A Double-Blind, Placebo-Controlled Phase Followed by An Open-Label Phase to Evaluate the Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks
Phase: PHASE2
Conditions: Flank Mass
Sponsor: Raziel Therapeutics Ltd.

 
RAZIEL THERAPEUTICS LTD. 
 
INVESTIGATIONAL NEW DRUG PROTOCOL 
 
RZL-012 
PROTOCOL NUMBER RZL-012-FL-P2US-001 
VERSION 1.1 
30 MAY 2022 
 
A DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 STUDY TO EVALUATE 
THE SAFETY AND EFFICACY OF RZL-012 TREATMENT IN SUBJECTS SEEKING 
FAT REDUCTION IN THE FLANKS  
SPONSOR: 
Raziel Therapeutics, Ltd. 
10 Plaut Str. 
Rehovot, Israel 7610000 
 
CONFIDENTIAL  
This document is a confidential communication of Raziel Therapeutics, Ltd. Acceptance of this 
document constitutes agreement by the recipient that no unpublished information contained herein 
will be published or disclosed without prior written approval, except for disclosure to the 
appropriate Institutional Review Board and/or Regulatory Authority under the condition that 
confidentiality is maintained. 
 
Version 1.0:  22 November 2021 
Version 1.1: 30 May 2022 
 
 
 
 
    

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KEY CONTACTS FOR THE STUDY 
SPONSOR’S  
REPRESENTATIVES: 
 
Sponsor Contact 
Richard E. Lowenthal, MSc, MBA 
Program Manager 
Pacific-Link Research Inc. 
Cell: +1-858-335-1300 
Tel: +1-858-227-3008 
E-mail: richard@pacificlinkconsulting.com 
 
Study Director 
Racheli Gueta, PhD 
Raziel Therapeutics 
Director, Clinical Development 
Cell:  +972-50-7837597 
E-mail: racheli@raziel-therapy.com 
 
Study Medical Monitor 
Patricia Walker MD, PhD, MD, PhD 
Chief Medical Officer,  
Raziel Therapeutics 
Cell: +1-805-705-5853 
E-mail: dr.patricia.walker@gmail.com 
 
Serious Adverse Event Reporting 
 
 
 
 
 
 
 
Fax:+1-858-769-0288 
Email: 
RazielSafety@pacificlinkconsulting.com 
 

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TABLE OF CONTENTS 
KEY CONTACTS FOR THE STUDY .......................................................................................... 2 
LIST OF TABLES .......................................................................................................................... 7 
LIST OF FIGURES ........................................................................................................................ 7 
LIST OF APPENDICES ................................................................................................................. 7 
STATEMENT OF COMPLIANCE .............................................................................................. 10 
INVESTIGATOR STATEMENT ................................................................................................ 11 
PROTOCOL SYNOPSIS ............................................................................................................. 13 
1.0 
INTRODUCTION ............................................................................................................. 19 
1.1. 
BACKGROUND ............................................................................................................... 19 
1.1.1. 
Scientific Background and Clinical Rationale ................................................................. 19 
1.1.2. 
RZL-012 Formulation Development ............................................................................... 20 
1.2. 
NONCLINICAL ASSESSMENTS ................................................................................... 20 
1.2.2. 
Toxicology ....................................................................................................................... 22 
1.2.3. 
Clinical Studies ................................................................................................................ 24 
2.0 
STUDY OBJECTIVES ...................................................................................................... 42 
2.1 
Study Objectives ................................................................................................................ 42 
2.1.1 Primary Objective .............................................................................................................. 42 
2.1.2 Secondary Objective .......................................................................................................... 42 
2.2 
Description of Study Design .............................................................................................. 42 
2.3 
Study Endpoints ................................................................................................................. 43 
2.3.1 Primary Endpoint ............................................................................................................... 43 
2.3.2 Secondary Endpoints ......................................................................................................... 43 
2.3.3 Randomization/Assignment to Study Drug ....................................................................... 43 
2.4 
Study Drugs ....................................................................................................................... 44 
2.4.1 Test Product and Dosing .................................................................................................... 44 
2.4.2 Dose Rationale ................................................................................................................... 45 
2.4.3 Serious Adverse Events Considered Related to the Investigational Drug ......................... 45 
2.5 
Concomitant Medications .................................................................................................. 46 
2.5.1 Prior and Concomitant Medications .................................................................................. 46 
3.0 
STUDY POPULATION .................................................................................................... 46 

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3.1 
Inclusion Criteria ............................................................................................................... 46 
3.2 
Exclusion Criteria .............................................................................................................. 47 
3.3 
Subject Identification ......................................................................................................... 48 
3.4 
Removal, Replacement or Early Withdrawal of Subjects from the Assessment Not Due to 
Intolerable Side Effects ................................................................................................................. 48 
4.0 
STUDY PROCEDURES AND ASSESSMENTS ............................................................. 48 
4.1 
Informed Consent............................................................................................................... 48 
4.2 
Complete Physical Examination ........................................................................................ 49 
4.3 
Medical History ................................................................................................................. 49 
4.4 
Vital Signs .......................................................................................................................... 49 
4.5 
ECG.................................................................................................................................... 49 
4.6 
Height and Weight ............................................................................................................. 49 
4.7 
Pharmacokinetics ............................................................................................................... 50 
4.8 
Clinical Laboratory Evaluations – Hematology and Serum Chemistry............................. 50 
4.8.1 Hematology ........................................................................................................................ 50 
4.8.2 Serum Chemistry ............................................................................................................... 50 
4.8.3 Pregnancy Tests ................................................................................................................. 51 
4.9 
2-D and 3-D Standardized Photography ............................................................................ 51 
4.10 Physician Global Assessment Improvement Scale (GAIS) .......................................... 51 
4.11 Subject’s Satisfaction Questionnaire ................................................................................. 52 
4.12 Evaluation of Response.................................................................................................... 52 
4.13 Compliance Monitoring................................................................................................... 52 
5.0 
SAFETY ASSESSMENTS ................................................................................................ 52 
5.1 
Collection of Adverse Events Data .................................................................................... 52 
5.2 
Complete or Targeted Physical Examination .................................................................... 53 
5.3 
Vital Signs .......................................................................................................................... 53 
6.0 
PHARMACOKINETICS ................................................................................................... 53 
7.0 
EFFICACY ........................................................................................................................ 53 
8.0 
STUDY VISITS AND PROCEDURES ............................................................................ 53 
8.1 
Screening (Days -28 to -1) ................................................................................................. 53 
8.2 
Baseline Evaluations (Day 0) ............................................................................................. 54 
8.3 
Study Randomization ......................................................................................................... 55 

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8.4 
Pre-dose Evaluation (Day 0) .............................................................................................. 55 
8.5 
Drug Administration .......................................................................................................... 55 
8.6 
Post-dose Evaluations (Day 0) and PK blood samples ...................................................... 56 
8.7 
Study Visits (Day 1, Week 1, 4, 8, and 12) ....................................................................... 57 
8.8 
Final Visit (Week 12) ....................................................................................................... 58 
8.9 
Open-Label Phase of the Study: ..................................................................................... 58 
9.0 
PREMATURE DISCONTINUATION FROM STUDY ................................................... 58 
10.0 PRODUCT SPECIFICATIONS ........................................................................................ 59 
10.1 Description ......................................................................................................................... 59 
10.2 Formulation, Packaging, and Labeling .............................................................................. 59 
10.3 Receipt, Storage and Stability of RZL-012........................................................................ 60 
10.4 Study Drug Administration ............................................................................................ 60 
10.5 Ordering and Distribution of Study Drug .......................................................................... 60 
10.6 Accountability of Study Drugs .......................................................................................... 60 
11.0 SAFETY MONITORING AND ADVERSE EVENTS .................................................... 61 
11.1 Adverse Events .................................................................................................................. 61 
11.2 Serious Adverse Events ..................................................................................................... 63 
11.2.1 Reporting Requirements for Serious Adverse Events ....................................................... 63 
11.2.2 Reporting pregnancy .......................................................................................................... 64 
11.2.3 Recording of Serious Adverse Events ............................................................................... 64 
12.0 STATISTICAL CONSIDERATIONS............................................................................... 64 
12.1 Sample Size Determination................................................................................................ 64 
12.2 Analysis Data Sets ............................................................................................................. 64 
12.3 Endpoints Analyses ............................................................................................................ 65 
12.4 Safety ................................................................................................................................. 65 
12.5 Efficacy .............................................................................................................................. 65 
13.0 DATA COLLECTION, STUDY MONITORING, AND DATA DISCLOSURE ............ 66 
13.1 Data Collection and Reporting........................................................................................... 66 
13.2 Study Monitoring ............................................................................................................... 66 
13.3 Audit and Inspection .......................................................................................................... 67 
13.4 Deviation from Clinical Trial Protocol .............................................................................. 67 
13.5 Retention of Records.......................................................................................................... 67 

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13.6 Data Disclosure and Subject Confidentiality ..................................................................... 67 
14.0 PROTECTION OF HUMAN SUBJECTS ........................................................................ 68 
14.1 Basic Principles .................................................................................................................. 68 
14.2 Institutional Review Board/Ethics Committee .................................................................. 68 
14.3 Informed Consent............................................................................................................... 69 
14.4 Subject Health Injury and Insurance .................................................................................. 69 
14.5 Completion of the Study .................................................................................................... 69 
 

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LIST OF TABLES 
Table 1 
Composition of RZL-012 ........................................................................................... 20 
Table 2 
Overview of Ongoing and Completed Clinical Studies ............................................. 25 
Table 3 
Dosages According to Lipomas Size .......................................................................... 37 
Table 4 
Dosing Regimen ......................................................................................................... 44 
Table 5 
Severity Assessment Terminology for Reporting Adverse Events (CTCAE v 5.0) .. 62 
Table 6 
Contact Information for SAE Reporting .................................................................... 64 
 
LIST OF FIGURES 
Figure 1:  Structural Formula of RZL-012 ................................................................................... 20 
Figure 2:  Injection Sites for Phase 0 Study .................................................................................. 30 
Figure 3:  Injection Sites for Phase 2A Study ............................................................................... 31 
Figure 4:  Injections Diagram According to Lipomas Size .......................................................... 33 
Figure 5:  Injection Scheme Lipedema Subjects........................................................................... 34 
Figure 6:  Diagram of Injection Pattern ........................................................................................ 35 
Figure 7 
Scheme of Injection Pattern Grid ............................................................................... 45 
 
LIST OF APPENDICES 
Appendix A:  Schedule of Study Procedures ............................................................................ 70 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase  
AST 
Aspartate aminotransferase 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
cGMP 
Current Good Manufacturing Practices 
CI 
Confidence interval 
cm 
Centimeter 
CNS 
Central nervous system 
CRF 
Case report form 
CV 
Coefficient of variable 
DD 
Dercum’s disease 
ECG 
Electrocardiograms 
FDA 
Food and Drug Administration 
FSH 
Follicle-Stimulating Hormone 
GAIS 
Global Aesthetics Improvement Scale 
GLP 
Good Laboratory Practice 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH-GCP 
International Conference on Harmonization Good Clinical Practice 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB/EC 
Institutional Review Board/Ethics Committee  

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ABBREVIATION 
DEFINITION 
kg 
Kilogram 
LDH 
Lactate dehydrogenase  
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter  
MOA 
Mechanism of action 
MRI 
Magnetic resonance imaging 
N 
Number of subjects 
NOAEL 
No observed adverse effect level 
NSAID 
Non-steroidal anti-inflammatory drugs 
PK 
Pharmacokinetics 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QOL 
Quality of life 
RBC 
Red blood count 
SAE 
Serious adverse event 
SFM 
Subcutaneous Fat Mass 
SMF 
Submental fat 
SOP 
Standard operating procedure 
TEAE 
Treatment emergent adverse event(s) 
US/USA 
United States of America 
WBC 
White blood cell 
WHODD 
World Health Organization Drug Dictionary 

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STATEMENT OF COMPLIANCE 
This clinical trial will be conducted in compliance with the protocol, International Conference on 
Harmonization Good Clinical Practice E6 and the applicable regulatory requirements. 
 
 

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INVESTIGATOR STATEMENT 
I have read and understand the protocol and agree to implement the study in accordance with the 
procedures set forth in the protocol and in accordance with the Sponsor's guidelines, all 
applicable government regulations, and the International Conference on Harmonization Good 
Clinical Practice Guidelines E6 (ICH-GCP). 
I will maintain accurate source documents from which data are transcribed onto case report 
forms and accurate drug accountability records that show the receipt and disposition of all study 
drugs. 
I will provide adequate protocol training to my associates, colleagues, and employees assisting in 
the conduct of the study. 
I will obtain Institutional Review Board/Ethics Committee (IRB/EC) approval of the protocol 
and Informed Consent Form (ICF) prior to enrollment of subjects in the study. I understand that 
any modifications to the protocol made during the course of the study must first be approved by 
the IRB/EC prior to implementation except when such modification is made to remove an 
immediate hazard to the subject. 
I will ensure that a fully executed IRB-approved Informed Consent Form is obtained from each 
subject prior to initiation of any study procedures. 
I will report (within 24 hours) any serious adverse event, regardless of relationship to study drug, 
or pregnancy that occurs during the course of the study, in accordance with the procedures 
described in Section 11.0 of the protocol. I will notify the Sponsor if I become aware that a 
partner of a study subject becomes pregnant while the subject was receiving this study drug. 
I will submit all protocol inclusion/exclusion violations to the Medical Monitor for approval 
prior to enrollment of the subject in the study. 
I will allow the Sponsor, Raziel Therapeutics Ltd. (Raziel) and its agents, as well as the United 
States (U.S.) Food and Drug Administration (FDA) and other regulatory agencies to inspect 
study facilities and pertinent records at reasonable times and in a reasonable manner, ensuring 
subject confidentiality. If I am notified that this study is to be inspected by a regulatory agency, I 
will notify the Sponsor as soon as possible thereafter (no later than one week). 
This protocol contains information that is proprietary to Raziel.  The information contained 
herein is provided for the purpose of conducting a clinical trial for Raziel. 
The contents of this protocol may be disclosed to study personnel under your supervision and to 
your IRB/EC. The contents of this protocol may not be disclosed to any other parties (unless 
such disclosure is required by government regulations or laws) without the prior written approval 
of Raziel. 
 
 

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______________________     ______________________________       
________________ 
Investigator’s Name                Investigator’s Signature 
 
 
Date 
 

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PROTOCOL SYNOPSIS 
Study Title 
A Phase 2 Clinical Trial Comprised of a Double-Blind, Placebo-Controlled Phase 
Followed by An Open-Label Phase to Evaluate the Safety and Efficacy of RZL-012 
in Subjects Seeking Fat Reduction in the Flanks (RZL-012-FL-P2US-001) 
Phase 
Phase 2 
Study Drug 
RZL-012 
Study Objectives and 
Endpoints 
Primary Objective:  
• 
To assess safety and tolerability of a single RZL-012 injection session into the 
flank. 
Secondary Objectives: 
• 
To evaluate the efficacy of RZL-012 treatment versus placebo treatment on fat 
reduction in the flanks 
• 
To assess the safety of a second dose of RZL-012  
Primary Endpoint: 
• 
Evaluate safety following a single injection session of RZL-012 vs. placebo into 
the flanks based on AEs, laboratory tests, ECG, and skin irritancy  
Secondary Endpoints: 
• 
Comparison of the proportion of flanks having an improvement as indicated by 
a score of 0 to 6 according to the Physician Global Assessment Scale (GAIS) in 
RZL-01-treated flanks vs placebo-treated flanks. 
• 
Comparison of the proportion of subjects who are satisfied with treatment results 
as indicated by a yes/no satisfaction questionnaire in RZL-012-treated flanks vs 
placebo-treated flanks.  
• 
Comparison of the mean reduction in volume at 12 weeks post treatment vs. 
baseline for each of the treated flanks, as measured by 3D images using the 
Canfield 3D system in RZL-012-treated flanks vs placebo-treated flanks. 
• 
Ability of blinded reviewers to correctly identify, per patient, the flank treated 
with test compound (active) vs the flank treated with vehicle (placebo). Success 
will be defined as at least 70% correct identification vs the expected 50% correct 
identification based on random guessing.  
• 
Evaluate safety following a second dose of RZL-012 based on AEs, laboratory 
tests, ECG, and skin irritancy.  
• 
Characterization of RZL-012 pharmacokinetic (PK) profile  
Study Design 
This clinical trial is comprised of a double-blind, placebo-controlled phase 
followed by an open-label phase. 
The double-blind, placebo-controlled phase of the trial will consist of a screening 
period, baseline visit and a 12-week post-treatment follow-up period.  At the 
baseline visit, each flank (right and left) of each study participant will be 
randomized into either the active RZL-012 treatment group or the placebo group 
and each flank will receive multiple injections in a single session of RZL-012 or 
placebo. Blood samples will be collected for 6 of the 12 subjects for PK analyses. 
All subjects will be followed up for 12 weeks after the single treatment session.  
Upon completion of the double-blind phase of the study, and the opening of codes 
subjects will be offered RZL-012 open-label treatment in the flank previously 

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treated with placebo.  Consenting subjects will be followed for safety and efficacy 
for an additional 12 weeks. 
In both the double-blind and open-label phases of the study, subjects will be 
monitored for adverse events (AEs). Subjects will return to the site for visits at 1 
week, 4 weeks, 8 weeks, and 12 weeks post treatment and will be monitored for 
safety and efficacy during these visits. 
Subjects who will be collected with PK will return to the clinic at Day 1 post 
injection for further PK samples.  
The dimensions of flanks will be measured using 3D images and volumetric 
calculations using Canfield 3D images. 
Sample Size 
12 subjects, 24 flanks 
Study Population 
Adult volunteers of age 18 to 65 years with visible and palpable fat in the flanks. 
Main Inclusion Criteria 
For a subject to be eligible for this study, he or she must meet all of the following 
criteria: 
1. Is a male or female subject between the ages of 18 and 65 years, inclusive. 
2. Has body mass index (BMI) BMI of ≥ 22 and < 30. 
3. Has clearly visible and palpable fat in the flanks 
4. Has symmetrical appearance of right and left flanks 
5. Agrees to maintain weight (i.e., within 5% of body weight)  by not making any 
changes in diet. 
6. Agree to avoid exposure of the treated area to the sun for at least 1 month after 
each treatment session. 
7. If female, is not pregnant or breastfeeding based on the following: 
a. 
agree to the use of highly effective contraceptive methods for at least 
2 weeks before baseline until 28 days after the last day of study drug 
and a negative urine pregnancy test at screening and baseline; or  
b. is of nonchildbearing potential defined as clinically infertile as the 
result of surgical sterilization (hysterectomy, bilateral tubal ligation, 
and/or bilateral oophorectomy); or  
c. 
is confirmed postmenopausal status (defined as either having 
amenorrhea for ≥ 12 consecutive months without another cause, having 
documented serum follicle-stimulating hormone (FSH) level > 40 
mIU/mL, or having another documented medical condition (e.g., was 
born without a uterus)) 
NOTE: The following are considered highly effective contraceptive 
methods: hormonal oral contraceptives, injectables, and patches; 
intrauterine devices; double-barrier methods (synthetic condom, 
diaphragm, or cervical cap used with spermicidal foam, cream, or gel); 
and male partner sterilization. 

