Phase 1 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Ascending Doses of Subcutaneous Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
Phase: PHASE1
Conditions: Hemophilia A, Hemophilia B, Hemophilia A With Inhibitor, Hemophilia B With Inhibitor, Hemophilia A Without Inhibitor, Hemophilia B Without Inhibitor
Sponsor: Catalyst Biosciences

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
 
Page 1 of 60 
CLINICAL STUDY PROTOCOL 
Study Title: 
Phase 1 study to evaluate the pharmacokinetics, 
pharmacodynamics, and safety of ascending doses of 
subcutaneous marzeptacog alfa (activated) in adult subjects with 
hemophilia  
Investigational Product: 
Factor VIIa, marzeptacog alfa (activated) [MarzAA] 
Protocol Number: 
MAA-102 
Developmental Phase: 
1 
US IND Number: 
14789 
Study Sponsor: 
Catalyst Biosciences, Inc. 
611 Gateway Blvd., Suite 710 
South San Francisco, CA 94080 
Study Sponsor Contact: 
Name: 
Linda Neuman, MD, MBA 
Title: 
Vice President, Clinical Development 
Telephone: 
+1.650.266.8667 
Fax: 
+1.650.871.2475 
E-mail: 
lneuman@catbio.com 
Protocol Version History: 
Original Protocol: 
17 Jan 2018 
Amendment 1.0: 
11 Mar 2019 
Amendment 2.0 
25 Nov 2019 
 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that are privileged or 
confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. In any 
event, persons to whom the information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure will apply equally to all 
future information supplied to you that is indicated as privileged or confidential. 
Compliance Statement 
This study will be conducted in accordance with the clinical research guidelines established by the US Code of 
Federal Regulations (CFR) (Title 21, Parts 50 [including Subpart D], 54, 56, and 312), the regulations and 
guidelines of the Therapeutic Goods Administration, and the International Conference on Harmonization 
Guidelines for Good Clinical Practice (ICH GCP). Study documents will be maintained in accordance with 
applicable regulations.  

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
 
Page 2 of 60 
INVESTIGATOR SIGNATURE PAGE 
Study Title: 
Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and 
safety of ascending doses of subcutaneous marzeptacog alfa (activated) in 
adult subjects with hemophilia 
Protocol No.: 
MAA-102 
Version: 
Amendment 2.0 
Investigator Statement 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and providing the 
Sponsor with complete and timely information, as outlined in the protocol. 
Furthermore, on behalf of the study staff and myself, I agree to conduct the study as outlined in 
the protocol in accordance with the guidelines outlined in the study protocol and all applicable 
government regulations. In addition, I agree to provide all the information requested in the CRFs 
presented to me by the Sponsor in a manner that assures legibility and accuracy. I also agree that 
all information provided to me by the Sponsor, including preclinical data, protocols, CRFs, 
verbal and written information, will be kept strictly confidential and confined to the clinical 
personnel involved in conducting the study. It is recognized that this information may be relayed 
in confidence to the Institutional Review Board (IRB)/ Independent Ethics Committee (IEC). In 
addition, no reports or information about the study or its progress will be provided to anyone 
who is not involved in the study, other than Sponsor or designee, the IRB/IEC, or the appropriate 
regulatory agencies. 
The trial will be conducted in accordance with ICH GCP, applicable United States (US) CFR 
(Title 21, Parts 50 [including Subpart D], 54, 56, and 312), the regulations and guidelines of the 
Therapeutic Goods Administration. The Principal Investigator will assure that no deviation from, 
or changes to the protocol will take place without prior agreement from the sponsor, funding 
agency and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
have completed Human Subjects Protection and ICH GCP Training. Study documents will be 
maintained in accordance with applicable regulations. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
 
Investigator Name (Printed) 
 
Institution 
 
 
 
Investigator Signature 
 
Date 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 3 of 60 
SPONSOR SIGNATURE PAGE 
Protocol Title: 
Phase 1 study to evaluate the pharmacokinetics, 
pharmacodynamics, and safety of ascending doses of 
subcutaneous marzeptacog alfa (activated) in adult subjects with 
hemophilia 
Protocol Number: 
MAA-102 
Version: 
Amendment 2.0 
 
 
 
 
Linda Neuman, MD, MBA 
Vice President Clinical Development, Catalyst Biosciences, 
Inc. 
 
Date 
 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 4 of 60 
LIST OF ABBREVIATIONS 
AE 
adverse event 
ALT 
alanine aminotransferase 
APCC 
activated prothrombin complex concentrates 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC0-inf 
area under the plasma concentration-time curve from time 0 to the time of the last 
measurable plasma concentration 
AUC0-t 
area under the plasma concentration-time curve from time 0 to infinity 
BsMAb 
bispecific monoclonal antibody  
BU 
Bethesda units  
CAD 
coronary artery disease 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
Cmax 
maximum plasma drug concentration 
CNS 
central nervous system 
Cr 
creatinine 
CRF 
case report form 
DNA 
deoxyribonucleic acid 
DVT 
deep venous thrombosis 
EC 
ethics committee 
ECG 
electrocardiogram 
EDC 
electronic data capture 
eCRF  
electronic case report forms 
F1+2 
prothrombin fragment 1+2 
FVII 
Factor VII 
FVIIa 
Factor VII activated 
FVIII 
Factor VIII 
FIX 
Factor IX 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
GIT 
gastrointestinal tract 
GLP 
good laboratory practices 
GMP 
good manufacturing practices 
GS 
Gilbert’s syndrome 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IDE 
investigational device exemption 
IEC 
Independent Ethics Committee 
IMT 
immunomodulatory therapy 
IND 
investigational new drug  

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 5 of 60 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
LLN 
lower limit of normal 
MarzAA 
marzeptacog alfa (activated) 
MedDRA 
Medical Dictionary for Regulatory Activities 
OHRP 
Office for Human Research Protections 
OTC 
over-the-counter 
PC 
peak concentration 
PCC 
prothrombin complex concentrates  
PD 
pharmacodynamic 
PE 
pulmonary embolism 
PI 
principal investigator 
PK 
pharmacokinetic 
PRO 
patient-reported outcome 
PT 
prothrombin time 
QA 
quality assurance 
QC 
quality control 
rFIX 
recombinant Factor IX  
rFVIIa 
recombinant activated Factor VIIa  
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SOA 
schedule of activities 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TAT 
thrombin-antithrombin complexes 
TBIL 
total bilirubin level 
TE 
thromboembolic event 
TGT 
thrombin generation time 
ULN 
upper limit of normal 
VOD 
volume of distribution 
VTE 
venous thromboembolic event 
Wt 
wild-type 
 
 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 6 of 60 
TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ...............................................................................................1 
INVESTIGATOR SIGNATURE PAGE......................................................................................2 
SPONSOR SIGNATURE PAGE ..................................................................................................3 
LIST OF ABBREVIATIONS .......................................................................................................4 
TABLE OF CONTENTS ..............................................................................................................6 
LIST OF TABLES .........................................................................................................................8 
LIST OF FIGURES .......................................................................................................................8 
PROTOCOL SYNOPSIS ..............................................................................................................9 
1.0 
INTRODUCTION............................................................................................................15 
1.1 
Study Rationale ......................................................................................................15 
1.2 
Background ............................................................................................................15 
1.2.1 
Rationale for Prophylaxis with SC Administration of FVIIa................17 
1.2.2 
Experience with MarzAA in the Clinic .................................................18 
2.0 
OBJECTIVES ..................................................................................................................19 
2.1 
Primary Objectives .................................................................................................19 
2.2 
Secondary Objectives .............................................................................................19 
3.0 
STUDY ENDPOINTS ......................................................................................................20 
3.1 
Primary Endpoint ...................................................................................................20 
3.2 
Secondary Endpoints .............................................................................................20 
3.3 
Safety Endpoints ....................................................................................................20 
4.0 
STUDY DESIGN ..............................................................................................................21 
4.1 
Overall Design .......................................................................................................21 
4.2 
Measures to Minimize Bias: Randomization and Blinding ...................................22 
4.3 
End of Study Definition .........................................................................................22 
5.0 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................................23 
5.1 
Inclusion Criteria ...................................................................................................23 
5.2 
Exclusion Criteria ..................................................................................................23 
5.3 
Subject Withdrawal Criteria and Procedures; Subjects Lost to Follow-Up; and 
Subject Replacement ..............................................................................................24 
5.3.1 
Subject Withdrawal Criteria and Procedures ........................................24 
5.3.2 
Subjects Lost to Follow-Up ..................................................................24 
5.3.3 
Subject Replacement .............................................................................25 
6.0 
STUDY DRUG .................................................................................................................26 
6.1 
Investigational Product ..........................................................................................26 
6.1.1 
Dosing and Administration ...................................................................26 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 7 of 60 
6.2 
Preparation, Handling, Storage, and Acountability ...............................................27 
6.2.1 
Acquisition and Accountability.............................................................27 
6.2.2 
Product Storage and Stability ................................................................27 
6.2.3 
Preparation ............................................................................................28 
6.3 
Monitoring Compliance .........................................................................................28 
6.4 
Concomitant Therapy.............................................................................................28 
6.5 
Rescue Therapy ......................................................................................................29 
6.6 
Meals and Dietary Restrictions ..............................................................................29 
7.0 
STUDY ASSESSMENT AND PROCEDURES ............................................................30 
7.1 
Study Procedures and General Assessments ..........................................................30 
7.2 
Pharmacokinetics and Pharmacodynamics Assessments .......................................30 
7.3 
Safety Assessments ................................................................................................31 
7.3.1 
AEs and SAEs .......................................................................................31 
7.3.2 
Injection site reactions ..........................................................................32 
7.3.3 
Adverse Events and Serious Adverse Events .......................................32 
7.3.4 
Time Period and Frequency for Event Assessment and Follow-Up .....33 
7.3.5 
Adverse Event Reporting ......................................................................34 
7.3.6 
Potential Risks .......................................................................................35 
7.3.7 
Serious Adverse Event Reporting .........................................................35 
7.3.8 
Adverse Events of Special Interest (AESIs) .........................................36 
7.3.9 
Reporting of Pregnancy.........................................................................36 
7.4 
Unscheduled Visit Procedures and Withrawals .....................................................37 
7.5 
End-of-Study Assessments/Follow-up...................................................................38 
8.0 
STATISTICAL CONSIDERATIONS ...........................................................................39 
8.1 
Primary Analysis Plan............................................................................................39 
8.2 
Sample Size Determination ....................................................................................39 
8.3 
Populations for Analyses .......................................................................................39 
8.4 
Statistical Analysis .................................................................................................39 
8.4.1 
Subject Disposition ...............................................................................39 
8.4.2 
General Approach .................................................................................39 
8.4.3 
Analysis of the Primary Pharmacokinetic Endpoint(s) .........................40 
8.4.4 
Analysis of the Secondary Endpoint(s) .................................................40 
8.4.5 
Safety Analysis .....................................................................................40 
8.4.6 
Baseline Descriptive Statistics ..............................................................41 
8.4.7 
Planned Interim Analyses .....................................................................41 
8.4.8 
Sub-Group Analyses .............................................................................41 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 8 of 60 
8.4.9 
Tabulation of Individual Participant Data .............................................41 
8.5 
Protocol Deviations ................................................................................................41 
9.0 
DIRECT ACCESS TO SOURCE DOCUMENTS: AUDIT AND INSPECTION .....42 
10.0 
QUALITY CONTROL AND QUALITY ASSURANCE .............................................43 
10.1 
Clinical Monitoring ................................................................................................43 
10.2 
Quality Control ......................................................................................................43 
10.3 
Quality Assurance ..................................................................................................43 
11.0 
ETHICS ............................................................................................................................44 
11.1 
Compliance with Ethical and Regulatory Guidelines ............................................44 
11.2 
Institutional Review Board/Independent Ethics Committee ..................................44 
11.3 
Informed Consent...................................................................................................45 
11.4 
Subject Confidentiality ..........................................................................................45 
12.0 
DATA HANDLING AND RECORD KEEPING ..........................................................46 
12.1 
Data Collection and Management Responsibilities ...............................................46 
12.2 
Study Records Retention ........................................................................................46 
13.0 
FINANCING AND INSURANCE ..................................................................................47 
14.0 
STUDY DISCONTINUATION AND CLOSURE ........................................................48 
15.0 
PUBLICATION AND DATA SHARING POLICY .....................................................49 
16.0 
REFERENCES .................................................................................................................50 
17.0 
APPENDICES ..................................................................................................................54 
APPENDIX A 
SCHEDULE OF ASSESSMENTS (SOA) .........................................55 
APPENDIX B 
CLINICAL SIGNS OF THROMBOSIS ...........................................59 
 
LIST OF TABLES 
Table 6-1 
MarzAA Dose & Mode of Administration by Dosing Stage .....................26 
Table 17-1 
Overview of Protocol Visits and Procedures .............................................55 
Table 17-2 
PK/PD Schedule of Assessments for Each Study Stage (Stage 1 to 7) .....57 
 
LIST OF FIGURES 
Figure 4-1 
Study Schema.............................................................................................21 
 
 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 9 of 60 
PROTOCOL SYNOPSIS 
Study Title: 
Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of 
ascending doses of subcutaneous marzeptacog alfa (activated) in adult subjects with 
hemophilia 
Protocol Number: 
MAA-102 
Investigational Product: 
marzeptacog alpha (activated) (MarzAA) 
Target Population: 
Males ≥18 years of age with confirmed diagnosis of Hemophilia A or B with or 
without an inhibitor. 
IND Number: 
14789 
Study Phase: 
1 
Study Centers Planned: 
Approximately 10 Global Sites 
Number of Subjects 
Planned: 
A total of at least 8 male subjects ≥18 years of age are planned within each dosing 
Stage (Stages 1 to 9). If a subject cannot participate in all 9 dosing stages of the 
study, the subject will be replaced so that at least 8 subjects participate in each stage 
of the study with adequate pharmacokinetic (PK) sampling for analysis.  
Estimated Study 
Duration: 
18 months 
Estimated Participant 
Duration: 
The maximum study duration for each study subject participating in all nine (9) 
stages will be approximately 3 months if done consecutively. The dosing period for 
each stage will be approximately 3 days, with approximately 10 weeks of study 
dosing, depending on participation in all 9 stages and time elapsed between each 
study stage. Following the end of SC dosing with MarzAA and completion of 
assessments for follow-up a 30-day visit will be performed.  
Primary Objective(s): 
• 
To evaluate the pharmacokinetics of ascending subcutaneous (SC) doses of 
MarzAA 
Secondary Objectives: 
• 
To determine the pharmacokinetics of single dose IV and SC MarzAA 
• 
To determine if pharmacokinetics behave in a dose proportional manner 
• 
To determine whether a split injection provides the same pharmacokinetics as a 
single injection 
• 
To determine the pharmacodynamics of IV and SC MarzAA 
• 
To evaluate for evidence of the development of antibodies to MarzAA, wild 
type recombinant Factor VIIa (wt-rFVIIa), and/or wt-FVII, and to determine if 
these are neutralizing antibodies 
• 
To evaluate the safety of IV and SC MarzAA 
Study Design Overview: 
This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, 
pharmacodynamics, and safety of a single IV dose of MarzAA followed by 
ascending SC doses of MarzAA in adult subjects with moderate or severe 
Hemophilia A or B, with or without an inhibitor. 
The study will enroll at least 8 adult male subjects with moderate or severe 
Hemophilia A or B with or without an inhibitor.  

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 10 of 60 
Each subject will receive escalating doses of MarzAA for each stage of the study 
(except for Stage 5, where subjects receive the same dose as in Stage 4 split between 
two sites) as detailed in Figure S-1. 
Figure S-1 
Study Schema 
 
