A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of a Single Dose of ASN100 for the Prevention of Staphylococcus Aureus Pneumonia in Heavily Colonized, Mechanically Ventilated Subjects
Phase: PHASE2
Conditions: Pneumonia, Ventilator-associated, Pneumonia, Staphylococcal
Sponsor: Arsanis, Inc.

 
 
CLINICAL STUDY PROTOCOL 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Determine the Safety and Efficacy of a Single Dose of ASN100 for 
the Prevention of Staphylococcus aureus Pneumonia in Heavily 
Colonized, Mechanically Ventilated Subjects  
 
Investigational Product: ASN100 
Protocol Number: ASN100-201 
IND Number: 128766 
EudraCT Number: 2016-002146-23 
 
Sponsor: 
Arsanis, Inc. 
890 Winter Street, Suite 230 
Waltham, MA  
02451-1472 
 Telephone: +1-781-819-5704 
Facsimile: +1-781-957-1267 
 
Version Number: 4.1 (Site Specific Amendment) 
Date: 23 April 2018 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of Arsanis, Inc. except to the extent that disclosure would be required by law and for the 
purpose of evaluating and/or conducting a clinical study for Arsanis, Inc. You are allowed to 
disclose the contents of this document only to your Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC) and study personnel directly involved with conducting this 
protocol. Persons to whom the information is disclosed must be informed/notified that the 
protocol content is confidential and proprietary to Arsanis, Inc. and that it may not be further 
disclosed to third parties. 

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INVESTIGATOR AGREEMENT 
By signing below I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by Arsanis, Inc. (Arsanis) to study personnel under my supervision. I will discuss this material 
with them to ensure they are fully informed about the study product and study procedures. I will 
let them know that this information is confidential and proprietary to Arsanis and that it may not 
be further disclosed to third parties. I understand that the study may be terminated or enrollment 
suspended at any time by Arsanis, with or without cause, or by me if it becomes necessary to 
protect the best interests of the study subjects. 
I agree to conduct this study in full accordance with the United States Food and Drug 
Administration (FDA) Regulations, Institutional Review Board/Ethic Committee Regulations and 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Guidelines for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 
  

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SYNOPSIS 
TITLE:  A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Determine the 
Safety and Efficacy of a Single Dose of ASN100 for the Prevention of Staphylococcus aureus 
Pneumonia in Heavily Colonized, Mechanically Ventilated Subjects 
PROTOCOL NUMBER:  ASN100-201 
INVESTIGATIONAL PRODUCT:  ASN100 
PHASE:  2 
INDICATION:  The prevention of Staphylococcus aureus (S. aureus) pneumonia in 
mechanically ventilated subjects who are heavily colonized with S. aureus. 
STUDY DEFINITION:  For the purposes of this study, heavy colonization of S. aureus will be 
defined as a quantitative threshold of ≥105 CFU/mL or 3+ to 4+ by semi-quantitative culture from 
an endotracheal aspirate. 
OBJECTIVES: 
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of a single 
dose of ASN100 (administered as ASN-1 and ASN-2 components) versus placebo for the 
prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized 
with S. aureus. 
The secondary objectives of this study are: 
• To compare the duration of mechanical ventilation post-treatment in subjects treated with 
ASN100 versus placebo;  
• To compare the length of stay in the intensive care unit (ICU) post-treatment for subjects 
treated with ASN100 versus placebo;  
• To determine the serum pharmacokinetics (PK) (i.e., maximum serum concentration 
[Cmax], time to maximum serum concentration [Tmax], area under the serum concentration-
time curve [AUC], and terminal elimination half-life [t1/2]) of ASN-1 and ASN-2 in 
mechanically ventilated subjects heavily colonized with S. aureus; and 
• To compare 28-day all-cause mortality in subjects treated with ASN100 versus placebo. 
The exploratory objectives are: 
• To compare the incidence of hospital-acquired bacterial pneumonia (HABP) occurring 
>48 hours post-extubation up to but not including Day 22 in extubated subjects treated 
with ASN100 versus placebo; 
• To compare the incidence of ventilator-associated bacterial pneumonia (VABP) up to but 
not including Day 22 in subjects treated with ASN100 versus placebo; 

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• To determine the immunogenicity of a single dose of ASN100; 
• To compare the incidence of other S. aureus-associated infections which occur after 
dosing up to but not including Day 22 in subjects treated with ASN100 versus placebo; 
and 
• To assess ASN-1 and ASN-2 levels in bronchoalveolar lavage (BAL) fluid and calculate 
a blood to epithelial lining fluid (ELF) ratio in those subjects participating in the BAL 
fluid PK sub-study. 
POPULATION: 
Inclusion Criteria 
Subjects must meet all of the following criteria at the Screening and Randomization Visits in order 
to be eligible for randomization into the study: 
1. Subject, legally authorized representative, or council of independent physicians (CIP) (if 
applicable) has provided written informed consent; 
2. Subject is ≥18 years of age at the time of enrollment; 
3. Subject is currently hospitalized and is mechanically ventilated endotracheally 
(i.e., orotracheal or nasotracheal) and, in the Investigator’s opinion, will require ongoing 
ventilator support for at least 48 hours; 
NOTE: Subjects with a tracheostomy at the time of enrollment are not eligible. After 
enrollment, conversion to tracheostomy is permitted per standard of care. 
4. Female subjects must not be pregnant or lactating. Female subjects of childbearing potential 
must have a documented negative pregnancy test at the Screening Visit. Female subjects may 
be enrolled on the basis of a negative urine pregnancy test, pending the result of a negative 
serum pregnancy test prior to randomization; and 
5. Female subjects of childbearing potential and non-surgically sterile male subjects who are 
sexually active must agree to use an approved highly effective form of contraception from the 
time of informed consent until 165 days post-dose. Approved forms of contraception include 
hormonal intrauterine devices, hormonal contraceptives (oral birth control pill, depo, patch, or 
injectable) together with supplementary double barrier methods such as condoms or 
diaphragms with spermicidal gel or foam. 
NOTE: The following categories define women who are NOT considered to be of childbearing 
potential: 
• Premenopausal female with 1 of the following: 
o Documented hysterectomy, 
o Documented bilateral salpingectomy, or 
o Documented bilateral oophorectomy, or 
• Postmenopausal female, defined as having amenorrhea for at least 12 months without an 
alternative medical cause.  

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Exclusion Criteria 
Subjects who meet any of the following criteria at the Screening and/or Randomization Visit will 
be excluded from participation in the study: 
1. Subject has received intravenous (IV) immunoglobulin therapy within 4 months prior to the 
Screening Visit; 
2. Subject has a chest X-ray or thoracic computed tomography (CT) scan that is definitive for a 
diagnosis of pneumonia; 
3. Subject demonstrates both of the following: 
a. Need for acute changes in ventilator support to enhance oxygenation or to the amount of 
positive end-expiratory pressure; AND 
NOTE: Changes made in ventilator support due to day-to-day maintenance other than 
those changes made to improve oxygenation will not exclude a subject from participation 
in the study. 
b. New onset of purulent suctioned respiratory secretions; 
4. Subject has a known and documented ETA culture showing heavy colonization with a 
Gram-negative organism at enrollment or at any time during the Screening period; 
NOTE: Randomization should not be delayed while waiting for Gram-negative results if heavy 
colonization with S. aureus has been confirmed. 
5. Subject has been diagnosed with neutropenia (absolute neutrophil count <500/mm3); 
6. Subject has a severe non-pulmonary source of infection which, in the Investigator’s opinion, 
would interfere with the conduct of the study or jeopardize the subject’s safety; 
7. Subject is currently on either continuous veno-venous hemodialysis or extracorporeal 
membrane oxygenation; 
8. Subject has been previously exposed to ASN100 or ASN-1 or ASN-2, individually; 
9. Subject has a known hypersensitivity to ASN100 or any of its excipients; 
10. Subject has received any investigational product within 30 days prior to the Screening Visit 
(or 5 half-lives of the investigational product, whichever is longer); 
11. Subject has, in the opinion of the Investigator, a high probability of death within 72 hours of 
enrollment;  
12. Subject is, in the opinion of the Investigator, not able or willing to comply with the protocol;  
13. Any condition that, in the opinion of the Investigator, would compromise the safety of the 
subject, the potential activity of the study drug, or the quality of the data; or 
14. Subjects with a known history or current (suspected) diagnosis of cytokine release syndrome 
associated with the administration of peptides, proteins, and/or antibodies.20 
NOTE: Subjects with a prior history of sepsis are not excluded. 
 

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Randomization Criteria 
At the Randomization Visit, subjects must meet all of the following requirements to be 
randomized into the study: 
1. Subject continues to meet all of the inclusion criteria and none of the exclusion criteria 
required at the Screening Visit; 
NOTE: Subjects who undergo tracheostomy after enrollment are still eligible for 
randomization, provided they remain mechanically ventilated (see criterion 3 below). 
2. Subject is heavily colonized with S. aureus as determined by either quantitative or 
semi-quantitative culture of an endotracheal aspirate (ETA);  
NOTE: The results of the qualifying ETA culture must allow randomization to occur within 
48 hours (or up to 60 hours with Medical Monitor approval) from the time the ETA sample 
was collected. Subjects with ETA culture results obtained after 60 hours showing heavy 
colonization of S. aureus may not be randomized and will be discontinued from the study. 
3. Subject remains mechanically ventilated and, in the Investigator’s opinion, will require 
ongoing ventilator support for at least 48 hours; and 
4. Subject has, in the opinion of the Investigator, a probability of survival beyond 72 hours 
post-randomization. 
STUDY DESIGN AND DURATION: 
This is a double-blind, randomized, single-dose, placebo-controlled study of ASN100 for the 
prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized 
with S. aureus. Subjects will be screened for eligibility; once an Informed Consent Form is signed 
(or, in countries where it is applicable, a decision is made by the CIP), and all entry criteria are 
met, a subject is considered to be enrolled in the study. All enrolled subjects will undergo an 
observational stage evaluating endotracheal colonization. Subjects who are randomized will 
undergo a treatment, monitoring, and follow-up period. 
Approximately 2250 eligible subjects who meet all of the inclusion criteria and none of the 
exclusion criteria will be screened daily (while mechanically ventilated) for up to 8 days to 
identify those subjects who are heavily colonized with S. aureus.  
Screening for heavy S. aureus colonization by ETA culture will continue on Day 11 and Day 14 
provided the subject remains mechanically ventilated, for a total Screening Period of up to 
14 days. Additional ETA screening may occur on Days 9, 10, 12, and 13 at the discretion of the 
Investigator and providing the subject remains mechanically ventilated.  
ETA specimens collected during Screening/Enrollment will be cultured by quantitative or 
semi-quantitative methods as required by the protocol. Sites are encouraged to perform 
semi-quantitative cultures using a chromogenic media that tests for both the presence of 
methicillin-susceptible S. aureus and methicillin-resistant S. aureus (e.g., CHROMagarTM Staph 
aureus) for more rapid and specific detection of S. aureus. If the site is not able to obtain 
chromogenic media for S. aureus, appropriate chromogenic media may be supplied by the 
Sponsor.  

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Semi-quantitative cultures using chromogenic media are preferred for determination of eligibility 
for randomization; however, any quantitative or semi-quantitative culture performed that indicates 
that a subject is heavily colonized with S. aureus is permitted if the culture results are available to 
randomize the subject within 48 hours (or up to 60 hours with Medical Monitor approval) from 
the time the ETA sample was collected. 
Once an enrolled subject has an ETA culture reported positive for heavy S. aureus colonization 
and meets all of the inclusion and none of the exclusion criteria, they are eligible for 
randomization. If they are not randomized on this occasion according to the protocol, they are no 
longer eligible for continued ETA sampling and randomization, and will be discontinued from the 
study; however, if subjects are extubated and subsequently re-intubated/mechanically ventilated, 
they are eligible for re-screening as a new subject enrollment. Subjects who were previously 
randomized are not eligible to be re-consented and re-screened. 
At the time of randomization, if a subject’s screening ETA culture also shows heavy colonization 
of a Gram-negative organism (i.e., heavy co-colonization of both Gram-positive and 
Gram-negative organisms), the subject will not be randomized into the study; however, 
randomization should not be delayed while waiting for Gram-negative results if heavy 
colonization with S. aureus has been confirmed. 
Nasal swab specimens (one from each nostril) will be obtained at the Randomization Visit and 
will be cultured by the central microbiology laboratory. Results from the nasal swab specimen 
cultures will be used to assess correlation with results of the qualifying ETA culture. 
Upon determination of eligibility, approximately 354 subjects will be randomized in a 1:1 ratio to 
1 of 2 treatment groups: 
• ASN100 administered either sequentially or simultaneously as 2 separate IV infusions of 
ASN-1 and ASN-2, or 
• Placebo administered either sequentially or simultaneously as 2 separate IV infusions. 
To ensure balance among the treatment groups, randomization for this study will be stratified by 
receipt or non-receipt of concomitant anti-staphylococcal antibiotics at the time of randomization 
that are potentially active against S. aureus pneumonia, including, but not limited to, nafcillin, 
oxacillin, vancomycin, linezolid, telavancin, ceftaroline, ceftobiprole, and teicoplanin. 
Following randomization on Day 1, subjects will receive either a single IV dose of 3600 mg of 
ASN100 (comprised of separate infusions each of 1800 mg ASN-1 and 1800 mg ASN-2) or 
matching placebos, per their assigned randomization scheme.  
Randomized subjects will be monitored daily for the signs and symptoms of pneumonia and other 
S. aureus-associated infections while hospitalized up to Day 21. 
All randomized subjects will undergo a study visit on Day 22 (+2 days). A follow-up visit will 
occur on Day 28 (+2 days) to assess mortality. This visit may be conducted via telephone if the 
subject is no longer hospitalized.  
For subjects who remain hospitalized between Day 40 and Day 90 at the institution where they 
receive study treatment, a follow-up safety visit will be performed on the day of discharge. 
All randomized subjects will return for a Safety Visit on Day 90 (±7 days) (if the subject is unable 
to return to the site, this visit may be conducted by telephone). Subjects who discontinue the study 

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prior to Day 22 will undergo an Early Termination Visit. The end of the study will occur upon 
completion of the last Day 90 visit by the last subject. 
Safety assessments for this study will include adverse event monitoring, clinical laboratory 
assessments (including chemistry, hematology, coagulation, and urinalysis), physical 
examinations, vital sign measurements, 12-lead electrocardiograms (ECGs), chest X-rays and/or 
thoracic CT scans, and the determination of the presence of ASN-1 and ASN-2 anti-drug 
antibodies (ADAs). Additional safety assessments may be performed throughout the duration of 
the study if clinically indicated. 
Procalcitonin testing will be performed at the Randomization Visit (Day 1 pre-dose), on the day 
of diagnosis of pneumonia (if applicable), and on Day 22 or Early Termination (if applicable). 
Blood samples will be obtained for the measurement of ASN-1 and ASN-2 in serum. Blood 
samples for PK analysis will be collected immediately following the completion of the second 
infusion (+15 minutes) and at 6 hours (± 4 hours) and 24 hours (±6 hours) post-dose following the 
second infusion. In addition, a PK sample will be obtained from all subjects on Days 4 (±1 day), 
7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will 
be collected on the day of discharge (if discharge occurs between Day 40 and Day 90), on Day 90 
(if hospitalized or if the subject is able to return to the clinic), or Early Termination (if applicable). 
Select sites will be invited to participate in a BAL fluid PK sub-study. Approximately 25 to 
35 subjects who volunteer will participate in this sub-study and will have BAL fluid collected 
48 hours (±36 hours) post-dose (on approximately Day 2 or Day 3, depending on time of study 
drug administration) to determine ASN-1 and ASN-2 levels and blood to ELF ratio. Subjects 
participating in the BAL fluid PK sub-study will have a blood sample collected for PK 
measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid collection 
or if BAL fluid is collected as part of a standard of care procedure from any subject enrolled in 
the sub-study at any time post-randomization). 
Blood samples obtained for ADA and PK analysis purposes will also be used to assess the amount 
of pre-existing anti-S. aureus toxin antibodies and the toxin neutralizing titer of the serum sample 
prior to and after randomization. Only antigen-specific antibody titers will be determined and no 
genetic information will be extracted from these samples. Samples will be destroyed following 
the completion of all S. aureus anti-toxin antibody analyses. 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
ASN100 is a combination product with 2 separate human monoclonal antibody (mAb) 
components of the immunoglobulin G1 isotype. The specific mAbs are formulated separately and 
called ASN-1 and ASN-2. Each component is supplied as a sterile, colorless, clear liquid solution 
formulated ready for injection. 
ASN-1 is a broadly cross-reactive anti-toxin mAb that targets alpha hemolysin and 
3 F-components (gamma hemolysin B, leukocidin F, and leukocidin D) involved in forming 4 of 
the 5 bi-component leukocidins of S. aureus. 
ASN-2 is directed against the fifth bi-component toxin of S. aureus, leukocidin GH. 
ASN-1 and ASN-2 will be supplied in separate 10 mL vials as a sterile solution for infusion with 
an extractable volume of 10 mL and a nominal mAb concentration of 20 mg/mL. Each vial will 

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contain 200 mg of ASN-1 or 200 mg of ASN-2. Matched vials of ASN-1 placebo and 
ASN-2 placebo will also be provided. 
ASN100 will be administered as separate infusions of 1800 mg ASN-1 and 1800 mg ASN-2 
(9 vials of each to be pooled aseptically according to the Pharmacy Manual into separate infusion 
bags) delivered either sequentially within a 3-hour window from the time of initiation of the first 
infusion to the completion of the second infusion, or simultaneously. 
Placebo will be administered as separate infusions of 9 vials of ASN-1 placebo and 9 vials of 
ASN-2 placebo (vials to be pooled aseptically according to the Pharmacy Manual into separate 
infusion bags) delivered either sequentially within a 3-hour window from the time of initiation of 
the first infusion to the completion of the second infusion, or simultaneously. 
ANALYSIS POPULATIONS: 
Intent-to-Treat (ITT) Population 
The ITT Population includes all subjects who are randomized to receive study drug.  
Modified Intent-to-Treat (MITT) Population 
The MITT Population includes all subjects in the ITT Population who receive study drug who are 
heavily colonized with S. aureus as determined by quantitative or semi-quantitative culture of an 
ETA. 
Per Protocol (PP) Population 
The PP Population includes all subjects in the MITT Population who also meet the following 
criteria: 
• Do not have any major protocol violations that would affect assessment of efficacy, and 
• Complete an adequate number of Monitoring Period assessments through and including 
Day 22. 
Pharmacokinetic (PK) Population 
The PK Population includes all subjects in the MITT Population with at least 1 serum PK sample 
collected post-dose. 
Safety Population 
The Safety Population includes all subjects who receive any amount of study drug and have at 
least 1 post-treatment safety assessment. 
EFFICACY VARIABLES:  
The primary efficacy endpoint is the proportion of subjects in the MITT Population who develop 
S. aureus pneumonia up to but not including Day 22. 
The secondary efficacy endpoints include: 
• Duration of mechanical ventilation during the first 21 days post-randomization for subjects 
in the MITT, ITT, and PP Populations; 

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• Length of ICU stay during the first 21 days post-randomization for subjects in the MITT, 
ITT, and PP Populations;  
• The Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum following a single dose of 
ASN100 in the PK Population; and 
• 28-day all-cause mortality in the MITT, ITT, and PP Populations. 
Exploratory efficacy endpoints include: 
• Proportion of subjects in the MITT and PP Populations with a diagnosis of HABP at 
>48 hours post-extubation up to but not including Day 22 in extubated subjects; 
• Proportion of subjects in the MITT and PP Populations with development of VABP up to 
but not including Day 22; 
• Incidence of all bacterial pneumonias in the MITT, ITT, and PP Populations; 
• Incidence of other non-S. aureus pneumonias up to but not including Day 22 in the MITT, 
ITT, and PP Populations; and  
• Incidence of other S. aureus infections acquired following study drug administration up 
to but not including Day 22 in the MITT, ITT, and PP Populations. 
MICROBIOLOGICAL AND CLINICAL ASSESSMENTS: 
ETA specimens will be collected for culture during Screening/Enrollment to determine the degree 
of S. aureus colonization. Additional respiratory specimens may be collected for culture 
throughout the Monitoring Period or Early Termination (if applicable) if clinically indicated 
according to standard of care. 
If, as part of routine standard of care, additional respiratory and/or other microbiological 
specimens are collected for culture during the study, results will be documented within the 
electronic Case Report Form. As fully described within the study laboratory manual, bacterial 
isolates recovered from these specimens that are deemed pathogens by the Investigator (if retained 
and available at the study site local microbiology laboratory) will be sent to a central microbiology 
laboratory for confirmation of pathogen identification (all isolates) and susceptibility testing 
(S. aureus isolates only). 
During the Monitoring Period, a diagnosis of S. aureus pneumonia will be determined if subjects 
have S. aureus identified from an adequate respiratory specimen and clinical signs and symptoms 
of pneumonia. For a diagnosis of S. aureus pneumonia, clinical signs and symptoms must occur 
±2 days from the time of collection of an adequate respiratory specimen culture that is positive for 
S. aureus.  
• For intubated subjects, a respiratory specimen obtained by BAL, non-bronchoscopic BAL, 
or protected specimen brush will be considered an adequate respiratory specimen; or 
• For extubated subjects, an adequate expectorated/induced sputum specimen is defined as 
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• For both intubated and extubated subjects, adequate respiratory specimens will undergo 
either semi-quantitative or quantitative culture in accordance with the local laboratory’s 
standard procedure. 
Subjects will be assessed daily throughout the Monitoring Period for the following clinical signs 
and symptoms: 
Clinical Signs and Symptoms 
Mechanically Ventilated Subjects 
Non-Mechanically Ventilated Subjects 
• 
Cough, 
• 
Rales, 
• 
Dullness on percussion,* 
• 
Bronchial breath sounds, 
• 
Egophony,* 
• 
Need for suctioning, 
• 
Need for ventilator support, and 
• 
Fever ≥38°C (≥100.4°F). 
• 
Cough, 
• 
Rales, 
• 
Dullness on 
percussion,* 
• 
Bronchial breath 
sounds, 
• 
Egophony,* 
• 
Dyspnea, 
• 
Tachypnea, 
• 
Respiratory rate, 
• 
Hypoxemia, and 
• 
Fever ≥38°C 
(≥100.4°F). 
*If routinely performed. 
A diagnosis of pneumonia (HABP or VABP) will be determined as defined below: 
Definition of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia 
Indication 
Definition 
HABP 
• 
A chest X-ray showing new or progressive infiltrates suggestive of pneumonia (as assessed by the 
Investigator);  
• 
At least ONE of the following: 
o 
Has been hospitalized for >48 hours, or 
o 
Developed clinical signs and symptoms within 7 days following hospital discharge; 
• 
At least ONE of the following: 
o 
New onset or worsening pulmonary signs/symptoms such as cough, dyspnea, tachypnea 
(e.g., respiratory rate >25 breaths per minute), expectorated sputum production, or the requirement for 
mechanical ventilation (if subject is not already ventilated); 
o 
Need for acute changes in ventilator support to enhance oxygenation or to the amount of PEEP; or 
o 
New onset of suctioned respiratory secretions; AND 
• 
At least ONE of the following clinical signs/symptoms: 
o 
Temperature >38°C or <35°C, 
o 
WBC count ≥10,000 cell/mm3 or ≤4500 cell/mm3, or 
o 
>15% immature neutrophils (bands) on peripheral blood smear. 
VABP 
• 
A chest X-ray showing new or progressive infiltrates suggestive of pneumonia (as assessed by the 
Investigator);  
• 
Subject has received mechanical ventilation via an endotracheal or nasotracheal tube for ≥48 hours; 
• 
At least ONE of the following: 
o 
New onset or worsening pulmonary signs/symptoms such as cough, dyspnea, tachypnea 
(e.g., respiratory rate >25 breaths per minute), expectorated sputum production, or the requirement for 
mechanical ventilation (if subject is not already ventilated); 
o 
Need for acute changes in ventilator support to enhance oxygenation or to the amount of PEEP; or 
o 
New onset of suctioned respiratory secretions; AND 
• 
At least ONE of the following clinical signs/symptoms: 
o 
Temperature >38°C or <35°C, 
o 
WBC count ≥10,000 cell/mm3 or ≤4500 cell/mm3, or 
o 
>15% immature neutrophils (bands) on peripheral blood smear. 
HABP = hospital-acquired bacterial pneumonia; PEEP = positive end-expiratory pressure; VABP = ventilator-associated bacterial 
pneumonia; WBC = white blood cell. 
 

