A Dose Finding Study for the Assessment of Delayed-type Hypersensitivity Reactions to SARS-CoV-2 Peptide Antigens in Uninfected Healthy Subjects, COVID-19 Convalescent Subjects, and COVID-19 Vaccinated Subjects
Phase: PHASE1
Conditions: Detection of Delayed-type Hypersensitivity Reactions to SARS-CoV-2 in Individuals Exposed to SARS-CoV-2
Sponsor: Tonix Pharmaceuticals, Inc.

NCT05216510

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 2 of 86
SIGNATURE PAGE 
Declaration of Sponsor  
Protocol Title: A Dose Finding Study for the Assessment of Delayed-type Hypersensitivity 
Reactions to SARS-CoV-2 Peptide Antigens in Uninfected Healthy Subjects, COVID-19 
Convalescent Subjects, and COVID-19 Vaccinated Subjects “COVID-19 DTH”
This clinical study protocol was subjected to critical review. The information it contains is 
consistent with current knowledge of the risks and benefits of the investigational product, as well 
as with the moral, ethical and scientific principles governing clinical research as set out in the 
guidelines on Good Clinical Practice (GCP) applicable to this clinical study.
Sponsor Signatory 
Date 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 3 of 86
SIGNATURE PAGE 
Declaration of the Principal Investigator 
Protocol Title A Dose Finding Study for the Assessment of Delayed-type Hypersensitivity 
Reactions to SARS-CoV-2 Peptide Antigens in Uninfected Healthy Subjects, COVID-19 
Convalescent Subjects, and COVID-19 Vaccinated Subjects “COVID-19 DTH” 
 
I have read the TNX-CA-C201 protocol and agree to conduct the study as outlined. This clinical 
study protocol was subjected to critical review and has been released by the Sponsor. The 
information it contains is consistent with current risk and benefit evaluation of the investigational 
product, as well as with the moral, ethical and scientific principles governing clinical research as 
set out in the guidelines on GCP applicable to this clinical study. 
I agree to maintain the confidentiality of all information received or developed in connection with 
this protocol.  
 
Principal Investigator 
Date 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 4 of 86
LIST OF STUDY STAFF 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 5 of 86
PROCEDURES IN CASE OF EMERGENCY 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 7 of 86
samples are collected. Follow-up visits to monitor safety and evaluate the presence or absence of DTH 
reactions will be conducted per the following schedule: Visit 2 (Day 2); Visit 3 (Day 3); Visit 4 (Day 4); 
Visit 5 (Day 5). Safety monitoring will continue at Visit 6 (Day 30) and Visit 7 (Day 180) by telephone 
calls.  
Eligible subjects who provide written informed consent and who satisfy eligibility criteria will undergo a 
nasopharyngeal swab for a polymerase chain reaction (PCR) (reverse transcriptase [RT]-PCR or other) 
test to detect active SARS-CoV-2 infection. A laboratory PCR test or a sponsor approved rapid PCR test 
(such as the Accula™ RT-PCR test) may be used. If a laboratory PCR test is used, subjects will complete 
a Screening Visit between Day -2 and Day -1 to allow processing of the sample prior to the Baseline/Skin 
Test Administration Visit 1 (Day 1). The rapid PCR test can be performed at Visit 1 (Day 1) and is 
preferred to facilitate enrollment by reducing the number of required site visits. If the test result is 
negative, the subject will proceed with the required blood draws followed by intradermal injection of the 
investigational products (IPs) and controls.  
The estimated study duration will be approximately six months. In addition, unscheduled visits may occur 
based on Investigator assessment and /or Sponsor Medical Monitor request, or as clinically indicated. 
Photography of the injection site (volar forearms) after IP administration at Visit 1 and at Visit 3, 4, and 5, 
or unscheduled in person visits, will be used for safety documentation of local skin reaction, such as 
redness and swelling, or unexpected findings such as rash, blistering and necrosis, which require 
assessment by the designated Investigator. 
A total of eight vials are provided, per subject. Three of the eight vials will be the ‘undiluted’ TNX-2110, 
TNX-2120 and TNX-2130 sterile solution (2.5 µg/mL) for injection. One vial will be the positive control 
CANDIN®. The remaining four vials are Diluent containing phosphate buffer pH 7.0 with 0.31% 
polysorbate 20 and 4.6% mannitol. Of these Diluent vials, three of them will be labeled as ‘1:10 Dilution 
TNX-2110’, ‘1:10 Dilution TNX-2120’, and ‘1:10 Dilution TNX-2130’ to represent the three “diluted” 
IPs. The remaining Diluent vial will be used as the negative control. 
Intradermal injections will be administered in two stages in the order shown in the table below Table 2. 
Three IPs (TNX-2110, TNX- 2120, TNX-2130) will be administered by intradermal injection (0.1 mL) in 
two concentration strengths (Stage 1: “1:10 dilution” and Stage 2: “undiluted”). Subjects will also receive 
one intradermal injection (0.1 mL) of a positive control (CANDIN®), and one intradermal injection
(0.1 mL) of a negative control “diluent”.  
In total, each subject will receive eight intradermal injections (four per forearm), spaced 2 inches apart at 
pre-determined sites on the volar aspect of the forearms.  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021
Page 14 of 86
Interim Analysis 
The skin test DTH result assessments are obtained at Visits 3, 4 and 5 (48, 72 and 96 hours post 
administration of skin test). An interim analysis will be conducted after all subjects have completed Visit 5 
(or early terminated prior to Visit 5), and a database lock of the efficacy and safety data up to Day 5 will 
occur. The purpose of the interim analysis will be to assess the presence of DTH reactions in response to 
intradermal injection of synthesized TNX-2100 SARS-CoV-2 peptide antigens, and to assess safety up to 
96 hours post-administration. A full database lock will occur after all subjects have completed Visit 7 (or 
early terminated prior to Visit 7). 
Sample Size 
Formal sample size calculations were not performed. The number of subjects were chosen based on 
feasibility and are considered sufficient to meet the study objectives.

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
 
CONFIDENTIAL 
 
Amendment 01, Final v2.0, 07 Dec 2021 
  
Page 17 of 86 
 Visit 3 will occur in person approximately 48 hours after administration of the intradermal injection of peptides. 
 Visit 4 will occur in person approximately 72 hours after administration of the intradermal injection of peptides. 
 Visit 5 will occur in person approximately 96 hours after administration of the intradermal injection of peptides. 
 Visit 6 will occur by telephone approximately 30 days after administration of the intradermal injection of peptides. 
 Visit 7 will occur by telephone approximately 180 days after administration of the intradermal injection of peptides. 
 Vital signs (systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate) will be measured at the beginning of Visit 1 for a Baseline reading. Vital 
signs will also be measured during Stage 1 and Stage 2 of skin test administration. In Stage 1, vital signs will be measured 30 minutes following administration of the 3 x 
0.025 µg peptides (dose strength “1:10 dilution” of IP), negative and positive control. If no systemic adverse reactions or unusual local site reactions per the Investigator’s 
judgement are observed after 60 minutes, the subjects will proceed to Stage 2 for administration of the of 3 x 0.25 µg TNX-2100 peptides per 100 µL (undiluted product). 
After Stage 2 administrations, subjects will be monitored over the course of 30 minutes for unusual local site reactions and systemic adverse reactions. At 30 minutes post-
administration, vital signs will be assessed. If no evidence of systemic adverse reactions or unusual local site reactions per the Investigator’s judgement have occurred, 
subjects will be free to leave the clinic. 
 A 12-lead electrocardiogram will be obtained at Visit 1. All electrocardiograms will be conducted and interpreted locally. 
 A nasopharyngeal swab will be collected at a Screening Visit between Day -2 to -1 if laboratory PCR test used, or Visit 1 (Day 1) if rapid PCR test used for detection of 
active SARS-CoV-2 infection. 
 Initially applicable to Cohort 2 (recovered subjects) only. Assessments will be required for any new COVID-19 infection. 
Clinical laboratory tests (hematology and serum chemistry) will be performed at Visit 1. Clinical laboratory tests may be repeated at the discretion of the investigator. 
 Details regarding the assessment and measurement of the TNX-2100 Skin Test are provided in the Pharmacy Manual (Appendix 5). 
 Photography of the injection site (volar forearms) after IP administration at Visit 1 and at Visit 3, 4, 5 and any unscheduled in person visits, will be used for safety 
documentation of local skin reaction, such as redness and swelling, or unexpected findings such as rash, blistering and necrosis, which require assessment by the designated 
Investigator. At Visit 1, the injection sites should be photographed after Stage 1, and again after Stage 2 (at the start of each safety monitoring period). Subject should lay 
arms flat, palms facing up. Site should photograph from above and in a well-lit area. Site should take photos uniformly for all subjects so that both forearms from inner elbow 
to wrist are visible.
If subjects opt for an in-person visit at Visit 2 or Unscheduled Visit, photography of the injection sites (volar forearms) will be used for safety documentation of local site 
and any unexpected findings. 
 Long term safety follow-up contact at Visit 6 and Visit 7 will consist of a brief medical history review and assessed for new or recent COVID-19 infection since the last 
visit. Unvaccinated subjects will also be asked to confirm any update to vaccination status. Subjects will be asked to confirm whether there is a complete resolution of DTH 
skin reaction to skin test peptides. 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 18 of 86
3. 
TABLE OF CONTENTS 
1.
TITLE PAGE ................................................................................................................1
2.
SYNOPSIS ...................................................................................................................6
3.
TABLE OF CONTENTS ...........................................................................................18
4.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................23
5.
INTRODUCTION ......................................................................................................25
5.1.
Overview of SARS-CoV-2 .........................................................................................25
5.2.
Background of TNX-2100 ..........................................................................................25
5.3.
Scientific Rationale .....................................................................................................27
5.4.
Risk-benefit Assessment .............................................................................................29
6.
TRIAL OBJECTIVES ................................................................................................30
6.1.
Primary Objectives .....................................................................................................30
6.2.
Secondary Objectives .................................................................................................30
7.
INVESTIGATIONAL PLAN .....................................................................................31
7.1.
Overall Study Design ..................................................................................................31
7.2.
Study Endpoints ..........................................................................................................33
7.2.1. 
Safety Endpoints.........................................................................................................33
7.2.2. 
Efficacy Endpoints......................................................................................................33
7.3.
Number of Subjects and Treatment Assignment ........................................................34
8.
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................35
8.1.
Informed Consent .......................................................................................................35
8.2.
Subject Inclusion Criteria ...........................................................................................35
8.3.
Subject Exclusion Criteria ..........................................................................................36
8.4.
Restrictions .................................................................................................................37
8.4.1. 
Medication ..................................................................................................................37
8.4.2. 
Contraception Rules ....................................................................................................37
8.5.
Randomization Criteria ...............................................................................................38
8.6.
Subject Withdrawal Criteria .......................................................................................38
8.6.1
Study Halting and Study Stopping Rules ...................................................................39
9.
TREATMENT OF SUBJECTS ..................................................................................40
9.1.
Prior and Concomitant Medications ...........................................................................40

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 19 of 86
10.
INVESTIGATIONAL PRODUCT ............................................................................41
10.1.
Identity of the Investigational Products ......................................................................41
10.2.
Study Drug Packaging, Labeling, and Storage...........................................................41
10.3.
Preparation of Investigational Products......................................................................42
10.4.
Administration of the Investigational Products ..........................................................42
11.
CONTROLS ...............................................................................................................45
11.1.
Release of Clinical Study Supplies to the Investigator ...............................................46
11.2.
Study Drug Accountability and Reconciliation ..........................................................46
12.
STUDY ASSESSMENTS AND PROCEDURES......................................................47
12.1.
Study Assessments ......................................................................................................47
12.1.1. 
Demographics .............................................................................................................47
12.1.2. 
Medical History ..........................................................................................................47
12.1.3. 
Previous and Concomitant Medications .....................................................................47
12.1.4. 
Physical Examination .................................................................................................47
12.1.5. 
Vital Signs ..................................................................................................................47
12.1.6. 
Pregnancy Test............................................................................................................47
12.1.7. 
PCR Test for SARS-CoV-2 ........................................................................................47
12.1.8. 
Immunological Assessments ......................................................................................48
12.1.9. 
Safety Laboratory Tests ..............................................................................................49
12.1.10. 
Skin test results assessment ........................................................................................49
12.1.11. 
Post-injection Safety Follow-up .................................................................................51
12.2.
Schedule of Study Procedures ....................................................................................52
12.2.1. 
Screening Visit (Day -2 to -1) ....................................................................................52
12.2.2.
Visit 1 (Baseline/Skin Test Administration: Day 1)...................................................52
12.2.3. 
Visit 2 (Day 2) ............................................................................................................55
12.2.4. 
Visit 3 (Day 3) ............................................................................................................55
12.2.5. 
Visit 4 (Day 4) ............................................................................................................55
12.2.6. 
Visit 5 (Day 5) ............................................................................................................56
12.2.7. 
Visit 6 (Day 30) ..........................................................................................................56
12.2.8. 
Visit 7 (Day 180) ........................................................................................................56
13.
STATISTICAL CONSIDERATIONS AND ANALYSES ........................................57
13.1.
Populations for Analysis .............................................................................................57

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 20 of 86
13.2.
General Considerations...............................................................................................57
13.3.
Demographics .............................................................................................................57
13.4.
Subject Disposition .....................................................................................................58
13.5.
Safety Analyses ..........................................................................................................58
13.5.1. 
Adverse Events ...........................................................................................................58
13.5.2. 
Clinical Laboratory Tests ...........................................................................................58
13.5.3. 
Vital Signs ..................................................................................................................58
13.5.4. 
Physical Examination .................................................................................................59
13.6.
Efficacy Analyses .......................................................................................................59
13.7.
Interim Analysis ..........................................................................................................59
14.
DEFINITIONS, RECORDING, AND REPORTING OF ADVERSE 
EVENTS .....................................................................................................................60
14.1
Definition of Adverse Events .....................................................................................60
14.2
Adverse Event Recording ...........................................................................................60
14.2.1 
Coding the Adverse Event..........................................................................................60
14.2.2 
Severity of Adverse Event..........................................................................................60
14.2.3 
Relationship of Adverse Events to Study Drug..........................................................61
14.2.4 
Local Adverse Event by 7-point Likert Scale .............................................................61
14.2.5 
Toxicity Assessment Scales ........................................................................................62
14.2.6 
Adverse Events of Special Interest .............................................................................63
14.3
Serious Adverse Events and Serious Adverse Drug Reactions ..................................64
14.3.1 
Reporting of Serious Adverse Events.........................................................................64
14.4
Pregnancy ...................................................................................................................66
15
ETHICAL CONSIDERATIONS................................................................................67
15.2
Ethical Conduct of the Study ......................................................................................67
15.3
Institutional Review Board .........................................................................................67
15.4
Written Informed Consent ..........................................................................................67
16
DATA HANDLING, RECORD KEEPING, MONITORING AND AUDITS ..........69
16.2
Maintaining Privacy and Confidentiality ....................................................................69
16.3
Maintaining Essential Clinical Documents ................................................................69
16.4
Data Handling.............................................................................................................70
16.5
Case Report Forms .....................................................................................................70
16.6
Clinical Laboratory Certification................................................................................70

