A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of Subcutaneously Administered ELX-02 in Patients With Alport Syndrome With Col4A5 and Col4A3/4 Nonsense Mutation
Phase: PHASE2
Conditions: Alport Syndrome
Sponsor: Eloxx Pharmaceuticals, Inc.

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Protocol EL-014 Version 2.1. 
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A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy 
of Subcutaneously Administered ELX-02 in Patients with Alport 
Syndrome with Col4A5 and Col4A3/4 Nonsense Mutation 
 
 
Compound: 
ELX-02 
Compound Name: 
6'-(R)-Methyl-5-O-(5-amino-5,6-dideoxy-α-L-
talofuranosyl)- paromamine sulfate  
European Clinical Trials Database (EudraCT) 
Number: 
Protocol Number: 
2022-000604-35  
 
EL-014 
Phase: 
2 
Sponsor: 
Eloxx Pharmaceuticals Inc 
480 Arsenal Way, Suite 130 
Watertown, MA 02472 
United States 
 
 
 
 
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agreed to in writing, by accepting or reviewing this document, you agree to hold this information in confidence 
and not copy or disclose it to others (except where required by applicable law, provided prompt written notice is 
provided to Eloxx Pharmaceuticals and an opportunity to accord confidential treatment to the requested 
disclosable information) or use it for unauthorized purposes. In the event of any actual or suspected breach of this 
obligation, Eloxx Pharmaceuticals must be promptly notified. 

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Signature of Sponsor Representative 
 
A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of 
Subcutaneously Administered ELX-02 in Patients with Alport Syndrome with 
Col4A5 and Col4A3/4 Nonsense Mutation 
 
 
 
‘This Clinical Study Protocol has been reviewed and approved by the Sponsor in order to 
ensure compliance with Good Clinical Practice.’ 
 
 
Print Name: 
Signature: 
Ali Hariri, MD 
Date: 
 
 
 
 
 
 

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Signature of Investigator 
 
A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of 
Subcutaneously Administered ELX-02 in Patients with Alport Syndrome with Col4A5 
and Col4A3/4 Nonsense Mutation 
 
 
Name: 
 
 
 
 
 
 
 
 
 
I declare that I have read and understood this study protocol. I agree to abide by this 
protocol (subject to any amendments agreed in writing between the Sponsor and Principal 
Investigator). Any changes in procedure will only be made if necessary, to protect the 
safety, rights, or welfare of the participants. 
This study will be conducted according to Good Clinical Practice (GCP), local regulations 
and to all stipulations, clinically and administratively, as stated in the protocol, including 
all statements as to confidentiality. It is agreed that the conduct and results of this study 
will be kept confidential. 
It is agreed that the protocol contains all necessary information required to conduct the 
study as outlined in the protocol, and that the study will not be initiated without the 
approval of the Independent Ethics Committee (IEC)/Institutional Review Board (IRB) 
and the local health authority. 
 
 
 
Signature: 
 
Date: 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS ............................................................................................................. 9 
ABBREVIATIONS ..................................................................................................................... 14 
STUDY ADMINISTRATIVE STRUCTURE .......................................................................... 18 
1 
INTRODUCTION AND RATIONALE ............................................................................ 19 
1.1 
Alport Syndrome ............................................................................................................................................ 19 
1.2 
Nonsense Mutation Readthrough .................................................................................................................. 20 
1.3 
ELX-02 .......................................................................................................................................................... 20 
1.4 
Mechanism of Action – The Effect of Aminoglycosides and ELX-02 on Nonsense Mutations ...................... 21 
1.5 
Pharmacology Studies ................................................................................................................................... 22 
1.6 
ELX-02 Clinical Studies ................................................................................................................................ 24 
1.6.1 
Clinical Studies in Healthy Volunteers ................................................................................................ 24 
1.6.2 
Clinical Safety in Healthy Volunteer Studies ....................................................................................... 25 
1.6.3 
Pharmacokinetics in Healthy Volunteer Studies .................................................................................. 26 
1.6.4 
Pharmacokinetics, Exposure and Daily Dosing in Alport Patients ..................................................... 27 
1.6.5 
Nonclinical Safety Studies ................................................................................................................... 27 
1.7 
Study Design .................................................................................................................................................. 29 
1.7.1 
Objectives ............................................................................................................................................ 29 
1.7.2 
Rationale for Patient Selection ............................................................................................................ 29 
1.7.3 
Rationale for Major Assessments ......................................................................................................... 29 
1.7.4 
Rationale for Dose and Dosing Schedule ............................................................................................ 30 
1.7.5 
Risk Benefit Analysis ............................................................................................................................ 30 
1.7.5.1 
Risks Related to ELX-02 ............................................................................................................ 30 
1.7.5.2 
Risks Related to Study Procedures ............................................................................................. 32 
1.7.5.3 
COVID-19 .................................................................................................................................. 33 
1.7.5.4 
Benefits ...................................................................................................................................... 33 
1.7.5.5 
Overall Risk Benefit Analysis .................................................................................................... 33 
2 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................... 35 
2.1 
Objectives ...................................................................................................................................................... 35 
2.1.1 
Primary Objectives .............................................................................................................................. 35 
2.1.2 
Secondary Objectives ........................................................................................................................... 35 
2.1.3 
Exploratory Objectives ........................................................................................................................ 35 
2.2 
Endpoints ....................................................................................................................................................... 35 
2.2.1 
Primary Endpoints ............................................................................................................................... 35 
2.2.2 
Secondary Endpoints ........................................................................................................................... 35 
2.2.3 
Exploratory Endpoints ......................................................................................................................... 35 
3 
STUDY DESIGN ................................................................................................................. 36 
3.1 
Stopping Rules ............................................................................................................................................... 36 
3.1.1 
Dose Stopping in an Individual Participant ......................................................................................... 36 

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3.2 
Study Design Schema .................................................................................................................................... 37 
4 
PARTICIPANT SELECTION .......................................................................................... 38 
4.1 
Inclusion Criteria .......................................................................................................................................... 38 
4.2 
Exclusion Criteria ......................................................................................................................................... 39 
4.3 
Rater Qualifications ...................................................................................................................................... 40 
4.4 
Participant Identification .............................................................................................................................. 40 
4.5 
Re-Screening of Participants ......................................................................................................................... 40 
4.6 
Treatment Interruption and Continuation ..................................................................................................... 40 
4.7 
Removal, Replacement or Early Withdrawal ................................................................................................ 40 
4.8 
Early Study Termination ............................................................................................................................... 41 
4.9 
Lost to Follow-up .......................................................................................................................................... 41 
5 
STUDY TREATMENTS .................................................................................................... 42 
5.1 
Participant Compliance ................................................................................................................................ 42 
5.2 
Investigational Product Supplies ................................................................................................................... 42 
5.2.1 
ELX-02 ................................................................................................................................................. 42 
5.2.1.1 
Dosage Form(s) and Packaging .................................................................................................. 42 
5.2.1.2 
Dispensing and Administration .................................................................................................. 42 
5.3 
Missed Doses ................................................................................................................................................. 43 
5.4 
Investigational Product Storage .................................................................................................................... 43 
5.5 
Investigational Product Accountability ......................................................................................................... 43 
5.6 
Destruction of Investigational Product Supplies ........................................................................................... 44 
6 
STUDY RESTRICTIONS .................................................................................................. 45 
6.1 
Concomitant Medications and Prohibited Medications ................................................................................ 45 
6.2 
Limit of Noise Exposure ................................................................................................................................ 45 
6.3 
Contraception ................................................................................................................................................ 45 
6.3.1 
Birth Control Methods Which May be Considered as Highly Effective ............................................... 46 
7 
STUDY ASSESSMENTS AND PROCEDURES ............................................................. 48 
7.1 
Study Assessments ......................................................................................................................................... 48 
7.1.1 
Screening Phase (Initial and Baseline Visits) ...................................................................................... 51 
7.1.2 
Treatment Period ................................................................................................................................. 52 
7.1.3 
Safety Follow-up (beginning 4 weeks following the last dose) ............................................................ 53 
7.1.4 
Unscheduled Visits ............................................................................................................................... 53 
7.1.5 
Participant Withdrawal ....................................................................................................................... 54 
7.1.6 
Physical Examination .......................................................................................................................... 54 
7.1.7 
Vital Signs ............................................................................................................................................ 54 
7.1.8 
ECGs .................................................................................................................................................... 54 
7.1.9 
Developmental Stage ........................................................................................................................... 54 
7.1.10 
Safety Blood Test ................................................................................................................................. 55 
7.1.11 
Blood Sampling for Pharmacokinetic Assessments ............................................................................. 56 

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7.1.11.1 
Additional Blood Tests ............................................................................................................... 56 
7.1.11.1.1 
Screening Phase.................................................................................................................... 56 
7.1.11.1.2 
Pregnancy Testing ................................................................................................................ 56 
7.1.12 
Urine Tests ........................................................................................................................................... 56 
7.1.13 
Audiology and Vestibular Assessments ................................................................................................ 56 
7.1.13.1 
Audiometric Testing ................................................................................................................... 57 
7.1.13.2 
Tympanometry ........................................................................................................................... 57 
7.1.13.3 
Otoscopy .................................................................................................................................... 57 
7.1.13.4 
Speech Reception Threshold ...................................................................................................... 57 
7.1.13.5 
Dizziness and Tinnitus Status ..................................................................................................... 57 
7.1.14 
Injection Site Reactions ....................................................................................................................... 57 
7.1.15 
Kidney Biopsy ...................................................................................................................................... 58 
7.1.15.1 
Future Use of Stored Specimens ................................................................................................ 58 
7.1.16 
Adverse Events ..................................................................................................................................... 59 
7.1.17 
Concomitant Medications .................................................................................................................... 59 
8 
ADVERSE EVENT REPORTING ................................................................................... 60 
8.1 
Adverse Events .............................................................................................................................................. 60 
8.2 
Reporting Period ........................................................................................................................................... 60 
8.3 
Definition of an Adverse Event ...................................................................................................................... 60 
8.4 
Medication Errors ......................................................................................................................................... 61 
8.5 
Abnormal Test Findings ................................................................................................................................ 61 
8.6 
Serious Adverse Events ................................................................................................................................. 61 
8.7 
Hospitalization .............................................................................................................................................. 62 
8.8 
Severity Assessment ....................................................................................................................................... 62 
8.9 
Causality Assessment .................................................................................................................................... 63 
8.10 Action Taken Regarding the Study Drugs ..................................................................................................... 64 
8.11 Outcome ........................................................................................................................................................ 64 
8.12 Unexpected Adverse Event ............................................................................................................................ 64 
8.13 Adverse Events of Special Interest ................................................................................................................ 64 
8.14 Criteria for Nephrotoxicity ............................................................................................................................ 65 
8.15 Criteria for Ototoxicity .................................................................................................................................. 65 
8.16 Exposure During Pregnancy ......................................................................................................................... 66 
8.17 Follow-up of Adverse Events ......................................................................................................................... 67 
8.17.1 
Data Safety Monitoring Board (DSMB) .............................................................................................. 68 
8.18 Occupational Exposure ................................................................................................................................. 68 
8.19 Withdrawal Due to Adverse Events ............................................................................................................... 68 
8.20 Eliciting Adverse Event Information ............................................................................................................. 68 
8.21 Recording of Adverse Events ......................................................................................................................... 68 
8.22 Reporting Requirements ................................................................................................................................ 69 
8.22.1 
Serious Adverse Event Reporting Requirements .................................................................................. 69 
8.22.2 
Nonserious Adverse Event Reporting Requirements ............................................................................ 69 

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8.22.3 
Sponsor’s Reporting Requirements to Regulatory Authorities ............................................................ 70 
9 
STATISTICAL METHODS .............................................................................................. 71 
9.1 
Sample Size Determination and General Statistical Methods ....................................................................... 71 
9.2 
Pharmacokinetic Analysis ............................................................................................................................. 71 
9.3 
Safety Analysis............................................................................................................................................... 71 
9.4 
Efficacy Analysis ........................................................................................................................................... 71 
10 ETHICS ............................................................................................................................... 73 
10.1 Institutional Review Board/Ethics Committee ............................................................................................... 73 
10.2 Ethical Conduct of the Study ......................................................................................................................... 74 
10.3 Participant Information and Consent/Assent ................................................................................................ 74 
10.4 Participant Recruitment ................................................................................................................................ 76 
10.5 Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP ............................................ 76 
10.6 Measures related to COVID-19..................................................................................................................... 76 
11 ADMINISTRATIVE REQUIREMENTS ......................................................................... 78 
11.1 Protocol Amendments.................................................................................................................................... 78 
11.2 Participant Identification, Enrollment, and Screening Logs ......................................................................... 78 
11.3 Study Termination ......................................................................................................................................... 78 
11.4 End of Trial ................................................................................................................................................... 78 
12 QUALITY CONTROL AND QUALITY ASSURANCE ................................................ 79 
13 DATA HANDLING AND RECORD KEEPING ............................................................. 80 
13.1 Case Report Forms ........................................................................................................................................ 80 
13.2 Record Retention ........................................................................................................................................... 80 
14 REFERENCES .................................................................................................................... 81 
 
Table of Tables 
 
Table 1: 
Schedule of Procedures and Assessments................................................................. 49 
Table 2: 
Safety Test ................................................................................................................ 55 
Table 3: 
DAIDS Grading Scale Site Reactions to Injection ................................................... 58 
Table 4: 
Rating Scale for the Outcome of Each Adverse Event ............................................. 64 
 
 
 

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Table of Figures 
 
Figure 1: 
Chemical Structure of ELX-02 ................................................................................. 20 
Figure 2: 
Kidney Concentration of Drugs vs Time Following Single and Repeated 
Subcutaneous Administration of ELX-02 (10 mg/kg) to CtnsY226X/Y226Y Mice ................... 23 
Figure 3: 
Effect of ELX-02 in CtnsY226X/Y226Y Mice ........................................................ 23 
Figure 4: 
Relationship Between Weekly Target Plasma Exposure in Preclinical Animal 
Models and Estimated Exposures of ELX-02 in Phase 2 Clinical Studies ................................... 24 
Figure 5: 
Study EL-014 Study Schematic ................................................................................ 37 
 

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PROTOCOL SYNOPSIS 
Study Title 
A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of Subcutaneously 
Administered ELX-02 in Patients with Alport Syndrome with Col4A5 and Col4A3/4 Nonsense 
Mutation 
Protocol No. 
EL-014 
Phase 
2 
Test Product, 
Dose, and 
Mode of 
Administration 
ELX-02: 6'-(R)-methyl-5-O-(5-amino-5,6-dideoxy-α-L-talofuranosyl)- paromamine sulfate 
ELX-02 is a synthetic ERSG formulated as lyophilized powder for injection producing a 
concentration of 50 mg/mL upon reconstitution. 
ELX-02 will be administered at a dose of 0.75 mg/kg SC daily for 60 days.  
Background 
and Rationale 
Alport Syndrome (AS) is a progressive hereditary renal disease frequently accompanied by 
extrarenal manifestations including sensorineural hearing loss, cataracts and slow decline 
in vision. AS is the second most common renal genetic disease occurring at a rate of 1 in 
2500–6000 live births. It is caused by mutations in the Col4A3, Col4A4 or Col4A5 
(Col IV) genes. These type IV collagens constitute the main basement membrane in kidney 
and ear responsible for structural integrity of the tissue. Defects in basement membrane in 
kidney glomerulus results in breaks in the glomerular capsule causing glomerular injury, 
proteinuria, hematuria, decrease in glomerular filtration leading to fibrosis and eventual 
renal failure. Similarly, loss of basement membrane integrity in the inner ear leads to 
progressive hearing loss. 
AS mutations are X linked (80%) and autosomal (20%), out of which approximately 6-8% 
are due to nonsense mutation. No approved treatment is available for AS patients; those 
with nonsense mutations have the most severe disease, with early onset of disease and 
significant morbidity and mortality (leading to early onset ESRD and deafness). So far, the 
main treatment for AS is off-label use of ACEi/ARBs to delay disease progression followed 
by renal replacement therapy to treat renal failure. 
ELX-02 is an investigational eukaryotic ribosomal selective glycoside (ERSG) optimized 
as a translational read-through molecule that induces read-through of nonsense mutations 
resulting in production of full-length functional proteins demonstrated across many diseases 
in vitro and in vivo in animal models. ELX-02 has also been tested in Alport Syndrome 
nonsense mutations in vitro where it has consistently shown read-through activity resulting 
in structural reconstitution of Col IV 3,4,5 trimer. The safety and pharmacokinetics (PK) of 
ELX-02 have been tested in single and multiple dose healthy volunteer studies, renal 
impairment volunteers, and in Cystinosis and Cystic Fibrosis patients. Physiologic Based 
Pharmacokinetic (PBPK) Modeling of ELX-02 has shown >50-fold increased exposure in 
kidney versus plasma creating a robust potential for Collagen IV 3, 4, 5 trimer reconstitution 
by readthrough of the nonsense mutation. This makes it an attractive approach to 
personalized Alport Syndrome therapy. 
Objectives 
Primary Objectives 
1. To assess the safety and tolerability of ELX-02 administered subcutaneously (SC) in 
patients with Alport syndrome with Col4A5 and Col4A3/4 nonsense mutations. 
 

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Secondary Objectives 
1. To assess the effect of ELX-02 on proteinuria. 
2. To assess the effect of ELX-02 on expression of Col IV protein in kidney. 
3. To assess the effect of ELX-02 on hematuria. 
Exploratory Objectives 
1. To assess the effect of ELX-02 on potential improvement in hearing of the patients 
with compromised hearing. 
2. To assess Col IV protein levels in urine and or kidney cells, if warranted.  
Endpoints 
Primary Endpoints: 
1. The incidence and characteristics of adverse events (AEs). Other safety assessments 
will include injection site reactions (DAIDS Grading Scale) and changes from 
baseline in vital signs, physical examination, electrocardiograms, blood and urine 
safety laboratory tests, audiometric testing (including high frequency audiometry), 
Tinnitus and Dizziness status.  
Secondary Endpoints: 
1. Change from baseline to EOT and EOS in proteinuria.  
2. Change from baseline to EOT in Col IV expression in renal biopsy  
3. Change from baseline to EOT and EOS in hematuria. 
Exploratory Endpoints: 
1. Potential improvement in audiometric testing (including high frequency 
audiometry) in individuals with baseline abnormalities. 
2. Change in Col IV protein levels in urine and/or kidney cells based on changes in 
urine. 
Study Design 
This is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously 
administered ELX-02 in patients with X-linked or autosomal recessive Alport Syndrome with 
Col4A5 and Col4A3/4 nonsense mutation. 
In total, up to 8 participants, with a minimum of 3 adults, will be enrolled in the trial. In case 
of a screen failure, participants may be re-screened at the discretion of the investigator. 
The study will be comprised of the following periods for each participant: 
• 
a Screening period of up to 6 weeks (42 days) 
• 
a total Treatment Period of 8 weeks (60 days) 
• 
a safety/efficacy Follow-up Period of 12 weeks (90 days) after the last treatment  
The Treatment Period will be a treatment of ELX-02 0.75 mg/kg SC QD for 8 weeks. 
During the treatment period, participants will receive their first dose of study drug at the clinic 
and have study assessments done (Day 1). Participants will return to the clinic for a study visit 
every 2 weeks for safety monitoring, efficacy and return/re-dispensing of study drug ELX-02. 
Except on study visits, treatment will be self-administered (or by a trained care provider) at 
participant’s home. Participants (and/or caregivers) will be instructed on self-administration 
to ensure safety and compliance. 