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8. If male (with or without vasectomy), agree to the use of highly effective 
contraceptive methods, e.g. condom, from study baseline until 7 days after the 
last day of study drug. 
9. Is willing to avoid strenuous exercise for seven (7) days post treatment. 
10. Is motivated to adhere to the visit schedule and protocol requirements. 
11. Is willing and able to sign an Institutional Review Board (IRB) approved 
informed consent form (ICF) indicating that they are aware of the 
investigational nature of the study. 
Main Exclusion Criteria  
Subjects must NOT meet any of the following exclusion criteria to be eligible for 
enrollment: 
1. Is unable to tolerate subcutaneous injections. 
2. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or 
cholecystitis). 
3. Has an uncontrolled systemic disease that is not stabilized (i.e., cardiovascular 
disease, mental illness). 
4. Has used anticoagulation therapies that may increase bleeding or bruising (i.e., 
aspirin, ibuprofen, vitamins, and herbal preparations) for seven (7) days prior 
to treatment. 
5. Has medication or a history of coagulopathy. 
6. Has a history or family history of venous thrombotic disease. 
7. Had a non-invasive fat reduction and/or body contouring procedure in the 
flanks within the past 12 months. 
8. Has any scars, unshaven hair, tattoos, on or near the proposed treatment area. 
9. Has significant history or current evidence of a medical, psychological or other 
disorder that, in the Investigator’s opinion, would preclude enrollment in the 
study. 
10. Has an active dermatitis or open wound in the proposed treatment area. 
11. Abnormal coagulation profile including: activated partial thromboplastin time 
(aPTT) > ULN, international normalized ratio (INR) > ULN reference range 
(> 1.3), prothrombin time (PT) > ULN. 
12. Has an active bacterial, fungal, or viral infection in the proposed treatment 
area. 
13. Has known allergic reactions to any injectables. 
14. Has been treated chronically in the past 3 months prior to study entry with 
systemic steroids or immunosuppressive drugs. 
15. Has been treated chronically at least one (1) week prior to study entry with 
non-steroidal anti-inflammatory drugs (NSAIDs). 
16. Current participation or participation within three (3) months prior to the start 
of this study in a drug or other investigational research study. 
Dose and Dosing 
Regimen and 
Administration of Study 
Drug 
At the start of the double-blind, placebo-controlled phase of the trial each flank 
(right and left) of each study participant will be randomized into either the active 
RZL-012 treatment group or the placebo group and each flank will be treated 
with multiple injections in a single injection session in accordance with the table 
below: 
 
RZL-012 (50mg/mL 
DP injectable solution) 
Placebo (Injectable sterile solution) 

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Upon completion of the double-blind phase of the study, and the opening of 
codes, subjects will be offered RZL-012 open-label treatment in the flank 
previously treated with placebo in the same manner as described in the table 
above.   
RZL-012/placebo  injections – Treatment will cover the area of each 
randomized flank. A surface area of 15 cm x 6 cm will be chosen for treatment 
as per the temporary tattoo grid shown below.  
Flanks will be injected with RZL-012/placebo with the needle pointing 
perpendicular (90°) to skin surface. An ice pack will be placed on the injected 
area for pain relief immediately after injections are completed. Subjects will 
remain in injection position for an additional 10 minutes after dosing. 
The injection pattern will be based on the following grid in which the distance 
between rows and columns will be 1.5°cm, as seen below. 
In the previous clinical studies, the injection dose at each of the injection points 
was 5.1°mg for a low dose and 7.5°mg for a high dose with a distance of 1°cm 
between the injection points. In the current study, a dose of 7.5°mg is planned to 
be administered in each injection point with a distance of 1.5°cm between each 
of the points. 
 
 
Needles of 27 G (1 inch needle length) will be used to allow delivery into the 
depth of fat tissue.  
Randomized Right or 
left flank 
12 
12 
Single Treatment* 
55 injections at 
7.5mg/0.15mL per 
each injection point –
A total of 412.5 
mg/8.25 mL total dose 
per flank 
55 injections at 0.15mL per each 
injection point –A total volume of 
8.25 mL total dose per flank  
* 55 injections is the maximum number of injections. In case of smaller flanks, the 
number of injections may be lower. 
Dose Justification 
The maximal dose of RZL-012 administered to subjects to date was 270 mg via 36 
injections of 7.5 mg/0.15 mL per injection in a submental area, with the distance 
between injection sites being 1 cm. This total dose per subject and the amount 
given per injection site were well tolerated and not associated with any significant 
safety issues. To cover the flank area in the current study, the maximal dose will be 
increased to 412.5 mg per session via 55 injections of 7.5 mg/0.15 mL per injection 

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site with the distance between injection sites of 1.5 cm. Subjects who receive a 
second RZL-012 dose will receive a maximal RZL-012 dose of 412.5°x°2=825 mg 
across 2 dosing sessions, with  a 3-month interval between injection sessions.     
The maximal dose of RZL-012 administered to non-rodents (pigs) to date was 
1,000 mg via 40 injections of 25 mg/0.5 mL per injection, with the distance 
between injection sites being 1-2 cm. This dose was given monthly at 4 injection 
sessions per pig, with every monthly injection administered to the contralateral 
side, and was well tolerated without any significant systemic or local side effects. 
Dosing pigs at 4°x°1,000 mg is equivalent to about 4°x°900 mg in humans, based 
on body surface area calculations. These preclinical studies provide a good margin 
vs anticipated human dosing both in terms of the total dose, dosing frequency (once 
monthly in pigs vs every 3 months in humans) and amount per injection site 
(25°mg in pigs vs 7.5°mg in humans). 
Safety Analysis 
The assessment of safety will be based on AEs which will be recorded throughout 
the study until the final study visit.  In case of ongoing AEs at the final study visit 
an unscheduled visit will be scheduled for further follow-up.   
The assessment of safety will also include vital signs and treatment area evaluation. 
Treatment area evaluation includes, but is not limited to, evaluation of edema, pain, 
bruising, erythema, induration, numbness, paresthesia, tenderness, and pruritus. 
ECG and laboratory tests including D-dimer, hematology and chemistry will be 
conducted at the 1 week, 4 weeks and 12 weeks visits.  
Statistical Analysis 
Descriptive statistics 
All measured variables and derived parameters will be listed individually and, if 
appropriate, tabulated by descriptive statistics.  
For categorical variables summary tables will be provided giving sample size, 
absolute and relative by study arm. 
For continuous variables summary tables will be provided giving sample size, 
arithmetic mean, standard deviation, median, minimum and maximum for means of 
variables by study arm.  
The data will be analyzed using the SAS ® version 9.4 (SAS Institute, Cary North 
Carolina). 
Primary Endpoints: 
1- Adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA, most updated version) terminology and presented in 
tables by System Organ Class (SOC) and Preferred Term (PT).  
2- AE data will be listed individually and summarized by SOC and by PT 
within a system organ class. 
3- Skin irritancy AEs related to the injection procedure will be evaluated for 
frequency, severity and duration by treatment group.  
4- Fisher's Exact test will be applied for testing the statistical significance of 
the difference in percent of subjects that experienced Skin irritancy AEs 
related to the injection procedure between the study groups. 
5- Laboratory tests and ECG results will be summarized in appropriate tables. 
Secondary Endpoints: 
• 
GAIS 
• 
Flank volume reduction from baseline to week 12, assessed by Physician Global 
Assessment score (GAIS).  The proportion of subjects for whom an 

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improvement in GAIS as indicated by a score of 0 to 6 will be compared in RZL-
012-treated flanks vs placebo-treated flanks, 
Fisher's Exact test will be applied for testing the statistical significance of the 
difference in percent of subjects for whom an improvement in GAIS was 
observed between treatment groups. This will be calculated along with 95% 
exact confidence interval by treatment group. 
• 
Correct pre and post-treatment identification 
The proportion of blinded reviewers able to correctly differentiate between 
treated flanks will be calculated along with 95% exact confidence interval by 
treatment group. 
• 
Satisfaction (Yes/No questionnaire) 
The proportion of satisfied subjects will be calculated along with 95% exact 
confidence intervals for each treatment group. Fisher's Exact test will be 
applied for testing the statistical significance of the difference in percent of 
satisfied subjects between treatment groups. 
• 
Reduction in Volume 
The change and relative change from baseline in Flank volume as measured by 
photographs at 12 weeks post-treatment will be calculated per each treatment 
group. 
The Signed rank test for two means (paired observations) will be applied for 
testing the statistical significance of the change and relative change from 
baseline at week 12 in flank volume between treatment groups. 
Study Duration 
Double-Blind Phase: each subject will participate in the study for 4 months, which 
comprises a screening period, baseline/treatment period, and follow up period. 
Open-Label Phase: Subjects who choose to continue with the open-label phase of 
the study will be followed up for an additional 3 months. 
Study Centers 
This will be a single center study 

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1.0 INTRODUCTION 
1.1. 
BACKGROUND 
1.1.1. Scientific Background and Clinical Rationale 
Raziel plans to test the effects of RZL-012 injection on fat accumulation in the flank area (the 
lower back). 
Raziel Therapeutics, Ltd. (Raziel) has discovered that a novel synthetic molecule (termed RZL-
012) can help reduce fat content in humans and pigs following its injection into the subcutaneous 
fat.  The suggested mechanism of action (MOA) of RZL-012 involves liponecrosis at the 
injection site, followed by a transient inflammatory response and finally by a healing process in 
which fibrotic tissue replaces previous fat tissue. A thermogenic effect is noted at the injection 
site, most likely due to a local inflammatory response. Studies in pigs show that necrosis of fat 
tissue at the injection site is seen as early as 24 hours after injection and is still evident 2 weeks 
later but is completely cleared at 12 weeks post dosing. A macrophage-mediated inflammatory 
response was also very prominent at 24 hours and 14 days after injection with only minimal 
signs of inflammation remaining at 12 weeks post dosing. Fibrosis followed a different pattern 
compared with liponecrosis and inflammation as it started at 14 days post dosing and became 
much more prominent at 12 weeks post dosing. In essence, RZL-012 enables de-novo generation 
of fibrotic tissue to replace excess fat tissue at selected anatomical sites. 
To date, Raziel has conducted several clinical studies under INDs to evaluate the safety and 
efficacy of RZL-012 for local fat reductions, including obesity (INDs 119941, 133324), lipomas 
of Dercum’s Disease patients and SMF (IND 135762) and SMF reduction (IND 154260). Based 
on the results of these studies, Raziel concluded that the safety profile of RZL-012 is good and 
acceptable and the compound demonstrated efficacy in long-term reduction of local 
subcutaneous fat . 
Based on the clinical study results received to date, Raziel continues to investigate the efficacy 
and safety of RZL-012 for the treatment of fat accumulation in larger parts in the body such as 
the flanks. 
Chemically, RZL-012 is 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium 
chloride. RZL-012 is generated by a single step reaction and the final product is >97% pure. 
The molecular weight is 488 gr/mole and its structural formula, C20H25Br2CIN2, is illustrated in 
Figure 1 below. 

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Figure 1:  Structural Formula of RZL-012 
 
C20H25Br2CIN2 
1.1.2. RZL-012 Formulation Development 
The active ingredient RZL-012 drug substance was manufactured by Cambrex,  NC, USA.  
RZL-012 drug product was manufactured in Patheon (Italy) and packed and labeled at 
ThermoFischer, USA. The drug product is provided in vials of 240 mg/4.8 mL (50°mg/mL).  
The active ingredient and formulation manufacturing and packing were in accordance with 
current Good Manufacturing Practices (cGMPs).  
RZL-012 is provided as a sterile liquid solution suitable for injection. The quantitative 
composition of RZL-012 is listed in Error! Reference source not found. below. 
Table 1 
Composition of RZL-012 
 
 
 
 
 
 
1.2. 
NONCLINICAL ASSESSMENTS 
The RZL-012 MOA was demonstrated in pig studies following its injection into subcutaneous 
fat. Pigs were chosen for these studies because their SC fat resembles that of humans. RZL-012 
injected into SC pig fat first caused liponecrosis at the injection site, followed by a transient 
inflammatory response and finally by a healing process in which fibrotic tissue replaced previous 
Component 
Concentration (mg/ml) 
RZL-012 
50  
Tween-80 
100 
Propylene glycol 
570 
Benzyl alcohol 
30 
Water 
250 

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fat tissue. The initial dose of RZL-012 to be used in clinical trials was extrapolated from the no 
observed adverse effect level (NOAEL) safety data obtained during animal testing. 
1.2.1.1. 
In-vivo Efficacy Studies 
A GLP study was conducted to evaluate the potential local and systemic toxicity, as well as 
efficacy of RZL-012, in domestic Yorkshire crossbred swine. Twenty-eight pigs received either 
control (0.9% Sodium Chloride for Injection) or 500 mg (20 injections of 25 mg RZL- 012) 
RZL-012 and observed 24 hours (3/group/sex), 14 days (2/group/sex), or 84 days (2/group/sex) 
post dose. Study results demonstrated that 84 days after dosing, the mean fat thickness in RZL-
012-treated males was reduced approximately by 16.8% as compared to a 1.1% increase in males 
treated with Saline. The mean fat thickness in females treated with RZL-012 was reduced 
approximately by 19.1% as compared to a 3.7% increase in females treated with Saline. This 
study also contributed to the understanding of RZL-012 MOA. Since all injection sites (20 
injection sites/pig) were quantified for necrosis, inflammation and fibrosis it was possible to 
demonstrate injection-related fat tissue damage followed by an acute inflammatory response 
which was already evident at 24 hours after injection and very prominent at 14 days. This 
transient inflammatory response involved mostly macrophages with little or no apparent 
lymphocytes seen at the injection site. Stepwise clearance of fat cell debris by surrounding 
macrophages was ongoing and by about 84 days after dosing the tissue was fully healed. A 
process of fibrosis was an active participant in this healing process, initiating already at 14 days 
after injection and becoming very prominent at 84 days post dose. In essence, injection of RZL-
012 resulted in a long-lasting replacement of fat tissue by fibrotic tissue art the injected areas 
causing shrinkage of treated tissues. 
1.2.1.2. 
Safety Pharmacology 
The effect of RZL-012 on the central and peripheral nervous systems was evaluated using the 
Functional Observational Battery (FOB) in male Sprague Dawley rats. RZL-012 was 
administered subcutaneously to rats (n = 8/group) as 10 mg/rat. From the results, it was 
concluded that RZL-012 did not affect any of the central nervous system (CNS) functions tested 
using FOB in rats.  
The effect of RZL-012 was evaluated on respiratory functions in male Sprague Dawley rats 
using head-out plethysmography. RZL-012 was administered subcutaneously at a fixed dose of 
10 recorded to cover the entire predetermined time points: Pre-dose, 1, 2, 3, and 4 hours post 
dose. RZL-012 did not affect any of the parameters tested; hence, it was concluded that RZL-012 
has no effects on the respiratory system at the tested dose of 10 mg/rat. 
A board-certified veterinary cardiologist conducted a qualitative and quantitative review of the 
electrocardiograms (ECGs) obtained pretest, pre-dose, 4 and 24 hours post-dose following the 
subcutaneous injection of 500 mg 5.0% RZL-012 or vehicle in Domestic Yorkshire Crossbred 
Swine. There was no effect of the subcutaneous injection of 5.0% RZL-012 on qualitative or 
quantitative ECG parameters or blood pressure. 