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 21 of 86
16.7
Site Monitoring and the Right to Review Records.....................................................71
16.8
Audits and Inspections ................................................................................................71
17
CONFIDENTIALITY ................................................................................................72
17.2
Protection of Subject Anonymity ...............................................................................72
17.3
Confidentiality of Study Information .........................................................................72
17.4
Publication of Data and Protection of Trade Secrets..................................................72
18
LIST OF REFERENCES ............................................................................................74
19
APPENDICES ............................................................................................................77
APPENDIX 1. WORLD ALLERGY ORGANIZATION GRADING SCALE FOR 
SYSTEMIC ALLERGIC REACTIONS ....................................................................78
APPENDIX 2. CDC UNDERLYING MEDICAL CONDITIONS ASSOCIATED 
WITH HIGHER RISK FOR SEVERE COVID-19 ....................................................80
APPENDIX 3. 7-POINT LIKERT SCALE ................................................................................83
APPENDIX 4. CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS ......................84
APPENDIX 5. PHARMACY MANUAL...................................................................................86

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 22 of 86
LIST OF TABLES 
Table 1:
Emergency Contact Information...................................................................................5
Table 2: 
Administration of In Vivo Investigational Products and Intradermal Controls ...........8
Table 3: 
Schedule of Activities.................................................................................................15
Table 4 
Administration of In Vivo Investigational Products and Intradermal Controls .........44
Table 5: 
Positive and Negative Controls for TNX-CA-C201 Study ........................................45
Table 6: 
Immunological Assessments for TNX-CA-C201 Study ............................................48
Table 7: 
Safety Laboratory Tests ..............................................................................................49
Table 8: 
Tables for Clinical Abnormalities (FDA, 2007).........................................................62
LIST OF FIGURES 
Figure 1 
Standardized Intradermal Injection for the TNX-2100 Skin Test ..............................44
Figure 2: 
Measurement of Area of Skin Induration ...................................................................51

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 23 of 86
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Term
Definition
AE 
Adverse event
AESI
Adverse events of special interest
BMI
Body mass index 
ALT 
Alanine aminotransferase  
AST
Aspartate aminotransferase
CANDIN® 
Candida albicans skin test antigen for cellular hypersensitivity
CBC
Complete blood count 
CD
Cluster of differentiation 
CDC 
Centers for Disease Control and Prevention
COVID-19
Coronavirus disease 2019 
CRF
Case report form 
CRU 
Clinical research unit
CRO 
Contract research organization 
DNA 
Deoxyribonucleic acid 
DTH 
Delayed-type hypersensitivity 
ECG
Electrocardiogram
ECLIA 
Electrochemiluminescence Immunoassay 
EDTA 
Ethylenediaminetetraacetic acid 
FDA
Food and Drug Administration 
GCP 
Good clinical practices 
GLP
Good laboratory practices  
HIPAA 
Health Insurance Portability and Accountability Act 
HLA 
Human leucocyte antigen
HPV
Human papillomavirus
HSV
Herpes simplex virus 
ICF 
Informed consent 
ICH
International Council for Harmonisation 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 24 of 86
ICS 
Intracellular cytokine staining 
IL 
Interleukin  
IP
Investigational product 
IRB 
Institutional review board 
ITT 
 
MCH
Mean corpuscular hemoglobin
MCHC 
Mean corpuscular hemoglobin concentration 
MCV
Mean corpuscular volume 
MedDRA
Medical Dictionary for Regulatory Activities 
mITT
 
MMR 
Measles, mumps, rubella
PCR
Polymerase chain reaction
PBMC
Peripheral blood mononuclear cells 
POC 
Proof-of-Concept 
PPD 
Purified protein derivative
QTcF 
QTc derived from Fridericia's Formula 
RBC
Red cell count
RBD 
Receptor binding domain
RDW 
Red cell distribution width 
RNA
Ribonucleic acid 
RT-PCR
Reverse transcription polymerase chain reaction  
SAE
Serious adverse event
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
TB
Tuberculosis 
Th
T helper cell 
TT
Tetanus toxin
US
United States
WBC
White blood cell count 
WHO
World Health Organization 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 25 of 86
5. 
INTRODUCTION 
5.1. 
Overview of SARS-CoV-2 
In late 2019, a new disease caused by severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) emerged in China that is now known as coronavirus disease 2019 (COVID-19). 
SARS-CoV-2 has emerged as an easily transmissible disease, affecting millions of people 
worldwide (Chan et al., 2020a; Chen et al., 2020; Li et al., 2020; Wang et al., 2020; Zhu et al., 
2020).  
The most common coronaviruses in clinical practice are 229E, OC43, NL63, and HKU1, which 
typically cause common cold symptoms in immunocompetent individuals. SARS-CoV-2, a 
member of the betacoronavirus genus, is closely related to SARS-CoV and several bat 
coronaviruses (Lu et al., 2020; Tan et al., 2020; Zhu et al., 2020). 
The spectrum of SARS-CoV-2 ranges from asymptomatic forms to severe viral pneumonia with 
respiratory failure, multiorgan and systemic dysfunctions, and death (Guan et al., 2020, Huang et 
al., 2020). The majority (80%) of cases are mild and self-limiting; severe disease requiring 
hospitalization occurs in the remaining 20% mainly due to fulminant pneumonia and respiratory 
failure (Wu et al., 2020). 
5.2. 
Background of TNX-2100 
Knowledge of diagnostic tests for SARS-CoV-2 is still evolving, and a clear understanding of the 
nature of the tests and interpretation of their findings is important. To date, the most commonly 
used and reliable test for diagnosis of SARS-CoV-2 has been the reverse transcription polymerase 
chain reaction (RT-PCR) test performed using nasopharyngeal swabs or other upper respiratory 
tract specimens, including throat swab or, more recently, saliva. A variety of RNA gene targets 
are used by different manufacturers, with most tests targeting 1 or more of the envelope, 
nucleocapsid, spike, RNA-dependent RNA polymerase, and ORF1 genes. False negative results 
and lengthy wait times for molecular RT-PCR tests question their usefulness in determining active 
infection. 
The only currently available methods to detect T cell immunity to SARS-CoV-2 require expensive, 
multi-step sample preparation and in vitro T cell stimulation in highly specialized laboratories 
using methods that have not been amenable to standardization.  The limitations of current testing 
methods underscore the unmet need for a rapid, sensitive, and specific test that may indicate 
present or past infection with SARS-CoV-2 and potentially predict protective immunity. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 26 of 86
Discovered in 1882 by Robert Koch, the delayed hypersensitivity skin test has been used for more 
than a century as a clinical test for cell-mediated immune reactions (Black, 1999). In the 1940s, 
Landsteiner and Chase proved that the reaction was mediated by the cellular and not the humoral 
arm of the immune system (Landsteiner and Chase, 1940). When small quantities of antigen are 
injected dermally, a hallmark response is elicited which includes induration, swelling and 
monocytic infiltration into the site of the lesion within 24 to 72 hours. This reaction has been shown 
to be absolutely dependent on the presence of memory T cells. Both the cluster of differentiation 
(CD)4+ and CD8+ fractions of cells have been shown to modulate a response.  
The delayed type hypersensitivity (DTH) skin tests have been commonly used to detect cell-
mediated immune responses to tuberculosis, fungal pathogens, and mumps virus. A skin test’s 
potential to be predictive of the quality and durability of immune responses, or 
infection/re-infection risk, or aid in diagnosis of current or previous infection could provide a 
method of testing for cellular immune response comparable to the rapid, reliable and scalable 
antibody tests that currently exist. Because both antibody-mediated and cellular-mediated immune 
responses are important to protection against the virus, having a fast, reliable and scalable test for 
cellular immunity is critical.  
Currently there is no standardized laboratory test available to measure T cell immune responses to 
CoV-2. T cell immunity to CoV-2 persists longer than antibody immunity, is sometimes present 
in the absence of a measurable antibody response and is believed to provide an important element 
of protection against serious illness after infection with SARS-CoV-2.  
TNX-2100 skin test is designed to measure T cell immunity to SARS-CoV-2 and uses peptide 
antigens presented in sterile solution administered intradermally. It is based on DTH reactions 
elicited after approximately 48 hours in individuals with preexisting T cell immunity to peptides 
in that mixture. The skin test comprises three different mixtures of synthetic peptides, which are 
designed to represent different protein components of the SARS-CoV-2 virus. Individuals who 
have been infected by or exposed to CoV-2 would be expected to respond to one or more of the 
three mixtures. 
The TNX-2100 skin test will complement the limited information that can be obtained from 
serological tests to provide clinicians, patients, employers and public health officials with 
information of potential diagnostic, safety and predictive significance in a timely and cost-effective 
manner. It has utility as a potential biomarker for cellular immunity and protective immunity, a 
method to stratify participants in COVID-19 vaccine trials, an endpoint in COVID-19 vaccine 
trials, a biomarker of durability of vaccines, and as a method to identify vaccine failure. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 27 of 86
5.3. 
Scientific Rationale 
Studies of immune responses to the SARS-CoV-2 virus involve antibody-mediated and cellular 
components. However, there is considerable individual variation in the pattern of these responses
(Wolfel et al., 2020; Ni et al., 2020, Wen et al., 2020). Both appear to be necessary for the 
development of protective immunity, but their relative contributions are subjects of intense 
investigation. Effective vaccines that confer long-term immunity are likely to require both 
components of the immune response. 
At present, assays for the detection and quantification of SARS-CoV-2-specific antibodies are in 
wide clinical use and have been scaled up to meet the needs of public health efforts on an 
international level. However, no comparable methodology exists to measure cell-mediated 
immunity. Cellular responses are currently measured in highly specialized laboratories using in 
vitro techniques to detect cytokine production following antigenic challenge. Such approaches 
measure surrogate markers of T cell reactivity that may not reflect functional in vivo immunity. In 
addition, these assays are expensive, time-consuming, and impossible to scale up for public health 
application.  
Tonix Pharmaceuticals Inc. (hereafter referred to as the Sponsor) proposes to develop a scalable 
skin test (TNX-2100) based on the DTH reaction to demonstrate the presence of functional cell 
mediated immune responses to SARS-CoV-2.  
The DTH skin test has long been the gold standard in the detection of cell-mediated immune 
responses. The general mechanism of the DTH response is based on the interaction of antigen with 
CD4+ and CD8+ lymphocytes followed by the secretion of interleukins and other lymphokines 
from macrophage cells. The release of effector molecules causes endothelial cells lining the blood 
vessels to become permeable and allows fibrinogen to escape into the surrounding tissue where it 
is converted to fibrin. The deposition of fibrin and the accumulation of T-cells and monocytes 
within the extracellular spaces cause the tissue to swell and become indurated. This process is 
usually detectable in 18 hours and peaks at 48 hours (Zweiman, 1998). 
Recently, a study of DTH skin test in 51 subjects with history of SARS-Cov-2 infection was 
conducted (Barrios et al., 2021a). Using intradermal injections of recombinant SARS-Cov-2 Spike 
protein (and a Candida Albicans control), subjects were followed over 48 hours for development 
of skin induration at the injection site. Forty-three of the subjects had positive reactions at 48 hours. 
The 14 control subjects with no history of SARS-Cov-2 showed no reactivity to the Spike protein. 
Analysis of anti-receptor binding domain (RBD) IgG in the exposed subjects showed an 84.3% 
concordance with skin DTH results. A second study of DTH response to SARS-Cov-2 Spike 
protein was conducted pre- and post-vaccination of 28 subjects with 12 BNT162b2 mRNA (Pfizer) 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 28 of 86
vaccine (Barrios et al., 2021b). Eight of eleven subjects tested after a single dose of vaccine showed 
a positive DTH skin response. Twenty-eight of 28 subjects tested after two doses showed positive 
DTH skin reactions 14 days after the second vaccine dose. All subjects developed anti-RBD IgG 
antibodies.  
The development of a DTH test for SARS-CoV-2 would provide clinicians with a straightforward 
way of evaluating the presence of functional cell-mediated immunity in patients with 
SARS-CoV-2. This information could assist in the diagnosis and clinical management of 
COVID-19 and help to evaluate the quality and durability of immune responses in recovering or 
convalescent SARS-CoV-2 patients.  
The TNX-2100 skin test will be based on DTH reactions elicited using three sets of peptide 
antigens presented in sterile solution (TNX-2110, TNX-2120 and TNX-2130), which are designed 
to represent different protein components of the SARS-CoV-2 virus.  
The TNX-2100 skin test is designed to be administered intradermally in the same way as skin tests 
for tuberculosis, or TB, sold as Tubersol® or Aplisol® or generically as the Mantoux tuberculin 
purified protein derivative (PPD) test. Each of these three synthetic peptides is expected to be 
administered as part of the same procedure, at separate locations on the forearm, and each is 
expected to elicit a DTH response after approximately 48 hours in individuals with pre-existing T 
cell immunity to peptides in that mixture. Individuals who have been infected by or exposed to 
SARS-CoV-2 would be expected to respond to one or more of these peptide mixtures. 
The TNX-2100 skin test can easily be deployed in vaccine trials and large-scale public health 
efforts because it is easily utilized in large number of people and there are no requirements for 
complex laboratories, cold chain logistics etc. It is expected to provide clinicians, patients, 
employers and public health officials with information of potential diagnostic, safety and 
predictive significance in a timely and cost-effective manner, including the durability of immune 
responses. 
The mixture of synthetic peptides that demonstrates optimal reactivity at the optimized dilution 
will be carried forward into a larger confirmatory study consisting of infected and uninfected 
subjects with the aim of implementing the optimized skin test within a late-phase vaccine trial for 
SARS-CoV-2. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 29 of 86
5.4. 
Risk-benefit Assessment  
The protocol has been designed to minimize the risk to research participants. Subjects will be 
monitored to detect adverse events (AEs) during the study and followed appropriately to ensure 
resolution of AEs.  
Peptide-based products do not need in vitro culture, making them biologically safe, and their 
selectivity allows accurate activation of immune responses. 
The skin test by intradermal injection is quick and virtually painless. The amount of allergen 
introduced into the skin is so small that a serious reaction is very unlikely. However, immediate 
hypersensitivity, to include severe systemic reactions, may occur following administration of skin 
test antigens. Medications and equipment (crash cart and adrenaline auto-injectors e.g. EpiPen, 
Jext or Emerade) to manage possible anaphylactic reactions will be available for immediate use. 
All investigative site staff will be trained in identifying anaphylaxis and a medically licensed 
professional trained in the clinical management of anaphylaxis will be present at the skin test 
administration visit (Visit 1, Day 1) for the duration of Stages 1 and 2. Subjects will be observed 
for a minimum of 30 minutes following administration to assess for adverse reactions. 
Venipuncture to obtain blood samples of peripheral blood mononuclear cells (PBMCs) may be 
associated with discomfort. It is very rare for a blood test to result in serious complications; 
however, there is a very small possibility of complications arising (infection, excessive bleeding, 
mild bruising or hematoma and fainting/ dizziness). 
The risk-benefit profile of the TNX-2100 skin test is considered to be acceptable for further 
evaluation and adequate monitoring of safety has been implemented into this protocol. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 30 of 86
6. 
TRIAL OBJECTIVES 
6.1. 
Primary Objectives 
The main objectives of the study are to evaluate the safety of intradermally-injected synthesized 
TNX-2100 SARS-CoV-2 peptide antigens and to assess the presence of DTH reactions in response 
to intradermal injection of synthesized TNX-2100 SARS-CoV-2 peptide antigens. 
6.2. 
Secondary Objectives 
The secondary objectives are: 
 To estimate sensitivity and specificity of TNX-2100 as a marker of recovered 
infection relative to clinical history of infection.  
 To identify the optimal synthesized SARS-CoV-2 peptide antigens and concentration 
for sensitive and specific DTH reaction.  
 To identify the optimal timepoint for assessment of the DTH reaction.  
 To correlate the DTH reaction with the adaptive T-cell immune response to 
SARS-CoV-2. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 31 of 86
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is a Proof-of-Concept (POC), dose finding, multi-cohort study designed to evaluate the 
safety of intradermally-injected synthesized TNX-2100 SARS-CoV-2 peptide antigens and 
assess the presence of DTH reactions in response to intradermal injection of synthesized 
TNX-2100 SARS-CoV-2 peptide antigens. This study is to be conducted in a total of 
approximately 90 subjects (30 subjects per cohort) who are either uninfected/unexposed healthy 
individuals (Cohort 1), who are confirmed to have recovered from SARS-CoV-2 infection 
independent of vaccination status (Cohort 2) or who have received a complete SARS-CoV-2 
vaccine course with no known history of natural infection (Cohort 3). The study will be 
conducted at 1-3 investigational sites in the United States.  
The study Schedule of Activities will consist of a Baseline/Skin Test Administration at Visit 1 
(Day 1) at which time baseline assessments are to be completed, the skin test is performed, and 
appropriate test samples are collected. Follow-up visits to monitor safety and evaluate the 
presence or absence of DTH reactions will be conducted per the following schedule: Visit 2 
(Day 2); Visit 3 (Day 3); Visit 4 (Day 4); Visit 5 (Day 5). Safety monitoring will continue at 
Visit 6 (Day 30) and Visit 7 (Day 180) by telephone calls.  
Eligible subjects who provide written informed consent and who satisfy eligibility criteria will 
undergo a nasopharyngeal swab for a polymerase chain reaction (PCR) (reverse transcriptase 
[RT]-PCR or other) test to detect active SARS-CoV-2 infection. A laboratory PCR test or a 
sponsor approved rapid PCR test (such as the Accula™ RT-PCR test) may be used. If a 
laboratory PCR test is used, subjects will complete a Screening Visit between Day -2 and Day -1 
to allow processing of the sample prior to the Baseline/Skin Test Administration Visit 1 (Day 1). 
The rapid PCR test can be performed at Visit 1 (Day 1) and is preferred to facilitate enrolment by 
reducing the number of required site visits. If the test result is negative, the subject will proceed 
with the required blood draws followed by intradermal injection of the investigational products 
(IPs) and controls. 
A total of eight vials are provided, per subject. Three of the eight vials will be the ‘undiluted’ 
TNX-2110, TNX-2120 and TNX-2130 sterile solution (2.5 µg/mL) for injection. One vial will 
be the positive control CANDIN®. The remaining four vials are Diluent containing phosphate 
buffer pH 7.0 with 0.31% polysorbate 20 and 4.6% mannitol. Of these Diluent vials, three of 
them will be labeled as ‘1:10 Dilution TNX-2110’, ‘1:10 Dilution TNX-2120’, and ‘1:10 
Dilution TNX-2130’ to represent the three “diluted” IPs. The remaining Diluent vial will be used 
as the negative control. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 32 of 86
Intradermal injections will be administered in two stages (Stage 1: “1:10 dilution” and Stage 2: 
“undiluted”) and each subject will receive a total of eight intradermal injections, spaced two
inches apart at pre-determined sites on the volar aspect of both forearms. A detailed Pharmacy 
Manual outlining the IP administration and DTH assessment process will be provided to 
investigative site staff and is included in Appendix 5. Details of the skin test administrations are 
illustrated in Sections 12.1.10 and 12.1.10, respectively.  Subjects will be contacted 24 hours 
later for a brief telephone or in-person safety follow-up visit (Visit 2, Day 2). 
Each site will have medications and equipment (eg, crash cart and adrenaline auto-injectors 
[EpiPen, Jext or Emerade]) available for immediate use to manage possible anaphylactic 
reactions (rapidly developing, life-threatening problems involving the airway [pharyngeal or 
laryngeal edema] and/or breathing [bronchospasm with tachypnoea] and/or circulation 
[hypotension and/or tachycardia] and, in most cases, associated skin and mucosal changes). All 
investigative site staff will be trained in identifying anaphylaxis and medically licensed 
professional trained in the clinical management of anaphylaxis will be present at the skin test 
administration visit (Visit 1, Day 1) for the duration of Stages 1 and 2. 
Local injection site skin reactions will be captured by a subject self-reported 7-point Likert scale 
indicating severity of: erythema (redness), pain, pruritis (itching), and swelling.
Clinically significant symptoms and other AEs will be assessed by the Investigator as defined in 
the Food and Drug Administration (FDA) guidance for industry: “Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” using 
a 4-point system (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = 
potentially life threatening). Adverse events of systemic allergic reaction will also be graded 
according to the World Allergy Organization Grading Scale for Systemic Allergic Reactions 
(Appendix 1). 
Subjects will be asked to return to the site for an Investigator’s in-person assessment of the skin 
test result at various time points starting with 48 hours post skin test administration (Visit 3, 
Day 3) followed by subsequent visits at 72 hours (Visit 4, Day 4) and at 96 hours (Visit 5, Day 5) 
post skin test administration. Photography of the injection site (volar forearms) after IP 
administration at Visit 1 and at Visit 3, 4, and 5, or unscheduled in person visit, will be used for 
safety documentation of local skin reaction, such as redness and swelling, or unexpected findings 
such as rash, blistering and necrosis, which require assessment by the designated Investigator. 
In addition, subjects will have two telephone safety follow-up visits (Visit 6, Day 30 and Visit 7, 
Day 180) and unscheduled visits may occur based on Investigator assessment and /or Sponsor 
Medical Monitor request, or as clinically indicated. 
The estimated study duration will be approximately six months.  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 33 of 86
7.2. 
Study Endpoints 
7.2.1. 
Safety Endpoints
Safety of intradermally administered TNX-2100 SARS-CoV-2 peptides, as measured by: 
 Incidence of AEs. 
o
Clinically significant symptoms and other AEs will be assessed as defined in the 
FDA Guidance for Industry: “Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (FDA, 
2007)  using a 4-point system (Grade 1 = mild, Grade 2 = moderate, Grade 3 = 
severe, and Grade 4 = potentially life threatening). 
o Adverse events of systemic allergic reaction will be graded according to the 
World Allergy Organization Grading Scale for Systemic Allergic Reactions 
(Appendix 1).
o Local skin reactions will be captured by a subject self-reported 7-point Likert 
scales indicating severity of: erythema, pain, pruritis and swelling. 
 Protocol-defined adverse events of special interest (AESI): 
o Anaphylactic reaction. 
o Enhanced disease from repeated exposure to SARS-CoV-2 (in subjects who have 
recovered from SARS-CoV-2 infection or in subjects recently vaccinated against 
SARS-CoV-2). 
7.2.2. 
Efficacy Endpoints 
The following study variables will be evaluated to assess the efficacy of intradermally 
administered TNX 2100 SARS-CoV-2 peptides: 
7.2.2.1. 
Primary Efficacy Endpoint 
 Maximal area of induration  5 mm at injection sites on the volar aspect of the forearms 
at 48 hours, 72 hours and 96 hours post skin test administration. 
7.2.2.2. 
Secondary Efficacy Endpoints
 Correlation of DTH reaction to clinical history of prior SARS-CoV-2 infection. 
 Correlation of DTH reaction to adaptive T-cell immune response to SARS-CoV-2 assessed 
by T-Detect COVID Test (Adaptive Biotechnologies). 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 34 of 86
 Correlation of DTH reaction with in vitro assays of immune response including 
SARS-CoV-2 antibody levels. 
 Characterization of Th1 and Th2 responses by measuring cytokine production and cell 
surface T-cell phenotype markers by intracellular cytokine staining. 
7.2.2.3. 
Exploratory Efficacy Endpoint 
 Characterization of Th17 response by enzyme linked immune assay.
7.3. 
Number of Subjects and Treatment Assignment 
A sufficient number of subjects will be enrolled to enable approximately 90 adult subjects to be 
enrolled in parallel into three cohorts according to the inclusion/exclusion criteria:
 Cohort 1: 30 healthy uninfected/unexposed subjects. 
 Cohort 2: 30 subjects who have recovered from SARS-CoV-2 infection at least 2 months 
prior to enrolment into the study independent of vaccination status. 
 Cohort 3: 30 subjects who have received a complete SARS-CoV-2 vaccine course at least 
four weeks prior to enrolment into the study with no known history of natural infection. 
A complete SARS-CoV-2 vaccine course is 1 dose of the Johnson & Johnson/Janssen COVID-19 
vaccine OR 2 doses of either the Moderna or Pfizer-BioNTech COVID-19 vaccine. To be eligible 
for this study, subjects must have received their final vaccination dose at least 28 days (4 weeks) 
prior to enrolment. Subjects who have received a COVID-19 vaccination booster dose are also 
eligible for enrolment if at least 28 days (4 weeks) have elapsed since administration of booster. 
 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 35 of 86
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Informed Consent 
A potential subject may be screened for eligibility only after the nature of the study, its purpose, 
and any other information relevant to the subject’s decision to participate have been explained to 
him or her and the subject has voluntarily confirmed his or her willingness to participate. Informed 
consent is documented by means of a written, signed, and dated informed consent form (ICF). 
Additional information is provided in Section 15.4. 
8.2. 
Subject Inclusion Criteria 
Subjects who meet the following criteria will be considered eligible to participate in the clinical 
study: 
Inclusion Criteria:
1. Male or female subjects aged 18 - 65 years of age, inclusive, in good general health as 
determined by medical evaluation (medical history, physical examination, vital signs, 
12-lead electrocardiogram [ECG] and clinical laboratory evaluations). 
2. Females who are not of childbearing potential (defined as at least 12 months natural 
spontaneous amenorrhea, or at least six weeks following surgical menopause) or females 
of childbearing potential who agree to comply with the contraceptive requirements of the 
protocol. 
3. Subject is willing and able to provide written informed consent prior to performing study 
procedures and be able to read and understand the study protocol. 
4. Subject understands and agrees to comply with all planned study procedures. 
5. Subject’s right and left forearms must be free of large tattoos or skin abnormalities that 
would interfere with skin test administration and assessment in the opinion of the 
Investigator. 
6. For healthy uninfected subjects (Cohort 1): Must have no history of signs or symptoms 
consistent with SARS-CoV-2 infection at any time within six months of enrollment AND 
in the Investigator’s opinion, have no known intimate exposure or close contact to persons 
confirmed positive for SARS-CoV-2 infection.  
7. For recovered subjects (Cohort 2): Must be > two months removed from confirmed 
diagnosis of SARS-CoV-2 infection independent of vaccination status.