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The study will initially enroll participants 12-30 years old only. Once the first two participants 
of ages 12-18 years complete 4 weeks of study drug treatment, a DSMB will evaluate the 
safety and PK data of these two sentinel participants. Following DSMB review and decision 
on the safety profile of the study drug, participants 6-11 years old can be dosed with the study 
drug.  
If needed, the DSMB will review reported potentially related serious adverse events (SAEs) 
leading to discontinuation or study stoppage as they are reported. The determination of 
relatedness will be made by the treating investigator (Section 8.9). 
At home, ELX-02 daily dose should preferably be taken at approximately the same time every 
day. Subcutaneous injection(s) of ELX-02 are to be administered to the abdominal area or any 
area with a significant fat deposit (such as the upper thigh). Caution should be taken to ensure 
the injection is not administered into muscle.  
A participant should not have elective injectable aminoglycoside during days of active 
ELX-02 treatment and at least 14 days before or after ELX-02 treatment. For any 
unplanned/urgent injectable aminoglycoside use, ELX-02 administration should be 
suspended and restarted 14 days after aminoglycoside treatment completion.  
All participants will proceed through the entire Treatment Period unless they meet an 
individual stopping criterion (shown below), or the study meets the stopping criteria (see 
Section 4.8). 
Dose stopping in an individual participant: 
• 
Injection site reactions: 
o 
The occurrence of a DAIDS grade 3 or higher injection site reaction 
• 
Nephrotoxicity as defined by Grade 2 Common Terminology Criteria for Adverse 
Events (CTCAE Version 5.0) based on serum creatinine 
• 
Participants who evidence a Grade 2 CTCAE hearing impairment in the conventional 
frequencies or high frequency threshold shift meet stopping criteria for suspected 
ototoxicity. For adults, this is specified as a worsening shift from baseline of >25 dB 
averaged at 2 contiguous test frequencies in at least one ear, or at least 5-point 
worsening on THI or DHI questionnaires and category change. For pediatric 
participants, this is specified as a worsening shift from baseline of >25 dB averaged 
at 2 contiguous test frequencies in at least one ear including a worsening shift of > 
20 dB at 4 kHz in at least one ear. 
• 
Any other adverse event (AE), which in the opinion of investigator puts the 
participant at undue risk 
If it is determined following a thorough review that the initial assessment was incorrect, 
treatment of the participant may be resumed. This determination will be made by the DSMB 
in agreement with the Sponsor. 
Participants who withdraw prior to study completion for non-safety reasons (e.g., personal 
reasons or non ELX-02 related AEs) may be replaced upon approval of the Sponsor. 
Inclusion 
Criteria 
Participants must meet all of the following criteria to participate in this study: 
 
1. Evidence of signed and dated informed consent/assent document(s) indicating that the 
participant (and/or their parent/legal guardian) has been informed of all pertinent aspects 
of the trial 

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2. Understands, and is willing and able to comply with all scheduled visits, treatment plan, 
laboratory tests, and other study procedures 
3. Male and female participants 
4. Ages between 6 years to 30 years 
5. A confirmed diagnosis of X-linked or autosomal recessive Alport Syndrome with a 
documented nonsense mutation of Col4A5 in a male or nonsense mutation of Col4A3 or 
Col4A4 (male or female) 
6. The nonsense mutation should be UAG or UGA 
7. eGFR≥60 ml/min/1.73 m2 (based on CKD-EPI for ages ≥18 and Schwartz formula for 
participants <18) 
8. Urinary protein based on two spot urine collections [urine protein/creatinine ratio (UPCR) 
≥ 500 mg/g] 
9. Stable regimen of ACEi/ARB for at least 4 weeks before screening (unless there is a 
contraindication) 
10. Must be willing to abstain from strenuous exercise during the 48 hrs prior study visits 
11. Females of childbearing potential and males capable of fathering a child must meet the 
contraception requirements outlined in Section 6.4  
12. Non-lactating females 
13. Females on hormone replacement therapy (estrogen or progesterone) or contraceptive 
therapy must be stabilized on a product and dose for at least 30 days prior to Screening 
14. Have not received systemic medications with potential to impair renal function on a 
frequent basis (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]) or with ototoxic 
potential (e.g., quinine or salicylates), or any injectable aminoglycosides for a period of 
at least 14 days prior to dosing 
15. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), 
and hepatitis C virus antigen (HCV Ag) serology tests at Screening 
16. No history of alcohol or drug abuse within the 6 months prior to Screening 
17. Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive). Participants with a lower BMI 
may be entered into the study at the discretion of the investigator following consultation 
with the Sponsor 
Exclusion 
Criteria 
Participants with any of the following characteristics/conditions will not be included in the 
study: 
1. Participants who are investigational site staff members directly involved in the conduct 
of the study and their family members, site staff members otherwise supervised by the 
Investigator, or participants who are Eloxx Pharmaceuticals employees directly involved 
in the conduct of the study 
2. Participation in clinical study including administration of any investigational drug or 
device in the last 30 days or 5 half-lives (whichever is longer) prior to investigational 
product dosing in the current study 
3. Use of prohibited medications as defined in Section 6.1 within the specified windows 
4. History of any comorbidity which in the opinion of the investigator might confound the 
study or pose an additional risk in administering the study drug to the participant 

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5. History of any organ transplantation 
6. Mutation consistent with autosomal dominant Alport Syndrome 
7. Liver disease characterized by cirrhosis or portal hypertension. Participants with alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 3.0 
times the upper limit of normal (ULN) will be excluded 
8. History of congestive heart failure diagnosed clinically or with documented left 
ventricular ejection fraction (LVEF) ≤ 40%  
9. Evidence or history of clinically relevant psychiatric condition  
10. A positive urine drug screen (amphetamines, benzodiazepines, cocaine and opiates) at 
Screening 
11. Screening supine 12-lead electrocardiogram (ECG) demonstrating any clinically 
significant findings as judged by the Investigator 
12. Participants with any abnormalities in clinical laboratory tests at Screening, considered 
by the study Investigator as clinically relevant 
13. Major surgery within 180 days (6 months) of Screening 
14. History of dialysis  
15. Known allergy to any aminoglycoside 
16. Participants with any acute medical situation unresolved within 14 days of first dose that 
is considered of significance by the Investigator 
17. Participants with >10 dB change in threshold between audiometric Initial test to Baseline 
test for the frequencies from 0.5 -12.5 kHz 
18. Dizziness Handicap Inventory (DHI) score at screening ≥16 for adults, and active 
dizziness reported for pediatric participants.  
Statistical 
Methods 
No formal sample size or power calculation has been performed.  
Safety analyses will be based on the Safety Population, defined as all treated participants who 
received at least one dose of study drug, including participants prematurely withdrawn from 
the study. PK analyses will be based on the PK Population defined as those treated participants 
who have analyzable PK data without relevant deviation interfering with the PK evaluations. 
Efficacy analyses will be based on the efficacy Population defined as those participants who 
have a valid baseline (before dosing) efficacy sample and at least 1 non-missing post-baseline 
value for an efficacy sample. 
Safety, PK and efficacy data will be summarized using descriptive statistics and/or graphical 
displays. Efficacy parameters will be described as changes from baseline in PD measurements 
during each treatment period. Changes in hematuria will be recorded as a categorial variable. 
Proteinuria will be evaluated as UPCR. The baseline value will be the geometric mean of the 
screening and pre-Day 1 dosing samples.  
 
 

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ABBREVIATIONS 
Abbreviation 
Term 
AAA 
American Academy of Audiology 
AE 
Adverse events 
Ae 
Cumulative amount of unchanged drug excreted into urine 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase (also known as glutamate-pyruvate 
transaminase-SGPT) 
ASHA 
American Speech-Language-Hearing Association 
AST 
Aspartate aminotransferase (also known as glutamate-
oxaloacetate transaminase-SGOT) 
AUCt 
Area under the plasma concentration-time curve calculated from 
time of administration to the last quantifiable concentration, 
computed using the linear trapezoidal rule 
AUCinf 
Area under the concentration-time curve from time 0 
extrapolated to infinity  
AUC24h 
Area under the plasma concentration-time curve calculated from 
time of administration to time 24h, computed using the linear 
trapezoidal rule 
BIW 
Twice weekly 
BMI 
Body mass index 
BP 
Blood pressure 
CF 
Cystic fibrosis 
CKD-EPI 
Chronic kidney disease epidemiology collaboration 
CL/F 
Apparent plasma clearance 
Cmax 
Maximum plasma concentration 
CNS 
COVID-19 
Central nervous system 
Coronavirus disease of 2019 
CPR 
C-reactive protein 
Cpredose 
Trough plasma concentration observed at the end of the dosing 
interval (i.e., at each predose starting from second dose) 
CRF 
Case report form 
CRO 
Clinical research organization 
CSA 
Clinical study agreement 
CTA 
Clinical trial application 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAIDS 
Division of Aids 
DHI 
Dizziness Handicap Inventory 
DMD 
Duchenne muscular dystrophy 
DNA 
Deoxyribonucleic acid  

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Abbreviation 
Term 
DOA 
Drugs of abuse 
DSMB 
EDC 
Data Safety Monitoring Board 
Electronic data capture 
EDP 
Exposure during pregnancy 
ECG 
Electrocardiogram 
ENT 
Ear, nose, and throat 
EOS 
End of study 
ESRD 
ERSG 
End-Stage Renal Disease 
Eukaryotic ribosomal specific glycoside 
eTMF 
Electronic trial master file 
EU 
European Union 
FDA 
Food and Drug Administration 
FSH 
Follicle stimulating hormone 
GAG 
Glycosaminoglycans 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HbsAg  
Hepatitis B surface antigen 
HCT 
Hematocrit 
HCV Ab 
Hepatitis C virus antibody 
HCV Ag 
Hepatitis C virus antigen 
HED 
Human equivalent dose 
HFA 
High frequency audiometry 
HIV 
Human Immunodeficiency Virus 
HR 
Heart rate  
Hr(s) 
Hour (s) 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
IEC 
Independent Ethics Committee 
IMP 
IMPD 
Investigational medicinal product 
Investigational Medicinal Product Dossier 
IRB 
ISR 
Institutional Review Board 
Injection Site Reaction 
IV 
Intravenous 
K 
Potassium 
LBM 
Lean body mass 

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Abbreviation 
Term 
LH 
Luteinizing hormone 
LLOQ 
Lower limit of quantification 
LPLV 
Last visit of the last participant in the study 
LS 
Life sciences 
LVEF 
Left ventricular ejection fraction 
MA 
Medical Affairs 
MDRD 
Modification of Diet in Renal Disease  
MPS 
Mucopolysaccharidose type I 
min 
Minute 
mmHg 
Millimeter mercury 
MRSD 
Maximum recommended starting dose 
MRT 
Mean residence time 
Mecp2 
Methyl-CpG-binding protein 2  
msec 
Millisecond 
MTD 
 
Maximum tolerated dose 
Na 
Sodium 
NOAEL 
No observed adverse effect level  
NSAIDs 
Non-steroidal anti-inflammatory drugs 
OTC 
Over the counter 
PBPK 
Physiologically based pharmacokinetics 
PD 
Pharmacodynamic(s) 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s)  
PT 
Preferred term 
PTA 
Pure tone audiometry 
Rac 
Accumulation ratio 
RBC 
Red blood cells 
RNA 
Ribonucleic acid 
rRNA 
Ribosome ribonucleic acid 
RR 
Respiratory rate 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous(ly) 
SD 
Standard deviation 
SOC 
System organ class 
SRT 
Speech Reception Threshold 

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Abbreviation 
Term 
SUSAR 
Suspected unexpected serious adverse reaction 
t½ 
Elimination half-life 
TEAE 
Treatment-emergent adverse event 
THI 
Tinnitus Handicap Inventory 
tmax 
Time to maximum concentration 
tRNA 
Transfer ribonucleic acid 
ULN 
Upper limit of normal 
UMC 
Uppsla Monitoring Center 
UPCR 
Urine Protein/Creatinine Ratio 
USA  
United States of America 
UTR 
Untranslated region 
Vd/F 
Apparent volume of distribution 
WBC 
White blood cell 
WHO 
World Health Organization 

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STUDY ADMINISTRATIVE STRUCTURE 
SPONSOR 
Eloxx Pharmaceuticals 
480 Arsenal Way, Suite 130 
Watertown, MA 02472 
United States 
Chief Medical Officer: 
Ali Hariri, MD  
Senior Director, Clinical Operations: 
Lior Horonchik, Ph.D. 
 
 
 

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1 
INTRODUCTION AND RATIONALE 
1.1 
Alport Syndrome 
Alport syndrome (AS) is a progressive hereditary renal disease frequently accompanied by extrarenal 
manifestations including sensorineural hearing loss, cataracts and slow decline in vision. AS is the 
second most common renal genetic disease occurring at a rate of 1 in 2500–6000 live births. It is 
caused by mutations in the Col4A3, Col4A4 or Col4A5 (Col IV) genes. These type IV collagens 
constitute the main basement membrane in kidney and ear responsible for structural integrity of the 
tissue. Defects in basement membrane in kidney glomerulus results in breaks in the glomerular 
capsule causing glomerular injury, proteinuria, hematuria, decrease in glomerular filtration leading 
to fibrosis and eventual renal failure. Similarly, loss of basement membrane integrity in the inner ear 
leads to progressive hearing loss.  
Renal progression of disease goes through several stages. Microscopic hematuria is the earliest 
manifestation of disease. This evolves to microalbuminuria (UACR30-300 mg/g) and gross 
proteinuria (UACR>300 mg/g). Consequently, proteinuria reduction and improvement in hematuria 
is the best representation of the reversal of the disease.(1) After initial glomerular injury due to 
basement membrane breaks, continued cycles of injury and scarring leads to fibrosis of the kidney 
and eGFR decline progressing to renal failure requiring dialysis or transplantation. It is not surprising 
that 0.5% and 12.9% of newly developed renal failure in adults and children respectively is due to 
AS, while particularly, patients with AS who harbor nonsense mutations suffer from juvenile onset 
of ESRD.(2)  
X-linked AS, is the most common inheritance pattern and is caused by mutations in Col4A5. 
Mutations in Col4A3 and Col4A4 result in autosomal transmission manifesting either as recessive or 
as dominant pattern of inheritance. The frequency of X-linked AS, autosomal recessive AS, and 
autosomal dominant AS are estimated to be 80%, 15% and 5% respectively.(3) AS is frequently 
underdiagnosed due to atypical presentation in a significant fraction of patients. Genetic analysis of 
patients with chronic kidney disease shows that only 38% of the patients with Col IV mutations are 
properly diagnosed as Alport patients.(4) 
Among the different mutations in these three genes, approximately 6% are due to nonsense 
mutations.(5) Patients with nonsense mutations along with those having large rearrangements, 
frameshift or splicing abnormalities resulting in truncated or absent protein, (2, 6) present with the most 
severe phenotype including early onset of disease, significant morbidity and mortality leading to early 
onset ESRD and deafness.(2, 7, 8) The mean age of ESRD in these patients is 20 years of age. In contrast, 
patients with missense Col4A5 mutations (such as glycine -XY mutations) have a mean age of ESRD 
as 30 years of age.(2) In a more recent study,(5) it was reported that nonsense mutations in Col4A5 and 
Col4A3/Col4A4 have an onset of ESRD of 21.4 and 17.9 years of age respectively. At the same time 
the less severe mutations have the age of ESRD of 26.7 (col4A5) and 24-26.6 (Col4A3/Col4A4). In 
patients with Col4A5 nonsense mutations, the onset of ESRD occurred as early as 16.9 years and in 
patients with Col4A4/Col4A3 nonsense mutations as early as 13.3 years. The early onset and rapid 
progression to renal failure in AS patients with nonsense mutations makes developing therapies in 
this pre-adolescent and adolescent patients urgent. 
Despite the high unmet need, there is no approved treatment for AS. Use of ACEi/ARBs to delay 
disease progression followed by renal replacement therapy to treat eventual renal failure is the main 
treatment approach. Recent studies have shown that early initiation of with ACEi/ARB in pediatric 

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age results in significant delay in renal progression.(9) Specifically, early proteinuria reduction by 
ramipril improved renal survival in children with AS (ESCAPE trial and PROTECT trials). While 
ACEi/ARBs provide a small degree of renal protection AS patients reach ESRD at a young age, there 
is no special treatment for hearing loss other than use of cochlear implants or hearing aids. 
1.2 
Nonsense Mutation Readthrough 
ELX-02 is an investigational eukaryotic ribosomal selective glycoside (ERSG) optimized as a 
translational read-through molecule that induces read-through of nonsense mutations resulting in 
production of full-length functional proteins demonstrated across many diseases in vitro and in vivo 
in animal models. Nonsense mutations are genetic mutations in a deoxyribonucleic acid (DNA) 
sequence that results in a shorter, truncated non-functional protein product. During protein formation, 
an RNA codon, comprising a three nucleotides sequence, corresponds to a specific amino acid or stop 
signal (stop codon). Nonsense codons do not code for an amino acid, but instead, together with a 
complex mechanism of translation termination at the  3’ untranslated region (UTR), including several 
release factors, signal the end of protein synthesis. Thus, nonsense mutations occur when a premature  
stop is introduced in the DNA sequence. When the mutated sequence is translated into a protein, the 
resulting protein is incomplete and shorter than normal. Consequently, most nonsense mutations 
result in nonfunctional proteins.(10, 11) 
Eloxx Pharmaceuticals is developing ELX-02 as a treatment for inherited conditions caused by 
nonsense mutations whereby the mutation leads to decreased or absent protein expression. ELX-02 
is intended to read through the nonsense mutation and induce the translation of full-length functional 
proteins to have a beneficial clinical effect in these diseases. Comprehensive preclinical testing of 
ELX-02 in vitro and in animal models of disease demonstrated its potential efficacy and decreased 
toxicity compared to traditional aminoglycosides. Thus, ELX-02 has the potential to treat any disease 
caused by nonsense mutations and thus may have broad applicability for many orphan diseases. In 
addition, based on the ELX-02 PK studies have shown 50X uptake in the kidney and ear. 
1.3 
ELX-02 
ELX-02 is a new non-antibiotic aminoglycoside analogue [6’-®-methyl-5-O-(5-amino-5,6-dideoxy-
α-L-talofuranosyl)-paromamine sulfate]. Its chemical structure is shown in Figure 1: 
Figure 1: Chemical Structure of ELX-02 
 
  
 
 
 
 
 
 
 
 
 
ELX-02 has poor oral bioavailability but rapid parenteral (subcutaneous [SC] and intravenous [IV]) 
absorption, reaching peak plasma concentrations within 30 to 60 minutes after administration. 

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ELX-02 is not metabolized and is excreted unchanged by the kidney via glomerular filtration in direct 
proportion to creatinine clearance and has concentration dependent activity whereby clearance 
depends on renal function and volume of distribution depends on weight. More details can be found 
in the Investigator’s Brochure (IB). 
The pharmacokinetic (PK) profile of ELX-02 in plasma in animals and humans shows dose 
proportionality and follows classic multi-exponential decay with a rapid and large elimination phase 
and a slower and low distribution phase. The PK profile of ELX-02 in animal tissues is complex. Like 
in plasma, ELX-02 follows a multi-phasic decay with a large elimination phase that accounts for 61 
to 95% of the AUC and a low distribution phase that accounts for 5 to 39% of the AUC after weekly 
or biweekly dose for 28-days. The kidneys account for the majority (68 to 75%) of the area under the 
plasma concentration-time curve (AUC) in the distribution phase. In some tissues, the half-life of 
ELX-02 is longer than the dosing interval so that, with multiple dosing, ELX-02 accumulates. Tissue 
half-life of ELX-02 ranges from 3.5 to 116 hrs. Extensive physiologically based pharmacokinetic 
(PBPK) modeling in animals and humans allows predictions of time-dependent ELX-02 tissue 
concentrations, given a dose and dosing interval so that, for example, measurement of plasma and 
urine ELX-02 levels inform on renal distribution.  
ELX-02 targets peripheral pharmacological compartments where it accumulates to varying degree 
and with compartment-specific PK. The therapeutic value of ELX-02 is a direct consequence of 
specific targeting of peripheral pharmacological compartments such as kidney, lung, muscle, and 
CNS with a controlled exposure sufficient to promote expression of functional protein that, in turn, 
leads to efficacious outcomes below toxic exposures, particularly in the kidney and ear. In this 
manner, ELX-02 is expected to induce controlled translational read-through of premature termination 
codons in each tissue for a mutated gene specific for a given genetic disease. 
1.4 
Mechanism of Action – The Effect of Aminoglycosides and ELX-02 on Nonsense 
Mutations  
ELX-02 is a rationally drug candidate designed to induce readthrough across the premature 
termination codon (also known as nonsense mutation) resulting in full-length protein production and 
restoration of protein function. The basis for rational design of ELX-02 is established readthrough 
activity noted for aminoglycoside antibiotics like gentamicin. 
Aminoglycosides bind to the decoding site in the small subunit of the ribosome ribonucleic acid 
(rRNA)(12) that normally monitors proper codon-anticodon interactions and is capable of inducing 
translational read-through. When aminoglycosides bind to the decoding site, they induce a 
conformational change that reduces the ability of rRNA to discriminate between cognate and near-
cognate aminoacyl-transfer(t)RNAs(13) and stabilizes 3 critical adenosine residues in a conformation 
suitable for read-through(14). This reduction in the accuracy of codon-anticodon recognition increases 
the probability that translational read-through of stop codons occurs. Despite promising results, 
aminoglycoside use as a long-term translational read-through therapy is restricted since their 
antibiotic activity may damage the microflora and lead to resistance against pathogenic bacteria. In 
addition, 
prolonged 
use 
of 
aminoglycosides 
is 
associated 
with 
ototoxicity 
and/or 
nephrotoxicity.(15,18,19) 
The readthrough activity of ELX-02 was optimized through successive rounds of medicinal chemistry 
that took into account the known structure activity relationship of aminoglycosides (20) 21,22,23,14)  
Rational design separated the structural elements of the aminoglycoside scaffold inducing read-
through from those elements affecting antibacterial activity.(24,25) This led to preferential binding of 