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1.2.2. Toxicology 
1.2.2.1. 
Single and multidose Toxicity Studies 
1.2.2.1.1. Rats 
Single subcutaneous administration of test item RZL-012 at the doses of 5, 10, and 20 mg/rat 
(about 20, 40 and 80mg/kg) in Sprague-Dawley rats resulted in non-systemic effects and/or local 
effects at the treated skin area. Few changes observed in hematological parameters (changes in 
white blood cells [WBC] count, neutrophils, monocytes and eosinophils) were considered 
secondary effects due to inflammatory response (local skin reactions). The changes observed in 
clinical chemistry parameters (increased blood urea nitrogen [BUN] in males and females and 
increased creatinine and aspartate aminotransferase [AST] levels in females) at all the doses 
tested and histopathological changes in kidneys (necrosis in tubular epithelium) at 20 mg/kg 
were considered systemic effects. Methods and results from the extended single dose toxicity 
study are described in the Investigator’s Brochure (IB). 
Considering skin changes as non-systemic effects and/or local effects, the NOAEL was 
determined at 5 mg/rat (approximately 20 mg/kg) under the test conditions and doses employed. 
In the 6-month chronic rat study (Study No. G20648), 7 monthly subcutaneous administrations 
of RZL-012 for 6 months in Sprague-Dawley rats were well tolerated systemically in both male 
and female rats up to the high doses tested in both males (21.4 mg/rat) and females (14.98 
mg/rat) which equated to an average mg/kg rat dose of 41.36 mg/kg in males and 49.08 mg/kg in 
females. Gross changes were observed at the injection sites in both sexes (males slightly worse 
possibly due to larger amounts of RZL-012 injected due to increased body weight compared to 
the females) at the end of the treatment period such as wound thickening and discoloration with 
inflammation, epidermal/dermal necrosis, epidermal hyperplasia or hemorrhage seen 
microscopically. Some of these local findings were test article (TA) related (inflammation, 
hyperplasia) while others were considered secondary to self-inflicted local injuries attempted by 
rats as a consequence of the irritation caused by test item/vehicle administration. 
1.2.2.1.2. Pigs 
This single dose study was conducted to evaluate the potential local and systemic toxicity as well 
as efficacy of the test article, RZL-012 (50 mg/mL), in domestic Yorkshire crossbred swine 
following one subcutaneous injection into the subcutaneous abdominal fat on Day 0. Methods 
and results from this extended single dose toxicity study are described in detail in the IB. 
Assessment of toxicity was based on mortality, clinical observations, body weight, qualitative 
food consumption, body temperature, subcutaneous fat temperature, blood pressure, physical and 
electrocardiographic examinations, and anatomic and clinical pathology. Blood samples were 
collected and analyzed for porcine stress syndrome testing and toxicokinetic assessment of the 
test article. 
Administration of the test article was not associated with any mortality, clinical observations 
(with the exception of transient redness and swelling at injection sites), body weight or food 

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consumption changes, effects on electrocardiographic endpoints, or changes in clinical chemistry 
or coagulation parameters. 
In the 3-month GLP pig study, Yorkshire swine were administered 250, 500 and 1000 mg/pig of 
RZL-012 on Study Days 1, 29, 57 and 85. RZL-012 administration was systemically well 
tolerated at all dose levels.  Significant local irritation was seen at injection sites (including 
placebo to a lesser extent) caused by the irritant properties of the compound and/or vehicle. 
Macroscopic findings at the injection sites included abrasions, skin scabs, and reddened skin and 
microscopic findings included fibrosis, inflammation, degeneration/necrosis, atrophy and 
regeneration of the muscularis carnosus and fibrosis and inflammation of subcutaneous tissue. 
The lesions were still present after an 8-week recovery period. These findings were not 
sufficiently severe, however to have any effects on the animals’ body weight/food consumption 
or other endpoints with the exception of two males (1 each, mid and high dose) having a mild 
increase in neutrophils (increased bands) considered due to the inflammatory response noted 
histologically. The only other finding was cytoplasmic vacuolation in the pancreas seen at a 
minimal level in multiple animals in all dose groups (including controls) with a higher severity 
(mild; 1 male, moderate 1 male; marked 1 female) in 3/8 high dose animals. This finding was 
considered an exacerbation of a background finding and non-adverse.  It was also not observed at 
the end of the post-dose period, demonstrating reversibility. Based upon the results of the study a 
no observable adverse effect level (NOAEL) for RZL-012 of 1000 mg/pig when injected 4 times, 
with an interval of 1 month between injections sessions. The establishment of the NOAEL was 
based upon the microscopic effects being limited to the subcutaneous tissue with no systemic 
effects and the evidence of complete healing at 84 Days. 
1.2.2.2 Reproduction toxicology studies 
Rat embryo-fetal Development (EFD) and Fertility and Early Embryo-fetal Development (FEED; 
fertility) studies have been conducted with RZL-012.  
In the EFD study, structural and / or other abnormalities were evaluated in fetuses of pregnant rats 
injected SC with 2.5 to 20 mg/rat RZL-012 on gestations days 5, 8, 11, & 14.  
Maternal parameters comprising of mean uterine weights, number of corpora lutea, implantations, 
and early and late resorptions/deaths and litter parameters (mean fetal weight and number of live 
fetuses were comparable between the placebo control group and treated groups up to the highest 
dose of 20 mg/rat. No test item-related changes were observed during external or fresh visceral 
observations of the fetuses and there were no skeletal malformations observed in any litter at any 
of the tested dose levels. Variants and anomalies observed in various skeletal components across 
RZL-012 treated groups were comparable to the vehicle control group. Based on the observations, 
the No Observed Adverse Effect Levels (NOAEL) for maternal toxicity is 5 mg/rat (15.3mg/kg) 
due to a treatment-related reduction in body weight and food consumption at > 10 mg/rat and the 
NOAEL for embryo-fetal developmental toxicity is 20 mg/rat as the cesarean section and litter 
parameters were unaffected by treatment up to the high dose of 20 mg/rat (62.5mg/kg). 
In the rat fertility study, functional effects (e.g., on libido, epididymal sperm maturation in males, 
effects on the estrous cycle, tubal transport, implantation and development of pre-implantation 
stages of the embryo in females) were evaluated in male and female rats injected SC with 2.5 to 
20 mg/rat RZL-012 on Study Days 1, 8, 15 and Gestation Day 7 in the females and 1, 8, 15, 22, 
29, 36 and 43 in the males.  

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In the males there were no treatment related mortality, clinical signs or toxicologically 
significant changes in body weight, body weight gain or food consumption. Mating and fertility 
indices, macropathology, organ weights, epididymal sperm count, sperm morphology, vas 
deferens sperm motility and histopathology investigations were unaffected by the treatment at 
any of the tested doses.  
In the females there were no treatment mortality, clinical signs or toxicologically significant 
changes in body weight, body weight gain or food consumption during premating and gestation 
period. The estrous cycle length, pre-coital interval, mating and fertility indices, mean number 
corpora lutea and implantations, percentage of pre and post implantation losses, mean number of 
fetuses, gross and histopathology were unaffected by the treatment at any of the tested doses. 
Subcutaneous administration of up to 20 mg/rat RZL-012 did not cause any treatment related 
changes on fertility and reproduction in males and females. Hence, the No Observed Adverse 
Effect Level (NOAEL) for males and females was considered to be 10-20 mg/rat/injection 
session (average mg/kg dose of 50.5 mg/kg for males and 46.2 mg/kg for females) when 
administered at weekly intervals 
1.2.3. Clinical Studies 
To date, safety data on RZL-012 has been collected from 6 clinical trials. The enrolment for an 
additional study for the indication of Submental Fat (SMF) is ongoing (study RZL-012-SMF-
P2b-us-001) and will be completed by December 2021. Since the SMF trial includes a placebo-
treatment group and is blinded, safety data is presented for the first 40 subjects injected in this 
study in a blinded manner, as of 19 September 2021. 
All clinical trials were conducted in the US, and in all trials RZL-012 was administered via multi 
injections during a single injection session. Across the 6 completed clinical trials 107 subjects 
have received single doses of RZL-012 ranging from 5 mg to 270 mg per subject.  In the ongoing 
RZL-012-SMF-P2b-us-001 trial, 74 subjects have been treated as of 01 November 2021. Since 
the trial includes 2 RZL-012 treatment groups and one placebo treatment group and subjects are 
randomized in a 1 to 1 to 1 ratio into one of the treatment groups, it can be estimated that an 
additional 48 subjects have been treated with RZL-012. Thus altogether, it is estimated that a 
total of 155 subjects have received single doses of RZL-012 ranging from 5 mg to 270 mg per 
subject. 
The planned clinical study for local fat reduction in the flank aims to inject 412.5  mg of RZL-
012 in one flank followed by an additional injection 3 months later to the contralateral flank. 
This will result in 2 sessions of injections per subject. 
A summary of the clinical studies conducted by Raziel Therapeutics in presented in Table 2 
below. 

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Table 2 
Overview of Ongoing and Completed Clinical Studies 

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IND No. 
Study ID 
Status 
Phase 
Study Title 
Study Design 
Dosing Regimen 
Study 
Population 
Number of 
treated subjects 
and dosing 
IND 119941 
RZL-012-
P0US-001.3 
 
 
COMPLETED 
 
0 
Phase 0 Study 
of Three 
Cohorts 
Aiming at the 
Evaluation of 
Safety and 
Thermogenesis-
induction of 
Three 
Escalating 
Doses of RZL-
012 Drug 
Product in 
Overweight, 
Healthy 
Volunteers 
A randomized, 
double-blind, 
vehicle-
controlled, 
dose-escalation 
study with 8 
subjects, 6 
active and 2 
control, in each 
of the 3 
cohorts.  
Cohort 1: 5 mg 
Cohort 2: 10 mg 
Cohort 3: 20 mg 
 
Healthy, 20-
40 years 
old, 
overweight 
by Body 
Mass Index 
(BMI) 
definition 
(25 < BMI 
≤ 34.9), 
adult males.  
 
18 RZL-012 (5-
20mmg) 
6 Placebo 
IND 133324 
RZL-012-
P2aUS-001.4 
 
 
COMPLETED 
 
2a 
A Double 
Blind, 
Randomized, 
Placebo 
Controlled, 
Dose 
Escalation 
Phase 2a 
Clinical Trial 
for the 
Evaluation of 
Safety and 
Thermogenesis-
induction of 
RZL-012 in 
Overweight and 
Obese 
Volunteers 
A randomized, 
double-blind, 
placebo-
controlled, 
dose-escalation 
study with 8 
subjects, 6 
active and 2 
control, in each 
of the 4 
cohorts.  
 
Cohort 1: 40 mg 
Cohort 2: 80 mg 
Cohort 3: 120 mg 
Cohort 4: 180 mg 
 
Adult male 
subjects 20–
60 years 
old, with 
27.5 < BMI 
≤ 34.9 
24 RZL-012 
(40-180mg) 
9 Placebo 

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IND 135762 
RZL-012-FD-
P2aUS-001.7 
 
 
COMPLETED 
2a 
An Open Label, 
Phase 2a 
Clinical Trial 
for the 
Evaluation of 
Safety and 
Efficacy of 
RZL-012 for 
the Treatment 
of Women with 
Lipedema 
Involving 
Substantial Fat 
above the Knee 
or of Women 
and Men with 
Nodular 
Dercum’s 
Disease 
Open-label 
safety and 
efficacy 
clinical trial  
6 active 
subjects in each 
cohort 
Cohort 1: Patients 
received up to 40 mg 
RZL-012  
Cohort 2: patients 
received 60 mg and 80 
mg RZL-012  
Post-
menopausal 
(at least 2 
years) 
women no 
more than 
65 years 
old, with 
lipedema 
involving 
substantial 
fat above 
the knee or 
nodular 
Dercum’s 
disease in 
such women 
and in men 
20–65 years 
with 
nodular 
Dercum’s 
disease 
DD: 6 RZL-012 
up to 40mg 
Lipedema: 6 
RZL-012 60-
80mg  
IND 135762 
RZL-012-SMF-
P2A-US-001.2 
 
COMPLETED 
(Study report 
filed to IND 
154260) 
2a 
A Single Blind, 
Randomized, 
Placebo-
controlled, 
Phase 2a, 2-
cohort Study 
for the 
Evaluation of 
Safety and 
Efficacy of 
RZL-012 for 
Submental Fat 
Reduction in 
Healthy 
Volunteers 
A single blind, 
2-cohorts (8 
active vs. 4 
control in 
cohort 1 and 10 
active vs. 6 
control in 
cohort 2),  to 
test safety and 
efficacy in 
healthy 
subjects 
Cohort 1: RZL-012 
subjects were dosed in a 
range of 70-90mg, based 
on SMF fullness. Cohort 
2: RZL-012 subjects 
were dosed in a range of 
125-210mg, based on 
SMF fullness. 
Men and 
women 18-
65 years old 
18 RZL-012 
(70-210mg) 
10 Placebo 

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IND 135762 
RZL-012-DD-
P2B-US-001.4 ,  
 
COMPLETED 
 
2b 
A Double 
Blind, 
Randomized, 
Multi-Center, 
Placebo-
Controlled 
Phase 2B 
Clinical Trial 
for the 
Evaluation of 
Efficacy and 
Safety of RZL-
012 in Subjects 
having 
Dercum’s 
Disease (DD) 
Lipomas 
A double blind 
clinical study 
to test efficacy 
and safety in 
DD subjects 
with painful 
lipomas 
A total of 38 
subjects with a 
randomization 
ratio of 1:1 
were treated. 
At the end of 
the study, 
codes were 
opened and 
placebo 
subjects were 
offered to be 
treated with 
RZL-012. 
This was an 
open label part 
and 9 patients 
were dosed 
with RZL-012 
At least 4 
lipomas/nodules, 
preferably 6, and no 
more than 8, are injected 
per subject. Dosing is 
according to lipoma size, 
where the total injected 
dose does not exceed 
240 mg per patient (48 
injections of 
5mg/injection). 
Women and 
men, 18- 70 
years old, 
diagnosed 
with DD 
having 
lipomas 
Double blind: 
20 RZL-012 
(40-200mg) 
18 Placebo 
 
Open label: 
9 RZL-012(60-
170mg) 
IND 135762 
RZL-012-
hADMEC14-
001 
COMPLETED 
 
1 
An Open-
Label, Single-
Dose Study to 
Assess the 
Absorption, 
Metabolism, 
Excretion, and 
Mass Balance 
of 
subcutaneous 
[14C]-RZL-012 
in Healthy 
Adult Male 
Subjects 
 
This is an 
open-label, 
single-
treatment 
session study 
with 
multi-injections 
to assess the 
absorption, 
metabolism, 
excretion, and 
mass balance 
of RZL-012. A 
total of 6 
subjects were 
enrolled and 
were followed 
up for up to 28 
days from 
injection 
 
~72.9 mg RZL-012 
containing 
[14C]-RZL-012 
(~71.4 µCi) 
(1.6 mL x [45.54 mg/mL 
solution for SC 
injection) 
Healthy, 
adult, male, 
19-55 years 
of age 
6 RZL-012 
(72.9mg) 

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IND 154260 
RZL-012-SMF-
P2b-us-001 
On-Going  
2b 
A double blind, 
randomized, 
three-arm, 
placebo-
controlled 
Phase 2b study 
to evaluate the 
efficacy and 
safety of RZL-
012 in subjects 
seeking 
submental fat 
reduction 
(RZL-012-
SMF-P2bUS-
001) 
Phase 2b, 
double-blind, 
randomized, 
three-arm, 
placebo-
controlled 
study.  Subjects 
will receive a 
single 
treatment 
session that 
consists of 
multiple 
injections of 
RZL-012 or 
placebo into 
the submental 
area under the 
chin, after 
which they will 
be monitored 
for safety and 
efficacy over 
84 days. A total 
of 135 subjects 
will be 
enrolled. 
1. 
RZL low dose 
– dose of 163.2±20.4 
mg/subject spreads over 
32±4 injection points  
2. 
RZL high dose 
– dose of 
240±30mg/subject 
spread over 32±4 
injection points 
3. 
Placebo – 
volume of 4.8±0.6ml 
vehicle/subject spread 
over 32±4 injection 
points 
Adult 
volunteers 
age 18 to 65 
years who 
have 
consented to 
participate 
in this study 
74 RZL-012 
and placebo 
(142.8mg-
270mg) 
 
