A Phase 1b/2 Dose Escalation Study of the Safety, Pharmacokinetics, and Efficacy of the Combination of TMB-365 and TMB-380 in HIV-1 Infected Individuals Suppressed With Combination Antiretroviral Therapy
Phase: PHASE1
Conditions: HIV-1-infection
Sponsor: TaiMed Biologics Inc.

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
I 
 
 
 
 
 
 
STUDY PROTOCOL 
 
A Phase 1b/2a Dose Escalation Study of the Safety, Pharmacokinetics, and 
Efficacy of the Combination of TMB-365 and TMB-380 in HIV-1 Infected 
Individuals Suppressed with Combination Antiretroviral Therapy 
 
 
PROTOCOL NUMBER: TMB-a21 
AMENDMENT 4 
 
 
Version: 
5.1 
Date of Protocol: 
23 JAN 2024 
Sponsor: 
TaiMed Biologics, USA Corp. 
4790 Irvine Blvd. STE 105-697 
Irvine, CA 92620 
 
 

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
II 
 
Sponsor Contact: 
YingAn Lai 
TaiMed Biologics 
4790 Irvine Blvd. STE 105-697 
Irvine, CA 92620 
Email: ylai@taimedbio.com 
Project Manager: 
Susan Denton, RN, MSN 
Westat 
1600 Research Blvd. 
Rockville, MD  20850 
Phone:  407-699-0540 
Medical Monitor: 
Martin Markowitz, M.D. 
TaiMed Biologics 
4790 Irvine Blvd. STE 105-697 
Irvine, CA 92620 
Phone: 212-448-5020, c: 917-415-6671 
Email: mm5654@cumc.columbia.edu 
Study Principal 
Investigator: 
Jacob Lalezari, MD 
Quest Clinical Research 
2300 Sutter Street, Suite #202 & #208 
San Francisco, CA 94115 
Phone: 415-353-0800 
Email: drjay@questclinical.com 
Serious Adverse 
Event Reporting: 
TaiMed Biologics 
4790 Irvine Blvd. STE 105-697 
Irvine, CA 92620 
 
Email :  pvreport@taimedbio.com 
Proprietary Notice: 
This document contains mainly unpublished data and is the sole 
property of TaiMed Biologics. Therefore, it is provided to you 
in strict confidence as an investigator, potential investigator, or 
consultant. The information may be reviewed by you, your staff, 
and your 
institutional 
review 
board/independent 
ethics 
committee. It is understood that this information will not be 
disclosed to others without written authorization from TaiMed 
Biologics, except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be 
administered. 
Ethics Statement: 
The study will be completed according to the International 
Conference on Harmonisation of Technical Requirements for 
Pharmaceuticals 
for Human 
Use 
guidelines 
Integrated 
Addendum to ICH E6(R1): Guideline for Good Clinical Practice 
E6(R2) and E2A: Clinical Safety Data Management: Definitions 
and Standards for Expedited Reporting. Compliance with this 
standard provides public assurance that the rights, safety, and 
well-being of trial participants are protected, consistent with the 
principles that have their origin in the Declaration of Helsinki.  

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
III 
 
 
INVESTIGATOR’S STATEMENT 
I agree to conduct the study as outlined in the protocol entitled, <A Phase 1b/2a dose 
escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of 
the combination of TMB-365 and TMB-380 as maintenance therapy in HIV-1 infected 
patients suppressed on combination antiretroviral therapy= in accordance with the 
guidelines and all applicable government regulations. 
 
I have read and understand all sections of the protocol, including the section on 
administrative considerations (Section 12). 
 
 
 
Principal Investigator’s Name 
 
 
Principal Investigator’s Institution 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
IV 
 
 
SPONSOR APPROVAL 
 
Approved by  
 
 
               
 
23 January 2024 
Martin Markowitz, M.D.  
Date 
Medical Director 
TaiMed Biologics 
 
 

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
V 
 
TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS ............................................................................................... 9 
ABBREVIATIONS ...................................................................................................... 17 
1 
INTRODUCTION ............................................................................................... 19 
1.1 
Background................................................................................................ 19 
1.2 
TMB-365 and TMB-380............................................................................ 19 
1.3 
Preclinical Studies ..................................................................................... 19 
1.3.1 
TMB-365...................................................................................... 19 
1.3.2 
TMB-380...................................................................................... 21 
1.3.3 
Determination of the Antiviral Activity of TMB-365/TMB-380 in 
Combination ................................................................................................. 22 
1.4 
Previous Human Experience ..................................................................... 22 
1.4.1 
TMB-365...................................................................................... 22 
1.4.2 
TMB-380...................................................................................... 24 
2 
STUDY OBJECTIVES ........................................................................................ 25 
3 
STUDY PLAN ..................................................................................................... 26 
3.1 
Overall Design ........................................................................................... 26 
3.1.1 
Sentinel Groups ............................................................................ 26 
3.1.2 
Core Group Subjects .................................................................... 27 
3.2 
Dose Selection and Rationale .................................................................... 27 
3.3 
Dose selection and rationale for the Core Group ...................................... 28 
3.3.1 
Safety ........................................................................................... 28 
3.3.2 
Pharmacokinetics/Pharmacodynamics ......................................... 28 
3.3 
Study Events and Procedures .................................................................... 30 
3.4 
Safety Assessments .................................................................................... 37 
3.5 
Pharmacokinetic and Antiviral Assessments ............................................. 37 
3.6 
Patient Reported Outcome Measures ........................................................ 37 
4 
STUDY TREATMENT ........................................................................................ 37 
4.1 
Study Drug Dosage and Administration .................................................... 37 
4.2 
Concomitant Medications and Restrictions ............................................... 38 
4.3 
Measurement of Participant Compliance .................................................. 39 
4.4 
Study Drug Description ............................................................................. 39 
4.5 
Study Drug Packaging, Storage, and Disposal .......................................... 39 
4.6 
Study Drug Accountability ........................................................................ 40 
4.7 
Infusion Reactions ..................................................................................... 40 
5 
PARTICIPANT ENROLLMENT......................................................................... 41 
5.1 
Inclusion Criteria ....................................................................................... 41 
5.2 
Exclusion Criteria ...................................................................................... 41 
5.3 
Participant Withdrawal and Discontinuation ............................................. 42 
5.3.1 
Reasons for Withdrawal ............................................................... 42 
5.3.2 
Stopping Rules ............................................................................. 43 
5.3.3 
Handling of Withdrawals and Discontinuations .......................... 43 
5.3.4 
Replacements ............................................................................... 44 
5.3.5 
Sponsor or Regulatory Agency Termination of Study ................. 44 
6 
STUDY PROCEDURES: SENTINEL GROUPS................................................ 44 
6.1 
Pre-Screening............................................................................................. 44 
6.2 
Screening Visit ........................................................................................... 44 
6.3 
Day 0 (Study Drug Administration) .......................................................... 45 

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PROTOCOL: TMB-a21  
 
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6.4 
Pharmacokinetic Assessments for Sentinel Group Subjects...................... 47 
6.5 
Sentinel Groups Comprehensive Safety Visits: ......................................... 47 
6.6 
Early Discontinuation ................................................................................ 48 
6.7 
Unscheduled Visits .................................................................................... 48 
7 
STUDY PROCEDURES: CORE GROUPS ........................................................ 48 
7.1 
Pre-Screening............................................................................................. 48 
7.2 
Screening Visit ........................................................................................... 48 
7.3 
Day 0 (Study Drug Administration) .......................................................... 49 
7.4 
Pharmacokinetic Assessments for Core Group Subjects ........................... 50 
7.5 
Additional Infusion Schedule: Core Participants ...................................... 50 
7.6 
Early Discontinuation ................................................................................ 51 
7.7 
Unscheduled Visits .................................................................................... 51 
7.8 
Stopping Criteria........................................................................................ 51 
8 
STUDY ASSESSMENTS .................................................................................... 52 
8.1 
Activities to Be Completed........................................................................ 52 
8.1.1 
Demographic 
Data, 
Medical 
History, 
and 
Concomitant 
Medications .................................................................................................. 52 
8.1.2 
Complete Physical Examination .................................................. 52 
8.1.3 
Directed Physical Examination .................................................... 52 
8.1.4 
Vital Sign Measurements ............................................................. 53 
8.2 
Blood and Urine Samples .......................................................................... 53 
8.2.1 
Clinical Laboratory Parameters ................................................... 53 
8.2.2 
Pregnancy Testing ........................................................................ 53 
8.2.3 
HIV EIA and Confirmatory Testing ............................................. 54 
8.2.4 
HIV RNA (Viral Load) ................................................................ 54 
8.2.5 
CD4+/CD8+ Cell Count ................................................................ 54 
8.2.6 
CD4 Receptor Density and Occupancy ....................................... 54 
8.2.7 
TMB-365 and TMB-380 Concentrations ..................................... 54 
8.2.8 
Immunogenicity ........................................................................... 54 
8.2.9 
Resistance Analysis in Core Group Subjects ............................... 54 
8.2.10 
Archive Sample ............................................................................ 55 
9 
ADVERSE EVENTS ........................................................................................... 55 
9.1 
Definitions ................................................................................................. 55 
9.2 
Eliciting Adverse Event Information ......................................................... 56 
9.3 
Reporting Adverse Events ......................................................................... 56 
9.4 
Assessment of Causality ............................................................................ 57 
9.5 
Assessment of Severity.............................................................................. 57 
9.6 
Infusion Reactions ..................................................................................... 57 
9.7 
Serious Adverse Event Reporting .............................................................. 59 
9.8 
Pregnancy .................................................................................................. 59 
9.9 
Data Monitoring Committee...................................................................... 60 
10 
STATISTICAL CONSIDERATIONS ............................................................... 61 
10.1 Determination of Sample Size ................................................................... 61 
10.2 Analysis Populations ................................................................................. 61 
10.3 Study Endpoints......................................................................................... 61 
10.3.1 
Efficacy Analysis ......................................................................... 62 
10.3.2 
Safety Analysis............................................................................. 62 
10.3.3 
Pharmacokinetic and Pharmacodynamic Analyses ...................... 62 
10.3.4 
Safety Endpoints .......................................................................... 62 
10.4 Statistical Analyses .................................................................................... 63 

TAIMED BIOLOGICS 
 
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PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
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10.4.1 
Participant Accountability ............................................................ 63 
10.4.2 
Demographic and Background Characteristics ............................ 64 
10.4.3 
Concomitant Medications ............................................................ 64 
10.4.4 
Treatment Emergent Adverse Events ........................................... 64 
10.4.5 
Vital Signs .................................................................................... 64 
10.4.6 
Laboratory Determinations .......................................................... 64 
10.4.7 
Physical Examinations ................................................................. 65 
10.4.8 
Immunogenicity Testing............................................................... 65 
10.4.9 
Pharmacokinetic Variables ........................................................... 65 
10.4.10 Other Information ........................................................................ 65 
11 
DATA HANDLING AND QUALITY ASSURANCE ......................................... 65 
11.1 Case Report Forms .................................................................................... 65 
11.2 Monitoring of the Study ............................................................................ 66 
11.3 Inspection of Records ................................................................................ 66 
11.4 Study Record Retention ............................................................................. 66 
12 
ADMINISTRATIVE CONSIDERATIONS...................................................... 66 
12.1 Confidentiality ........................................................................................... 66 
12.2 Ethics Review Committee ......................................................................... 67 
12.3 Modification of the Protocol...................................................................... 67 
12.4 Informed Consent ...................................................................................... 67 
12.5 Protocol Violations and Deviations ........................................................... 68 
12.6 Study Reporting Requirements.................................................................. 68 
12.7 Financial Disclosure and Obligations ........................................................ 68 
12.8 Investigator Documentation ...................................................................... 69 
12.9 Study Conduct ........................................................................................... 69 
12.10 Publications ............................................................................................... 69 
13 
REFERENCES ................................................................................................. 70 
 
 
 

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PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
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LIST OF IN-TEXT FIGURES 
Figure 1  TMB-365-101 Single Dose Viral Load Reductions ..................................... 24 
 
LIST OF IN-TEXT TABLES 
Table 1 Pharmacokinetics Parameters of TMB-365 ................................................. 24 
Table 2 Pharmacokinetic parameters after 40 mg/kg TMB-380 IV administration 
(Mean (SD)) ................................................................................................. 25 
Table 3 Schedule of Events and Procedures for Sentinel Groups receiving 2400 mg 
or 3200 mg of TMB-365 and TMB-380 ...................................................... 30 
Table 4 Schedule of Events and Procedures for Sentinel Group receiving 4800 mg of 
TMB-365 and TMB-380 .............................................................................. 32 
Table 5 Schedule of Events and Procedures for Core Groups receiving every 8-week 
dosing ........................................................................................................... 34 
 
LIST OF APPENDICES 
Appendix A:  DAIDS Table for Grading Severity of Adult and Pediatric Adverse 
Events V. 2.1 
Appendix B: <The diagnosis and management of anaphylaxis: An updated practice 
parameter=  
Appendix C:  HIVTSQ – Treatment Satisfaction Questionnaires and User Guidelines 
 
 
 
 
 
 
 
 
 

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
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PROTOCOL SYNOPSIS 
Protocol Number: 
TMB-a21 
Title: 
A Phase 1b/2a Dose Escalation Study of the Safety, 
Pharmacokinetics, and Efficacy of the Combination of 
TMB-365 and TMB-380 in HIV-1 Infected Individuals 
Suppressed with Combination Antiretroviral Therapy 
Sponsor: 
TaiMed Biologics 
Study Phase: 
1b / 2a  
Participants and 
Investigator Sites:  
Up to 70 participants from approximately 6-8 sites in 
North America 
Study Drug, Dosage, and 
Route of Administration 
and Controls: 
The investigational products, TMB-365 and TMB-380 
are monoclonal antibodies (MAbs) to be administrated 
via intravenous (IV) infusion. Doses to be tested 
include – 2400 mg, 3200 mg and 4800 mg for each 
antibody in the Sentinel Groups of 10 subjects. 4800 
mg of each antibody will be tested every 8 weeks in a 
Core Group. If indicated by safety, PK, and efficacy, 
an amendment may be made to the current protocol to 
test higher doses of either antibody in consultation 
with the Data Monitoring Committee and the FDA. 
 There are no controls. 
Objectives: 
The primary objectives of this study are to: 
ý 
Evaluate the safety and tolerability of various 
doses and dosing regimens of IV infusions of 
TMB-365 and TMB-380 given q8wks in 
suppressed, cART treated HIV-1 infected 
participants.  
ý 
Define the pharmacokinetic (PK) profile of 
TMB-365 and TMB-380 when given q8wks  
in suppressed, cART treated HIV-1 infected 
participants  
ý 
Evaluate the antiviral activity of TMB-365 in 
combination with TMB-380 as maintenance 
therapy in suppressed HIV-infected individuals. 
(Core only) 
Exploratory objectives of this study are to: 
ý 
Determine the immunogenicity of TMB-365 
and TMB-380 in HIV-1 infected suppressed 
participants 
ý 
Determine the resistance profiles of TMB-365 
and TMB-380 in vivo. 
Study Population: 
Males and females aged between 18-70 years who are 
HIV-1 seropositive, suppressed on continuous cART 
for at least 6 months with documentation of HIV-1 

