................................................................................. 59 
8.18.4. 
Regulatory Reporting Requirements for SAEs ................................................................. 59 
8.18.5. 
Pregnancy ......................................................................................................................... 60 
8.19. 
Treatment of Overdose .......................................................................................................... 60 
8.20. 
Pharmacokinetics .................................................................................................................. 60 
8.21. 
Pharmacodynamics ............................................................................................................... 60 
8.22. 
Genetics ................................................................................................................................. 61 
9. 
Statistical Considerations ........................................................................................................ 62 
9.1. 
Statistical Hypotheses ........................................................................................................... 62 
9.2. 
Sample Size Determination ................................................................................................... 62 
9.3. 
Populations for Analyses ....................................................................................................... 62 
9.4. 
Statistical Analyses ................................................................................................................ 63 
9.4.1. 
Statistical Analysis Plan .................................................................................................... 63 
9.4.2. 
General considerations ..................................................................................................... 63 
9.4.3. 
Statistical Analysis ............................................................................................................ 64 
9.4.4. 
Primary Efficacy Analysis ................................................................................................. 64 
9.4.5. 
Secondary Efficacy Analysis ............................................................................................ 65 
9.4.6. 
Tertiary/exploratory Analysis ............................................................................................ 66 
9.4.7. 
Safety Analyses ................................................................................................................ 66 
9.4.8. 
Pharmacokinetic Analysis ................................................................................................. 66 
9.5. 
Interim Analyses .................................................................................................................... 67 

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10. 
Supporting Documentation and Operational Considerations.............................................. 68 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ................................ 68 
10.1.1. 
Regulatory and Ethical Considerations ............................................................................ 68 
10.1.2. 
Financial Disclosure ......................................................................................................... 68 
10.1.3. 
Informed Consent Process ............................................................................................... 68 
10.1.4. 
Data Protection ................................................................................................................. 69 
10.1.5. 
Committees Structure ....................................................................................................... 69 
10.1.6. 
Dissemination of Clinical Study Data ............................................................................... 70 
10.1.7. 
Data Quality Assurance .................................................................................................... 70 
10.1.8. 
Source Documents ........................................................................................................... 70 
10.1.9. 
Study Discontinuation ....................................................................................................... 71 
10.1.10. 
Publication Policy.............................................................................................................. 71 
10.2. 
Appendix 2: Clinical Laboratory Tests ................................................................................... 72 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting .................................................................................................................. 74 
10.3.1. 
Adverse Event .................................................................................................................. 74 
10.3.2. 
Adverse Drug Reaction .................................................................................................... 75 
10.3.3. 
Unexpected Adverse (Drug) Reaction .............................................................................. 75 
10.3.4. 
Serious Adverse Event ..................................................................................................... 75 
10.3.5. 
Suspected Unexpected Serious Adverse Reaction.......................................................... 76 
10.3.6. 
Recording, Assessment and Follow-up of AE and/or SAE .............................................. 76 
10.3.7. 
Reporting of SAEs ............................................................................................................ 82 
10.3.8. 
Reporting of SUSARs ....................................................................................................... 83 
10.3.9. 
Adverse Reactions to non-IMPs ....................................................................................... 84 
10.3.10. 
Post-study AEs and SAEs ................................................................................................ 84 
10.3.11. 
Pregnancy ......................................................................................................................... 84 
10.4. 
Appendix 4: Normal Ranges .................................................................................................. 85 
10.5. 
Appendix 5: Abbreviations ..................................................................................................... 86 
10.6. 
Appendix 6: Definitions .......................................................................................................... 88 
10.6.1. 
General ............................................................................................................................. 88 
10.6.2. 
Study definition of infection and illness ............................................................................ 88 
11. 
References ................................................................................................................................. 90 
 
 
 

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List of Tables 
Table 1: Risk Assessment ..................................................................................................................... 27 
Table 2: Study Intervention ................................................................................................................... 42 
Table 3: Prohibited Medication (Healthy Participants) .......................................................................... 46 
Table 4: Permitted Medication .............................................................................................................. 47 
Table 5: Study Stopping Rules ............................................................................................................. 50 
Table 6: Methods for Analysis of Secondary Endpoints ....................................................................... 65 
Table 7: Protocol-Required Safety Laboratory Assessments ............................................................... 72 
Table 8: Classification of Adverse Events Severity .............................................................................. 79 
Table 9: Classification of Adverse Events Relationship ........................................................................ 80 
Table 10: Classification of Adverse Events Outcome ........................................................................... 82 
Table 11: Contact Details for Reporting All Serious Adverse Events ................................................... 83 
 

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1. 
Protocol Synopsis 
Phase 
Phase 2a 
Clinical Study Site 
Single centre, hVIVO Services Limited 
Indication 
Treatment of influenza caused by Type A and Type B influenza viruses 
Study Type 
Interventional 
Design 
Up to 60 eligible participants will be randomized in a 1:1 ratio to receive 
either SAB-176 (up to 50 mg/kg dose) or placebo. Healthy adult 
participants will be pre-screened for serosuitability for Influenza 
A/California/2009 H1N1 challenge virus. Serosuitable participants who 
sign the study specific informed consent form (ICF) will be challenged 
with an intranasal administration of Influenza A/California/2009 H1N1 
virus on Day 0. Participants will be given an intravenous (IV) infusion of 
SAB-176 or placebo on Day 1. Participants will be held in quarantine 
until Day 8. 
Investigational Medicinal 
Product (IMP) 
SAB-176 (a quadrivalent anti-seasonal influenza immunoglobulin 
product) 
IMP dose 
Single dose up to 50 mg/kg 
Pharmaceutical form 
Purified human immunoglobulin G (hIgG) in a sterile liquid formulated 
in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 
0.05 mg/mL Tween 80, pH 5.5, administered as a liquid solution for 
injection in 0.9% sodium chloride (saline). 
IMP route 
Intravenous infusion 
Control compound 
Placebo 
Randomisation 
1:1 ratio active:placebo 
Challenge virus  
Influenza A/California/2009 H1N1 virus 
Challenge virus route 
Intranasal delivery 
Challenge virus titre 
Approximately 3.5 x 106 log10 tissue culture infectious dose (TCID50) 
Study population 
Healthy male and/or female participants, between 18 to 45 years of age, 
pre-screened for serosuitability for Influenza A/California/2009 H1N1 
challenge virus i.e., have levels of influenza antibodies compatible with 
susceptibility to influenza infection. 
Summary of study design 
This is an exploratory randomised, Phase 2a, double blind, 
placebo-controlled study to evaluate the safety and treatment efficacy 

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of SAB-176 against Influenza A/California/2009 H1N1 virus infection in 
healthy adult participants. 
The study is divided into the following study phases: 
Screening phase: 
• 
Screening from 56 days (90 days for influenza serology) up to 
Day -3. Historical pre-screening data collected through the hVIVO 
Generic Screening process within 56 days (90 days for influenza 
serology) up to Day -3 may be transferred to this study after the 
study specific ICF has been signed by the participant. 
Inpatient phase: 
• 
Admission to the Quarantine Unit on Day -2 / -1; resident in the 
Quarantine Unit for approximately 11 days (e.g., from admission on 
Day -2 to planned discharge on Day 8). 
• 
Inoculation with Challenge virus on Day 0. 
• 
IV infusion with SAB-176 or placebo on Day 1. 
• 
Discharge from the Quarantine Unit planned on Day 8. 
Outpatient phase: follow-up visit: 
• 
Day 28 (±3 days). 
Expected duration of 
participant participation 
Approximately 5 weeks from signing study specific ICF to the 
participant’s last scheduled visit. 
Overall duration of clinical 
phase 
The length of the clinical phase is estimated to last approximately 
15 weeks from first participant first visit to last participant last visit. 
End of study 
The end of the study is defined as the date of the last scheduled visit of 
the last participant in the study. 
Procedures and 
assessments 
During the study, the following assessments and procedures will be 
performed:  
• 
Informed Consent 
• 
Eligibility Criteria 
• 
Medical & Medication History 
• 
Demographics 
• 
Height & Weight and Body Mass Index 
• 
Alcohol Breath Testing 
• 
Urine Sample Collection (safety, drugs of abuse, cotinine, 
pregnancy) 
• 
Complete Physical Examination 
• 
Directed Physical Examination 
• 
Vital Signs 
• 
Tympanic Temperature 
• 
Electrocardiogram 
• 
Spirometry 
• 
Symptom Diary Cards 
o 
Categorical 
o 
Visual Analogue Scale 
• 
Patient Health Questionnaire (PHQ-9) 

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• 
Generalised Anxiety Disorder Questionnaire (GAD-7) 
• 
Wearable, if applicable 
• 
Inoculation with Challenge virus 
• 
IV Infusion SAB-176 or placebo 
• 
Nasal Discharge Collection 
• 
Blood Sample Collection 
• 
Nasal Sample Collection 
• 
Adverse events (AEs) and Concomitant Medications. 
Sample size 
Up to 60 participants will be inoculated with the Challenge virus. 
Note: A participant will be considered ‘enrolled’ into the study once 
he/she has signed the study specific ICF and eligibility is confirmed and 
has been inoculated with the Challenge virus. Potential participants who 
are screened under hVIVO generic screening process for the purpose 
of determining suitability for the study, but do not sign the study specific 
ICF to participate in the study, are not considered enrolled. 
Replacement policy 
If a participant discontinues from study intervention OR withdraws from 
the study a replacement participant may be enrolled if deemed 
appropriate by the Investigator and Sponsor. The replacement 
participant will generally receive the same allocated blinded study 
intervention as the participant being replaced. The replacement 
participant will be assigned a new unique randomization number. 
Statistics 
Sample size justification 
Up to 60 participants will be inoculated with the Challenge virus. 
The statistical powering selected for this study is estimated to be 
sufficient for the primary objective and based upon only the primary 
endpoint. The targeted power for this study’s endpoint is for 80% using 
a two-sided type-one error rate of 5%. The sample size of 
60 participants (30 in each arm) will allow detecting a 60% relative 
reduction in the quantitative reverse transcriptase-polymerase chain 
reaction (qRT-PCR) area under the curve (AUC) virology with SAB-176 
assuming an 81% coefficient of variation in the control arm. 
The PCR-AUC data is based on log-transformed PCR data. 
The sample size indicates the number of participants to be inoculated 
with the Challenge virus. 
Primary efficacy analysis 
The main estimator of the primary endpoint (the median area under the 
viral load-time curve [VL-AUC] of Influenza A/California/2009 H1N1 
virus as determined by qRT-PCR on nasal samples [virology]), will be 
analysed on the Per Protocol (PP) Analyses Set. 
The calculation of the VL-AUC will be performed on log10-transformed 
PCR data using the trapezoidal summation rule based on actual time 
intervals in hours. 

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Descriptive statistics and the 95% confidence interval (CI) will be 
presented by treatment group. The difference between the two groups 
will be analysed using the Wilcoxon rank sum test. The two-sided 
p-value will be presented. 
Objectives 
Endpoints 
Primary 
• 
To evaluate the effect of SAB-176, in 
reducing influenza viral load qRT-PCR 
when compared to placebo. 
• 
Area under the viral load-time curve 
(VL-AUC) of Influenza A/California/2009 
H1N1 virus, as determined by qRT-PCR on 
nasal samples. 
Secondary 
• 
To further evaluate the effect of SAB-176, 
in reducing viral loads / viral shedding in 
qRT-PCR 
due 
to 
Influenza 
A/California/2009 H1N1 virus, compared to 
placebo. 
• 
Peak viral load as defined by the maximum 
viral 
load 
determined 
by 
quantifiable 
qRT-PCR measurements. 
• 
Duration of influenza quantifiable qRT-PCR 
measurements. 
• 
To evaluate the effect of SAB-176, in 
reducing viral loads / viral shedding in cell 
culture due to Influenza A/California/2009 
H1N1 virus, compared to placebo. 
• 
VL-AUC of 
Influenza 
A/California/2009 
H1N1 virus, as determined by cell culture 
measurements. 
• 
Peak viral load as defined by the maximum 
viral load determined by quantifiable cell 
culture measurements. 
• 
Duration of influenza quantifiable cell culture 
measurements. 
• 
To evaluate the effect of SAB-176, in 
reducing symptoms due to Influenza 
A/California/2009 H1N1 virus, compared to 
placebo. 
• 
Area under the curve over time of total 
clinical symptoms score (TSS-AUC) as 
measured by graded symptom scoring 
system (categorical and visual analogue 
scales). 
• 
Peak symptom diary card score: peak total 
clinical symptoms (TSS) as measured by 
graded 
symptom 
scoring 
system 
(categorical and visual analogue scales). 
• 
Peak daily symptom score: Individual 
maximum daily sum of symptom score. 
• 
Number (%) of participants with Grade 2 or 
higher symptoms. 

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Objectives 
Endpoints 
• 
To evaluate the effect of SAB-176, in 
reducing the incidence of symptomatic 
infection due to Influenza A/California/2009 
H1N1 virus, compared to placebo. 
• 
RT-PCR-confirmed symptomatic influenza 
infection defined as: 
o 
RT-PCR-confirmed influenza infection, 
AND 
o 
Clinical symptoms. 
• 
Culture 
lab-confirmed 
reduction 
of 
symptomatic influenza infection defined as: 
o 
Lab-confirmed 
culturable 
influenza 
infection, AND 
o 
Clinical symptoms. 
• 
To evaluate the safety of SAB-176, when 
compared to placebo. 
• 
Occurrence of unsolicited adverse events 
(AEs) from IV infusion up to Day 28 
follow-up. 
• 
Occurrence of serious adverse events 
(SAEs) from IV infusion up to Day 28 follow-
up. 
• 
To evaluate the safety of the Influenza 
A/California/2009 H1N1 virus challenge 
model. 
• 
Occurrence of unsolicited AEs related to the 
viral challenge from viral challenge (Day 0) 
up to Day 28 follow-up. 
• 
Occurrence of SAEs related to the viral 
challenge from viral challenge (Day 0) up to 
Day 28 follow-up. 
• 
Use of concomitant medications from viral 
challenge (Day 0) up to Day 28 follow up. 
Tertiary/Exploratory* 
• 
To further explore the effect of SAB-176, in 
reducing the incidence of influenza illness 
due to Influenza A/California/2009 H1N1 
virus, compared to placebo. 
• 
Upper Respiratory Tract illness, 
• 
Lower Respiratory Tract illness, 
• 
Systemic Illness, 
• 
Febrile Illness, 
• 
Mild to moderate symptoms. 
• 
To explore the Minimal Clinically Important 
Difference (MCID) in instrument change 
(e.g., symptom diary cards). 
• 
The 
average 
amount 
of 
instrument-
assessed change for all participants who 
rate themselves as "a little better" or 
"somewhat better. 
• 
Additional endpoints may be considered for 
this objective and added at a later stage. 

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Objectives 
Endpoints 
• 
To explore the effect of SAB-176, in 
reducing the incidence of infection due to 
Influenza A/California/2009 H1N1 virus, 
compared to placebo. 
• 
Influenza viral infection rates in upper 
respiratory samples by qRT-PCR and cell 
culture. 
• 
To further explore the safety of the 
Influenza A/California/2009 H1N1 virus 
challenge model. 
• 
Occurrence 
of 
haematological 
and 
biochemical laboratory abnormalities during 
the quarantine period. 
• 
To 
explore 
the 
utility 
of 
wearable 
continuous 
monitoring 
for 
assessing 
Influenza A/California/2009 H1N1 virus 
infection/disease. 
• 
Measures 
captured 
by 
continuous 
monitoring may be explored in relation to 
Influenza challenge. 
• 
To explore genomic, transcriptomic, and 
immunological 
markers 
of 
Influenza A/California/2009 H1N1 virus 
infection, as well as the effect of SAB-176. 
• 
Blood and respiratory samples may be 
investigated to assess i) the host baseline 
status, ii) response to infection, and 
iii) impact on SAB-176, for example: 
o 
Immune markers e.g., cytokines / 
chemokines, immunoglobulins 
o 
Deoxyribonucleic 
acid 
(DNA) 
(e.g., 
single 
nucleotide 
polymorphisms 
[SNPs], genome-wide association study 
[GWAS]) 
o 
Ribonucleic acid (RNA) transcriptomics 
(e.g., RNA sequencing, microarray) 
This is a non-exhaustive list. 
*Note that tertiary objectives and endpoints are optional and might be assessed only if needed; 
therefore, not all tests might be performed and reported. 
 

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1.1. 
Study Schematic: On-study Participant Progression 
CLINIC / 
SCREENING 
 
QUARANTINE / SAB-176 OR PLACEBO INFUSION AND 
CHALLENGE PHASE 
 
CLINIC / 
FINAL 
STUDY 
CONTACT 
 
 
 
 
 
 
 
 
 
 
 
Day -56 
(Day -90 for 
influenza 
serology) to 
Day -3 
Screening 
 
Day -2 / -1 
Admission to 
quarantine 
 
Day 0 
Viral 
Challenge 
 
Days 1 to 7 
IV Infusion 
and 
assessments 
 
Day 8 
Discharge 
from 
quarantine* 
 
Day 28 
(±3 days) 
Follow–up 
visit / Final 
contact 
 
 
 
 
 
 
 
 
 
 
 
*NOTE: Release from quarantine is foreseen at Day 8 (8 days post-inoculation) in case no virus is 
detected by qualitative virus antigen test or polymerase chain reaction (PCR) (negative virus antigen 
test or PCR below Ct cut-off) and the participant has no clinically significant symptoms. If the participant 
continues to have clinically significant symptoms and/or detectable virus on Day 8, additional extended 
quarantine stay may be required at the discretion of the Investigator. 
 