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 36 of 86
8. For subjects who have received a SARS-CoV-2 vaccine (Cohort 3): must have received 
their final vaccination or booster dose at least four weeks prior to enrolment into the study
with no known history of natural infection. 
9. Subject receives a negative SARS-CoV-2 PCR test result at their screening or baseline 
visit. 
8.3. 
Subject Exclusion Criteria 
Subjects who meet one or more of the following criteria will not be considered eligible to 
participate in the clinical study: 
Exclusion Criteria: 
1. Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time 
through 90 days after the Screening Visit.
2. Diagnosed with clinically significant and currently relevant cardiac disease: 
o Significant arrhythmia; heart block; heart failure; symptomatic coronary artery 
disease), recent myocardial infarction [within the past 2 years]) or QTcF >450 msec 
(male) or >470 msec (female). 
3. Presence of erythema nodosum, eczema, psoriasis, or cellulitis. 
4. Treatment with systemic corticosteroids, immunosuppressive drugs or any anti-viral 
treatment within two weeks prior to Screening. 
5. History of immunosuppressive disease. 
6. Prior adverse reaction to phlebotomy. 
7. Prior adverse reaction to CANDIN® or similar material.  
8. History of hypersensitivity to the study materials used for phlebotomy (i.e., latex, rubbing 
alcohol, cotton swabs, bandaids). 
9. Documented allergic reaction to any of the excipients contained in the IP (e.g., 
polysorbate). 
10. Subjects with dermatographism.  
11. Subjects will be excluded if they have clinically significant underlying conditions 
associated with high risk for severe COVID-19 infections as identified by the Centers for 
Disease Control and Prevention (CDC) (Appendix 2). These conditions include, but are 
not limited to: chronic obstructive pulmonary disease, diabetes mellitus (Type 1 and 2), 
obesity, hypertension, heart disease, and cerebrovascular disease. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 37 of 86
o Investigators should contact the Medical Monitor with questions regarding 
clinical significance of underlying conditions. 
12. The subject has any clinically significant, uncontrolled, or unstable medical or surgical 
condition that could affect his or her ability to participate in the study or potentially 
compromise his or her well-being during the study.
13. Unable to understand the protocol requirements, instructions and study related restrictions, 
the nature, scope and possible consequences of the clinical study. 
14. Healthy uninfected subjects who have any history of SARS-CoV-2 infection by clinical 
history or laboratory diagnosis (Cohort 1 only). 
8.4. 
Restrictions 
8.4.1. 
Medication 
Medication restrictions applicable before dosing are described in Section 8.3 (exclusion criteria).
Prior medication will be recorded. 
Any medicinal product, prescribed or over-the-counter, taken by a subject other than the IPs, is 
considered concomitant medication. Any concomitant treatment will be given only if deemed 
strictly necessary by the Investigator or designee. Use of concomitant medication will be 
recorded and reported.
Subjects will be asked to report any vaccinations and/or boosters from time of study entry 
(signing of informed consent) until after study exit (early termination or completion of Visit 7, 
Day 180). 
8.4.2. 
Contraception Rules
Female subjects are allowed to participate in the study if they are:  
a) Not of childbearing potential defined as: post-menopausal (defined as at least 12 months 
natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause), or  
b) Naturally or surgically sterile (hysterectomy; bilateral oophorectomy; bilateral tubal 
ligation with surgery at least six weeks prior to study initiation).  
c) Non-pregnant, non-lactating with negative pregnancy test at the Screening Visit and who 
use at least one of the following effective contraception options: 
i. 
 90 days prior to screening and for at least 
seven days after final dose. If < 90 days prior to the study, additional use of one other 
effective contraception method until 90 days are reached is required, or 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 38 of 86
ii. 
Placement of an intrauterine device or intrauterine hormone-releasing system, or 
iii.
Use of double barrier methods of contraception (eg, male condom with diaphragm, 
male condom with cervical cap), or
iv. 
Successful male sterilization of the sole partner (subject must verbally confirm that 
appropriate post-vasectomy documentation of the absence of sperm in the ejaculate 
was provided after the procedure), or
v. 
True abstinence, when in line with the preferred and usual lifestyle of the subject. 
Note: Periodic abstinence, such as calendar, ovulation, symptothermal, post-ovulation methods, 
and withdrawal are not acceptable methods of contraception.  
8.5. 
Randomization Criteria 
Not applicable as this will be an open-label study. 
8.6. 
Subject Withdrawal Criteria 
Subjects may withdraw from the study at any time at their own request without stating the reason(s) 
for withdrawal. A subject must be withdrawn by the Investigator (or by the Sponsor via the 
Investigator) from the study if one or more of the following occur: 
 Withdrawal of consent by the subject. 
 Withdrawal of subject by the Investigator or designee if inter-current illnesses occur that may 
invalidate the study data, if the subject was enrolled in violation of the study protocol, or if a 
significant study protocol violation occurred, at the discretion of the Investigator or designee. 
 If discovered that the subject has entered the study in violation of the inclusion/exclusion 
criteria stated in the protocol. 
 Critical protocol violation occurs during the study. 
 Pregnancy during the treatment period. 
 Lost to follow-up (i.e., following at least two telephone contact attempts and 1 certified letter).  
 Investigator or the Sponsor stops the study, for any reason (e.g., suspension or discontinuation 
of study drug development). 
 Investigator, medical monitor and/or Sponsor decision for any other reason not listed above 
that may jeopardise the health and/or safety of a subject or invalidate the results of the study. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 39 of 86
A genuine effort must be made to determine the reason(s) why a subject fails to return for the 
necessary visits or is discontinued from the study. If the subject is unreachable by telephone, a 
registered letter, at the minimum, should be sent to the subject requesting him/her to contact the 
clinical unit.
8.6.1
Study Halting and Study Stopping Rules 
Dosing may be halted temporarily to investigate before the entire study is terminated. If any of the 
below events occur, enrollment and dosing should be halted study-wide pending review by the 
Sponsor, Investigator, and/or Medical Monitor. Subjects enrolled in the study must continue to be 
followed for the duration of the study. 
 One or more subjects with a serious adverse event (SAE) considered definitely, probably, 
or possibly related to the IPs. 
 Three or more subjects with the same or similar grade 3 or higher AEs of the same type 
considered definitely, probably, or possibly related to IPs. 
 One AESI, considered at least possibly related to the IPs. 
If any of these events occur, enrollment and dosing should be paused study-wide pending review 
by the Sponsor, Investigator, and/or Medical Monitor. Subjects enrolled in the study must continue 
to be followed for the duration of the study. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 40 of 86
9. 
TREATMENT OF SUBJECTS 
9.1. 
Prior and Concomitant Medications 
All prescription and over-the-counter medications used in the last three months before screening 
should be recorded at each visit (scheduled or unscheduled) in the case report form (CRF).
The use of corticosteroids, immunosuppressive drugs or any anti-viral treatment within two weeks 
prior to Screening is prohibited (see Section 8.3). 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 41 of 86
10. 
INVESTIGATIONAL PRODUCT 
10.1. 
Identity of the Investigational Products 
TNX-2100 skin test comprises of three distinct IPs named TNX-2110, TNX-2120 and TNX-2130
examined in this proposed POC study. These IPs fall into three distinct groupings based on the 
source:  
 TNX-2110 – consists of 37 individual peptides which are representative of the 
dominant SARS-CoV T cell epitopes (Grifoni et al., 2020).  
 TNX-2120 – consists of 98 individual peptides of approximately 20-mer with an 
approximate overlap of 10 amino acids. These peptides represent 1273 AA in SARS-
CoV-2 spike (NCBI Reference Sequence: YP_009724390.1).  
 TNX-2130 – consists of 16 individual peptides of approximately 20-mer with an 
approximate overlap of 10 amino acids. These peptides represent Orf3b (57 residue 
variant: Chan et al., 2020b; 57 and 22 residue variants: Konno et al., 2020) and Orf8 
(Chan et al., 2020b)  
Each IP contains 2.5 µg / mL per each peptide per vial (2 mL total volume per vial) in addition to 
compendial excipients. The IPs are provided as frozen liquid formulations containing phosphate 
buffer pH 7.0 with 0.31% polysorbate 20 and 4.6% mannitol. All IPs need to be thawed prior to 
use. 
In addition, a “Diluent” is provided for a further manual dilution of the IPs. TNX-2100 “Diluent” 
is provided as a sterile solution consisting of phosphate buffer pH 7.0 with 0.31% polysorbate 20 
and 4.6% mannitol. 
All IPs will be manufactured under current Good Manufacturing Practices as sterile solutions for 
injection. All excipients are compendial. Refer to the current Investigational Brochure for 
composition details.  
10.2. 
Study Drug Packaging, Labeling, and Storage 
IPs will be packaged and labeled according to applicable local and regulatory requirements.  
All supplies of IPs must be stored in accordance with the manufacturer’s instructions.  
The IPs will be stored in a securely locked area, accessible to authorized persons only, until needed 
for dosing. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 42 of 86
All IPs shall be stored under the following conditions: 
1. Long term storage. IP should remain frozen 
until ready to thaw on the day of Visit 1 
(Day 1). Thawed IP must not be re-frozen. 
-80 C +/- 10 C
2. After material is thawed (approximately 2-
3 hours at ambient temperature) IP should 
be stored at 2 - 8°C until ready to 
administer. Thawed material should be 
discarded if not used within 8 hours on the 
day of thawing. Thawed IP must not be re-
frozen. 
2 - 8°C (upon thawing) 
10.3. 
Preparation of Investigational Products 
A total of 7 vials containing investigational drug product are involved in the 2-stage dilution and 
skin test administration process for each subject. Three (3) of the 7 vials are the ‘undiluted’ 
TNX-2110, TNX-2120 and TNX-2130 sterile solutions (2.5 µg/mL) for injection.  
The remaining 4 vials are Diluent containing mannitol, polysorbate 20 and a phosphate buffer pH 
7.0. Of the 4 Diluent vials, label 3 of them as ‘1:10 Dilution TNX-2110’, ‘1:10 Dilution TNX-
2120’, and ‘1:10 Dilution TNX-2130’ to represent the three “diluted” IPs. The remaining Diluent 
vial will be used as the negative control.  
To prepare the “1:10 Dilution” solution, remove 222 µL from each of the “undiluted” vials of IP 
and add to the “1:10 Dilution” vial of the corresponding Diluent. Gently shake the solution for 
2 minutes to ensure adequate mixing. Repeat the same process for each of the three IP.  
Note: There is an 8th vial (in vivo positive control) involved in skin test administration, which is 
Nielsen Biosciences commercially available Candida albicans antigens (CANDIN®). Thus, is not 
considered an IP. Please refer to Section 11 and the Pharmacy Manual (Appendix 5) for further 
details. 
10.4. 
Administration of the Investigational Products  
In total, each subject will receive 8 intradermal injections (four injections per forearm), spaced two
inches apart at pre-determined sites on the volar aspect of the forearms.  
The three IPs (TNX-2110, TNX- 2120, TNX-2130) will be administered by intradermal injection 
(0.1 mL) in two concentration strengths (“1:10 dilution” and “Undiluted”).  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 43 of 86
Subjects will also receive one intradermal injection of a positive control (CANDIN®), and 
one intradermal injection (0.1 mL) of a negative control “diluent”. The three IPs (TNX-2110, 
TNX- 2120, TNX-2130) will be administered by intradermal injection (0.1 mL) in two 
concentration strengths (“1:10 dilution” and “undiluted”). 
Each vial containing IP, diluent, or CANDIN® will be limited to use of one subject. Remaining 
material will be discarded. 
A detailed Pharmacy Manual outlining the IP administration and DTH assessment process will 
be provided to investigative site staff and is included in Appendix 5. A minimum of 2 members 
of the investigative site staff will be trained to administer the IPs and controls. Training 
materials, such as the CDC video for tuberculosis skin testing methodology1, will be utilized. 
Injections will be administered as shown in Figure 1 in two stages by the order and location 
illustrated in Table 4. In total, each subject will receive 8 intradermal injections, spaced two 
inches apart at pre-determined sites on the volar aspect of each forearm. Place injections 
approximately 3 inches from the antecubital crease. 
In Stage 1 administration, subjects will receive the diluent (negative control), followed by the 
“1:10 dilution” strength of TNX-2110, TNX-2120, TNX-2130 in their left forearm, and 
CANDIN® (positive control) in their right forearm in the order and at specific locations indicated 
in Table 4 and the Pharmacy Manual (Appendix 5). Subjects will be monitored for local site 
reactions and systemic adverse reactions for 60 minutes. A photo of the injection sites (volar 
forearms) will be taken at the start of the post-administration safety monitoring period. At 30 
minutes post-administration, vital signs (systolic and diastolic blood pressure, heart rate, 
respiratory rate, and temperature) will be measured. If no systemic adverse reactions or unusual 
local site reactions per the Investigator’s judgement are observed after 60 minutes, the subjects 
will proceed to Stage 2 administrations.  
In Stage 2 administrations, subjects will receive the “undiluted” dose strength of TNX-2110, 
TNX-2120, TNX-2130 in the right forearm in the order and at specific locations indicated in 
Table 4 and the Pharmacy Manual (Appendix 5). After Stage 2 administrations, subjects will be 
monitored over the course of 30 minutes for unusual local site reactions and systemic adverse 
reactions. A photo of the injection sites (volar forearms) will be taken at the start of the post-
administration safety monitoring period. At 30 minutes post-administration, vital signs will be 
assessed. If no evidence of systemic adverse reactions or unusual local site reactions per the 
Investigator’s judgement have occurred, subjects will be free to leave the clinic and will be 
 