TAIMED BIOLOGICS 
 
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PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
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RNA levels below the limit of detection on at least one 
occasion within 3 months prior to screening. 
Inclusion Criteria: 
Participants must meet all of the following criteria to 
be included in the study: 
1. Male or female at least 18 years of age and no 
greater than 70 years on the day of Screening. 
2. Asymptomatic HIV-1 infection, documented by 
any licensed rapid HIV test or HIV enzyme or 
chemiluminescence immunoassay (E/CIA) test kit 
at any time prior to study entry and confirmed by 
Geenius™ or a second antibody test by a method 
other than the initial rapid HIV and/or E/CIA test, 
or by HIV-1 antigen, plasma HIV-1 RNA viral 
load at or prior to screening. 
3. 
On continuous suppressive cART for 6 months 
prior to Screening with one documented HIV-1 
RNA level below the level of detection within 3 
months of Screening. Continuous cART is defined 
as no interruptions greater than 3 consecutive 
days. cART is defined as a DHHS recommended 
regimen. Study participants should be on a stable 
regimen for at least 3 months.  
4. Screening plasma HIV-1 RNA below the limit of 
detection.  
5. CD4+ T cell count ≧350 cells/mm3 
6. Laboratory values obtained within 30 days prior to 
the first dose: 
• 
Hemoglobin ≥ 10.0 g/dL; 
• 
Platelet count ≥ 100,000/mm3; 
• 
Absolute neutrophil count ≥ 1,000/mm3; 
• 
Serum aspartate aminotransferase (AST) and 
alanine aminotransferase (ALT) < 1.5 x upper 
limit of normal (ULN); and 
• 
Creatinine clearance (CrCl) of ≥ 50 mL/min. 
7. Willing to comply with the requirements of the 
protocol and available for follow-up for the 
planned duration of the study. 
8. In the opinion of the principal investigator or 
designee, has understood the information 
provided; written informed consent needs to be 
given before any study-related procedures are 
performed.  
9. Females of childbearing potential, sexually active 
with a male sex partner, must agree to use one 
effective method of contraception from the time of 
signing the consent to completion of the study, 
and agree to pregnancy testing as per the Schedule 
of Events and Procedures. Females of 
childbearing potential are female participants who 

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PROTOCOL: TMB-a21  
 
DATE: 23 JAN 2024 
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are not surgically sterile (no history of bilateral 
tubal ligation, hysterectomy, or bilateral salpingo-
oophorectomy), are not postmenopausal (at least 
one year without menses), and are not otherwise 
sterile by medical evaluation. 
Exclusion Criteria: 
Participants having or meeting any of the following 
conditions or characteristics will be excluded from the 
study: 
1. 
Suppressed subjects who have not been on a stable 
DHHS recommended cART regimen for at least 3 
months. 
2. 
Receipt of any monoclonal antibody for the 
treatment or prevention of HIV infection except 
for receipt of TMB-365 and TMB-380 by Sentinel 
subjects eligible for enrollment into Core groups. 
3. 
Suppressed subjects receiving cabotegravir and 
rilpivirine intramuscularly as maintenance therapy 
for HIV-1 infection. 
4. 
Pregnant, planning a pregnancy during the trial 
period, or lactating.  
5. 
Known allergy/sensitivity or any hypersensitivity 
to components of the study drug or its formulation, 
or known allergy to a MAb. 
6. 
History of severe allergic reactions to medications, 
vaccinations or monoclonal antibody therapy for 
other conditions such as COVID. 
7. 
Major psychiatric illness including any history of 
schizophrenia or severe psychosis, uncontrolled 
bipolar disorder requiring acute therapy, or suicide 
attempt in the previous three years.  
8. 
Serious illness requiring systemic treatment and/or 
hospitalization within 21 days prior to the first 
dose. 
9. 
Receipt of immunomodulatory agents (e.g., 
interleukins, interferons, cyclosporine, high dose 
systemic corticosteroids), HIV vaccine, systemic 
cytotoxic chemotherapy, or investigational therapy 
within 180 days prior to the first dose. 
10. Any chronic or acute medical condition, including 
chronic Hepatitis B infection, chronic and 
Hepatitis C infection with viremia, drug use and 
alcohol abuse, which in the opinion of the 
investigator would interfere with evaluation of the 
study drug. 

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11. Lack of adequate venous access. 
12. Individuals who have experienced virologic 
failure during treatment with two or more cART 
treatment regimens and those being treated with 
regimens containing either ibalizumab, 
enfuvirtide, maraviroc, or fostemsavir. Note that 
a change in treatment regimen for intolerance 
does not meet criteria for treatment failure.  
Study Design and 
conduct: 
This is an adaptive dose-escalation study of various 
dosing regimens of TMB-365 and TMB-380 
administered intravenously to HIV-1 infected 
individuals suppressed on combination antiretroviral 
therapy (cART). 
This adaptive study design will be comprised of 
Sentinel Groups (N=10) and Core Groups (N=20).  
Study participants must be on a continuous DHHS-
recommended suppressive cART regimen for at least 6 
months and have documented viral suppression below 
the limit of detection within the 3 months prior to 
Screening. Study participants should be on a stable 
regimen for at least 3 months. Switches of components 
of regimens may be allowed for intolerance and other 
adverse events, both anticipated and unanticipated.  
Sentinel Groups: 
Sentinel Groups will be comprised of 10 cART 
suppressed HIV-1 infected volunteers who receive a 
single IV dose of the combination of TMB-365 and 
TMB-380 while continuing cART.  
Sentinel group dosing:  
Single intravenous doses of 2400 mg, 3200 mg, 4800 
mg of each antibody. 
Sentinel group dose escalation:  
1. Sentinel group 1 will dose both antibodies at 
2400 mg. Sentinel group 2 will dose both 
antibodies at 3200 mg. The third sentinel group 
will dose both antibodies at 4800 mg. 
2. An independent Data Monitoring Committee 
(DMC) will review all available 14-day post 
dose safety data for at least 7 of 10 subjects in 
a Sentinel group before a request for dose 
escalation to the next Sentinel group will be 
approved.   
 
 

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Core Groups: 
Safety and PK results obtained in Sentinel Group 
participants will inform the conduct of Core Groups.  
Core Groups will be comprised of 20 cART 
suppressed HIV-1 infected volunteers who receive 
multiple IV doses of the combination of TMB-365 and 
TMB-380 as a stand-alone maintenance regimen. 
Criteria for initiation of Core Group enrollment based 
on Sentinel group results: 
Safety: No SAEs probably or definitely due to TMB-
365/380. 
No more than one Grade 3 or 4 adverse event possibly 
or definitely due to the monoclonal antibody infusions 
within 14 days of treatment. 
PK: Target trough concentrations are achieved in 
approximately 80% of Sentinel participants at 8 
weeks. 
Asymmetric doses of TMB-365 and TMB-380 may be 
used in Core groups should safety and PK results 
support such an approach.  
Core group dosing: 
TMB-365: 4800 mg q 8 weeks (3 infusions).  
TMB-380: 4800 mg q 8 weeks (3 infusions). 
If indicated by safety, PK, and efficacy, an amendment 
may be made to the current protocol to test higher 
doses of either antibody in consultation with the Data 
Monitoring Committee and the FDA. 
Participants in the Core Groups will discontinue cART 
during antibody infusions and restart cART at Week 
24. 
If there is evidence of virologic rebound defined as 2 
consecutive HIV-1 RNA levels above 50 copies/mL at 
least 2 weeks apart in any Core subject, then oral cART 
must be restarted.  
Stopping criteria for an individual subject within a Core 
Group:  
Safety: Any SAE or Grade 3 or 4 adverse event 
probably or definitely due to the monoclonal antibody 
infusions within 14 days of treatment. 
Antiviral activity: Documented virologic failure in an 
individual. Resistance analysis including phenotype 
and genotype will be performed in subjects in whom 

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virologic failure is documented.  
 
Stopping criteria for dosing of a Core Group: 
Safety: An SAE probably or definitely due to the 
monoclonal antibody infusions. 
More than one Grade 3 or 4 adverse event probably or 
definitely due to the monoclonal antibody infusions.   
Antiviral activity: Documented virologic failure in 
more than two individuals in a Core Group who have 
received scheduled infusions of the combination of 
TMB-365 and TMB-380. Resistance analysis including 
phenotype and genotype will be performed in subjects 
in whom virologic failure is documented.  
To ensure participant safety: 
¯ All Grade 3, Grade 4, SAEs, and cases of 
virologic failure will be reviewed by the DMC. 
¯ The DMC may terminate enrollment and dosing 
in the Core Group at any time.  
 
Study duration:  
Screening period: 6 weeks/45 days – Sentinel Groups; 
8 weeks/60 days – Core Group 
Sentinel Groups: 12 to 16 weeks (4 weeks follow-up 
post infusions) 
Core Groups: 28 weeks (4 weeks follow-up post 
infusions and cART reinstitution) 
Dose escalation in the Sentinel groups will require 
approval 
of 
an 
independent 
Data 
Monitoring 
Committee based on 14-day safety data collected on 
7/10 Sentinel Group subjects. 
Initiation of a Core group will require approximately 
80% of Sentinel Group subjects at the selected dose 
level having met the safety and PK criteria.  
Toxicity evaluations will be guided by the DAIDS Table 
for Grading Severity of Adult and Pediatric Adverse 
Events Version 2.1. The Common Terminology Criteria 
for Adverse Events (CTCAE) v. 5.0 scale will be used 
for assessment of any infusion reactions, or 
anaphylactic events. 

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Safety Assessments: 
ý 
Physical examinations; 
ý 
Vital sign measurements; 
ý 
Clinical laboratory parameters (hematology, 
serum chemistry, lipid panel, and urinalysis); 
ý 
Pregnancy tests; 
ý 
Adverse events (AEs); and 
ý 
Serious adverse events (SAEs) 
Pharmacokinetic, 
Pharmacodynamic 
Antiretroviral 
Assessments and Patient 
Reported Outcomes 
Measurements: 
ý 
Quantification of TMB-365 and TMB-380 
levels at varying time points in order to 
characterize the PK profile; 
ý 
In vitro quantification of the number of CD4 
receptors and the percentage of CD4 T-cell 
receptors bound by TMB-365; 
ý 
HIV-1 RNA (viral load) assessment in Core 
subjects; 
ý 
HIVTSQs and HIVTSQc at various time points 
in Core subjects; 
Statistical 
Considerations: 
Sample Size: 
Up to 70 HIV-positive participants will be enrolled 
into the study. The sample size is not statistically 
driven. Individuals who discontinue the study for 
reasons other than adverse events may be replaced. 
Analysis Populations: 
The full analysis set (FAS) includes all participants 
who are administered any fraction of study drug. The 
PK population consists of all participants in the FAS. 
The analysis of study data will be primarily 
descriptive, with emphasis on tabular and graphical 
displays. Summary descriptive statistics will be 
calculated, along with point and interval estimates of 
solicited and unsolicited AEs. This study is 
exploratory, and any statistical inferences will be 
hypothesis generating, and not confirming. 
Statistical Analyses: 
All data collected at each visit will be summarized by 
dose group and overall where applicable. Continuous 
variables (e.g., age, weight) will be summarized using 
descriptive statistics consisting of number of 
participants, mean, standard deviation, minimum, 
median, and maximum values. Categorical variables 
(e.g., gender) will be summarized using the number 
and percentage of participants in each category. If 
there are unscheduled assessments between visits or 
repeat assessments at a visit, the one closest to the 
scheduled time of the visit will be used in the 
summaries. The association of data collected with a 
visit (i.e., whether it is scheduled, unscheduled, or a 
repeat) will be unambiguous in the Case Report Form 

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(CRF). All data collected will be included in the data 
listings. 

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ABBREVIATIONS 
ABBREVIATION 
TERM 
ADCC 
antibody-dependent cellular cytotoxicity 
ADCP 
antibody-dependent cellular phagocytosis 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase  
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase  
AUC 
area under the curve 
cART 
combination antiretroviral therapy 
CD4 
glycoprotein expressed on the surface of T-helper cells 
CD4+ 
type of white blood cell, also called T-lymphocytes, T-cells, 
or T-helper cells 
CDC 
complement dependent cytotoxicity 
Cmax 
maximum serum concentration 
CrCl 
Creatinine clearance 
CRF 
Case Report Form 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DHHS 
Department of Health and Human Services 
DLT 
dose limiting toxicity 
DMC 
Data Monitoring Committee 
EDTA 
ethylenediaminetetraacetic acid 
EI 
entry inhibitor 
ELISA 
enzyme-linked immunosorbent assay 
ERC 
ethics review committee 
FAS 
full analysis set 
FcRn 
neonatal Fc receptor 
FDA 
Food and Drug Administration 
HEENT 
head, eyes, ears, nose, throat 
HIV-1 
human immunodeficiency virus type-1 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ID 
Identification 
IgG 
immunoglobulin G 
IM 
Intramuscular 
INI 
integrase inhibitor 
IRB  
institutional review board 
IV 
Intravenous 

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ABBREVIATION 
TERM 
ADCC 
antibody-dependent cellular cytotoxicity 
ADCP 
antibody-dependent cellular phagocytosis 
Mab 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
major histocompatibility complex 
NNRTI 
non-nucleoside reverse transcriptase inhibitor 
NOAEL 
no observed adverse effect level 
NRTI 
nucleoside reverse transcriptase inhibitor 
PBMC 
peripheral blood mononuclear cell 
PCS 
potentially clinically significant 
PD 
Pharmacodynamic 
PI 
protease inhibitor 
PK 
Pharmacokinetic 
PT 
preferred term 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
Tmax 
the time taken to reach the maximum concentration 
ULN 
upper limit of normal 
US 
United States 
USP 
United States Pharmacopeia 
 
 

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1 
INTRODUCTION 
1.1 
Background 
In 2019, 38 million people worldwide were living with HIV infection and 690,000 
people died from HIV/AIDS1. Africa remains most severely affected, accounting for 
around 67% of the people living with HIV worldwide.  
Many infected patients have been successfully treated with combination antiretroviral 
therapy (cART). Patients treated with cART have experienced profound and continuous 
viral suppression, often associated with substantial immune system recovery and halt 
of progression to clinical disease.  
That said, there remain individuals with the need for novel therapies. There is interest 
in the use of long acting antiretroviral agents 2 and broadly neutralizing antibodies 
(bNAbs) to HIV and receptors required for viral entry3, 4 for both the treatment and 
prevention of HIV-1 infection. 
Long acting therapies provide advantage in that HIV-infected patients do not have the 
burden of daily pill taking. Agents given intravenously, particularly bNAbs may be 
associated with less side effects. Long acting agents may also reduce the risk of the 
emergence of resistance as oral regimes require high levels of adherence over time.  
In this study we are proposing to use the combination of 2 bNAbs, TMB-365 and TMB-
380, to maintain virologic suppression in HIV-1 infected participants suppressed on 
daily oral therapy.  
1.2 
TMB-365 and TMB-380 
TMB-365 is a second generation CD4-directed post-attachment inhibitor with the same 
binding specificity as Trogarzo® (ibalizumab), but with modifications to improve its 
stability, pharmacokinetics and drug resistance profiles. The improved breadth of 
inhibition, stability and half-life of TMB-365 make it a promising candidate for future 
use in treatment of human immunodeficiency virus type 1 (HIV-1) infections. TMB-
365 is being developed by TaiMed and the phase 1 clinical trial has been concluded.  
TMB-380 (VRC07-523LS) is a potent and broadly neutralizing monoclonal antibody 
(bNAb) directed against the CD4-binding site of the HIV-1 glycoprotein 120 (gp120). 
TMB-380 is being developed by the Vaccine Research Center (VRC), National Institute 
of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). The 
clinical experience with TMB-380 to date includes 15 clinical studies (three completed 
and 12 ongoing) conducted in the United States, the Republic of South Africa and/or 
Switzerland.5 
With different yet complementary mechanisms against HIV-1 entry, combining TMB-
365 and TMB-380 is proposed as a safe and potent non-oral maintenance therapy for 
virologically suppressed HIV-1 infected individuals on standard orally administered 
cART.  
1.3 
Preclinical Studies 
1.3.1 TMB-365 
TMB-365 is a humanized MAb and a member of an emergent class of HIV therapies 