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1.2. 
Schedule of Activities (SoA) 
Study phase ➔ 
Screening 
phase* 
QUARANTINE ISOLATION 
Clinic visit 
  
Early 
withdrawal 
visit 
Admission to 
quarantine 
Human viral challenge 
(HVC) 
Post HVC days 
Discharge 
  
Study day ➔ 
Day -56 
(Day -90 for 
influenza 
serology) to 
Day -3 
Day 
Day 
Day 0 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Follow-up 
  
 
Procedure  
-2 
-1 
Pre 
Challenge 
Post  
1 
2 
3 
4 
5 
6 
7 
8 
Day 28 
(± 3 days) 
  
Written consent (a) 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria (b) 
X 
Xo 
X 
 
 
 
 
 
 
 
 
 
 
 
  
 
Medical & medication history, 
and changes 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Height & weight, and body 
mass index (BMI) (c) 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
(X) 
(X) 
  
(X) 
Alcohol breath test 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Urinalysis 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
X 
Urine drugs of abuse 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Urinary cotinine test 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test (d) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Complete physical 
examination 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
X 
X 
  
X 
Directed physical examination 
(incl. nasal) 
 
 
 
X 
 
X 
Xq 
X 
X 
X 
X 
X 
X 
 
 
  
 
Vital signs (heart rate [HR], 
respiratory rate [RR], blood 
pressure [BP] systolic BP and 
diastolic BP, peripheral arterial 
oxygen saturation [SpO2]) (e) 
X 
Xo 
TDS 
TDS 
8X 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
X 
  
X 
Tympanic temperature 
X 
Xo 
TDS 
TDS 
TDSq 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
X 
  
X 
Symptom diary card 
 
Xo 
TDS 
TDS 
TDSq 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
 
 
 
24-hour tissue count and nasal 
discharge (f) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
(X) 
12-lead electrocardiogram 
(ECG) 
X 
Xo 
 
 
 
Xr 
 
X 
 
 
 
X 
 
X 
 
X 
Spirometry (g) 
X 
Xo 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 

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Study phase ➔ 
Screening 
phase* 
QUARANTINE ISOLATION 
Clinic visit 
  
Early 
withdrawal 
visit 
Admission to 
quarantine 
Human viral challenge 
(HVC) 
Post HVC days 
Discharge 
  
Study day ➔ 
Day -56 
(Day -90 for 
influenza 
serology) to 
Day -3 
Day 
Day 
Day 0 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Follow-up 
  
 
Procedure  
-2 
-1 
Pre 
Challenge 
Post  
1 
2 
3 
4 
5 
6 
7 
8 
Day 28 
(± 3 days) 
  
Patient Health Questionnaire 
(PHQ-9) 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generalised Anxiety Disorder 
Questionnaire (GAD-7) 
X 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wearable (continuous 
monitoring e.g., vital signs, 
temperature, ECG), if 
applicable 
 
 
 
 
 
continuouss 
 
 
 
 
 
 
 
 
X 
Product Administration 
Challenge virus inoculation 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomisation 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Investigational medicinal 
product (IMP) / placebo dosing 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Collection of Blood Samples 
Serum follicle stimulating 
hormone (FSH) (h) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum beta-human chorionic 
gonadotrophin (β-HCG) 
pregnancy test (i) 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
Human immunodeficiency 
virus (HIV), Hepatitis A, B, and 
C tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Haematology (j) 
X 
Xo 
 
 
 
Xq 
 
X 
 
 
 
X 
(X) 
X 
 
X 
Biochemistry (j) 
X 
Xo 
 
 
 
 
 
X 
 
 
 
X 
(X) 
X 
 
X 
Coagulation (j) 
X 
Xo 
 
 
 
Xq 
 
X 
 
 
 
X 
(X) 
 
 
X 
Cardiac enzymes 
X 
Xo 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
Thyroid function test 
X 
(X)o 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood - immune markers (k) 
X 
Xo 
X 
X 
 
 
Xq 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Blood – transcriptomics 
markers 
 
 
BD 
X 
 
X 
BDq 
BD 
BD 
BD 
BD 
BD 
BD 
X 
 
 
 

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Study phase ➔ 
Screening 
phase* 
QUARANTINE ISOLATION 
Clinic visit 
  
Early 
withdrawal 
visit 
Admission to 
quarantine 
Human viral challenge 
(HVC) 
Post HVC days 
Discharge 
  
Study day ➔ 
Day -56 
(Day -90 for 
influenza 
serology) to 
Day -3 
Day 
Day 
Day 0 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Follow-up 
  
 
Procedure  
-2 
-1 
Pre 
Challenge 
Post  
1 
2 
3 
4 
5 
6 
7 
8 
Day 28 
(± 3 days) 
  
Blood – deoxyribonucleic acid 
(DNA) - genomics 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood - Pharmacokinetics (PK) 
 
Xo 
 
 
 
2Xt 
X 
 
X 
 
X 
 
X 
X 
 
X 
Blood - anti-drug antibodies 
(ADA) 
 
Xo 
 
 
 
2Xt 
X 
 
X 
 
X 
 
X 
X 
 
X 
Collection of Respiratory Samples 
Nasopharyngeal swab / nasal 
wash - Respiratory pathogen 
screen (l) 
T 
Xo 
(X)p 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nasopharyngeal swab / nasal 
wash - Rapid viral antigen test 
or polymerase chain reaction 
(PCR) 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X)p 
 
 
(X) 
Nasopharyngeal swab / nasal 
wash – Virology (m) and 
exploratory research 
T 
 
X 
 
 
 
BDq 
BD 
BD 
BD 
BD 
BD 
BD 
X 
 
 
X 
Nasal sample (nasosorption / 
mid turbinate swab) – PK and 
exploratory immunology 
 
 
X 
 
 
 
Xq 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Safety Assessments 
Adverse events (n) 
X 
continuous 
 
X 
Concomitant medications (n) 
X 
continuous 
 
X 
 
KEY NOTES FOR SCHEDULE OF EVENTS 
X 
Once 
BD 
Twice Daily. The timing of the baseline assessment will be the guide to establish the windows for subsequent measurements. For scheduling purposes, the baseline assessment will 
be defined as the first day when BD measurements are performed. Subsequent sampling / measures will be performed at the same time ±1 hour. 
TDS 
Three Times Daily. The timing of the baseline assessment will be the guide to establish the windows for subsequent measurements. For scheduling purposes, the baseline 
assessment will be defined as the first day when TDS measurements are performed. Subsequent sampling / measures will be performed at the same time ±1 hour 
T 
To determine tolerance of the procedure only (sample will not be tested). 
* 
All screening assessments will be performed under hVIVO Generic Screening process. Historical pre-screening data collected through the hVIVO Generic Screening process within 
56 days (90 days for influenza serology) up to Day -3 may be transferred to this study after the study specific ICF has been signed by the participant. 

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a 
Study specific consent may occur on the day of admission, providing all required eligibility information has been collected through hVIVO Generic Screening process. 
b 
Only the applicable Inclusion / Exclusion criteria will be reviewed at each time point. 
c 
Height will be taken at Screening only. 
d 
Urine pregnancy tests will be performed in female participants of childbearing potential. 
e 
Vital signs will be taken at the same time(s) each day (±1 hour). On Day 1 the vital signs will be performed pre-infusion, and at 15 minutes, 30 minutes, 60 minutes, 90 minutes, 
2 hours, 4 hours, and 8 hours after the start of the drug infusion. 
f 
Distribution of paper tissues and bags will start on Day -1, with the first collection on Day 0. Thereafter collection of tissues will occur at the same time points (±1 hour) with tissues 
distributed 24 hours ahead. 
g 
Assessments will be performed at the same time points (±1 hour) during quarantine. 
h 
A serum FSH test will be performed in all post-menopausal female participants. 
i 
Blood serum pregnancy test (β-hCG) will be performed in all female participants. 
j 
Blood may be drawn under non-fasted conditions. 
Repeat bloods may be drawn under fasted conditions if a lipid profile (triglyceride) or glucose is required (at Principal Investigators [PIs] discretion). 
k 
Blood will be collected for: i) virus serology (influenza antibody assay) to determine eligibility (at screening) and seroconversion (at Day -2 / -1 & Day 28), and ii) exploratory immune 
markers. 
l 
Nasopharyngeal swab or nasal wash for respiratory virus screen to assess for the presence of other respiratory viruses; if found positive the participant will not be eligible for the 
current quarantine. 
m 
Nasopharyngeal swabs (or nasal wash, if appropriate) will be collected for viral load assessments and exploratory immunology. Post inoculation nasal virology samples will be 
collected and used for qRT-PCR and viral culture assay. 
n 
Adverse events and concomitant mediations are reviewed throughout the study including pre- and post-infusion with IMP/placebo and pre- and post-inoculation. 
o 
Can be performed on Day -2 or Day -1. If admission at Day -1, all procedures scheduled for Day -2 can be performed on Day -1, as appropriate. 
p 
Optional and may be collected or not as per PI discretion for exploratory research. 
q 
Pre-infusion (only applicable to the first assessment on Day 1). 
r 
Post-dose ECG. 
s 
An exploratory wearable may be used to capture continuous measures parameters such as: HR, heart rate variability, SpO2, temperature, ECG. This may include a period of up to 
4 weeks prior to quarantine admission and up to 4 weeks post discharge from quarantine. 
t 
PK and ADA samples to be taken on Day 1 (IMP / placebo administration day): one sample pre-infusion and one sample at 1-hour post-infusion end (infusion end includes any time 
required for flushing). 
Notes: 
Parenthesis indicates the assessment may be optional, or at the PI's discretion.  
For all participants TDS assessments will commence on Day 0, the first assessment will be pre-virus challenge. 
The PI may perform additional safety assessments as required. 
Where any nasal sampling time points occur together, the order of sampling will typically be (1) nasosorption, (2) nasopharyngeal swab followed by (3) nasal wash 

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GENOMIC, TRANSCRIPTOMIC AND PROTEOMIC SAMPLES 
Deoxyribonucleic acid (DNA) / ribonucleic 
acid (RNA) / proteomic sample collection: 
Yes 
☒ 
No 
☐ 
DNA. 
RNA. 
Proteomics. 
Consent considerations:  
Genetic consent. 
Future use of remaining samples for exploratory research: blood samples (including processed blood) and 
respiratory samples for biomarker analysis relevant to the exploratory objectives of the study. 
 
 

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2. 
Introduction 
SAB-176 is a purified human immunoglobulin G (hIgG) designed to specifically bind to Type A and Type B 
influenza viruses. The product is in development for use as a therapeutic agent to treat patients who are 
infected with Type A and Type B influenza viruses. The hIgG is purified from the plasma of immunized 
trans chromosomic (Tc) bovines that were immunized with a quadrivalent recombinant haemagglutinin (HA) 
protein vaccine produced in insect cells. 
For more information on the non-clinical and clinical data regarding SAB-176, refer to the latest version of 
the Investigator’s Brochure (IB Edition 1.2, 2021). 
2.1. 
Background 
Influenza causes substantial morbidity and mortality worldwide despite available antivirals and vaccines. 
Influenza is responsible for 226,000 excess hospitalizations and 30,000 to 50,000 deaths each year in the 
United States (US) alone (Thompson et al. 2003). Effective therapeutics are needed to prevent mortality or 
morbidity in those afflicted with severe influenza. Human plasma (delivered as Fresh Frozen Plasma units) 
or human intravenous immunoglobulin (hIVIg) with anti-influenza antibodies have been proposed as 
treatments for severe influenza (Luke et al. 2006). A limitation with plasma or hIVIg is that large numbers 
of human plasma donors/units must be screened to identify those few with a higher-than-average 
haemagglutination inhibition (HAI) titer to multiple strains of influenza. However, recent clinical trials have 
not shown benefit to hospitalized patients with severe Type A influenza infections treated with human-
derived anti-influenza plasma or hIVIg (Beigel et al. 2019, Davey et al. 2019). 
SAB Biotherapeutics, Inc., has developed SAB-176 to address the production limitations and lack of clinical 
efficacy of human-derived plasma or hIVIg. SAB-176 is a unique anti-influenza hIgG containing fully human 
polyclonal IgG antibodies with extremely high HAI and microneutralization titers against past, current, and 
potentially future strains of Type A influenza (H1N1/H3N2) and both lineages of Type B influenza 
(Yamagata/Victoria). SAB-176 is purified from the plasma of immunized Tc bovines that were immunized 
with a quadrivalent recombinant HA protein vaccine produced in insect cells. The HA antigens match the 
four influenza strains recommended yearly for the Northern hemisphere by the Center for Disease Control 
and Prevention. 
Furthermore, Tc bovine hIgGs have an IgG1 subclass content of approximately 80-90% versus 
approximately 60% for human derived IVIg. IgG1 strongly activates complement and effector cells (natural 
killer cells, neutrophils, monocytes, etc.) of the innate immune system. SAB-176 is therefore much different 
than human-derived anti-influenza hIVIgs. SAB Biotherapeutics, Inc. believes that SAB-176’s distinct 
attributes, in combination with early treatment of severe influenza disease, could demonstrate that the 
product reduces morbidity and mortality in patients with Type A and/or B influenza. 
The genome of Tc bovines contains a human artificial chromosome comprising the entire human Ig gene 
repertoire (human Ig heavy chain [IgH] and human kappa light chain) that reside on two different human 
chromosomes (hChr), specifically the IgH locus from hChr14 and the immunoglobulin kappa (Igκ) locus 
from hChr2. The system maintains the ability to use the genetic information provided by the immunoglobulin 
gene repertoires for generating the seemingly unlimited diversity of human polyclonal antibodies (pAbs). 

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Fully hIgG (hIgG/hIgκ) can then be produced in these Tc bovines after vaccination with suitable antigens, 
and these animals produce up to 15 g/L of IgG antibodies in their plasma (similar to humans which have 
7 to 16 g/L IgG). SAB-176 is an anti-influenza hIgG prepared in this system. Tc bovines receive repeated 
doses of a quadrivalent recombinant HA protein vaccine produced in insect cells. Just prior to immunization 
of the Tc bovine, the HA proteins are mixed with adjuvants. 
Plasma is collected using an automated plasmapheresis system. After collection of sufficient volume, 
plasma undergoes Quality Control testing, is frozen and stored. Once it is ready to be processed, qualified 
frozen plasma is thawed, pooled, fractionated by caprylic acid and clarified by depth filtration in the 
presence of filter aid. The clarified sample containing hIgG is further purified by affinity chromatography, 
first using an anti-human IgG kappa affinity column to capture hIgG pAbs and remove residual non-hIgG 
and bovine plasma proteins. The sample is subsequently passed through an anti-bovine IgG heavy chain 
specific affinity column to further remove residual IgG molecules that contain a bovine heavy chain. The 
hIgG fraction is then subjected to a Q Sepharose chromatography polishing step to further reduce impurities, 
nanofiltration, final buffer exchange, concentration, and sterile filtration. Finally, the product is terminally 
filtered and filled into vials. 
SAB-176 will be administered intravenously (IV) and will be diluted in saline. 
2.2. 
Study Rationale 
this study is to evaluate the safety and treatment efficacy of SAB-176 in a population inoculated with 
Influenza A/California/2009 H1N1 virus. This will both advance treatments for Type A and Type B influenza 
viruses, as well as establish the safety of the platform that could be used to quickly develop therapeutics 
for other emerging infectious diseases. 
The Influenza A/California/2009 H1N1 virus challenge strain has been used for over 5 years by several 
groups globally and has helped assess influenza disease and therapies (Watson et al. 2015, Sloan et al. 
2020). Specifically, hVIVO has direct experience with a range of H3N2, H1N1, and B influenza challenge 
viruses and have safety and inoculated over 1400 healthy participants, and specifically given over 
100 participants a different batch of Influenza A/California/2009 H1N1 virus (Pleguezuelos et al. 2020). 
The rationale for the study design is presented in Section 4.2. 
2.3. 
Benefit/Risk Assessment 
Healthy participants will not benefit from this clinical study. The study is designed to provide information 
about safety and efficacy of SAB-176. 
More detailed information about the known and expected benefits and risks and reasonably expected 
adverse events (AEs) of SAB-176 may be found in the Investigator’s Brochure. 
2.3.1. 
Risk Assessment 
The known risks to participants are detailed in Table 1. However, there may also be risks that are 
unforeseen and not anticipated (e.g., unknown allergies). Every effort will be made to monitor the health of 
the participants to ensure that such risks are minimised. Trained medical personnel and facilities will be 
available to provide medical emergency care. 

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2.3.1.1. 
Risks of SAB-176 
SAB-176 is currently concluding a Phase 1 clinical trial (ClinicalTrials.gov identifier: NCT04471038). All 
participants have been infused with no serious adverse events (SAEs) reported through the highest dose 
cohort of 50 mg/kg and it appears to be safe and well tolerated. A previous Phase 1 study of SAB-301 
(anti-Middle Eastern Respiratory Syndrome virus immunoglobulin) also derived from Tc bovines was shown 
to be safe and well tolerated at the highest dose of 50 mg/kg (ClinicalTrials.gov identifier: NCT02788188). 
It is anticipated that the risks for this Phase 2a study will be similar to the Phase 1 studies of SAB-176 and 
SAB-301 and the use of hIVIg with some unique considerations for proteins of animal origin as discussed 
below. 
Based on hIVIg, common side effects may include: 
• 
headache 
• 
injection site reaction 
• 
nausea 
• 
urticaria 
• 
fatigue 
• 
arthralgia 
• 
pyrexia. 
Less common side effects may include: 
• 
vomiting 
• 
back pain 
• 
rash. 
Serious side effects seen with hIVIg that could be seen with SAB-176 include:  
• 
Hyperproteinaemia, with resultant changes in serum viscosity and electrolyte imbalances may 
occur in patients receiving IVIg therapy (Steinberger et al. 2003). Humans routinely receive up to 
1 to 2 grams/kg of hIVIg to treat Guillain-Barre syndrome and other immune related neuropathies. 
Therefore, the addition of 50 mg/kg IgG as SAB-176 is a relatively small amount and is unlikely 
to cause AEs related to increased viscosity. 
• 
Aseptic Meningitis Syndrome has been reported with IVIg treatments, especially with high doses 
or rapid infusion. This risk is anticipated to be minimized given the low amount of protein and 
relatively slow infusion. 
• 
Haemolysis, either intravascular or due to enhanced red blood cell (RBC) sequestration, can be 
seen with human IVIg. This risk is anticipated to be low given the lack of exposure of the cows to 
human RBC antigens. 
• 
Volume overload has been reported with human IVIg. This risk is anticipated to be minimized 
given the low amount of protein and small total volumes administered. 
There may be additional risks of SAB-176 given its animal origin. SAB-176 is a fully human IgG so it is 
anticipated the risk would be less, though there may be residual animal proteins. The most similar product 
would be Horse Heptavalent Botulism Antitoxin which is an equine derived non-human polyclonal IgG 
polyclonal: 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/Licensed
ProductsBLAs/FractionatedPlasmaProducts/UCM345147.pdf), 

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There is the risk of off-target binding of the IVIg. In the worst case, this could cause immune activation 
(cytokine storm). The tissue cross reactivity assays do not predict any off-target binding, and this has not 
been seen in any other animal IVIg (of antigen-binding fragment [Fab]) preparations, so this risk is 
considered low. 
For Horse Heptavalent Botulism Antitoxin, the most common adverse reactions (ARs) in all healthy 
participants were headache (9%), pruritus (5%), nausea (5%), and urticaria (5%). Other ARs reported in 
less than 4% of participants included pyrexia and throat discomfort. All reported ARs were considered mild 
or moderate. No serious ARs were reported. Two moderate acute allergic reactions that required premature 
termination of the infusion and treatment were reported. Reactions were predefined as mild if the participant 
was aware but could tolerate the symptoms. Moderate reactions were predefined as discomfort enough to 
interfere with normal daily activity. 
The development of antibodies to bovine proteins and potential for food allergies is a theoretical concern. 
There is precedent for animal antibodies (or Fabs) being obtained from animal plasma and given to humans. 
• 
Rabbit Anti-thymocyte Globulin [Thymoglobulin] (http://products.sanofi.ca/en/thymoglobulin.pdf). 
• 
Horse Anti-thymocyte Globulin [Atgam] 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts
/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM199603.pdf). 
• 
Horse Heptavalent Botulism Antitoxin 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts
/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM345147.pdf). 
• 
Sheep Digoxin Immune Fab [DigiFab] 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts
/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm117626.pdf). 
• 
Sheep Digoxin Immune Fab [DigiBind] 
(http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=19044). 
• 
Sheep Crotalidae Polyvalent Immune Fab [CroFab] (http://www.crofab.com/documents/CroFab-
Prescribing_Information.pdf). 
Upon review of these package inserts, the development of anti-drug antibodies (ADAs) was noted only in 
Horse Heptavalent Botulism Antitoxin (11 of 271 participants). There was no warning in any of these 
products concerning the development of allergies to other animal proteins, nor of any food allergies. As 
SAB-176 is a transgenic human IgG, the risk should be even further minimized. However, given that 
American / European diet is often heavy in bovine products (milk and/or beef, including derivatives), there 
is the risk of development of anti-bovine antibodies that is stimulated with repeated exposure. Given the 
data above and the lack of precedent for the development of food allergies after exposure to similar 
products, it is anticipated this risk with SAB-176 is very small. 
Patients exposed to topical bovine thrombin products (previously used in surgical procedures e.g., fibrin 
glue) have developed antibodies towards bovine thrombin and contaminating bovine factor V; these 
antibodies can cross react with human clotting factors and may cause coagulopathy (Insight Flu IVIg Pilot 
Study Group 2016). In that series, postoperative coagulation abnormalities were more common in patients 
with antibodies to human coagulation proteins. SAB-176 clinical lots contain less than 5 ppm (parts per 
million) of bovine plasma proteins, but the clinical significance of this level of bovine contaminants is not 
known. Regardless, the serial assessment of prothrombin time/partial thromboplastin time (PT/PTT) in the 
study will monitor for any coagulation abnormalities in the participants receiving SAB-176. 