1 https://tools.cdc.gov/podcasts/media/mp4/Mantoux_OC mp4 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 45 of 86
11. 
CONTROLS 
Positive controls (Table 5) will used to confirm that study participants have intact T cell 
immunity and are not immunodeficient and include: 
1. CANDIN® (Candida albicans Skin Test Antigen for Cellular Immunity) will be 
administered as an in vivo positive control to assess cell-mediated hypersensitivity to 
Candida albicans. Please see the Pharmacy Manual (Appendix 5) for further details.  
2. A Tetanus Toxin Peptide Pool (TT) containing a pool of 326 overlapping peptides from a 
scan (15mers with 11 aa overlap) through Tetanus toxin (UniProt ID: P04958) of 
Clostridium tetani will be used as in vitro positive control for flow cytometry analysis 
3. PepMix™ Candida (MP65) containing a pool of 92 peptides derived from a peptide scan 
(15mers with 11 aa overlap) through Mannoprotein MP65 (Swiss-Prot ID: Q9HEP1) of 
Candida albicans, will be used as in vitro control for flow cytometry analysis.  
The negative control will contain ONLY the diluent (Table 5). The purpose of it is to rule out 
any irritant dermal response to cutaneous injection and will provide an indication of the size of 
the induration response to the negative control. 
Table 5: 
Positive and Negative Controls for TNX-CA-C201 Study 
Control
Composition 
In Vitro/ 
In Vivo 
Positive/ 
Negative 
Control 
Purpose  
Diluent  
Phosphate buffer 
pH 7.0 with 0.31% 
polysorbate 20 and 
4.6% mannitol 
In Vitro 
and  
In Vivo 
Negative 
To rule out irritant 
dermal response to 
cutaneous 
injection 
CANDIN®  
Candida albican 
antigen 
In Vivo 
Positive 
 
To confirm that 
study participants 
have intact T cell 
immunity and are 
not 
immunodeficient 
Tetanus Toxin Peptide Poola
Pool of 326 
overlapping 
peptides from a 
scan (15mers with 
11 aa overlap) 
through Tetanus 
toxin (UniProt ID: 
P04958) of 
Clostridium tetani 
(strain 
Massachusetts / 
E88) for T cell 
assays 
In Vitro  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 46 of 86
Control
Composition 
In Vitro/ 
In Vivo 
Positive/ 
Negative 
Control 
Purpose  
PepMix™ Candida b
Pool of 92 peptides 
derived from a 
peptide scan 
(15mers with 11 aa 
overlap) through 
Mannoprotein 
MP65 (Swiss-Prot 
ID: Q9HEP1) of 
Candida albicans 
(Yeast) for T cell 
assays. 
In Vitro 
 