For Stage 1, specimens will be obtained for pharmacokinetics (MarzAA activity 
levels) at predose and then at 5, and 60 minutes ±5 minutes; 2, 6, 9 hours ±15 
minutes; 12 and 24 hours ±2 hours after dosing with MarzAA. For Stages 2 to 7 
specimens will be obtained for pharmacokinetics (MarzAA activity levels) at 
predose and then at 30, 60, and 90 minutes ±5 minutes; 2, 6, 9 hours ±15 minutes; 
24 and 48 hours ±2 hours after dosing with MarzAA. For stages 8 and 9, PK 
parameters will be obtained hourly starting at 2 through 9 hours, then at 12, 24,48 
and 72 hours. 
For Stage 1 coagulation and thrombogenicity parameters will be obtained at predose 
and then at 5 minutes ±5 minutes; 2 and 6 hours ±15 minutes; and 24 hours ±2 
hours. For Stages 2 to 9, coagulation and thrombogenicity parameters will be 
obtained at predose and then at 2 and 6 hours ±15 minutes; and 24 and 48 hours ±2 
hours. For stages 8 and 9, coagulation and thrombogenicity parameters will also be 
obtained at 72 hours.  
For Stage 1 (IV), Stage 2 (SC) may be initiated immediately after the 24-hour 
specimens have been obtained. If Stage 2 is initiated immediately after Stage 1, then 
the 48-hour specimens can be used as the predose specimens for the next Stage 
(Stage 2). 
For Stages 2 to 9, each subsequent stage may be initiated immediately after the 
48-hour specimens have been obtained. If the stage is initiated immediately after the 
previous stage, then the 48-hour specimens can be used as the predose specimens 
for the next stage. For Stages 1 to 9, a maximum of 7 days may elapse between the 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 11 of 60 
48-hour blood draw and when the next stage commences (unless delayed because of 
dose interruption as specified in the protocol).  
For subjects previously enrolled and completing the EOS visit prior to 
Amendment 2, if participation resumes, no additional screening parameters will be 
required and the 7-day maximum between Stage 7 and 8 does not apply.All predose 
assessment will be required. If a new subject is enrolled in the study in Amendment 
2, the subject will need to complete IV dosing and assessments (Stage 1) prior to 
advancing to Stages 2 to 9. 
Investigators will record study drug administration, route of administration (IV or 
SC), anatomical location of administration, injection site assessment, any adverse 
events (AEs) the subject may experience, and any bleeding episodes (location, 
inciting event if not spontaneous), and concomitant treatment administered. 
Inclusion Criteria: 
Study candidates must meet all the following inclusion criteria to be eligible for 
participation in this study: 
1) Confirmed diagnosis of moderate or severe congenital Hemophilia A or B, with 
or without an inhibitor 
2) Male, age ≥18 years 
3) Agreement to use highly effective birth control throughout the study 
4) Affirmation of informed consent with signature confirmation before any 
trial-related activities  
Note: trial related activities are any procedure that would not have been 
performed during normal clinical management of the subject 
5) Stated willingness to comply with all study procedures and availability for the 
duration of the study 
Exclusion Criteria: 
Study candidates who meet any of the following criteria will not be eligible for 
participation in this study: 
1) Inability to discontinue and washout prophylaxis treatment 72 hours prior to 
dosing 
2) Previous participation in a trial involving SC administration of rFVIIa 
(NovoSeven or MOD-5014) or any trial using a modified amino-acid sequence 
FVIIa such as: NN1731 or BAY86-6150. Prior participation in a trial of 
intravenous (IV) LR769 or rFVIIa-FP (CSL689) is permissible.  
3) Previous participation in a clinical trial with subsequent treatment within the 
previous 30 days or 5-half-lives or absence of clinical effect, whichever is 
longer 
4) Known positive antibody to FVII or FVIIa detected by central laboratory at 
screening 
5) History of clinically relevant coagulation disorders other than congenital 
Hemophilia A or B, with or without an inhibitor 
6) Platelet count <100,000 /µL based on screening laboratory assessments 
7) Advanced atherosclerotic disease (ie, known history of coronary artery disease 
(CAD), ischemic stroke, etc.), or known deep venous thrombosis (DVT) or 
considered to be at a high risk of venous thromboembolic event (VTE) as 
judged by the Investigator 
8) Known or suspected allergy to trial product or related products. 
9) Receiving immunomodulatory therapy (IMT). 
10) Compromised hepatic or renal function: 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 12 of 60 
a. 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
levels ≥5 x the upper limit of normal (ULN) 
b. Total bilirubin (TBIL) level ≥2 mg/dL (>35 μmol/L) unless there is a 
known history of Gilbert’s syndrome (GS) 
c. 
Serum albumin (ALB) level ≤1 × the lower limit of normal (LLN) 
d. Serum creatinine (Cr) level >1.25 × ULN.  
11) Inability or medical, psychosocial, or familial issues that might prevent full 
participation and cooperation with the procedures and requirements of the 
clinical trial as determined by the potential subject and physician/investigator 
Study Procedures: 
See Schedule of Study Assessments (Table 17-1, Table 17-2, Table 17-3) 
Investigational Product 
Recombinant FVII variant, MarzAA 
Dose and Route of Administration: 
Dosing, route, and frequency of administration are provided in Table S-1.  
Table S-1 
MarzAA Dose & Mode of Administration by Dosing Stage 
Stage 
Dose a 
Route 
Number 
of Doses 
Timing b 
1 
18 µg/kg 
IV 
1 
NA 
2 
30 µg/kg 
SC 
1 
24 hours after Stage 1 
3 
45 µg/kg 
SC 
1 
48 hours after Stage 2 
4 
60 µg/kg 
SC 
1 
48 hours after Stage 3 
5 
2 × 30 µg/kg c 
2 × SC 
1 
48 hours after Stage 4, 2 sites c 
6 
2 × 45 µg/kg d 
2 × SC 
1 
48 hours after Stage 5, 2 sites d 
7 
2 × 60 µg/kg e 
2 × SC 
1 
48 hours after Stage 6, 2 sites e 
8 
2 × 60 µg/kg f  
(120 µg/kg/day)  
SC 
2  
48 hours after Stage 7, unless 
subjects were enrolled in the 
study prior to Amendment 2 b, 
2 doses at 3-hour intervals , f 
9 
3 × 60 µg/kg g 
(180 µg/kg/day) 
SC 
3 
72 hours after Stage 8, 3 doses 
at 3-hour intervals g 
Abbreviations:  
IV=intravenous; MarzAA=marzeptacog alfa (activated); 
SC=subcutaneous. 
a 
For subjects requiring more than 2 vials of supplied study drug, the number of SC 
injections should be commensurate with the number of vials needed. Injection sites 
should be different for each injection but should be at the same anatomic location. 
b 
Timing provided is minimum time after dosing. Maximum time after dosing should not 
exceed 7 days if a subject continues to the next stage of the study except for subjects 
completing their EOS visit prior to Amendment 2. 
c 
2 × 30 µg/kg MarzAA (total dose 60 µg/kg) injected at two different anatomic locations 
(which must drain into separate lymphatic tributary areas [eg, left and right thigh, or 
different sides of abdomen, or abdomen and thigh]) 
d 
2 × 45 µg/kg MarzAA (total dose 90 µg/kg) injected at two different sites at the same 
anatomic location  
e 
2 × 60 µg/kg MarzAA (total dose 120 µg/kg) injected at two different sites at the same 
anatomic location and timepoint 
f 
60 µg/kg MarzAA (total dose 120 µg/kg/day) administered at two separate timepoints 
with 3-hour intervals between each dose and in the same anatomic location 
g 
60 µg/kg MarzAA (total dose 180 µg/kg/day) administered at three separate timepoints 
with 3-hour intervals between each dose and in the same anatomic location  

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 13 of 60 
Dose  
Adjustments and Dosing Stage Interruption: 
No dose adjustments are planned for this study. Advancing to the next dosing stage 
is stopped as needed, if there is a need for a surgical procedure; an event requiring 
extended (>48 hours) hospitalization; a thrombotic event; clinical evidence of 
inhibitor formation; or laboratory results suggesting an antibody to MarzAA may be 
developing.  
The subject may continue to the next dosing stage once the bleeding event is 
resolved and the subject has stopped treatment for the bleed for at least 72 hours 
prior to dosing. 
A study stage may be repeated in a subject if PK assessments are interrupted by 
treatment of a bleed or inadequate PK samples for analysis. 
Reference Therapy: 
Not applicable 
Rescue Therapy or 
Emergency Procedures 
(if applicable):  
Treatment of spontaneous or traumatic bleeding:  
Subjects with spontaneous or traumatic bleeds can use their current treatment 
regimen. A washout period of 72 hours after the subject is stablized must be 
completed before the subject continues to the next stage of the study. 
Concomitant 
Medication: 
There are no concomitant medication restrictions unless otherwise noted (in 
exclusion criteria and prohibited medications) or required. 
Prohibited Medication: 
There are no concomitant medication restrictions. However, individuals are 
excluded if they have been on a prophylactic treatment regimen with a FVIII or FIX 
replacement factor or a bypassing agent prior to enrollment and cannot discontinue 
and washout this therapy prior to dosing. 
Efficacy Endpoints: 
Primary: 
• 
Comparative pharmacokinetics of MarzAA by dose level/stage 
Secondary: 
• 
Comparative pharmacokinetics of IV and SC MarzAA 
• 
Effect of split injections on pharmacokinetics 
• 
Change in coagulation parameters (prothrombin time [PT], activated partial 
thromboplastin time [aPTT], fibrinogen, MarzAA activity levels, and thrombin 
generation time [TGT]) from predose 
• 
Occurrence of an antibody response to MarzAA and whether it is inhibitory and 
cross-reactive to wt-rFVIIa or wt-FVII 
Safety Endpoints:  
• 
Occurrence of clinical thrombotic event not attributable to another cause, and 
occurrence of antibody formation resulting in a decreased endogenous level of 
FVII or FVIIa 
• 
Treatment emergent adverse events (TEAEs) and serious adverse events 
(SAEs) 
Statistical Methods: 
Primary Analysis Plan:  
• 
PK analysis by route of administration, dose level/ stage  
• 
Analysis for dose proportionality 
• 
Appropriate statistics of all recorded, measured and calculated parameters will 
be reported, including 95% confidence intervals, n, mean, standard deviation, 
median, minimum and maximum 

Marzeptacog alfa (activated), (MarzAA): 
IND 14789 
Study MAA-102, Amendment 2.0 
Catalyst Biosciences, INC 
CONFIDENTIAL 
Page 14 of 60 
Safety Analysis Plan:  
• 
Subject disposition (ie, number of subjects treated, subjects who completed the 
study, subjects who discontinued and the primary reasons for discontinuation) 
will be tabulated 
• 
All AEs will be listed by preferred term and system organ class as classified by 
using Medical Dictionary for Regulatory Activities (MedDRA) and type, 
frequency, course, outcome, severity, and causality to study drug will be 
documented. Verbatim terms on CRFs will be mapped to preferred terms and 
related system organ class using the Medical Dictionary for Regulatory 
Activities (MedDRA). 
• 
Vital signs (blood pressure, heart rate, termperature, respiratory rate) and 
laboratory values with descriptive statistical summaries of shifts for each stage 
Sample size justification: 
The sample size estimate is based on PK guidance for the development of 
hemophilia factors published by regulatory agencies. 
Analysis Sets 
Safety: 
any subject who receives at least one dose of study drug. 
The Safety population will be used for safety analysis 
PK Population: 
any subject who completes an entire stage including the 
PK assessments and has adequate samples for analyses. 
Safety:  
The safety of MarzAA will be monitored closely by a medical monitor and the 
Sponsor on aongoing basis. All SAEs will be reported to the medical monitor and 
Sponsor. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
and the applicable regulatory requirement(s), including the archiving of essential documents. 

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1.0 
INTRODUCTION 
1.1 
Study Rationale 
A significant number of patients with Hemophilia A develop neutralizing antibodies 
(“inhibitors”) against FVIII and become refractory to standard factor replacement treatment 
(Kempton, 2009; Ma, 2006; Peyvandi, Mannucci, , 2016; Walsh, 2015). Hemophilia A is four 
times as common as Hemophilia B (National Hemophilia Foundation, 2019). Patients with 
Hemophilia B can also develop neutralizing antibodies and become refractory to factor 
replacement therapy (Martensson, 2016; Wieland, 2011; Zhou, 2015). Currently, available 
treatment for patients with Hemophilia A or B with inhibitors, is with rFVIIa, activated 
prothrombin complex concentrates (APCCs), or with bispecific monoclonal antibody (BsMAb). 
The prevention of bleeding episodes, referred to as prophylaxis, requires frequent IV dosing 
(NovoSeven RT US Package Insert, 2019). Catalyst Biosciences has created a FVIIa variant, 
marzeptacog alfa (activated) (MarzAA), with preclinical properties that suggest increased 
potency and duration, as well as the ability to be administered subcutaneously for daily use as 
prophylaxis and potentially, for the SC treatment of bleeding.  
1.2 
Background 
Hemophilia 
Hemophilia A and B are X-linked, recessive, hereditary bleeding disorders caused by an 
impaired deficiency of coagulation FVIII (Hemophilia A) or FIX (Hemophilia B) (Mannucci, 
2001). The prevalence of Hemophilia A is 1 in 5000 live male births and Hemophilia B is 1 in 
30,000 (Hemophilia A is four times as common as Hemophilia B) 
(National Hemophilia Foundation, 2019). Disease classification of mild (>5 and <40% of normal 
levels of active clotting factor), moderate (1 to 5%) or severe (<1%) is based on plasma FVIII 
and FIX levels (White, 2001). Bleeding is the main clinical manifestation, which can occur 
spontaneously, especially in severe hemophilia. Bleeding most often affects the joints, causing 
arthropathy with significant impairment of mobility and quality of life. Other sites can include 
the soft tissue, gastrointestinal tract (GIT) and central nervous system (CNS) (Franchini, 2013; 
Manco-Johnson, 2007). Treatment of Hemophilia A or Hemophilia B typically involves factor 
replacement therapy by IV injection of FVIII or FIX concentrate, respectively, to treat or provide 
prophylaxis against bleeding episodes (Mannucci, 2001). Factor replacement therapy is also used 
for surgical hemostasis and to maintain hemostasis during the postoperative wound healing 
period. Neutralizing antibodies (inhibitors) to the injected FVIII or FIX are a complication of 
factor replacement therapy that develops in approximately one-third of patients with Hemophilia 
A and in up to 5% of patients with Hemophilia B (Astermark, 2010; Franchini, 2011; Sultan, 
1992; Wight, 2003). Inhibitors can occur at high or low titer (quantitated in Bethesda units 
[BU]), can neutralize the activity of the replacement therapy, and can make treatment of bleeding 
episodes unsuccessful, resulting in potentially catastrophic clinical consequences for the patient, 
including an increased morbidity and mortality risk (Astermark, 2010; Mannucci, 2001). 

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Current Therapies 
For hemophilia patients with high titer inhibitors to FVIII or FIX and for those hemophilia 
patients with low titer inhibitors for whom it is not possible to achieve hemostasis using FVIII or 
FIX replacement therapy, respectively, the current standard of care includes treatment with wt-
rFVIIa (NovoSeven RT) or APCCs, including AICC, (FEIBA) (FEIBA US Package Insert, 
2018; Kempton, 2014; Kempton, 2009; NovoSeven RT US Package Insert, 2019; 
World Federation of Hemophilia, 2012). These agents fall in the category of bypass agents and 
effect hemostasis by achieving conversion of prothrombin to thrombin via the tissue factor 
pathway (extrinsic pathway) of coagulation or via a combination of the tissue factor pathway and 
the final common pathway of coagulation respectively (Franchini, 2013). NovoSeven, a wt-
rFVIIa, was approved by the FDA in March 1999, for the treatment of bleeding episodes in 
Hemophilia A (FVIII-deficient) or Hemophilia B (FIX-deficient) patients with inhibitors, and in 
patients with congenital FVII deficiency. It is also approved for prevention of bleeding prior to 
surgery or invasive procedures in these patients with inhibitors or FVII deficiency. Based on its 
very short (2.3 hours) half-life, administration of NovoSeven is repeated approximately every 2 
hours to control hemorrhage in patients with Hemophilia A or B with inhibitors (Kempton, 2014; 
Kempton, 2009; NovoSeven RT US Package Insert, 2019; World Federation of Hemophilia, 
2012). Often, multiple doses (3 or more) are required to complete treatment of a bleeding episode 
(NovoSeven RT US Package Insert, 2019).  
Activated prothrombin complex concentrates were introduced for treatment of inhibitors in 
patients with hemophilia in the 1970s (FEIBA US Package Insert, 2018). The only activated 
prothrombin complex concentrates (APCC) currently available on a commercial basis is FEIBA 
which was first marketed in 1977 and was first licensed in the US as FEIBA VH (vapor heat-
treated FEIBA). FEIBA VH was manufactured via vapor heat treatment to inactivate lipid-
enveloped ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) viruses and nonenveloped 
RNA viruses. In 2006, Baxter introduced nanofiltration to the manufacturing process of FEIBA 
VH to create FEIBA NF. During 2010, FEIBA VH was completely replaced by FEIBA NF on a 
worldwide basis. FEIBA was previously licensed in the United States as FEIBA VH and FEIBA 
NF and is now available as FEIBA. FEIBA, and FEIBA NF are identical in formulation to 
FEIBA VH (FEIBA US Package Insert, 2018). FEIBA is indicated for the control and prevention 
of bleeding episodes, routine prophylaxis to prevent or reduce the frequency of bleeding episodes 
and to cover surgical interventions in Hemophilia A and Hemophilia B patients with inhibitors. 
For treatment of bleeding episodes in hemophilia patients with inhibitors, FEIBA is typically 
administered in doses of 50 to 100 units/kg, determined by the type of bleeding episode. Repeat 
administration, if required, is typically administered at 6-12-hour intervals until resolution of 
bleed or alleviation of symptoms. For prophylaxis, the approved dose of FEIBA is 85 units/kg 
administered every other day (FEIBA US Package Insert, 2018). 
Treatment of inhibitor patients with wt-rFVIIa or with APCCs has limitations with regard to 
efficacy, safety, and/or convenience (Abshire, 2004; Lusher, 1998; Pipe, 2005), and therefore, 
presents opportunities for development of improved or alternative biotherapeutics to satisfy an 
unmet medical need in this patient population. Efficacy of wt-rFVIIa or APCCs in patients with 
inhibitors is suboptimal in terms of ability to control bleeds, route of administration, and 

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regarding duration of action. These therapies fall short of the efficacy achieved with 
conventional factor replacement therapies in patients without inhibitors (Mannucci, 2001; 
Santagostino, 1999; Santagostino, 2006). Because efficacy is suboptimal with these agents, 
elective surgical procedures may be deferred for patients with inhibitors who may need such 
procedures (Rodriguez-Merchan, 2010). Pathogen transmission, thromboembolic events, 
hypersensitivity and anamnestic response resulting in an increase in inhibitory antibody titers 
have been the main safety concerns when treating patients with hemophilia with inhibitors 
(FEIBA US Package Insert, 2018; NovoSeven RT US Package Insert, 2019). Thrombotic events 
in association with NovoSeven treatment in hemophilia patients with inhibitors have been 
reported in up to 4% of patients (Abshire, 2008; Neufeld, 2011; 
NovoSeven RT US Package Insert, 2019; O'Connell, 2006). Reported incidence of thrombotic 
events in association with FEIBA use ranges from 4 to 8.24/100,000 infusions (Aledort, 2008; 
FEIBA US Package Insert, 2018; Gomperts, 2006; Luu, 2004). NovoSeven is not approved for 
prophylaxis and its use for that purpose is not generally feasible for many reasons, including 
short duration of action that precludes administration schedules practical for routine use 
(NovoSeven RT US Package Insert, 2019; Young, 2011). The percent reduction in annual bleed 
rate during prophylaxis of hemophilia patients with inhibitors with FEIBA (Antunes, 2014) is 
less than that reported for factor replacement therapy in hemophilia patients without inhibitors 
(Tagliaferri, 2008). FEIBA also contains small amounts of FVIII and has the potential to boost 
inhibitor titers in Hemophilia A patients with inhibitors (Kempton, 2009). 
Once-weekly emicizumab-kxwh (HEMLIBRA), a BsMAb, was approved by the FDA in 
November 2017 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes 
in adults and children with Hemophilia A with FVIII inhibitors and in October 2018 for routine 
prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages 
newborn and older, with Hemophilia A without FVIII inhibitors 
(HEMLIBRA US Package Insert, 2018). 
1.2.1 
Rationale for Prophylaxis with SC Administration of FVIIa 
Intravenous dosing often requires a medical professional or family member to achieve venous 
access making home prophylaxis cumbersome, particularly for pediatric patients (Hartmann, 
2016; Peyvandi, Garagiola, , 2016). Other challenges include patient adherence, and reliable IV 
access (Hacker, 2001; Stoner, 2014). IV administration requires direct venipuncture or sterile 
entry into a central venous access device on a regular basis, which makes it time-consuming and 
negatively influences adherence (Hacker, 2001; Stoner, 2014). 
SC administration presents a major advantage over IV administration because it enables at-home 
injection, improves quality of life, and reduces health care costs (Stoner, 2014). While home IV 
administration has been essential to the provision of comprehensive hemophilia care, it 
nonetheless remains a significant barrier (Hacker, 2001). SC dosing allows improved ease of 
self-administration and obviates the need for home nursing or a visit to a hemophilia center to 
provide an IV infusion when a patient or a family member has not been able to do so (Stoner, 
2014). Compared with the IV route, SC administration of wt-rFVIIa has been shown to extend 
half-life (12.4 hours vs 2.7 hours) and significantly reduces the large daily fluctuations of 