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As SAB-176 is bovine derived, it may contain galactose-alpha-1,3-galactose (alpha-Gal) glycosylation of 
the IgG. In other products, the alpha-Gal glycosylation has been shown to be the source of immune based 
hypersensitivity reactions. For example, the epidermal growth factor receptor inhibitor cetuximab is a 
monoclonal antibody with alpha-Gal glycosylation. Cetuximab, while a marketed product, has been 
associated with hypersensitivity reactions, including anaphylaxis. In most participants that had 
hypersensitivity reaction to cetuximab, IgE antibodies were present in pretreatment samples (Chung et al. 
2008). 
Lastly, SAB’s Tc-bovine production system and the US cattle population have a negligible risk for 
transmissible bovine spongiform encephalopathy (BSE), also known as “Mad Cow Disease”. Only 
three reported cases of BSE infection in cattle have been documented in the US in the last decade. Risk 
assessments for infectious diseases were completed on the production herd, and documented procedures 
are in place to reduce or eliminate certain infectious diseases in the production animals. All inputs (feed, 
medications, and vaccines) have been evaluated for the transmission of viral and BSE agents. The 
manufacturing process was also evaluated for the clearance and removal of viruses and BSE. Virus 
removal has been validated. The BSE Western blot analysis was done to demonstrate clearance and 
removal of prions. 
There may be additional risks not apparent or predicted by preclinical testing. 
2.3.1.2. 
Risks Associated with COVID-19 Pandemic  
This clinical trial seeks to address the ongoing burden of severe Influenza infections worldwide, 
particularly in terms of hospitalisation and mortality, especially in clinically vulnerable groups, which 
remains ongoing during the covid-19 pandemic. 
hVIVO implemented enhanced infection control measures during the pandemic to minimise risks of 
COVID-19 infection.  
o 
Risk of increased severity of COVID-19 infection if contracted after challenge virus inoculation: 
It has not been established that severity of COVID-19 infection could increase if contracted after 
inoculation. 
Participants will be tested for respiratory pathogens, including COVID-19 on the arrival to the quarantine 
unit. They will be advised on protective measures and will need to follow infection control regimen.  
o 
Risk of increased severity of COVID-19 infection after SAB-176 administration     
There is no evidence that severity of COVID-19 infection would increase if contracted after SAB-176 
administration. Participants will be tested for COVID-19 on the day of admission to the quarantine unit. 
They will be instructed on the infection control measures to follow.  
All participants will be instructed to follow UK Government Covid-19 guidelines and will provided with 
Personal Protective Equipment (PPE). 
COVID-19 related emerging data will be monitored ongoingly. 
 

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2.3.1.3. 
Other Risks 
Table 1: Risk Assessment 
Potential Risk of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
Study procedures 
Intravenous (IV) Catheter 
The primary risks of the placement of 
an 
IV 
catheter 
include 
local 
discomfort; occasional bleeding or 
bruising of the skin at the site of 
needle puncture; haematoma; and, 
rarely, infection or fainting. 
The participant will be closely 
monitored and asked about these 
symptoms 
and 
before 
being 
allowed to stand up. 
Blood Sampling 
Pain or bruising at the site where 
blood is drawn. 
Blood samples will be obtained by 
a trained professional. 
Syncope 
(fainting) 
can 
occur 
following or even before any blood 
draw as a psychogenic response to 
the needle insertion. 
Blood samples will be obtained by 
a 
trained 
professional 
and 
procedures will be put in place to 
avoid injury from fainting. 
There is a possibility that in the 
process of collecting blood a nerve 
may be injured. 
Procedure to be performed by 
qualified personnel. 
Blood tests performed to address the 
health 
of 
the 
participants 
at 
screening and during the study may 
indicate that a participant has an 
infection 
that 
he/she 
was 
not 
previously aware of (such as human 
immunodeficiency virus (HIV) or 
hepatitis) or an unexpected illness. 
The hVIVO doctor will provide the 
participant’s general practitioner 
(GP), or doctor with a referral letter 
if the participant agrees. 
Nasal sampling 
Collection of nasal wash samples or 
nasopharyngeal swabs may cause 
discomfort, sneezing, watery eyes, 
irritated nose, or nose bleeding. 
Sample 
collection 
will 
be 
performed 
by 
appropriately 
qualified and trained study staff to 
minimise the discomfort 
Virus infection from inoculation 

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Potential Risk of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
Influenza A/California/2009 
H1N1 virus infection and 
severe complications 
Approximately 65% chance of 
becoming infected with Influenza 
A/California/2009 H1N1 virus 
(Sloan et al. 2020). Typical 
Influenza A/California/2009 H1N1 
virus illness: abrupt onset of 
rhinitis, nasal stuffiness, fever, 
malaise, myalgia (muscle aches), 
and sore throat. 
 
Influenza, like many viruses, can 
cause more substantial health 
issues such as myocarditis 
(inflammation or damage to the 
heart muscle). However, the 
chance of this resulting in serious 
or permanent changes is rare, as 
most cases are minor and resolve 
without any lasting changes. 
The safety profile of this batch of 
Influenza A/California/2009 H1N1 
virus has been used for over 
5 years by several groups 
globally. 
At hVIVO over 100 participants 
have been challenged with a 
different batch of Influenza 
A/California/2009 H1N1 virus.  
Influenza A/California/2009 H1N1 
virus infection in healthy adults 
usually resolves without treatment 
within 3 to 7 days (Sloan et al. 
2020). 
 
Strict inclusion and exclusion 
criteria will apply to ensure only 
healthy adults are enrolled in this 
study. 
 
There will be a daily medical 
monitoring in a Quarantine Unit for 
at least 8 days post-challenge. 
 
Qualified medical and nursing staff 
in the Quarantine Unit will monitor 
for and manage any symptoms. 
Participants will be closely followed 
up while being in quarantine. 
 
Electrocardiogram (ECG) will be 
performed, and cardiac enzymes 
will be tested at least 3 days, and 
7 days post-viral challenge. 
Transient 
increase 
in 
alanine 
aminotransferase 
(ALT) 
or 
aspartate aminotransferase (AST) 
without clinical presentation, with a 
good prognosis upon improvement 
of infection.  
ALT and AST will be monitored. 
 
Transmission of Influenza 
A/California/2009 H1N1 
virus to participants’ close 
contacts 
Influenza A/California/2009 H1N1 
virus presence in nasal secretions 
can 
cause 
infection 
in 
close 
contacts. 
Virus is usual absent from the nose 
by 
the 
time 
participants 
are 
discharged from quarantine. This 
will be confirmed by testing a nasal 
swab sample using by a qualitative 
virus antigen test or polymerase 
chain reaction (PCR) to determine 

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Potential Risk of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
participants’ 
suitability 
for 
departure. 
In addition, participants will be 
instructed to avoid close contact 
with 
vulnerable 
people 
as 
described in Section 2.3.1.4 for 
two weeks after they leave the 
Quarantine Unit. 
Risk of reactivation of 
herpes infection. 
If a participant ever had a herpes 
infection (e.g., cold sores, genital 
herpes, or shingles), there is a small 
possibility that this infection could 
return after challenge. 
Participants will be instructed to 
inform the study staff if they 
currently have an active herpes 
infection or have had one during 
the 30 days before enrolment. 
Consult the Investigator’s Brochure for detailed information on study intervention. 
2.3.1.4. 
Vulnerable Persons 
For the purposes of possible contact, a vulnerable individual is a person who has close or household (i.e., 
share the same apartment or house) high-risk contacts including but not limited to: 
• 
Persons ≥65 years of age. 
• 
Children ≤2 years of age. 
• 
Residents of nursing homes. 
• 
Women who are pregnant or who are trying to become pregnant. 
• 
Persons of any age with significant chronic medical conditions such as:  
o 
Chronic pulmonary disease (e.g., severe asthma, Chronic Obstructive Pulmonary 
Disease). 
o 
Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac 
surgery, ischemic heart disease, known anatomic defects). 
o 
Contacts that required medical follow-up or hospitalisation during the past 5 years because 
of chronic metabolic disease (e.g., insulin dependent diabetes mellitus, renal dysfunction, 
haemoglobinopathies). 
o 
Immunosuppression or cancer. 
o 
Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, 
seizures). 
2.3.2. 
Benefit Assessment 
Healthy participants in clinical studies will not receive direct benefit from treatment during their participation. 
Participants may develop some immunity to Influenza A/California/2009 H1N1 virus and benefit from a 
general health check at Screening. Benefit may also be derived from the medical evaluations and 

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assessments associated with study procedures. In addition, participants are contributing to the process of 
developing new therapies in an area of unmet medical need. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures taken to minimise risk to participants in this study, the potential risks 
identified in association with SAB-176 are justified by the anticipated benefits linked to the evaluation of 
SAB-176 in a viral challenge model of healthy adults, which will subsequently facilitate future assessment 
of influenza antibody therapies. 

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3. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To evaluate the effect of SAB-176, in 
reducing influenza viral load quantitative 
reverse 
transcriptase-polymerase 
chain 
reaction (qRT-PCR) when compared to 
placebo. 
• 
VL-AUC of Influenza A/California/2009 H1N1 
virus, as determined by qRT-PCR on nasal 
samples. 
Secondary 
• 
To further evaluate the effect of SAB-176, in 
reducing viral loads / viral shedding in 
qRT-PCR due to Influenza A/California/2009 
H1N1 virus, compared to placebo. 
• 
Peak viral load as defined by the maximum viral 
load determined by quantifiable qRT-PCR 
measurements. 
• 
Duration of influenza quantifiable qRT-PCR 
measurements. 
• 
To evaluate the effect of SAB-176, in 
reducing viral loads / viral shedding in cell 
culture due to Influenza A/California/2009 
H1N1 virus, compared to placebo. 
• 
Area under the viral load-time curve (VL-AUC) 
of Influenza A/California/2009 H1N1 virus, as 
determined by cell culture measurements. 
• 
Peak viral load as defined by the maximum viral 
load determined by quantifiable cell culture 
measurements. 
• 
Duration of influenza quantifiable cell culture 
measurements. 
• 
To evaluate the effect of SAB-176, in 
reducing 
symptoms 
due 
to 
Influenza 
A/California/2009 H1N1 virus, compared to 
placebo. 
• 
Area under the curve over time of total clinical 
symptoms score (TSS-AUC) as measured by 
graded symptom scoring system (categorical 
and visual analogue scales). 
• 
Peak symptom diary card score: peak total 
clinical symptoms (TSS) as measured by 
graded symptom scoring system (categorical 
and visual analogue scales). 
• 
Peak daily symptom score: Individual maximum 
daily sum of symptom score. 
• 
Number (%) of participants with Grade 2 or 
higher symptoms. 

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Objectives 
Endpoints 
• 
To evaluate the effect of SAB-176, in 
reducing the incidence of symptomatic 
infection due to Influenza A/California/2009 
H1N1 virus, compared to placebo. 
• 
RT-PCR-confirmed 
symptomatic 
influenza 
infection defined as: 
o 
RT-PCR-confirmed influenza infection, AND 
o 
Clinical symptoms. 
• 
Culture lab-confirmed reduction of symptomatic 
influenza infection defined as: 
o 
Lab-confirmed 
culturable 
influenza 
infection, AND 
o 
Clinical symptoms. 
• 
To evaluate the safety of SAB-176, when 
compared to placebo. 
• 
Occurrence of unsolicited AEs from IV infusion 
up to Day 28 follow-up. 
• 
Occurrence of SAEs from IV infusion up to 
Day 28 follow-up. 
• 
To evaluate the safety of the Influenza 
A/California/2009 H1N1 virus challenge 
model. 
• 
Occurrence of unsolicited AEs related to the 
viral challenge from viral challenge (Day 0) up 
to Day 28 follow up. 
• 
Occurrence of SAEs related to the viral 
challenge from viral challenge (Day 0) up to 
Day 28 follow up. 
• 
Use of concomitant medications from viral 
challenge (Day 0) up to Day 28 follow up. 
Tertiary/Exploratory* 
• 
To further explore the effect of SAB-176, in 
reducing the incidence of influenza illness 
due to Influenza A/California/2009 H1N1 
virus, compared to placebo. 
• 
Upper Respiratory Tract illness, 
• 
Lower Respiratory Tract illness, 
• 
Systemic Illness, 
• 
Febrile Illness, 
• 
Mild to moderate symptoms. 
• 
To explore the Minimal Clinically Important 
Difference (MCID) in instrument change 
(e.g., symptom diary cards). 
• 
The average amount of instrument-assessed 
change for all participants who rate themselves 
as "a little better" or "somewhat better. 
• 
Additional endpoints may be considered for this 
objective and added at a later stage. 

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Objectives 
Endpoints 
• 
To 
explore the 
effect 
of SAB-176, 
in 
reducing the incidence of infection due to 
Influenza A/California/2009 H1N1, virus 
compared to placebo. 
• 
Influenza 
viral 
infection 
rates 
in 
upper 
respiratory samples by qRT-PCR and cell 
culture. 
• 
To further explore the safety of the Influenza 
A/California/2009 H1N1 virus challenge 
model. 
• 
Occurrence of haematological and biochemical 
laboratory abnormalities during the quarantine 
period. 
• 
To explore the utility of wearable continuous 
monitoring 
for 
assessing 
Influenza 
A/California/2009 
H1N1 
virus 
infection/disease. 
• 
Measures captured by continuous monitoring 
may be explored in relation to Influenza 
challenge. 
• 
To explore genomic, transcriptomic, and 
immunological 
markers 
of 
Influenza A/California/2009 
H1N1 
virus 
infection, as well as the effect of SAB-176. 
• 
Blood and respiratory samples may be 
investigated to assess i) the host baseline 
status, ii) response to infection, and iii) impact 
on SAB-176, for example: 
o 
Immune 
markers 
e.g., 
cytokines 
/ 
chemokines, immunoglobulins 
o 
Deoxyribonucleic acid (DNA) (e.g., single 
nucleotide 
polymorphisms 
[SNPs], 
genome-wide association study [GWAS]) 
o 
Ribonucleic acid (RNA) transcriptomics 
(e.g., RNA sequencing, microarray) 
This is a non-exhaustive list. 
*Note that tertiary objectives and endpoints are optional and might be assessed only if needed; therefore, 
not all tests might be performed and reported. 

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4. 
Study Design 
4.1. 
Overall Design 
This is an exploratory randomised, Phase 2a, double blind, placebo-controlled study to evaluate the safety 
and treatment efficacy of SAB-176 against Influenza A/California/2009 H1N1 virus infection in healthy adult 
participants. 
Up to 60 eligible participants will be randomized in a 1:1 ratio to receive either SAB-176 (up to 50 mg/kg 
dose) 
or 
placebo. 
Healthy 
adult 
participants 
will 
be 
pre-screened 
for 
serosuitability 
for 
Influenza A/California/2009 H1N1 virus challenge. Serosuitable participants who sign the study specific 
informed consent form (ICF) will be challenged with an intranasal administration of Influenza 
A/California/2009 H1N1 virus on Day 0. Participants will be given an IV infusion of SAB-176 or placebo on 
Day 1. Participants will be held in quarantine until Day 8. 
The Study Schematic - showing participant progression through the study - is presented in Section 1.1; the 
Schedule of Activities (SoA) is presented in Section 1.2. 
The total duration of study participation for a participant is approximately 5 weeks from signing study specific 
ICF to the participant’s last scheduled visit, with the following sequence and duration of study phases: 
▪ 
Screening phase: from 56 days (90 days for influenza serology) up to Day -3. Historical pre-screening 
data collected through the hVIVO Generic Screening process within 56 days (90 days for influenza 
serology) up to Day -3 may be transferred to this study after the study specific ICF has been signed by 
the participant. 
▪ 
Inpatient phase: Participants will be resident in the Quarantine Unit for approximately 11 days (e.g., 
from admission on Day -2 to planned discharge on Day 8). Procedures will include: 
• 
Pre-human viral challenge (HVC): 
o 
Admission to Quarantine Unit on Day -2 / -1. 
• 
HVC:  
o 
Inoculation with Challenge virus on Day 0. 
• 
Post-HVC: 
o 
IV infusion with SAB-176 or placebo on Day 1. 
o 
Day 1 to 7 onwards and each day – study assessments will be conducted as per SoA. 
o 
Participants will be discharged from the Quarantine Unit on Day 8 (or may remain 
longer at the Principal Investigator’s [PIs] discretion). 
▪ 
Outpatient phase:  
• 
Follow-up visit: Day 28 (±3 days). 
4.2. 
Scientific Rationale for Study Design 
4.2.1. 
Rationale for Study Design 
The study will be conducted by hVIVO Services Limited, which has extensive experience with challenge 
studies. The Influenza A/California/2009 H1N1 virus strain has been shown to cause symptoms and virus 
shedding that closely match natural infection. 
Administration of study intervention and challenge with Influenza A/California/2009 H1N1 virus will take 
place in hVIVO’s specialised Clinical Units, either in the Quarantine Unit or Screening Clinic Units. Standard 

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study procedures (including collection of blood, urine, and nasopharyngeal secretions for assessment of 
safety and efficacy) have been employed in previous studies conducted by hVIVO. 
The placebo control will be used to establish the frequency and magnitude of changes in endpoints that 
may occur in the absence of active treatment. Blinded treatment will enable the avoidance of bias in the 
interpretation of results. 
Randomization will be used to minimize bias in the assignment of participants to treatment groups (active 
treatment or placebo), to increase the likelihood that known and unknown participant characteristics 
(e.g., demographic and baseline characteristics) are equally balanced across treatment groups, and to 
enhance the validity of statistical comparisons across treatment groups. 
4.2.2. 
Justification for Dose 
A dose up to 50 mg/kg SAB-176 will be administered as a single IV infusion and is supported by the data 
of the previous clinical trial and the relevant non-clinical data for this investigational medicinal product (IMP). 
Based on the non-clinical toxicology results in New Zealand white rabbits, the no observed adverse effect 
level was 725.30 mg/kg/day or higher. The 725.30 mg/kg dose was the maximum dose available to test 
due to dose volume limitations for the species. Using body surface area calculations (FDA guidance for 
industry 2005) and 5X safety factor, a dose up to 50 mg/kg (the maximum therapeutic target dose for 
SAB-176) is equivalent to 770.8 mg/kg in rabbits. 
4.3. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the study 
including the last scheduled visit or the last unscheduled visit as applicable. If a safety visit is required after 
the last scheduled visit, this will be at the PI’s discretion as a duty of care, e.g., repeat spirometry or 
laboratory tests. These discretionary follow-up visits will not be considered part of the trial data unless they 
represent follow-up and closure on an AE or SAE identified during the study period. 
The end of the study is defined as the date of the last scheduled visit of the last participant in the study. 