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PHARMACOKINETIC VARIABLES: 
The primary PK endpoints are the Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum 
following a single IV dose of ASN100 in the PK Population. 
Blood samples will be obtained for the measurement of ASN-1 and ASN-2 in serum. At the 
completion of the second infusion, blood samples for PK analysis will be collected immediately 
following the completion of the second infusion (+15 minutes) and at 6 hours (±4 hours) and 
24 hours (±6 hours) post-dose. 
In addition, a PK sample will be obtained from all subjects on Days 4 (±1 day), 7 (±1 day), 
14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will be collected 
on the day of discharge (if discharge occurs between Day 40 and Day 90), on Day 90 (if 
hospitalized or if the subject is able to return to the clinic), or Early Termination (if applicable). 
Subjects participating in the BAL fluid PK sub-study will have a blood sample collected for PK 
measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid collection 
or if BAL fluid is collected as part of a standard of care procedure from any subject enrolled in 
the sub-study at any time post-randomization). 
In order to maintain the study blind, all subjects, including those randomized to receive placebo, 
will have PK samples obtained at the above time points. 
The levels of ASN-1 and ASN-2 will be measured in BAL fluid in a PK sub-study (to include 
approximately 25 to 35 subjects who volunteer) which will allow the calculation of a blood to ELF 
ratio. Subjects participating in this sub-study will have BAL fluid collected 48 hours (±36 hours) 
post-dose (on approximately Day 2 or Day 3, depending on time of study drug administration) to 
determine ASN-1 and ASN-2 levels and blood to ELF ratio. If BAL fluid is collected as part of a 
standard of care procedure from any subject enrolled in the sub-study at any other time 
post-randomization for any other reason, if possible, a sample for PK analysis will also be 
obtained.  
SAFETY VARIABLES: 
Safety variables for this study will include adverse event monitoring, clinical laboratory 
assessments (including chemistry, hematology, coagulation, and urinalysis), physical 
examinations, vital sign measurements, 12-lead ECGs, chest X-rays and/or thoracic CT scans, and 
the determination of the presence of ASN-1 and ASN-2 (i.e., ASN100) ADAs.  
STATISTICAL ANALYSES: 
Continuous variables will be summarized by using the number of non-missing observations, 
arithmetic mean, standard deviation, median, minimum, and maximum values as descriptive 
statistics. Categorical variables will be summarized by using the frequency count and the 
percentage of subjects in each category as descriptive statistics.  
All statistical tests will be performed at the 0.05 significance level using 2-sided tests, except 
where otherwise noted. 
The primary efficacy endpoint is whether the subject has developed S. aureus pneumonia up to 
but not including Day 22. The summary measure for efficacy is the proportion of subjects in the 
MITT Population who develop S. aureus pneumonia up to but not including Day 22. Analysis for 

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the primary endpoint will compare the proportion of subjects who develop S. aureus pneumonia 
in the ASN100 arm versus the placebo arm in the MITT Population. The statistical test for 
comparing 2 event rates is based on a 2-sided test with a false positive rate of 5%.  
Analyses of the primary efficacy endpoint will also be performed separately for the ITT and 
PP Populations. 
Duration of mechanical ventilation and length of hospital ICU stay during the first 21 days 
post-randomization will be compared between treatment groups using a Wilcoxon rank sum test. 
Other efficacy endpoints will be summarized by treatment group. 
All subjects in the Safety Population will be included in the safety analyses and analyzed based 
on the actual treatment received. 
One interim analysis will be conducted during the study, when approximately 125 subjects have 
reached Day 22. The interim analysis is for futility assessment of the study, and for a potential 
study sample size adjustment based on an overall blinded efficacy evaluation pooled across the 
treatment arms. Based on this assessment, the sample size may be increased. The interim analysis 
of futility assessment will be reviewed by an independent Data Review Committee (DRC).  
Adverse events will be coded using the Medical Dictionary for Regulatory Activities. 
Treatment-emergent adverse events (TEAEs) will be summarized by system organ class and 
preferred term. A TEAE is defined as an adverse event with a start date and time on or after the 
first dose of study treatment. Listings will be provided for serious adverse events and adverse 
events leading to drug discontinuation. In addition, all adverse events will be listed. 
Safety laboratory data and vital signs will be presented by each scheduled time point and for 
change from baseline to each time point. The results of all laboratory tests, physical examination 
findings, vital signs, and ADAs will be presented in data listings. 
Descriptive statistics will be provided for all PK concentration data and PK parameters. All PK 
analyses will be performed using the PK Population. Subject PK profiles will be determined using 
parameters such as Cmax, Tmax, AUC, and t1/2 for each of ASN-1 and ASN-2 in serum. Epithelial 
lining fluid PK will also be analyzed and an ELF/serum PK ratio will be calculated. 
SAMPLE SIZE DETERMINATION: 
The estimated incidence of progression to S. aureus pneumonia in mechanically ventilated 
subjects with heavy colonization is approximately 25% within 22 days of randomization.  
Assuming a 2-sided significance level of 0.05 and a desired power of 80% to detect a significant 
difference between S. aureus pneumonia incidence rates of 25% in the placebo group and 12.5% 
in the ASN100 treatment group (50% reduction), 152 evaluable subjects are required in each 
treatment group. A sample size of 304 subjects (152 subjects per treatment group) will yield 
80% power to detect a 50% reduction in the incidence of S. aureus pneumonia with ASN100 
treatment when assuming a 25% incidence rate of S. aureus pneumonia in placebo-treated 
subjects. Assuming a 14% non-evaluable rate, approximately 354 subjects (177 subjects per 
treatment group) will be randomized. Assuming the screen failure rate is about 84%, 
approximately 2250 subjects will be screened. 

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SITES:  Approximately 70 global sites. 
SPONSOR: 
Arsanis, Inc. 
890 Winter Street, Suite 230 
Waltham, MA  
02451-1472 
Telephone: +1-781-819-5704 
Facsimile: +1-781-957-1267 

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TABLE OF CONTENTS 
 
SIGNATURE PAGE ...................................................................................................................... 2 
INVESTIGATOR AGREEMENT.................................................................................................. 3 
SYNOPSIS ...................................................................................................................................... 4 
TABLE OF CONTENTS .............................................................................................................. 16 
LIST OF TABLES ........................................................................................................................ 21 
LIST OF FIGURES ...................................................................................................................... 22 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................................. 23 
1 
INTRODUCTION AND BACKGROUND INFORMATION ........................................ 25 
1.1 
Background ................................................................................................................. 25 
1.2 
Rationale ..................................................................................................................... 26 
1.3 
Risk/Benefit ................................................................................................................ 27 
2 
STUDY OBJECTIVES ..................................................................................................... 29 
2.1 
Primary Objective ....................................................................................................... 29 
2.2 
Secondary Objectives.................................................................................................. 29 
2.3 
Exploratory Objectives ............................................................................................... 29 
3 
STUDY DESCRIPTION .................................................................................................. 30 
3.1 
Definition of Heavy Colonization ............................................................................... 30 
3.2 
Summary of Study Design .......................................................................................... 30 
Figure 1. Study Schematic ............................................................................................................ 30 
3.3 
Study Indication .......................................................................................................... 33 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .................................................... 34 
4.1 
Inclusion Criteria ........................................................................................................ 34 
4.2 
Exclusion Criteria ....................................................................................................... 34 
4.3 
Randomization Criteria ............................................................................................... 35 
4.4 
Withdrawal Criteria .................................................................................................... 36 
5 
STUDY TREATMENTS .................................................................................................. 38 
5.1 
Treatment Groups ....................................................................................................... 38 
5.2 
Stratification ................................................................................................................ 38 
5.3 
Rationale for Dosing ................................................................................................... 38 

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5.4 
Randomization and Blinding ...................................................................................... 39 
5.5 
Breaking the Blind ...................................................................................................... 39 
5.6 
Drug Supplies.............................................................................................................. 39 
5.6.1 Formulation and Packaging .................................................................................. 39 
5.6.2 Study Drug Preparation and Dispensing ............................................................... 40 
5.6.3 Study Drug Administration ................................................................................... 40 
5.6.4 Treatment Compliance .......................................................................................... 41 
5.6.5 Storage and Accountability ................................................................................... 41 
5.7 
Prior and Concomitant Medications and/or Procedures ............................................. 41 
5.7.1 Excluded Medications and/or Procedures ............................................................. 41 
5.7.2 Documentation of Prior and Concomitant Medication Use .................................. 41 
6 
STUDY PROCEDURES .................................................................................................. 42 
6.1 
Informed Consent........................................................................................................ 42 
6.2 
Screening/Enrollment (Up to Day -14) ....................................................................... 42 
6.3 
Randomization Visit (Day 1 Pre-Dose) ...................................................................... 43 
6.4 
Treatment Period (Day 1) ........................................................................................... 44 
6.5 
Monitoring Period ....................................................................................................... 44 
6.5.1 Day 2/Day 3 – Bronchoalveolar Lavage Fluid Pharmacokinetic Sub-Study ....... 44 
6.5.2 Day 2 to Day 21 .................................................................................................... 45 
6.5.3 Day 22 ................................................................................................................... 46 
6.6 
Follow-Up Period........................................................................................................ 47 
6.6.1 Day 28 (+2 Days) Follow-Up ............................................................................... 47 
6.6.2 Day 40 to Day 89 (Follow-Up Safety Visit) ......................................................... 47 
6.6.3 Safety Visit (Day 90 [±7 Days]) ........................................................................... 47 
6.7 
Early Termination Visit and Withdrawal Procedures ................................................. 48 
7 
EFFICACY ASSESSMENTS .......................................................................................... 49 
7.1 
Primary Efficacy Endpoint ......................................................................................... 49 
7.2 
Secondary Efficacy Endpoints .................................................................................... 49 
7.3 
Exploratory Efficacy Endpoints .................................................................................. 49 
7.4 
Microbiological and Clinical Assessments ................................................................. 50 
7.4.1 Microbiological Assessment ................................................................................. 50 
7.4.2 Assessment of Clinical Signs and Symptoms ....................................................... 50 

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Table 1. Clinical Signs and Symptoms ......................................................................................... 50 
Table 2. Definition of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia ........ 51 
8 
PHARMACOKINETIC ASSESSMENTS ....................................................................... 52 
8.1 
Pharmacokinetic Endpoint .......................................................................................... 52 
8.2 
Pharmacokinetic Assessments .................................................................................... 52 
8.2.1 Serum Pharmacokinetic Sampling ........................................................................ 52 
8.2.2 Bronchoalveolar Lavage Fluid Pharmacokinetic Sampling ................................. 53 
8.2.3 Analysis of Anti-Staphylococcus aureus Toxin Antibody Titers ......................... 53 
9 
SAFETY ASSESSMENTS ............................................................................................... 54 
9.1 
Adverse Events ........................................................................................................... 54 
9.1.1 Adverse (Drug) Reaction ...................................................................................... 55 
9.1.2 Unexpected Adverse Drug Reaction ..................................................................... 55 
9.1.3 Assessment of Adverse Events by the Investigator .............................................. 55 
9.2 
Serious Adverse Events .............................................................................................. 56 
9.3 
Serious Adverse Event Reporting − Procedures for Investigators.............................. 57 
9.4 
Pregnancy Reporting ................................................................................................... 58 
9.5 
Expedited Reporting ................................................................................................... 58 
9.6 
Clinical Laboratory Evaluations ................................................................................. 58 
9.7 
Radiographs and Imaging ........................................................................................... 59 
9.8 
Vital Signs ................................................................................................................... 59 
9.9 
Electrocardiograms ..................................................................................................... 60 
9.10 
Physical Examinations ................................................................................................ 60 
9.11 
Immunogenicity .......................................................................................................... 60 
10 
STATISTICS .................................................................................................................... 61 
10.1 
Analysis Populations ................................................................................................... 61 
10.2 
Statistical Methods ...................................................................................................... 61 
10.2.1 Disposition ............................................................................................................ 61 
10.2.2 Demographic and Baseline Characteristics .......................................................... 61 
10.2.3 Analysis of Efficacy .............................................................................................. 62 
10.2.4 Analysis of Safety ................................................................................................. 62 
10.2.5 Analysis of Pharmacokinetics ............................................................................... 62 
10.2.6 Sample Size Determination................................................................................... 62 

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10.2.7 Interim Analysis .................................................................................................... 63 
11 
DATA MANAGEMENT AND RECORD KEEPING..................................................... 64 
11.1 
Data Management ....................................................................................................... 64 
11.1.1 Data Handling ....................................................................................................... 64 
11.1.2 Computer Systems ................................................................................................ 64 
11.1.3 Data Entry ............................................................................................................. 64 
11.1.4 Medical Information Coding................................................................................. 64 
11.1.5 Data Validation ..................................................................................................... 64 
11.2 
Record Keeping .......................................................................................................... 64 
12 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL ............................. 65 
12.1 
Ethical Conduct of the Study ...................................................................................... 65 
12.2 
Institutional Review Board/Independent Ethics Committee....................................... 65 
12.3 
Informed Consent........................................................................................................ 65 
12.4 
Study Monitoring Requirements ................................................................................. 66 
12.5 
Protocol Deviations ..................................................................................................... 66 
12.6 
Disclosure of Data....................................................................................................... 67 
12.7 
Retention of Records................................................................................................... 67 
12.8 
Publication Policy ....................................................................................................... 67 
12.9 
Financial Disclosure.................................................................................................... 67 
12.10 Insurance and Indemnity ............................................................................................. 67 
12.11 Legal Aspects .............................................................................................................. 68 
13 
STUDY ADMINISTRATIVE INFORMATION ............................................................. 69 
13.1 
Protocol Amendments ................................................................................................. 69 
13.2 
Address List ................................................................................................................ 69 
13.2.1 Sponsor ................................................................................................................. 69 
13.2.2 Global Contract Research Organization ............................................................... 69 
13.2.3 Drug Safety ........................................................................................................... 69 
13.2.4 Biological Specimens............................................................................................ 70 
13.2.5 Study Drug Packaging, Labeling, and Distribution .............................................. 70 

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14 
REFERENCES ................................................................................................................. 71 
Appendix A: Schedule of Procedures ........................................................................................... 73 
Appendix B: Clinical Laboratory Analytes .................................................................................. 77 
Appendix C: Site-Specific Sub-Study for Subjects Diagnosed with Pneumonia ......................... 78 
 
 
 
 

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LIST OF TABLES 
Table 1. 
Clinical Signs and Symptoms ..................................................................................... 50 
Table 2. 
Definition of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia .... 51 
 
 

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LIST OF FIGURES  
Figure 1. Study Schematic.......................................................................................................... 30 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
ADA 
Anti-drug antibody 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
ALT 
Alanine aminotransferase 
ASN-1 
Broadly cross-reactive anti-toxin monoclonal antibody that targets
alpha hemolysin (Hla) and 3 F-components (HlgB, LukF, LukD)
involved in forming 4 of the 5 bi-component leukocidins of
Staphylococcus aureus 
ASN-2 
Anti-toxin monoclonal antibody that targets the fifth bi-component
toxin of Staphylococcus aureus, LukGH 
ASN100 
A combination of 2 fully human monoclonal antibodies (ASN-1 and 
ASN-2) 
AST 
Aspartate aminotransferase 
AUC 
Area under the serum concentration-time curve 
BAL 
Bronchoalveolar lavage 
CFR 
Code of Federal Regulations 
CFU 
Colony forming units 
CIP 
Council of independent physicians 
Cmax 
Maximum serum concentration 
CRA 
Clinical research associate 
CRO 
Contract research organization 
CT 
Computed tomography 
CTA 
Clinical trial authorization 
DRC 
Data Review Committee 
ECG 
Electrocardiogram  
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
ELF 
Epithelial lining fluid 
ET 
Early Termination 
ETA 
Endotracheal aspirate 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HABP 
Hospital-acquired bacterial pneumonia 
Hla 
Alpha hemolysin 
HlgAB 
Gamma hemolysin AB 
HlgB 
Gamma hemolysin B 
HlgCB 
Gamma hemolysin CB 
ICF 
Informed Consent Form 

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Abbreviation 
Definition 
ICH 
International Council for Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use 
ICU 
Intensive care unit 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin G1 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
IV 
Intravenous  
LAR 
Legally authorized representative 
LukD 
Leukocidin D 
LukED 
Leukocidin ED 
LukF 
Leukocidin F 
LukGH 
Leukocidin GH 
LukSF 
Leukocidin SF or Panton-Valentine Leukocidin 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Modified Intent-to-Treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-susceptible Staphylococcus aureus 
NIMP 
Non-investigational medical product 
PCT 
Procalcitonin  
PD 
Pharmacodynamic  
PK 
Pharmacokinetic  
PMN 
Polymorphonuclear cell 
PP 
Per Protocol 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
PVL 
Panton-Valentine Leukocidin or leukocidin SF 
RBC 
Red blood cell 
S. aureus 
Staphylococcus aureus 
SAE 
Serious adverse event  
t1/2 
Terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum serum concentration 
VABP 
Ventilator-associated bacterial pneumonia 
WBC 
White blood cell 

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1 
INTRODUCTION AND BACKGROUND INFORMATION 
1.1 
Background 
Staphylococcus aureus (S. aureus) is a human pathogenic bacterium that causes severe infections, 
including pneumonia and sepsis. Hospital-acquired bacterial pneumonia (HABP) caused by 
S. aureus, including ventilator-associated bacterial pneumonia (VABP) in mechanically ventilated 
patients, is a significant public health threat despite efforts to optimize antibiotic treatment. 
The primary exotoxins of S. aureus are alpha hemolysin (Hla), which damages lung epithelial 
cells, facilitating pneumonia and systemic bacterial invasion, and a group of exotoxins known as 
bi-component, pore-forming leukocidins.1,2 Staphylococcus aureus isolates are capable of 
producing up to 5 potent leukocidins: 2 gamma hemolysins (gamma hemolysin AB [HlgAB] and 
gamma hemolysin CB [HlgCB]), the Panton-Valentine Leukocidin (PVL or leukocidin SF 
[LukSF]), leukocidin ED (LukED), and leukocidin GH (LukGH). Alpha hemolysin, the gamma 
hemolysins, and LukGH genes are present in all clinical isolates; however, LukSF and LukED are 
found in approximately 5% to 10% and approximately 60% of strains, respectively. The most 
prevalent community-acquired methicillin-resistant S. aureus (MRSA) strain in the United States 
is the USA300 pulsotype, which possesses genes for all 5 of these potent leukocidins. 
Alpha hemolysin and the bi-component leukocidins bind to various cell surface receptors and this 
leads to cell type specific cytotoxicity. The combined effect of these exotoxins in staphylococcal 
pathogenesis is multifold:  
• Hla destroys the epithelial barrier by direct cytolysis;  
• Leukocidins target phagocytic cells for lysis, reducing the capacity of immune cells to 
eliminate S. aureus; and 
• All cytotoxins induce inflammatory responses that lead to further tissue damage. 
Inflammatory signals further enhance the susceptibility of human polymorphonuclear 
cells (PMNs) to lysis by LukGH rendering this toxin dominant among the S. aureus 
leukocidins in vitro.3 
Counteracting these functions of staphylococcal toxins by means of monoclonal antibodies (mAbs) 
may contribute to or induce the prevention and/or treatment of S. aureus pneumonia. 
ASN100 is a combination of 2 fully human mAbs (ASN-1 and ASN-2, both of the 
immunoglobulin G1 [IgG1] subclass) that target these exotoxins of S. aureus. ASN-1 is a broadly 
cross-reactive anti-toxin mAb that targets Hla and 3 F-components (gamma hemolysin B [HlgB], 
leukocidin F [LukF], and leukocidin D [LukD]) involved in forming 4 of the 5 bi-component 
leukocidins of S. aureus, while ASN-2 is directed against the fifth bi-component toxin of S. aureus, 
LukGH.4,5,6  
The 2 antibodies (i.e., ASN-1 and ASN-2) are dosed in a 1:1 ratio and operate as follows: 
• ASN-1 binds to and neutralizes Hla and 4 bi-component S. aureus cytotoxins 
(leukocidins): HlgAB, HlgCB, LukED, and LukSF (also known as PVL); and 
• ASN-2 binds to and neutralizes the fifth S. aureus leukocidin, LukGH. 
While ASN-1 and ASN-2 each provide partial protection of human phagocytic cells against a 
combination of staphylococcal exotoxins, the 2 mAbs act in synergy to prevent lysis of human 