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systemic drug concentrations, though with a reduced bioavailability (21 to 30% vs 100%) (Tiede, 
2011). Consequently, there is a clear need for the development of rFVIIa variants with greater 
bioavailability and extended effect for SC administration to facilitate effective bleeding 
prophylaxis in hemophilia patients with inhibitors. Furthermore, the ability to treat bleeding 
episodes by SC administration would be ideal. 
MarzAA, a novel rFVIIa variant, is being developed by Catalyst Biosciences (the Sponsor) to 
address the unmet need for medical management of Hemophilia A and B patients with inhibitors. 
MarzAA was developed using a structure-based rational protein design approach intended to 
enhance the biological properties of wt-rFVIIa and contains a total of 4 amino acid substitutions. 
The 2 amino acid substitutions in the protease domain (Q286R and M298Q) increase catalytic 
activity for Factor X activation in both a tissue factor-dependent and tissue factor independent 
manner. The 2 others are in the light chain (T128N and P129A) and yield an additional N-linked 
glycosylation site designed to provide an extended duration of effect. These qualities are 
expected to prolong the interval between doses, improve convenience of treatment, and facilitate 
use of the product for bleeding prophylaxis, and potentially for treating breakthrough bleeding. 
1.2.2 
Experience with MarzAA in the Clinic 
To date, the safety, pharmacokinetics, and pharmacodynamics of MarzAA IV administration has 
been evaluated in one clinical study (B3051001), which recruited 25 adult subjects with 
Hemophilia A or B (all male) with or without inhibitors, with 1 subject in the 0.5 μg/kg dose 
group and 6 subjects in each of the 4.5, 9, 18, and 30 μg/kg dose groups. Cmax was reached at 5 to 
15 minutes after IV bolus administration. Both clearance and volume of distribution (VOD) were 
similar at 18 to 30 μg/kg dose level but decreased across the 3 lower doses (4.5 to 18 μg/kg). 
MarzAA terminal half-life (~3.5 hours) was similar across all doses. The MarzAA 
pharmacokinetic (PK) profile observed in clinical study B3051001 was consistent with 
projections based on preclinical data. All hemophilia and nonhemophilia AEs were mild or 
moderate in severity; there were no severe TEAEs, no SAEs and no AEs leading to treatment 
discontinuation. Overall, the most common nonhemophilia-related AEs were dizziness, 
headache, and oropharyngeal pain (2 subjects each). Hemophilia-related AEs consisted of 3 AEs 
of arthralgia, and 1 AE each of flank pain, hemarthrosis, joint swelling, muscle swelling, and 
limb injury. MarzAA demonstrated good pharmacodynamic (PD) effects, with drug-related 
(most often dose-related) changes observed for a variety of coagulation parameters. Thus, 
MarzAA showed an acceptable safety profile and promising PD effects in the Phase 1 study.  
A Phase 2 study is currently being conducted to evaluate the pharmacokinetics, bioavailability, 
pharmacodynamics, efficacy and safety of a daily SC treatment regimen with MarzAA for 
bleeding prophylaxis in adult subjects with Hemophilia A and B with an inhibitor. 

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2.0 
OBJECTIVES 
2.1 
Primary Objectives 
• To evaluate the pharmacokinetics of ascending SC doses of MarzAA 
2.2 
Secondary Objectives 
• To determine the pharmacokinetics of single dose IV and SC MarzAA  
• To determine if pharmacokinetics behave in a dose proportional manner 
• To determine whether a split injection provides the same pharmacokinetics as a single 
injection 
• To determine the pharmacodynamics of IV and SC MarzAA 
• To evaluate for evidence of the development of antibodies to MarzAA, wild-type 
recombinant FVIIa (wt-rFVIIa), and/or wt-FVII, and to determine if these are neutralizing 
antibodies 
• To evaluate the safety of IV and SC MarzAA 

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3.0 
STUDY ENDPOINTS 
3.1 
Primary Endpoint 
• Comparative pharmacokinetics of MarzAA by dose level/stage 
3.2 
Secondary Endpoints 
The secondary endpoints are as follows: 
• Comparative pharmacokinetics of IV and SC MarzAA 
• Effect of split injections on pharmacokinetics 
• Change in coagulation parameters (PT, activated prothrombin complex concentrates [aPTT], 
fibrinogen, MarzAA activity levels, and thrombin generation time [TGT]) from predose 
• Occurrence of an antibody response to MarzAA and whether it is inhibitory and 
cross-reactive to wt-rFVIIa or wt-FVII 
3.3 
Safety Endpoints 
• Occurrence of clinical thrombotic event not attributable to another cause, and occurrence of 
antibody formation resulting in a decreased endogenous level of FVII or FVIIa 
• Treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) 

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4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 1 study designed to evaluate the pharmacokinetics, pharmacodynamics, and 
safety of a single IV dose and ascending doses of SC MarzAA in adult subjects with 
Hemophilia A or B, with or without an inhibitor. It is an open-label study, so subjects and 
members of the clinical study team will not be blinded to treatment. The study is summarized in 
the study schema (Figure 4-1). 
Figure 4-1 
Study Schema 
 
The study will be completed in approximately 18 months (from when the study opens enrollment 
until completion of data analyses). The study will enroll at least 8 adult male subjects with 
moderate or severe Hemophilia A or B with or without an inhibitor in each dosing stage.  
Each subject may continue on to the next stage of MarzAA dosing if they wish to continue the 
study provided they do so no more than 7 days after the end of the previous stage and that any 

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spontaneous or traumatic bleeds have been resolved and that the subject has undergone a 72-hour 
washout period of the treatment used for the spontaneous or traumatic bleed. If any subject 
completes the EOS assessments prior to Amendment 2 and wishes to participatein Stages 8 
and/or 9, the 7-day requirement does not apply, and no screening assessment will need to be 
repeated. All predose assessments will be required. If a new subject is enrolled in the study in 
Amendment 2, the subject will need to complete IV dosing and assessments (Stage 1) prior to 
advancing to Stages 2 to 9. 
Each subject may receive the study drug in nine (9) dosing stages (Stage 1 to 9) as detailed in 
Section 6.1.1.  
Study endpoints are provided in Section 3.0. Investigators will record study drug administration, 
route of administration, anatomical location, injection site assessment, any AEs the subject may 
experience, and any bleeding episodes (location, inciting event if not spontaneous), and 
concomitant treatment administered. 
Subjects will sign an informed consent form (ICF) at screening and prior to any study 
procedures. Eligibility to participate in the study will be determined by inclusion and exclusion 
criteria elicited from medical history, physical examination, laboratory assessments and an ECG. 
The screening period may be up to 4 weeks prior to dosing. 
Additional details on study assessments and procedures are provided in Section 7.0. 
No dose adjustments are planned for this study. Guidelines for the interruption of dose escalation 
are provided in Section 6.1.1.1. 
4.2 
Measures to Minimize Bias: Randomization and Blinding 
The study is an open-label study; subjects and members of the clinical study team will not be 
blinded to treatment.  
4.3 
End of Study Definition 
The maximum study duration for each study subject participating in all nine (9) stages will be 
approximately 4 months. The dosing period for each stage will be approximately 3 days, with a 
maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and 
time elapsed between each study stage. Following the end of dosing with MarzAA and 
completion of assessments, then a 30-day visit will be performed for safety and follow-up.  
The end-of-study visit will be 30 days after the last dose of study drug. For subjects previously 
enrolled and completing the EOS visit prior to Amendment 2, if participation resumes (, EOS 
assessments should be repeated (ie, after Stage 8 and/or 9). 
A participant is considered to have completed the study if he has completed all assessments in a 
stage of the study and returned for procedures listed under end of study visit, as shown in the 
SOA (Table 17-1, Table 17-2, and Table 17-3). 

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5.0 
SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1 
Inclusion Criteria 
An individual must meet all the following criteria to be eligible to participate in this study: 
1) Confirmed diagnosis of moderate or severe congenital Hemophilia A or B, with or without 
an inhibitor 
2) Male, age 18 or older 
3) Agreement to use highly effective birth control throughout the study 
4) Affirmation of informed consent with signature confirmation before any trial-related 
activities 
NOTE: Trial related activities are any procedure that would not have been performed 
during normal clinical management of the subject. 
5) Stated willingness to comply with all study procedures and availability for the duration of the 
study 
5.2 
Exclusion Criteria  
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1) Inability to discontinue and washout prophylaxis treatment 72 hours prior to dosing. 
2) Previous participation in a trial involving SC Administration of rFVIIa (Novo Seven or 
MOD-5014) or any trial using a modified amino-acid sequence FVIIa such as: NN1731 or 
BAY86-6150. Prior participation in a trial of IV LR769 or rFVIIa-FP (CSL689) is 
permissible.  
3) Previous participation in and subsequent treatment in a clinical trial within the previous 30 
days or 5-half-lives or absence of clinical effect, whichever is longer.  
4) Known positive antibody to FVII or FVIIa detected by central laboratory at screening. 
5) History of clinically relevant coagulation disorders other than congenital Hemophilia A or B, 
with or without an inhibitor. 
6) Platelet count <100,000 /µL based on screening laboratory assessments. 
7) Advanced atherosclerotic disease (ie, known history of CAD, ischemic stroke, etc.), or 
known DVT or considered to be at a high risk of VTE as judged by the Investigator. 
8) Known or suspected allergy to trial product or related products. 
9) Receiving IMT. 
10) Compromised hepatic or renal function: 
a) Alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels 
≥5 × ULN 

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b) TBIL ≥2 mg/dL (>35 μmol/L) unless there is a known history of GS 
c) Serum albumin <1 × LLN 
d) Serum Cr level >1.25 × ULN 
11) Inability or medical, psychosocial, or familial issues that might prevent full participation and 
cooperation with the procedures and requirements of the clinical trial as determined by the 
potential subject and physician investigator. 
5.3 
Subject Withdrawal Criteria and Procedures; Subjects Lost to Follow-Up; and 
Subject Replacement 
5.3.1 
Subject Withdrawal Criteria and Procedures 
Subjects are free to withdraw from participation in the study at any time upon request.  
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
• Significant study intervention noncompliance  
• If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the 
participant 
• If the participant meets a criterion (either newly developed or not previously recognized) that 
precludes further study participation 
• Decision by Investigator or Sponsor 
The reason for participant discontinuation or withdrawal from the study and the date must be 
recorded on the eCRF.  
Any remaining study procedures should be completed as indicated by the study protocol. Any 
new clinically relevant finding will be reported as an AE. 
If the subject withdraws from the study and withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
5.3.2 
Subjects Lost to Follow-Up 
A participant will be considered lost to follow-up if he fails to return for two consecutive 
scheduled visits and is unable to be contacted by the study site staff.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study 

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• Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the participant’s medical record 
or study file.  
• Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up 
In any circumstance, every effort should be made to document subject outcome, if possible. The 
investigator should inquire about the reason for withdrawal, request the subject to return for a 
final visit, if applicable, and follow up with the subject regarding any unresolved AEs. 
5.3.3 
Subject Replacement 
If a subject does not complete a stage of the study or withdraws from the study, a replacement 
subject will be added for that stage. If a replacement subject is enrolled in the study on 
Amendment 2, the subject will need to complete Stage 1 (IV) dosing and assessments prior to 
advancing to Stages 2 to 9.  
Study stages are detailed in Section 6.1.1. All replacement subjects  completingat the lowest 
incomplete stage of the study for all stages except for Stage 5. If subject does not complete Stage 
5, the replacement subject will complete Stage 1 (IV) dosing and assessments and then  start at 
Stage 4 (duplicating Stage 4) and then complete Stage 5 to have the same subject complete Stage 
4 and 5.  
For all other stages when the completion of a stage has occurred, the replacement subject 
complete Stage 1 (IV) dosing and assessments before advancing to the next incomplete stage. 

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6.0 
STUDY DRUG 
6.1 
Investigational Product 
All study subjects will be treated with MarzAA. MarzAA will be provided as a powder for 
injection, at a 4.62 mg/vial dosage strength. The drug product will be supplied in a 5-mL vial that 
is sealed with a 20 mm lyophile stopper and 20 mm aluminum over-seal. The lyophilized drug 
product must be reconstituted for SC injection or IV use. 
6.1.1 
Dosing and Administration 
This is an open-label study. Each subject may receive the study drug in nine (9) dosing stages 
(Stage 1 to 9). Detailed dosing, route of administration, and timing of each dose is provided in 
Table 6-1. 
Table 6-1 
MarzAA Dose & Mode of Administration by Dosing Stage 
Stage 
Dose a 
Route 
Number of Doses 
Frequency, Timing b 
1 
18 µg/kg 
IV 
1 
NA 
2 
30 µg/kg 
SC 
1 
24 Hours after Stage 1 
3 
45 µg/kg 
SC 
1 
48 hours after Stage 2 
4 
60 µg/kg 
SC 
1 
48 hours after Stage 3 
5 
2 × 30 µg/kg c 
2 × SC 
1 
48 hours after Stage 4, 2 sites c 
6 
2 × 45 µg/kg d 
2 × SC 
1 
48 hours after Stage 5, 2 sites d 
7 
2 × 60 µg/kg e 
2 × SC 
1 
48 hours after Stage 6, 2 sites e 
8 
2 × 60 µg/kg f  
(120 µg/kg/day)  
SC 
2  
48 hours after Stage 7, unless subjects were 
enrolled in the study prior to Amendment 2 b, 2 
doses at 3-hour intervals f 
9 
3 × 60 µg/kg g 
(180 µg/kg/day) 
SC 
3 
72 hours after Stage 8, 3 doses at 3-hour 
intervals g 
Abbreviations:  
IV=intravenous; MarzAA=marzeptacog alfa (activated); SC=subcutaneous. 
a. 
For subjects requiring more than 2 vials of supplied study drug, the number of SC injections should be commensurate with 
the number of vials needed. Injection sites should be different for each injection but should be at the same anatomic location. 
b. 
Timing provided is minimum time after dosing. Maximum time after dosing should not exceed 7 days if a subject continues 
to the next stage of the study except for subjects completing their EOS visit prior to Amendment 2. 
c. 
2 × 30 µg/kg MarzAA (total dose 60 µg/kg) injected at two different anatomic locations (which must drain into separate 
lymphatic tributary areas [eg, left and right thigh, or different sides of abdomen, or abdomen and thigh]) 
d. 
2 × 45 µg/kg MarzAA (total dose 90 µg/kg) injected at two different sites at the same anatomic location 
e. 
2 × 60 µg/kg MarzAA (total dose 120 µg/kg) injected at two different sites at the same anatomic location at the same 
timepoint 
f. 
60 µg/kg MarzAA (total dose 120 µg/kg/day) administered at two separate timepoints with 3-hour intervals between each 
dose and in the same anatomic location  
g. 
60 µg/kg MarzAA (total dose 180 µg/kg/day) administered at three separate timepoints with 3-hour intervals between each 
dose and in the same anatomic location  
NOTE: All subjects enrolled in Stage 4, who will receive a SC dose of 60 µg/kg MarzAA 
injected at a single anatomic location, must also continue to Stage 5 to receive an equal 
split SC dose of 60 µg/kg MarzAA injected at two different anatomic locations 

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(2 × 30 µg/kg) for an accurate comparison, so it is possible that more than 8 subjects 
will be dosed in Stage 4. 
If a subject moves on to another dosing stage, each subsequent injection site must be different 
from all prior injection sites. There is no efficacy-based dose escalation in this study.  
6.1.1.1 
Guidelines for Interruption of Dose Escalation 
Dose escalataion will be interrupted when: 
• A surgical procedure is needed 
• There is a medical event requiring extended (>48 hours) hospitalization 
• If there is a thrombotic event 
• If there is clinical evidence of inhibitor formation 
• If there are laboratory results suggesting an antibody may be developing 
• A spontaneous bleeding event occurs 
• A traumatic bleeding event occurs 
Subjects will use their current treatment regimen for any spontaneous or traumatic bleed that 
occurs while on study. There is a 72-hour washout period after subjects are stabilized on their 
treatment. 
A study stage may be repeated in a subject if PK assessments are interrupted by treatment of a 
bleed or if PK samples are inadequate for analysis. 
6.2 
Preparation, Handling, Storage, and Acountability 
6.2.1 
Acquisition and Accountability 
Upon receipt of the MarzAA shipment, the pharmacist, or a designee, will conduct an inventory 
and return an acknowledgement that all investigational product (IP) was received frozen and 
undamaged, thereby maintaining the Good Manufacturing Practice (GMP) status of the product 
during shipment. 
The investigator, or approved representative (eg, pharmacist) must maintain adequate records 
documenting the receipt, use, loss, or other disposition of the IP. The sponsor will supply drug 
accountability forms to be used in this study. 
The sponsor or designee will arrange for the return of unused IP. The IP destruction procedure 
for used vials is to be decided locally to comply with local regulations and procedures. 
Drug accountability will be reviewed by the monitor during routine monitoring visits. No IP can 
be destroyed or returned until the study monitor has reconciled all vials of IP. 
6.2.2 
Product Storage and Stability 
The investigator, or an approved representative (eg, pharmacist) will ensure that all IP are stored 
in a secured area with controlled access under recommended storage conditions and in 