 
1.2.3.1.1. Protocol No. RZL-012-P0US-001.3 Status: Completed 
The first-in-man clinical trial was an exploratory, randomized, double-blind, vehicle-controlled 
Phase 0 study, conducted under IND 119941, to evaluate the safety and thermogenesis-induction 
of three escalating doses of RZL-012 in overweight and obese subjects. This study also evaluated 
the RZL-012 pharmacokinetics from the baseline visit (Day 0) through Day 1. 
The primary objective of the study was to evaluate the overall safety of RZL-012 after 
subcutaneous injection and the existence of a thermogenic effect. A thermogenic effect was 
defined as an increase of 1 °C in the injected site when compared to the surroundings and/or the 
contra-lateral (non-injected site), apparent at least 28 days after injection. This was monitored by 
sensitive (± 0.1 °C) Infra-Red thermal camera. 
The secondary objective was the determination of RZL-012 pharmacodynamics. The evaluation 
of the extent, duration and tissue associated changes of the thermogenic response to RZL-012 via 
minimal invasive means, including injected-site thermogenesis imaging, Magnetic Resonance 
Imaging (MRI) and punch biopsy, following injection into the subcutaneous fat are summarized 
below. 
The study was composed of 3 cohorts, with 8 subjects per cohort. Each subject was injected with 
either RZL-012 (6 subjects) or vehicle (2 subjects). This was a dose escalation study; therefore, 
RZL-012 was injected at doses of 5, 10, and 20 mg/subject at cohorts 1, 2, and 3, respectively. 
Subjects received a single treatment in multiple sites (1 - 4) of injection diagonally (45°) to the 

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skin surface at 3 centimeter (cm) lateral to the umbilicus lateral wall. The distance between 
injected sites was 1 cm (see Figure 2).  
Figure 2:  Injection Sites for Phase 0 Study 
 
 
 
 
RZL-012-P0US-001.3 Study Results: 
RZL-012 was generally found to be safe in all cohorts. There were no clinically significant 
changes in vital signs, ECG and almost all blood laboratory tests. Most AEs associated with 
RZL-012 injection were confined to the injection site and were transient. Biopsy from the 
injection site revealed no damage to the skin 56 days following RZL-012 injection. The only 
significant local AE was an abscess in one subject in the lower abdomen at the surrounding of 
injected side (but away from the injected site). 
One systemic AE involved a severe elevation of alanine transaminase (ALT) blood levels and a 
moderate elevation of AST blood levels 17 days following injection of the highest dose (AST 
169 U/L; ALT 411 U/L) of active treatment. This elevation was transient. Resolution for AST 
elevated levels and reduction for ALT levels to Grade 1 according to MeDRA coding dictionary 
occurred 11 days following detection. ALT levels were normal on the next visit on Day 56. 
Other liver enzymes such as GGT and alkaline phosphatase, as well as bilirubin levels remained 
within normal range. There were no other systemic clinically significant AEs. 
PK profile results demonstrated an association between dose and Cmax with values of 
13.11 ng/mL at the lower dose level (Cohort 1), 23.02 ng/mL at the next (double) dose level 
(Cohort 2) and 51.46 ng/mL at the highest (x4 of the lowest dose) dose level (Cohort 3). 
The exploration of thermogenesis induction by RZL-012 in humans was successful. A raise in 
temperature at the injection site was mostly evident in cohort 3 (the highest dose) at Day 14 or 
Day 21 following injection in RZL-012 treated subjects only. 
MRI results demonstrated a decrease over time in Subcutaneous Fat Mass (SFM) ratio 
(injected/non-injected side) vs baseline in most RZL-012 treated subjects of Cohort 3. This 
reduction was not statistically significant. Biopsy did not yield enough tissue (because punch 
biopsy did not penetrate deep enough to reach the remodeled tissue) and therefore it was not 
possible to demonstrate changes in the adipose tissue. 
Raziel concludes that the potential risk-benefit balance for RZL-012 is favorable, and it is likely 
that higher doses of RZL-012 will generate better results.  

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1.2.3.1.2. Protocol No. RZL-012-P2aUS-001.4 Status: Completed 
An additional clinical trial was a double-blind, randomized, placebo controlled, dose escalation 
Phase 2a study, conducted under IND 133324 to evaluate the safety and thermogenesis-induction 
of RZL-012 in overweight and obese subjects. 
The primary objective of the study was the evaluation of the overall safety and preliminary 
efficacy of RZL-012 after subcutaneous injection. The primary endpoint for efficacy was a 
significant thermogenic effect, apparent at least 28 days after injection, at the injected site 
compared with the contra-lateral, non-injected site. 
The secondary objective was the determination of RZL-012 pharmacodynamics and 
pharmacokinetics. The secondary efficacy endpoints included the following: 
1. Duration of the thermogenic effect, defined as a net-delta ≥ 1. 
2. Local reduction in fat mass as determined by MRI. 
3. Clinical laboratory changes from baseline. 
4. Establishing the PK profile for RZL-012. 
5. Anthropometric changes from baseline. 
6. Elucidation of the histological changes that may account for the thermogenic effect by 
biopsy of the injection site. 
7. Change from baseline in inflammatory markers and cytokines. 
The study was composed of 4 cohorts. Each cohort was designed to enroll 8 subjects (6 active 
and 2 control). In Cohort 3, 3 subjects were injected with control vehicle and not 2 as planned 
due to subject’s dropout. The overall number of subjects in the study was 33. 
Subjects received a single treatment at multiple sites (8 - 36) of injection diagonally (45°) to the 
skin surface at 5 cm lateral to the umbilicus lateral wall. The distance between injected sites was 
2 cm in cohorts 1 - 3 and 1 cm in Cohort 4 as seen in Figure 3.  
Figure 3:  Injection Sites for Phase 2A Study 
 
 
 
 
RZL-012-P2aUS-001.4 Study Results: 
In this study, in which significantly higher doses were tested (up to 180 mg), RZL-012 was 
found to be safe in all cohorts. There were no clinically significant changes in vital signs, ECG 
and all blood laboratory parameter. The most commonly reported AEs for which there seemed to 
be a causal relationship to active treatment, due to the higher incidence in the active treatment 
groups compared to the placebo groups, were injection site pain and injection site edema. Most 

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AEs were transient. There was only a single case in the highest injected dose, Cohort 4, where 
erythema and edema were still observed up to Day 140. 
The only systemic effect due to the subcutaneous injection of RZL-012 was elevation in d-dimer 
values at the highest injected dose of 180 mg. However, this increase was transient, up to 3 days 
after injection, and non-clinically significant. Further review of coagulation parameters revealed 
there was no clinically significant activation of the coagulation system nor any presence of 
Disseminated Intravascular Coagulation (DIC). The absence of any clinical symptoms related to 
elevation of D-dimer supports a direct link between RZL-012 induced inflammation and elevated D-
dimer levels, unrelated to venous thromboembolic disease 
Biopsies taken from two injection sites revealed no damage to the skin 56 days following RZL-
012 injection. Based on the histology results, the process that seemed to be dominant is fat 
necrosis and infiltration of macrophages into the necrotic fat tissue that resulted in a replacement 
of the local fat tissue by fibrotic tissue. 
A decrease from baseline in SFM ratio (injected/non-injected side), as assessed by MRI, was 
noted in RZL-012 treated subjects of Cohorts 2 – 4 at all study time points. In addition, a dose 
dependent response was evident and statistically significant differences in SFM were found in 
RZL-012 treatment groups versus placebo. Among Cohorts 4 subjects who were monitored until 
168 days post injection, a clear reduction in SFM was noticed (-14.32%). Cohort 4 subjects 
demonstrated the largest reduction in SFM at Day 56 (-18.10%). 
There were no major changes over time and no specific trend to suggest a dose correlation 
response in any of the parameters of lipid profile (TC, TG, LDL, HDL, and FFA) and fasting 
glucose. 
The PK profile of RZL-012 demonstrated dose proportionality. The maximal plasma 
concentration of RZL-012 was less than than 0.5 µg/mL (500 ng/mL) in all subjects and Tmax 
was obtained at about 2 hours following injection. 
No significant decrease in BMI or in subjects’ weight values was evident in all cohorts, 
compared to vehicle injected subjects. There was no consistent pattern to suggest an association 
between inflammation markers and cytokines levels. Therefore, the inflammation reaction due to 
macrophage infiltration into the necrotic tissue seems to be local and without any systemic 
effect. 
Raziel concluded that the risk benefit profile of RZL-012 as seen in the clinical trials to date, is 
in favor of RZL-012. RZL-012 may be useful in treating conditions in which removal of excess 
fat is desired (i.e., excess in SMF). 
1.2.3.1.3. Protocol No. RZL-012-FD-P2aUS-001.7 Status: Completed 
An additional clinical trial was an open label Phase 2a study conducted under IND 135762 to 
evaluate the safety and efficacy of RZL-012 for the treatment of women with lipedema involving 
substantial fat above the knee or of women and men with nodular Dercum’s disease (DD). 

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The primary objective was to evaluate the overall safety of RZL-012 following injection into the 
subcutaneous fat in patients with lipedema or DD. 
The secondary objective was to evaluate local fat reduction, its extent, duration and tissue 
associated changes, in response to RZL-012 treatment, utilizing minimal invasive means 
(ultrasound) following subcutaneous injection of RZL-012 into fatty tissue below the skin. 
The study was composed of 2 cohorts. Cohort 1 was comprised of 6 subjects with DD and 
Cohort 2 was comprised of lipedema subjects having substantial fat above the knee. 
Cohort 1 (Subjects with DD): 
Several lipomas were injected per subject. Dosing was calculated according to the size of the 
nodule (diameter), reaching a maximal dose of 40 mg per subject.  
Subjects received a single treatment in multiple sites (2 - 8 cm lipoma size) of injection 
according to the design in Figure 4. 
Figure 4:  Injections Diagram According to Lipomas Size 
 
 
 
 
Cohort 2 (lipedema subjects with substantial fat above the knee): 
The first 3 subjects received 30 mg RZL-012 in 6 injections (0.1 mL each) in one leg followed 
by 30 mg RZL-012 (6 injections, 0.1 mL each) in the second leg, for a total of 12 injections of 60 
mg RZL-012 (see Figure 5 for injection scheme). 
The last 3 subjects received 40 mg RZL-012 in 8 injections (0.1 mL each) in one leg followed by 
40 mg RZL-012 (8 injections, 0.1 mL each) in the second leg, for a total of 16 injections of 80 
mg RZL-012 (Figure 5).  

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Figure 5:  Injection Scheme Lipedema Subjects 
 
 
 
 
 
 
RZL-012-FD-P2aUS-001.7 Results: 
Overall, 11 out of 12 subjects reported at least 1 AE, with a total of 42 reported AEs. One 
lipedema subject reported no AEs. Most AEs were mild or moderate in intensity. 
The AEs with the highest incidence were injection site pain and headache, each of which was 
reported by 3 of 12 subjects (25%). Pain, contusion, sleep disorders/insomnia, and muscle 
spasms were each reported by 2 of 12 subjects (16.7%). All remaining AEs were reported by 
single subjects only. 
There were 6 AEs with severe intensity, all of which were reported by a single DD subject, and 
included swelling (injection site, joint swelling, peripheral swelling) and pain. Following an 
investigation by the Principal Investigator, it was found that the subject had a tendency to scratch 
or rub painful lipomas and, therefore, following compound injection, lipoma scratching led to 
swelling and pain in the injected lipomas as well as in the surrounding areas. Most severe AEs 
resolved within 14 days after injection and the AE of pain resolved at 35 days. No medical 
intervention was required. 
Measurements of lipoma size in 6 DD subjects included ultrasound measurements of height, 
width and length for 21 injected lipomas. Lipoma surface area was calculated by multiplying 
lipoma width by its length. Lipoma height was the dominant parameter when referring to its 
dimensions as it included aesthetic considerations and pressure application on nerves. The mean 
reduction in lipoma height on day 56 after injection versus baseline was -47.9±44.1% (P<0.001). 
The mean change in surface area versus baseline was 30.4±82.5% (NS). 
Lipoma pain was measured by the comparative pain scale in 19 of 21 injected lipomas in 6 DD 
subjects (specific pain assessment per each lipoma). The mean reduction in lipoma pain on day 
56 after injection versus baseline was 70±36.9% (P<0.0001). Sixteen (16) lipomas reported 
having lower pain scores compared to baseline and only 3 remained without change. 
Fat thickness in 6 lipedema subjects was evaluated by averaging ultrasound measurements of fat 
thickness at 84 injection points (6 - 8 injection points per leg per subject). The mean reduction in 
fat thickness on day 56 after injection as compared to baseline was approximately 7% (NS). No 
improvement was noted in quality of life (QOL) measurements. 

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Based on the study results, Raziel concluded that RZL-012 could be beneficial in treating 
patients with fat disorders such as DD.  
1.2.3.1.4. Protocol No. RZL-012-SMF-P2aUS-001.2 Status: Completed 
An additional study was a single blind, randomized, placebo-controlled, phase 2a, 2-cohort study 
for the evaluation of safety and efficacy of RZL-012 for SMF reduction in healthy volunteers 
was conducted under IND 135762. 
The primary objective was to evaluate safety following injection of RZL-012 vs. placebo 
injection into SMF. Skin irritancy and AEs related to injection procedure were mainly evaluated 
for its frequency, severity and duration. Specifically, the assessment of the following AEs was 
monitored: bruising, pain, induration erythema and swelling/edema. 
The following secondary endpoints evaluated treatment efficacy of active treatment versus 
placebo subjects: 
1. Reduction from baseline in SMF volume, as measured with MRI on Day 84 as compared 
to screening, in RZL-012 treated subjects versus placebo treated subjects. 
2. Improvement of Physician’ global assessment questionnaire for treatment efficacy in 
active versus placebo treated subjects on Day 84 visit to evaluate treatment response. 
3. Improvement from baseline in subject’s satisfaction rating by using validated FACE-Q 
questionnaire (Satisfaction of chin) on Day 84 visit to evaluate treatment response among 
RZL-012 treated subjects versus placebo treated subjects. 
Twenty-Eight (28) subjects (12 for cohort 1 and 16 for cohort 2) were included in the study. 
Subjects in each cohort were injected with a different dose.  Subjects in each cohort were 
randomized in a ratio of 2:1 of active versus placebo. A total of 28 subjects were enrolled in 
2 clinical sites. Subjects were blinded to study treatment while physicians were not blinded. 
Cohort 1 (N=12) – Each subject was dosed with up to 120 mg RZL-012 (depending on SMF 
area) or up to 2.4 mL of vehicle. Averaged injected dose was 80 mg. 
Cohort 2 (N=16) – Each subject was dosed with up to 240 mg RZL-012 (depending on SMF 
area) or up to 4.8 mL of vehicle. Averaged injected dose was 158.5 mg. 
The injection pattern in both cohorts was based on a submental area shaped grid in which the 
distance between rows was 1cm and distance between columns was also was 1 cm as seen in the 
figure below. Physicians chose two points at the edge of the 50-point pattern that were not 
injected (up to 48 injections) as seen in Figure 6 below: 
 
Figure 6:  Diagram of Injection Pattern 

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Subjects were injected with RZL-012 or vehicle perpendicularly (90) to the skin. An ice pack 
was placed on the injected area for pain relief immediately after injection. Subjects had to remain 
seated in the injection position for an additional 10 minutes after dosing. 
RZL-012-SMF-P2a-US-001 Results: 
AEs were closely followed up throughout the study to determine the safety profile of RZL-012. 
Different scales were used to grade the severity degree of edema and erythema, pain, bruising 
and induration. Most of AEs were treatment related. 
The most commonly reported AEs were bruising, induration, edema, pain and erythema all of 
which were reported with a similar incidence in the RZL-012 and placebo treatment groups. A 
difference was evident in the severity of some of the AEs in the RZL-012 high-dose treatment 
group vs. placebo with 3 reports by 3 subjects of severe edema and 2 reports by 2 subjects of 
severe induration in the high dose group. However, these AEs were characterized as such only 
within the first 24 hours of administration. The intensity then went from moderate to mild in the 
days following the RZL-012 injection and were completely resolved by 56 days after injection 
without any specific treatment or medication. Erythema, and bruising were not dose related and 
were mostly resolved at 14 days after injection. There were no clinically significant changes in 
vital signs, no deaths and no SAEs in any subjects. 
Based on the objective MRI, it can be concluded that the efficacy of RZL-012 in reducing SMF 
in this Phase 2a study was demonstrated. This is evident by both the change in the submental 
depth (thickness) as well as volume.  The robustness of these results is supported by the dose 
response that shows larger effects for the higher dose of RZL, i.e., a volume reduction of -
22.2%±14.9 vs. Volume reduction of -10.6%±14.5 and -0.4%±13.9 for RZL-012 low dose and 
placebo, respectively. 
The objective MRI assessments were supported by the Physician Impression scale. This scale 
which shows a more pronounced improvement at days 56 and 84 compared to day 28 may 
indicate that the effects of RZL-012 on SMF progress and cumulate in the weeks following the 
administration of the product. All besides 1 of the 18 RZL-012-treated subjects demonstrated 
improvement in SMF at 84 days after treatment.  On the other hand, at Day 84, none of the 
placebo subjects demonstrated any change in their SMF. 
Subjects were clearly satisfied by RZL-012 effect as indicated by the improvement of score 
according to Subject Face-Q Questionnaire. Subjects that were treated with RZL-012 low dose 
showed a 2.4-fold increase in the mean subject satisfaction. Subjects that were treated with RZL-

