A Phase 1/2, Randomized, Double-Blinded, Placebo-Controlled, Combined Single and Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Biological Activity of MRT5005 Administered by Nebulization to Adult Subjects With Cystic Fibrosis
Phase: PHASE1
Conditions: Cystic Fibrosis
Sponsor: Sanofi

CLINICAL STUDY PROTOCOL: MRT5005-101
TITLE:
A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Combined 
Single and Multiple Ascending Dose Study Evaluating the Safety, 
Tolerability, and Biological Activity of MRT5005 
(
mRNA/
 LNP) Administered by Nebulization to Adult 
Subjects with Cystic Fibrosis 
DRUG: 
MRT5005 
(
mRNA [
mRNA] complexed with 
 lipid nanoparticle [
LNP]) 
IND: 
IND 017747 
EUDRACT NO.: 
Non-EUDRACT 
SPONSOR: 
Translate Bio, Inc. 
29 Hartwell Ave 
Lexington, MA 02421 USA 
RESPONSIBLE 
PHYSICIAN: 
29 Hartwell Ave 
Lexington, MA 02421 USA 
PROTOCOL 
HISTORY:
Original Protocol: 12 September 2017
Amendment 1: 18 January 2018 
Amendment 2: 28 February 2019
Amendment 3: 29 July 2019 
Amendment 4: 30 July 2020 
This document contains confidential and proprietary information of Translate Bio, Inc. and is disclosed pursuant to 
confidentiality and non-disclosure obligations. This information should be used solely for the purposes for which it 
was provided and should not be copied, shared with, or disclosed to any third party without the express written 
consent of Translate Bio. 
NCT Number: NCT03375047

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
2 
COORDINATING INVESTIGATORS:
PART A: 
New Orleans Center for Clinical Research (NOCCR) 
University of Tennessee Medical Center (4 and 5 North) 
1924 Alcoa Highway 
Knoxville, TN 37920 
Telephone: 
  Fax:
E-mail:
PARTS B and D: 
Dept. of Pulmonary, Allergy, and Critical Care Medicine 
University of Alabama School of Medicine, MCLM 706 
1918 University Blvd. 
Birmingham, AL 35294 
Phone:  
E-mail:

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
3 
PROTOCOL SIGNATURE PAGE
Sponsor’s (Translate Bio) Approval: 
Chief Medical Officer 
Translate Bio, Inc. 
29 Hartwell Ave 
Lexington, MA 
Date 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
4 
INVESTIGATOR’S ACKNOWLEDGEMENT
I have read this protocol for Translate Bio Clinical Study MRT5005-101. 
Title: A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Combined Single and 
Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Biological Activity of 
MRT5005 (
 mRNA/
 LNP) Administered by Nebulization to Adult Subjects with 
Cystic Fibrosis 
Amendment/Version: Amendment 4, Version 5.0, dated 30 July 2020 
I have fully discussed the objectives of this study and the contents of this protocol with the 
Sponsor’s representative. 
I understand that the information in this protocol is confidential and should not be disclosed, 
other than to those directly involved in the execution or the scientific/ethical review of the study, 
without written authorization from the Sponsor. It is, however, permissible to provide the 
information contained herein to a subject in order to obtain their consent to participate. 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with International Conference on Harmonisation guidelines on Good Clinical 
Practice and with the applicable regulatory requirements. 
I understand that failure to comply with the requirements of the protocol may lead to the 
termination of my participation as an Investigator for this study. 
I understand that the Sponsor may decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing. Conversely, 
should I decide to withdraw from execution of the study I will communicate my intention 
immediately in writing to the Sponsor. 
_____________ 
Printed Name of Investigator 
Signature of Investigator 
Date 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
5 
MEDICAL MONITOR CONTACT INFORMATION
For protocol- or safety-related issues, the Investigator should contact the Medical Monitor. In the 
event of a fatal or life-threatening serious adverse event (SAE), the Investigator must contact the 
Medical Monitor immediately by phone. The SAE must also be entered into the electronic data 
capture (EDC) system as soon as possible to notify Rho Product Safety. 
Medical Monitor: 
Responsible Physician: 

MRT5005-101 
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL 
6 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES
TABLE OF CONTENTS 
INVESTIGATOR’S ACKNOWLEDGEMENT .............................................................................4
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ....................................6 
ABBREVIATIONS .......................................................................................................................13 
STUDY SYNOPSIS ......................................................................................................................15 
1.
BACKGROUND INFORMATION...........................................................................50
1.1. 
Cystic fibrosis .............................................................................................................50 
1.2. 
Overview of MRT5005 ...............................................................................................51 
1.3. 
Indication and Current Treatment Options .................................................................53 
1.3.1. 
Indication for MRT5005 .............................................................................................53 
1.3.2. 
Current Treatment Options for Cystic Fibrosis ..........................................................53 
1.4. 
Product Background ...................................................................................................53 
1.4.1. 
Preclinical Information ...............................................................................................54 
1.4.1.1. 
Proof-of-Concept Pharmacology Studies ...................................................................54 
1.4.1.2. 
Pharmacokinetic Studies .............................................................................................54 
1.4.1.3. 
Toxicology Studies .....................................................................................................55 
1.4.2. 
Clinical Information ....................................................................................................55 
1.5. 
Risk/Benefit and Ethical Assessment .........................................................................55 
2.
STUDY OBJECTIVES AND PURPOSE ..................................................................58
2.1. 
Rationale for the Study ...............................................................................................58 
2.2. 
Rationale for Study Design, Study Population, and Dose Selection ..........................58 
2.2.1.
Study Design...............................................................................................................58
2.2.2. 
Study Population .........................................................................................................60 
2.2.3. 
Dose Selection ............................................................................................................61 
2.3. 
Study Objectives .........................................................................................................63 
2.3.1. 
Primary Objective .......................................................................................................63 
2.3.2. 
Secondary Objective ...................................................................................................64 
2.4. 
Study Endpoints ..........................................................................................................64 
2.4.1. 
Primary Endpoint ........................................................................................................64 
2.4.2. 
Secondary Endpoint ....................................................................................................64 
3.
STUDY DESIGN .......................................................................................................65 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
7 
3.1. 
Overall Study Design and Plan ...................................................................................65 
3.2.
Subject Enrollment and Treatment Allocation ...........................................................69
3.2.1.
Part A..........................................................................................................................70
3.2.2. 
Part B ..........................................................................................................................70 
3.2.3. 
Part D ..........................................................................................................................72 
3.3. 
Planned Number of Subjects ......................................................................................72 
3.4.
Criteria for Dose-Escalation in Parts A and B / Criteria for Initiation of Part 
B..................................................................................................................................73
3.4.1. 
Protocol Safety Review Committee (PSRC) ..............................................................73 
3.4.1.1. 
Composition and Responsibilities ..............................................................................73 
3.4.1.2. 
Other Oversight Roles ................................................................................................74 
3.4.2. 
Dose Escalation Criteria for Parts A and B ................................................................75 
3.4.3. 
Criteria to Initiate Enrollment and Treatment in Part B .............................................76 
3.5. 
Duration and Study Completion Definition ................................................................77 
3.6. 
Sites and Regions ........................................................................................................77 
4. 
STUDY POPULATION .............................................................................................78 
4.1. 
Inclusion Criteria ........................................................................................................78 
4.2. 
Exclusion Criteria .......................................................................................................79 
4.3. 
Restrictions .................................................................................................................81 
4.4. 
Reproductive Potential ................................................................................................81 
4.4.1.
Female Contraception.................................................................................................81
4.4.2. 
Male Contraception ....................................................................................................82 
4.5.
Discontinuation of Subjects and Individual Stopping Rules......................................82
4.5.1. 
Reasons for Discontinuation and Individual Stopping Rules .....................................83 
4.5.2. 
Replacement of Subjects .............................................................................................85 
4.5.3. 
Subjects Lost to Follow-up Prior to Last Scheduled Visit .........................................85 
4.5.4. 
Dose Group Stopping Criteria ....................................................................................85 
4.5.5. 
Part D Stopping Criterion ...........................................................................................86 
4.5.6. 
Study Stopping Criteria ..............................................................................................86 
5. 
PRIOR AND CONCOMITANT TREATMENT AND PROCEDURES ..................88 
5.1. 
Prior and Concomitant Medications and Therapies ....................................................88 
5.1.1. 
Permitted Medications and Therapies ........................................................................88 
5.1.1.1. 
Modifications of Subject’s Routine Pulmonary Medications and Therapies .............89 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
8 
5.1.2. 
Prohibited Medications ...............................................................................................89 
5.2.
Concomitant Surgical Procedures...............................................................................89
6.
INVESTIGATIONAL PRODUCT ............................................................................90
6.1. 
Identity of Investigational Product .............................................................................90 
6.1.1. 
MRT5005 ....................................................................................................................90 
6.1.2. 
Placebo Comparator ....................................................................................................90 
6.1.3.
Blinding the Treatment Assignment...........................................................................90
6.2.
Administration of IP ...................................................................................................91
6.2.1. 
Allocation of Subjects to Treatment ...........................................................................91 
6.2.2. 
Preparation of IP .........................................................................................................91 
6.2.2.1. 
Dosing of IP ................................................................................................................93 
6.2.2.2. 
Secondary Exposure to Study Staff ............................................................................93 
6.2.3. 
Unblinding Treatment Assignments ...........................................................................93 
6.3. 
Labeling, Packaging, Storage, and Handling ..............................................................94 
6.3.1. 
Labeling and Packaging ..............................................................................................94 
6.3.1.1. 
MRT5005 ....................................................................................................................95 
6.3.1.2. 
Placebo Comparator ....................................................................................................95 
6.3.2. 
Storage of IP ...............................................................................................................95 
6.4. 
Drug Accountability ...................................................................................................96 
6.5. 
Subject Compliance ....................................................................................................96 
7.
STUDY PROCEDURES............................................................................................97
7.1. 
Part A Study Schedule ................................................................................................97 
7.1.1.
Screening Period: Day -28 to Day -2..........................................................................98
7.1.1.1. 
Screening Failure ........................................................................................................98 
7.1.1.2. 
Rescreening of Subjects ..............................................................................................99 
7.1.2. 
Treatment Period: Day -1 to Day 2 .............................................................................99 
7.1.3. 
Follow-up Period: Day 3 to Day 337 ........................................................................101 
7.2. 
Part B Study Schedule ..............................................................................................102 
7.2.1. 
Screening Period: Day -28 to Day -2 ........................................................................103 
7.2.1.1. 
Screening Failure ......................................................................................................103 
7.2.1.2. 
Rescreening of Subjects ............................................................................................104 
7.2.2. 
Treatment Period: Day -1 to Day 33 .........................................................................104 
7.2.3. 
Follow-up Period: Day 36 to Day 365 ......................................................................106 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
9 
7.3. 
Part D Study Schedule ..............................................................................................106 
7.3.1.
Screening Period: Day -28 to Day -1........................................................................107
7.3.2.
Treatment Period: Day 1 to Day 5............................................................................108
7.3.3. 
Follow-up Period: Day 6 to Day 341 ........................................................................109 
7.4. 
Additional Care of Subjects after the Study .............................................................110 
7.5. 
Study Evaluations and Procedures ............................................................................110 
7.5.1.
Demographic and Other Baseline Characteristics ....................................................110
7.5.2.
Safety ........................................................................................................................110
7.5.2.1. 
Medical and Medication History ..............................................................................111 
7.5.2.2. 
Physical Examination (Including Height and Weight) .............................................111 
7.5.2.3. 
Adverse Event Collection .........................................................................................113 
7.5.2.4. 
Vital Signs ................................................................................................................113 
7.5.2.5. 
Pulse Oximetry .........................................................................................................114 
7.5.2.6. 
Clinical Laboratory Evaluations ...............................................................................115 
7.5.2.7. 
Serum Inflammatory Markers (Part B 20 mg and Part D only) ...............................116 
7.5.2.8. 
Pregnancy Test ..........................................................................................................117 
7.5.2.9. 
Drug and Alcohol Screen ..........................................................................................117 
7.5.2.10. 
Viral Screen ..............................................................................................................117 
7.5.2.11. 
Electrocardiogram (ECG) .........................................................................................117 
7.5.2.12. 
Spirometry ................................................................................................................118 
7.5.2.13.
Chest x-ray................................................................................................................118
7.5.2.14. 
Measurement of 
 mRNA and 
in Blood ....................................................................................................................119
7.5.2.15. 
Measurement of Immune Responses to CFTR Protein ............................................119 
7.5.3. 
Volume of Blood to be Drawn from Each Subject ...................................................120 
7.5.4. 
Cystic Fibrosis Questionnaire-Revised (CFQ-R) .....................................................120 
7.6. 
Coronavirus Disease Contingency Measures ...........................................................121 
8. 
ADVERSE AND SERIOUS ADVERSE EVENT ASSESSMENT ........................122 
8.1. 
Definition of Adverse Events, Period of Observation, Recording of Adverse 
Events .......................................................................................................................122 
8.1.1. 
Severity Categorization ............................................................................................122 
8.1.2. 
Relationship Categorization ......................................................................................123 
8.1.3. 
Outcome Categorization ...........................................................................................124 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
10 
8.1.4. 
Clinical Laboratory and Other Safety Evaluations ...................................................124 
8.1.4.1.
Evaluation of Elevations in Liver Function Tests ....................................................124
8.1.4.2.
Development of Immune Responses to CFTR Protein or PEG................................125
8.1.5. 
Pregnancy .................................................................................................................125 
8.1.6. 
Abuse, Misuse, Overdose, and Medication Error .....................................................126 
8.1.7. 
Classification of Events as Pulmonary Exacerbations ..............................................127 
8.1.8.
Adverse Events of Special Interest...........................................................................127
8.1.8.1.
Allergic/Hypersensitivity Reactions.........................................................................127
8.2. 
Serious Adverse Event Procedures ...........................................................................128 
8.2.1. 
Reference Safety Information ...................................................................................128 
8.2.2. 
Reporting Procedures ................................................................................................128 
8.2.3. 
Serious Adverse Event Definition ............................................................................128 
8.2.4. 
Suspected Unexpected Serious Adverse Reaction ...................................................129 
8.2.5. 
Serious Adverse Event Collection Time Frame .......................................................129 
8.2.6. 
Serious Adverse Event Onset and Resolution Dates ................................................130 
8.2.7. 
Fatal Outcome ...........................................................................................................130 
8.2.8. 
Regulatory Agency, Institutional Review Board, Ethics Committee, and Site 
Reporting ..................................................................................................................130 
9. 
DATA MANAGEMENT AND STATISTICAL METHODS .................................131 
9.1. 
Data Collection .........................................................................................................131 
9.2.
Clinical Data Management .......................................................................................131
9.3. 
Data Handling Considerations ..................................................................................131 
9.4.
Statistical Analysis Process ......................................................................................131
9.5. 
Planned Interim Analysis, Adaptive Design, and Data Monitoring 
Committee .................................................................................................................132 
9.6. 
Sample Size Calculation and Power Considerations ................................................133 
9.7. 
Analysis Populations ................................................................................................133 
9.8. 
Analyses ....................................................................................................................133 
9.8.1. 
Safety Analyses ........................................................................................................133 
9.8.2. 
Other Analyses ..........................................................................................................133 
10. 
SPONSOR’S AND INVESTIGATOR’S RESPONSIBILITIES .............................134 
10.1. 
Sponsor’s Responsibilities ........................................................................................134 
10.1.1. 
Good Clinical Practice Compliance..........................................................................134 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
11 
10.1.2. 
Indemnity/Liability and Insurance ............................................................................134 
10.1.3.
Public Posting of Study Information ........................................................................134
10.1.4.
Submission of Summary of Clinical Study Report to Competent Authorities 
of Member States Concerned and Ethics Committees .............................................134 
10.1.5. 
Study Suspension, Termination, and Completion ....................................................135 
10.2. 
Investigator’s Responsibilities ..................................................................................135 
10.2.1.
Good Clinical Practice Compliance..........................................................................135
10.2.2.
Protocol Adherence and Investigator Agreement.....................................................135
10.2.3. 
Documentation and Retention of Records ................................................................136 
10.2.3.1. 
Case Report Forms ...................................................................................................136 
10.2.3.2. 
Recording, Access, and Retention of Source Data and Study Documents ...............136 
10.2.3.3. 
Audit/Inspection .......................................................................................................137 
10.2.3.4. 
Financial Disclosure .................................................................................................137 
10.3. 
Ethical Considerations ..............................................................................................137 
10.3.1. 
Informed Consent .....................................................................................................137 
10.3.2. 
Institutional Review Board or Ethics Committee .....................................................138 
10.4. 
Privacy and Confidentiality ......................................................................................138 
10.5. 
Study Results / Publication Policy ............................................................................139 
11. 
REFERENCES .........................................................................................................141 
12. 
PROTOCOL AMENDMENTS ................................................................................144 
13.
APPENDICES..........................................................................................................145

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
12 
LIST OF TABLES
Table 1: 
Part A - Schedule of Procedures for the Screening and Treatment Periods 
- Day -28 to Day 2 .................................................................................... 26 
Table 2:
Part A - Schedule of Procedures for the Follow-up Period - Day 3 to Day 
85 .............................................................................................................. 30 
Table 3: 
Part A - Schedule of Procedures for the Follow-up Period - Day 113 to 
Day 337 .................................................................................................... 32
Table 4:      Part B - Schedule of Procedures for the Screening and Treatment Periods 
- Day -28 to Day 33 .................................................................................. 34 
Table 5:      Part B  - Schedule of Procedures for the Follow-up Period - Day 36 to 
Day 113 .................................................................................................... 38 
Table 6: 
Part B - Schedule of Procedures for the Follow-up Period - Day 141 to 
Day 365 .................................................................................................... 40 
Table 7: 
Part B - Schedule of Procedures for Dosing Days - Weeks 1 Through 5 42 
Table 8: 
Part D  - Schedule of Procedures for Screening through Day 18 ............. 45 
Table 9: 
Part D - Schedule of Procedures for the Follow-up Period - Day 25 to 
Day 341 .................................................................................................... 48 
Table 10  
Basis for Human Dose Determination ...................................................... 62 
Table 11:   Dosing of MRT5005 - Volumes and Nebulization Times ..................... 92 
 
LIST OF FIGURES 
Figure 1: 
Study Design Flow Chart ......................................................................... 66 
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
13 
ABBREVIATIONS
AE
adverse event
AESI
adverse event of special interest
ALP 
alkaline phosphatase  
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATP 
adenosine triphosphate 
-hCG
beta-human chorionic gonadotropin 
BMI 
body mass index 
CF 
cystic fibrosis 
CFR 
Code of Federal Regulations 
CFTR
cystic fibrosis transmembrane regulator 
CRA 
clinical research associate 
CRF 
case report form 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EU 
European Union 
FDA
Food and Drug Administration
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
g 
gram 
GCP  
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practices 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
hCFTR 
human cystic fibrosis transmembrane regulator  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
14 
HCV 
hepatitis C virus 
HED 
human equivalent dose 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
ICH 
International Conference on Harmonisation 
 LNP 
lipid nanoparticle 
IP
investigational product
IRB
Institutional Review Board
Kg
kilogram
LNP 
lipid nanoparticle 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
milligram 
mL 
milliliter 
mRNA 
messenger ribonucleic acid 
NOAEL 
no-observed-adverse-effect-level 
PEG 
polyethylene glycol 
PSRC 
Protocol Safety Review Committee 
qPCR 
quantitative polymerase chain reaction 
rhDNase 
recombinant human deoxyribonuclease I  
RNA 
ribonucleic acid 
SAE 
serious adverse event 
µg 
microgram 
ULN 
upper limit of normal 
US
United States
USP
United States Pharmacopeia

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
15 
STUDY SYNOPSIS
Name of Sponsor/Company:
Translate Bio, Inc. 
Name of Investigational Product: 
mRNA [
mRNA] complexed with 
 lipid nanoparticle [
 LNP] (MRT5005) 
Name of Active Ingredient: 
 messenger ribonucleic acid encoding for 
 (MRT5005 
 mRNA) 
Title of the study: A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Combined Single and 
Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Biological Activity of 
MRT5005 (
mRNA/
 LNP) Administered by Nebulization to Adult Subjects with Cystic 
Fibrosis 
Study Center(s): 
Multi-center in the US 
Phase of Development: 1/2 
Number of subjects (planned, total and for each treatment arm): 
The study will be conducted at multiple centers in the US with expertise in treating cystic fibrosis (CF) 
patients. At least 40 male and female subjects with CF, 18 years of age or older, are planned to 
participate in the study. This will be a 3-part study with 16 subjects participating in Part A; 16 subjects 
participating in Part B; and 8 subjects participating in Part D. There will be an option to enroll and treat 
one additional group of subjects, with up to a maximum of 44 evaluable subjects participating in the 
study. Subjects will not be allowed to participate in more than 1 part of the study. 
Part A: Single Ascending Dose (SAD) Groups (N=16) 
In Part A, 4 groups consisting of 4 subjects each will be enrolled sequentially to receive single doses of 
nebulized MRT5005 (8, 16, 24, or 20 mg of 
 mRNA, the active drug substance of 
MRT5005 [nominal doses]) or placebo (normal saline). The 20 mg treatment group was added after 
blinded safety information from Group 3 revealed the occurrence of febrile reactions in 3 of 4 subjects.  
Within each dose group, subjects will be randomized in a 3:1 ratio to receive a single dose of either 
MRT5005 or placebo (3 subjects to receive MRT5005 and 1 subject to receive placebo per dose group).  
Part B: Multiple Ascending Dose (MAD) Groups (N=16) 
In Part B, 4 groups consisting of 4 subjects each will receive multiple doses of nebulized MRT5005 or 
placebo administered by nebulization. Three groups will be enrolled sequentially to receive dose levels 
of MRT5005 investigated as single doses in Part A (ie, 8 mg, 16 mg, and 20 mg). An additional dose 
level that was not investigated in Part A (ie, 12 mg) will also be evaluated in Part B. Within each dose 
group, subjects will be randomized in a 3:1 ratio to receive 5 doses of either MRT5005 or placebo (3 
subjects to receive MRT5005 and 1 subject to receive placebo per dose group), administered 1 dose per 
week for 5 weeks.    
Although 2 dose escalations are planned in both Parts A and B of the study, escalation to the next 
higher dose level may not occur if dose limiting toxicity is encountered at the current dose level. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
16 
Therefore, the number of subjects and groups required to complete the dose escalation sequences in 
either the SAD or MAD parts of the study may be less than planned.  
If subjects do not complete the study or complete certain procedures, additional subjects will be 
enrolled at the Sponsor’s discretion to ensure that at least 16, 16, and 8 evaluable subjects complete 
Parts A, B, and D of the study, respectively. 
Part C (bronchoscopy groups) was removed from the protocol in the 3rd amendment to the protocol 
(Version 4.0 dated 29 July 2019).
Part D: Daily Dose Group (N=8)  
In Part D, 8 subjects will be randomized in a 3:1 ratio to receive 5 consecutive daily doses of either 4 
mg MRT5005 or placebo. Enrollment and treatment of subjects will not be staggered. Part D was added 
to the protocol (Version 5.0 dated 30 July 2020) to evaluate whether febrile reactions observed with 
higher doses (ranging from 8 mg to 24 mg) of MRT5005 are dose dependent or idiosyncratic. 
Investigation of a daily dosing regimen in Part D is attractive given the estimated short half-life of 
CFTR mRNA (14 hours) and translated CFTR protein (29 hours). The anticipated safety of 4 mg 
administered daily for 5 days (20 mg total) can be predicted from the safety and tolerability of 20 mg 
administered as a single dose in Part A.   
Enrollment and Treatment of Additional Groups  
A SAD dose group may be repeated in a new group of subjects in Part A to further assess the safety of 
the dose level before escalating to the next higher dose level, or before allowing it to proceed from 
Part A (SAD) to Part B (MAD). 
It is expected that no more than 1 additional group of 4 subjects will be enrolled into the study. 
Therefore, up to a maximum of 44 evaluable subjects may participate in the study.     
Principal/Coordinating Investigators: 
Objectives: 
Primary 
The primary objective of the study is to evaluate the safety and tolerability of single and multiple 
escalating doses of MRT5005 administered by nebulization to adult subjects with CF.
Secondary
The secondary objective of the study is to evaluate the effect on percent predicted forced 
expiratory volume in 1 second (ppFEV1) and other spirometry parameters after single and 
multiple escalating doses of MRT5005 administered by nebulization to adult subjects with CF. 
Rationale: 
Cystic fibrosis is an autosomal recessive genetic disorder that affects most critically the lungs, but also 
the pancreas, liver, and intestine. Cystic fibrosis is caused by a mutation in the gene encoding for the 
cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a channel for 
transporting chloride across the plasma membrane. The CFTR protein is an important regulator of salt 
and water balance, and absent or decreased function of CFTR in the airway epithelium of CF patients 
results in thick, viscous secretions, which clog the airways and impair mucociliary clearance and other 
host defense mechanisms. This leads to chronic bacterial infection and inflammation of the lungs 
resulting in extensive damage and eventually respiratory failure. Lung disease is the major cause of 
morbidity and mortality in CF patients. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
17 
Messenger RNA (mRNA) therapy represents a new and novel approach for treating CF lung disease. In 
this therapeutic application, mRNA encoding for the wild-type CFTR protein is delivered directly by 
aerosol to the respiratory tract of CF patients resulting in the expression of normally functioning CFTR 
protein in the lungs. The efficient delivery and uptake of mRNA by bronchial epithelial cells is 
facilitated by formulation of the mRNA within cationic lipid-based nanoparticles. Following cellular 
uptake, translation of CFTR mRNA in the cytoplasm leads to the production of normal CFTR protein 
and restoration of CFTR chloride channel activity in the lungs. 
This strategy was used to develop MRT5005, which utilizes an
lipid 
nanoparticle 
 LNP) as the vehicle to deliver 
 mRNA (
 mRNA) to the lungs. 
 mRNA is the active drug 
substance of MRT5005. The primary component of the 
 LNP is the cationic lipid 
 which is mixed with two other non-cationic lipids, 
, to 
form the lipid nanoparticle (LNP). Complexation within the 
 LNP protects 
 mRNA from 
degradation and facilitates its aerosol delivery and uptake by the target bronchial epithelial cells in the 
lungs of CF patients. 
Study MRT5005-101 represents an important first step in the evaluation of mRNA therapy as an 
approach to restoring CFTR function in the lungs of CF patients. The goal was to design a single study 
that could achieve both Phase 1 and 2 objectives while ensuring subject safety. This Phase 1/2, first-in-
human study will evaluate the safety and tolerability of single and multiple escalating doses of 
MRT5005 administered by nebulization to the respiratory tract of adult subjects with CF.  
Investigational Product, Dose, and Mode of Administration: 
MRT5005 is a lipid nanoparticle suspension consisting of 
mRNA (
 mRNA), the active drug substance, 
formulated with the  lipids, 
 MRT5005 is dosed based on its content 
of 
 mRNA.   
MRT5005 will be supplied as a sterile suspension in single-use vials. Each vial contains approximately 
3.2 mL of MRT5005 at a concentration of 0.6 mg/mL of 
mRNA. An InnoSpire Go 
nebulizer will be used to administer MRT5005 by nebulization at a flow rate of approximately 
0.3 mL/minute. MRT5005 will be administered to subjects at the following 5 dose levels: 4, 8, 12, 16, 
20, and 24 mg of 
 mRNA (nominal dose levels). The table below shows the volume of 
MRT5005 suspension to be nebulized and approximate nebulization time for each of the 5 dose levels 
of MRT5005 to be administered. As the medication cup of the InnoSpire Go holds only a maximum of 
8 mL and will not be refilled during nebulization, multiple nebulizers may be used to administer the 
specified volume for each of the dose levels of MRT5005.  
Sterile normal saline (Sodium Chloride Inhalation Solution, USP 0.9%) will be used as placebo. To 
maintain the blind of the study, the volume and nebulization time of placebo, and number of nebulizers 
used to deliver placebo will match that of the MRT5005 dosing group. 
 
Dosing of MRT5005 - Volumes and Nebulization Times 
Dose of MRT5005 (mg)a 
4 
8 
12 
16 
20 
24 
Total Nebulization Volume (mL)b 
7 
14 
21 
28 
35 
42 
Nebulization Time (minutes)c 
22 
44 
66 
89 
110 
133 
No. of Nebulizersd 
1 
2 
3 
4 
5 
6 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
18 
a Nominal dose of 
 mRNA. 
 
bIncludes an additional 0.3 mL per each nebulizer to account for the expected residual volume after nebulization. Based on the measurement 
accuracy of a 10 mL syringe, the volume per nebulizer has been rounded to the nearest 0.2 mL. The total nebulization volume is based on the 
rounded volume per nebulizer and the number of nebulizers. 
c Approximate nebulization time is based on a flow rate of 0.3 mL/minute for the InnoSpire Go nebulizer. This represents actual nebulization 
time and does not include the rest periods between nebulizer changes.       
d The medication cup of the InnoSpire Go nebulizer holds a maximum of 8 mL of solution. As nebulizers will not be refilled during nebulization, 
multiple nebulizers, as shown in the table, will be used to deliver the specified volume for each of the dose levels of MRT5005. The MRT5005 
suspension will be divided equally among the nebulizers.  
Storage of Investigational Product: 
MRT5005 vials should be stored frozen at -80°C ± 5°C (-112°F ± 9°F) in an appropriate freezer until 
the day of use. 
Normal saline solution (placebo comparator) should be stored at controlled room temperature from 
15°C to 30°C (59°F to 86°F).  
Methodology: 
General Study Design 
At least 40 adult male and female patients with CF, 18 years of age or older, are planned to participate in 
the study. Patients who are clinically stable with a forced expiratory volume in 1 second (FEV1
for the study. Women of childbearing potential will also be eligible to participate if they are willing and 
able to comply with contraception requirements. Subjects will be enrolled at multiple centers in the US.  
This Phase 1/2 study is designed as a randomized, double-blind, placebo-controlled, combined single and 
multiple ascending dose (SAD and MAD) trial, which will be conducted in 3 parts. Subjects will be 
administered single and multiple escalating doses of MRT5005 in Parts A and B of the study, 
respectively. In Part D, subjects will be administered 5 consecutive daily doses of 4 mg MRT5005 or 
placebo. There will be an option to enroll and treat additional groups, with up to a maximum of 44 
evaluable subjects participating in the study. Subjects will not be allowed to participate in more than one 
part of the study. 
Flow diagrams of subject enrollment and treatment allocation for Parts A, B, and D of the study are 
presented in Appendix 1. 
In Part A of the study, 4 groups consisting of 4 subjects each will be enrolled sequentially to receive 
single doses of MRT5005 or placebo (normal saline) administered by nebulization. Four dose levels of 
MRT5005 will be investigated: 8, 16, 24, and 20 mg of 
 mRNA (the active drug substance of 
MRT5005). Within each dose group, the enrollment and treatment of the 4 subjects will be staggered by 
at least 1 week. Subjects will be randomized in a 3:1 ratio to receive a single dose of either MRT5005 or 
placebo (3 subjects to receive MRT5005 and 1 subject to receive placebo per dose group).  
The Protocol Safety Review Committee (PSRC) will review blinded safety data to determine if escalation 
to the next higher dose level can proceed, as explained in Section 3.2.2.  
The decision to begin enrollment and treatment of the initial 8 mg multiple-dose group in Part B will also 
be made by the PSRC, based on a review of at least 28 days of safety follow-up for all subjects who 
received a single dose of the 8 mg dose level in Part A. 
In Part B, 4 groups consisting of 4 subjects each will receive multiple doses of nebulized MRT5005 or 
placebo administered by nebulization. Three groups will be enrolled sequentially to receive dose levels 
of MRT5005 investigated as single doses in Part A (8 mg, 16 mg, and 20 mg). An additional dose level 
that was not investigated in Part A (12 mg) will also be evaluated in Part B. The 12 mg dose group may 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
19 
be enrolled in parallel with the 16 and/or 20 mg dose group. Within each dose group, subjects will be 
randomized in a 3:1 ratio to receive 5 doses of either MRT5005 or placebo (3 subjects to receive 
MRT5005 and 1 subject to receive placebo per dose group), administered 1 dose per week for 5 weeks.  
The enrollment and treatment of the 4 subjects within each dose group will be staggered by at least 
2 weeks (the next subject in the dose group will only be enrolled and treated when the previous subject 
has received their second dose and there is approximately 1 week of safety follow-up), with the exception 
of the 12 mg dose group in Part B which will not require staggered treatment under the circumstances 
described in Section 3.1.  
Escalation from 8 mg dose group to the 16 and 12 mg dose groups, and from 16 mg to the 20 mg dose 
group in Part B will occur after review of the following safety data by the PSRC:  
1. At least 1 week of safety follow-up after the 3rd dose of the 4th (last) subject of the previous 
(lower) dose.  
2. At least 28 days of safety follow-up after the dose of the 4th (last) subject of the corresponding 
single dose cohort. For instance, for the decision to escalate from the 8 mg to the 16 mg multiple 
dose cohort, the PSRC will review at least 7 days of safety follow-up after the 3rd dose of the 4th 
(last) subject receiving multiple doses of 8 mg, as well as at least 28 days of safety follow-up 
after the single dose of the 4th (last) subject receiving a single dose of 16 mg.  Note that there is 
no corresponding single dose cohort for the 12 mg multiple dose group and therefore this 
requirement is not applicable. 
In Part D, 8 subjects will be randomized in a 3:1 ratio to receive 5 doses of either 4 mg MRT5005 or 
placebo, administered at 1 dose per day for 5 consecutive days. Because single doses up to 20 mg, as 
well as 5 weekly doses up to 16 mg have been tolerated in Parts A and B, the enrollment and treatment 
of the 8 subjects within Part D will not be staggered. During the treatment of subjects in Part D, should 
AEs occur that indicate the study drug is not tolerated well, the enrollment and treatment of subjects 
may be terminated by the PSRC and Sponsor, and enrollment and treatment of a lower dose strength 
may be considered in the remaining subjects in the cohort. For example, if the tolerability of the 4 mg 
daily dose level is found to be unacceptable, then the 2 mg dose level can be considered for 
investigation.    
The treatment randomization for the 8 mg, 16 mg, and 24 mg single dose groups will be unblinded 1 
month after the last dose of the last subject in the 24 mg single dose group in Part A. The blind will be 
maintained in the 20 mg single dose group in Part A, as well as the 8, 16, and 12 mg multiple dose groups 
in Part B until the 1-month timepoint after the last dose (Day 57) of the last subject dosed in the 12 mg 
dose group. For the 20 mg multiple dose group in Part B (if applicable), the blind will be maintained until 
the last subject in this group has reached the 1-month timepoint after the last dose day (Day 57).  For Part 
D, the blind will be maintained until the 1-month timepoint after the last dose (Day 32) of the last subject 
in Part D. 
All subjects in the study will be monitored for safety for 12 months after administration of the last dose 
of investigational product (IP; post-single dose in Part A; post-fifth dose in Parts B and D). The safety 
and tolerability of nebulized MRT5005 will be assessed based on the types, frequency, and severity of 
treatment-emergent adverse events (AEs) reported including the number of pulmonary exacerbations; 
concomitant medication use; and changes from baseline in physical examination, weight, vital signs, 
oxygen saturation (pulse oximetry), electrocardiogram (ECG), standard clinical laboratory tests, chest x-
ray, and spirometry as a measure of pulmonary function. As part of the safety evaluation, assays to detect 
 mRNA and 
 in the blood post-treatment will be performed along with assays to detect 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
20 
antibody and T cell immune responses to CFTR protein and anti-PEG antibodies. 
To maintain the study blind, the Investigators and all study staff involved in the evaluation of subject 
eligibility, administration of IP, and assessment of study outcomes will be blinded to treatment 
assignment (MRT5005 vs. placebo within each dose group) until planned unblinding. All subjects and 
their families, as well as Sponsor personnel in direct contact with the study center, will also be blinded. 
As the MRT5005 suspension and normal saline placebo will appear different, designated unblinded 
members of the study staff and/or pharmacy will be responsible for preparing and dispensing the IP into 
the nebulizers, as well as for randomizing subjects. The unblinded individuals will not participate in any 
other part of the study. 
Schedule of Procedures for Screening, Treatment, and Follow-up Periods 
Each part of the study will consist of 3 periods: a screening period, a treatment period, and a follow-up 
period. The procedures and tests to be performed during each of these periods in Parts A, B, and D of the 
study are presented in Table 1 through Table 9.  
Part A: Screening Period (Day -28 to Day -2, Table 1) 
During the screening period (from Day -28 to Day -2), informed consent will be obtained from the 
subject; inclusion and exclusion criteria will be reviewed; and subject eligibility for the study will be 
determined based on the procedures and tests performed during this period. Collection of AEs and serious 
adverse events (SAEs), regardless of relationship, and concomitant medications will begin from the time 
the subject signs the informed consent.  
Part A: Treatment Period (Day -1 to Day 2, Table 1)  
During the treatment period, subjects participating in Part A will be confined to the study center 
(inpatient) from Day -1 to Day 2. On Day -1, eligible subjects will perform the baseline procedures and 
tests. On Day 1, the pre-dose assessments should be performed immediately prior to IP administration. 
The procedures and tests performed on Day -1 and pre-dose on Day 1 will be used to confirm eligibility. 
Prior to IP administration on Day 1, subjects should undergo their routine pulmonary therapies (airway 
clearance and pulmonary medications). If a subject is receiving inhaled rhDNase (PULMOZYME), this 
treatment should be withheld 24 hours before and after dosing with IP. The administration of IP should 
optimally occur within 2 to 3 hours after subjects have completed their pulmonary therapies for the day. 
Following randomization, IP will be administered by the respiratory route using an InnoSpire Go 
nebulizer. 
Following IP administration, the Day 1 and 2 post-treatment procedures and tests will be performed at 
the protocol-specified time points. Subjects can be discharged when all of the Day 2 assessments have 
been completed and when subjects have been deemed clinically stable by the Investigator with no ongoing 
AEs or safety concerns. Subjects will be housed overnight close to the study center until the clinic visit 
on the following day (Day 3). 
Part A: Follow-up Period (Day 3 to Day 337, Table 2 and Table 3)  
Safety will be monitored for 12 months after administration of IP. Subjects will return for outpatient 
clinic visits on Days 3, 8, 15, 29, 57, 85, 169, 253, and 337 to perform the follow-up procedures and tests 
scheduled for this period. Telephone contact with the subject will occur on Days 5, 11, 18, 22, 43, 71, 
113, 141, 197, 225, 281, and 309 to query the subject about the occurrence of any AEs/SAEs and any 
changes in concomitant medications. 
Part B: Screening Period (Day -28 to Day -2, (Table 4)  
The subjects participating in Part B of the study will perform the same procedures and tests during the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
21 
screening period as in Part A. 
Part B: Treatment Period (Day -1 to Day 33, Table 4 and Table 7)  
No confinement will be required of subjects in Part B; subjects will perform all clinic visits in the 
treatment period as outpatients.  
On Day -1, eligible subjects will perform the baseline procedures and tests. On days in which IP is 
administered (Days 1, 8, 15, 22, and 29), the pre-dose assessments should be performed immediately 
prior to IP administration. The procedures and tests performed on Day -1 and Day 1 will be used to 
confirm eligibility. As described for Part A, prior to the administration of IP, subjects should undergo 
their routine pulmonary therapies (airway clearance and pulmonary medications). The administration of 
IP should optimally occur within 2 to 3 hours after subjects have completed their pulmonary therapies 
for the day. Following randomization, IP will be administered by the respiratory route using an InnoSpire 
Go nebulizer. 
On dosing days, subjects will remain in the clinic for safety monitoring for at least 6 hours after 
administration of IP and will be discharged only when deemed clinically stable by the Investigator with 
no ongoing AEs or safety concerns of clinical significance. Discharged subjects can go home if they live 
locally (within 1 hour driving distance from the study center) or if not should be housed overnight close 
to the study center until the clinic visit on the following day (Days 2, 9, 16, 23, and 30). The subject will 
be contacted by telephone approximately 3 days after the clinic visit (Days 5, 12, 19, 26, and 33), to query 
the subject about the occurrence of any AEs/SAEs and any changes in concomitant medications. 
Subjects will be provided a digital thermometer and Body Temperature Recording Log for measuring 
and recording body temperature on dosing days after discharge, at regular intervals until bedtime, and as 
needed overnight should febrile symptoms awaken the subject. 
Part B: Follow-up Period (Day 36 to Day 365, Table 5 and Table 6)  
Safety will be monitored for 12 months after administration of the fifth dose of IP. Subjects will return 
for outpatient clinic visits on Days 36, 43, 57, 71, 85, 113, 197, 281, and 365 to perform the follow-up 
procedures and tests scheduled for this period. Telephone contact with the subject will occur on Days 39, 
46, 50, 64, 78, 99, 141, 169, 225, 253, 309, and 337 to query the subject about the occurrence of any 
AEs/SAEs and any changes in concomitant medications. 
Part D: Screening Period (Day -28 to Day -1, Table 8) 
Subjects participating in Part D of the study will perform the same procedures and tests during the 
screening period as in Parts A and B. 
Part D: Treatment Period (Day 1 to Day 5, Table 8) 
No confinement will be required of subjects in Part D; subjects will perform all clinic visits in the 
treatment period as outpatients. Pre-dose assessments on Day 1 should be performed prior to IP 
administration. 
Prior to IP administration, subjects should undergo their routine pulmonary therapies (airway clearance 
and pulmonary medications).  The administration of IP should optimally occur within 2 to 3 hours after 
subjects have completed their pulmonary therapies for the day. Following randomization, IP will be 
administered by the respiratory route using an InnoSpire Go nebulizer. 
On each dosing day, subjects will remain in the clinic for safety monitoring for at least 2 hours after 
administration of IP and will be discharged only when deemed clinically stable by the Investigator with 
no ongoing AEs or safety concerns of clinical significance. Discharged subjects may go home if they live 
locally (within 1 hour driving distance from the study center) or if not should be housed overnight close to 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
22 
the study center until the clinic visit on the following day. If a subject is experiencing an ongoing AE or 
there is a safety concern at the 2-hour time point (eg, decreased oxygen saturation by pulse oximetry or 
airway symptoms), based on the judgment of the Investigator, the subject should remain in the study 
center or hospital until the AE or safety concern has resolved and the subject is sufficiently stable to be 
discharged. 
Subjects will be provided a digital thermometer and Body Temperature Recording Log for measuring 
and recording body temperature on dosing days after discharge, at regular intervals until bedtime, and as 
needed overnight should febrile symptoms awaken the subject. 
Part D: Follow-up Period (Day 8 to Day 341, Table 8 and Table 9) 
Safety will be monitored for approximately 12 months after administration of the fifth dose of IP. 
Subjects will return for outpatient clinic visits on Days 11, 18, 32, 60, 145, 229, and 341 to perform the 
follow-up procedures and tests scheduled for this period. Telephone contact with the subject will occur 
on Days 8, 25, 46, 89, 117, 173, 201, 257, 285, and 313 to query the subject about the occurrence of any 
AEs/SAEs and any changes in concomitant medications. 
Inclusion and Exclusion Criteria: 
To be considered for inclusion in this study, patients must meet all of the following inclusion and none 
of the exclusion criteria.  
Inclusion Criteria: 
1. Male and female patients with CF, 18 years of age or older 
2. Confirmed diagnosis of CF as defined by both of the following: 
 
Two CF disease-causing CFTR mutations in Class I or II (genotype confirmed at the 
screening visit).  CFTR genotyping will only be performed if adequate prior documentation 
is not available. 
 