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phagocytic cells in the presence of Hla and all 5 bi-component leukocidins. By neutralizing Hla 
and inactivating HlgAB, HlgCB, LukED, and LukSF, ASN-1 prevents the lysis of granulocytes 
(PMNs) caused by these leukocidins. ASN-1 demonstrated superior efficacy compared to 
Hla-neutralizing mAbs against S. aureus pneumonia in a rabbit in vivo model.7 By neutralizing 
LukGH, ASN-2 protects PMNs, monocytes, and macrophages from lysis. 
ASN100 (i.e., ASN-1 and ASN-2) has demonstrated potency and efficacy against a wide range of 
S. aureus strains in in vitro studies and in vivo models of S. aureus pneumonia.4,5 Collectively, 
these studies support the synergy of ASN-1 and ASN-2 and the need for both mAbs in ASN100 to 
protect patients in the clinical setting against the full range of S. aureus strains 
(methicillin-susceptible S. aureus [MSSA] and MRSA).  
1.2 
Rationale 
Published studies have demonstrated that microbiologic screening of mechanically ventilated 
patients to determine those who are heavily colonized with S. aureus increases the probability of 
correctly predicting those patients who will eventually develop S. aureus pneumonia.8,9 
Approximately one-third of heavily colonized mechanically ventilated patients progressed to 
S. aureus pneumonia and these same studies demonstrated that patients still develop S. aureus 
pneumonia despite treatment with potentially effective anti-staphylococcal antibiotics. Secondary 
analyses of these studies have shown that antibiotic treatment is ineffective in reducing S. aureus 
colonization in the lower airways and preventing ventilator-associated tracheobronchitis or VABP, 
and S. aureus seems to be in competition for colonization with the normal respiratory flora.10 
Staphylococcus aureus, particularly MRSA, is frequently identified as the causative pathogen of 
pneumonia and the incidence of healthcare-related MRSA pneumonia among hospitalized patients 
is increasing.11,12,13 According to the American Thoracic Society and the Infectious Diseases 
Society of America, MRSA is associated with >50% of intensive care unit (ICU) infections in the 
United States.14  
Despite the availability of microbiologically appropriate antibiotics, mortality in patients with 
S. aureus pneumonia remains high.15 No specific prevention strategies have proven effective 
against S. aureus pneumonia in mechanically ventilated patients. While general pneumonia 
prevention measures demonstrate efficacy in many cases, not all ICU types benefit from these 
efforts.17 Although reported pneumonia rates have decreased over time, the remaining S. aureus 
cases are unlikely to be prevented by non-specific measures.17,18  
Data from retrospective observational studies indicate that mechanically ventilated patients who 
have moderate to heavy colonization with S. aureus as determined by culture of endotracheal 
aspirate (ETA) specimens (i.e., ≥3+ by semi-quantitative culture) have a higher risk of developing 
pneumonia.8,19 As noted above, many of these patients still ultimately develop S. aureus 
pneumonia despite treatment with potentially effective antibiotics.  
The USA300 pulsotype is the most prevalent community-acquired MRSA strain in the 
United States and is known to possess all 5 leukocidins produced by S. aureus. When Hla and the 
bi-component leukocidins bind to various cell surface receptors, cell type specific cytotoxicity 
results. In addition, Hla expression level of colonizing S. aureus MSSA strains have been observed 
as a biomarker for progression to VABP in ventilated patients.19  

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Monoclonal antibodies may counteract these toxin activities and thereby offer benefit in the 
prevention of S. aureus pneumonia. Together, the components of ASN100 (i.e., ASN-1 and 
ASN-2) have demonstrated potency and efficacy against a wide range of S. aureus strains in 
in vitro studies and in vivo models of S. aureus pneumonia, positioning ASN100 to be a needed 
therapy for the prevention of S. aureus pneumonia. The design of this Phase 2 prevention study 
with ASN100 is based on an assumption of a 50% reduction in the incidence of S. aureus 
pneumonia in these subjects, irrespective of the concomitant use of potentially effective 
antibiotics. 
A series of pharmacokinetic (PK) and pharmacodynamic (PD) experiments was conducted using 
the rabbit S. aureus pneumonia model and measured PK in both healthy rabbits and rabbits with 
pneumonia caused by several S. aureus strains. The range of effective doses for preventing 
S. aureus pneumonia in animal models was 2.5 to 10 mg/kg of each component of ASN100. 
The 20 mg/kg dose (10 mg ASN-1 and 10 mg ASN-2) translated into a 1600 mg dose for an 80 kg 
subject. 
ASN100 was well tolerated up to 8000 mg (i.e., 4000 mg ASN-1 and 4000 mg ASN-2) in a single 
ascending dose study conducted in healthy human volunteers. There were no reported related 
serious adverse events (SAEs) and 2 related treatment-emergent adverse events (TEAEs) of 
headache and fatigue were reported in this study. These data and data obtained from the nonclinical 
program determined that ASN100 3600 mg (i.e., 1800 mg ASN-1 and 1800 mg ASN-2) will be an 
appropriate dose to assess safety and efficacy in this first study in mechanically ventilated subjects 
who are heavily colonized with S. aureus. 
The significant unmet need, the lack of existing therapies to prevent S. aureus pneumonia in 
high-risk patients, and the demonstrated in vitro potency and in vivo efficacy of ASN100 provide 
sufficient rationale for this Phase 2 study in the prevention of S. aureus pneumonia in high-risk, 
mechanically ventilated subjects. 
1.3 
Risk/Benefit 
In mechanically ventilated subjects heavily colonized with S. aureus, ASN100 may prevent 
S. aureus pneumonia, a condition associated with significant morbidity and mortality and 
representing a significant unmet clinical need. 
The ASN100 drug components ASN-1 and ASN-2 are fully human mAbs belonging to the IgG1 
immunoglobulin subclass glycoproteins. They share a high degree of sequence homology with 
endogenous IgGs of the same subclass (approximately 90% to 95%) and are manufactured using 
standard mammalian cell expression and purification technologies (including 4 orthogonal viral 
clearance steps); therefore, they are expected to carry mammalian glycosylation pattern and to 
continue to be well tolerated in humans. 
The target toxins recognized by ASN-1 and ASN-2 are bacterial, non-human, and are not 
expressed in human tissues. Lack of off-target reactivity is supported by the results of human tissue 
cross-reactivity studies involving a panel of 33 tissue types that demonstrated no cross-reactivity 
with human tissues. The antibody function of ASN100 is based solely on neutralization; 
complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) 
mechanisms in the mode of action are irrelevant. ASN-1 and ASN-2 cannot bind to toxins already 
bound to human tissues and therefore unwanted ADCC reactions toward human cells and tissues 
is unlikely. 

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A single ascending dose study conducted with ASN100 in doses up to 8000 mg 
(i.e., 4000 mg ASN-1 and 4000 mg ASN-2) demonstrated that ASN100 was well tolerated with 
no reported related SAEs and 2 reported possibly related adverse events of headache and fatigue. 
No dose-limiting toxicity was observed up to the highest dose tested. 
The potential immunogenicity of the antibodies and resulting immune complex formation 
following the production of anti-drug immunoglobulin M and IgG antibodies by the host immune 
system cannot be excluded; however, the risk for this outcome is considered to be low. 
ASN100 belongs to the class of mAbs targeting foreign (bacterial), non-human antigens and is 
expected to yield a low risk of adverse events resulting from immunogenicity due to the 
single-dose administration used in this study. 
Subjects participating in this study will be closely monitored following study drug administration 
via means of adverse event monitoring, clinical laboratory assessments, vital sign measurements, 
physical examinations, 12-lead electrocardiograms (ECGs), chest X-rays and/or thoracic 
computed tomography (CT) scans, and the determination of the presence of ASN-1 and/or ASN-2 
anti-drug antibodies (ADAs). Additional safety assessments may be performed throughout the 
duration of this study if clinically indicated. Concomitant antibiotics are permitted per standard of 
care throughout the duration of this study. 
 

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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of a single 
dose of ASN100 (administered as ASN-1 and ASN-2 components) versus placebo for the 
prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized 
with S. aureus. 
2.2 
Secondary Objectives 
The secondary objectives of this study are: 
• To compare the duration of mechanical ventilation post-treatment in subjects treated with 
ASN100 versus placebo;  
• To compare the length of stay in the ICU post-treatment for subjects treated with ASN100 
versus placebo;  
• To determine the serum PK (i.e., maximum serum concentration [Cmax], time to maximum 
serum concentration [Tmax], area under the serum concentration-time curve [AUC], and 
terminal elimination half-life [t1/2]) of ASN-1 and ASN-2 in mechanically ventilated 
subjects heavily colonized with S. aureus; and 
• To compare 28-day all-cause mortality in subjects treated with ASN100 versus placebo. 
2.3 
Exploratory Objectives 
The exploratory objectives are: 
• To compare the incidence of HABP occurring >48 hours post-extubation up to but not 
including Day 22 in extubated subjects treated with ASN100 versus placebo; 
• To compare the incidence of VABP up to but not including Day 22 in subjects treated with 
ASN100 versus placebo; 
• To determine the immunogenicity of a single dose of ASN100; 
• To compare the incidence of other S. aureus-associated infections which occur after 
dosing up to but not including Day 22 in subjects treated with ASN100 versus placebo; 
and 
• To assess ASN-1 and ASN-2 levels in bronchoalveolar lavage (BAL) fluid and calculate 
a blood to epithelial lining fluid (ELF) ratio in those subjects participating in the BAL 
fluid PK sub-study. 
 

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Screening for heavy S. aureus colonization by ETA culture will continue on Day 11 and Day 14 
provided the subject remains mechanically ventilated, for a total Screening Period of up to 14 days. 
Additional ETA screening may occur on Days 9, 10, 12, and 13 at the discretion of the Investigator 
and providing the subject remains mechanically ventilated.  
ETA specimens collected during Screening/Enrollment will be cultured by quantitative or 
semi-quantitative methods as required by the protocol. Sites are encouraged to perform 
semi-quantitative cultures using a chromogenic media that tests for both the presence of MSSA 
and MRSA (e.g., CHROMagarTM Staph aureus) for more rapid and specific detection of S. aureus. 
If the site is not able to obtain chromogenic media for S. aureus, appropriate chromogenic media 
may be supplied by the Sponsor.  
Semi-quantitative cultures using chromogenic media are preferred for determination of eligibility 
for randomization; however, any quantitative or semi-quantitative culture performed that indicates 
that a subject is heavily colonized with S. aureus is permitted if the culture results are available to 
randomize the subject within 48 hours (or up to 60 hours with Medical Monitor approval) from 
the time the ETA sample was collected. 
Once an enrolled subject has an ETA culture reported positive for heavy S. aureus colonization 
and meets all of the inclusion and none of the exclusion criteria, they are eligible for randomization. 
If they are not randomized on this occasion according to the protocol, they are no longer eligible 
for continued ETA sampling and randomization, and will be discontinued from the study; however, 
if subjects are extubated and subsequently re-intubated/mechanically ventilated, they are eligible 
for re-screening as a new subject enrollment. Subjects who were previously randomized are not 
eligible to be re-consented and re-screened. 
At the time of randomization, if a subject’s screening ETA culture also shows heavy colonization 
of a Gram-negative organism (i.e., heavy co-colonization of both Gram-positive and 
Gram-negative organisms), the subject will not be randomized into the study; however, 
randomization should not be delayed while waiting for Gram-negative results if heavy colonization 
with S. aureus has been confirmed. 
Nasal swab specimens (one from each nostril) will be obtained at the Randomization Visit and will 
be cultured by the central microbiology laboratory. Results from the nasal swab specimen cultures 
will be used to assess correlation with results of the qualifying ETA culture. 
Upon determination of eligibility, approximately 354 subjects will be randomized in a 1:1 ratio to 
1 of 2 treatment groups: 
• ASN100 administered either sequentially or simultaneously as 2 separate intravenous (IV) 
infusions of ASN-1 and ASN-2, or 
• Placebo administered either sequentially or simultaneously as 2 separate IV infusions. 
To ensure balance among the treatment groups, randomization for this study will be stratified by 
receipt or non-receipt of concomitant anti-staphylococcal antibiotics at the time of randomization 
that are potentially active against S. aureus pneumonia (see Section 5.2). 
Following randomization on Day 1, subjects will receive either a single IV dose of 3600 mg of 
ASN100 (comprised of separate infusions each of 1800 mg ASN-1 and 1800 mg ASN-2) or 
matching placebos, per their assigned randomization scheme.  

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If, as part of routine standard of care, additional respiratory and/or other microbiological 
specimens are collected for culture during the study, results will be documented within the 
electronic Case Report Form (eCRF). As fully described within the study laboratory manual, 
bacterial isolates recovered from these specimens that are deemed pathogens by the 
Investigator (if retained and available at the study site local microbiology laboratory) will be 
sent to a central microbiology laboratory for confirmation of pathogen identification (all 
isolates) and susceptibility testing (S. aureus isolates only).   
NOTE: Subjects who are heavily colonized and who would have otherwise qualified for 
randomization, but who are found to have already progressed to pneumonia, may be 
eligible to enroll in a site-specific pilot treatment sub-study.  See Appendix C for criteria. 
Randomized subjects will be monitored daily for the signs and symptoms of pneumonia 
(see Section 7.4.2 and Table 1) and other S. aureus-associated infections while hospitalized up to 
Day 21.  
All randomized subjects will undergo a study visit on Day 22 (+2 days). A follow-up visit will 
occur on Day 28 (+2 days) to assess mortality. This visit may be conducted via telephone if the 
subject is no longer hospitalized.  
For subjects who remain hospitalized between Day 40 and Day 90 at the institution where they 
receive study treatment, a follow-up safety visit will be performed on the day of discharge. 
All randomized subjects will return for a Safety Visit on Day 90 (±7 days) (if the subject is unable 
to return to the site, this visit may be conducted by telephone). Subjects who discontinue the study 
prior to Day 22 will undergo an Early Termination Visit. The end of the study will occur upon 
completion of the last Day 90 visit by the last subject. 
Safety assessments for this study will include adverse event monitoring, clinical laboratory 
assessments (including chemistry, hematology, coagulation, and urinalysis), physical 
examinations, vital sign measurements, 12-lead ECGs, chest X-rays and/or thoracic CT scans, and 
the determination of the presence of ASN-1 and ASN-2 ADAs. Additional safety assessments may 
be performed throughout the duration of the study if clinically indicated. 
Procalcitonin testing will be performed at the Randomization Visit (Day 1 pre-dose), on the day 
of diagnosis of pneumonia (if applicable), and on Day 22 or Early Termination (if applicable). 
Blood samples will be obtained for the measurement of ASN-1 and ASN-2 in serum. Blood 
samples for PK analysis will be collected immediately following the completion of the second 
infusion (+15 minutes) and at 6 hours (± 4 hours) and 24 hours (±6 hours) post-dose following the 
second infusion. In addition, a PK sample will be obtained from all subjects on Days 4 (±1 day), 
7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will 
be collected on the day of discharge (if discharge occurs between Day 40 and Day 90), on Day 90 
(if hospitalized or if the subject is able to return to the clinic), or Early Termination (if applicable).  
Select sites will be invited to participate in a BAL fluid PK sub-study. Approximately 25 to 
35 subjects who volunteer will participate in this sub-study and will have BAL fluid collected 
48 hours (±36 hours) post-dose (on approximately Day 2 or Day 3, depending on time of study 
drug administration) to determine ASN-1 and ASN-2 levels and blood to ELF ratio. Subjects 
participating in the BAL fluid PK sub-study will have a blood sample collected for PK 
measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid collection 

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or if BAL fluid is collected as part of a standard of care procedure from any subject enrolled in the 
sub-study at any time post-randomization). 
Blood samples obtained for ADA and PK analysis purposes will also be used to assess the amount 
of pre-existing anti-S. aureus toxin antibodies and the toxin neutralizing titer of the serum sample 
prior to and after randomization. Only antigen-specific antibody titers will be determined and no 
genetic information will be extracted from these samples. Samples will be destroyed following the 
completion of all S. aureus anti-toxin antibody analyses. 
3.3 
Study Indication 
The prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily 
colonized with S. aureus. 

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4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects must meet all of the following criteria at the Screening and Randomization Visits in order 
to be eligible for randomization into the study: 
1. Subject, legally authorized representative (LAR), or CIP (if applicable) has provided written 
informed consent; 
2. Subject is ≥18 years of age at the time of enrollment; 
3. Subject is currently hospitalized and is mechanically ventilated endotracheally 
(i.e., orotracheal or nasotracheal) and, in the Investigator’s opinion, will require ongoing 
ventilator support for at least 48 hours; 
NOTE: Subjects with a tracheostomy at the time of enrollment are not eligible. After 
enrollment, conversion to tracheostomy is permitted per standard of care. 
4. Female subjects must not be pregnant or lactating. Female subjects of childbearing potential 
must have a documented negative pregnancy test at the Screening Visit. Female subjects may 
be enrolled on the basis of a negative urine pregnancy test, pending the result of a negative 
serum pregnancy test prior to randomization; and 
5. Female subjects of childbearing potential and non-surgically sterile male subjects who are 
sexually active must agree to use an approved highly effective form of contraception from the 
time of informed consent until 165 days post-dose. Approved forms of contraception include 
hormonal intrauterine devices, hormonal contraceptives (oral birth control pill, depo, patch, or 
injectable) together with supplementary double barrier methods such as condoms or 
diaphragms with spermicidal gel or foam. 
NOTE: The following categories define women who are NOT considered to be of childbearing 
potential: 
• Premenopausal female with 1 of the following: 
o Documented hysterectomy, 
o Documented bilateral salpingectomy, or 
o Documented bilateral oophorectomy, or 
• Postmenopausal female, defined as having amenorrhea for at least 12 months without an 
alternative medical cause. 
4.2 
Exclusion Criteria 
Subjects who meet any of the following criteria at the Screening and/or Randomization Visit will 
be excluded from participation in the study: 
1. Subject has received IV immunoglobulin therapy within 4 months prior to the Screening Visit; 
2. Subject has a chest X-ray or thoracic CT scan that is definitive for a diagnosis of pneumonia; 

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3. Subject demonstrates both of the following: 
a. Need for acute changes in ventilator support to enhance oxygenation or to the amount of 
positive end-expiratory pressure; AND 
NOTE: Changes made in ventilator support due to day-to-day maintenance other than those 
changes made to improve oxygenation will not exclude a subject from participation in the 
study. 
b. New onset of purulent suctioned respiratory secretions; 
4. Subject has a known and documented ETA culture showing heavy colonization with a 
Gram-negative organism at enrollment or at any time during the Screening period; 
NOTE: Randomization should not be delayed while waiting for Gram-negative results if heavy 
colonization with S. aureus has been confirmed. 
5. Subject has been diagnosed with neutropenia (absolute neutrophil count <500/mm3); 
6. Subject has a severe non-pulmonary source of infection which, in the Investigator’s opinion, 
would interfere with the conduct of the study or jeopardize the subject’s safety; 
7. Subject is currently on either continuous veno-venous hemodialysis or extracorporeal 
membrane oxygenation; 
8. Subject has been previously exposed to ASN100 or ASN-1 or ASN-2, individually; 
9. Subject has a known hypersensitivity to ASN100 or any of its excipients; 
10. Subject has received any investigational product within 30 days prior to the Screening Visit 
(or 5 half-lives of the investigational product, whichever is longer); 
11. Subject has, in the opinion of the Investigator, a high probability of death within 72 hours of 
enrollment;  
12. Subject is, in the opinion of the Investigator, not able or willing to comply with the protocol; 
13. Any condition that, in the opinion of the Investigator, would compromise the safety of the 
subject, the potential activity of the study drug, or the quality of the data; or 
14. Subjects with a known history or current (suspected) diagnosis of cytokine release syndrome 
associated with the administration of peptides, proteins, and/or antibodies.20 
NOTE: Subjects with a prior history of sepsis are not excluded. 
4.3 
Randomization Criteria 
Following the Screening Visit, eligible subjects who meet all of the inclusion criteria and none of 
the exclusion criteria will be screened daily (while mechanically ventilated) for up to 8 days via 
quantitative or semi-quantitative culture of an ETA to identify those subjects who are heavily 
colonized with S. aureus (see Section 3.1).  
Screening for heavy S. aureus colonization by ETA culture will continue on Day 11 and Day 14 
provided the subject remains mechanically ventilated, for a total Screening Period of up to 14 days. 
Additional ETA screening may occur on Days 9, 10, 12, and 13 at the discretion of the Investigator 
and providing the subject remains mechanically ventilated.  

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Once an enrolled subject has an ETA culture reported positive for heavy S. aureus colonization 
and meets all of the inclusion and none of the exclusion criteria, they are eligible for randomization. 
If they are not randomized on this occasion according to the protocol, they are no longer eligible 
for continued ETA sampling and randomization, and will be discontinued from the study; however, 
if subjects are extubated and subsequently re-intubated/mechanically ventilated, they are eligible 
for re-screening as a new subject enrollment. Subjects who were previously randomized are not 
eligible to be re-consented and re-screened. 
At the time of randomization, if a subject’s screening ETA culture also shows heavy colonization 
of a Gram-negative organism (i.e., heavy co-colonization of both Gram-positive and 
Gram-negative organisms), the subject will not be randomized into the study. 
NOTE: Randomization should not be delayed while waiting for Gram-negative results if heavy 
colonization with S. aureus has been confirmed. 
At the Randomization Visit, subjects must meet all of the following requirements to be randomized 
into the study: 
1. Subject continues to meet all of the inclusion criteria and none of the exclusion criteria required 
at the Screening Visit; 
NOTE: Subjects who undergo tracheostomy after enrollment are still eligible for 
randomization, provided they remain mechanically ventilated (see criterion 3 below). 
2. Subject is heavily colonized with S. aureus as determined by either quantitative or 
semi-quantitative culture of an ETA (see Section 3.1);  
NOTE: The results of the qualifying ETA culture must allow randomization to occur within 
48 hours (or up to 60 hours with Medical Monitor approval) from the time the ETA sample 
was collected. Subjects with ETA culture results obtained after 60 hours showing heavy 
colonization of S. aureus may not be randomized and will be discontinued from the study. 
3. Subject remains mechanically ventilated and, in the Investigator’s opinion, will require 
ongoing ventilator support for at least 48 hours; and 
4. Subject has, in the opinion of the Investigator, a probability of survival beyond 72 hours 
post-randomization. 
4.4 
Withdrawal Criteria 
Participation of a subject in this clinical study may be discontinued for any of the following 
reasons: 
• The subject or LAR withdraws consent from the study for any reason; 
• The subject or LAR requests discontinuation from the study for any reason; 
• Occurrence of any medical condition or circumstance that exposes the subject to 
substantial risk and/or does not allow the subject to adhere to the requirements of the 
protocol; 
• Any SAE, clinically significant adverse event, severe laboratory abnormality, intercurrent 
illness, or other medical condition which indicates to the Investigator that continued 
participation is not in the best interest of the subject; 

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• Pregnancy; 
• Requirement of prohibited concomitant medication; 
• Subject failure to comply with protocol requirements or study-related procedures; or  
• Termination of the study by the Sponsor or the regulatory authority. 
If a subject withdraws prematurely from the study due to the above criteria (except in the case of 
withdrawal of consent) or any other reason, study staff should make every effort to complete the 
full panel of assessments scheduled for the Early Termination Visit. The reason for subject 
withdrawal must be documented in the eCRF. 
In the case of subjects lost to follow-up, attempts to contact the subject must be made and 
documented in the subject’s medical records. 
Randomized subjects who are withdrawn will not be replaced.  