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5. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as protocol 
waivers or exemptions, is not permitted. 
Up to 60 participants having passed both the hVIVO Generic Screening process and meeting the 
inclusion / exclusion criteria of the study and inoculated with Influenza A/California/2009 H1N1 virus on 
Day 0, will be randomised onto the study in a 1:1 ratio active:placebo. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply: 
NO 
INCLUSION CRITERIA 
1 
An informed consent document signed and dated by the participant and the 
Investigator. 
2 
Aged between 18 and 45 years on the day of signing the study specific ICF. 
3 
In good health with no history, or current evidence, of clinically significant medical 
conditions, and no clinically significant test abnormalities that will interfere with 
participant safety, as defined by medical history, physical examination, (including vital 
signs), ECG, and routine laboratory tests as determined by the Investigator. 
4 
A documented medical history prior to enrolment. 
5 
The following criteria are applicable to female participants participating in the study. 
a) Females of childbearing potential must have a negative pregnancy test prior 
to enrolment. 
b) Females of non-childbearing potential: 
a. Post-menopausal females: defined as having a history of amenorrhea 
for >12 months with no alternative medical cause, and /or by follicle 
stimulating hormone (FSH) level >40mIU/mL, confirmed by laboratory. 
b. Documented status as being surgically sterile (e.g., tubal ligation, 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). 
6 
The following criteria apply to female and male participants: 
a) Female participants of childbearing potential must use one form of highly 
effective contraception. Hormonal methods must be in place from at least 
2 weeks prior to the first study visit. The contraception use must continue until 
28 days after the date of dosing with IMP. Highly effective contraception is as 
described below: 
a. Established use of hormonal methods of contraception described 
below (for a minimum of 2 weeks prior to the first study visit). When 
hormonal methods of contraception are used, male partners are 
required to use a condom with a spermicide:  

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NO 
INCLUSION CRITERIA 
i. combined (oestrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  
1. Oral. 
2. Intravaginal. 
3. Transdermal. 
ii. progestogen-only hormonal contraception associated with 
inhibition of ovulation:  
1. Oral. 
2. Injectable. 
3. Implantable. 
b. Intrauterine device. 
c. Intrauterine hormone-releasing system. 
d. Bilateral tubal ligation. 
e. Male sterilisation (with the appropriate post vasectomy documentation 
of the absence of sperm in the ejaculate) where the vasectomised 
male is the sole partner for that woman. 
f. 
True abstinence - sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in relation 
to the duration of the clinical trial and the preferred and usual lifestyle 
of the participant. 
b) Male participants must agree to the contraceptive requirements below at entry 
to quarantine and continuing until 28 days after the date of dosing with IMP: 
a. Use a condom with a spermicide to prevent pregnancy in a female 
partner or to prevent exposure of any partner (male and female) to the 
IMP. 
b. Male sterilisation with the appropriate post vasectomy documentation 
of the absence of sperm in the ejaculate (please note that the use of 
condom with spermicide will still be required to prevent partner 
exposure). 
c. In addition, for female partners of childbearing potential, that partner 
must use another form of contraception such as one of the highly 
effective methods mentioned above for female participants. 
d. True abstinence - sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in relation 
to the duration of the clinical trial and the preferred and usual lifestyle 
of the participant. 
c) In addition to the contraceptive requirements above, male participants must 
agree not to donate sperm following discharge from quarantine until 28 days 
after the date of dosing with IMP. 
7 
Serosuitable to the Challenge virus, as defined in the study Analytical Plan (AP). 

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5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
NO 
EXCLUSION CRITERIA 
Medical History 
1 
History of, or currently active, symptoms or signs suggestive of upper or lower respiratory 
tract (LRT) infection within 4 weeks prior to the first study visit. 
2 
a) Any history or evidence of any other clinically significant or currently active 
systemic comorbidities including psychiatric disorders (includes participants with 
a history of depression and/or anxiety). 
b) And/or other major disease that, in the opinion of the Investigator, may put the 
participant at undue risk, or interfere with a participant completing the study and 
necessary investigations. 
The following conditions apply: 
• 
Participants with clinically mild atopic eczema/atopic dermatitis and clinically mild 
psoriasis may be included at the Investigator's discretion (e.g., if small amounts 
of regular topical steroids are used, no eczema in cubital fossa; moderate to 
large amounts of daily dermal corticosteroids is an exclusion). 
• 
Rhinitis (including hay fever) which is clinically active or history of moderate to 
severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time 
of inclusion into the study and/or requiring regular nasal corticosteroids on an at 
least weekly basis, within 30 days of admission to quarantine will be excluded. 
Participants with a history of currently inactive rhinitis (within the last 30 days) or 
mild rhinitis may be included at the PI’s discretion. 
• 
Participants with a physician diagnosed underactive thyroid who have been 
controlled on treatment for at least 6 months with evidence of a normal thyroid 
function test can be included at the discretion of the PI. 
• 
Any concurrent serious illness including history of malignancy that may interfere 
with the aims of the study or a participant completing the study. Basal cell 
carcinoma within 5 years of initial diagnosis or with evidence of recurrence is 
also an exclusion. 
• 
Participants with a history of resolved mild depression and/or anxiety 3 or more 
years ago can be included if the Patient Health Questionnaire (PHQ-9) and / or 
the Generalised Anxiety Disorder Questionnaire (GAD-7) is less than or equal to 
4 on admission.  Participants with a history of stress related illness, which is not 
ongoing or requiring current therapy, with good evidence of preceding stressors 
may be included at the PI's discretion.  All participants will be assessed prior to 
enrolment with a PHQ-9 and GAD-7 questionnaire.  
• 
Participants reporting physician diagnosed migraine, cluster headache/migraine 
or prophylactic treatment for migraine is an exclusion. 
• 
Participants with physician diagnosed mild irritable bowel syndrome not requiring 
regular treatment can be included at the discretion of the PI. 

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NO 
EXCLUSION CRITERIA 
3 
Participants who have smoked ≥10 pack years at any time (10 pack years is equivalent 
to one pack of 20 cigarettes a day for 10 years). 
4 
A total body weight ≤50 kg or body mass index (BMI) ≤18 kg/m2 or ≥35 kg/m2. 
5 
Females who: 
a) Are breastfeeding, or 
b) Have been pregnant within 6 months prior to the study. 
6 
History of anaphylaxis-and/or a history of severe allergic reaction or significant 
intolerance to any food or drug, as assessed by the PI. 
7 
Venous access deemed inadequate for the phlebotomy and cannulation demands of the 
study. 
8 
a) Any significant abnormality altering the anatomy of the nose in a substantial way 
or nasopharynx that may interfere with the aims of the study and in particular any 
of the nasal assessments or viral challenge, (historical nasal polyps can be 
included, but large nasal polyps causing current and significant symptoms and/or 
requiring regular treatments in the last month will be excluded). 
b) Any clinically significant history of epistaxis (large nosebleeds) within the last 
3 months of the first study visit and/or history of being hospitalised due to 
epistaxis on any previous occasion.  
c) Any nasal or sinus surgery within 3 months of the first study visit. 
Prior or Concomitant Medications and Assessments 
9 
a) Evidence of vaccinations within the 4 weeks prior to the planned date of viral 
challenge, unless medically necessary (e.g., during an outbreak or pandemic 
situation) and at the PI’s discretion. 
b) Intention to receive any vaccination(s) before the day of Follow-up visit. (NB. No 
travel restrictions will apply after the Day 28 Follow-up visit). 
c) Receipt of influenza vaccine in the last 6 months prior to the planned date of viral 
challenge. 
10 
Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more 
of blood during the 3 months prior to the planned date of viral challenge or planned during 
the 3 months after the final visit. 
11 
a) Receipt of any investigational drug within 3 months prior to the planned date of 
viral challenge.  
b) Receipt of three or more investigational drugs within the previous 12 months 
prior to the planned date of viral challenge. 
c) Prior inoculation with a virus from the same virus-family as the Challenge virus. 
d) Prior participation in another HVC study with a respiratory virus in the preceding 
3 months, taken from the date of viral challenge in the previous study to the date 
of expected viral challenge in this study. 
e) Receipt of a pAb or biologic within the previous 12 months prior to the planned 
date of viral challenge. 

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NO 
EXCLUSION CRITERIA 
12 
a) Confirmed positive test for drugs of abuse and cotinine on first study visit. 
One repeat test allowed at PI discretion. 
b) History or presence of alcohol addiction, or excessive use of alcohol (weekly 
intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small 
glass of wine or a measure of spirits), or excessive consumption of xanthine 
containing substances (e.g., daily intake in excess of 5 cups of caffeinated drinks 
e.g., coffee, tea, cola). 
13 
A forced expiratory volume in 1 second (FEV1) <80%. 
14 
Positive HIV, active hepatitis A, B, or C test. 
Other 
15 
Those employed or immediate relatives of those employed at hVIVO or the Sponsor. 
16 
Any other finding that, in the opinion of the Investigator, deems the participant unsuitable 
for the study. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
No dietary restrictions are required before or after dose administration. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
Participants must abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, tea, cola 
drinks, and chocolate) for 48 hours prior and during quarantine and for 48 hours prior to all visits requiring 
spirometry. 
Participants must not consume alcohol for 72 hours prior and during quarantine and for 72 hours prior to 
any study site visits. 
Participants must not smoke or use tobacco or nicotine containing products for 72 hours prior to and during 
quarantine. Participants that are current smokers may be continued in the study if, in the opinion of the PI, 
cessation of smoking during quarantine will not lead to withdrawal symptoms which could interfere with the 
accurate recording on the symptom diary card. 
5.3.3. 
Activity 
Participants must refrain from strenuous exercise for 48 hours prior and during quarantine and for 48 hours 
prior to each study site visit (unless it is within the usual activity of the participant) in order to avoid potential 
spurious elevation of clinical laboratory safety parameters. 

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5.3.4. 
Other Restrictions 
Participants will be instructed to avoid close contact with vulnerable people as described in Section 2.3.1.4 
for two weeks after they leave the Quarantine Unit. 
5.4. 
Screen Failures 
Screen failures are defined as participants who sign the study specific ICF but are not subsequently enrolled 
into the study. 
For individuals who do not meet the criteria for participation in this study (screen failure), the Investigator 
will decide whether the participant should be permanently excluded from the study or invited back for repeat 
assessments (i.e., repeat clinical laboratory test) if the initial screening assessments are still within the 
allowed screening windows or rescreening for a later quarantine, as appropriate. 
 
 

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6. 
Study Intervention 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study protocol. 
Study interventions administered to participants are described in Table 2. 
6.1. 
Study Interventions Administered 
Participants will be inoculated with an Influenza A/California/2009 H1N1 virus on Day 0. Participants will 
receive an IV infusion with SAB-176 or placebo on Day 1. 
Table 2: Study Intervention 
Intervention 
Name 
SAB-176 
Placebo 
Influenza A/California/ 
2009 H1/N1 virus 
Type  
Drug 
Other 
Virus 
Dose 
Formulation 
Purified hIgG in a sterile liquid 
formulated in 10 mM glutamic 
acid monosodium salt, 262 mM 
D-sorbitol, 0.05 mg/mL 
Tween 80, pH 5.5, administered 
as a liquid solution for injection 
in 0.9% sodium chloride 
Sodium chloride 0.9% 
solution (normal 
saline) 
Ampoule, Liquid 
Unit Dose 
Strengths 
Up to 50 mg/kg 
Not applicable 
The inoculum virus titre 
is determined in an 
infectivity assay, the titre 
is reported in tissue 
culture infectious dose 
(TCID50) per mL 
(log10TCID50/mL). The 
challenge dose is 
approximately 3.5 x 106 
log10TCID50. 
Dosage Levels 
A single dose up to 50 mg/kg 
A single dose of 
0 mg/kg 
A single dose of virus 
will be delivered. 
Dose volume delivery 
method is provided in 
the AP. 
Route of 
Administration 
IV infusion 
IV infusion 
Intranasal 
Use 
Experimental 
Placebo-comparator 
Infectious challenge 
agent  
IMP and 
Non-IMP 
IMP 
IMP (Placebo) 
- 
Challenge 
- 
- 
Challenge virus 

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Intervention 
Name 
SAB-176 
Placebo 
Influenza A/California/ 
2009 H1/N1 virus 
Sourcing 
Sponsor 
Provided centrally by 
HVIVO 
Provided centrally by 
hVIVO 
Packaging and 
Labelling 
SAB-176 will be supplied in 
clear glass vials as a liquid 
purified hIgG in a sterile liquid 
formulated in 10 mM glutamic 
acid monosodium salt, with 
262 mM D-sorbitol, and 
0.05 mg/mL Tween 80, at a pH 
of 5.5. Each vial contains 
74.17 mg / mL. The vials will be 
labeled and packaged in an 
outer vial box. Packs of up to 15 
vials/boxes will be packaged 
together for ease of 
shipment/storage 
Placebo (normal 
saline) will be supplied 
by the study site 
Virus Challenge 
Inoculum will be 
provided in vials. The 
details of the virus 
challenge agent 
packaging and labelling 
will be provided in the 
AP 
Current/Former 
Name or Alias 
SAB 176 
n/a 
n/a 
 
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Interventional Product / Placebo 
SAB-176 is diluted in normal (0.9%) sterile saline under aseptic conditions. The diluted product is intended 
for administration by the IV route. The dose of IMP will be calculated. The pharmacy will prepare a bag 
containing the dose of SAB-176 plus as much normal (0.9%) saline as is needed to reach the concentrations 
for the study. The infusion of SAB-176 (active treatment) or normal saline control (placebo) will be provided 
in an opaque bag to obscure the bag (as SAB-176 may develop bubbles like IVIg if agitated). The drip 
chamber will also be covered, but accessible if needed by nursing staff for verification of flow rate, etc. The 
infusion will continue at a stable rate of up to 2.0 mL/min. Further details can be found in the Investigator’s 
Brochure. 
Participants randomised to the control (placebo) infusion will receive normal (0.9%) saline in approximately 
the same volume as they would have received if randomized to the active arm. 
hVIVO will receive supplies of investigational product / placebo after it has had Qualified Person sign off by 
the Good Manufacturing Practice (GMP) Pharmacy provider and it has been verified ready for dispatch by 
the unblinded Study Monitor. All investigational product / placebo supplies will be used only for this protocol 
and for no other purpose.  
Ready-to-dispense investigational product / placebo will be supplied by the pharmacy for each quarantine 
prior dosing. Once received at hVIVO, hVIVO will perform stock level accountability and the investigational 
product / placebo will be stored at 15 to 25ºC securely. Investigational product / placebo accountability will 
be controlled by hVIVO and monitored by the Study Monitor throughout the study and at study close-out. 

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The Investigator will ensure that all supplies are received by a responsible person, all deliveries and returns 
are documented and signed for, and the condition of the investigational product / placebo is monitored. 
Accurate records will be kept of when and how much investigational product / placebo is dispensed and 
used in the study. Any reasons for departure from the protocol dispensing regimen will be recorded. 
Accountability records will be available for verification by the Study Monitor at each monitoring visit. At the 
completion of the study, there will be a final reconciliation of all investigational product / placebo. 
6.2.2. 
Challenge Virus 
Challenge virus inoculum will be prepared according to the hVIVO AP and administered in accordance with 
hVIVO's standard operating procedures (SOPs). Each participant will be allocated a unique vial containing 
the Challenge virus and will receive the inoculum intranasally. 
The Challenge virus stock, Influenza A/California/2009 H1N1, was manufactured under current GMP. The 
Challenge virus stock has undergone quality testing performed during manufacturing (identity, appearance, 
sterility, infectivity, and contaminants) according to pre-determined specifications, and has subsequently 
also passed an extensive panel of adventitious agent testing. The Challenge virus is stored in a 
secure -80°C freezer (normal temperature range -60°C to -90°C). 
The time from the Challenge virus inoculum thawing to inoculation should be no longer than 4 hours. All 
administrations will be made by a member of the clinical team and witnessed by a second member of the 
team. The exact time of inoculation will be recorded in the administration log. Accurate records will be kept 
of when and how much study inoculum is prepared and used. The oversight process will be signed off prior 
to administration of the Challenge virus. Any non-compliance or problems with the inoculation will be 
recorded in the participant’s source notes and reported to the PI. 
6.2.3. 
All Study Interventions 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported and 
resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only authorised study 
site staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance with 
the labelled storage conditions with access limited to the Investigator and authorised study site 
staff. 
3. The Investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study intervention accountability, reconciliation, and record maintenance (i.e., receipt, 
reconciliation, and final disposition records) 
4. Further guidance and information for the final disposition of unused study interventions are provided 
in the Study Reference Manual or other specified location. 
6.3. 
Randomisation and Blinding 
hVIVO assigns a unique 6 digits number to each participant in the hVIVO database. This number will be 
used to identify a participant up to the point of randomisation, on source documents, on all study 

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correspondence and in the study database. A separate randomisation number will be allocated to the 
participants at randomisation and will be used for allocation of study intervention (SAB-176 or placebo). 
A computer-generated randomisation schedule will be generated using SAS. Once assigned, that 
randomisation number shall not be reassigned. 
Randomisation numbers will follow a 3-digit format e.g., [001]. A copy of the randomisation code list will be 
sent to the unblinded pharmacist preparing the study intervention, so that study intervention (SAB-176 or 
placebo) can be prepared for each participant as appropriate. The randomisation number encodes the 
participant’s assignment to receive SAB-176 or placebo in a 1:1 ratio. 
Each participant will be dispensed blinded study intervention, labelled with his/her unique randomisation 
number, throughout the study. With the exception of the unblinded pharmacist, the unblinded person 
preparing the randomisation code list, the unblinded Clinical Research Associate and the Quality Assurance 
auditors where necessary, the Investigator and all other clinical and non-clinical staff, (including the Study 
Statistician, data management staff), and the participants will remain blinded to the treatment allocation 
until after the database has been locked and approval for study unblinding has been given. 
Following database lock, on receipt of authorisation from the Sponsor, a copy of the randomisation code 
list will be provided to the Study Statistician to conduct study unblinding prior to analysis. 
Participants who are replaced as per Section 7.4 will be replaced and assigned a new, unique 
randomisation number equalling the randomisation number of the replaced participant, plus 100. This will 
ensure that the replacement participant receives the same allocated blinded study intervention as the 
participant who is being replaced. 
An individual access to a secured website will be provided to the Investigator. The website, compliant with 
21CFR part 11 guidelines, will be used if unblinding is required. In case of an emergency, the Investigator 
has the sole responsibility for determining if unblinding of a participant’s study intervention assignment is 
warranted. Participant safety must always be the first consideration in making such a determination. If the 
Investigator decides that unblinding is warranted, the Investigator should make a reasonable attempt to 
contact the Sponsor prior to unblinding a participant’s intervention assignment, provided that this would not 
delay emergency treatment of the participant. When the Investigator breaks the code, they will have to 
indicate on the website the reason for unblinding. The person who carried out the unblinding and the date 
and time of code breaking will be automatically recorded. After confirmation of the code break, the treatment 
allocation will appear on the screen. A notification with the treatment allocation will also be provided by 
email. A notification, without the treatment allocation, will be provided to the study team. Furthermore, the 
Sponsor must be notified within 24 hours after breaking the blind. Once the study is complete, the unblinded 
database will be provided to the Sponsor. 
Even if the code is broken, blood samples for safety will continue to be drawn for the remainder of the 
planned study period following the last dose as long as doing so will not compromise participant welfare. 
The study intervention must be discontinued after unblinding, but the participant will be followed up until 
resolution of any AEs. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the study site, they will receive study intervention and Challenge virus 
directly from the Investigator or designee, under medical supervision. The date and time of each dose 

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administered at the study site will be recorded in the source documents and recorded in the case report 
form (CRF). The dose of study intervention and study participant identification will be confirmed at the time 
of dosing by a member of the study site staff other than the person administering the study intervention. 
Any non-compliance or problems with the administration of the study intervention will be recorded in the 
participant’s source notes and reported to the Sponsor if appropriate. 
6.5. 
Concomitant Therapy 
Any medications taken and changes in medications from the time the participant signing the study specific 
ICF, up to final study contact Day 28 (±3 days), will be recorded in the source data. Any medication 
(including over-the-counter or prescription medicines, vitamins, and/or herbal supplements) or other 
specific categories of interest that the participant is receiving at the time of enrolment or receives during the 
quarantine/outpatient stage will be stored, prescribed and administered in line with their label-specific 
requirements, and recorded according to the parameters required by the clinical database. 
Participants will be reminded to refrain from using any over-the-counter medication without the approval of 
the Investigator and must notify the study site as soon as possible if they are prescribed any medication. 
All medications must be stopped prior to the planned date of viral challenge unless in the opinion of the 
Investigator and/or Sponsor’s Medical Expert (SME), the medication will not interfere with the study 
procedures or compromise participant safety. 
Medications prohibited throughout the study are shown in Table 3. 
Table 3: Prohibited Medication (Healthy Participants) 
Prohibited medication 
Washout 
Systemic (oral and parenteral) antiviral drugs. 
4 weeks prior to first study visit. 
Influenza vaccine 
6 months prior to first study visit. 
Use or anticipated use during conduct of the study 
of concomitant medications (prescription and non-
prescription), including vitamins or herbal and 
dietary supplements within the specified windows, 
unless in the opinion of the Investigator the 
medication will not interfere with the study 
procedures or compromise participant safety. 
Within 7 days prior to the planned date of viral 
challenge: 
• 
Herbal supplements 
• 
Any medication or product (prescription or over 
the counter) for symptoms of nasal congestion  
• 
Short and long-acting antihistamines. 
 