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accordance with applicable regulatory requirements. The IP and its storage and preparation 
requirements will be provided by the Sponsor, or designee. 
Investigational product should be stored in its original container and in accordance with the drug 
label. The Sponsor will provide the Investigator with packaged IP in accordance with specific 
country label requirements.  
Site systems must be capable of measuring and documenting (eg, via a log), at a minimum, daily 
minimum and maximum temperatures for all site storage locations (as applicable, including 
frozen, refrigerated and/or room temperature products). This should be captured from the time of 
IP receipt throughout study. Even for continuous monitoring systems, a log or site procedure 
which ensures active daily evaluation for excursions should be available. The operation of the 
temperature monitoring device and storage unit (eg, refrigerator), as applicable, should be 
regularly inspected to ensure it is maintained in working order.  
Any excursions from the product storage conditions should be reported upon discovery. The site 
should actively pursue options for returning the product to appropriate storage conditions, as 
soon as possible. Deviations from the storage requirements, including any actions taken, must be 
documented and reported to the Sponsor, or designee.  
Once an excursion is identified, the IP must be quarantined and not used until the Sponsor, or 
designee, provides documentation of permission to use the IP. Specific details regarding 
information the site should report for each excursion will be provided to the site.  
Receipt of materials, door opening and closing, and other routine handling operations where the 
product(s) are briefly out of labeled temperature range are not considered excursions.  
6.2.3 
Preparation 
MarzAA will be provided as a powder for injection, at a 4.62 mg/vial dosage strength, and is 
supplied in a 5-mL vial. The lyophilized drug product will be reconstituted for IV administration 
or SC injection. 
Details regarding the dosing administration, will be provided by the Sponsor, or designee. 
MarzAA will be prepared and administered by an appropriately qualified and experienced 
member of the study staff (eg, physician, nurse, physician assistant, nurse practitioner, or 
pharmacist) as allowed by local, state, and institutional guidance.  
6.3 
Monitoring Compliance 
The study drug is administered at the study site and will be reported in the eCRF. 
6.4 
Concomitant Therapy 
Enrolled subjects will inform the study investigator about all prior and concomitant medications 
administered from the Screening Visit to Study termination (including the date and time of 
administration). 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the electronic Case 

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Report Form (eCRF) are concomitant prescription medications, over-the-counter (OTC) 
medications and supplements.] 
There are no concomitant medication restrictions or requirements. However, individuals are 
excluded if they have been on a prophylactic treatment regimen with a FVIII or FIX replacement 
factor or a bypassing agent prior to enrollment and cannot discontinue and washout this therapy 
for 72 hours prior to dosing. 
If an individual has previously been enrolled on a clinical trial evaluating a treatment for 
prophylaxis other than a modified rFVIIa (as specified in exclusion criteria #2) or 
emicizumab-kxwh, fitusiran, or one of the anti-TFPI agents (eg, concizumab, BAY1093884, or 
PF-06741086) in clinical investigation, he will be permitted to enroll onto this study, provided 30 
days since exposure to that study drug have passed. 
6.5 
Rescue Therapy 
In the event of spontaneous or traumatic bleeding in subjects with inhibitors, treatment for a 
spontaneous or traumatic bleeding episode will be permitted using the subject’s current treatment 
regimen which could be FEIBA, NovoSeven, HEMLIBRA, or a FVIII or FIX product. A 
washout period of 72 hours after the subject is stablized is required before the subject continues 
to the next stage of the study. 
6.6 
Meals and Dietary Restrictions 
Five days prior to dosing through 48 hours postdosing in each stage, subjects should be advised 
to refrain from food and drinks that may influence blood clotting. Food and drink that may 
influence blood clotting are high in “salicylates.” Examples of these include, but is not limited to, 
some herbs and spices (ginkgo, garlic, ginger, ginseng, horse chestnut, turmeric, and white 
willow) and some fruits (raisins, prunes, cherries, cranberries, blueberries, grapes, strawberries, 
tangerines, and oranges). Furthermore, advise subjects that grapefruit or grapefruit related juices 
may not be consumed from 7 days prior to the first dose of study medication until the final 
sample collections are done 48 hours after dosing in Stage 9. 

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7.0 
STUDY ASSESSMENT AND PROCEDURES 
Study endpoints are detailed in Section 3.0. A schedule of assessments and procedures is 
provided in Appendix A. 
7.1 
Study Procedures and General Assessments 
General Assessments are summarized in Table 17-1. 
Investigators will document:  
• Subject demographics (sex, age, race and ethnicity) at the screening visit 
• All ongoing conditions and relevant medical history (including all major hospitalizations and 
surgeries), as well as the subject’s current medical status at the screening visit 
• Diagnosis of moderate or severe congenital Hemophilia A or B with or without an inhibitor  
• Prior medications and any nondrug treatments 
• Concomitant medication use including treatment used for control of spontaneous or traumatic 
bleeding events (infusion therapies, anti-fibrinolytic agents, local agents) and for 
management of pain and other complications related to hemophilia 
• Vital signs, height, weight, and general physical examination will be performed at screening 
• Administration of study drug (MarzAA) for each stage (route [IV or SC], anatomical location 
of administration, inject site assessment) 
7.2 
Pharmacokinetics and Pharmacodynamics Assessments 
For Stage 1, specimens will be obtained for pharmacokinetics (MarzAA activity levels) at 
predose and then at 5, and 60 minutes ±5 minutes; 2, 6, 9 hours ±15 mins; 12 and 24 hours 
±2 hours after dosing with MarzAA. For Stages 2 to 7 specimens will be obtained for 
pharmacokinetics (MarzAA activity levels) at predose and then at 30, 60, and 90 minutes ±5 
mins; 2, 6, 9 hours ±15 mins; 24 and 48 hours ±2 hours after dosing with MarzAA. For stage 8 
and 9, specimens for PK parameters will be obtained hourly starting at 2 through 9 hours, then at 
12, 24, 48 and 72 hours 
For Stage 1 coagulation and thrombogenicity parameters will be obtained at predose and then at 
5 minutes ±5 minutes; 2 and 6 hours ±15 minutes; and 24 hours ±2 hours. For Stages 2 to 
9 coagulation and thrombogenicity parameters will be obtained at predose and then at 2 and 
6 hours ±15 minutes; and 24 and 48 hours ±2 hours. For stage 8 and 9,  coagulation and 
thrombogenicity assessments will also be obtained at 72 hours. 
For Stage 1 (IV), Stage 2 (SC) may be initiated immediately after the 24-hour specimens have 
been obtained. If Stage 2 is initiated immediately after Stage 1, then the 48-hour specimens can 
be used as the predose specimens for the next Stage 2. 
For Stages 2 to 9, each subsequent stage may be initiated immediately after the 48-hour 
specimens have been obtained. If the stage is initiated immediately after the previous stage, then 
the 48-hour specimens can be used as the predose specimens for the next stage. A maximum of 
7 days may elapse between the 48-hour blood draw and when the next stage commences (unless 

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delayed because of dose interruption as specified in the protocol). For subjects previously 
enrolled and completing the EOS visit prior to Amendment 2, if participation resumes, there are 
no additional screening parameters required and the 7-day maximum between Stage 7 and 8 does 
not apply. All predose assessment will be required. If a new subject is enrolled in the study in 
Amendment 2, the subject will need to complete IV dosing and assessments (Stage 1) prior to 
advancing to Stages 2 to 9. 
Pharmacokinetic and PD assessments are detailed in Appendix A, Table 17-2, Table 17-3 and 
include: 
• MarzAA activity levels at various timepoints throughout the study. Calculation of standard 
PK parameters and bioavailability will be performed at a central laboratory. 
• Coagulation parameters including PT, aPTT, and TGT (performed at a central laboratory) 
• Thrombogenicity markers including fibrinogen, D-dimer, F1+2, and TAT (performed at a 
central laboratory) 
Subjects will need to inform the study investigator about all spontaneous or traumatic bleeding 
episodes and concomitant medications administered, including (but not limited to) the following: 
• Bleeding episode (date/time of onset and date/time of resolution) 
• Cause of bleeding (spontaneous or traumatic) 
• Bleeding site: joint (ankle, knee, elbow, other [right or left]); muscle (iliopsoas, calf, forearm, 
other [right or left]); mucous membranes (mouth, gums, nose, genitourinary tract); 
gastrointestinal (gastric ulcer, fissure, other [requiring transfusion – yes, no]), neck/throat, 
intracranial 
• Hemostatic drugs used for treatment of bleeding episodes (time/date of administration, type, 
amount [international units or mg and/or number of infusions]) 
A spontaneous bleeding episode is defined as one that is precipitated by normal activities of 
daily living. 
7.3 
Safety Assessments 
Safety will be evaluated by assessment of AEs including SAEs as described in Section 8.4.5. 
Additional safety evaluations include the following parameters:  
• Vital signs and weight 
• Physical examinations 
• Clinical laboratory tests (chemistry and hematology)  
• Use of concomitant medications 
7.3.1 
AEs and SAEs 
Subjects will inform study investigator/nurse about any AEs that occur during the study.  

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7.3.2 
Injection site reactions 
Subjects will inform study investigator/nurse about any injection site reactions. Photographic 
documentation is desirable and should include a coin as a size marker. 
7.3.3 
Adverse Events and Serious Adverse Events 
7.3.3.1 
Definition of Adverse Events (AE) 
An AE is any untoward medical occurrence in a patient or clinical trial subject administered a 
medicinal product that may not necessarily have a causal relationship with the study drug. An 
AE can therefore be any unfavorable and unintended sign (including a clinically significant 
laboratory abnormality, for example), symptom, or disease temporarily associated with the use of 
a medicinal (investigational) product, irrespective of the relationship to the medicinal 
(investigational) product. 
Pre-existing conditions, diseases or disorders are not considered AEs unless there is a change in 
the intensity, frequency or quality. 
Note: 
Bleeding events should not be recorded as an adverse event unless considered 
serious and then the reporting process for a serious adverse event should be followed. 
7.3.3.2 
Definition of Serious Adverse Events (SAE) 
An AE or suspected 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 AE, 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, 
or require hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the participant and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
7.3.3.3 
Classification of an Adverse Event 
7.3.3.3.1 
Severity of Event 
All AEs will be assessed by the study clinician using the CTCAE v4.0 where applicable.57  
For those AEs that are not included under the CTCAE v4.0, the following guidelines will be used 
to describe severity: 
Mild: 
Events require minimal or no treatment and do not interfere with the participant’s 
daily activities.  
Moderate: Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 

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Severe: 
Events interrupt a participant’s usual activities of daily living and may require 
systemic drug therapy or other treatment. Severe events are usually potentially life-
threatening or incapacitating. Of note, the term “severe” does not necessarily equate 
to “serious”. 
7.3.3.4 
Relationship to Study Drug 
All AEs must have their relationship to study drug assessed by the clinician who examines and 
evaluates the participant based on temporal relationship and his/her clinical judgment. During the 
assessment of causality, the most plausible etiology should be considered. The degree of 
certainty about causality will be graded using the categories below: 
Related: 
The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal 
relationship between the study intervention and event. Reasonable possibility 
means that there is evidence to suggest a causal relationship between the study 
intervention and the AE. 
Not Related: There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 
7.3.3.5 
Action Taken  
None: 
no changes were made to study drug administration and dose. 
Permanently 
discontinued: 
study drug was discontinued and not restarted. 
Next dosing (stage) 
temporarily 
delayed: 
advancement to the next study drug dosing stage was delayed due to an 
AE and restarted at the next stage (if AE occurs during Stage 4 subject 
would repeat Stage 4 as noted in Section 6.1.1). 
7.3.3.6 
Expectedness 
The Principle Investigator (or Co-PI) will be responsible for determining whether an AE is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study drug in the Investigator’s Brochure. 
7.3.4 
Time Period and Frequency for Event Assessment and Follow-Up 
Subjects will be instructed regarding direct reporting of AEs at each visit and subjects queried if 
evidence of an AE recorded. 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review by a 
study monitor.  

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All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
on the appropriate CRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while on study must be documented appropriately regardless of relationship. All 
AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
7.3.5 
Adverse Event Reporting 
Members of the study team will record all reportable events with start dates occurring any time 
after informed consent is obtained until study completion, or discharge, for nonserious AEs. At 
each study visit, the investigator will inquire about the occurrence of AE since the last visit. 
Events will be followed for outcome information until resolution or stabilization. 
The Investigator will categorize the outcome of each AE according to the definitions below: 
Resolved: 
the subject recovered from the AE. 
Ongoing: 
at the time of the last assessment, the event is ongoing, with an undetermined 
outcome. 
Note: Ongoing AEs are not considered resolved as a result of death. No AE 
stop-date should be recorded with an AE that is ongoing. 
Chronic/ 
Stable: 
at the time of the last assessment, the event is ongoing and stabilized, with no 
change to the event outcome anticipated. 
Unknown 
There is an inability to access the subject or the subject’s records to determine 
the outcome (ie, subject withdraws consent or is lost to follow-up). 
All protocol-defined AEs will be reported from the time a subject is enrolled in the study until 
the end of study visit with the exception of nonserious spontaneous or traumatic bleeding events.  
Nonserious spontaneous or traumatic bleeds are not considered adverse events for the purpose of 
this protocol and should not be reported as adverse event in the eCRF; however, all nonserious 
bleeds should continue to be logged in the eCRFs, including spontaneous bleeds, traumatic 
bleeds or bleeds related to procedure/surgery. A separate log line in the eCRF will be provided to 
record nonserious bleeds. 
NOTE: Bleeds considered serious should be reported per the standard process for SAE 
reporting. 

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7.3.6 
Potential Risks 
The study drug has the potential risk of causing the following AEs based on information 
associated with other drugs in the same category (ie, bypassing agents for treatment of 
hemophilia); these are: 
• Thrombotic events (The study drug has the potential risk of causing thrombotic events based 
on information associated with other drugs for treatment of hemophilia. A list of signs and 
symptoms of thrombotic events requiring urgent reporting attention is provided in 
Appendix B. 
• Development of anti-Drug Antibodies and Inhibitors 
There is a risk with the study drug of developing an immune response resulting in antibody 
formation and potentially an inhibitory antibody response. This will also be monitored 
throughout the study. 
• Skin injection site may become reddened or painful 
• Risks associated with blood collection: 
o A blood draw may cause faintness, inflammation of the vein, pain, bruising, or bleeding 
at the site of puncture. There is also a slight chance of infection. 
o Fasting could cause dizziness, headache, stomach discomfort, or fainting 
7.3.7 
Serious Adverse Event Reporting 
Members of the study team will record all reportable events within 24 hours of knowledge of the 
SAE with start dates occurring any time after informed consent is obtained until 30 days after the 
last day of study participation. At each study visit, the investigator will inquire about the 
occurrence of SAEs since the last visit. Events will be followed for outcome information until 
resolution or stabilization. 
The Investigator will categorize the outcome of each SAE according to the definitions below: 
Resolved: 
The subject recovered from the AE. 
Ongoing: 
At the time of the last assessment, the event is ongoing, with an undetermined 
outcome. 
Note: Ongoing AEs are not considered resolved as a result of death. No AE 
stop-date should be recorded with an AE that is ongoing. 
Chronic/ 
Stable: 
At the time of the last assessment, the event is ongoing and stabilized, with no 
change to the event outcome anticipated.  
Death: 
The AE directly caused death. 
Unknown 
There is an inability to access the subject or the subject’s records to determine 
the outcome (ie, subject withdraws consent or is lost to follow-up). 

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7.3.7.1 
Definitions 
Death: 
Any event resulting in a subject’s death must be reported as an SAE. 
However, death, in and of itself, is not an AE; it is only an outcome. The 
cause of death is the AE. Therefore, the investigator should make every 
effort to obtain and document the cause of death for all subjects who die 
during the study. If, despite all efforts, the cause of death remains unknown, 
the AE should be documented as an “unspecified fatal event”. 
Life 
threatening AE: 
Any AE that places the patient or subject, in the view of the investigator, at 
immediate risk of death from the reaction as it occurred (ie, it does not 
include a reaction that, had it occurred in a more severe form, might have 
caused death). 
Hospitalization: It should be noted that hospitalization, in and of itself, does not represent an 
SAE. It is the AE leading to the subject’s hospitalization that becomes 
“serious” when it requires inpatient care. Consequently, an SAE should not 
be reported in the case of preplanned hospitalizations for pre-existing 
conditions that did not worsen during the study. 
Disability: 
A substantial disruption of a person’s ability to conduct normal life 
functions. 
7.3.8 
Adverse Events of Special Interest (AESIs) 
The study drug has the potential risk of causing the following AESIs based on information 
associated with other drugs in the same category. These are: 
• Thromboembolic events (TEs) based on information associated with other drugs for 
treatment of hemophilia. TEs include myocardial infarction (MI); venous thrombosis, and 
pulmonary embolism (PE); and stroke. Signs and symptoms of TEs requiring urgent 
reporting and attention are listed in Appendix B. 
• Immune response resulting in antibody formation and potentially an inhibitory antibody 
response. This will also be monitored for throughout the study.  
7.3.9 
Reporting of Pregnancy 
Although pregnancy itself is not considered an adverse event or a serious adverse event, the 
partner of a male participant should be followed until termination or to term to ensure absence of 
congenital anomaly or birth defect that may have resulted from maternal exposure or 
transmission of the study drug via semen following paternal exposure. 
Please advise all participants to use a highly effective method of birth control from the first dose 
of study drug through 28 days after dosing to protect the health and safety of the mother and/or 
child. Despite the warnings provided and precautions taken, pregnancy may occur during 
research participation. Investigators must be aware of the requirements related to reporting and 
follow-up in the event a research participant’s partner becomes pregnant. 

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If a participant’s partner becomes pregnant during this study, please provide a consent 
authorization form to present to the partner. If she agrees, that authorization will function as 
consent to approve the study doctor’s access to medical information to allow the regulatory 
required monitoring of the pregnancy, and the birth and the health of the child.  
Please report the pregnancy of a participant’s partner to Catalyst Biosciences, or it’s designee, 
and the IRB, and include the following information: expected date of delivery, last menstruation, 
estimated conception date and pregnancy result (if known).  
Pregnancy should be reported as “Information” (not as an “Adverse Event” or “Other Problem or 
Event”). 
• Pregnancy does NOT have to be reported to the IRB if the subject is receiving follow-up 
only, and conception occurred outside of the time-period that the study protocol requires 
contraception (ie, 28 days after the last dose of the study drug and the pregnancy occurred 
after that time) 
• Subsequent reports containing follow-up information regarding a pregnancy is not required 
unless the pregnancy results in a congenital anomaly. The congenital anomaly should be 
promptly reported.  
NOTE: 
If you suspect that exposure to a medical product prior to conception or during 
pregnancy may have resulted in an adverse outcome in the child, it must be reported 
to the FDA. 
7.4 
Unscheduled Visit Procedures and Withrawals 
If during the duration of the trial, a subject requires medical attention from the study team, the 
following should be recorded. If a subject requires medical attention, not previously planned, 
from another medical practitioner or team, this should be considered an indication of an adverse 
event unless demonstrated otherwise. At the unscheduled visit, the following assessments may 
need to be conducted based on the judgement of the clinical study team. 
• Vital signs 
• Weight 
• Physical examination 
• Concomitant medications 
• Adverse events  
• Clinical signs of thrombosis (Appendix B) 
• Hematology and chemistry (Appendix A, Table 17-1, Footnote F) 
• Coagulation assays: PT, aPTT, and TGT 
• Thrombogenicity markers: fibrinogen, D-dimer, F1+2, and TAT 
• Pharmacokinetics: MarzAA activity 
• Immunogenicity assays to FVII, FVIIa, and MarzAA 

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If a subject discontinues or withdraws early, it is essential to capture the rationale for withdrawal 
during the final visit. Criteria for study withdrawal and discontinuation are provided in 
Section 5.3. 
7.5 
End-of-Study Assessments/Follow-up 
Following the end of dosing with MarzAA and the completion of all assessments, then a 30-day 
visit will be performed for safety and follow-up.  
The end of study visit will be 30 days after completing the last stage possible in the study. 
For example, if a subject completes Stage 6 but withdraws then the subject will have their end-
of-study assessment 30 days after dosing for Stage 6.  
A participant is considered to have completed the study if he has completed all assessments in a 
stage of the study and returned for procedures listed under end of study visit, as detailed 
Appendix A. 