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known as post-attachment inhibitors. It is the second generation of a US FDA approved 
HIV medicine, TROGARZO® (ibalizumab-uiyk), with an improved PK profile in 
cynomolgus monkeys 6  and broader viral strain coverage in vitro 7 , 8 . As with 
TROGARZO®, TMB-365 binds to CD4, the primary receptor for HIV infection, 
thereby interfering with virus entry9. TMB-365 preserves the sequence and binding 
specificity of the ibalizumab variable region and therefore as with the parent antibody, 
likely binds to a unique epitope in domain 2 of the extracellular portion of the CD4 
receptor and blocks HIV entry by steric hindrance after attachment10. Antibody binding 
to this epitope has also been shown to prevent viral transmission via cell-cell fusion11. 
As was shown for TROGARZO®, the TMB-365 binding site on CD4 domain 2 is likely 
to be distinct from the binding site required for interaction of CD4 with major 
histocompatibility complex (MHC) proteins, which map to CD4 domain 1. Because of 
this, TMB-365 is not expected to interfere with immunologic functions involving 
antigen presentation. 
TMB-365 incorporates modifications, relative to TROGARZO®, including an IgG1 
backbone with mutations in the Fc region to block effector functions, a glycan addition 
to the light chain variable region to improve breadth of inhibition, and amino acid 
substitutions to improve PK, including substitutions in the neonatal Fc receptor (FcRn) 
binding site and histidine substitutions in the variable region. The Fc mutations largely 
eliminate effector functions such as antibody-dependent cellular cytotoxicity (ADCC) 
and antibody-dependent cellular phagocytosis (ADCP), and complement dependent 
cytotoxicity (CDC).12 With the glycan addition to the light chain variable region, TMB-
365 has potent antiretroviral activity against diverse HIV strains, including ibalizumab-
resistant isolates, regardless of HIV subtype, coreceptor tropism, or resistance to 
approved antiretroviral agents (PI, NRTI, NNRTI, INI, and EI), including 
TROGARZO®.7, 8 Amino acid substitutions in the FcRn binding site and histidine 
substitutions in the variable region were designed to prolong the serum half-life of 
TMB-365 with enhanced recycling from acidic endosomes to plasma and reduced 
lysosomal degradation9. The pH-dependency of TMB-365 was demonstrated in vitro9 
and the prolonged half-life of TMB-365 was demonstrated in vivo as compared with 
ibalizumab. 6 
Three single dose PK studies and two repeated dose toxicity studies of intramuscular 
(IM) and IV TMB-365 have been conducted in cynomolgus monkeys.6, 13, 14, 15, 16 In 
the single dose PK studies, at the dose range of 15-150 mg/kg, the elimination half-
lives were 4.5-12.8 days and 4.4-9.1 days for IM and IV administration, respectively. 
The Tmax was one day for IM administration. The Cmax increased in approximately a 
dose proportional manner and the area under the curve (AUC) increased in a close to 
or more than dose proportional manner from 15 mg/kg to 150 mg/kg dose following 
IM and IV administration. The apparent volume of distribution was 36.6-51.4 mL/kg. 
It was less than the total body water, 0.7 L/kg, indicating that TMB-365 was mainly 
confined to the bloodstream. The bioavailability of TMB-365 following IM 
administration in monkeys was 78-88%. In the repeated dose toxicity studies, there was 
accumulation of drug in the serum, indicated by increased systemic exposure (Cmax and 
AUC). No gender differences in the systemic exposure were observed at any dose level 
for both IM and IV TMB-365. Curve fitting of paired concentration and receptor 
occupancy data suggested that TMB-365 concentrations greater than 3.9 μg/mL 
supported 85% CD4 receptor occupancy, which is expected to be associated with 
significant virologic responses and is a good indicator for efficacy. 

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In the repeated dose toxicity studies, administration of TMB-365 at doses up to 80 
mg/kg/week once weekly for total four injections by IM and IV administration to 
cynomolgus monkeys was well-tolerated and did not result in any treatment-related 
mortality or morbidity. No test article-related adverse effects were observed in terms of 
clinical signs, body weight, food consumption, ophthalmology, safety pharmacology, 
clinical pathology, and pathology. The median Tmax was observed at one day post-dose 
following IM injection. The dose-normalized systemic exposure (Cmax and AUC) was 
comparable for all three dose groups and the values were consistent with the PK study 
results for IM and IV administration. Drug accumulation was observed with a 2-3-fold 
increase in Cmax and AUC with repeated dosing over time. The systemic exposure (Cmax 
and AUC) appeared to be similar in both sexes at any dose level. The no observed 
adverse effect level (NOAEL) was suggested and projected to be 80 mg/kg/week for 
IM and IV administration. The corresponding AUC and Cmax of IM TMB-365 following 
the last dose at NOAEL were 10,083 day*μg/mL and 1,840 μg/mL for males, and 
11,542 day*μg/mL and 2,150 μg/mL for females, respectively. The corresponding AUC 
and Cmax of IV TMB-365 following the last dose at NOAEL were 22,470 day*μg/mL 
and 5,178 μg/mL for males, and 18,306 day*μg/mL and 4,294 μg/mL for females, 
respectively. In a tissue cross-reactivity study against human tissues, no unexpected 
specific staining was observed. 
1.3.2 TMB-380 
TMB-380 is a recombinant human immunoglobulin G1 (IgG1) antibody produced in 
the Chinese Hamster Ovary (CHO) DG44 cell line. It was initially developed by the 
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases 
(NIAID) and manufactured at the VRC Pilot Plant. The nonclinical and clinical data 
presented in the protocol were obtained using the drug product manufactured by the 
VRC. The drug supply used in this protocol and in the future clinical studies will be 
manufactured by TaiMed, and has demonstrated comparability with the drug product 
manufacture by the VRC based on the physical, chemical and functional properties. 
TMB-380 is an engineered variant of VRC01, which was originally discovered in a 
subject infected with HIV-1 for more than 15 years and whose immune system 
controlled the virus without antiretroviral therapy (ART).17 Through advances in B-cell 
immunology, cloning, and structure-guided optimization techniques, numerous HIV-1 
neutralizing monoclonal antibodies (mAb), including VRC07-523LS, were isolated 
with potency and breadth greater than those of early antibodies. 
An in vitro neutralization activity results showed that TMB-380 neutralized 96% of 
strains with an IC50 of less than 50 μg/mL and 92% of strains with an IC50 of less than 
1 μg/mL.18 The overall breath (96% versus 89%) and potency (5- to 8-fold increase) 
are improved compared to VRC01. An in vivo challenge study showed that TMB-380 
was >5-fold more potent than VRC01LS, a VRC01 variant conferring an increased 
plasma half-life. It was consisted with the in vitro neutralization activity results. 
A pharmacokinetic study has been conducted male rhesus macaques.18 Following 10 
mg/kg TMB-380 intravenously (IV) administration, the half-life was 9.8 days. The 
concentrations of TMB-380 in rectal secretions were detectable for at least 14 days (last 
collection point). 
A GLP repeat dose toxicity study with TMB-380 IV and subcutaneously (SC) was 
performed in male and female Sprague-Dawley rats.19 Treatment with TMB-380, at 

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doses up to 400 mg/kg IV or 40 mg/kg SC with three doses at 10-day intervals was 
generally well tolerated as most findings were reversible and no longer seen at the end 
of the recovery period. IV administration of either 40 or 400 mg/kg TMB-380 had peak 
concentrations within one hour post-dose, whereas SC administration of 40 mg/kg 
TMB-380 resulted in a slower absorption at either 24 or 48 hours post-dose. Exposure 
(AUC) values were approximately 4-fold higher after the first dose in the 400 mg/kg 
IV group compared to the 40 mg/kg IV group. AUC values after the third IV dose were 
higher compared to the first dose, whereas the AUC values after the third SC dose were 
lower compared to the first SC dose. The SC bioavailablity is 36-42%. No large or 
consistent gender differences in exposure were noted between males and females within 
each dosing route. Additionally, histologic changes were not observed in the GLP repeat 
dose toxicology study in the cell types with staining observed in the GLP tissue cross 
reactivity study.20 
1.3.3 Determination of the Antiviral Activity of TMB-365/TMB-380 in 
Combination 
The in vitro antiviral activity of TMB-380 in combination with TMB-365 or with 
ibalizumab (TMB-355) was evaluated in TZM-bl cell based, HIV-1 pseudovirus 
neutralization assays. The antiviral activity of the antibodies was determined by the 
Combinational Index (CI), which is the sum of fold changes of the IC50 under 
combination treatment relative to that of individual antibody. A CI > 1 is consistent with 
antagonism. If the CI is > 0.5 and < 1 the antibody effects are additive, and if the CI is 
< 0.5 then the combination is synergistic. 
The in vitro antiviral activity of the combination TMB-365/TMB-380 was 0.007 ug/ml 
in comparison to 0.006 ug/ml of antiviral activity in the combination of ibalizumab 
(TMB-355) and TMB-380 (ibalizumab/TMB-380, TMB-355/TMB-380); the 
individual antibody antiviral activities are 0.010 ug/ml for TMB-365, 0.009 µg/mL for 
ibalizumab (TMB-355), and 0.025 µg/mL for TMB-380. The results demonstrate that 
combinations of TMB-365/TMB-380 and ibalizumab/TMB-380 are highly similar to 
each other. The combination index (CI) of TMB-365/TMB-380 is 1.0, whereas the CI 
value of ibalizumab/TMB-380 is 0.9. These data are consistent with the additive 
antiviral activity of TMB-365 and TMB-380 when used combination.21 ,22 Additive 
antiviral activity is also demonstrated between ibalizumab and TMB-380.  
1.4 
Previous Human Experience 
Both TMB-365 and TMB-380 have been developed independently under various INDs 
with documented safety and efficacy in humans, including healthy subjects and HIV-1 
infected patients. 
1.4.1 TMB-365 
The completed first-in-human clinical study of TMB-365 is a phase 1, randomized, 
double-blinded, placebo-controlled, sequential single dose escalation study in HIV-1 
infected patients (protocol TMB-365-101, IND 141891). In this trial, three groups of 8-
9 patients each received intravenously administered TMB-365 at 400, 800 and 1600 mg, 
respectively, or matching placebo (active:placebo = 6:2). The study populations for 400 
and 800 mg dose groups were HIV-1 seropositive and had not received antiretroviral 
therapy (ART) for at least 4 weeks prior to the first dose, with HIV-1 RNA 1,000 
copies/mL and <100,000 copies/mL. Protocol amendment 3 was submitted to the FDA 

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on March 18, 2021 (S-0013, IND 141891) to allow for the rapid recruitment and 
treatment of 8 HIV-1 infected and cART-suppressed participants for the 1600 mg dose 
group – the identical target population for this clinical trial. 
A total of 17 viremic and 8 aviremic, suppressed HIV-1-infected participants were 
enrolled in this study. The pharmacokinetics (PK) parameters were calculated by non-
compartmental analysis (Table 1). Total exposure (Cmax and AUC) was dose-dependent 
and increased disproportionately to dose. Systemic clearance (CL) decreased and half-
life (T1/2) increased with increasing dose. Such nonlinear effects in clearance are 
common for monoclonal antibody targeting cell surface molecules, such as CD4. The 
behavior is characteristic of saturable (capacity-limited) elimination kinetics. At the 
higher doses, tri-phasic kinetics were observed: a rapid distribution phase followed by 
a slower terminal elimination phase and then a rapid final elimination. Therefore, T1/2,s 
and T1/2,b were estimated to describe the slow elimination rate at saturation and rapid 
elimination rate below saturation, respectively. During the saturated elimination phase, 
the effective half-life was on the order of roughly 6 to 11 days. As the TMB-365 
concentration fell to levels associated with uncoating of CD4+ T-cells, elimination was 
more rapid, on the order of 2-4 days. 
As shown in Figure 1, robust virologic responses were observed after 400 mg or 800 
mg TMB-365 administration. There was no virologic response with placebo treatment. 
The maximum mean change from baseline in HIV viral load occurred at Day 15 post-
dose and was -1.55 (±0.29) and -1.57 ( 0.32) log10 HIV RNA copies/mL for the 
subjects received 400 and 800 mg, respectively. Viral load rebound occurred after 2 and 
4 weeks post-dose for the 400 and 800 mg dose group, respectively. This timing 
coincided with the loss of measurable serum TMB-365 levels. 
A single dose of TMB-365 at 400 mg, 800 mg, and 1600 mg was well tolerated, with 
no serious adverse events (SAEs) or grade 3 or 4 treatment emergent adverse events 
(TEAEs). Eleven participants (44%) experienced one or more TEAEs. Two of them 
received placebo. The number and percentage of participants experiencing TEAEs did 
not increase with increasing dose. The majority of TEAEs were mild in severity. 
Moderate events included headache in 2 participants (8%), suspected COVID-19, 
urticarial and periorbital oedema in 1 participant each (4%). The most frequent TEAEs 
were headache and orpharyngeal pain in 2 participants (8%). Three participants (12%) 
reported at least one TEAE that was possibly related to the study drug. The possible 
related TEAEs included headache, pyrexia, oropharyngeal pain, wheezing, urticarial 
and periorbital oedema. There was no evidence of immunogenicity from the study drug. 

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Table 1 
Pharmacokinetics Parameters of TMB-365 
Dose 
(mg) 
Tmax 
(day) 
Cmax 
(μg/mL) 
AUC 
(day*μg/mL) 
Vd (L) 
CL 
(L/day) 
T1/2 
(day) 
T1/2,s 
(day) 
T1/2, b 
(day) 
400 
0.20  
0.40 
138.22  
45.27 
469.45  
121.02 
2.84  
1.28 
0.89  
0.21 
2.17  
0.76 
NA 
NA 
800 
0.20  
0.36 
441.43  
79.65 
2173.19  
1318.47 
2.14  
1.33 
0.45  
0.22 
3.39  
1.48 
6.34  
1.28 
2.43  
1.36 
1600 
0.02  
0.02 
705.67  
67.36 
7471.84  
1691.80 
1.97  
0.91 
0.22  
0.04 
6.39  
3.02 
10.59 
 2.01 
3.67  
1.04 
NA: Not available; Tmax: time to maximum concentration; Cmax: maximum concentration; AUC: area 
under curve; Vd: volume of distribution; CL: clearance; T1/2: half-life; T1/2,s: half-life at saturation; T1/2,b: 
half-life below saturation 
Figure 1  
TMB-365-101 Single Dose Viral Load Reductions  
 
1.4.2 TMB-380 
The clinical experience with TMB-380 is derived from 16 clinical trials (5 
completed/terminated and 11 ongoing) conducted in the United States, the Republic of 
South Africa and Switzerland (as of February 2022).  
Based on the available results from 2 studies (Studies VRC605 and VRC607/A5378), 
TMB-380 has been administered IV or SC to 25 HIV-uninfected adults and 9 HIV-
infected patients. Single dose regimens of TMB-380 ranging from 1 to 40 mg/kg IV or 

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5 mg/kg SC and repeat-dose regimens of 20 mg/kg IV have been shown to be well 
tolerated. All reported local and systemic reactogenicity was mild to moderate in 
severity. There have been no SAEs assessed as related to TMB-380. For the 26 
participants who received TMB-380 IV, the most commonly reported systemic 
reactions were malaise in 5 participants (19%), myalgia in 4 participants (15%) and 
headache in 3 participants (12%). Four (15%) participants reported local reactions, 
including pain/tenderness and bruising. For the 8 participants who received TMB-380 
SC, the most commonly reported symptoms were pain and tenderness in four 
participants (50%) and malaise or headache in three (38%) participants. 
TMB-380 showed excellent PK with half-life of 38 and 33 days after IV and SC 
administrations in the HIV-uninfected participants (n=25).23 Maximum (Cmax) and 12-
week (C84D) serum concentrations increased proportionally with IV doses from 5-40 
mg/kg. The time after infusion where the maximum serum concentration (Tmax) was 
measured occurred within the first few hours after IV administration, and 
approximately 10 days following SC administration. 
In the HIV-infected participant (n=9), a single IV dose of TMB-380 at 40 mg/kg 
achieved a 1.7 log10 viral load reduction within 14 days.5  The PK parameters are 
shown in Table 2. 
Table 2 
Pharmacokinetic parameters after 40 mg/kg TMB-380 IV 
administration (Mean (SD)) 
Cmax 
(μg/mL) 
Tmax 
(days) 
C28D 
(μg/mL) 
C84D 
(μg/mL) 
AUC 
(μg*day/mL) 
CL 
(mL/day) 
T1/2 
(day) 
1295.2 
(375.9) 
0.06 
(0.05) 
162.6 
(42.7) 
60.7 (20.8) 17967 (4563) 
188.7 
(55.8) 
56.5 
(13.2) 
2 
STUDY OBJECTIVES 
The primary objectives of this study are to: 
ý 
Evaluate the safety and tolerability of various doses and dosing regimens of IV 
infusions of TMB-365 and TMB-380 given q8wks in suppressed, cART 
treated HIV-1 infected participants.  
ý 
Define the pharmacokinetic (PK) profile of TMB-365 and TMB-380 when 
given q8wks in suppressed, cART treated HIV-1 infected participants.  
ý 
Evaluate the antiviral activity of TMB-365 in combination with TMB-380 as 
maintenance therapy in suppressed HIV infected individuals. (Core only) 
Exploratory objectives of this study are to: 
ý 
Determine the immunogenicity of TMB-365 and TMB-380 in HIV-1 infected 
suppressed participants. 
ý 
Determine the resistance profiles of TMB-365 and TMB-380 in vivo. 