Within 21 days prior to the planned date of viral 
challenge: 
• 
Chronically used medications, vitamins, or 
dietary supplements, including any medication 
known to be moderate/potent inducers or 
inhibitors of cytochrome P450 (CYP) enzyme. 
Any IMP used in another trial 
Within 3 months (or 5 half-lives of the IMP used in 
the other trial), whichever is greater, prior to the 
planned date of viral challenge. 

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Any concomitant medication required for the participant’s welfare may be given by the Investigator. 
However, it is the responsibility of the Investigator to ensure that details regarding the medication and the 
reason for its use are recorded appropriately in the source notes to permit their transfer to the clinical 
database. 
The use of paracetamol and/or other allowed medications is permissible up to 7 days before the date of 
viral challenge. During the study periods, the Investigator may permit a limited amount of paracetamol (no 
more than 4 g per day i.e., maximum daily dose) or topical medication, as clinically required for the treatment 
of headache or any other pain. Other medication to treat AEs may be prescribed if required. 
Medications which are permitted throughout the study are shown in Table 4. 
Table 4: Permitted Medication 
Permitted medication 
Time period 
Paracetamol 
Maximum 4 g daily during the study period at PI 
discretion. 
Oral contraceptives 
Allowed at any time during the study. 
Prescription and non-prescription medications, including vitamins or herbal and dietary supplements, not 
listed in prohibited medications are subject to approval by the PI. 
6.6. 
Dose Modification 
Not applicable. 

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7. 
Discontinuation of Study Intervention/Withdrawal 
7.1. 
Participant Withdrawal 
A participant may withdraw his/her consent to participate in the study at any time, for any reason, without 
prejudice to his/her future medical care. Participants may decline to give a reason for their withdrawal. 
Additionally, the PI may withdraw a participant if, in their clinical judgement, it is in the best interest of the 
participant or if the participant cannot comply with the protocol. Wherever possible, the tests and 
evaluations listed for the Early Withdrawal visit should be carried out, and if clinically indicated, the 
participant should be invited back for a final follow up visit.  
The Sponsor should be notified of all study withdrawals in a timely manner, and in cases where the 
withdrawal is due to a medical reason the participant would be referred to his/her GP. 
Participants will be counselled that early withdrawal from the viral challenge phase of the study is strongly 
discouraged, as it may pose a risk both to the participant and his/her contacts. In the event of a participant 
insisting on early withdrawal during the challenge isolation period, the participant will be encouraged to stay 
and would be advised of the potential risks of carrying Influenza A/California/2009 H1N1 virus infection into 
the community, and to vulnerable groups in particular as described in Section 2.3.1.4. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken and not 
tested, and the Investigator must document this in the site study records. 
7.2. 
Participant Discontinuation 
Participants will be withdrawn from study intervention for the reasons listed below. These participants must 
not receive any additional intervention but should continue to be followed for safety and immunogenicity. 
Additional unscheduled visits may be performed for safety reasons. 
• 
Non-compliance with the study requirements and restrictions. 
• 
Clinically significant abnormal laboratory findings, which in the opinion of the Investigator(s) 
and/or Sponsor, precludes further participation in the study. 
• 
Development of inter-current illness which, in the opinion of the Investigator would compromise 
the health of the participant or the study objectives. 
• 
The Investigator’s decision that withdrawal from further participation would be in the participant’s 
best interest. 
• 
Termination of the study at the discretion of the Investigator(s) or Sponsor for safety, behavioural, 
or administrative reasons. 
• 
The wish of the participant. 
• 
Any intervention related SAEs. 
• 
Anaphylactic reaction following dosing. 
• 
The participant becomes pregnant. 
Participants who are withdrawn from the study, will be requested to attend an Early Withdrawal Visit, with 
assessments as detailed in the SoA (Section 1.2). 

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7.2.1. 
Temporary Discontinuation / Temporary Delay in Enrolment  
At the first study visit if a participant is found to be ineligible due to transient circumstances (such as acute 
disease and/or fever), dosing with IMP or inoculation will be postponed until the transient circumstances 
have been resolved and the participant will be re-invited to a later quarantine group within the allowed time 
window. For participant rescreening refer to Section 5.4. 
7.3. 
Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits 
and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the study site for a required study visit: 
• 
The study site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain whether or not the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the Investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a follow-up letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1. 
7.4. 
Participant Replacement Strategy 
Participants may be replaced in this study. 
If a participant discontinues from study intervention OR withdraws from the study a replacement participant 
may be enrolled if deemed appropriate by the Investigator and Sponsor. The replacement participant will 
generally receive the same allocated blinded study intervention as the participant being replaced. The 
replacement participant will be assigned a new unique randomization number. 
7.5. 
Stopping Rules 
The PI and the SME will perform safety reviews on available clinical and virology data as appropriate during 
the quarantine period. 
Three clinical scenarios relating to the incidence of SAEs/suspected unexpected adverse reactions 
(SUSARs) during the study and the procedures that should be performed in each case are presented in the 
Table 5 below: 

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Table 5: Study Stopping Rules 
Status 
Criterion 
Procedure 
1 
A report has been received of one (or 
more) SUSAR(s) in any, one (or more) 
participant(s). 
If such a status occurs at any point during the 
study, then further administration of SAB-176 
will not take place. The PI and the SME will 
review the data and make decisions on 
whether it is appropriate to recommence 
dosing (approval of a substantial amendment 
from the competent authorities is required) or 
terminate the study. 
2 
No SUSAR have been reported but an 
overall pattern of clinical changes or 
symptoms exists, attributed to the IMP, 
which may appear minor or moderate in 
terms of individual AEs, but which 
collectively represent a concern for safety. 
If such a status occurs at any point during the 
study, then further administration of IMP will 
not take place. The PI and the SME will review 
the data and decide on whether it is 
appropriate to recommence dosing (approval 
of 
a 
substantial 
amendment 
from 
the 
competent authorities is required) or terminate 
the study. 
3 
Unexpected 
virus-related 
SAE 
or 
unexpected virus-related AEs of clinical 
concern have been reported following 
HVC. 
*Expectedness will be assessed by 
referring to the Challenge virus dossier. 
If such a status occurs at any point during the 
study, then the PI and the SME will review the 
data and decide based on expectedness* of 
the viral event. 
If 
the 
event 
is 
unexpected, 
further 
administration of the virus will not take place. 
The PI and the SME will review the data and 
decide on whether it is appropriate to 
recommence 
inoculation 
(approval 
of 
a 
substantial amendment from the competent 
authorities is required) or terminate the study. 
In any event, participant follow-up should continue until resolution or stabilisation of AEs and final follow-up 
on Day 28 (±3 days). 
Further enrolment into the study may be either temporarily or permanently discontinued if: 
• 
An unacceptable number of severe or life-threatening exacerbations take place (as determined 
by the PI). 
• 
If two or more (or a group of participants) experience clinically significant life-threatening AEs 
that are deemed to be significant by the PI. 
Development of a group or cluster of clinically significant AEs that represent a safety risk to participants 
that are deemed to be significant by the PI. 
 
 

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8. 
Study Assessments and Procedures 
Unless otherwise stated, study assessments will be performed according to hVIVO SOPs. 
Study procedures and their timing are summarised in the SoA (Section 1.2). Protocol waivers or exemptions 
are not allowed. Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. Immediate safety concerns should be discussed with the Sponsor 
upon occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
All screening evaluations must be completed and reviewed to confirm that potential participants meet all 
eligibility criteria. The Investigator will maintain a screening log to record details of all participants screened 
and to document eligibility or record the reasons for screening failure, as applicable. 
For all study assessments, the nearest value obtained prior to dosing will be used as the baseline measure 
for assessments, unless stated otherwise.  
Procedures conducted as part of the hVIVO Generic Screening process and obtained before signing of the 
study specific ICF may be utilised for screening or baseline purposes provided the procedures met the 
protocol-specified criteria and were performed within the time frame defined in the SoA. 
Where applicable, unless otherwise stated, normal ranges will be identified in the Investigator Trial Master 
File (TMF). 
• 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 550 mL for any given 
8-week period. Repeat or unscheduled samples may be taken for safety reasons or for 
technical issues with the samples. 
8.1. 
Medical and Medication History 
Medical and medication histories including any allergies will be recorded at screening and on Day -2 / -1, 
including, but not limited to, detailed histories on allergies (e.g., rhinitis, dermatitis, food, 
aspirin / non-steroidal anti-inflammatory drugs and asthma). 
8.2. 
Demographics 
Demographic data will be recorded at screening. 
8.3. 
Height, Weight and Body Mass Index 
Height and weight measurements will be recorded in compliance with hVIVO’s standard procedures. 
BMI will be calculated as: BMI (kg/m2) = Weight (kg) 
 
 
 
 
 
 
 
 
 
 
 
Height (m)2 
8.4. 
Alcohol Breath Testing 
Alcohol breath testing will be conducted to determine compliance with the study alcohol restrictions. 
Additional tests may be conducted for assessing eligibility at the discretion of the Investigator. Results will 
be recorded in the source documents. 

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8.5. 
Urine Samples and Assessments 
8.5.1. 
Urinalysis 
Clinical urine safety analysis will be undertaken using commercially available urine test strips that provide 
an instant result that will be documented in the source data. 
Urinalysis will be performed to evaluate the parameters described in Appendix 2. 
If the dipstick yields abnormal results, a urine sample may be sent for microscopy, culture, and sensitivity 
(MCS), at the Investigator’s discretion. MCS will include but is not limited to RBC, WBC, epithelial cells, 
crystals, casts, and bacteria. 
Urine safety analysis values will be evaluated by the Investigator for clinical relevance. Those deemed to 
be clinically significant will be reported as AEs. 
8.5.2. 
Drugs of Abuse 
Urinalysis will be performed for drugs of abuse and cotinine using commercially available kits that provide 
an instant result, which will be documented in the source data. 
Drugs of abuse screen will include (but is not limited to) amphetamines, barbiturates, cocaine, opiates, 
cannabinoids, and benzodiazepines. 
8.5.3. 
Pregnancy Test 
Female participants of childbearing potential are to have a urine pregnancy test at screening. Participants 
will only be enrolled if the pregnancy test is negative. 
Note: Pregnancy test must be performed even if the participant is menstruating at the time of the study 
visit. 
All female participants will have a serum sample tested for β-human chorionic gonadotrophin (β-hCG) on 
admission to quarantine. 
Blood samples will be tested for serum FSH in post-menopausal female participants only. 
8.6. 
Complete Physical Examination 
A complete physical examination to include a full systemic assessment. 
8.7. 
Directed Physical Examination 
Directed physical examinations will be conducted as deemed appropriate by the Investigator and will 
include examination of the ears, nose, throat, and chest (via stethoscope). 
Assessment and grading of any upper respiratory tract (URT) (nasal discharge, otitis, pharyngitis, sinus 
tenderness) and LRT symptoms (abnormal breath sounds externally [e.g., stridor] and on chest auscultation 
[wheezing or rhonchi, crepitations] will be performed. Physician-reported assessments of viral challenge 
related illness will be graded in accordance with their intensity and documented in the source data. 

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Following viral challenge, URT and LRT symptoms (as described above) will be expected and presumed 
to represent virus infection consequent to viral challenge and will not be additionally captured as AEs unless 
they meet the definition of an AE and are deemed to be clinically significant (in the opinion of the 
Investigator) to be classed as AEs. 
Following viral challenge all unexpected (in the opinion of the Investigator) directed physical examination 
findings will be captured as AEs, along with all other occurrences that meet the criteria for an AE. 
8.8. 
Vital Signs 
Vital signs assessments will be recorded as follows: 
• 
Heart rate (HR) will be recorded in beats per minute. 
• 
Respiratory rate (RR): respirations will be counted and recorded as breaths per minute. 
• 
Blood pressure (BP): systolic BP and diastolic BP will be measured in millimetres of mercury 
(mmHg); measurements will be made supine. Where possible, the same arm will be used for all 
measurements. 
• 
Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry. 
In the event of a participant having an unexpected abnormal or out of normal range result, the assessment 
may be repeated after at least 2 minutes to exclude a technical fault and confirm the original reading. The 
assessment may then be repeated at the PI’s discretion and in accordance with hVIVO’s SOPs. 
Study specific normal ranges are provided in Appendix 4. If a result is out of the normal range and meets 
the criteria for an AE, the severity of the AE will be guided by the Division of Microbiology and Infectious 
Diseases (DMID) Adult Toxicity Table November 2007. 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the deterioration 
fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated vital sign will be considered as additional 
information. 
8.9. 
Tympanic Temperature 
The study specific normal range for tympanic temperature is detailed in Appendix 4.The severity of out of 
normal range values will be assigned using the DMID toxicity scale as a guide. 
Temperature may be more frequently monitored in quarantine if appropriate. 
Following viral challenge, pyrexia will be expected and presumed to represent virus infection consequent 
to viral challenge and will not be additionally captured as an AE unless it meets the definition of an AE and 
is deemed to be clinically significant (in the opinion of the Investigator) to be classed as an AE. 
Following viral challenge all unexpected (in the opinion of the Investigator) pyrexia will be captured as an 
AE, along with all other occurrences that meet the criteria for an AE. 
Febrile illness is defined as any occurrence of temperature ≥37.9oC. 

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8.10. 
Exploratory Wearables and Continuous Monitoring 
Participants may be given the option to take part in a separate ethically approved exploratory 
non-interventional trial that aims to collect physiological data via a wearable device. Participants will have 
the wearable device trial explained to them and a choice to opt into the trial, which will require them to 
consent to wear a wearable device (such as a wrist-or armband during the challenge trial, via an additional 
informed consent, which will be separately ethically approved). There will be no impact on participants 
eligibility and/or safety follow-up or treatment in the challenge trial. The wearable device will not replace 
any conventional safety monitoring. All participants will be monitored for AEs related to the wearable device 
from signing of the wearable device ICF to the end of data capture. An AE related to the wearable device 
may lead to discontinuation of the exploratory wearable study, without having an impact on the human 
challenge trial. 
8.11. 
Participant Diary Cards 
Symptom Diary Card (Categorical and Visual Analogue Scale) 
Participants will report and assess the severity of any Challenge virus-related symptoms using the hVIVO 
symptom diary card. This information will be collected using a paper form. 
The following symptoms in the 13-item symptom questionnaire will be graded on a scale of 0-3 (Grade 0: 
No symptoms; Grade 1: just noticeable; Grade 2: clearly bothersome from time to time but does not interfere 
with me doing my normal daily activities; Grade 3: Quite bothersome most or all the time, and it stops me 
participating in activities: Shortness of Breath and Wheeze have an additional Grade 4: Symptoms at rest: 
• 
Runny nose 
• 
Stuffy nose 
• 
Sneezing 
• 
Sore throat 
• 
Earache 
• 
Malaise/tiredness 
• 
Headache 
• 
Muscle and/or joint ache 
• 
Chilliness/Feverishness 
• 
Cough 
• 
Chest tightness 
• 
Shortness of breath 
• 
Wheeze 
Additional to the categorical symptom diary card, a Visual Analogue Scale dairy card using a 100 mm scale, 
with the same symptoms, will be completed by the participants. 
Participant cold perception questions 
Two additional cold-related questions will be answered by the participant each morning. The first question 
asks whether the participant’s perception of whether they have a cold or not, the second asks the 
participant’s perception of improvement/worsening of the cold. 
1. Do you have a cold: Yes/No 

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If the participant selects Yes to having a cold, then the second 7-point Likert scale “global change since 
yesterday” question is completed by the participant, as below: 
2. Compared to yesterday, I feel that my cold is: 
• 
Very much better 
• 
Somewhat better 
• 
A little better 
• 
The same 
• 
A little worse 
• 
Somewhat worse 
• 
Very much worse 
8.12. 
Nasal Discharge Collection from Paper Tissues 
Each participant will be given pre-weighed packets of paper tissues. Participants will be asked to place 
single tissues used for nose blowing or sneezing into a specified bag (for that participant only). 
A daily 24-hour collection will take place throughout the quarantine period. Distribution of paper tissues and 
bags will start on Day -1, with the first collection on Day 0. Thereafter distribution and collection of tissues 
will occur at the same time points (±1 hour) with tissues distributed 24 hours ahead. Tissues will be handed 
out daily and collection will occur until the discharge from quarantine. 
In the event of a participant staying in quarantine beyond the planned day of discharge, the 24-hour 
distribution and collection of tissues and bags will continue until the participant is finally discharged from 
quarantine. 
24-hour paper tissue collections will be analysed to determine the following over the quarantine period: 
• 
24-hour nasal discharge weight. 
• 
The number of paper tissue used for nasal discharge over 24-hour period. 
8.13. 
Electrocardiogram 
Study specific normal ranges are provided in Appendix 4. 
Twelve-lead ECGs will be obtained to evaluate the electrical activity of the heart. ECGs will be read on site 
by an appropriately qualified Investigator. Wherever possible the same Investigator will review subsequent 
ECGs from the same participant for the assessment of any change from baseline. 
Any changes from baseline during the study will be assessed for their clinical significance. Clinically 
significant changes will be reported as AEs. The PI or delegate will assess non-clinically significant changes 
to determine whether they should be recorded. 
8.14. 
Spirometry 
Spirometry will be performed according to hVIVO’s procedures. Height at screening will be used as the 
baseline measurement for all spirometry assessments. 
Spirometry should meet the American Thoracic Society/European Respiratory Society guidelines criteria 
(Miller et al. 2005). For FEV1 and forced vital capacity (FVC), the highest value from a minimum of 