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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
Following Screening/Enrollment and upon determination that a subject is heavily colonized with 
S. aureus as determined by a positive quantitative or semi-quantitative culture of an ETA (see 
Section 3.1), eligible subjects will be randomized in a 1:1 ratio to 1 of 2 treatment groups: 
• ASN100 administered either sequentially or simultaneously as 2 separate IV infusions of 
ASN-1 and ASN-2, or 
• Placebo administered either sequentially or simultaneously as 2 separate IV infusions. 
Whether ASN-1, ASN-2, or placebo are administered sequentially or simultaneously will be 
determined by operational considerations of IV access at the time of dosing. If 2 IV lines are 
available for simultaneous administration this is preferable; however, if IV access or other 
considerations support sequential administration, this is allowed provided that both infusions are 
completed within 3 hours.  
Following randomization on Day 1, subjects will receive either a single IV dose of 3600 mg of 
ASN100 (comprised of separate infusions each of 1800 mg ASN-1 and 1800 mg ASN-2) or 
matching placebos, per their assigned randomization scheme.  
5.2 
Stratification 
To ensure balance among the treatment groups, randomization for this study will be stratified by 
receipt or non-receipt of concomitant anti-staphylococcal antibiotics at the time of randomization 
that are potentially active against S. aureus pneumonia, including, but not limited to, nafcillin, 
oxacillin, vancomycin, linezolid, telavancin, ceftaroline, ceftobiprole, and teicoplanin. 
5.3 
Rationale for Dosing 
A series of PK and PD experiments was conducted using the rabbit S. aureus pneumonia model 
and measured PK in both healthy rabbits and rabbits with pneumonia caused by several S. aureus 
strains. The range of effective doses for preventing S. aureus pneumonia in animal models was 
2.5 to 10 mg/kg of each component of ASN100. The 20 mg/kg dose (10 mg ASN-1 and 
10 mg ASN-2) translated into a 1600 mg dose for an 80 kg subject. 
ASN100 was well tolerated up to 8000 mg (i.e., 4000 mg ASN-1 and 4000 mg ASN-2) in a 
single-ascending dose study conducted in healthy human volunteers. There were no reported 
related SAEs and 2 related TEAEs of headache and fatigue were reported in this study. These data 
and data obtained from the nonclinical program determined that ASN100 3600 mg (i.e., 1800 mg 
ASN-1 and 1800 mg ASN-2) will be an appropriate dose to assess safety and efficacy in this first 
study in mechanically ventilated subjects who are heavily colonized with S. aureus.  
This study did not identify a maximum tolerated dose. Based on these observations from the single 
ascending dose study, as well as data obtained from the nonclinical program conducted to date, it 
is reasonable to select a dose of ASN100 of 3600 mg (i.e., 1800 mg ASN-1 and 1800 mg ASN-2) 
as an appropriate dose to assess safety and efficacy in this first study in mechanically ventilated 
subjects who are heavily colonized with S. aureus. 

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5.4 
Randomization and Blinding 
Randomization will occur at the Randomization Visit following determination of the subject’s 
eligibility. Subjects will be randomized via a centralized Interactive Response Technology (IRT) 
system in a 1:1 ratio to receive a single dose (2 infusions) of either ASN100 or matching placebo. 
The study follows a double-blind, placebo-controlled design. All study personnel, including 
investigators, site personnel, site pharmacist, Sponsor and contract research organization (CRO) 
staff involved in the conduct of the study (e.g., clinical research associate [CRA]/monitor), and 
subjects will be blinded to treatment assignment. ASN100 and placebo will be identical in 
appearance to preserve blinding. 
5.5 
Breaking the Blind 
Randomization data will be kept strictly confidential until the time of unblinding and will not be 
accessible by subjects, Investigators, or anyone performing assessments and having access to study 
data until unblinding occurs. Individual subject unblinding will only occur in the case of subject 
emergencies, with complete unblinding at the conclusion of the study. 
Emergency breaking of the assigned treatment code should only be undertaken when it is essential 
that knowledge of the treatment assignment is necessary to treat the subject’s emergency safely 
and effectively. Emergency treatment code breaks will be performed using the IRT. When the 
Investigator contacts the system to break a treatment code for a subject, he/she must provide the 
requested subject’s identifying information and confirm the necessity to break the treatment code 
for the subject. The Investigator will then receive details of the investigational drug treatment for 
the specified subject and a fax or email confirming this information. The system will automatically 
inform the Sponsor and Medpace study personnel that the code has been broken. 
5.6 
Drug Supplies 
5.6.1 
Formulation and Packaging 
ASN100 is a combination product with 2 separate human mAb components of the IgG1 isotype. 
The specific mAbs are formulated separately and called ASN-1 and ASN-2.  
ASN-1 is a broadly cross-reactive anti-toxin mAb that targets Hla and 3 F-components (HlgB, 
LukF, and LukD) involved in forming 4 of the 5 bi-component leukocidins of S. aureus. 
ASN-2 is directed against the fifth bi-component toxin of S. aureus, LukGH. 
Each component is supplied as a sterile, colorless, clear liquid solution formulated ready for 
injection. 
ASN-1 and ASN-2 will be supplied in separate 10 mL vials as a sterile solution for infusion with 
an extractable volume of 10 mL and a nominal mAb concentration of 20 mg/mL. Each vial will 
contain 200 mg of ASN-1 or 200 mg of ASN-2. Matched vials of ASN-1 placebo and ASN-2 
placebo will also be provided. 
Additional details regarding formulation and packaging will be provided in the Pharmacy Manual 
and the Investigator’s Brochure. 

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5.6.2 
Study Drug Preparation and Dispensing 
Blinded study drug and reference preparations will be delivered to the study site. The site 
pharmacist will prepare the study drug for administration by extracting all volume from each set 
of 9 vials and inserting into an empty IV bag for each set, using aseptic technique according to the 
Pharmacy Manual. These will be delivered to the study site research staff in 2 blinded, ready-to-use 
infusion bags. 
Additional details regarding study drug preparation and dispensing will be provided in the 
Pharmacy Manual. 
5.6.3 
Study Drug Administration 
Subjects will receive ASN100 or matching placebo via 2 IV infusions over a duration of 
approximately 50 to 60 minutes per infusion.  
Both ASN100 and placebo will be administered as 2 separate infusions (either sequentially or 
simultaneously). The last infusion will be completed within 5 hours from initiation of drug 
preparation in the pharmacy. 
Infusions delivered simultaneously must be administered via distinct IV lines (either peripheral or 
central lines; in the instance that a multi-port central line is used, infusions will be delivered 
through separate ports) such that the infusions do not mix before entering the blood stream.  
In the occasion that the 2 infusion bags cannot be hung simultaneously, the blinded IV bags will 
indicate which bag should be infused first and which bag should be infused second. If administered 
sequentially, no more than a 3-hour window should elapse from the time of initiation of the first 
infusion to the completion of the second infusion.  
ASN100 will be administered as separate infusions of 1800 mg ASN-1 and 1800 mg ASN-2 
(9 vials of each to be pooled aseptically according to the Pharmacy Manual into separate infusion 
bags) delivered either sequentially within a 3-hour window from the time of initiation of the first 
infusion to the completion of the second infusion, or simultaneously. 
Placebo will be administered as separate infusions of 9 vials of ASN-1 placebo and 9 vials of 
ASN-2 placebo (vials to be pooled aseptically according to the Pharmacy Manual into separate 
infusion bags) delivered either sequentially within a 3-hour window from the time of initiation of 
the first infusion to the completion of the second infusion, or simultaneously. 
The infusion catheter and tubing will be flushed with sterile saline for injection immediately before 
and following completion of the infusion. 
Either infusion may be discontinued if deemed medically necessary at any time. 
If the first infusion is stopped at any point due to the concern of an adverse event, the second 
infusion will not be administered. 
Refer to the Pharmacy Manual for additional details regarding study drug administration. 

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5.6.4 
Treatment Compliance 
Study drug will be administered at the clinical site by blinded study personnel. The date and time 
of administration, including start and completion times of each infusion, will be accurately logged 
in the source documentation. Due to the single dose design of this study, treatment compliance is 
anticipated to be high. 
5.6.5 
Storage and Accountability 
Study drug (ASN-1, ASN-2, and matching placebos) will be stored at 2°C to 8°C, will be protected 
from light, and will be kept in a secure area with access limited to authorized personnel. The 
primary packaging (vials) is to be kept within the secondary packaging (carton box). 
Investigational site personnel (e.g., study pharmacist) will perform an ongoing inventory of study 
drug products. At the end of the study, a full reconciliation of drug inventory will be performed 
and the results of the inventory will be recorded in the drug accountability log. Any unused vials 
should be returned for destruction.  
Additional details regarding study drug storage and accountability will be provided in the 
Pharmacy Manual. 
5.7 
Prior and Concomitant Medications and/or Procedures 
5.7.1 
Excluded Medications and/or Procedures 
The use of any investigational product within 30 days prior to the Screening Visit (or 5 half-lives 
of the investigational product, whichever is longer) is prohibited. Any immunoglobulin preparation 
for any medical indication is prohibited through follow-up Day 90 of the study. 
Prior use of ASN100, ASN-1, or ASN-2 is prohibited. 
5.7.2 
Documentation of Prior and Concomitant Medication Use 
All prior medications received by the subject within 14 days prior to study drug administration and 
any concomitant medications used throughout the duration of the study will be recorded in the 
source documents and on the appropriate eCRF. The medication name, route of administration, 
dose, frequency, indication, and duration of treatment (start and stop dates) will be recorded. 
 

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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Written informed consent will be obtained from all subjects prior to any study-specific procedures 
being performed. A separate consent will be obtained from those subjects who participate in the 
BAL fluid PK sub-study. 
See Section 12.3 for additional details regarding informed consent. 
6.2 
Screening/Enrollment (Up to Day -14) 
Screening/Enrollment may be performed up to 14 days prior to randomization. Subjects who meet 
all of the inclusion criteria and none of the exclusion criteria will be screened daily (while 
mechanically ventilated) for up to 8 days to identify those subjects who are heavily colonized with 
S. aureus (see Section 3.1). 
Screening for heavy S. aureus colonization by ETA culture will continue on Day 11 and Day 14 
provided the subject remains mechanically ventilated, for a total Screening Period of up to 14 days. 
Additional ETA screening may occur on Days 9, 10, 12, and 13 at the discretion of the Investigator 
and providing the subject remains mechanically ventilated.  
Once an enrolled subject has an ETA culture reported positive for heavy S. aureus colonization 
and meets all of the inclusion and none of the exclusion criteria, they are eligible for randomization. 
If they are not randomized on this occasion according to the protocol, they are no longer eligible 
for continued ETA sampling and randomization, and will be discontinued from the study; however, 
if subjects are extubated and subsequently re-intubated/mechanically ventilated, they are eligible 
for re-screening as a new subject enrollment. Subjects who were previously randomized are not 
eligible to be re-consented and re-screened. 
The following procedures will be performed during Screening/Enrollment: 
• Obtain informed consent; 
• Review inclusion and exclusion criteria; 
• Record medical history;  
• Record demographics; 
• Record antibiotic and other medication history; 
• Obtain height and body weight measurements; 
• Perform complete physical examination; 
• Obtain vital sign measurements, including oxygenation status; 
• Perform pregnancy test for female subjects of childbearing potential only. Female subjects 
may be enrolled on the basis of a negative urine pregnancy test, pending the result of a 
negative serum pregnancy test prior to randomization; 
• Assess ventilator device status; 
• Perform chest X-ray or thoracic CT scan. A chest X-ray or thoracic CT scan obtained as 
part of standard of care within 24 hours prior to the initial Screening Visit is sufficient 

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provided there are no changes in the subject’s clinical status (e.g., no change in ventilation 
status, secretions, or signs/symptoms that may be suggestive of pneumonia) within the 24 
hours following imaging; 
• Obtain ETA for culture;  
• Assess for other S. aureus-associated infections; and 
• Perform adverse event assessment (adverse events that occur between the time the subject 
signs the ICF and the Randomization Visit will only be recorded if related to a study-
specific procedure). 
6.3 
Randomization Visit (Day 1 Pre-Dose) 
The Randomization Visit will occur pre-dose on Day 1. At the time of randomization, if a subject’s 
screening ETA culture also shows heavy colonization of a Gram-negative organism (i.e., heavy 
co-colonization of both Gram-positive and Gram-negative organisms), the subject will not be 
randomized into the study; however, randomization should not be delayed while waiting for 
Gram-negative results if heavy colonization with S. aureus has been confirmed. 
The following procedures will be performed at the Randomization Visit: 
• Review inclusion, exclusion, and randomization criteria; 
• Review and record medical history (if changes occurred since the Screening Visit); 
• Review and record antibiotic and other medication history (if changes occurred since the 
Screening Visit); 
• Perform limited physical examination (to include, at a minimum, a pulmonary 
examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 
• Perform clinical laboratory assessments, including chemistry, hematology, coagulation, 
and urinalysis; 
• Obtain a blood sample for procalcitonin testing; 
• Assess ventilator device status; 
• Perform chest X-ray or thoracic CT scan. A chest X-ray or thoracic CT scan obtained 
within 24 hours of the Randomization Visit is sufficient, provided there are no changes in 
the subject’s clinical status (e.g., no change in ventilation status, secretions, or 
signs/symptoms that may be suggestive of pneumonia) since the time of imaging; 
NOTE: Subjects who are heavily colonized and who would have otherwise qualified for 
randomization, but who are found to have already progressed to pneumonia, may be 
eligible to enroll in a site-specific pilot treatment sub-study. See Appendix C for criteria. 
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 
• Assess for other S. aureus-associated infections; 
• Obtain nasal swab specimens for culture (one from each nostril); 

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• Randomize to study treatment; 
• Obtain a blood sample for ADA and assessment of pre-existing anti-S. aureus toxin 
antibodies; 
• Perform 12-lead ECG; 
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.4 
Treatment Period (Day 1) 
The following procedures will be performed on Day 1 following administration of study drug: 
• Obtain vital sign measurements, including oxygenation status; 
• Assess ventilator device status; 
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 
NOTE:  Subjects who had already progressed to pneumonia while being evaluated for 
randomization under the VAP Prevention study, and who met eligibility criteria for the 
pilot treatment sub-study, will have the same study assessments and protocol required 
procedures as outlined in this and subsequent sections of this protocol, however the nature 
of the assessments may vary slightly to accommodate the sub-study endpoint of resolution 
of pneumonia. See Appendix C for criteria. 
• Assess for other S. aureus-associated infections; 
• Administer study drug; 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies (to be collected immediately following the completion of the second infusion 
[+15 minutes] and at 6 hours [±4 hours] and 24 hours [±6 hours] post-dose); 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization; 
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.5 
Monitoring Period 
6.5.1 
Day 2/Day 3 – Bronchoalveolar Lavage Fluid Pharmacokinetic Sub-Study 
The following procedures will be performed 48 hours (±36 hours) post-dose (Day 2 or Day 3 
depending on the time of study drug administration) for those subjects participating in the 
BAL fluid PK sub-study only or if BAL fluid is collected as part of a standard of care procedure 
for any subject at any other time post-randomization for any other reason: 
• Obtain vital sign measurements, including oxygenation status; 
• Assess ventilator device status; 

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• Perform chest X-ray or thoracic CT scan; 
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 
• Assess for other S. aureus-associated infections; 
• Obtain BAL fluid to determine ASN-1 and ASN-2 concentrations (48 hours [±36 hours] 
post-dose) for those subjects participating in the BAL fluid PK sub-study (if BAL fluid is 
collected as part of a standard of care procedure from any subject enrolled in the sub-study 
at any other time post-randomization for any other reason, if possible, a sample for PK 
analysis will also be obtained);  
• Obtain a blood sample for PK measurement ±1 hour relative to BAL fluid collection 
(including scheduled BAL fluid collection or if BAL fluid is collected as part of a standard 
of care procedure from any subject enrolled in the sub-study at any time post-
randomization); 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization;  
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.5.2 
Day 2 to Day 21 
The following procedures will be performed daily (unless otherwise indicated) from Day 2 to 
Day 21 while the subject is hospitalized. For subjects participating in the BAL fluid PK sub-study, 
procedures noted for the Day 2 visit only need to be performed 1 time: 
• Perform limited physical examination (to include, at a minimum, a pulmonary 
examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 
• Perform clinical laboratory assessments, including chemistry, hematology, coagulation, 
and urinalysis. Blood samples for chemistry, hematology, and coagulation will be obtained 
on Days 2 (+1 day), 4 (±1 day), and 6 (±1 day) of the Monitoring Period, and twice weekly 
during Week 2 (Day 8 through Day 14) and/or Week 3 (Day 15 through Day 21) of the 
Monitoring Period while the subject remains hospitalized. Urine for urinalysis will be 
obtained on Day 6 (±1 day) of the Monitoring Period only; 
• Obtain a blood sample for procalcitonin testing (on day of diagnosis of pneumonia only, 
if applicable); 
• Assess ventilator device status (if applicable); 
• Perform chest X-ray or thoracic CT scan (required during the Monitoring Period for those 
subjects presenting with signs and symptoms of a respiratory infection such as dyspnea, 
tachypnea, fever, or cough); 
• Obtain adequate respiratory specimen for culture (if clinically indicated); 
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 

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• Assess for other S. aureus-associated infections; 
• Obtain a blood sample for ADAs (to be obtained only upon discharge from the ICU, if 
discharge occurs prior to Day 22); 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies (Days 4 [±1 day], 7 [±1 day], and 14 [±2 days] only); 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization;  
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.5.3 
Day 22 
The following procedures will occur on Day 22 (+2 days): 
• Perform limited physical examination (if subject is hospitalized) (to include, at a 
minimum, a pulmonary examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 
• Perform pregnancy test for female subjects of childbearing potential only (additional 
pregnancy testing may occur throughout the duration of the study, per applicable country 
requirements); 
• Perform clinical laboratory assessments including chemistry, hematology, coagulation, 
and urinalysis; 
• Obtain a blood sample for procalcitonin testing; 
• Assess ventilator device status (if applicable); 
• Perform chest X-ray or thoracic CT scan (required during the Monitoring Period for those 
subjects presenting with signs and symptoms of a respiratory infection such as dyspnea, 
tachypnea, fever, or cough); 
• Obtain adequate respiratory specimen for culture (if clinically indicated); 
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 
• Assess for other S. aureus-associated infections; 
• Obtain a blood sample for ADAs; 
• Perform 12-lead ECG; 
• Assess for survival and discharge disposition; 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies; 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization;  

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• Record concomitant medications; and 
• Perform adverse event assessment. 
6.6 
Follow-Up Period 
6.6.1 
Day 28 (+2 Days) Follow-Up 
The following procedures will occur during a follow-up telephone call or visit, if the subject 
remains hospitalized, on Day 28 (+2 days): 
• Assess ventilator device status (if applicable); and 
• Assess for survival and discharge disposition. 
6.6.2 
Day 40 to Day 89 (Follow-Up Safety Visit) 
For subjects who remain hospitalized between Day 40 and Day 90 at the institution where they 
receive study treatment, a follow-up safety visit will be performed on the day of discharge.  
The following procedures will occur on the day of hospital discharge for subjects who are 
discharged between Day 40 and Day 90: 
• Perform limited physical examination (to include, at a minimum, a pulmonary 
examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 
• Assess ventilator device status (if applicable); 
• Obtain a blood sample for ADAs; 
• Perform 12-lead ECG; 
• Assess for survival and discharge disposition; 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies; 
• Track days on ventilator from randomization (if applicable); 
• Track days in ICU (or other observation area) from randomization; 
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.6.3 
Safety Visit (Day 90 [±7 Days]) 
The following procedures will be performed at the Safety Visit on Day 90 (±7 days). If the subject 
is unable to return to the site, this visit may be conducted by telephone, with procedures performed 
as appropriate (i.e., concomitant medications and adverse events collected): 
• Perform limited physical examination (to include, at a minimum, a pulmonary 
examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 

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• Assess ventilator device status (if applicable); 
• Obtain a blood sample for ADAs; 
• Perform 12-lead ECG; 
• Assess for survival and discharge disposition; 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies; 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization; 
• Record concomitant medications; and 
• Perform adverse event assessment. 
6.7 
Early Termination Visit and Withdrawal Procedures 
For subjects who are withdrawn from the study prior to Day 22, the following procedures will be 
performed at an Early Termination Visit: 
• Perform limited physical examination (to include, at a minimum, a pulmonary 
examination [including auscultation]); 
• Obtain vital sign measurements, including oxygenation status; 
• Perform pregnancy test for female subjects of childbearing potential only; 
• Perform clinical laboratory assessments including chemistry, hematology, coagulation, 
and urinalysis (if clinically indicated); 
• Obtain a blood sample for procalcitonin testing; 
• Assess ventilator device status (if applicable); 
• Obtain adequate respiratory specimen for culture (if clinically indicated);  
• Assess for clinical signs/symptoms of pneumonia (Section 7.4.2; Table 1); 
• Assess for other S. aureus-associated infections; 
• Obtain a blood sample for ADAs; 
• Perform 12-lead ECG; 
• Assess for survival and discharge disposition; 
• Obtain a blood sample for PK measurement and assessment of anti-S. aureus toxin 
antibodies; 
• Track days on ventilator from randomization; 
• Track days in ICU (or other observation area) from randomization;  
• Record concomitant medications; and 
• Perform adverse event assessment. 

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7 
EFFICACY ASSESSMENTS 
7.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects in the MITT Population who develop 
S. aureus pneumonia as defined in Section 7.4 up to but not including Day 22. 
7.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints include: 
• Duration of mechanical ventilation during the first 21 days post-randomization for 
subjects in the MITT, Intent-to-Treat (ITT), and Per Protocol (PP) Populations; 
• Length of ICU stay during the first 21 days post-randomization for subjects in the MITT, 
ITT, and PP Populations;  
• The Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum following a single dose of 
ASN100 in the PK Population; and 
• 28-day all-cause mortality in the MITT, ITT, and PP Populations. 
7.3 
Exploratory Efficacy Endpoints 
Exploratory efficacy endpoints include: 
• Proportion of subjects in the MITT and PP Populations with a diagnosis of HABP at 
>48 hours post-extubation up to but not including Day 22 in extubated subjects; 
• Proportion of subjects in the MITT and PP Populations with development of VABP up to 
but not including Day 22; 
• Incidence of all bacterial pneumonias in the MITT, ITT, and PP Populations; 
• Incidence of other non-S. aureus pneumonias up to but not including Day 22 in the MITT, ITT, 
and PP Populations; and  
• Incidence of other S. aureus infections acquired following study drug administration up 
to but not including Day 22 in the MITT, ITT, and PP Populations. 

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7.4 
Microbiological and Clinical Assessments 
7.4.1 
Microbiological Assessment 
ETA specimens will be collected for culture during Screening/Enrollment to determine the degree 
of S. aureus colonization. Additional respiratory specimens may be collected for culture 
throughout the Monitoring Period or Early Termination (if applicable) if clinically indicated 
according to standard of care. 
If, as part of routine standard of care, additional respiratory and/or other microbiological specimens 
are collected for culture during the study, results will be documented within the eCRF. As fully 
described within the study lab manual, bacterial isolates recovered from these specimens that are 
deemed pathogens by the Investigator (if retained and available at the study site local microbiology 
laboratory) will be sent to a central microbiology laboratory for confirmation of pathogen 
identification (all isolates) and susceptibility testing (S. aureus isolates only). 
During the Monitoring Period, a diagnosis of S. aureus pneumonia will be determined if subjects 
have S. aureus identified from an adequate respiratory specimen (Section 7.4.1) and clinical signs 
and symptoms of pneumonia. For a diagnosis of S. aureus pneumonia, clinical signs and symptoms 
must occur ±2 days from the time of collection of an adequate respiratory specimen culture that is 
positive for S. aureus (Section 7.4.2).  
• 
For intubated subjects, a respiratory specimen obtained by BAL, non-bronchoscopic BAL, 
or protected specimen brush will be considered an adequate respiratory specimen; or 
• 
For extubated subjects, an adequate expectorated/induced sputum specimen is defined as 
<10 squamous epithelial cells and >25 PMNs/100× field; and 
• 
For both intubated and extubated subjects, adequate respiratory specimens will undergo 
either semi-quantitative or quantitative culture in accordance with the local laboratory’s 
standard procedure. 
7.4.2 
Assessment of Clinical Signs and Symptoms 
Subjects will be assessed daily throughout the Monitoring Period for the following clinical signs 
and symptoms presented in Table 1. 
Table 1. Clinical Signs and Symptoms 
Mechanically Ventilated Subjects 
Non-Mechanically Ventilated Subjects 
• 
Cough, 
• 
Rales, 
• 
Dullness on percussion,* 
• 
Bronchial breath sounds, 
• 
Egophony,* 
• 
Need for suctioning, 
• 
Need for ventilator support, and 
• 
Fever ≥38°C (≥100.4°F). 
• 
Cough, 
• 
Rales, 
• 
Dullness on 
percussion,* 
• 
Bronchial breath 
sounds, 
• 
Egophony,* 
• 
Dyspnea, 
• 
Tachypnea, 
• 
Respiratory rate, 
• 
Hypoxemia, and 
• 
Fever ≥38°C 
(≥100.4°F). 
*If routinely performed. 