Chronic sinopulmonary disease and/or gastrointestinal/nutritional abnormalities consistent 
with CF disease. 
3. Clinically stable CF disease, as judged by the Investigator  
4. FEV1
5. 
oximetry) 
6. 
2
7. Willing to remain on stable CF medications for the duration of the study 
Patients who are receiving lumacaftor/ivacaftor or tezacaftor/ivacaftor combination drugs 
(ORKAMBI or SYMDEKO) are eligible for the study; however, patients must have been 
on stable treatment with this medication for at least 28 days prior to the screening visit, and 
should remain on it for the duration of the study preferably at a stable dose. 
8. Non-smoking for a minimum of 2 years   
9. Willing and able to give written, signed, and dated informed consent to participate in the study 
10. Willing and able to comply with scheduled visits, treatment, laboratory tests, restrictions, 
contraception requirements (Section 4.4), and other study procedures  
 
Patients must have adequate clinical condition to safely undergo the planned study 
procedures 
 
Willing and able to receive nebulized IP through a mouthpiece for up to 133 minutes 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
23 
Exclusion Criteria:  
1. History of any comorbidity that, in the opinion of the Investigator, could confound the results of the 
study, pose an additional risk from the IP or study procedures, could potentially contribute to the 
clinical instability of the subject during the study, or would make the subject unlikely to complete 
the study. This may include, but is not limited to a history of cardiovascular, renal, or central nervous 
system disease; history of serious mental illness; history or presence of clinically significant 
pathology including liver cirrhosis and/or portal hypertension; or history of uncontrolled CF-related 
diabetes.   
2. An acute upper or lower respiratory infection, pulmonary exacerbation, or clinically significant 
episode of hemoptysis (>30 mL or in the opinion of the Investigator) within 28 days prior to Day 1.  
3. Any of the following changes in medication prior to Day 1: 
 
Any change in chronic respiratory medication within 28 days prior to Day 1. 
Initiation of any new chronic therapy (eg, inhaled hypertonic saline, or inhaled antibiotic 
(tobramycin [TOBI], aztreonam [CAYSTON]) within 28 days prior to Day 1. 
 
Use of antibiotics or oral steroids for acute symptoms within 14 days prior to Day 1.  
4. Receiving treatment with ivacaftor monotherapy (KALYDECO). 
5. Parts A and B only: Receiving treatment with triple combination therapy (TRIKAFTA). Patients with 
a prior history of treatment with TRIKAFTA are eligible to participate if treatment has been 
discontinued at least 28 days prior to Day 1. 
6. Patients with a Class III, IV, or V CFTR gene mutation in at least 1 allele. 
 
See Appendix 2 for guidance on the classification of CFTR mutations. As the phenotype 
and classification of some CFTR mutations remains uncertain, the eligibility of a patient 
with 1 of these mutations will be at the discretion of the Investigator and Sponsor, based on 
the patient’s medical history. 
7. Any of the following abnormal laboratory values at screening: 
 
Hemoglobin <10 g/dL. 
 
Serum albumin <2.5 g/dL. 
 
Abnormal liver function defined as meeting any 3 or more of the following: ALT 
>3x upper limit of normal (ULN); AST >3x ULN; GGT >2.5x ULN; alkaline phosphatase 
>2.5x ULN; and total bilirubin >1.5x ULN (except for patients with isolated Gilbert 
Syndrome).  
8. Any clinically significant abnormal laboratory test result prior to Day 1 that would interfere with the 
study assessments or indicate clinical instability of the patient, as judged by the Investigator. 
9. Infection with highly virulent bacteria associated with accelerated decline in pulmonary function 
and/or decreased survival (eg, Burkholderia cenocepacia, Burkholderia dolosa, Mycobacterium 
abscessus). For a patient with a history of positive culture, he/she can be considered free of infection 
based on the following guidance: 
 
All cultures obtained within the past 12 months should be negative for these bacteria. The 
patient should have had at least 2 cultures performed within the past 12 months, at least 
3 months apart, with at least 1 culture obtained within 6 months of screening for this study. 
10. History of or listed for solid organ or hematological transplantation.   
11. Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface antigen 
(HBsAg), or hepatitis C virus (HCV) antibodies at screening. 
12. Positive test for drugs of abuse or alcohol at the screening visit.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
24 
13. Donation of blood or blood products within 60 days prior to the initial screening visit.
14. Participation in an investigational product or device study within 30 days prior to the initial screening 
visit or at any time during this Translate Bio-Sponsored study. (The 30-day window applies to 
investigational products with elimination half-lives of <6 days. If the elimination half-life of the 
 days, then the window should be extended to at least 5 half-lives from 
the last dose administered.)   
15. Prior enrollment in this study, with the exception of subjects who discontinued treatment after one 
dose of study drug for a reason unrelated to safety as specified in Section 7.1.1.2. (A patient is 
considered enrolled into the study when he or she has been randomized.) 
16. Any suspicion of, or history of, alcohol and/or other substance abuse or addiction within the past 
year. 
17. Pregnant or lactating females. 
18. History of drug allergy or other allergy that, in the opinion of the Investigator, contraindicates 
participation (eg, history of allergy reactions that could interfere with the safety assessment of the 
IP). 
19. History of allergic reactions to any component of the IP including its excipients. 
Maximum duration of subject involvement in the study: 
Planned maximum duration of study participation in Part A: up to 368 days. This consists of an initial 
screening period of up to 27 days, followed by 338 days [+3-day window] of the treatment and follow-
up periods of the study. 
Planned maximum duration of study participation in Part B: up to 396 days. This consists of an initial 
screening period of up to 27 days, followed by 366 days [+3 day window] of the treatment and follow-
up periods of the study. 
Planned maximum duration of study participation in Part D: up to 372 days. This consists of an initial 
screening period of up to 28 days, followed by 341 days (+ 3-day window) of the treatment and follow-
up periods of the study. 
Study Endpoints:
Primary endpoint 
The safety and tolerability of nebulized MRT5005 will be assessed based on the types, frequency, and 
severity of treatment-emergent AEs including pulmonary exacerbations; concomitant medication use; 
and changes from baseline in physical examination, weight, vital signs, oxygen saturation (pulse 
oximetry), ECG, standard clinical laboratory tests, chest x-ray, and spirometry as a measure of 
pulmonary function.  
Secondary endpoint 
The biological activity of nebulized MRT5005 will be assessed based on changes from baseline in 
ppFEV1 and other spirometry parameters. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
25 
Statistical analysis: 
The sample size is not based on any statistical considerations. The sample size is based on traditional 
Phase 1/2, first-in-human study designs for this disease population.  
All analyses will use descriptive rather than inferential approaches given the objectives of the study. 
This includes the primary endpoint analyses for safety as well as for the analyses of the secondary 
endpoints. All summaries will be displayed by treatment group. Summary statistics for continuous 
variables will include the number of subjects (N), mean, standard deviation, minimum, median, and 
maximum. For categorical data, summaries will include the frequency and percentage. 
The primary analysis population for safety will be the safety analysis set, which will include all 
randomized subjects who received IP. Subject disposition, demographics and baseline characteristics, 
IP exposure, and prior and concomitant medications will be summarized. The number and percentage 
of treatment-emergent AEs will be calculated overall, by system organ class, by preferred term, and by 
treatment group. Treatment-emergent AEs will be further summarized by severity and relationship to 
IP. Adverse events related to IP, AEs leading to withdrawal, SAEs, and deaths will be similarly 
summarized or listed. Results from vital sign and pulse oximetry measurements, clinical laboratory 
tests, ECGs, spirometry testing, and chest x-rays will be summarized by treatment, dose group, and 
visit. Clinically important findings will also be summarized or listed. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
26 
Table 1:
Part A - Schedule of Procedures for the Screening and Treatment Periods - Day -28 to Day 2
 
Screening 
Period 
Treatment Period 
Study Week 
 
Baseline 
Week 1 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Day 2 
Time point 
(Hours post nebulization) 
 
Pre-
dosea 
Dosing 
0b 
(±5 min) 
0.5 
(±5 min) 
1 
(±5 min) 
2 
(±5 min)
4 
(±15 min) 
6 
(±15 min) 
8c 
(±15 min) 
24d
(±2 hours)
Screening Visit(s)e 
X 
 
 
 
 
 
 
 
 
In-house confinement at study center 
(inpatient) 
X 
X 
X 
X 
X 
X 
X
X
X 
X 
X 
Informed consent (Part A) 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demography and medical/medication 
history 
X 
X 
 
 
 
 
 
 
 
Physical examination 
X 
X 
Xf 
 
Xf 
 
Xf 
Xf 
Xf
 
Xf
X
Vital signsg 
 
 
 
 
 
 
 
 
 
 Blood pressure, pulse rate, body 
temperature 
X 
X 
X 
Xh 
X 
X 
X 
X
X
X 
X 
X 
 Respiratory rate 
X 
X 
X 
 
X 
X 
X 
X
X
X 
X 
X 
Pulse oximetry 
X 
X 
X 
Xi 
X 
X 
X 
X
X
X 
X 
X 
Heightj 
X 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
Electrocardiogram (ECG) 
X 
X 
Xq 
 
 
 
 
 
 
X
X 
Serum chemistrys, hematology, 
coagulation, urinalysis, CRP 
X 
X 
 
 
 
 
 
 
 
X
Serum or urine pregnancy testk 
X 
X 
 
 
 
 
 
 
 
Drug and alcohol screening 
X 
 
 
 
 
 
 
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
27 
Table 1:
Part A - Schedule of Procedures for the Screening and Treatment Periods - Day -28 to Day 2
 
Screening 
Period 
Treatment Period 
Study Week 
 
Baseline 
Week 1 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Day 2 
Time point 
(Hours post nebulization) 
 
Pre-
dosea 
Dosing 
0b 
(±5 min) 
0.5 
(±5 min) 
1 
(±5 min) 
2 
(±5 min)
4 
(±15 min) 
6 
(±15 min) 
8c 
(±15 min) 
24d
(±2 hours)
Spirometryl 
X 
X 
Xq 
 
 
 
 
 
 
Xl
X 
Viral screen (HIV, HBV, HCV) 
X 
 
 
 
 
 
 
 
 
Chest x-raym 
X 
 
 
 
 
 
 
 
 
mRNA and 
 assayso 
 
X 
 
 
 
 
 
 
 
X
X 
Immune response assaysn,o 
X 
 
 
 
 
 
Adverse event collectionp 
X 
X 
X 
X 
X 
X 
X 
X
X
X 
X 
X 
Concomitant medication collectionp 
X 
X 
X 
X 
X 
X 
X 
X
X
X 
X 
X 
Concomitant surgical procedure 
collectionp 
X 
X 
X 
X 
X 
X 
X 
X
X
X 
X 
X 
Randomizationq 
 
 
X 
 
 
 
 
 
 
IP dosingr 
 
 
 
X 
 
 
 
 
 
Abbreviations: CRP: C reactive protein; HIV: human immunodeficiency virus; HBV: hepatitis B virus; HCV: hepatitis C virus; 
a  The pre-dose assessments should be performed immediately prior to IP administration. If the subject is receiving treatment with a short-acting bronchodilator 
as part of their routine pulmonary therapies, pre-dose spirometry testing may be scheduled before the subject’s pulmonary therapies (if the subject’s schedule 
permits) so that it can be performed “pre-bronchodilator.” See footnotes l and q.      
b  Hour 0 corresponds to the end of nebulization of IP. 
c  If there is ongoing AE or safety concern of clinical significance at the 8-hour time point (eg, decreased oxygen saturation or airway symptoms), appropriate 
monitoring should continue until the AE or safety concern has resolved.       
d  Subjects can be discharged when all of the Day 2 assessments have been completed and when subjects have been deemed clinically stable by the Investigator 
with no ongoing AEs or safety concerns of clinical significance. Discharged subjects should be housed overnight close to the study center until the clinic visit 
on the following day (Day 3). If a subject is experiencing an ongoing AE or there is a safety concern on Day 2, based on the judgment of the Investigator, the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
28 
subject can remain in the study center overnight or can be hospitalized for continued monitoring until the clinic visit on the following day (Day 3). The subject 
should remain in the study center or hospital until the AE or safety concern has resolved and the subject is sufficiently stable to be discharged.     
e  Multiple visits during the screening period may be necessary for the subject to complete all of the required screening procedures and tests. 
f  A limited physical examination will be performed at these time points.  
g  Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
h  Blood pressure and pulse rate will be monitored continuously during nebulization of IP (except during rest periods), and will be recorded at the end of 
nebulization with each of the multiple nebulizers used to deliver the total volume of IP (eg, for the 16 mg dose, blood pressure and pulse rate will be recorded 
at the end of nebulization with each of the 4 nebulizers used to deliver the 28 mL total volume); the final recording will count as the Hour 0 time point. Blood 
pressure or pulse rate may be recorded more frequently, if clinically indicated. (Body temperature will not be monitored during the dosing period.)  
i Oxygen saturation, measured by pulse oximetry, will be monitored continuously during nebulization of IP, and will be recorded at the end of nebulization with 
each of the multiple nebulizers used to deliver the total volume of IP (see footnote h for example); the final recording will count as the Hour 0 time point. 
Oxygen saturation may be recorded more frequently, if clinically indicated.   
j All body mass index calculations will use the subject’s height measured at the initial screening visit. 
k  
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the initial screening visit and on 
Day -l 
l  If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting 
bronchodilator (Section 7.5.2.12). The spirometry testing at the 8-hour time point on Day 1 has an expanded window of ±1 hour to accommodate this. If a 
subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be performed when 
the subject is stable. 
m Chest x-rays will consist of routine posterioranterior and lateral views. The baseline chest x-ray can be performed at any time from Day -14 to Day -2 during 
the screening period. 
n  Assays will measure antibody and T cell responses to CFTR protein as well as anti-PEG antibodies.  
o  In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays and/or 
 mRNA and 
 assays 
may also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or unexplained bronchospasm. 
p  All AEs and SAEs, regardless of relationship, concomitant medications, and concomitant surgical procedures will be collected from the time the subject signs 
the inform consent.   
q  Subjects should be randomized following confirmation of eligibility on Day 1. Confirmation of eligibility on Day 1 requires a review of the Day -1 results and 
pre-dose Day 1 results of physical exam, AE, conmeds, vital signs and pulse oximetry. A subject is considered enrolled into the study when he or she has been 
randomized. 
r  The Day 1 pre-dose ECG and spirometry must be reviewed before the first dose may be administered.  The administration of IP should optimally occur within 
2-3 hours after subjects have completed their routine pulmonary therapies (airway clearance and pulmonary medications) for the day. For subjects whose 
pulmonary medications do not include an inhaled short-acting beta-agonist (or it is not given within the 2 to 3 hour window prior to IP administration), 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
29 
albuterol (2 to 4 puffs) will be administered approximately 20 minutes before treatment with IP. IP will be administered by the respiratory route using an 
InnoSpire Go nebulizer. Depending on the dose level, nebulization times will range from approximately 44 to 133 minutes (represents actual nebulization 
times, and does not include the rest periods between nebulizer changes). During nebulization of IP, the subject should be monitored closely for any signs or 
symptoms of respiratory distress (eg, dyspnea, wheezing, bronchospasm) 
s  Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry blood collections. 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
30 
Table 2: 
Part A - Schedule of Procedures for the Follow-up Period - Day 3 to Day 85 
 
Follow-up Period 
Study Week 
Week 1 (cont’d)  
Week 2a 
Week 3a 
Week 
4 
Week 5 
Week 
7
Week 9 
Week 11 
Week 13 
Study Day 
Day 3 
Day 5 
Day 8 
(±1 day) 
Day 11 
(+3 or +4 
days post 
Day 8) 
Day 15 
(±1 day) 
Day 18 
(+3 or +4 
days post 
Day 15) 
Day 22
(±2 
days) 
Day 29
(±2 days) 
Day 43 
(±3 
days) 
Day 57 
(±3 days) 
Day 71 
(±3 days) 
Day 85 
(±3 days)
Clinic visit (outpatient)b 
X 
X 
 
X 
 
 
X
 
X 
 
X 
Telephone contact 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
Physical examination 
X 
 
X 
 
X 
 
 
X
 
X 
 
X 
Vital signsc 
 
 
 
 
 
 
 
 
 
 
 
 
 Blood pressure, pulse rate, 
body temperature 
X 
 
X 
 
X 
 
 
X
 
X 
 
X 
 Respiratory rate 
X 
 
X 
 
X 
 
 
X
 
X 
 
X 
Pulse oximetry 
X 
 
X 
 
X 
 
 
X
 
X 
 
X 
Weight 
 
 
X 
 
X 
 
 
X
 
X 
 
X 
Electrocardiogram (ECG) 
 
 
X 
 
X 
 
 
X
 
X 
 
X 
Serum chemistryh, hematology, 
coagulation, urinalysis, CRP 
 
 
X 
 
X 
 
 
X
 
 
 
X 
Spirometryd 
X 
X 
 
X 
 
 
X
 
X 
 
X 
Chest x-raye 
 
 
X 
 
 
 
 
X
 
 
 
 
 mRNA and 
 
assaysg 
 
 
X 
 
X 
 
 
X 
 
Immune response assaysf,g 
 
 
 
 
X 
 
 
X
 
 
 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X
X 
X
X 
X

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
31 
Table 2: 
Part A - Schedule of Procedures for the Follow-up Period - Day 3 to Day 85 
 
Follow-up Period 
Study Week 
Week 1 (cont’d)  
Week 2a 
Week 3a 
Week 
4 
Week 5 
Week 
7
Week 9 
Week 11 
Week 13 
Study Day 
Day 3 
Day 5 
Day 8 
(±1 day) 
Day 11 
(+3 or +4 
days post 
Day 8) 
Day 15 
(±1 day) 
Day 18 
(+3 or +4 
days post 
Day 15) 
Day 22
(±2 
days) 
Day 29
(±2 days) 
Day 43 
(±3 
days) 
Day 57 
(±3 days) 
Day 71 
(±3 days) 
Day 85 
(±3 days)
Concomitant medication 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X 
Concomitant surgical procedure 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X 
Abbreviations: CRP: C reactive protein; 
. 
 
a  The timing of the telephone contacts during Weeks 2 and 3 is based on the number of days (+3 or +4) after the actual visits for Days 8 and 15.   
b Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 
c  Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
d   If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator 
(Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be 
performed when the subject is stable. 
e  Chest x-rays will consist of routine posterioranterior and lateral views. At the discretion of the Investigator, an unscheduled chest x-ray may be performed at any 
time during the follow-up period if the subject is experiencing respiratory symptoms that warrant it.  
f  Assays will measure antibody and T cell responses to CFTR protein and anti-PEG antibodies. 
g In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays and/or 
 mRNA and 
 assays may 
also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or unexplained bronchospasm. 
h  Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry study blood collections.  
 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
32 
Table 3: 
Part A - Schedule of Procedures for the Follow-up Period - Day 113 to Day 337 
 
Follow-up Period 
Study Week 
Week 17
Week 21 
Week 25 
Week 29 
Week 33 
Week 37 
Week 41
Week 45
Week 49 
Study Day 
Day 113 
(±3 days) 
Day 141 
(±3 days) 
Day 169 
(±3 days) 
Day 197 
(±3 days) 
Day 225 
(±3 days) 
Day 253 
(±3 days)
Day 281 
(±3 days) 
Day 309 
(±3 days)
Day 337 
(±3 days) 
Clinic visit (outpatient)a 
 
 
X 
 
 
X 
 
 
X 
Telephone contact 
X 
X 
 
X 
X 
 
X
X
 
Physical examination 
 
 
X 
 
 
X 
 
 
X 
Vital signsb 
 
 
 
 
 
 
 
 Blood pressure, pulse, body 
temperature 
 
 
X 
 
 
X 
 
 
X
 Respiratory rate 
 
 
X 
 
 
X 
 
 
X
Pulse oximetry 
 
 
X 
 
 
X 
 
 
X
Weight 
 
 
X 
 
 
X 
 
 
X
Electrocardiogram (ECG) 
 
 
X 
 
 
X 
 
 
X
Serum chemistryf, hematology, 
coagulation, urinalysis, CRP 
 
 
X 
 
 
 
 
 
X
Spirometryc 
 
 
X 
 
 
X 
 
 
X
Immune response assaysd 
 
 
X 
 
 
 
 
 
Xc
Serum or urine pregnancy teste 
 
 
 
 
 
 
 
 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X
Concomitant medication collection 
X 
X 
X 
X 
X 
X 
X 
X 
X
Concomitant surgical procedure 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X
Abbreviations: CRP: C reactive protein. 
a Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
33 
b Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
c If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator 
(Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be 
performed when the subject is stable. 
d Assays will measure antibody and T cell responses to CFTR protein and anti-PEG antibodies. The blood collections for any of these assays on the final study day 
(Day 337) are optional and will be driven by the observation of a de novo positive immune response after treatment (see Section 7.5.2.15). In the event of 
inconclusive, invalid, or missing assay results at the Day 169 visit, the blood collection for one or more of these assays will be taken at Day 337 at the discretion of 
the Sponsor. In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays and/or 
mRNA and
assays may also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or unexplained bronchospasm. 
e 
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the end of the study on Day 337. In addition, 
a serum or urine -hCG pregnancy test should be performed on female subjects at any time pregnancy is suspected or upon withdrawal from the study (the latter 
applies to all female subjects, regardless of childbearing potential). 
f Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry blood collections. 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
34 
Table 4:      Part B - Schedule of Procedures for the Screening and Treatment Periods - Day -28 to Day 33   
 
Screening 
Period 
Treatment Period 
Study Week  
 
Base-
line 
Week 1a 
Week 2 
Week 3 
Week 4 
Week 5 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Day 2 
Day 5 
+4 days 
post  
Dose 1 
(±1 day) 
Day 8 
(±1 day) 
 
Day 9 
+1 day 
post  
Dose 2 
Day 12 
+4 days 
post  
Dose 2 
(±1 day) 
Day 15 
(±1 day) 
Day 16 
+1 day 
post 
Dose 3
Day 19 
+4 days 
post 
Dose 3
(±1 day)
Day 22 
(±1 day) 
Day 23 
+1 day 
post  
Dose 4 
Day 26 
+4 days 
post 
Dose 4
(±1 day)
Day 29 
(±1 day)
Day 30 
+1 day 
post 
Dose 5
Day 33 
+4 days 
post 
Dose 5
(±1 day)
Investigational Product 
 
 
Dose 1 
 
 
Dose 2 
 
 
Dose 3 
 
 
Dose 4 
 
Dose 5 
 
 
Screening Visit(s)b 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinic visit - outpatientc 
 
X 
Xd 
X 
 
Xd 
X 
 
Xd 
X 
 
Xd
X 
 
Xd
X 
 
Telephone contact 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Informed consent e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and 
medical/medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
Xe 
Xf 
 
Xe 
Xf 
 
Xe 
Xf 
 
Xe
Xf 
 
Xe 
Xf
 
Vital signsg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Blood pressure, pulse, 
body temperature 
X 
X 
Xh 
X 
 
Xh 
X 
 
Xh 
X 
 
Xh
X 
 
Xh
X 
 
 Respiratory rate 
X 
X 
Xh 
X 
 
Xh 
X 
 
Xh 
X 
 
Xh
X 
 
Xh
X 
 
Pulse oximetry 
X 
X 
Xi
X 
 
Xi 
X 
 
Xi 
X 
 
Xi 
X 
 
Xi 
X 
 
Heightj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
Xk 
 
 
Xk 
 
 
Xk
 
Xk
 
 
Serum chemistryw, 
hematology, coagulation, 
urinalysis, CRP 
X 
X 
 
 
 
 
 
Xl 
 
 
 
 
Xl 
X 
 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
35 
Table 4:      Part B - Schedule of Procedures for the Screening and Treatment Periods - Day -28 to Day 33   
 
Screening 
Period 
Treatment Period 
Study Week  
 
Base-
line 
Week 1a 
Week 2 
Week 3 
Week 4 
Week 5 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Day 2 
Day 5 
+4 days 
post  
Dose 1 
(±1 day) 
Day 8 
(±1 day) 
 
Day 9 
+1 day 
post  
Dose 2 
Day 12 
+4 days 
post  
Dose 2 
(±1 day) 
Day 15 
(±1 day) 
Day 16 
+1 day 
post 
Dose 3
Day 19 
+4 days 
post 
Dose 3
(±1 day)
Day 22 
(±1 day) 
Day 23 
+1 day 
post  
Dose 4 
Day 26 
+4 days 
post 
Dose 4
(±1 day)
Day 29 
(±1 day)
Day 30 
+1 day 
post 
Dose 5
Day 33 
+4 days 
post 
Dose 5
(±1 day)
Investigational Product 
 
 
Dose 1 
 
 
Dose 2 
 
 
Dose 3 
 
 
Dose 4 
 
Dose 5 
 
 
Serum or urine pregnancy 
testm 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and alcohol screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry 
X 
X 
Xn 
X 
 
Xn 
X 
 
Xn 
X 
 
Xn
X 
 
Xn
X 
 
Viral screening (HIV, HBV, 
HCV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest x-rayo 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Electrocardiogram (ECG) 
X 
X 
X 
 
 
 
 
Xp 
 
 
 
 
Xp
X 
 
 mRNA and 
 
assayss 
 
X 
X 
 
Xq 
 
 
 
 
 
 
 
Xq
X 
 
Immune response assaysr,s 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CFQ-R 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event collections 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
collectiont 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant surgical 
procedure collectiont 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomizationu 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IP dosingv 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
Dispense thermometer  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
36 
Table 4:      Part B - Schedule of Procedures for the Screening and Treatment Periods - Day -28 to Day 33   
 
Screening 
Period 
Treatment Period 
Study Week  
 
Base-
line 
Week 1a 
Week 2 
Week 3 
Week 4 
Week 5 
Study Day 
Day -28 to -2 
Day -1 
Day 1 
Day 2 
Day 5 
+4 days 
post  
Dose 1 
(±1 day) 
Day 8 
(±1 day) 
 
Day 9 
+1 day 
post  
Dose 2 
Day 12 
+4 days 
post  
Dose 2 
(±1 day) 
Day 15 
(±1 day) 
Day 16 
+1 day 
post 
Dose 3
Day 19 
+4 days 
post 
Dose 3
(±1 day)
Day 22 
(±1 day) 
Day 23 
+1 day 
post  
Dose 4 
Day 26 
+4 days 
post 
Dose 4
(±1 day)
Day 29 
(±1 day)
Day 30 
+1 day 
post 
Dose 5
Day 33 
+4 days 
post 
Dose 5
(±1 day)
Investigational Product 
 
 
Dose 1 
 
 
Dose 2 
 
 
Dose 3 
 
 
Dose 4 
 
Dose 5 
 
 
Distribute Body Temp Log  
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
Collect Body Temp Log  
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
20 mg Dose Group Only 
 
Serum inflammatory 
markerss 
 
X 
X 
 
Xq 
 
 
 
 
 
 
 
Xq, 
X 
 
Abbreviations: CRP: C reactive protein; HIV: human immunodeficiency virus; HBV: hepatitis B virus; HCV: hepatitis C virus; 
 CFQ-
R: Cystic Fibrosis Questionnaire-Revised. 
a  IP dosing should occur on approximately the same day of Weeks 1 through 5 (eg, every Tuesday [the day of the week is defined by the first dose given on Day 1 of 
Week 1]), but may occur ±1 day of the target day for Weeks 2 through 5 in order to facilitate subject scheduling. If at all possible, missed dosing of IP should be 
avoided. As such, if a subject is outside of the recommended window, the subject can be administered IP up to 3 days after the target day (eg, if the target day is 
Tuesday, then IP can be administered up to Friday). The subsequent dosing of IP can return to the original schedule. Except for Day 2 of Week 1, the timing of the 
clinic visits and telephone contacts post-treatment during Weeks 1 through 5 is based on the number of days after actual dosing of IP during that week.  
b   Multiple visits during the screening period may be necessary for the subject to complete all of the required screening procedures and tests. 
c  Subjects will perform all clinic visits in Part B of the study as outpatients.   
d  See Table 7 for the schedule of procedures and tests, and instructions on safety monitoring and discharge of subjects on the day of dosing. Discharged subjects can 
go home if they live locally (within 1 hour driving distance from the study center) or if not should be housed overnight close to the study center until the clinic visit 
on the following day. 
e  See Table 7 for the schedule and details of the physical examinations to be performed on the day of dosing.  
f  A limited physical examination will be performed at these time points.  

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
37 
g  Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
h  See Table 7 for the schedule of vital sign measurements to be performed on the dosing days. 
i  See Table 7 for the schedule of pulse oximetry measurements to be performed on the dosing days.    
j   All body mass index calculations will use the subject’s height measured at the initial screening visit. 
k  Weight will be measured as a pre-dose assessment on dosing Days 8, 15, 22, and 29 (Table 7).     
l  Serum chemistry, hematology, coagulation, urinalysis, and CRP will be measured as pre-dose assessments on dosing Days 15 and 29 (Table 7).     
m  
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the initial screening visit and on Day -1.     
n   Spirometry will be performed pre-dose and at the 6-hour post-treatment time point on all dosing days (Table 7). If feasible for the subject, all spirometry testing 
should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator (Section 7.5.2.12). If a subject experiences 
respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be performed when the subject is stable. 
o  Chest x-rays will consist of routine posterioranterior and lateral views. The baseline chest x-ray can be performed at any time from Day -14 to Day -2 during the 
screening period. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be performed at any time during the treatment period if the subject 
is experiencing respiratory symptoms that warrant it. 
p   An electrocardiogram will be performed pre-dose on dosing Day 15; and pre-dose and 6 hours after treatment on dosing Day 29 (Table 7).     
q  Inflammatory markers (20 mg dose group only), as well as 
 mRNA and 
 will be measured as pre-dose assessments on dosing Days 8 and 29 
(Table 7).      
r  Assays will measure antibody and T cell responses to CFTR protein and anti-PEG antibodies.  
s  In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays, inflammatory markers (20 mg dose group only), 
and/or 
 mRNA and 
 assays may also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or 
unexplained bronchospasm.  
t   All AEs and SAEs, regardless of relationship, concomitant medications, and concomitant surgical procedures will be collected from the time the subject signs the 
informed consent form.   
u  See Table 7 for instructions on randomization of subjects on Day 1. 
v  See Table 7 for details on dosing of IP.      
w  Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry study blood collections.  

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
38 
Table 5:      Part B  - Schedule of Procedures for the Follow-up Period - Day 36 to Day 113  
 
Follow-up Period 
Study Week 
Week 6a 
Week 7a 
Week 8 
Week 9 
Week 10 
Week 11 
Week 12 
Week 13 
Week 15 
Week 17 
Study Day 
Day 36 
(±1 day) 
Day 39 
(+3 or +4 
days post 
Day 36) 
Day 43 
(±1 day) 
Day 46 
(+3 or +4 
days post 
Day 43) 
Day 50 
(±2 days) 
Day 57 
(±2 days) 
Day 64 
(±3 days) 
Day 71 
(±3 days) 
Day 78 
(±3 days) 
Day 85 
(±3 days) 
Day 99 
(±3 days) 
Day 113
(±3 days) 
Clinic visit - outpatientb 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Telephone contact 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
Physical examination 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Vital signsc 
 
 
 
 
 
 
 
 
 
 
 
 
 Blood pressure, pulse, 
body temperature 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 Respiratory rate 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Pulse oximetry 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Weight 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Electrocardiogram (ECG) 
X 
 
X 
 
 
X 
 
 
 
X 
 
X 
Serum chemistryh, 
hematology, coagulation, 
urinalysis, CRP 
X 
 
X 
 
 
X 
 
 
 
 
 
X 
Serum inflammatory 
markers (20 mg dose group 
only)g 
X 
 
 
 
 
 
 
 
 
 
 
 
Spirometryd 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Chest x-raye 
X 
 
 
 
 
X 
 
 
 
 
 
 mRNA and 
 assaysg 
X 
 
X 
 
 
X 
 
 
 
 
 
 
Immune response assaysf,g 
X 
 
 
 
 
X 
 
 
 
 
 
X 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
39 
Table 5:      Part B  - Schedule of Procedures for the Follow-up Period - Day 36 to Day 113  
 
Follow-up Period 
Study Week 
Week 6a 
Week 7a 
Week 8 
Week 9 
Week 10 
Week 11 
Week 12 
Week 13 
Week 15 
Week 17 
Study Day 
Day 36 
(±1 day) 
Day 39 
(+3 or +4 
days post 
Day 36) 
Day 43 
(±1 day) 
Day 46 
(+3 or +4 
days post 
Day 43) 
Day 50 
(±2 days) 
Day 57 
(±2 days) 
Day 64 
(±3 days) 
Day 71 
(±3 days) 
Day 78 
(±3 days) 
Day 85 
(±3 days) 
Day 99 
(±3 days) 
Day 113
(±3 days) 
CFQ-R 
X 
 
X 
 
 
X 
 
 
 
X 
 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant surgical 
procedure collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: CRP: C reactive protein; 
; CFQ-R: Cystic Fibrosis Questionnaire-Revised. 
a   The timing of the telephone contacts during Weeks 6 and 7 is based on the number of days (+3 or +4) after the actual visits for Days 36 and 43.   
b Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 
c  Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
d  If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator 
(Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be 
performed when the subject is stable. 
e  Chest x-rays will consist of routine posterioranterior and lateral views. At the discretion of the Investigator, an unscheduled chest x-ray may be performed at any 
time during the follow-up period if the subject is experiencing respiratory symptoms that warrant it.  
f  Assays will measure antibodies and T cell responses to CFTR protein and anti-PEG antibodies.  
g   In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays, inflammatory markers (20 mg dose group only), 
and/or 
 mRNA and
 assays may also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or 
unexplained bronchospasm. 
h  Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry study blood collections.  

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
40 
Table 6: 
Part B - Schedule of Procedures for the Follow-up Period - Day 141 to Day 365 
 
Follow-up Period 
Study Week 
Week 21 
Week 25 
Week 29 
Week 33 
Week 37 
Week 41 
Week 45  
Week 49 
Week 53 
Study Day 
Day 141 
(±3 days) 
Day 169 
(±3 days) 
Day 197 
(±3 days) 
Day 225 
(±3 days) 
Day 253 
(±3 days) 
Day 281 
(±3 days) 
Day 309 
(±3 days) 
Day 337 
(±3 days) 
Day 365 
(±3 days) 
Clinic visit (outpatient)a 
 
 
X 
 
 
X 
 
 
X 
Telephone contact 
X 
X 
 
X 
X 
 
X 
X 
 
Physical examination 
 
 
X 
 
 
X 
 
 
X 
Vital signsb 
 
 
 
 
 
 
 
 
 
 Blood pressure, pulse, body 
temperature 
 
 
X 
 
 
X 
 
 
X 
 Respiratory rate 
 
 
X 
 
 
X 
 
 
X 
Pulse oximetry 
 
 
X 
 
 
X 
 
 
X 
Weight 
 
 
X 
 
 
X 
 
 
X 
Electrocardiogram (ECG) 
 
 
X 
 
 
X 
 
 
X 
Serum chemistryf, hematology, 
coagulation, urinalysis, CRP 
 
 
X 
 
 
 
 
 
X 
Spirometryc 
 
 
X 
 
 
X 
 
 
X 
Immune response assaysd 
 
 
X 
 
 
 
 
 
Xc 
Serum or urine  pregnancy teste 
 
 
 
 
 
 
 
 
X 
CFQ-R 
 
 
X 
 
 
X 
 
 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant surgical procedure collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: CRP: C reactive protein; CFQ-R: Cystic Fibrosis Questionnaire-Revised. 

MRT5005-101  
Translate Bio, Inc.
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
41 
a  Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 
b Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
c  If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator 
(Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled spirometry testing may be 
performed when the subject is stable. 
d  Assays will measure antibody and T cell responses to CFTR protein and anti-PEG antibodies. The blood collections for any of these assays on the final study day 
(Day 365) are optional and will be driven by the observation of a de novo positive immune response after treatment (Section 7.5.2.15). In the event of inconclusive, 
invalid, or missing assay results at the Day 197 visit, the blood collection for one or more of these assays will be taken at Day 365 at the discretion of the Sponsor. In 
addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays, inflammatory markers (20 mg dose group only), 
and/or 
 mRNA and 
 assays may also be performed when immunogenicity is suspected, such as allergy/hypersensitivity events or unexplained 
bronchospasm. 
e  
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the end of the study on Day 365. In 
addition, a serum or urine -hCG pregnancy test should be performed on female subjects at any time pregnancy is suspected or upon withdrawal from the study (the 
latter applies to all female subjects, regardless of childbearing potential).  
f  Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry study blood collections.  
 