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8.0 
STATISTICAL CONSIDERATIONS 
8.1 
Primary Analysis Plan 
• PK analysis by route of administration, dose level/stage of the study  
• Analysis for dose proportionality 
• Appropriate statistics of all recorded, measured and calculated parameters will be reported, 
including 95% confidence intervals, n, mean, standard deviation, median, minimum and 
maximum 
• Safety results will be tabulated. The numbers of subjects who were treated, who completed 
the study, who discontinued and the primary reasons for discontinuation will be tabulated. 
8.2 
Sample Size Determination 
The sample size estimate is based on PK guidance for the development of hemophilia factors 
published by regulatory agencies. 
8.3 
Populations for Analyses 
Intent to Treat 
(ITT) population: 
any subject who receives at least one dose of study drug. The ITT 
population will be used for all safety analyses. 
PK population: 
any subject who completes an entire dosing stage including the PK 
assessments and has adequate samples for analysis.  
8.4 
Statistical Analysis  
8.4.1 
Subject Disposition 
A disposition listing of all enrolled subjects will be generated for each stage of the study to 
describe study center, subject number, first study drug dosing date, dose stage, total duration of 
study drug dosing, the reason for discontinuing study drug dosing, and reason for discontinuing 
the study. 
8.4.2 
General Approach 
Standard PK parameters such as terminal half-life, area under the plasma concentration-time 
curve from time 0 to infinity (AUC0-t) and area under the plasma concentration-time curve from 
time 0 to the time of the last measurable plasma concentration (AUC0-inf), clearance, volume of 
distribution, mean residence time and bioavailability (of the subcutaneous administration) will be 
calculated. A semi-parametric model described by Lee et al (Lee, 1990; Lee, 1997) will be used 
to calculate the terminal half-life. A noncompartmental approach based on the trapezoidal rule 
will be used to compute the area under curve (AUC) and the parameters derived from them. 
Descriptive statistics will be reported for each parameter and will include mean ± standard 
deviation and median ± interquartile range. 
All statistical tests will be performed at the 0.05 significance level using two-sided tests, where 
appropriate. 

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There will be a formal Statistical Analysis Plan (SAP) completed prior to database lock and 
unblinding of the study data.  
8.4.3 
Analysis of the Primary Pharmacokinetic Endpoint(s) 
The analysis of the primary endpoint (comparative pharmacokinetics of MarzAA by dose level) 
will be based on the examination of the AUC0-t/dose for each of the six dose groups. Under the 
hypothesis of dose proportionality, a mixed linear model will be used (accounting for patient 
effect) to test for the equality of the mean ratio across dose group. A similar model will be used 
to compare the results for the split dose with the same dose (60 µg/kg) given at a single location. 
The comparison of the dose means for the other PK parameters calculated will also be evaluated 
with a mixed linear model with dose being the primary main effect. 
In addition, all PK parameters will be summarized at each of the dosing levels using means and 
standard deviations. 
8.4.4 
Analysis of the Secondary Endpoint(s) 
Study drug exposure of IV and SC dosing will be provided for all stages.  
The following parameters will be documented: 
• Occurrence of clinical thrombotic event not attributable to another cause, and occurrence of 
antibody formation resulting in a decreased endogenous level of FVII or FVIIa 
• Change in coagulation parameters (PT, aPTT, fibrinogen, MarzAA activity levels, and TGT) 
from predose 
• Occurrence of an antibody response to MarzAA and whether it is inhibitory and cross-
reactive to wt-rFVIIa or wt-FVII 
• Clinically significant levels of thrombogenicity markers resulting from daily administration 
of MarzAA  
The frequencies of these events will be summarized as proportions and counts. 
8.4.5 
Safety Analysis  
8.4.5.1 
Adverse Events 
All AEs will be listed by preferred term and system organ class as classified by the Medical 
Dictionary for Regulatory Activities (MedDRA) and type, frequency, course, outcome, severity, 
and causality to study drug will be documented. Verbatim terms on CRFs will be mapped to 
preferred terms and related system organ class using MedDRA.  
Incidence rates of AEs and the proportion of subjects prematurely withdrawn from the study due 
to AEs will be provided for all stages. Incidence rates will also be displayed based on severity 
and relationship to study drug as determined by the clinician who examines and evaluates the 
study subject (Section 7.3.3.4). AEs with a relationship of “possibly” or “probably” related will 
be considered as “related” to the study drug. Events assessed as “unrelated”, “unlikely” related, 
or will be considered as “not related” to the study drug. The incidence of SAEs will be provided 

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for each phase. All incidence rates will be categorized and displayed by system organ class and 
preferred term. 
8.4.5.2 
Vital Signs  
Safety analyses will include descriptive statistical summaries of shifts in vital signs (blood 
pressure, heart rate, temperature, respiratory rate) and in laboratory values for each phase. 
8.4.6 
Baseline Descriptive Statistics  
Demographic and baseline measurement variables will be summarized using descriptive 
statistics.  
8.4.7 
Planned Interim Analyses 
Not applicable to this study. 
8.4.8 
Sub-Group Analyses 
Not applicable to this study. 
8.4.9 
Tabulation of Individual Participant Data 
Individual participant data will be listed by measure and time point. 
8.5 
Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the study design or procedures 
that is under the PI’s responsibility and oversight (as defined by regulations) without prior 
written IRB/IEC approval or favorable opinion of an appropriate amendment and that does not 
have a major impact on the patient’s rights, safety, or well-being, or on the integrity and 
authenticity of the study data. Deviations may include, but are not limited to, departure from 
inclusion/exclusion criteria, dosing, duration of study drug dosing, failure to perform the 
required assessments at specified time points, scheduling of visits not in accordance with 
specifications, or patient safety. Deviating from the protocol is permitted only if necessary for 
the safety or clinical management of study subjects and must immediately be reported to Catalyst 
Biosciences, Inc. or its designee. 
Protocol deviations must be reported to the Sponsor either verbally or electronically within 
5 working days from the day of discovery. 

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9.0 
DIRECT ACCESS TO SOURCE DOCUMENTS: AUDIT AND INSPECTION 
Authorized representatives of the sponsor, a regulatory authority, an independent ethics 
committee (IEC) or an institutional review board (IRB) may visit the investigator site to perform 
audits or inspections, including source data verification. The investigator will allow the sponsor 
auditor, regulatory authority or ethics committee (EC) representative to inspect the drug storage 
area, study drug stocks, drug accountability records, subject charts and study source documents, 
and other records relative to study conduct.  
The purpose of an audit or inspection is to systematically and independently examine all study-
related activities and documents to determine whether these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of 
the International Conference on Harmonization, and any applicable regulatory requirements.  
The investigator should contact the sponsor immediately if contacted by a regulatory agency 
about an inspection. 

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10.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 
conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Conference on Harmonisation Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s). 
Independent audits may be conducted by the Sponsor, or designee, or regulatory authority 
inspectors to inspection the Study Center facilities (eg, pharmacy, drug storage areas, 
laboratories) and review of study related records to evaluate the trial conduct and compliance 
with the protocol, ICH GCP, and applicable regulatory requirements. 
The Principal Investigator will sign and date the indicated places on the CRF. These signatures 
will indicate that the principal Investigator inspected or reviewed the data on the CRF, the data 
queries, and the Study Center notifications, and agrees with the content. 
10.2 
Quality Control 
Following site prequalification and/or initiation of the study site, periodic monitoring visits and 
site closeout visits will be made by Catalyst Biosciences, Inc. or its designee. As noted in 
Section 9.0, the Investigator must provide direct access to, and allocate sufficient space and time 
for, the monitor to inspect subject source records, eCRFs, queries, collection of local laboratory 
normal ranges (if applicable), investigational product accountability records, and regulatory 
documents in accordance with GCP and the ICH E6 guideline. 
The purpose of trial monitoring is to verify the following: 
• The rights and well-being of human subjects are protected 
• The reported data are accurate, complete, and verifiable from source documents 
• All data are collected, tracked, and submitted by the site to the sponsor or designee, including 
unscheduled and missed assessments 
10.3 
Quality Assurance 
The following steps will be taken to assure that the study is conducted by the study site in 
compliance with the study protocol, GCP, and other applicable regulatory requirements. 
• Investigator meeting and/or Investigator site initiation 
• Routine study site monitoring 
• Documented study and system training 
• CRF and query review against source documents 
• As needed, local laboratory normal ranges will be collected from each local laboratory at the 
onset of the study and throughout the study whenever there are changes to the normal ranges 

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11.0 
ETHICS 
11.1 
Compliance with Ethical and Regulatory Guidelines  
The investigator will ensure that this study is conducted in accordance with the protocol and in 
accordance to the ICH GCP E6 guidelines, or with the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection for the rights, safety 
and well-being of the study subjects. For studies conducted under a US investigational new drug 
application (IND), the investigator will ensure adherence to the basic principles of GCP as 
outlined in 21 CFR 312, Subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
Part 50, 1998, and 21 CFR, Part 56, 1998.  
11.2 
Institutional Review Board/Independent Ethics Committee 
Before initiation of the study, the investigator must submit for approval the protocol, ICF, 
Investigator’s Brochure, and any advertisements to an IRB/IEC for written approval. The 
Investigator must ensure IRB/IEC compliance with the applicable regulations. A copy of written 
IRB/IEC approval of the protocol, ICF, and all advertisements must be provided to Sponsor or 
designee prior to initiation of the study and shipment of study drug. The Investigator is 
responsible for obtaining continued review of the clinical research at intervals not exceeding one 
year or at more frequent intervals if specified by the IRB/IEC. The Investigator must supply 
Sponsor or designee with written documentation of continued review of the clinical research. 
The Investigator is responsible for reporting the following to the IRB/IEC: 
• All SAEs (including deaths) regardless of cause and whether anticipated or unanticipated 
(reported immediately) 
• Significant findings that become known in the course of the study that might affect the 
willingness of subjects to continue to participate  
• Protocol, or consent amendments prior to the implementation of the change 
• Study progress reports at least once a year, if applicable 
• Notification of study completion or termination 
The sponsor may amend the protocol as needed to ensure that the clinical investigation is being 
conducted as intended. Sponsor will initiate protocol amendments in writing if any change 
significantly affects the safety of subjects, the scope of the investigation, or the scientific quality 
of the study. Protocol changes must be submitted to the IRB/IEC as a protocol amendment. If 
necessary, the ICF will be revised to reflect the changes in the amendment and will be submitted 
to the IRB/IEC for review and approval. A copy of the amendment must be signed by the 
Investigator and returned to Sponsor or designee. Written documentation of IRB/IEC approval is 
required before the amendment is implemented. Investigators may not perform study-specific 
assessments that are not included in the protocol unless agreed to by Sponsor.  

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11.3 
Informed Consent  
The written informed consent documents will be prepared in the language(s) of the potential 
subject population, based on an English version provided by the Sponsor and should be easy to 
understand.  
Each subject must provide his or her consent in compliance with all applicable laws for the 
region.  
Before a subject’s participation in the trial, the investigator is responsible for obtaining written 
information consent from the subject after adequate explanation of the aims, methods, 
anticipated benefits, and potential hazards of the study and before any protocol specific screening 
procedures or any study drugs are administered. Sufficient time must be given to consider 
whether to participate in the study. 
The ICF should be signed and personally dated by the subject and by the study person who 
conducted the informed consent discussion. The original signed ICF should be retained in the 
Study Master File and in any other locations required by institutional policy, and a copy of the 
signed consent form should be provided to the subject. 
11.4 
Subject Confidentiality 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor, or designee. The study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study, or 
the data will be released to any unauthorized third party without prior written approval of the 
sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the 
IRB/IEC, or regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the participants in this study. The clinical study site will 
permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB/IEC, Institutional policies, 
or sponsor requirements. 

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12.0 
DATA HANDLING AND RECORD KEEPING 
12.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into Medidata Rave EDC, a 21 CFR Part 11-compliant 
data capture system. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents.] 
12.2 
Study Records Retention 
Study documents should be retained as required by local regulations. No records will be 
destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
sponsor to inform the investigator when these documents no longer need to be retained 

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13.0 
FINANCING AND INSURANCE 
Financing and insurance are addressed in a separate document. 

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14.0 
STUDY DISCONTINUATION AND CLOSURE  
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study subjects, 
investigator, and regulatory authorities. If the study is prematurely terminated or suspended, the 
PI will promptly inform study participants, the IRB/IEC, and sponsor and will provide the 
reason(s) for the termination or suspension. Study subjects will be contacted, as applicable, and 
be informed of changes to study visit schedule. 
When a study is prematurely terminated, refer to Section 5.3 for handling of enrolled study 
participants. 

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15.0 
PUBLICATION AND DATA SHARING POLICY 
The final clinical study report is also intended to form the basis for a manuscript intended for 
publication in a peer-reviewed scientific journal. The authorship, timetable and any arrangements 
for review by the participating investigators will be coordinated by Catalyst Biosciences. 
No partial subset of data from individual investigational sites can be presented or published until 
after the primary manuscript for the entire study has been accepted for publication in a peer 
reviewed scientific journal. 

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16.0 
REFERENCES 
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in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost, 2(6), 899-909. 
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Abshire, T., & Kenet, G. (2008). Safety update on the use of recombinant factor VIIa and the treatment of 
congenital and acquired deficiency of factor VIII or IX with inhibitors. Haemophilia, 14(5), 898-902. 
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Aledort, L. M. (2008). Factor VIII inhibitor bypassing activity (FEIBA) - addressing safety issues. 
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Antunes, S. V., Tangada, S., Stasyshyn, O., Mamonov, V., Phillips, J., Guzman-Becerra, N., . . . Wong, 
W. Y. (2014). Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the 
treatment of haemophilia A and B with inhibitors. Haemophilia, 20(1), 65-72. doi:10.1111/hae.12246 
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Suppl 5, 54-60. doi:10.1111/j.1365-2516.2010.02294.x 
FEIBA US Package Insert. (2018). FEIBA Prescribing Insert. Retrieved from 
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Franchini, M. (2013). The modern treatment of haemophilia: a narrative review. Blood Transfus, 11(2), 
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2125.2010.03899.x 
Gomperts, E. D. (2006). The need for previously untreated patient population studies in understanding the 
development of factor VIII inhibitors. Haemophilia, 12(6), 573-578. doi:10.1111/j.1365-
2516.2006.01341.x 
Hacker, M. R., Geraghty, S., & Manco-Johnson, M. (2001). Barriers to compliance with prophylaxis 
therapy in haemophilia. Haemophilia, 7(4), 392-396.  
Hartmann, J., & Croteau, S. E. (2016). 2017 Clinical trials update: Innovations in hemophilia therapy. Am 
J Hematol, 91(12), 1252-1260. doi:10.1002/ajh.24543 
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from https://www.gene.com/download/pdf/hemlibra_prescribing.pdf 
Kempton, C. L., & Meeks, S. L. (2014). Toward optimal therapy for inhibitors in hemophilia. Blood, 
124(23), 3365-3372. doi:10.1182/blood-2014-05-577643 
Kempton, C. L., & White, G. C., 2nd. (2009). How we treat a hemophilia A patient with a factor VIII 
inhibitor. Blood, 113(1), 11-17. doi:10.1182/blood-2008-06-160432 
Lee, M. L., Poon, W. Y., & Kingdon, H. S. (1990). A two-phase linear regression model for biologic half-
life data. J Lab Clin Med, 115(6), 745-748.  