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A diagnosis of pneumonia (HABP or VABP) will be determined as defined in Table 2. 
Table 2. 
Definition of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia 
Indication 
Definition 
HABP 
• 
A chest X-ray showing new or progressive infiltrates suggestive of pneumonia (as assessed 
by the Investigator); 
• 
At least ONE of the following: 
o 
Has been hospitalized for >48 hours, or 
o 
Developed clinical signs and symptoms within 7 days following hospital discharge; 
• 
At least ONE of the following: 
o 
New onset or worsening pulmonary signs/symptoms such as cough, dyspnea, tachypnea 
(e.g., respiratory rate >25 breaths per minute), expectorated sputum production, or the 
requirement for mechanical ventilation (if subject is not already ventilated); 
o 
Need for acute changes in ventilator support to enhance oxygenation or to the amount of 
PEEP; or 
o 
New onset of suctioned respiratory secretions; AND 
• 
At least ONE of the following clinical signs/symptoms: 
o 
Temperature >38°C or <35°C, 
o 
WBC count ≥10,000 cell/mm3 or ≤4500 cell/mm3, or 
o 
>15% immature neutrophils (bands) on peripheral blood smear. 
VABP 
• 
A chest X-ray showing new or progressive infiltrates suggestive of pneumonia (as assessed 
by the Investigator);  
• 
Subject has received mechanical ventilation via an endotracheal or nasotracheal tube for 
≥48 hours; 
• 
At least ONE of the following: 
o 
New onset or worsening pulmonary signs/symptoms such as cough, dyspnea, tachypnea 
(e.g., respiratory rate >25 breaths per minute), expectorated sputum production, or the 
requirement for mechanical ventilation (if subject is not already ventilated); 
o 
Need for acute changes in ventilator support to enhance oxygenation or to the amount of 
PEEP; or 
o 
New onset of suctioned respiratory secretions; AND 
• 
At least ONE of the following clinical signs/symptoms: 
o 
Temperature >38°C or <35°C, 
o 
WBC count ≥10,000 cell/mm3 or ≤4500 cell/mm3, or 
o 
>15% immature neutrophils (bands) on peripheral blood smear. 
HABP = hospital-acquired bacterial pneumonia; PEEP = positive end-expiratory pressure; VABP = ventilator-associated 
bacterial pneumonia; WBC = white blood cell. 

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8 
PHARMACOKINETIC ASSESSMENTS 
8.1 
Pharmacokinetic Endpoint 
The primary PK endpoints are the Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum 
following a single IV dose of ASN100 in the PK Population. 
The levels of ASN-1 and ASN-2 will be measured in BAL fluid in a PK sub-study which will 
allow the calculation of a blood to ELF ratio.  
8.2 
Pharmacokinetic Assessments 
Samples for PK analysis will be obtained to determine the PK of ASN-1 and ASN-2 in serum and 
BAL fluid (for subjects participating in the BAL fluid PK sub-study only). Instructions for the 
collection, handling, and storage of biological samples will be provided in a separate Laboratory 
Manual.  
In order to maintain the study blind, all subjects, including those randomized to receive placebo, 
will have PK samples obtained at the specified time points. The actual date and time of each sample 
will be recorded. 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded Sponsor or CRO personnel until the study has been unblinded. 
8.2.1 
Serum Pharmacokinetic Sampling 
Blood samples will be obtained for the measurement of ASN-1 and ASN-2 in serum. At the 
completion of the second infusion, blood samples for PK analysis will be collected immediately 
following the completion of the second infusion (+15 minutes) and at 6 hours (±4 hours) and 
24 hours (±6 hours) post-dose. 
In addition, a PK sample will be obtained from all subjects on Days 4 (±1 day), 7 (±1 day), 
14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will be collected 
on the day of discharge (if discharge occurs between Day 40 and Day 90), on Day 90 (if 
hospitalized or if the subject is able to return to the clinic), or Early Termination (if applicable). 
The following serum PK parameters will be assessed: 
• Maximum serum concentration (Cmax), 
• Time to maximum serum concentration (Tmax), 
• Area under the serum concentration-time curve (AUC), and 
• Terminal elimination half-life (t1/2). 
Subjects participating in the BAL fluid PK sub-study will have a blood sample collected for 
PK measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid 
collection or if BAL fluid is collected as part of a standard of care procedure from any subject 
enrolled in the sub-study at any time post-randomization). 

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8.2.2 
Bronchoalveolar Lavage Fluid Pharmacokinetic Sampling 
Select sites will be invited to participate in a BAL fluid PK sub-study. Approximately 25 to 
35 subjects who volunteer will participate in this sub-study and will have BAL fluid collected 
48 hours (±36 hours) post-dose (on approximately Day 2 or Day 3, depending on time of study 
drug administration) to determine ASN-1 and ASN-2 levels and blood to ELF ratio. If BAL fluid 
is collected as part of a standard of care procedure from any subject enrolled in the sub-study at 
any other time post-randomization for any other reason, if possible, a sample for PK analysis will 
also be obtained.  
8.2.3 
Analysis of Anti-Staphylococcus aureus Toxin Antibody Titers 
Blood samples obtained for ADA and PK analysis purposes will also be used to assess the amount 
of pre-existing anti-S. aureus toxin antibodies and the toxin neutralizing titer of the serum sample 
prior to and after randomization. Only antigen-specific antibody titers will be determined and no 
genetic information will be extracted from these samples. Samples will be destroyed following the 
completion of all S. aureus anti-toxin antibody analyses. 

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9 
SAFETY ASSESSMENTS 
9.1 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An adverse event can therefore be any unfavorable and/or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of an investigational medicinal product, whether or not related to the investigational medicinal 
product. All adverse events, including observed or volunteered problems, complaints, or 
symptoms, are to be recorded on the appropriate eCRF. 
Adverse events that occur between the time the subject signs the ICF and the Randomization Visit 
will only be recorded if related to a study-specific procedure. Beginning with randomization all 
adverse events, which include clinical laboratory test and physical examination variables, will be 
monitored and documented until study participation is complete. Subjects should be instructed to 
report any adverse event that they experience to the Investigator. Site personnel will ensure each 
adverse event is recorded on the appropriate adverse event eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate adverse event on the eCRF. 
Additionally, the condition that led to a medical or surgical procedure (e.g., surgery, endoscopy, 
tooth extraction, or transfusion) should be recorded as an adverse event, not the procedure.  
Any medical condition already present at the time of randomization should not be reported as an 
adverse event unless the medical condition or signs or symptoms present at baseline change in 
severity or seriousness at any time during the study. In this case, it should be reported as an adverse 
event. 
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study or are present at the time of randomization and significantly worsen 
during the study should be reported as adverse events. The Investigator will exercise his or her 
medical and scientific judgment in deciding whether an abnormal laboratory finding or other 
abnormal assessment is clinically significant. Clinically significant abnormal laboratory values 
occurring during the clinical study will be followed until repeat tests return to normal, stabilize, or 
are no longer clinically significant. Any abnormal test that is determined to be an error does not 
require reporting as an adverse event. 
Lack of efficacy (i.e., development of pneumonia as defined in Section 7.4) will be captured as an 
efficacy measure and in general will not be considered an adverse event; however, new onset of 
specific pulmonary symptoms that do not meet the study-specific definition of pneumonia or 
worsening of baseline signs and symptoms should be captured as adverse events. Events that meet 
the criteria for an SAE (Section 9.2) should follow the procedures for SAE reporting as detailed in 
Section 9.3. 

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9.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product mean that a causal 
relationship between a medicinal product and an adverse event is at least a reasonable possibility, 
i.e., the relationship cannot be ruled out. 
9.1.2 
Unexpected Adverse Drug Reaction 
An Unexpected Adverse Drug Reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information.  
The reference safety information for ASN100 is included in the current version of the 
Investigator’s Brochure. The reference safety information will be reviewed yearly and the 
periodicity of the review will be harmonized with the reporting period of the Development Safety 
Update Report. 
9.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each adverse event as mild, moderate, or 
severe, and will also categorize each adverse event as to its potential relationship to study drug 
using the categories of yes or no. 
Assessment of Severity: 
Mild – An event that is easily tolerated and generally not interfering with normal daily activities. 
Moderate – An event that is sufficiently discomforting to interfere with normal daily activities. 
Severe – An event that is incapacitating with inability to work or perform normal daily activities. 
Causality Assessment: 
The relationship of an adverse event to the administration of the study drug is to be assessed 
according to the following definitions: 
No (unrelated, not related, no relation) – The time course between the administration of study drug 
and the occurrence or worsening of the adverse event rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc.) is suspected. 
Yes (related) – The time course between the administration of study drug and the occurrence or 
worsening of the adverse event is consistent with a causal relationship and no other cause 
(concomitant drugs, therapies, complications, etc.) can be identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 

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The following factors should also be considered: 
• The temporal sequence from study drug administration: 
o The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event; 
• Underlying, concomitant, intercurrent diseases: 
o Each report should be evaluated in the context of the natural history and course of the 
disease being treated and any other disease the subject may have; 
• Concomitant drugs: 
o The other drugs the subject is taking or the treatment the subject receives should be 
examined to determine whether any of them might be recognized to cause the event in 
question; 
• Known response pattern for this class of study drug: 
o Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect; 
• Exposure to physical and/or mental stresses: 
o The exposure to stress might induce adverse changes in the recipient and provide a logical 
and better explanation for the event; and 
• The pharmacology and PK of the study drug: 
o The known pharmacologic properties (absorption, distribution, metabolism, and excretion) 
of the study drug should be considered. 
9.2 
Serious Adverse Events 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes: 
• Death; 
• A life-threatening adverse event; 
o NOTE: An adverse event or adverse reaction is considered “life-threatening” if, in the view 
of either the Investigator or Sponsor, its occurrence places the subject at immediate risk of 
death. It does not include an event that, had it occurred in a more severe form, might have 
caused death. 
• Requires hospitalization or prolongation of existing hospitalizations; 
o NOTE: Any hospital admission with at least 1 overnight stay will be considered an 
inpatient hospitalization. An emergency room visit without hospital admission will not be 
recorded as a SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent. However, unexpected complications and/or 
prolongation of hospitalization that occur during elective surgery should be recorded as 
adverse events and assessed for seriousness. Admission to the hospital for social or 

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situational reasons (i.e., no place to stay, live too far away to come for hospital visits) will 
not be considered inpatient hospitalizations.  
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions; 
• A congenital anomaly/birth defect; or 
• An important medical event. 
o NOTE: Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention 
to prevent one of the outcomes listed above. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalizations, or the 
development of drug dependency. 
9.3 
Serious Adverse Event Reporting − Procedures for Investigators 
Initial Reports 
Serious adverse events related to a study-specific procedure that occur between the Screening Visit 
and the Randomization Visit, and all SAEs occurring from the time of randomization until the 
Day 90 Safety Visit, must be reported to Medpace Clinical Safety within 24 hours of the 
knowledge of the occurrence (this refers to any adverse event that meets any of the aforementioned 
serious criteria). All SAEs that the Investigator considers related to study drug occurring after the 
Day 90 Safety Visit must be reported to the Sponsor. 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, Medpace Safety personnel will be notified 
electronically and will retrieve the form.  
If the event meets serious criteria and it is not possible to access the EDC system, send an email 
to Medpace Safety at Medpace-safetynotification@medpace.com or call the Medpace SAE hotline 
(phone number listed below), and fax the completed paper SAE form to Medpace (fax number 
listed below) within 24 hours of awareness. When the EDC system becomes available, the SAE 
information must be entered within 24 hours of the system becoming available.  
Safety Contact Information: Medpace Clinical Safety 
Medpace SAE hotline – USA: 
Telephone: +1-800-730-5779, Dial 3 or +1-513-579-9911, Dial 3 
Facsimile: +1-866-336-5320 or +1-513-579-0444 
Email: medpace-safetynotification@medpace.com 
Medpace SAE hotline – Europe: 
Telephone: +49-89-89-55-718-44 
Facsimile: +49-89-89-55-718-104 
Email: medpace-safetynotification@medpace.com 

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Follow-Up Reports 
The Investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the subject 
dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(e.g., subject discharge summary or autopsy reports) to Medpace Clinical Safety via fax or email. 
If it is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs.  
9.4 
Pregnancy Reporting 
If the subject or partner of a subject participating in the study becomes pregnant from the time of 
randomization until the Day 90 Safety Visit, the Investigator should report the pregnancy to 
Medpace Clinical Safety within 24 hours of being notified. Medpace Clinical Safety will then 
forward the Exposure In Utero form to the Investigator for completion.  
The subject or partner should be followed by the Investigator until completion of the pregnancy. 
If the pregnancy ends for any reason before the anticipated date, the Investigator should notify 
Medpace Clinical Safety. At the completion of the pregnancy, the Investigator will document the 
outcome of the pregnancy. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
9.5 
Expedited Reporting 
The Sponsor will report all relevant information about suspected unexpected serious adverse 
reactions that are fatal or life-threatening as soon as possible to the FDA, applicable competent 
authorities in all the Member States concerned, and to the Central Ethics Committee, and in any 
case no later than 7 days after knowledge by the Sponsor of such a case, and that relevant follow-up 
information will subsequently be communicated within an additional 8 days.  
All other suspected unexpected serious adverse reactions will be reported to the FDA, applicable 
competent authorities concerned, and to the Central Ethics Committee concerned as soon as 
possible but within a maximum of 15 days of first knowledge by the Sponsor.  
The Sponsor will also inform all Investigators as required.  
Expedited reporting of suspected unexpected serious adverse reactions related to 
non-investigational medical products (NIMPs) used in this study (and any other NIMPs) will not 
be necessary. Listings of cases related to NIMPs will be included in the Development Safety 
Update Report. 
9.6 
Clinical Laboratory Evaluations 
Standard clinical laboratory profiles for safety assessments (including chemistry, hematology, 
coagulation, and urinalysis) will be collected and evaluated at the Randomization Visit 
(Day 1 pre-dose).  
Blood samples for chemistry, hematology, and coagulation will be obtained on Days 2 (+1 day), 
4 (±1 day), and 6 (±1 day) of the Monitoring Period, or Early Termination (if applicable and if 

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clinically indicated). During Week 2 (Day 8 through Day 14) and/or Week 3 (Day 15 through 
Day 21) of the Monitoring Period, clinical laboratory assessments of chemistry, hematology, and 
coagulation will be performed twice a week while the subject remains hospitalized.  
Urine for urinalysis will be obtained at the Randomization Visit (Day 1 pre-dose), on Day 6 
(±1 day) of the Monitoring Period, or Early Termination (if applicable and if clinically indicated). 
Procalcitonin testing will be performed at the Randomization Visit (Day 1 pre-dose), on the day 
of diagnosis of pneumonia (if applicable), and on Day 22 or Early Termination (if applicable). 
Study required laboratory samples will be sent to the central laboratory for analysis. Subject care 
should be directed by local laboratory testing. 
See Appendix B for a list of clinical laboratory analytes to be assessed. 
9.7 
Radiographs and Imaging 
A chest X-ray or thoracic CT scan is required on 4 occasions during the study as defined below 
for (1) initial Screening Visit, (2) Randomization Visit, (3) Post-BAL sampling for those subjects 
participating in the optional BAL sub-study, and (4) Monitoring Period (Day 2 through Day 22) 
for those subjects presenting with signs/symptoms suggestive of a respiratory infection. 
• Initial Screening Visit: A chest X-ray or thoracic CT scan will be obtained at the initial 
Screening Visit to ensure that the subject does not have pneumonia. A chest X-ray or 
thoracic CT scan obtained as part of standard of care within 24 hours of the initial 
Screening Visit is sufficient provided there are no changes in the subject’s clinical status 
(e.g., no change in ventilation status, secretions, or signs/symptoms that may be suggestive 
of pneumonia) within the 24 hours since the imaging procedure. 
• Randomization Visit: A chest X-ray or thoracic CT scan will be obtained at the 
Randomization Visit to ensure that the subject does not have pneumonia. A chest X-ray 
or thoracic CT scan obtained as part of standard of care within 24 hours of the 
Randomization Visit is sufficient provided there are no changes in the subject’s clinical 
status (e.g., no change in ventilation status, secretions, or signs/symptoms that may be 
suggestive of pneumonia) since the time of imaging. 
• BAL sub-study: A chest X-ray or thoracic CT scan will be obtained on Day 2/Day 3 
post-BAL sampling for all subjects participating in the optional BAL fluid PK sub-study. 
• Monitoring Period (Day 2 through Day 22): A chest X-ray or thoracic CT scan is required 
during the Monitoring Period for those subjects presenting with signs and symptoms of a 
respiratory infection such as dyspnea, tachypnea, fever, or cough. 
Imaging should be conducted per institutional guidelines and assessed by the Investigator. 
The results of radiographs or imaging obtained at the Screening Visit and any subsequent visits 
should be documented on the appropriate eCRF. Radiograph or imaging reports and/or films will 
be collected for future analysis and will be captured within the EDC system. 
9.8 
Vital Signs 
Vital sign measurements will be obtained at the Screening Visit, the Randomization Visit (Day 1 
pre-dose), on Day 1 following administration of study drug, daily during the Monitoring Period (if 
subject is hospitalized), on Day 22, on the day of hospital discharge (for subjects who are 

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discharged between Day 40 and Day 90), at the Day 90 Safety Visit (if the visit occurs onsite), or 
Early Termination (if applicable). 
Vital sign measurements will include temperature, systolic and diastolic blood pressure, pulse, 
respiratory rate, and oxygenation status (as measured by pulse oximetry or arterial blood gas). 
Vital sign measurements will be recorded on the appropriate eCRF. 
Blood pressure and pulse will be assessed via an automated device. Manual techniques are only to 
be used if an automated device is not available. 
Oxygenation status will be determined at the Screening and Randomization Visits via 
measurement of arterial blood gas, provided the subject has an arterial line placed. If no arterial 
line is present, pulse oximetry may be used. Oxygenation status may be determined at subsequent 
visits by either measurement of arterial blood gas or pulse oximetry, if no arterial line is present. 
9.9 
Electrocardiograms 
A 12-lead ECG will be performed for all eligible subjects at the Randomization Visit 
(Day 1 pre-dose), on Day 22, on the day of hospital discharge (for subjects who are discharged 
between Day 40 and Day 90), at the Day 90 Safety Visit (if the visit occurs onsite), or 
Early Termination (if applicable). 
9.10 
Physical Examinations 
A complete physical examination will be performed at the Screening Visit and as deemed 
necessary by the Investigator and will include, at a minimum, a pulmonary examination (including 
auscultation) and assessments of the skin, abdomen, cardiovascular, gastrointestinal, and 
neurological systems. Body weight and height will also be measured.  
A limited physical examination will be performed at the Randomization Visit, daily during the 
Monitoring Period, on Day 22, on the day of hospital discharge (for subjects who are discharged 
between Day 40 and Day 90), at the Day 90 Safety Visit (if the visit occurs onsite), or 
Early Termination (if applicable). The limited physical examination will include, at a minimum, a 
pulmonary examination (including auscultation). 
9.11 
Immunogenicity 
Samples to evaluate ADA response including neutralizing antibodies to ASN-1 and ASN-2 will 
be collected from all subjects at the Randomization Visit (Day 1 pre-dose), upon discharge from 
the ICU (if discharge occurs prior to Day 22), on Day 22, on the day of hospital discharge (for 
subjects who are discharged between Day 40 and Day 90), and at the Day 90 Safety Visit (if the 
visit occurs onsite).  
Subjects who discontinue early or are withdrawn from the study should also have samples 
collected as part of their Early Termination Visit. These samples will be sent to the central 
laboratory for analysis. 
Samples will be screened for antibodies binding to ASN-1 and ASN-2 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to ASN-1 or ASN-2 and/or to further characterize the immunogenicity of ASN-1 and 
ASN-2. 
The impact of ADAs on safety, efficacy, and PK will be addressed in the Statistical Analysis Plan.  

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10 
STATISTICS 
10.1 
Analysis Populations 
Intent-to-Treat (ITT) Population 
The ITT Population includes all subjects who are randomized to receive study drug.  
Modified Intent-to-Treat (MITT) Population 
The MITT Population includes all subjects in the ITT Population who receive study drug who are 
heavily colonized with S. aureus as determined by quantitative or semi-quantitative culture of an 
ETA. 
Per Protocol (PP) Population 
The PP Population includes all subjects in the MITT Population who also meet the following 
criteria: 
• Do not have any major protocol violations that would affect assessment of efficacy, and 
• Complete an adequate number of Monitoring Period assessments through and including 
Day 22. 
Pharmacokinetic (PK) Population 
The PK Population includes all subjects in the MITT Population with at least 1 serum PK sample 
collected post-dose. 
Safety Population 
The Safety Population includes all subjects who receive any amount of study drug and have at 
least 1 post-treatment safety assessment. 
10.2 
Statistical Methods 
All statistical analyses will be provided in the Statistical Analysis Plan. Continuous variables will 
be summarized by using the number of non-missing observations, arithmetic mean, standard 
deviation, median, minimum, and maximum values as descriptive statistics. Categorical variables 
will be summarized by using the frequency count and the percentage of subjects in each category 
as descriptive statistics.  
All statistical tests will be performed at the 0.05 significance level using 2-sided tests, except where 
otherwise noted. All confidence intervals will have a confidence level of 95%. 
10.2.1 
Disposition 
The number of subjects randomized, treated, completed, and discontinued early from the study 
and the reasons for discontinuation will be summarized descriptively. In addition, reasons leading 
to study discontinuation will be summarized for each treatment group. The number and percentage 
of subjects for the randomized subjects included in each analysis population will also be presented. 
10.2.2 
Demographic and Baseline Characteristics 
Summary statistics will be provided by treatment group for demographics (e.g., age, gender, race, 
and ethnicity) and for baseline characteristics. 