 
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
42 
Table 7:
Part B - Schedule of Procedures for Dosing Days - Weeks 1 Through 5   
Study Day 
Dosing Days 1, 8, 15, 22, and 29  
Time point 
(Hours post nebulization) 
Pre-dosea
Dosing 
0b 
(±5 min) 
0.5 
(±5 min) 
1 
(±5 min) 
2 
(±5 min) 
4 
(±15 min)
6c 
(±15 min)
Physical examination 
Xd 
 
Xe 
 
Xe
Xe
Xe 
Xe 
Vital signsf 
 
 
 
 
 
 
 
 
 Blood pressure, pulse, body temperature 
X 
Xg 
X 
X 
X 
X
X 
X 
 Respiratory rate 
X 
 
X 
X 
X 
X
X 
X 
Pulse oximetry 
X 
Xh 
X 
X 
X 
X
X 
X 
Spirometryi 
X 
 
 
 
 
 
 
Xi
Adverse event collection 
X 
X 
X 
X 
X 
X
X 
X 
Concomitant medication collection 
X 
X 
X 
X 
X 
X
X 
X 
Concomitant surgical procedure collection 
X 
X 
X 
X 
X 
X
X 
X 
IP dosingj 
 
X 
 
 
 
 
 
 
 
Dosing Day 1 only
Randomizationk 
X 
 
 
 
 
 
 
 
 
Dosing Days 15 and 29 only  
Serum chemistrym, hematology, coagulation, 
urinalysis, CRP 
X 
 
 
 
 
 
 
 
Electrocardiogram (ECG) 
Xl 
 
 
 
 
 
 
Xl
 
Dosing Days 8 and 29 only  
mRNA and
 assays 
X 
 
 
 
 
 
 
 
Serum inflammatory markers (20 mg dose 
group only) 
X 
 
 
 
 
 
 
 
 
Dosing Days 8, 15, 22 and 29 only
Weight 
X 
 
 
 
 
 
 
 
Abbreviations: CRP: C reactive protein; 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
43 
a  The pre-dose assessments should be performed immediately prior to IP administration. If the subject is receiving treatment with a short-acting bronchodilator 
as part of their routine pulmonary therapies, pre-dose spirometry testing may be scheduled before the subject’s pulmonary therapies (if the subject’s schedule 
permits) so that it can be performed “pre-bronchodilator.” (See footnotes i and k).     
b  Hour 0 corresponds to the end of nebulization of IP. 
c  Subjects will remain in the study center for safety monitoring for at least 6 hours after the administration of IP and will be discharged only when deemed 
clinically stable by the Investigator with no ongoing AEs or safety concerns of clinical significance. Discharged subjects can go home if they live locally 
(within 1 hour driving distance from the study center) or if not should be housed overnight close to the study center until the clinic visit on the following day. 
If a subject is experiencing an ongoing AE or there is a safety concern (eg, decreased oxygen saturation or airway symptoms), based on the judgment of the 
Investigator, the subject can remain in the study center overnight or can be hospitalized for continued monitoring until the clinic visit on the following day. The 
subject should remain in the study center or hospital until the AE or safety concern has resolved and the subject is sufficiently stable to be discharged. 
d  The pre-dose physical examination on Day 1 will be a limited physical examination as a complete baseline physical examination will have already been 
performed the day before on Day -1. On all other dosing days (Days 8, 15, 22, and 29), a complete physical examination will be performed at the pre-dose time 
point.   
e  A limited physical examination will be performed at these time points.  
f   Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
g  Blood pressure and pulse rate will be monitored continuously during nebulization of IP (except during rest periods), and will be recorded at the end of 
nebulization with each of the multiple nebulizers used to deliver the volume of IP (eg, for the 16 mg dose, blood pressure and pulse rate will be recorded at the 
end of nebulization with each of the 4 nebulizers used to deliver the 28 mL total volume); the final recording will count as the Hour 0 time point. Blood 
pressure or pulse rate may be recorded more frequently, if clinically indicated. (Body temperature will not be monitored during the dosing period).  
h  Oxygen saturation, measured by pulse oximetry, will be monitored continuously during nebulization of IP (except during rest periods), and will be recorded at 
the end of nebulization with each of the multiple nebulizers used to deliver the total volume of IP (see footnote g for example); the final recording will count as 
the Hour 0 time point. Oxygen saturation may be recorded more frequently, if clinically indicated. 
i  If feasible for the subject, spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting bronchodilator 
(Section 7.5.2.12). The spirometry testing at the 6-hour time point has an expanded window of ±1 hour to accommodate this.  
j  The Day 1 pre-dose ECG and spirometry must be reviewed prior to the first dose. The administration of IP should optimally occur within 2-3 hours after 
subjects have completed their routine pulmonary therapies (airway clearance and pulmonary medications) for the day. For subjects whose pulmonary 
medications do not include an inhaled short-acting beta-agonist (or it is not given within the 2-3 hour window prior to IP administration), albuterol (2 to 
4 puffs) will be administered approximately 20 minutes before treatment with IP. IP will be administered by the respiratory route using an InnoSpire Go 
nebulizer. Depending on the dose level, nebulization times will range from approximately 44 to 133 minutes. During nebulization of IP, the subject should be 
monitored closely for any signs or symptoms of respiratory distress (eg, dyspnea, wheezing, bronchospasm).  
k  Subjects should be randomized following confirmation of eligibility on Day 1. Confirmation of eligibility on Day 1 requires a review of the Day -1 results and 
pre-dose Day 1 results of physical exam, AE, conmeds, vital signs and pulse oximetry. A subject is considered enrolled into the study when he or she has been 
randomized. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
44 
l  An electrocardiogram will be performed pre-dose on dosing Day 15; and pre-dose and 6 hours after treatment on dosing Day 29.       
m Subjects will be in a fasted state (8hrs without food or drink except water) for serum chemistry study blood collections.  
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
45 
 
Table 8: 
Part D - Schedule of Procedures for Screening through Day 18  
 
Screening 
Period 
Treatment Period 
Follow-Up Period 
Study Day 
Day -28   
to -1 
Day 1a 
Day 2 
Day 3 
Day 4 
Day 5 
Day 8 
(±1 day) 
Day 11 
(±1 day) 
Day 18 
(±1 day) 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Clinic visit (outpatient)a 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Telephone contact 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and 
medical/medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
Full Physical examination  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Limited physical exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Vital signs (BP, HR, body 
temperature, RR)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Pulse oximetry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Heightc 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistry, 
hematology, coagulation, 
urinalysis, CRP 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
Serum inflammatory 
markersh 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
Serum or urine pregnancy 
testd 
X 
X 
 
 
 
 
  
 
 
 
 
 
 
 
Drug and alcohol screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometrye 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
X 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
46 
Table 8: 
Part D - Schedule of Procedures for Screening through Day 18  
 
Screening 
Period 
Treatment Period 
Follow-Up Period 
Study Day 
Day -28   
to -1 
Day 1a 
Day 2 
Day 3 
Day 4 
Day 5 
Day 8 
(±1 day) 
Day 11 
(±1 day) 
Day 18 
(±1 day) 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Pre-
Dose 
2 hours 
post-dose 
Viral screening (HIV, HBV, 
HCV) 
X 
 
 
 
 
 
 
 
 
 
 
 
Chest x-rayf 
X 
 
 
 
 
 
 
 
 
 
X 
 
Electrocardiogram (ECG) 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
mRNA and 
 
assaysh 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Immune response assaysg,h 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant surgical 
procedure collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense thermometer & 
Body Temp Log 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Collect Body Temp Log 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
Randomizationi 
 
X 
 
 
 
 
 
 
 
 
 
Abbreviations: BP: blood pressure; CRP: C reactive protein; HR: heart rate;
 RR: respiratory rate 
a Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 
b Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
c All body mass index calculations will use the subject’s height measured at the initial screening visit. 
d 
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the initial screening visit and on Day 1 
(pre-dose) 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
47 
e  If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting 
bronchodilator (Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled 
spirometry testing may be performed when the subject is stable. 
f  Chest x-rays will consist of routine posterior, anterior and lateral views. At the discretion of the Investigator, an unscheduled chest x-ray may be performed at 
any time during the follow-up period if the subject is experiencing respiratory symptoms that warrant it.  
g  Assays will measure antibody and T cell responses to CFTR protein as well as anti-PEG antibodies.  
h  In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays, inflammatory markers, and/or 
mRNA and 
 may be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or unexplained bronchospasm. 
i  Subjects should be randomized following confirmation of eligibility on Day 1. Confirmation of eligibility on Day 1 requires a review of the pre-dose Day 1 
results of physical exam, AE, conmeds, vital signs, pulse oximetry, and pregnancy test (female subjects only). A subject is considered enrolled into the study 
when he or she has been randomized. 
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
48 
 
Table 9: 
Part D - Schedule of Procedures for the Follow-up Period - Day 25 to Day 341 
 
Follow-up Period 
Study Day 
Day 25 
(±1 day) 
Day 32 
(±2 days) 
Day 46 
(±2 days) 
Day 60 
(±2 days) 
Day 89 
(±3 days) 
Day 117 
(±3 days) 
Day 145
(±3 days) 
Day 173 
(±3 days)
Day 201  
(±3 days)
Day 229 
(±3 days)
Day 257, 
Day 285, 
Day 313 
(±3 days) 
Day 341 
(±3 days)
Clinic visit (outpatient)a 
 
X
 
X 
 
 
X 
 
 
X 
 
X 
Telephone contact 
X 
 
X
 
X 
X 
 
X 
X 
 
X 
 
Physical examination 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Vital signs (BP, HR, body 
temperature, RR)b 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Pulse oximetry 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Weight 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Electrocardiogram (ECG) 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Serum chemistry, 
hematology, coagulation, 
urinalysis, CRP 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Serum Inflammatory 
markerse 
 
X 
 
 
 
 
 
 
 
 
 
 
Spirometryc 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
Chest x-ray 
 
X 
 
 
 
 
 
 
 
 
 
 
mRNA and 
 
assayse 
 
X 
 
 
 
 
 
 
 
 
 
 
Immune response assaysd,e 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
Serum or urine pregnancy 
testf 
 
 
 
 
 
 
 
 
 
 
 
X 
Adverse event collection 
X 
X
X
X 
X 
X 
X 
X 
X 
X
X
X 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
 
CONFIDENTIAL  
49 
Table 9: 
Part D - Schedule of Procedures for the Follow-up Period - Day 25 to Day 341 
 
Follow-up Period 
Study Day 
Day 25 
(±1 day) 
Day 32 
(±2 days) 
Day 46 
(±2 days) 
Day 60 
(±2 days) 
Day 89 
(±3 days) 
Day 117 
(±3 days) 
Day 145
(±3 days) 
Day 173 
(±3 days)
Day 201  
(±3 days)
Day 229 
(±3 days)
Day 257, 
Day 285, 
Day 313 
(±3 days) 
Day 341 
(±3 days)
Concomitant medication 
collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant surgical 
procedure collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BP: blood pressure; CRP: C reactive protein; HR: heart rate; 
RR: respiratory rate 
a Refer to Section 7.6 for onsite clinic visit flexibility due to coronavirus disease. 
b Blood pressure and pulse rate should be taken in a seated position after at least 5 minutes of rest.  
c If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the subject is receiving treatment with a short-acting 
bronchodilator (Section 7.5.2.12). If a subject experiences respiratory distress or pulmonary symptoms, at the discretion of the Investigator, unscheduled 
spirometry testing may be performed when the subject is stable. 
d Assays will measure antibody and T cell responses to CFTR protein and anti-PEG antibodies. The blood collections for any of these assays on the final study 
day (Day 341) are optional and will be driven by the observation of a de novo positive immune response after treatment (see Section 7.5.2.15). In the event of 
inconclusive, invalid, or missing assay results at the Day 145 visit, the blood collection for one or more of these assays will be taken at Day 341 at the 
discretion of the Sponsor.  
e  In addition to the time points specified in the schedule of assessments, ad hoc testing for immune response assays, inflammatory markers, and/or 
 
mRNA and 
 may also be performed when immunogenicity is suspected, such as febrile and/or allergy/hypersensitivity events or unexplained 
bronchospasm. 
f 
-hCG pregnancy test will be performed on all female subjects, regardless of childbearing potential, at the end of the study on Day 341. In 
addition, a serum or urine -hCG pregnancy test should be performed on female subjects at any time pregnancy is suspected or upon withdrawal from the 
study (the latter applies to all female subjects, regardless of childbearing potential). 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
50 
1.
BACKGROUND INFORMATION
1.1. 
Cystic fibrosis 
Cystic fibrosis (CF), also known as mucoviscidosis, is an autosomal recessive genetic disorder
that affects most critically the lungs, but also the pancreas, liver, and intestine.1–3 It is 
characterized by abnormal transport of chloride and sodium across the epithelium, leading to 
thick, viscous secretions resulting from mutations in the gene for the protein cystic fibrosis 
transmembrane conductance regulator (CFTR).3,4 This protein functions as a channel that 
transports chloride ions across the membrane of cells and is required to regulate the components 
of mucus, sweat, saliva, tears, and digestive enzymes. Most CF patients develop severe, chronic 
lung disease related to airway obstruction partly due to increased levels of sulfated mucins, 
inflammation and recurrent bacterial infections that are eventually lethal; the median predicted 
survival age in the US of those born in 2017 is 46.2 years.5 CF is the most frequent lethal genetic 
disease in the white population. There are approximately 30,000 individuals affected in the US, 
and 70,000 worldwide.1,6–8  Incidence varies widely according to country and ethnicity. In the 
US, estimates of incidence range from 1 in 1,900-3,700 white Americans.1,6 CF is present, but 
less frequent, in other US groups: estimated incidences in Hispanic, Asian, and Black American 
populations have been reported to be 1 in 9,200, 1 in 31,000, and 1 in 15,000, respectively.9 
There is wide country variability within Europe, ranging from 1 in 1,800 in Ireland to 1 in 25,000 
in Finland.10 CF is uncommon in Africa and Asia, with an incidence of 1 in 350,000 reported in 
Japan.3   
Symptoms of CF often appear in infancy and childhood, the most frequent of which are 
respiratory symptoms, followed by failure to thrive, steatorrhea, and meconium ileus.1 The lungs 
of individuals with CF are colonized and infected by bacteria from an early age. This leads to 
chronic airway infection and inflammation, progressing to bronchiectasis, gas trapping, 
hypoxemia, and hypercarbia. Pulmonary insufficiency is responsible for 70.5% of CF-related 
deaths in the US.5 In the initial stage, common bacteria such as Staphylococcus aureus and 
Hemophilus influenzae colonize and infect the lungs. Eventually, Pseudomonas aeruginosa (and 
sometimes Burkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic CF 
harbor P. aeruginosa, and 3.5% harbor B. cepacia. Once within the lungs, these bacteria adapt to 
the environment and develop resistance to commonly used antibiotics. 
Non-pulmonary complications of CF result from blockages of affected organs with thickened 
mucosal secretions. These blockages cause damage in the pancreas, liver, and intestines leading 
to exocrine pancreatic insufficiency, malabsorption, and recurrent pancreatitis; CF-related 
diabetes; chronic hepatobiliary disease and cirrhosis; and meconium ileus and distal intestinal 
obstructive syndrome.1,3 Male infertility due to azoospermia secondary to congenital absence of 
the vas deferens is also a common complication of CF.       
The underlying defect causing CF is abnormal epithelial anion transport due to the lack of 
expression or dysfunction of the CFTR protein. The CFTR protein primarily functions as a 
chloride channel in epithelial cell membranes; however, it also involved in a number of other 
cellular membrane functions such as inhibition of sodium transport through the epithelial sodium 
channel, regulation of the outwardly rectifying chloride channel, and regulation of adenosine 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
51 
triphosphate (ATP) channels.3 CF is caused by mutations in the gene encoding for the CFTR 
protein, of which more than 2,000 mutations have been identified.11 The more common gene 
mutations result in the lack of synthesis of the CFTR protein (class I), defective processing and 
maturation of the CFTR protein (class II), or the expression of a CFTR protein defective in 
regulation, eg, diminished ATP binding and hydrolysis (class III).4 A deletion of phenylalanine 
at position 508 (F508del) is the most common CFTR mutation worldwide and is a class II defect 
in which the misfolded CFTR protein is rapidly degraded by the cell soon after synthesis.4 The 
lack of a functional CFTR protein causes mucosal obstruction of exocrine glands in CF patients 
secondary to abnormal transport of chloride and sodium across the epithelium. In the lung, this 
leads to the development of thick, tenacious secretions that obstruct the airways and submucosal 
glands, which in turn leads to chronic bacterial infection and inflammation, as described above.   
Management of CF has been focused primarily on the treatment of CF lung disease with 
antibiotics and with other therapies directed at optimizing airway clearance.1 Improved nutrition 
has also played a vital role in prolonging survival of CF patients.3 Until recently, there have been 
no therapies available that directly address the underlying CFTR defect in CF patients. 
Pharmacological compounds that are intended to correct mutation-specific functional defects in 
the CFTR protein have been under active investigation. Four of these therapies, ivacaftor 
(KALYDECO®, Vertex Pharmaceuticals Inc.), ivacaftor combined with lumacaftor 
(ORKAMBI®, Vertex Pharmaceuticals Inc.), ivacaftor combined with tezacaftor (SYMDEKO®, 
Vertex Pharmaceuticals Inc.), and ivacaftor combined with elexacaftor and tezacaftor 
(TRIKAFTA®, Vertex Pharmaceuticals Inc.) have shown clinical benefit in trials and have been 
recently approved in the US for patients with the specific targeted gene mutations (Section 
1.3.2).  
Newborn screening for CF is now routinely performed in the US and in Europe in the United 
Kingdom, France, Italy, Spain, Austria, Poland, and the Czech Republic as well as in Australia 
and New Zealand.12,13 The screening methodology incorporates measurement of immunoreactive 
trypsinogen on dried blood spots as a first step, followed by either repeat immunoreactive 
trypsinogen testing and/or DNA testing for CF mutations as a second step.12 Sweat testing is then 
performed to confirm a diagnosis of CF.  
1.2.
Overview of MRT5005  
The ultimate treatment goal is to restore CFTR function in the lungs of all CF patients, 
irrespective of the patient’s underlying CFTR gene mutation. One approach has been the 
insertion of a normal copy of the CFTR DNA gene into affected cells by gene therapy. Since 
1993, more than 25 clinical studies have been conducted using adenovirus, adeno-associated 
virus serotype 2, or non-viral vectors to deliver the CFTR DNA gene to the upper and/or lower 
respiratory tract of CF patients.14 Unfortunately, this approach has proven to be difficult and has 
yielded disappointing results.14,15  
An alternative to DNA gene therapy is the delivery of a CFTR-encoding messenger RNA 
(mRNA) directly into affected cells, bypassing the need for the CFTR DNA gene to enter the cell 
nucleus to be transcribed into mRNA. The CFTR-encoding mRNA would express CFTR protein 
instantly once it reached the cytoplasm of the cell. There are many other advantages of an 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
52 
mRNA-based therapy as compared to DNA gene therapy, particularly with respect to safety.16 In 
contrast to DNA, mRNA cannot integrate into the genome, which excludes the possibility of 
insertional mutagenesis, and without CpG motifs, has reduced immunogenic effects. In addition, 
as mRNA has a limited half-life, levels of the expressed protein can be controlled more precisely 
by dose and dosing frequency, which is an important consideration for both safety and efficacy 
of the therapy. There are a number of mRNA-based cancer immunotherapies and infectious 
disease vaccines that have entered clinical development.17
MRT5005 is a new molecular entity and first-in-class pharmaceutical agent, which has been 
designed to restore CFTR function in the lungs of CF patients by respiratory delivery of mRNA 
encoding for the wild-type human CFTR protein. Once delivered to the surface of the respiratory 
epithelium, cellular uptake and translation of the mRNA would then result in the expression of 
normally functioning CFTR protein and restoration of CFTR chloride channel activity in the 
lungs. MRT5005 takes advantage of cationic lipid-based nanoparticle technology to deliver the 
mRNA to the target bronchial epithelial cells. Lipid nanoparticles containing ionizable cationic 
lipids represent the most promising non-viral vectors for delivering DNA and RNA.18–22 
The active drug substance of MRT5005 is a biosynthetic 
mRNA (
 mRNA), which encodes for the 
normal human CFTR protein. 
 and several elements within the 
 
mRNA structure were incorporated to promote activity through increased stability and enhanced 
translation by the ribosome. 
 mRNA is formulated with an 
lipid nanoparticle (
 LNP) as the vehicle to deliver 
mRNA to the lungs. The 
primary component of the 
 LNP is the cationic lipid 
, which 
is mixed with two other non-cationic lipids, 
in the formation of the lipid nanoparticle (LNP). 
Complexed within the 
 LNP, 
 mRNA is protected from degradation and can be 
delivered by aerosol to the respiratory tract. The lipid nanoparticle facilitates penetration of the 
airway mucus layer, uptake by the target bronchial epithelial cells, and release of 
 
mRNA into the cytoplasm. The coding region of 
 mRNA subsequently undergoes 
translation and produces the desired normal human CFTR protein. The newly expressed CFTR 
protein is processed and trafficked to its normal site in the apical plasma membrane where it is 
intended to restore CFTR chloride channel activity at the epithelial cell surface of the lung. 
MRT5005 is delivered in the form of an aerosol, administered to the lungs by a vibrating mesh 
nebulizer commonly used in medical practice. Additional information on MRT5005 can be 
found in the Investigator’s Brochure.  
Study MRT5005-101 represents an important first step in the evaluation of mRNA therapy as an 
approach to restoring CFTR function in the lungs of CF patients. The goal was to design a single 
study that could achieve both Phase 1 and 2 objectives while ensuring subject safety. This 
Phase 1/2, first-in-human study will evaluate the safety and tolerability of single and multiple 
escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects 
with CF. This study will also characterize its biological activity by measuring changes in ppFEV1 
and other spirometry parameters post-treatment. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
53 
1.3.
Indication and Current Treatment Options 
1.3.1. 
Indication for MRT5005 
The intended indication for MRT5005 is for the treatment of patients with cystic fibrosis.  
1.3.2. 
Current Treatment Options for Cystic Fibrosis 
Treatment options for CF have been primarily supportive. The main focus of CF treatment is the 
control and prevention of pulmonary infections with antibiotics. Other therapies are directed at 
optimizing airway clearance and the management of CF-related gastrointestinal disease. 
Antibiotic therapies fall into 3 categories: regimens to delay colonization of the lungs by P. 
aeruginosa; chronic maintenance antibiotics to reduce the frequency and morbidity of pulmonary 
exacerbations (eg, inhaled tobramycin); and treatment of pulmonary exacerbations with 
intravenous antibiotics for 2 to 3 weeks. Other therapies directed at airway clearance include 
inhaled treatments with mucolytics (recombinant human deoxyribonuclease I [rhDNase, dornase 
alfa, PULMOZYME®]), hypertonic saline, and bronchodilators; inhaled and systemic therapy 
with anti-inflammatory agents; and chest physiotherapy. For pancreatic insufficiency, CF 
patients are treated with pancreatic enzyme supplements and multivitamins to maintain adequate 
nutrition.  
Four therapies are available that target the underlying CFTR defect in CF patients. These 
pharmacological compounds are intended to correct mutation-specific functional defects in the 
CFTR protein. Ivacaftor is approved for the treatment of CF patients with certain Class III (eg, 
G551D) and Class IV (eg, R117H) gene mutations (KALYDECO, Vertex Pharmaceuticals, Inc.). 
These 38 mutations account for approximately 15% of CF cases in the US.23 Ivacaftor combined 
with lumacaftor is approved for the treatment CF patients who are homozygous for the F508del 
mutation in the CFTR gene (ORKAMBI, Vertex Pharmaceuticals, Inc.) Ivacaftor combined with 
tezacaftor is approved for the treatment of CF patients who are homozygous for the F508del 
mutations or at least one of 26 (mostly Class IV and Class V) specified mutations (SYMDEKO,
Vertex Pharmaceuticals Inc.). Patients who are homozygous for the F508del mutations account 
for 45.3% of CF cases in the US.5 Ivacaftor combined with tezacaftor (SYMDEKO®, Vertex 
Pharmaceuticals, Inc.) is approved for the treatment of CF patients who are homozygous for the 
F508del mutations or who have at least one of 26 (mostly Class IV and Class V) specified mutations. 
A triple-combination CFTR modulator therapy (TRIKAFTA, Vertex Pharmaceuticals, Inc.) recently 
received marketing approval in the US and has expanded the coverage of CFTR mutations to 
approximately 90% of CF patients. Nonetheless, there remains a significant unmet need for the 
approximately 10% of CF patients whose mutations are non-amenable to CFTR modulators. 
1.4. 
Product Background 
A description of MRT5005 is provided in Section 1.2 and in Section 6.1. Information on study 
drug preparation and management is provided in Section 6.2.2.    
Additional information on MRT5005 can be found in the Investigator’s Brochure. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
54 
1.4.1.
Preclinical Information
The results of the nonclinical studies conducted with MRT5005 are summarized below. More 
detailed information on these studies and their results can be found in the MRT5005 
Investigator’s Brochure.  
1.4.1.1. 
Proof-of-Concept Pharmacology Studies 
Nonclinical pharmacology studies have demonstrated in vitro production and functionality of 
human CFTR protein following transfection of HEK293T and Fischer rat thyroid cells with 
mRNA. Following transfection with increasing amounts of 
 mRNA, a dose-
dependent increase in human CFTR protein expression was observed in both cell lines and a 
dose-dependent increase in functional ion channel activity was observed in Fischer rat thyroid 
cells based on Ussing chamber measurements.  
In vivo pharmacological activity of MRT5005 has been explored in a CFTR knock-out 
[CFTRtm1Unc(Tg-FABP)] mouse model, as well as in normal mice. The pharmacological activity of 
MRT5005 was also examined as part of non-GLP and GLP-compliant toxicology studies in 
normal rats and non-human primates (cynomolgus monkeys). These studies have demonstrated 
that aerosol administration of single and multiple doses of MRT5005 (five once weekly doses) 
resulted in a dose-dependent deposition of 
mRNA in the lungs of treated animals at 
levels that were orders of magnitude higher than the endogenous levels of wild type CFTR 
mRNA (up to 1500-fold higher). 
 mRNA was found to be broadly distributed 
throughout the lungs and was detected in bronchial epithelial cells as well as in alveolar regions.  
More importantly, widespread expression human CFTR protein was observed in the lungs of 
treated animals. Consistent with the deposition of 
 mRNA, human CFTR protein 
production was detected in both bronchial epithelial as well as alveolar regions of the lungs. 
Furthermore, dose-dependent increases in human CFTR protein were observed after both single 
and multiple dose administrations of MRT5005 in rats and non-human primates, and human CFTR 
protein was found to persist for up to 28 days after treatment at the higher doses. 
1.4.1.2. 
Pharmacokinetic Studies 
The active substance of MRT5005, 
 mRNA, is a high molecular weight biomolecule 
(approximately 1630 kD) and therefore is expected to be transported across lung epithelia and 
into blood only to a limited degree. This is what has been observed in both rats and non-human 
primates. As a result, dedicated pharmacokinetic studies of 
 mRNA were not 
performed, but instead biodistribution and toxicokinetics were examined as part of non-GLP and 
GLP-compliant toxicology studies in rats and non-human primates. 
The MRT5005 pharmacokinetic/toxicokinetic data have been generated from the following 
toxicology studies: a single-dose, dose range-finding toxicity study in non-human primates; and 
GLP multiple-dose inhalation toxicity studies in rats and non-human primates treated with 5 once 
weekly doses of MRT5005.  
The results show high levels of 
 mRNA in lung tissue and associated respiratory tract 
tissues such as larynx, trachea, tracheobronchial lymph nodes, and nasal turbinates with very low 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
55 
or background levels in heart, brain, liver, kidney, spleen, testis, and ovary. Lung tissue levels 
were high and dose-responsive in both rats and non-human primates. Blood levels of 
mRNA were very low and variable, preventing a reliable analysis of toxicokinetic parameters.   
The toxicokinetics of 
 LNP were also examined using an assay that could measure 
 lipid 
in the blood. There were no measurable levels of 
 lipid in whole blood post-treatment with 
MRT5005. There were, however, measurable and dose-responsive levels of 
 lipid in the lung 
tissue of both rats and non-human primates treated with MRT5005.   
An analysis of the kinetics of lung clearance of 
mRNA in rats indicated a single 
component exponential decay with a half-life of approximately 2-3 days. Lung clearance of 
mRNA was less reliably determined in non-human primates as only two data points were 
available; however, these data appeared to be consistent with the rat data when the differences in 
dose were taken into account. 
1.4.1.3. 
Toxicology Studies 
The nonclinical program has characterized MRT5005 in a standard battery of safety 
pharmacology and toxicity studies. MRT5005 has been evaluated in the following safety studies: 
1) GLP inhalation safety pharmacology study in rats (cardiovascular evaluation); 2) single-dose, 
dose range-finding toxicity study in non-human primates; and 3) GLP multiple-dose inhalation 
toxicity studies in rats and non-human primates treated with 5 once weekly doses of MRT5005.  
All toxicology studies with MRT5005 have resulted in no adverse effects up to the highest 
achievable dose levels. MRT5005 was well tolerated at all doses tested. There were no clinical 
signs associated with treatment, and there were no clinically important effects on cardiovascular 
and respiratory parameters (heart rate; ECG rhythm and intervals; respiration rate, tidal volume, 
and derived minute volume), body temperature, clinical pathology, and macroscopic and 
microscopic pathology. Importantly, there were no histopathologic effects in the respiratory tract 
that were considered adverse following repeated exposure to MRT5005 at all dose levels tested 
up to the maximum achievable dose.    
Based on the absence of adverse effects at any of the dose levels tested of MRT5005, the 
no-observed-adverse-effect-levels (NOAELs) are the maximum inhaled doses for each study. In 
the GLP multiple-dose inhalation toxicity studies, the maximum doses tested in rats and non-
human primates were 6.70 mg/kg and 0.69 mg/kg, respectively.  
1.4.2. 
Clinical Information 
Study MRT5005-101 will be the first evaluation of MRT5005 in human subjects.  
1.5. 
Risk/Benefit and Ethical Assessment  
At this early stage in the development of MRT5005, the benefits of MRT5005 therapy remain to 
be established. As such, there are no known or expected benefits for the CF subjects participating 
in this study in relation to the investigational product (IP) MRT5005. However, their 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
56 
participation may contribute to the development of a new therapy that could provide significant 
clinical benefit for CF patients in the future.  
Adult CF patients were selected as the first subjects to receive MRT5005, as the balance between 
the anticipated risks and potential benefits of the study were judged as acceptable for adult 
patients with CF and unfavorable for healthy volunteers. The ability to detect and interpret the 
activity of MRT5005 in CF patients, either adverse or beneficial, was an important consideration 
in the selection of CF patients as the clinically relevant population for the study. In addition, due 
to the potential for persistent effects resulting from the treatment (eg, immunogenicity of the 
expressed protein), the risk-benefit profile was considered unacceptable for healthy volunteers.     
As this will be the first human exposure to MRT5005, potential risks associated with MRT5005 
treatment will be mitigated through the following study elements: 
 There will be an extensive safety follow-up of all subjects in the study. All subjects 
will be monitored for safety for 12 months (48 weeks) after administration of the last 
dose of IP (post-single dose in Part A; post-fifth dose in Parts B and D). 
 The exposure to MRT5005 will be limited to a single dose in Part A and to 5 total 
doses in Part B (administered 1 dose per week for 5 weeks) of the study. The 
exposure to MRT5005 in Part D will be also limited to 5 total doses (administered as 
1 dose per day for 5 consecutive days) at a dose strength that is equivalent to a single 
well-tolerated weekly dose divided over 5 days. After each dose, the exposure to 
 mRNA, the active drug substance of MRT5005, and the resulting translated 
CFTR protein is expected to be transient with half-lives estimated to be 14 and 
29 hours, respectively.24,25 
 In Parts A and B of the study, a dose escalation design, with staggered enrollment and 
treatment of subjects within the dose group, will be utilized to minimize risk to 
subjects. The enrollment and treatment of subjects within each dose group will be 
staggered by at least 1 week (Part A) or 2 weeks (Part B), with the exception of the 12 
mg dose group in Part B which will not have staggered enrollment under the 
circumstances described in Section 3.1.  
The Protocol Safety Review Committee (PSRC) will have oversight of the dose 
escalation process; the safety data from each of the dose groups will be reviewed by 
the PSRC to determine if escalation to the next higher dose level can proceed safely 
(Section 3.4). The PSRC will also conduct a safety data review before initiation of 
enrollment and treatment of subjects in the  MAD groups in Part B.  (Section 3.4.3).  
 Safety-related stopping criteria are defined and will be employed in the study 
(Sections 4.5.4, 4.5.5, and 4.5.6). 
 Women of childbearing potential are eligible to participate in the study. The study 
design includes measures to minimize the possibility of fetal exposure to the IP 
(Section 4.4.1). The informed consent will provide female subjects with sufficient 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
57 
information so that they may make informed decisions about the potential risks and 
benefits of the therapy and the study.  
As part of the safety evaluation, assays to detect immune responses to CFTR protein 
post-treatment will be performed (Section 7.5.2.15). In addition to the time points specified in 
the schedule of assessments, immunogenicity testing will also be performed when 
immunogenicity is suspected, such as allergy/hypersensitivity events or unexplained 
bronchospasm. 
Based on the risk mitigation elements discussed above, in combination with the knowledge that 
will be gained on MRT5005 as a potential therapeutic for CF lung disease, Translate Bio 
believes that the risk-benefit balance of this study is acceptable for adult CF subjects. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
58 
2.
STUDY OBJECTIVES AND PURPOSE
Study objectives are provided in Section 2.3. Study endpoints are provided in Section 2.4.   
2.1.
Rationale for the Study
Therapy with MRT5005 is intended to correct the underlying CFTR defect in the lungs of CF 
patients by delivering human CFTR-encoding mRNA into affected cells, which can then be 
translated into normal functioning CFTR protein. This approach is supported by nonclinical 
proof-of-concept studies, which demonstrated that aerosol delivery of MRT5005 leads to a dose-
dependent deposition of 
 mRNA in the lungs of animals and subsequent expression 
of human CFTR protein (Section 1.4.1.1).  
Study MRT5005-101 is a Phase 1/2, first-in-human evaluation of MRT5005 as a novel mRNA-
based therapeutic approach for treating CF lung disease. Study objectives and endpoints are 
provided in Section 2.3 and Section 2.4. 
Study MRT5005-101 was designed to evaluate the safety, tolerability, and biological activity of 
nebulized MRT5005 in CF subjects. The results of this study will guide dose selection for all 
future Phase 2 and 3 clinical studies in CF subjects.   
2.2. 
Rationale for Study Design, Study Population, and Dose Selection 
2.2.1. 
Study Design  
Study MRT5005-101 is a Phase 1/2, first-in-human trial that is designed to achieve both Phase 1 
and 2 objectives while ensuring subject safety. The objectives and endpoints of the study are 
described in Section 2.3 and Section 2.4.
Study MRT5005-101 is designed as a randomized, double-blind, placebo-controlled, combined 
single and multiple ascending dose (SAD and MAD) trial, which will be conducted in 3 parts. 
Subjects will be administered single and multiple escalating doses of MRT5005 in Parts A and B 
of the study, respectively. Multiple dosing in Part B will consist of 5 doses of MRT5005, 
administered 1 dose per week for 5 consecutive weeks. In Part D, subjects will be administered 4 
mg of MRT5005 or placebo administered as 1 dose per day for 5 consecutive days. 
The overall design of the study is shown in Appendix 1. The rationale behind the selection of the 
dose levels to be investigated is discussed in Section 2.2.3.    
In all 3 parts of the study, subjects will be randomized to receive either MRT5005 or placebo 
(normal saline) in a 3:1 ratio. Blinded, placebo-treated subjects are included in the study to 
facilitate interpretation of the safety and tolerability data, and to provide controls for assessing 
the delivery of 
mRNA and its biological activity as reflected by changes in CFTR 
protein levels and CFTR chloride channel activity. Study MRT5005-101 will be conducted at a 
limited number of study centers, so that safety can be monitored effectively across all 
participating subjects, and decisions with respect to dosing and dose escalation can be performed 
efficiently. A PSRC will have responsibility for the overall safety of the subjects participating in 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
59 
the study, and will have oversight of the dose-escalation process and decisions to initiate Part B 
of the study (Section 3.4.1). 
This study is primarily intended to assess the safety and tolerability of single and multiple 
escalating doses of nebulized MRT5005. The 8 mg dose level of MRT5005 will be the SAD 
starting dose in Part A, followed by sequential escalation to the 16 mg and 24 mg dose levels of 
MRT5005. An additional 20 mg dose level will be evaluated in Part A resulting from the 
observation of febrile reactions in 3 of 4 subjects treated in the 24 mg single dose level. The 8 
mg dose level of MRT5005 will be the MAD starting dose in Part B, followed by sequential 
escalation to the 16 mg and 20 mg dose level of MRT5005. An additional 12 mg dose level will 
be evaluated in Part B. In both Parts A and B of the study, 4 groups consisting of 4 subjects each 
will receive single or multiple doses of MRT5005 or placebo at a 3:1 ratio. Part B subjects will 
receive 5 doses of IP, administered 1 dose per week for 5 weeks. 
The dose escalation design in Parts A and B will incorporate staggered enrollment and treatment 
of the subjects within each dose group to minimize risks to subjects. Within each dose group, the 
enrollment and treatment of the 4 subjects will be staggered by at least 1 week in Part A and by 
at least 2 weeks in Part B (the next subject in the Part B dose group will only be enrolled and 
treated when the previous subject has received their second dose and there is approximately 1 
week of safety follow-up). Under the circumstances described in Section 3.1, the 12 mg multiple 
dose group in Part B may not require staggered enrollment. When the specified safety follow-up 
has been performed for the fourth subject in the dose group, and no dose limiting toxicity has 
been observed and there are no safety concerns for the dose group overall, the enrollment and 
treatment of subjects at the next higher dose level will be initiated. Dose escalation criteria are 
further described in Section 3.4. 
Part C (bronchoscopy groups) was removed from the protocol in the 3rd amendment to the 
protocol (Version 4.0 dated 29 July 2019). 
Part D was added to the protocol (Version 5.0 dated 30 July 2020) and will evaluate the safety
and tolerability of daily dosing over 5 consecutive days. Eight subjects in Part D will be 
randomized in a 3:1 ratio to receive 5 consecutive daily doses of either 4 mg MRT5005 or 
placebo. Enrollment and treatment of subjects will not be staggered in Part D.
As assessment of safety is the primary outcome of the study, an extended safety follow-up for 
each of the subjects will be performed. All subjects in the study will be monitored for safety for 
12 months (48 weeks) after administration of the last dose of IP (post-single dose in Part A; post-
fifth dose in Parts B and D). The safety and tolerability of nebulized MRT5005 will be assessed 
based on the types, frequency, and severity of treatment-emergent adverse events (AEs) reported 
as well as on the results of a standard battery of clinical procedures and tests. As part of the 
safety evaluation, assays to detect 
 mRNA and 
 in the blood post-treatment will 
be performed along with assays to detect immune responses to CFTR protein or anti-PEG 
antibodies. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
60 
2.2.2.
Study Population
Adult CF subjects with mild to moderate disease were selected as the first subjects to receive 
MRT5005, as the risk to benefit ratio was judged as acceptable for this patient population 
(Section 1.5). Inclusion and Exclusion criteria are described in Section 4.1 and Section 4.2 .  
Male and female adult subjects with CF will be enrolled into the study. Subjects will have 
clinically stable disease with an FEV1
mild disease. As this is the first human exposure to MRT5005, patients with severe lung disease 
were excluded. Subjects with a comorbidity that would pose an additional risk from the IP or 
study procedures were also excluded. 
Eligibility will be limited to those patients with 2 severe CF disease-causing CFTR mutations in 
Class I or II. Patients with these classes of mutations express very little to no mature functional 
CFTR protein, which will increase the ability to detect MRT5005-mediated increases in CFTR 
protein levels and chloride channel activity assessed in the secondary endpoints of the study.  
Although exploratory in nature, the secondary endpoint is still viewed as an important proof-of-
concept evaluation of MRT5005 therapy. Therefore, CF patients who have the potential of 
confounding the evaluation of the secondary endpoint, because their mutations result in residual 
levels of CFTR protein and/or CFTR function, will be excluded from the study as described 
below.  
 Patients with a Class III, IV, or V CFTR gene mutation in at least 1 allele will be 
excluded from the study. Patients with Class III and IV mutations produce normal 
quantities of CFTR protein but with reduced function due to defective channel gating 
or conductance. In contrast, patients with Class V mutations express reduced 
quantities of CFTR protein, which function normally. Patients with Class IV or V 
mutations typically have a milder CF phenotype due to residual CFTR function.  
Note: As the phenotype and classification of some CFTR mutations remains 
uncertain, the eligibility of a patient with one of these mutations will be at the 
discretion of the Investigator and Sponsor, based on the patient's medical history.
 Patients with Class III and IV mutations will also be excluded on the basis of 
receiving ivacaftor monotherapy, which can potentiate CFTR chloride channel 
activity.  
 Patients with one or more unclassified mutations will be evaluated on a case-by-case 
basis to determine whether the mutation(s) confers partial CFTR function in the 
opinion of the Investigator and Sponsor. The Parts B and D Coordinating Investigator 
will adjudicate eligibility of unclassified mutations as needed. 
Patients who are receiving treatment with lumacaftor/ivacaftor or tezacaftor/ivacaftor 
combination drugs (ORKAMBI or SYMDEKO) will not be excluded from the study. It was felt 
that these therapies would not significantly interfere with the evaluation of the secondary 
endpoint based on their modest effect on CFTR protein levels and function, as determined in 
vitro and in vivo.25,26 Patients who are receiving treatment with ivacaftor monotherapy 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
61 
(KALYDECO) will be excluded because KALYDECO is not approved for use in patients with 
Class I or Class II mutations. For Parts A and B only, elexacaftor/tezacaftor/ivacaftor triple 
combination therapy (TRIKAFTA) will be excluded because of the potential of this therapy to 
confound the evaluation of the secondary endpoint. Subjects in Parts A and B who are eligible 
for TRIKAFTA may switch/start on TRIKAFTA; however, subjects must not start/switch until at 
least 2 months after their last dose of study drug so as not to confound the interpretation of the 
primary and secondary endpoints. Patients who are receiving treatment with TRIKAFTA will not 
be excluded from Part D of the study. 
Women of childbearing potential may participate in the study based on the rationale that CF 
disease is serious and affects women. The study design includes measures to minimize the 
possibility of fetal exposure to the IP. This consists of pregnancy testing prior to participation in 
the study and the use of an acceptable form of contraception if the subject is sexually active 
during the course of the study (Section 4.4.1). Females of childbearing potential currently taking 
the lumacaftor/ivacaftor combination drug (ORKAMBI) and using oral hormonal contraceptives 
will be required to take an additional or alternative method of contraception to prevent pregnancy 
in this study. The informed consent provides female subjects with sufficient information so that 
they may make informed decisions about the potential risks and benefits of the therapy and the 
study. 
2.2.3. 
Dose Selection 
The maximum dose to be evaluated in study MRT5005-101 was established from nonclinical 
toxicology studies using lung exposure in animals, expressed as mg of 
mRNA 
deposited in the lung per g of lung weight, as the basis for dose determination in human subjects. 
This approach assumes that the lung will be the main site for any potential adverse effects 
associated with inhaled MRT5005, which is dosed based on its active drug substance 
mRNA. Using this approach, a 10-fold margin of safety means that the animal NOAEL calculated 
on the basis of deposited dose per g of lung is 10-fold greater than the estimated human deposited 
dose per g of lung.  
The no-observed-adverse-effect-level (NOAEL), expressed as inhaled dose of 
 