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ELX-02 to the eukaryotic ribosome with no antibiotic activity. Low affinity of ELX-02 for the 
prokaryotic ribosome decouples the antibacterial activity from read-through activity. When compared 
to gentamicin, ELX-02 demonstrates a 100-fold lower antibacterial activity and 9-fold higher 
read-through activity, which is attributed to higher selectivity towards the cytoplasmic ribosome. 
ELX-02 interacts selectively with the eukaryotic ribosome G1408 residue, through the 5’ amine group 
of the 3rd ring stabilizing the flipping out of the two conserved alanine residues in the rRNA caused 
by binding of cognate tRNAs.(14) 
1.5 
Pharmacology Studies  
A series of preclinical studies has been conducted to evaluate the primary pharmacodynamics of 
ELX-02 in several genetic disease indications including CF, cystinosis, Duchenne muscular 
dystrophy, Mucopolysaccharidosis type 1, and Rett syndrome. This includes in vitro [organoid, 
human bronchial epithelial (HBE) cells, Fischer rat thyroid (FRT) cells, plasmid-based] and in vivo 
models of CF. Likewise, for cystinosis, both in vitro (fibroblast, plasmid-base) and in vivo models 
have been evaluated. These studies demonstrate that ELX-02 induces functional restoration of CFTR 
across the most common nonsense mutations in CF and cystinosis and estimate a weekly therapeutic 
exposure range of 20 to 190 µg*hr/mL. 
In Vitro Efficacy Studies 
ELX-02 has been evaluated across multiple in vitro model systems and demonstrates consistent, dose-
dependent evidence of activity against several nonsense mutations.  
ELX-02 read-through of the Col4A5 R1563X nonsense mutation that causes Alport syndrome was 
demonstrated in a reporter assay expressing Col4A5 fused to a C-terminal NanoLuc reporter. ELX-
02 treatment significantly increased the read-through of Col4A5 R1563X reporter by 7-to10- fold.(26)  
In cystinosis patient fibroblasts homozygous for the W138X mutation, incubation of ELX-02 at 
escalating dose for 72 hours resulted in reduced half-cystine levels (at  100 μg/mL) up to normal 
levels. ELX-02 also significantly increased CTNS mRNA levels ( 200 μg/mL) by 2.5- to 3.5-fold.  
ELX-02 has also been evaluated across multiple cystic fibrosis (CF) in vitro model systems and 
demonstrates consistent, dose-dependent evidence of activity against the most common CFTR 
nonsense mutations. These CF models include reporter and overexpression systems, patient-derived 
primary HBE cells and patient-derived organoids. The results of these models have been favorably 
correlated with in vivo human clinical results.  
Reporter and Overexpression Systems: Initially, ELX-02 mediated read-through of CF 
nonsense mutations was demonstrated in a luciferase reporter system supporting that CF 
nonsense alleles were amendable to read-through. Next, ELX-02 demonstrated an increase in 
functional CFTR by increasing stimulated CFTR current using the FRT cell model 
overexpressing either G542X or R1162X bearing CFTR transgenes. These models supported 
our evaluation of patient-derived cells.  
Patient-derived Organoids: An organoid is a three-dimensional, multi-cellular in vitro system 
derived from stem cells isolated from rectal biopsies. Similar to measuring CFTR conductivity 
in other systems, such as HBE cells, CFTR activity is stimulated in the organoid system with 
forskolin to produce cyclic adenosine monophosphate, a signaling molecule that stimulates 

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CFTR channel activity. Organoids derived from nonsense mutation CF patients lack apparent 
swelling in this system due to their lack of functional CFTR. These studies demonstrate that 
across the most common CF causing nonsense alleles (G542X, W1282X, R553X, R1162X, and 
E60X) accounting for >75% of the CF nonsense allele population, ELX-02 significantly 
increases CFTR function in a dose dependent fashion. While approved CF therapies lack 
efficacy against nonsense CF mutation, organoids with responsive mutations to approved 
therapies (e.g. G551D, F508del) demonstrate activity in the organoid swelling assay in a 
manner that correlates with clinical responsiveness in informative endpoints such as FEV1 
and sweat chloride change. When considering the ELX-02 results with the correlation reports 
of other approved molecules in this assay, the response mediated by ELX-02 read-through 
meets or exceeds the activity necessary to significantly improve FEV1 and sweat chloride 
concentration.  Additionally, ivacaftor in combination with ELX-02 further increased CFTR 
channel activity supporting that the read-through CFTR product may be potentiated. 
 
In Vivo Efficacy Studies and Therapeutic Exposure Estimates 
ELX-02 pharmacokinetic properties drive its pharmacologic activity. Since it is an aminoglycoside, 
excellent systemic exposure ca be achieved along with elevated exposures in kidney. This has driven 
the exposure estimates in different diseases. 
A cystinosis nonsense mouse model, CtnsY226X/Y226X, was evaluated for reduction in cystine 
accumulation.(15) In vitro evaluation of CtnsY226X/Y226X mouse embryonic fibroblasts demonstrated 
significant reduction in cellular cystine accumulation within 24-hours using 100-400 µg/mL ELX-
02. Mice with the same genetic background were treated with ELX-02 at 10 mg/kg or 30 mg/kg 
subcutaneously bi-weekly for 3 weeks (7 total injections). In mice, as expected, there were higher 
levels of ELX-02 in kidney versus plasma. After treatment, ELX-02 reduced kidney cystine levels by 
30% in treated animals compared to untreated animals. 
Figure 2: Kidney Concentration of Drugs vs Time Following Single and Repeated 
Subcutaneous Administration of ELX-02 (10 mg/kg) to CtnsY226X/Y226Y Mice 
 
  
Figure 3: Effect of ELX-02 in CtnsY226X/Y226Y Mice 
 
ELX-02 read-through was also evaluated using a CFTR knockout mouse model that expressed a 
human G542X CFTR transgene and the results of these studies show that ELX-02 restores CFTR 
function.(27, Eloxx Report CF-01) In these studies, the effect of ELX-02 on CFTR activity was tested 
in Cftr knockout mice expressing a human CFTR-G542X transgene under intestine-specific rat fatty 
acid binding protein (referred to hereafter as Cftr−/− hCFTR-G542X or G542X transgenic mice).(28,29) 
Mice were administered ELX-02 (30 and 60 mg/kg) by SC injection once daily for 14 days. CFTR 
activity was then assayed by Ussing chamber analysis to determine whether cAMP-stimulated 
transepithelial short circuit currents (Isc) could be detected. Significant increases in forskolin-
stimulated Isc were observed in Cftr−/− hCFTR-G542X mice treated with 30 mg/kg ELX-02 (14.7 
μA/cm2). The increases in Isc in these ELX-02-treated mice was 5.8% of the forskolin-stimulated Isc 

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observed in wild-type control mice, and the response to 30 mg/kg ELX-02 was roughly 2.5-fold 
greater than the currents observed in controls treated with the same dose of gentamicin. 
Efficacious therapeutic exposure estimates are derived from a compilation of the in vivo nonsense 
models evaluated with ELX-02. This includes Cftr−/− hCFTR-G542X transgenic mice and a cystinosis 
mouse model.(27,15, ELX-01, Eloxx Report CF-01). Inclusion of additional models serves to better 
estimate the full range at which tissue level read-through has been observed with ELX-02. Kidney 
level efficacy in a cystinosis mouse model was observed at a weekly plasma exposure of 20 µg*hr/mL 
while efficacy was observed between 47.5 and 190 µg*hr/mL in the gut of the Cftr−/− hCFTR-G542X 
transgenic model. The targeted efficacious dose for Alport is similar to cystinosis as both are diseases 
of the proximal nephron in the kidney. 
 
Figure 4: Relationship Between Weekly Target Plasma Exposure in Preclinical Animal 
Models and Estimated Exposures of ELX-02 in Phase 2 Clinical Studies 
 
For additional details of the nonclinical studies, please consult the IB. 
1.6 
ELX-02 Clinical Studies  
1.6.1 Clinical Studies in Healthy Volunteers 
Eloxx Pharmaceuticals has completed three studies in healthy volunteers: 
• EL-001 and EL-006 were two monocentric, randomized, double-blinded placebo-controlled 
single ascending dose (SAD) studies.(30)  
• EL-002 was a Phase 1, randomized, double-blinded, placebo-controlled, third party open, 
multiple ascending dose (MAD) escalation study. 
Both SAD studies evaluated single doses of ELX-02 between 0.3 mg/kg and 7.5 mg/kg (N=40) or 
placebo (N=20) in a total of 60 normal volunteers and characterized general and specialized safety 
parameters and PK. ELX-02 was generally well tolerated, showed typical pharmacokinetic 
parameters for an aminoglycoside, and showed an acceptable safety profile without severe or serious 
study drug-related adverse events (AE). 
The MAD study EL-002 evaluated the safety, tolerability and PK of subcutaneously administered 
ELX-02 in independent consecutive cohorts of healthy participants. The study was designed to 
include 7 cohorts of 9 participants (2:1 active study drug to placebo). Doses ranged from 0.1 mg/kg 
to 5.0 mg/kg SC twice a week over 29 days for a total of nine doses. The 1.0 mg/kg and 2.5 mg/kg 
doses were administered at final injection concentrations of 100 mg/mL and 50 mg/mL while other 
doses levels were administered at 50 mg/mL. A total of 41 participants received ELX-02 and 21 
participants received placebo in the study. ELX-02 demonstrated dose-proportional PK in this study, 
with no evidence of accumulation for up to 29 days of bi-weekly administration. ELX-02 was 
generally well tolerated, there were no reported SAEs or renal findings. 
 
Eloxx Pharmaceuticals has completed two other clinical trials: 
• EL-008 – A Phase 1 study in participants with various severities of renal dysfunction and 
healthy volunteers. In this study, the mean plasma concentration profiles for Group 1 (mild 
renal impairment, eGFR between 60 and 89 mL/min/1.73m2) and Group 4 (control, normal 

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renal function, eGFR ≥90 mL/min/1.73m2) were nearly identical. Mean maximum plasma 
ELX-02 concentrations were higher and mean terminal elimination half-life was longer in 
Group 2 (moderate renal impairment, eGFR between 30 and 59 mL/min/1.73m2) and Group 
3 (severe renal impairment, eGFR <30 mL/min/1.73m2, not undergoing dialysis) versus 
Group 4. Mean t½ values were similar at 2.8 and 3.3 h for normal renal function and mild renal 
impairment; half-life increased to 6.4 and 21.2 h in moderate and severe renal impairment, 
respectively. Renal clearance of ELX-02 showed similar trends as plasma, with decreasing 
clearance as the severity of renal impairment increased.  
• EL-003 – A Phase 2 study in patients with nephropathic Cystinosis. This study was 
discontinued due to non-safety reasons and did not proceed with the second cohort as planned 
in the original protocol. Once daily SC administration of ELX-02 targeting a plasma exposure 
of 95 µg*hr/mL/week for seven days (Treatment Period 2) in the first cohort resulted in a 
measurable percent reduction in white blood cell (WBC) cystine levels following seven days 
of treatment with ELX-02. Following 14 days of treatment at 190 µg*hr/mL/week (Treatment 
Period 3), two out of three participants showed a reduction in WBC cystine levels. During the 
hiatuses between Treatment Periods 1 and 2, and 2 and 3, the Day 1 pre-dose WBC cystine 
levels continued to increase above the pre-treatment baseline, which made interpretation of 
the results challenging. Therefore, this study was discontinued. There were no treatment-
related SAEs. All TEAEs were mild or moderated in severity. 
There are two ongoing Phase 2 clinical trials in patients with Cystic Fibrosis (Studies EL-004 in 
Israel, Germany and Australia and EL-012 in the United States and Canada). Overall, the ongoing 
Phase 2 studies for ELX-02 are considered to provide an adequate safety profile for CF patients. The 
adverse events experienced reflect the underlying disease state. 
In conclusion, the overall safety profile of ELX-02 is adequate and manageable. The most common 
TEAE is injection site reaction which can be delayed by several days and the most severe reactions 
observed to date may require weeks to months to completely resolve. There have been no clinically 
meaningful changes in kidney function or hearing. 
1.6.2 Clinical Safety in Healthy Volunteer Studies 
Studies EL-001 and EL-006 (Single Ascending Dose or SAD) 
Over the dose ranges tested (0.3 mg/kg to 7.5 mg/kg), ELX-02 was shown to be safe and generally 
well tolerated. For the pooled data of both studies, the most common treatment-emergent adverse 
events (TEAEs) occurring in ≥ 3 participants were injection site reactions (6 participants [10%]), 
headache (5 participants [8%]), injection site erythema (3 participants [5%]), and ear discomfort (3 
participants [5%]). All of these TEAEs were considered mild in severity except for one case of 
moderate headache (placebo) and one event of high frequency threshold shift (5 mg/kg dose) on pure 
tone audiometry (PTA). This moderate AE of abnormal acoustic stimulation test was recorded in one 
participant on Day 8 after administration of ELX-02 5.0 mg/kg SC. The AE was considered possibly 
related to study drug by the Investigator, who also deemed it a serious adverse event (SAE). The AE 
was not resolved at the end of the study. This AE was evaluated in detail with the assistance of an 
independent audiology expert, and it was observed that there were random, bidirectional fluctuations 
in audiometry not consistent with aminoglycoside-induced ototoxicity, and that they were likely the 
result of equipment mis-calibration and maintenance, improper audiophone placement and/or 
uncontrolled noise in the environment. Overall, the conclusion by the Sponsor was that the AE was 
unrelated to the study drug, and it did not meet the criterion for SAE.  
Study 002 (Multiple Ascending Dose or MAD) 

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ELX-02 was generally well tolerated, there were no reported SAEs or renal findings. Thirty-four 
(82.9%) participants in the ELX-02 treatment groups and 9 (42.9%) in the placebo groups 
experienced TEAEs related to the study drug, the majority of which were injection site reactions. All 
TEAEs were mild or moderate in severity, and none were classified as serious. The duration of 
observed injection site reactions was reduced from 28 days to 12 days for the 1 mg/kg dose and from 
45 days to 19 days for the 2.5 mg/kg dose when the final injection concentration was reduced from 
100 mg/mL to 50 mg/mL. One of 12 participants who received 2.5 mg/kg of ELX-02 and 3 of 6 
participants who received 5.0 mg/kg of ELX-02 had significant hearing threshold shifts.  The 
threshold shifts were largely confined to the high frequency range (10-16 kHz), above the 
conventional range (0.25-8 kHz) needed for normal human communication. No irreversible 
permanent and stable or progressive hearing threshold shift, or clinical impact was observed in any 
participant, nor did any participant demonstrate significant tinnitus or vestibular disorders that are 
commonly affiliated with ototoxicity. While the threshold changes were inconsistent with 
aminoglycoside induced ototoxicity in the participant who received 2.5 mg/kg, ototoxicity at the 5.0 
mg/kg twice weekly dose could not be completely ruled out because the partially to fully reversable 
hearing threshold shifts in the very high frequency range in two participants were consistent with 
early ototoxicity. In Cohort 7 (for the 5.0 mg/kg group), 2 of 3 participants received placebo also 
experienced threshold changes, indicating that some variability in the audiometry test results may 
have contributed to the findings. 
Study 008 (Renal Impairment Study) 
ELX-02 was generally well tolerated following a single SC dose of 1.0 mg/kg. Overall, 6 participants 
had a total of 11 TEAEs. Five (20.8%) participants had TEAEs that were considered related to study 
drug. All TEAEs were classified as mild in severity. There were no deaths or SAEs reported in the 
study. None of the TEAEs lead to study discontinuation.  
A majority of participants (83.3%) in the placebo group and 1/6 participants (16.7%) in Group 3 
experienced at least 1 TEAE. All TEAEs were classified by the investigator as being related to the 
study drug. The most frequently reported TEAE was injection site erythema [observed in 4/6 (66.7%) 
participants in the placebo group and 1/6 (16.7%) participants in Group 3. 
Study 003 (Study in Patients with Nephropathic Cystinosis) 
In the cohort of three adult participants (≥18 years old with eGFR ≥40 mL/min/1.73m2) in this study, 
ELX-02 was generally well tolerated following SC injection of ELX-02. Overall, a total of 16 Aes 
were reported in the three participants treated in the study. All AEs were considered mild (Grade 1) 
in severity, except for two events (choking, anemia) that were considered moderate (Grade 2) in 
severity. All events were resolved.  
There were no adverse events of special interest (nephrotoxicity, ototoxicity, intolerable injection 
reactions) reported. There were 2 serious AEs (choking and allergic reaction to Venofer®) in one 
participant (101-001). The episode of choking related to underlying disease occurred during the 
screening period and the drug hypersensitivity reaction to Venofer® occurred during the hiatus 
between Treatment Periods 2 and 3. Both of these events resolved without complication and were not 
related to ELX-02. There were no TEAEs leading to death or study discontinuation. 
 
1.6.3 Pharmacokinetics in Healthy Volunteer Studies 
Studies EL-001 and EL-006 (Single Ascending Dose or SAD) 

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ELX-02 given SC was rapidly absorbed with a time to maximum concentration (tmax) of about 0.5 to 
1.0 hr. AUC0-inf changed linearly with ELX-02 dose (24-fold increase for a 25-fold dose increase) and 
maximum plasma concentration (Cmax) changed in a quasi-proportional way with ELX-02 dose as 
significant dose effects were seen (17-fold increase for a 25-fold increase). The apparent terminal 
half-life (t1/2) was 2 to 8 hr in the dose range tested (0.3 mg/kg to 7.5 mg/kg).  
Plasma concentration profiles were linearly and proportionally related to the dose administered. 
ELX-02 had a rapid elimination phase and a slower distribution phase. ELX-02 was excreted and 
recovered almost quantitatively in the urine during the first 12 hrs. 
Study EL-002 (Multiple Ascending Dose or MAD) 
In Study EL-002, ELX-02 was rapidly absorbed following SC administration to healthy participants 
across a dose range of 0.1 to 5.0 mg/kg, with median tmax ranging from 45 minutes to 1-hr post-dose. 
Plasma ELX-02 exposure was dose proportional across the dose ranges evaluated, and no evidence 
of accumulation was observed following twice-weekly administration for up to 9 doses over 29 days. 
Volume of distribution was high, suggesting distribution beyond the blood compartment. Systemic 
ELX-02 was rapidly excreted in urine, with approximately 76 to 94% of the administered dose 
excreted within 12 hrs post-dose. Both plasma and renal clearance were high and independent of dose, 
consistent with the short elimination half-life of approximately 2 to 3 hrs. Plasma ELX-02 exposure 
was generally similar following SC administration of either a 50 or 100 mg/mL diluted injection 
solution, indicating no formulation-related differences in PK. 
1.6.4 Pharmacokinetics, Exposure and Daily Dosing in Alport Patients 
ELX-02 is an aminoglycoside which has a preferential uptake in the kidney. Megalin is a polybasic 
transporter which uptakes aminoglycosides (such as ELX-02). Due to the high expression of Megalin 
in the kidney (podocytes and proximal tubules) and the inner ear, a significantly lower dose of ELX-
02 is required for treatment of Alport patients. The PBPK model developed from previous EX-02 PK 
studies predicts 52 times higher ELX-02 exposure in the kidney compared to the plasma at an ELX-
02 SC dose of 1 mg/kg. A dose of 0.75 mg/kg is expected to be in the therapeutic range and will 
require only one SC injection daily to achieve consistent exposures. 
1.6.5 Nonclinical Safety Studies 
In a core battery of safety pharmacology studies, ELX-02 had no effect on cardiovascular, 
neurobehavior, or respiratory functions and no off-target pharmacological activity, or antibacterial 
activity. It displayed a short plasma half-life, long tissue half-life, with linear dose-dependent PK in 
mice, rats and dogs, dose proportional exposure in mice, rats, and dogs, and near 100% bioavailability 
between SC and IV dosing. ELX-02 does not undergo hepatic metabolism and is excreted unchanged 
in urine; tissue exposures were significantly longer than plasma exposure.  At pharmacologic doses 
it showed no accumulation in plasma, and relatively low accumulation in the kidney and cochlear 
tissue. It also has negligible in vitro plasma protein binding in rat, dog, and human plasma, and high 
binding to brain tissue homogenates of CD-1 mice. 
• In definitive repeat-dose toxicity studies using adult rats and dogs, ELX-02 administered in 
SC doses twice weekly (BIW) over a 28-day period had little or no effect on body weight, 
food consumption, clinical signs of toxicity, ophthalmology, cardiovascular parameters, or 
hematology or coagulation parameters. Clinical chemistry alterations reflected that of renal 
dysfunction. In these 4-week toxicology studies, the exposures at the highest dose without 
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(corresponding to weekly AUC of approximately 174 and 250 µg*h/mL, respectively). The 
highest exposure at which no ototoxicity findings were observed was 413 µg*h/mL 
(corresponding to weekly AUC of approximately 826 µg*h/mL, respectively). In a 
confirmatory rat 4-week daily dosing tox study, the NOAEL was 30 mg/kg/day with a weekly 
exposure of 385 µg*h/mL, suggesting enhanced safety for daily compared to BIW dosing. 
Dosing. This result is consistent with a 29-day QD toxicity study in male beagle dogs daily 
ELX-02 at 13.5 kg/mg/day demonstrated no indications of nephrotoxicity with daily exposure 
of 38.4 µg*h/mL (weekly exposure of 268.8 µg*h/mL). Longer term GLP tox studies (rat 6-
month tox and dog 9-month tox) identified similar NOAEL exposures with BIW dosing. 
• The justification in patients <18 is based on the 13 weeks study in juvenile rats. In this GLP 
study, juvenile rats, PND 28, were given ELX-02 for 13 weeks and a subset of animals 
underwent a 28-day recovery period. Doses were given SC on a twice-weekly basis alternating 
between two injection sites located on each side of the scapular region and two sites on each 
side of the gluteal region of the animal.  Dose levels were set at 0, 15, 30, and 45 mg/kg/dose 
(MPI Report 2490-002) based upon three assumptions: no adverse renal findings in adult rats 
at 60 mg/kg/dose for 4-weeks (Aptuit Report VPT4700); increased exposure duration may 
result in target organ toxicity at lower dose levels; and anticipated greater sensitivity to 
aminoglycosides in juvenile animals. 
There were no ELX-02 related adverse findings on survival, functional observational battery 
evaluations, body weight, body weight change, food consumption, ophthalmoscopic 
evaluations, motor activity, learning and memory, bone length or density, clinical pathology 
(hematology, clinical chemistry, coagulation, or urinalysis), organ weights, or 
neurohistopathological evaluations at any ELX-02 dose level. Furthermore, there were no 
adverse ELX-02 related effects on sexual maturation, reproductive and fertility indices, 
maternal uterine examinations, or sperm evaluations at any dose level. ELX-02-related non-
adverse observations of scabbed area and red discoloration of the skin were evident in both 
genders at all dose levels. These changes correlated with macroscopic observations of skin 
abrasions/scabs at or around the lumbar injection sites in males at ≥30 mg/kg/dose and in 
females at 45 mg/kg/dose. These changes also correlated with microscopic findings of 
myofiber degeneration in the cutaneous trunci muscle, hemorrhage, SC edema, SC fibrosis, 
and mononuclear cell infiltration in the subcutis or muscle. There were occasional findings at 
the injection sites that were present in control animals and treated animals, indicative of a 
dosing procedure-related effect which showed a trend to recovery throughout the recovery 
period. At the terminal necropsy, minimal tubular degeneration and apoptosis in one kidney 
was observed in one female given 45 mg/kg/dose. These findings were multifocal and were 
characterized by cytoplasmic vacuolation and individual tubuloepithelial cell necrosis in 
several proximal tubules within the outer medulla. There were no findings in recovery 
animals. The findings were not considered adverse based on the minimal severity and the 
abundance of unaffected parenchyma. 
As there were no adverse ELX-02-related effects in this study, the NOAEL was the highest 
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respectively), and an AUC0-24 hr of 63 and 58 µg*hr/mL (male/female, respectively, on Day 
91. 
1.7 
Study Design 
This is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously 
administered ELX-02 in patients with Alport Syndrome with Col4A5 and Col4A3/4 nonsense 
mutation. 
1.7.1 Objectives 
Primary objective: Safety and tolerability of ELX-02 will be evaluated in this trial.  
Secondary objectives: The readthrough effect of ELX-02 in expression of Col IV will be evaluated 
in kidney and ear. The expression of the Col IV in the kidney will be evaluated functionally by the 
changes in proteinuria and hematuria, two main early hallmarks of kidney disease in AS. 
Histologically, the expression of Col IV will be evaluated by expression of Col IV in the basement 
membrane. While the focus of the trial is to evaluate the efficacy in the kidney, and as such the 
patients are not selected based on their auditory phenotype. However, it is expected that most of the 
participants to have auditory phenotypes. The evaluation of the hearing of the participants is an 
exploratory endpoint. 
1.7.2 Rationale for Patient Selection 
Alport patients with nonsense mutations in Col4A5, Col4A4, and Col4A3 can benefit from treatment 
with a nonsense readthrough agent that can functionally restore Col IV as demonstrated in pre-clinical 
experiments. Patients 6-30 years of age will be included in this trial.  
Patients who harbor nonsense mutations have an early onset of the disease leading to ESRD at age 
17.9-21.4 years (Col4A5 and Col4A4/Col4A3 respectively). Due to the early onset and rapid 
progression to ESRD, it is imperative to initiate treatment early to restore collagen IV function in 
these patients if there is a chance to delay disease progression.  It is important to note that patients as 
young as 13.3 years old with Col4A3/A4 reach ESRD.(31,32) 
Phase 1 and Phase 2 studies of ELX-02 in at least 126 adults who received at least one dose of ELX-02 
has shown to be well tolerated with no serious ELX-02 related adverse events seen. In addition, rat 
juvenile toxicology study showed no adverse ELX-02-related effects up to 45 mg/kg twice weekly 
dose with a corresponding Cmax of 68 and 67 μg/mL (male/female, respectively), and an AUC0-24 hr 
of 63 and 58 µg∙hr/mL (male/female, respectively, on Day 91. 
1.7.3 Rationale for Major Assessments 
Urine collection: Hematuria and proteinuria are the earliest manifestations of AS. Hence, the primary 
and secondary endpoints of this study are proteinuria and hematuria, respectively. It is hypothesized 
that expression of functional Col IV in patients with nonsense mutations due to readthrough induced 
by ELX-02 can partially restore glomerular integrity thus reducing dysfunction and further injury 
resulting in an improvement of proteinuria and hematuria. Effective Col IV expression may also be 
measured in urine cells to correlate with changes in hematuria and proteinuria. Urine collection is 
required to evaluate the efficacy of ELX-02 in this study. 
Audiometric test: While the patients in this study are not selected based on their hearing status, due 
to the early onset of the of the manifestation of disease in AS patients with nonsense mutation, a large 
number of the patients are expected to have sensorineural hearing problem. Restoring the expression 