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10.2.3 
Analysis of Efficacy 
The primary efficacy endpoint is whether the subject has developed S. aureus pneumonia up to 
but not including Day 22. The summary measure for efficacy is the proportion of subjects in the 
MITT Population who develop S. aureus pneumonia up to but not including Day 22. Analysis for 
the primary endpoint will compare the proportion of subjects who develop S. aureus pneumonia 
in the ASN100 arm versus the placebo arm in the MITT Population. The statistical test for 
comparing 2 event rates is based on a 2-sided test with a false positive rate of 5%.  
Analyses of the primary efficacy endpoint will also be performed separately for the ITT and 
PP Populations. 
Duration of mechanical ventilation and length of hospital ICU stay during the first 21 days 
post-randomization will be compared between treatment groups using a Wilcoxon rank sum test. 
Other efficacy endpoints will be summarized by treatment group.  
10.2.4 
Analysis of Safety 
All subjects in the Safety Population will be included in the safety analyses and analyzed based on 
the actual treatment received.  
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
Treatment-emergent adverse events will be summarized by system organ class and preferred term. 
A TEAE is defined as an adverse event with a start date and time on or after the first dose of study 
treatment. Listings will be provided for SAEs and adverse events leading to drug discontinuation. 
In addition, all adverse events will be listed.  
Safety laboratory data and vital signs will be presented by each scheduled time point and for 
change from baseline to each time point. The results of all laboratory tests, physical examination 
findings, vital signs, and ADAs will be presented in data listings.  
10.2.5 
Analysis of Pharmacokinetics 
Descriptive statistics will be provided for all PK concentration data and PK parameters. All PK 
analyses will be performed using the PK Population. Subject PK profiles will be determined using 
parameters such as Cmax, Tmax, AUC, and t1/2 for each of ASN-1 and ASN-2 in serum. Epithelial 
lining fluid PK will also be analyzed and an ELF/serum PK ratio will be calculated.  
A description of the PK parameter analysis will be included in the Statistical Analysis Plan. 
10.2.6 
Sample Size Determination 
The estimated incidence of progression to S. aureus pneumonia in mechanically ventilated subjects 
with heavy colonization is approximately 25% within 22 days of randomization.  
Assuming a 2-sided significance level of 0.05 and a desired power of 80% to detect a significant 
difference between S. aureus pneumonia incidence rates of 25% in the placebo group and 12.5% 
in the ASN100 treatment group (50% reduction), 152 evaluable subjects are required in each 
treatment group. A sample size of 304 subjects (152 subjects per treatment group) will yield 
80% power to detect a 50% reduction in the incidence of S. aureus pneumonia with ASN100 
treatment when assuming a 25% incidence rate of S. aureus pneumonia in placebo-treated subjects. 
Assuming a 14% non-evaluable rate, approximately 354 subjects (177 subjects per treatment 

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group) will be randomized. Assuming the screen failure rate is about 84%, approximately 
2250 subjects will be screened. 
10.2.7 
Interim Analysis 
One interim analysis will be conducted during the study, when approximately 125 subjects have 
reached Day 22. The interim analysis is for futility assessment of the study, and for a potential 
study sample size adjustment based on an overall blinded efficacy evaluation pooled across the 
treatment arms. Based on this assessment, the sample size may be increased. The interim analysis 
of futility assessment will be reviewed by an independent Data Review Committee (DRC).  

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11 
DATA MANAGEMENT AND RECORD KEEPING 
11.1 
Data Management 
11.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the CRA during monitoring visits. The 
CRAs will verify data recorded in the EDC system with source documents. All corrections or 
changes made to any study data must be appropriately tracked in an audit trail in the EDC system. 
An eCRF will be considered complete when all missing, incorrect, and/or inconsistent data has 
been accounted for. 
11.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
11.1.3 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel with a 
role designated for data entry must log into the system using their secure user name and password 
in order to enter, review, or correct study data. These procedures must comply with Title 21 of the 
Code of Federal Regulations (21 CFR Part 11) and other appropriate international regulations. All 
passwords will be strictly confidential. 
11.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
• MedDRA for adverse events, and 
• World Health Organization Drug Dictionary for prior and concomitant medications. 
11.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
11.2 
Record Keeping 
Records of subjects, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data is defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  

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12 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
12.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study subjects 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
12.2 
Institutional Review Board/Independent Ethics Committee 
The IRB/IEC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of subjects. The study will only be conducted at sites where IRB/IEC 
approval has been obtained. The protocol, Investigator’s Brochure, ICF, advertisements (if 
applicable), written information given to the subjects, safety updates, annual progress reports, and 
any revisions to these documents will be provided to the IRB/IEC by the Investigator. 
Federal regulations and ICH require that approval be obtained from an IRB/IEC prior to 
participation of subjects in research studies. Prior to study onset, the protocol, any protocol 
amendments, ICFs, advertisements to be used for subject recruitment, and any other written 
information regarding this study to be provided to a subject or subject’s legal guardian must be 
approved by the IRB/IEC. Where applicable, the requirements of the CIP, as well as the 
decision-making process regarding inclusion of subjects into the study, must be approved by the 
IEC. 
No drug will be released to the site for dosing until written IRB/IEC authorization has been 
received by the Sponsor. 
It is the responsibility of the Sponsor or CRO to obtain the approval of the responsible ethics 
committees according to the national regulations.  
The study will only start at the respective sites once the respective committee’s written approval 
has been given. 
12.3 
Informed Consent 
The ICF, the ICF for the BAL fluid PK sub-study, and any changes to the ICFs made during the 
course of the study must be agreed to by the Sponsor or designee and the IRB/IEC prior to use and 
must be in compliance with all ICH GCP, local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
subject has been informed of his/her rights to privacy. The Investigator will obtain written 
informed consent from each subject or the subject’s legal representative (if applicable) before any 
study-specific activity is performed and should document in the source documentation that consent 
was obtained prior to enrollment in the study. In the case that the subject is not fully conscious, a 
shortened version of informed consent will be signed by the subject and a complete version of 
informed consent will be signed, dependent on the country-specific requirements, by the subject’s 
legal representative or close person (e.g., husband/wife, child, or sibling), or by the CIP (if 
applicable), by an impartial witness, and by the Investigator prior to any study-specific procedure 

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being performed. A subject who is not fully conscious will be required to sign the complete version 
of informed consent once fully conscious. The original signed copy of the ICF must be maintained 
by the Investigator and is subject to inspection by a representative of the Sponsor, their 
representatives, auditors, the IRB/IEC, and/or regulatory agencies. A copy of the signed ICF will 
be given to the subject. 
In countries only where it is applicable, for subjects who are unable to read and sign either version 
of the ICF (i.e., shortened or complete version), decisions regarding the subject’s enrollment will 
be made by the CIP. The decision of the CIP to include the subject in the study must be documented 
in the minutes of the CIP meeting, signed by the members of the CIP, and the decision must be 
entered in the medical records of the subject. The minutes of the CIP meeting should contain the 
names of all physicians included in the composition of the CIP, the subject’s diagnosis, the 
subject’s condition at the time the decision was made, the interpretation of clinical, laboratory, 
instrumental, and other data, and the decision of the CIP. The documents supporting the CIP 
decision must be maintained by the Investigator. 
12.4 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, ICH GCP, Directive 2001/20/EC, applicable regulatory requirements, and the 
Declaration of Helsinki (Seoul 2008), and that valid data are entered into the eCRFs. 
To achieve this objective, the monitor’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well-organized, and easily retrievable data. 
Before the enrollment of any subject in this study, the Sponsor or their designee will review with 
the Investigator and site personnel the following documents: protocol, Investigator’s Brochure, 
eCRFs and procedures for their completion, informed consent process, and the procedure for 
reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
12.5 
Protocol Deviations 
Deviations from the protocol are not permitted. If a protocol deviation occurs, the CRA will ensure 
the deviation is appropriately documented. Substantial deviations will be compiled into a listing 
for inclusion in the final clinical study report and minor deviations will be recorded in the source 
documents at the site. Investigators must comply with all applicable IRB/IEC and local 
requirements in the reporting of protocol deviations.  

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12.6 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable national or regional health authorities, and the IRB/IEC as appropriate. 
Subjects or their legal representatives may request their medical information be given to their 
personal physician or other appropriate medical personnel responsible for their welfare. 
Subject medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 
12.7 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating subjects (sufficient information to link 
records, e.g., CRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, 
source documents, and detailed records of treatment disposition. The records should be retained 
by the Investigator according to specifications in the ICH guidelines, local regulations, or as 
specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor.  
12.8 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. However, the Investigator will be afforded the right to 
publish their individual results after the end of the trial if no agreement on the publication can be 
achieved within 2 years of database lock. 
12.9 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR §54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 
12.10 
Insurance and Indemnity 
In accordance with the relevant national regulations, the Sponsor has taken out subject liability 
insurance for all subjects who have given their consent to the clinical study. This cover is designed 
for the event that a fatality, physical injury, or damage to health occurs during the clinical study’s 
execution. 

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12.11 
Legal Aspects 
The clinical study is submitted to the relevant national competent authorities in all participating 
countries to achieve a clinical trial authorization (CTA). 
The study will commence (i.e., initiation of study centers) when the CTA and favorable Ethics 
opinion have been received from those bodies governing those study centers.  

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13 
STUDY ADMINISTRATIVE INFORMATION 
13.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by Medpace or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB/IEC, unless immediate implementation of the change is necessary for subject safety. In this 
case, the situation must be documented and reported to the IRB/IEC within 5 working days. 
13.2 
Address List 
13.2.1 
Sponsor 
Arsanis, Inc. 
890 Winter Street, Suite 230 
Waltham, MA 02451-1472 
Telephone: +1-781-819-5704 
Facsimile: +1-781-957-1267 
13.2.2 
Global Contract Research Organization 
Medpace, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 
Telephone: +1-513-579-9911 
Facsimile: +1-513-579-0444 
13.2.3 
Drug Safety 
Medpace Clinical Safety 
5375 Medpace Way 
Cincinnati, OH 45227 
Telephone: +1-800-730-5779, Dial 3 or +1-513-579-9911, Dial 3 
Facsimile: +1-866-336-5320 or +1-513-579-0444 
Email: Medpace-safetynotification@medpace.com 

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13.2.4 
Biological Specimens 
Clinical and Microbiology Laboratory 
ACM Global 
160 Elmgrove Park 
Rochester, NY 14624 
Telephone: +1-585-429-2374 or +1-866-405-0400 
Pharmacokinetic and Immunogenicity Laboratory 
Eurofins | ADME BIOANALYSES 
75 A, Avenue de Pascalet 
30310 Vergèze, France 
Telephone: +33-(0)4-66-73-17-73 
Facsimile: +33-(0)4-66-73-17-74 
13.2.5 
Study Drug Packaging, Labeling, and Distribution 
ABF Pharmaceutical Services GmbH 
Gastgebgasse 5-13 
1230 Vienna, Austria 
Telephone: +43-1-890-12-00-30 
Facsimile: +43-1-890-12-00-11 
 
 

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14 
REFERENCES 
1. Berube BJ, Bubeck Wardenburg J. Staphylococcus aureus α-toxin: nearly a century of intrigue. 
Toxins (Basel). 2013;5(6):1140-66. 
2. Reyes-Robles T, Torres VJ. Staphylococcus aureus pore-forming toxins. Curr Top Microbiol 
Immunol. 2016. Epub ahead of publication. DOI: 10.1007/82_2016_16. 
3. Janesch P, Rouha H, Weber S, et al. Selective Sensitization of Human Neutrophils to LukGH 
Mediated Cytotoxicity by Staphylococcus aureus and IL-8. J Infect 2017. Epub ahead of 
publication. 
4. Rouha H, Badarau A, Visram ZC, et al. Five birds, one stone: neutralization of 
alpha-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single 
human monoclonal antibody. MAbs. 2015;7(1):243-54. 
5. Badarau A, Rouha H, Malafa S, et al. Context matters: The importance of dimerization-induced 
conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of 
neutralizing antibodies. MAbs. 2016;8(7):1347-60. 
6. Badarau A, Rouha H, Malafa S, et al. Structure-function analysis of heterodimer formation, 
oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin 
LukGH. J Biol Chem. 2015;290(1):142-56. 
7. Diep BA, Le VT, Visram ZC, et al. Improved Protection in a Rabbit Model of 
Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia 
upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin. Antimicrob Agents 
Chemother. 2016; 60(10):6333-40. 
8. Craven DE, Lei Y, Ruthazer R, Sarwar A, Hudcova J. Incidence and outcomes of 
ventilator-associated tracheobronchitis and pneumonia. Am J Med. 2013;126(6):542-9. 
9. Arsanis, Inc. Data on file. 
10. Stulik L, Hudcova J, Craven DE, Nagy G, Nagy E. Low Efficacy of Antibiotics against 
Staphylococcus aureus Airway Colonization in Ventilated Patients. Clin Infect Dis. 2017. 
Epub ahead of publication. 
11. Smith SB, Ruhnke GW, Weiss CH, Waterer GW, Wunderink RG. Trends in pathogens among 
patients hospitalized for pneumonia from 1993 to 2011. JAMA Intern Med. 
2014;174(11):1837-9. 
12. Lewis SS, Walker VJ, Lee MS, et al. Epidemiology of methicillin-resistant 
Staphylococcus aureus pneumonia in community hospitals. Infect Control Hosp Epidemiol. 
2014;35(12):1452-7. 
13. Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator 
associated bacterial pneumonia. Clin Infect Dis. 2010;51(S1):S81-7. 
14. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and 
ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases 
Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. 

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15. Melsen WG, Rovers MM, Koeman M, Bonten MJ. Estimating the attributable mortality of 
ventilator-associated pneumonia from randomized prevention studies. Crit Care Med. 
2011;39(12):2736-42. 
16. Croce MA, Brasel KJ, Coimbra R, et al. National Trauma Institute prospective evaluation of 
the ventilator bundle in trauma patients: does it really work? J Trauma Actue Care Surg. 
2013;74(2):354-60. 
17. Blot S, Lisboa T, Angles R, Rello J. Prevention of VAP: is zero rate possible? Clin Chest Med. 
2011;32(3):591-9. 
18. Klompas M, Kleinman K, Khan Y, et al. Rapid and reproducible surveillance for 
ventilator-associated pneumonia. Clin Infect Dis. 2012;54(3):370-7. 
19. Stulik L, Malafa S, Hudcova J, et al. α-Hemolysin activity of methicillin-susceptible 
Staphylococcus aureus predicts ventilator-associated pneumonia. Am J Respir Crit Care Med. 
2014;190(10):1139-48. 
20. Doessegger L and Banholzer ML. clinical development methodology for infusion-related 
reactions with monoclonal antibodies. Clin Transl Immunology. 2015;4(7):e39. 
 

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Appendix A: Schedule of Procedures 
 
 
Study Period 
Screening/ 
Enrollment 
Randomization 
Treatment 
Monitoring Period 
 
Follow-Up Period 
ET 
Study Day 
 
Up to 
Day -14a 
Day 1 pre-dose 
Day 1 
Day 2/3b 
(BAL PK 
sub-study) 
Day 2 to 
Day 21c 
Day 22 
(+2 days)  
Day 28 
(+2 days)d  
Day 40 
to 
Day 89e 
 
 
Day 90 
(±7 days) 
Safety 
Visitf 
Unschedg 
Study Procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion/ 
randomization criteria 
Xh,i 
Xj 
 
 
 
 
 
 
 
 
Medical history 
Xh 
Xk 
 
 
 
 
 
 
 
 
Demographics 
Xh 
 
 
 
 
 
 
 
 
 
Antibiotic/medication historyl 
X 
X 
 
 
 
 
 
 
 
 
Height/weight 
Xh 
 
 
 
 
 
 
 
 
 
Physical examinationm 
Xh 
X 
 
 
X 
X 
 
X 
X 
X 
Vital signsn 
Xh 
X 
X 
X 
X 
X 
 
X 
X 
X 
Pregnancy testo 
Xh 
 
 
 
 
X 
 
 
 
X 
Clinical laboratory 
assessments (chemistry, 
hematology, and coagulation)  
  
X 
 
 
Xp 
X 
 
 
 
Xq 
Urinalysis 
 
X 
 
 
Xr 
X 
 
 
 
Xq 
Procalcitonin (analysis 
performed at central lab) 
 
X 
 
 
Xs 
X 
 
 
 
X 
Ventilator device status 
X 
X 
X 
X 
Xt 
Xt 
Xt 
Xt 
Xt 
Xt 
Chest X-ray/thoracic CT scan 
Xu 
Xv 
 
X 
Xw 
Xw 
 
 
 
 
Nasal swab specimens for 
culture 
 
X 
 
 
 
 
 
 
 
 
ETA for culturex 
X 
 
 
 
 
 
 
 
 
 
Collection/culture of 
additional microbiological 
specimensy 
 
 
 
 
X 
X 
 
 
 
X 
Clinical assessment of 
signs/symptoms of pneumonia  
 
X 
X 
X 
X 
X 
 
 
 
X 
Other S. aureus infection 
assessment  
X 
X 
X 
X 
X 
X 
 
 
 
X 
Footnotes begin on the next page. 

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Appendix A:  Schedule of Procedures (continued) 
Study Period 
Screening/ 
Enrollment 
Randomization 
Treatment 
Monitoring Period 
 
Follow-Up Period 
ET 
Study Day 
Up to 
Day -14a 
Day 1 pre-dose 
Day 1 
Day 2/3b 
(BAL PK 
sub-study) 
Day 2 to 
Day 21c 
Day 22 
(+2 days)  
Day 28 
(+2 days)d  
Day 40 
to 
Day 89e 
 
 
Day 90 
(±7 days) 
Safety 
Visitf 
Unschedg 
Study Procedures 
Randomization 
 
X 
 
 
 
 
 
 
 
 
Blood collection for ADA and 
anti-S. aureus toxin antibodies 
 
X 
 
 
Xz 
X 
 
X 
X 
X 
12-lead ECG 
 
X 
 
 
 
X 
 
X 
X 
X 
Assess survival and discharge 
disposition 
 
 
 
 
 
X 
X 
X 
X 
X 
Study drug administrationaa 
 
 
X 
 
 
 
 
 
 
 
BAL for PKbb 
 
 
 
X 
 
 
 
 
 
 
Blood collection for PK 
sampling and anti-S. aureus 
toxin antibodies 
 
 
Xcc 
Xdd 
Xee 
Xee 
 
Xee 
X 
X 
Track days on ventilator from 
randomization 
 
 
X 
X 
X 
X 
 
X 
X 
X 
Track days in ICU (or other 
observation area)  
 
 
X 
X 
X 
X 
 
X 
X 
X 
Concomitant medicationsl 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Adverse event assessment 
Xff 
X 
X 
X 
X 
X 
 
X 
X 
X 
a. 
Eligible subjects will be screened daily (while mechanically ventilated) for up to 8 days to identify those subjects who are heavily colonized with S. aureus (see Section 3.1). 
Screening for heavy S. aureus colonization by ETA culture will continue on Day 11 and Day 14 provided the subject remains mechanically ventilated, for a total Screening 
Period of up to 14 days. Additional ETA screening may occur on Days 9, 10, 12, and 13 at the discretion of the Investigator and providing the subject remains mechanically 
ventilated.  
b. 
Procedures are to be performed 48 hours (±36 hours) post-dose on approximately Day 2 or Day 3, depending on time of study drug administration, for those subjects participating 
in the BAL fluid PK sub-study only or if BAL fluid is collected as part of a standard of care procedure for any subject at any other time post-randomization for any other reason. 
c. 
Procedures are to be performed daily (unless otherwise indicated) from Day 2 to Day 21 while the subject is hospitalized. For subjects participating in the BAL fluid PK 
sub-study, procedures noted for the Day 2 visit only need to be performed 1 time. 
d. 
A follow-up visit will occur on Day 28 (+2 days) to assess mortality. This visit may be conducted via telephone if the subject is no longer hospitalized. 
e. 
For subjects who remain hospitalized between Day 40 and Day 90 at the institution where they receive study treatment, a follow-up safety visit will be performed on the day of 
discharge. 
f. 
If the subject is unable to return to the site, this visit may be conducted by telephone, with procedures performed as appropriate (i.e., concomitant medications and adverse 
events collected). 
g. 
An ET visit will be conducted for subjects who are withdrawn from the study prior to Day 22. 

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h. 
To be performed at the initial Screening Visit only. 
i. 
At the Screening Visit, subjects must meet all of the inclusion criteria and none of the exclusion criteria in order to be eligible to return for the Randomization Visit. 
j. 
At the Randomization Visit, subjects must continue to meet all of the inclusion criteria and none of the exclusion criteria. Subjects must also meet all randomization criteria to 
be eligible to be randomized into the study. 
k. 
Review and record medical history (if changes occurred since the Screening Visit). 
l. 
All prior medications received by the subject within 14 days prior to study drug administration and any concomitant medications used throughout the duration of the study will 
be recorded in the source documents and on the appropriate eCRF. 
m. A complete physical examination will be performed at the Screening Visit and as deemed necessary by the Investigator and will include, at a minimum, a pulmonary examination 
(including auscultation) and assessments of the skin, abdomen, cardiovascular, gastrointestinal, and neurological systems. A limited physical examination will be performed at 
the Randomization Visit, daily during the Monitoring Period (if the subject is hospitalized), on Day 22 (if the subject is hospitalized), at the time of hospital discharge (if 
discharge occurs between Day 40 and Day 90), at the Safety Visit (Day 90) if the visit occurs onsite, and at ET (if applicable). The limited physical examination will include, 
at a minimum, a pulmonary examination (including auscultation). 
n. 
Vital sign measurements will include temperature, systolic and diastolic blood pressure, pulse, respiratory rate, and oxygenation status. Blood pressure and pulse will be assessed 
via an automated device. Manual techniques are only to be used if an automated device is not available. Oxygenation status will be determined via measurement of arterial 
blood gas, provided the subject has an arterial line placed. If no arterial line is present, pulse oximetry may be used. 
o. 
Female subjects of childbearing potential must have a documented negative pregnancy test at the Screening Visit. Female subjects may be enrolled on the basis of a negative 
urine pregnancy test, pending the result of a negative serum pregnancy test prior to randomization. A pregnancy test will also be performed on Day 22 or ET (if applicable). 
Additional pregnancy testing may occur throughout the duration of the study, per applicable country requirements. 
p. 
Blood samples for chemistry, hematology, and coagulation will be obtained on Days 2 (+1 day), 4 (±1 day), and 6 (±1 day) of the Monitoring Period, and twice weekly during 
Week 2 (Day 8 through Day 14) and/or Week 3 (Day 15 through Day 21) of the Monitoring Period while the subject remains hospitalized. 
q. 
To be obtained if clinically indicated. 
r. 
Urinalysis to be obtained on Day 6 (±1 day) of the Monitoring Period only. 
s. 
Procalcitonin testing to occur on the day of diagnosis of pneumonia, if applicable. 
t. 
If applicable. 
u. 
A chest X-ray or thoracic CT scan is to be obtained 1 time at the initial Screening Visit. A chest X-ray or thoracic CT scan obtained as part of standard of care within 24 hours 
prior to the initial Screening Visit is sufficient provided there are no changes in the subject’s clinical status (e.g., no change in ventilation status, secretions, or signs/symptoms 
that may be suggestive of pneumonia) within the 24 hours following imaging. 
v. 
A chest X-ray or thoracic CT scan obtained within 24 hours of the Randomization Visit is sufficient, provided there are no changes in the subject’s clinical status (e.g., no 
change in ventilation status, secretions, or signs/symptoms that may be suggestive of pneumonia) since the time of imaging. 
w. A chest X-ray or thoracic CT scan is required during the Monitoring Period for those subjects presenting with signs and symptoms of a respiratory infection such as dyspnea, 
tachypnea, fever, or cough. 
x. 
ETA specimens collected during Screening/Enrollment will be cultured by quantitative or semi-quantitative methods as required by the protocol. Sites are encouraged to perform 
semi-quantitative cultures using a chromogenic media that tests for both the presence of MSSA and MRSA (e.g., CHROMagarTM Staph aureus) for more rapid and specific 
detection of S. aureus. If the site is not able to obtain chromogenic media for S. aureus, appropriate chromogenic media may be supplied by the Sponsor. Semi-quantitative 
cultures using chromogenic media are preferred for determination of eligibility for randomization; however, any quantitative or semi-quantitative culture performed that indicates 
that a subject is heavily colonized with S. aureus is permitted if the culture results are available to randomize the subject within 48 hours (or up to 60 hours with Medical Monitor 
approval) from the time the ETA sample was collected. If subjects are extubated and subsequently re-intubated/mechanically ventilated, they are eligible for re-screening as a 
new subject enrollment. Subjects who were previously randomized are not eligible to be re-consented and re-screened. Subjects with a screening ETA culture that also shows 
heavy colonization of a Gram-negative organism (i.e., heavy co-colonization of both Gram-positive and Gram-negative organisms), will not be randomized into the study; 
however, randomization should not be delayed while waiting for Gram-negative results if heavy colonization with S. aureus has been confirmed. 
y. 
Adequate respiratory specimen or other microbiological specimens to be obtained if clinically indicated. If, as part of routine standard of care, additional respiratory and/or other 
microbiological specimens are collected for culture during the study, results will be documented within the eCRF. 
z. 
Obtain sample for ADA (to be obtained only upon discharge from the ICU, if discharge occurs prior to Day 22). 