mRNA in mg per kg body weight, was determined for both rats and non-human primates 
(cynomolgus monkeys) in GLP 29-day toxicity studies. In these studies, animals were exposed to 
5 doses of MRT5005 (weekly dosing), which was administered to the respiratory tract using an 
Aerogen Solo vibrating mesh nebulizer similar to the InnoSpire Go nebulizer to be used in this 
study. (The InnoSpire Go and Aerogen Solo utilize the same Aerogen vibrating mesh for aerosol 
generation.)     
It is important to note that both of the NOAELs were observed at the maximum feasible dose for 
both species, ie no adverse effects were observed for MRT50005 in either species up to the 
maximum inhaled dose achieved in the studies. Because of the ability to expose rats for a longer 
period of time than non-human primates (6 vs. 2 hours), a higher maximum dose and therefore 
NOAEL was achieved in rats than in non-human primates. The longer exposure and higher dose 
enabled a more thorough assessment of potential toxicity in rats. Based on the much higher 
maximum feasible dose achieved in rats combined with the sensitivity of this species to the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
62 
adverse effects of an earlier polymer-based hCFTR mRNA formulation and to other inhaled 
agents in general,27,28 the NOAEL observed in the GLP 29-day rat study was used to determine 
the maximum clinical dose to be evaluated in this first-in-human Phase 1/2 study.   
As shown in Table 10, the NOAEL in rats was determined to be 6.70 mg/kg, which corresponds 
to a deposited lung dose of 0.134 mg of 
 mRNA per g lung weight. For non-human 
primates, the NOAEL was determined to be 0.69 mg/kg, which corresponds to a deposited lung 
dose of 0.024 mg of 
mRNA per g lung weight (see footnote b in Table 10 for 
calculations of the deposited lung doses from the NOAELs.29,30   
Table 10  
Basis for Human Dose Determination 
 
Repeat-Dose Toxicity Studies 
Clinical Study MRT5005-101  
 
NOAELa
(mg 
mRNA/kg body wt) 
Deposited Lung 
Doseb 
(mg 
mRNA/g lung wt) 
Human 
Equivalent 
Dose (HED)c 
(mg 
 
mRNA) 
Maximum Dose
(mg 
mRNA) 
Safety Factor
Rats 
6.70 mg/kg 
0.134 mg/g lung 
268.0 mg 
24.0 mg 
11.2x 
Non-human 
Primates 
0.69 mg/kg 
0.024 mg/g lung 
48.0 mg 
24.0 mg 
2.0x 
a  NOAEL: No-observed-adverse-effect-level. NOAEL is expressed as the inhaled dose in mg 
 mRNA 
per kg body weight.  
b  Rat - The deposited lung dose was calculated by multiplying the NOAEL inhaled dose (mg/kg) by an assumed 
body weight of 0.3 kg for rats, and then multiplying by 0.1 assuming a 10% deposition in the lung. The deposited 
dose (mg) was then divided by a typical lung weight of 1.5 gm for a 0.3 kg rat, to obtain a deposited dose on a 
lung weight basis.  
Non-human primate - The deposited lung dose was calculated by multiplying the NOAEL inhaled dose (mg/kg) 
by an assumed body weight of 3 kg for non-human primates, and then multiplying by 0.25 assuming a 25% 
deposition in the lung. The deposited dose (mg) was then divided by a typical lung weight of 22 g for a 3 kg non-
human primate, to obtain a deposited dose on a lung weight basis. 
c  The human equivalent dose (nominal dose) was calculated by multiplying the deposited lung dose (mg/g lung 
weight) for both rats and non-human primates by an assumed lung weight of 1000 g for a 60 kg human subject, 
and then dividing by 0.5 assuming a 50% deposition of the dose in the lung from an InnoSpire Go nebulizer. 
The deposited lung doses for the NOAELs were then converted to human equivalent doses 
(HEDs) expressed as mg of 
 mRNA (nominal dose). Assuming a lung weight of 1000 
g for a 60 kg human subject and 50% deposition of the dose in the lung from an InnoSpire Go 
nebulizer, the HEDs were calculated by first multiplying the NOAEL deposited lung dose by 
1000, and then dividing by 0.5 (see footnote c in Table 10). Deposition from an Aerogen Solo 
nebulizer used in clinical settings (identical Aerogen vibrating mesh as in the InnoSpire Go) has 
been found to be 16% to 26% and, as such, 50% deposition represents a conservative value.31,32 
HEDs of 268.0 and 48.0 mg of 
mRNA were determined, respectively, from the rat 
and non-human primate NOAELs.  
For the reasons stated above, the NOAEL established in the rat study was used to determine the 
maximum clinical dose. As such, a safety margin of at least 10 was applied to the HED of the rat 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
63 
NOAEL. Although the achieved exposure of non-human primates was much lower, it was still 
desirable to have the clinical dose meet a minimum safety margin of at least 2 relative to the 
HED of the non-human primate NOAEL.  
The MRT5005 dose containing 24 mg of 
mRNA was selected as the highest dose to 
be evaluated in study MRT5005-101. As shown in Table 10, this dose fulfills the desired safety 
margin criteria: it exceeds the safety factor of 10 based on the HED derived from the rat NOAEL 
and also provides an added assurance of safety based on a safety factor of 2.0 relative to the 
HED derived from the non-human primate NOAEL. Two dose levels lower than the 24 mg dose 
level, 8 and 16 mg, were then chosen as part of the dose escalation strategy. The rationale for the 
dose range was based on i) escalation from a safe starting dose of 8 mg, which represents safety 
margins of 33.5 and 6.0 relative to the HEDs derived from the rat and non-human primate 
NOAELs, respectively, and ii) exploration of a range of doses that possess biological activity as 
determined in the nonclinical studies.      
The 8, 16, and 24 mg human doses provide lung exposures (0.004, 0.008, and 0.012 mg of 
 mRNA deposited per g lung, respectively) that are comparable to those of the lower 
doses given to the rats and non-human primates in the single and multiple-dose toxicity studies 
(0.19 to 0.77 mg/kg dose levels corresponding to 0.0065 to 0.0154 mg of 
 mRNA 
deposited per g lung, and calculated HEDs of 13 to 31 mg). These dose levels deposited 
significant levels of 
 mRNA in the lungs of both species compared to endogenous 
levels and, importantly, expressed detectable levels of human CFTR protein by 
immunohistochemistry at 24 hours post-treatment. Persistence of the human CFTR protein was 
also detected in rats at 7 days post-treatment following a single dose of MRT5004 at 0.53 mg/kg 
(HED of 22 mg); and at 28 days post-treatment following 5 once weekly doses of MRT5005 at 
0.77 mg/kg (HED of 31 mg). These observations supported the dose levels and weekly dosing 
interval of MRT5005 that will be investigated in Parts A and B of this study.    
The 4 mg dose strength was selected for evaluation in Part D based on observations of mild to 
moderate febrile reactions reported in 7 subjects who received a single dose of MRT5005 
ranging from 8 to 24 mg (1 subject each in the 8 mg, 16 mg, 20 mg single dose groups in Part A, 
3 subjects in the 24 mg single dose group in Part A, 1 subject in the 16 mg multiple dose group 
in Part B who discontinued treatment after first dose). Evaluation of a lower dose will help 
determine whether febrile reactions associated with MRT5005 are dose dependent or 
idiosyncratic. Investigation of a daily dosing regimen in Part D is attractive given the estimated 
short half-life of CFTR mRNA (14 hours) and translated CFTR protein (29 hours). The 
anticipated safety of 4 mg administered daily for 5 days (20 mg total) can be predicted from the 
safety and tolerability of 20 mg administered as a single dose in Part A. 
2.3. 
Study Objectives 
2.3.1. 
Primary Objective 
To evaluate the safety and tolerability of single and multiple escalating doses of MRT5005 
administered by nebulization to adult subjects with CF. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
64 
2.3.2.
Secondary Objective
The secondary objective of the study is to evaluate the effect on percent predicted forced 
expiratory volume in 1 second (ppFEV1) and other spirometry parameters after single and 
multiple escalating doses of MRT5005 administered by nebulization to adult subjects with CF. 
2.4. 
Study Endpoints 
2.4.1. 
Primary Endpoint 
The safety and tolerability of nebulized MRT5005 will be assessed based on the types, 
frequency, and severity of treatment-emergent AEs including pulmonary exacerbations; 
concomitant medication use; and changes from baseline in physical examination, weight, vital 
signs, oxygen saturation (pulse oximetry), ECG, standard clinical laboratory tests, chest x-ray, 
and spirometry as a measure of pulmonary function. 
2.4.2. 
Secondary Endpoint 
The biological activity of nebulized MRT5005 will be assessed based on changes from baseline 
in ppFEV1 and other spirometry parameters. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
65 
3.
STUDY DESIGN
3.1. 
Overall Study Design and Plan 
The study will be conducted at multiple centers in the US with expertise in treating CF patients. 
At least 40 adult male and female patients with CF, 18 years of age or older, are planned to 
participate in the study. Patients who are clinically stable with an FEV1
predicted, and who meet all inclusion criteria and none of the exclusion criteria will be eligible 
for the study. Women of childbearing potential will also be eligible to participate if they are 
willing and able to comply with contraception requirements.  
This Phase 1/2 study is designed as a randomized, double-blind, placebo-controlled, combined 
single and multiple ascending dose (SAD and MAD) trial, which will be conducted in 3 parts. 
Subjects will be administered single and multiple escalating doses of MRT5005 in Parts A and B 
of the study, respectively. In Part D, subjects will be administered 5 consecutive daily doses of 4 
mg MRT5005 or placebo.  
If subjects do not complete the study or complete certain procedures, additional subjects will be 
enrolled at the Sponsor’s discretion to ensure that at least 16, 16, and 8 evaluable subjects 
complete Parts A, B, and D of the study, respectively (Section 3.3). As described in Section 3.3, 
an additional group of new subjects may be enrolled and treated in Part A, with up to a 
maximum of 44 evaluable subjects participating in the study.   
As shown in Figure 1, each part of the study will consist of a screening period, a treatment 
period, and a follow-up period. Multiple visits during the screening period, from Day -28 to Day 
-2 (Parts A and B) or from Day -28 to Day -1 (Part D), may be necessary for the subject to 
complete all of the required screening procedures and tests. During the treatment period, subjects 
participating in Part A will be confined to the study center from Day -1 to Day 2 and will receive 
a single dose of IP. This will be followed by a safety follow-up period, which continues up to the 
final study visit on Day 337. During the safety follow-up, clinic visits for Part A subjects will be 
performed on an outpatient basis. 
No confinement will be required of subjects in Parts B and D of the study; these subjects will 
perform all clinic visits in the treatment and follow-up periods as outpatients. During the 
treatment period of Part B (Day -1 to Day 33), subjects will receive 5 doses of IP, administered 1 
dose per week for 5 weeks. During the treatment period of Part D (Day 1 to Day 5), subjects will 
receive 5 doses of IP, administered 1 dose per day for 5 days. The safety follow-up period will 
continue up to the last study visit on Day 365 for Part B and Day 341 for Part D.  

MRT5005-101 
Translate Bio, Inc.
Version 5.0
30 July 2020
CONFIDENTIAL 
66
Figure 1:
Study Design Flow Chart
Part A
Part B 
Part D
Screening Period
Treatment Period
In-House Confinement and Treatment
Follow-up Period
Outpatient Safety Follow-up
Day -1 
Admission to Study 
Center (inpatient) 
Baseline Assessments
Screening Period
Treatment Period
Outpatient Treatment
Day 1 
Pre-Dose Assessments 
Study Drug Dosing 
Day 1 to Day 2 
Post-Dose Assessments
Safety Follow-up
Day 3 to Day 337
(on specified days)
Screening Assessments
Day -28 to Day -2
Screening Assessments
Day -28 to Day -2
Day -1 
Baseline
Assessments
Days 1, 8, 15, 22, 29 
Pre-Dose Assessments
Study Drug Dosing 
Day 1 to Day 33  
Post-Dose Assessments
(on specified days)
Safety Follow-up
Day 36 to Day 365
(on specified days)
Follow-up Period
Outpatient Safety Follow-up
Screening Period
Treatment Period
Outpatient Treatment
Follow-up Period
Outpatient Safety Follow-up
Day 1 
Baseline Assessments (pre-dose)
Study Drug Dosing
Post-Dose Assessments 
Day 2, Day 3, Day 4, Day 5
Pre-Dose Assessments
Study Drug Dosing
Post-Dose Assessments
Safety Follow-up
Day 8 to Day 341
(on specified days)
Screening Assessments
Day -28 to Day -1

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
67 
See Table 1 through Table 9 for the schedule of procedures and tests to be performed during 
each of the 3 periods in Parts A, B, and D of the study. Flow diagrams of subject enrollment and 
treatment allocation are presented in Appendix 1. 
In Part A (SAD groups), 4 groups consisting of 4 subjects each will be enrolled sequentially to 
receive single doses of MRT5005 or placebo (normal saline) administered by nebulization. Three 
dose levels of MRT5005 were planned to be investigated: 8, 16, and 24 mg of 
mRNA (the active drug substance of MRT5005; nominal dose). An additional treatment group 
(20 mg) was added after blinded safety information from the 24 mg dose group revealed the 
occurrence of febrile reactions in 3 of 4 subjects. Within each dose group, the enrollment and 
treatment of the 4 subjects will be staggered by at least 1 week.  Subjects will be randomized in a 
3:1 ratio to receive a single dose of either MRT5005 or placebo (3 subjects to receive MRT5005 
and 1 subject to receive placebo per dose group). For details on subject enrollment and treatment 
allocation for Part A, see Section 3.2.1.   
The PSRC will be responsible for reviewing safety data and, based on this review, making the 
decision to dose escalate from the 8 mg starting SAD dose level to the 16 mg dose level, and 
then to the 24 mg maximum dose level. The 20 mg dose level will be evaluated after the 24 mg
dose level. The dose escalation process for Part A is described in detail in Sections 3.2.1 and 
3.4.2. 
The decision to begin enrollment and treatment of the initial 8 mg multiple-dose group in Part B 
will also be made by the PSRC, based on a review of at least 28 days of safety follow-up for all 
subjects who received a single dose of the 8 mg dose level in Part A. The initiation of enrollment 
and treatment of subjects in Part B is described in Sections 3.2.2 and 3.4.3.  
In Part B (MAD groups), 4 groups consisting of 4 subjects each will receive multiple doses of 
MRT5005 or placebo administered by nebulization. Three groups will be enrolled sequentially to 
receive dose levels of MRT5005 investigated as single doses in Part A (8 mg, 16 mg, and 20 
mg). An additional dose level that was not investigated in Part A (12 mg) will also be evaluated 
in Part B. The 12 mg dose group may be enrolled in parallel with the 16 and/or 20 mg dose 
group. Within each dose group, subjects will be randomized in a 3:1 ratio to receive 5 doses of 
either MRT5005 or placebo (3 subjects to receive MRT5005 and 1 subject to receive placebo per 
dose group), administered 1 dose per week for 5 weeks. The enrollment and treatment of the 
4 subjects within the 8 mg, 16 mg, and 20 mg dose groups will be staggered by at least 2 weeks 
(the next subject in the dose group will only be enrolled and treated when the previous subject 
has received their second dose and there is approximately 1 week of safety follow-up). The 
enrollment and treatment of the 4 subjects within the 12 mg dose group may occur in a staggered 
or non-staggered fashion depending on the timing of the PSRC review of the 16 mg multiple 
dose group data, as follows: 
 Staggered enrollment and treatment will be required if the 12 mg multiple dose group 
starts enrolling prior to the PSRC meeting to review the 16 mg multiple dose data.   

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
68 
 Non-staggered enrollment and treatment is acceptable after the PSRC has reviewed the 
16 mg multiple dose data and deemed the 16 mg multiple dose level was well tolerated. 
 If the PSRC meeting to review the 16 mg multiple dose group occurs while the 12 mg 
dose group is open for enrollment, all subjects who enroll after the PSRC has met and  
deemed the 16 mg dose level was well tolerated may be enrolled and treated in a 
non-staggered fashion. 
Similar to Part A, the PSRC will be responsible for reviewing safety data and making the 
decision to dose escalate. The dose escalation process for Part B is described in detail in Sections 
3.2.2 and 3.4.2.    
In Part D, 8 subjects will be randomized in a 3:1 ratio to receive 5 doses of either 4 mg 
MRT5005 or placebo, administered at 1 dose per day for 5 consecutive days. 
Because single doses up to 20 mg, as well as 5 weekly doses up to 16 mg have been tolerated in 
Parts A and B, the enrollment and treatment of the 8 subjects within Part D will not be staggered.  
All subjects in the study will be monitored for safety for 12 months after administration of the 
last dose of IP (post-single dose in Part A; post-fifth dose in Parts B and D). The safety and 
tolerability of nebulized MRT5005 will be assessed based on the types, frequency, and severity 
of treatment-emergent AEs reported including the number of pulmonary exacerbations; 
concomitant medication use; and changes from baseline in physical examination, weight, vital 
signs, oxygen saturation (pulse oximetry), electrocardiogram (ECG), standard clinical laboratory 
tests, chest x-ray, and spirometry as a measure of pulmonary function. As part of the safety 
evaluation, assays to detect 
 mRNA and 
in the blood post-treatment will be 
performed along with assays to detect antibody and T cell immune responses to CFTR protein 
and anti-PEG antibodies. 
This will be conducted as a double-blind study, except for the last part of the 12 months follow-
up. All subjects in the study will be followed for 12 months after their last dose, but the treatment 
randomization for the 8 mg, 16 mg, and 24 mg single dose groups will be unblinded 1 month 
after the last dose of the last subject in the 24 mg single dose group in Part A.  The blind will be 
maintained in the 20 mg single dose group in Part A, as well as the 8, 16, and 12 mg multiple 
dose groups in Part B until the 1-month timepoint after the last dose (Day 57) of the last subject 
dosed in the 12 mg dose group. For the 20 mg multiple dose group in Part B (if applicable), the 
blind will be maintained until the last subject in this group has reached the 1-month timepoint 
after the last dose day (Day 57). For Part D, the blind will be maintained until the 1-month 
timepoint after the last dose (Day 32) of the last subject in Part D. 
During the double-blind period, the Investigators and all study staff involved in the evaluation of 
subject eligibility and assessment of the study outcomes will be blinded to treatment assignment 
(MRT5005 vs. placebo within each dose group). All subjects and their families, as well as 
Sponsor personnel in direct contact with the study center, will also be blinded (Section 6.1.3). 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
69 
3.2.
Subject Enrollment and Treatment Allocation 
Subjects will be recruited from multiple CF centers in the US. Forty male and female patients 
with CF, 18 years of age or older, are planned to participate in the study. This will be a 3-part 
study with 16 subjects participating in Part A; 16 subjects participating in Part B; and 8 subjects 
participating in Part D.   
Subjects will not be allowed to participate in more than 1 part of the study. 
At the initial screening visit, informed consent will be obtained from the subject. A unique 
subject identification number will then be assigned, which will serve as the subject’s identifier 
throughout the study and in the case report form (CRF). Subjects in Parts A and B will be 
randomized to treatment and thereby enrolled in the study after the following 2 conditions have 
been met:  
1. Subject meets all of the inclusion criteria and none of the exclusion criteria during the 
screening period and Day -1. 
2. Confirmation of eligibility on Day 1. Results from the Day -1 and pre-dose tests on Day 1 
(AE, conmeds, pulse oximetry, physical exam, vital signs) do not reveal a new safety 
issue making the subject ineligible for randomization. A subject is considered enrolled 
into the study when he or she has been randomized to treatment. Pre-dose tests that may 
occur after randomization but MUST occur and be reviewed by the PI prior to first dose 
include spirometry and ECG. If the pre-dose Day 1 ECG or spirometry results reveal a 
safety issue making it inadvisable to administer the dose to the randomized subject, then 
the subject will be considered an Early Discontinuation.  
Subjects in Part D will be randomized to treatment and thereby enrolled in the study after the 
following 2 conditions have been met: 
1. Subject meets all of the inclusion criteria and none of the exclusion criteria during the 
screening period.
2. Confirmation of eligibility on Day 1 prior to randomization. Results from the Day 1 pre-
dose assessments (AE, conmeds, pulse oximetry, physical exam, vital signs, pregnancy 
test [female subjects only]) do not reveal a new safety issue making the subject ineligible 
for randomization. A subject is considered enrolled into the study when he or she has 
been randomized to treatment. 
The PSRC will be responsible for reviewing safety data and, based on this review, making 
decisions to dose escalate in Parts A and B, and to initiate enrollment and treatment of subjects in 
Parts B. See Section 3.4.1 for a description of the PSRC and its responsibilities.  
Subject enrollment and treatment allocation are described below and flow diagrams for the 
3 parts of the study are provided in Appendix 1.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
70 
3.2.1.
Part A
See Appendix 1, Part A, for a flow diagram
Three groups consisting of 4 subjects each will be enrolled sequentially to receive single 
escalating doses of IP. Within each dose group, subjects will be randomized to receive a single 
dose of either MRT5005 (in mg of 
 mRNA; nominal doses) or placebo (normal 
saline) in a 3:1 ratio. The treatment groups, which will be studied in the order presented, will be 
as follows: 
 Group 1 (N=4): 3 subjects randomized to receive a single dose of 8 mg of MRT5005 
and 1 subject randomized to receive a single dose of placebo.
 Group 2 (N=4): 3 subjects randomized to receive a single dose of 16 mg of MRT5005 
and 1 subject randomized to receive a single dose of placebo.
 Group 3 (N=4): 3 subjects randomized to receive a single dose of 24 mg of MRT5005 
and 1 subject randomized to receive a single dose of placebo. 
The 8 mg dose level will be the starting SAD dose, followed by sequential escalation to the 16 
mg and 24 mg dose levels of MRT5005.  
An additional treatment group was added after blinded safety information from Group 3 revealed 
the occurrence of febrile reactions in 3 of 4 subjects. The additional treatment group will be as 
follows:
 Group 4 (N=4): 3 subjects randomized to receive a single dose of 20 mg of MRT5005 
and 1 subject randomized to receive a single dose of placebo. 
The enrollment and treatment of the 4 subjects within each dose group will be staggered by at 
least 1 week. When 1 week of safety follow-up has been performed for the fourth subject in the 
dose group (applies to Groups 1 and 2), blinded safety data for the 4 subjects in the group will be 
reviewed by the PSRC. If no dose limiting toxicity has been observed and there are no safety 
concerns for the dose group overall, the enrollment and treatment of subjects at the next higher 
dose level will be initiated (see Section 3.4.2 for dose-escalation criteria for Part A and definition 
of dose limiting toxicity). 
Based on the judgment of the PSRC, a Part A dose group may be repeated in a new group of 
subjects to further assess the safety of the dose level before escalating to the next higher dose 
level or before multiple dosing is allowed to proceed in Part B. The enrollment and treatment of 
the 4 new subjects in the repeated dose group will continue to be staggered by at least 1 week to 
minimize risks to subjects. Subjects will also continue to be randomized in a 3:1 ratio to receive 
a single dose of either MRT5005 or placebo.  
3.2.2. 
Part B 
See Appendix 1, Part B, for a flow diagram 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
71 
The 8 mg dose level of MRT5005 will be the MAD starting dose in Part B. The decision to begin 
enrollment and treatment of the first MAD group will be made by the PSRC, based on a review 
of at least 28 days of safety follow-up for all subjects who received a single dose of the 8 mg 
dose level in Part A (see Section 3.4.3 for criteria to initiate enrollment and treatment in Part B). 
If no dose limiting toxicity has been observed and there are no safety concerns for the single-
dose group overall, the enrollment and treatment of subjects in the first MAD group at the 8 mg 
dose level will be initiated.  
Three groups consisting of 4 subjects each will be enrolled sequentially to receive multiple doses 
of IP. Within each dose group, subjects will be randomized to receive 5 doses of either 
MRT5005 (in mg of 
mRNA; nominal doses) or placebo (normal saline) in a 3:1 
ratio. The 5 doses of IP will be administered 1 dose per week for 5 weeks. The treatment groups 
will be as follows: 
 Group 1 (N=4): 3 subjects randomized to receive 5 doses of 8 mg of MRT5005 and 
1 subject randomized to receive 5 doses of placebo.   
 Group 2 (N=4): 3 subjects randomized to receive 5 doses of 16 mg of MRT5005 and 
1 subject randomized to receive 5 doses of placebo. 
 Group 3 (N=4): 3 subjects randomized to receive 5 doses of 20 mg of MRT5005 and 
1 subject randomized to receive 5 doses of placebo. 
The 8 mg dose level will be followed by sequential escalation to the 16 mg and 20 mg dose 
levels of MRT5005.  
An additional treatment group was added to explore the safety profile at an intermediate dose 
level that was not investigated as a single dose in Part A as follows:
 Group 4 (N=4): 3 subjects randomized to receive 5 doses of 12 mg of MRT5005 and 
1 subject randomized to receive 5 doses of placebo. 
After the PSRC deems the 8 mg dose level to have been well-tolerated and approves dosing at 
the 16 mg dose level, the 12 mg dose level may begin enrollment in parallel with the 16 mg dose 
level. The enrollment and treatment of the 4 subjects within each MAD dose group will be 
staggered by at least 2 weeks (the next subject in the dose group will only be enrolled and treated 
when the previous subject has received their second dose and there is approximately 1 week of 
safety follow-up), with the exception of the 12 mg dose group in Part B which may not require 
staggered treatment under the circumstances described in Section 3.1.  
Escalation from the 8 mg to the 16 mg and 12 mg, and from the 16 mg to the 20 mg multiple 
dose group in part B will occur after review of the following safety data by the PSRC:  
1. At least 1 week of safety follow-up after the 3rd dose of the 4th (last) subject of the 
previous (lower) dose.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
72 
2. At least 28 days of safety follow-up after the dose of the 4th (last) subject of the 
corresponding single ascending dose cohort in Part A.  Note that there is no 
corresponding single dose cohort for the 12 mg multiple dose group and therefore this 
requirement is not applicable. 
For instance, for the decision to escalate from the 8 mg dose group to the 16 and 12 mg multiple 
dose group, the PSRC will review at least 7 days of safety follow-up after the 3rd dose of the 4th 
(last) subject receiving multiple doses of 8 mg, as well as at least 28 days of safety follow-up 
after the single dose of the 4th (last) subject receiving a single dose of 16 mg.   
Similar to Part A, if no dose limiting toxicity has been observed and there are no safety concerns 
for the dose group overall, the enrollment and treatment of subjects at the next higher dose level 
will be initiated (see Section 3.4.2 for dose-escalation criteria and definition of dose limiting 
toxicity).  
3.2.3. 
Part D 
Eight subjects will be randomized in a 3:1 ratio to receive 5 doses of either 4 mg MRT5005 at or 
placebo, administered at 1 dose per day for 5 consecutive days. Based on the safety experience 
gained in Parts A and B, the enrollment and treatment of the 8 subjects in Part D will not be 
staggered. During the treatment of subjects in Part D, should AEs occur that indicate the study 
drug is not tolerated well, the enrollment and treatment of subjects may be terminated by the 
PSRC and Sponsor, and enrollment and treatment of a lower dose strength may be considered in 
the remaining subjects in the cohort . For example, if the tolerability of the 4 mg daily dose level 
is found to be unacceptable, then the 2 mg dose level can be considered for investigation.    
3.3. 
Planned Number of Subjects 
At least 40 male and female subjects with CF, 18 years of age or older, are planned to participate 
in the study. If subjects do not complete either certain procedures or the study, additional 
subjects will be enrolled at the Sponsor’s discretion to ensure that at least 16, 16, and 8 evaluable 
subjects complete Parts A, B, and D of the study, respectively (see Section 4.5.2).
Potential changes in the planned number of subjects are summarized as follows:
Although dose escalations are planned in each of Parts A and B, escalation to the next 
higher dose level may not occur if dose limiting toxicity is encountered at the current 
dose level. Therefore, the number of subjects and groups required to complete the 
dose escalation sequences in either the SAD or MAD parts of the study may be fewer 
than planned.  
 A SAD dose group may be repeated in a new group of subjects in Part A to further 
assess the safety of the dose level before escalating to the next dose level, or before 
allowing it to proceed from Part A (SAD) to Part B (MAD).  
It is expected that no more than 1 additional group of 4 subjects will be enrolled into the study in 
Part A. Therefore, up to a maximum of 44 evaluable subjects may participate in the study. If this 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
73 
subject number is to be exceeded, the Investigators will notify their IRBs and a justification for 
enrolling beyond 44 subjects will be provided.    
3.4. 
Criteria for Dose-Escalation in Parts A and B / Criteria for Initiation 
of Part B 
3.4.1.
Protocol Safety Review Committee (PSRC)
3.4.1.1.
Composition and Responsibilities
A PSRC will be formed and will have responsibility for the overall safety of the subjects 
participating in the study; and will have oversight of the dose-escalation process and decisions to 
initiate Part B of the study. The PSRC will be composed of the following members: 
 Medical Monitor  
 Coordinating Investigators 
 An independent CF clinical expert 
 Independent DMC Chair from the Cystic Fibrosis Foundation Therapeutic 
Development Network (CFF TDN)     
The PSRC will conduct a safety data review before each dose-escalation in Parts A and B and 
before initiation of enrollment and treatment of subjects in the first MAD group in Part B. Based 
on these safety data reviews, the PSRC will decide whether to proceed at each of these time 
points in the study.     
Based on the judgment of the PSRC:
A Part A dose group may be repeated in a new group of subjects to further assess the 
safety of the dose level before escalating to the next higher dose level or before 
multiple dosing is allowed to proceed in Part B (see Section 3.2.1).   
Safety data reviews will be based on unmonitored data at the time a review takes place. Blinded 
safety data reports will include a listing of the AEs and clinical laboratory test results for the 
dose group as well as any other relevant clinical data. To facilitate review of the data, the PSRC 
may request unblinding the treatment assignment(s) for an individual subject or for an entire 
dose group, as described below in Sections 3.4.2 and 6.2.3. 
The members of the PSRC, which includes the Medical Monitor, coordinating Investigators, the 
DMC Chair from the Cystic Fibrosis Foundation Therapeutics Development Network, and 
independent CF clinical expert, will review the safety data blinded.   
After each safety data review by the PSRC, all decisions will be documented in writing and must 
include the following: 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
74 
 List of participants 
A summary of the data considered
A summary of the decision, including any concerns which were raised
The final decision, stating that the decision was agreed upon by the PSRC 
In the absence of a principal/coordinating Investigator, decisions may be delegated in writing to 
a medically qualified sub-Investigator at the coordinating Investigator’s study center, on the 
provision that this is in agreement with Translate Bio. 
Each decision must be confirmed in writing (scanned copy via email or fax is acceptable) to the 
other members of PSRC and study Investigators by the Medical Monitor before the escalated 
dose level is administered to subjects in Part A or Part B, or before initiating Part B of the study.  
The Study Investigators will have the responsibility to ensure that IRBs are notified in writing of 
any changes from the planned escalation sequence in Parts A and B, or of any changes from the 
planned initiation of Part B of the study. In the event that a dose group is repeated in Part A, 
dosing will occur concurrently with the submission of the notification to the IRB.  
3.4.1.2. 
Other Oversight Roles 
The PSRC will have responsibility for the overall safety of the subjects participating in the study 
as well as for making key decisions in the conduct of the study. These are summarized below. 
All decisions by the PSRC must be documented in writing.   
The PSRC will be notified of 2 occurrences of significant febrile reactions in different participants 
fever [>39.0°C] associated with systemic symptomatology [eg, body aches, 
malaise, nausea]) within 24 hours following administration of IP. The PSRC will also be notified of 
all serious adverse events deemed possibly, probably, or definitely related to investigational product 
in real-time and will receive treatment-emergent SAE listings following each dose group and may 
choose to receive more frequent SAE listings at any time during the study.  
If dose group stopping criteria described in Section 4.5.4 or Part D stopping criteria described in 
Section 4.5.5 are met during the study, the relevant data will be reviewed by the PSRC. 
Following this review, the PSRC will decide whether the dose group and other ongoing higher 
dose groups will continue or be terminated.
If study stopping criteria are met during the study, all available data relating to the safety of the 
IP will be reviewed by the PSRC. Following this review, the PSRC will decide whether the study 
will continue or be terminated (Section 4.5.6).    
If an adverse event of special interest (AESI), as described in Section 8.1.8, is reported during 
the study, the PSRC will be notified by the Sponsor in real-time.  
To ensure subject safety, the PSRC may request unblinding the treatment assignment(s) for an 
individual subject or for an entire dose group. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
75 
For example, if IP administration is halted based on the stopping criteria of the study, the 
subsequent safety review may necessitate unblinding a subject’s treatment assignment; or the 
safety data for an individual subject or the dose group may be unblinded before making the 
decision to dose escalate (eg, to determine if a treatment-emergent AE occurred in a placebo 
subject or not).  
If there are any tolerability issues identified at the current single or multiple dose level 
(eg, tolerability of the prolonged nebulization time as the dose escalates), the PSRC, which 
includes the coordinating Investigators of the study, will ensure that the other Investigators and 
next group of subjects enrolled at the next higher dose level are informed of the issues. 
During the treatment of subjects in Part D, should AEs occur that are not tolerated well, the 
enrollment and treatment of subjects may be terminated by the PSRC and Sponsor, and 
enrollment and treatment of a lower dose level may be considered (Section 3.2.3).       
The PSRC’s data review will include review of the immunogenicity data, where available, to 
determine whether there is any association with allergy/hypersensitivity events, pulmonary 
exacerbations, and decreased pulmonary function. 
3.4.2. 
Dose Escalation Criteria for Parts A and B 
In Part A of the study, the 4 dose groups will be enrolled sequentially; the enrollment and 
treatment of the 4 subjects within each dose group will be staggered by at least 1 week. When 
1 week of safety follow-up has been performed for the fourth subject in the group (Groups 1 and 
2), the PSRC will review the blinded safety data for the 4 subjects in the group to determine if 
escalation to the next higher dose level (single dose) can proceed. If no dose limiting toxicity has 
been observed and there are no safety concerns for the dose group overall, the enrollment and 
treatment of subjects at the next higher single-dose level will be initiated.  
In Part B of the study, the 8, 16, and 20 mg dose groups will be enrolled sequentially. The 12 mg 
dose group may be enrolled in parallel with the 16 and/or 20 mg dose group. The enrollment and 
treatment of the 4 subjects within each dose group will be staggered by at least 2 weeks (the next 
subject in the dose group will only be enrolled and treated when the previous subject has 
received their second dose and there is approximately 1 week of safety follow-up), with the 
exception of the 12 mg dose group in Part B which may not require staggered treatment under 
the circumstances described in Section 3.1. 
Escalation from the 8 mg to the 16 and 12 mg, and from the 16 mg to the 20 mg multiple-dose 
group in Part B will occur after review of the following safety data by the PSRC:  
1. At least 1 week of safety follow-up after the 3rd dose of the 4th (last) subject of the 
previous (lower) dose.  
2. At least 28 days of safety follow-up after the dose of the 4th (last) subject of the 
corresponding single ascending dose cohort in Part A. Note that there is no corresponding 
single dose cohort for the 12 mg multiple dose group and therefore this requirement is not 
applicable. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
76 
For instance, for the decision to escalate from the 8 mg dose group to the 16 mg multiple 
dose group, the PSRC will review at least 7 days of safety follow-up after the 3rd dose of 
the 4th (last) subject receiving multiple doses of 8 mg, as well as at least 28 days of safety 
follow-up after the single dose of the 4th (last) subject receiving a single dose of 16 mg.  
When the fourth subject in the dose group (Groups 1 and 2) has completed at least 1 week of 
safety follow-up after the third dose, the PSRC will review the blinded safety data for the 4 
subjects in the group. The PSRC will also review the blinded safety data for the Part A subjects 
who received a single dose of the next higher dose level to be escalated to. Similar to Part A, if 
no dose limiting toxicity has been observed and there are no safety concerns for the dose group 
overall, the enrollment and treatment of subjects at the next higher dose level will be initiated. 
In both Parts A and B of the study, escalation to the next higher dose level may not proceed if 
2 or more subjects at the current dose level experience a Grade 3 (severe) treatment-emergent 
AE that is assessed as both clinically significant (based on the nature and duration of the toxicity) 
and probably or definitely related to IP by the Investigator. The PSRC will review these 
treatment-emergent AEs along with all available safety data to determine if dose escalation can 
proceed or will be stopped due to dose limiting toxicity. Other scenarios, which include but are 
not limited to the occurrence of possibly related Grade 3 (severe) treatment-emergent AEs, or 
probably or definitely related Grade 2 (moderate) treatment-emergent AEs that are judged as 
clinically significant, will be reviewed and assessed on a case-by-case basis by the PSRC.  
If deemed necessary by the PSRC, a dose group may be repeated in a new group of subjects to 
further assess the safety of the dose level prior to dose escalation in Part A or to further assess 
the tolerability of the dose level before deciding to advance it from single dosing in Part A to 
multiple dosing in Part B (see below).  
The PSRC may request unblinding the treatment assignment(s) for an individual subject or for 
the entire dose group to help clarify decisions to dose escalate, to repeat a dose group, or to 
initiate Part B (Section 6.2.3).    
3.4.3. 
Criteria to Initiate Enrollment and Treatment in Part B  
The 8 mg dose level of MRT5005 will be the MAD starting dose in Part B. The decision to begin 
enrollment and treatment of the first MAD group will be made by the PSRC, based on a review 
of at least 28 days of safety follow-up for all subjects who received a single dose of the 8 mg 
dose level in Part A. The review will take into consideration the clinical significance of the 
treatment-emergent AEs reported during the period (based on the nature, severity, and duration 
of the AE), and their relationship to IP (includes any available safety data from subjects who 
received a single dose of the higher 16 mg dose level in Part A).  
If no dose limiting toxicity has been observed and there are no safety concerns for the single-
dose group overall, the enrollment and treatment of subjects in the first MAD group at the 8 mg 
dose level will be initiated.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
77 
3.5.
Duration and Study Completion Definition
The subject’s maximum duration of participation is summarized below.  
 Planned maximum duration of study participation in Part A: up to 368 days. This 
consists of an initial screening period of up to 27 days, followed by 338 days (+3 day 
window) of the treatment and follow-up periods of the study.     
 Planned maximum duration of study participation in Part B: up to 396 days. This 
consists of an initial screening period of up to 27 days, followed by 366 days (+3-day 
window) of the treatment and follow-up periods of the study.    
 Planned maximum duration of study participation in Part D: up to 372 days. This 
consists of an initial screening period of up to 28 days, followed by 341 days (+ 3-day 
window) of the treatment and follow-up periods of the study. 
The study completion date is defined as the date the last subject completes their final protocol-
defined assessment. The study completion date is used to determine the timing for study results 
posting and reporting. 
3.6. 
Sites and Regions 
This study will be conducted at multiple centers in the US. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
78 
4.
STUDY POPULATION
Each subject must participate in the informed consent process and provide written informed 
consent before any procedures specified in the protocol are performed. 
4.1. 
Inclusion Criteria 
Patients will not be considered eligible for the study without meeting all of the inclusion criteria 
below. Patients cannot be enrolled before all inclusion criteria (including test results) are 
confirmed. 
1. Male and female patients with CF, 18 years of age or older. 
2. Confirmed diagnosis of CF as defined by both of the following: 
 Two CF disease-causing CFTR mutations in Class I or II (genotype confirmed at the 
screening visit). CFTR genotyping will only be performed if adequate prior 
documentation is not available. 
 Chronic sinopulmonary disease and/or gastrointestinal/nutritional abnormalities 
consistent with CF disease. 
3. Clinically stable CF disease, as judged by the Investigator.  
4. FEV1 
 
5. 
 