a https://www.peptides.de/2597/tetanus-toxin-peptide-pool 
b https://shop.jpt.com/1-PepMix-trade-Peptide-Pools/6-Infectious-Disease-Antigens/10-PepMix-trade-Candida-
MP65 html 
11.1. 
Release of Clinical Study Supplies to the Investigator 
The Sponsor or the Sponsor’s designee’s standard operating procedures for releasing clinical trial 
supplies to the site will be followed. 
11.2. 
Study Drug Accountability and Reconciliation 
The Investigator or designee is responsible for maintaining accurate accountability records of the 
IPs throughout the clinical study.  
The Sponsor (or designee) will provide all study products. Study sites will acknowledge receipt of 
the IPs indicating shipment content and condition. IPs are not to be administered prior to 
confirmation from the Sponsor that the shipment temperatures were within range. Damaged 
supplies are not to be used and will be replaced. Accurate records of all IPs dispensed from and 
returned to the study site should be maintained by the site personnel. All unopened, expired, 
unused, partially used or empty materials must be accounted for and disposed, as directed by the 
Sponsor (or designee). 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 47 of 86
12. 
STUDY ASSESSMENTS AND PROCEDURES 
12.1. 
Study Assessments 
12.1.1.
Demographics
Demographic information collected during the Baseline/Skin Test Administration Visit (Visit 1) 
will include the subject’s age, gender, race and ethnicity as well as weight, height, and body mass 
index (BMI). 
12.1.2. 
Medical History 
A medical and allergy history including details regarding all illnesses, surgeries (to assess 
eligibility) must be obtained at Visit 1 and recorded in the CRF. 
12.1.3. 
Previous and Concomitant Medications 
All prescription and over-the-counter medications used in three months prior to Visit 1 should be 
recorded in the CRF. 
12.1.4. 
Physical Examination 
A complete physical examination will be performed at Visit 1. Rectal, breast, pelvic and/or 
urogenital examinations will not be performed. Height and weight are included in the Visit 1 
physical examination. 
12.1.5. 
Vital Signs 
Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and body temperature) 
will be measured at Visit 1 prior to skin test administration. Vitals will also be collected after Stage 
1 and Stage 2 skin test administrations, 30 minutes post-administration of IPs and controls. 
12.1.6. 
Pregnancy Test 
Women of childbearing potential (not menopausal, i.e., last period within the last year, or not 
surgically sterile) will have a urine pregnancy test performed at the Screening Visit (Visit 1) to 
determine/confirm their eligibility. 
12.1.7. 
PCR Test for SARS-CoV-2 
Nasopharyngeal samples will be collected from subjects to detect the presence or absence of 
SARS-CoV-2 viral RNA via PCR (reverse transcriptase [RT] or other) test. A laboratory PCR test 
or a sponsor approved rapid PCR (such as the Accula™ RT-PCR) test may be utilized. The test 
will be used as a screening tool. If a laboratory PCR test is used, subjects will complete a Screening 
Visit between Day -2 and Day -1 to allow processing of the sample prior to the Baseline/Skin Test 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 49 of 86
12.1.8.3. Enzyme-linked Immune Assay 
To characterize the Th17 response, IL-17 will be evaluated using an enzyme linked immune 
assay. 
12.1.8.4. T-Detect COVID Test
The T-Detect COVID Test is a next generation sequencing based test to aid in identifying 
individuals with an adaptive T cell immune response to SARS-CoV-2. 
The test analyzes DNA sequences from T cells to aid in identifying individuals with an adaptive 
T cell immune response to SARS-CoV-2, indicating recent or previous SARS-CoV-2 infection. 
A positive test result indicates recent or prior infection with SARS-CoV-2, while a negative test 
result indicates that a subject is unlikely to have been infected with SARS-CoV-2.  
A 4 mL whole blood sample will be collected from which T cell receptor sequencing will be 
conducted using extracted genomic DNA. 
12.1.9. 
Safety Laboratory Tests 
The laboratory tests listed in Table 7 will be measured according to the study schedule in Table 3. 
The Investigator will review the laboratory results and judge values outside of their normal range 
as clinically significant or not clinically significant. 
Table 7: 
Safety Laboratory Tests 
Safety Laboratory Test 
Descriptions 
Serum Chemistry 
Alanine aminotransferase (ALT/SGPT); albumin:globulin (A:G) ratio; 
albumin, serum; alkaline phosphatase, serum; aspartate aminotransferase 
(AST/SGOT); bilirubin, total; BUN; BUN:creatinine ratio; calcium, 
serum; carbon dioxide, total; chloride, serum; creatinine, serum; eGFR 
calculation; globulin, total; glucose, serum; potassium, serum; protein, 
total, serum; sodium, serum (LabCorp Comprehensive Metabolic Panel 
(14) TEST: 322000 CPT: 80053)  
Hematology 
Hematocrit; hemoglobin; mean corpuscular volume (MCV); mean 
corpuscular 
hemoglobin 
(MCH); 
mean 
corpuscular 
hemoglobin 
concentration (MCHC); red cell distribution width (RDW); percentage and 
absolute differential counts; platelet count (RBC); red cell count; white 
blood cell count (WBC) (LabCorpComplete Blood Count With 
Differential, TEST: 005009 CPT: 85025) 
12.1.10. 
Skin test results assessment  
Investigational products are administered in two stages at Visit 1, as described in Section 10.4. In 
Stage 1 administration, subjects will receive the diluent (negative control), followed by the “1:10 
dilution” strength of TNX-2110, TNX-2120, TNX-2130 in their left forearm, and CANDIN® 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 50 of 86
(positive control) in their right forearm. In Stage 2 administrations, subjects will receive the 
“undiluted” dose strength of TNX-2110, TNX-2120, TNX 2130 in the right forearm. The order 
and specific locations of injections are indicated in Table 4 and the Pharmacy Manual
(Appendix 5). A ballpoint pen will be used to mark the arm but also describe precise location of 
injections (i.e., start three inches from antecubital crease). 
The area of induration will be measured at injection sites on the volar aspect of each forearm 
(Figure 2). To ensure standardization, calipers will be used to ensure accurate measurement of 
induration. A member of the study team will visually inspect injection site under good light and 
measure the induration (thickening of the skin), not erythema (reddening of the skin).
Measurements will be made across two diameters. The mean of the longest and midpoint 
orthogonal diameters of the indurated area should be reported as the DTH response. For example, 
a reaction that is 10 mm (longest diameter) by 8 mm (orthogonal diameter) has a sum of 18 mm 
and a mean of 9 mm. The DTH response is therefore 9 mm. The diluent (negative control) is 
expected to elicit a negative skin test result (i.e., <5 mm), and the CANDIN (positive control) is 
expected to elicit a positive skin test result (i.e.
 mm).
A digital caliper will be used to measure the area of induration as shown in above diagram. All the 
information (e.g., date and time of test administration, injection site location, lot number of peptide
and measurement of area of induration) will be recorded in the CRF. 
Further details regarding skin test administration and measurement are provided in the Pharmacy 
Manual (Appendix 5). 
Photography of the injection site (volar forearms) after IP administration will be used for safety 
documentation of local skin reaction, such as redness and swelling, or unexpected findings such 
as rash, blistering and necrosis, which require assessment by the designated Investigator. Subject 
should lay arms flat, palms facing up. Site should photograph from above and in a well-lit area. 
Site should take photos uniformly for all subjects so that both forearms from inner elbow to wrist 
are visible. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 51 of 86
Figure 2: 
Measurement of Area of Skin Induration 
 
Ref: Ghosh et al, 2015. 
12.1.11. 
Post-injection Safety Follow-up 
Local (injection site) and systemic AEs will be evaluated 60 minutes post-Stage 1 administration 
and 30 min post-Stage 2 administration at Day 1 and at Visits 2, 3, 4 and 5; AEs will also be 
monitored at Visits 6 and 7. Subjects will also be asked to confirm that any areas of DTH reaction 
to skin test peptides (area of induration) have resolved. If in the unlikely event that visible evidence 
of the skin test exists on the subject’s forearm at Visit 6 or 7, subject will be asked to return to the 
clinic for Investigator assessment at an unscheduled visit.  
Local Adverse Events 
The injection site should be visually inspected for local reactions and observed changes should be 
measured and recorded as AEs on the CRF page. Subjects should be asked about their general 
wellbeing (i.e., not prompted by specific questions regarding symptoms and side effects) and any 
reports of pain and/or itching or any unexpected symptoms should be evaluated and recorded in 
the CRF. 
Local injection site skin reactions will be captured by subject self-reported 7-point Likert scales 
indicating severity of: erythema (redness), pain, tenderness, pruritis (itching), and swelling.
Photography of the injection site (volar forearms) after IP administration at Visit 1 and at Visit 3, 
4, and 5, or unscheduled in person visit, will be used for safety documentation of local skin 
reaction, such as redness and swelling, or unexpected findings such as rash, blistering and necrosis, 
which require assessment by the designated Investigator.
For further information with regard to AEs, please refer to Section 14. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 52 of 86
Systemic Adverse Events 
Systemic adverse events will be assessed and graded using the toxicity scales defined in the FDA 
guidance for industry (FDA, 2007). Systemic adverse events will be graded using a 4-point system 
(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life threatening). 
Any AEs of systemic allergic reaction will be graded according to the World Allergy Organization 
Grading Scale for Systemic Allergic Reactions (Appendix 1). Any reported or observed systemic 
AEs will be recorded on the systemic AE section of the CRF.
Medications and equipment (crash cart and adrenaline auto-injectors [EpiPen, Jext or Emerade]) 
to manage possible anaphylactic reactions will be available for immediate use. All investigative 
site staff will be trained in identifying anaphylaxis and a medically licensed professional trained 
in the clinical management of anaphylaxis will be present at Visit 1 for the duration of Stages 1 
and 2. 
12.2. 
Schedule of Study Procedures 
The overall and detailed schedule for study procedures and visits is provided in Table 3.  
12.2.1. 
Screening Visit (Day -2 to -1)
The Screening Visit is only required if a laboratory PCR test will be used to detect presence of 
active SARS-CoV-2 infection. The following procedures will be performed by the study 
personnel in the order given: 
 Informed Consent: Before the potential subject has undergone any study-related screening 
procedures, the nature of the TNX-CA-C201 study, and the potential risks associated with 
it, will be explained to the subject, and the subject will be given an opportunity to ask 
questions to his or her satisfaction. After the questions are answered, but before proceeding 
further, the subject must read and sign a written ICF for protocol TNX-CA-C201. The 
signed ICFs will be retained in the Investigator’s study file, and the date the subject signed 
the forms will be entered into the CRF. The subject will be provided with a copy of his or 
her signed and dated ICFs. The subject will be required to sign all updated informed 
consents.
 Perform nasopharyngeal swabbing for SARS-CoV-2 viral RNA detection via laboratory 
PCR test (note this result must be negative before proceeding to blood sample collection 
and skin test administration). 
12.2.2. 
Visit 1 (Baseline/Skin Test Administration: Day 1) 
The following procedures will be performed by study site personnel preferably in the order 
given: 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 53 of 86
 Informed Consent (if subject did not previously consent at a Screening Visit): Before the 
potential subject has undergone any study-related screening procedures, the nature of the 
TNX-CA-C201 study, and the potential risks associated with it, will be explained to the 
subject, and the subject will be given an opportunity to ask questions to his or her 
satisfaction. After the questions are answered, but before proceeding further, the subject
must read and sign a written ICF for protocol TNX-CA-C201. The signed ICFs will be 
retained in the Investigator’s study file, and the date the subject signed the forms will be 
entered into the CRF. The subject will be provided with a copy of his or her signed and 
dated ICFs. The subject will be required to sign all updated informed consents. 
 Collect the medical history; if (based on the history) all of the inclusion and none of the 
exclusion criteria are fulfilled, continue with the following assessments. 
 Subjects in Cohort 2 only. Data to be collected from each subject recovered from 
SARS-CoV-2 infection will include: 
o Information regarding where, when and what test was used to confirm  
SARS-CoV-2 infection.
o Clinical symptoms/signs preceding SARS-CoV-2 diagnosis. 
o Time from onset of clinical signs of SARS-CoV-2. 
o Maximum SARS-CoV-2 severity experienced or contact. 
o Time from onset of exposure to person with SARS-CoV-2. 
o Therapies received for SARS-CoV-2. 
o Information regarding vaccination, if applicable. 
 Determine that women of childbearing potential are using or will use highly effective 
method of contraception (i.e., double barrier method of contraception [e.g., intrauterine 
device and condom, spermicide and condom], a stable hormonal contraceptive for 
90 days prior to the study or, if <90 days, additional use of a double barrier method until 
90 days are reached, sexual abstinence or have a vasectomised partner until study 
completion). 
 Review and document prior/current medications. 
 Collect demographics. Data to be collected from each subject will include: 
o
Age; 
o
Sex; 
o
Self-reported race and ethnicity; 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 54 of 86
o Weight and height (BMI); 
o Underlying health conditions (if any); 
o Use of tobacco products or e-cigarettes (if any).
 Collect vital signs and ECG. 
 Perform physical examination.
 Perform a urine pregnancy test for women of childbearing potential; do not test 
postme
ar) or surgically sterile women. 
 Perform nasopharyngeal swabbing for SARS-CoV-2 viral RNA detection via rapid PCR 
test (note: only required for subjects who did not have a laboratory PCR test at a 
Screening Visit between Day -2 and -1. Test result must be negative before proceeding to 
blood sample collection and skin test administration). 
 Collect blood samples for: 
o T-Detect COVID Test; 
o ICS/Flow Cytometry; 
o SARS-CoV-2 antibody testing; 
o Comprehensive Metabolic Panel; 
o Complete blood count (CBC) with differential. 
 Administer each of the IPs (peptides) 1:10 diluted dose first as outlined in Stage 1 of skin 
test administration.  
 Adverse event monitoring. Subjects will be monitored for local site reactions and 
systemic adverse reactions for 60 minutes. A photo of the injection sites (volar forearms) 
will be taken at the start of the post-administration safety monitoring period. Vital signs 
(systolic and diastolic blood pressure, heart rate, respiratory rate, and body temperature) 
will be measured 30 minutes following administration of the “1:10 dilution” strength of 
TNX-2110, TNX-2120, TNX-2130, diluent (negative control) and CANDIN® (in vivo 
positive control). If no systemic adverse reactions or unusual local site reactions per the 
Investigator’s judgement are observed after 60 minutes, the subjects will proceed to Stage 
2 administration. 
 Administration of IP (peptides) “undiluted” as outlined in Stage 2 (Section 12.1.10).
 Adverse event monitoring. Subjects will be monitored over the course of 30 minutes for 
unusual local site reactions and systemic adverse reactions. A photo of the injection sites 
(volar forearms) will be taken at the start of the post-administration safety monitoring 
period. At 30 minutes post-administration, vital signs will be assessed. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 55 of 86
12.2.3. 
Visit 2 (Day 2) 
Visit 2 will occur approximately 24 hours after administration of the intradermal injection of 
peptides. Subjects will have the option of an in person visit or a remote visit (i.e., telephone). 
Subjects will be asked if they have experienced any AEs or unusual skin reactions following 
administration of the IP.  
If subjects opt for an in-person visit, photography of the injection sites (volar forearms) will be 
used for safety documentation of local site and any unexpected findings. 
12.2.4. 
Visit 3 (Day 3) 
The subject will return to the study site and the intradermal skin test will be read approximately 
48 hours after administration of the intradermal injection of peptides. The basis of reading is the 
presence or absence of induration, which may be determined by inspection (from a side view 
against the light as well as by direct light) and by palpation.  
The area of induration will be measured at injection sites on the volar forearms (Section 12.1.10). 
To ensure standardization, calipers will be used to ensure accurate measurement of induration. A 
member of the study team will visually inspect injection site under good light and measure the 
induration (thickening of the skin), not erythema (reddening of the skin). Measurements will be 
made across two diameters. The mean of the longest and midpoint orthogonal diameters of the 
indurated area should be reported as the DTH response.  
The exact measurement of the induration in millimeters (mm) should be recorded in the subjects 
CRF. 
Subjects will be asked if they have experienced any AEs or unusual skin reactions following 
administration of the investigational product. An AE occurring since the last visit will be 
documented in the subjects CRF.  
Photography of the injection sites (volar forearms) will be used for safety documentation of local 
site and any unexpected findings. 
12.2.5. 
Visit 4 (Day 4) 
Visit 4 will occur in person approximately 72 hours after administration of the intradermal 
injection of peptides to conduct a brief medical review (general health inquiry) and to document 
AEs that occurred since the last study site visit.
The area of induration will be measured at injection sites on the volar aspect of both forearms. 
Photography of the injection sites (volar forearms) will be used for safety documentation of local 
site and any unexpected findings. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 56 of 86
12.2.6. 
Visit 5 (Day 5) 
Visit 5 will occur in person approximately 96 hours after administration of the intradermal 
injection of peptides to conduct a brief medical review (general health inquiry) and to document 
AEs that occurred since the last study site visit.
The area of induration will be measured at injection sites on the volar aspect of each forearm.
Photography of the injection sites (volar forearms) will be used for safety documentation of local 
site and any unexpected findings.
12.2.7.
Visit 6 (Day 30)
Visit 6 will occur by telephone approximately 30 days (720 hours) after administration of the 
intradermal injection of peptides to conduct a brief medical review (general health inquiry) and to 
document AEs that occurred since the last study site visit.
12.2.8. 
Visit 7 (Day 180) 
Visit 7 will occur by telephone approximately 180 days after administration of the intradermal 
injection of peptides to conduct a brief medical review (general health inquiry) and to document 
AEs that occurred since the last study site visit. 
 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 57 of 86
13. 
STATISTICAL CONSIDERATIONS AND ANALYSES 
Before database lock, a detailed statistical analysis plan (SAP) will be developed and finalized, 
which will include full description of the statistical analyses and the exact definition of variables 
to be analysed.
13.1. 
Populations for Analysis 
The following analysis populations will be used during the study: 
 Safety Population: includes any subjects in Cohort 1, 2, or 3 who receive at least 1 
intradermal injection of the IPs. 
 Intent-to-Treat (ITT) Population: includes any subjects in Cohort 1, 2, or 3 who provide 
written informed consent, satisfy all inclusion/exclusion criteria, and have a negative test 
result from PCR detection of SARS-CoV-2 viral RNA.
 Modified Intent-to-Treat (mITT) Population: includes subjects from ITT who complete 
stages 1 and 2 of administration and have induration responses for at least one post skin 
test administration visit at hour 48, 72, or 96. 
13.2. 
General Considerations 
Tabulations will be produced for appropriate demographic and assay parameters. For categorical 
variables, summary tabulations of the number and percentage within each category of the 
parameter will be presented. For continuous variables, the mean, median, standard deviation, 
minimum and maximum values will be presented.  
All descriptive statistical analyses will be performed using SAS statistical software (Version 9.4 
or higher), unless otherwise noted. Medical History will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA; dictionary Version 24.0). 
13.3. 
Demographics 
Demographic characteristics (age, sex, ethnicity and race) and anthropometric characteristics 
(height, weight and BMI) will be listed by subject and summarized by cohorts using descriptive 
statistics for all subjects in the safety population. 
 Age (years) at screening as continuous summary  
 Sex
 Ethnicity 
 Race 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 58 of 86
 Weight  
 Height  
 BMI  
13.4. 
Subject Disposition 
The disposition of subjects who were enrolled (i.e., signed the ICF) in the study as well as reasons 
and the time period of discontinuation from the study and from treatment will be summarised for 
each treatment group (and overall). 
13.5.
Safety Analyses
The safety of intradermally administered TNX-2100 SARS-CoV-2 peptides will be measured as 
detailed in Section 7.2.1. All safety analyses will be conducted using the Safety Population. 
13.5.1. 
Adverse Events 
All AEs will be listed. The number and percent of subjects experiencing an event will be tabulated 
for each System Organ Class and Preferred Term. The AEs will also be tabulated according to 
severity and causality. 
For this study, AESIs are anaphylactic reactions and enhanced disease from repeated exposure to 
SARS-CoV-2 (in subjects who have recovered from SARS-CoV-2 infection or in subjects recently 
vaccinated against SARS-CoV-2).  
Serious AEs (SAE) will be listed separately. 
13.5.2. 
Clinical Laboratory Tests 
Individual data listings of laboratory results will be presented for each subject. Flags will be 
attached to values outside of the laboratory’s reference limits along with the Investigator’s 
assessment.  Clinically significant laboratory test abnormalities that were considered AEs by the 
Investigator will be presented in the AE listings. 
Clinical laboratory tests (observed values) will be summarized descriptively in tabular format.  
Shift tables will be presented for select laboratory parameters. 
13.5.3. 
Vital Signs 
Individual data listings of vital signs (observed and change from baseline) will be presented for 
each subject.  Individual clinically significant vital signs findings that were considered AEs by the 
Investigator will be presented in the AE listings. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 59 of 86
Observed values as well as change from baseline data will be summarized descriptively in tabular 
format. 
13.5.4. 
Physical Examination
Abnormal physical examination findings will be listed. 
13.6. 
Efficacy Analyses 
The efficacy analyses include primary, secondary, and exploratory endpoints as outlined in 
Section 7.2.2. Efficacy analyses will be conducted using the mITT population. 
The frequency and percentage of subjects with a maximal area of induration of 5 mm will be 
summarized within each cohort and by overall subjects.  
Cytokine and cell surface T-cell phenotype markers will be summarized descriptively within 
each cohort and by overall subjects. 
Enzyme linked immune assay parameters will be summarized descriptively by study visit within 
each cohort and by overall subjects. 
Results obtained from subjects deemed to be T-cell-specific immunodeficient will be collected, 
documented and reported, but will not be included in the analysis of the efficacy of the assay to 
detect a DTH response to SARS-CoV-2 peptides. 
13.7. 
Interim Analysis 
The skin test DTH result assessments are obtained at Visits 3, 4 and 5 (48, 72 and 96 hours post 
administration of skin test). An interim analysis will be conducted after all subjects have completed 
Visit 5 (or early terminated prior to Visit 5), and a database lock of the efficacy and safety data up 
to Visit 5 will occur. The purpose of the interim analysis will be to assess the presence of DTH 
reactions in response to intradermal injection of synthesized TNX-2100 SARS-CoV-2 peptide 
antigens, and to assess safety up to 96 hours post-administration. A full database lock will occur 
after all subjects have completed Visit 7 (or early terminated prior to Visit 7).