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of the Col IV may improve the hearing of the patients. This is a non-invasive assessment and is 
required for assessment of safety and efficacy in this study. 
Kidney biopsy: In this pilot study, it is important to assess for a signal of clinical efficacy in a 
comprehensive manner. The first indication of drug effect in Alport patients due to readthrough across 
a nonsense mutation is the formation of full-length COL IV protein. To assess the molecular 
restoration of protein function, kidney biopsies will be performed and assayed for COL IV protein 
levels and structural changes upon COL IV restoration, if any. 
1.7.4 Rationale for Dose and Dosing Schedule 
ELX-02 will be administered at 0.75 mg/kg SC daily. Patients with cystic fibrosis have received the 
same or higher doses of ELX-02 in previous Phase 2 studies. Extensive pharmacokinetic experience 
across studies, physiologically based pharmacokinetic modeling and pre-clinical pharmacology has 
provided a firm basis for dose selection. It is important to note that physiologic based PK modeling 
shows a >50 times exposure in the kidney compared to plasma at 1 mg/kg dosing in human. This 
preferential kidney targeting of ELX-02 underlies the robust results seen in preclinical study in 
cystinosis with half-cysteine reductions in kidney and is also anticipated to drive favorable exposures 
in Alport kidneys (see Section 1.5). 
The ELX-02 fixed dose level for this study is 0.75 mg/kg/day (5.25 mg/kg/week). This dose 
corresponds with the MAD study dose of 2.5 mg/kg BIW (5 mg/kg/week). Based on the MAD healthy 
volunteer data, the weekly exposure is expected to be about 65 µg*h/mL. This exposure reaches the 
target therapeutic range and its safety is supported by healthy volunteer data as well as animal 
toxicology data. 
• In a Phase 1 study (EL-008) in participants with various severities of renal dysfunction and 
healthy volunteers, the mean ELX-02 plasma concentration profiles for those with mild renal 
impairment (eGFR between 60 and 89 mL/min/1.73 m2) were nearly identical to those in the 
control group with normal renal function (eGFR ≥90 mL/min/1.73 m2). Hence by inclusion 
of participants with eGFR ≥60 mL/min/1.73 m2), no dose adjustment is needed. 
Dosing Schedule  
The apparent terminal half-life (t1/2) of single ascending doses in healthy volunteers was 2 to 8 hr (0.3 
mg/kg to 7.5 mg/kg), with similar pharmacokinetics and no accumulation in multiple ascending doses 
when administered twice weekly (BIW). Given the short t1/2 in healthy volunteers, ELX-02 will be 
administered daily in this trial to ensure consistent daily exposure, and avoid any possible increased 
risk of nephrotoxicity associated with multiple daily doses (e.g. three times/day). Daily administration 
will also minimize the injection volume of each dose, thereby improving tolerability in comparison 
with the significantly larger injection volumes administered BIW in the Phase 1 studies.  
Once daily dosing has been well tolerated at doses up to 3 mg/kg/day in CF patients. The participants 
in this study will receive a dose of 0.75 mg/kg/day. This provides adequate safety margin based on 
clinical and non-clinical data. 
1.7.5 Risk Benefit Analysis 
1.7.5.1 
Risks Related to ELX-02 
ELX-02-mediated Nephrotoxicity: Nephrotoxicity from aminoglycosides is a known toxicity, 
generally dose related, observed with repeated dosing (cumulative total dose) and generally 

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reversible. However, the pattern of aminoglycoside nephrotoxicity is distinct from the manifestation 
of chronic kidney disease in Alport patients and can be evaluated based on the pattern of the decline 
of renal function.   As described in Section 1.6.5, ELX-02 causes nephrotoxicity in preclinical animal 
studies at high doses and after repeated doses. The administration of 0.75 mg/kg SC is significantly 
below the upper limit of toxicity. In ongoing trials, ELX-02 is administered as high as 3 mg/kg in CF 
patients. 
Based on the toxicology studies, the rat and dog NOAELs were associated with renal findings that 
were reversible with a lack of progression for renal toxicity following chronic administration. 
Consistent with Section 1.6.5., and as related to nephrotoxicity: 
• the rat 6-month toxicology data identified NOAEL doses, with BIW dosing, corresponding to 
weekly exposures of 244 µg*h/mL (3.8x safety margin). 
• the dog  9-month toxicology data identified NOAEL doses, with BIW dosing, corresponding 
to weekly exposures of 172µg*h/mL (2.7x safety margin). 
• a confirmatory rat 4-week daily dosing toxicology study identified a NOAEL corresponding 
to 30 mg/kg/day and a weekly exposure of 385 µg*h/mL, suggesting enhanced safety for daily 
compared to BIW dosing, and which is about 6.1-fold greater than the exposure targeted in 
this study.  
• a 29-day QD toxicity study in male beagle dogs dosed ELX-02 at 13.5 kg/mg/day and 
demonstrated no indications of nephrotoxicity with daily exposure of 38.4 µg*h/mL (weekly 
exposure of 268.8 µg*h/mL). These data correspond to a >4.1-fold safety margin compared 
to the exposure targeted in this study. 
Overall based on rat and dog toxicology data the safety margin of 0.75 mg/kg SC QD dosing is at 
least 2.7x chronic dosing in beagle dogs in 9 months. In addition, the 26-week juvenile toxicology 
safety margin is approximately 2 (exposure of 122 µg*h/mL).  
 
In addition to the toxicology data, as described in Section 1.6.3, single doses of 7.5 mg/kg (single 
dose Cmax = 20 µg/mL and exposure of 95 µg*h/mL) were administered to healthy volunteers with 
no signals of nephrotoxicity (increases in serum creatinine or biomarkers of acute kidney injury 
[KIM-1 and clusterin]). 
Participant exposure, safety and labs (every 2 weeks monitoring of renal function) will be carefully 
followed through all clinic visits during the Treatment Period as well as during the safety Follow-up 
Period after administration of the last dose (every month). While patients with Alport in this trial have 
chronic kidney disease, any acute worsening of the renal function will be further evaluated during 
this trial.  
ELX-02-mediated Ototoxicity 
Cochleotoxicity and vestibulotoxicity are class effects of aminoglycosides observed to a varying 
extent with different agents. However, the acuity of the effect is different from the clinical pattern of 
Alport patients. In the preclinical studies with ELX-02, no ototoxicity was observed in rats exposed 
to ELX-02 up to 240 mg/kg BIW for 4 weeks. At this dose, the approximate weekly exposure was 
826 µg*h/mL, which is approximately 11.8-fold higher than the expected exposure in this study. 
The data observed in clinical studies to date is noted in Section 1.6.2. There have been no reports of 
vestibulotoxicity in any participants dosed with ELX-02 to date. For the purpose of cochleotoxicity 

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monitoring, it should be noted that one participant in the SAD study receiving a single dose of ELX-
02 at 0.3 mg/kg IV had a reversible high frequency threshold shift in one ear that was not considered 
related to ELX-02 by the Investigator, and another participant administered a single dose of 5 mg/kg 
had a high frequency threshold shift that showed bidirectional fluctuation and was attributed to 
methodological issues by an audiometry expert. These AEs were evaluated in detail with the 
assistance of an independent audiology expert, and it was observed that there were random, 
bidirectional fluctuations in audiometry not consistent with aminoglycoside-induced ototoxicity, and 
that they were likely the result of equipment mis-calibration and maintenance, improper audiophone 
placement and/or uncontrolled noise in the environment. Overall, these auditory-related events were 
considered not related to the study drug. In the EL-002 MAD study ELX-02 did not demonstrate 
evidence of ototoxicity in the 0.1, 0.3, and 1.0 mg/kg groups. One of the participants in the 2.5 mg/kg 
group had reversible, high-frequency threshold changes inconsistent with aminoglycoside induced 
ototoxicity. Furthermore, three participants had partially- to fully reversible hearing threshold shifts 
at the 5.0 mg/kg twice weekly dose level. At this top dose, the hearing threshold shifts in the very 
high frequency range (10-16 kHz), above the conventional range (0.25-8 kHz) needed for normal 
human communication, were clearly observed in two participants and partially in a third. No 
irreversible permanent and stable or progressive hearing threshold shift, or clinical impact was 
observed in any participant, nor did any participant demonstrate significant tinnitus or vestibular 
disorders that are commonly affiliated with ototoxicity. Two out of three placebo-treated participants 
in Cohort 7 (in the 5.0 mg/kg group) were also found to have significant hearing threshold changes, 
indicating some variability inherent in this audiometry assessment. Overall, while changes were 
inconsistent with aminoglycoside induced ototoxicity, ototoxicity at the 5.0 mg/kg twice weekly dose 
level could not be ruled out. 
Participant hearing and audiometry will be carefully monitored at baseline, Days 30 and 60 of the 
Treatment Period, and Days 90, 120 and 150 of the safety Follow up Period.  If any abnormalities are 
observed, they will receive close audiometry follow up. The administration of 0.75 mg/kg SC is 
substantially below the upper limit of toxicity. In addition, improvement or stabilization of hearing is 
expected in AS patients due to the expression of Col IV. 
Potential for Neuromuscular Blockade 
Use of ELX-02 should be avoided in participants with known neuromuscular disorders or those that 
are being given neuromuscular blocking agents because structurally similar aminoglycoside 
compounds have been associated with neuromuscular blockade. No preclinical or clinical data exist 
at present with ELX-02 to support or refute this effect. 
1.7.5.2 
Risks Related to Study Procedures 
ELX-02-mediated Potential for Local Injection Site Reaction 
Limited and tolerable injection site reactions have been observed with ELX-02 in preclinical and 
clinical studies to date, and consistent tolerability data are emerging from ongoing Phase 2 studies. 
The injection site reaction is dose dependent and is also impacted by the number of injections. In this 
trial, the ELX-02 administration will be limited to one daily injection so the potential for injection 
site reaction is reduced. In addition, once daily injection is expected to result in improved tolerability. 
Potential Risks Associated with Kidney Biopsy 
Recent studies show that the rate of minor complications due to the biopsy procedure is 4.5-15.1% 
(hematuria, resolving hematoma, bleeding), and the major complication rate is consistently about 
1.5% (active bleeding, arteriovenous fistula, complicated hematoma). The patients with major 

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complication had abnormal baseline coagulation (abnormal PTT and PT) and severe anemia (Hb<10) 
and these patients will not be included in this study as they will not satisfy the inclusion/exclusion 
criteria. Furthermore, in this high-risk patients who are not candidates for the trial, the risk is operator 
dependent. In this study, kidney biopsies will be performed in major academic centers with operators 
having years of experience in performing biopsies thus reducing risks further. 
1.7.5.3 
COVID-19 
ELX-02 is not expected to have immunomodulatory effects that would present an increased risk to 
participants enrolled in the study, either contracting or experiencing a more serious disease if infected 
with COVID-19. Eloxx Pharmaceuticals will assist, as needed, to clinical sites to apply site-level 
procedures regarding COVID-related precautions for patients and staff. The study visit schedule has 
also been carefully reviewed to minimize unnecessary visits and patient exposure. 
Eloxx Pharmaceuticals will continue to assess risk during the course of the clinical study due to 
COVID-19 impact. This includes risk assessment for the overall study, as well as at the 
country/regional levels since changes/adaptations may be needed at a local level depending on the 
local COVID-19 situation. This may include impacts on visit schedules, assessments performed in-
person or virtually, and alternative options for IMP re-supply for patients.  
Further COVID-19 information can be found in Section 10.6. 
1.7.5.4 
Benefits 
ELX-02 is being developed for patients with genetic disorders caused by nonsense mutations, 
including patients with Alport Syndrome. Multiple in vitro and in vivo models support the mechanism 
of action and read-through potential of ELX-02, supporting the potential efficacy of ELX-02 in 
patients with Alport Syndrome caused by nonsense mutations. Despite the significant morbidity and 
mortality of AS, there is currently no approved drug for Alport patients. 
ELX-02 has a potential to induce the production of functional Col IV in patients with AS harboring 
nonsense mutations. This induction of functional Col IV is based on its unique mechanism of action 
and unique pharmacology of preferential absorption in the proximal nephron of the kidney (including 
the glomerulus) and the inner ears. Similar strong absorption of ELX-02 is known to occur in the 
inner ear. This potential functional replacement of Col IV early in the course of the disease prior to 
the deleterious effects of kidney fibrosis may slow down or halt the progression of the disease. For 
example, treatment with a readthrough agent, gentamicin, an agent with 10-fold lower readthrough 
than ELX02, in patients with recessive dystrophic epidermolysis bullosa harboring COL7A1 
nonsense mutations led to replacement of Collagen VII at the dermo-epidermal junction and induced 
wound healing.( 27) 
1.7.5.5 
Overall Risk Benefit Analysis 
At this time, there is no treatment for AS patients. In general, the most common expected risk 
associated with the administration of ELX-02 is injection site reaction based on treatment of adults. 
However, this is the first-time children as young as 6 years old will be exposed to ELX-02. It is 
important to note that ELX-02 is a non-antibiotic aminoglycoside, and no additional risk is known in 
pediatric population for this class of molecules. Consistent with this, adult safety data from prior 
ELX-02 studies and non-clinical juvenile toxicology study, no specific pediatric monitoring is 
required. Renal and cochlear/vestibular monitoring, as has been specified for adults, will also apply 
to children. The other risk associated with this trial is the performance of kidney biopsy which is 

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significantly de-risked by the patient population and the procedure being performed in expert major 
academic centers. In terms of benefit, AS patients may have renal and sensorineural hearing 
stabilization after treatment with ELX-02. Based on the overall safety profile of ELX-02 and the 
current limited pilot study in AS patients, the overall risk benefit analysis justifies conducting this 
trial.  

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2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
2.1.1 Primary Objectives 
1. To assess the safety and tolerability of ELX-02 administered subcutaneously (SC) in 
patients with Alport Syndrome with Col4A5 and Col4A3/4 nonsense mutation. 
2.1.2 Secondary Objectives 
1. To assess the effect on ELX-02 in proteinuria. 
2. To assess the effect on ELX-02 in expression of Col IV protein in kidney. 
3. To assess the effect on ELX-02 in hematuria. 
2.1.3 Exploratory Objectives 
1. To assess the effect of ELX-02 on potential improvement in hearing of the patients with 
compromised hearing. 
2. To assess Col IV protein levels in urine and or kidney cells, if warranted. 
2.2 
Endpoints 
2.2.1 Primary Endpoints 
1. The incidence and characteristics of adverse events (AEs). Other safety assessments will 
include injection site reactions (DAIDS Grading Scale) and changes from baseline in vital 
signs, physical examination, electrocardiograms, blood and urine safety laboratory tests, 
audiometric testing (including high frequency audiometry) and Tinnitus and Dizziness status.  
2.2.2 Secondary Endpoints 
1. Change from baseline to EOT and EOS in proteinuria.  
2. Change from baseline to EOT in Col IV protein expression in renal biopsy  
3. Change from baseline to EOT and EOS in hematuria. 
2.2.3 Exploratory Endpoints 
1. Change in audiometric testing (including high frequency audiometry) in individuals with 
baseline abnormalities. 
2. Change in Col IV protein levels in urine and/or kidney cells based on changes in urine. 
 