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3 
STUDY PLAN 
3.1 
Overall Design 
This study is a phase 1b / 2a adaptive open-label dose escalation study of the 
combination of TMB-365 and TMB-380. This adaptive study design will be 
comprised of Sentinel Groups (N=10) and Core Groups (N=20). Safety and 
pharmacokinetic (PK) data obtained from Sentinel group participants will guide the 
conduct of Core Group execution. 
Participants will be HIV-infected and suppressed for at least 6 months on continuous 
daily oral combination antitretroviral therapy (cART). Continuous is defined as no more 
than 3 consecutive days of missed cART. There are three doses of each antibody being 
explored, 2400 mg, 3200 mg, and 4800 mg. 
3.1.1 Sentinel Groups 
Sentinel Groups will be comprised of 10 cART suppressed HIV-1 infected volunteers 
who receive a single IV dose of the combination of TMB-365 and TMB-380 while 
continuing cART.  
Sentinel Group 1 will be dosed with 2400 mg of each antibody and will continue daily 
oral cART throughout the screening, infusion, and post-infusion observation period of 
12 weeks and be assessed for safety and pharmacokinetics. 
Sentinel group 2 will dose both antibodies at 3200 mg. The third sentinel group will 
dose both antibodies at 4800 mg. 
 
Criteria for safety of a dose of either TMB-365 or TMB-380 include: 
i) 
No SAEs probably or definitely due to TMB-365 or TMB-380 
ii) 
No more than one Grade 3 or Grade 4 adverse event probably or definitely 
related to TMB-365 or TMB-380 at any dose level.  
Toxicity evaluations will be guided by the DAIDS Table for Grading Severity of Adult 
and Pediatric Adverse Events Version 2.1. The Common Terminology Criteria for 
Adverse Events (CTCAE) v. 5.0 scale will be used for assessment of any infusion 
reactions, or anaphylactic events. 
PK targets: 
i. 
TMB-365: serum levels >0.3 μg/mL 
ii. 
TMB-380: serum levels >65 μg/mL 
Should a dose of either antibody prove safe and approximately 80% of subjects studied 
in a given Sentinel dose group meet specified safety and PK criteria, then a Core group 
of 20 subjects will be enrolled and treated with that dose of TMB-365 and TMB-380 as 
a stand-alone complete maintenance regimen for 24 weeks (see below).  
Safety must be established prior to any request for dose escalation to the next higher 
Sentinel dose group. A review of 14-day safety data in 7 of 10 subjects after infusion 
must be available for review prior to any request for dose escalation. Dose escalation 
may only occur with the approval of an independent Data Monitoring Committee 

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(DMC) as described in Section 9.9. 
The maximum dose of TMB-365 and TMB-380 that will be tested in Sentinel groups 
is 4800 mg. 
The first 3 subjects in each Sentinel group will be treated at designated sites selected 
for demonstration of expertise in the use of monoclonal antibody therapy. Subjects will 
remain at the study site for at least 3 and up to 5 hours post-infusion for monitoring of 
vital signs every 15 minutes beginning 15 minutes prior to the infusion of TMB-365 
and TMB-380 as well as observation for the presence of infusion reactions. It is at the 
discretion of the Principal Investigator at the study site to determine the duration of 
observation.  
Should the infusions be well tolerated and no Grade 3 or 4 AEs, or SAE’s occur due to 
study drugs within 7 days of infusion, then the remaining 7 subjects in that group may 
be recruited/treated. These subjects will remain at study sites for at least 1 hour and up 
to 3 hours post-infusion for monitoring of vital signs and the presence of infusion 
reactions. It is at the discretion of the Principal Investigator at the study site to determine 
the duration of observation.  
3.1.2 Core Group Subjects 
Core Groups will be comprised of 20 cART suppressed HIV-1 infected volunteers 
and will receive multiple IV doses of the combination of TMB-365 and TMB-380 as a 
stand-alone maintenance regimen for 24 weeks. Oral cART will be restarted in the 
clinic at the Week 24 visit. 
Core group participants will complete the study at Day 196 / Week 28, 4 weeks after 
reinstituting oral cART.  
Sentinel group participants may be enrolled in a Core group if infusions are well 
tolerated and the subject is willing to discontinue oral cART.  
Dosing of Core participants is based on safety and PK findings in the Sentinel Group 
and include 
TMB-365: 4800 mg q 8 weeks.  
TMB-380: 4800 mg q 8 weeks.  
If indicated by safety, PK, and efficacy, an amendment may be made to the current 
protocol to test higher doses of either antibody in consultation with the Data 
Monitoring Committee and the FDA. 
Asymmetric doses of TMB-365 and TMB-380 may be used in Core groups should 
safety and PK results support such an approach. Sentinel Group participants that wish 
to participate in Core Groups must repeat all screening procedures including signing a 
second Informed Consent Form. 
3.2 
Dose Selection and Rationale for Sentinel Groups 
TMB-365 has demonstrated in vitro antiviral activity superior to its parent compound, 
ibalizumab.7,24 The exposure-response relationship of ibalizumab showed the response 
rate (the percentage of patients with HIV-1 RNA levels <50 copies/mL at Week 24) 
achieved a plateau when ibalizumab concentrations were >0.3 μg/mL.25 Therefore the 
target effective concentration of TMB-365 is set to 0.3 μg/mL. Results in the Phase 1 

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study revealed that TMB-365 demonstrates antiviral activity at 0.3 μg/mL supporting 
this target effective concentration. 
In the Phase 1 study, a direct relationship between TMB-365 concentrations and viral 
load reduction for 400 and 800 mg doses was demonstrated. A direct relationship 
between TMB-365 concentrations and RO for 800 and 1600 mg doses was also 
demonstrated. This suggests that TMB-365 concentrations can be used as a surrogate 
to predict the antiviral activity for dose selection. 
Simulations based on the available 400 mg, 800 mg, and 1600 mg pharmacokinetic 
results suggest that the proposed dosing regimens can maintain concentrations above 
the target concentration during the treatment period in this study.  
The proposed TMB-380 dose is based on the ongoing clinical study designs. In the 
IGHID 11802 (NCT03803605) and A5357 (NCT03739996) studies, the TMB-380 dose 
is 40 mg/kg every 60 days and 8 weeks, respectively. The antiviral activity has been 
demonstrated in a single dose study (Study VRC607-A5378, NCT02840474). A single 
40 mg/kg dose reduced HIV viral RNA levels by 1.7 log10 copies/mL and the mean time 
to the nadir was 9 days. Along these lines, a 3200 mg dose (40 mg/kg for an 80 kg 
person) is promising for bimonthly dosing.  
In a post-hoc analysis of a Phase 1 clinical trial of TMB-380, neutralization coverage 
over the first 24 weeks after a single administration was predicted.23 With the predicted 
coverage as 90%, the correlate concentration is ~65 μg/mL, which is the target effective 
concentration in this study. Simulations were performed based on the available PK data 
from study VRC607-A5378. The results suggest that the proposed q8wk and q12wk 
dosing regimens can maintain concentration above the target effective concentration 
during the treatment period. The dose of 3200 mg (~40 mg/kg) of TMB-380 every 8 
weeks has been studied in several completed and ongoing clinical trials for HIV 
treatment and demonstrated antiviral activity when the concentration is greater than the 
target effective concentration. 
3.3 
Dose selection and rationale for the Core Group 
3.3.1 Safety 
Thirty subjects from Sentinel groups received one of 3 doses of both TMB-365 and 
TMB-380 as detailed above and were followed for 12-16 weeks. One Group 3 subject 
(4800 mg/4800 mg) was erroneously dosed with 1600 mg of each antibody. No SAEs, 
Grade 3 or 4 adverse events, or acute infusion events were observed. Treatment 
emergent AEs (N=32) were mild to moderate. Five were probably or definitely 
attributed to infusions with the study drug bNAbs. Two subjects experienced the 
delayed onset of fatigue and chills, one moderate and one mild, interpreted as 
hypersensitivity. Other AEs included sneezing (N=1), fatigue (N=1), and cold feet 
(N=1). 
3.3.2 Pharmacokinetics/Pharmacodynamics 
Nine subjects received 4800 mg/4800 mg TMB-365 and TMB-380 in Sentinel Group 
3. At Week 8, the mean TMB-365 and TMB-380 concentrations were 15.1 (± 13.5) and 
86.4 (± 24.1) g/ml, respectively, and approximately 80% (7/9) of participants met pre-
defined trough targets. In addition, TMB-365 CD4 receptor occupancy was above 80%, 

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DATE: 23 JAN 2024 
29 
 
which is an indicator of good efficacy, in 8/9 of Group 3 participants at Week 8. 
Therefore, 4800 mg/4800 mg q8wk was selected for the Core Group. 
If indicated by safety, PK, and efficacy, an amendment may be made to the current 
protocol to test higher doses of either antibody in consultation with the Data Monitoring 
Committee and the FDA. 
 

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3.3 
Study Events and Procedures 
Table 3 through Table 5 below provide the schedules of events and procedures for the study.  
Table 3 
Schedule of Events and Procedures for Sentinel Groups receiving 2400 mg or 3200 mg of TMB-365 and TMB-380 
Study Visit 
Screening 
Day 0 
Baseline 
Day 7 
Week 1 
Day 14 
Week 2 
Day 28 
Week 4 
Day 42 
Week 6 
Day 49 
Week 7 
Day 56 
Week 8 
Day 63 
Week 9 
Day 70 
Week 10 
Day 84 
Week 12 
Failure 
Confirmation or 
Premature 
Discontinuation 
Visit window (days) 
(-45 days) 
N/A 
± 1 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
N/A 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
UV 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
 
 
 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Interim History 
 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Directed Physical Exam 
 
X 
X 
X 
X 
 
 
X 
 
 
 
X 
Adverse Event Monitoring 
 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Weight 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Enrollment 
 
X 
 
 
 
 
 
 
 
 
 
 
TMB-365 
and 
TMB-380 
infusion1 
 
X 
 
 
 
 
 
 
 
 
 
 
Serum PK TMB-365 (pre-
dose if drug administered on 
this day) 
 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PK TMB-380 (pre-
dose if drug administered on 
this day) 
 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PK TMB-365 post-
dose 10 min 
 
X 
 
 
 
 
 
 
 
 
 
 
Serum PK TMB-380 post-
dose 10 min 
 
X 
 
 
 
 
 
 
 
 
 
 

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Study Visit 
Screening 
Day 0 
Baseline 
Day 7 
Week 1 
Day 14 
Week 2 
Day 28 
Week 4 
Day 42 
Week 6 
Day 49 
Week 7 
Day 56 
Week 8 
Day 63 
Week 9 
Day 70 
Week 10 
Day 84 
Week 12 
Failure 
Confirmation or 
Premature 
Discontinuation 
Visit window (days) 
(-45 days) 
N/A 
± 1 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
N/A 
CD4 RDRO (receptor density 
and occupancy) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
Archive samples 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIV EIA and Confirmatory 
Testing 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV RNA PCR  
X 
X 
 
 
 
 
 
 
 
 
X 
X 
CD4 and CD8 Lymphocyte 
Count 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Complete Blood Count  
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Blood Chemistry 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Creatinine  
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Fasting lipid profile3 
 
X 
 
 
 
 
 
 
 
 
X 
X 
HBV Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
HCV Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy4 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine HCG4 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
X 
 
 
X 
X 
Serum collection for 
immunogenicity 
 
X 
 
X 
 
 
 
X 
 
 
X 
X 
NOTE: 
 
All specimens other than post-dose serum concentrations are collected pre-dose on the days of study drug administration 
1  The first 3 participants in each Sentinel dose group will be closely observed for at least 180 minutes (3 hours) and up to 300 minutes (5 hours) after IP administration with 
the duration to be at the discretion of the site PI according to Protocol procedures (see Section 6.3). The remaining Sentinel group participants will be observed anywhere 
from 60 minutes (1 hour) to 180 minutes (3 hours) after IP administration with the duration to be at the discretion of the site PI. 
2  Pre-Dose specimens to be collected within 1 hour before the start of study drug infusion. 
3   Lipid profile should be a fasting specimen, that is, 8 hours after eating. Water, black coffee or tea are permissible. Medication may be taken prior to blood draw with water. 
4  Pregnancy testing will be performed only for participants of childbearing potential. 
 
 

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Table 4 
Schedule of Events and Procedures for Sentinel Group receiving 4800 mg of TMB-365 and TMB-380 
Study Visit 
Screening 
Day 0 
Baseline 
Day 14 
Week 2 
Day 28 
Week 4 
Day 56 
Week 8 
Day 70 
Week 10 
Day 77 
Week 11 
Day 84 
Week 12 
Day 91 
Week 13 
Day 98 
Week 14 
Day 112 
Week 16 
Failure Confirmation 
or Premature 
Discontinuation 
Visit window (days) 
(-45 days) 
N/A 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
N/A 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
UV 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
 
 
 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Interim History 
 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Directed Physical Exam 
 
X 
X 
X 
X 
 
 
X 
 
 
 
X 
Adverse Event Monitoring 
 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Weight 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Enrollment 
 
X 
 
 
 
 
 
 
 
 
 
 
TMB-365 and TMB-380 
infusion1 
 
X 
 
 
 
 
 
 
 
 
 
 
Serum PK TMB-365 (pre-
dose if drug administered 
on this day) 
 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PK TMB-380 (pre-
dose if drug administered 
on this day) 
 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PK TMB-365 post-
dose 10 min 
 
X 
 
 
 
 
 
 
 
 
 
 
Serum PK TMB-380 post-
dose 10 min 
 
X 
 
 
 
 
 
 
 
 
 
 
CD4 
RDRO 
(receptor 
density and occupancy) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Archive samples 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study Visit 
Screening 
Day 0 
Baseline 
Day 14 
Week 2 
Day 28 
Week 4 
Day 56 
Week 8 
Day 70 
Week 10 
Day 77 
Week 11 
Day 84 
Week 12 
Day 91 
Week 13 
Day 98 
Week 14 
Day 112 
Week 16 
Failure Confirmation 
or Premature 
Discontinuation 
Visit window (days) 
(-45 days) 
N/A 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
N/A 
HIV EIA and Confirmatory 
Testing 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV RNA PCR  
X 
X 
 
 
 
 
 
 
 
 
X 
X 
CD4 and CD8 Lymphocyte 
Count 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Complete Blood Count  
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Blood Chemistry 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Creatinine  
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
Fasting lipid profile3 
 
X 
 
 
 
 
 
 
 
 
X 
X 
HBV Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
HCV Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy4 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine HCG4 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
Serum collection for 
immunogenicity 
 
X 
X 
 
X 
 
 
 
 
 
X 
X 
NOTE: 
 
All specimens other than post-dose serum concentrations are collected pre-dose on the days of study drug administration 
1  The first 3 participants in each Sentinel dose group will be closely observed for at least 180 minutes (3 hours) and up to 300 minutes (5 hours) after IP administration with the duration 
to be at the discretion of the site PI according to Protocol procedures (see Section 6.3). The remaining Sentinel group participants will be observed anywhere from 60 minutes (1 
hour) to 180 minutes (3 hours) after IP administration with the duration to be at the discretion of the site PI. 
 
2  Pre-Dose specimens to be collected within 1 hour before the start of study drug infusion. 
3   Lipid profile should be a fasting specimen, that is, 8 hours after eating. Water, black coffee or tea are permissible. Medica tion may be taken prior to blood draw with water. 
4  Pregnancy testing will be performed only for participants of childbearing potential. 
 