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three technically satisfactory attempts will be considered. For FEV1 and FVC the highest and the second 
highest value should not exceed more than 150 mL or 5% (whichever is greater). If the difference is larger, 
up to eight technically acceptable measurements will be made with repeatability assessed after each 
additional attempt. If after eight technically acceptable attempts the difference remains greater than 150 mL 
or 5% (whichever is greater) the highest values will be reported, and an operator comment will be made to 
the source data. FEV1 and FVC will be assessed and reported as the highest values regardless of curve. 
Predicted values will be calculated according to the formula of the European Coal and Steel Community.  
Spirometry may be repeated at any time in the event of respiratory signs or symptoms (repeated coughing, 
bradypnea, tachypnoea, rales, and rhonchi) or respiratory difficulties. 
8.15. 
Questionnaires 
Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder Questionnaire (GAD-7) 
PHQ-9 and GAD-7 questionnaires will be used to assess participants’ eligibility and current mental state 
regarding ability to tolerate isolation in the Quarantine Unit. 
8.16. 
Blood Samples 
A maximum volume of 550 mL of blood may be taken from each participant for any given 8-week period. If 
additional samples are required in excess of this amount, e.g., to monitor abnormalities, these will be 
collected at the discretion of the Investigator. 
8.16.1. 
Safety Blood Analysis and Assessments 
Appendix 2 describes the safety blood tests that will be performed including, but not limited to, serology, 
haematology, coagulation, biochemistry, thyroid function test and cardiac enzymes. Additional safety 
assessments will be conducted at the discretion of the PI/Investigator, as required. 
Serum samples will be tested for serum FSH in post-menopausal female participants only and for serum 
pregnancy test in all female participants. 
8.16.2. 
Challenge Virus Serology Samples 
A participant must be serosuitable to take part in the study, i.e., he/she must have no or low pre-existing 
serum levels of antibodies specific to the Challenge virus. This antibody titre cut-off for serosuitability will 
be described in the AP. 
Serum levels of pre-existing Virus specific antibodies to the Challenge virus will be determined using 
HAI influenza or as described in the AP. 
8.16.3. 
Pharmacokinetic Blood Samples 
Blood samples for determination of SAB-176 serum concentrations will be collected as outlined in the 
pharmacokinetic (PK) sampling schedule below: 

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Sampling schedule: 
Day 1 (IMP / placebo administration day): one sample pre-infusion and one sample at 1-hour post-infusion 
end (infusion end includes any time required for flushing), and at Days 2, 4, 6, 8, and 28. 
The allowable time windows for the sampling are as follows: 
• 
±5 minutes from the scheduled time for time points ≤1-hour post-infusion end. 
• 
Allowable time windows from the scheduled time for time points >1-hour post-infusion end: 
o 
Day 2 timepoint (24 hours after infusion end): ±1 hour window. 
o 
Day 4 timepoint (72 hours after infusion end): ±2 hours window. 
o 
Day 6 timepoint (120 hours after infusion end): ±2 hours window. 
o 
Day 8 timepoint (168 hours after infusion end): ±2 hours window. 
o 
Day 28 timepoint (648 hours after infusion end): ±2 days window. 
• 
There is no time window requirement for the pre-infusion sample. The pre-infusion PK sample 
must be taken on the same day prior to infusion. 
Blood samples will be transported, processed, and stored in accordance with the AP. Pharmacokinetic 
analysis will be performed using HAI and neutralisation assays against the H1N1 strain at each participant 
collection timepoint. This analysis will be conducted at both hVIVO and Sponsor designated laboratories. 
8.16.4. 
Anti-drug Antibodies 
Blood (serum) samples will be collected to measure the incidence of ADAs to SAB-176 during the trial and 
follow the same sampling schedule for the PK blood samples as outlined in Section 8.16.3. 
Blood samples will be transported, processed, and stored in accordance with the AP. ADA sample 
evaluations will be performed by the Sponsor designated laboratory. 
8.16.5. 
Blood for Immunology Biomarker Evaluations 
Blood may be used for exploratory analysis related to viral infection, for example: 
• 
Genomics (e.g., GWAS, SNPs). 
• 
Transcriptomics (e.g., microarray, RNA sequencing). 
• 
Immunological markers (proteomics, cytokines, and chemokines) 
8.17. 
Nasal Samples 
Nasal sampling procedures will be performed for the following purposes during the study: 
• 
Respiratory Pathogen Screen. 
• 
Influenza discharge test. 
• 
Viral load assays. 
• 
Exploratory purposes: 
o 
Nasal PK 
o 
Viral resistance 
o 
Immunological markers. 
Where any nasal sampling time points occur together the order of sampling will typically be (1) nasosorption 
or mid turbinate swab, (2) nasopharyngeal swab (3) nasal wash. 

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Tolerance of the nasal procedure(s) may be determined at the screening visit, as appropriate. 
Remaining cells and epithelial lining fluid from the nasopharyngeal swabs may be stored for exploratory 
purposes. 
8.17.1. 
Respiratory Pathogen Screen 
On entry to quarantine, a nasopharyngeal swab (or nasal wash) will be collected and tested to detect the 
presence of a set of respiratory pathogens that could potentially contraindicate a participant’s participation 
in the study. The methodology to be used to conduct the respiratory virus screen will be documented in the 
AP. Additional test may be conducted if the results from the first test were invalid to support study eligibility 
prior to virus inoculation, or if a community acquired infection is suspected during quarantine. 
Any additional screening tests will be conducted at the discretion of the PI. 
8.17.2. 
Rapid Influenza Discharge Test 
A rapid viral antigen test will be used to determine the presence of influenza only in a nasopharyngeal swab 
(or nasal wash) sample taken prior to discharge from the Quarantine Unit on Day 8. A qualitative PCR 
screening test may be used as an alternative test for this purpose. 
8.17.3. 
Viral Load 
Nasopharyngeal swabs (or nasal washes) will be collected for viral load assays. Viral load may be 
determined by qRT-PCR and a cell-based infectivity assay (TCID50) if PCR positive, to investigate the 
following parameters: 
• 
infectivity status and rate. 
• 
viral dynamics (e.g., duration, peak, time to peak). 
8.17.4. 
Exploratory Analyses 
8.17.4.1. Nasal Pharmacokinetics 
Nasal sample aliquots (nasosorption / mid turbinate swab) may be processed, stored, and analysed for 
exploratory PK analysis in accordance with the AP. 
8.17.4.2. Viral Resistance 
A portion of each nasal sample may be processed, stored, and analysed for resistance analysis, in 
accordance with the AP. 
8.17.4.3. Immunology 
A portion of each nasal sample may be processed, stored, and analysed for immunological markers, in 
accordance with the AP. 

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8.18. 
Recording of Adverse Events and Serious Adverse Events 
The PI/Investigator is responsible for ensuring that all AEs, SAEs, and pregnancies are identified, 
evaluated, recorded, and reported in a timely manner as per Regulatory requirements and hVIVO’s SOPs, 
and also for ensuring that the medical management (including follow up) of AEs, SAEs and, where 
appropriate, pregnancy symptoms/complications is provided by competent Investigator site staff. 
The Sponsor of the study will also perform an evaluation of seriousness, causality, and expectedness of all 
SAEs.  
The definitions of an AE or SAE, as well as the method of recording, evaluating, and assessing causality 
of AE and SAE and the procedures for completing and transmitting AE, SAE, and other reportable safety 
event reports can be found in Appendix 3. 
8.18.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs / SAEs will be collected from the signing of the study specific ICF until the last follow-up visit at the 
time points specified in the SoA (Section 1.2). 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study participation. 
However, if the Investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and he/she considers the event to be reasonably related to the study intervention 
or study participation, the Investigator must promptly notify the Sponsor. 
8.18.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures for 
completing and transmitting SAE reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about AE occurrences. 
8.18.3. 
Follow-up of AEs and SAEs 
After the initial AE / SAE report, the Investigator is required to proactively follow each participant at 
subsequent visits/contacts. All AEs / SAEs will be followed until resolution, stabilisation, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further information 
on follow-up procedures is provided in Appendix 3. 
8.18.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal obligations and 
ethical responsibilities towards the safety of participants and the safety of a study intervention under clinical 
investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other regulatory 
agencies about the safety of a study intervention under clinical investigation. The Sponsor will comply with 
country-specific regulatory requirements relating to safety reporting to the regulatory authority, Research 
Ethics Committee (REC) and Investigators. 

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Investigator safety reports must be prepared for SUSARs according to local regulatory requirements and 
Sponsor policy and forwarded to Investigators, as necessary. 
An Investigator who receives an investigator safety report describing an SAE or other specific safety 
information (e.g., summary or listing of SAEs) from the Sponsor will review and then file it along with the 
Investigator’s Brochure and will notify the REC, if appropriate according to local requirements. 
Further information on regulatory reporting requirements is provided in Appendix 3. 
8.18.5. 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male participants will 
be collected from signing study specific ICF onwards until the last study assessment as outlined in the SoA 
(Section 1.2). If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 3. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) are considered SAEs. 
8.19. 
Treatment of Overdose 
For this study, any dose of any drug administered as part of the study greater than the dose prescribed by 
the protocol will be considered an overdose. 
In the event of an overdose. the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities associated with 
overdose and participants will be clinically followed up until the AE has resolved. 
3. Document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
The Sponsor is responsible for notifying the Medicines and Healthcare Regulatory Agency (MHRA) and 
REC of the potential serious breach within 7 days of becoming aware of it.  
8.20. 
Pharmacokinetics 
Further details on PK sampling and analysis are outlined in Section 8.16.3 and 8.17.4.1. 
Drug concentration information that may unblind the study will not be reported to blinded study site 
personnel until the study has been unblinded. 
8.21. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 

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8.22. 
Genetics 
A blood sample for DNA isolation will be collected from participants who have consented to participate in 
the genetic analysis component of the study. Participation is optional. Participants who do not wish to 
participate in the genetic research may still participate in the study. 
Details on processes for collection and shipment and destruction of these samples can be found in the AP. 

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9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
The main study hypothesis is that treatment with SAB-176 will reduce the VL-AUC as determined by 
qRT-PCR in healthy adult participants after they have been challenged with Influenza A/California/2009 
H1N1 virus when compared to treatment with placebo. The conclusions on efficacy will be based on the 
result of the primary analysis. Some other statistical tests will be performed for illustrative and exploratory 
purposes only. Consequently, no adjustment for multiplicity will be performed. 
9.2. 
Sample Size Determination 
Up to 60 participants will be inoculated with the Challenge virus. 
The statistical powering selected for this study is estimated to be sufficient for the primary objective and 
based upon only the primary endpoint. The targeted power for this study’s endpoint is for 80% using a 
two-sided type-one error rate of 5%. The sample size of 60 participants (30 in each arm) will allow detecting 
a 60% relative reduction in the qRT-PCR-AUC virology with SAB-176 assuming an 81% coefficient of 
variation in the control arm (taking into consideration Watson et al. 2015, Sloan et al. 2020). 
The PCR-AUC data is based on log transformed PCR data. 
The sample size indicates the number of participants to be inoculated with the Challenge virus. 
9.3. 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Enrolled  
All participants who signed the study specific ICF, their eligibility is 
confirmed, and have been inoculated with the Challenge virus. 
Randomised 
All enrolled participants randomly assigned to study intervention. 
Intent to Treat (ITT) Analysis 
Set 
All participants randomly assigned to study intervention who received 
the study intervention (SAB-176 or placebo). 
The Intent to Treat Infected 
(ITT-I) 
All participants randomly assigned to study intervention who received 
the study intervention and were infected with Challenge virus as per the 
definition of laboratory confirmed infection for this protocol 
Per Protocol (PP) Analysis 
Set (or Evaluable set) 
All participants randomly assigned to study intervention who received 
the study intervention (ITT Analysis Set participants) who have no major 
protocol deviation likely to impact the efficacy evaluation, and who 
complete the quarantine period up to the final day of quarantine, (Day 8). 

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Population 
Description 
Safety Analysis Set 
All participants randomly assigned to study intervention and who 
received at least one dose of study intervention. Participants will be 
analysed according to the intervention they actually received. 
PK Analysis Set 
All participants randomly assigned to study intervention with at least 
three post-dose PK results. 
The primary efficacy analysis will be on the PP Analysis Set. The ITT and ITT-I Analysis Sets will be used 
for supportive analyses on all or part of the primary and secondary efficacy endpoints, as defined in the 
Statistical Analysis Plan (SAP). The safety evaluation will be performed on the Safety Analysis Set. 
Additional analysis sets may be defined in the SAP. 
9.4. 
Statistical Analyses 
This section is a summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 
Venn Life Sciences will perform the statistical analyses for the study. 
Data will be analysed and reported using SAS® version 9.4 or later. 
9.4.1. 
Statistical Analysis Plan 
The SAP will be developed by Venn Life Sciences and approved by the Sponsor. The SAP will be finalised 
and signed prior to any look at unblinded of the data. The SAP will provide a more technical, detailed, and 
comprehensive description of the statistical analyses that will be computed, expanding on the protocol 
specified analyses. 
Any deviation(s) from the original statistical plan should be described and justified in an amendment to the 
protocol and/or SAP as appropriate and referenced also in the final clinical trial report. 
Further post-hoc evaluations of any exploratory endpoints may be conducted and reported separately. 
9.4.2. 
General considerations 
9.4.2.1. 
Descriptive Statistics 
Continuous variables will be summarised using the following statistics: number of available data, number 
of missing values, mean (and/or geometric mean where applicable), standard deviation, median, Q1, Q3, 
minimum and maximum values. When relevant, confidence intervals (CIs) will be computed for the mean 
or the median. 
Categorical variables will be summarised using number of available data, number of missing values, 
frequency counts for each category and corresponding percentage. Percentages will be calculated using 
the number of available data as the denominator (i.e., not including missing values). When relevant, CIs 
will be computed. If not otherwise specified in the SAP, the Wilson Score method will be used to compute 
CIs for proportions. 

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9.4.2.2. 
Inferential Statistics and Significance Testing 
Between group comparisons will be performed using appropriate two-sided hypothesis tests at the 
5% two-sided significance level, except if otherwise specified. 
For continuous variables (either raw data or log-transformed data) the difference in means, the standard 
error and the 95% two-sided CI will be presented. In case of log-transformed variables, in addition to the 
previous statistics on the log-transformed data, the geometric means and geometric mean ratio and its 
95% two-sided CI for the original variable will be presented. The Wilcoxon Rank-Sum test or the t-test or 
analysis of covariance will be used, depending on whether the endpoints are normally distributed. Details 
on the method used for each endpoint will be provided in the SAP. Methods for checking statistical model 
assumptions and alternative methods of analysis if the assumptions are not fulfilled will be described in the 
SAP. 
For categorical variables, differences in absolute frequency and/or relative risks will be presented, with their 
95% two-sided CIs. Except otherwise specified in the SAP, the Chi-square test (or Fisher exact test) will be 
used to compare frequencies between groups. 
9.4.3. 
Statistical Analysis 
9.4.3.1. 
Participant Accountability 
The number of participants receiving SAB-176 or placebo, receiving Challenge virus, withdrawing from 
study (also split by reason for withdrawal), and completing the study, and the numbers in each analysis set 
will be summarized. 
9.4.3.2. 
Protocol Deviations 
Participants data will be reviewed for major protocol deviations prior to main analysis database lock at a 
planned blinded data review meeting, and decisions will be documented within the meeting minutes. At this 
meeting, participants will be reviewed for their inclusion/exclusion in the different analysis sets. 
9.4.3.3. 
Demographic and Baseline Characteristics 
Descriptive statistics of demographics (age, sex, height, weight, BMI, and ethnicity) will be presented by 
treatment group and across all participants. Medical history information will be listed. Other baseline 
characteristics will be defined in the SAP. 
9.4.3.4. 
Compliance to Study Intervention 
Compliance with study intervention will be computed for each participant as proportion of prescribed study 
intervention actually taken. 
9.4.4. 
Primary Efficacy Analysis 
The main estimator of the primary endpoint, the median VL-AUC of Influenza A/California/2009 H1N1 virus 
as determined by qRT-PCR on nasal samples (virology), will be analysed on the PP Analysis Set. 

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The calculation of the VL-AUC will be performed on log10-transformed PCR data using the trapezoidal 
summation rule based on actual time intervals in hours. Results below the lower limit of quantification 
(LLOQ) will be given values as detailed in the SAP. 
Descriptive statistics and the 95% CI will be presented by treatment group. The difference between the two 
groups will be analysed using the Wilcoxon rank sum test. The two-sided p-value will be presented. 
The primary efficacy analysis will be complemented by the analyses of a supportive estimator (Median 
VL-AUC of Influenza A/California/2009 H1N1 virus as determined by quantitative viral culture) as well 
two sensitivity estimators: 
• 
Geometric mean of VL-AUC of Influenza A/California/2009 H1N1 virus as determined by 
qRT-PCR. 
• 
Geometric mean of VL-AUC of Influenza A/California/2009 H1N1 virus as determined by 
quantitative viral culture. 
9.4.5. 
Secondary Efficacy Analysis 
Table 6 summarises the methods for analysis of secondary endpoints. More details will be provided in the 
SAP. 
Table 6: Methods for Analysis of Secondary Endpoints 
Endpoints 
Planned analysis 
Peak viral load of VL-AUC of Influenza A/California/2009 H1N1 virus 
as defined by the maximum viral load determined by quantifiable 
qRT-PCR measurements in nasal samples starting two days post viral 
challenge (Day 2) up to discharge from quarantine. 
Wilcoxon-rank-sum test 
(alternative: t-test if underlying 
assumptions valid) 
Duration of influenza quantifiable qRT-PCR measurements in nasal 
samples. 
Wilcoxon-rank-sum test 
(alternative: t-test if underlying 
assumptions valid) 
Area under the curve over time of total clinical symptoms score 
(TSS-AUC) as measured by graded symptom scoring system 
(categorical and visual analogue scales). 
t-test if underlying assumptions 
valid 
(alternative: Wilcoxon-rank-
sum test) 
Peak symptoms diary card score: peak total clinical symptoms score 
(TSS) as measured by graded symptom scoring system (categorical 
and visual analogue scales). 
t-test if underlying assumptions 
valid 
(alternative: Wilcoxon-rank-
sum test) 
Peak daily symptom score: Individual maximum daily sum of symptom 
score. 
t-test if underlying assumptions 
valid 

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Endpoints 
Planned analysis 
(alternative: Wilcoxon-rank-
sum test) 
Number (%) of participants with Grade 2 or higher symptoms. 
Chi-square test 
Incidence of symptomatic infection due to Influenza A/California/2009 
H1N1 virus, compared to placebo as measured by: 
RT-PCR-confirmed symptomatic influenza infection defined as: 
• 
RT-PCR-confirmed influenza infection, AND  
• 
Clinical symptoms 
Chi-square test (on the 
composite and each 
component) 
 
9.4.6. 
Tertiary/exploratory Analysis 
Except if otherwise specified, no formal statistical testing will be conducted for tertiary / exploratory 
endpoints. Only the descriptive statistics will be computed. These analyses will be described in the SAP. 
9.4.7. 
Safety Analyses 
All safety analyses will be computed on the Safety Analysis Set. 
Adverse events will be coded using the most current version of the Medical Dictionary for Regulatory 
Activities (MedDRA) and tabulated by system organ class, preferred term, and treatment group for the 
number of AEs reported and the number and percentage of participants reporting each AE. 
A by-participant AE data listing including onset and resolution dates, verbatim term, preferred term, blinded 
treatment, severity, relationship to treatment, action taken, and outcome will be provided. 
Other safety data, including laboratory evaluations (biochemistry, haematology, coagulation, cardiac 
enzymes, thyroid function, and urine analysis), vital signs assessments, physical examinations, 12-lead 
ECG and spirometry will be summarized by time of collection and by treatment group. In addition, change 
from baseline will be summarized for vital signs and clinical laboratory results. 
The frequency of participants with abnormal safety laboratory results will be tabulated by treatment. 
9.4.8. 
Pharmacokinetic Analysis 
Blood PK analysis for SAB-176 will be performed using HAI and neutralisation assays against the 
H1N1 strain at each participant collection time point. This analysis will be conducted at both hVIVO and 
Sponsor designated laboratories. 
PK parameters of interest may include:  
Cmax, AUC0-t, AUC0-∞, tmax, t½ 

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Pharmacokinetic parameters will be calculated using non-compartmental methods. Parameters will be 
summarised descriptively. 
Exploratory nasal PK analysis may be performed, and parameters may be summarised descriptively. 
9.5. 
Interim Analyses  
No interim analysis (i.e., an analysis of early trial data, before enrolment is completed, to detect trends that 
might warrant modification of the protocol, change in data being collected or trial termination) is planned for 
the study. 