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3 
STUDY DESIGN 
This is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously 
administered ELX-02 in patients with X-linked or autosomal recessive Alport Syndrome with 
Col4A5 and Col4A3/4 nonsense mutation. 
In total, up to 8 participants, with a minimum of 3 adults, will be enrolled in the trial. In case of a 
screen failure, participants may be re-screened at the discretion of the Investigator. 
The study will be comprised of the following periods for each participant: 
• a Screening period of up to 6 weeks (42 days) 
• a total Treatment Period of 8 weeks (60 days) 
• a safety/efficacy Follow-up Period of 12 weeks (90 days) after the last treatment.  
The Treatment Period will be a treatment of ELX-02 0.75 mg/kg SC QD for 8 weeks (60 days). 
During the treatment period, participants will receive their first dose of study drug at the clinic and 
have study assessments done (Day 1). Participants will return to the clinic for a study visit every 2 
weeks for dosing, safety monitoring, efficacy and return/re-dispensing of study drug ELX-02. Outside 
of study visit days, treatment will be self-administered (or by a trained care provider) at participant’s 
home. Participants (and/or caregivers) will be instructed on self-administration to ensure safety and 
compliance.  
The study will initially enroll participants 12-30 years old only. Once the first two participants of ages 
12-18 years complete 4 weeks of study drug treatment, a DSMB will evaluate the safety and PK data 
of these two sentinel participants.  Following DSMB review and decision on the safety profile of the 
study drug, participants younger than 12 years of age (6-11 years old) can be dosed with the study 
drug. 
If needed, the DSMB will review reported potentially related serious adverse events (SAEs) leading 
to discontinuation or study stoppage as they are reported. The determination of relatedness will be 
made by the treating investigator (Section 8.9). 
At home, ELX-02 daily dose should preferably be taken at approximately the same time every day. 
Subcutaneous injection of ELX-02 is to be administered to the abdominal area or any area with a 
significant fat deposit (such as the upper thigh). Caution should be taken to ensure the injection is not 
administered into muscle.  
A participant should not have elective injectable aminoglycoside during days of active ELX-02 
treatment and at least 14 days before or after ELX-02 treatment. For any unplanned/urgent injectable 
aminoglycoside use, ELX-02 administration should be suspended and restarted 14 days after 
aminoglycoside treatment completion. 
3.1 
Stopping Rules 
All participants will proceed through the entire Treatment Period unless they meet an individual 
stopping criterion (see Section 3.1.1), or the study meets the stopping criteria (see Section 4.8). 
3.1.1 Dose Stopping in an Individual Participant 
• Injection site reactions: 
o 
The occurrence of a DAIDS grade 3 or higher injection site reaction 

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• Nephrotoxicity as defined by Grade 2 Common Terminology Criteria for Adverse Events 
(CTCAE Version 5) based on serum creatinine 
• Participants who evidence a Grade 2 CTCAE hearing impairment in the conventional 
frequencies or high frequency threshold shift meet stopping criteria for suspected ototoxicity. 
For adults, this is specified as a worsening shift from baseline of >25 dB averaged at 2 
contiguous test frequencies in at least one ear, or at least 5-point worsening on THI or DHI 
questionnaires and category change. For pediatric participants, this is specified as a worsening 
shift from baseline of >25 dB averaged at 2 contiguous test frequencies in at least one ear 
including a worsening shift of > 20 dB at 4 kHz in at least one ear. 
• Any other adverse event (AE), which in the opinion of investigator puts the participant at 
undue risk  
If it is determined following a thorough review that the initial assessment was incorrect, treatment of 
the participant may be resumed. This determination will be made by the DSMB in agreement with 
the Sponsor. 
Participants who withdraw prior to study completion for non-safety reasons (e.g., personal reasons or 
non ELX-02 related AEs) may be replaced upon approval of the Sponsor. 
3.2 
Study Design Schema 
The design of the study is presented in Figure 5. 
Figure 5: Study EL-014 Study Schematic 
 
 
 
 

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4 
PARTICIPANT SELECTION 
In total, up to 8 participants, with a minimum of 3 adults, will be enrolled in the trial. In case of a 
screen failure, participants may be re-screened at the discretion of the Investigator. 
This study can fulfill its objectives only if appropriate participants are enrolled. The following 
eligibility criteria are designed to select participants for whom participation in the study is 
considered appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular participant is suitable for this protocol.  
Participant eligibility should be reviewed and documented by an appropriate member of the 
Investigator’s study team before the participant is included in the study. 
4.1 
Inclusion Criteria 
Participants must meet all of the following criteria to participate in this study: 
1. Evidence of signed and dated informed consent/assent document(s) indicating that the 
participant (and/or their parent/legal guardian) has been informed of all pertinent aspects of the 
trial 
2. Understands, and is willing and able to comply with all scheduled visits, treatment plan, 
laboratory tests, and other study procedures 
3. Male and female participants 
4. Ages between 6 years and 30 years 
5. A confirmed diagnosis of X-linked or autosomal recessive Alport Syndrome with a 
documented nonsense mutation of Col4A5 in a male or nonsense mutation of Col4A3 or 
Col4A4 (male or female).  
6. The nonsense mutation should be UAG or UGA 
7. eGFR≥60 ml/min/1.73 m2 (based on CKD-EPI for ages ≥18 and Schwartz formula for 
participants <18) 
8. Urinary protein based on two spot urine collections [urine protein/creatinine ratio (UPCR) ≥ 
500 mg/g] 
9. Stable regimen of ACEi/ARB for 4 weeks before screening (unless there is a contraindication) 
10. Must be willing to abstain from strenuous exercise during the 48 hrs prior study visits 
11. Females of childbearing potential and males capable of fathering a child must meet the 
contraception requirements outlined in Section 6.3  
12. Non-lactating females 
13. Females on hormone replacement therapy (estrogen or progesterone) or contraceptive therapy 
must be stabilized on a product and dose for at least 30 days prior to Screening 
14. Have not received systemic medications with potential to impair renal function on a frequent 
basis (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]) or with ototoxic potential (e.g., 
quinine or salicylates), or any injectable aminoglycosides for a period of at least 14 days prior 
to dosing 

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15. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and 
hepatitis C virus antigen (HCV Ag) serology tests at Screening 
16. No history of alcohol or drug abuse within the 6 months prior to Screening 
17. Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive). Participants with a lower BMI 
may be entered into the study at the discretion of the investigator following consultation with 
the Sponsor 
4.2 
Exclusion Criteria 
Participants with any of the following characteristics/conditions will not be included in the study: 
1. Participants who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the Investigator, 
or participants who are Eloxx Pharmaceuticals employees directly involved in the conduct of 
the study 
2. Participation in clinical study including administration of any investigational drug or device in 
the last 30 days or 5 half-lives (whichever is longer) prior to investigational product dosing in 
the current study 
3. Use of prohibited medications as defined in Section 6.1 within the specified windows 
4. History of any comorbidity which in the opinion of the investigator might confound the study 
or pose an additional risk in administering the study drug to the participant 
5. History of any organ transplantation 
6. Mutation consistent with autosomal dominant Alport Syndrome 
7. Liver disease characterized by cirrhosis or portal hypertension. Participants with alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 3.0 times 
the upper limit of normal (ULN) will be excluded 
8. History of congestive heart failure diagnosed clinically or with documented left ventricular 
ejection fraction (LVEF) ≤ 40%  
9. Evidence or history of clinically relevant psychiatric condition  
10. A positive urine drug screen (amphetamines, benzodiazepines, cocaine and opiates) at 
Screening 
11. Screening supine 12-lead electrocardiogram (ECG) demonstrating any clinically significant 
findings as judged by the Investigator 
12. Participants with any abnormalities in clinical laboratory tests at Screening, considered by the 
study Investigator as clinically relevant 
13. Major surgery within 180 days (6 months) of Screening 
14. History of dialysis  
15. Known allergy to any aminoglycoside 
16. Participants with any acute medical situation unresolved within 14 days of first dose that is 
considered of significance by the Investigator 

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17. Participants with >10 dB change in threshold between audiometric Initial test to Baseline test 
for the frequencies from 0.5 -12.5 kHz 
18. Dizziness Handicap Inventory (DHI) score at screening ≥16 for adults, and active dizziness 
reported for pediatric participants.    
4.3 
Rater Qualifications 
Audiometric and vestibular tests will be performed by an audiologist or ear, nose, and throat (ENT) 
specialist. More details are provided in Section 7.1.13. 
4.4 
Participant Identification 
Each participant who has signed the informed consent will be assigned a unique study number.  
Participant identification will be confirmed by the study staff at each study visit. 
4.5 
Re-Screening of Participants 
If dosing is not expected to occur within 42 days of initial Screening procedure for any reason, the 
following re-Screening assessments will be performed to allow his/her participation: weight with 
BMI, vital signs, physical examination, ECG, blood safety lab tests, blood test for pregnancy, 
general urinalysis and urine for proteinuria. Audiometry, Tympanometry, SRT, Otoscopy and 
THI/DHI questionnaires must be repeated if ELX-02 dosing cannot occur within 7 days of the 
baseline assessment (if already completed). 
Participants who fail to meet the enrollment criteria at any stage during the Screening period are 
defined as screen failures. All screen failures will be recorded in the identification and screening 
logs. The reason(s) for screen failure will be documented. The screening log will be kept in the 
Investigators Site File.  
Screen failure participants will be withdrawn from the study and will not count towards the total 
enrolled or total eligible participants but can be rescreened once at the discretion of the 
Investigator.   
4.6 
Treatment Interruption and Continuation 
If deemed necessary by the investigator, or requested by the participant, and approved by the 
Sponsor, the participant may have a treatment interruption. Reasons for this may include a medical 
reason unrelated to an adverse event (e.g, a planned procedure), or important social or 
administrative events, or the occurrence of an adverse event, due to the participants underlying 
disease state. The reason for the treatment interruption is to be documented. 
If treatment is interrupted for up to 7 days inclusive, then treatment will resume from the same 
timepoint treatment was stopped. Dosing count will continue the day after last dose was taken. If 
treatment is interrupted for more than 7 days, then treatment will be restarted. Dosing will restart 
from Day 1 and the participant will complete a new 60-day Treatment Period.  
4.7 
Removal, Replacement or Early Withdrawal 
Participants are free to discontinue their participation in the study at any time and without prejudice 
to further treatment. The Investigator must withdraw any participant from the study if that 
participant requests to be withdrawn or if it is determined that continuing in the study would result 
in a safety risk to the participant. 

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The individual’s participation in this study may be discontinued due to the following reasons: 
1. Request by regulatory agency, Sponsor, primary care physician, or Investigator. 
2. Participant withdraws consent. 
3. Female participant is pregnant. 
4. Substance abuse during the study 
5. AE or SAE meeting criteria for study drug-related event and meeting stopping criteria (See 
Section 3.1).  
6. Participant is unwilling or unable to continue the study or is lost-to-follow-up. 
7. Investigator decides that withdrawal from the study is in the best interest of the participant. 
8. Participant needs medication not allowed in the protocol. 
9. Any clinically significant change in participant’s medical condition.  
Participants who withdraw prior to study completion for non-safety reasons (e.g., personal reasons 
or non-ELX-02 related AE) may be replaced upon approval of the Sponsor. 
4.8 
Early Study Termination  
The study may be discontinued prematurely at a study site any time and for any reason. Such 
reasons may be any of, but not limited to, the following:  
1. Occurrence of SAEs of an unanticipated nature in accordance with the stopping rules, severity, 
and duration or the unexpected incidence of known SAEs (SUSAR). 
2. Medical or ethical reasons affecting the continued performance of the study. 
3. Administrative reasons. 
4. Exposure of the participant to unacceptable health risks. 
5. A regulatory authority decision. 
6. Change in opinion of the Independent Ethics Committee (IEC)/Institutional Review Board 
(IRB). 
7. Following DSMB recommendation.  
8. At the discretion of the Sponsor (e.g., decision of the Sponsor to discontinue development of 
ELX-02 at any time). 
If the study is prematurely terminated or discontinued, the Sponsor will promptly notify the 
Investigator. After notification, the Investigator must contact all participants and the site pharmacy 
within 48 hrs. As directed by the Sponsor, all study materials must be collected, and the database 
must be completed to the greatest extent possible. 
4.9 
Lost to Follow-up  
A participant will be considered lost to follow-up if the participant misses 2 consecutive study 
visits and is subsequently unable to be contacted by telephone (3 documented attempts by 
telephone within 2 weeks following the second missed visit). 
For participants considered lost to follow-up, the CRF must be completed up to the last visit 
performed. 
 

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5 
STUDY TREATMENTS  
For the purposes of this study, and per International Council for Harmonization (ICH) guidelines 
investigational product is defined as a pharmaceutical form of an active ingredient or placebo being 
tested or used as a reference in a clinical trial, including a product with a marketing authorization 
when used or assembled (formulated or packaged) in a way different from the approved form, or 
when used for an unapproved indication, or when used to gain further information about an 
approved use (ICH E6 1.33). In this study, ELX-02 is considered an investigational product. 
5.1 
Participant Compliance 
ELX-02 will be administered by the appropriately designated study staff at the investigational site, 
or at home, self-administered by the participant or a trained caregiver. 
5.2 
Investigational Product Supplies 
5.2.1 ELX-02 
ELX-02 will be prepared in accordance with Good Manufacturing Practice (GMP) as required by 
the current Good Clinical Practice (GCP). 
ELX-02 will be labeled according to local law and regulatory requirements.  
5.2.1.1 Dosage Form(s) and Packaging 
TEST PRODUCT: The active ingredient (ELX-02) is a synthetic aminoglycoside, manufactured 
in compliance with GMP standards. The drug product is manufactured  Additional manufacturer 
information is provided in the IMPD. The study drug is manufactured as a lyophilized powder for 
injection, to be reconstituted with 0.9% sodium chloride (NaCl) to a concentration of 50 mg/mL 
prior to dose administration. A schedule for dose volumes will be provided in the pharmacy 
manual. 
5.2.1.2 Dispensing and Administration 
A 9-day supply of ELX-02 will be dispensed to each participant at study visits during the 
Treatment Period (except for Day 60) for in-clinic administration and for home self-administration. 
Instructions for study drug handling will be provided to the participant/caregiver at the Day 1 visit 
and at following visits as needed. Additional study drug will be shipped to the participant’s home 
between scheduled study visits to ensure a continuous supply of ELX-02 (detailed explanation of 
study drug dispensation will be described in the Pharmacy Manual).  
ELX-02 will be administered to each participant at study visits during the Treatment Period by a 
designated study nurse or Investigator. Participants/caregivers will have injection administration 
training at the Day 1 visit, and at each following study visit as needed, to support self-
administration at home.   
The study drug will be administered as SC injection to the abdominal region around the umbilicus 
or to any area with a significant subcutaneous adipose tissue (e.g., thigh).  
Details of each ELX-02 administration will be recorded by site staff when administered in the 
clinic and by the participant/caregiver in the participant diary when administered outside the 
clinic.  

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Unused and used vials from which the study drug was administered to the participants will be 
retained for dose confirmation. For details on the study drug accountability, refer to the 
pharmacy manual.  
5.3 
Missed Doses  
If a participant misses a dose and recall the missed dose within 8 hours of their usual dosing time, 
then the participant should inject their daily dose on that day as soon as the participant recalls. If 
the participant recalls of the missed dose more than 8 hours after their usual dosing time, the 
participant should skip that dose and resume their normal schedule for the following dose on the 
next day. 
5.4 
Investigational Product Storage  
ELX-02 will be stored at or below 25°C, and once reconstituted, the product should be stored in 
a refrigerator (2°C to 8°C). 
Regular temperature logging of the study drug storage conditions at the clinic pharmacy should be 
performed. In case a deviation in storage conditions should occur, the clinic or pharmacy must not 
further dispense the affected study drug and notify the Sponsor. 
The Investigator, or an approved representative, e.g., pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required storage 
conditions and in accordance with applicable regulatory requirements. 
Investigational product should be stored in its original container and in accordance with the label. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations. This should 
be captured from the time of investigational product receipt throughout the study. Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation for 
excursions should be available. The operation of the temperature monitoring device and storage 
unit (for example, refrigerator), as applicable, should be regularly inspected to ensure it is 
maintained in working order. 
Any excursions from the product label storage conditions should be reported to the Sponsor upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions as described in the labeling, as soon as possible. Deviations from the storage 
requirements, including any actions taken, must be documented and reported to the Sponsor. Once 
an excursion is identified, the investigational product must be quarantined and not used until the 
Sponsor provides documentation of permission to use the investigational product. It will not be 
considered a protocol deviation if the Sponsor approves the use of the investigational product after 
the temperature excursion. Use of the investigational product prior to Sponsor approval will be 
considered a protocol deviation.   
Specific details regarding information the site should report for each excursion will be provided to 
the site. 
5.5 
Investigational Product Accountability  
The investigative site must maintain adequate records documenting the receipt, use, loss, or other 
disposition of the investigational product supplies, including dispensing to and return from 
participants.  

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The Sponsor’s designated site monitor will periodically check the supplies of study drug held by 
the Investigator or pharmacist to ensure accountability and appropriate storage conditions of the 
study drug used. 
Unused study drug must be available for verification by the site monitor during on-site monitoring 
visits. Any discrepancies between returned and expected returned study drug should be explained 
and documented. All used vials must be stored until the end of the study. 
After the last visit of the last participant in the study (LPLV), any unused study drug will be 
returned to the Sponsor or destroyed at the clinic pharmacy with the Sponsor’s written permission 
[in this case a certificate of destruction will be provided and filed in the electronic trial master file 
(eTMF)]. 
Hazardous materials, such as used needles, syringes containing hazardous liquids, should be 
disposed of immediately in a safe manner, and therefore, will not be retained for study drug 
accountability purposes. 
5.6 
Destruction of Investigational Product Supplies  
The Sponsor or designee will provide guidance on the destruction of unused investigational 
product (e.g., at the site). If destruction is authorized to take place at the study site, the Investigator 
must ensure that the materials are destroyed in compliance with applicable environmental 
regulations, institutional policy, and any special instructions provided by Eloxx Pharmaceuticals, 
and all destruction must be adequately documented. 
 

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6 
STUDY RESTRICTIONS 
6.1 
Concomitant Medications and Prohibited Medications 
Participants must be on a stable regimen of ACEi/ARB for 4 weeks before screening (unless there 
is a contraindication). 
Acetaminophen/paracetamol may be used at doses of ≤2 g/day. Herbal supplements should be 
discontinued at least 30 days prior to administration of the study drug.  
A participant should not have elective injectable aminoglycoside, during days of active ELX-02 
treatment, and at least 14 days before or after ELX-02 treatment, if possible. For any 
unplanned/urgent injectable aminoglycoside use, ELX-02 should be suspended and restarted 14 
days after aminoglycoside treatment completion. 
Co-administration of inhaled aminoglycosides are allowed during the study. 
Use of daily scheduled ibuprofen (>200 mg/day) is not allowed during the study. 
Since ELX-02 is an aminoglycoside derivative, special care should be placed in avoiding 
concomitant medications which interact with aminoglycosides such as:  
• Antimicrobials (such as other aminoglycosides, cephalosporins, clindamycin, polymyxin 
B) which may increase the risk of nephrotoxicity and/or neurotoxicity or ototoxicity 
• Cholinergic agents (e.g., neostigmine, pyridostigmine): Gentamicin antagonizes the effect 
of neostigmine and pyridostigmine 
• Loop diuretics (e.g., furosemide) which increase the risk for ototoxic and nephrotoxic 
effects of aminoglycosides 
• Neuromuscular blocking agents and opioid-analgesics (e.g., fentanyl, succinylcholine)  
• Anti-neoplastic agents (e.g., carboplatin, cisplatin) which increase the risk of 
nephrotoxicity and/or neurotoxicity 
• Immunosuppressive agents (e.g., cyclosporine, tacrolimus) which increase the risk of 
nephrotoxicity and/or neurotoxicity  
• Mannitol which increases the risk of nephrotoxicity and/or neurotoxicity 
• Magnesium which may increase neuromuscular blockade 
• Quinine: an agent with ototoxic potential 
• Salicylates: an agent with ototoxic potential 
 
6.2 
Limit of Noise Exposure 
All participants will be instructed to minimize excessive noise exposure from Screening until the 
completion of the final ENT exams.  
In addition, participants will be required to wear silicone earplugs when exposed to louder than 
normal noise. Participants should avoid loud concerts, visiting a shooting range, and so on. 
6.3 
Contraception 
All sexually active male and female participants should use one effective barrier method (a condom 
or a diaphragm) to avoid transfer of and exposure to ELX-02 to their partners. All male participants 

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who are able to father a child and female participants who are of childbearing potential and are 
sexually active and at risk for pregnancy must agree to use two highly effective methods of 
contraception consistently and correctly with their male or female partner throughout the study. 
All contraceptive methods must be used from Screening to at least 30 days after the last dosing for 
both female and male participants. The Investigator or designee, in consultation with the 
participant, will confirm that the participant has selected appropriate methods of contraception 
from the permitted list of contraception methods (see Section 6.3.1 below). In addition, the 
Investigator or designee will instruct the participant to call the site immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the participant or 
the participant’s partner. All this will be documented in the participant’s source documents. 
Female participants that have not achieved menarche (has not had her first menstrual period) are 
considered not to be of childbearing potential only as long as they have not had their first menstrual 
period. Female participant who has experienced menarche and who has not undergone successful 
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not 
postmenopausal (defined as amenorrhea ≥12 consecutive months; or women on hormone 
replacement therapy with documented serum follicle-stimulating hormone level ≥35 mIU/mL), is 
considered of childbearing potential.  
6.3.1 Birth Control Methods Which May be Considered as Highly Effective 
For the purpose of this document, methods that can achieve a failure rate of less than 1% per year 
when used consistently and correctly are considered as highly effective birth control methods.  
Acceptable contraceptive methods for females include the following: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o 
implantable 
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized partner (conducted at least 90 days before Screening, and documented 
azoospermia) 
• Sexual abstinence (In the context of this document sexual abstinence is considered a highly 
effective method only if defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments and is the preferred and usual 
lifestyle of the participant). 
 
Acceptable contraceptive methods for males include the following: 
• Condom and spermicide 
o In countries where spermicide is not available, condom without spermicide will 
be considered acceptable. 

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o Local regulations may require use of an additional acceptable method of 
contraception.  
• Vasectomy 6 months or more previously, with a negative post-vasectomy semen analysis 
for sperm. 
• Sexual abstinence (In the context of this document sexual abstinence is considered a highly 
effective method only if defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments and is the preferred and usual 
lifestyle of the participant). 
 