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 60 of 86
14. 
DEFINITIONS, RECORDING, AND REPORTING OF ADVERSE 
EVENTS 
14.1
Definition of Adverse Events 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
A treatment-emergent adverse event (TEAE) is an AE that either commenced following initiation 
of study treatment or was present prior to study treatment but increased in frequency or severity 
following initiation of study treatment. 
Other untoward events occurring in the framework of a clinical study will be recorded as AEs, 
e.g., those occurring during treatment-free periods (including Screening or post-treatment follow-
up periods; see the Schedule of Activities, Table 3) in association with study-related procedures 
and assessments, or under placebo. For study drugs, lack of efficacy may be an expected potential 
outcome and should not be reported as an AE unless the event is unusual in some way, e.g., greater 
in severity. 
Concomitant illnesses, which existed prior to entry into the clinical study, will not be considered 
AEs unless they worsen during the treatment period.  Pre-existing conditions will be recorded as 
part of the subject’s medical history. 
14.2
Adverse Event Recording 
14.2.1 
Coding the Adverse Event
Standard medical terminology should be used in describing AEs. MedDRA Version 24.0 will be 
used as the standard coding dictionary for AEs and in describing the subject’s medical history, and 
the World Health Organization (WHO) Drug Dictionary (B3 Global VMAR 2021) will be used to 
code concomitant medications. Informal descriptions should be avoided. 
14.2.2 
Severity of Adverse Event 
The severity of an AE refers to the extent of clinical abnormalities and to the extent of which an 
AE affects the subject's daily activities (Table 8, FDA Guidance for Industry; Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, 
2007). The term “severity” is used to describe the intensity of an event. This is not the same as 
“serious”. Seriousness, not severity, serves as the guide for defining regulatory reporting 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 61 of 86
obligations. The highest severity grade attained should be reported, for AEs with divergent 
severities.  
Severity will be categorized according to event category (local, systemic, other).
14.2.3 
Relationship of Adverse Events to Study Drug 
The Investigator will assess the potential relationship of the AE to study drug using the following 
descriptions. 
 Not Related: This category applies to an AE that is clearly not related to the study 
drug beyond a reasonable doubt.  That is, another cause of the event is most plausible; 
and/or a clinically plausible temporal sequence is inconsistent with the onset of the 
event and the administration of study drug and/or a causal relationship is considered 
biologically implausible. 
 Unlikely Related: This category applies to an AE that could reasonably be considered 
caused by something else, and where there is no known or expected response pattern 
to the suspected study drug. 
 Possibly Related: This category applies to an AE that follows a reasonable temporal 
sequence from administration of the study drug and that follows a known or expected 
response pattern to the suspected study drug, but that could readily have been produced 
by a number of other factors.
 Probably Related: This category applies to an AE that follows a reasonable temporal 
sequence from administration of study drug and that follows a known or expected 
response pattern to the suspected study drug. The AE could have been produced by a 
number of other factors, but the alternatives are not likely. 
 Definitely Related: This category applies to an AE that is clearly related to study drug. 
The AE follows a clear temporal sequence from administration of study drug, follows 
a known or expected response pattern to the study drug, that is confirmed by 
improvement on stopping and reappearance of the event on repeated exposure and that 
could not be reasonably explained by the known characteristics of the subject’s clinical 
state. 
14.2.4 
Local Adverse Event by 7-point Likert Scale
The subject self-reported severity of local AEs will be graded by the subject using a 7-point Likert 
scale. The scale will assess the subjects’ evaluation of severity of erythema (redness), pain, pruritis 
and swelling following the intradermal injection. 
Full details can be found in Appendix 3. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 62 of 86
14.2.5 
Toxicity Assessment Scales 
Clinically significant symptoms and other adverse events will be assessed and graded by the 
Investigator as defined in the FDA guidance for industry: “Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” using a 4-point 
system (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life 
threatening) (Table 8).  
Table 8: 
Tables for Clinical Abnormalities (FDA, 2007) 
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2)
Severe (Grade 3)
Potentially Life
Threatening 
(Grade 4) 
Fever (°C) **
(°F) **
38.0 – 38.4
100.4 – 101.1 
38.5 – 38.9
101.2 – 102.0
39.0 – 40
102.1 – 104
> 40
> 104 
Tachycardia - beats per 
minute 
101 – 115 
116 – 130 
> 130 
ER visit or 
hospitalization for 
arrhythmia
Bradycardia - beats per
minute*** 
50 – 54 
45 – 49
< 45 
ER visit or 
hospitalization for 
arrhythmia
Hypertension (systolic) -
mm Hg 
141 – 150 
151 – 155 
> 155 
ER visit or 
hospitalization for 
malignant 
hypertension
Hypertension (diastolic) -
mm Hg 
91 – 95 
96 – 100 
> 100 
ER visit or 
hospitalization for 
malignant 
hypertension
Hypotension (systolic) – 
mm Hg 
85 – 89 
80 – 84
< 80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate – breaths
per minute
17 – 20
21 – 25
> 25
Intubation
* Subject should be at rest for all vital sign measurements. 
** Oral temperature; no recent hot or cold beverages or smoking. 
*** When resting heart rate is between 60 – 100 beats per minute. Use clinical judgement when characterizing 
bradycardia among some healthy subject populations, for example, conditioned athletes. 
 
 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 63 of 86
Systemic (General) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3)
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting 
No interference
with activity or 1 – 2
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily
activity, requires 
outpatient IV
hydration
ER visit or
hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools or
< 400 gms/24 hours 
4 – 5 stools or 
400 – 800 gms/24 
hours 
6 or more watery 
stools or 
> 800gms/24 hours
or requires 
outpatient IV 
hydration
ER visit or
hospitalization 
Headache 
No interference with
activity 
Repeated use of non-
narcotic pain 
reliever > 24 hours or 
some interference 
with activity
Significant; any
use of narcotic 
pain reliever or 
prevents daily 
activity 
ER visit or
hospitalization 
Fatigue
No interference with
activity 
Some interference 
with activity 
Significant;
prevents daily 
activity 
ER visit or
hospitalization 
Myalgia 
No interference with
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or
hospitalization 
Illness or clinical adverse
event (as defined 
according to applicable 
regulations) 
No interference with
activity 
Some interference 
with activity not 
requiring medical 
intervention
Prevents daily
activity and 
requires medical 
intervention 
ER visit or
hospitalization 
Local AEs will be graded as described in Section 14.2.4. Adverse events of systemic allergic 
reaction will be graded according to the World Allergy Organization Grading Scale for Systemic 
Allergic Reactions (see Appendix 1). 
14.2.6
Adverse Events of Special Interest
In consideration of the limited safety data available on prior skin test studies, two specific AESIs 
have been identified:
 Anaphylactic reaction (Appendix 4). 
Enhanced disease from repeated exposure to SARS-CoV-2 (in subjects who have 
recovered from SARS-CoV-2 infection or in subjects recently vaccinated against 
SARS-CoV-2). 
Adverse events of special interest are events of scientific and medical interest specific to the further 
understanding of the TNX-2100 skin test. Investigators are advised to monitor subjects carefully
for potential development of these adverse events as well as other adverse events (eg. local site 
reaction) and are required to have the appropriate safety equipment on site (crash cart and 
adrenaline auto-injectors [EpiPen, Jext or Emerade]). All investigative site staff will be trained in 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 64 of 86
identifying anaphylaxis and a medically licensed professional trained in the clinical management 
of anaphylaxis will be present at the skin test administration visit (Visit 1, Day 1) for the duration 
of Stages 1 and 2. Investigators are required to communicate such events immediately to the 
Sponsor. An AESI can be serious or non-serious. All AESIs should be entered in the Electronic 
Data Capture (EDC) within 24 hours of reported onset and will be recorded in the CRF. Serious 
AESIs will be recorded and reported as per Section 14.3.1. 
14.3 Serious Adverse Events and Serious Adverse Drug Reactions 
A serious adverse event (SAE; experience) or reaction is any untoward medical occurrence that, 
at any dose:
Results in death;
Is life-threatening;
Requires in-patient hospitalization or prolongation of existing hospitalization;
 Results in persistent or significant disability/incapacity; 
 Is a congenital anomaly/birth defect, or; 
 Is an important medical event. 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event.  It does not refer to an event that hypothetically 
might have caused death if it were more severe. 
14.3.1 Reporting of Serious Adverse Events 
The investigative site is required to report any SAE within 24 hours of becoming aware of the 
event, directly to Premier PV using the contact information provided in the protocol. Premier PV 
will confirm the receipt of any formally submitted information regarding a reportable event to 
the sender within one business day by email. Premier Pharmacovigilance will document and 
archive the appropriate receipt confirmation sent to the sender. 
Events that are subject to immediate notification (within 24 hours of knowledge by any 
investigational site personnel) include the following:  
 Serious AE (whether or not deemed drug-related or expected); 
 AESI as specified in the protocol, i.e., anaphylactic reaction, and enhanced disease 
from repeated exposure to SARS-CoV-2 (in subjects who have recovered from 
SARS-CoV-2 infection or in subjects recently vaccinated against SARS-CoV-2). 
Note an AESI can be serious or non-serious. (see Section 14.2.6). 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 65 of 86
 Pregnancy. 
Any SAE that occurs at any time during the study, including a clinically significantly abnormal 
laboratory test result that is considered serious, must be reported to the Sponsor or its designee(s) 
so that the Sponsor may comply with regulatory obligations.  If the SAE is life-threatening or 
fatal, it must be reported to the Sponsor or its designee(s) immediately, by facsimile and 
telephone.  For these and all other SAEs, an SAE report form must be completed and sent by 
facsimile or email to the Sponsor or its designee(s) within 1 working day of the site’s initial 
awareness of the event. These requirements apply equally to all subjects, regardless of the study 
phase or the at-risk subject’s treatment assignment or dosage. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above.  These should also 
usually be considered serious.  Examples of such events are intensive treatment in an emergency 
room, anaphylaxis requiring respiratory support, blistering, rash, or necrosis.  
All SAEs have to be reported, whether or not considered causally related to the investigational 
product, or to the study procedure(s).  All SAEs will be recorded in the CRF.  
Any death occurring during the study, during the per-protocol follow-up period, or reported to the 
Investigator after study participation (no required post-study time limit) must be reported to the 
Sponsor or its designee(s) immediately, whether or not it is considered treatment-related.   
If any SAE occurs in the course of the study, then Investigators or other site personnel inform the 
Premier PV team and Tonix Medical Monitor within 24 hours of becoming aware of the event. 
Initial SAE reports must be followed by detailed descriptions. These should include copies of 
hospital case records and other documents when requested. Telephone and e-mail reports must be 
confirmed promptly either by facsimile or by email.   
For reporting SAEs, the Sponsor’s designated Medical Monitor should be called, and the relevant 
forms submitted to Premier Pharmacovigilance Department within 24 hours of the site’s awareness 
of the SAE.  
The contact information for the Medical Monitor is as follows: 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 66 of 86
The Investigator, or the Sponsor or designee in the case of a central Institutional Review Board 
(IRB), also must notify the IRB of the occurrence of the SAE, in writing, as soon as is 
practicable and in accordance with local law. A copy of this notification must be provided to the 
Sponsor or its designee. 
In the event of an SAE that meets the criteria for expedited reporting, an investigational new drug 
(IND) Safety Report will be prepared for submission to the FDA. Emergency unblinding is not 
applicable as this is an open label study. 
14.4
Pregnancy
Subjects found to be pregnant at the Baseline/Skin Test Administration Visit will be discontinued 
from study participation prior to drawing blood samples and administering IP.  
Subjects who become pregnant within 30 days of IP administration should be discontinued from 
the study and followed until birth or any pregnancy termination. If a pregnancy is reported within 
the 30 days, the investigator should inform the Sponsor within 24 hours of learning of the 
pregnancy. Abnormal pregnancy outcomes (e.g., spontaneous abortion beyond first trimester, fetal 
death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs.  
If a pregnancy is reported during the study, the investigator should send email the SAE Pregnancy 
Report Form to 
  within 1 day of learning of the pregnancy. If 
e-mail is unsuccessful, 
  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 67 of 86
15 
ETHICAL CONSIDERATIONS 
15.2 Ethical Conduct of the Study 
This protocol is written in accordance with the principles established by the 18th World Medical 
Assembly General Assembly (Helsinki, 1964) and amendments and clarifications adopted by 
subsequent General Assemblies. The Investigator will make sure that the study described in this 
protocol is conducted in full conformance with those principles, the protocol, current FDA 
regulations, ICH Good Clinical Practices (GCP) guidelines, Good Laboratory Practices (GLP) 
guidelines, local ethical and regulatory requirements, including the Federal Food, Drug and
Cosmetic Act, US applicable Code of Federal Regulations (title 21), any EC requirements relative 
to clinical studies. As required by the US FDA, the study drug may not be shipped to any 
participating Investigator until the requisite study documentation has been submitted to the 
Investigational New Drug Application. 
Should a conflict arise, the Investigator will follow whichever law or guideline affords the greater 
protection to the individual subject. The Investigator will also make sure he or she is thoroughly 
familiar with the appropriate administration and potential risks of administration of the study drug, 
as described in this protocol and the Investigator’s Brochure, prior to the initiation of the study. 
15.3 Institutional Review Board  
The IRB must be a properly constituted board or committee operating in accordance with 21 CFR 
Part 56, “Institutional Review Boards.” This protocol, any protocol amendments, the associated 
informed consent forms, and the informed consent procedures must be submitted to the IRB for 
review and approved before the enrollment of any subject into the trial. 
All types of subject recruitment or advertising information must be submitted to the Sponsor or its 
designee and to the IRB for review and approval prior to implementation. IRB approval of any 
protocol amendments must be received before any of the changes outlined in the amendments are 
put into effect, except when the amendment has been enacted to eliminate a potential hazard to 
study subjects. In such cases, the chair of the IRB should be notified immediately and the 
amendment forwarded to the IRB for review and approval.
15.4 Written Informed Consent 
It is the responsibility of the Investigator to obtain signed written informed consent from each 
potential study subject prior to the conduct of any screening or other study procedures. This written 
informed consent will be obtained after the methods, objectives, and potential risks of the study 
have been fully explained to the potential subject. The Investigator must explain to each subject 
that he or she is completely free to refuse to enter the study or to withdraw from it at any time.   