6.
kg/m2 
 
7. Willing to remain on stable CF medications for the duration of the study. 
 Patients who are receiving lumacaftor/ivacaftor or tezacaftor/ivacaftor combination 
drugs (ORKAMBI or SYMDEKO) are eligible for the study; however, patients must 
have been on stable treatment with this medication for at least 28 days prior to the 
screening visit, and should remain on it for the duration of the study preferably at a 
stable dose.
8. Non-smoking for a minimum of 2 years.  
9. Willing and able to give written, signed, and dated informed consent to participate in the 
study.
10. Willing and able to comply with scheduled visits, treatment, laboratory tests, restrictions, 
contraception requirements (Section 4.4), and other study procedures.  
 Patients must have adequate clinical condition to safely undergo the planned study 
procedures.  
 Able and willing to receive nebulized IP through a mouthpiece for up to 133 minutes. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
79 
4.2.
Exclusion Criteria
Patients will be excluded from the study if any of the following exclusion criteria are met. 
Patients cannot be enrolled before it is determined that the patient does not meet any of the 
exclusion criteria (including test results). 
1. History of any comorbidity that, in the opinion of the Investigator, could confound the 
results of the study, pose an additional risk from the IP or study procedures, could 
potentially contribute to the clinical instability of the subject during the study, or would 
make the subject unlikely to complete the study. This may include, but is not limited to a 
history of cardiovascular, renal, or central nervous system disease; history of serious 
mental illness; history or presence of clinically significant pathology including liver 
cirrhosis and/or portal hypertension; and history of uncontrolled CF-related diabetes.   
2. An acute upper or lower respiratory infection, pulmonary exacerbation, or clinically 
significant episode of hemoptysis (>30 mL or in the opinion of the Investigator) within 
28 days prior to Day 1. 
3. Any of the following changes in medication prior to Day 1:  
 Any change in chronic respiratory medication within 28 days prior to Day 1. 
 Initiation of any new chronic therapy (eg, inhaled hypertonic saline, or inhaled 
antibiotic (tobramycin [TOBI], aztreonam [CAYSTON]) within 28 days prior to 
Day 1.   
 Use of antibiotics or oral steroids for acute symptoms within 14 days prior to Day 1.    
4. Receiving treatment with ivacaftor monotherapy (KALYDECO). 
5. Parts A and B only: Receiving treatment with triple combination therapy (TRIKAFTA). 
Patients with a prior history of treatment with TRIKAFTA are eligible to participate if 
treatment has been discontinued at least 28 days prior to Day 1.  
6. Patients with a Class III, IV, or V CFTR gene mutation in at least 1 allele. 
 See Appendix 2 for guidance on the classification of CFTR mutations. (As the 
phenotype and classification of some CFTR mutations remains uncertain, the 
eligibility of a patient with 1 of these mutations will be at the discretion of the 
Investigator and Sponsor, based on the patient’s medical history). 
7. Any of the following abnormal laboratory values at screening: 
 Hemoglobin <10 g/dL. 
 Serum albumin <2.5 g/dL. 
 Abnormal liver function defined as meeting any 3 or more of the following: ALT 
>3x upper limit of normal (ULN); AST >3x ULN; GGT >2.5x ULN; alkaline 
phosphatase >2.5x ULN; and total bilirubin >1.5x ULN (except for patients with 
isolated Gilbert Syndrome).  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
80 
8. Any clinically significant abnormal laboratory test result prior to Day 1 that would 
interfere with the study assessments or indicate clinical instability of the patient, as 
judged by the Investigator. 
9. Infection with highly virulent bacteria associated with accelerated decline in pulmonary 
function and/or decreased survival (eg, Burkholderia cenocepacia, Burkholderia dolosa, 
Mycobacterium abscessus). For a patient with a history of positive culture, he/she can be 
considered free of infection based on the following guidance: 
 All cultures obtained within the past 12 months should be negative for these bacteria. 
The patient should have had at least 2 cultures performed within the past 12 months, 
at least 3 months apart, with at least 1 culture obtained within 6 months of screening 
for this study. 
10. History of or listed for solid organ or hematological transplantation.   
11. Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B surface 
antigen (HBsAg), or hepatitis C virus (HCV) antibodies at screening. 
12. Positive test for drugs of abuse or alcohol at the screening visit.  
13. Donation of blood or blood products within 60 days prior to the initial screening visit. 
14. Participation in an IP or device study within 30 days prior to the initial screening visit or 
at any time during this Translate Bio-Sponsored study. (The 30-day window applies to 
IPs with elimination half-lives of <6 days. If the elimination half-
then the window should be extended to at least 5 half-lives from the last dose 
administered.)   
15. Prior enrollment in this study, with the exception of subjects who discontinued treatment 
after one dose of study drug for a reason unrelated to safety as specified in Section 
7.1.1.2. (A patient is considered enrolled into the study when he or she has been 
randomized.)  
16. Any suspicion of, or history of, alcohol and/or other substance abuse or addiction within 
the past year. 
17. Pregnant or lactating females. 
18. History of drug allergy or other allergy that, in the opinion of the Investigator, 
contraindicates participation (eg, history of allergic reactions that could interfere with the 
safety assessment of the IP). 
19. History of allergic reactions to any component of the IP including its excipients.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
81 
4.3.
Restrictions 
The following restrictions apply to the in-house stay in the study center (Day -1 to Day 2) for 
subjects participating in Part A of the study. 
1. Subjects should refrain from strenuous physical exercise 48 hours prior to admission to 
the study center and during the in-house stay at the study center. 
2. Subjects should refrain from alcohol 48 hours prior to admission to the study center and 
during the in-house stay at the study center. 
3. Subjects will be required to eat the provided meals while housed in the study center. 
4.4.
Reproductive Potential
4.4.1. 
Female Contraception 
Sexually active females of childbearing potential should be using an acceptable form of 
contraception. These subjects must be advised to use an acceptable method of contraception, as 
defined below, from the time the informed consent is signed until the final study visit on 
Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 341 (±3 days) in Part D of the 
study. If hormonal contraceptives are used, they should be administered according to the package 
insert. 
Females of childbearing potential who are not currently sexually active must agree to use an 
acceptable method of contraception, as defined below, if they become sexually active during the 
study.   
Acceptable methods of contraception are: 
 Intrauterine devices plus condoms. 
 Double-barrier methods (eg, condoms and diaphragms with spermicidal gel or foam). 
 Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring), stabilized for 
at least 30 days prior to the administration of the IP, plus condoms. Note: if a subject 
becomes sexually active during the study, they should use one of the other acceptable 
methods noted above in addition to the hormonal contraceptive until it has been 
stabilized for 30 days. 
Females of childbearing potential currently taking the lumacaftor/ivacaftor 
combination drug (ORKAMBI) and using oral hormonal contraceptives will be 
required to take an additional or alternative method of contraception to prevent 
pregnancy in this study.
Vasectomized partner (at least 6 months post-procedure).
Exclusively same-sex (female) partner.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
82 
Female subjects of non-childbearing potential are defined as either:
Post-menopausal (12 consecutive months of spontaneous amenorrhea and 51 years 
of age)
or 
Surgically sterile (having undergone one of the following procedures: hysterectomy, 
bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy) and at 
least 6 weeks post-sterilization. 
-hCG pregnancy tests will be performed on all female subjects, regardless of 
childbearing potential, as described in Section 7.5.2.8. 
4.4.2. 
Male Contraception 
All sexually active male subjects who are able to have children must agree to consistently use a 
barrier method from the time the informed consent is signed until the final study visit on 
Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 341 (±3 days) in Part D of the 
study. Female partners of these subjects must also use at least one of the acceptable methods of 
contraception listed in Section 4.4.1 during the same time period.  
Male subjects who are able to have children must agree not to donate sperm for the purposes of 
making a woman pregnant from the time the informed consent is signed up to the final study 
visit. 
For this study, male subjects will be considered as unable to have children if they are 1) infertile 
due to congenital bilateral absence of the vas deferens documented in the subject’s medical 
record based on ultrasonography and/or semen analysis, 2) sterilized (vasectomy), 3) not 
sexually active, or 4) exclusively same sex (male) partner.
4.5.
Discontinuation of Subjects and Individual Stopping Rules 
A subject may withdraw from the study at any time for any reason without prejudice to their 
future medical care by the physician or at the institution. The Investigator or Sponsor may 
withdraw the subject at any time (eg, in the interest of subject safety). The Investigator is 
encouraged to discuss withdrawal of a subject with the Medical Monitor when possible. 
If a subject is discontinued from the study, regardless of the reason, the early withdrawal 
evaluations listed below are to be performed as completely as possible. Comments (spontaneous 
or elicited) or complaints made by the subject must be recorded in the source documents. The 
reason for termination must be recorded in the CRF and source documents (Section 4.5.1). 
If enrolled subjects discontinue from the study, these subjects may be replaced at the Sponsor’s 
discretion, as described in Section 4.5.2. 
Early withdrawal evaluations: 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
83 
 Physical examination 
Vital signs (blood pressure, pulse, body temperature, respiratory rate)
Pulse oximetry
Weight
Spirometry
 Clinical laboratory tests (serum chemistry, hematology, coagulation, urinalysis, 
C-reactive protein [CRP])
ECG
 AE/serious adverse event (SAE) reporting 
 Recording of concomitant medications and concomitant surgical procedures 
 Serum or urine pregnancy test  
 Testing for immune response assays, inflammatory markers, and/or 
 
mRNA and 
 assays at the discretion of the Investigator and/or Sponsor 
4.5.1. 
Reasons for Discontinuation and Individual Stopping Rules 
Individual Subjects will be discontinued by the Investigator if they meet any of the stopping 
rules described below:  
1. 
 fever (>39.0 °C) associated with 
systemic symptomatology (eg, body aches, malaise, nausea) within 24 hours following 
administration of IP.  
2. An absolute decrease in predicted FEV1 of at least 25% compared to the baseline value 
(defined as the average of the Day -1 and Day 1 pre-dose values) during the 5-week 
treatment period in Part B or through Day 11 (1 week post-5th dose) in Part D that cannot 
be explained, in the opinion of the PI, by the underlying disease of CF and that is 
confirmed on 2 separate occasions at least 3 days apart  
3. A suspected moderate to severe allergic/hypersensitivity reaction, including but not 
limited to anaphylaxis, generalized rash, edema or bronchospasm possibly related to drug 
treatment 
4. Deterioration of liver function as explained below and in Section 8.1.4.1 
a. Elevation of ALT or AST to >5x ULN in a subject regardless of baseline value         
b. Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, with the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
84 
appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, 
fever, rash, and/or eosinophilia (>5%). 
c.
Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, and total 
bilirubin >2x ULN or INR >1.5.  
If any of the above criteria is met by a Part B or Part D subject who has not completed dosing 
with IP, treatment must be interrupted immediately and the Medical Monitor notified of this 
action.    
A thorough investigation of other potential causes should be conducted in all cases. If no 
convincing alternative etiology (eg, pre-existing CF-related liver disease, viral hepatitis, alcohol 
ingestion, concomitant medication [such as antibiotic treatment]) for the elevated transaminases 
and symptoms is identified, regardless of whether ALT or AST levels have improved, treatment 
of the subject must be discontinued, in consultation with the Medical Monitor. If a convincing 
alternative etiology for the elevated transaminases is identified and the subject’s symptoms and 
laboratory findings have improved, the Investigator may consider resuming IP treatment with 
close monitoring, in consultation with the Medical Monitor. 
The reason for withdrawal must be determined by the Investigator and recorded in the subject’s 
medical record and on the CRF. If a subject is withdrawn for more than 1 reason, each reason 
should be documented in the source document and the most clinically relevant reason should be 
entered on the CRF. 
Reasons for discontinuation include but are not limited to: 
AE
Pregnancy
Protocol deviation
Withdrawal by subject
Lost to follow-up
Physician decision
Study terminated by Sponsor
Other (if “Other” is selected, the Investigator must specify on the CRF)
For all discontinued subjects who received the IP, every attempt must be made to follow each 
subject for the duration of the study.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
85 
4.5.2.
Replacement of Subjects
If the planned number of subjects do not complete the study or complete certain procedures, 
additional subjects will be enrolled at the Sponsor’s discretion to ensure that at least 16, 16, and 
8 evaluable subjects complete Parts A, B, and D of the study, respectively.    
4.5.3. 
Subjects Lost to Follow-up Prior to Last Scheduled Visit 
A minimum of 3 documented attempts must be made to contact any subject lost to follow-up at 
any time point prior to the final scheduled study visit on Day 337 (±3 days) in Part A, Day 365 
(±3 days) in Part B, or Day 341 (±3 days) in Part D of the study. At least 1 of these documented 
attempts must include a written communication sent to the subject’s last known address via 
courier or mail (with an acknowledgement of receipt request) asking that they return to the study 
center for their final safety evaluations. 
4.5.4. 
Dose Group Stopping Criteria 
IP administration will be halted for all subjects in a dose group, as well as any subjects in an 
ongoing higher dose group if any of the following stopping criteria are met:  
a. Two subjects in a dose group 
Grade 2 fever [>39.0 °C] associated with systemic symptomatology [eg, body aches, 
malaise, nausea]) within 24 hours following administration of IP. 
b. Two subjects in a dose group experience a suspected moderate to severe 
allergic/hypersensitivity reaction, including but not limited to anaphylaxis, 
generalized rash, edema or bronchospasm possibly related to drug treatment. 
To determine whether this dose group stopping rule has been met, the relevant data will be 
reviewed by the PSRC. The treatment assignment of one or more subjects may be unblinded at 
the request of the PSRC, as described in Section 3.4.1.2. Following this review, the PSRC will 
decide if the dose group and other ongoing higher dose groups will:  
 Resume unchanged or      
 Resume with modifications to the protocol or  
 Be terminated.  
The Sponsor is responsible for notifying the relevant regulatory authorities and the Investigator 
is responsible for promptly notifying the relevant IRB of the decision. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
86 
4.5.5.
Part D Stopping Criterion
IP administration will be halted for all subjects in Part D if the following stopping criterion is 
met: 
a. Three subjects experience Grade 1 fevers (38.0 to 39.0 °C) associated with systemic 
symptomatology (eg, body aches, malaise, nausea) onset within 24 hours following 
administration of IP on 3 separate occasions. 
To determine whether this dose group stopping rule has been met, the relevant data will be 
reviewed by the PSRC. The treatment assignment of one or more subjects may be unblinded at 
the request of the PSRC, as described in Section 3.4.1.2. Following this review, the PSRC will 
decide if the dose group and other ongoing higher dose groups will:  
 Resume unchanged or      
 Resume with modifications to the protocol or  
 Be terminated.  
The Sponsor is responsible for notifying the relevant regulatory authorities and the Investigator 
is responsible for promptly notifying the relevant IRB of the decision.
4.5.6. 
Study Stopping Criteria 
IP administration will be halted for all subjects if any of the following stopping criteria are met: 
a. A subject experiences a Grade 4, life-threatening treatment-emergent AE or death that 
is considered probably or definitely related to IP by the Investigator  
b. Two or more subjects in a dose group experience 1 or more moderate or severe 
pulmonary exacerbations during the 5-week treatment period in Part B or through 
Day 11 (1 week post-5th dose) in Part D
c. Two or more subjects in a dose group experience an absolute decrease in predicted 
FEV1 of at least 25 % compared to the baseline value (defined as the average of the 
Day -1 and Day 1 pre-dose values) during the 5-week treatment period in Part B or 
through Day 11 (1 week post-5th dose) in Part D that cannot be explained, in the 
opinion of the Investigator, by the underlying disease of CF and that is confirmed on 
2 separate occasions at least 3 days apart  
d. Two or more subjects in the study experience a suspected serious 
allergic/hypersensitivity reaction, including but not limited to anaphylaxis, 
generalized rash or bronchospasm likely to be related to drug treatment
e.
Two or more subjects in a dose group experience a deterioration in liver function, as 
detailed below:
i. 
Elevation of ALT or AST to >5x ULN in a subject regardless of baseline value 
ii. 
Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, with the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
87 
appearance of fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%).  
iii. 
Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, and total 
bilirubin >2x ULN or INR >1.5.  
To determine whether these stopping rules have been met, all available data relating to the safety 
of the IP will be reviewed by the PSRC. The treatment assignment of one or more subjects may 
be unblinded at the request of the PSRC, as described in Section 3.4.1.2. Following this review, 
the PSRC will decide if the study will:  
 Resume unchanged or      
Resume with modifications to the protocol or
 Be terminated.  
The Sponsor is responsible for notifying the relevant regulatory authorities and the Investigator 
is responsible for promptly notifying the relevant IRB of the decision. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
88 
5.
PRIOR AND CONCOMITANT TREATMENT AND 
PROCEDURES 
5.1. 
Prior and Concomitant Medications and Therapies 
Information on all prior and concomitant medications administered from 30 days before the date 
of informed consent signing through the final study visit on Day 337 (±3 days) in Part A, Day 
365 (±3 days) in Part B, or Day 341 (±3 days) in Part D of the study must be recorded on the 
appropriate CRF page. This includes the subject’s routine and non-routine CF medications, other 
medications, and herbal and homeopathic preparations. 
All therapies being taken by the patients on entry to the study or at any time during the study are 
regarded as concomitant therapies and will be documented on the appropriate pages of the CRF. 
These include but are not limited to airway clearance techniques.   
5.1.1. 
Permitted Medications and Therapies 
Subjects should remain on a stable medication regimen for CF from at least 28 days prior to the 
screening visit through the final study visit on Day 337 (±3 days) in Part A, Day 365 (±3 days) in 
Parts B, or Day 341 (±3 days) in Part D of the study. These may include but are not limited to 
routine inhaled therapies directed at airway clearance and management of respiratory infections, 
such as bronchodilators, rhDNase (PULMOZYME), hypertonic saline, antibiotics, and steroids; 
and other routine CF-related therapies such as systemic antibiotics, pancreatic enzymes, 
multivitamins, and diabetes and liver medications. The timing of subject participation and 
routine treatment with cycled inhaled antibiotics will be left up to the discretion of the 
Investigator. 
Hormone replacement therapies, thyroid hormone replacement therapy, and non-steroidal 
inflammatory drugs are also permitted.  
Any other medications which are considered necessary for the subject’s safety and well-being 
may be given at the discretion of the Investigator. For example, for subjects experiencing a 
pulmonary exacerbation, therapeutic interventions may include oral or intravenous 
administration of antibiotics, oral or parenteral nutritional support, frequent airway clearance 
techniques, augmented bronchodilator therapy, and corticosteroids. 
Other specific medications permitted during the study are listed below: 
 Hormonal contraceptives for females of childbearing potential administered 
according to the package insert (see Section 4.4.1).  
 Lumacaftor/ivacaftor combination drug (ORKAMBI) or tezacaftor/ivacaftor 
combination drug (SYMDEKO). For Part D only: elexacaftor/tezacaftor/ivacaftor 
triple combination (TRIKAFTA). To be eligible, subjects must have been on stable 
treatment with these medications for at least 28 days prior to the screening visit and 
should remain on it for the duration of the study. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
89 
Subjects should remain on their routine CF therapies, which include but are not limited to airway 
clearance techniques.   
5.1.1.1. 
Modifications of Subject’s Routine Pulmonary Medications and Therapies  
If feasible for the subject, all spirometry testing should be performed “pre-bronchodilator” if the 
subject is receiving treatment with a short-acting beta-agonist or anticholinergic bronchodilator 
(eg, beta-agonist medication such as albuterol or anticholinergic agent such as ipratropium 
bromide). These medications should be withheld for at least 4 hours before spirometry testing 
(Section 7.5.2.12). 
On the days of IP dosing, the administration of IP should optimally occur within 2-3 hours after 
subjects have completed their routine pulmonary therapies (airway clearance and pulmonary 
medications) for the day. For subjects whose routine airway clearance therapies do not include 
an inhaled short-acting beta-agonist (or it is not given within the 2 to 3 hour window prior to IP 
administration), albuterol (2 to 4 puffs) will be administered via metered-dose inhaler 
approximately 20 minutes before nebulization with IP to minimize any bronchoconstrictive 
effects. Note that administration of short-acting beta-agonist via nebulization is also permitted at 
the discretion of the Investigator. 
5.1.2. 
Prohibited Medications  
Specific medications not permitted during the study are listed below: 
 Ivacaftor monotherapy (KALYDECO)  
 Parts A and B only: Triple-combination therapy (TRIKAFTA)  
Starting on or switching to TRIKAFTA is acceptable during the follow-up period; however, 
subjects should not start/switch until at least 2 months after their last dose of study drug so as not 
to confound the interpretation of the primary and secondary endpoints. 
5.2. 
Concomitant Surgical Procedures 
Surgical procedures (eg, ventral hernia repair, tooth extraction, sinus surgery) that occur from the 
date of informed consent signing through the final study visit must be recorded on the 
Concomitant Surgical Procedure CRF page. The date(s) of the procedure and the indication for 
the procedure will be documented. The indication must have a corresponding entry on the 
Medical History page (for pre-existing conditions) or Adverse Event page (for new or worsened 
pre-existing conditions), unless the surgical procedure was prophylactic in nature (eg, PICC line 
placement for CF cleanout). 
For any unplanned hospitalization or prolongation of hospitalization, the procedures for safety 
reporting should be followed (see Section 8).  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
90 
6.
INVESTIGATIONAL PRODUCT
See the Pharmacy Manual for detailed instructions on the preparation of the IP.  
Information on the preparation of study product is provided in Section 6.2.2. Labeling and 
packaging descriptions are provided in Section 6.3.1, and storage conditions are described in 
Section 6.3.2. 
6.1.
Identity of Investigational Product
6.1.1. 
MRT5005  
MRT5005 is a lipid nanoparticle suspension consisting of 
mRNA (
 mRNA), the active drug substance, 
formulated with the  lipids, 
. MRT5005 is dosed based on its 
content of 
 mRNA.   
MRT5005 will be supplied as a sterile suspension in single-use vials. Each vial contains 
approximately 3.2 mL of MRT5005 at a concentration of 0.6 mg/mL of 
 mRNA. An 
InnoSpire Go nebulizer will be used to administer MRT5005 to the lungs by nebulization. 
MRT5005 is dosed based on its content of 
 mRNA. 
Refer to the MRT5005 Investigator’s Brochure for further information about the drug product. 
6.1.2. 
Placebo Comparator 
Sterile normal saline solution (Sodium Chloride Inhalation Solution, USP 0.9%) will be used as 
the placebo comparator. 
6.1.3.
Blinding the Treatment Assignment
This study will be conducted as a randomized, double-blinded, placebo-controlled trial. The 
blinding of the study will be maintained as described below.
The Investigators and all study staff involved in the evaluation of subject eligibility, 
administration of IP, and assessment of study outcomes will be blinded to treatment assignment 
(MRT5005 vs. placebo within each dose group). All subjects and their families, as well as 
Sponsor personnel in direct contact with the study center, will also be blinded. The blinded 
Investigator and study staff must not be allowed to know the IP assigned to any study subject and 
must not be allowed to see the randomization code; IP, its containers or its preparation; or 
treatment records until planned interim analyses are completed, as specified in Section 6.2.3. In 
addition, study staff who will be administering IP (and monitoring the subject for any signs or 
symptoms of respiratory distress) will be instructed not to open the nontransparent medication 
cup of the InnoSpire Go to visualize the study drug as MRT5005 will appear different than the 
normal saline placebo (see below). As such, all relevant individuals will be blinded to treatment 
assignment, thus maintaining the double-blinded conduct of the study.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
91 
As the MRT5005 suspension and normal saline placebo will appear different (normal saline will 
also be supplied in its commercial presentation and stored at a different temperature), designated 
unblinded members of the study staff and/or pharmacy will be responsible for preparing and 
dispensing IP into the nebulizers. The unblinded members of the study staff and/or pharmacy 
will also be responsible for randomizing subjects once their eligibility has been confirmed. The 
unblinded members of the study staff and pharmacy will be fully trained in their study-related 
responsibilities. They will not participate in any other part of the study and will maintain the 
subject treatment assignments in strict confidence. Their roles will be documented on the study 
center’s delegation of authority log. 
Sponsor designated unblinded monitors will be permitted access to monitor the IP preparation, 
dispensing, and accountability records as well as randomization codes during the study. 
Circumstances in which treatment assignments may be broken are presented in Section 6.2.3.  
6.2. 
Administration of IP 
6.2.1. 
Allocation of Subjects to Treatment 
Within each dosing group in Parts A, B and D of the study, subjects will be randomly assigned to 
receive either MRT5005 or placebo in a 3:1 ratio. As stated in Section 6.1.3, a designated 
unblinded member of the study staff or pharmacist will be responsible for randomizing subjects 
once their eligibility has been confirmed. The randomization will be performed centrally across 
the multiple sites; the designated unblinded member of the study staff or pharmacist will retrieve 
the subject’s treatment assignment using an interactive web response (IWR) system. Treatment 
assignments will be held in strict confidence by the unblinded study staff member or pharmacist. 
If a treatment assignment has been allocated incorrectly, the study monitor must be notified as 
soon as the error is discovered.  
As defined in Section 3.2, a subject is considered enrolled into the study when he or she has been 
randomized. 
Information on unblinding procedures is provided in Section 6.2.3. 
6.2.2. 
Preparation of IP 
Designated unblinded members of the study staff and/or pharmacy will be responsible for 
preparing and dispensing the IP for administration.  
MRT5005 will be supplied as a sterile suspension in single-use vials. Each vial contains 
approximately 3.2 mL of MRT5005 at a concentration of 0.6 mg/mL of 
 mRNA. 
Vials of MRT5005 should be stored frozen as described in Section 6.3.2. Prior to administration, 
the appropriate number of vials to deliver the dose of MRT5005 should be thawed completely at 
room temperature (typically requires 40 minutes). The MRT5005 suspension should be brought 
to room temperature prior to dispensing into the nebulizers.    

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
92 
MRT5005 is dosed based on its content of 
 mRNA, the active drug substance. An 
InnoSpire Go nebulizer will be used to administer MRT5005 by nebulization at a flow rate of 
approximately 0.3 mL/minute. MRT5005 will be administered to subjects at the following 5 dose 
levels: 4, 8, 12, 16, 20, and 24 mg of 
 mRNA (nominal dose levels). Table 11 shows 
the volume of MRT5005 suspension to be nebulized and approximate nebulization time for each 
of the 5 dose levels of MRT5005 (time does not include the scheduled rest periods between 
nebulizer changes; see Dosing of IP below). The nebulization times are only targets and will 
vary; as such, these variations should not be reported as protocol deviations.     
The medication cup of the InnoSpire Go nebulizer holds a maximum of 8 mL of solution (see 
instruction manual for InnoSpire Go nebulizer in Appendix 3). As nebulizers will not be refilled 
during nebulization, multiple nebulizers, as shown in Table 11, will be used to deliver the 
specified volume for each of the dose levels of MRT5005. The MRT5005 suspension will be 
divided equally among the nebulizers.  
Table 11:  
Dosing of MRT5005 - Volumes and Nebulization Times 
 
Dose of MRT5005 (mg)a 
4 
8 
12 
16 
20 
24 
Total Nebulization Volume 
(mL)b 
7 
14 
21 
28 
35 
42 
Nebulization Time 
(minutes)c 
22 
44 
66 
89 
110 
133 
No. of Nebulizersd 
1 
2 
3 
4 
5 
6 
a  Nominal dose of 
 mRNA. 
 
b  Includes an additional 0.3 mL per each nebulizer to account for the expected residual volume after nebulization. 
Based on the measurement accuracy of a 10 mL syringe, the volume per nebulizer has been rounded to the nearest 
0.2 mL. The total nebulization volume is based on the rounded volume per nebulizer and the number of 
nebulizers. 
c Approximate nebulization time is based on a flow rate of 0.3 mL/minute for the InnoSpire Go nebulizer. This 
represents actual nebulization time and does not include the rest periods between nebulizer changes.       
d  The medication cup of the InnoSpire Go nebulizer holds a maximum of 8 mL of solution. As nebulizers will not 
be refilled during nebulization, multiple nebulizers, as shown in the table, will be used to deliver the specified 
volume for each of the dose levels of MRT5005. The MRT5005 suspension will be divided equally among the 
nebulizers.  
Sterile normal saline (Sodium Chloride Inhalation Solution, USP 0.9%) will be used as placebo. 
To maintain the blind of the study, the volume and nebulization time of placebo, and number of 
nebulizers used to deliver placebo will match that of the MRT5005 dosing group. Normal saline 
should be stored (see Section 6.3.2) and administered at room temperature.   
For the purposes of this study, the mouthpiece of the nebulizer, which includes the medication 
cup and filter attachment with its filter, will be considered single-use and will not reused for 
another administration. Nebulizer handles will not be reused for single dosing of subjects in Part 
A. However, nebulizer handles will be reused for multiple dosing in Parts B and D. In this case, 
nebulizer handles will be assigned to and used by only one subject.    