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aa. Study drug will be administered in a double-blind manner. Subjects will receive ASN100 or matching placebo via 2 IV infusions over a duration of approximately 50 to 
60 minutes per infusion. Both ASN100 and placebo will be administered as 2 separate infusions (either sequentially or simultaneously). The last infusion will be completed 
within 5 hours from initiation of drug preparation in the pharmacy. 
bb. Obtain BAL fluid 48 hours (±36 hours) post-dose to determine ASN-1 and ASN-2 levels and blood to ELF ratio. If BAL fluid is collected as part of a standard of care procedure 
from any subject enrolled in the sub-study at any other time post-randomization for any other reason, if possible, a sample for PK analysis will also be obtained. 
cc. Blood samples for PK analysis will be collected immediately following the completion of the second infusion (+15 minutes) and at 6 hours (±4 hours) and 24 hours (±6 hours) 
post-dose. 
dd. Obtain a blood sample for PK measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid collection or if BAL fluid is collected as part of a standard 
of care procedure from any subject enrolled in the sub-study at any time post-randomization). 
ee. A PK sample will be obtained from all subjects on Days 4 (±1 day), 7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will be collected 
on the day of discharge (if discharge occurs between Day 40 and Day 90). 
ff. 
Adverse events that occur between the time the subject signs the ICF and the Randomization Visit will only be recorded if related to a study-specific procedure. 
ADA = anti-drug antibody; BAL = bronchoalveolar lavage; CT = computed tomography; ECG = electrocardiogram; eCRF = electronic Case Report Form; ELF = epithelial lining 
fluid; ET = Early Termination; ETA = endotracheal aspirate; ICF = Informed Consent Form; ICU = intensive care unit; IV = intravenous; MRSA = methicillin-resistant S. aureus; 
MSSA = methicillin-susceptible S. aureus; PK = pharmacokinetic; S. aureus = Staphylococcus aureus; Unsched = unscheduled.

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Appendix B: Clinical Laboratory Analytes 
Chemistry 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase (AST) 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatinine 
Direct bilirubin 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Hematology  
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count with 
differential (basophils, eosinophils, 
lymphocytes, monocytes, and neutrophils) 
RBC indices: mean corpuscular volume 
(MCV), mean corpuscular hemoglobin 
(MCH), %Reticulocytes 
Coagulation  
Prothrombin time (PT) 
Partial thromboplastin time (PTT) 
Urinalysis  
pH 
Blood 
Ketones 
Specific Gravity 
Leukocyte esterase 
Bilirubin  
Glucose 
Nitrite 
Protein 
 
Other Screening Tests as Needed (for female subjects of childbearing potential only) 
Urine and/or serum pregnancy test 
Other Tests 
Procalcitonin (PCT)  
 
 
 
 

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Appendix C: Site-Specific Sub-Study for Subjects Diagnosed with Pneumonia 

 
CLINICAL STUDY PROTOCOL 
Site-Specific Addendum 
PRIMARY STUDY TITLE:  A Phase 2, Randomized, Double-
Blind, Placebo-Controlled Study to Determine the Safety and 
Efficacy of a Single Dose of ASN100 for the Prevention of 
Staphylococcus aureus Pneumonia in Heavily Colonized, 
Mechanically Ventilated Subjects  
SITE-SPECIFIC SUB-STUDY TITLE:  Safety and Efficacy of a 
Single Dose of ASN100 (versus Placebo) in Heavily Colonized 
Mechanically Ventilated Subjects Who Develop Pneumonia Prior 
to Randomization in Study ASN100-201 
 
Investigational Product: ASN100 
Protocol Number: ASN100-201 
IND Number: 128766 
EudraCT Number: 2016-002146-23 
 
Sponsor: 
Arsanis, Inc. 
890 Winter Street, Suite 230 
Waltham, MA 02451-1472 
 Telephone: +1-781-819-5704 
Facsimile: +1-781-957-1267 
 
Site-Specific Addendum:  23 April 2018 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written consent of 
Arsanis, Inc. except to the extent that disclosure would be required by law and for the purpose of 
evaluating and/or conducting a clinical study for Arsanis, Inc. You are allowed to disclose the contents of 
this document only to your Institutional Review Board (IRB) or Independent Ethics Committee (IEC) and 
study personnel directly involved with conducting this protocol. Persons to whom the information is 
disclosed must be informed/notified that the protocol content is confidential and proprietary to Arsanis, 
Inc. and that it may not be further disclosed to third parties. 
 

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TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................................. 81 
1. 
PURPOSE OF THIS SITE-SPECIFIC ADDENDUM ..................................................... 83 
2. 
SUB-STUDY OBJECTIVES............................................................................................ 84 
2.1. 
Primary Objective ....................................................................................................... 84 
2.2. 
Additional Objectives ................................................................................................. 84 
3. 
SUB-STUDY DESIGN AND DURATION ..................................................................... 85 
4. 
SELECTION OF SUB-STUDY SUBJECTS ................................................................... 88 
4.1. 
Inclusion Criteria ........................................................................................................ 88 
4.2. 
Exclusion Criteria ....................................................................................................... 88 
5. 
SUB-STUDY TREATMENTS ......................................................................................... 89 
5.1. 
Study Medication ........................................................................................................ 89 
5.1.1 ASN100................................................................................................................. 89 
5.1.2 Placebo .................................................................................................................. 89 
6. 
SUB-STUDY PROCEDURES ......................................................................................... 90 
7. 
EFFICACY ASSESSMENTS .......................................................................................... 91 
7.1. 
Primary Efficacy Endpoint ......................................................................................... 91 
7.2. 
Additional Efficacy Endpoints .................................................................................... 91 
7.3. 
Microbiological and Clinical Assessments ................................................................. 91 
7.3.1 Microbiological Assessment ................................................................................. 91 
7.3.2 Assessment of Clinical Signs/Symptoms and Pneumonia Progression Status ..... 92 
7.3.3 Evaluation of Pneumonia Outcomes ..................................................................... 92 
8. 
Pharmacokinetics .............................................................................................................. 95 
9. 
STATISTICAL ANALYSES ........................................................................................... 96 
9.1. 
Analysis Populations ................................................................................................... 96 
9.2. 
Sample Size Determination......................................................................................... 96 
9.3. 
Statistical Methods ...................................................................................................... 96 
10. 
APPENDICES .................................................................................................................. 98 
10.1. Schedule of Procedures for Sub-Study ....................................................................... 98 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation 
Definition 
ADA 
Anti-drug antibody 
AE 
Adverse event 
ASN100 
A combination of 2 fully human monoclonal antibodies (ASN-1 and ASN-2) 
AUC 
Area under the serum concentration-time curve 
BAL 
Bronchoalveolar lavage 
CFU 
Colony forming units 
CIP 
Council of independent physicians 
CT 
Computed tomography 
Cmax 
Maximum serum concentration 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
ELF 
Epithelial lining fluid 
E-mMITT 
Expanded Microbiologically Evaluable Modified Intent-to-Treat 
ET 
Early termination 
ETA 
Endotracheal aspirate 
FDA 
Food and Drug Administration 
FiO2 
Fraction of inspired oxygen 
GCP 
Good Clinical Practice 
HABP 
Hospital-acquired bacterial pneumonia 
ICF 
Informed consent form 
ICU 
Intensive care unit 
ITT 
Intent-to-Treat 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Modified Intent-to-Treat 
mMITT 
Microbiologically Evaluable Modified Intent-to-Treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-susceptible Staphylococcus aureus 
PaO2 
Partial pressure of oxygen in arterial blood 
PCT 
Procalcitonin  
PEEP 
Positive end-expiratory pressure 
PK 
Pharmacokinetic  
PSB 
Protected specimen brush 
S. aureus 
Staphylococcus aureus 
t1/2 
Terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum serum concentration 
VABP 
Ventilator-associated bacterial pneumonia 

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Term 
Definition 
Adequate respiratory specimen 
Intubated Subjects:  A respiratory specimen obtained by BAL, non-
bronchoscopic BAL, or protected specimen brush 
Extubated Subjects:  An expectorated/induced sputum specimen that yields 
<10 squamous cells and >25 polymorphonuclear cells/100× field 
Heavy colonization of S. aureus 
An endotracheal culture result of ≥105 CFU/mL (quantitative culture) or 3+/4+ 
(semi-quantitative culture) 
S. aureus pneumonia 
Pneumonia with the growth of S. aureus from an adequate respiratory sample 

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1. 
PURPOSE OF THIS SITE-SPECIFIC ADDENDUM 
This addendum contains a detailed description of the additions made to the protocol for Study 
ASN100-201. These additions apply to selected sites only. Approximately 50 subjects will 
participate in this site-specific sub-study. The purpose of this addendum is to allow subjects who 
meet the criteria for heavy endotracheal colonization with S. aureus, but who have progressed to 
pneumonia prior to randomization into the primary study, to be randomized and receive ASN100 
(or placebo) as adjunct therapy for treatment of the pneumonia.  (Note: Subjects enrolled in the 
primary ASN100-201 study, who are found to have heavy endotracheal colonization with 
S. aureus, but who have already progressed to pneumonia, are not eligible for randomization into 
the primary study.) 

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2. 
SUB-STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of the sub-study is to evaluate the safety, tolerability, and efficacy of a 
single dose of ASN100 (administered as ASN-1 and ASN-2 components) versus placebo, in 
addition to standard of care, as adjunctive therapy for the treatment of ventilator-associated 
S. aureus pneumonia. 
2.2. 
Additional Objectives  
Additional objectives of this sub-study are to compare ASN100 versus placebo (added to standard 
of care) with regard to the following: 
• The duration of mechanical ventilation post-treatment; 
• The resolution time for S. aureus pneumonia, all bacterial pneumonias, and non-S. aureus 
bacterial pneumonia;  
• The length of stay in the intensive care unit (ICU) and length of hospital stay post-
treatment;  
• 28-day all-cause mortality; 
• The incidence of other S. aureus-associated infections which occur after dosing up to but 
not including Day 22; and 
• Serum pharmacokinetics (PK) (i.e., maximum serum concentration [Cmax], time to 
maximum serum concentration [Tmax], area under the serum concentration-time curve 
[AUC], and terminal elimination half-life [t1/2]) of ASN-1 and ASN-2 in mechanically 
ventilated subjects heavily colonized with S. aureus who developed pneumonia;  
• ASN-1 and ASN-2 levels in bronchoalveolar lavage (BAL) fluid and calculate a blood to 
epithelial lining fluid (ELF) ratio in those subjects who undergo BAL as part of their 
microbiological evaluation of their pneumonia or as part of their standard of care; 
• Immunogenicity (development of anti-drug antibodies) of a single dose of ASN100. 

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3. 
SUB-STUDY DESIGN AND DURATION 
This is a double-blind, randomized, single-dose, placebo-controlled, site-specific, sub-study of 
ASN100 as adjunctive treatment of S. aureus pneumonia. In the primary study, subjects will be 
screened for eligibility; once an informed consent form is signed (or, in countries where it is 
applicable, a decision is made by the council of independent physicians [CIP]), and all entry 
criteria are met, a subject is considered to be enrolled in the study. All enrolled subjects will 
undergo an observational stage evaluating endotracheal colonization. Subjects who are 
randomized will undergo Treatment, Monitoring, and Follow-Up Periods. 
In the parent study, approximately 2250 eligible subjects who meet all of the inclusion criteria and 
none of the exclusion criteria will be screened daily (while mechanically ventilated) for up to 
8 days to identify those subjects who are heavily colonized with S. aureus.  
Screening for heavy S. aureus colonization by endotracheal aspirate (ETA) culture will continue 
on Days 11 and 14 (provided the subject remains mechanically ventilated) for a total Screening 
Period of up to 14 days. Additional ETA screening may occur on Days 9, 10, 12, and 13 at the 
discretion of the Investigator and providing the subject remains mechanically ventilated.  
ETA specimens collected during Screening/Enrollment will be cultured by quantitative or 
semi-quantitative methods as required by the protocol. Sites are encouraged to perform 
semi-quantitative cultures using a chromogenic media that tests for both the presence of 
methicillin-susceptible S. aureus and methicillin-resistant S. aureus (e.g., CHROMagarTM Staph 
aureus) for more rapid and specific detection of S. aureus. If the site is not able to obtain 
chromogenic media for S. aureus, appropriate chromogenic media may be supplied by the 
Sponsor.  
Semi-quantitative cultures using chromogenic media are preferred for determination of eligibility 
for randomization; however, any quantitative or semi-quantitative culture performed that indicates 
that a subject is heavily colonized with S. aureus is permitted if the culture results are available to 
randomize the subject within 48 hours (or up to 60 hours with Medical Monitor approval) from 
the time the ETA sample was collected. 
If an enrolled subject has an ETA culture reported positive for heavy S. aureus colonization and 
subsequently develops pneumonia, they are ineligible for the primary study but then become 
eligible for this sub-study. If they meet all of the inclusion and none of the exclusion criteria of 
this sub-study, they are eligible for randomization into this sub-study.  
At the time of randomization, if a subject’s screening ETA culture also shows heavy colonization 
of a Gram-negative organism (i.e., heavy co-colonization of both Gram-positive and 
Gram-negative organisms), the subject will not be randomized into this sub-study; however, 
randomization should not be delayed while waiting for Gram-negative or other culture results if 
heavy colonization with S. aureus has been confirmed. 
 
 

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Also, at the time of randomization, subjects will be stratified into 3 groups according to their 
previous and/or current anti-staphylococcal antibiotic exposure that is potentially effective against 
S. aureus pneumonia:   
• Group 1:  <24 hours (for example one dose of a daily antibiotic, 2 doses of a twice-daily 
antibiotic) 
• Group 2:  ≥24 but <72 hours  
• Group 3:  ≥72 hours   
This stratification will ensure balance of prior effective antibiotic treatment between the ASN100 
and placebo groups. 
Nasal swab specimens (one from each nostril) will be obtained at the Randomization Visit and will 
be cultured by the central microbiology laboratory. Results from the nasal swab specimen cultures 
will be used to assess correlation with results of the qualifying ETA culture. 
Upon determination of eligibility, approximately 50 subjects will be randomized in a 1:1 ratio to 
1 of 2 treatment groups: 
• ASN100 administered either sequentially or simultaneously as 2 separate intravenous (IV) 
infusions of ASN-1 and ASN-2, or 
• Placebo administered either sequentially or simultaneously as 2 separate IV infusions. 
Following randomization on Day 1, in addition to any standard-of-care therapy for their 
pneumonia, subjects will receive either a single IV dose of 3600 mg of ASN100 or matching 
placebo. 
An adequate respiratory sample (defined in the primary study) to determine the microbiological 
etiology of the pneumonia is to be collected within 36 hours of randomization, although all 
attempts should be made to obtain the specimen as close as possible to when the diagnosis of 
pneumonia is made.  Note:  Any time a BAL/non-bronchoscopic BAL or protected specimen brush 
(PSB) is performed to collect a respiratory microbiological sample, then a PK sample should also 
be collected to determine ASN-1 and ASN-2 levels to derive blood to ELF ratio, and to measure 
S. aureus toxins. 
While hospitalized, randomized subjects will be monitored daily for up to 21 days for pneumonia 
resolution or recurrence, and the occurrence of other S. aureus-associated infections. If a subject’s 
clinical symptoms of pneumonia improve such that no further antibiotic therapy is required, or if 
the pneumonia persists requiring a change in antibiotic therapy, then all attempts will be made to 
collect an adequate respiratory specimen. 
All randomized subjects will undergo a study visit on Day 22 (+2 days) for assessment of 
pneumonia. An adequate respiratory specimen should be obtained from subjects who remain 
ventilated and non-ventilated subjects who are able to produce sputum. 
A Follow-Up Visit will occur on Day 28 (+2 days) to assess mortality.  This visit may be conducted 
via telephone if the subject is no longer hospitalized.  

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For subjects who remain hospitalized between Days 40 and 90 at the institution where they receive 
study treatment, the Follow-Up Visit will be performed on the day of discharge. 
All randomized subjects will return for a Safety Visit on Day 90 (±7 days) (if the subject is unable 
to return to the site, this visit may be conducted by telephone). Subjects who discontinue the study 
prior to Day 22 will undergo an Early Termination Visit. The end of the study will occur upon 
completion of the last study visit (e.g., Day 90) visit by the last subject. 
Safety assessments for this study will include adverse event (AE) monitoring, clinical laboratory 
assessments (including chemistry, hematology, coagulation, and urinalysis), physical 
examinations, vital sign measurements, 12-lead electrocardiograms (ECGs), chest X-rays and/or 
thoracic computed tomography (CT) scans, and the determination of the presence of ASN-1 and 
ASN-2 anti-drug antibodies (ADAs).  Additional safety assessments may be performed throughout 
the duration of the study if clinically indicated. 
Procalcitonin testing will be performed at the Randomization Visit (Day 1 pre-dose), and on Day 
22 or Early Termination (if applicable). 
Blood samples will be obtained for the measurement of ASN-1 and ASN-2 in serum. Blood 
samples for PK analysis will be collected immediately following the completion of the second 
infusion (+15 minutes) and at 6 hours (±4 hours) and 24 hours (±6 hours) post-dose following the 
second infusion. In addition, a PK sample will be obtained from all subjects on Days 4 (±1 day), 
7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will 
be collected on the day of discharge (if discharge occurs between Day 40 and Day 90), on Day 90 
(if hospitalized or if the subject is able to return to the clinic), or Early Termination (if applicable).  
Blood samples obtained for ADA and PK analysis purposes will also be used to assess the amount 
of pre-existing anti-S. aureus toxin antibodies and the toxin neutralizing titer of the serum sample 
prior to and after randomization. Only antigen-specific antibody titers will be determined, and no 
genetic information will be extracted from these blood samples.  Blood samples will be destroyed 
following the completion of all S. aureus anti-toxin antibody analyses. 
BAL fluid obtained during the procedure to assess the baseline pneumonia pathogen (within 
36 hours of randomization), and in subjects who participate in the BAL PK sub-study, will be 
analyzed for the presence of S. aureus toxins. No genetic information will be extracted from these 
samples, which will be destroyed following the completion of this analysis. 

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4. 
SELECTION OF SUB-STUDY SUBJECTS 
4.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria at the Randomization Visit in order to be eligible 
for randomization into the sub-study: 
1. Subject is currently hospitalized and enrolled in the Arsanis Protocol ASN100-201; 
2. Subject is presumed to have S. aureus pneumonia as determined by heavy S. aureus 
colonization of ETA (defined as quantitative threshold of ≥105 CFU/mL or 3+ to 4+ by 
semi-quantitative culture); 
3. Subject has both signs and symptoms supporting a clinical diagnosis of pneumonia per 
the Investigator and has an imaging study (chest X-ray or thoracic CT) supportive of the 
diagnosis of pneumonia; and 
4. Subject is randomized within 24 hours of the imaging study supporting the diagnosis of 
pneumonia (see Criterion 3 above). 
4.2. 
Exclusion Criteria 
Subjects who meet any of the following criteria at the Randomization Visit will be excluded from 
participation in the sub-study: 
1. Subject has a known and documented ETA culture showing heavy colonization with a 
non-Staphylococcus aureus organism (e.g., a Gram-negative organism)  
NOTE: Randomization should not be delayed while waiting for other culture results if 
heavy colonization with S. aureus has been confirmed. 
2. Subject has been diagnosed with neutropenia (absolute neutrophil count <500/mm3); 
3. Subject has a severe non-pulmonary source of infection which, in the Investigator’s 
opinion, would interfere with the conduct of the study or jeopardize the subject’s safety; 
4. Subject has been previously exposed to ASN100 or ASN-1 or ASN-2, individually; 
5. Subject has a known hypersensitivity to ASN100 or any of its excipients; 
6. Subject has received any investigational product within 30 days prior to the Screening 
Visit (or 5 half-lives of the investigational product, whichever is longer); 
7. Subject has, in the opinion of the Investigator, a high probability of death within 72 hours 
of randomization;  
8. Subject is, in the opinion of the Investigator, not able or willing to comply with the 
protocol;  
9. Subject has any condition that, in the opinion of the Investigator, would compromise the 
safety of the subject, the potential activity of the study drug, or the quality of the data; or 
10. Subjects with a known history or current (suspected) diagnosis of cytokine release 
syndrome associated with the administration of peptides, proteins, and/or antibodies. 
NOTE: Subjects with a prior history of sepsis are not excluded. 

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5. 
SUB-STUDY TREATMENTS 
5.1. 
Study Medication 
Study medication (ASN100 or placebo) will be administered at the same dose and following the 
same preparation and administration procedures as per the primary study. 
5.1.1 
ASN100 
ASN-1 and ASN-2 will be supplied in separate 10-mL vials as a sterile, colorless, clear solution 
for infusion with an extractable volume of 10 mL and a nominal mAb concentration of 20 mg/mL. 
Each vial will contain 200 mg of ASN-1 or 200 mg of ASN-2.  ASN100 will be administered as 
separate infusions of 1800 mg ASN-1 and 1800 mg ASN-2 (9 vials of each to be pooled aseptically 
according to the Pharmacy Manual into separate infusion bags), each delivered over 50-60 minutes 
intravenously, either sequentially within a 3-hour window from the time of initiation of the first 
infusion to the completion of the second infusion, or simultaneously. 
5.1.2 
Placebo 
Matched vials of ASN-1 placebo and ASN-2 placebo will be provided. 
Placebo will be administered as separate infusions of 9 vials of ASN-1 placebo and 9 vials of 
ASN-2 placebo (vials to be pooled aseptically according to the Pharmacy Manual into separate 
infusion bags), each delivered over 50-60 minutes intravenously, either sequentially within a 3-
hour window from the time of initiation of the first infusion to the completion of the second 
infusion, or simultaneously. 