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 68 of 86
The subject should also be asked in the ICF for permission for the Investigator or his/her designee 
to contact the subject’s other personal physicians, as appropriate, concerning participation in the 
study. 
The method of obtaining and documenting informed consent and the contents of the ICF will 
comply with ICH GCP guidelines, the requirements of 21 CFR Part 50, “Protection of Human 
Subjects”, the Health Insurance Portability and Accountability Act (HIPAA) regulations, and all 
other applicable regulatory requirements. A properly executed written ICF shall be read, signed, 
and dated by each subject prior to entering the trial or prior to performing any study procedure.  
The original signed and dated ICF will be kept on file at the study site. Subjects will be given a 
copy of the signed ICF and will be informed of any new developments during the course of the 
study that might influence their continued participation in the study. 
The Investigator or a qualified designee will be available to answer each subject’s questions 
throughout the study, and all questions must be answered to the subject’s satisfaction. If the 
protocol is amended and a revised ICF is introduced during the study, each subject’s further 
consent must be obtained. The new version of the ICF must be approved by the IRB, prior to 
subsequently obtaining each subject’s consent. 
Receipt of written informed consent will be documented in each subject’s or potential subject’s 
CRF. The signed ICF must remain in each subject’s study file and must be available for verification 
by study monitors at all times. 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 69 of 86
16 
DATA HANDLING, RECORD KEEPING, MONITORING AND 
AUDITS 
16.2 Maintaining Privacy and Confidentiality 
In order to maintain subject privacy, all CRFs, study drug accountability records, and other 
documents, including communications between the study site and the Sponsor, will identify 
subjects only by their initials and their assigned study identification numbers. If required, the 
Investigator will grant monitors and auditors from the Sponsor or its designee and/or regulatory 
authority’s access to subjects’ original medical records for verification of the data gathered on the 
CRFs and to audit the data collection process. Subjects’ confidentiality will be maintained and will 
not be made publicly available unless mandated by applicable laws and regulations. 
16.3 Maintaining Essential Clinical Documents 
Study site files for the retention of regulatory documents will be established at the beginning of 
the study, maintained for the duration of the study, and retained according to FDA and ICH/GCP 
guidelines and applicable regulatory requirements.  The records maintained must be adequate to 
fully document appropriate protection of study subjects, the validity of the study, the integrity of 
the data, and the manner in which the study was conducted. 
The Investigator’s site file, copies of protocols, CRFs, originals of test result reports, drug 
disposition logs, correspondence, records of written informed consent, and other documents 
pertaining to the conduct of the study must be kept on file by the Investigator and in readily 
accessible order for at least 2 years after the last approval of a marketing application, until at least 
2 years have elapsed after formal discontinuation of the clinical development of the investigational 
product, or according to local regulatory requirements. No study document may be destroyed 
without prior written consent from the Sponsor or its designee.  Should the Investigator wish to 
withdraw from the responsibility of keeping the study records, custody must be transferred to a 
person willing to accept the responsibility. The Sponsor must be notified in writing in advance if 
a custodial change is to occur. It is important that the Investigator remain ready to provide 
background information from the archived study records on request. 
The Sponsor or designee will maintain adequate study records for at least two years after the last 
approval of a marketing application or for at least two years after clinical development of the study 
drug for the indication being studied has been discontinued. After that period, the sponsor will be 
contacted to determine whether the study records will be forwarded to the Sponsor, destroyed, or 
kept at the location of the designee or another facility for a longer period of time. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 70 of 86
16.4 Data Handling 
Unless otherwise specified, procedures, data collection and evaluation will be conducted as per the 
Standard Operating Procedures of the contract research organization (CRO).  The Investigator will 
assume the responsibility of ensuring the completeness and accuracy of the clinical data.  All data 
will be verified for quality control and will also be subject to audits from the Sponsor or designee 
to ensure quality. 
All laboratory results will be analyzed by an accredited and licensed clinical laboratory facility.  
Clinical laboratory data will be transferred from the central laboratory to the clinical database 
maintained by the CRO using systems which are validated and Part 11-compliant.
The responsible clinical study monitor(s) will check data at the monitoring visits to the clinical 
study site.  The Investigator will ensure that the data collected are accurate, complete, and legible.  
Any changes made to the clinical data will be documented with a full audit trail.
Aspects of the clinical and statistical phases of the study, including all associated documentation 
may be reviewed by the Quality Assurance Unit of the contract research organization using a risk-
assessment approach. The final clinical and statistical report will be audited to ensure that, as far 
as can be reasonably established, the methods described and the results reported accurately reflect 
the raw data generated during the study. 
16.5 Case Report Forms 
The Investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the study for each study subject. Data must 
be recorded on CRFs approved by the Sponsor or its designee. Data (including AEs) will be 
recorded on raw data sheets and/or electronic or paper source documents. 
If selected data is collected via paper (subject questionnaires, etc.), the data must be entered into 
the CRF and verified that it has been transcribed correctly. 
16.6 Clinical Laboratory Certification 
A central clinical laboratory will be used to analyze all samples in this study. The Investigator
must maintain, on file, written evidence that the central clinical laboratory to be used is certified 
under the Clinical Laboratory Improvement Act or equivalent certification (depending on local 
regulations). Further, the Investigator will maintain a copy of the certification, the range of normal 
values, the effective dates for the ranges, and the units of measurement for all laboratory tests 
requested in the protocol.  If any of the laboratory measurements will be transformed and/or 
categorized in any way, a description of the procedures(s) used should be included. The 
Investigator is expected to receive these documents before the shipment of clinical supplies. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 71 of 86
16.7 Site Monitoring and the Right to Review Records 
Monitoring and auditing procedures developed by the Sponsor and/or its designee will be 
implemented to ensure compliance with FDA and ICH GCP and GLP guidelines. 
The Sponsor’s designated representative (the monitor or auditor) will contact the Investigator and 
conduct regular visits to the clinical site.  In extenuating circumstances related to the COVID-19 
pandemic, remote monitoring will be permissible. The monitor will be expected and allowed to 
verify the Investigator’s qualifications, to inspect clinical site facilities, and to inspect study 
records, including proof of IRB review, with the stipulation that subjects confidentiality will be 
maintained in accordance with local and federal regulations, including HIPAA requirements. The 
monitor will also be responsible for confirming adherence to the study protocol, inspecting CRFs 
and source documents, and ensuring the integrity of the data. CRFs will be checked for accuracy, 
completeness, and clarity and will be cross-checked for consistency with source documents, 
including laboratory test reports and other subject records.  Instances of missing or uninterpretable 
data will be resolved in coordination with the Investigator. 
The monitor/auditor will also investigate any questions concerning adherence to regulatory 
requirements. Any administrative concerns will be clarified and followed. The monitor will 
maintain contact with the site through frequent direct communications with the study site by 
e-mail, telephone, facsimile, and mail. The Investigator and all other site personnel agree to 
cooperate fully with the monitor and will work in good faith with the monitor to resolve any and 
all questions raised and difficulties detected by the monitor.
16.8 Audits and Inspections 
The Investigator understands that regulatory authorities, the IRB, and/or the Sponsor or their 
designees have the right to access all CRFs, source documents, and other study documentation for 
on-site audit or inspection and will retain this right from the start of the study to at least two years 
after the last approval of a marketing application or for at least two years after clinical development 
of the study drug for the indication being studied has been discontinued. The Investigator is 
required to guarantee access to these documents and to cooperate with and support such audits and 
inspections. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 72 of 86
17 
CONFIDENTIALITY 
17.2 Protection of Subject Anonymity 
The Investigator must make sure that each subject’s anonymity is maintained. On CRFs or other 
documents submitted to the Sponsor or its agent, subjects should not be identified by their names, 
but rather by their initials and the assigned study identification numbers. The Investigator should 
keep a separate record of the subject initials, randomization codes, subject names, address, and 
contact information. Documents that contain the names associated with these initials and codes are 
not for submission to the Sponsor or its agents (e.g., written informed consent forms). These 
records should be maintained by the Investigator in strict confidence except to the extent necessary 
to allow auditing by regulatory authorities, the Sponsor, or its agents. These records should be kept 
in compliance with HIPAA regulations. 
17.3 Confidentiality of Study Information 
All information relevant to this study, whether supplied by the Sponsor or its agents to the 
Investigator or collected by the Investigator in support of this study, is privileged and confidential.  
The Investigator agrees to use this information to carry out the study and will not use it for other 
purposes without written consent from the Sponsor.  It is understood that the Investigator is under 
obligation to provide the Sponsor with all data obtained during the study. The information obtained 
from this study will be used by the Sponsor towards the clinical development of the indicated 
investigational drug and may be disclosed by the Sponsor to regulatory authorities, other 
Investigators, corporate partners, or consultants as required. 
17.4 Publication of Data and Protection of Trade Secrets 
No presentations, abstracts (including meeting abstracts), or other publications based on the 
conduct or results of this study will be permitted without the express written permission of the 
Sponsor or its designated agent. All such presentations or publications will proceed only as 
collaborations between the Sponsor and the Investigators. 
If the Investigator wishes to publish the results of this study, a copy of the proposed manuscript or 
abstract (including meeting abstracts) will be provided to the Sponsor or its designee for review, 
revision, and approval at least sixty (60) days before the expected date of submission for 
publication, unless otherwise arranged with the Sponsor in writing.  This will enable the Sponsor
to protect its proprietary information and augment the publication with insights or information of 
which the Investigator may not be aware.  

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 73 of 86
Subject names and other identifiers, such as photographs or audio or video recordings, may not be 
disclosed in any publication or public forum without prior written authorization from the subjects
involved or their legal guardians.   