Additional notes: 
• Male and female participants who are not sexually active at the time of screening must 
agree to follow the contraceptive requirements of this study if they become sexually active 
with a partner of the opposite sex. 
• Male participant must not donate sperm after the first dose of study drug, throughout the 
study, and for 30 days following the last dose of study drug. 
• Female participants and female partners of male participants should not plan to become 
pregnant during the study through 30 days following the last dose of study drug. 
• Female participants should not nurse a child from the start of study drug dosing through 30 
days following the last dose of study drug. 

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7 
STUDY ASSESSMENTS AND PROCEDURES 
This study is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously 
administered ELX-02 in patients with X-linked or autosomal recessive Alport Syndrome with 
Col4A5 and Col4A3/4 nonsense mutation. 
In total, up to 8 participants, with a minimum of 3 adults, will be enrolled in the trial.  In case of a 
screen failure, participants may be re-screened at the discretion of the investigator. 
The study will be comprised of the following periods for each participant: 
• a Screening Period of up to 6 weeks (42 days) 
• a total Treatment Period of 8 weeks (60 days) 
• a safety/efficacy Follow-up Period of 12 weeks (90 days) after the last treatment.  
The Treatment Period will be a treatment of ELX-02 0.75 mg/kg SC QD for 8 weeks (60 days). 
7.1 
Study Assessments 
The timing and types of assessments are specified in Table 1 below. 
 
 

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Table 1: 
Schedule of Procedures and Assessments 
Period Identifier 
Screening Period 
Treatment Period 
Follow-up 
Day in Study1,17 
Day 
-42 to -7 
Initial 
Day  
-7 to -1 
Baseline16 
Day 1 
Day 15 
Day 30 
Day 45 
Day 60 
EOT 
Day 90 
Day 120 
Day 150 
EOS 
Allowed windows (±days) 
-- 
 
+/-3 
+/-3 
+/-3 
+/-3 
+/-3 
+/-3 
+/-3 
+/-3 
Informed consent2 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history3 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
X 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Weight, body mass index 
X 
 
X 
 
 
 
X 
 
 
 
Vital signs4 
X 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination5 
X 
 
X 
X 
X 
X 
X 
 
 
 
12-lead ECG6 
X 
 
 
 
 
 
X 
 
 
 
Development Stage7 
 
 
X 
 
 
 
X 
 
 
 
Kidney Biopsy8 
X 
 
 
 
 
X 
 
 
 
Confirmation of nonsense 
mutation AS 
X 
 
 
 
 
 
 
 
 
 
Blood safety lab tests 
(central)9 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
HIV, HBsAg, HCV Ab 
X 
 
 
 
 
 
 
 
 
 
Urinalysis and urine pellet10  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Proteinuria (UPCR) 
collection11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum FSH, LH (females)12 
X 
 
 
 
 
 
 
 
 
 
Blood test for pregnancy12 
X 
 
 
 
 
 
 
 
 
 
Blood collection for PK13 
 
 
X 
X 
X 
X 
X 
 
 
 
Urine test for pregnancy12  
 
 
X 
X 
X 
X 
X 
 
 
 
Urine for drugs of abuse 
X 
 
 
 
 
 
 
 
 
 
Audiometry assessment14 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Tympanometry14 
X 
X 
 
 
 
 
 
 
 
 
Speech Reception 
Threshold14 
X 
X 
 
 
 
 
 
 
 
 
Otoscopy14 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Dizziness and Tinnitus 
status14 
X 
X 
 
 
X 
 
X 
X 
X 
X 
Clinic dosing 
 
 
X 
X 
X 
X 
X 
 
 
 
Dispense study drug 
 
 
X 
X 
X 
X 
 
 
 
 
Injection administration 
training 
 
 
X 
 
 
 
 
 
 
 
Evaluation of injection site15 
 
 
X 
X 
X 
X 
X 
 
 
 
Return unused study drug 
 
 
 
X 
X 
X 
X 
 
 
 
Adverse events monitoring 
All visits 
Concomitant medications 
All visits 

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1. In case of emergency, all site visits except Initial, Baseline and Day 1 visits, can be performed at home. The study 
drug can be shipped to the participant. UPCR can be performed at a central lab. Audiology assessments to be 
performed once site visits are resumed. 
2. No invasive study assessments will be performed prior to signing Informed Consent/Assent. 
3. Including Alport Syndrome history and historical lab values of proteinuria, creatinine, hematuria up to 5 years 
back. Participants that performed kidney biopsy in the last 5 years, will be asked to provide the biopsy sample for 
further analysis to evaluate collagen IV expression.   
4. Heart rate (HR), blood pressure (BP), respiratory rate, and oral/tympanic temperature. Vital signs will be 
measured in supine position after at least 5 min rest. Vital signs will be performed before blood sampling 
collection. On dosing days, vital signs will be measured up to 90 min before dosing and 1hr ± 15 min post-dosing.  
5. Detailed physical examination will be performed on Screening. On other visits, a brief physical examination is to 
be performed prior to dosing, focusing on CV, pulmonary, and hearing. 
6. An ECG will be done at Screening and at 1hr ± 15 min post-dosing on Day 60. The 12-lead ECG will be performed 
before blood sampling collection. 
7. Participants < 18 years will be evaluated for developmental stages based on Tanner stages. 
8. Kidney biopsy is mandatory for adult participants (age determined per country regulation) and optional for 
pediatric participants at the Screening Period (after all eligibility assessments have been completed and patient 
eligibility has been confirmed) and on Day 60 ± 3 days. 
9. Blood samples will be collected before dosing (see Table 2). Blood sample processing is described in detail at the 
lab manual. 
10. Urine sample will be collected before dosing for urinalysis (gross, dipstick and microscopic) as well as urine 
pellet. Urine collected from participants at the day of the Initial visit as well as on the Day 30 and Day 60 visits, 
will be further analyzed for urine pellet. At the Baseline Visit, urine will be collected for urine pellet only. Urine 
sample processing is described in detail at the lab manual.  
11. Two urine collections are needed for UPCR assessment at each visit. One sample will be collected at home the 
day before the visit and the second sample on the day of the visit. Both samples will be the collection of second 
void at each day after discarding the first morning void. Samples should be collected in separate cups, kept 
separately, and refrigerated until they are provided at the site. If second void on the day of the visit is collected at 
the study center, then it can also be used for urinalysis. At the initial visit, sample will be collected at the day of 
the visit at the study site and a second sample will be collected on the following day. 
12. In female participants between the ages 12 years to 30 years of age. For female participants <12-year-old, no 
urine pregnancy tests are required. Pregnancy test will be conducted if investigator judges it to be necessary. 
13. Pharmacokinetic (PK) blood samples will be taken pre-dose (up to 90 min before dosing) and after 1 hr ± 15 min 
post dosing at each site visit during the Treatment Period. Blood may be drawn either by direct venipuncture or 
through an indwelling IV cannula. If meals and blood collections coincide, blood will be collected before eating. 
14. During the Screening period, two sets of audiology assessments will be performed to address Exclusion Criterion 
#17: Initial assessments and Baseline assessments. Bone-conduction, SRT and Tympanometry will be performed 
at the Initial and Baseline assessments and must be repeated at other study visits only if there is any suspicion of 
a threshold shift or hearing loss on audiometry (≥ 15 dB at any frequency), or if requested by the Investigator. In 
any case of audiometry significant change criteria from Baseline on other visit days, a re-test must be performed 
after 15 min, or up to 24 hours. Dizziness and Tinnitus status will be evaluated by THI and DHI self-assessment 
questionnaires for adults. Pediatric participants will be questioned by the site staff about their tinnitus/dizziness 
condition, following by Pediatric DHI if dizziness status is active.  
15. The injection sites will be assessed pre-dose (at all visits except for Day 1) and at 1 hr ± 15 min post dose. 
16. Baseline visit must be performed within 7 days prior to dosing and at least 2 weeks after the Audiology Initial 
assessments were performed at the Initial Visit. 
17. All assessments may be repeated at the investigator's discretion and Sponsor approval. 
 

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7.1.1 Screening Phase (Initial and Baseline Visits) 
The Screening Phase of the study will take place 42 to 1 day prior to administration of the first 
dose of study drug. Participants will be assessed for their eligibility to participate in the study and 
must sign an informed consent form prior to performing any invasive study related procedures. 
The participants will have two visits during the Screening Period. 
The following information will be gathered, and screening assessments will be performed for each 
participant. 
• Kidney biopsy - at the Screening Period (after all eligibility assessments have been 
completed and patient eligibility has been confirmed) 
Initial Visit (Day -42 to -7) 
• Collect Inform Consent Form 
• Demographics 
• Medical history (including Alport Syndrome history and historical lab values of 
proteinuria, creatinine, hematuria up to 5 years back) 
• Review of inclusion/exclusion criteria 
• Height 
• Weight and BMI 
• Vital signs  
• Detailed physical examination 
• 12-lead ECG 
• Confirmatory testing of nonsense mutation of Col4A5 in a male or nonsense mutation of 
Col4A4 or Col4A3 (male or female) 
• Blood safety lab tests 
• HIV, HBsAg, HCV Ab 
• Serum FSH and LH (in female participants 12 to 30 years of age) 
• Blood test for pregnancy (only for females 12 to 30 years of age) 
• Urinalysis and urine pellet 
• Urine for proteinuria (UPCR) 
• Urine test for drugs of abuse 
• Audiometry assessment  
• Tympanometry  
• Speech reception threshold  
• Otoscopy  
• Dizziness and Tinnitus status  
• Adverse event monitoring 
• Assessment of concomitant medications 
 
Baseline Visit (Day -7 to -1) 
 
Visit should be performed within 7 days prior to dosing and at least 2 weeks after the Audiology 
assessments were performed at the Initial Visit. 
 
• Urinalysis (only urine pellet) 

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• Urine for proteinuria (UPCR) 
• Audiometry assessment  
• Tympanometry  
• Speech reception threshold  
• Otoscopy  
• Dizziness and Tinnitus status  
• Adverse event monitoring 
• Assessment of concomitant medications 
 
7.1.2 Treatment Period 
The following series of procedures will be done during the Treatment Period. If there is a break in 
treatment of >7 days, the participant will need restart a new 60-day Treatment Period and all of 
the procedures scheduled on Day 1 will have to be performed.  
Day 1 
Prior to dosing: 
• Reconfirmation of inclusion/exclusion criteria 
• Weight and BMI 
• Vital signs (up to 90 minutes before dosing) 
• Brief physical examination  
• Development Stage (pediatric participants only)  
• Blood for safety lab tests 
• Blood collection for PK (up to 90 minutes before dosing) 
• Urinalysis (no urine pellet) 
• Urine pregnancy test (only for female 12 to 30 years of age) 
• Urine for proteinuria (UPCR) 
• Adverse event monitoring 
• Assessment of concomitant medications 
• Injection administration training  
Clinic dosing 
Post-dosing 
• Vital signs (1 hrs ± 15 min) 
• Blood collection for PK (1 hrs ± 15 min) 
• Evaluation of injection site (1 hrs ± 15 min)  
• Dispense study drug  
 
Days 15, 30, 45 and 60 
 
Prior to dosing: 
• Weight, body mass index (on Day 60 only) 
• Vital signs (up to 90 min before dosing) 

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• Brief physical examination 
• Development Stage (pediatric participants on Day 60 only) 
• Kidney biopsy (on Day 60 ± 3 days) 
• Blood safety lab tests 
• Blood collection for PK (up to 90 minutes before dosing) 
• Urinalysis (including urine pellet on Days 30 and 60 only) 
• Urine pregnancy test (only for females 12 to 30 years of age) 
• Urine for proteinuria (UPCR) 
• Evaluation of injection site 
• Adverse event monitoring  
• Assessment of concomitant medications 
• Return unused study drug 
Clinic dosing (self-administration, participant will be observed during injection of ELX-02, and 
re-trained if necessary) 
Post-dosing 
• Vital signs (1 hrs ± 15 min)  
• 12-lead ECG (on Day 60 only at 1 hrs ± 15 min) 
• Blood collection for PK (1 hrs ± 15 min) 
• Audiometry assessment (on Days 30 and 60 only) 
• Otoscopy (on Days 30 and 60 only) 
• Dizziness and Tinnitus status (on Days 30 and 60 only) 
• Evaluation of injection site (1 hrs ±15 min) 
• Adverse event monitoring  
• Dispense study drug (on Days 15, 30 and 45 only) 
 
7.1.3 Safety Follow-up (beginning 4 weeks following the last dose) 
For participants who completed the Treatment Period, safety follow up visits will take place on 
Days 90, 120 and 150. For participants who terminated early, a safety follow-up visit, Day 150, 
will take place 90 days after last day of study drug administration. 
• Blood for safety lab tests 
• Urinalysis (no urine pellet) 
• Urine for proteinuria (UPCR) 
• Audiometry assessment 
• Otoscopy 
• THI and DHI questionnaires 
• Adverse event monitoring 
• Assessment of concomitant medications 
7.1.4 Unscheduled Visits 
An unscheduled visit may take place at any time during the study at the participant's request or as 
deemed necessary by the Investigator due to medical considerations. The date and reason for the 
unscheduled visit will be recorded. AE monitoring and concomitant medications will be recorded. 

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Other procedures and evaluations will be completed as deemed necessary by the Investigator and 
may include (but not limited to) safety laboratory tests, ECG, vital signs, and physical examination. 
7.1.5 Participant Withdrawal 
If a participant's participation in the study is prematurely terminated for any reason or participant 
fails to return for a scheduled visit, every effort should be made to determine the reason. This 
information will be recorded.  
Upon withdrawal from the study after dosing has taken place, all efforts should be made to invite 
the participant to complete at least one safety follow-up visit. 
If for any reason the participant does not agree to return to the clinic for the above visit, the reason 
and/or efforts made will be recorded. 
If the participant withdraws from the study treatment and also withdraws consent for disclosure of 
future information, no further evaluations should be performed, and no additional data should be 
collected. The Sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
7.1.6 Physical Examination 
A complete physical examination will be performed at Screening. On other visits, a brief physical 
examination, focusing on CV, pulmonary, and hearing, will be performed prior to dosing or at any 
time if the participant is not being dosed on that day. Clinically significant changes from the 
baseline examination at Screening will be recorded as AEs. 
7.1.7 Vital Signs 
Vital signs (supine BP, heart rate [HR], respiratory rate [RR], and oral/tympanic temperature) will 
be measured in supine position after at least 5 minutes of supine rest at the time points specified 
in Table 1. 
On days when vital signs parameters need to be assessed and blood samples need to be collected, 
the vital signs will be performed before blood sampling. 
Changes in vital signs determined by the Investigator to be clinically significant will be noted as 
an AE in the eCRF. Such abnormalities will be closely monitored until stabilized or resolved. 
7.1.8 ECGs 
The following values will be collected: QT, QTcF, HR, QRS, PR and RR at the time points 
specified in Table 1. 
Any ECG abnormality compared to screening reading determined by the Investigator to be 
clinically significant will be recorded as an AE. Such abnormalities will be closely monitored until 
stabilized or resolved. 
7.1.9 Developmental Stage 
Participants younger than 18 years old will be evaluated for developmental stages based on Tanner 
stages.(33) 

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7.1.10 Safety Blood Test 
Safety laboratory evaluations will be performed at the timepoints specified in (Table 1). Processing 
and storage of the samples are detailed in the laboratory manual provided by the Sponsor. 
The safety laboratory assessment variables that will be analyzed are outlined in Table 2. 
Table 2: 
Safety Test 
Safety Blood Tests 
Hematology and Coagulation 
Red Blood Cell 
(RBC) count 
Mean corpuscular 
hemoglobin (MCH) 
White blood cells 
(WBC) 
International normalized 
ratio (INR) 
Hemoglobin 
Mean corpuscular 
hemoglobin 
concentration (MCHC) 
Platelets 
WBC differential count 
Hematocrit 
Mean cell volume 
(MCV) 
Prothrombin 
 
Biochemistry 
Total Protein 
Aspartate 
aminotransferase 
(AST) 
Alkaline Phosphatase 
(ALP) 
Blood urea nitrogen 
Albumin 
Gamma glutamyl 
transferase (GGT) 
Glucose 
Serum Creatinine 
Total Bilirubin 
Lactate dehydrogenase 
(LDH) 
Sodium 
Glomerular filtration 
rate (GFR*, only at 
Initial visit)  
Alanine 
aminotransferase 
(ALT) 
Creatine 
Phosphokinase 
Potassium 
Magnesium 
Phosphate 
Calcium 
 
 
Hormones 
LH  
FSH  
Blood pregnancy test 
 
Serology 
HIV Ab 
HBsAg 
HCV Ab 
 
*Based on CKD-EPI for ages ≥18 and Schwartz formula for participants <18 
Abnormal safety tests may be confirmed by a single repeat, if deemed necessary. 
After dosing, all lab tests outside the normal range will be repeated as clinically indicated until the 
values return to normal, or until the etiology has been determined and the condition is considered 
stable. Abnormal laboratory test results that are considered to be clinically significant by the 
Investigator will be reported as an AE. 

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7.1.11 Blood Sampling for Pharmacokinetic Assessments 
Blood samples for determination of ELX-02 plasma concentrations will be taken at the timepoints 
specified in Table 1. 
Sample handling, processing, and shipment are described in the laboratory manual. 
The actual sample collection date and exact clock time will be recorded. Sampling problems will 
be noted in the source and missed samples/timepoints confirmed in the eCRF. 
Blood may be drawn either by direct venipuncture or through an indwelling IV cannula. If meals 
and blood collections coincide, blood will be collected before eating. 
For any additional information related to laboratory related procedures, requirements and supplies, 
refer to the laboratory manual. 
7.1.11.1 Additional Blood Tests 
7.1.11.1.1 Screening Phase 
Blood samples will also be drawn at Screening for confirmation of nonsense mutation Alport 
Syndrome, and antibodies for HIV, HBsAg, HCV. 
7.1.11.1.2 Pregnancy Testing 
For female participants of childbearing potential (see definition in Section 6.3), age 12 years and 
older, serum pregnancy test will be performed at the timepoint specified in Table 1. Pregnancy test 
for female participants <12 years of age, will be conducted if investigator judges to be necessary. 
A negative pregnancy result is required before the participant may receive study drug. Pregnancy 
tests will also be done whenever 1 menstrual cycle is missed during the active treatment period or 
when potential pregnancy is otherwise suspected. Pregnancy tests may also be repeated as per 
request of IRBs/ IECs or if required by local regulations. 
7.1.12 Urine Tests 
Urine laboratory evaluations will be performed at the timepoints specified in (Table 1). Processing 
and storage of the samples are detailed in the laboratory manual provided by the Sponsor. 
7.1.13  Audiology and Vestibular Assessments 
Detailed information on Audiology and Vestibular Assessments will be provided on the Audiology 
and Vestibular manual.  
Participants will have audiometry assessments at Screening Period, Days 30 and 60 (Treatment 
Period), as well as Days 90, 120 and 150 (Safety Follow-up Period).  
During the Screening Period, two sets of audiology assessments will be performed to address 
Exclusion Criterion #17, designated as Initial and Baseline: 
• Initial assessments should be performed within days -42 to-7.  
• Baseline assessments should be performed within 7 days prior to dosing and at least 2 
weeks after Initial assessments.  

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7.1.13.1 Audiometric Testing 
Participants will be scheduled for audiometric tests conducted by an ENT specialized department 
and will include PTA and HFA with frequencies up to 16 kHz. Bone conduction should be 
performed during the Initial and Baseline visits, and must be completed on other visits only if there 
is a threshold shift (≥15 dB) from Baseline by air conduction frequencies of 4 kHz or lower. 
In any case of audiometric significant change (see criteria) from Baseline to days 30, 60, 90, 120, 
150, a re-test must be performed after 15 min or up to 24 hours (see section 8.15). The re-test 
results should be entered into the EDC, and all audiology worksheets required to be shared with 
the Sponsor.  
7.1.13.2 Tympanometry 
The measurement of sound reflection from the tympanic membrane as changes in air pressure 
occur. This procedure should be performed before the Audiometric testing during the Initial and 
Baseline visits, and must be repeated on other visits only if there is any suspicion of a threshold 
shift or hearing loss on audiometry (≥ 15 dB at any frequency), or if requested by the Investigator.  
7.1.13.3 Otoscopy 
A visual inspection of the inner structures of the ear using the otoscope. This test is performed by 
a qualified physician or audiologist prior to any hearing testing.  
7.1.13.4 Speech Reception Threshold 
Speech reception threshold (SRT) is the softest intensity sound at which a participant correctly 
repeats spondee words (bisyllabic words with equal emphasis on both syllables) at least 50% of 
the time. SRT is to be performed on Initial and Baseline visits, and must be repeated on other visits 
only if there is any suspicion of a threshold shift or hearing loss on audiometry (≥ 15 dB at any 
frequency), or if requested by the Investigator.  
7.1.13.5 Dizziness and Tinnitus Status 
For adults, the status will be evaluated by THI and DHI questionnaires, a self-assessment scale. 
These questionnaires will be completed just prior to each audiological assessment in the study. 
Pediatric participants will be questioned by the site staff about their tinnitus/dizziness condition, 
following by Pediatric DHI if dizziness status is active. Additional information is described on the 
Audiometry and Vestibular Manual.  
7.1.14 Injection Site Reactions 
Injection sites will be assessed using the US NIH Division of AIDS (DAIDS) criteria (Table 3). 
on days when the medication is administered at the clinic. Local reaction will be assessed at the 
timepoints specified in Table 1. 
 