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Lee, M. L., Ross, R. A., & Onderdonk, A. B. (1997). Statistical models for vaginal microflora: identifying 
women at risk for group B streptococcus colonization as a test of concept. Infect Dis Obstet Gynecol, 
5(5), 336-340. doi:10.1155/S1064744997000586 
Lusher, J. M. (1998). Early treatment with recombinant factor VIIa results in greater efficacy with less 
product. Eur J Haematol Suppl, 63, 7-10.  
Luu, H., & Ewenstein, B. (2004). FEIBA safety profile in multiple modes of clinical and home-therapy 
application. Haemophilia, 10 Suppl 2, 10-16. doi:10.1111/j.1365-2516.2004.00935.x 
Ma, A. D., & Carrizosa, D. (2006). Acquired factor VIII inhibitors: pathophysiology and treatment. 
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B. L. (2007). Prophylaxis versus episodic treatment to prevent joint disease in boys with severe 
hemophilia. N Engl J Med, 357(6), 535-544. doi:10.1056/NEJMoa067659 
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Martensson, A., Letelier, A., Hallden, C., & Ljung, R. (2016). Mutation analysis of Swedish haemophilia 
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Rodriguez-Merchan, E. C., Jimenez-Yuste, V., Gomez-Cardero, P., Alvarez-Roman, M., Martin-Salces, 
M., & Rodriguez de la Rua, A. (2010). Surgery in haemophilia patients with inhibitors, with special 
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7836.2006.01772.x 
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Drug Administration. Which Do Patients Prefer? A Systematic Review. Patient. doi:10.1007/s40271-014-
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Tiede, A., Friedrich, U., Stenmo, C., Allen, G., Giangrande, P., Goudemand, J., . . . Berntorp, E. (2011). 
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X. S. (2001). Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII 
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Young, G., Auerswald, G., Jimenez-Yuste, V., Konkle, B. A., Lambert, T., Morfini, M., . . . Blanchette, 
V. (2011). When should prophylaxis therapy in inhibitor patients be considered? Haemophilia, 17(5), 
e849-857. doi:10.1111/j.1365-2516.2011.02494.x 
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doi:10.1111/hae.12684 
 

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17.0 
APPENDICES 
Appendix A 
Schedule of Assessments (SOA) ...............................................................55 
Appendix B 
Clinical Signs of Thrombosis.....................................................................59 
 

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APPENDIX A 
SCHEDULE OF ASSESSMENTS (SOA) 
Table 17-1 
Overview of Protocol Visits and Procedures 
Study Period 
Screening a 
Enrollment 
(prior to 1st 
dose) 
Stages 1 to 9 b 
Stages 2 to 9 
Stages 8 to 9 
Unscheduled c 
EOS d 
Study Day/Hour 
Day 
−28 to −1 
Predose 
(−15 min) 
Day 1 
Day 2 
Day 3 
Day 4 
Hours 
0 
24 
48 
72 
Informed consent 
X 
 
 
 
 
 
 
 
 
Demographic parameters 
X 
X 
 
 
 
 
 
 
 
Inclusion & exclusion review 
X 
X 
 
 
 
 
 
 
 
Medical & hemophilia History 
X 
X 
 
 
 
 
 
 
 
Enrollment confirmation 
 
X a 
 
 
 
 
 
 
 
Prior medications & nondrug treatment 
X 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
 
X 
X 
X 
X 
X 
X 
Height (screening only) & weight 
X 
X 
 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
 
 
 
Clinical signs of thrombosis e 
X 
X 
 
X 
X 
X 
X 
X 
X 
Hematology & chemistry f 
X 
 
X 
 
X 
X 
X 
X 
X 
Coagulation assays g 
X 
 
X 
X 
X 
X 
X 
X 
X 
Thrombogenicity markers g 
X 
 
X 
X 
X 
X 
X 
X 
X 
PK sampling g 
 
 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity assays g 
X 
 
X 
 
 
X 
X 
X 
X 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MarzAA administration h 
 
 
 
X 
 
 
 
 
 
Study drug accountability 
 
 
 
X 
 
 
 
 
 
Abbreviations: 
AE=adverse events; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ConMeds=concomictant medications; ECG=electrocardiogram; 
MarzAA=marzeptacog alfa (activated); PK=pharmacokinetic; PD= pharmacodynamic. 
Footnotes Provided on Next Page 

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Table 17-1 
Footnotes 
a. All Screening procedures must be completed and reviewed prior to enrollment. Sample 
collection and shipment to the Central Laboratory should take place at least 2 weeks prior 
to scheduled enrollment. For subjects previously enrolled and completing the EOS visit  
prior to Amendment 2, if participation resumes, there are no additional screening 
parameters required. 
b. For PK/PD assessments for Stages 1 to 7, refer to Table 17-2 and Stages 8 and 9, refer to 
Table 17-3. Pharmacokinetic assessments should be performed before all other 
assessments for each time point. If a new subject is enrolled in the study in Amendment 
2, the subject will need to complete IV dosing and assessments (Stage 1) prior to 
advancing to Stages 2 to 9. 
c. At an Unscheduled Visit, perform only the assessments that are appropriate for the reason 
of the visit. 
d. End of Study visit will occur 30 days after the last stage has been completed by the 
subject ±5 days. For subjects previously enrolled and completing the EOS visit prior to 
Amendment 2, if participation resumes, EOS assessments should be repeated. 
e. Clinical signs of thrombosis per protocol. 
f. Local Laboratory: Hematology – CBC and platelet count. Chemistry – Sodium, 
potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, 
creatinine. For each stage, blood will be collected at Predose (−5 minutes), 24 and 48 
hours postdose. For Stages 8 to 9, blood will also be collected at 72 hours postdose. 
g. Central laboratory: Coagulation assays – PT, aPTT and TGT. Thrombogenicity 
markers – Fibrinogen, D-dimer, F1+2, and TAT. Pharmacokinetics – MarzAA activity. 
Immunogenicity assays – to FVII, FVIIa, and MarzAA. For PK/PD assessments for 
Stages 1 to 7, refer to Table 17-2 and Stages 8 to 9, refer to Table 17-3.  
h. At Hour 0 of each Stage, an IV or SC dose of MarzAA will be given.  

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Table 17-2 
PK/PD Schedule of Assessments for Each Study Stage (Stage 1 to 7) 
Study Day/Hour 
Predose 
(−15 min)
IV/SC Admin 
Stage 1 
Stages 2 to 7 
Day 1 
Day 2 
Day 3 
Minutes 
Hours 
Minutes 
Hours 
5 
60 
2 
6 
9 
12 
24 
30 
60 
90 
2 
6 
9 
24 
48 
±5 minutes 
±15 minutes 
±2 hours 
±5 minutes 
±15 minutes 
±2 hours 
Vital Signs a 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Signs of Thrombosis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology & Chemistry 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Coagulation 
X 
 
X 
 
X 
X 
 
 
X 
 
 
 
X 
X 
 
X 
X 
Thrombogenicity 
X 
 
X 
 
X 
X 
 
 
X 
 
 
 
X 
X 
 
X 
X 
Pharmacokinetics 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity b 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MarzAA administration c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 
AE=adverse events; ConMeds=concomitant medications; IV=intravenous; MarzAA=marzeptacog alfa (activated); min=minutes; PD=pharmacodynamics; 
PK=pharmacokinetics; SC=subcutaneous. 
NOTE: 
After Stage 1, each subsequent stage may be initiated immediately after the 48-hour specimens have been obtained. If a stage is initiated immediately after, 
then the 48-hour specimens can be used as the predose specimens for the next stage. A maximum of 7 days may elapse between the 48-hour blood draw and 
when the next stage commences (unless delayed because of dose interruption as specified in the protocol). 
a. 
Pharmacokinetic assessments should be performed before all other assessments for each time point. Vital signs performed include measure supine blood pressure, pulse, 
temperature and respiratory rate 
b. 
For subjects who complete all stages, starting at an initial dose of 18 µg/kg, immunogenicity will be done at predose for Stage 3 and Stage 6 only, and end of study. For 
replacement subjects starting at a higher dose level, specimens will be drawn at screening and at the end of the study 
c. 
After the IV dose of 18 µg/kg, the initial SC dose at 30 µg/kg, followed by an increase to 45, 60, 90, and 120 µg/kg if the subject continues enrollment in the study. If a 
subject does not proceed through all stages, then a replacement subject will be added at the missing stage to achieve 8 subjects. If a replacement subject is enrolled in the 
study in Amendment 2, subject will need to complete Stage 1 (IV) dosing and assessments prior to advancing to Stages 2 to 9. If asubject discontinues Stage 5the 
replacement subject will complete Stage 1 (IV) dosing and assessments and then repeat Stage 4 and then continue with the remaining doses such that the same subject 
completes Stages 4 and 5. For all other stages when the completion of a dose level has occurred, the replacement subject will complete Stage 1 (IV) dosing and 
assessments and then will start at the next incomplete dose level. There are two doses at 60 µg/kg: Stage 4 injected at a single anatomic location and Stage 5 an equal 
split SC dose injected at two different anatomic locations, which drain into separate lymphatic tributary areas (eg, left and right thigh, or different sites of abdomen, or 
abdomen and thigh). 
 
 

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Table 17-3 
PK/PD Schedule of Assessments for Each Study Stage (Stage 8 and 9) 
Study Day/Hour 
Predose 
(−15 min) 
SC Admin 
Stages 8 to 9 
Day 1 
Day 2 
Day 3 
Day 4 
Hour 
2 
3 
4 
5 
6 
7 
8 
9 
12 
24 
48 
72 
±15 minutes 
±2 hours 
Vital Signs a 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Physical Exam 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Clinical Signs of Thrombosis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology & Chemistry 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Coagulation 
X 
 
 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
Thrombogenicity 
X 
 
 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
Pharmacokinetics 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity b 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MarzAA administration a, c 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 
AE=adverse events; ConMeds=concomitant medications; IV=intravenous; MarzAA=marzeptacog alfa (activated); min=minutes; PD=pharmacodynamics; 
PK=pharmacokinetics; SC=subcutaneous. 
NOTE: 
After Stage 1, each subsequent stage may be initiated immediately after the 48-hour specimens have been obtained. If a stage is initiated immediately after, 
then the 48-hour specimens can be used as the predose specimens for the next stage. A maximum of 7 days may elapse between the 48-hour blood draw and 
when the next stage commences (unless delayed because of dose interruption as specified in the protocol or had previously completed dosing prior to 
Amendment 2). 
a. 
Pharmacokinetic assessments should be performed before all other assessments for each time point.Vital signs performed include measure supine blood pressure, pulse, 
temperature and respiratory rate 
b. 
For subjects who complete all stages, starting at an initial dose of 18 µg/kg, immunogenicity will be done at predose for Stage 3 and Stage 6 only, and end of study. For 
replacement subjects starting at a higher dose level, specimens will be drawn at screening and at the end of the study 
c. 
Stage 8 will give 2 separate doses of 60 µg/kg dosed at 3-hour intervals, and Stage 9 will give 3 separate doses of 60 µg/kg, dosed at 3-hour intervals  If a subject does 
not proceed to Stage 9, then a replacement subject will be added at the missing stage to achieve 8 subjects in each stage. The replacement subject will need to complete 
Stage 1 (IV) dosing and assessments prior to advancing to Stage 8 to 9 
 

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APPENDIX B 
CLINICAL SIGNS OF THROMBOSIS 
Common signs and symptoms of thrombosis are provided in Table 17-4. The clinical spectrum 
of venous thromboembolism (VTE) ranges from deep vein thrombosis (DVT) to pulmonary 
embolism (PE). The symptoms of VTE depend on the location of the affected vessel and whether 
the vessel is totally or partially occluded by the clot and described in Table 17-5. 
Table 17-4 
Common Signs and Symptoms of Thrombosis 
Symptoms and Signs of Venous 
Thromboembolism –DVT and PE: 
Common Heart Attack 
Warning Signs 
Stroke Signs 
• 
Leg pain or tenderness of thigh or 
calf 
• 
Leg swelling (edema) 
• 
Skin that feels warm to the touch 
• 
Reddish discoloration or red streaks 
• 
Unexplained shortness of breath 
• 
Rapid breathing 
• 
Chest pain anywhere under the rib 
cage (may be worse with deep 
breathing) 
• 
Fast heart rate 
• 
Light headedness or passing out 
• 
Pain or discomfort in 
the chest 
• 
Lightheadedness, 
nausea, or vomiting 
• 
Jaw, neck, or back pain 
• 
Discomfort or pain in 
arm or shoulder 
• 
Shortness of breath 
• 
Face drooping 
• 
Arm weakness 
• 
Speech difficulty 
• 
Sudden confusion, trouble 
speaking or understanding 
speech 
• 
Sudden numbness or weakness 
of face, arm or leg. especially 
on one side of the body 
• 
Sudden trouble seeing in one or 
both eyes 
• 
Sudden trouble walking, 
dizziness, loss of balance or 
coordination 
• 
Sudden severe headache with 
no known cause 
Abbreviations: 
DVT=deep vein thrombosis; PE=pulmonary embolism. 
Source: 
American Heart Association (http://www.ihtc.org/payors/conditions-we-treat/clotting-disorders/signs-and-
symptoms-of-thrombosis); Accessed on 9 Mar 2017).  
 
Table 17-5 
Clinical Spectrum of Venous Thromboembolism (VTE) 
Type 
Signs and Symptoms 
Physical Examination 
Deep vein thrombosis (DVT) 
• 
Blood clots may form in the deep blood 
vessels, most commonly in the legs and 
groin, and can block normal blood flow 
returning from the legs to the heart 
• 
Venous clots that form in regions of slow to 
moderate flow are composed of a mixture of 
red cells, platelets, and fibrin and are known 
as mixed platelet fibrin thrombi 
• 
Partially occlusive venous thrombosis of the 
deep veins in the legs or abdomen may 
present with subtle symptoms and sometimes 
• 
Pain 
• 
Swelling of the affected 
extremity/area with 
erythema and warmth 
over the vicinity of the 
clot 
• 
Discoloration including a 
bluish or suffused color 
• 
Positive Homan’s sign: 
pain with dorsiflexion 
of the foot 
• 
Swelling 
• 
Pain on palpation 
• 
Presence of a palpable 
cord 
• 
Evidence of collateral 
circulation usually 
manifested by increased 

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Type 
Signs and Symptoms 
Physical Examination 
may not present until significant collateral 
circulation has developed 
prominence of 
superficial veins 
• 
Some people with a 
DVT may be 
asymptomatic 
Pulmonary Embolism (PE) 
• 
PE results from a piece or all of a blood clot 
that breaks off and is carried by the blood 
stream to the lung where it obstructs the 
blood vessel. 
• 
The size of the clot and the site of the 
obstruction of blood flow in the vessel 
determine the extent and severity of the 
pulmonary embolus. 
• 
Proximal vein thrombosis is more likely to 
lead to fatal PE as compared to calf vein 
thrombosis. 
• 
The incidence of fatal PE can be markedly 
reduced if DVT is treated with anticoagulant 
therapy. 
• 
Pulmonary emboli may 
present subtly with the 
following complaints 
listed in order of 
frequency: 
• 
Dyspnea 
• 
Rapid breathing, fast 
heartbeat and chest pain 
especially with inhalation 
• 
Pleural pain: Some 
patients notice only a 
dull ache in their chest 
• 
Apprehension, anxiety 
• 
Cough 
• 
Hemoptysis 
• 
Sweats 
• 
Syncope 
• 
Fatigue 
• 
Tachypnea 
• 
Tachycardia 
• 
Rales 
• 
Fever 
• 
Sweating 
• 
Thrombophlebitis 
• 
Accentuation of the 
pulmonary closure 
sound 
• 
Gallop heart sound 
• 
Cyanosis 
• 
Some people with a PE 
may be asymptomatic 
Superficial Thrombophlebitis 
• 
Superficial thrombophlebitis is due to blood 
clots that form in veins that are closer to the 
surface of the skin and are associated with 
inflammation 
• 
Superficial thrombophlebitis is often 
observed in individuals who are 
heterozygous or homozygous for the Factor 
V Leiden mutation 
• 
These clots often partially block blood flow in affected 
veins and may cause pain and irritation 
• 
Redness and inflammation along the vein may occur; if 
hard and erythematous, the affected vein is often visible 
and most commonly occurs in the legs or arms 
• 
Other associated symptoms include warmth and 
tenderness, surrounding purities and swelling 
• 
Pain along the vein: patients may report a throbbing or 
burning sensation beneath the skin’s surface; these 
symptoms may interfere with sleep as they progress 
• 
Fever: Patients with venous inflammation may develop 
an elevated temperature associated with an episode of 
thrombophlebitis 
Abbreviations: 
DVT=deep vein thrombosis; IHTC=Indiana Hemophilia and Thrombosis Center, Inc.; PE=pulmonary 
thrombosis; VTE=venous thromboembolism. 
Source: 
Adapted from IHTC. Signs and Symptoms of Thrombosis (http://www.ihtc.org/payors/conditions-we-
treat/clotting-disorders/signs-and-symptoms-of-thrombosis); Accessed on 9 Mar 2017). 

Catalyst Biosciences, INC 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
PROTOCOL MAA-102 
Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of 
ascending doses of subcutaneous marzeptacog alfa (activated) in adult subjects 
with hemophilia 
 
Protocol Code: 
MAA-102 
SAP Version: 
Final 
SAP Date: 
16-JUN-2020 
Author:  
Tina Dube, Senior Statistician, PSI 
 

DOCUMENT HISTORY 
VERSION HISTORY 
Version # 
Version Date 
NA 
Initial release 
 
 
REVISION HISTORY 
Version # 
Chapter 
Revision Summary 
Reason(s) for Revision 
 
N/A 
Initial release 
N/A 
 
 
 
 
 
 
 
 

Statistical Analysis Plan: MAA-102 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
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Page 3 of 20 
APPROVAL SIGNATURES 
STUDY TITLE: Phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, 
and safety of ascending doses of subcutaneous marzeptacog alfa (activated) in adult 
subjects with hemophilia 
PROTOCOL NUMBER: MAA-102 
SAP Final, 16-JUN-2020 
 
AUTHORED BY: 
Tina Dube, Senior Statistician, PSI 
Electronically signed & dated 
APPROVED BY: 
Alexey Maximovich, Group Leader Biostatistics, PSI 
Electronically signed & dated 
APPROVED BY: 
Alexander Afanasyev, Lead Project Manager, PSI 
Electronically signed & dated 
APPROVED BY: 
Enid Jacobus, Medical Writer, PSI 
Electronically signed & dated 
APPROVED BY: 
Linda Neuman, Vice President, Clinical Development, Catalyst 
Biosciences, INC 
Electronically signed & dated 
 
 

Statistical Analysis Plan: MAA-102 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
CONFIDENTAL 
Page 4 of 20 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS .................................................................................................................. 5 
2. 
INTRODUCTION ................................................................................................................................... 6 
3. 
STUDY OBJECTIVES ........................................................................................................................... 6 
3.1 
PRIMARY OBJECTIVES .................................................................................................................................... 6 
3.2 
SECONDARY OBJECTIVES ............................................................................................................................... 6 
4. 
STUDY DESCRIPTION ......................................................................................................................... 6 
4.1 
STUDY DESIGN ................................................................................................................................................ 6 
4.2 
STUDY TREATMENT ....................................................................................................................................... 76 
4.3 
DATA AND SAFETY MONITORING BOARD ....................................................................................................... 7 
5. 
RANDOMIZATION AND BLINDING .................................................................................................... 7 
6. 
SAMPLE SIZE AND POWER CALCULATION ................................................................................... 7 
7. 
ANALYSIS ENDPOINTS ..................................................................................................................... 87 
7.1 
PRIMARY ENDPOINT ...................................................................................................................................... 87 
7.2 
SECONDARY ENDPOINTS ............................................................................................................................... 87 
7.3 
SAFETY ENDPOINTS ........................................................................................................................................ 8 
8. 
ANALYSIS POPULATIONS ................................................................................................................. 8 
9. 
ANALYTICAL PLAN AND STATISTICAL METHODS ....................................................................... 8 
9.1 
GENERAL CONVENTIONS AND STATISTICAL CONSIDERATIONS ..................................................................... 8 
9.2 
DEFINITION OF BASELINE, STUDY VISITS, AND VISIT WINDOWS ................................................................. 98 
9.3 
HANDLING OF MISSING DATA .......................................................................................................................... 9 
9.4 
PATIENT DISPOSITION ..................................................................................................................................... 9 
9.5 
PROTOCOL DEVIATIONS .................................................................................................................................. 9 
9.6 
PATIENT CHARACTERISTICS ....................................................................................................................... 109 
9.6.1 
Screening and Demographic Characteristics ................................................................................ 109 
9.6.2 
Medical History and Current Medical Conditions .......................................................................... 109 
9.6.3 
Prior and Concomitant Medications .................................................................................................. 10 
9.7 
PK ENDPOINTS AND ANALYSIS .................................................................................................................1110 
9.7.1 
Analysis of Primary Pharmacokinetic Endpoint .............................................................................. 11 
9.7.2 
Analyses of Secondary Pharmacokinetic Endpoints ..................................................................1211 
9.8 
ANALYSES OF SECONDARY ENDPOINTS ...................................................................................................1211 
9.9 
SAFETY ENDPOINTS AND ANALYSIS ............................................................................................................. 12 
9.9.1 
Exposure to Study Treatment ........................................................................................................1312 
9.9.2 
Adverse Events ................................................................................................................................1312 
9.9.3 
Laboratory Data ...............................................................................................................................1413 
9.9.4 
Vital Signs and Other Safety Parameters ........................................................................................ 14 
10. 
DEVIATIONS FROM ANALYSIS AS DESCRIBED IN THE PROTOCOL .................................... 1514 
11. 
PROGRAMMING SPECIFICATIONS .............................................................................................. 1514 
12. 
LIST OF TABLES, LISTINGS AND FIGURES ............................................................................... 1615 
13. 
REFERENCES .................................................................................................................................. 1615 
14. 
APPENDIX I. SCHEDULE OF ASSESMENT ................................................................................. 1716 
 