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012 high dose showed a 2.5- fold increase in the mean subject satisfaction. Placebo subjects did 
not demonstrate a satisfaction on Day 84 vs. baseline. 
1.2.3.1.5. Protocol No. RZL-012-DD-P2bUS-001.4 Status: Completed 
Another study for DD patients, a double-blind, randomized, multi-center, placebo-controlled 
phase 2b clinical trial for the evaluation of efficacy and safety of RZL-012 in subjects having 
DD, is being conducted under IND 135762. 
The primary objective is to evaluate of the efficacy of RZL-012 following injection into 
lipomas/nodules of DD subjects. Efficacy is determined by ultrasound assessment of the 
lipoma/nodule dimensions after treatment as compared to baseline assessments. 
The key secondary objective is the assessment of lipoma/nodule associated pain using the 
Comparative Pain Scale. Safety is assessed by the frequency of AEs and by change-from-
baseline values for vital signs, clinical laboratory and ECG. An exploratory objective is to follow 
improvement in Quality of Life by using QOL questionnaire. 
A total of 38 subjects have been enrolled into the study. Subjects were randomized in a 1:1 ratio 
into either the RZL-012 or the placebo arm. 
At least 4 lipomas/nodules, preferably 6, and no more than 8, were injected per subject. Dosing 
was determined according to lipoma size, where the total injected dose did exceed 240 mg per 
patient (48 injections of 5mg/injection). Table 3 describes the dosages according to lipoma size. 
Table 3 
Dosages According to Lipomas Size 
 
 
 
 
 
 
 
The injections are spread randomly on the lipoma surface with a distance between injections of 
at least 1 cm. Injections are given at 90° to the injected skin surface. 
Once the study ends and codes are opened, 84 days after dosing, placebo-treated subjects will be 
offered the option of receiving treatment with RZL-012. Subjects who choose to receive 
treatment with RZL-012 will be followed for an additional 84 days. 
Number of Subjects – 
Active/Placebo 
20/18 
Lipoma/Nodule size – 
diameter (cm) 
1-1.9 
2-3.9 
4-5.9 
6-7.9 
8-10 
Total Dose of RZL-012 
in the RZL group (mg) 
10 
20 
40 
50 
60 
Number of Injections  
2 
4 
8 
10 
12 

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RZL-012-DD-P2b-US-001.4 Results for the Double blind part: 
A total of 20 subjects were injected with RZL-012 and 18 subjects were injected with placebo. 
The maximal dose of RZL-012 that was injected was 200mg per subject, based on painful 
lipomas size. 
Change in Lipoma Height 
Dimensions of treated lipomas were measured at baseline visit prior to injection and at each of 
the follow up visits by using ultrasound. 
Lipoma dimensions were compared between the active and placebo treatment groups on 2 levels 
– (1) on the patient level and (2) by lipomas, i.e. comparison between all injected lipomas before 
and after injection. 
The Non-parametric Wilcoxon-Mann-Whitney Rank sum test for independent samples was 
applied for testing the statistical significance of the difference between study groups in percent 
reduction of lipoma/nodule height at day 84 after injection vs. baseline per patient. 
The MMRM model (Mixed-effect model for repeated measures) was applied for analyzing the 
difference between the groups in percent reduction of lipoma/nodule height from baseline to day 
84. 
A total of 125 lipomas were measured at baseline in the RZL-012-treatment group and 109 
lipomas in the placebo group in the double-blind phase of the study.  
The by-patient analysis demonstrated an average height reduction of 11.18%±22.70 (standard 
deviation) in the RZL-012 treated subjects vs. an average height reduction of 15.26%±21.05 in 
the placebo-treated subjects (P>0.05).  
The average height reduction change by lipoma analysis demonstrated a reduction of 
11.22%±33.77 in the RZL-012 treated group vs. 16.28%±29.60 in the placebo group (P>0.05). 
Changes in lipoma dimensions using the analysis per lipoma demonstrate a similar trend, i.e., no 
statistically significant changes from baseline in lipoma height were found between active and 
placebo lipomas. The P value was calculated by a Mixed model with repeated measure. 
More than 90% of injected lipomas contained fibrotic tissue and this was the hypothesis for not 
demonstrating an effect on lipoma size.  
Change in Lipoma Pain 
Pain of each injected lipoma was assessed by a blinded subject at baseline visit prior to injection 
and at each of the follow-up visits by using the Comparative Pain Scale. The comparative pain 
scale is a scale that contains 11 grades where 0 is categorized as ‘no pain’ and 10 is categorized 
as ‘extreme, non tolerable pain’. 
Pain was compared between the RZL-012 and placebo treatment groups on 2 levels – (1) on the 
patient level and (2) by lipomas, i.e. comparison between all injected lipomas before and after 
injection. 

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The Non-parametric Wilcoxon-Mann-Whitney Rank sum test for independent samples was 
applied for testing the statistical significance of the difference between study groups in percent 
reduction of lipoma/nodule pain at day 84 after injection vs. baseline per patient. 
The two-sample T-test for independent samples was applied for analyzing the difference between 
the groups in percent reduction of lipoma/nodule height from baseline to day 84. 
The MMRM model (Mixed-effect model for repeated measures) was applied for analyzing the 
difference between the groups in percent reduction of lipoma/nodule pain from baseline to day 
84. 
A total of 125 lipomas were assessed for pain in baseline in the RZL-012-treatment group and 
108 lipomas in the placebo group.  
The all-lipoma analysis demonstrated an average pain reduction of 59.06%±40.41 in the RZL-
012 treated group vs. -37.50%±49.69. The statistical significance tested by Mixed model with 
repeated measure generated a p value of 0.079. Calculation of statistical difference using t-test 
generated a p value of 0.0004.  
An additional analysis calculated the proportion of subjects with at least 40% reduction in pain in 
each treatment group. According to the medical literature, in patients with general chronic pain, a 
difference in pain intensity of >30% is considered a clinically important improvement. 
It was calculated that 14 out of 20 patients (70%) in the RZL-012 treated-group vs. 8 out of 18 
patients (44%) in the placebo-treated group had more than 40% pain reduction. This supports the 
ability of RZL-012 in producing a clinical meaningful reduction in pain.     
No significant change in QOL was noted according to the completed questionnaire, possibly due 
to the relatively small number of lipomas treated per patient. 
RZL-012-DD-P2b-US-001.6 Results for the open label extension phase: 
Nine (9) subjects treated with placebo in the double-blind phase of the study agreed to enter the 
open-label phase in which they were treated with RZL-012. A total of 65 painful lipomas were 
treated and followed up for pain reduction on Day 84, and 63 lipomas were followed up until 
Day 84 for change in dimensions. 
Study results demonstrated a reduction in lipoma height of ~20% on Day 84 vs. baseline. Based 
on the per-patient analysis there was a mean reduction of -20.57±19.26% in lipoma height and 
based on the all treated lipomas analysis there was an average reduction of -21.12±29.69% in 
lipoma height. 
No serious adverse events were reported in the study. 
1.2.3.1.6. Protocol No. RZL-012-hADMEC14-001 Status: completed 
A Phase 1 study which  assessed the absorption, metabolism, excretion (ADME), and mass 
balance of 72.9mg subcutaneous injection of [14c]-RZL-012 in 6 healthy male subjects. The 
study was conducted under IND 135762.  

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The study results showed a total recovery of the administered radioactivity was approximately 
85.37% (by 2 weeks after dosing), of which 2.542% and 82.83% were recovered in urine and 
feces, respectively, indicating that hepatobiliary excretion into the feces is the main elimination 
route for [14C]-RZL-012-realated material in humans, with renal elimination playing a 
secondary role. The PK profile of the [14C]-RZL-012 was similar to the profile shown in 
previous clinical studies. 
[14C]-RZL-012-injected radioactivity is rapidly absorbed (Tmax = 2hr) and widely distributed 
across body tissues. This is followed by a slow elimination stage with ~85% of the drug being 
excreted within 2 weeks. In addition, study demonstrated low/no radioactivity is remaining at 
one month post dose of [14C]-RZL-012 compound. Therefore, no accumulation is expected in 
case of once monthly or less frequent dosing regimen. 
 
1.2.3.1.7. Protocol No. RZL-012-SMF-P2bUS-001.2 Status: Ongoing  
A double blind, randomized, three-arm, placebo-controlled Phase 2b study to evaluate the 
efficacy and safety of RZL-012 in subjects seeking submental fat reduction, is being conducted 
under IND 154260. 
The primary objective is to the efficacy of RZL-012 versus placebo on submental fat (SMF) 
reduction measured on Day 84 versus baseline using the Clinician Assessment Tool (C-CAT). 
The secondary objectives are: 
• To determine the efficacy of RZL-012 versus placebo on SMF reduction measured on Day 
84 versus baseline using the Subject Self-Chin Assessment Tool (S-CAT);  
• To assess the reduction in SMF on Day 84 versus baseline using the caliper measured 
submental thickness and magnetic resonance imaging (MRI); 
• To assess the safety of RZL-012 in the treatment of SMF reduction. 
 
Each subject will be randomized to either active treatment (high or low dose RZL-012) or 
placebo at a ratio of 1:1:1 per group and receive one of the following: 
• low dose (concentration of injected solution 34 mg/mL RZL-012) of 5.1 mg/0.15 
mL/injection point that results in a dose/volume of 183.6mg/5.4 mL RZL-012, 
• high dose (concentration of injected solution 50 mg/mL RZL-012) of 7.5 mg/0.15 
mL/injection point that results in a maximum total dose/volume of 270 mg/5.4 mL RZL-
012, 
• placebo of 0.15 mL/injection point that results in a total maximum volume of 4.8±0.6 
mL. 
The injection pattern will be based on a submental area shaped grid in which the distance 
between rows and columns will be 1 cm, as seen in the figure below. The Investigator will 
choose 32±4 sequential points on the grid that will mark the injected area according to SMF 

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fullness and convexity. The treatment area boundary: superiorly by a line 1 cm inferior to the 
mandibular margin, laterally by the sternocleidomastoid muscles, and inferiorly by the hyoid 
bone. 
 
Results of study RZL-012-SMF-P2bUS-001.2: 
The study is blinded and still on-going. 
As of 01 November 2021,  total of 74 subjects have been enrolled into the study out of 155 
planned subjects. Safety data that was collected for these subjects. 
Overall, 97 AEs were reported in 32 out of 40 subjects (80.0%) (based on data entry as of 19 
September 2021 as part of safety committee ).  Thirty-one subjects (77.5%) experienced AEs that 
were considered as related to study drug, 9 (22.5%) experienced AEs that were considered 
“Related to skin irritancy” and 30 (75.0%) experienced AEs that were considered “Related to 
injection procedure” as determined by the Investigator.  
There were 5 events that were assessed as severe.  Except the event of oedema, of which the 
outcome was not available at the time of report, all of them recovered within 28 days (1/40 = 
2.5% may not have been recovered beyond 28 days).  
Among 97 AEs, the most common events based on preferred term (PT) were oedema (20 events, 
20 subjects), pain (15 events, 15 subjects), contusion (13 events, 13 subjects), hypoaesthesia (11 
events, 11 subjects), swelling (11 events, 9 subjects), pruritus (4 events, 4 subjects), and 
ecchymosis (3 events, 3 subjects). Out of 97 AEs, 74 AEs (76.3%) were mild, 18 AEs (18.6%) 
were moderate, and 5 AEs (5.2%) were severe. Eighty AEs (82.5%) were considered as related. 
Eighty AEs (82.4%) were reported as recovered/resolved or recovering/resolving at the time of 
the report. No AEs were considered severe or life-threatening or resulted in death. No AEs were 
serious or resulted in discontinuation from the study. 
There were 306 findings of abnormal laboratory values reported in 39 subjects after dosing. The 
abnormal laboratory values observed ≥ 10% (≥ 4 subjects) during the visit is as below.  After 
dosing at Day 1, more than 10 subjects (≥ 25%) reported D-dimer, high, glucose, high, and LDH, 
high, whereas no subjects experienced elevated fibrinogen activity, abnormal INR, or abnormal 
APTT and one subject experienced slightly longer prothrombin time (12.4 sec).  The ratio of 
number of such subjects who experienced abnormal increase at Day 1 decreased over visits and 
became closer to the number at screening by Day 28 except blood glucose. Of note, glucose was 
not necessarily measured at fasting condition.  

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Two (2) out of the forty injected subjects demonstrated an increase of 3-4 fold of ALT levels at 
day 1 and 7 post injection compared to screening levels , however these levels did not reach 
values that are higher than 2xULN. The other reported out-of-normal-range levels of ALT (for 
additional 5 subjects) were slightly elevated above normal range or were higher in screening and 
remained higher after injection.   None of the reported subjects had elevation of 2xULN in AST 
values. Furthermore, there are no subjects with total serum bilirubin values or alkaline 
phosphatase above the normal range. 
2.0 STUDY OBJECTIVES 
2.1 
Study Objectives 
The objective of the study is to assess the safety and efficacy of RZL-012 injections  into the 
flank area. 
2.1.1 
Primary Objective 
The primary objective of this study is: 
• 
To assess safety and tolerability of a single RZL-012 injection session into the flank. 
2.1.2 
Secondary Objective 
The secondary objectives are: 
• 
To evaluate the efficacy of RZL-012 treatment versus placebo treatment on fat reduction in 
the flanks  
• 
To assess the safety of a second dose of RZL-012  
 
2.2 
Description of Study Design 
This clinical trial is comprised of a double-blind, placebo-controlled phase followed by an open-
label phase. 
The double-blind, placebo-controlled phase of the trial will consist of a screening period, 
baseline visit and a 12-week post-treatment follow-up period.  At the baseline visit, each flank 
(right and left) of each study participant will be randomized into either the active RZL-012 
treatment group or the placebo group and each flank will be treated with multiple injections in a 
single injection session of RZL-012 or placebo. Subjects will be followed up for 12 weeks after 
the single treatment session.  
Upon completion of the double-blind phase of the study and the opening of codes, subjects will 
be offered RZL-012 open-label treatment in the flank previously treated with placebo.  
Consenting subjects will be followed for safety and efficacy for an additional 12 weeks. 

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2.3 
Study Endpoints 
2.3.1 
Primary Endpoint 
The primary endpoint of this study is: 
• 
To evaluate safety following a single injection session of RZL-012 vs. placebo into the flanks. 
This is the first time RZL-012 is tested at a dose of 412mg per subject (highest previous dose, 
270mg/subject). Lab tests, ECG, skin irritancy and AEs related to the injection procedure will 
be evaluated for frequency, severity and duration up to 84 days after dosing.  
2.3.2 
Secondary Endpoints 
The secondary endpoints of this study are as follows: 
• 
Comparison of the proportion of flanks having an improvement as indicated by a score of 0 to 
6 according to the Physician Global Assessment Scale (GAIS) in RZL-012 vs placebo treated 
flanks. 
• 
Comparison of the proportion of subjects who are satisfied with treatment results as indicated 
by a yes/no satisfaction questionnaire in RZL-012 treated flanks vs placebo treated flanks.  
 
• 
Mean reduction in volume at 12 weeks post treatment vs. baseline for each of the treated 
flanks, as measured by 3D photographs. 
• 
Ability of blinded reviewers to correctly identify, per patient, the flank treated with test 
compound (active) vs the flank treated with vehicle (placebo). Success will be defined as at 
least 70% correct identification vs the expected 50% correct identification based on random 
guessing 
• .  
• 
Evaluate safety following a second dose of RZL-012 based on AEs, laboratory tests, ECG, 
skin irritancy. 
• 
Characterization of RZL-012 pharmacokinetic (PK) profile.  
 
2.3.3 
Randomization/Assignment to Study Drug 
Each flank (right and left) of each study participant (12 subjects) will be randomized into either 
the active RZL-012 treatment group or the placebo group and each flank will be treated with 
multiple injections in a single injection session of RZL-012 or placebo. Upon completion of the 
double-blind phase of the study, and the opening of codes, subjects will be offered RZL-012 
open-label treatment in the flank previously treated with placebo.   

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2.4 
Study Drugs 
2.4.1 
Test Product and Dosing 
RZL-012 is a novel synthetic molecule provided as a sterile liquid solution suitable for injection. 
At the start of the double-blind, placebo-controlled phase of the trial each flank (right and left) of 
each study participant will be randomized into either the active RZL-012 treatment group or the 
placebo group and each flank will be treated with multiple injections in a single injection session 
in accordance with Table 4 below: 
Table 4 
Dosing Regimen 
 
 
 
 
 
 
 
Upon completion of the double-blind phase of the study and the opening of codes, subjects will 
be offered RZL-012 open-label treatment in the flank previously treated with placebo in the same 
manner as described in Table 4 above.   
RZL-012/placebo  injections –Treatment will cover the area of each randomized flank. A surface 
area of 15cm x6 cm will be chosen for treatment as per the temporary tattoo grid shown below.  
Flanks will be injected with RZL-012/placebo with the needle pointing perpendicular (90°) to 
skin surface. An ice pack will be placed on the injected area for pain relief immediately after 
injections are completed. Subjects will remain in injection position for an additional 10 minutes 
after dosing. 
The injection pattern will be based on the following grid in which the distance between rows and 
columns will be 1.5 cm, as seen below. 
Injections will be conducted with a 27G needle (1 inch needle length) in order to allow direct 
injections into the depth of fat tissue. 
 