 

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Table 3: 
DAIDS Grading Scale Site Reactions to Injection 
PARAMETER  
GRADE 1 MILD  
GRADE 2 
MODERATE  
GRADE 3 SEVERE  
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING  
Injection Site Pain or 
Tenderness  
Report only one  
Pain or tenderness 
causing no or minimal 
limitation of use of 
limb  
Pain or tenderness 
causing greater than 
minimal limitation of 
use of limb  
Pain or tenderness 
causing inability to 
perform usual social 
& functional activities  
Pain or tenderness 
causing inability to 
perform basic self-
care function OR 
Hospitalization 
indicated  
Injection Site 
Erythema or 
Redness 
Report only one  
>15 years of age  
2.5 to < 5 cm in 
diameter OR 6.25 to < 
25 cm2 surface area 
AND Symptoms 
causing no or minimal 
interference with usual 
social & functional 
activities  
≥ 5 to < 10 cm in 
diameter OR ≥ 25 to < 
100 cm2 surface area 
OR Symptoms 
causing greater than 
minimal interference 
with usual social & 
functional activities  
≥ 10 cm in diameter 
OR ≥ 100 cm2 surface 
area OR Ulceration 
OR Secondary 
infection OR Phlebitis 
OR Sterile abscess OR 
Drainage OR 
Symptoms causing 
inability to perform 
usual social & 
functional activities  
Potentially life-
threatening 
consequences (e.g., 
abscess, exfoliative 
dermatitis, necrosis 
involving dermis or 
deeper tissue)  
Injection Site 
Induration or 
Swelling  
Report only one  
>15 years of age  
Same as for Injection 
Site Erythema or 
Redness 
Same as for Injection 
Site Erythema or 
Redness 
Same as for Injection 
Site Erythema or 
Redness  
Same as for Injection 
Site Erythema or 
Redness  
Injection Site 
Pruritus  
Itching localized to 
the injection site that 
is relieved 
spontaneously or in < 
48 hrs of treatment  
Itching beyond the 
injection site that is 
not generalized OR 
Itching localized to 
the injection site 
requiring ≥ 48 hrs 
treatment  
Generalized itching 
causing inability to 
perform usual social 
& functional activities  
NA  
 
7.1.15 Kidney Biopsy 
The tissue of participants (mandatory for adult participants and optional for pediatric participants) 
will be evaluated for Col IV expression and kidney structural changes. 
Upon participants’ consent, participants that performed kidney biopsy in the last 5 years, will be 
asked to provide the biopsy sample for further analysis to evaluate collagen IV expression.   
7.1.15.1 Future Use of Stored Specimens  
Pending participant’s consent, storage and use of left-over kidney biopsy samples collected as part 
of study assessments, will be performed for future research related to Alport Syndrome. The left-
over biopsy samples will be maintained for up to 5 years.  
Pending participant’s consent, storage and use of historically collected kidney biopsy will be 
maintained for up to 5 years.  
Genetic testing will not be performed on these samples. 

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7.1.16 Adverse Events 
Adverse events will be collected continuously starting from signing the informed consent form 
(ICF) until EOS visit for enrolled participants.  
Adverse events reported prior to dosing will be considered non-treatment emergent. Any new 
systemic effect that occurs between scheduled visits should be brought to the attention of the 
Investigator and recorded in the participant’s files. 
Common Terminology Criteria for Adverse Events (CTCAC Version 5) will be used to determine 
the AE safety profile of ELX-02. For more information refer to Section 8. 
7.1.17 Concomitant Medications 
Use of and any changes in concomitant medication will be recorded continuously starting from 
Screening until EOS visit. Contraindicated drugs are listed in Section 6.1. 

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8 
ADVERSE EVENT REPORTING 
8.1 
Adverse Events 
All observed or volunteered AEs regardless of treatment group with suspected causal relationship 
to the investigational product(s) will be reported as described in the following sections.  
For all AEs, the Investigator must pursue and obtain information adequate both to determine the 
outcome of the AE and to assess whether it meets the criteria for classification as a SAE requiring 
immediate notification to Eloxx Pharmaceuticals or its designated representative. For all AEs, 
sufficient information should be obtained by the Investigator to determine the causality of the AE. 
The Investigator is required to assess causality, and may consider participant’s medical history, 
the temporal relationship of drug administration to the event, possible adverse events attributed to 
the drug class and/or a biologically plausible mechanism when assessing causality (Section 8.9). 
For events considered related to study drug, follow-up by the Investigator may be required until 
the event or its sequelae resolve or stabilize at a level acceptable to the Investigator, and 
Eloxx- Pharmaceuticals concurs with that assessment. 
To assist in the determination of case seriousness, further information may be requested from the 
Investigator to provide clarity and understanding of the event in the context of the clinical study. 
8.2 
Reporting Period 
For SAEs, the active reporting period to Eloxx Pharmaceuticals or its designated representative 
begins from the time that the participant provides informed consent, which is obtained prior to the 
participant’s enrollment in the study, i.e., prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 90 calendar days after the last 
administration of the investigational product.  SAEs occurring to a participant after the active 
reporting period has ended should be reported to the Sponsor if the Investigator becomes aware of 
them; at a minimum, all SAEs that the Investigator believes have at least a reasonable possibility 
of being related to investigational product are to be reported to the Sponsor. On an ad hoc basis 
the safety committee will review potentially related serious adverse events leading to 
discontinuation as they are reported. 
8.3 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation participant administered a 
product or medical device; the event does not necessarily need have a causal relationship with the 
treatment or usage.  Examples of AEs, include, but are not limited to:  
• Abnormal test findings 
• Clinically significant symptoms and signs 
• Changes in physical examination findings 
• Hypersensitivity 
• Drug abuse 
• Drug dependency 
Additionally, they may include the signs or symptoms resulting from: 
• Drug overdose 
• Drug withdrawal 
• Drug misuse  

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• Drug interactions 
• Extravasation 
• Exposure during pregnancy (EDP) 
• Exposure via breastfeeding 
• Medication error 
• Occupational exposure 
8.4 
Medication Errors 
Medication errors may result, in this study, from the administration or consumption of the wrong 
product, by the wrong participant, at the wrong time, in the wrong way (eg, into muscle) or at the 
wrong dosage strength. Such medication errors occurring to a study participant are to be captured. 
In the event of medication dosing error, the Sponsor should be notified immediately. 
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including: 
• Medication errors involving participant exposure to the investigational product 
• Potential medication errors or uses outside of what is foreseen in the protocol that do or do 
not involve the participating participant 
Whether or not the medication error is accompanied by an AE, as determined by the Investigator, 
the medication error is captured as an AE in the eCRF and, if applicable, any associated AE(s) are 
also captured as AEs in the case report form (CRF). 
8.5 
Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
AE are as follows:  
• Test result is associated with accompanying symptoms, and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
• Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or 
• Test result is considered to be an AE by the Investigator or Sponsor 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
8.6 
Serious Adverse Events 
A SAE is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening (immediate risk of death) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (substantial disruption of the ability 
to conduct normal life functions) 
• Results in congenital anomaly/birth defect 

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• Medical and scientific judgment is exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life-
threatening and/or result in death or hospitalization. However, if it is determined that the 
event may jeopardize the participant or may require intervention to prevent one of the other 
AE outcomes, the important medical event should be reported as serious. Examples of such 
events are intensive treatment in an emergency room or at home for allergic bronchospasm; 
blood dyscrasias or convulsions that do not result in hospitalization; or development of 
drug dependency or drug abuse. 
8.7 
Hospitalization 
Hospitalization is defined as any initial admission (even less than 24 hrs) in a hospital or equivalent 
healthcare facility or any prolongation of an existing admission. Admission also includes transfer 
within the hospital to an acute/intensive care unit (e.g., from the psychiatric wing to a medical 
floor, medical floor to a coronary care unit, or neurological floor to a tuberculosis unit). An 
emergency room visit does not necessarily constitute a hospitalization; however, the event leading 
to the emergency room visit should be assessed for medical importance. 
Hospitalization does not include the following: 
• Rehabilitation facilities 
• Hospice facilities 
• Respite care (e.g., caregiver relief) 
• Skilled nursing facilities 
• Nursing homes 
• Same-day surgeries (as outpatient/same-day/ambulatory procedures) 
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not be 
reported as AEs. However, the medical condition for which the procedure was performed should 
be reported if it meets the definition of an AE. For example, an acute appendicitis that begins 
during the AE reporting period should be reported as the AE, and the resulting appendectomy 
should be recorded as treatment of the AE. 
8.8 
Severity Assessment 
Severity assessment will be performed per categories specified in the CTCAE for all AEs except 
injection site reactions (ISR) which will be classified and graded as per DAIDS guidelines at 
protocol-defined timepoints. Injection site reactions reported by the participant or assessed outside 
of defined DAIDS timepoints should be recorded as AEs. 
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self care 
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• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE 
8.9 
Causality Assessment 
The Investigator’s assessment of causality must be provided for all AEs (serious and non-serious); 
the Investigator must record the causal relationship in the CRF, as appropriate, and report such an 
assessment in accordance with the SAE reporting requirements if applicable. An Investigator’s 
causality assessment is the determination of whether there exists a reasonable possibility that the 
investigational product caused or contributed to an AE; generally the facts (evidence) or arguments 
to suggest a causal relationship should be provided. The Investigator may consider the participant’s 
medical history, the temporal relationship of study drug administration to the event, possible 
adverse events attributed to the drug class and/or a biologically plausible mechanism when 
assessing causality. If the Investigator does not know whether or not the investigational product 
caused the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the Sponsor. If the Investigator's causality assessment is "unknown but not 
related to investigational product," this should be clearly documented on study records.   
In addition, if the Investigator determines that a SAE is associated with study procedures, the 
Investigator must record this causal relationship in the source documents and CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements, if applicable. 
Causality of each AE must be assessed according to the World Health Organization (WHO)-
Uppsala Monitoring Center (UMC) system for standardized case causality assessment: 
Note: all of the assessment criteria per causality should be reasonably complied to. 
Certain 
• Event or laboratory test abnormality with plausible time relationship to study drug intake 
• Cannot be explained by disease or other drugs  
• Response to withdrawal plausible (pharmacologically, pathologically)  
• Event definitive pharmacologically or phenomenologically (i.e., an objective and specific 
medical disorder or a recognized pharmacological phenomenon) 
• Rechallenge satisfactory, if necessary 
Probable/Likely 
• Event or laboratory test abnormality with reasonable time relationship to study drug 
intake  
• Unlikely to be attributable to disease or other drugs  
• Response to withdrawal clinically reasonable 
• Rechallenge not required 
Possible 
• Event or laboratory test abnormality with reasonable time relationship to study drug 
intake 
• Could also be explained by disease or other drugs 
• Information on drug withdrawal may be lacking or is unclear 
Unlikely 
• Event or laboratory test abnormality with a time to study drug intake that makes a 
relationship improbable (but not impossible) 

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• Disease or other drugs provide plausible explanations 
Unrelated 
• It does not follow a reasonable temporal sequence from the administration of the study 
drug 
• It could readily have been produced by the participant’s clinical state, environmental or 
toxic factors, or other modes of therapy administered to the participant 
• It does not follow a known pattern of response to the study drug 
8.10 
Action Taken Regarding the Study Drugs 
The action taken towards the study drugs must be described as follows: 
• Permanently discontinued 
• Stopped temporarily 
• Dose reduced 
• No action taken 
• Unknown/not applicable 
8.11 
Outcome 
The outcome of each AE must be rated as follows (Table 4): 
Table 4: 
Rating Scale for the Outcome of Each Adverse Event 
Outcome 
Clarification 
Recovered/Resolved 
Participant has fully recovered with no residual effects 
observable 
Recovered with sequelae/Resolved 
with sequelae 
Participant has recovered with residual effects observable 
Not yet recovered/Not Resolved 
Participant status improved but has not yet been recovered 
Ongoing/Not Recovered/Not 
Resolved 
Participant has not recovered and has no improvement 
Fatal 
Resulted in death of the participant 
Unknown 
e.g., lost to follow 
8.12 
Unexpected Adverse Event 
An unexpected AE is any AE which is not listed in the IB or is not listed at the specificity or 
severity that has been observed for an unapproved study drug or package insert/summary of 
product characteristics for an approved product (package inserts are available separately at the 
participating center). 
Serious Unexpected Suspected Adverse Reaction (SUSAR) is a serious adverse reaction 
assessed as unexpected by the Sponsor and that is judged by either the reporting Investigator or 
the Sponsor to have a reasonable causal relationship to a study drug. 
8.13 
Adverse Events of Special Interest 
For this study, adverse events of special interest (AESI) include the following: 

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a. Nephrotoxicity – graded based on CTCAE. Further criteria are described in 
Section 8.14. 
b. Ototoxicity – Further criteria are described in Section 8.15. 
An AESI report must be completed and sent via fax or email within 24 hrs of Investigator’s 
knowledge of the event to the study monitor and Sponsor's representative. In case an AESI is 
classified as SAE, only the SAE report will be completed and SAE reporting procedures and 
timelines would be applicable. 
8.14 
Criteria for Nephrotoxicity 
Grading of any nephrotoxic event will be based on CTCAE Grade, which is assessed as degree of 
elevation of serum creatinine compared to pre-dosing baseline. For stopping dosing in an 
individual participant based on nephrotoxicity, criteria noted in Section 3.1.1 must be met. 
8.15 
Criteria for Ototoxicity  
8.15.1 Pure Tone Audiometry including High Frequency Audiometry 
For PTA (frequencies up to 8000 Hz), CTCAE criteria will be used to define ototoxicity. Any 
event meeting the criteria for CTCAE Grade 1 or more will be evaluated for potential ototoxicity. 
For HFA (frequencies 10,000-16,000 Hz), a threshold shift from baseline of >25 dB averaged at 3 
contiguous test frequencies in at least one ear, will be considered potential ototoxicity. 
For severity grading of all AEs relating to ototoxicity (including HFA changes), the criteria for AE 
severity grading based on clinical symptoms as described in Sections 8.6 and 8.8 will be used.  
For PTA and HFA, the Significant Change Criteria as defined by American Speech-Language-
Hearing Association (ASHA) and American Academy of Audiology (AAA) will be used to trigger 
a review when threshold shifts in PTA and HFA are worse by the following criteria: 
1. 
≥ 20 dB change at any frequency,  
2. 
≥ 10 dB change at any 2 adjacent frequencies, or  
3. 
loss of response at 3 consecutive frequencies where responses were obtained at baseline.    
Participants serve as their own controls for hearing change; if ASHA significant change criteria 
are met in at least one ear, PTA including HFA should be re-tested 15 minutes later or up to 24 
hours (preferably immediately) to confirm the results and all worksheets should be submitted to 
the Sponsor. In addition to the above criteria being met in at least one ear to suspect ototoxicity, 
there should be no indication of middle ear abnormality. If ototoxicity is considered, or findings 
are unclear, especially if middle ear abnormalities are suspected, the Investigator should discuss 
the results with medical monitor immediately and inform the Sponsor. The Sponsor will consult 
with the study Auditory and Vestibular expert(s).  
Note that above are criteria for defining AE of potential ototoxicity but not the criteria to stop 
dosing. For an individual participant, stopping criteria noted in Section 3.1 must be met.  
Further details are provided in an Auditory and Vestibular Manual. 
 
 

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8.15.2 Tympanometry 
Abnormalities in tympanometry will not determine ototoxicity but will be used to ascertain normal 
middle ear compliance and the presence of a conductive hearing loss that may compromise 
interpretation of test.  
8.15.3 Speech Reception Threshold 
Speech reception threshold (SRT) will be used to determine the reliability of PTA measurements.  
8.15.4 Tinnitus Status 
If an adult participant has a post-dosing score showing a 5 point increase in THI score from 
baseline accompanied by a shift in category (e.g., from mild to moderate handicap), the event will 
be discussed between the Investigator and the medical monitor to determine if further auditory 
testing will be required. In a pediatric participant, any change of tinnitus status from baseline, will 
trigger a review by the Sponsor and the Auditory and Vestibular expert(s). Any findings consistent 
with drug-induced toxicity leading to tinnitus or exacerbation of pre-existing tinnitus on formal 
evaluation will be re-evaluated 3 months after initial examination and, if persistent, will be deemed 
permanent. 
8.15.5 Dizziness Status  
If an adult participant has a post-dosing score showing a 5 point increase in DHI score from 
baseline accompanied by a shift in category (e.g., from mild to moderate handicap), the event will 
be discussed between the Investigator and the medical monitor to determine if further vestibular 
testing will be required. In a pediatric participant, any change of dizziness status from baseline, 
will trigger a review by the Sponsor and the Auditory and Vestibular expert(s). Any findings 
consistent with drug-induced vestibular toxicity on formal evaluation will be re-evaluated 3 
months after initial examination and, if persistent, will be deemed permanent. 
8.16 
Exposure During Pregnancy 
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if: 
1. A female becomes or is found to be pregnant either while receiving or having been exposed 
(e.g., because of treatment or environmental exposure) to the investigational product; or 
the female becomes or is found to be pregnant after discontinuing and/or being exposed to 
the investigational product.  
2. An example of environmental exposure would be a case involving direct contact with a 
Eloxx Pharmaceuticals product in a pregnant woman (e.g., a nurse reports that she is 
pregnant and has been exposed to chemotherapeutic products). 
3. A male has been exposed (e.g., because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.  
If a study participant or study participant’s partner becomes or is found to be pregnant during the 
study participant’s treatment with the investigational product, the Investigator must submit this 
information to the CRO on a pregnancy form A. In addition, the Investigator must submit 
information regarding environmental exposure product in a pregnant woman (e.g., a participant 

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reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or spillage). 
This must be done irrespective of whether an AE has occurred and within 24 hrs of awareness of 
the exposure. The information submitted should include the anticipated date of delivery (see below 
for information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy and its outcome. The 
Investigator will follow the pregnancy until completion (or until pregnancy termination) and notify 
the CRO and Eloxx Pharmaceuticals of the outcome as a follow-up by forwarding the completed 
pregnancy form B. In the case of a live birth, the structural integrity of the neonate can be assessed 
at the time of birth. In the event of a termination, the reason(s) for termination should be specified 
and, if clinically possible, the structural integrity of the terminated fetus should be assessed by 
gross visual inspection (unless pre-procedure test findings are conclusive for a congenital anomaly 
and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (i.e., ectopic pregnancy, spontaneous 
abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live-born baby, a 
terminated fetus, an intrauterine fetal demise, or a neonatal death]), the Investigator should follow 
the procedures for reporting SAEs. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
Spontaneous abortion includes miscarriage and missed abortion 
Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs 
when the Investigator assesses the infant death as related or possibly related to exposure 
to the investigational product  
Additional information regarding the EDP may be requested by the Investigator. Further follow-
up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on preterm infants to 
identify developmental delays). In the case of paternal exposure, the Investigator will provide the 
study participant with the Pregnant Partner Release of Information Form to deliver to his partner. 
The Investigator must document in the source documents that the participant was given the 
Pregnant Partner Release of Information Form to provide to his partner. 
8.17 
Follow-up of Adverse Events 
Participants who have had an AE during the Treatment Period must be followed clinically until all 
parameters (including laboratory) have either returned to normal or have stabilized or are otherwise 
explained.  
Any newly emergent SAE within 30 days after early discontinuation or study completion, that is 
considered to be related to the study drug or study participation should be recorded and reported 
immediately. The post-study period for the purpose of SAE reporting is until the SAE is resolved 
or stabilized or maximum up to 30 days following last visit of the study. 
Unless decided otherwise, the study will terminate 30 days after last participant has attended the 
last expected safety follow-up visit and the end of study (EOS visit). If additional follow-up of an 
AE is warranted, it will be documented in the participant's source data but will not be part of the 
eCRF. The PI is required to report on any significant findings to the Sponsor. 