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
93 
6.2.2.1.
Dosing of IP
The administration of IP will be performed by a blinded, qualified member of the study staff. For 
scheduling of IP administration with respect to the subjects’ routine pulmonary medications and 
therapies, refer to Section 5.1.1.1.   
For administration of the IP, the subject should be seated comfortably in a chair and the 
nebulizer should be held in an upright position; the arm holding the nebulizer may be supported 
according to the subject’s preference (eg, resting the elbow on the arm of a phlebotomy chair). 
The subject will be instructed to place the mouthpiece of the nebulizer between their teeth, with 
their lips firmly sealed around the mouthpiece, and to breathe through their mouth at their normal 
rate and tidal volume until the aerosol formation completely stops (see instruction manual for 
InnoSpire Go micropump nebulizer in Appendix 3). The subject should turn off the nebulizer 
when taking the mouthpiece out of their mouth (eg, to talk) to avoid loss of IP and to minimize 
secondary exposure (see below). As described above, multiple nebulizers may be used to deliver 
IP (Table 11); to reduce the burden of administration, the subject will be offered a 15 to 20-
minute rest period before changing to the next nebulizer (if applicable; this interval may be 
extended if needed for subject tolerability). For example, subjects receiving the 16 mg dose level 
may have rest periods after the first, second, and third nebulizers for a total of 3 rest periods 
during the nebulization. 
During nebulization of IP, the subject will be monitored closely for any signs or symptoms of 
respiratory distress (eg, dyspnea, wheezing, bronchospasm). In Part A and Part B, blood 
pressure, pulse rate, and oxygen saturation measured by pulse oximetry will be continuously 
monitored during nebulization (except during rest periods) and will be recorded at the end of the 
nebulization with each of the multiple nebulizers used to deliver the total volume of IP (eg, for 
the 16 mg dose, values will be recorded at the end of the nebulization with each of the 4 
nebulizers used to deliver the 28 mL of total volume); the final recording will count as the Hour 
0 time point. Blood pressure, pulse rate, and/or oxygen saturation may be recorded more 
frequently, if clinically indicated. Body temperature will not be monitored during the dosing 
period.  
6.2.2.2. 
Secondary Exposure to Study Staff 
To mitigate any secondary exposure of study staff to MRT5005 as well as any potential 
environmental exposure, the exhalation port of the InnoSpire Go will be fitted with a filter. The 
exhalation port is the primary source of secondary exposure during nebulization; the filter will 
minimize the amount of IP that could be inhaled by study staff. To further mitigate any potential 
secondary exposure, as described above, the subject should turn off the nebulizer when taking 
the mouthpiece out of their mouth during nebulization (eg, to talk). As an added precaution, 
study staff should wear gloves, a gown, eyewear, and a disposable particulate filtering facepiece 
respirator (N95 Respirator or equivalent based on institutional policy) during administration of 
IP. Respirators should be discarded after each use.   
6.2.3. 
Unblinding Treatment Assignments 
A description of the blinding procedures is provided in Section 6.1.3. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
94 
The treatment assignments for subjects will be kept strictly confidential, accessible only to 
authorized persons (Section 6.1.3), until the time of unblinding.  
The blind will be maintained in the 8, 16, and 24 mg single dose groups in Part A until 1 month 
after the last dose (Day 29) of the last subject in the 24 mg dose group. The blind will be 
maintained in the 20 mg single dose group in Part A, as well as the 8, 16, and 12 mg multiple 
dose groups in Part B until the 1-month timepoint after the last dose (Day 57) of the last subject 
dosed in the 12 mg dose group. For the 20 mg multiple dose group in Part B (if applicable), the 
blind will be maintained until the last subject in this group has reached the 1-month timepoint 
after the last dose day (Day 57). For Part D, the blind will be maintained until the 1-month 
timepoint after the last dose (Day 32) of the last subject in Part D. Data collection for each 
subject will continue until 12 months after their last dose. 
The treatment assignments should not normally be broken during the study, but may be broken in 
the following circumstances: 
 In an emergency situation where knowledge of the treatment assignment would be 
necessary for medical management of the subject. Prior to emergency unblinding, and 
if the situation allows it, the Investigator should first contact the Medical Monitor. If 
the treatment assignment is broken for an individual subject, the date and time of 
code break as well as the reason for unblinding must recorded on the CRF. 
 In circumstances where unblinding the treatment assignment for an individual subject 
would be necessary for the assessment of safety. Such unblinding would occur on a 
case-by-case basis at the request of the PSRC (Section 3.4.1). For example, if IP 
administration is halted based on the stopping criteria of the study (Section 4.5.6), the 
safety review may necessitate unblinding of a subject’s treatment assignment. 
 To ensure subject safety, the PSRC may request unblinding the treatment 
assignment(s) for an individual subject or for the entire dose group in Parts A or B of 
the study to help clarify decisions to dose escalate, to repeat a dose group, or to 
initiate Part B of the study (Sections 3.4.1 and 3.4.2).   
 If a reportable safety event occurs in a subject receiving MRT5005, then the subject’s 
treatment assignment will be unblinded and an unblinded MedWatch form and Dear 
Doctor Letter will be provided to sites and IRBs by the Rho clinical team.  
Subjects participating in the study will be informed of their treatment assignment after the 
interim analysis of the part of the study in which the subject participated is completed. 
6.3. 
Labeling, Packaging, Storage, and Handling 
6.3.1. 
Labeling and Packaging 
The Sponsor or designee will provide MRT5005 and placebo for this study. These will be 
packaged in the labeled containers as described below. Changes to Sponsor-supplied packaging 
prior to dosing may not occur without full agreement in advance by the Sponsor. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
95 
6.3.1.1.
MRT5005
MRT5005 will be supplied to clinical sites in single-use vials, which will be packaged in cartons 
containing multiple vials. The vials and cartons will be labeled with a minimum of the protocol 
number, dosage form including IP name, medication identification number (Lot#), dosing 
instructions, storage conditions, the statements “CAUTION: New Drug - Limited by Federal 
(United States) Law to Investigational Use” and the Sponsor's name and address. 
6.3.1.2. 
Placebo Comparator 
Commercially available single-use, sterile, normal saline solution (Sodium Chloride Inhalation 
Solution, USP 0.9%) will be used as placebo in the study. The normal saline solution will be 
supplied in their commercial vials, which will be over-labeled with an IP label. The placebo vials 
will be packaged in cartons containing multiple vials; the carton will also be labeled with an IP 
label.      
6.3.2. 
Storage of IP 
 MRT5005 vials should be stored frozen at -80°C ± 5°C (-112°F ± 9°F) in an 
appropriate freezer until the day of use. 
 Normal saline solution (placebo comparator) should be stored at controlled room 
temperature from 15°C to 30°C (59°F to 86°F).  
The Investigator has overall responsibility for ensuring that IP (MRT5005 and placebo) is stored 
in a secure, limited-access location. Responsibility may be delegated to the pharmacy, but this 
delegation must be documented. IP should only be prepared by the designated unblinded 
pharmacist or qualified person, who will enter the unique subject identifier on the IP labels 
(MRT5005 and placebo vial labels). 
MRT5005 and placebo must be stored in accordance with labeled storage conditions. 
Temperature monitoring is required at the storage location to ensure that IP is maintained within 
an established temperature range. The Investigator is responsible for ensuring that the 
temperature is monitored throughout the duration of the study and that records are maintained; 
the temperature should be monitored continuously by using either an in-house system, a 
mechanical recording device such as a calibrated chart recorder, or by manual means, such that 
both minimum and maximum thermometric values over a specific time period can be recorded 
and retrieved as required. Such a device (ie, certified min/max thermometer) would require 
manual resetting upon each recording. The Sponsor must be notified immediately upon 
discovery of any excursion from the established range. Temperature excursions will require site 
investigation as to cause and remediation. The Sponsor will determine the ultimate impact of 
excursions on IP and will provide supportive documentation as necessary. Under no 
circumstances should the product be dispensed to subjects until the impact has been determined 
and the product is deemed appropriate for use by the Sponsor. 
The Sponsor should be notified immediately if there are any changes to the storage area of IP 
that could affect the integrity of the product(s), eg, fumigation of a storage room. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
96 
The Sponsor designated unblinded monitors will be permitted access to monitor the IP storage 
area during the study. 
6.4. 
Drug Accountability 
Investigators will be provided with sufficient amounts of the IP to carry out this protocol for the 
agreed number of subjects. The Investigator or designee will acknowledge receipt of IP, 
documenting shipment content and condition. Accurate records of all IP dispensed, used, 
returned, and/or destroyed must be maintained as detailed further in this section. 
The Investigator has overall responsibility for administering IP. However, to maintain the blind, 
this task will be delegated to a qualified designee (eg, a pharmacist) who is adequately trained in 
the protocol and who works under the direct supervision of the Investigator. This delegation 
must be documented in the applicable study delegation of authority form. 
The Investigator or his/her designee (as documented by the Investigator in the applicable study 
delegation of authority form) will administer the IP only to subjects included in this study 
following the procedures set out in the study protocol. Each subject will be given only the IP 
carrying his/her treatment assignment. All administered medication will be documented on the 
CRFs and/or other IP record. 
No IP stock or returned inventory from a Translate Bio-Sponsored study may be removed from 
the site where originally shipped without prior knowledge and consent by the Sponsor. If such 
transfer is authorized by the Sponsor, all applicable local, state, and national laws must be 
adhered to for the transfer.
The Sponsor designated unblinded monitors will be permitted access to monitor the IP supplies 
storage, preparation, dispensing, and accountability records as well as randomization codes 
during the study. 
With the written agreement of the Sponsor, at the end of the study all unused stock and 
empty/used IP packaging may be destroyed at the site or a local facility. In this case, destruction 
records identifying what was destroyed, when and how, must be obtained with copies provided 
to the Sponsor. Destruction of IP must be in accordance with local, state, and national laws. 
Based on entries in the site drug accountability forms, it must be possible to reconcile IPs 
delivered with those used, destroyed, or returned. All IPs must be accounted for and all 
discrepancies investigated and documented to the Sponsor’s satisfaction. 
6.5. 
Subject Compliance 
IP is administered under controlled conditions by the Investigator’s designee; therefore, full 
subject compliance with study treatment is anticipated in this study. 
The designated person will record details on the drug accountability log(s) and/or source 
documents. In addition, details of the dosing time (time and date) will be captured in the 
appropriate CRF. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
97 
7.
STUDY PROCEDURES
7.1. 
Part A Study Schedule 
Details regarding the procedures and tests to be performed during each study period and time 
point for Part A are provided in the Schedule of Procedures in Table 1, Table 2, and Table 3.    
Part A of this study consists of 3 periods: a screening period, a treatment period, and a follow-up 
period (see Figure 1). The duration of the screening period is up to 27 days (Day -28 through 
Day -2); the duration of the treatment period is 3 days (Day -1 to Day 2); and the duration of the 
follow-up period is up to 327 days (Day 3 through Day 337 [±3 days]). During the treatment 
period, Part A subjects will be admitted to the study center on Day -1 and will be confined to the 
study center (inpatient) until discharged on Day 2 of the study. During the follow-up period, 
subjects will perform all clinic visits as outpatients.  
All AEs and SAEs, regardless of relationship, will be collected from the time the subject signs 
the informed consent until the final study visit on Day 337 (±3 days). Information on all prior 
and concomitant medications administered from 30 days before the date of informed consent 
signing through the final study visit on Day 337 (±3 days) must be recorded on the appropriate 
CRF page.  
Time Windows for the Schedule of Procedures: 
No obligatory time windows are set for the study time points in order to allow for flexibility in 
the conduct of the study. The time windows provided in Table 1, Table 2, and Table 3 are 
suggested guidelines to be followed during the conduct of Part A. As these guidelines are only 
suggestions, they will not result in protocol deviations.  
Priority Order for Performing Procedures and Tests: 
The following “priority order” will be in effect when more than 1 procedure or test is required at 
a particular time point. 
Review of AEs, concomitant medications, and concomitant surgical procedures 
 Vital signs, pulse oximetry 
 Physical examination 
 Spirometry 
 Clinical laboratory tests (serum chemistry, hematology, coagulation, urinalysis, CRP) 
 ECG 
 Chest x-ray 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
98 
 Other procedures with lower priorities (weight measurement; blood sampling for 
 mRNA and 
 assays; and blood sampling for immune response assays) 
On the days when serum or urine pregnancy testing is being performed, scheduled or 
unscheduled, this test has priority. 
7.1.1. 
Screening Period: Day -28 to Day -2  
See Table 1 for the Schedule of Procedures for the screening period of Part A.
Written, signed, and dated informed consent (specific for Part A) must be obtained by the 
Investigator or a designee from the subject prior to the performance of any study-related 
procedures or tests. A copy of the informed consent form must be given to the subject for their 
records.    
At the initial screening visit, informed consent will be obtained from the subject. A unique 
subject identification number will then be assigned, which will serve as the subject’s identifier 
throughout the study and in the CRF. Inclusion and exclusion criteria will be reviewed to assess 
the subject’s eligibility; and demographic information, and medical and medication history will 
be collected. Collection of AEs, concomitant medications, and concomitant surgical procedures 
will begin from the time the subject signs the informed consent. 
All screening procedures and tests must be completed during the screening period and prior to 
returning to the study center on Day -1. Multiple visits may be necessary for the subject to 
complete all of the required screening procedures and tests. If a screening test is considered to be 
invalid upon subsequent review (eg, spirometry testing) or not representative of the subject’s 
usual baseline status, it may be repeated at the discretion of the Investigator. All screening 
procedures and tests are to be performed by the Investigator or a qualified designee.  
The baseline chest x-ray may be performed at any time from Day -14 to Day -2 during the 
screening period. If feasible for the subject, all spirometry testing for the study should be 
performed “pre-bronchodilator” for those subjects receiving treatment with a short-acting beta-
agonist or anticholinergic bronchodilator, as described in Section 7.5.2.12.  
Subject eligibility for the study will be determined based on the procedures and tests performed 
during the screening period. (As described in Section 7.1.2, subsequent testing performed on 
Day -1 and pre-dose on Day 1 will be used to confirm eligibility; these results will only be 
exclusionary for subjects if there is a clinically significant or relevant change in a result, as 
determined by the Investigator.)  
7.1.1.1. 
Screening Failure 
A screen failure is a subject who has given informed consent and failed to meet the inclusion 
criteria or met at least 1 of the exclusion criteria and has not been enrolled into the study (ie, not 
randomized). 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
99 
For the purposes of data collection, consented subjects who were fully eligible for the study but 
were otherwise not enrolled (eg, example alternates/reserve subjects) will also be considered 
screen failures. 
7.1.1.2. 
Rescreening of Subjects 
Based on Investigator discretion and Sponsor approval, subjects who initially failed to meet the 
inclusion/exclusion criteria may be rescreened at a later time if their eligibility status has 
changed (eg, resolution of a transient event such as an acute upper respiratory infection or 
pulmonary exacerbation). 
For subjects who initially met all inclusion/exclusion criteria, but due to scheduling conflicts or 
study delays were unable to enroll into the study within the screening period window, based on 
the Investigator’s discretion and Sponsor’s approval, the subject may be allowed to enroll by 
extending the window for the screening period or may choose to be rescreened at a later time.   
Enrolled subjects who discontinue treatment after one dose of study drug for a reason unrelated 
to safety (eg, interrupted clinical research activities due to coronavirus disease pandemic) may be 
rescreened at a later time at the discretion of the Sponsor. Such subjects may receive no more 
than 5 weekly doses of study drug in total. 
In all cases of rescreening, a new informed consent form must be signed by the subject. 
Rescreened subjects who did not enroll in the study will retain the same subject identification 
number that he/she was assigned at the first screening. Rescreened subjects who previously 
enrolled in the study will be assigned a new subject identification number. 
7.1.2. 
Treatment Period: Day -1 to Day 2 
See Table 1 for the Schedule of Procedures for the treatment period of Part A. 
Following screening, eligible subjects will return to the study center on Day -1 of the treatment 
period. Subjects will be admitted to the study center on Day -1 and will be confined to the study 
center (inpatient) until discharged on Day 2. 
On Day -1, the baseline procedures and tests as described in Table 1 will be performed. The 
Day -1 results must be reviewed by the Investigator to ensure that subjects continue to be eligible 
for study enrollment (see Section 7.1.1.1 for definition of screening failure). 
Pre-dose assessments on Day 1 include a limited physical examination, measurement of vital 
signs and oxygen saturation (pulse oximetry), and ECG and spirometry testing. The limited 
physical examination, vital signs and pulse oximetry must be performed prior to randomization. 
ECG and spirometry may be performed after randomization, but MUST be performed, and 
reviewed prior to the dose, to confirm continued eligibility.  
Subjects will be randomized to treatment and thereby enrolled in the study after the following 2 
conditions have been met:  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
100 
1. Subject meets all of the inclusion criteria and none of the exclusion criteria during the 
screening period and Day -1 (as applicable) as specified in the eligibility criteria in 
Section 4.1 and Section 4.2. 
2. Confirmation of eligibility on Day 1. Results from the Day -1 and pre-dose tests on Day 1 
(AE, conmeds, pulse oximetry, physical exam, vital signs) do not reveal a new safety 
issue making the subject ineligible for randomization. A subject is considered enrolled 
into the study when he or she has been randomized to treatment. Pre-dose tests that may 
occur after randomization but MUST occur and be reviewed by the PI prior to first dose 
include spirometry and ECG. If the pre-dose Day 1 ECG or spirometry results reveal a 
safety issue making it inadvisable to administer the dose to the randomized subject, then 
the subject will be considered an Early Discontinuation.  
If the subject is receiving treatment with an inhaled short-acting bronchodilator as part of their 
routine pulmonary therapies (see below), pre-dose spirometry testing may be scheduled before 
the subject’s pulmonary therapies so that it can be performed “pre-bronchodilator.” Recording of 
any AEs and concomitant medications should continue at this time. The procedures and tests 
performed on Day -1 and Day 1will be used to confirm eligibility. A clinically significant or 
relevant change in a result during pre-dose assessments, as determined by the Investigator, may 
be exclusionary (new or worsening adverse event or worsened pulse oximetry reading).  
Prior to IP administration, subjects should undergo their routine pulmonary therapies (airway 
clearance and pulmonary medications) at the study center. These may include but are not limited 
to chest physiotherapy, and treatment with inhaled bronchodilators, hypertonic saline, antibiotics, 
and steroids (Section 5.1.1). The administration of IP should optimally occur within 2 to 3 hours 
after subjects have completed their pulmonary therapies for the day. For subjects whose routine 
pulmonary medications do not include an inhaled short-acting beta-agonist (or it is not given 
within the 2 to 3 hour window prior to IP administration), albuterol (2 to 4 puffs) will be 
administered via metered-dose inhaler approximately 20 minutes before treatment with IP to 
minimize any potential bronchoconstrictive effects (Section 5.1.1.1). Note that administration of 
short-acting beta-agonist via nebulization is also permitted at the discretion of the Investigator.  
Following confirmation of eligibility, subjects will be randomized to receive a single dose of 
either MRT5005 or placebo (subjects who are randomized are considered enrolled into the 
study). The administration of IP will be performed by a blinded, qualified member of the study 
staff. IP will be administered by the respiratory route using an InnoSpire Go nebulizer. 
Depending on the dose level, nebulization times will range from approximately 44 to 133 
minutes. Blood pressure, pulse rate, and oxygen saturation measured by pulse oximetry will be 
monitored continuously during nebulization. The subject will also be monitoring closely for any 
signs or symptoms of respiratory distress (eg, dyspnea, wheezing, bronchospasm). See Section 
6.2.2 for details on the preparation and dosing of IP, which includes minimizing secondary 
exposure to study staff during nebulization of IP.     
Following IP administration, the procedures and tests (Table 1) will be performed at the 
specified time points on Days 1 and 2. If there are any ongoing AEs or safety concerns of clinical 
significance at the 8-hour time point on Day 1 (eg, decreased oxygen saturation or airway 
symptoms), appropriate monitoring should continue until the AE or safety concern has resolved. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
101 
Subjects can be discharged when all of the Day 2 assessments have been completed and when 
subjects have been deemed clinically stable by the Investigator with no ongoing AEs or safety 
concerns of clinical significance. Discharged subjects should be housed overnight close to the 
study center until the clinic visit on the following day (Day 3). If a subject is experiencing an 
ongoing AE or there is a safety concern on Day 2, based on the judgment of the Investigator, the 
subject can remain in the study center overnight or can be hospitalized for continued monitoring 
until the clinic visit on the following day (Day 3). The subject should remain in the study center 
or hospital until the AE or safety concern has resolved and the subject is sufficiently stable to be 
discharged.   
At discharge, all subjects will be instructed to return to the study center for their scheduled clinic 
visit on Day 3 (or for their next scheduled clinic visit, if not Day 3). Subjects will be instructed to 
return to the study center or call the study staff immediately if they are experiencing any 
symptoms of concern, either new or worsening, or were hospitalized or required a visit to the 
emergency department for any reason. 
7.1.3. 
Follow-up Period: Day 3 to Day 337 
See Table 2 and Table 3 for the Schedule of Procedures for the follow-up period of Part A. 
Safety will be monitored for 12 months (48 weeks) after administration of IP. The safety follow-
up period continues through the final study visit on Day 337 (±3 days).  
Subjects will return for outpatient clinic visits on Days 3, 8, 15, 29, 57, 85, 169, 253, and 337 to 
perform the follow-up procedures and tests scheduled for this period, as described in Table 2 and 
Table 3. Telephone contact with the subject will occur on Days 5, 11, 18, 22, 43, 71, 113, 141, 
197, 225, 281, and 309 to query the subject about the occurrence of any AEs/SAEs, any changes 
in concomitant medications or concomitant surgical procedures.  
During the clinic visits and telephone contacts, subjects will be reminded to return to the study 
center or call the study staff immediately if they are experiencing any symptoms of concern, 
either new or worsening, or were hospitalized or required a visit to the emergency department for 
any reason. 
If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
Investigator’s judgment, unscheduled spirometry testing may be performed when the subject is 
stable. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be 
performed at any time during the follow-up period if the subject is experiencing respiratory 
symptoms that warrant it.   
In addition to the time points specified in the schedule of assessments, immunogenicity testing 
will also be performed when immunogenicity is suspected, such as allergy/hypersensitivity 
events or unexplained bronchospasm. 
Study completion for each subject is defined as the last study assessment for that subject on 
Day 337 (±3 days). All ongoing AEs on Day 337 must be followed to closure (the subject’s 
health has returned to his/her baseline status or all variables have returned to normal). Closure 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
102 
indicates that an outcome is reached, stabilization achieved (the Investigator does not expect any 
further improvement or worsening of the event), or the event is otherwise explained. When 
appropriate, medical tests and examinations are performed so that resolution of event(s) can be 
documented.  
7.2. 
Part B Study Schedule 
Details regarding the procedures and tests to be performed during each study period and time 
point for Part B are provided in the Schedule of Procedures in Table 4, Table 5, Table 6, and 
Table 7.    
Similar to Part A of this study, Part B will consist of a screening period, a treatment period, and a 
follow-up period (see Figure 1). The duration of the screening period is up to 27 days (Day -28 
through Day -2); the duration of the treatment period is 36 days (Day -1 to Day 35); and the 
duration of the follow-up period is up to 332 days (Day 36 through Day 365 [±3 days]). No 
confinement (inpatient) will be required of subjects in Part B; subjects will perform all clinic 
visits as outpatients.  
All AEs and SAEs, regardless of relationship, will be collected from the time of informed 
consent signing until the final study visit on Day 365 (±3 days). Information on all prior and 
concomitant medications administered from 30 days before the date of informed consent signing 
through the final study visit on Day 365 (±3 days) must be recorded on the appropriate CRF 
page.   
Time Windows for the Schedule of Procedures: 
No obligatory time windows are set for the study time points in order to allow for flexibility in 
the conduct of the study. The time windows provided in Table 4, Table 5, Table 6, and Table 7 
are suggested guidelines to be followed during the conduct of Part B. As these guidelines are 
only suggestions, they will not result in protocol deviations. 
Priority Order for Performing Procedures and Tests: 
The following priority order will be in effect when more than 1 procedure or test is required at a 
particular time point. 
 AE, concomitant medication, and concomitant surgical procedure reporting  
 Vital signs, pulse oximetry 
 Physical examination 
 Spirometry 
 Clinical laboratory tests (serum chemistry, hematology, coagulation, urinalysis, CRP) 
 ECG 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
103 
 Chest x-ray 
Other procedures with lower priorities (weight measurement; blood sampling for 
 mRNA and 
 assays, and for immune response assays) 
On the days when serum or urine pregnancy testing is being performed, scheduled or 
unscheduled, this test has priority.  
7.2.1. 
Screening Period: Day -28 to Day -2  
See Table 4 for the Schedule of Procedures for the screening period of Part B. 
Written, signed, and dated informed consent must be obtained by the Investigator or a designee 
from the subject prior to the performance of any study-related procedures or tests. A copy of the 
signed informed consent form must be given to the subject for their records. 
At the initial screening visit, informed consent will be obtained from the subject. A unique 
subject identification number will then be assigned, which will serve as the subject’s identifier 
throughout the study and in the CRF. Inclusion and exclusion criteria will be reviewed to assess 
the subject’s eligibility; and demographic information, and medical and medication history will 
be collected. Collection of AEs and concomitant medications will begin from the time the 
subject signs the informed consent. 
Subjects participating in Part B of the study will perform all of the same procedures and tests 
during the screening period as in Part A. All screening procedures and tests must be completed 
during the screening period and prior to returning to the study center on Day -1. Multiple visits 
during the screening period may be necessary for the subject to complete all of the required 
screening procedures and tests. If a screening test is considered to be invalid upon subsequent 
review (eg, spirometry testing) or not representative of the subject’s usual baseline status, it may 
be repeated at the discretion of the Investigator. All screening procedures and tests are to be 
performed by the Investigator or a qualified designee.  
The baseline chest x-ray may be performed at any time from Day -14 to Day -2 during the 
screening period. If feasible for the subject, all spirometry testing for the study should be 
performed “pre-bronchodilator” for those subjects receiving treatment with a short-acting beta-
agonist or anticholinergic bronchodilator, as described in Section 7.5.2.12.  
Subject eligibility for the study will be determined based on the procedures and tests performed 
during the screening period. As described in Section 7.1.2, subsequent testing performed on 
Day -1 and Day 1 will be used to confirm eligibility. A clinically significant or relevant change 
in a result during pre-dose assessments, as determined by the Investigator, may be exclusionary 
(eg, new or worsening adverse event or worsened pulse oximetry reading).  
7.2.1.1. 
Screening Failure 
The definition of a subject who is a screen failure, as described in Section 7.1.1.1 for Part A, also 
applies to Part B.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
104 
7.2.1.2.
Rescreening of Subjects
Rescreening of subjects, as described in Section 7.1.1.2 for Part A, also applies to Part B. 
7.2.2. 
Treatment Period: Day -1 to Day 33  
See Table 4 and Table 7 for the Schedule of Procedures for the treatment period of Part B.  
Following screening, eligible subjects will return to the study center on Day -1 and will perform 
the baseline procedures and tests, as described in Table 4. The Day -1 results must be reviewed 
by the Investigator to ensure that subjects continue to be eligible for study enrollment (see 
Section 7.1.1.1 for definition of screening failure).  
Subjects will return to the study center the following day (Day 1). Pre-dose assessments on Day 
1 should be performed immediately prior to IP administration; these assessments include a 
limited physical examination, measurement of vital signs and oxygen saturation (pulse 
oximetry), and spirometry testing. If the subject is receiving treatment with an inhaled short-
acting bronchodilator as part of their routine pulmonary therapies (see below), pre-dose 
spirometry testing may be scheduled before the subject’s pulmonary therapies (if the subject’s 
schedule permits) so that it can be performed “pre-bronchodilator.” Alternatively, the subject 
may choose to delay the bronchodilator treatment until after the pre-dose spirometry testing is 
performed and receive the treatment just prior to the administration of IP, as described below. 
Recording of any AEs and concomitant medications should continue at this time. The procedures 
and tests performed on Day -1 and pre-dose on Day 1 will be used to confirm eligibility; these 
results will only be exclusionary for subjects if there is a clinically significant or relevant change 
in a result, as determined by the Investigator (eg, positive pregnancy test).  
Prior to IP administration, subjects should undergo their routine pulmonary therapies (airway 
clearance and pulmonary medications). These may be administered either at home or at the study 
center and may include but are not limited to chest physiotherapy, and treatment with inhaled 
bronchodilators, hypertonic saline, antibiotics, and steroids (Section 5.1.1). The administration of 
IP should optimally occur within 2 to 3 hours after subjects have completed their pulmonary 
therapies for the day. For subjects whose routine pulmonary medications do not include an 
inhaled short-acting beta-agonist (or it is not given within the 2 to 3 hour window prior to IP 
administration), albuterol (2 to 4 puffs) will be administered via metered-dose inhaler 
approximately 20 minutes before treatment with IP to minimize any potential 
bronchoconstrictive effects (Section 5.1.1.1). Note that administration of a short-acting beta-
agonist via nebulization is also permitted at the discretion of the Investigator 
Following confirmation of eligibility, subjects will be randomized to receive the first dose of 
either MRT5005 or placebo (subjects who are randomized are considered enrolled into the 
study). The administration of IP will be performed by a blinded, qualified member of the study 
staff. IP will be administered by the respiratory route using an InnoSpire Go nebulizer. 
Depending on the dose level, nebulization times will range from approximately 44 to 
133 minutes. During nebulization, blood pressure, pulse rate, and oxygen saturation measured by 
pulse oximetry will be monitored continuously, together with close monitoring of the subject for 
any signs or symptoms of respiratory distress (eg, dyspnea, wheezing, bronchospasm). See 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
105 
Section 6.2.2 for details on the preparation and dosing of IP, which includes minimizing 
secondary exposure to study staff during nebulization of IP.     
The second through fifth doses of IP will be administered on Days 8, 15, 22, and 29, 
respectively. IP dosing should occur on approximately the same day of Weeks 1 through 5 
(eg, every Tuesday [the day of the week is defined by the first dose given on Day 1 of Week 1]), 
but may occur ±1 day of the target day for Weeks 2 through 5 in order to facilitate subject 
scheduling. The pre-dose assessments will be identical to those performed for the first dose (with 
some additional pre-dose assessments on Days 8, 15, 22, and 29 as noted in Table 7), and IP 
should continue to be administered within 2 to 3 hours after subjects have completed their 
routine pulmonary therapies. In addition, instructions regarding the use of rhDNase 
(PULMOZYME) and short-acting beta-agonist therapies should continue to be followed for all 
doses.  
On dosing days (Table 7), subjects will remain in the clinic for safety monitoring for at least 6 
hours after administration of IP and will be discharged only when deemed clinically stable by the 
Investigator with no ongoing AEs or safety concerns of clinical significance. Discharged subjects 
can go home if they live locally (within 1 hour driving distance from the study center) or if not 
should be housed overnight close to the study center until the clinic visit on the following day. If 
a subject is experiencing an ongoing AE or there is a safety concern at the 6-hour time point (eg, 
decreased oxygen saturation by pulse oximetry or airway symptoms), based on the judgment of 
the Investigator, the subject can remain in the study center overnight or can be hospitalized for 
continued monitoring until the clinic visit on the following day. The subject should remain in the 
study center or hospital until the AE or safety concern has resolved and the subject is sufficiently 
stable to be discharged. 
Subjects will be provided a digital thermometer and Body Temperature Recording Log for 
measuring and recording his/her body temperature after discharge on each dosing day. Subjects 
will be asked to record his/her body temperature at regular intervals until bedtime and as needed 
overnight should febrile symptoms (eg, chills, night sweats) awaken the subject from sleep on 
each dosing day. 
At discharge on each dosing day, subjects will be instructed to return to the clinic on the 
following day (Days 2, 9, 16, 23, and 30). The procedures and tests, as described in Table 4, will 
be performed at this post-treatment clinic visit. Following these outpatient clinic visits, subjects 
will be contacted approximately 3 days later by telephone on Days 5, 12, 19, 26, and 33, to query 
the subject about the occurrence of any AEs/SAEs and any changes in concomitant medications.  
If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
Investigator’s judgment, unscheduled spirometry testing may be performed when the subject is 
stable. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be 
performed at any time during the treatment period if the subject is experiencing respiratory 
symptoms that warrant it.   
During the clinic visits and telephone contacts, subjects will be reminded to return to the study 
center or call the study staff immediately, if they are experiencing any symptoms of concern, 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
106 
either new or worsening, or were hospitalized or required a visit to the emergency department for 
any reason. 
7.2.3. 
Follow-up Period: Day 36 to Day 365 
See Table 5 and Table 6 for the schedule of procedures for the follow-up period of Part B. 
Safety will be monitored for 12 months after administration of the fifth dose of IP in Part B. The 
safety follow-up period continues through the last study visit on Day 365 (±3 days).  
Subjects will return for outpatient clinic visits on Days 36, 43, 57, 71, 85, 113, 197, 281, and 365 
to perform the follow-up procedures and tests scheduled for this period. Telephone contact with 
the subject will occur on Days 39, 46, 50, 64, 78, 99, 141, 169, 225, 253, 309, and 337 to query 
the subject about the occurrence of any AEs/SAEs and any changes in concomitant medications. 
Subjects will also be instructed at every clinic visit and telephone contact to return to the study or 
call the study staff immediately if they are experiencing any symptoms of concern, either new or 
worsening, or were hospitalized or required a visit to the emergency department for any reason. 
If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
Investigator’s judgment, unscheduled spirometry testing may be performed when the subject is 
stable. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be 
performed at any time during the follow-up period if the subject is experiencing respiratory 
symptoms that warrant it.    
Study completion for each subject is defined as the last study assessment for that subject on 
Day 365 (±3 days). All ongoing AEs on Day 365 must be followed to closure (when the 
subject’s health has returned to his/her baseline status or when all variables have returned to 
normal). Closure indicates that an outcome is reached, stabilization achieved (the Investigator 
does not expect any further improvement or worsening of the event), or the event is otherwise 
explained. When appropriate, medical tests and examinations may be performed so that 
resolution of event(s) can be documented.
7.3.
Part D Study Schedule
Details regarding the procedures and tests to be performed during each study period and time 
point for Part D are provided in the Schedule of Procedures in Table 8 and Table 9. 
Part D will consist of a screening period, a treatment period, and a follow-up period (see Figure 
1). The duration of the screening period is up to 28 days (Day -28 through Day -1); the duration 
of the treatment period is 5 days (Day 1 to Day 5); and the duration of the follow-up period is up 
to 336 days (Day 6 through Day 341 [±3 days]). No confinement (inpatient) will be required of 
subjects in Part D; subjects will perform all clinic visits as outpatients.  
All AEs and SAEs, regardless of relationship, will be collected from the time of informed 
consent signing until the final study visit on Day 341 (±3 days). Information on all prior and 
concomitant medications administered from 30 days before the date of informed consent signing 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
107 
through the final study visit on Day 341 (±3 days) must be recorded on the appropriate CRF 
page.    
Time Windows for the Schedule of Procedures: 
No obligatory time windows are set for the study time points in order to allow for flexibility in 
the conduct of the study. The time windows provided in Table 8 and Table 9 are suggested 
guidelines to be followed during the conduct of Part D. As these guidelines are only suggestions, 
they will not result in protocol deviations if they cannot be adhered to. 
Priority Order for Performing Procedures and Tests: 
The same priority order as for Part B (Section 7.2) will be in effect when more than 1 procedure 
or test is required at a particular time point in Part D. 
7.3.1. 
Screening Period: Day -28 to Day -1 
See Table 8 for the Schedule of Procedures for the screening period of Part D. 
Written, signed, and dated informed consent must be obtained by the Investigator or a designee 
from the subject prior to the performance of any study-related procedures or tests. A copy of the 
signed informed consent form must be given to the subject for their records. 
At the initial screening visit, informed consent will be obtained from the subject. A unique 
subject identification number will then be assigned, which will serve as the subject’s identifier 
throughout the study and in the CRF. Inclusion and exclusion criteria will be reviewed to assess 
the subject’s eligibility; and demographic information, and medical and medication history will 
be collected. Collection of AEs and concomitant medications will begin from the time the 
subject signs the informed consent. 
Subjects participating in Part D of the study will perform all of the same procedures and tests 
during the screening period as in Parts A and B. All screening procedures and tests must be 
completed during the screening period and prior to returning to the study center on Day 1. 
Multiple visits during the screening period may be necessary for the subject to complete all of 
the required screening procedures and tests. If a screening test is considered to be invalid upon 
subsequent review (eg, spirometry testing) or not representative of the subject’s usual baseline 
status, it may be repeated at the discretion of the Investigator. All screening procedures and tests 
are to be performed by the Investigator or a qualified designee. 
The baseline chest x-ray may be performed at any time from Day -14 to Day -1 during the 
screening period. If feasible for the subject, all spirometry testing for the study should be 
performed “pre-bronchodilator” for those subjects receiving treatment with a short-acting 
beta-agonist or anticholinergic bronchodilator, as described in Section 7.5.2.12.
Subject eligibility for the study will be determined based on the procedures and tests performed 
during the screening period. As described in Section 7.1.2, subsequent testing performed on 
Day 1 will be used to confirm eligibility. A clinically significant or relevant change in a result 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
108 
during pre-dose assessments, as determined by the Investigator, may be exclusionary (eg, new or 
worsening adverse event or worsened pulse oximetry reading).  
7.3.1.1. 
Screening Failure 
The definition of a subject who is a screen failure, as described in Section 7.1.1.1 for Part A, also 
applies to Part D.  
7.3.1.2. 
Rescreening of Subjects 
Rescreening of subjects, as described in Section 7.1.1.2 for Part A, also applies to Part D.  
7.3.2. 
Treatment Period: Day 1 to Day 5 
See Table 8 for the Schedule of Procedures for the treatment period of Part D.  
Following screening, eligible subjects will return to the study center on Day 1 and will perform 
the baseline procedures and tests, as described in Table 8.  
Pre-dose assessments on Day 1 should be performed prior to IP administration; these 
assessments include a pregnancy test (female subjects only), collection of blood for safety labs, 
limited physical examination, measurement of vital signs and oxygen saturation (pulse 
oximetry), and spirometry testing. If the subject is receiving treatment with an inhaled short-
acting bronchodilator as part of their routine pulmonary therapies (see below), pre-dose 
spirometry testing may be scheduled before the subject’s pulmonary therapies (if the subject’s 
schedule permits) so that it can be performed “pre-bronchodilator.” Alternatively, the subject 
may choose to delay the bronchodilator treatment until after the pre-dose spirometry testing is 
performed and receive the treatment just prior to the administration of IP, as described below. 
Recording of any AEs and concomitant medications should continue at this time. The only 
procedures and tests performed pre-dose on Day 1 that will be used to confirm eligibility are the 
limited physical exam, vital signs, pregnancy test, and pulse oximetry; these results will only be 
exclusionary for subjects if there is a clinically significant or relevant change in a result, as 
determined by the Investigator (eg, positive pregnancy test). 
Prior to IP administration, subjects should undergo their routine pulmonary therapies (airway 
clearance and pulmonary medications). These may be administered either at home or at the study 
center and may include but are not limited to chest physiotherapy, and treatment with inhaled 
bronchodilators, hypertonic saline, antibiotics, and steroids (Section 5.1.1). The administration of 
IP should optimally occur within 2 to 3 hours after subjects have completed their pulmonary 
therapies for the day. For subjects whose routine pulmonary medications do not include an 
inhaled short-acting beta-agonist (or it is not given within the 2 to 3 hour window prior to IP 
administration), albuterol (2 to 4 puffs) will be administered via metered-dose inhaler 
approximately 20 minutes before treatment with IP to minimize any potential 
bronchoconstrictive effects (Section 5.1.1). Note that administration of a short-acting 
beta-agonist via nebulization is also permitted at the discretion of the Investigator  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
109 
Following confirmation of eligibility, subjects will be randomized to receive the first dose of 
either MRT5005 or placebo (subjects who are randomized are considered enrolled into the 
study). The administration of IP will be performed by a blinded, qualified member of the study 
staff. IP will be administered by the respiratory route using an InnoSpire Go nebulizer. 
Nebulization time is expected to be approximately 22 minutes or less. See Section 6.2.2 for 
details on the preparation and dosing of IP, which includes minimizing secondary exposure to 
study staff during nebulization of IP.     
The second through fifth doses of IP will be administered on Days 2, 3, 4, and 5, respectively. 
Pre-dose assessments will occur on each dosing day (as noted in Table 8) and IP should continue 
to be administered within 2 to 3 hours after subjects have completed their routine pulmonary 
therapies.  
On each dosing day, subjects will remain in the clinic for safety monitoring for at least 2 hours 
after administration of IP and will be discharged only when deemed clinically stable by the 
Investigator with no ongoing AEs or safety concerns of clinical significance. Discharged subjects 
may go home if they live locally (within 1 hour driving distance from the study center) or if not 
should be housed overnight close to the study center until the clinic visit on the following day. If 
a subject is experiencing an ongoing AE or there is a safety concern at the 2-hour time point (eg, 
decreased oxygen saturation by pulse oximetry or airway symptoms), based on the judgment of 
the Investigator, the subject should remain in the study center or hospital until the AE or safety 
concern has resolved and the subject is sufficiently stable to be discharged. 
If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
Investigator’s judgment, unscheduled spirometry testing may be performed when the subject is 
stable. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be 
performed at any time during the treatment period if the subject is experiencing respiratory 
symptoms that warrant it. 
Subjects will be provided a digital thermometer and Body Temperature Recording Log for 
measuring and recording his/her body temperature after discharge on each dosing day. Subjects 
will be asked to record his/her body temperature at regular intervals until bedtime and as needed 
overnight should febrile symptoms (eg, chills, night sweats) awaken the subject from sleep.  
7.3.3. 
Follow-up Period: Day 6 to Day 341 
See Table 8 and Table 9 for the schedule of procedures for the follow-up period of Part D. 
After being discharged after the final dosing day on Day 5, subjects will be contacted 
approximately 3 days later by telephone on Day 8 to monitor the occurrence of any AEs/SAEs 
and any changes in concomitant medications. Subjects will return to the clinic on Day 11 for the 
first outpatient follow-up clinic visit including the procedures and tests, as described in Table 8.  
Safety will be monitored for 48 weeks after administration of the fifth dose of IP in Part D. The 
safety follow-up period continues through the last study visit on Day 341 (±3 days).  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
110 
Subjects will return for outpatient clinic visits on Days 18, 32, 60, 145, 229, and 341 to perform 
the follow-up procedures and tests scheduled for this period, as described in Table 9. Telephone 
contact with the subject will occur on Days 25, 46, 89, 117, 173, 201, 257, 285, and 313 to query 
the subject about the occurrence of any AEs/SAEs and any changes in concomitant medications. 
Subjects will also be instructed at every clinic visit and telephone contact to return to the study or 
call the study staff immediately if they are experiencing any symptoms of concern, either new or 
worsening, or were hospitalized or required a visit to the emergency department for any reason. 
If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
Investigator’s judgment, unscheduled spirometry testing may be performed when the subject is 
stable. In addition, at the discretion of the Investigator, an unscheduled chest x-ray may be 
performed at any time during the follow-up period if the subject is experiencing respiratory 
symptoms that warrant it.    
Study completion for each subject is defined as the last study assessment for that subject on 
Day 341 (±3 days). All ongoing AEs on Day 341 must be followed to closure (when the 
subject’s health has returned to his/her baseline status or when all variables have returned to 
normal). Closure indicates that an outcome is reached, stabilization achieved (the Investigator 
does not expect any further improvement or worsening of the event), or the event is otherwise 
explained. When appropriate, medical tests and examinations may be performed so that 
resolution of event(s) can be documented. 
7.4. 
Additional Care of Subjects after the Study 
No after care is planned for this study. 
7.5. 
Study Evaluations and Procedures 
All procedures and tests are to be performed by the Investigator or a qualified designee who has 
been trained in the protocol. All procedures and tests are to be performed according to the 
Schedule of Procedures in Table 1 through Table 9.
7.5.1. 
Demographic and Other Baseline Characteristics 
Demographic characteristics (age, sex, and race) will be collected at the initial screening visit 
and reviewed on Day -1 (Parts A and B only). Weight will be taken at both the screening visit 
and on Day -1 (Parts A and B only); height will only be taken at the initial screening visit. In Part 
D, demographic characteristics, weight, and height will only be recorded at the Screening visit. 
BMI will be calculated based on the subject’s weight and height collected at the initial screening 
visit.   
7.5.2. 
Safety 
The name and address of each third party vendor used in this study will be maintained in the 
Investigator’s and Sponsor’s files, as appropriate. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
111 
Actual safety assessment times will be monitored and recorded. The Sponsor’s expectation is 
that the Investigator will ensure that every effort is made to perform all assessments at the 
protocol-scheduled time according to the suggested guidelines described in Section 7.1.  
The Investigator can use their judgment in performing the following procedures as described in 
the Schedule of Procedures in Table 1 through Table 9.        
 If a subject is experiencing respiratory distress or respiratory symptoms, based on the 
judgment of the Investigator, unscheduled spirometry testing may be performed when 
the subject is stable. 
 At the Investigator’s discretion, a chest x-ray may be performed at any time during 
the study if the subject is experiencing respiratory symptoms that warrant it.   
At the discretion of the Investigator, other unscheduled procedures or tests may be performed if 
needed to ensure subject safety.  
7.5.2.1. 
Medical and Medication History 
A complete medical and medication history, as well as demographic information, will be 
collected at the screening visit by the Investigator or a qualified designee. The medical history 
will be reviewed and recorded, including:
Date of birth
 Sex 
 Race, ethnicity 
 Medication history starting from 30 days prior to entering the screening period 
 History of respiratory, cardiovascular, renal, gastrointestinal, hepatic, endocrine, 
hematological, neurological, psychiatric, and other diseases 
 Smoking habits 
Note: Participation in previous clinical trials evaluating investigational CF therapies directed at 
expressing functional CFTR protein will also be recorded (eg, CFTR gene therapy studies or 
therapies that allow read-through of premature stop codons of CFTR gene). 
7.5.2.2. 
Physical Examination (Including Height and Weight) 
A comprehensive physical examination or limited physical examination will be performed by the 
Investigator or a qualified designee at the time points described in the Schedule of Procedures. 
The comprehensive physical examination will include a review of the following body systems: 
 General appearance 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
112 
 Skin 
Head, eyes, ears, nose, and throat
Spine/neck/thyroid
Musculoskeletal
Respiratory
Cardiovascular
 Neurological 
 Abdomen (including liver, spleen, and kidneys) 
The limited physical examination will be driven by any new problems or issues reported by the 
subject since the last clinic visit or telephone contact. At minimum, the limited physical 
examination will include a review of the following body systems: 
 Respiratory 
 Cardiovascular 
Abnormalities identified during the physical examination at the initial screening visit will be 
documented in the subject’s source documents and on the medical history CRF page. Any post-
baseline new or worsening abnormalities identified after the initial physical examination should 
be recorded on the AE CRF page, as deemed by the Investigator. 
The height and weight collected at the initial screening visit will be used to calculate the 
subject’s body mass index (BMI) using the formula below:  
BMI = 
Weight [kg] 
(Height [m])2 
 