RZL-012 (50mg/mL 
DP injectable solution) 
Placebo (Injectable sterile solution) 
Randomized Right or 
left flank 
12 
12 
Single Treatment 
55 injections at 
7.5mg/0.15mL per 
each injection point –
A total of 412.5 
mg/8.25 mL total dose 
per flank 
55 injections at 0.15mL per each 
injection point –A total volume of 
8.25 mL total dose per flank  
* 55 injections are the maximum number of injections. In case of smaller flanks, the 
number of injections may be lower. 

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Figure 7 
Scheme of Injection Pattern Grid 
 
 
 
 
 
 
 
2.4.2 
Dose Rationale 
The maximal dose of RZL-012 administered to subjects to date was 270 mg via 36 injections of 
7.5 mg/0.15 mL per injection, with the distance between injection sites being 1 cm. This total 
dose per subject and the amount given per injection site were well tolerated and not associated 
with any significant safety issues. To cover the flank area in the current study, the maximal dose 
will be increased to 412.5 mg per session via 55 injections of 7.5 mg/0.15 mL per injection with 
the distance between injection sites of 1.5 cm. Subjects who receive a second RZL-012 dose will 
receive a maximal RZL-012 dose of 412.5X2=825 mg across 2 dosing sessions, at a 3-month 
interval between injection sessions.     
The maximal dose of RZL-012 administered to non-rodents (pigs) to date was 1,000 mg via 40 
injections of 25 mg/0.5 mL per injection, with the distance between injection sites being 1-2 cm. 
This dose was given monthly at 4 injection sessions per pig and was well tolerated without any 
significant systemic or local side effects. Dosing pigs at 4°x°1,000mg is equivalent to about 
4°x°900 mg in humans, based on body surface area calculations. These preclinical studies 
provide a good margin vs anticipated human dosing both in terms of the total dose, dosing 
frequency (once monthly in pigs vs every 3 months in humans) and amount per injection site 
(25°mg in pigs vs 7.5°mg in humans). 
2.4.3 
Serious Adverse Events Considered Related to the Investigational Drug 
AEs and serious adverse events (SAEs) will be monitored throughout the study. 
Study discontinuation is to be considered by the investigator in any case of SAEs and the actions 
taken are to be fully documented in source documents and Case Report Forms (CRFs).  
SAEs are considered to be related to the study drug. 
Subjects experiencing an SAEs will be followed for their skin condition. 
SAE should be reported within 24 hours to the medical monitor. 

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The study may also be prematurely terminated in any of the following cases:  
• Recurring serious or severe Adverse Drug Reaction (ADR) clinically evaluated by PI as 
warranting study termination. 
• A decision made by Sponsor/medical monitor and/or IRBEC and/or local regulatory 
agency to terminate the study 
2.5 
Concomitant Medications 
2.5.1 
Prior and Concomitant Medications 
Prior medications are defined as medications that were taken within 30 days prior to initial 
dosing with study drug. 
Concomitant medications are defined as medications taken any time after the start of dosing until 
discharge assessments. All concomitant medication, including blood and blood products, dietary 
supplements, and non-prescription drugs, will be listed at screening/baseline. Each entry will 
include the treatment's start date, treatment name (Generic), reason for use, dosing regimen (dose 
and frequency of use), route of administration, and stop date (if applicable). The clinical 
significance of the medication use will be decided by the investigator. Study subjects will be 
routinely questioned for changes in the administration of concomitant medication during the trial 
and changes should be updated from medical records as well. 
3.0 STUDY POPULATION 
The study population will include healthy volunteers age 18 to 65 years with visible and palpable 
fat in the flanks  
3.1 
Inclusion Criteria 
For a subject to be eligible for this study, he or she must meet all of the following criteria: 

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1.  Is a male or female subject between the ages of 18 and 65 years, inclusive. 
2. Has body mass index (BMI) BMI of ≥ 22 and < 30. 
3. Has clearly visible and palpable fat in the flanks 
4. Has symmetrical appearance of right and left flanks 
5. Agrees to maintain weight (i.e., within 5% of body weight)  by not making any changes in 
diet. 
6. Agree to avoid exposure of the treated area to sun for at least 1 month after each treatment 
session. 
7. If female, is not pregnant or breastfeeding based on the following: 
a. agree to the use of highly effective contraceptive methods for at least 2 weeks before 
baseline until 28 days after the last day of study drug and a negative urine pregnancy 
test at screening and baseline; or  
b. is of nonchildbearing potential defined as clinically infertile as the result of surgical 
sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy); or  
c. is confirmed postmenopausal status (defined as either having amenorrhea for ≥ 12 
consecutive months without another cause, having documented serum follicle-
stimulating hormone (FSH) level > 40 mIU/mL, or having another documented medical 
condition (e.g., was born without a uterus)) 
NOTE: The following are considered highly effective contraceptive methods: hormonal 
oral contraceptives, injectables, and patches; intrauterine devices; double-barrier methods 
(synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or 
gel); and male partner sterilization. 
8. If male (with or without vasectomy), agree to the use of highly effective contraceptive 
methods, e.g. condom, from study baseline until 7 days after the last day of study drug. 
9. Is willing to avoid strenuous exercise for seven (7) days post treatment. 
10. Is able to adhere to the visit schedule and protocol requirements and be available to complete 
the study. 
11. Is willing and able to sign an Institutional Review Board (IRB) approved informed consent 
form (ICF) indicating that they are aware of the investigational nature of the study. 
3.2 
Exclusion Criteria 
Subjects must NOT meet any of the following Exclusion criteria to be eligible for enrollment: 
1. Is unable to tolerate subcutaneous injections. 
2. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis). 
3. Has any uncontrolled systemic disease that is not stabilized (i.e., cardiovascular disease, 
mental illness). 
4. Has used anticoagulation therapies that may increase bleeding or bruising (i.e., aspirin, 
ibuprofen, vitamins, and herbal preparations) for seven (7) days prior to treatment. 
5. Has medication or a history of coagulopathy. 
6. Has a history or family history of venous thrombotic disease. 
7. Has a known sensitivity to cold or has any condition with a known response to cold exposure 
that limits blood flow to the skin, such as cold urticaria, Raynaud's disease, or chilblains 
(pernio). 

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8. Had a non-invasive fat reduction and/or body contouring procedure in the flanks within the 
past 12 months. 
9. Has any scars, unshaven hair, tattoos, on or near the proposed treatment area. 
10. Has significant history or current evidence of a medical, psychological or other disorder that, 
in the Investigator’s opinion, would preclude enrollment in the study. 
11. Has an active dermatitis or open wound in the proposed treatment area. 
12. Abnormal coagulation profile including: activated partial thromboplastin time (aPTT) > 
ULN, international normalized ratio (INR) > ULN reference range (> 1.3), prothrombin time 
(PT) > ULN. 
13. Has an active bacterial, fungal, or viral infection in the proposed treatment area. 
14. Has known allergic reactions to any injectables. 
15. Has been treated chronically in the past three (3) months prior to study entry with systemic 
steroids or immunosuppressive drugs. 
16. Has been treated chronically at least one (1) week prior to study entry with non-steroidal 
anti-inflammatory drugs (NSAIDs). 
17. Current participation or participation within three (3) months prior to the start of this study in 
a drug or other investigational research study. 
 
3.3 
Subject Identification 
At each site, a unique code numbers will be assigned by the Investigator to the trial subject rather 
than the subjects’ name, personal identification numbers, and/or addresses to protect the 
subject’s identity. The code numbers and initials will be used in lieu of the subject’s name when 
the Investigator reports AE and/or other trial related data. 
3.4 
Removal, Replacement or Early Withdrawal of Subjects from the Assessment Not 
Due to Intolerable Side Effects 
Subjects experiencing serious side effects will be followed until the event resolves or becomes 
stable.  
4.0 STUDY PROCEDURES AND ASSESSMENTS 
4.1 
Informed Consent 
Prior to initiation of any study procedures, each subject will undergo an Informed Consent 
process in which the subject voluntarily confirms their willingness to participate in the trial. The 
Investigator or his/her approved designee must explain the nature of the study protocol and 
associated risks to the potential study participant. The potential participant must be allowed to 
review the study information and to ask questions before being asked to sign the Informed 
Consent Form (ICF). Written informed consent must be provided by the potential study 
participant prior to initiation of any screening evaluations or other study-related procedures. The 

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signature date and the name of the individual at the site who obtained the informed consent will 
be recorded in the subject’s medical record. 
The ICF approved by the IRB/EC will contain a description of the study’s purpose, purpose, 
procedures, inconveniences and potential risks, and anticipated benefits. Prior to participation in 
the trial, the subject will receive a copy of the signed and dated written ICF. During participation 
in the trial, the subject will receive a copy of the signed and dated consent form updates and a 
copy of any amendments to the ICF provided to the subjects. 
After written informed consent is obtained, the subject will be assigned a screening number and 
will undergo the designated screening procedures listed in Appendix A. The Investigator, sub-
investigator or delegate will assess the results of these screening evaluations to determine 
eligibility for entry into the study according to the inclusion/exclusion criteria listed in Section 
3.0. 
4.2 
Complete Physical Examination 
The Investigator (or medically qualified nominee) will perform a complete physical exam at 
screening and on 12 weeks visit. Additional examinations that will be performed during the 
screening include height and weight to determine BMI to confirm eligibility. 
4.3 
Medical History 
A medical history will be obtained at screening.  Subject’s medical history should be fully 
documented to confirm eligibility. Medical history must include, but not limited to, past and 
present medical conditions, concomitant non-drug treatments, and hypersensitivity to drugs. 
4.4 
Vital Signs 
Vital signs (systolic and diastolic sitting position blood pressure, pulse rate, respiratory rate, and 
body oral temperature) are to be obtained at screening to ensure compliance. 
Additional vital sign measurements to assess subject’s safety will be performed at baseline (Day 
0) prior to treatment Week 1, Week 4, Week 8 and Week 12 visit. 
4.5 
ECG 
ECG test is to be obtained at screening to ensure compliance. ECG will be done in triplicates. 
Additional ECG will be performed on Week 1, Week 4 and Week 12 visit. 
4.6 
Height and Weight 
Height will be reported in centimeters at screening.  Body weight will be reported in kilograms 
(kg) at screening.  
Weight measurement will be performed at screening to determine the BMI value. An additional 
weight measurement will be performed at baseline and at study visits on Week 4, Week 8 and 

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Week 12 visit to verify no significant changes in weight throughout the assessment of flank 
changes during the study. 
4.7 
Pharmacokinetics 
Samples for testing of RZL-012 Pharmacokinetics will be taken from 6 subjects at the baseline 
visit till the following day (Day 0-1).  Subjects will stay in a hotel nearby the clinic area.  Blood 
samples (10 mL blood per sample in K2EDTA vials, 100 mL/subject/24h) will be taken after 
study injection at the given time points: 0, 30, 60 min, 2h, 3h, 4h, 6h, 8h, 24h and 30h.  Whole 
blood samples (10 mL x10 time points) will be stored on an ice block or wet ice until 
centrifuged.  Samples will be placed in the centrifuge and spin cycle started within 60 minutes of 
collection.  Samples will be centrifuged at 1200 g in 4 °C for 10 minutes.  Plasma will be 
removed and placed in aliquots (4 aliquots of 1 mL each) within 20 minutes of centrifugation and 
flash frozen on dry ice.  Processed samples will be placed in frozen (-60 to -90 °C) storage.  
Determination of RZL-012 in K2EDTA human plasma a validated method of Liquid 
Chromatography-Tandem Mass Spectrometry will be conducted and analyzed further. Samples 
(2 aliquots/subject/time point) will be sent frozen on dry ice and 2 aliquots will be retained for 
possible future analysis 
4.8 
Clinical Laboratory Evaluations – Hematology and Serum Chemistry 
Screening blood samples and urine specimens for laboratory evaluation will be collected at 
screening to confirm eligibility. Additional blood samples will be collected at Week 1, Week 4 
and Week 12 study visits for an assessment of hematology and serum chemistry. 
If there are clinically significant alerts obtained at any visit, an unscheduled visit will be added 
for additional blood sampling. 
4.8.1 
Hematology 
Complete blood cell count (CBC) will include a standard red blood cell (RBC), white blood cell 
(WBC) with differential, hemoglobin, hematocrit, platelets, D-dimer, Fibrinogen and coagulation 
(International normalized ratio [INR], partial thromboplastin time [PTT] and prothrombin time 
[PT]). 
4.8.2 
Serum Chemistry 
Comprehensive metabolic panel will include serum alkaline phosphatase (ALP), alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), glucose, calcium, globulin 
(calculated), phosphorus, chloride, sodium, potassium, blood urea nitrogen (BUN)/creatinine 
ratio (calculated), creatinine with GFR estimated,  total bilirubin, albumin, albumin/globulin 
ratio (calculated), total protein, amylase, bicarbonate/carbon dioxide (CO2), uric acid, gamma-
glutamyl transferase (GGT), and lactate dehydrogenase (LDH).  

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4.8.3 
Pregnancy Tests 
A serum (ß-hCG) pregnancy test will be administered to females of childbearing potential at 
screening and a urine pregnancy test will be administered at baseline prior to dosing. Additional 
serum pregnancy tests will be done at any time during the study (up to 12 weeks), if pregnancy is 
suspected. 
4.9 
2-D and 3-D Standardized Photography 
Standardized photography (2-dimensional and 3- dimensional) of the flanks area will be 
conducted at screening in order to establish a baseline value for assessment of treatment efficacy.  
Additional photography will be conducted on week 1, 4, 8 and 12 to evaluate qualitative and 
quantitative changes in flanks area at study visits.  
The 2D photos will be used by the blinded committee to assess which of the flanks for the same 
subject was treated with RZL-012 or placebo by comparing each of the left and each of the right 
flanks images before and 12 weeks after treatment. 
The 3D photos will be used to compare the images of each treated flank in screening vs. 12 
weeks visit and to calculate the volumetric change before and after treatment. 
4.10 
Physician Global Assessment Improvement Scale (GAIS)  
Investigator will assess the improvement of each flank (right and left)  following treatment by 
comparing the photographs of the subject taken at screening versus the photographs taken at 
study visits on Week 4, 8 and 12 visits. 
At each study visit, the Investigator will assess the improvement degree based on the following 
scale: 
Grade 
Description 
0 
Completely clear 
No evidence of fat; 100% improvement 
1 
Almost clear 
Very significant clearance (≥90% to <100%); only 
trace remain 
2 
Marked 
improvement 
Significant improvement (≥75% to <90%); some 
evidence of  fat remains 
3 
Moderate 
improvement 
Intermediate between slight and marked improvement 
(≥50% to <75%) 
4 
Slight 
improvement 
Some improvement (≥25% to <50%); significance 
evidence of fat remains 

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5 
No change 
Fat has not changed from baseline condition (±25%) 
6 
Worse 
Fat is worse than at baseline evaluation by ≥25% or 
more  
 
 
4.11 
Subject’s Satisfaction Questionnaire  
Subject’s satisfaction questionnaire (yes/no questions) will be conducted by the subjects for each 
of the treated flank (right and left) at study visits on Week 4, 8, and 12 to assess the subject’s 
satisfaction with their flanks after treatment. Subjects will be asked with the following questions 
and answers for each question will be Yes/No: 
For the right/left flank, are you satisfied with the treatment? 
Would you have the treatment again in the right/left flank? 
Would you recommend the treatment to a friend? 
4.12 
Evaluation of Response 
Evaluation of response will be conducted on 12 weeks following injection of RZL-012 or 
placebo. 
4.13 
Compliance Monitoring 
Compliance monitoring will include compliance assessment by site coordinator at the study 
visits, including but not limited to subject questioning. 
5.0 SAFETY ASSESSMENTS 
5.1 
Collection of Adverse Events Data 
Data regarding treatment-emergent AEs (TEAEs) will be collected in this study.  TEAEs are 
events that are not present at baseline, or if present at baseline, have worsened in severity. AEs 
will be assessed while the subjects are in the study. AEs assessed by the Investigator as related to 
study drug and “ongoing” at discharge will be monitored by the Investigator until resolved or 
until the subject is deemed “lost to follow-up”. 
Any AEs reported by the subject or noted by the Investigator or his/her designee will be recorded 
on the eCRF regardless of the Investigator opinion of causality. The following information will 
be recorded for each AE: description of the event, date and time of onset, date and time of 
resolution, severity, causal relationship to study drug, outcome, action taken with the study drug 
and any treatment given. 