 

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Table 5 
Schedule of Events and Procedures for Core Groups receiving every 8-week dosing 
Study Visit 
Screening 
Day 0 
Baseline 
Day 14 
Week 2 
Day 28 
Week 4 
Day 56 
Week 8 
Day 84 
Week 12 
Day 112 
Week 16 
Day 140 
Week 20 
Day 168 
Week 24 
Day 196 
Week 28 
Failure 
Confirmation or 
Premature 
Discontinuation 
Visit window (days) 
(-60 days) 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
N/A 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
UV 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
History 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
 
 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Interim History 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Directed Physical Exam 
 
X 
X 
X 
X 
 
X 
X 
 
 
 
Adverse Event Monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
 
X 
 
 
 
 
 
 
 
X 
X 
Enrollment 
 
X 
 
 
 
 
 
 
 
 
 
Discontinue cART Therapy1 
 
X 
 
 
 
 
 
 
 
 
 
Restart cART Therapy1 
 
 
 
 
 
 
 
 
X 
 
 
TMB-365 and TMB-380 
infusion2 
 
X 
 
 
X 
 
X 
 
 
 
 
Serum PK TMB-365 (pre-dose 
if drug administered on this 
day) 
 
X3 
X 
X 
X3 
X 
X3 
X 
X 
X 
X 
Serum PK TMB-380 (pre-dose 
if drug administered on this 
day) 
 
X3 
X 
X 
X3 
X 
X3 
X 
X 
X 
X 
Serum PK TMB-365 post-dose 
10 min 
 
X 
 
 
X 
 
X 
 
 
 
 
Serum PK TMB-380 post-dose 
10 min 
 
X 
 
 
X 
 
X 
 
 
 
 
CD4 RDRO (receptor density 
and occupancy) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study Visit 
Screening 
Day 0 
Baseline 
Day 14 
Week 2 
Day 28 
Week 4 
Day 56 
Week 8 
Day 84 
Week 12 
Day 112 
Week 16 
Day 140 
Week 20 
Day 168 
Week 24 
Day 196 
Week 28 
Failure 
Confirmation or 
Premature 
Discontinuation 
Visit window (days) 
(-60 days) 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
N/A 
Archive samples 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIV EIA and Confirmatory 
Testing 
X 
 
 
 
 
 
 
 
 
 
 
HIV RNA PCR  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CD4 and CD8 Lymphocyte 
Count 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete Blood Count  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Creatinine  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid profile4 
 
X 
 
 
 
 
 
 
X 
 
X 
HBV Screening 
X 
 
 
 
 
 
 
 
 
 
 
HCV Screening 
X 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy5 
X 
 
 
 
 
 
 
 
 
 
 
Urine HCG5 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis6 
X 
X 
 
 
X 
 
 
 
X 
X 
X 
Serum collection for 
immunogenicity 
 
X 
X 
 
 
 
X 
 
 
X 
X 
Plasma Storage for Resistance 
Testing 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIVTSQs administration7 
 
X 
 
 
X 
 
 
 
X 
X 
 
HIVTSQc administration8 
 
 
 
 
 
 
 
 
X 
 
 
NOTE:  
All specimens other than post-dose serum concentrations are collected pre-dose on the days of study drug administration 
1  Record the time of cART dose which should be taken in the clinic, and prior to study drug administration at the Baseline visit 
2  Core group participants will be observed for 60 minutes (1 hour) after IP administration per protocol procedures (See Section 7.3) 
3  Pre-Dose specimens to be collected within 1 hour before the start of study drug infusion. 
4   Lipid profile should be a fasting specimen, that is, 8 hours after eating. Water, black coffee or tea are permissible. Medication may be taken prior to blood draw with water. 
5  Pregnancy testing will be performed only for participants of childbearing potential. 
6  Urinalyses are performed on site by dipstick and should reflex to a complete urinalysis sending the sample to the central laboratory if the dipstick result is abnormal 
7  HIVTSQs is the HIV Treatment Satisfaction Questionnaire - status version to be completed by study subject. The questionnaire should be completed prior to any other study 
procedures at visits where it is administered, including the restarting of oral cART at Week 24. 
8   HIVTSQc is the HIV Treatment Satisfaction Questionnaire - change version to be completed by study subject. The questionnaire should be completed after completing the 

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HIVTSQs and prior to any other study procedures at visits where it is administeredincluding the restarting of oral cART at Week 24. 

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3.4 
Safety Assessments 
Safety assessments will include the results of the following measurements: 
• 
Physical examinations; 
• 
Vital sign measurements; 
• 
Patient weight at baseline and end-of-study; 
• 
Anti-TMB-365 and TMB-380 antibody levels (immunogenicity of TMB-365 and 
TMB-380); 
• 
Clinical laboratory parameters (hematology, serum chemistry, lipid panel, and 
urinalysis); 
• 
Pregnancy tests; 
• 
AEs; 
• 
SAEs; 
• 
Infusion reactions 
3.5 
Pharmacokinetic and Antiviral Assessments 
Pharmacokinetic and antiviral assessments will include the results of the following 
measurements: 
• 
Quantification of serum TMB-365 and TMB-380 levels at varying time points in order 
to characterize the PK profile; 
• 
In vitro quantification of the number of CD4 receptors and the percentage of CD4 T-
cell receptors bound by TMB-365;  
• 
HIV-1 RNA (viral load) assessments to assess maintenance of suppression in Core 
subjects.  
3.6 
Patient Reported Outcome Measures 
Patient reported outcome measures (PROM) will be assess at various time points using the 
following validated questionnaires (see Appendix C): 
• HIV Treatment Satisfaction Questionnaire-status (HIVTSQs)  
• HIV Treatment Satisfaction Questionnaire-change (HIVTSQc) 
4 
STUDY TREATMENT 
4.1 
Study Drug Dosage and Administration 
Study drugs TMB-365 and TMB-380 will be administered together in one IV bag of 250 
mL normal saline by IV infusion. Potential doses and dosing regimens include: 
  
Sentinel groups (N=10 for each group): 
TMB-365: 2400 mg, 3200 mg, 4800 mg x single dose  
TMB-380: 2400 mg, 3200 mg, 4800 mg x single dose  
 

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Anticipated Core groups (N=20 for each group): 
TMB-365: 4800 mg q8wks for 24 weeks  
TMB-380: 4800 mg q8wks for 24 weeks 
If indicated by safety, PK, and efficacy, an amendment may be made to the current 
protocol to test higher doses of either antibody in consultation with the Data 
Monitoring Committee and the FDA. 
 
Study drug will be provided in single-use vials containing 16 mL of TMB-365 or TMB-380 
at a concentration of 100 mg/mL.  
The site research pharmacist or designee will prepare the study drug. 
Study drugs will be thawed by the following steps.  
1. Thaw vial(s) for a minimum of 2 hours until no ice is observed at controlled room 
temperature (maximum 27°C), or overnight (e.g., 6 pm to 8 am) in the refrigerator after 
removing from the freezer. 
2. The refrigerated product must be equilibrated at controlled room temperature (maximum 
27°C) for a minimum of 30 minutes before preparation. 
3. The thawed drug can be kept at controlled room temperature (maximum 27°C) for 24 
hours and in the refrigerator (2-8°C) for two weeks. 
4. Before preparation for administration, vials should be swirled for 30 seconds, yet avoid 
foaming. DO NOT SHAKE THE VIALS. 
TMB-365 and TMB-380 will be mixed and diluted in one IV bag for infusion. The study 
drug should be administered using sterile technique within four hours after the time of 
preparation. The IV infusion should be administered with an 1.2 Micro in-line filter infusion 
set in the cephalic vein of the participant’s right or left arm. If this vein is not accessible, an 
appropriate vein located elsewhere can be used.  
Antibodies will be administered over 60 minutes to all participants.   
The first 3 subjects in each Sentinel group will be treated at designated sites selected for 
demonstration of expertise in the use of monoclonal antibody therapy. Subjects will remain 
at the study site for at least 3 hours and up to 5 hours post-infusion for monitoring of vital 
signs every 15 minutes beginning 15 minutes prior to the infusion of TMB-365 and TMB-
380 as well as observation for the presence of infusion reactions. The duration of observation 
post-infusion is at the discretion of the site PI.  Should the infusions be well tolerated and 
no Grade 3 or 4 AEs, or SAE’s occur due to study drugs within 7 days of infusion, then the 
remaining 7 subjects in that group may be recruited/treated. These subjects will remain at 
study sites at least 1 hour and up to 3 hours post-infusion for monitoring of vital signs and 
the presence of infusion reactions. The duration of observation post-infusion is at the 
discretion of the site PI. 
See Section 6.3 for details regarding monitoring the period pre-, post- and during infusion. 
4.2 
Concomitant Medications and Restrictions 
Use of and changes in concomitant medications will be recorded in the participant’s source 
documents. All prescription drugs, herbal products, vitamins, minerals, and over-the-
counter medications are to be recorded.  
Any concomitant medication with the exception of those listed below may be given at the 

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discretion of the investigator. However, the investigator has the responsibility of ensuring 
that details regarding the concomitant medication are recorded for the participant in the Case 
Report Form (CRF). Complete information is expected for any medication prescribed 
during the trial.  
The prescribing information for all concomitant medications should be reviewed carefully. 
The guidance provided in the respective contraindications, warnings, and precautions 
section for any medication must be followed to prevent any potentially serious or life-
threatening drug interactions.  
The following medications are not to be administered: 
• Vaccines other than for influenza and COVID-19. 
• All investigational drugs. 
 
Participants in all Sentinel groups are expected to continue suppressive combination 
antiretroviral therapy with the same medications being taken at the time of the screening 
throughout study participation. Participants in Core groups will discontinue cART on day 
0, the day of first infusion, through the Week 24 week visit unless they are instructed to 
reinitiate cART in the event of virologic failure or intolerance.   
First-dose, generalized, self-limiting skin rash has been described with therapeutic MAbs26, 
27. Any participant that experiences anaphylactoid symptoms during monoclonal antibody 
infusion should have the drug administration stopped immediately. Severe post-
administration reaction management may include use of corticosteroids, antihistamines, 
oxygen, and IV fluids based on the severity and symptoms28. Refer to Appendix B for further 
information on the management of suspected anaphylactoid reactions. Participants should 
be followed until any such symptoms resolve. 
4.3 
Measurement of Participant Compliance 
Participant compliance will require the availability of the participant at the study site to 
receive the combination of TMB-365 and TMB-380 and the participant’s willingness/ability 
to receive the dose. Participants who fail to receive the administration of study drug may be 
withdrawn from the study at the discretion of the Sponsor or designee or the principal 
investigator. 
4.4 
Study Drug Description 
The Sponsor or designee will provide the Research Pharmacists at the sites with open-label 
vials containing TMB-365 and TMB-380. TMB-365 is provided as a parenteral formulation 
in a 20 mL, clear-glass vial. The drug product contains TMB-365 at a concentration of 100 
mg/mL, polysorbate 80, sucrose, and water for injection USP at pH 4.5 with acetate buffer. 
Each vial contains 16 mL of fluid to be withdrawn. TMB-380 is provided as a parenteral 
formulation in a 20 mL, clear-glass vial. The drug product contains TMB-380 at a 
concentration of 100 mg/mL, histidine, sodium chloride, sucrose, sorbitol, and water for 
injection at pH 6.8. Each vial contains 16 mL of fluid to be withdrawn. 
TMB-365 solution is brownish-yellow, and TMB-380 solution is yellow. 
4.5 
Study Drug Packaging, Storage, and Disposal  
TMB-365 is provided as a single-use parenteral formulation in a 20 mL, clear-glass vial 
containing 16 mL of study drug. The stability of the TMB-365 drug product at -20ºC is 

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40 
 
evaluated in on-going studies. Study drug will be shipped under frozen conditions with a 
temperature-monitoring device. TMB-365 should be stored frozen at -20ºC and protected 
from light during storage (not during the preparation and administration).  
TMB-380 is provided as a single-use parenteral formulation in a 20 mL, clear-glass vial 
containing 16 mL of study drug. The stability of the TMB-380 drug product at -20ºC is 
evaluated in on-going studies. Study drug will be shipped under frozen conditions with a 
temperature-monitoring device. TMB-380 should be stored frozen at -20ºC and protected 
from light during storage (not during the preparation and administration).  
Investigator sites must store the investigational product in a secure location and maintain a 
temperature log of the storage conditions. The temperature must be continuously monitored 
with a continuous-monitoring temperature device. Temperature logs must be available for 
review at each site monitoring visit. Temperature excursions outside the required limits 
should be reported promptly to the Sponsor or designee and the affected study drug should 
not be administered to any participants until further instruction. The Sponsor or designee 
will investigate temperature excursions and adjudicate disposition of affected study drug.  
Any spent vials or remaining contents of used vials (TMB-365 or TMB-380) should be 
destroyed, according to the site’s procedures for spent vial destruction and disposal, after 
reconciliation of the study drug, and the destruction should be recorded. 
4.6 
Study Drug Accountability 
The research pharmacist will maintain accurate records of the disposition of the entire 
supply of study drugs, including when, how much, and the condition under which the study 
drugs are received, dispensed, and destroyed by site personnel. In addition, the Research 
Pharmacist should maintain accurate records of the administration of each study drug to 
each participant at the vial level for each administration (i.e. lot number of every vial for 
that administration, number of vials, time of administration preparation, study ID number, 
and initials of the participant for whom the prepared dose is intended).  
The study personnel should maintain accurate records of the study ID number and initials 
of the participant receiving the dose, date and time of administration, and site(s) of 
administration(s) for each participant and dose.  
Drug accountability will be reviewed and documented. Reconciliation and accountability of 
study drugs will be done throughout the study during the monitoring visits. After the 
completion of the study, the Sponsor or designee may authorize the site to dispose of unused 
supplies of the investigational drugs, provided this alternative disposition does not expose 
humans to risks from the drugs. The Sponsor or designee shall maintain written records of 
all drug disposition, which will include the name of the investigator, the date, quantity, batch 
or code of each vial, and method of disposal. 
4.7 
Infusion Reactions 
Study drugs should be administered in an area that allows for rapid access to emergency 
cardiopulmonary support services in the event of a life threatening infusion reaction. The 
Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 scale will be used for 
assessment of any infusion reactions, or anaphylactic events (see Section 9.6) 

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5 
PARTICIPANT ENROLLMENT 
5.1 
Inclusion Criteria 
Participants must meet all of the following criteria to be included in the study: 
1. 
Male or female at least 18 years of age and no greater than 70 years on the day of 
Screening. 
2. 
Asymptomatic HIV-1 infection, documented by any licensed rapid HIV test or HIV 
enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study 
entry and confirmed by Geenius™ or a second antibody test by a method other than 
the initial rapid HIV and/or E/CIA test, or by HIV-1 antigen, plasma HIV-1 RNA viral 
load at or prior to screening. 
3. 
On continuous suppressive cART for 6 months prior to screening with one documented 
HIV-1 RNA level below the level of detection within 3 months of screening. 
Continuous cART is defined as no interruptions greater than 3 consecutive days. cART 
is defined as a DHHS recommended regimen. Study participants should be on a stable 
regimen for at least 3 months.  
4. 
Screening plasma HIV-1 RNA below the limit of detection.  
5. 
CD4+ T cell count >350 cells/mm3 
6. 
Laboratory values obtained within 30 days prior to the first dose: 
• 
Hemoglobin > 10.0 g/dL; 
• 
Platelet count ≥ 100,000/mm3; 
• 
Absolute neutrophil count ≥ 1,000/mm3; 
• 
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 
1.5 x upper limit of normal (ULN); and 
• 
Creatinine clearance (CrCl) of ≥ 50 mL/min. 
7. 
Willing to comply with the requirements of the protocol and available for follow-up 
for the planned duration of the study. 
8. 
In the opinion of the principal investigator or designee, has understood the information 
provided; written informed consent needs to be given before any study-related 
procedures are performed.  
9. 
Females of childbearing potential, sexually active with a male sex partner, must agree 
to use one effective method of contraception from the time of signing the consent to 
completion of the study, and agree to pregnancy testing as per the Schedule of Events 
and Procedures. Females of childbearing potential are female participants who are not 
surgically sterile (no history of bilateral tubal ligation, hysterectomy, or bilateral 
salpingo-oophorectomy), are not postmenopausal (at least one year without menses), 
and are not otherwise sterile by medical evaluation. 
5.2 
Exclusion Criteria 
Participants having or meeting any of the following conditions or characteristics will be 
excluded from the study: 
1. Suppressed subjects who have not been on a stable DHHS recommended cART 