BMI calculated at subsequent time points will continue to use the subject’s height collected at 
the initial screening visit.      
Height should be measured in centimeters (cm) and weight should be measured in kilograms 
(kg). Measurements should be taken in light clothing and stocking feet (without shoes) with 
empty pockets. The subject’s height should be recorded to the nearest centimeter and weight 
should be recorded to the nearest 0.1 kg.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
113 
7.5.2.3.
Adverse Event Collection
Refer to Section 8.1 for definitions of an AE and SAE, period of observation for the collection of 
AEs, and recording of AEs. 
Collection of all AEs and SAEs, regardless of relationship, concomitant mediations, and 
concomitant surgical procedures will begin from the time the subjects signs the informed consent 
until study completion for each subject, which is defined as the last study assessment for that 
subject on Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 341 (±3 days) in 
Part D of the study. As such, all AEs and SAEs will be collected throughout the study for each 
subject.    
At each clinic visit and telephone contact during the study, subjects will be questioned in a 
general way to ascertain if AEs/SAEs have occurred since the previous visit (eg, “Have you had 
any health problems since your last visit?”) or if any changes in concomitant medications had 
occurred. Subjects will be reminded to return to the site or call the study staff immediately if they 
are experiencing any symptoms of concern, either new or worsening, or were hospitalized or 
required a visit to the emergency department for any reason. 
See Section 8.1 for more detail on follow-up of AEs to closure and reporting of AEs after the end 
of the study. 
7.5.2.4. 
Vital Signs 
Blood pressure, pulse rate, and body temperature will be measured at the times specified in the 
Schedule of Procedures. Additional blood pressure, pulse rate, and/or body temperature 
measurements may be performed, as determined by the Investigator, in order to ensure 
appropriate monitoring of subject safety and accurate recording of vital sign measurements.  
Any changes from baseline that are deemed clinically significant by the Investigator are to be 
recorded as an AE. 
Blood Pressure and Pulse Rate
The same method for obtaining blood pressure measurement (auscultatory or oscillometric) 
should be used throughout the study for the subject. In addition, the conditions of vital sign 
measurements should be controlled and as consistent as possible during the study, in order to 
minimize external variability of the readings. It is advised that measurements be collected at a 
comfortable room temperature with little to no background noise, using the same (appropriately 
sized) cuff placed at the same location of the same arm during the study. The cuff should have a 
bladder length that is 80% and a width that is at least 40% of arm circumference (a length-to-
width ratio of 2:1). The bladder deflation rate should be deflated (calibrated for oscillometric 
method or manually by auscultatory method) at a rate of 2 to 3 mmHg/second (and the first and 
last audible sounds recorded as systolic and diastolic pressure) after at least 5 minutes of rest in a 
seated position.  
The subject should be asked to remove all clothing that covers the location of cuff placement. 
The subject should be instructed to relax as much as possible for at least 5 minutes prior to 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
114 
collection. The subject should remain quiet during this time and through the measurement. If 
possible, the same arm should be used for all blood pressure measurements in the study, which 
require only 1 reading.  
The use of automated devices for measuring pulse rate is acceptable although, when done 
manually, pulse rate will be measured in the brachial/radial artery for at least 30 seconds. When 
the timing of these measurements coincides with a blood collection, blood pressure and pulse 
rate should be obtained prior to the nominal time of the blood collection. 
During the nebulization of IP in Parts A and B only, blood pressure and pulse rate will be 
monitored continuously (except during rest periods) with measurements to be recorded every 5 
minutes (8 mg dose level) or 10 minutes (12, 16, 20, and 24 mg dose levels), or more frequently 
if clinically indicated. Any changes from baseline that are deemed clinically significant by the 
Investigator are to be recorded as an AE. 
Body Temperature 
Oral temperature should be taken by placing a digital thermometer under the tongue for at least 
10 seconds and the temperature reported in degrees Celsius. Other methods to measure the 
subject’s temperature must be approved by the Sponsor.  
Respiratory Rate 
The respiratory rate should be taken when the subject is at rest in a comfortable position. The 
observer should hold the extremity of the subject as a distraction for the subject (ie, pretending 
he/she is taking the subject’s radial pulse) and count the number of respirations for 30 seconds. 
The respiratory rate is reported as the number of breaths per minute.  
7.5.2.5.
Pulse Oximetry
Blood oxygen saturation will be measured by pulse oximetry at the times specified in the 
Schedule of Procedures. Additional measurements may be performed, as determined by the 
Investigator, in order to ensure appropriate monitoring of subject safety and accurate recording 
of oxygen saturation measurements. During the nebulization of IP in Parts A and B only, pulse 
oximetry will be monitored continuously (except during rest periods) with measurements to be 
recorded every 5 minutes (8 mg dose level) or 10 minutes (12, 16, 20, and 24 mg dose levels), or 
more frequently if clinically indicated. Any changes from baseline that are deemed clinically 
significant by the Investigator are to be recorded as an AE.
The index finger is the recommended site of application of the pulse oximeter sensor. Other sites 
include other fingers, a thumb, a toe, hand or a foot. Avoid extremities with catheters or blood 
pressure cuffs in place. Allow several seconds for the pulse oximeter to detect the pulse and 
calculate the oxygen saturation. Look for the displayed pulse indicator that shows that the 
machine has detected a pulse. Without a pulse signal, any readings are meaningless. Oximeters 
may occasionally give a false reading; if in doubt, rely on your clinical judgment, rather than the 
machine. Always make sure the alarms are on. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
115 
Blood oxygen saturation level measured by pulse oximetry (peripheral capillary oxygen 
saturation [SpO2]) will be reported as a percentage.  
7.5.2.6. 
Clinical Laboratory Evaluations 
All clinical laboratory assays will be performed according to the laboratory’s normal procedures 
and test-appropriate samples will be collected at the time points specified in the Schedule of 
Procedures. All blood samples will be collected via venipuncture. Subjects in Parts A and B will 
be in a fasted state (8 hours without food or drink except water) for serum chemistry study blood 
collections. Subjects will be at rest and in a seated or supine position during blood collection. 
Reference ranges are to be supplied by the laboratory and will be used to assess the clinical 
laboratory data for clinical significance and out-of-range pathological changes. The Investigator 
should assess out-of-range clinical laboratory values for clinical significance, indicating if the 
value(s) is/are not clinically significant or clinically significant. Abnormal clinical laboratory 
values, which are unexpected or not explained by the subject’s clinical condition, may, at the 
discretion of the Investigator or Sponsor, be repeated as soon as possible until confirmed, 
explained, or resolved. 
Serum Chemistry 
Blood samples (approximately 8.5 mL) for serum chemistry will be collected into a serum 
separator tube. The following parameters will be assessed:   
Albumin
Glucose 
Alkaline phosphatase (ALP)
Lactate dehydrogenase
Alanine transaminase (ALT)
Magnesium
Aspartate transaminase (AST)
Phosphorus
Blood urea nitrogen 
Potassium
Calcium
Sodium
Carbon dioxide (Bicarbonate)
Total and direct bilirubin
Chloride
Total protein 
Creatinine 
Uric acid
Creatinine kinase
C-reactive protein (CRP)
 
Gamma-glutamyl transferase (GGT) 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
116 
Hematology
Blood samples (approximately 4.0 mL) for hematology will be collected into an 
ethylenediaminetetraacetic acid (EDTA) tube. The following parameters will be assessed: 
Hemoglobin (Hgb) 
White blood cell (WBC) count  
Hematocrit (Hct) 
WBC differential (absolute and percent)
 
Neutrophils 
Eosinophils 
 
Monocytes 
 
Basophils 
Lymphocytes
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin concentration 
(MCHC)
Platelet count 
Red blood cell (RBC) count 
Coagulation 
Blood samples (approximately 4.5 mL) for coagulation will be collected into a sodium citrate 
tube. The following parameters will be assessed: 
Prothrombin time (PT), PT International normalized ratio (INR) 
Activated partial thromboplastin time (PTT) 
Urinalysis 
A urine sample will be collected and analyzed for the following parameters: 
pH 
Bilirubin 
Glucose 
Nitrites 
Protein 
Leukocyte esterase 
Blood
Specific gravity
Ketones 
Microscopic examination will be conducted if protein and/or blood is/are detected during 
urinalysis. At a minimum, the microscopic examination will consist of red blood cells, white 
blood cells, casts, and bacteria.  
7.5.2.7. 
Serum Inflammatory Markers (Part B 20 mg and Part D only) 
Serum samples will be analyzed for various inflammatory markers (Part B, 20 mg and Part D 
only), including interferon (IFN)-
-
-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, 
IL-13, and tumor necrosis factor (TNF)-
enzyme-linked immunosorbent assay (ELISA). 
The inflammatory marker testing is considered as exploratory and results will not be provided to 
or reviewed by the Investigator. 
In addition to the time points specified in the schedule of assessments, ad hoc inflammatory 
marker testing may also be performed when immunogenicity is suspected, such as febrile and/or 
allergy/hypersensitivity events, or unexplained bronchospasm. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
117 
7.5.2.8.
Pregnancy Test 
A urine or serum beta-human chorionic gonadotropin ( -hCG) pregnancy test will be performed 
on all females, regardless of childbearing potential, at the initial screening visit, on Day -1 (Parts 
A and B) or Day 1 (Part D), and at discharge on Day 337 in Part A, Day 365 in Part B, or Day 
341 in Part D of the study; or if pregnancy is suspected or upon withdrawal of a female subject 
from the study. The pregnancy test on Day -1 (Part A and Part B) or Day 1 (Part D) must be 
confirmed as negative before the subject can be enrolled and randomized.  
7.5.2.9. 
Drug and Alcohol Screen  
A blood or urine screen for drugs of abuse and alcohol will be performed at the initial screening 
visit. Additional drug and alcohol screens may be performed at the Investigator’s discretion. 
Samples are to be tested for amphetamines, barbiturates, benzodiazepines, cocaine, methadone, 
opiate metabolite, and phencyclidine.  
Results of drug and alcohol screens will be reviewed and verified by the study monitor, but will 
not be collected in the CRF. Any positive result for drugs of abuse or alcohol at the screening 
visit will exclude the subject from further participation in the study. Note that drug screen results 
that are positive for a drug of abuse may be acceptable with confirmation of valid prescription 
for medical use (eg, methylphenidate for the treatment of attention deficit hyperactivity 
disorder). 
7.5.2.10. Viral Screen  
At the initial screening visit, a blood sample of approximately 8.5 mL will be drawn into a serum 
separator tube to test for the presence of human immunodeficiency virus (HIV) type 1 or 2 
antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies. 
The test results must be confirmed negative at the screening visit. If a test result is positive, the 
subject will be excluded from enrolling into the study. Results of the viral screen will be 
reviewed and verified by the study monitor but will not be collected in the CRF database. 
7.5.2.11. Electrocardiogram (ECG)  
ECGs will be performed at the times specified in the Schedule of Procedures. The following 
parameters will be recorded: heart rate, PR, QRS, QT, QTcB, and QTcF. ECG interval 
measurements and interpretations will be centralized and performed by a single certified 
cardiologist.      
The ECG collected on Day -1 will serve as the subject’s baseline ECG for Parts A and B. The 
ECG collected during Screening will serve as the subject’s baseline ECG for Part D. If there is a 
clinically significant change from baseline, the ECG change should be reported as an AE.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
118 
7.5.2.12.
Spirometry
Spirometry will be performed according to the guidelines published by the American Thoracic 
Society for standardization of spirometry (American Thoracic Society 1995).  The following 
parameters will be assessed during the spirometry testing: 
 Forced expiratory volume in 1 second (FEV1): absolute volume (L) and percent 
predicted for age, gender, and height. 
 Forced vital capacity (FVC): absolute volume (L) and percent predicted for age, 
gender, and height.   
 FEV1/FVC: ratio and percent predicted for age, gender, and height.
Forced expiratory flow over the middle one-half of the FVC (FEF25-75%): absolute 
volume (L) and percent predicted for age, gender, and height. 
The parameters will be normalized using the ERS Global Lung Function Initiative (GLI) 
prediction equations.33 The average of the results from the testing on Day -1 and at pre-dose on 
Day 1 will serve as the subject’s baseline for Parts A and B. The average of the results from the 
testing on Screening and at pre-dose on Day 1 will serve as the subject’s baseline for Part D. 
Instructions on Bronchodilator Use in Relation to Spirometry Testing 
 If feasible for the subject, all spirometry testing should be performed “pre-
bronchodilator” if the subject is receiving treatment with a short-acting beta-agonist 
or anticholinergic bronchodilator (eg, beta-agonist medication such as albuterol or 
anticholinergic agent such as ipratropium bromide). These medications should be 
withheld for at least 4 hours before spirometry testing.
 If the subject is receiving treatment with a long-acting bronchodilator (eg, 
salmeterol), these medications do not have to be withheld and spirometry testing can 
be performed at any time in relation to dosing with the long-acting bronchodilator.
Instructions on Subject’s Routine Pulmonary Therapies in Relation to Spirometry Testing 
 For testing consistency within a subject, it is suggested that all spirometry testing for 
a subject be consistently performed either before or after receiving their daily routine 
pulmonary therapies (airway clearance and pulmonary medications). It will be at the 
discretion of the Investigator and study staff to determine what is most feasible for 
each subject and to maintain this testing consistency throughout the study.     
If a subject is experiencing respiratory distress or respiratory symptoms, based on the judgment 
of the Investigator, unscheduled spirometry testing may be performed when the subject is stable. 
7.5.2.13. Chest x-ray 
Chest x-rays will consist of routine posterioranterior and lateral views.  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
119 
 For all subjects participating in the study, the baseline chest x-ray may be performed 
at any time from Day -14 to Day -2 (Parts A and B) or any time from Day -14 to 
Day -1 (Part D) during the screening period.  
 In Part A, chest x-rays are scheduled on Day 8 and Day 29 of the study, representing 
intervals of 1 and 4 weeks after administration of the single dose of IP. 
 In Part B, chest x-rays are scheduled on Day 36 and Day 57 of the study, representing 
intervals of 1 and 4 weeks after administration of the fifth dose of IP.  
 In Part D, chest x-rays are scheduled on Day 11 and Day 32 of the study, representing 
intervals of 1 and 4 weeks after administration of the 5th dose of IP. 
At the Investigator’s discretion, a chest x-ray may be performed at any time during the study if 
the subject is experiencing respiratory symptoms that warrant it.  
7.5.2.14. Measurement of 
 mRNA and 
 in 
Blood 
See the Laboratory Manual for instructions on collection and handling of samples. 
Whole blood samples will be analyzed for 
 mRNA and 
 levels. In Part A, a 
baseline sample will be obtained on Day -1 and post-treatment samples will be collected on 
Day 1 (at 8 hours), and on Days 2, 8, 15, and 29. In Part B, a baseline sample will be obtained on 
Day -1 and post-treatment samples will be collected on Days 2, 8 (pre-dose), 29 (pre-dose), 30, 
36, 43, and 57. In Part D, a baseline sample will be obtained pre-dose on Day 1 and post-
treatment samples will be collected on Day 1 (2 hours post-dose), Days 2 (pre-dose and 2 hours 
post-dose), 3 (pre-dose and 2 hours post-dose), 4 (pre-dose and 2 hours post-dose), 5 (pre-dose 
and 2 hours post-dose), 11, 18 and 32. 
The quantification of 
 mRNA will be performed by qPCR on RNA purified from the 
whole blood sample. qPCR results will be reported as the number of copies of 
mRNA per µg of total RNA.   
The quantification of 
 in whole blood samples will performed by high performance liquid 
chromatography/mass spectrometry. 
In addition to the time points specified in the schedule of assessments, ad hoc testing for 
measuring 
 mRNA and 
 may also be performed when immunogenicity is 
suspected, such as febrile and/or allergy/hypersensitivity events, or unexplained bronchospasm. 
7.5.2.15. Measurement of Immune Responses to CFTR Protein 
See the Laboratory Manual for instructions on collection and handling of samples. 
The presence of potential antibodies to CFTR protein will be measured by an enzyme-linked 
immunosorbent assay in serum samples collected on Days -1 (baseline), 15, 29, 85, 169, and 337 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
120 
(optional) in Part A; and on Days -1 (baseline), 36, 57, 113, 197, and 365 (optional) in Parts B; 
and on Days 1 (pre-dose, baseline), 11, 18, 32, 145, 229, 341 (optional) in Part D. Antibodies to 
PEG will also be measured.  
CFTR-specific T cell responses will be assessed using peripheral blood mononuclear cells 
collected at the same time points. T cell responses to CFTR will be measured by a human 
interferon-
-linked immunospot assay as described by Calcedo et al.34   
As noted above, the blood collections for these assays on the final study day (Day 337 in Part A; 
Day 365 in Part B; Day 341 in Part D) are optional. The blood collection for any of these assays 
will only be taken if there has been a de novo positive result detected at one or more post-
treatment time points. In the event of inconclusive, invalid, or missing assay results at the Day 
169, Day 197, or Day 145 visit for Part A, Part B, or Part D, respectively, the blood collection 
for one or more of these assays will be taken at the final study day at the discretion of the 
Sponsor. 
In addition to the time points specified in the schedule of assessments, ad hoc immunogenicity 
testing may also be performed when immunogenicity is suspected, such as febrile and/or 
allergy/hypersensitivity events or unexplained bronchospasm. 
7.5.3. 
Volume of Blood to be Drawn from Each Subject 
The assessments, the number of samples and sample volumes for each assessment, and total 
volume of blood to be drawn from each subject are presented in Appendix 4. 
During Part A of the study, approximately 350.5 mL of blood will be drawn from all subjects, 
regardless of sex, over the duration of the study (up to 368 days or approximately 53 weeks). 
During Part B of the study, approximately 405.5 mL of blood will be drawn from all subjects, 
regardless of sex, over the duration of the study (up to 396 days or approximately 57 weeks). 
During Part D of the study, approximately 469.0 mL of blood will be drawn from all subjects, 
regardless of sex, over the duration of the study (up to 372 days or approximately 54 weeks). 
These volumes include the optional blood samples to be collected on the final study day (Day 
337 in Part A; Day 365 in Part B; Day 341 in Part D), if needed for assessment of immune 
responses to CFTR protein (Section 7.5.2.15). 
When more than one blood assessment is to be done at the time point, the assessments may be 
combined if they require the same type of tube. 
The total amount of blood to be drawn is an estimate, as it may vary depending on the study 
center’s sample volume requirements for the safety tests (serum chemistry, hematology, 
coagulation, CRP), pregnancy test ( -hCG), and viral screen (HIV, HBsAg, and HCV tests).     
7.5.4. 
Cystic Fibrosis Questionnaire-Revised (CFQ-R) 
The Cystic Fibrosis Questionnaire-Revised (CFQ-R; version for adolescents and adults [patients 
14 years old and older]) will be completed by Part B subjects at baseline on Day -1, and on Days 
36, 43, 57, 85, 113, 197, 281, and 365.35 The results of the respiratory domain of the CFQ-R will 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
121 
be of primary interest; the minimal change from baseline representing a clinically important 
improvement in the 
36     
7.6. 
Coronavirus Disease Contingency Measures 
Consistent with FDA Guidance on the conduct of clinical trials during the coronavirus disease 
(COVID-19) public health emergency (March 2020), ensuring the safety of trial participants is 
paramount. Public health measures implemented by Federal and State authorities to control the 
COVID-19 pandemic have made compliance with protocol-mandated in-person study visits 
unfeasible. As such, protocol-mandated in-person study visits may be conducted as telephone 
visits to query the subject about the occurrence of any AEs/SAEs and any changes in 
concomitant medications or surgical procedures. Such changes from the protocol will be 
captured as protocol deviations due to COVID-19. 
For subjects participating in Part A, the clinic visits at Day 29 and Day 337 are the highest 
priority and should be conducted in-person within 4 weeks of the target visit date, if possible. 
For subjects participating in Part B, other than the clinic visits on dosing days (which are 
mandatory), clinic visits during the treatment period (through Day 30), as well as at Days 36, 57, 
and 365 are the highest priority and should be conducted in-person within 4 weeks of the target 
visit date, if possible. 
For subjects participating in Part D, other than the clinic visits on dosing days (which are 
mandatory), the clinic visits at Day 11, Day 32, and Day 341 are the highest priority and should 
be conducted in-person within 4 weeks of the target visit date, if possible. 
At the discretion of the Sponsor and with subject consent, planned onsite visits (excluding dosing 
visits) may be conducted at the subject’s home (or designated space) by a study coordinator or 
qualified home health professional, as available. Assessments conducted at these visits will be 
focused on patient safety and may include collection of safety labs, vital signs, ECG, adverse 
events, concomitant medications/surgical procedures. 
As the epidemiological conditions and risks may differ across different geographies in the United 
States, the threat of COVID-19 may differ at each clinical site.  Once the risk has diminished in a 
particular region as determined by Federal and State public health officials and subjects and site 
staff are comfortable returning to in-person visits, all protocol-mandated in-person study visits 
should resume as planned. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
122 
8.
ADVERSE AND SERIOUS ADVERSE EVENT ASSESSMENT 
8.1. 
Definition of Adverse Events, Period of Observation, Recording of 
Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product and that does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product (ICH 
Guidance E2A 1995). 
Where possible, a diagnosis rather than a list of symptoms should be recorded. If a diagnosis has 
not been made, then each symptom should be listed individually. If a pulmonary exacerbation is 
suspected, sufficient information should be recorded to determine if the event can be classified as 
a pulmonary exacerbation based on the criteria defined in Section 8.1.7. All AEs should be 
captured on the appropriate AE pages in the CRF and in source documents. In addition to 
untoward AEs, unexpected benefits outside the IP indication should also be captured on the AE 
CRF.  
All AEs and SAEs, regardless of relationship, will be collected for each subject from the time the 
subject signs the informed consent until study completion, which is defined as the last study 
assessment for that subject on Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 
341 (±3 days) in Part D of the study. As such, all AEs and SAEs will be collected throughout the 
study for each subject.  
All AEs must be followed to closure (the subject’s health has returned to his/her baseline status 
or all variables have returned to normal), regardless of whether the subject is still participating in 
the study. Closure indicates that an outcome is reached, stabilization achieved (the Investigator 
does not expect any further improvement or worsening of the event), or the event is otherwise 
explained. When appropriate, medical tests and examinations are performed so that resolution of 
event(s) can be documented.  
If the Investigator considers it necessary to report an AE in a study subject after the end of the 
study, he or she should contact the Medical Monitor to determine how the AE should be 
documented and reported. 
8.1.1. 
Severity Categorization 
The severity of AEs must be recorded during the course of the event including the start and stop 
dates for each change in severity. An event that changes in severity should be captured as a new 
event. Worsening of pre-treatment events, after initiation of IP, must be recorded as new AEs 
(for example, if a subject experiences mild intermittent dyspepsia prior to dosing of IP, but the 
dyspepsia becomes severe and more frequent after first dose of IP has been administered, a new 
AE of severe dyspepsia [with the appropriate date of onset] is recorded on the appropriate CRF).  

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
123 
The Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (Published: May 
28, 2009 [v4.03: June 14, 2010]), should be referenced when assessing the severity of an AE. If 
an AE is not described in the CTCAE, the severity should be recorded based on the scale below: 
Severity
(Grade) 
Definition
Mild 
(Grade 1) 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
Moderate
(Grade 2) 
A type of AE that is usually alleviated with specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses 
no significant or permanent risk of harm to the research subject. 
Severe 
(Grade 3) 
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
Life-Threatening 
(Grade 4) 
Life-threatening consequences; urgent intervention indicated.  
Death 
(Grade 5) 
Death related to AE 
A life-threatening event (Grade 4 severity) is defined as an AE in which the subject was at risk of 
death at the time of the event; it does not refer to an event which hypothetically might have 
caused death if it was more severe (Section 8.2.3). 
8.1.2. 
Relationship Categorization 
Relationship of an AE or SAE to IP is to be determined by the Investigator based on the 
following definitions:
Relationship to IP 
Definition 
Not Related 
Unrelated to IP. 
Possibly Related 
A clinical event or laboratory abnormality with a reasonable time sequence to 
administration of IP, but which could also be explained by concurrent disease 
or other drugs or chemicals. 
Probably Related 
A clinical event or laboratory abnormality with a reasonable time sequence to 
administration of IP, unlikely to be attributable to concurrent disease or other 
drugs and chemicals and which follows a clinically reasonable response on de-
challenge. The association of the clinical event or laboratory abnormality must 
also have some biological plausibility, at least on theoretical grounds. 
Definitely Related 
The event follows a reasonable temporal sequence from administration of the 
IP, follows a known or suspected response pattern to the IP, is confirmed by 
improvement upon stopping the IP (de-challenge), and reappears upon 
repeated exposure (re-challenge). Note that this is not to be construed as 
requiring re-exposure of the subject to IP; however, the determination of 
definitely related can only be used when recurrence of the event is observed. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
124 
8.1.3.
Outcome Categorization
The outcome of AEs must be recorded during the course of the study on the CRF. Outcomes are 
as follows: 
Fatal
Not Recovered/Not Resolved
Recovered/Resolved
Recovered/Resolved with Sequelae
Recovering/Resolving
 Unknown 
8.1.4. 
Clinical Laboratory and Other Safety Evaluations 
A change in the value of a clinical laboratory test, vital sign, ECG parameter, or other safety 
assessment (eg, oxygen saturation by pulse oximetry, spirometry testing, chest x-ray) can 
represent an AE if the change is clinically relevant or if, during treatment with the IP, a shift of a 
parameter is observed from a normal value to an abnormal value, or a further worsening of an 
already abnormal value. When evaluating such changes, the extent of deviation from the 
reference range, the duration until return to the reference range, either while continuing treatment 
or after the end of treatment with the IP, and the range of variation of the respective parameter 
within its reference range, must be taken into consideration. 
If, at the end of the treatment phase, there are abnormal clinical laboratory, vital sign, or ECG 
values, or abnormal values in any other safety assessments which were not present at the 
pretreatment value observed closest to the start of study treatment, further investigations should 
be performed until the values return to within the reference range or until a plausible explanation 
(eg, concomitant disease) is found for the abnormal values. 
The Investigator should decide, based on the above criteria and the clinical condition of a 
subject, whether a change in a clinical laboratory, vital sign or ECG parameter, or a change in 
any other safety assessment performed in the study is clinically significant and therefore 
represents an AE. 
8.1.4.1. 
Evaluation of Elevations in Liver Function Tests  
Subjects meeting any of the 3 criteria listed below must be followed closely with repeat 
confirmatory testing within 48 to 72 hours of the initial finding (should include ALT, AST, ALP, 
GGT, INR, and total bilirubin testing) to determine if these parameters are increasing or 
decreasing. Subjects should be followed closely for clinical progression and there should be 
monitoring of ALT, AST, ALP, GGT, INR, and total bilirubin levels, as clinically indicated. 
Subjects should be followed until their transaminases and other laboratory parameters normalize 
or return to baseline. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
125 
 Elevation of ALT or AST to >5x ULN in a subject regardless of baseline value         
Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, with the 
appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, 
fever, rash, and/or eosinophilia (>5%).  
Elevation of ALT or AST to >3x ULN in a subject with a normal baseline or 
elevation of >3x ULN from the subject’s actual baseline if not normal, and total 
bilirubin >2x ULN or INR >1.5.  
If any of the above criteria is met by a Part B or Part D subject who has not completed dosing 
with IP, treatment must be interrupted immediately and the Medical Monitor notified of this 
action.    
A thorough investigation of other potential causes should be conducted in all cases. If no 
convincing alternative etiology (eg, pre-existing CF-related liver disease, viral hepatitis, alcohol 
ingestion, concomitant medication [such as antibiotic treatment]) for the elevated transaminases 
and symptoms is identified, regardless of whether ALT or AST levels have improved, treatment 
of the subject must be discontinued, in consultation with the Medical Monitor. If a convincing 
alternative etiology for the elevated transaminases is identified and the subject’s symptoms and 
laboratory findings have improved, the Investigator may consider resuming IP treatment with 
close monitoring, in consultation with the Medical Monitor. 
8.1.4.2.
Development of Immune Responses to CFTR Protein or PEG
In addition to the time points specified in the schedule of assessments, immunogenicity testing 
will also be performed when immunogenicity is suspected, such as allergy/hypersensitivity 
events or unexplained bronchospasm. 
8.1.5.
Pregnancy
All pregnancies are to be reported from the time the subject signs the informed consent until the 
final study visit on Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 341 
(±3 days) in Part D of the study.
Any report of pregnancy for any female study participant or the partner of a male study 
participant must be reported within 24 hours to Rho Product Safety. The pregnancy report and 
any applicable follow-up information will also be sent to the Medical Monitor by Rho Product 
Safety. The pregnant female study participant must be withdrawn from the study.
Every effort should be made to gather information regarding the pregnancy outcome and 
condition of the infant. It is the responsibility of the Investigator to obtain this information within 
30 calendar days after the initial notification and approximately 30 calendar days postpartum.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
126 
Pregnancy complications such as spontaneous abortion/miscarriage or congenital abnormality 
are considered SAEs and must be reported to Rho Product Safety (Section 8.2.2). Note: An 
elective abortion for non-medical reasons is not considered an SAE. 
In addition to the above, if the Investigator determines that the pregnancy complication meets 
serious criteria, it must be reported as an SAE to Rho Product Safety (Section 8.2.2). The test 
date of the first positive serum -hCG test or ultrasound result will determine the pregnancy 
onset date. 
8.1.6. 
Abuse, Misuse, Overdose, and Medication Error 
Abuse, misuse, overdose, or medication error (as defined below) must be reported to the Sponsor 
according to the SAE reporting procedure whether or not they result in an AE/SAE as described 
in Section 8.2.  Note: The 24-hour reporting requirement for SAEs does not apply to reports of 
abuse, misuse, overdose, or medication errors unless these result in an SAE.  
The categories below are not mutually exclusive; the event can meet more than 1 category. 
 Abuse – Persistent or sporadic intentional intake of IP when used for a non-medical 
purpose (eg, to alter one’s state of consciousness or get high) in a manner that may be 
detrimental to the individual and/or society 
 Misuse – Intentional use of IP other than as directed or indicated at any dose (Note: 
this includes a situation where the IP is not used as directed at the dose prescribed by 
the protocol) 
 Overdose – Intentional or unintentional intake of a dose of IP higher than the 
protocol-prescribed dose 
 Medication Error – An error made in prescribing, dispensing, administration, and/or 
use of an IP. For studies, medication errors are reportable to the Sponsor only as 
defined below. 
Medication errors should be collected/reported for all products under investigation. 
The administration and/or use of the unassigned treatment is/are always reportable as a 
medication error. 
The administration and/or use of an expired IP should be considered as a reportable medication 
error. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
127 
8.1.7.
Classification of Events as Pulmonary Exacerbations
The number of pulmonary exacerbations experienced by subjects will be assessed in this study. 
A pulmonary exacerbation will be defined as a new or change in antibiotic therapy (intravenous, 
inhaled, or oral) for a subject experiencing any 4 or more of the following signs or symptoms 
according to the modified Fuchs criteria presented by Ramsey et al.37
Change in sputum
New or increased hemoptysis
Increased cough
Increased dyspnea
 Malaise, fatigue, or lethargy 
 Temperature above 38°C 
 Anorexia or weight loss 
 Sinus pain or tenderness 
 Change in sinus discharge 
 Change in physical examination of the chest 
 Decrease in pulmonary function by 10% 
 Radiographic changes indicative of pulmonary infection 
In addition to pulmonary exacerbations defined by the above criteria, physician-reported 
pulmonary exacerbations will also be recorded.  Severity of pulmonary exacerbations will be 
scored according to the general principles described in Section 8.1.1. 
8.1.8. 
Adverse Events of Special Interest 
An AESI can be serious or nonserious. Ongoing monitoring and rapid communication (within 
24 hours) by the Investigator to the Sponsor is required to allow for further characterization and 
reporting to the PSRC and regulatory authorities (as required). The Investigator should report all 
AESIs within 24 hours on the AE CRF in the EDC system. 
8.1.8.1. 
Allergic/Hypersensitivity Reactions 
A suspected moderate to severe allergic/hypersensitivity reaction, including but not limited to 
anaphylaxis, generalized rash, edema or bronchospasm deemed possibly related to study drug is 
an AESI for MRT5005. The study site should report the occurrence of such a reaction to the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
128 
Sponsor within 24 hours of their first knowledge of the event and record the details of the event 
on the AE CRF in the EDC system.  
8.2. 
Serious Adverse Event Procedures 
8.2.1.
Reference Safety Information
The reference for safety information for this study is the current MRT5005 Investigator’s 
Brochure, which Translate Bio has provided under separate cover to all Investigators. 
8.2.2. 
Reporting Procedures 
All SAEs must be reported by the Investigator to Rho Product Safety, through the EDC system, 
within 24 hours of the first awareness of the event. The Medical Monitor will be notified of the 
SAE by Rho Product Safety. In the event of a fatal or life-threatening SAE, the Investigator must 
contact the Medical Monitor immediately by phone. The SAE must also be entered into the EDC 
system as soon as possible to notify Rho Product Safety.  
Medical Monitor: 
 