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The AEs reported during the trial will be graded, documented, and assessed in regards to their 
clinical significance and relation to study drug. Treatment area evaluation includes, but is not 
limited to, evaluation of edema, pain, bruising, erythema, induration, numbness, paresthesia, 
tenderness, and pruritus. 
All abnormal changes from baseline will be collected, graded with regards to severity or clinical 
significance, assessed for causal relationship and recorded on the eCRF. 
5.2 
Complete or Targeted Physical Examination  
The Investigator will perform a complete PE at screening and on 12 weeks visit. 
5.3 
Vital Signs 
Vital signs (systolic and diastolic sitting position blood pressure, pulse rate, respiratory rate, and 
body oral temperature) are to be obtained at screening to ensure compliance. 
Additional vital sign measurements to assess subject’s safety will be performed at baseline (Day 
0) prior to treatment and after treatment, and during study visits on Week 1, 4, 8 and 12. 
6.0 PHARMACOKINETICS 
PK measures will be assessed during this study for 6 of 12 subjects in the study. Description of 
the procedure is detailed in section 4.7.  
7.0 EFFICACY 
Efficacy measures include the following: 
• Efficacy of RZL-012 versus placebo on fat reduction measured on 12 weeks visit versus 
baseline using the physician’s GAIS and blinded committee images identification of 
flanks before and after treatment for each of the subject’s flanks. 
• Assessment of the reduction in flanks volume on 12 weeks visit compared to baseline 
using 3D photos.  
• Assessment of flanks improvement using the subject’s satisfaction questionnaire.  
8.0 STUDY VISITS AND PROCEDURES 
Refer to Appendix A for the Schedule of Study Procedures. 
8.1 
Screening (Days -28 to -1) 
The Investigator or his/her approved designee must explain the nature of the study protocol and 
associated risks to the potential study participant. The potential participant must be allowed to 
review the study information and to ask questions before being asked to sign the Informed 
Consent Form (ICF). Written informed consent must be provided by the potential study 
participant prior to initiation of any screening evaluations or other study-related procedures. The 

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signature date and the name of the individual at the site who obtained the informed consent will 
be recorded in the subject’s medical record. 
After written informed consent is obtained, the subject will be assigned a screening number and 
will undergo the designated screening procedures listed in Appendix A. The Investigator, sub-
investigator or delegate will assess the results of these screening evaluations to determine 
eligibility for entry into the study according to the inclusion/exclusion criteria listed in Section 
3.0. 
Screening evaluations may be performed up to 28 days in advance of dosing but must be 
completed at least 1 day prior to Day 0. 
The following study evaluations and procedures are required to determine eligibility: 
• Obtain and record a medical history, including demographics, prior medications, and 
concomitant medications. 
• Complete physical examination 
• Vital signs  
• ECG 
• Height and weight measurements 
• Blood and serum samples for the following laboratory evaluations: 
o Hematology 
o Serum chemistry 
o Coagulation  
o Pregnancy (if applicable) 
• 2D photography 
• 3D photography 
Subjects may be re-screened if they were screened and not dosed within 28 days. The following 
procedures will be performed: vital signs and weight measurements.  
8.2 
Baseline Evaluations (Day 0) 
Following the screening visit, subjects determined to be eligible for participation in the study 
will undergo baseline assessments. Baseline evaluations will be performed upon admission to the 
clinical research unit on Day 0. 

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Baseline assessments include the following: 
• Confirm eligibility  
• Vital signs  
• Weight measurement 
• Concomitant medications  
• Urine pregnancy test (if applicable) 
Once subjects are confirmed to be eligible, each of the flanks will randomized to one of the 
treatment groups based on the randomization schedule. 
8.3 
Study Randomization 
Each left and right flank will be randomized to each treatment group according to a predefined 
randomization scheme in a ratio of 1:1 per each subject. Assignment to treatment group will be 
disclosed only after subject eligibility is confirmed and immediately prior to injection treatment. 
The Investigator, clinical staff and the subjects will be blinded to treatment group.  
8.4 
Pre-dose Evaluation (Day 0) 
Pre-dose assessments on Day 0 include the following: 
• Vital signs 
• First blood sample for PK  for 6 out of 12 subjects  
8.5 
Drug Administration 
RZL-012 and placebo will be supplied as a single treatment in multiple sites of injection (55 
injections). The injection dosing regimen and technique is crucial for the therapy safety. 
The following procedures prior to injection into the flanks will be applied: 
1. The flank area will be cleaned with an appropriate topical antiseptic. 
2. Ice/cold pack or topical local anesthesia (i.e., lidocaine cream) may be used prior to drug 
administration to enhance subject’s comfort. 
3. Injection grid pattern will be applied by pressing the grid firmly onto the clean, dry skin, 
with the printed grid pattern facing the skin. The grid paper backing will be thoroughly 
wetted with a cotton pad soaked with sterile water. After 15 seconds, the grid cover will 
be peeled off. 
4. An area of 55 adjacent injection points will be determined following the Investigator’s 
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5. Syringes will be filled with 1 mL RZL-012 or placebo and the number of syringes will be 
compatible with the total volume of injection. Up to 9 syringes for a total volume of 8.25 
mL will be used for each of the flanks. 
6. All injections will be administered perpendicularly in 90 degrees, using a 1 mL Luer-lock 
syringe and a 27G x 1” needle, respectively. 
7. The hole of the needle should be pointing into the fat layer and the injection direction 
should be towards the earth. An attempt to pull the plunger should be made prior to 
injecting to ensure no blood is coming out. If so, the plunger should be pushed down to 
inject 0.15 ml the medicine. The formulation is viscous; therefore, resistance is expected 
during injection. 
8. Immediately following completion of the injections, an ice/cold pack will be applied for 
immediate pain relief. It will be held by the subject for at least two (2) minutes. 
9. The Investigator will record the number of injections administered for each subject. 
The injection pattern used will be based on the flanks area, where distance between injection 
rows will be 1.5 cm and distance between the injection columns will be 1.5 cm.   
Each RZL-012 kit contains 2 vials that will be assigned to each subject: 
• RZL-012 will be provided in vials of 240 mg/4.8 mL (50 mg/mL) 
 
Treatment with placebo will be conducted in the same manner as above. 
 
The calendar date and 24-hour clock time of all doses will be recorded on the CRF. 
8.6 
Post-dose Evaluations (Day 0) and PK blood samples 
Post-dose assessments on Day 0 include the following: 
• Vital signs 
• Concomitant medication 
• AEs 
Following completion of injection treatment, an ice/cold pack will be placed on the injected area 
for pain relief. Subjects will remain in the injection position for an additional ten (10) minutes 
after injections. Six subjects will remain in the clinic up for 1 hour post dosing to collect blood 
for PK at time points of 30 and 60 minutes post dosing and AEs assessments. Additional blood 
samples for PK will be collected at: 2h, 3h, 4h, 6 and 8 hours  post injection. 
The other six subjects will stay up to 20 minutes post injection for medical supervisions and AEs 
assessment.   

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8.7 
Study Visits (Day 1, Week 1, 4, 8, and 12) 
Subjects will return to the clinical site for study visits on Day 1*,Week 1, 4 8 and 12 visits. Study 
visit assessments include the following: 
• Vital signs 
• Concomitant medication 
• AEs 
• Weight measurement  
• Clinical laboratory tests (Weeks 1, 4, 12) 
• Serum pregnancy test (in case pregnancy is suspected) 
• ECG (Weeks 1, 4, 12) 
• Physician’s GAIS (Weeks  4, 8, 12) 
• 2D and 3D  Photography  
• Subject’s satisfaction questionnaire (Weeks 4,8, 12) 
• Blinded committee to identify which of the flanks was treated with placebo and which of 
the flanks was treated with RZL-012 (Week 12) 
 
*Blood sampling for PK is only relevant for 6 of 12 subjects and will be conducted on Day 1 
visit after injection.  
 
In the case of clinically significant laboratory values at any visit, the subject will return for an 
unscheduled visit and a repeat of hematology and serum chemistry. 

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8.8 
Final Visit (Week 12) 
Final study visit assessments include the following: 
• Vital signs 
• ECG 
• Physical Exam 
• Concomitant medication 
• AEs 
• Clinical laboratory tests (including serum pregnancy test, in case pregnancy is suspected) 
• Weight measurement  
• 2D  and 3D Photography  
• Physician GAIS and physician assessment 
• Subject’s satisfaction questionnaire 
• Blinded committee identification for treated flanks 
8.9 
Open-Label Phase of the Study: 
Upon completion of the double-blind phase of the study and the opening of codes, subjects will 
be offered RZL-012 open-label treatment in the flank previously treated with placebo. 
Consenting subjects will be followed for safety and efficacy for an additional 12 weeks. 
The following visits and procedures will take place following RZL-012 injection to the placebo 
treated flank (there will be no screening visit in the open label part): 
• Week 1 visit – vital signs, concomitant medication, ECG, labs, 2D and 3D photos, AEs. 
• Week 4 visit – vitals signs, concomitant medication ,ECG, weight, labs, 2D and 3D 
photos, physician GAIS, subject’s satisfaction questionnaire, AEs 
• Week 8 visit  - vitals signs, concomitant medication, weight, 2D and 3D photos, 
physician GAIS, subject’s satisfaction questionnaire, AEs 
• Week 12 visit – vitals signs, concomitant medication , physical examination, ECG, 
weight, labs, 2D and 3D photos, physician GAIS, subject’s satisfaction questionnaire, 
AEs 
 
9.0 PREMATURE DISCONTINUATION FROM STUDY 
A premature discontinuation from study will occur when a subject who signed informed consent 
ceases participation in this study, regardless of circumstances, prior to completion of the 

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protocol. Subjects can be prematurely discontinued from the study for one of the following 
reasons:  
• Failure to meet inclusion/exclusion criteria before receiving first dose of study drug has 
been administered 
• Death 
• Significant safety event that in the opinion of the Investigator warrants discontinuation. 
Raziel will attempt to follow up all subjects for safety. 
• Lost to follow-up after every attempt has been made to contact the subject, including 
sending a registered letter 
• Subject withdraws consent 
The Principal Investigator and the Institutional Review Board/Ethics Committee (IRB/EC) 
reserve the right to prematurely terminate the study in the interest of subject safety and welfare. 
The Sponsor reserves the right to prematurely terminate the study at any time for administrative 
reasons. 
10.0 
PRODUCT SPECIFICATIONS 
10.1 
Description 
RZL-012 is a novel synthetic molecule (termed RZL-012) that can help reduce fat content 
following its injection into the subcutaneous fat. Chemically, RZL-012 is 5-(3,6-dibromo-9H-
carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride. RZL-012 is generated by a single 
step reaction and the final product is >97% pure. 
RZL-012 is provided as a sterile liquid solution suitable for injection. RZL-012 investigational 
drug is intended to be administered as a single dose via multiple injections into the subcutaneous 
fat. 
Placebo will be supplied as a vehicle control of tween-80, propylene glycol, benzyl alcohol and 
water. 
10.2 
Formulation, Packaging, and Labeling 
The active ingredient RZL-012 drug substance was manufactured by Cambrex, NC, USA. RZL-
012 drug product was manufactured in Patheon (Italy) and packed and labeled at ThermoFischer, 
USA. The drug product is provided in vials of 240 mg/4.8 mL (50 mg/mL).  
The active ingredient and formulation manufacturing and packing were in accordance with 
cGMPs. 
RZL-012 will be provided in strength of 240 mg/4.8 mL (50 mg/mL). 
The placebo is a ready to use liquid to be injected into the subcutaneous fat, supplied in a 2 vials 
kit. Each vehicle vial contains 4.8 mL solution volume. 

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10.3 
Receipt, Storage and Stability of RZL-012 
The RZL-012 kit and placebo vehicle will be stored in the site at monitored room temperature 
conditions (15 - 30 degrees Celsius) protected from light. 
Drug product stability has successfully reached three (3) years. Site inventory will be managed 
by the Sponsor according to accumulating stability data. Suitability of the product’s expiration 
date must take into consideration and comply with First In First Out (FIFO) principals. 
10.4 
Study Drug Administration 
Each kit containing 2 vials must be kept and handled at room temperature. The vials should be 
manually shaken prior to injection. 
1 mL Luer-lock syringes with RZL-012 solution should be filled with 27 G 1”  sterile needle for 
a maximal dose of 412.5mg. Two vials will be used for each subject. Breached vials will not be 
used for another subject. Each vial must be placed back into the container. All open vials will be 
kept until the end of study when the Sponsor will determine if study drug should be returned or 
destroyed. 
10.5 
Ordering and Distribution of Study Drug 
RZL-012 drug product was manufactured in Patheon (Italy) and packed and labeled at 
ThermoFischer, USA. The drug product is provided in vials of 240 mg/4.8 mL (50 mg/mL). 
RZL-012 will be dispensed to the sites under monitored conditions by ThermoFischer USA. 
The active ingredient and formulation manufacturing and packing were in accordance with 
current Good Manufacturing Practices (cGMPs). 
10.6 
Accountability of Study Drugs 
All study drugs received, dispensed, and returned must be accounted for in the study drug 
Dispensing Log, including: 
• Subject number and initials 
• Date study drug was dispensed 
• Quantity dispensed 
• Quantity returned 
• Quantity wasted, as applicable 
All study drug received and dispensed by the Investigator will be inventoried and accounted for 
throughout the study. The study drug must be stored in a restricted area with limited access. 
Contents of the study drug containers must not be combined.  

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The Investigator must maintain an accurate, up to date Dispensing Log for all study drugs 
supplied by the Sponsor. Study drug dispensed for all subjects must be recorded on the Drug 
Accountability Form. The study drug Dispensing Log and remaining drug inventory will be 
reviewed at each monitoring visit by the Sponsor-designated clinical monitor. 
The study drug supplied for this study is for use only in subjects properly consented and enrolled 
into this protocol. Study drugs must be kept in a secure location physically separated from 
standard clinic or office drug supplies. 
11.0 
SAFETY MONITORING AND ADVERSE EVENTS 
11.1 
Adverse Events 
Data regarding AEs will be collected in this study. AEs are events that are not present at 
baseline, or if present at baseline, have worsened in severity. 
AEs reported during the trial will be graded, documented, and assessed for relationship to study 
drug. Specifically, assessment of AEs related to skin condition and injection procedure will be 
closely monitored, including evaluation of edema, pain, bruising, erythema, induration, 
numbness, paresthesia, tenderness, and pruritus. 
Definition of Adverse Events and Adverse Drug Reactions: 
AEs in the eCRF will be classified according to the most recent FDA definitions and in a manner 
consistent with International Conference on Harmonization (ICH) guidelines. As such the 
following definitions will be used: 
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with 
the use of an investigational (medicinal) product (IP) or other protocol-imposed intervention, 
regardless of attribution.  An AE may include intercurrent illnesses or injuries that represent an 
exacerbation (increase in frequency, severity, or specificity) of pre-existing conditions (e.g., 
worsening of asthma).  A laboratory abnormality will be reported on the “Adverse Event” case 
report forms only if it is associated with clinical sequelae or requires therapeutic intervention.  
Whenever possible, it is preferable to record a diagnosis as the AE term rather than a series of 
symptoms relating to a diagnosis.  AEs will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA) and graded according to the Common Terminology Criteria for 
Adverse Events (CTCAE) v 5.0 (Error! Reference source not found.). 
The reporting period for AEs starts after dosing of study drug and will end at final study visit on 
12 weeks visit for the double-blind phase of the study. Once codes are opened after 12 weeks 
visit, subjects will be offered RZL-012 in the placebo treated flanks. After dosing with a second 
administration, AEs will be recorded according to planned schedule in the open-label phase. 
If an AE remains unresolved at discharge, the subject will be followed, at the Investigator’s 
discretion, until resolution of the event or until the subject is deemed “lost to follow-up”.  AEs 
assessed by the Investigator as related to study drug and “ongoing” at discharge will be 
monitored by the Investigator until resolved or until the subject is deemed “lost to follow-up”.  