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regimen for at least 3 months. 
2. Receipt of any monoclonal antibody for the treatment or prevention of HIV infection 
except for receipt of TMB-365 and TMB-380 by Sentinel subjects eligible for 
enrollment into Core groups. 
3. Suppressed subjects receiving cabotegravir and rilpivirine intramuscularly as 
maintenance therapy for HIV-1 infection. 
4. Pregnant, planning a pregnancy during the trial period, or lactating.  
5. Known allergy/sensitivity or any hypersensitivity to components of the study drug or 
its formulation, or known allergy to a MAb. 
6.  History of severe allergic reactions to medications, vaccinations, or monoclonal 
antibody therapy for other conditions such as COVID.  
7. Major psychiatric illness including any history of schizophrenia or severe psychosis, 
uncontrolled bipolar disorder requiring acute therapy, or suicide attempt in the previous 
three years.  
8. Serious illness requiring systemic treatment and/or hospitalization within 21 days prior 
to the first dose. 
9. Receipt of immunomodulatory agents (e.g., interleukins, interferons, cyclosporine, 
high dose systemic corticosteroids), HIV vaccine, systemic cytotoxic chemotherapy, or 
investigational therapy within 180 days prior to the first dose. 
10. Any chronic or acute medical condition, including chronic Hepatitis B infection, 
chronic and Hepatitis C infection with viremia, drug use and alcohol abuse, which in 
the opinion of the investigator would interfere with evaluation of the study drug. 
11. Lack of adequate venous access. 
12. Individuals who have experienced virologic failure during treatment with two or more 
cART treatment regimens and those being treated with regimens containing either 
ibalizumab, enfuvirtide, maraviroc, or fostemsavir. Note that a change in treatment 
regimen for intolerance does not meet criteria for treatment failure.  
5.3 
Participant Withdrawal and Discontinuation 
5.3.1 Reasons for Withdrawal 
Participants may withdraw consent to participate at any time during the study though this 
should be strongly discouraged by the site study team. 
A Medical Monitor designated by the Sponsor, along with the investigator, will routinely 
review safety data, including lab results, AEs, and SAEs.  
Participants are encouraged to continue participation throughout the study period in the 
event that they decide or it is decided that they discontinue infusions with TMB-365 and 
TMB-380. 
A participant may be withdrawn from the study if the participant: 
• 
Is in violation of the protocol including non-adherence to study visits;  
• 
Requires a medication that is prohibited by the protocol;  
• 
Requests an early discontinuation for any reason; 

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• 
Is intolerant to infusions of TMB-365 or TMB-380 (safety); 
• 
Is in a Core group and has evidence of documented virologic rebound defined by 2 
consecutive HIV-1 RNA levels above 50 copies/mL plasma at least two weeks apart. 
Note that any participant with an HIV-1 RNA value above 50 copies/mL will be asked 
to return to clinic for an unscheduled visit at least 2 weeks later for a repeat value. If 
virologic failure is documented then participants should be immediately started on the 
same combination antiretroviral regimen that was being administered at the time of 
screening. Participants who demonstrate virologic rebound should be encouraged to 
complete the clinic visits as outlined in the Schedule of Events (Table 3 through Table 
5).  
A participant will be withdrawn if the Sponsor or the local regulatory agency terminates the 
study. Upon occurrence of an SAE, the principal investigator will notify the Sponsor or 
designee of these events via the SAE hotline. Any participant may withdraw his/her consent 
at any time.  
5.3.2 Stopping Rules 
Stopping criteria for an individual subject within a Core Group:  
Safety:  Any SAE, or Grade 3 or 4 adverse event probably or definitely due to the 
monoclonal antibody infusions within 14 days of treatment. 
Antiviral activity: Documented virologic failure in an individual. Resistance analysis 
including phenotype and genotype will be performed in subjects in whom virologic failure 
is documented.  
Stopping criteria for dosing a Core Group: 
Safety: An SAE probably or definitely due to the monoclonal antibody infusions. 
More than one Grade 3 or 4 adverse event probably or definitely due to the monoclonal 
antibody infusions..  
Antiviral activity: Documented virologic failure in more than two individuals in a Core 
Group who have received scheduled infusions of the combination of TMB-365 and TMB-
380.  
Resistance analysis including phenotype and genotype will be performed in subjects in 
whom virologic failure is documented. 
To ensure participant safety all SAEs, Grade 3 and Grade 4 AEs will be reviewed by the 
Data Monitoring Committee (DMC) (Section 9.9) to assess causality. All cases of virologic 
failure will be similarly reviewed. The DMC may elect to terminate enrollment and dosing 
of individuals in the Core Group at any juncture based on the assessment of safety and 
antiviral activity.  
Should the study be halted due to safety concerns of lack of efficacy then all enrolled 
subjects will cease dosing with bNAbs and resume oral cART as per the week 24 and week 
28 visits in the Schedule of Events (Table 5). 
5.3.3 Handling of Withdrawals and Discontinuations 
Study withdrawals and premature discontinuations should be strongly discouraged. It is 
preferable that participants who insist on withdrawing from the study or meet criteria as 

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outlined in Section 5.3.1 be offered an opportunity to return to clinic less frequently than 
outlined in the Schedule of Events and Procedures. The reason for any change in the planned 
visit schedule must be clearly stated in the source documents. 
If the participant refuses then whenever possible, all participants who withdraw, or are 
discontinued from the study prematurely, will undergo all Premature Discontinuation Visit 
procedures as described in the Schedule of Events and Procedures (see Table 3 through Table 
5). Participants who fail to return for final assessments will be contacted by the site 
personnel in an attempt to have the participant comply with the protocol. A minimum of two 
documented phone calls should be made over the course of one week. If the site personnel 
receive no response, they should send a certified letter requesting that the participant contact 
the site regarding his/her status in the study. If the participant does not respond at this point, 
the date the certified letter was mailed will be considered the date of study withdrawal.  
In the event of a participant death during the study, the date of death (as listed on the death 
certificate) will be used for the date of study discontinuation.  
It is vital to obtain follow-up data on any participant withdrawn because of an AE or SAE. 
In such cases, the participant will be followed to satisfactory resolution or until the principal 
investigator deems the event to be chronic/stable. In any case, every effort must be made to 
undertake protocol-specified safety follow-up procedures. 
5.3.4 Replacements 
Participants who prematurely discontinue for reasons other than safety or virologic rebound 
may be replaced. 
5.3.5 Sponsor or Regulatory Agency Termination of Study 
Although the Sponsor intends to complete the study, the right is reserved to discontinue the 
study at any time for clinical or administrative reasons, or if required by the local regulatory 
authority. 
6 
STUDY PROCEDURES: SENTINEL GROUPS  
6.1 
Pre-Screening 
Potential participants will first undergo pre-Screening to assess medical history and 
qualification for the study. They will have the opportunity to discuss the study and ask 
questions of the study recruiter at this time. Those who are eligible and interested in 
participation will attend a Screening Visit. No study-specific procedures are to be performed 
prior to review and signature of an approved informed consent document. 
6.2 
Screening Visit 
During the Screening Visit, study personnel will answer all questions posed about the study. 
Written site-specific informed consent, including information provided to the participant in 
case there is an allergic reaction, will be obtained prior to conducting any study procedures. 
To ensure informed consent, the principal investigator or designee will discuss the following 
information individually with each potential participant:  
 
That all study participants must agree to use one effective method of contraception if 
engaging in sexual activity that may result in pregnancy at any time throughout the 

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study and the follow-up period. Acceptable methods of birth control for this study are: 
oral contraceptives, barrier methods, hormonal injectable or implanted contraceptives, 
tubal ligation, or vasectomy.  
 
To watch for any signs of an allergic reaction and the steps to take to follow up.  
If the participant consents to participate, site personnel will:  
 
Perform complete medical history (including concomitant medications).  
 
Record demographics. 
 
Record vital signs as per Section 8.1.4. 
 
Perform a complete physical examination as detailed in the Schedule of Events and 
Procedures including confirmation of venous access for study drug infusion. 
 
Collect blood and urine specimens for all tests as indicated in the Schedule of Events 
and Procedures.  
 
Perform a blood pregnancy test for all female participants with reproductive potential. 
The Screening Visit may be performed at two separate visits. There will be no participants 
entered into the study who do not meet all inclusion criteria and who meet any of the 
exclusion criteria unless a waiver is granted by the Medical Monitor after discussion with 
the Site PI. Laboratory testing may be repeated once within the 45 day Screening window 
at the discretion of the site investigator, should laboratory values alone result in exclusion.   
No more than 45 days may elapse between signing of the informed consent and study drug 
administration. If this occurs, then study procedures for the Screening Visit must be repeated 
unless a waiver is issued by the Medical Monitor. However, the complete medical history 
may be replaced by an interim medical history and the informed consent form may be 
reviewed without signing again. 
6.3 
Day 0 (Study Drug Administration) 
Prior to the administration, site personnel will:  
 
Review the informed consent form administered at the Screening Visit with the 
participant and answer any questions about the study.  
 
Review interim medical history (including concomitant medications).  
 
Review safety laboratory data from the Screening Visit(s). 
 
Vital signs measurements as per Section 8.1.4 within 15 minutes of study drug 
administration. 
 
Perform a directed physical examination as per the Schedule of Events and Procedures. 
 
Confirm participant is fasting. 
 
Collect blood and urine specimens for all tests pre-dose as indicated in the Schedule of 
Events and Procedures, including PK, CD4RO, immunogenicity, fasting lipids and 
CD4+ cell count samples. 
 
Perform a urine pregnancy test for all female participants with reproductive potential 
and obtain results prior to study drug administration. 
 
Sentinel group subjects will be educated as to the importance of maintaining oral cART 
regimens. 
 
At the discretion of the site PI, participants may be dosed with 2 tablets of 325 mg of 
acetaminophen or 2 tablets of 200 mg of ibuprofen combined with 10 mg of loratadine 
or cetirizine.  
 
 
 
 

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Dosing:  
Sentinel groups (N=10 for each group) 
Sentinel group 1:  
TMB-365: 2400 mg x single dose  
TMB-380: 2400 mg x single dose 
Sentinel group 2: 
TMB-365: 3200 mg x single dose  
TMB-380: 3200 mg x single dose 
Sentinel group 3: 
TMB-365: 4800 mg x single dose  
TMB-380: 4800 mg x single dose 
    
Administration Procedure 
Study drugs will be administered via IV infusion in the cephalic vein of a study 
participant. Using a sterile syringe, a corresponding volume of NS for each dose arm is 
withdrawn from a 250 mL infusion bag of NS and discarded. Then the appropriate dose of 
each antibody will be added to the infusion bag and the contents of the bag infused over 60 
minutes. Low sorb IV lines or equivalent with a 1.2 Micron filter, and an infusion pump 
and saline lock should be used for the IV IP administration. The 
clinician/physician/Research Nurse will attach the IV line to the 250mL IV saline bag with 
added IP and prime the IV line with IP from the IV saline bag.  
The infusion rate and volume will be programmed in to the pump so that the IP is infused 
over a period of approximately 60 minutes. The calculation of the flow rate must be the 
total volume in the IP bag, as received from the Pharmacy, over 60 minutes. Both the dose 
and the infusion rate calculations will be checked by a second staff member and must be 
documented by the staff administering the IP in the participant’s source documents. At the 
end of the infusion of IP, the empty IV saline bag containing IP will be replaced with a 
normal 0.9% saline bag to flush the IV line with 30 mL of normal saline at the same 
infusion rate, to ensure all the remaining IP is administered to the participant. The stop 
time will then be recorded.  
After completing the infusion(s), the physician/clinical designee/Research Nurse will 
record the start time, duration, end time, and date of IP administration on the Participant-
Specific IP Accountability Log or site-specific chain of custody document.  
• 
Start time for the infusion is defined as the time that the IP starts flowing from the 
IV saline bag containing the IP.  
• 
Stop time for the infusion is defined as the point when the normal saline flush post 
IP infusion has completed and the pump alarm sounds. 
Any infusion reaction or adverse event during study drug administration will be recorded. 
Vital signs should be recorded every 15 minutes beginning 15 minutes prior to the IP 
infusion and through completion of the required observation times of either 180 minutes or 
60 minutes. Participants should be monitored in an area where immediate treatment for any 

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hypersensitivity reaction can be administered. Any local and systemic immunogenicity 
events, as well as any other event that occurs, will be recorded. 
 
Post-Administration Procedures 
The first 3 participants in each Sentinel dose group will be closely observed for at least 180 
minutes (3 hours) and up to 300 minutes (5 hours) after IP administration with the duration 
of post-infusion observation at the discretion of the site PI. The remaining Sentinel group 
participants at that dose level will be observed for at least 60 minutes (1 hour) and up to 180 
minutes (3 hours) with the duration of post-infusion observation at the discretion of site PI 
after IP administration unless there are safety issues identified, specifically Grade 3 or 
greater adverse events observed within 7 days in the first 3 subjects treated with IP. Safety 
issues identified during these infusions will result in the temporary cessation of dosing at 
that dose level and will result in an adhoc meeting of the Data Monitoring Committee and 
the Medical Monitor to discuss modifications to the administration procedure and additional 
dosing. Vital signs (pulse, respiratory rate, blood pressure, and temperature) will be 
monitored at 15 minute (+5 minutes) intervals after administration and recorded. 
Participants should be monitored in an area where immediate treatment for any 
hypersensitivity reaction can be administered. Any local and systemic immunogenicity 
events, as well as any other event that occurs, will be recorded. 
PK samples will be collected at 10 minutes after the end of IP infusion. 
The investigator will remind the participant to watch for signs and symptom of any allergic 
reactions once he/she leaves the study site, and to contact study personnel as appropriate.  
6.4 
Pharmacokinetic Assessments for Sentinel Group Subjects 
Sentinel group participants receiving either 2400 mg or 3200 of either antibody will return 
to clinic for blood draws for serum levels of TMB-365 and 380 and CD4 receptor occupancy 
levels of TMB-365 as follows: 
Days 0, 7 (± 1d), 14 (± 2d), 28 (± 2d), 42 (± 2d), 49 (± 2d), 56 (± 2d), 63 (± 2d), 70 (± 2d), 
84 (± 2d).  
Sentinel group participants receiving 4800 mg of either antibody will return to clinic for 
blood draws for serum levels of TMB-365 and 380 and CD4 receptor occupancy levels of 
TMB-365 as follows: 
Days 0, 14 (± 2d), 28 (± 2d), 56 (± 2d), 70 (± 2d), 77 (± 2d), 84 (± 2d), 91 (± 2d), 98 (± 2d), 
112 (± 2d). 
6.5 
Sentinel Groups Comprehensive Safety Visits:  
Participants receiving 2400 mg or 3200 mg of either antibody will be scheduled for safety 
visits on Days 7 (week 1), 14 (week 2), 28 (week 4) and every 28 days (4 weeks) until Day 
84 (week 12) 
Participants receiving 4800 mg of both antibodies will be scheduled for safety visits on Days 
14 (week 2), Day 28 (week 4) and every 28 days (4 weeks) until Day 112 (week 16). 
Visits will include: 
• 
Review of interim medical history and use of concomitant medications.  
• 
Assess AEs by asking open ended questions.   

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• 
Perform a directed physical examination and vital signs as per Section 8.1.4 and as per 
the Schedule of Events and Procedures.  
• 
Collect blood and urine specimens for all tests as indicated in the Schedule of Events 
and Procedures (Table 3 and Table 4). 
6.6 
Early Discontinuation 
Participants who withdraw from the study at any time before the Day 168 / Week 24 visit 
will be asked to complete all Premature Discontinuation Visit procedures to ensure safety 
and to collect as much data as possible (Table 3 and Table 4).  
Participants may be asked to complete a Premature Discontinuation Visit and be replaced 
for non-adherence to the study visit schedule. Critical visits include Day 0, Day 14, and PK 
assessments Days 49-70 for dose groups 1 and 2 and Day 0, Day 14, and PK assessments 
days 70-91 for dose group 3. 
6.7 
Unscheduled Visits 
Unscheduled Visits may be completed for the following reasons:  
• 
To perform confirmatory laboratory testing for clinically significant abnormal values.  
• 
If in the judgement of the investigator or his/her designee it is determined that a visit is 
in the best interest of the participant’s safety and required clinical evaluation. 
Findings during these Unscheduled Visits must be reported in the CRF in the Unscheduled 
Visit section. 
7 
STUDY PROCEDURES: CORE GROUPS 
The decision to initiate screening of Core Group participants in each arm will be based on 
achieving pharmacokinetic (PK) targets in Sentinel Group participants as well as 
establishing safety. The rationale for dose groups and PK targets can be found in Sections 
3.2.and 3.3. To initiate the enrollment of a Core group, approximately 80% of participants 
in Sentinel groups should meet PK criteria as well as safety criteria as outlined above. 
Should safety criteria and PK targets not be met then enrollment into a Core group at that 
dose will not occur.  
Asymmetric dosing of Core groups participants may occur should doses of TMB-365 and 
TMB-380 meet specified safety criteria and PK targets as outlined above.  
7.1 
Pre-Screening 
Potential participants will first undergo pre-Screening to assess medical history and 
qualification for the study. They will have the opportunity to discuss the study and ask 
questions of the study recruiter at this time. Those who are eligible and interested in 
participation will attend a Screening Visit. No study-specific procedures are to be performed 
prior to review and signature of an approved informed consent document. 
7.2 
Screening Visit 
During the Screening Visit, study personnel will answer all questions posed about the study. 
Written site-specific informed consent, including information provided to the participant in 
case there is an allergic reaction, will be obtained prior to conducting any study procedures. 
To ensure informed consent, the principal investigator or designee will discuss the following 
information individually with each potential participant:  

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 
All participants should understand that oral cART will be discontinued on the day of 
the first infusion and restarted at the Day 168 (Week 24) visit, 4 weeks (28 days) prior 
to the end of study visit. 
 