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 74 of 86
18 
LIST OF REFERENCES 
Black CA. Delayed type hypersensitivity: current theories with an historic perspective. Dermatol 
Online J. 1999 May;5(1):7. PMID: 10673450. 
Barrios, Y., Franco, A., Sanchez-Machin, I., Poza-Guedes, P., Gonzalez-Perez, R., & Matheu, V. 
(2021a). A novel application of delayed-type hypersensitivity reaction to measure cellular 
immune response in SARS-CoV-2 exposed individuals. Clinical Immunology, 226, 108730. 
Barrios, Y., Franco, A., Sánchez-Machín, I., Poza-Guedes, P., González-Pérez, R., & Matheu, V. 
(2021b). The Beauty of Simplicity: Delayed-Type Hypersensitivity Reaction to Measure Cellular 
Immune Responses in RNA-SARS-CoV-2 Vaccinated Individuals. Vaccines, 9(6), 575. 
Chan KW, Wong VT, Tang SCW. COVID-19: An Update on the Epidemiological, Clinical, 
Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine 
for the Management of 2019 Novel Coronavirus Disease. Am J Chin Med. 2020a;48(3):737-762. 
doi:10.1142/S0192415X20500378. 
Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 
2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after 
visiting Wuhan. Emerg Microbes Infect. 2020(b) Jan 28;9(1):221-236. doi: 
10.1080/22221751.2020.1719902. Erratum in: Emerg Microbes Infect. 2020 Dec;9(1):540. 
PMID: 31987001; PMCID: PMC7067204. 
Chen J, Qi T, Liu L, et al. Clinical progression of patients with COVID-19 in Shanghai, China. J 
Infect. 2020;80(5):e1-e6. doi:10.1016/j.jinf.2020.03.004. 
Cox LS, Sanchez-Borges M, Lockey RF. World Allergy Organization Systemic Allergic 
Reaction Grading System: Is a Modification Needed? J Allergy Clin Immunol Pract. 2017 Jan-
Feb;5(1):58-62. e5. doi: 10.1016/j.jaip.2016.11.009. PMID: 28065342.
FDA. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. 2007. Available at 
https://www.fda.gov/media/73679/download.
Ghosh, P. & Bhattacharjee, Debotosh & Nasipuri, Mita. (2015). Automation in Sputum 
microscopy: A Hybrid Intelligent Techniques in Diagnostic Device Automation. IGI Global. 
Grifoni A, Sidney J, Zhang Y, et al. A Sequence Homology and Bioinformatic Approach Can 
Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell Host Microbe. 
2020;27(4):671-680.e2. doi:10.1016/j.chom.2020.03.002. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 75 of 86
Guan W.J., Ni Z.Y., Hu Y. Clinical characteristics of coronavirus disease 2019 in China 
[published online ahead of print, 2020 Feb 28] N Engl J Med. 2020 doi: 
10.1056/NEJMoa2002032. NEJMoa2002032. 
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus 
in Wuhan, China [published correction appears in Lancet. 2020 Jan 30;:]. Lancet. 
2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5. 
Landsteiner K, Chase MW. Studies on the sensitization of animals with simple chemical 
compounds : vii. Skin sensitization by intraperitoneal injections. J Exp Med. 1940;71(2):237-
245. doi:10.1084/jem.71.2.237. 
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-
infected pneumonia. N Engl J Med. 2020. 10.1056/NEJMoa2001316. 
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, 
Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan 
J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. 
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus 
origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-
6736(20)30251-8. Epub 2020 Jan 30. PMID: 32007145; PMCID: PMC7159086. 
Konno Y, Kimura I, Uriu K, Fukushi M, Irie T, Koyanagi Y, Sauter D, Gifford RJ; USFQ-
COVID19 Consortium, Nakagawa S, Sato K. SARS-CoV-2 ORF3b Is a Potent Interferon 
Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant. Cell Rep. 
2020 Sep 22;32(12):108185. doi: 10.1016/j.celrep.2020.108185. Epub 2020 Sep 4. PMID: 
32941788; PMCID: PMC7473339. 
Ni L, Ye F, Cheng ML, et al. Detection of SARS-CoV-2-Specific Humoral and Cellular 
Immunity in COVID-19 Convalescent Individuals. Immunity. 2020;52(6):971-977.e3. 
doi:10.1016/j.immuni.2020.04.023. 
People with Certain Medical Conditions. cdc.gov. Updated October 14, 2021. Accessed 
December 7, 2021. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-
with-medical-conditions.html.  
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report-Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
Symposium. J Allergy Clin Immunol 2006;117(2):391- 7.
Surface glycoprotein [Severe acute respiratory syndrome coronavirus 2]. NCBI Reference 
Sequence: YP_009724390.1. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 76 of 86
Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, Wang Q, Miao H. Lymphopenia 
predicts disease severity of COVID- 19: a descriptive and predictive study. Signal Transduct 
Target Ther. 2020; 5:33.
Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 
Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. 
doi:10.1001/jama.2020.1585
Wen, W., Su, W., Tang, H. et al. Immune cell profiling of COVID-19 patients in the recovery 
stage by single-cell sequencing. Cell Discov 6, 31 (2020). https://doi.org/10.1038/s41421-020-
0168-9. 
Wölfel, R., Corman, V.M., Guggemos, W. et al. Virological assessment of hospitalized patients 
with COVID-2019. Nature 581, 465–469 (2020). https://doi.org/10.1038/s41586-020-2196-x. 
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 
2019 (COVID-19) Outbreak in China: Summary of a Report of 72
Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. 
doi:10.1001/jama.2020.2648. 
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan 
F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and 
Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J 
Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24. PMID: 
31978945; PMCID: PMC7092803. 
Zweiman, B. Cell-mediated immunity in health and disease. Allergy Principles and Practices, 
Mosby, Saint Louis, Chapter 50: 696, 1998. 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 77 of 86
19 
APPENDICES 
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 78 of 86
APPENDIX 1. WORLD ALLERGY ORGANIZATION GRADING SCALE 
FOR SYSTEMIC ALLERGIC REACTIONS 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Symptom(s)/sign(s) 
of 1 organ system 
presenta 
Cutaneous 
Generalized pruritus, 
urticaria, flushing, or 
sensation of heat or 
warmthb 
or 
Angioedema (not 
laryngeal, tongue, or 
uvular) 
or 
Upper respiratory 
Rhinitis – (eg, 
sneezing, rhinorrhea, 
nasal pruritus and/or 
nasal congestion) 
or 
Throat-clearing 
(itchy throat) 
or 
Cough perceived to 
originate in the 
upper airway, not 
the lung, larynx, or 
trachea 
or 
Conjunctival 
Erythema, pruritus 
or tearing 
Other 
Nausea, metallic 
taste, or headache 
Symptom(s)/sign(s) 
of more than 1 
organ system 
present 
or 
Lower Respiratory 
Asthma, cough, 
wheezing, shortness 
of breath (eg, less 
than 40% PEF or 
FEV1 drop, 
responding to an 
inhaled 
bronchodilator) 
or 
Gastrointestinal 
Abdominal cramps, 
vomiting, or 
diarrhea 
or 
Other 
Uterine cramps 
Lower Respiratory 
Asthma (eg, 40% 
PEF or FEV1 drop 
NOT responding to 
an inhaled 
bronchodilator) 
or 
Upper Respiratory 
Laryngeal, uvula, or 
tongue edema with 
or without stridor 
Lower or upper 
respiratory 
Respiratory failure 
with or without loss 
of consciousness 
or 
Cardiovascular 
Hypotension with or 
without loss of 
consciousness 
Death 
Patients may also have a feeling of impending doom, especially in grades 2, 3, or 4. 
Note: Children with anaphylaxis seldom convey a sense of impending doom and their behavior changes may be a 
sign of anaphylaxis; eg, becoming very quiet or irritable and cranky. 
Scoring includes a suffix that denotes if and when epinephrine is or is not administered in relationship to 
onset of symptom(s)/sign(s) of the SR: a, 
 minutes; b, >5 
 minutes; c, >10 minutes to 
 minutes; d, >20 minutes; z, epinephrine not administered. 
The final grade of the reaction will not be determined until the event is over, regardless of the medication 
administered. The final report should include the first symptom(s)/sign(s) and the time of onset after the 
subcutaneous allergen immunotherapy injectionc and a suffix reflecting if and when epinephrine was or was not 
administered, eg, Grade 2a; rhinitis: 10 minutes. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 79 of 86
Final Report: Grade a-d, or z_____________  First symptom(s)/sign(s)______________ 
Time of onset of first symptom_____________________ 
Commentsd
a Each grade is based on organ system involved and severity. Organ systems are defined as cutaneous, 
conjunctival, upper respiratory, lower respiratory, gastrointestinal, cardiovascular, and other. A reaction from a 
single organ system such as cutaneous, conjunctival, or upper respiratory, but not asthma, gastrointestinal, or 
cardiovascular is classified as a grade 1. Symptom(s)/sign(s) from more than one organ system or asthma, 
gastrointestinal, or cardiovascular are classified as grades 2 or 3. Respiratory failure or hypotension with or 
without loss of consciousness define grade 4 and death grade 5. The grade is determined by the physician’s 
clinical judgement. 
b This constellation of symptoms may rapidly progress to a more severe reaction. 
c Symptoms occurring within the first minutes after the injection may be a sign of severe anaphylaxis. Mild 
symptoms may progress rapidly to severe anaphylaxis and death. 
d If signs or symptoms are not included in the table or the differentiation between a SR and vasovagal 
(vasodepressor) reaction, which may occur with any medical intervention, is difficult, please include comments, 
as appropriate.  
Source: Cox et al., 2017 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 80 of 86
APPENDIX 2. CDC UNDERLYING MEDICAL CONDITIONS 
ASSOCIATED WITH HIGHER RISK FOR SEVERE 
COVID-19 
From the Centers for Disease Control and Prevention (CDC) COVID-19 Information for People 
with Certain Medical Conditions (https://www.cdc.gov/coronavirus/2019-ncov/need-extra-
precautions/people-with-medical-conditions.html) dated 14 October 2021. 
 
This list is presented in alphabetical order and not in order of risk. 
CDC completed an evidence review process for each medical condition on this list to ensure they 
met criteria for inclusion on this list. CDC conducts ongoing reviews of additional underlying 
condition and some of these conditions might have enough evidence to be added to the list. 
As we are learning more about COVID-19 every day, this list does not include all medical 
conditions that place a person at higher risk of severe illness from COVID-19. Rare medical 
conditions, including many conditions that primarily affect children, may not be included below. 
The list will be updated as the science evolves. 
A person with a condition that is not listed may still be at greater risk of severe illness from 
COVID-19 than people of similar age who do not have the condition and should talk with their 
healthcare provider. 
 
Medical Conditions
1. Cancer 
a. Having cancer can make you more likely to get severely ill from COVID-19. 
Treatments for many types of cancer can weaken your body’s ability to fight off 
disease. At this time, based on available studies, having a history of cancer may
increase your risk.
2. Chronic kidney disease 
a. Having chronic kidney disease of any stage can make you more likely to get 
severely ill from COVID-19.
3. Chronic liver disease
a. Having chronic liver disease, such as alcohol-related liver disease, non-alcoholic 
fatty liver disease, and autoimmune hepatitis, and especially cirrhosis, or scarring 
of the liver, can make you more likely to get severely ill from COVID-19. 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 81 of 86
4. Chronic lung diseases 
a. Having chronic lung diseases can make you more likely to get severely ill from 
COVID-19. These chronic lung diseases may include: 
i. Asthma, if it’s moderate to severe 
ii. Bronchiectasis (thickening of the lungs airways) 
iii. Bronchopulmonary dysplasia (chronic lung disease affecting newborns) 
iv. Chronic obstructive pulmonary disease (COPD), including emphysema 
and chronic bronchitis
v. Having damaged or scarred lung tissue such as interstitial lung disease 
(including idiopathic pulmonary fibrosis) 
vi. Cystic fibrosis, with or without lung or other solid organ transplant 
vii. Pulmonary embolism (blood clot in the lungs) 
viii. Pulmonary hypertension (high blood pressure in the lungs) 
5. Dementia or other neurological conditions
a. Having neurological conditions, such as dementia, can make you more likely to 
get severely ill from COVID-19. 
6. Diabetes (type 1 or type 2) 
a. Having either type 1 or type 2 diabetes can make you more likely to get severely 
ill from COVID-19. 
7. Down syndrome 
a. Having Down syndrome can make you more likely to get severely ill from 
COVID-19. 
8. Heart conditions 
a. Having heart conditions such as heart failure, coronary artery disease, 
cardiomyopathies, and possibly high blood pressure (hypertension) can make you 
more likely to get severely ill from COVID-19. 
9. HIV infection 
a. Having HIV (Human Immunodeficiency Virus) can make you more likely to get 
severely ill.  
10. Immunocompromised state (weakened immune system) 
a. Having a weakened immune system can make you more likely to get severely ill 
from COVID-19. Many conditions and treatments can cause a person to be 
immunocompromised or have a weakened immune system. Primary 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 82 of 86
immunodeficiency is caused by genetic defects that can be inherited. Prolonged 
use of corticosteroids or other immune weakening medicines can lead to 
secondary or acquired immunodeficiency. 
11. Mental health conditions 
a. Having mood disorders, including depression, and schizophrenia spectrum 
disorders can make you more likely to get severely ill from COVID-19.
12. Overweight and obesity 
a. Overweight (defined as a body mass index 
2 but < 30 kg/m2), 
2 but < 40 kg/m2), or severe obesity (BMI of 
kg/m2), can make you more likely to get severely ill from COVID-19. The risk of 
severe COVID-19 illness increases sharply with 
13. Pregnancy 
a. Pregnant and recently pregnant people (for at least 42 days following end of 
pregnancy) are more likely to get severely ill from COVID-19 compared with 
non-pregnant people.
14. Sickle cell disease or thalassemia 
a. Having hemoglobin blood disorders like sickle cell disease (SCD) or thalassemia 
can make you more likely to get severely ill from COVID-19.
15. Smoking, current or former
a. Being a current or former cigarette smoker can make you more likely to get 
severely ill from COVID-19. If you currently smoke, quit. If you used to smoke, 
don’t start again. If you’ve never smoked, don’t start.
16. Solid organ or blood stem cell transplant 
a. Having had a solid organ or blood stem cell transplant, which includes bone 
marrow transplants, can make you more likely to get severely ill from COVID-19.
17. Stroke or cerebrovascular disease, which affects blood flow to the brain
a. Having cerebrovascular disease, such as having a stroke, can make you more 
likely to get severely ill from COVID-19. 
18. Substance use disorders
a. Having a substance use disorder (such as alcohol, opioid, or cocaine use disorder) 
can make you more likely to get severely ill from COVID-19. 
19. Tuberculosis 
a. Having tuberculosis can make you more likely to get severely ill from 
COVID-19.

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 83 of 86
APPENDIX 3. 7-POINT LIKERT SCALE 
The 7-point Likert scale is self-reported by the subject after the context of the scale, described 
below, is either read to them, or alternatively, it is read by the subjects themselves. 
Please take a few moments to think about the symptoms you have had due to your DTH Skin Test 
in the (specified time period). It is very important for us to get this information. We will be using 
it as one of the ways to identify the severity of local skin reactions.  
According to the scale below, please indicate the severity of erythema, pain, pruritis and swelling 
following the intradermal injection over the (specified time period).
1. No problem. 
2. Minimal problem (can be easily ignored without effort). 
3. Mild problem (can be easily ignored with effort). 
4. Moderate problem (cannot be ignored but does not influence my daily activities).
5. Moderately severe problem (cannot be ignored and occasionally limits my daily activities.
6. Severe problem (cannot be ignored and often limits my concentration on daily activities). 
7. Very severe problem (cannot be ignored and markedly limits my daily activities and often 
requires rest).
 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 84 of 86
APPENDIX 4. CLINICAL CRITERIA FOR DIAGNOSING 
ANAPHYLAXIS  
As detailed by Sampson et al., (2006), anaphylaxis is broadly defined as “a serious allergic reaction 
that is rapid in onset and may cause death.” Diagnostic criteria defined by the National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network during the second 
symposium on the definition and management of anaphylaxis, modified from Sampson et al. are 
as follows: 
Anaphylaxis is highly likely when any of the following three criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-
uvula) and at least one of the following:  
a. respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia).
b. reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., 
hypotonia [collapse], syncope, incontinence). 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that subject (minutes to several hours):  
a. involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula)  
b. respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
c. reduced blood pressure or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence)  
d. persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting).
3. Reduced blood pressure after exposure to known allergen for that subject (minutes to 
several hours): 
a. adult: systolic blood pressure <90 mm Hg or >30% decrease from that person’s 
baseline.
In the event of suspected anaphylaxis or severe hypersensitivity, vital signs, including oxygen 
saturation and respiration rate, will be measured. Other assessments will be performed at the 

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 85 of 86
discretion of the Investigator. As a precaution, each investigational site should have a resuscitation 
cart nearby.

Tonix Pharmaceuticals, Inc. 
Protocol No. TNX-CA-C201 
CONFIDENTIAL
Amendment 01, Final v2.0, 07 Dec 2021 
Page 86 of 86
APPENDIX 5. PHARMACY MANUAL