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SAEs must be followed until resolution by the PI, even if this extends beyond the study-reporting 
period.  Resolution is defined as the return to baseline status or stabilization of the condition with 
the expectation that it will remain chronic. 
The Investigator will assess AEs for severity, relationship to IP, and as to whether the event 
meets one or more of the definitions of an SAE.  The assessments will be recorded on the source 
documents and AE CRF, using the categories defined below.  
Causality 
Category 
Description 
Un-related 
A clinical event, including laboratory test abnormality, with a 
temporal relationship to drug administration which makes a causal 
relationship improbable, and in which other drugs, chemicals or 
underlying disease provide plausible explanations. For the purpose of 
this protocol, the term unlikely will be considered not related to study 
medication and an “Adverse Event”. 
Related 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, but which 
could also be explained by concurrent disease or other drugs or 
chemicals. Information on drug withdrawal may be lacking or unclear. 
For the purpose of this protocol, an event that has possible or probable 
relationship to study medication will be defined as a “Suspected 
Adverse Drug Reaction”.   
In order to classify AEs and diseases, preferred terms will be assigned by the sponsor or its 
designee to the original terms entered on the CRF, using MedDRA. 
For those AEs that are not described on the CTCAE v 5.0, such AEs will be graded on a 5-point 
scale (mild, moderate, severe) and reported as indicated on the CRF. Intensity of such an AE is 
defined as follows: 
Table 5 
Severity Assessment Terminology for Reporting Adverse Events (CTCAE v 
5.0) 
CTCAE 
Grade 
Common 
Term 
Description 
1 
Mild 
Mild; asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not indicated. 
2 
Moderate 
Moderate; minimal, local or noninvasive intervention 
indicated; limiting age-appropriate instrumental Assisted 
Daily Living (ADL). 
3 
Severe 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care 

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CTCAE 
Grade 
Common 
Term 
Description 
ADL. 
4 
Life-
Threatening 
Life-threatening consequences; urgent intervention 
indicated. 
5 
Death 
Death related to AE  
11.2 
Serious Adverse Events 
According to the ICH Guidelines for Good Clinical Practice (E6), an SAE is any untoward 
medical occurrence during the course of a clinical investigation that is characterized by one or 
more of the following: 
• Results in death 
• Is life-threatening 
• Requires in-subject hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Important medical events 
Although not an SAE, exposure to study drug during pregnancy, even if no AE is reported in the 
mother, should be reported within 24 hours. 
11.2.1 
Reporting Requirements for Serious Adverse Events 
All SAEs must be reported to the Sponsor by the Investigator, study coordinator, other 
designated study personnel, or clinical research associate within 24 hours of notification of the 
SAE. To report such events, an SAE form must be completed by the Investigator and sent within 
24 hours by email or fax with relevant information. 
Within the 48 hours following the initial report, the Investigator must provide further information 
on the SAE if available. This should include a copy of the completed SAE form, and any other 
information that will assist the understanding of the event. Significant new information on 
ongoing SAEs should be provided promptly as a follow-up. 
The Investigator also must report all SAEs promptly to the appropriate IRB/EC as required by 
the institution within 24 hours or 48 hours if on weekend/holiday. 
Report SAEs by fax or email to: 
Fax:  +1-858-436-1401 
Email:  RazielSafety@pacificlinkconsulting.com/dr.patricia.walker@gmail.com 

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Table 6 
Contact Information for SAE Reporting 
Primary Contact 
Sponsor Contact 
Medical Monitor  
Study Director: 
Patricia Walker, MD, PhD 
Racheli Gueta, PhD 
Mobile: 
1-805-705-5853 
Mobile: 
972-50-7837597 
Email: 
dr.patricia.walker@gmail.com 
Email: 
racheli@raziel-therapy.com 
11.2.2 
Reporting pregnancy 
Pregnancy testing must be preformed on all women of childbearing potential prior to dosing, and 
all the results of all pregnancy tests are to be recorded in the eCRF’s. All women must have a 
negative pregnancy test to be enrolled into the study. If a pregnancy test turns positive after study 
drug treatment, the patient will be discontinued and protocol-required procedures for study 
discontinuation and follow-up must be preformed. The subject will be followed to determine the 
outcome of the pregnancy.  All women of childbearing potential should be instructed to contact 
the investigator if they suspect they might be pregnant (e.g. missed or late menstrual period) at 
any time during the study.  
The investigator must notify the sponsor of any pregnancies in accordance with the SAE 
reporting procedures described in section 11.2.1.  Note, while the pregnancy is not considered an 
AE or an SAE, any pregnancy complication or newborn complication will be reported as an AE 
or SAE if it meets the criteria.  Follow-up information regarding the course of pregnancy, 
including perinatal and neonatal outcomes and, where applicable, offspring information must be 
reported on the Pregnancy Outcome eCRF.   
11.2.3 
Recording of Serious Adverse Events 
All SAE information must be recorded on the SAE form provided by the Sponsor. Additional 
follow-up information (e.g., test results, autopsy, and discharge summary) must be obtained to 
supplement the SAE report form. A copy of all initial and follow-up reports must be filed with 
the subject’s eCRF. 
12.0 
STATISTICAL CONSIDERATIONS 
12.1 
Sample Size Determination 
A total of 12 subjects will be included in the study. Each subject will be treated with RZL-012 in 
one randomized flank and placebo in the other randomized flank.  
This will results in comparison of 12 active treated flanks vs. 12 placebo treated flanks. 
12.2 
Analysis Data Sets 
Subjects who receive study treatment will be included in the safety analyses.  

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12.3 
Endpoints Analyses 
All measured variables and derived parameters will be listed individually and, if appropriate, 
tabulated by descriptive statistics. 
For categorical variables, summary tables will be provided giving sample size, absolute and 
relative frequency, and 95% confidence interval (CI) for proportions by study arm. 
For continuous variables, summary tables will be provided giving sample size, arithmetic mean, 
standard deviation, coefficient of variations (CV%), median, minimum and maximum, and 95% 
CI for means of variables by study arm. 
The data will be analyzed using the SAS version 9.4 (SAS Institute, Cary North Carolina). 
12.4 
Safety 
Safety data will be summarized by dose group and based on their initial dose level or treatment 
group (i.e., if a dose reduction occurs, they will be considered in their initial group). Descriptive 
statistics will be provided for actual values and change from baseline values for vital signs, blood 
parameters, ECG . 
AE assessment and treatment area evaluation including, but not limited to evaluation of edema, 
pain, bruising, erythema, induration, numbness, paresthesia, tenderness, and pruritus. 
The incidence and severity of AEs reported during the study and their relationship to study drug 
will be tabulated. AEs will be coded using MedDRA™ and will be presented by body system. 
AEs will be graded according to the Common Terminology Criteria for Adverse Events 
(CTCAE) v 5.0 (Error! Reference source not found.).  
AE data will be listed individually and summarized by SOC and by PT within a system organ 
class. 
Skin irritancy AEs related to the injection procedure will be evaluated for frequency, severity 
and duration by treatment group.  
Fisher's Exact test will be applied for testing the statistical significance of the difference in 
percent of subjects that experienced Skin irritancy AEs related to the injection procedure 
between the study groups. 
Laboratory tests and ECG results will be summarized in appropriate table. 
12.5 
Efficacy 
The secondary endpoints will be analyzed as follows: 
• Physician’s GAIS 
 

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• 
Flank volume reduction from baseline to week 12, assessed by Physician Global Assessment 
score (GAIS). The proportion of flanks having an improvement as indicated by a score of 0-6 
according to the Physician Global Assessment Scale (GAIS) in RZL-012 vs placebo treated 
flanks will be assessed. 
 
Fisher's Exact test will be applied for testing the statistical significance of the difference in 
percent of subjects for whom an improvement in GAIS was observed between treatment 
groups. Will be calculated along with 95% exact confidence interval by treatment group. 
• 
Correct pre and post-treatment identification 
The proportion of correctly identified photos (flank’s treatment) by blinded reviewers will be 
calculated along with 95% exact confidence interval by treatment group. 
• 
Satisfaction (Yes/No question) 
The proportion of satisfied subjects will be calculated along with 95% exact confidence 
intervals for each treatment group. Fisher's Exact test will be applied for testing the statistical 
significance of the difference in percent of satisfied subjects between treatment groups. 
• 
Reduction in Volume 
The change and relative change from baseline in Flank volume as measured by photographs 
at 12 weeks post-treatment will be calculated per each treatment group. The Signed rank test 
for two means (paired observations) will be applied for testing the statistical significance of 
the change and relative change from baseline at week 12 in flank volume between treatment 
groups. 
13.0 
DATA COLLECTION, STUDY MONITORING, AND DATA DISCLOSURE 
13.1 
Data Collection and Reporting 
An eCRF will be completed for each subject who receives at least one dose of study drug. All 
entries on the eCRF must be supported by original source documentation (e.g., laboratory 
reports, medical records) maintained at the investigational site. 
The Investigator will make all safety assessments (AEs and vital signs) on an ongoing basis. The 
Investigator is required to review all entries on the eCRF and sign at appropriate time intervals. 
13.2 
Study Monitoring 
All aspects of the study will be monitored carefully by the Sponsor’s designees with respect to 
current Good Clinical Practice (GCP) and Standard Operating Procedures (SOP) for compliance 
with applicable government regulations. It is the responsibility of the Investigator to provide all 
study records, including eCRFs, source documents, etc., for review and source document 
verification by the clinical monitor. 
All eCRFs will be 100% source verified against corresponding source documentation (e.g., 
office and clinical laboratory records) for each subject. Clinical monitors will evaluate 
periodically the progress of the study, including the verification of appropriate consent form 
procedures, review of drug accountability and preparation procedures, adherence to dosing 

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procedures, and the verification of the accuracy and completeness of eCRFs. Clinical monitors 
will also ensure that all protocol requirements, applicable FDA regulations, other requirements, 
and Investigator’s obligations are being fulfilled. 
13.3 
Audit and Inspection 
The sponsor or representative may conduct audits at the trial site(s). Audits will include, but are 
not limited to protocol compliance, drug supply, presence of required documents, the informed 
consent process, and comparison of eCRFs with source documents. The investigator agrees to 
participate with audits conducted at a reasonable time in a reasonable manner. 
Regulatory authorities worldwide may inspect the trial site during or after the trial. The 
investigator should contact the sponsor immediately if this occurs and must fully cooperate with 
the inspections conducted at a reasonable time in a reasonable manner.  
13.4 
Deviation from Clinical Trial Protocol 
Deviations from the protocol are to be avoided. If a deviation occurs, the Investigator must 
promptly report the deviation to the study monitor. 
The Investigator (or designee) will record any failure to follow the protocol because of any other 
medical unavoidable reason to avoid the subject's urgent risk and record a document as soon as 
possible stating this and the reason. It must be submitted to the sponsor and the director of the 
study site. 
13.5 
Retention of Records 
The Investigator must retain all study records required by Raziel and by the applicable 
regulations in a secure and safe facility. The Investigator must notify Raziel of any change in the 
location, disposition or custody of the study files. The Investigator /institution must take 
measures to prevent accidental or premature destruction of essential documents, that is, 
documents that permit evaluation of the conduct of a study and the quality of the data produced, 
including paper copies of study records (e.g., subject charts) as well as any original source 
documents that are electronic as required by applicable regulatory requirements. 
All study records must be retained until whichever is the later day in the following: (1) At least 
the date of approval for the drug or (2) the date when 3 years have passed since the 
discontinuation or completion of the study. No records relating to this study should be disposed 
of without the written approval of Raziel. It is the responsibility of Raziel to inform the 
Investigator/institution as to when these documents no longer need to be retained. 
13.6 
Data Disclosure and Subject Confidentiality 
Subject medical information and video recordings obtained as a result of this study is considered 
confidential and used only for study evaluation purposes. Disclosure to third parties other than 
those noted below is prohibited. All reports and communications relating to subjects in this study 
will identify each subject only by number. Medical information resulting from a subject’s 

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participation in this study may be given to the subject’s personal physician or to the appropriate 
medical personnel responsible for the subject’s welfare. Data generated as a result of this study 
are to be available for inspection on request by FDA or other government regulatory agency 
auditors, the Sponsor clinical monitor (or designee), and the IRB/EC. 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will be 
identified by a coded number to maintain subject confidentiality. All records will be kept in a 
locked and secured area. All computer entry and networking programs will be identifiable only 
by coded numbers. Clinical information will not be released without written permission from the 
subject, except as necessary for monitoring by the IRB, the FDA, or the study Sponsor. 
Any information, inventions, or discoveries (whether patentable or not), innovations, 
suggestions, ideas, and reports, made or developed by the Investigator(s) as a result of 
conducting this study shall be promptly disclosed to the Sponsor and shall be the sole property of 
the Sponsor. The Investigator agrees, upon the Sponsor’s request and at the Sponsor's expense, to 
execute such documents and to take such other actions, as the Sponsor deems necessary or 
appropriate, to obtain patents in the Sponsor’s name covering any of the foregoing. 
The results of this study will be published under the direction of the Sponsor. Results will not be 
published without prior review and approval by the Sponsor and Study Investigator. 
14.0 
PROTECTION OF HUMAN SUBJECTS 
14.1 
Basic Principles 
The study will be conducted in accordance with the relevant regulatory requirements, this 
protocol, and ethical principles that are consisted with the GCP guideline developed by the 
International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH). This clinical trial will also be conducted in compliance 
with Declaration of Helsinki, protocol, Standard specified in the relevant local regulations. Prior 
to initiation of the study, the investigator and the sponsor should obtain approval from the 
IRB/IEC on this protocol and any further amendments, and the subject information and informed 
consent form. 
Any suspected serious breaches must be immediately reported to the sponsor. A serious breach is 
a breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety of the subjects or the scientific value 
of the study. 
Personnel involved in the study will be qualified by education, training, and experience to 
perform their respective tasks. 
14.2 
Institutional Review Board/Ethics Committee 
The Investigator or designee agrees to provide the IRB/EC with all appropriate material, 
including a copy of the ICF. The study will not be initiated until the Investigator obtains written 
approval of the research plan and the ICF from the appropriate IRB/EC and copies of these 

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Version: 1.1 
 
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documents are received by the Sponsor. Appropriate reports on the progress of this study will be 
made by the Investigator to the IRB/EC and Sponsor in accordance with applicable government 
regulations and in agreement with the policies established by the Sponsor. The Sponsor ensures 
that the IRB/EC complies with the requirements set forth in 21 CFR Part 56 (Code of Federal 
Regulations). 
14.3 
Informed Consent 
The investigator is responsible for: 
• Explain the subject of the study, the risks and benefits expected from participating in the study, 
and that the participation is voluntary so that the subject can understand. 
• Obtain informed consent to participate in the trial from the subject by signing or signing the 
consent form and entering the date before starting the study procedure and study drugs. 
• Properly answer questions from subjects at any time during the trial and if new information that 
can affect the subject's intention to continue the trial is obtained while the subject is participating 
in the trial, the information is promptly communicated to the subject. 
• Give a copy of the written consent form to the study participants and keep one copy at the 
study site. 
14.4 
Subject Health Injury and Insurance 
In general, if a subject is health-injured as a direct result of the investigational products, the 
sponsor or its contracted insurance company will pay for reasonable and necessary medical 
treatment for the health-injury. If laws or regulations of the locality in which the study is taking 
place require additional payment of expenses, the sponsor should comply with such laws or 
regulations. Where applicable, the sponsor will arrange for specific insurance coverage. If health 
damage occurred in subject participating the clinical trial due to the willful or gross negligence 
of investigator’s site, indemnification will be discussed based on the contract with the site. The 
indemnification for the health damage and the payment to subjects will be described in the ICF. 
14.5 
Completion of the Study 
If the clinical trial is completed at the study site, the investigator will notify the director of the 
study site that the trial has been completed and provide an approximate summary in writing.  The 
director of the study site will promptly notify the IRB/EC and the Sponsor in writing about the 
completion. 
 

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Protocol RZL-012-FL-P2US-001 
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Version: 1.1 
 
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Appendix A:  Schedule of Study Procedures 

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Protocol RZL-012-FL-P2US-001 
RZL-012 
Version:1.0 
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Table 1: Schedule of Study Procedures 
Study 
Procedure 
Screenin
g Day 
 
Double Blind Phase 
Open Label Phase 
Study Day 
Day -
28 
throug
h Day 
-1 
Baseli
ne 
Day 0 
a 
Da
y 1 
e 
Wee
k 
1(±2 
day
s) 
Wee
k 4 
(±5 
day
s) 
Wee
k 8 
(±5 
days
) 
Wee
k 12 
(±5 
day
s) 
Da
y 0 
a 
Wee
k 
1(±2 
day
s) 
Wee
k 4 
(±5 
day
s) 
Wee
k 8 
(±5 
day
s) 
Wee
k 12 
(±5 
days
)/ 
Fina
l 
visit 
Signed 
informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
criteria 
X 
Prec 
X 
 
 
 
 
 
 
 
 
 
 
Medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical 
Exam 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Concomitant 
Medication 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy ß-
hCG 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight 
measurement
s 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
Pharmacokin
etics blood 
samples  
 
X 
X 
 
 
 
 
 
 
 
 
 
Hematology 
and 
Chemistryb 
X 
 
 
X 
X 
 
X 
 
X 
X 
 
X 
ECG 
X 
 
 
X 
X 
 
X 
 
X 
X 
 
X 
Vital signs 
X 
Prec 
X 
postc 
 
X 
X 
X 
X 
Pre
c X 
pos
tc 
X 
X 
X 
X 
Injection of 
RZL-012 or 
placebo 
 
X 
 
 
 
 
 
X 
 
 
 
 
Physician’s 
GAIS 
 
 
 
 
X 
X 
X 
 
 
X 
X 
X 
Subject 
Satisfaction 
questionnaire 
 
 
 
 
X 
X 
X 
 
 
X 
X 
X 

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RZL-012 
Version:1.0 
22 November  2021                                                    72 of 72                                                 CONFIDENTIAL                                    
a. 
Day 0 defined as the day of RZL-012 or placebo injection. 
b. 
In case of clinically significant values at any visit, an unscheduled visit will be added 
c. 
Pre/post – refers to before/after injection, respectively 
d. 
AEs will be recorded throughout the study until the final study visit.  In case of ongoing AEs at the final study visit an 
unscheduled visit will be scheduled for further follow-up.  Treatment area will be evaluated including, but is not limited 
to, evaluation of edema, pain, bruising, erythema, induration, numbness, paresthesia, tenderness, and pruritus. 
e. 
Day 1 visit is only for subjects who volunteer for PK blood samples 
 
 
 
Study 
Procedure 
Screenin
g Day 
 
Double Blind Phase 
Open Label Phase 
Study Day 
Day -
28 
throug
h Day 
-1 
Baseli
ne 
Day 0 
a 
Da
y 1 
e 
Wee
k 
1(±2 
day
s) 
Wee
k 4 
(±5 
day
s) 
Wee
k 8 
(±5 
days
) 
Wee
k 12 
(±5 
day
s) 
Da
y 0 
a 
Wee
k 
1(±2 
day
s) 
Wee
k 4 
(±5 
day
s) 
Wee
k 8 
(±5 
day
s) 
Wee
k 12 
(±5 
days
)/ 
Fina
l 
visit 
2D 
Standardized 
photography 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3D 
photography 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEsd 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X