That all study participants must agree to use one effective method of contraception if 
engaging in sexual activity that may result in pregnancy at any time throughout the 
study and the follow-up period. Acceptable methods of birth control for this study are: 
oral contraceptives, barrier methods, hormonal injectable or implanted contraceptives, 
tubal ligation, or vasectomy.  
 
To watch for any signs of an allergic reaction and the steps to take to follow up.  
If the participant consents to participate, site personnel will:  
 
Perform complete medical history (including concomitant medications).  
 
Record demographics. 
 
Record vital signs as per Section 8.1.4 
 
Perform a complete physical examination as detailed in the Schedule of Events and 
Procedures including confirmation of venous access for study drug infusion. 
 
Collect blood and urine specimens for all tests as indicated in the Schedule of Events 
and Procedures.  
 
Perform a blood pregnancy test for all female participants with reproductive potential. 
The Screening Visit may be performed at two separate visits. There will be no participants 
entered into the study who do not meet all inclusion criteria and who meet any of the 
exclusion criteria unless a waiver is granted by the Medical Monitor after discussion with 
the Site PI. Laboratory testing may be repeated once within the 60 day Screening window 
at the discretion of the site investigator, should laboratory values alone result in exclusion.   
No more than 60 days may elapse between signing of the informed consent and study drug 
administration. If this occurs, then study procedures for the Screening Visit must be repeated 
unless a waiver is issued by the Medical Monitor. However, the complete medical history 
may be replaced by an interim medical history and the informed consent form may be 
reviewed without signing again. 
7.3 
Day 0 (Study Drug Administration) 
Prior to the administration, site personnel will:  
 
Review the informed consent form administered at the Screening Visit with the 
participant and answer any questions about the study.  
 
Review interim medical history (including concomitant medications).  
 
Review safety laboratory data from the Screening Visit(s). 
 
Vital signs measurements as per Section 8.1.4 within 15 minutes of study drug 
administration. 
 
Perform a directed physical examination as per the Schedule of Events and Procedures. 
 
Confirm participant is fasting. 
 
Collect blood and urine specimens for all tests pre-dose as indicated in the Schedule of 
Events and Procedures, including PK, CD4RO, immunogenicity, fasting lipids and 
CD4+ cell count samples. 
 
Perform a urine pregnancy test for all female participants with reproductive potential 
and obtain results prior to study drug administration. 
Core group participants will be asked to take their last dose of oral cART in the clinic 
prior to infusion. Clinic personnel will record the time of the last dose of antiretroviral 
medications. 

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7.4 
Pharmacokinetic Assessments for Core Group Subjects 
Core group participants receiving 4800 mg of TMB-365/TMB-380 will return to clinic for 
blood draws for serum levels of TMB-365 and 380 and CD4 receptor occupancy levels of 
TMB-365 as follows: 
Days 0, 14 (± 3d), 28 (± 3d), 56 (± 3d), 84 (± 3d), 112 (± 3d), 140 (± 3d), 168 (± 3d), 196 
(± 3d).  
7.5 
Additional Infusion Schedule: Core Participants 
Core group participants will receive study drug at Day 0, Day 56 (Week 8) and Day 112 
(Week 16) as described in Section 6.3. 
 
 
Administration Procedure 
Study drugs will be administered via IV infusion in the cephalic vein of a study 
participant. Using a sterile syringe, corresponding volume of NS for each antibody is 
withdrawn from a 250 mL infusion bag of NS and discarded. Then the appropriate dose of 
each antibody will be added to the infusion bag and the contents of the bag infused over 60 
minutes. Low sorb IV lines or equivalent with a 1.2 Micron filter, and an infusion pump 
and saline lock should be used for the IV IP administration. The 
clinician/physician/Research Nurse will attach the IV line to the 250mL IV saline bag with 
added IP and prime the IV line with IP from the IV saline bag.  
The infusion rate and volume will be programmed in to the pump so that the IP is infused 
over a period of approximately 60 minutes. The calculation of the flow rate must be the 
total volume in the IP bag, as received from the Pharmacy, over 60 minutes. Both the dose 
and the infusion rate calculations will be checked by a second staff member and must be 
documented by the staff administering the IP in the participant’s source documents. At the 
end of the infusion of IP, the empty IV saline bag containing IP will be replaced with a 
normal 0.9% saline bag to flush the IV line with 30 mL of normal saline at the same 
infusion rate, to ensure all the remaining IP is administered to the participant. The stop 
time will then be recorded.  
After completing the infusion(s), the physician/clinical designee/Research Nurse will 
record the start time, duration, end time, and date of IP administration on the Participant-
Specific IP Accountability Log or site-specific chain of custody document.  
• 
Start time for the infusion is defined as the time that the IP starts flowing from the 
IV saline bag containing the IP.  
• 
Stop time for the infusion is defined as the point when the normal saline flush post 
IP infusion has completed and the pump alarm sounds. 
Any infusion reaction or adverse event during study drug administration will be recorded. 
Vital signs should be recorded every 15 minutes beginning 15 minutes prior to the IP 
infusion and through completion of the required observation times of 60 minutes. 
Participants should be monitored in an area where immediate treatment for any 
hypersensitivity reaction can be administered. Any local and systemic immunogenicity 
events, as well as any other event that occurs, will be recorded. 

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Post-Administration Procedures 
Core group participants will be observed for 60 minutes (1 hour) after IP administration. 
Vital signs (pulse, respiratory rate, blood pressure, and temperature) will be monitored at 15 
minute (+5 minutes) intervals after administration and recorded. Participants should be 
monitored in an area where immediate treatment for any hypersensitivity reaction can be 
administered. Any local and systemic immunogenicity events, as well as any other event 
that occurs, will be recorded. 
PK samples will be collected at 10 minutes after the end of IP infusion. 
The investigator will remind the participant to watch for signs and symptom of any allergic 
reactions once he/she leaves the study site, and to contact study personnel as appropriate.  
 
Study Procedures Days 14, 28 and every 28 days through Day 196: 
Visits will include: 
• 
Review of interim medical history and use of concomitant medications.  
• 
Assess AEs by asking open ended questions.   
• 
Perform a directed physical examination and vital signs as per Section 8.1.4 and as per 
the Schedule of Events and Procedures.  
• 
Collect blood and urine specimens for all tests, which include safety and PK/PD 
assessments at each scheduled visit, as indicated in the Schedule of Events and 
Procedures (Table 5). 
• 
Restart the oral cART regimen being taken at the time of screening in clinic at the Day 
168 (Week 24) visit. Clinic personnel should record the time of dosing. 
7.6 
Early Discontinuation 
Participants who withdraw from the study at any time before the Day 168 / Week 24 visit 
will be asked to complete all Premature Discontinuation Visit procedures to ensure safety 
and to collect as much data as possible (Table 5). Study subjects who fail to complete the 
first 8 weeks of participation due to non-adherence to the schedule may be replaced.  
7.7 
Unscheduled Visits 
Unscheduled Visits may be completed for the following reasons:  
• 
To perform confirmatory laboratory testing for clinically significant abnormal values.  
• 
To confirm virologic failure, defined as 2 consecutive viral load determinations above 
50 copies/mL plasma at least 2 weeks apart. 
• 
If in the judgement of the investigator or his/her designee it is determined that a visit is 
in the best interest of the participant’s safety and required clinical evaluation. 
Findings during these Unscheduled Visits must be reported in the CRF in the Unscheduled 
Visit section. 
7.8 
Stopping Criteria 
Stopping criteria for an individual subject within a Core Group:  
Safety: Any SAE, Grade 3 or 4 adverse event probably or definitely due to the monoclonal 
antibody infusions within 14 days of treatment. 
Antiviral activity: Documented virologic failure in an individual. Resistance analysis 
including phenotype and genotype will be performed in subjects in whom virologic failure 

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is documented.  
Stopping criteria for dosing of a Core Group: 
Safety: An SAE probably or definitely due to the monoclonal antibody infusions. 
More than one Grade 3 or 4 adverse event probably or definitely due to the monoclonal 
antibody infusions..  
Antiviral activity: Documented virologic failure in more than two individuals in a Core 
Group who have received scheduled infusions of the combination of TMB-365 and TMB-
380. Resistance analysis including phenotype and genotype will be performed in subjects in 
whom virologic failure is documented.  
To ensure participant safety all SAEs, Grade 3 and Grade 4 AEs will be reviewed by the 
Data Monitoring Committee (DMC) (Section 9.9) to assess causality. All cases of virologic 
failure will be similarly reviewed. The DMC may elect to terminate dosing of individuals 
in the Core Group at any juncture based on their assessment of safety and antiviral activity.  
Should the study be halted due to safety concerns of lack of efficacy then all enrolled 
subjects will cease dosing with bNAbs and resume oral cART as per the week 24 and week 
28 visits in the Schedule of Events (Table 5). 
8 
STUDY ASSESSMENTS 
8.1 
Activities to Be Completed 
The following assessments will be conducted at the times indicated in the Schedule of 
Events and Procedures (Table 3 through Table 5) and recorded in source documents as per 
the standard operating procedures of the clinical site. Samples will be processed using 
standard procedures as described in the laboratory procedures manual, and will be analyzed 
by a central laboratory unless otherwise noted.   
8.1.1 Demographic Data, Medical History, and Concomitant Medications 
Demographic data, a complete medical history (per participant report), and documentation 
of prior medications used within 30 days of the Screening Visit and all prior ART will be 
collected at Screening; information about concomitant medications will be obtained at each 
visit.  
8.1.2 Complete Physical Examination 
A complete physical examination will include the following assessments: skin, head, eyes, 
ears, nose, throat (HEENT), chest including breasts and lungs, heart, abdomen, extremities, 
and neurological exam. 
8.1.3 Directed Physical Examination 
Directed physical examination will be limited to assessment of HEENT, chest, heart, 
abdomen, and assessment of any site related to specific signs and symptoms reported by the 
patient. 

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8.1.4 Vital Sign Measurements 
Vital sign measurements will include the participant’s heart rate (beats/minute taken for 
one minute), blood pressure (mm Hg), respiratory rate (breaths/minute taken for one minute), 
and temperature (ºC) as per the Schedule of Events and Procedures (Table 3 through Table 
5). On the day of dosing measurements will be taken within 15 minutes before the study 
drug administrations and every 15 minutes for at least 1 hour and up to 5 hours after the 
study drug is administered as per Sections 6.3 and 7.3 and 7.4. Blood pressure and heart rate 
measurements will be obtained after the participant has been seated or reclining for at least 
five minutes. Ideally, each participant’s blood pressure should be measured using the same 
arm and the same size cuff at each visit.  
8.2 
Blood and Urine Samples 
8.2.1 Clinical Laboratory Parameters 
Collection of blood and urine samples for clinical laboratory assessments will be part of a 
normal safety profile assessment for the study participant. Samples will be processed using 
standard procedures as described in the laboratory procedures manual, and will be analyzed 
by a central laboratory unless otherwise noted.  
The samples will be analyzed for the following: 
Hematology: Complete white blood cell count with differential, hemoglobin, 
hematocrit, and platelets. 
Serum Chemistry Profile: ALT, AST, chloride, creatinine, potassium, sodium, total 
and direct bilirubin, albumin, alkaline phosphatase, blood urea nitrogen, magnesium 
and creatine phosphokinase, amylase, lipase, and phosphorus. 
Fasting Lipid Profile: Includes total cholesterol, HDL, LDL, and triglycerides at 
designated visits indicated in Schedule of Event and Procedures (Table 3 to Table 5). 
Urinalysis: Visual inspection for appearance and dipstick assessment for color, pH, 
specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and 
leukocyte esterase. If dipstick assessment is abnormal then urine should be sent to 
the Central laboratory for a complete urinalysis. Urinalysis should be done at 
designated visits indicated in Schedule of Event and Procedures (Table 3 to Table 5) 
Screening for Chronic Hepatitis: HBV and HCV screening will be performed for all 
potential participants at the study Screening visit (Table 3 to Table 5).  
Tests with Grade 2 or greater abnormal results according to the DAIDS Table for Grading 
Severity of Adult and Pediatric Adverse Events Version 2.1 must be reported as AEs if 
deemed clinically significant by the investigator or his/her designee. Tests with Grade 2 or 
greater abnormal results may be repeated within two days of the site becoming aware of the 
abnormal value(s). See Appendix A for abnormality grading scales. Grade 3 and Grade 4 
abnormal test results should be repeated for confirmation within 2 days of the site becoming 
aware of the abnormal value, independent of assessment of relation to investigational 
products. 
8.2.2 Pregnancy Testing 
A serum pregnancy test will be performed at Screening Visit to confirm that a female is not 
pregnant prior to enrolling the study. A urine pregnancy test will be performed at defined 

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study visits to confirm that a female has not become pregnant during the study. These tests 
are performed for the protection and safety of the fetus, as the risk to the fetus is unknown. 
See Section 9.8 for a description of procedures to be followed in case of pregnancy. 
8.2.3 HIV EIA and Confirmatory Testing 
Blood samples will be obtained at the screening visit for HIV-1/HIV-2 EIA (enzyme 
immunoassay) and subsequent confirmatory testing to ensure that the participant is eligible 
for study participation as per Section 5.1. 
8.2.4 HIV RNA (Viral Load) 
Blood samples for viral load will be used to determine whether the combination of 
antibodies as a stand-alone maintenance regimen can maintain virologic suppression in 
cART treated individuals. Results will be expressed as copies/mL plasma as well as log 
copies/mL plasma. 
8.2.5 CD4+/CD8+ Cell Count 
Blood samples for CD4+/CD8+ T-cell levels will be taken over the course of the study to 
monitor for any effect of TMB-365 and TMB-380 on levels of CD4+/CD8+ T-cells in study 
participants. Results will be expressed as the number of cells per mm3 of blood and relative 
%. 
8.2.6 CD4 Receptor Density and Occupancy 
Blood samples for CD4 receptor density will be taken to determine if the binding of TMB-
365 induces any changes in surface expression of CD4. It is unknown if the number of CD4 
molecules on the cell surface, or receptor density, could be altered during TMB-365 therapy. 
CD4 receptor occupancy is the proportion of total CD4 molecules on participant blood cells 
that are occupied by bound TMB-365. Blood samples used to measure receptor density will 
also be used to measure receptor occupancy as a PD effect of TMB-365 administration. 
Results are expressed as % receptor occupancy and/or CD4 receptor density.  
8.2.7 TMB-365 and TMB-380 Concentrations 
Measurements of concentrations of TMB-365 and TMB-380 in serum will be used to 
determine the concentration-time profile of TMB-365 and TMB-380 in all participants. 
TMB-365 and TMB-380 serum concentrations will be measured using validated enzyme-
linked immunosorbent assays (ELISAs). Results will be expressed as ng/mL serum.  
8.2.8 Immunogenicity 
Serum samples will be collected to test for the development of antibodies against TMB-365 
and TMB-380 throughout the study. The incidence of anti-TMB-365 and anti-TMB-380 
antibody production will be determined by ELISA that has been validated for the detection 
of anti-TMB-365 and anti-TMB-380 antibodies in human serum.  
8.2.9 Resistance Analysis in Core Group Subjects 
Plasma samples will be drawn as per the Schedule of Events and Procedures for resistance 