 
Responsible Physician: 
Note: The 24-hour reporting requirement for SAEs does not apply to reports of abuse, misuse, 
overdose, or medication errors (Section 8.1.6) unless they result in an SAE. 
If there are any questions regarding the reporting of SAEs, the Investigator should contact Rho 
Product Safety. For protocol- or safety-related issues, the Investigator should contact the Medical 
Monitor. 
Rho Product Safety:  
SAE Help Line: 888-746-7231 or 919-595-6486 
Safety E-mail: rho_productsafety@rhoworld.com   
8.2.3. 
Serious Adverse Event Definition 
A Serious Adverse Event (SAE) is any untoward medical occurrence (whether considered to be 
related to IP or not) that at any dose: 
 Results in death 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
129 
 Is life-threatening. Note: The term ‘life-threatening’ in the definition of “serious” 
refers to an event in which the subject was at risk of death at the time of the event; it 
does not refer to an event which hypothetically might have caused death if it was 
more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization. Note: 
Hospitalizations, which are the result of elective or previously planned or scheduled 
surgery for pre-existing conditions, which have not worsened after initiation of 
treatment, should not be classified as SAEs. Hospitalizations for prophylactic 
antibiotic therapy and respiratory treatment (eg, CF cleanouts) should also not be 
classified as SAEs. For example, an admission for a previously scheduled ventral 
hernia repair would not be classified as an SAE; however, complication(s) resulting 
from a hospitalization for an elective or previously scheduled surgery that meet(s) 
serious criteria must be reported as SAE(s).  
 Results in persistent or significant disability/incapacity 
 Is a congenital abnormality/birth defect 
 Is an important medical event. Note: Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered an SAE when, 
based upon appropriate medical judgment, they may jeopardize the subject and may 
require medical or surgical intervention to prevent 1 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. 
8.2.4. 
Suspected Unexpected Serious Adverse Reaction  
A SUSAR is a Serious Adverse Reaction that is not listed in the Investigator’s brochure or is not 
listed at the specificity or severity that has been observed; or, if an Investigator’s brochure is not 
required or available, is not consistent with the risk information described in the General 
Investigational Plan or Investigator’s Brochure. Adverse Drug Reaction is defined as an Adverse 
Event with a reasonable plausibility of drug related causality.  
8.2.5. 
Serious Adverse Event Collection Time Frame 
All SAEs, regardless of relationship, will be collected for each subject from the time the subject 
signs the informed consent until study completion, which is defined as the last study assessment 
for that subject on Day 337 (±3 days) in Part A, Day 365 (±3 days) in Part B, or Day 341 
(±3 days) in Part D of the study. As such, all SAEs will be collected throughout the study for 
each subject. 
As described in Section 8.2.2, all SAEs must be reported by the Investigator to Rho Product 
Safety, through the electronic data capture (EDC) system, within 24 hours of the first awareness 
of the event. The Medical Monitor will be notified of the SAE by Rho Product Safety. In the 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
130 
event of a fatal or life-threatening SAE, the Investigator must contact the Medical Monitor 
immediately by phone.  
In addition, any SAE(s) considered “related” to the IP and discovered by the Investigator at any 
interval after the study has been completed must be reported to the Rho Product Safety and the 
Medical Monitor within 24 hours of the first awareness of the event.  
If the Investigator considers it necessary to report an SAE in a study subject after the end of the 
study, he or she should contact the Medical Monitor to determine how the SAE should be 
documented and reported. 
8.2.6. 
Serious Adverse Event Onset and Resolution Dates 
The onset date of the SAE is defined as the date the event meets serious criteria. The resolution 
date is the date the event no longer meets serious criteria, the date the symptoms resolve, or the 
event is considered chronic. In the case of hospitalizations, the hospital admission and discharge 
dates are considered the onset and resolution dates, respectively. 
In addition, any signs or symptoms experienced by the subject after signing the informed consent 
form, or leading up to the onset date of the SAE, or following the resolution date of the SAE, 
must be recorded as an AE, if appropriate. 
8.2.7. 
Fatal Outcome 
Any SAE that results in the subject’s death (ie, the SAE was noted as the primary cause of death) 
must have fatal checked as an outcome with the date of death recorded as the resolution date. For 
all other events ongoing at the time of death that did not contribute to the subject’s death, the 
outcome should be considered not resolved, without a resolution date recorded. 
For any SAE that results in the subject’s death or any ongoing events at the time of death, unless 
another IP action was previously taken (eg, drug interrupted, reduced, withdrawn), the action 
taken with the IP should be recorded as “dose not changed” or “not applicable” (if the subject 
never received IP). The IP action of withdrawn should not be selected solely as a result of the 
subject’s death. 
8.2.8. 
Regulatory Agency, Institutional Review Board, Ethics Committee, and Site 
Reporting 
The Sponsor is responsible for notifying the relevant regulatory authorities and the site is 
responsible for promptly notifying the relevant IRB of related, unexpected SAEs. 
In addition, the Sponsor is responsible for notifying active sites of all unexpected SAEs related to 
MRT5005 occurring during all interventional studies across the MRT5005 program.  
The Investigator is responsible for notifying the local IRB, local ethics committee, or the relevant 
local regulatory authority of all SAEs that occur at his or her site as required. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
131 
9.
DATA MANAGEMENT AND STATISTICAL METHODS
9.1. 
Data Collection 
The Investigators’ authorized site personnel must enter the information required by the protocol 
on the CRF. A study monitor will visit each site in accordance with the monitoring plan and 
review the CRF data against the source data for completeness and accuracy. Discrepancies 
between source data and data entered on the CRF will be addressed by qualified site personnel. 
When a data discrepancy warrants correction, the correction will be made by authorized site 
personnel. Data collection procedures will be discussed with the site at the site initiation visit 
and/or at the Investigator’s meeting. Once a subject is randomized, it is expected that site 
personnel will complete the CRF entry within approximately 2 to 3 business days of the subject’s 
visit. 
9.2. 
Clinical Data Management 
Data are to be entered into a clinical database as specified in the data management plan. Quality 
control and data validation procedures are applied to ensure the validity and accuracy of the 
clinical database.
Data are to be reviewed and checked for omissions, errors, and values requiring further 
clarification using computerized and manual procedures. Data queries requiring clarification are 
to be communicated to the site for resolution. Only authorized personnel will make corrections to 
the clinical database, and all corrections are documented in an auditable manner. 
9.3. 
Data Handling Considerations 
Data that may potentially unblind the treatment assignment (ie, IP blood concentrations, 
antibodies to IP, treatment allocation, IP preparation/accountability data) will be handled with 
special care during the data cleaning and review process. These data will be handled in such a 
way that, prior to unblinding, any data that may unblind study team personnel will be presented 
as blinded information or otherwise will not be made available. If applicable, unblinded data may 
be made available to quality assurance representatives for the purposes of conducting 
independent drug audits.
9.4. 
Statistical Analysis Process 
The study will be analyzed by the Sponsor or its agent. 
The statistical analysis plan will provide the statistical methods for the analysis of the safety data 
as well as describe the approaches to be taken for summarizing other study information such as 
subject disposition, demographics and baseline characteristics, IP exposure, and prior and 
concomitant medications. Subjects randomized to placebo in each dose level group (single or 
multiple-dose) will be combined and presented as placebo, and subjects randomized to the active 
product will be combined and presented for each MRT5005 dose level (single or multiple-dose). 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
132 
To preserve the integrity of the statistical analysis and study conclusions, the statistical analysis 
plan will be finalized prior to database lock. 
All statistical analyses will be performed using SAS (SAS Institute, Cary, NC 27513). 
9.5. 
Planned Interim Analysis, Adaptive Design, and Data Monitoring 
Committee 
There are no planned data monitoring committee meetings for this study, but a PSRC will review 
safety data, as explained in Section 3.4.1. In addition, there is a Sponsor-independent data
monitoring committee (DMC) affiliated with the Cystic Fibrosis Foundation to safeguard the 
interests of study participants in conjunction with PSRC. The DMC has a representative member 
on the PSRC who reports back to the DMC potential safety signals that require a wider 
discussion with CF experts. 
An adaptive design is incorporated as described below and in Sections 3.1 and 3.2. 
 Part A: Based on the judgment of the PSRC, a single-dose group in Part A may be 
repeated to further assess the safety of the dose level prior to dose escalation and/or 
before multiple dosing is allowed to proceed in Part B. 
The blind will be maintained in the 8, 16, and 24 mg single dose groups in Part A until the 1-
month timepoint after the last dose (Day 29) of the last subject in the 24 mg dose group. The 
blind will be maintained in the 20 mg single dose group, as well as the 8, 16, and 12 mg multiple 
dose groups in Part B until the 1-month timepoint after the last dose (Day 57) of the last subject
dosed in the 12 mg multiple dose group. For the 20 mg multiple dose group in Part B (if 
applicable), the blind will be maintained until the last subject in this group has reached the 1-
month timepoint after the last dose day (Day 57).  For Part D, the blind will be maintained until 
the 1-month timepoint after the last dose (Day 32) of the last subject in Part D. After that point,
the data will be gathered in an unblinded fashion for the remainder of the study duration, to 
enable a better evaluation of the relatedness of observed AEs to the drug treatment. Details will 
be provided in the SAP.  
Four interim analyses are planned and will include data as follows: 
 All available data for the 8, 16, and 24 mg single dose groups in Part A, including at least 
four weeks of data (Day 29) following the 4th subject dosed in the 24 mg single dose 
group. 
 All available data for the 8, 16, and 12 mg multiple dose groups in Part B, including at 
least four weeks of data following the last dose (Day 57) of the last subject dosed in these 
dose groups. All available data for the 8, 16, 20, and 24 mg single dose groups in Part A 
through four weeks of data (Day 29) for all subjects. 
 All available data for Part D, including at least four weeks of data following the last dose 
(Day 32) of the last subject in Part D. 
 All available data for all groups in Part B, including at least 6 months of data following 
the last dose (Day 197) of the last subject in Part B. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
133 
These interim data will be used to inform decisions related to the dose and design of Phase 2 
studies. Details of the interim analyses will be provided in the interim analysis plan.       
9.6. 
Sample Size Calculation and Power Considerations 
The sample size is not based on any statistical considerations. The sample size is based on 
traditional Phase 1 first-in-human study designs for this disease population. In Parts A and B of 
the study, the inclusion of 4 subjects per dose group (3 subjects randomized to MRT5005 and 
1 subject randomized to placebo) will provide basic information on safety and tolerability during 
dose escalation of MRT5005. In Part D, subjects treated 4 mg MRT5005 or placebo will provide 
further safety and tolerability data on MRT5005.  
As described in Section 9.5, this study is also designed with the flexibility to enroll additional 
groups of subjects to support meeting its objectives. 
9.7.
Analysis Populations
The primary analysis population for safety will be the safety analysis set, which will include all 
randomized subjects who received IP. For all safety analyses, subjects will be analyzed 
according to the treatment they actually received.
9.8. 
Analyses 
All analyses will use descriptive rather than inferential approaches given the objectives of the 
study. All summaries will be displayed by treatment group. Summary statistics for continuous 
variables will include the sample size (N), mean, standard deviation, minimum, median, and 
maximum. For categorical data, summaries will include the frequency and percentage.  
9.8.1.
Safety Analyses
Full details of the safety analyses will be provided in the statistical analysis plan.
Subject disposition, demographics and baseline characteristics, IP exposure, and prior and 
concomitant medications will be summarized. Adverse events will be coded using the MedDRA. 
The number and percentage of subjects with treatment-emergent AEs will be calculated overall, 
by system organ class, by preferred term, and by treatment group. Treatment-emergent AEs will 
be further summarized by severity and relationship to IP. Adverse events related to IP, AEs 
leading to withdrawal, SAEs, and deaths will be similarly summarized or listed. The number and 
incidence of pulmonary exacerbations will be analyzed by treatment group. Results from vital 
sign measurements, clinical laboratory tests, ECGs, spirometry testing, pulse oximetry, and chest 
x-rays will be summarized by treatment, dose group, and visit. Clinically important findings will 
also be summarized or listed. 
9.8.2. 
Other Analyses 
Details of other analyses (eg, analysis of the CFQ-R) will be provided in the statistical analysis 
plan. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
134 
10.
SPONSOR’S AND INVESTIGATOR’S RESPONSIBILITIES
This study is conducted in accordance with current applicable regulations, ICH, EU Directive 
2001/20/EC and its updates, and local ethical and legal requirements. 
The name and address of each third party vendor (eg, contract research organization) used in this 
study will be maintained in the Investigator’s and Sponsor’s files, as appropriate. 
10.1.
Sponsor’s Responsibilities
10.1.1. 
Good Clinical Practice Compliance 
The study Sponsor and any third party to whom aspects of the study management or monitoring 
have been delegated will undertake their assigned roles for this study in compliance with all 
applicable industry regulations, ICH GCP Guideline E6 (1996), as well as all applicable national 
and local laws and regulations. 
Visits to sites are conducted by representatives of the study Sponsor and/or the company 
organizing/managing the research on behalf of the Sponsor to inspect study data, subjects’ 
medical records, and CRFs in accordance with current GCP and the respective local and 
inter/national government regulations and guidelines. Records and data may additionally be 
reviewed by auditors or by regulatory authorities. 
The Sponsor ensures that local regulatory authority requirements are met before the start of the 
study. The Sponsor (or a nominated designee) is responsible for the preparation, submission, and 
confirmation of receipt of any regulatory authority approvals required prior to release of IP for 
shipment to the site. 
10.1.2.
Indemnity/Liability and Insurance
The Sponsor ensures that suitable clinical study insurance coverage is in place prior to the start 
of the study. An insurance certificate is supplied to the Investigator as necessary.
10.1.3.
Public Posting of Study Information
The Sponsor is responsible for posting appropriate study information on applicable websites. 
Information included in clinical study registries may include participating Investigators’ names 
and contact information. 
10.1.4. 
Submission of Summary of Clinical Study Report to Competent Authorities of 
Member States Concerned and Ethics Committees 
The Sponsor will provide a summary of the clinical study report to the competent authority of the 
member state(s) concerned as required by regulatory requirement(s) and to comply with the 
Community guideline on GCP. This requirement will be fulfilled within 6 months of the end of 
the study completion date for pediatric studies and within 1 year for non-pediatric studies as per 
guidance. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
135 
10.1.5.
Study Suspension, Termination, and Completion
The Sponsor may suspend or terminate the study, or part of the study, at any time for any reason. 
If the study is suspended or terminated, the Sponsor will ensure that applicable sites, regulatory 
agencies and IRBs/ECs are notified as appropriate. Additionally, the discontinuation of a 
registered clinical study which has been posted to a designated public website will be updated 
accordingly. 
10.2.
Investigator’s Responsibilities
10.2.1. 
Good Clinical Practice Compliance 
The Investigator must undertake to perform the study in accordance with ICH GCP Guideline E6 
(1996), EU directive 2001/20/EC, and applicable regulatory requirements and guidelines.  
It is the Investigator’s responsibility to ensure that adequate time and appropriately trained 
resources are available at the site prior to commitment to participate in this study. The 
Investigator should also be able to estimate or demonstrate a potential for recruiting the required 
number of suitable subjects within the agreed recruitment period. 
The Investigator will maintain a list of appropriately qualified persons to whom the Investigator 
has delegated significant study-related tasks, and shall, upon request of the Sponsor, provide 
documented evidence of any licenses and certifications necessary to demonstrate such 
qualification. Curriculum vitae for Investigators and sub-Investigators are provided to the study 
Sponsor (or designee) before starting the study. 
If a potential research subject has a primary care physician, the Investigator should, with the 
subject’s consent, inform them of the subject’s participation in the study.
The coordinating principal Investigators will review the final clinical study report. Agreement 
with the final clinical study report is documented by the signed and dated signature of the 
coordinating principal Investigators, in compliance with Directive 2001/83/EC as amended by 
Directive 2003/63/EC and ICH Guidance E3 (1995).
10.2.2.
Protocol Adherence and Investigator Agreement
The Investigator and any co-Investigators must adhere to the protocol as detailed in this 
document. The Investigator is responsible for enrolling only those subjects who have met 
protocol eligibility criteria. Investigators are required to sign an Investigator agreement to 
confirm acceptance and willingness to comply with the study protocol.
If the Investigator suspends or terminates the study at their site, the Investigator will promptly 
inform the Sponsor and the IRB/EC and provide them with a detailed written explanation. The 
Investigator will also return all IP, containers, and other study materials to the Sponsor. Upon 
study completion, the Investigator will provide the Sponsor, IRB/EC, and regulatory agency with 
final reports and summaries as required by (inter)national regulations.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
136 
Communication with local IRBs/ECs, to ensure accurate and timely information is provided at 
all phases during the study, may be done by the Sponsor, applicable contract research 
organization, Investigator, or for multicenter studies, the coordinating principal Investigator 
according to national provisions and will be documented in the Investigator agreement. 
10.2.3. 
Documentation and Retention of Records 
10.2.3.1. Case Report Forms 
Case report forms (CRFs) are supplied by the Sponsor or Sponsor designee and should be 
handled in accordance with instructions from the Sponsor. 
The Investigator is responsible for maintaining adequate and accurate medical records from 
which accurate information is recorded to CRFs, which have been designed to record all 
observations and other data pertinent to the clinical investigation. Case report forms must be 
completed by the Investigator or designee as stated in the site delegation log.  
All data will have separate source documentation; no data will be recorded directly onto the 
CRF. 
All data sent to the Sponsor must be endorsed by the Investigator. 
The clinical research associate (CRA)/study monitor will verify the contents against the source 
data per the monitoring plan. If the data are unclear or contradictory, queries are sent for 
corrections or verification of data. 
10.2.3.2. Recording, Access, and Retention of Source Data and Study Documents 
Original source data to be reviewed during this study will include, but are not limited to subject’s 
medical file, study-related print-outs (eg, ECGs), and original clinical laboratory and test reports. 
All key data must be recorded in the subject’s medical records. 
The Investigator must permit authorized representatives of the Sponsor, the respective national, 
local, or foreign regulatory authorities, the IRB/EC, and auditors to inspect facilities and to have 
direct access to original source records relevant to this study, regardless of media. 
The CRA/study monitor (and auditors, IRB/EC or regulatory inspectors) may check the CRF 
entries against the source documents. The consent form includes a statement by which the 
subject agrees to the monitor/auditor from the Sponsor or its representatives, national or local 
regulatory authorities, or the IRB/EC, having access to source data (eg, subject’s medical file, 
appointment books, original laboratory reports, chest x-rays).  
These records must be made available within reasonable times for inspection and duplication, if 
required, by a properly authorized representative of any regulatory agency (eg, the US FDA, 
EMA, the Medicines and Healthcare products Regulatory Agency) or an auditor. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
137 
Essential documents must be maintained according to ICH GCP requirements and may not be 
destroyed without written permission from the Sponsor. 
10.2.3.3. Audit/Inspection 
To ensure compliance with relevant regulations, data generated by this study must be available 
for inspection upon request by representatives of, for example, the US FDA (as well as other US 
national and local regulatory authorities), the EMA, the Medicines and Healthcare products 
Regulatory Agency, other regulatory authorities, the Sponsor or its representatives, and the 
IRB/EC for each site. 
10.2.3.4. Financial Disclosure 
The Investigator is required to disclose any financial arrangement during the study and for 1 year 
after, whereby the outcome of the study could be influenced by the value of the compensation for 
conducting the study, or other payments the Investigator received from the Sponsor. The 
following information is collected: any significant payments from the Sponsor or subsidiaries 
such as a grant to fund ongoing research, compensation in the form of equipment, retainer for 
ongoing consultation or honoraria; any proprietary interest in IP; any significant equity interest 
in the Sponsor or subsidiaries as defined in 21 CFR 54.2(b) (1998). 
10.3. 
Ethical Considerations 
10.3.1. 
Informed Consent 
It is the responsibility of the Investigator to obtain written informed consent from all study 
subjects prior to any study-related procedures including screening assessments. All consent 
documentation must be in accordance with applicable regulations and GCP. Each subject or the 
subject’s legally-authorized representative, as applicable, is requested to sign and date the subject 
informed consent form or a certified translation if applicable, after the subject has received and 
read (or been read) the written subject information and received an explanation of what the study 
involves, including but not limited to: the objectives, potential benefits and risk, inconveniences, 
and the subject’s rights and responsibilities. A copy of the informed consent documentation (ie, a 
complete set of subject information sheets and fully executed signature pages) must be given to 
the subject or the subject’s legally authorized representative, as applicable. This document may 
require translation into the local language. Signed consent forms must remain in each subject’s 
study file and must be available for verification at any time.
The principal Investigator provides the Sponsor with a copy of the consent form which was 
reviewed by the IRB/EC and which received their favorable opinion/approval. A copy of the 
IRB/EC’s written favorable opinion/approval of these documents must be provided to the 
Sponsor, prior to the start of the study unless it is agreed to and documented (abiding by 
regulatory guidelines and national provisions) prior to study start that another party (ie, Sponsor 
or coordinating principal Investigator) is responsible for this action. Additionally, if the IRB/EC 
requires modification of the sample subject information and consent document provided by the 
Sponsor, the documentation supporting this requirement must be provided to the Sponsor.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
138 
10.3.2.
Institutional Review Board or Ethics Committee
For sites outside the EU, it is the responsibility of the Investigator to submit this protocol, the 
informed consent document (approved by the Sponsor or their designee), relevant supporting 
information and all types of subject recruitment information to the IRB/EC for review, and all 
must be approved prior to site initiation. 
For sites within the EU, the applicant for an EC opinion can be the Sponsor, the Investigator, or 
for multicenter studies the coordinating principal Investigator or Sponsor, according to national 
provisions. 
Responsibility for coordinating with IRBs/ECs is defined in the clinical trial agreement. 
Prior to implementing changes in the study, the Sponsor and the IRB/EC must approve any 
revisions of all informed consent documents and amendments to the protocol unless there is a 
subject safety issue. 
IP supplies will not be released until the Sponsor has received written IRB/EC approval of and 
copies of revised documents. 
For sites outside the EU, the Investigator is responsible for keeping the IRB/EC apprised of the 
progress of the study and of any changes made to the protocol, but in any case at least once a 
year; for sites within the EU, this can be done by the Sponsor, the Investigator or for multicenter 
studies the coordinating principal Investigator, according to national provisions. The Investigator 
must also keep the local IRB/EC informed of any serious and significant AEs. 
10.4. 
Privacy and Confidentiality 
All US-based sites and laboratories or entities providing support for this study, must, where 
applicable, comply with HIPAA of 1996. A site that is not a covered entity as defined by HIPAA 
must provide documentation of this fact to the Sponsor.
The confidentiality of records that may be able to identify subjects will be protected in 
accordance with applicable laws, regulations, and guidelines.
After subjects have consented to take part in the study, the Sponsor and/or its representatives’ 
reviews their medical records and data collected during the study. These records and data may, in 
addition, be reviewed by others including the following: independent auditors who validate the 
data on behalf of the Sponsor; third parties with whom the Sponsor may develop, register, or 
market MRT5005; national or local regulatory authorities; and the IRB/EC which gave approval 
for the study to proceed. The Sponsor and/or its representatives accessing the records and data 
will take all reasonable precautions in accordance with applicable laws, regulations, and 
guidelines to maintain the confidentiality of subjects’ identities. 
Subjects are assigned a unique identifying number; however, their initials and date of birth may 
also be collected and used to assist the Sponsor to verify the accuracy of the data (eg, to confirm 
that laboratory results have been assigned to the correct subject). 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
139 
The results of studies - containing subjects’ unique identifying number, relevant medical records, 
and possibly initials and dates of birth - will be recorded. They may be transferred to, and used 
in, other countries which may not afford the same level of protection that applies within the 
countries where this study is conducted. The purpose of any such transfer would include to 
support regulatory submissions, to conduct new data analyses to publish or present the study 
results, or to answer questions asked by regulatory or health authorities. 
10.5.
Study Results / Publication Policy
Translate Bio will endeavor to publish the results of all qualifying, applicable, and covered 
studies according to external guidelines in a timely manner regardless of whether the outcomes 
are perceived as positive, neutral, or negative. Additionally, Translate Bio adheres to external 
guidelines (eg, Good Publication Practices 2) when forming a publication steering committee. 
The purpose of the publication steering committee is to act as a non-commercial body that 
advises or decides on dissemination of scientific study data in accordance with the scope of this 
policy. 
All publications relating to Translate Bio products or projects must undergo appropriate technical 
and intellectual property review, with Translate Bio agreement to publish prior to release of 
information. The review is aimed at protecting the Sponsor’s proprietary information existing 
either at the commencement of the study or generated during the study. To the extent permitted 
by the publisher and copyright law, the principal Investigator will own (or share with other 
authors) the copyright on his/her publications. To the extent that the principal Investigator has 
such sole, joint or shared rights, the principal Investigator grants the Sponsor a perpetual, 
irrevocable, royalty-free license to make and distribute copies of such publications. 
The term “publication” refers to any public disclosure including original research articles, review 
articles, oral presentations, abstracts and posters at medical congresses, journal supplements, 
letters to the editor, invited lectures, opinion pieces, book chapters, electronic postings on 
medical/scientific websites, or other disclosure of the study results, in printed, electronic, oral or 
other form.
Subject to the terms of the paragraph below, the Investigator shall have the right to publish the 
study results, and any background information provided by the Sponsor that is necessary to 
include in any publication of study results, or necessary for other scholars to verify such study 
results. Notwithstanding the foregoing, no publication that incorporates the Sponsor’s 
confidential information shall be submitted for publication without the Sponsor’s prior written 
agreement to publish, and shall be given to the Sponsor for review at least 60 days prior to 
submission for publication. If requested in writing by Translate Bio, the institution and principal 
Investigator shall withhold submission of such publication for up to an additional 60 days to 
allow for filing of a patent application. 
If the study is part of a multicenter study, the first publication of the study results shall be made 
by the Sponsor in conjunction with the Sponsor’s presentation of a joint, multicenter publication 
of the compiled and analyzed study results. If such a multicenter publication is not submitted to a 
journal for publication by the Sponsor within an 18-month period after conclusion, abandonment, 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
140 
or termination of the study at all sites, or after the Sponsor confirms there shall be no multicenter 
study publication of the study results, an Investigator may individually publish the study results 
from the specific site in accordance with this section. The Investigator must, however, 
acknowledge in the publication the limitations of the single-site data being presented. 
Unless otherwise required by the journal in which the publication appears, or the forum in which 
it is made, authorship will comply with the International Committee of Medical Journal Editors 
current standards. Participation as an Investigator does not confer any rights to authorship of 
publications. 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
141 
11.
REFERENCES
1.  
Gibson RL, Burns JL, Ramsey BW. Pathophysiology and Management of Pulmonary 
Infections in Cystic Fibrosis. Am J Respir Crit Care Med. 2003;168(8):918-951. 
doi:10.1164/rccm.200304-505SO 
2.  
Ratjen F, Döring G. Cystic fibrosis. Lancet Lond Engl. 2003;361(9358):681-689. 
doi:10.1016/S0140-6736(03)12567-6 
3.  
O’Sullivan BP, Freedman SD. Cystic fibrosis. Lancet Lond Engl. 2009;373(9678):1891-
1904. doi:10.1016/S0140-6736(09)60327-5 
4.  
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352(19):1992-2001. 
doi:10.1056/NEJMra043184 
5.  
Cystic Fibrosis Foundation 2017. Patient Registry Annual Data Report 2017. Available at: 
https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2017-Patient-
Registry-Annual-Data-Report.pdf . Accessed 17 Jun 2019. 
6.  
Welsh MJ, Rogers CS, Stoltz DA, Meyerholz DK, Prather RS. Development of a porcine 
model of cystic fibrosis. Trans Am Clin Climatol Assoc. 2009;120:149. 
7.  
About Cystic Fibrosis. Cystic Fibrosis Foundation. Available at: https://www.cff.org/What-
is-CF/About-Cystic-Fibrosis/?gclid=CIPEl6H1pscCFYEYHwodpxsM5A. Accessed August 
13, 2015. 
8.  
What is Cystic Fibrosis? Cystic Fibrosis Worldwide. Available at: 
http://www.cfww.org/about/article/400/What_is_Cystic_Fibrosis. Accessed August 13, 
2015. 
9.  
Hamosh A, FitzSimmons SC, Macek M, Knowles MR, Rosenstein BJ, Cutting GR. 
Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J 
Pediatr. 1998;132(2):255-259. 
10.  Bobadilla JL, Macek M, Fine JP, Farrell PM. Cystic fibrosis: A worldwide analysis 
ofCFTR mutations?correlation with incidence data and application to screening. Hum 
Mutat. 2002;19(6):575-606. doi:10.1002/humu.10041 
11.  Clinical and Functional Translation of CFTR. Resources. Available at: 
https://cftr2.org/resources. Accessed 17 Jun 2019. 
12.  Ross LF. Newborn Screening for Cystic Fibrosis: A Lesson in Public Health Disparities. J 
Pediatr. 2008;153(3):308-313. doi:10.1016/j.jpeds.2008.04.061 
13.  Southern KW, Munck A, Pollitt R, et al. A survey of newborn screening for cystic fibrosis 
in Europe. J Cyst Fibros. 2007;6(1):57-65. doi:10.1016/j.jcf.2006.05.008 
14.  Griesenbach U, Alton EWFW, UK Cystic Fibrosis Gene Therapy Consortium. Gene 
transfer to the lung: lessons learned from more than 2 decades of CF gene therapy. Adv 
Drug Deliv Rev. 2009;61(2):128-139. doi:10.1016/j.addr.2008.09.010 
15.  Kreindler JL. Cystic fibrosis: Exploiting its genetic basis in the hunt for new therapies. 
Pharmacol Ther. 2010;125(2):219-229. doi:10.1016/j.pharmthera.2009.10.006 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
142 
16. Tavernier G, Andries O, Demeester J, Sanders NN, De Smedt SC, Rejman J. mRNA as 
gene therapeutic: How to control protein expression. J Controlled Release. 
2011;150(3):238-247. doi:10.1016/j.jconrel.2010.10.020
17.  Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics — developing a new class of 
drugs. Nat Rev Drug Discov. 2014;13(10):759-780. doi:10.1038/nrd4278 
18.  Fenton OS, Kauffman KJ, McClellan RL, et al. Bioinspired Alkenyl Amino Alcohol 
Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery. Adv Mater. 
2016;28(15):2939-2943. doi:10.1002/adma.201505822 
19.  McLachlan G, Davidson H, Holder E, et al. Pre-clinical evaluation of three non-viral gene 
transfer agents for cystic fibrosis after aerosol delivery to the ovine lung. Gene Ther. 
2011;18(10):996–1005. 
20.  Tam YYC, Chen S, Cullis PR. Advances in Lipid Nanoparticles for siRNA Delivery. 
Pharmaceutics. 2013;5(3):498-507. doi:10.3390/pharmaceutics5030498 
21.  Hope MJ. Enhancing siRNA delivery by employing lipid nanoparticles. Ther Deliv. 
2014;5(6):663-673. doi:10.4155/tde.14.37 
22.  Rehman Z ur, Zuhorn IS, Hoekstra D. How cationic lipids transfer nucleic acids into cells 
and across cellular membranes: recent advances. J Control Release Off J Control Release 
Soc. 2013;166(1):46-56. doi:10.1016/j.jconrel.2012.12.014 
23.  Cystic Fibrosis Foundation 2013. Annual Report 2013. Available at: 
https://www.cff.org/About-Us/Assets/2013-Annual-Report/. Accessed 18 Feb 2019. 
24.  Besancon F, Przewlocki G, Baro I, Hongre AS, Escande D, Edelman A. Interferon-gamma 
downregulates CFTR gene expression in epithelial cells. Am J Physiol-Cell Physiol. 
1994;267(5):C1398–C1404. 
25.  McShane AJ, Bajrami B, Ramos AA, et al. Targeted Proteomic Quantitation of the 
Absolute Expression and Turnover of Cystic Fibrosis Transmembrane Conductance 
Regulator in the Apical Plasma Membrane. J Proteome Res. 2014;13(11):4676-4685. 
doi:10.1021/pr5006795 
26.  Van Goor F, Hadida S, Grootenhuis PDJ, et al. Correction of the F508del-CFTR protein 
processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 
2011;108(46):18843-18848. doi:10.1073/pnas.1105787108 
27.  Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an 
investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for 
the F508del-CFTR mutation. Thorax. 2012;67(1):12-18. doi:10.1136/thoraxjnl-2011-
200393 
28.  Wolff RK. Toxicology Studies for Inhaled and Nasal Delivery. Mol Pharm. 
2015;12(8):2688-2696. doi:10.1021/acs.molpharmaceut.5b00146 
29.  Conway H, Dix KJ, McDonald JD, et al. Comparison of inhalation toxicity studies of 
gentamicin in rats and dogs. Inhal Toxicol. 2013;25(13):714-724. 
doi:10.3109/08958378.2013.843043 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
143 
30. Wolff RK, Dorato MA. Toxicologic testing of inhaled pharmaceutical aerosols. Crit Rev 
Toxicol. 1993;23(4):343–369.
31. Tepper JS, Kuehl PJ, Cracknell S, Nikula KJ, Pei L, Blanchard JD. Symposium Summary: 
“Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled 
Drugs.” Int J Toxicol. 2016;35(4):376-392. doi:10.1177/1091581815624080 
32.  Abelin AC, Marinov GK, Williams BA, McCue K, Wold BJ. A ratiometric-based measure 
of gene co-expression. BMC Bioinformatics. 2014;15(1):331. doi:10.1186/1471-2105-15-
331 
33.  Alcoforado L, de Melo J, Galindo V, Brandão S, Fink J, Dornelas de Andre A. Deposition 
of radioaerosol with jet and mesh nebulizers in healthy adults. Abstract P-162. J Aerosol 
Med Pulm Drug Del. 28(3):A36-A37. 
34.  Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for 
the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 
2012;40(6):1324-1343. doi:10.1183/09031936.00080312 
35.  Calcedo R, Griesenbach U, Dorgan DJ, et al. Self-Reactive CFTR T Cells in Humans: 
Implications for Gene Therapy. Hum Gene Ther Clin Dev. 2013;24(3):108-115. 
doi:10.1089/humc.2012.249 
36.  Quittner AL, Buu A, Messer MA, Modi AC, Watrous M. Development and validation of 
The Cystic Fibrosis Questionnaire in the United States: a health-related quality-of-life 
measure for cystic fibrosis. Chest. 2005;128(4):2347-2354. doi:10.1378/chest.128.4.2347 
37.  Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination 
of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-
Revised respiratory symptom scale in two populations of patients with cystic fibrosis and 
chronic Pseudomonas aeruginosa airway infection. Chest. 2009;135(6):1610-1618. 
doi:10.1378/chest.08-1190 
38.  Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic 
fibrosis and the G551D mutation. N Engl J Med. 2011;365(18):1663-1672. 
doi:10.1056/NEJMoa1105185 
39.  Green DM, McDougal KE, Blackman SM, et al. Mutations that permit residual CFTR 
function delay acquisition of multiple respiratory pathogens in CF patients. Respir Res. 
2010;11:140. doi:10.1186/1465-9921-11-140 
 
 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
144 
12.
PROTOCOL AMENDMENTS
The below table describes any substantial changes applied to the protocol since the previous 
version (Version 4.0, dated 29 July 2019). In addition to these changes, various non-substantial 
changes have been made (including but not limited to correction of typographical errors, 
formatting, and edits which do not affect the safety of subjects, or the scientific value or conduct 
of the study).  
Protocol Amendment 4 (Version 5.0), dated 30 July 2020 
Description of Substantial Change 
Section(s) Affected 
Replaced Part B Expansion with new Part D to evaluate the safety of 5 consecutive 
daily doses of 4 mg MRT5005/placebo in 8 subjects. 
 
Synopsis
Tables 8 and 9 
Section 2.2 
Section 2.2.3 
Section 3.2.3 
Section 7.3 
Appendix 1 
Appendix 4 
A digital thermometer will be provided to remaining subjects enrolled in the study 
(Part B 12 mg, Part B 20 mg, Part D). Subjects will be instructed to self-record body 
temperature in a paper diary at regular intervals on each dosing day in order to 
document the occurrence of fevers on each dosing day. 
Synopsis 
Tables 4 and 8 
Section 7.2.2 
Section 7.3.2 
Split Exclusion Criterion #4 into 2 separate criteria to clarify that concomitant 
KALYDECO is exclusionary for all study parts, whereas concomitant TRIKAFTA is 
exclusionary for Parts A and B only. 
Synopsis 
Section 4.2 
Based on the observation of a potential hypersensitivity reaction in the Part A, 20 mg 
dose group, broadened the individual stopping rule for hypersensitivity reactions per 
PSRC and DMC recommendation. 
Section 4.5.1 
Added new dose group stopping criterion for potential hypersensitivity reaction per 
PSRC and DMC recommendation. 
Section 4.5.4 
Per PSRC and DMC recommendation, designated potential hypersensitivity reactions 
as adverse events of special interest requiring rapid communication to Sponsor and 
notification of PSRC in real-time.  
Section 8.1.8 
Added a new inflammatory marker panel to measure IFN-
-
-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, and TNF-  in Part B 20 mg and Part D. 
Tables 1-9 
Section 7.5.2.7 
Removed requirement from Inclusion Criterion #10 for withholding rhDNase 
(PULMOZYME) for 24 hours before and after administration of IP based on the 
results of an in vitro study concluding that there is no effect of Pulmozyme on 
MRT5005 stability. 
Synopsis 
Section 4.1 
 

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
145 
13.
APPENDICES

MRT5005-101 
Translate Bio, Inc.
Version 5.0
30 July 2020
CONFIDENTIAL 
146
APPENDIX 1.
ENROLLMENT AND TREATMENT ALLOCATION
Overview of Subject Enrollment and Treatment Allocation
PART A: Single Ascending 
Dose (SAD) Groups
PART B: Multiple Ascending 
Dose (MAD) Groups
PART D: Daily Dose Group
SAD - 8 mg Dose Group
SAD - 16 mg Dose Group
SAD - 24 mg Dose Group
MAD - 20 mg Dose Group
MAD - 8 mg Dose Group
MAD - 16 mg Dose Group
Daily Dose Group
SAD - 20 mg Dose Group
MAD - 12 mg Dose Group

MRT5005-101 
Translate Bio, Inc.
Version 5.0
30 July 2020
CONFIDENTIAL 
147
Part A: Safety Assessment of Single Ascending Doses (SAD)
Group 1 - 8 mg Dose 
Four subjects enrolled and treated: 3 subjects randomized to receive a 
single dose of 8 mg of MRT5005 and 1 subject randomized to receive a 
single dose of placebo. The enrollment and treatment of the 4 subjects 
will be staggered by at least 1 week.
Group 2 – 16 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to receive a 
single dose of 16 mg of MRT5005 and 1 subject randomized to receive a 
single dose of placebo. The enrollment and treatment of the 4 subjects 
will be staggered by at least 1 week. 
Group 3 - 24 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to receive a 
single dose of 24 mg of MRT5005 and 1 subject randomized to receive a 
single dose of placebo. The enrollment and treatment of the 4 subjects will 
be staggered by at least 1 week. 
When the fourth subject has 
completed at least 1 week of safety 
follow-up, all available safety data 
for the group will be reviewed by 
the Protocol Safety Review 
Committee.
If no dose limiting toxicity is 
observed and there are no safety 
concerns overall, the enrollment 
and treatment of subjects at the 
next higher dose level will be 
initiated. 
Based on the judgment of the Protocol Safety Review Committee, a dose group may be 
repeated to further assess the safety of the dose level prior to dose escalation and/or 
before multiple dosing is allowed to proceed in Part B. 
Group 4 - 20 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to receive a 
single dose of 20 mg of MRT5005 and 1 subject randomized to receive a 
single dose of placebo. The enrollment and treatment of the 4 subjects will 
be staggered by at least 1 week.

MRT5005-101 
Translate Bio, Inc.
Version 5.0
30 July 2020
CONFIDENTIAL 
148
Part B: Safety Assessment of Multiple Ascending Doses (MAD) of MRT5005
Group 2 – 16 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to 
receive 5 doses of 16.0 mg of MRT5005 and 1 subject 
randomized to receive 5 doses of placebo, administered 1 
dose per week for 5 weeks. The enrollment and treatment of 
the 4 subjects will be staggered by at least 2 weeks.*
Group 3 - 20 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to 
receive 5 doses of 20 mg of MRT5005 and 1 subject 
randomized to receive 5 doses of placebo, administered 1 
dose per week for 5 weeks. The enrollment and treatment of 
the 4 subjects will be staggered by at least 2 weeks.*
When the fourth subject has 
completed at least 1 week of safety 
follow-up after the third dose, all 
available safety data for the group 
will be reviewed by the Protocol 
Safety Review Committee. The 
Committee will also review the 
safety data for the Part A subjects 
who received a single dose of the 
next higher dose level to be 
escalated to.  
If no dose limiting toxicity is 
observed and there are no safety 
concerns overall, the enrollment 
and treatment of subjects at the next 
higher dose level will be initiated. 
Group 1 - 8 mg Dose 
Four subjects enrolled and treated: 3 subjects randomized to 
receive 5 doses of 8.0 mg of MRT5005 and 1 subject
randomized to receive 5 doses of placebo, administered 1 
dose per week for 5 weeks. The enrollment and treatment of 
the 4 subjects will be staggered by at least 2 weeks.*
The decision to begin enrollment and treatment of the initial 8 mg multiple-dose group 
in Part B will be made by the Protocol Safety Review Committee, based on a review of 
at least 28 days of safety follow-up for all subjects who received a single dose of the 8 
mg dose level in Part A.
Group 4 - 12 mg Dose
Four subjects enrolled and treated: 3 subjects randomized to 
receive 5 doses of 12 mg of MRT5005 and 1 subject 
randomized to receive 5 doses of placebo, administered 1 dose 
per week for 5 weeks. The enrollment and treatment of the 
4 subjects may occur in a staggered or non-staggered fashion 
as described in Section 3.1.*
*The next subject in the dose group will only be enrolled and treated when the previous subject has received their second dose and 
there is at approximately 1 week of safety follow-up.

MRT5005-101  
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL  
150 
APPENDIX 3.
INSTRUCTION MANUAL: INNOSPIRE GO NEBULIZER

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 20
CONFIDENTIAL
1 1

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 20
CONFIDENTIAL
1 3

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 20
CONFIDENTIAL
1 4

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 20
CONFIDENTIAL
1 5

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 20
CONFIDENTIAL
1 6

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 2
CONFIDENTIAL
1

MRT5005-101 
Version .0
Translate Bio, Inc. 
 July 2
CONFIDENTIAL
1 9

MRT5005-101 
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL 
1
 
APPENDIX 4.
BLOOD VOLUMES TO BE DRAWN
Total Volume of Blood to be Drawn from Each Subject in Part A 
Assessment 
Sample Volume (mL) 
Number of Samples 
Total Volume (mL) 
Viral screen (HIV, HBV, HCV)
8.5
1 
8.5
Safety
Serum chemistry, 
CRP, -hCGa
8.5 
9 
76.5 
Hematology 
4.0 
9 
36.0 
Coagulation 
4.5 
9 
40.5 
 mRNA assay 
5.0 
6 
30.0 
 assay
2.5
6 
15.0
CFTR and PEG antibody assay
4.0
6b
24.0
CFTR T cell assay 
20.0 
6b 
120.0 
Total Volume for Study (mL) 
- 
- 
350.5 
-hCG=beta-human chorionic gonadotropin; CRP=C-reactive protein; HIV=human immunodeficiency virus; 
HBV=hepatitis B virus; HCV=hepatitis C virus. 
a  Female subjects only. 
b  Includes the optional blood sample to be collected on the final study day (Day 337 in Part A), if needed for 
assessment of immune responses to CFTR protein (Section 7.5.2.15). 
Total Volume of Blood to be Drawn from Each Subject in Part B 
Assessment 
Sample Volume (mL) 
Number of Samples 
Total Volume (mL) 
Viral screen (HIV, HBV, HCV) 
8.5 
1 
8.5 
Safety 
Serum chemistry, 
CRP, -hCGa 
8.5 
11 
93.5 
Hematology 
4.0 
11 
44.0 
Coagulation
4.5
11
49.5
Inflammatory markersc 
1.0 
6 
6.0 
 mRNA assay 
5.0 
8 
40.0 
 assay 
2.5 
8 
20.0 
CFTR and PEG antibody assay 
4.0 
6b 
24.0 
CFTR T cell assay 
20.0 
6b 
120.0 
Total Volume for Study (mL) 
- 
- 
405.5 
-hCG=beta-human chorionic gonadotropin; CRP=C-reactive protein; HIV=human immunodeficiency virus; 
HBV=hepatitis B virus; HCV=hepatitis C virus.  
a Female subjects only. 
b  Includes the optional blood sample to be collected on the final study day (Day 365 in Part B), if needed for 
assessment of immune responses to CFTR protein (Section 7.5.2.15). 
c Inflammatory markers to be collected in the 20 mg dose group only. 

MRT5005-101 
Translate Bio, Inc. 
Version 5.0 
30 July 2020 
CONFIDENTIAL 
1
 
Total Volume of Blood to be Drawn from Each Subject in Part D 
Assessment
Sample Volume (mL)
Number of Samples
Total Volume (mL)
Viral screen (HIV, HBV, HCV)
8.5
1 
8.5
Safety 
Serum chemistry, 
CRP, -hCGa 
8.5 
11 
93.5 
Hematology 
4.0 
11 
44.0 
Coagulation 
4.5 
11 
49.5 
Inflammatory markers
1.0
8 
8.0
 mRNA assay
5.0
13
65.0
 assay 
2.5 
13 
32.5 
CFTR and PEG antibody assay 
4.0 
7b 
28.0 
CFTR T cell assay 
20.0 
7b 
140.0 
Total Volume for Study (mL) 
- 
- 
469.0 
-hCG=beta-human chorionic gonadotropin; CRP=C-reactive protein; HIV=human immunodeficiency virus; 
HBV=hepatitis B virus; HCV=hepatitis C virus.  
a Female subjects only. 
b  Includes the optional blood sample to be collected on the final study day (Day 341 in Part D), if needed for 
assessment of immune responses to CFTR protein (Section 7.5.2.15).