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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
o 
Consensus ethical principles derived from international guidelines including the Declaration of 
Helsinki and Council for International Organizations of Medical Sciences International Ethical 
Guidelines 
o 
Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
o 
Applicable laws and regulations 
• 
In addition to regulatory submission, the protocol, protocol amendments, ICF, Investigator’s 
Brochure, and other relevant documents (e.g., advertisements) must be submitted to an REC by 
the Investigator and reviewed and approved by the REC before the study is initiated. 
• 
Any amendments to the protocol will require REC approval before implementation of changes made 
to the study design, except for changes necessary to eliminate an immediate hazard to study 
participants. 
• 
The Investigator will be responsible for the following: 
o 
Providing written summaries of the status of the study to the REC annually or more frequently 
in accordance with the requirements, policies, and procedures established by the REC. 
o 
Notifying the REC of SAEs or other significant safety findings as required by REC procedures. 
o 
Providing oversight of the conduct of the study at the study site and adherence to requirements 
of ICH guidelines, the REC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations. 
10.1.2. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial information 
as requested to allow the Sponsor to submit complete and accurate financial certification or disclosure 
statements to the appropriate regulatory authorities. Investigators are responsible for providing information 
on financial interests during the course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
The Investigator will obtain a signed study specific ICF from each participant before any study specific 
procedures are performed.  
When historical screening data collected through the hVIVO Generic Screening process is used for 
screening, the study specific ICF will be obtained at quarantine admission (Day -2 / -1) from each participant 
before any study specific procedures are performed. 
Potential participants will typically be sent a copy of the ICF when their Screening Visit / Quarantine 
admission visit (as applicable) is arranged and at least a day prior to the visit and will be encouraged to 

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read it prior to their appointment. Upon arrival at the Screening Visit / Quarantine admission visit (as 
applicable), the ICF is discussed by the Investigator, and they will be given the opportunity to ask any 
questions and may take the information sheet away to consider their participation. 
All participants will be required to have a good understanding of English and the Investigator will be 
responsible for ensuring that the participant understands the information contained in the ICF. Once the 
Investigator has confirmed that the participant has understood the study, including the benefits and risks of 
participation, the participant and the Investigator can sign and date the ICF. 
The ICF must be signed and dated by the participant and countersigned by the Investigator (whoever 
conducted the consent discussion). A copy of the ICF will be given to the participant, and the original will 
be held in the hVIVO TMF. 
Participants will be assured that they can withdraw from the study at any time and for any reason without 
prejudice to their future medical care, and that they will be informed in a timely manner if new information 
becomes available that may affect their willingness to continue their participation in the study. This 
information will be included within in the ICF. 
The ICF will contain a separate section that addresses the use of samples for future research. The 
Investigator or authorised designee will explain to each participant the objectives of the exploratory 
research. Participants will be told that they are free to refuse to participate and may withdraw their consent 
at any time and for any reason.  
Participants may be given the option to take part in a separate ethically approved exploratory 
non-interventional trial that aims to collect physiological data which will require them to wear a wearable 
device via an additional informed consent, which will be separately ethically approved (for further details 
see Section 8.10). 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by hVIVO. Any participant records or datasets that are 
transferred to the Sponsor will contain the identifier only; participant names or any information which would 
make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the Sponsor in 
accordance with local data protection law. The level of disclosure must also be explained to the participant 
in ICF. 
The participant must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate REC members, 
and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
This study will not include an early safety data review. However, participant safety will be continuously 
monitored by the Sponsor’s internal/external safety review committee which includes safety signal detection 
at any time during the study. 

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10.1.6. 
Dissemination of Clinical Study Data 
The key design elements of this Protocol will be posted on publicly accessible registers, such as 
ClinicalTrials.gov. Where required, protocol summaries will also be posted on national or regional clinical 
trial registers or databases (e.g., EudraCT database) in compliance with the applicable regulations. 
It is the Sponsor’s (or Sponsor delegate) responsibility to send the Clinical Trial Summary Report to the 
REC and MHRA (if required) within 1 year of the end of the trial. In addition, the Sponsor or Sponsor 
delegate is responsible for entering appropriate data into the EudraCT results database within 1 year of the 
end of the trial. 
The PI/Investigator shall provide assurance to participants that their confidentiality will be maintained hVIVO 
have a legal obligation to protect at all times the confidentiality of participant personal data from the point 
of capture, through processing, dissemination in line with consent from the participant and to its final 
disposition. 
10.1.7. 
Data Quality Assurance 
Participant data will be collected at study site using paper source casebooks which will then be data entered 
into the electronic CRF database unless transmitted to the Sponsor or designee electronically (e.g., 
laboratory data). The Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
The Investigator must maintain accurate documentation (source data) that supports the information entered 
in the CRF. This can be paper source and/or eSource. 
The Investigator must permit study-related monitoring, audits, REC review, and regulatory agency 
inspections and provide direct access to source data documents. Monitoring details describing strategy 
(e.g., risk-based initiatives in operations and quality such as Risk Management and Mitigation Strategies 
and Analytical Risk-Based Monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues and monitoring techniques (remote or on-site monitoring) are provided in the 
Monitoring Plan. 
Study monitors will perform ongoing source data verification to confirm that data entered into the CRF by 
authorized study site personnel are accurate, complete, and verifiable from source documents; that the 
safety and rights of participants are being protected; and that the study is being conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be retained by 
the Investigator during the retention period as agreed with the Sponsor and as required by local regulations 
or institutional policies.  
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the integrity of the 
data collected. Source documents are filed at the Investigator’s site. 
Data reported on the CRF or entered in the electronic CRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The Investigator 

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may need to request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
Definition of what constitutes source data for the study can be found in the Source Data Agreement. 
10.1.9. 
Study Discontinuation 
The Sponsor reserves the right to temporarily suspend or discontinue the study for any reason at any time. 
In addition, the study may be stopped at any time if, in the opinion of the PI, the safety data suggest that 
the medical safety of participants is being compromised. 
If the study is suspended or terminated for safety reason(s), the Sponsor will promptly inform the PI, and 
will also inform the regulatory authorities of the suspension or termination of the study and the reason(s) 
for the action.  
The PI/Investigator is responsible for promptly informing the REC and providing the reason(s) for the 
suspension or termination of the study. 
If the study is prematurely terminated, all study data must be returned to the Sponsor. In addition, the study 
site must conduct final disposition of all unused IMPs in accordance with the Sponsor’s procedures for the 
study. 
Termination of the clinical trial may also be initiated by the MHRA or the REC. 
10.1.10. Publication Policy 
By signing the study protocol, the PI agrees that the results of this study may be used for the purposes of 
national and international registration, publication, and information for medical and pharmaceutical 
professionals by the Sponsor. 
If necessary, the authorities will be notified of the PI’s name, address, qualifications, and extent of 
involvement. In order to allow the use of the information derived from this clinical study, the PI understands 
that he has an obligation to provide complete test results and all data developed during this study to the 
Sponsor. 
If the study is to be published, the Sponsor and hVIVO may jointly prepare and co-author manuscript(s) 
that could result from the clinical trial. In the case the Sponsor acts as fully responsible for the publication, 
the Sponsor agrees to allow the PI time to review all manuscripts and abstracts prior to submission for 
publication. The Sponsor reserves the right to include the report of this study in any regulatory 
documentation or submission or in any informational materials. The Sponsor also reserves the right to 
delete any confidential information from any proposed manuscripts prior to submission for publication. 
Confirmation of study specific arrangements can be found in the clinical study agreement. 
Verbal or written discussion of results prior to study completion and full reporting should only be undertaken 
with written consent from the Sponsor. 
 
 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 7 will be performed by the central laboratory. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 of the 
protocol. 
Additional tests may be performed at any time during the study as determined necessary by the Investigator 
or required by local regulations. 
Table 7: Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet count. 
White blood cell (WBC) count (absolute) 
WBC differential: 
Neutrophils 
Lymphocyte 
Monocytes 
Eosinophils 
Basophils 
Red blood cell (RBC) count 
Reticulocyte count (% and absolute) 
Haemoglobin 
Haematocrit 
Mean corpuscular volume (MCV) 
Mean corpuscular haemoglobin (MCH) 
MCH concentration (MCHC) 
Coagulation 
Prothrombin time (PT) 
Activated Partial Thromboplastin Time (APTT) 
Biochemistry 
Sodium 
Potassium 
Glucose (random) 
Albumin 
Chloride 
Bicarbonate 
Calcium 
Uric acid 
Total protein 
Creatinine 
Total, direct, and indirect bilirubin 
Inorganic phosphate 
Blood urea nitrogen 
C-reactive protein (CRP) 
Gamma glutamyl transferase (GGT) 
Alkaline phosphatase (ALP) 
Alanine aminotransferase (ALT) 
Lactate dehydrogenase 

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Laboratory 
Assessments 
Parameters 
Aspartate aminotransferase (AST) 
Urea 
Thyroid function 
Thyroid Stimulating Hormone (TSH) at screening only 
Thyroxine at screening only 
Cardiac enzymes 
Creatine Kinase (CK) 
Troponin (T) 
Routine urinalysis 
Colour 
Specific gravity 
Appearance 
pH 
Presence of blood, glucose, leukocytes, ketones, nitrites, proteins, 
urobilinogen, bilirubin by dipstick 
Microscopy, culture, and sensitivity (MCS) examination (If the 
dipstick yields clinically significant abnormal results) 
Other 
screening/eligibility 
tests 
Follicle stimulating hormone (FSH)* 
β-human chorionic gonadotrophin (β-hCG) 
Glycated haemoglobin A1c (HbA1c)** 
Total cholesterol 
TSH, free thyroxine (T4) 
Antibodies against HIV-1 and HIV-2 
Hepatitis A immunoglobulin M (HepA) 
Hepatitis B surface antigen (HbsAg) 
Hepatitis C antibodies (HepC) 
Immunoglobulin A (IgA) antibodies** 
*Only for post-menopausal female participants 
**Optional at PIs discretion 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unblind the study will not be reported to investigative sites or other 
blinded personnel until the study has been unblinded. 
 
 

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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Adverse Event 
AE Definition 
An AE is defined as any untoward medical occurrence in participants. An AE can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of an IMP, whether or not considered related to the IMP, or for the 
purposes of HVC studies, the Challenge virus. 
 
Events Meeting the AE Definition 
• 
Exacerbation of a pre-existing illness. 
• 
Increase in frequency or severity of a pre-existing episodic condition. 
• 
A condition detected or diagnosed after IMP or inoculum administration even though it may have 
been present prior to the start of the study. 
• 
A complication that occurs during a hospitalisation. 
• 
A clinically significant change in laboratory parameter. 
 
Events NOT Meeting the AE Definition 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); the 
condition that leads to the procedure is an AE. 
• 
Pre-existing disease or conditions present or detected prior to start of IMP or Challenge virus 
inoculation administration that does not worsen (including screening findings such as abnormal 
laboratory results). 
• 
Hospitalisation for elective surgery, social and/or convenience admissions provided they are 
arranged before the start of IMP administration. 
• 
Over-administration of either the Challenge virus, IMP or concomitant medication without any 
signs or symptoms. 
• 
An uncomplicated pregnancy or an induced elective abortion to terminate a pregnancy without 
medical reason. 
• 
Typical/normal viral symptoms on symptom diary cards 
• 
Procedural related events may be noted during the study whilst conducting nasal sampling 
(collection of nasal wash samples or nasopharyngeal swabs), specifically: 
o 
Nasal discomfort/irritation 
o 
Nasal abrasions 
o 
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o 
Sneezing 
o 
Watery eyes 
When mild in nature and as expected in the opinion of the PI or Delegated Physician, these 
events will not be reported as AEs. 
10.3.2. 
Adverse Drug Reaction 
An adverse drug reaction is any untoward and unintended response in a participant to an IMP which is 
related to any dose administered to that participant. 
‘Response’ in this context means that a causal relationship between a medicinal product and an AE is at 
least a reasonable possibility. 
All AEs assessed by either the reporting Investigator or the Sponsor as having a reasonable causal 
relationship to a medicinal product qualify as adverse drug reactions. The expression ‘reasonable causal 
relationship’ means to convey in general that there is evidence or argument to suggest a causal relationship. 
10.3.3. 
Unexpected Adverse (Drug) Reaction 
An “Unexpected Adverse (Drug) Reaction” means an AR, the nature and severity of which is not consistent 
with the information about the medicinal product in question set out: 
(a) In the case of a product with a marketing authorisation, in the Summary of Product Characteristics for 
that product, 
(b) In the case of any other IMP, in the Investigator’s Brochure relating to the trial in question’. 
10.3.4. 
Serious Adverse Event 
SAE Definition  
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. 
Results in death. 
b. 
Is life-threatening. 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have caused 
death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
• 
In general, hospitalisation signifies that the participant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether “hospitalisation” occurred 
or was necessary, the AE should be considered serious. 

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• 
Hospitalisation for elective treatment of a pre-existing condition that did not worsen from baseline 
is not considered an AE. 
d. 
Results in persistent disability/incapacity. 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhoea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect. 
f. 
Is an important medical event: 
• 
Important medical events’ – some medical events may jeopardise the participant or may require 
an intervention to prevent one of the above characteristics/consequences. Such events should 
also be considered as ‘serious’ in accordance with the above definition.  
• 
Medical judgement should be exercised in deciding whether an AE/AR is serious. Important 
AEs/ARs that are not immediately life threatening or do not result in death or hospitalisation but 
may jeopardise the participant or may require intervention to prevent one of the other outcomes 
listed in the definition above occurring, should also be considered serious. Details of the SAE 
must be provided. 
10.3.5. 
Suspected Unexpected Serious Adverse Reaction 
A SUSAR is ‘a serious AR, the nature and severity* of which is not consistent with the information about 
the medicinal product in question, as defined in the Investigator’s Brochure relating to the trial in question. 
Medical events will be assessed for expectedness against the Reference Safety Information section of the 
Investigator’s Brochure or equivalent. Any changes to the Reference Safety Information will be deemed as 
a change to the risk/benefit profile and will require a substantial amendment to be submitted to the MHRA. 
This amendment must be approved before the changes are implemented in the study. 
*The term ‘severity’ is used here to describe the intensity of a specific event. This is not the same as ‘serious’ 
which is based on participant/event outcome or action criteria. 
10.3.6. 
Recording, Assessment and Follow-up of AE and/or SAE 
10.3.6.1. AE and SAE Recording  
All AEs and SAEs will be collected from the time of written informed consent until study completion/final 
study contact or until the resolution of the AE. AEs will be fully recorded in the source documents as they 
are reported whether spontaneously volunteered by a participant or in response to questioning about 
wellbeing at each face-to-face study visit and during telephone calls. Enquiries about AEs should cover the 
period between the previous and current visit. 

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The following are examples of open ended, non-leading questions that may be used to obtain this 
information:  
• 
How are you feeling? 
• 
Have you had any medical problems since your last visit/assessment?  
• 
Have you taken any new medicines, other than those given to you in this study, since your last 
visit/assessment? 
Following the reporting of AEs and concomitant medication, the Investigator should assess the participant’s 
eligibility to continue in the study.  
The PI will record all relevant information regarding an AE/SAE in the source documents and evaluate AEs 
using the following guidelines:  
• 
Description of events (if the event consists of a cluster of signs and symptoms, a diagnosis should 
be recorded) 
• 
Seriousness 
• 
Severity (or grade) 
• 
Onset date and time 
• 
Frequency 
• 
Date and time of resolution (or ‘continuing’ if unresolved) 
• 
Action taken 
• 
Concomitant medication 
• 
Clinical outcome 
• 
Relationship or causality (IMP/Challenge virus/ study procedures/ concomitant medication/other). 
Any clinically significant abnormal laboratory result, vital sign or other measure will be followed until it 
returns to normal or baseline values, stabilises, or is judged by the Investigator to be no longer clinically 
significant.  
If an AE is not resolved at the end of the study, the AE should be followed until it has resolved or (in the 
case of pregnancy) the pregnancy has been terminated (including spontaneous abortion), resulted in a 
birth, or a decision has been made by the Sponsor that no further follow-up is required. 
Even if the AE or SAE is assessed by the PI as not reasonably attributable to the Challenge virus, its 
occurrence must be fully documented in the source notes. 
10.3.6.2. Assessment 
Description 
If the event consists of a cluster of signs and symptoms, a diagnosis should be recorded (e.g., 
gastroenteritis) rather than each sign and symptom. 
Onset and end 
The dates and times of the onset and end of the event should be recorded. 

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Assessment  
Challenge Virus Symptoms 
The Investigator will assess, and review Challenge virus related symptoms recorded in participants’ 
hVIVO symptom diary cards. Symptoms greater than Grade 0 will be expected and presumed to 
represent virus infection consequent to Viral Challenge and will not be additionally captured as AEs 
unless they meet the definition of an AE and are deemed to be clinically significant (in the opinion of the 
Investigator) to be classed as AEs. 
Following Viral Challenge all unexpected (in the opinion of the Investigator) symptoms post inoculation 
will be captured as AEs, along with all other occurrences that meet the criteria for an AE. 
Physical Examination 
Any clinically significant change in complete physical examination findings during the study will be 
documented as an AE. 
Directed Physical Examination 
Following Viral Challenge, URT and LRT symptoms (nasal discharge, otitis, pharyngitis, sinus 
tenderness, new wheezes, rales, and rhonchi) will be expected and presumed to represent virus infection 
consequent to Viral Challenge and will not be additionally captured as AEs unless they meet the definition 
of an AE and are deemed to be clinically significant (in the opinion of the Investigator) to be classed as 
AEs. 
Vital Signs 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the deterioration 
fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated vital sign will be considered as 
additional information. 
Temperature 
Following Viral Challenge, pyrexia will be expected and presumed to represent virus infection 
consequent to Viral Challenge and will not be additionally captured as an AE unless it meets the definition 
of an AE and is deemed to be clinically significant (in the opinion of the Investigator) to be classed as an 
AE. 
Following Viral Challenge all unexpected (in the opinion of the Investigator) pyrexia post inoculation will 
be captured as an AE, along with all other occurrences that meet the criteria for an AE. 
Spirometry 
A 15% drop in a spirometry value (compared to baseline) confirmed by a repeat on the same day, will 
be a Grade 1 (mild) AE. The PI/Investigator will use his/her clinical judgement to assign severity grades 
above Grade 1, based on evaluation of clinical signs and symptoms. If the repeated value has returned 
to normal an AE will not be raised. 