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8.17.1 Data Safety Monitoring Board (DSMB) 
DSMB will be comprised of group of independent experts. The DSMB objectives and operational 
details will be defined in a separate document (DSMB Charter). In this study, once the first 2 
participants (age 12-18 years old) complete 4 weeks of treatment, the DSMB will review safety 
data for the 2 participants and recommend continuation of the study (including possible enrollment 
of pediatric participants 6-11 years old) or discontinuation due to safety concerns. Outside of this 
planned meeting, the DSMB will also review potentially related serious adverse events (SAEs) 
leading to discontinuation or study stoppage as they are reported.   
8.18 
Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person (whether a 
healthcare professional or otherwise) has an unplanned direct exposure to the investigational 
product, which may or may not lead to the occurrence of an AE or SAE. 
An occupational exposure must be reported to the study drug safety unit within 24 hrs, using the 
SAE report form, regardless of whether there is an associated AE/SAE. A copy of the completed 
SAE report form is maintained in the Investigator site file. Since the information does not pertain 
to a participant enrolled in the study, the information is not entered into the eCRF. 
8.19 
Withdrawal Due to Adverse Events  
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, according 
to the definition of AE noted earlier, and recorded in source and the appropriate AE CRF page. 
When a participant withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below. 
8.20 
Eliciting Adverse Event Information 
The Investigator is to report all directly observed AEs and all AEs spontaneously reported by the 
study participant. In addition, each study participant will be questioned about AEs at each study 
visit. 
8.21 
Recording of Adverse Events 
All (S)AEs occurring during the clinical investigation must be documented in the source 
documents and eCRF. 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (e.g., cough, runny nose, sneezing, sore throat, and head congestion should be reported as 
“upper respiratory infection”). Investigators must record their opinion concerning the relationship 
of the (S)AE to the study drugs in the source documents and in the eCRF]. All measures required 
for (S)AE management must be recorded in the source documents and reported according to 
Sponsor’s instructions. 
All AEs occurring at any time during the study (including the Follow-up Period) will be followed 
by the Investigator until satisfactory resolution (e.g., value back to baseline value) or stabilization 
or until final database lock. If necessary, in order to obtain additional information to ensure safety 
to the participant, additional blood and urine samples may be taken at the discretion of the 
Investigator. Certain long-term AEs related to therapy cannot be followed until resolution within 

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the setting of this study. In these cases, follow-up will be the responsibility of the treating 
physician. 
8.22 
Reporting Requirements 
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, expedited 
reporting will follow local and international regulations, as appropriate. 
8.22.1 Serious Adverse Event Reporting Requirements 
All SAEs independent of the circumstances or suspected cause must be reported on a SAE Form 
by the Investigator to the CRO within 24 hrs of their knowledge of the event, preferably by fax or 
by e-mail. Contact information will be provided in a separate document. 
The SAE form should include a clearly written narrative describing signs, symptoms, and 
treatment of the event, diagnostic procedures, as well as any relevant laboratory data and any 
sequelae, in order to allow a complete medical assessment of the case and independent 
determination of the possible causality.  
Follow-up and outcomes should be reported for all participants who experience an SAE. 
It is critical that the information provided on the SAE form matches the information recorded in 
the source documents and in the eCRF for the same event. 
Copies of additional laboratory tests, consultation reports, postmortem reports, hospital case 
reports, autopsy reports, and other documents should be sent when requested and applicable. 
Follow-up reports relative to the participant’s subsequent course must be submitted to the CRO 
until the event has subsided or, in case of permanent impairment, until the condition stabilizes. 
If an SAE occurs, Eloxx Pharmaceuticals is to be notified within 24 hrs of Investigator awareness 
of the event by the CRO.  
As noted in Section 8.6, should an Investigator judge one of the identified protocol-specified SAEs 
to have a causal relationship with the investigational product, the event must be reported to the 
Sponsor within 24 hrs of Investigator awareness. The SRC will review potentially related SAEs 
leading to discontinuation as they occur.  
In particular, if the SAE is fatal or life-threatening, notification to Eloxx Pharmaceuticals must be 
made immediately, irrespective of the extent of available AE information. This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as well as 
to the initial and follow-up reporting of EDP, exposure via breastfeeding, and occupational 
exposure cases.   
In the rare event that the Investigator does not become aware of the occurrence of an SAE 
immediately (e.g., if an outpatient study participant initially seeks treatment elsewhere), the 
Investigator is to report the event within 24 hrs after learning of it and document the time of his or 
her first awareness of the AE. 
8.22.2 Nonserious Adverse Event Reporting Requirements 
All AEs will be reported on the AE page(s) of the CRF. It should be noted that the form for 
collection of SAE information is not part of the eCRF. Where the same data are collected, the 
forms must be completed in a consistent manner. For example, the same AE term should be used 

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on both forms. AEs should be reported using concise medical terminology on the CRFs as well as 
on the form for collection of SAE information. 
8.22.3 Sponsor’s Reporting Requirements to Regulatory Authorities 
Adverse events reporting, including SUSARs, will be carried out in accordance with applicable 
local regulations. 
The Sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The Sponsor or his designee will also report to the Investigator all SAEs that are unlisted 
(unexpected) and associated with the use of the study drug. The Investigator (or the CRO where 
required) must report these events to the appropriate IRB/IEC that approved the protocol, unless 
otherwise required and documented by the IRB/IEC. 
Adverse events reporting, including SUSARs will be carried out in accordance with applicable 
local regulations. 
After completion of the clinical study (determined as LPLV), any unexpected safety issue that 
changes the risks benefit analysis and is likely to have an impact on the participants who have 
participated in the study, together with proposed actions, will be reported by the Sponsor to the 
competent authority(ies) concerned as soon as possible. 
 

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9 
STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a statistical analysis plan (SAP). 
9.1 
Sample Size Determination and General Statistical Methods 
No formal sample size or power calculation is performed. The study sample size is based on 
empirical considerations rather than statistical determination.  
Descriptive statistics will be used to summarize demographics, baseline characteristics, and safety 
data. 
For categorical data, summary tabulations of the number and percentage of participants within 
each category of the parameter will be presented. For continuous data, the number of participants, 
mean, median, standard deviation (SD), minimum, interquartile range (Q1 and Q3), and maximum 
will be presented. 
9.2 
Pharmacokinetic Analysis 
PK analyses will be based on the PK Population defined as those treated patients who have 
analyzable PK data without relevant deviation interfering with the PK evaluations. 
No formal calculation of pharmacokinetic parameters will be performed. Plasma ELX-02 
concentration data will be summarized with descriptive statistics (mean, standard deviation, 
minimum, median, maximum, geometric mean, N).  
9.3 
Safety Analysis 
Safety evaluation will be based on the Safety population defined as all treated participants who 
received at least one dose of study medication, including participants prematurely withdrawn from 
the study.  
Adverse events will be classified by system-organ classes and preferred terms and then 
summarized by number and percentage of participants experiencing AEs. 
Summary tables using descriptive statistics will be provided for changes from baseline in vital 
signs, electrocardiograms and safety laboratory tests. Shift tables will be presented for safety 
laboratory tests. 
Summary tables will be generated for PTA, tympanometry, and THI and DHI questionnaires. The 
degree of hearing loss and any abnormalities detected in ENT examination will be summarized by 
time point. 
Changes in hematuria will be recorded as a categorial variable. Proteinuria will be evaluated as 
UPCR. The baseline value will be the geometric mean of the screening and pre-Day 1 dosing. 
9.4 
Efficacy Analysis 
Efficacy analyses will be based on the Efficacy Population defined as those participants who 
have a valid baseline (before dosing) efficacy sample and at least 1 non-missing post-baseline 
value for an efficacy sample.  
Efficacy data will be summarized using descriptive statistics and/or graphical displays. 

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Efficacy parameters will be described as changes from baseline in PD measurements during 
Treatment Period. The relationship between ELX-02 and response variables (safety and efficacy) 
will be explored graphically and, if applicable, using regression models. 

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10 ETHICS 
10.1 
Institutional Review Board/Ethics Committee 
It is the responsibility of the Investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, e.g., 
recruitment advertisements, if applicable, from the IRB/IEC. All correspondence with the IRB/IEC 
should be retained in the Investigator file. Copies of IRB/IEC approvals should be forwarded to 
Eloxx Pharmaceuticals. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is where 
the change is necessary to eliminate apparent immediate hazards to the participants. In that event, 
the Investigator must notify the IRB/EC and Eloxx Pharmaceuticals in writing immediately after 
the implementation. 
An IRB/IEC should safeguard the rights, safety, and well-being of all study participants. Special 
attention should be paid to studies that may include vulnerable participants. 
Before the start of the study, the Investigator (or Sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents: 
• Final protocol and, if applicable, amendments 
• Sponsor-approved ICF (and any updates or any other written materials to be provided to 
the participants) 
• Sponsor-approved participant recruiting materials 
• IB (or equivalent information) and addenda 
• Available safety information 
• Information on compensation for study-related injuries or payment to patients for 
participation in the study, if applicable 
• Investigator’s current curriculum vitae or other documentation evidencing qualifications 
(unless not required, as documented by the IEC/IRB) 
• Information regarding funding, name of the Sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for participants 
• Any other documents that the IEC/IRB may require to fulfill its obligation 
This study will be undertaken only after the IEC/IRB has given full written approval of the final 
protocol and amendments (if any), the ICF(s) and updates (if any), applicable recruiting materials, 
and any other written information to be provided to the participants, and the Sponsor has received 
a copy of this approval. This approval letter must be dated and must clearly identify the IEC/IRB 
and the documents being approved. 
During the study, the Investigator (or Sponsor where required) will send the following documents 
and updates to the IEC/IRB for its review and approval, where appropriate:  
• Protocol amendments 
• Revision(s) to the ICF and any other written materials to be provided to the participants 
• New or revised participant recruiting materials approved by the Sponsor 
• Revisions to compensation for study-related injuries or payment to participants for 
participation in the study 
• Investigator’s Brochure addenda or new edition(s) 

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• Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually) 
• Reports of AEs that are serious, unlisted, and associated with the investigational medicinal 
product (IMP) 
• New information that may adversely affect the safety of the participants or the conduct of 
the study 
• Deviations from or changes to the protocol to eliminate immediate hazards to the 
participants 
• Report of death of any participants under the Investigator’s care 
• Notification if a new Investigator is responsible for the study 
• Development Safety Update Report, Short-Term Study Specific Safety Summary and Line 
Listings, where applicable 
• Any other requirements of the IEC/IRB 
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of the 
change(s), except when necessary to eliminate immediate hazard to the study participants. If a 
deviation from or a change to the protocol was implemented to eliminate an immediate hazard to 
study participants, then the implemented deviation or change, the reasons for it, and, if appropriate, 
the protocol amendment should be submitted to the IEC/IRB as soon as possible. 
The Investigator (or Sponsor where required) will notify the IEC/IRB about the study completion 
within 90 days after the EOS (LPLV). 
10.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as the 
general principles set forth in the International Ethical Guidelines for Biomedical Research 
Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), 
Guidelines for GCP (ICH 1996 and revisions), and the Declaration of Helsinki (World Medical 
Association).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws. 
The Investigator(s) should be qualified by education, training, and experience to assume 
responsibility for the proper conduct of the study, should meet all the qualifications specified by 
the applicable regulatory requirement(s), and should provide evidence of such qualifications 
through up-to-date curriculum vitae or other relevant documentation requested by the Sponsor, the 
IRB/IEC, or the regulatory authority(ies). 
10.3 
Participant Information and Consent/Assent 
All parties will ensure protection of participant personal data and will not include participant 
names or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. The use of participant initials should be avoided. 
When study data are compiled for transfer to Eloxx Pharmaceuticals and other authorized parties, 
participant names, addresses, and other identifiable data will be replaced by a numerical code based 
on a numbering convention in order to de-identify study participants. The study site will maintain 

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a confidential list of participants who participated in the study, linking each participant’s numerical 
code to his or her actual identity. In case of data transfer, Eloxx Pharmaceuticals will maintain 
high standards of confidentiality and protection of participants’ personal data consistent with 
applicable privacy laws. 
The informed consent/Assent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws. 
The informed consent documents used during the informed consent/Assent process must be 
reviewed and approved by the Sponsor, approved by the IRB/IEC before use, and available for 
inspection.   
Potential participants will be fully informed of the nature of the study and of the risks and 
requirements of the study before any invasive study-related assessment will be carried out. Each 
participant at the age of consent (per local requirements) must sign and date a study-specific ICF. 
Participants not of age of consent must assent, if applicable per local requirements, to participate 
in the study, and the participant's parent or legal guardian must sign and date a study specific ICF. 
During the study, participants will be given any new information that may affect their decision to 
continue participation. They will be informed that their participation in the study is voluntary and 
that they may withdraw from the study at any time with no reason given and without penalty or 
loss of benefits to which they would otherwise be entitled. Only participants or a parent/ legal 
guardian of a participant child, who are fully able to understand the risks, benefits, and potential 
AEs of the study, and who provide their consent voluntarily will be enrolled in the study. 
Finally, they will be told that the Investigator will maintain a participant identification register for 
the purposes of long-term follow-up if needed and that their records may be accessed by health 
authorities and authorized Sponsor staff without violating the confidentiality of the participant to 
the extent permitted by the applicable law(s) or regulations. By signing the ICF/Assent, the 
participant is authorizing such access and agrees to allow his or her study physician to recontact 
the participant for the purpose of obtaining consent for additional safety evaluations, if needed. 
The language about the study used in the oral and written information, including the ICF/Assent, 
should be non-technical and practical and should be understandable to the participant (or the 
participant’s legally acceptable representative). The participant or parent/legal guardian will be 
given sufficient time to read the ICF and the opportunity to ask questions. After this explanation 
and before entry into the study, consent should be appropriately recorded by means of the 
participant's personally dated signature. After having obtained consent, a copy of the ICF must be 
given to the participant. 
The collection and processing of personal data from participants enrolled in the study will be 
limited to those data that are necessary to investigate the safety, quality, and utility of the study 
drug used in the study. 
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized disclosures 
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place. 
Sponsor personnel whose responsibilities require access to personal data need to agree to keep the 
identity of the study participants confidential. 

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The informed consent obtained from the participants includes explicit consent for the processing 
of personal data and for the Investigator to allow direct access to participants’ original medical 
records for study-related monitoring, audit, IEC/IRB review, and regulatory inspection. This 
consent also addresses the transfer of the data to other entities and to other countries. 
10.4 
Participant Recruitment 
Advertisements approved by IRBs/IECs and Investigator databases may be used as recruitment 
procedures. 
Eloxx Pharmaceuticals will have an opportunity to review and approve the content of any study 
recruitment materials directed to potential study participants before such materials are used.  
10.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the Investigator is aware of any new information 
that might influence the evaluation of the benefits and risks of the investigational product, Eloxx 
Pharmaceuticals should be informed immediately.   
In addition, the Investigator will inform Eloxx Pharmaceuticals immediately of any urgent safety 
measures taken by the Investigator to protect the study participants against any immediate hazard, 
and of any serious breaches of this protocol or of ICH GCP that the Investigator becomes aware 
of. 
10.6 Measures related to COVID-19 
As described in Section 1.1, the early onset and rapid progression to renal failure in AS patients 
with nonsense mutations makes developing therapies in this pre-adolescent and adolescent patients 
urgent. Despite the high unmet need, there is no approved treatment for AS, therefore this study is 
required, even during the pandemic. 
In order to accommodate study conduct and procedures to the ongoing COVID-19 pandemic 
situation, the following measures will be taken:  
- Enrollment, participant travel and visits are to be performed according to local country and 
institution regulations, as well as site guidelines 
- A study participant who tests positive for COVID-19 is not eligible to participate in the study 
until the participant is considered recovered, per local country regulations.  
- Monitoring visits should be performed according to local country and site guidelines and are 
permitted to be performed remotely, excluding remote source data verification (SDV) 
- Dose interruption in case of COVID-19 occurrence:  
o 
COVID-19 should be reported as any other Adverse Event  
o 
The Investigator should perform a full AE assessment and decide on the required action 
to be taken regarding the study drug, as described in Section 8.10 of the protocol  
- If in-clinic study visits during the Treatment and Safety Follow Up Periods (except for Day 1 
visit) are not allowed due to regional lockdown or individual participant quarantine: 

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o 
Site visits will be performed at home. The study drug will be shipped to the participant 
and UPCR will be performed at a central lab. 
O 
Audiology assessments will be performed once site visits are resumed.  

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11 ADMINISTRATIVE REQUIREMENTS 
11.1 
Protocol Amendments 
Neither the Investigator nor the Sponsor will modify this protocol without a formal amendment. All 
protocol amendments must be issued by the Sponsor and signed and dated by the Investigator. 
Protocol amendments must not be implemented without prior IEC/IRB approval nor when the 
relevant competent authority has raised any grounds for non-acceptance, except when necessary to 
eliminate immediate hazard to the Participants, in which case an amendment must be promptly 
submitted to the IEC/IRB and relevant competent authority. Documentation of amendment 
approval by the Investigator and IEC/IRB must be provided to the Sponsor or his designee. When 
the change(s) involves only logistic or administrative aspects of the study, the IRB (and IEC where 
required) only needs to be notified. 
11.2 
Participant Identification, Enrollment, and Screening Logs 
The Investigator agrees to complete a participant identification and enrollment log to permit easy 
identification of each participant during and after the study. This document will be reviewed by the 
Sponsor site contact for completeness. 
The participant identification and enrollment log will be treated as confidential and will be filed by 
the Investigator in the study file. All reports and communications related to the study will identify 
Participants by initials and/or assigned number only. 
The Investigator must also complete a participant screening log which reports on all participants 
who were seen to determine eligibility for inclusion in the study. 
11.3 
Study Termination 
Premature termination of this study may occur because of a regulatory authority decision, change 
in opinion of the IRB/IEC, investigational product safety problems, or at the discretion of Eloxx 
Pharmaceuticals. In addition, Eloxx Pharmaceuticals retains the right to discontinue development 
of the study drug at any time. 
If a study is prematurely terminated or discontinued, Eloxx Pharmaceuticals will promptly notify 
the Investigator. After notification, the Investigator must contact all participating participants and 
the site pharmacy within 15 days. As directed by Eloxx Pharmaceuticals, all study materials must 
be collected and the database must be completed to the greatest extent possible. 
In case of an early termination of the study for safety reasons, or temporary halt by the Sponsor, 
the IEC/IRB should be notified within 15 calendar days and should be provided with a detailed 
written explanation for the termination/halt. 
An end-of-study declaration will be submitted to the regulatory authorities and IEC/IRB after the 
complete study has ended. This notification will be submitted within 90 days after the end of the 
study. 
11.4 
End of Trial 
End of trial is defined as last participant in all participating countries, completing all Treatment 
Period study assessments. 

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12 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor or its designee will conduct periodic monitoring visits during study conduct to ensure 
that the protocol and study requirements as well as GCP are being followed. The monitor will 
review source documents to confirm that the data recorded on CRFs are accurate (refer to Section 
13 for details on how data are to be recorded). The Investigator and institution will allow the 
Sponsor monitor/auditors or its designee and appropriate regulatory authorities, direct access to 
source documents. Monitoring visits and/or audits may also occur after study completion. 
During study conduct and/or after study completion, the study site may be subject to review by the 
IEC, and/or to quality assurance audits performed by the Sponsor, or companies working with or 
on behalf of Eloxx Pharmaceuticals, and/or to inspection by relevant regulatory authorities. 
The Investigator or designee will notify the Sponsor, and/or its designee, immediately of any 
regulatory inspection notification in relation to the study. Furthermore, the Investigator will 
cooperate with the Sponsor and/or its designee to prepare the study site for the inspection and will 
allow the Sponsor and/or its designee, whenever feasible, to be present during the inspection. The 
Investigator will promptly provide copies of the inspection findings to the Sponsor and/or its 
designee. Before submitting a response to the regulatory authorities, the Investigator will provide 
the Sponsor or its agents with an opportunity to review and comment on responses to any such 
findings. 
It is important that the Investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
 

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13 
DATA HANDLING AND RECORD KEEPING 
13.1 
Case Report Forms 
Electronic data capture (EDC) and information management systems (CTMS for protocol 
deviations, if applicable) will be used for this study. Clinical data will be entered into the 
EDC system by site staff. Laboratory data from external vendors will be reported directly 
to the sites and received via external data transfers to be processed into SAS datasets by the 
Sponsor/designee, although site staff may be asked to enter select laboratory data directly 
into the EDC system. Study documents identifying which data are electronic source and 
which are paper-based will be created. 
The Investigator will ensure that the data collected are accurate, complete, and legible. Data 
within the EDC system will be monitored by the study monitor, who has read-only access 
to review entered data, during monitoring visits to the clinical site. Following the ICH GCP 
guidelines, direct access to source documentation (medical records) by the study monitor 
must be allowed. Any changes required following monitoring will be made by site personnel 
or the Investigator. Changes made in the EDC system will be documented with a full audit 
trail within the system. 
It is recommended that the author of an entry in the source documents is identifiable. 
13.2 
Record Retention 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
agrees to keep records, including the identity of all participants (sufficient information to link 
records, e.g., CRFs, study source documentation, and hospital records), all originally signed ICFs, 
safety reporting forms, source documents, and detailed records of treatment disposition, and 
adequate documentation of relevant correspondence (e.g., letters, meeting minutes, and telephone 
call reports). The records should be retained by the Investigator according to the ICH guidelines, 
according to local regulations, or as specified in the clinical study agreement (CSA), whichever is 
longer. 
If the Investigator becomes unable for any reason to continue to retain study records for the required 
period (e.g., retirement or relocation), the Sponsor should be prospectively notified. The study 
records must be transferred to a designee acceptable to the Sponsor, such as another Investigator, 
another institution, or an independent third party arranged by the Sponsor. Study records must be 
kept for a minimum of 15 years after completion or discontinuation of the study or for longer if 
required by applicable local regulations.   
The Investigator must obtain the Sponsor's written permission before disposing of any records, even 
if retention requirements have been met. If required to prolong the retention time, this will be 
subject to an agreement with the clinical center. 
 
 

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note 
CFTR allele variant classification is based on cellular phenotype. Some CFTR 
variants may be cross-classified or lack classification altogether. Therefore, 
additional variants may be eligible for the study that are not be listed here. Please 
refer questions to the sponsor.