Statistical Analysis Plan: MAA-102 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
CONFIDENTAL 
Page 5 of 20 
1. 
LIST OF ABBREVIATIONS 
Abbreviation Description 
Μg 
Microgram 
Ƒ 
Bioavailability 
AE 
Adverse event 
aPTT 
Activated prothrombin complex concentrates 
ATC 
Anatomical therapeutic chemical (class) 
AUC0-inf 
Area under the plasma concentration-time curve from time 0 to infinity 
AUC0-t 
Area under the plasma concentration-time curve from time 0 to the time of 
the last measurable plasma concentration 
CL 
Clearance 
CV% 
Percent coefficient of variation 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EOS 
End of study 
F1+2 
Prothrombin fragment 1+2 
FVII 
Factor VII 
FVIIa  
Factor VII activated  
IRF 
Immune response/antibody formation 
IV 
Intravenous 
Kg 
Kilogram 
MarzAA 
Marzeptacog alfa (activated)  
MRT 
Mean residence time 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
PK 
Pharmacokinetic 
PT 
Preferred term 
rFVIIa 
Recombinant activated Factor VII 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SD 
Standard deviation 
SOC 
System organ class 
t1/2 
Terminal half-life 
TAT 
Thrombin-antithrombin complexes 
TE 
Thromboembolic event 
TEAE 
Treatment-emergent adverse event 
TGT 
Thrombin generation time 
Vd 
Volume of distribution 
WHO-DDE 
World Health Organization Drug Dictionary Enhanced 
Wt 
Wild-type 

Statistical Analysis Plan: MAA-102 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
CONFIDENTAL 
Page 6 of 20 
2. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) covers the statistical analysis and reporting for the protocol 
MAA-102 final version 1.0 (Amendment 1.0) dated 11 March 2019, and electronic case report 
form (eCRF) production version of 05 August 2019. 
3. 
STUDY OBJECTIVES 
3.1 
PRIMARY OBJECTIVES 
To evaluate the pharmacokinetics of ascending subcutaneous (SC) doses of marzeptacog alfa 
(activated) (MarzAA). 
3.2 
SECONDARY OBJECTIVES 
 
To determine the pharmacokinetics of single dose intravenous (IV) and SC MarzAA. 
 
To determine if the pharmacokinetics of increasing SC doses behave in a dose 
proportional manner. 
 
To determine whether a split injection provides the same pharmacokinetics as a single 
injection. 
 
To determine the pharmacodynamics of IV and SC MarzAA. 
 
To evaluate for evidence of the development of antibodies to MarzAA, wild-type (wt) 
recombinant activated Factor VII (rFVIIa), and/or wt-FVII, andv to determine if these are 
neutralizing antibodies. 
 
To evaluate the safety of IV and SC MarzAA. 
4. 
STUDY DESCRIPTION 
4.1 
STUDY DESIGN 
This is a Phase 1 study designed to evaluate the pharmacokinetics, pharmacodynamics, and 
safety of a single IV dose and ascending doses of SC MarzAA in adult subjects with hemophilia 
A or B, with or without an inhibitor. It is an open-label study, so subjects and members of the 
clinical study team will not be blinded to treatment. 
The study will be completed in approximately 18 months (from when the study opens enrollment 
until completion of data analyses). The study will enroll at least 8 adult male subjects with 
moderate or severe Hemophilia A or B with or without an inhibitor in each dosing stage. 
Each subject may continue on to the next stage of MarzAA dosing if they wish to continue the 
study provided they do so no more than 7 days after the end of the previous stage, and that any 
spontaneous or traumatic bleeds have been resolved, and that the subject has undergone a 
72-hour washout period of the treatment used for the spontaneous or traumatic bleed.  
If any subject completes the EOS assessments prior to Amendment 2 and wishes to participate 
in Stages 8 and/or 9, the 7-day requirement will not apply, and no screening assessment will 
need to be repeated. All predose assessments will be required. If a new subject enrolls in the 
study in Amendment 2, the subject will need to complete IV dosing and assessments (Stage 1) 
prior to advancing to Stages 2 to 9.  

Statistical Analysis Plan: MAA-102 
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Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
CONFIDENTAL 
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4.2 
STUDY TREATMENT 
All study subjects will be treated with MarzAA. Each subject may receive the study drug in nine 
dosing stages (Stage 1 to 9). Detailed dosing, route of administration, and timing of each dose 
are provided in Table 4-1Table 4-1.  
Table 4-1 MarzAA Dose and Mode of Administration by Dosing Stage 
Stage  
Dose a  
Route  
Frequency, Timing b  
1  
18 μg/kg  
IV  
Once  
2  
30 μg/kg  
SC  
Once 24 Hours after Stage 1  
3  
45 μg/kg  
SC  
Once, 48 hours after Stage 2  
4  
60 μg/kg  
SC  
Once, 48 hours after Stage 3  
5  
2 × 30 μg/kg c  
2 × SC  
Once, 48 hours after Stage 4, 2 sites c  
6  
2 × 4590 μg/kg d  
2 × SC  
Once, 48 hours after Stage 5, 2 sites d  
7  
2 × 60120 μg/kg e  
2 × SC  
Once, 48 hours after Stage 6, 2 sites e  
8 
2 × 60 μg/kg d  
2 × SC  
48 hours after Stage 7, unless subjects were 
enrolled in the study prior to Amendment 2 b, 2 
doses at 3-hour intervals f  
9  
3 × 60 μg/kg e  
32 × SC  
72 hours after Stage 8, 3 doses at 3-hour 
intervals g  
Abbreviations: IV=intravenous; MarzAA=marzeptacog alfa (activated); SC=subcutaneous. 
a For subjects requiring more than 2 vials of supplied study drug, the number of SC injections should be 
commensurate with the number of vials needed. Injection sites should be different for each injection but should be 
at the same anatomic location. 
b Timing provided is minimum time after dosing. Maximum time after dosing should not exceed 7 days if a subject 
continues to the next stage of the study 
c 2 × 30 μg/kg MarzAA (total dose 60 μg/kg) injected at two different anatomic locations (which must drain into 
separate lymphatic tributary areas [eg, left and right thigh, or different sides of abdomen, or abdomen and thigh]) 
d 2 × 45 μg/kg MarzAA (total dose 90 μg/kg) injected at two different sites at the same anatomic location 
e 2 × 60 μg/kg MarzAA (total dose 120 μg/kg) injected at two different sites at the same anatomic location 
f 60 μg/kg MarzAA (total dose 120 μg/kg/day) administered at two separate timepoints with 3-hour intervals 
between eachdose and in the same anatomic location 
g 60 μg/kg MarzAA (total dose 180 μg/kg/day) administered at three separate timepoints with 3-hour intervals 
between each dose and in the same anatomic location 
 
4.3 
DATA AND SAFETY MONITORING BOARD 
There is no Data and Safety Monitoring Board in this study. 
5. 
RANDOMIZATION AND BLINDING 
The study is an open-label single-arm study; subjects and members of the clinical study team 
will not be blinded to treatment. 
6. 
SAMPLE SIZE AND POWER CALCULATION 
No formal sample size calculation was performed. The sample size estimate is based on 
pharmacokinetic (PK) guidance for the development of hemophilia factors published by 
regulatory agencies. 
Commented [SD1]: In the protocol it is single dose of 
90ug not 2 x 45 ug for this stage 
Commented [SD2]: As such, don’t think this footnote 
is needed 
Commented [SD3]: In the protocol it is single dose of 
1200ug not 2 x 60 ug for this stage 
Commented [SD4]: As such, don’t think this footnote 
is needed 

Statistical Analysis Plan: MAA-102 
Review Status: Final 
 
Version: 2.0 
 
Version Date: 16-JUN-2020
 
 
CONFIDENTAL 
Page 8 of 20 
7. 
ANALYSIS ENDPOINTS 
7.1 
PRIMARY ENDPOINT 
Comparative pharmacokinetics of MarzAA by dose level/stage. 
7.2 
SECONDARY ENDPOINTS 
The secondary endpoints are as follows: 
 
Comparative pharmacokinetics of IV and SC MarzAA. 
 
Comparative pharmacokinetics of split injections versus single injection (60 μg/kg)  
 
Change in coagulation parameters (prothrombin time, activated prothrombin complex 
concentrates [aPTT], fibrinogen, MarzAA activity levels, and thrombin generation time 
[TGT]) from pre-dose. 
 
Occurrence of an antibody response to MarzAA and whether it is inhibitory and cross-
reactive to wt-rFVIIa or wt-FVII. 
 
Clinically significant levels of thrombogenicity markers resulting from administration of 
MarzAA. 
7.3 
SAFETY ENDPOINTS 
 
Occurrence of clinical thrombotic event not attributable to another cause, and 
occurrence of antibody formation resulting in a decreased endogenous level of FVII or 
FVIIa. 
 
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). 
 
8. 
ANALYSIS POPULATIONS 
Screened population: all screened subjects. 
Safety population: any subject who receives at least one dose of study drug. The Safety 
population will be used for subject disposition, protocol deviations, subject characteristics, 
secondary endpoints, and safety analyses. 
PK population: any subject who receives the full planned dose and completes an entire PK 
assessment for the stage and has adequate samples for analysis. The PK population will be 
used for all PK and secondary endpoints analyses. 
9. 
ANALYTICAL PLAN AND STATISTICAL METHODS 
9.1 
GENERAL CONVENTIONS AND STATISTICAL CONSIDERATIONS 
All statistical analyses will be performed and data appendices will be created using the SAS 
system version 9.4 or higher. 
Data collected in this study will be presented in summary tables and subject data listings.  
Descriptive statistics (number of non-missing values, mean, standard deviation (SD), median, 
Q1, Q3, minimum, and maximum) will be presented for continuous variables. Frequency 
distributions (counts and percentages) will be presented for categorical variables. If not 

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specified otherwise, the number of observations with non-missing values will be the 
denominator for percentage calculation. 
Data on screening and demographic characteristics, medical and disease history will be 
summarized by dosing stage. A subject is included in the summary for a certain stage, if he/she 
was enrolled under that stage. 
All data collected will be presented in the data listings. 
9.2 
DEFINITION OF BASELINE, STUDY VISITS, AND VISIT WINDOWS 
Results obtained at pre-dose of each stage will be considered baseline. For hematology and 
chemistry the pre-dose results are collected under eCRF visit Day 1 for each stage. For vital 
signs, coagulation, and thrombogenicity marker, the results obtained at the pre-dose timepoint 
will be used as baseline, unless “pre-dose sample equivalent to post dose sample from previous 
study stage” is selected on the eCRF, and then results from the 48-hours post dose sample 
from the previous study stage will be used as baseline. 
The data will be analyzed according to the visits and timepoints recorded in the eCRF. 
9.3 
HANDLING OF MISSING DATA 
 
Partial or missing start and end dates of adverse events (AEs) and concomitant medications, as 
well as missing attributes of AEs will not be imputed. All data will be analyzed as collected. 
9.4 
PATIENT DISPOSITION 
The number of subjects screened and the reasons for screen failure, including exclusion criteria 
met and inclusion criteria not met, will be summarized in the Screened population. 
The number and percentage of subjects who enrolled in the study will be summarized by dosing 
stage subject entered the study and overall in the Safety population. The number and 
percentage of subjects discontinued from the study and the reasons for study discontinuation 
will be summarized by stage subject discontinued and overall in the Safety population. The 
number and percentage of subjects who completed the study will be summarized for the overall 
Safety population. 
The number and percentage of subjects included in the Safety and PK populations will also be 
summarized by stage and overall. 
A consort diagram with subject disposition will be created. 
A listing with all enrolled subjects will be generated for each dosing stage, including 
country/study center, subject number, first and last study drug dosing date, dose stage, total 
duration of study drug dosing, end of study date, and reason for discontinuation from the study. 
9.5 
PROTOCOL DEVIATIONS 
The number and percentage of subjects with at least one major protocol deviation and the 
categories of the major protocol deviations will be summarized in the overall Safety population. 
Protocol deviations will be classified as major and minor as specified in the Protocol Deviations 

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Management Plan. 
All protocol deviations will be provided in a listing. 
9.6 
PATIENT CHARACTERISTICS 
9.6.1 SCREENING AND DEMOGRAPHIC CHARACTERISTICS 
Descriptive statistics for continuous variables (age at screening, height, weight, and body mass 
index) and frequency counts and percentages for categorical demographic variables (ethnicity 
and race) will be summarized in the Safety population and tabulated by dosing stage.  
Screening and demographic characteristics will be provided in a listing. 
9.6.2 MEDICAL HISTORY AND CURRENT MEDICAL CONDITIONS 
Disease characteristics will be summarized by dosing stage in the Safety population using 
descriptive statistics for age at diagnosis and Factor VIII/IX level at screening; and using 
frequency counts and percentages for the type of hemophilia, severity, history of inhibitors, and 
prescribed hemophilia treatment.  
Medical history will be coded using the version 22.0 of Medical Dictionary for Regulatory 
Activities (MedDRA) classification and summarized by System Organ Class (SOC) and 
preferred term (PT), by dosing stage and overall in the Safety population. Subjects having the 
same medical condition (based on SOC and PT) more than once will be counted only once for a 
particular SOC and PT. 
Disease characteristics and medical history will be listed. 
9.6.3 PRIOR AND CONCOMITANT MEDICATIONS 
All prior and concomitant medications will be coded using March 2019 Format Global B3 version 
of World Health Organization Drug Dictionary Enhanced (WHO-DDE). 
The number and percentages of subjects with at least one prior or concomitant medication will 
be summarized by anatomical therapeutic chemical class (ATC) level 4 and ATC level 2 class in 
the PK and Safety populations. Prior and concomitant non-hemophilia medications and prior 
hemophilia specific medications will be summarized in overall. 
Concomitant hemophilia-specific medications will be tabulated by dosing stage and overall. 
Concomitant hemophilia-specific medication is considered taken at a certain stage, if 
administered on or after the date of study drug administration for that stage, and before the date 
of study drug administration for the next stage, or until the end of study for the last stage the 
subject participated in. One medication can be considered concomitant for multiple stages. 
A medication is considered prior if the end date of the medication is prior to the first study drug 
dose date. A medication is considered concomitant if it is administered after the first study drug 
dose date.  
Medications having both start and end dates missing will be considered concomitant; in the 
case of a missing start date and not a missing end date, the medication will be considered 
concomitant, unless the end date is prior to the date of the first dose. In such case, the 

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medication will be reported in the overall summary only. 
Subjects receiving the same medication more than once will be counted only once for a 
particular medication class and stage, where applicable. 
All prior and concomitant medications will be provided in a listing. 
9.7 
PK ENDPOINTS AND ANALYSIS 
 
PK parameters derivation will be performed by Catalyst and described in a separate PK SAP.  
The following PK parameters will be calculated: 
 
terminal half-life (t1/2); 
 
area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf); 
 
area under the plasma concentration-time curve from time 0 to the time of the last 
measurable plasma concentration (AUC0-t); 
 
clearance (CL); 
 
volume of distribution (Vd); 
 
mean residence time (MRT); 
 
bioavailability (ƒ) (of the SC administration). 
A semi-parametric model described by Lee et al (Lee, 1990; Lee, 1997) will be used to 
calculate the terminal half-life. A noncompartmental approach based on the trapezoidal rule 
will be used to compute the AUC and the parameters derived from them. These include:  
 
AUC0-inf; 
 
AUC0-t; 
 
CL; 
 
Vd; 
 
MRT; 
 
ƒ (of the SC administration). 
PK data will be analyzed for the PK population defined in section 8. 
9.7.1 ANALYSIS OF PRIMARY PHARMACOKINETIC ENDPOINT 
The analysis of the primary endpoint (comparative pharmacokinetics of MarzAA by dose level) 
will be based on the examination of the AUC0-t/dose for each dose group. Under the hypothesis 
of dose proportionality, a mixed linear model will be used (accounting for subject effect) to test 
for the equality of the mean ratio across dose groups.  
The sample code for mixed linear model, assuming dose level as categorical fixed effect and 
subject as random effect, is provided below: 
proc mixed data=sample; 
class DOSE_LEVEL; 
model AUC0-t_dose_ratio= DOSE_LEVEL/cl; 
random intercept/Subject=SUBJID; 
run; 

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In the tables, parameter estimates with standard errors, significance of parameter estimates 
(95% confidence intervals and type III hypothesis test) will be provided.  
9.7.2 ANALYSES OF SECONDARY PHARMACOKINETIC ENDPOINTS  
Mean ratio of the AUC0-t/dose for the split dose (2*30 μg/kg) with the same dose (60 μg/kg) 
given at a single location will be compared using mixed linear model as defined in section 9.7.1. 
The analysis of the primary endpoint will be repeated for each PK parameter listed in section 9.7 
of the SAP. 
Descriptive statistics will be reported for each parameter by dosing stage. PK parameter results 
will be listed. 
9.8 
ANALYSES OF SECONDARY ENDPOINTS  
Secondary endpoints will be analyzed in the PK and Safety populations. 
MarzAA activity levels will be summarized by dosing stage using descriptive statistics, including 
percent coefficient of variation (CV%), geometric mean, and geometric SD.  
Results of thrombogenicity markers (fibrinogen, D-dimer, prothrombin fragment 1+2 [F1+2] and 
thrombin-antithrombin complexes [TAT]), coagulation tests (prothrombin time, aPTT and TGT 
values) results and changes from pre-dose will be tabulated by timepoint and stage, and 
summarized using descriptive statistics. Immunogenicity assay result will be tabulated by stage 
and visit. For coagulation tests descriptive statistics will include CV%, geometric mean and 
geometric SD, calculated as: geo SD= exp (SQRT(v)) where v is the squared standard deviation 
of the log-transformed values.  
The number and percentage of subjects with clinical signs of thrombosis will be tabulated by 
timepoint, stage, and overall. 
If a subject is unable to complete all of the PK assessments and repeats a stage, MarzAA 
activity levels, thrombogenicity markers, coagulation tests, and immunogenicity assay results 
obtained during the original stage will not be included in the tables and analyzed, as this patient 
will not be included in the PK population for the original stage. 
For analysis of all secondary endpoints in the Safety population, if a subject is unable to 
complete all of the PK assessments and repeats a stage, all data collected will be included in 
the analysis. The subject will be counted twice for that stage and at each repeated timepoint.  
MarzAA activity levels, thrombogenicity markers, immunogenicity assay, and coagulation test 
results will be listed. 
9.9 
SAFETY ENDPOINTS AND ANALYSIS 
All safety outcomes will be analyzed in the Safety population. 
Safety will be evaluated by presenting summaries of exposure to study treatment, AEs, vital 
signs, and laboratory evaluations (hematology and chemistry). 