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6. 
SUB-STUDY PROCEDURES 
Following randomization into the sub-study, procedures and assessments will follow those of the 
primary study, with minor modifications given the treatment aims of this sub-study. See 
Section 10.1 for a schedule of procedures for this sub-study. 

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7. 
EFFICACY ASSESSMENTS  
7.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the resolution of S. aureus pneumonia in the microbiologically 
evaluable modified intent-to-treat (mMITT) Population up to, but not including, Day 22. 
7.2. 
Additional Efficacy Endpoints 
• The time to resolution of S. aureus pneumonia in the modified intent-to-treat (MITT), 
mMITT, and expanded microbiologically evaluable modified intent-to-treat (E-
mMITT) Populations; 
• The time to resolution of all bacterial pneumonia in the MITT and mMITT Populations; 
• The time to resolution of non-S. aureus pneumonia in the MITT and mMITT 
Populations; 
• Duration of mechanical ventilation during the first 21 days post-randomization for 
subjects in the MITT, mMITT, and E-mMITT Populations; 
• Length of ICU and hospital stay during the first 21 days post-randomization for subjects 
in the MITT, mMITT, and E-mMITT Populations; 
• Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum following a single dose of 
ASN100 in the pharmacokinetic (PK) Population;  
• 28-day all-cause mortality in the MITT, mMITT, and E-mMITT Populations; 
• Development of ADAs to a single dose of ASN100; 
• ASN-1 and ASN-2 levels in BAL fluid and blood to ELF ratio; and 
• Incidence of other non-pulmonary S. aureus infections acquired following study drug 
administration up to the final study visit (e.g., Day 90, Early Termination, etc.) in the 
mMITT and E-mMITT Populations. 
7.3. 
Microbiological and Clinical Assessments 
7.3.1 
Microbiological Assessment 
In the primary study, ETA specimens will be collected for culture during the Screening/Enrollment 
Period to determine the degree of S. aureus colonization. Additional respiratory specimens may 
be collected for culture throughout the Monitoring Period or at Early Termination (if applicable) 
if clinically indicated according to standard of care. 
If, as part of routine standard of care, additional respiratory and/or other microbiological specimens 
are collected for culture during the study, results will be documented within the electronic case 
report form. As described within the study laboratory manual, bacterial isolates recovered from 
these specimens that are deemed pathogens by the Investigator (if retained and available at the 
study site local microbiology laboratory) will be sent to a central microbiology laboratory for 
confirmation of pathogen identification (all isolates) and susceptibility testing (S. aureus isolates 
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For a Sponsor diagnosis of S. aureus pneumonia, an adequate respiratory specimen culture that is 
positive for S. aureus must be obtained within 36 hours from randomization.   
• For intubated subjects, a respiratory specimen obtained by BAL, non-bronchoscopic BAL, 
or PSB will be considered an adequate respiratory specimen; 
• For extubated subjects, an adequate expectorated/induced sputum specimen is defined as 
<10 squamous epithelial cells and >25 PMNs/100× field; and 
• Adequate respiratory specimens will undergo either semi-quantitative or quantitative 
culture in accordance with the local laboratory standard procedure.  For each subject, the 
sampling and testing method should be consistent for microbiological diagnosis of both 
pneumonia and its resolution. 
7.3.2 
 Assessment of Clinical Signs/Symptoms and Pneumonia Progression Status 
Subjects will be assessed daily throughout the Monitoring Period for the following clinical signs 
and symptoms and pneumonia progression status: 
Clinical Signs and Symptoms and Pneumonia Progression Status 
Mechanically Ventilated Subjects 
Non-Mechanically Ventilated Subjects 
Cough 
Rales 
Dullness on percussion * 
Bronchial breath sounds 
Egophony* 
Need for suctioning 
Need for ventilator support 
Fever ≥38°C (≥100.4°F) 
Presence of purulent secretions 
PaO2 (if measured) 
FiO2 (most representative setting) 
PEEP (most representative setting) 
Cough 
Rales 
Dullness on percussion * 
Bronchial breath sounds 
Egophony * 
Dyspnea 
Tachypnea 
Respiratory rate 
Hypoxemia 
Fever ≥38°C (≥100.4°F) 
Supplemental oxygen (i.e., nasal canula 2L, face mask at 30% O2) 
Presence of purulent secretions 
Fi02 = fraction of inspired oxygen; PaO2 = partial pressure of oxygen in arterial blood; PEEP = Positive end-expiratory 
pressure  
*If routinely performed. 
7.3.3 
 Evaluation of Pneumonia Outcomes 
7.3.3.1. 
Clinical Outcomes of Pneumonia According to Investigator 
In addition to the daily assessment of respiratory signs and symptoms, the Investigator will make 
a determination of pneumonia resolution if the subject meets all four of the following criteria:  
• Complete resolution of all or most of the pneumonia clinical signs and symptoms; 
• No new signs, symptoms, or complications of pneumonia; 
• No additional antibiotic therapy administered for pneumonia; and 
• Subject is alive. 

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7.3.3.2. 
Clinical Outcomes at Day 22 (Test of Cure) 
Clinical outcome will be assessed by the Sponsor as cured, failure, or indeterminate using the 
criteria below.  The classifications will be determined at Study Day 22 based on data collected and 
reported by the Investigator during the monitoring period. 
Cured  
To be classified as cured, subjects must meet all of the following criteria: 
1. Alive 
2. Resolution of signs and symptoms of infection or significant improvement of the index 
infection, including all of the following: 
• Improvement in signs and symptoms since diagnosis of pneumonia; 
• Improvement in oxygenation, as defined by any of the following:  
o Extubation (or removal of tracheostomy tube); 
o Improvement in PaO2:FiO2 by ≥20 mmHg [≥2.7 kPa]; or  
o Reduction in PEEP ≥2 cm for at least 2 consecutive days.  
(Note:  Failure of extubation should not be considered a clinical failure if it is due 
to reasons other than pneumonia; the reason for failure of extubation should be 
documented.) 
• Absence of fever (core temperature of >38.0ºC [>100.4ºF]) or hypothermia (<35ºC 
[<95 ºF]); 
• Absence of purulent sputum or other deep respiratory specimen; and 
• A 25% or more decrease in WBC count from the peak value associated with the 
diagnosis of pneumonia if the WBC was greater than 11,000/mm3 
3. No requirement for new or additional antimicrobial therapy for treatment of pneumonia 
and did not require antibiotic therapy beyond Study Day 14   
Failure 
Subjects meeting either of the following criteria will be classified as failures: 
1. Subject fails to meet any of the criteria for cure (above) or 
2. Subject dies of pneumonia >48 hours post-treatment with study medication 
Indeterminate  
Subjects meeting any the following criteria will be classified as indeterminate: 
1. Subjects lost to follow-up;  
2. Subjects for whom data are unavailable to allow for a determination of clinical cure or 
failure;  
3. Subjects who die within the first 48 hours; or  

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4. Subjects who change antibiotic therapy within the first 48 hours based on insufficient 
therapeutic effect.   
7.3.3.3. 
Microbiological Outcomes at Day 22 (Test of Cure)  
Eradication (documented or presumed) of the baseline pathogen(s) will be considered 
microbiological success while any new pathogen or persistence (documented or presumed) will be 
considered microbiological failure.  Specific microbiological outcomes definitions are as follows: 
 
Eradication: 
Absence of the baseline pathogen in an adequate post-
baseline respiratory specimen. 
Presumed Eradication: 
Absence of an adequate post-baseline respiratory 
specimen to culture in a subject deemed a clinical 
cure.  
Persistence: 
Presence of the baseline pathogen in an adequate 
post-baseline respiratory specimen. 
Presumed Persistence: 
Absence of an adequate post-baseline respiratory 
specimen to culture in a subject deemed a clinical 
failure. 
Indeterminate: 
Non-qualifying growth from the baseline respiratory 
culture or any confounding factors (e.g., early 
discontinuation from study medication) that prevent 
the assignment of an appropriate microbiologic 
outcome. 
Recurrence or Relapse: 
Isolation of a S. aureus strain from an adequate post-
baseline respiratory specimen after documented 
eradication. 
Emergent Infections or Superinfection: 
Isolation of a different pathogen, other than a baseline 
pathogen, from an adequate post-baseline respiratory 
specimen obtained in a subject with signs and 
symptoms of infection, while the subject is still on 
antibiotic therapy for the original infection. 
New Infection: 
Isolation of a different pathogen, other than the 
baseline pathogen, from a culture obtained after 
completion of antibiotic therapy in a subject with 
signs and symptoms of infection.  
 

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8. 
PHARMACOKINETICS 
The PK endpoints are the Cmax, Tmax, AUC, and t1/2 of ASN-1 and ASN-2 in serum following a 
single IV dose of ASN100 in the PK Population. 
Blood samples for the measurement of ASN-1 and ASN-2 in serum will be collected from all 
subjects in the sub-study on the same schedule as for the parent study. Samples will be collected 
at the following timepoints: 
• Immediately following the completion of the second infusion (+15 minutes), and at 
6 hours (±4 hours) and 24 hours (±6 hours) post-dose following the second infusion.  
• Days 4 (±1 day), 7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period.  
• Day of hospital discharge (if discharge occurs between Day 40 and Day 90), on Day 90 
(if hospitalized or if the subject is able to return to the clinic), or Early Termination (if 
applicable).  
Subjects may also participate in an optional BAL fluid PK sub-study as part of the primary study. 
If adequate fluid is obtained and available, lung fluid will be analyzed to measure S. aureus toxins.   
Please refer to Section 8.2 in the primary study protocol for additional specifics regarding the BAL 
sub-study. 
 

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9. 
STATISTICAL ANALYSES 
9.1. 
Analysis Populations 
Intent-to-Treat (ITT) Population 
The ITT Population includes all subjects who are randomized to receive study drug. 
Modified Intent-to-Treat (MITT) Population 
The MITT Population includes all subjects in the ITT Population who receive study drug who are 
heavily colonized with S. aureus as determined by quantitative or semi-quantitative culture of an 
ETA specimen. 
Microbiologically Evaluable Modified Intent-to-Treat (mMITT) Population 
The mMITT Population includes those subjects in the MITT Population that have confirmation by 
an adequate respiratory sample of a microbiological etiology of pneumonia as S. aureus, either 
MSSA or MRSA, without recovery of any other bacterial pathogens 
Expanded Microbiologically Evaluable Modified Intent-to-Treat (E-mMITT) Population  
The E-mMITT Population includes those subjects in the MITT Population that have confirmation 
by an adequate respiratory sample of a microbiological etiology of pneumonia as S. aureus, either 
MSSA or MRSA, with or without recovery of other bacterial pathogens. 
Pharmacokinetic (PK) Population 
The PK Population includes all subjects in the MITT Population with at least one serum PK sample 
collected post-dose. 
Safety Population 
The Safety Population includes all subjects who receive any amount of study drug and have at 
least one post-treatment safety assessment. 
9.2. 
Sample Size Determination 
This is a sub-study examining the potential benefit of ASN100 as an adjunct therapy to standard 
of care for the treatment of S. aureus pneumonia.  No formal statistical assessment for sample size 
determination has been conducted. The sample size is based on practical considerations. An 
estimated sample size of approximately 50 subjects derived from the observed number of subjects 
to date who have developed pneumonia prior to randomization in the primary study. 
9.3. 
Statistical Methods 
To insure balance among the treatment groups, randomization for the sub-study will be stratified 
by the number of days a subject has received anti-staphylococcal antibiotics on or prior to the time 
of randomization which are potentially effective against S. aureus pneumonia (further described 
in Section 3 of this Site-specific Addendum).  
Continuous variables will be summarized by using the number of non-missing observations, 
arithmetic mean, standard deviation, median, minimum, and maximum values as descriptive 
statistics. Categorical variables will be summarized by using the frequency count and the 
percentage of subjects in each category as descriptive statistics.  

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The primary endpoint reflecting clinical activity is the resolution of S. aureus pneumonia up to but 
not including Day 22. Analysis will include the comparison of the proportion of subjects who 
resolve S. aureus pneumonia in the ASN100 arm versus the placebo arm in the mMITT Population. 
An additional endpoint includes the time to resolution of S. aureus pneumonia. 
Duration of mechanical ventilation and length of hospital and ICU stay up to but not including 
Day 22 post-randomization will be compared between treatment groups. 
Other endpoints will be summarized by treatment group. 
All subjects in the Safety Population will be included in the safety analyses and analyzed based on 
the actual treatment received. 
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment-emergent adverse events (TEAEs) will be summarized by system organ 
class and preferred term. A TEAE is defined as an adverse event with a start date and time on or 
after the first dose of study treatment. Listings will be provided for serious adverse events and 
adverse events leading to drug discontinuation. In addition, all adverse events will be listed. 
Safety laboratory data and vital sign measurements will be presented by each scheduled time point 
and for change from baseline to each time point. The results of all laboratory tests, physical 
examination findings, vital sign measurements, and ADAs will be presented in data listings. 
Descriptive statistics will be provided for all PK concentration data and PK parameters. All PK 
analyses will be performed using the PK Population.  Subject PK profiles will be determined using 
parameters such as Cmax, Tmax, AUC, and t1/2 for each of ASN-1 and ASN-2 in serum. Epithelial 
lining fluid PK will also be analyzed and a serum/ELF PK ratio will be calculated. 
 
 
 

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10. 
APPENDICES 
10.1. 
Schedule of Procedures for Sub-Study 
 
Study Period 
Random-
ization 
Treatment 
Monitoring Period 
Follow-Up Period 
ET 
Study Day 
Day 1  
Pre-dose 
Day 1 
Day 2/3j 
(BAL PK 
Sub-study) 
Days 2 
to 21k 
Day 22 
(+2 days)  
Day 28 
(+2 days)l  
Days 40 
to 89m 
Day 90 
(±7 days) 
Safety Visitn 
Unschedo 
Study Procedures 
Inclusion/exclusion criteria 
Xp 
 
 
 
 
 
 
 
 
Medical history a 
X 
 
 
 
 
 
 
 
 
Antibiotic/medication history a 
X 
 
 
 
 
 
 
 
 
Physical examination b 
X 
 
 
X 
X 
 
X 
X 
X 
Vital signs c 
X 
X 
X 
X 
X 
 
X 
X 
X 
Pregnancy test d 
X 
 
 
 
X 
 
 
 
X 
Clinical lab assessments e 
X 
 
 
X 
X 
 
 
 
Xy 
Urinalysis 
X 
 
 
Xq 
X 
 
 
 
Xy 
Procalcitonin (central lab) 
X 
 
 
 
X 
 
 
 
X 
Ventilator device status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest X-ray/thoracic CT scan 
X 
 
X 
Xr 
X 
 
 
 
Xr 
Nasal swab for culture 
X 
 
 
 
 
 
 
 
 
Collection/culture of respiratory 
microbiological specimens f 
X 
 
Xs 
Xt 
 
 
 
Xt 
Collection/culture of additional 
microbiological specimens g 
 
 
 
X 
X 
 
 
 
X 
Clinical assessment of 
signs/symptoms of pneumonia  
X 
X 
X 
X 
X 
 
 
 
X 
Other S. aureus infection assessment  
X 
X 
X 
X 
X 
 
 
 
X 
Randomization 
X 
 
 
 
 
 
 
 
 
Blood collection for ADA and  
anti-S. aureus toxin antibodies 
X 
 
 
Xu 
X 
 
X 
X 
X 
12-lead ECG 
X 
 
 
 
X 
 
X 
X 
X 
Survival and discharge disposition 
 
 
 
 
X 
X 
X 
X 
X 

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Study Period 
Random-
ization 
Treatment 
Monitoring Period 
Follow-Up Period 
ET 
Study Day 
Day 1  
Pre-dose 
Day 1 
Day 2/3j 
(BAL PK 
Sub-study) 
Days 2 
to 21k 
Day 22 
(+2 days)  
Day 28 
(+2 days)l  
Days 40 
to 89m 
Day 90 
(±7 days) 
Safety Visitn 
Unschedo 
Study Procedures 
Study drug administration h 
 
X 
 
 
 
 
 
 
 
BAL for PK (Optional) 
 
 
X 
 
 
 
 
 
 
Blood collection for PK sampling and 
anti-S. aureus toxin antibodies 
 
Xv 
Xw 
Xx 
Xx 
 
Xx 
X 
X 
Track days on ventilator from 
randomization 
 
X 
X 
X 
X 
 
X 
X 
X 
Track days in ICU (or other 
observation area)  
 
X 
X 
X 
X 
 
X 
X 
X 
Concomitant medications i 
X 
X 
X 
X 
X 
 
X 
X 
X 
Adverse event assessment 
X 
X 
X 
X 
X 
 
X 
X 
X 
ADA = anti-drug antibody; BAL = bronchoalveolar lavage; CT = computed tomography; ECG = electrocardiogram; eCRF = electronic Case Report Form; ELF = epithelial lining 
fluid; ET = Early Termination; ETA = endotracheal aspirate; ICF = Informed Consent Form; ICU = intensive care unit; IV = intravenous; MRSA = methicillin-resistant S. aureus; 
MSSA = methicillin-susceptible S. aureus; PK = pharmacokinetic; S. aureus = Staphylococcus aureus; Unsched = unscheduled. 
 
a. 
Review and record medical history and antibiotic/medication history 
b. 
A limited physical examination will be performed at the Randomization Visit, daily during the Monitoring Period (if the subject is hospitalized), on Day 22 (if the subject is 
hospitalized), at the time of hospital discharge (if discharge occurs between Day 40 and Day 90), at the Safety Visit (Day 90) if the visit occurs onsite, and at ET (if 
applicable). The limited physical examination will include, at a minimum, a pulmonary examination (including auscultation). 
c. 
Vital sign measurements will include temperature, systolic and diastolic blood pressure, pulse, respiratory rate, and oxygenation status. Blood pressure and pulse will be 
assessed via an automated device. Manual techniques are only to be used if an automated device is not available. Oxygenation status will be determined via measurement of 
arterial blood gas, provided the subject has an arterial line placed. If no arterial line is present, pulse oximetry may be used. 
d. 
Pregnancy test. Female subjects of childbearing potential must have a documented negative pregnancy test at the Day 1 Pre-Dose (Randomization) Visit. A pregnancy test 
will also be performed on Day 22 or ET (if applicable). Additional pregnancy testing may occur throughout the duration of the study, per applicable country requirements. 
e. 
Blood samples for chemistry, hematology, and coagulation will be obtained on Days 2 (+1 day), 4 (±1 day), and 6 (±1 day) of the Monitoring Period, and twice weekly during 
Week 2 (Days 8 through 14) and/or Week 3 (Days 15 through 21) of the Monitoring Period while the subject remains hospitalized. 
f. 
An adequate respiratory sample to determine the microbiological etiology of the pneumonia should be collected within 36 hours of randomization, although all attempts 
should be made to obtain the specimen as close as possible to when the diagnosis of pneumonia was made.  Note:  Any time a BAL/non-bronchoscopic BAL or protected 
specimen brush (PSB) is performed to collect a respiratory microbiological sample, then a PK sample also should be will be collected to determine ASN-1 and ASN-2 levels 
to derive blood to ELF ratio, and to measure S. aureus toxins. 
g. 
If, as part of routine standard of care, additional non-respiratory microbiological specimens are collected for culture during the study, results will be documented within the 
eCRF; follow laboratory manual for which pathogens should be sent to central lab if isolates are available. 

Arsanis, Inc. 
Protocol ASN100-201 
 
 
Confidential & Proprietary 
 
Version 4.1, 23 April 2018 (Site Specific Amendment) 
100 
h. 
Study drug will be administered in a double-blind manner. Subjects will receive ASN100 or matching placebo via 2 IV infusions over a duration of approximately 50 to 60 
minutes per infusion. Both ASN100 and placebo will be administered as 2 separate infusions (either sequentially or simultaneously). The last infusion will be completed 
within 5 hours from initiation of drug preparation in the pharmacy. 
i. 
All prior medications received by the subject within 14 days prior to study drug administration and any concomitant medications used throughout the duration of the study 
will be recorded in the source documents and on the appropriate eCRF. 
j. 
Procedures are to be performed 48 hours (±36 hours) post-dose on approximately Day 2 or Day 3, depending on time of study drug administration, for those subjects 
participating in the BAL fluid PK sub study only or if BAL fluid is collected as part of a standard of care procedure for any subject at any other time post-randomization for 
any other reason. 
k. 
Procedures are to be performed daily (unless otherwise indicated) from Day 2 to Day 21 while the subject is hospitalized. For subjects participating in the BAL fluid PK sub 
study, procedures noted for the Day 2 visit only need to be performed 1 time. 
l. 
A follow-up visit will occur on Day 28 (+2 days) to assess mortality. This visit may be conducted via telephone if the subject is no longer hospitalized. 
m. For subjects who remain hospitalized between Day 40 and Day 90 at the institution where they receive study treatment, a follow-up safety visit will be performed on the day 
of discharge. 
n. 
If the subject is unable to return to the site, this visit may be conducted by telephone, with procedures performed as appropriate (i.e., concomitant medications and adverse 
events collected). 
o. 
An ET visit will be conducted for subjects who are withdrawn from the study prior to Day 22. 
p. 
At the Day 1 Pre-Dose (Randomization) Visit, subjects must meet all of the inclusion criteria and none of the exclusion criteria in order to be eligible for this sub-study. 
q. 
Urinalysis to be obtained on Day 6 (±1 day) of the Monitoring Period only 
r. 
Any chest X-ray or thoracic CT scan performed during the monitoring period as part of standard of care will be documented in EDC  
s. 
All respiratory specimens collected as part of standard of care are to be documented in EDC and any isolates stored for transport to the central laboratory.  Additionally, if a 
subject’s clinical symptoms of pneumonia improve such that no further antibiotic therapy is required, or if the pneumonia persists requiring a change in antibiotic therapy, 
then all attempts will be made to collect an adequate respiratory specimen. 
t. 
When possible, an adequate respiratory specimen should be obtained from subjects who remain ventilated and non-ventilated subjects who are able to produce sputum. 
u. 
Obtain sample for ADA (to be obtained only upon discharge from the ICU, if discharge occurs prior to Day 22). 
v. 
Blood samples for PK analysis will be collected immediately following the completion of the second infusion (+15 minutes) and at 6 hours (±4 hours) and 24 hours (±6 hours) 
post dose. 
w. Obtain a blood sample for PK measurement ±1 hour relative to BAL fluid collection (including scheduled BAL fluid collection or if BAL fluid is collected as part of a 
standard-of-care procedure from any subject enrolled in the sub-study at any time post-randomization). 
x. 
A PK sample will be obtained from all subjects on Days 4 (±1 day), 7 (±1 day), 14 (±2 days), and 22 (+2 days) of the Monitoring Period. Additional PK samples will be 
collected on the day of discharge (if discharge occurs between Day 40 and Day 90). 
y. 
To be obtained if clinically indicated.