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Assessment  
Laboratory Values 
Deterioration in a laboratory value (compared to baseline) should only be reported as an AE if the 
deterioration fulfils the criteria for an AE. If deterioration in a laboratory result is associated with clinical 
signs and symptoms, the sign or symptom will be reported as an AE and the associated laboratory result 
will be considered as additional information. 
The Investigator and/or SME will judge whether abnormal laboratory values are clinically significant or 
not clinically significant, and record this in the source document. This entry should be signed and dated 
by the relevant Investigator. Laboratory abnormalities detected at screening will be considered as part 
of the medical history and will not be reported as AEs. 
Challenge virus associated laboratory abnormalities (e.g.: elevated ALT, AST or GGT; decreased 
neutrophils) may be recorded as AEs (at the discretion of the Investigator). 
C-reactive Protein 
Any value above 5 mg/L but less than 60 mg/L will be a Grade 1 (mild) AE (unless deemed non clinically 
significant by the PI). The PI will use his/her clinical judgement to assign severity grades above Grade 1, 
based on evaluation of clinical signs and symptoms. 
10.3.6.3. Assessment of Intensity 
The term ’severe’ is often used to describe the intensity (severity) of a specific event. This is not the same 
as ‘serious’ which is based on participant/event outcome or action criteria. 
The Investigator will use the DMID toxicity scale as a reference when collecting, reporting, and clarifying 
database queries of AEs, SAEs, and ARs. 
The severity of an AE that does not appear in the DMID toxicity scale should be determined according to 
the definitions in Table 8. 
Table 8: Classification of Adverse Events Severity 
Grade 
Classification 
Definition 
Grade 1 
Mild 
Mild level of discomfort, and does not interfere with regular activities 
Grade 2 
Moderate 
Moderate level of discomfort and significantly interferes with regular 
activities 
Grade 3 
Severe 
Significant level of discomfort and prevents regular activities 
Grade 4 
Life-threatening  
Extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalisation or 
hospice care probable 

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An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
10.3.6.4. Frequency 
The frequency of the AE should be categorised as one of the following: 
• 
Single 
• 
Intermittent 
• 
Continuous 
10.3.6.5. Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE / SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
• 
The Investigator will also consult the Investigator’s Brochure and/or Product Information, for 
marketed products, in his/her assessment. 
• 
For each AE / SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE / SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to Sponsor’s Pharmacovigilance provider. However, it is 
very important that the Investigator always assesses causality for every event before the initial 
transmission of the SAE data. 
• 
The Investigator may change his/her opinion of causality considering follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
• 
The relationship of an AE to the IMP will be categorised as shown in Table 9: 
Table 9: Classification of Adverse Events Relationship 
Classification 
Definition 
Not related 
The AE is related to an aetiology other than the IMP (the alternative 
aetiology must be documented in the participant’s medical record). 
Unlikely to be related 
The AE is unlikely to be related to the IMP and likely to be related to 
factors other than IMP. 

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Classification 
Definition 
Possibly related 
There is an association between the AE and the administration of the 
IMP, and there is a plausible mechanism for the AE to be related to the 
IMP, but there may also be alternative aetiology, such as characteristics 
of the participant’s clinical status or underlying disease. 
Probably related 
A reasonable temporal sequence of the AE and the IMP administration 
exists and based upon the known pharmacological action of the drug, 
known or previously reported ARs to the drug or class of drugs, or 
judgment based on the Investigator’s clinical experience, the association 
of the AE with the IMP seems likely. 
Definitely related 
A definite causal relationship exists between the AE and the 
administration of the IMP, and other conditions do not appear to explain 
the AE. 
Unless an AE is ‘definitely related’ to the IMP, a causal relationship to one of the following should be 
considered, and full details provided on the AE reporting form as appropriate. 
• 
Challenge virus. 
• 
Study procedures. 
• 
Concomitant medication. 
• 
Other. 
10.3.6.6. Action Taken 
The Investigator should ensure that adequate medical care is provided to participants for any AEs, including 
clinically significant laboratory values related to the IMP. In addition, the Investigator will describe whether 
any treatment was given for the AE. 
The Investigator will classify the action taken with regard to the AE. The action taken should be classified 
according to the following categories and full details provided as appropriate: 
• 
None. 
• 
Non-drug therapy given. 
• 
Concomitant medication taken. 
• 
IMP dose not changed. 
• 
IMP dose adjusted. 
• 
IMP administration temporarily interrupted. 
• 
IMP administration permanently discontinued. 
• 
Participant withdrawn. 
• 
Participant hospitalised. 
• 
Other. 
10.3.6.7. Outcome 
An AE should be followed until the Investigator has determined and recorded the outcome or an alternative 
explanation. The outcome should be classified according to the categories shown in Table 10. 

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Table 10: Classification of Adverse Events Outcome 
Classification 
Definition 
Resolved 
Resolution of the AE with no residual signs or symptoms 
Resolved with sequelae 
Resolution of the AE with residual signs or symptoms 
Ongoing 
Either incomplete improvement or no improvement of the AE, 
such that it remains on-going 
Fatal 
Outcome of the AE was death. ‘Fatal’ should be used when 
death was at least possibly related to the AE. 
Unknown (e.g., Lost to follow-up) 
Outcome of the AE is not known (e.g., the participant is lost to 
follow-up). 
10.3.6.8. Follow-up 
All AEs and SAEs must be followed-up by the Investigator, or where appropriate, be referred to the 
Participant’s GP or other healthcare professional for follow-up until they are: 
• 
Resolved (return to normal or baseline values), or 
• 
Stabilised, or 
• 
Judged by the PI/Investigator to be no longer clinically significant, or 
• 
An alternative explanation has been provided. 
Additional measurements and/or evaluations may be necessary to investigate the nature and/or causality 
of an AE or SAE. This may include additional laboratory tests, diagnostic procedures, or consultation with 
other healthcare professionals. If the participant dies, any post-mortem findings (including histopathology) 
will be provided to the Sponsor if possible. 
10.3.7. 
Reporting of SAEs 
SAEs must be documented and reported as per hVIVO’s SOPs. 
Prompt notification of SAEs by the Investigator to the Sponsor is essential so that the Sponsor can meet 
its regulatory and REC reporting obligations for the study. If the Investigator does not have all the details 
regarding the SAE, he/she will not wait until this information becomes available before making the initial 
report to Sponsor. Contact details are detailed in Table 11. 
• 
Notification should be made: 
• 
By telephone as soon as possible and within 24 hours of the Investigator being made aware of 
the event. 
• 
In a detailed written report within 24 hours of the Investigator becoming aware of the event. 
All reports should be directed to the SME. The Investigator at the study site is responsible for ensuring that 
a member of the Sponsor study team is made aware of any SAE reports that have been transmitted. 

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Table 11: Contact Details for Reporting All Serious Adverse Events 
Contact 
Details 
Name of SME 
Thomas C. Luke 
SME SAE telephone number:  
(240) 462 2505 
Pharmacovigilance reporting email:  
hvivo-clinical@arriello.com 
Pharmacovigilance telephone reporting: 
+370 37 247 987 
SAE e-mail address:  
tluke@sabbiotherapeutics.com 
In addition, any AE resulting in permanent study discontinuation for a participant, even if not serious and 
regardless of expectedness or causality, must be reported by telephone, email, or fax to the Sponsor within 
7 calendar days of the PI or any other study site personnel’s knowledge of the event. 
The SAE form, AE record and relevant concomitant medication record should be faxed/emailed to the 
Sponsor within 24 hours of the Investigator or any study site personnel’s knowledge of a SAE. An updated 
SAE report form should be forwarded to the Sponsor within 24 hours of receipt of the new/updated 
information as relevant. 
Information relating to the participant’s subsequent medical progress must be submitted to the Sponsor as 
available, until the SAE has subsided or, in the case of permanent impairment, until it stabilises, and the 
overall clinical outcome has been ascertained. 
The Investigator will also provide additional information, including a copy of the following documents (where 
applicable): 
• 
Copies of test results, as available. 
• 
Hospital discharge summary (as soon as it is available to the PI). 
• 
Autopsy report (as soon as it is available to the PI). 
The Investigator must report SAEs/SUSARs to the relevant REC in accordance with applicable regulatory 
requirements and within the relevant timelines.  
The REC will be sent annual safety updates in order to facilitate their continuing review of the study. 
10.3.8. 
Reporting of SUSARs 
The Sponsor is responsible for assessing SUSARs, unblinding potential SUSARs, and reporting SUSARs 
to the MHRA and REC.  
The Sponsor shall ensure that all relevant information about a SUSAR that occurs during the course of a 
clinical trial in the UK and is fatal or life threatening, is reported as soon as possible to the MHRA and the 
REC. This needs to be done within 7 calendar days after the Sponsor became aware of the event. Any 
additional relevant information should be sent within 8 days of the first report being sent. 
The Sponsor shall ensure that a SUSAR which is not fatal or life-threatening is reported as soon as possible 
and in any event within 15 calendar days after the Sponsor became aware of the event. 

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10.3.9. 
Adverse Reactions to non-IMPs 
Any AEs and SAEs which are related to/caused by a concomitant medication or Challenge agent, should 
not be classed as ARs, serious ARs, or SUSARs (ARs, serious ARs, SUSARs relate only to IMP by 
definition). However, an SAE caused by a non-IMP would need to be reported to the MHRA/REC for the 
appropriate action to be taken. 
10.3.10. Post-study AEs and SAEs 
All SAEs that occur during the study from ICF signature until the last participant last scheduled visit must 
be reported by the Investigator to the SME as soon as possible, in accordance with hVIVO’s SOPs, and at 
the latest within 24 hours of becoming aware of the event. 
All SAEs that have not resolved by the end of the study, or that have not resolved upon discontinuation of 
the participant’s participation in the study, must be followed-up until the event is considered resolved, until 
the participant is lost during follow-up, or until the PI in conjunction with the Sponsor deem the event stable 
and a decision for no further follow-up has been taken. 
10.3.11. Pregnancy  
If a female participant or partner of a male participant becomes pregnant during the course of the study, 
this must be reported by the Investigator to the SME and Study Monitor by telephone as soon as possible, 
in accordance with hVIVO’s SOPs, and at the latest within 24 hours of becoming aware of the event.  
Following the telephone notification, the Investigator must fully and accurately complete the appropriate 
pregnancy reporting form, which must be e-mailed to the SME and the Study Monitor at the latest within 
24 hours of becoming aware of the pregnancy.  
Participants will be advised to contact their GP or a specialist, as appropriate.  
Consent for follow-up of the pregnancy and pregnancy outcome will be sought from the pregnant study 
participant or the pregnant partner of the male study participant as applicable. Consent for follow-up will be 
documented on an hVIVO Pregnancy Follow-up ICF.  
Provided that the appropriate consent is in place, information related to the pregnancy will be collected as 
per hVIVO’s SOPs and the Sponsor’s requirements. The completed reporting form(s) will be sent to the 
Sponsor for review and assessment, and subsequent reporting as required. 
• 
A complete evaluation will be documented in the source data to permit transfer to the clinical 
database.  
• 
The emergency code break envelopes will be requested (Section 6.3) to break the blind for the 
appropriate study participant to ensure that further care can be based on the actual identity of the 
study treatment that the participant received. 
• 
hVIVO will maintain contact with the participant for a protracted period of time, but certainly until 
after the birth, in order to assess for outcomes that may be reportable as related AEs, and for 
reporting to the Sponsor as appropriate.  
• 
hVIVO in consultation with the participant will keep the participant’s GP informed.  
• 
All cases of foetal drug exposure via the parent as a study participant will be reported to the 
Sponsor and the REC. 
 

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10.4. 
Appendix 4: Normal Ranges 
hVIVO Normal Ranges for Healthy Participants 
Vital signs normal ranges  
Vital signs 
Lower limit 
Higher limit 
Units 
Tympanic temperature 
(above 37.8 classed as 
pyrexia) 
35.5 
37.8 
oC 
Oxygen saturation 
Normal is ≥95 
% 
Respiratory rate (RR) 
10 
20 
breaths per minute 
Heart rate (HR) 
40 
100 
beats per minute 
Systolic BP 
90 
140 
mmHg 
Diastolic BP 
60 
90 
mmHg 
ECG normal ranges 
ECG Parameters 
Lower limit 
Higher limit 
Units 
HR 
40 
100 
bpm 
QRS 
60 
120 
ms 
PR interval 
120 
220 
ms 
QT 
320 
450 
ms 
QTc 
Normal for females is <450  
ms 
Normal for males is <430 
QTcF 
320 
450 
ms 
QTcB 
320 
450 
ms 
Spirometry normal ranges 
Spirometry parameters 
Lower limit 
Higher limit 
Units 
FEV1  
Normal if ≥80% of the predicted value 
litres 
FEV1/FVC 
Normal if ≥70% (≥0.7) of the predicted value  
litres  
No single value should be used in isolation, all spirometry reference ranges require physician interpretation 
of the participant’s overall status to determine their relevance. 
 

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10.5. 
Appendix 5: Abbreviations 
Abbreviation  
Term 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
alpha-Gal 
Galactose-alpha-1,3-Galactose 
AP 
Analytical Plan 
APTT 
Activated Partial Thromboplastin Time 
AR  
Adverse Reaction 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
β-hCG 
β-human chorionic gonadotrophin 
BD 
Twice Daily 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BSE 
Bovine Spongiform Encephalopathy 
CI 
Confidence Interval 
CK 
Creatine Kinase 
CRF 
Case Report Form 
CRP 
C-reactive Protein 
CYP 
Cytochrome P450 
DNA 
Deoxyribonucleic acid 
DMID 
Division of Microbiology and Infectious Disease 
ECG 
Electrocardiogram  
EU 
European Union  
Fab 
Antigen-binding Fragment 
FEV1 
Forced Expiratory Volume in one second 
FSH 
Follicle Stimulating Hormone 
FVC 
Forced Vital Capacity 
GAD 
Generalised Anxiety Disorder 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GGT 
Gamma Glutamyl Transferase 
GMP 
Good Manufacturing Practice 
GP 
General Practitioner  
GWAS 
Genome-wide Association Study 
HA 
Haemagglutinin 
HAI 
Haemagglutination Inhibition 
HbA1c 
Haemoglobin A1c 
HbsAg 
Hepatitis B Surface Antigen 
hChr 
Human Chromosomes 
HepA 
Hepatitis A Immunoglobulin M 
HepC 
Hepatitis C Antibodies 
hIgG 
Human Immunoglobulin G 
HIV (1 / 2) 
Human Immunodeficiency Virus (Type 1 / 2) 
hIVIg 
Human Intravenous Immunoglobulin 
HR 
Heart Rate 
HVC 
Human Viral Challenge  
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IgA 
Immunoglobulin A 

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IgH 
Human Ig Heavy Chain 
Igκ 
Immunoglobulin kappa 
IMP 
Investigational Medicinal Product 
ITT 
Intent to Treat 
ITT-I 
Intent to Treat Infected 
IV 
Intravenous(ly) 
LLOQ 
Lower Limit of Quantification 
LRT 
Lower Respiratory Tract 
MCH 
Mean Corpuscular Haemoglobin 
MCHC 
Mean Corpuscular Haemoglobin Concentration 
MCID 
Minimal Clinically Important Difference 
MCS 
Microscopy, Culture, and Sensitivity 
MCV 
Mean Corpuscular Volume 
MedDRA 
 
MHRA 
Medicines and Healthcare products Regulatory Agency 
pAbs 
Polyclonal Antibodies 
PCR 
Polymerase Chain Reaction 
PHQ 
Patient Health Questionnaire 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
qRT-PCR 
Quantitative Reverse Transcriptase-Polymerase Chain Reaction 
RBC 
Red Blood Cell 
REC 
Research Ethics Committee 
RNA 
Ribonucleic acid 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SME 
Sponsor’s Medical Expert 
SNP 
Single Nucleotide Polymorphism 
SoA 
Schedule of Activities  
SOP 
Standard Operating Procedure  
SpO2 
Peripheral Arterial Oxygen Saturation 
SUSAR 
Suspected Unexpected Adverse Reaction 
T 
Troponin 
Tc 
Trans Chromosomic 
TCID50 
Tissue Culture Infectious Dose 
TDS 
Three Times Daily 
T4 
Free Thyroxine 
TMF 
Trial Master File 
TSH 
Thyroid Stimulating Hormone 
TSS 
Total Symptoms Score 
UK 
United Kingdom 
US 
United States 
URT 
Upper Respiratory Tract 
VL-AUC 
Area Under the Viral Load-time Curve 
WBC 
White Blood Cell 

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10.6. 
Appendix 6: Definitions 
10.6.1. 
General 
TERM 
hVIVO Services Limited Definition 
Completion (of a participant’s 
participation in the study) 
A participant will be considered to have completed the study after 
his/her attendance at the last planned study visit, or the last 
unscheduled visit as applicable. 
Baseline 
For safety assessments the nearest assessments completed prior 
to dosing will be used as the baseline measure, unless stated 
otherwise. 
Enrolment (of a participant into 
the study) 
A participant will be considered to be ‘enrolled’ into the study once 
he/she has been inoculated. 
Infectious titre 
The titre of virus inoculum producing viral infection in a participant. 
The term ‘titre’ applies to the quantity or concentration of virus 
inoculum (depending on the units documented). 
Quarantine group 
A group of participants who are admitted to and are resident in the 
Quarantine Unit for a particular quarantine period (i.e., participants 
whose Day 0 and scheduled discharge date are the same). 
Quarantine period 
The period of time when clinical trial participants are isolated in the 
Quarantine Unit during a HVC study. 
Randomisation number 
The number allocated to a participant at randomisation. 
Participant number 
The unique number assigned to a participant on the hVIVO 
participant database, which is used to identify the participant prior 
to randomisation. 
Viral Challenge (or Challenge) 
The inoculation of a participant with virus inoculum. By definition, 
the day of Viral Challenge is Day 0. 
 
10.6.2. 
Study definition of infection and illness 
TERM 
CRITERIA (RESPIRATORY SYNCYTIAL VIRUS, HEART RATE 
VARIABILITY AND INFLUENZA STUDIES)  
Seroconversion 
A ≥4-fold increase in Virus specific antibodies from baseline to 
follow-up post-quarantine 
The following definitions should only be applied to data collected from Day 1 onwards 

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TERM 
CRITERIA (RESPIRATORY SYNCYTIAL VIRUS, HEART RATE 
VARIABILITY AND INFLUENZA STUDIES)  
Lower Respiratory Tract Illness 
Any one of the following signs and/or symptoms on two consecutive 
scheduled assessments, at least one of which must feature Grade 
2 severity, or if any of the following attain Grade 3 severity once: 
• 
Self-reported symptoms: cough, shortness of breath, chest 
tightness and wheeze. 
• 
Physician findings: Abnormal breath sounds externally 
(e.g., stridor, wheezing) and on chest auscultation (rhonchi, 
crepitations or other). 
Upper Respiratory Tract Illness 
Any one of the following signs and/or symptoms on two consecutive 
scheduled assessments, at least one of which must feature Grade 
2 severity, or if any of the following attain Grade 3 severity once: 
• 
Self-reported symptoms: rhinorrhoea (runny nose), nasal 
congestion (stuffy nose), sore throat, sneezing. 
• 
Physician findings: nasal discharge, otitis, pharyngitis, 
sinus tenderness. 
Systemic Illness 
Fulfils the criteria for febrile illness, or fulfils the definition of upper 
respiratory tract illness and/or lower respiratory tract illness 
and 
any one of the following symptoms on two consecutive scheduled 
assessments, at least one of which must feature Grade 2 severity, 
or if any of the following attain Grade 3 severity once: 
• 
malaise 
• 
headache  
• 
muscles and/or joint ache 
• 
chilliness  
• 
feverishness. 
Febrile Illness 
Any occurrence of temperature ≥37.9oC (confirmed by a repeat 
measurement as ≥37.9oC within 20 to 60 minutes). 
Viral shedding 
One or both of the following definitions must be met: 
• 
At least two positive quantifiable detections by viral load 
qPCR assay specific for the Challenge virus, reported on 
two or more consecutive days and from two independent 
samples (which can either be the same type of sample or 
different e.g., throat swab and nasal wash or two nasal 
wash samples). 
• 
One positive detection by viral load qPCR assay, specific 
for the Challenge virus, in which an aliquot of the same 
sample has also tested positive in a viral culture assay 
appropriate for detecting the Challenge virus. 
Laboratory confirmed Virus 
infection 
Viral shedding definition has been met.   
 
 

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11. 
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