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9.9.1 EXPOSURE TO STUDY TREATMENT 
The actual dose received in micrograms (μg) and the extent of exposure, calculated as last 
dose date – first dose date +1, will be summarized using descriptive statistics by dosing stage 
and overall. 
If a subject is unable to complete all of PK assessments and repeats a stage, each actual dose 
received by the subject will be counted separately for that stage. 
Data on exposure will be listed. 
9.9.2 ADVERSE EVENTS 
AEs will be coded using the version 22.0 of MedDRA and will be graded according to the 
National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE).  
Injection site reactions will be summarized separately, and will not be included in AE summaries 
described below. 
A TEAE is defined as an AE that occurs or worsens after the first study drug administration. AEs 
having both onset and end dates missing will be considered as TEAEs. AEs having a missing 
onset date and not missing an end date will be considered as TEAEs unless the end date is 
prior to the date of the first dose.  
Each summary table with AEs will be presented by dosing stage and overall. An AE is reported 
under the stage specified if it occurs or worsens on or after the date of study drug administration 
during the stage, and before the date of study drug administration in the next stage, or until the 
end of study for the last stage the subject participated in. 
An overall summary of AEs will include the number of subjects who experienced at least one AE 
of the following categories: any TEAE, any SAE, any thromboembolic event (TE), any immune 
response/antibody formation (IRF), any drug-related TEAE, any TEAE leading to premature 
discontinuation from study, and any TEAE leading to death. 
The incidence of TEAEs will be summarized by SOC and PT; by SOC, PT and severity; and by 
SOC, PT and relatedness. If the same AE (based on SOC, PT, and stage) is reported for the 
same subject more than once, the AE is counted only once for that SOC, PT, and stage, if 
applicable, and at the highest severity or relatedness, respectively. 
In addition, the incidence of SAEs, TEs, IRFs, and TEAEs leading to discontinuation from study 
will be presented by SOC and PT and will be tabulated by dosing stage and overall. If the same 
AE (based on SOC, PT, and stage) is reported for the same subject more than once, the AE is 
counted only once for that SOC, PT, and stage, if applicable. 
Number of subjects with injection site reactions will be tabulated by type of injection site reaction 
and severity in the Safety population by dosing stage and overall. Injection site reaction will be 
reported under a stage if occurs on or after the date of study drug administration during the 
stage and before the date of study drug administration in the next stage, or until the end of study 
for the last stage the subject participated in. 
Separate listings will be prepared for all AEs, SAEs, TEs, IRFs, AEs leading to discontinuation 
from the study, AEs leading to death, and injection site reactions. 

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9.9.3 LABORATORY DATA 
Pre-dose results, maximum results, and change from pre-dose to maximum results for 
hematology and clinical chemistry data, collected by local laboratories, will be summarized by 
dosing stage using descriptive statistics. In addition, maximum change from pre-dose across all 
stages will be calculated and summarized.  
Shift tables classified by reference range indicator (low [<lower limit of normal], normal [within 
normal limits], and high [>upper limit of normal]) from pre-dose to maximum result per stage will 
be presented separately by laboratory test, where applicable. In addition, shift tables from 
maximum pre-dose result to maximum result across all stages, classified as low, normal, and 
high, will be presented by laboratory test. 
If a subject is unable to complete all of PK assessments and repeats a stage, the subject will be 
counted twice for that stage, i.e., two pre-dose results, two maximum values and two maximum 
changes from pre-dose will be analyzed.  
For laboratory results reported with a prefix, i.e., “<”, “<=”, “=>” or “>”, the value derived from 
reported results without a prefix will be analyzed. 
Data listings will be produced for all collected laboratory data.  
9.9.4 VITAL SIGNS AND OTHER SAFETY PARAMETERS 
9.9.4.1 
VITAL SIGNS 
Pre-dose results, maximum results and change from pre-dose to maximum results of vital signs 
(temperature [degree C], systolic and diastolic blood pressure [mmHg], heart rate [bpm], and 
respiratory rate [breaths/min]) will be summarized by stage using descriptive statistics. In 
addition, maximum change from pre-dose across all stages will be calculated and summarized. 
If a subject is unable to complete all of PK assessments and repeats a stage, the subject will be 
counted twice for that stage, i.e., two pre-dose results, two maximum values and two maximum 
changes from pre-dose will be analyzed.  
9.9.4.2 
12-LEAD ELECTROCARDIOGRAM (ECG) AND PHYSICAL EXAMINATION 
Data listings of ECG and physical examination data collected at screening will be provided. 
9.9.4.3 
BLEEDING EPISODES 
Descriptive statistics for number of bleeding episodes per subject and overall number of 
bleeding episodes will be tabulated by stage and overall. Frequency counts and percentages for 
cause of bleeding, bleeding site, whether the subject required transfusion (yes/no), and use of 
hemostatic drugs for treatment (yes/no) will be summarized on bleeding level and tabulated by 
stage and overall. Bleeding episodes will be analyzed under a certain stage if they occur on or 
after the date of study drug administration during the stage and before the date of study drug 
administration in the next stage, or until the end of study for the last stage the subject 
participated in. Medications used to treat the bleeding episode will also be summarized and 
tabulated by ATC 4 and ATC 2 level, and by dosing stage during which the bleeding episode 
occurred and overall.  

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10. 
DEVIATIONS FROM ANALYSIS AS DESCRIBED IN THE 
PROTOCOL 
Section 8: The safety population will be used in the safety analysis, not the intent-to-treat (ITT) 
population.  
11. PROGRAMMING SPECIFICATIONS 
All outputs will be produced using SAS version 9.4 or a later version. 
The margins should be at least 1.50 inches for the binding edge and 1.0 inches for all others. 
In the top left portion of each output, the protocol number will be presented. On the next line, a 
table/listing number followed by the title of the table/listing and population information will be 
displayed. Horizontal lines will appear after the column heading of the table/listing. Footnotes 
will be put under the main body of text at the bottom of the page. The source listing number will 
be displayed for all tables. The SAS program name will appear on the bottom left in a string and 
the page number will appear on the bottom right corner of each table/listing. The date and time 
of creation of table/listing will appear on the bottom left under the SAS program name line. 
Example: 
 
MAA-102 
 
Table 14.x.x Title - Population 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
Program:\\xxx\xxx\MAA-102_table XXX.sas 
 
 
 
  
Source: Listing XXX 
Created DDMMMYYYY at HH:MM 
 
 
 
 
 
 
 
Page 1 of x 
Courier New 8-point font will be used for all tables and listings. Landscape layout will be used. 
Any date information in the listing will use the date9. format, for example, 25OCT2019. 
Tables and listings will be produced in “rtf” format, each output in separate file and all tables, all 
figures and all listings in one file each. 
Percentages for categorical data summaries will be displayed with 1 decimal point (e.g. 51.4), 
except for 100% which will be presented with no decimals (i.e. 100).  
Use of decimal places in descriptive statistics: 
 
Min, Max: same as the actual data, 
 
Mean, Geometric mean, Median, 95% CI: actual data + 1 decimal, 
 
Standard deviation (SD), CV%: actual data + 2 decimals. 
A maximum of 3 significant digits will be displayed. 
All raw data will be presented to the original number of decimal places in the listings. 
In case table break across multiple pages, the heading rows should be repeated. 
In case there are no data to present in a table, listing or figure, the file will still be created, 

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containing only a short message to explain: e.g., the listing of SAEs will only show a message 
like ‘No SAEs in the study’ if there were no SAEs in the study. 
For listings, if the answer to a question is “other”, “other” should be displayed and then what the 
other represents should be specified in parentheses in the cell. 
12. 
LIST OF TABLES, LISTINGS AND FIGURES 
Shells for unique tables, listings and figures are provided in a separate Mock-Up TFLs 
document. 
13. 
REFERENCES 
Lee, M. L., Poon, W. Y., & Kingdon, H. S. (1990). A two-phase linear regression model for 
biologic half-life data. J Lab Clin Med, 115(6), 745-748. 
Lee ML, Schroth P, Bray G, Gomperts ED.  The use of robust regression techniques to obtain 
improved coagulation factor half-life estimates.  XVIth Congress of the International Society for 
Thrombosis and Hemostasis, Florence, Italy, 1997. 

APPENDIX I. SCHEDULE OF ASSESMENT 
Table 0-1 
Study Period 
Screening a 
Enrollment 
(prior to 1st 
dose) 
Stages 1 to 9 b 
Stages 2 to 9 
Stages 8 to 9 
Unscheduled c 
EOS d 
Study Day/Hour 
Day 
−28 to −1 
Predose 
(−15 min) 
Day 1 
Day 2 
Day 3 
Day 4 
Hours 
0 
24 
48 
72 
Informed consent 
X 
 
 
 
 
 
 
 
 
Demographic parameters 
X 
X 
 
 
 
 
 
 
 
Inclusion & exclusion review 
X 
X 
 
 
 
 
 
 
 
Medical & hemophilia History 
X 
X 
 
 
 
 
 
 
 
Enrollment confirmation 
 
X a 
 
 
 
 
 
 
 
Prior medications & nondrug treatment 
X 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
 
X 
X 
X 
X 
X 
X 
Height (screening only) & weight 
X 
X 
 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
 
 
 
Clinical signs of thrombosis e 
X 
X 
 
X 
X 
X 
X 
X 
X 
Hematology & chemistry f 
X 
 
X 
 
X 
X 
X 
X 
X 
Coagulation assays g 
X 
 
X 
X 
X 
X 
X 
X 
X 
Thrombogenicity markers g 
X 
 
X 
X 
X 
X 
X 
X 
X 
PK sampling g 
 
 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity assays g 
X 
 
X 
 
 
X 
X 
X 
X 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MarzAA administration h 
 
 
 
X 
 
 
 
 
 
Study drug accountability 
 
 
 
X 
 
 
 
 
 
Abbreviations: 
AE=adverse events; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ConMeds=concomitant medications; 
ECG=electrocardiogram; MarzAA=marzeptacog alfa (activated); PK=pharmacokinetic; PD= pharmacodynamic. 
 
Footnotes Provided on Next Page 

a. All Screening procedures must be completed and reviewed prior to enrollment. Sample collection and shipment to 
the Central Laboratory should take place at least 2 weeks prior to scheduled enrollment. For subjects previously 
enrolled and completing the EOS visit prior to Amendment 2, if participation resumes, there are no additional 
screening parameters required. 
b. For PK/PD assessments for Stages 1 to 7, refer to Table 14-2 and for  Stages 8 and 9, refer to Tables 14-3. 
Pharmacokinetic assessments should be performed before all other assessments for each time point. If a new 
subject is enrolled in the study in Amendment 2, the subject will need to complete IV dosing and assessments (Stage 
1) prior to advancing to stages 2 to 9. 
c. At an Unscheduled Visit, perform only the assessments that are appropriate for the reason of the visit. 
d. End of Study visit will occur 30 days after the last stage has been completed by the subject ±5 days. For subjects 
previously enrolled and completing the EOS visit prior to Amendment 2, if participation resumes, EOS assessments 
should be repeated. 
e. Clinical signs of thrombosis per protocol. 
f. Local Laboratory: Hematology – CBC and platelet count. Chemistry – Sodium, potassium, chloride, bicarbonate, 
hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, creatinine. For each stage, blood will be collected at Predose 
(−5 minutes), 24 and 48 hours postdose. For Stages 8 to 9, blood will also be collected at 72 hours postdose. 
g. Central laboratory: Coagulation assays – prothrombin time, aPTT and TGT. Thrombogenicity markers – Fibrinogen, 
D-dimer, F1+2, and TAT. Pharmacokinetics – MarzAA activity. Immunogenicity assays – to FVII, FVIIa, and MarzAA. 
For PK/PD assessments for Stages 1 to 7, refer to Error! Reference source not found.Table 14-2 and Stages 8 to 
9, refer to Error! Reference source not found.Table 14-3.  
h. At Hour 0 of each Stage, an IV or SC dose of MarzAA will be given.

 
Table 0-2 
Study Day/Hour 
Predose 
(−15 min)
IV/SC Admin 
Stage 1 
Stages 2 to 7 
Day 1 
Day 2 
Day 3 
Minutes 
Hours 
Minutes 
Hours 
5 
60 
2 
6 
9 
12 
24 
30 
60 
90 
2 
6 
9 
24 
48 
± 5 minutes 
± 15 minutes 
± 2 hours 
± 5 minutes 
± 15 minutes 
± 2 hours 
Vital Signs a 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Signs of Thrombosis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology & Chemistry 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Coagulation 
X 
 
X 
 
X 
X 
 
 
X 
 
 
 
X 
X 
 
X 
X 
Thrombogenicity 
X 
 
X 
 
X 
X 
 
 
X 
 
 
 
X 
X 
 
X 
X 
Pharmacokinetics 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity b 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MarzAA administration c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 
AE=adverse events; ConMeds=concomitant medications; IV=intravenous; MarzAA=marzeptacog alfa (activated); min=minutes; 
PD=pharmacodynamics; PK=pharmacokinetics; SC=subcutaneous. 
 
NOTE: After Stage 1, each subsequent stage may be initiated immediately after the 48-hour specimens have been obtained. If a stage is initiated immediately 
after, then the 48-hour specimens can be used as the predose specimens for the next stage. A maximum of 7 days may elapse between the 48-hour blood draw 
and when the next stage commences (unless delayed because of dose interruption as specified in the protocol). 
a. Pharmacokinetic assessments should be performed before all other assessments for each time point. Vital signs performed include measure supine blood 
pressure, pulse, temperature and respiratory rate 
b. For subjects who complete all stages, starting at an initial dose of 18 μg/kg, immunogenicity will be done at predose for Stage 3 and Stage 6 only, and end of 
study. For replacement subjects starting at a higher dose level, specimens will be drawn at screening and at the end of the study. 
c. After the IV dose of 18 μg/kg, the initial SC dose at 30 μg/kg, followed by an increase to 45, 60, 90, and 120 μg/kg if the subject continues enrollment in the 
study. If a subject does not proceed through all stages, then a replacement subject will be added at the missing stage to achieve 8 subjects.  If a replacement 
subject is enrolled in the study in Amendment 2, subject will need to complete Stage 1 (IV) dosing and assessments prior to advancing to Stages 2 to 9. If a 
subject discontinues Stage 5, the replacement subject will complete Stage 1 (IV) dosing and assessments and then repeat Stage 4 and then continue with the 
remaining doses such that the same subject completes Stages 4 and 5. For all other stages when the completion of a dose level has occurred, the replacement 
subject will complete Stage 1 (IV) dosing and assessments and then will start at the next incomplete dose level. There are two doses at 60 μg/kg: Stage 4 injected 
at a single anatomic location and Stage 5 an equal split SC dose injected at two different anatomic locations, which drain into separate lymphatic tributary areas 
(eg, left and right thigh, or different sites of abdomen, or abdomen and thigh). 

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Table 0-3 
Study Day/Hour 
Predose 
(−15 min) 
SC Admin 
Stages 8 to 9 
Day 1 
Day 2 
Day 3 
Day 4 
Hour 
2 
3 
4 
5 
6 
7 
8 
9 
12 
24 
48 
72 
±15 minutes 
±2 hours 
Vital Signs a 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Physical Exam 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Clinical Signs of Thrombosis 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology & Chemistry 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Coagulation 
X 
 
 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
Thrombogenicity 
X 
 
 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
Pharmacokinetics 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity b 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MarzAA administration a, c 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
AEs & ConMeds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: 
AE=adverse events; ConMeds=concomitant medications; IV=intravenous; MarzAA=marzeptacog alfa (activated); min=minutes; 
PD=pharmacodynamics; PK=pharmacokinetics; SC=subcutaneous. 
NOTE: After Stage 1, each subsequent stage may be initiated immediately after the 48-hour specimens have been obtained. If a stage is initiated immediately 
after, then the 48-hour specimens can be used as the predose specimens for the next stage. A maximum of 7 days may elapse between the 48-hour blood draw 
and when the next stage commences (unless delayed because of dose interruption as specified in the protocol or had previously completed dosing prior to 
Amendment 2). 
a. Pharmacokinetic assessments should be performed before all other assessments for each time point. Vital signs performed include measure supine blood 
pressure, pulse, temperature and respiratory rate. 
b. For subjects who complete all stages, starting at an initial dose of 18 µg/kg, immunogenicity will be done at predose for Stage 3 and Stage 6 only, and end of 
study. For replacement subjects starting at a higher dose level, specimens will be drawn at screening and at the end of the study. 
c. Stage 8 will give 2 separate doses of 60 µg/kg dosed at 3-hour intervals, and Stage 9 will give 3 separate doses of 60 µg/kg, dosed at 3-hour intervals  If a 
subject does not proceed to Stage 9, then a replacement subject will be added at the missing stage to achieve 8 subjects in each stage. The replacement subject 
will need to complete Stage 1 (IV) dosing and assessments prior to advancing to Stage 8 to 9.