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analyses. Phenotypic susceptibility determinations and genotypic analyses in participants 
with documented virologic rebound will be performed at the discretion of the Study 
Virologist. 
Virologic rebound will be defined as: 
ý 
Two consecutive viral load determinations above 50 copies/mL plasma at least 2 
weeks apart.  
In the event of virologic rebound then resistance studies will be performed to assess 
susceptibility to TMB-365 and/or TMB-380 at virologic rebound. Additionally genotypic 
analyses will be performed in an attempt to identify genotypic signatures within the env 
coding region that may be associated with the observed phenotypic change or changes, 
reduced susceptibility or cross resistance. Core subjects meeting criteria for virologic failure 
will be immediate restarted on oral cART. 
8.2.10 
Archive Sample 
A separate serum sample will be taken as the backup sample for assays in the study. 
9 
ADVERSE EVENTS 
9.1 
Definitions 
The investigator is responsible for reporting to the Sponsor or designee all SAEs that are 
observed or reported by the participant during the study, regardless of their relationship to study 
drug or their clinical significance. Participants will be instructed to contact study site personnel 
at any time after informed consent is obtained if any symptoms develop.  
Adverse Events 
An AE is defined as any untoward medical occurrence in a participant regardless of its 
causal relationship to study drug. An AE can therefore be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding, symptom, or disease temporally associated with 
the use of a medicinal product), whether or not considered related to the study drug.  
Treatment-Emergent Adverse Events 
A treatment-emergent AE (TEAE) is defined as any event not present before exposure to 
study drug or any event already present that worsens in either intensity or frequency 
following exposure to study drug.  
Serious Adverse Event 
An SAE is defined as any event that results in death, is immediately life-threatening, 
requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is 
deemed by the investigator to be an important medical event based upon appropriate medical 
judgement.  
An important medical event may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. It may expose 
the participant to danger, even though the event is not immediately life-threatening or fatal, 
or does not result in hospitalization. 
The term <immediately life-threatening= refers to an event in which the participant was at 

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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. 
9.2 
Eliciting Adverse Event Information 
At every study visit, participants will be asked a standard, non-directive question, such as 
<How have you been feeling since your last visit?= to elicit any medically related changes 
in their well-being. They will also be asked if they have been hospitalized, had any accidents, 
used any new medications, or changed concomitant medication regimens (both prescription 
and over-the-counter medications). 
In addition to participant observations, AEs will be documented from any clinically 
significant diagnosis resulting from abnormal laboratory test values, physical examination 
findings, or from other documents that are relevant to participant safety.  
9.3 
Reporting Adverse Events 
Recording of AEs will begin after the participant signs the informed consent form. However, 
any AE that occurs after the informed consent is signed but before the first administration 
of the study drug will be recorded as medical history, unless it is related to a study procedure. 
Any AE that occurs after the first dose of study drug and until seven days after the last study-
required sample collection at the end of the follow-up period, regardless of its relationship 
to study drug, will be recorded in the AE section of the CRF. 
All AEs reported or observed during the study must be reported in detail in the AE section 
of the CRF and followed to a satisfactory resolution or until the principal investigator deems 
the event to be chronic/stable. 
Information to be collected includes type of event, date of onset, date of resolution, 
investigator-specified assessment of severity and relationship to study drug, whether or not 
it qualifies as an SAE, as well as any required treatment or evaluations and outcome.  
Preexisting conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and should NOT be recorded as AEs. However, if the pre-
existing condition worsens in severity, the investigator must report is as an AE. Each AE 
should be recorded to represent a single diagnosis. Accompanying signs or symptoms should 
NOT be recorded as additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should 
be recorded as AE(s). Changes in laboratory values are only considered to be AEs if they 
are judged to be clinically significant (i.e., if some action or intervention is required). If 
abnormal laboratory values are the result of pathology for which there is an overall diagnosis 
(e.g., increased creatinine in renal failure), the diagnosis only should be reported as an AE. 
Pre-planned procedures (surgeries or therapies) that were scheduled prior to the start of AE 
collection are not considered AEs. However, if a pre-planned procedure is performed early 
(e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening of 
the condition should be captured as an AE. Elective procedures performed where there is no 
change in the participant’s medical condition should not be recorded as AEs, but should be 
documented in the participant’s source documents.  
The Medical Dictionary for Regulatory Activities (MedDRA) will be used by the sites to 
code all AEs. 
All AEs, whether serious or not, should be followed to a satisfactory resolution or until the 
principal investigator deems the event to be chronic/stable, and the AE is determined to be 
not clinically significant.  

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9.4 
Assessment of Causality 
The investigator’s assessment of an AE's relationship to study drug is part of the 
documentation process. If there is any doubt as to whether or not a clinical observation is 
an AE, the event should be reported. 
The relationship or association of the study drug in causing or contributing to the AE will 
be characterized by the investigator using the following classifications and criteria: 
Unrelated: This relationship suggests that there is no association between the study drug and 
the reported event. 
Probable: This relationship suggests that a reasonable temporal sequence of the event with 
drug administration exists and, based upon the known pharmacological action of the drug, 
known or previously reported adverse reactions to the drug or class of drugs, or judgement 
based on the investigator’s clinical experience, the association of the event with study drug 
administration seems likely. 
Definite: This relationship suggests that a definite causal relationship exists between the 
drug 
administration and 
the AE, 
and 
other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do not appear to 
explain the event. 
9.5 
Assessment of Severity 
The intensity of the AE will be rated by the investigator as mild, moderate, severe, or 
potentially life-threatening using the following criteria: 
Mild: Symptoms causing no or minimal interference with usual social and functional 
activities. 
Moderate: Symptoms causing greater than minimal interference with usual social and 
functional activities. 
Severe: Symptoms causing inability to perform usual social and functional activities. 
Potentially Life-Threatening: Symptoms causing inability to perform basic self-care 
functions OR medical or operative intervention indicated to prevent permanent impairment, 
persistent disability, or death. 
Details for grading severity are given in Appendix A. Increases in the severity of an AE 
should be documented to allow an assessment of the duration of the event at each level of 
intensity to be performed.  
9.6 
Infusion Reactions 
The Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 scale will be used 
for assessment of any infusion reactions, or anaphylactic events. All other adverse events 
will be graded as per the DAIDS Table for Grading Severity of Adult and Pediatric Adverse 
Events Version 2.1 (see Appendix A).

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For infusion reaction, the following assessment of severity per the CTCAE toxicity table should be used: 
 
CTCAE 
Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 
5 
Infusion 
Related 
Reaction 
Mild transient reaction; infusion 
interruption 
not 
indicated; 
intervention not indicated 
Therapy or infusion interruption 
indicated but responds promptly 
to symptomatic treatment (e.g., 
antihistamines, 
NSAIDS, 
narcotics, IV fluids); prophylactic 
medications indicated for <=24 
hrs 
Prolonged 
(e.g., not rapidly 
responsive 
to 
symptomatic 
medication 
and/or 
brief 
interruption 
of 
infusion); 
recurrence 
of 
symptoms 
following initial improvement; 
hospitalization 
indicated 
for 
clinical sequelae 
Life-threatening 
consequences; 
urgent intervention indicated 
Death 
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. 
Anaphylaxis 
- 
- 
Symptomatic bronchospasm, with 
or without urticaria; parenteral 
intervention indicated; allergy-
related 
edema/angioedema; 
hypotension 
Life-threatening 
consequences; 
urgent intervention indicated 
Death 
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from mast cells, causing a 
hypersensitivity immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness and may lead to death. 

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9.7 
Serious Adverse Event Reporting 
Any AE considered serious by the principal investigator according to the previously 
described criteria must be reported by  email within 24 hours from the time when site 
personnel first learn about the event.  
SAE Email:  
pvreport@taimedbio.com 
 
 
The site should notify the Sponsor or designee within 24 hours of the site becoming aware 
of the event. Sites will submit information using the appropriate reporting form and 
mechanism, as required by the safety management provider/Sponsor or designee. This 
report should include the following information regarding the study participant and the event: 
demographics, medical history, complete information on the SAE, and concomitant 
medications information. If the participant is hospitalized because of or during the course 
of an SAE, then a copy of the hospital discharge summary and any pertinent laboratory or 
diagnostic reports should be faxed or mailed to the Sponsor or designee as soon as it 
becomes available.  
The investigator should forward to the safety management provider/Sponsor or designee 
any additional written documentation on the event that becomes available after the first 
report. The information should be sent as instructed by the safety management 
provider/Sponsor or designee immediately or within one working day of receipt.  
The Sponsor or designee will notify the appropriate regulatory agencies of any fatal or life-
threatening unexpected SAEs associated with the use of the study drug as soon as possible 
but no later than seven calendar days after the initial receipt of the information. Initial 
notification will be followed by a written report within 15 calendar days. For other SAEs 
that do not meet the life-threatening or fatal criteria, but are reported to be unexpected and 
associated with the use of the study drug, the Sponsor or designee will notify the proper 
regulatory agency in writing as soon as possible but no later than 15 calendar days from the 
initial receipt of information. Copies of any reports to regulatory agencies regarding serious 
and unexpected SAEs will be provided to the investigators by the Sponsor or designee for 
review and submission to the institutional review board (IRB) or ethics review committee 
(ERC).  
The principal investigator is responsible for informing his/her IRB/ERC of any SAEs at that 
site. Copies of SAE correspondence with the principal investigator, regulatory authorities, 
ethics committees, and Sponsor must be submitted to the Sponsor or designee for filing. 
A participant experiencing one or more SAEs will receive treatment and follow-up 
evaluations by the principal investigator, or he/she will be referred to another appropriate 
physician for treatment and follow-up. Withdrawal from the study and all therapeutic 
measures will be at the discretion of the principal investigator at the site.  
All AEs, whether serious or not, should be followed to a satisfactory resolution or until the 
principal investigator deems the event to be chronic/stable and the AE is determined to be 
not clinically significant.  
9.8 
Pregnancy 
Childbearing Potential 
Females of childbearing potential are female participants who are not surgically sterile (no 
history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-oophorectomy), are not 
postmenopausal (at least one year without menses), and are not otherwise sterile by medical 

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evaluation. These participants must use one adequate form of birth control.  
Suspected Pregnancy 
During the study, all females of childbearing potential will be instructed to contact the 
investigator immediately if they suspect they might be pregnant (e.g., late or missed 
menstrual period). Male participants will be instructed to contact the investigator if a sexual 
partner suspects she may be pregnant. 
If a participant or investigator suspects that the participant may be pregnant before study 
drug administration, the study drug must be withheld until the results of laboratory 
pregnancy testing are available. If pregnancy is confirmed, the participant must not receive 
the study drug and must be withdrawn from the study. If a participant already on the study 
is confirmed to be pregnant, the investigator must immediately notify the Medical Monitor 
of a pregnancy associated with study drug exposure and record the event on the Pregnancy 
Surveillance Form that will be provided to each site. Other appropriate follow-up procedures 
should be considered if indicated.  
Women who are found to be pregnant and participants in the Core Group should be taken 
off study and restart cART as per the DHHS Perinatal Guidelines with the guidance of her 
primary care physician. 
The investigator must follow up with a pregnant participant or the pregnant partner of any 
sexually active male participant every 4 weeks while the woman is pregnant and every 4 
weeks thereafter for at least 12 weeks, to follow perinatal and neonatal outcome. The 
investigator must report follow-up information regarding the course of the pregnancy, 
including perinatal and neonatal outcome on the appropriate Pregnancy Surveillance Form. 
9.9 
Data Monitoring Committee 
An independent DMC will review the progress of the trial and the accumulating data to 
detect evidence of safety issues for participants while the trial is ongoing.  
The DMC will make recommendations regarding the continuation, modification, or 
termination of the trial to the Sponsor or designee following each meeting. The DMC will 
consist of three independent clinicians and a statistician. The DMC will consist of 
independent individuals who have no relationship to the principal investigator and sub-
investigators involved in the trial or financial interest in the Sponsor. No member of the 
DMC will have any direct responsibility for the clinical care of trial participants. The DMC 
may invite the principal investigator or designee and Sponsor representative to an open 
session of a DMC meeting to provide information on study conduct, present data, or to 
respond to the DMC members' questions.  
The name, university affiliation and title, area of expertise, and contact information of each 
of the DMC members will be provided to the IRB/ERC. All updated versions of the protocol 
and Investigator’s Brochure (IB) will be provided to the DMC members. 
The DMC will review the trial data after the first 7 sentinel participants have completed 
infusions and 2 weeks follow-up to consider dose escalation to a higher dose of either 
antibody to meet both safety and PK criteria for initiation of a Core group. 
Should there be Grade 3 or higher adverse events in the first 3 subjects in any Sentinel group 
then dosing should cease and the DMC should meet ad hoc with the Medical Monitor to 
discuss possible changes to the administration of TMB-365 and TMB-380.  
The DMC will be responsible for adhering to study stopping guidelines outlined in Section 

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5.3.2. 
In the event of a Grade 3 or Grade 4 infusion reaction as per the Common Terminology 
Criteria for Adverse Events (CTCAE) v. 5.0 (Section 9.6) in any dosing group, further 
dosing will be immediately stopped. The DMC will be immediately notified and will 
determine whether additional dosing may occur.   
During dosing of Core Subjects the DMC will be notified of all SAEs, Grade 3 and 4 adverse 
events deemed possibly or probably due to study drug as well as all cases of virologic failure 
to determine whether continued enrollment and treatment of Core Subjects is safe and 
potentially effective. Stopping rules for individuals in Core as well as dosing of Core 
subjects is stated in Sections 5.3.2 and 7.8. 
10 STATISTICAL CONSIDERATIONS 
10.1 Determination of Sample Size 
The sample size is not statistically driven and will be primarily descriptive with emphasis 
placed on tabular and graphical displays. Summary statistics will be calculated along with 
interval estimates of solicited and unsolicited adverse events and measurement of antiviral 
activity.  
10.2 Analysis Populations 
The full analysis set (FAS) includes all participants who are administered any fraction of 
study drug. The efficacy population consists of all participants who receive at least one 
infusion of TMB-365 and TMB-380 (FAS). Similarly the PK population consists of all 
participants in the FAS. The analysis of study data will be primarily descriptive, with 
emphasis on tabular and graphical displays. Summary descriptive statistics will be 
calculated, along with point and interval estimates of solicited and unsolicited AEs. This 
study is exploratory, and any statistical inferences will be hypothesis generating, and not 
confirming. 
10.3 Study Endpoints 
The primary objectives of this study are to: 
 
ý 
Evaluate the safety and tolerability of various doses and dosing regimens of IV 
infusions of TMB-365 and TMB-380 given q8wks in suppressed, cART treated 
HIV-1 infected participants.  
ý 
Define the pharmacokinetic (PK) profile of TMB-365 and TMB-380 when given 
q8wks in suppressed, cART treated HIV-1 infected participants  
ý 
Evaluate the antiviral activity of the combination of TMB-365 in combination with 
TMB-380 as maintenance therapy in suppressed HIV infected individuals (Core 
only) 
 
Exploratory objectives of this study are to: 
ý 
Characterize the emergence of viral resistance to TMB-365 and TMB-380 in HIV-1 
infected participants who fail to maintain suppression on the combination of TMB-
365/TMB-380 

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ý 
Determine the immunogenicity of TMB-365 and TMB-380 in HIV-1 infected 
suppressed participants  
  
10.3.1 
Efficacy Analysis 
Efficacy will be assessed by longitudinal measurements of plasma HIV-1 RNA levels. The 
efficacy of the combination of TMB-365 and TMB-380 as maintenance therapy in 
suppressed HIV-1 infected participants will be expressed as the percent of participants who 
remain suppressed that is a plasma HIV-1 RNA below detection, at Day 168 / Week 24.  
10.3.2 
Safety Analysis 
Safety will be assessed by both clinical and laboratory examinations. Laboratory results that 
are Grade 2 or greater according to the DAIDS Table for Grading Severity of Adult and 
Pediatric Adverse Events Version 2.1 must be reported as AEs if the investigator deems 
the abnormal result as clinically significant. Standard panels of hematology, chemistry, 
lipids, and urinary analyses will be performed at regular intervals as per the schedule of 
events and procedures. Additionally, TMB-365- and TMB-380-specific laboratory 
assessments will be obtained and include serum TMB-365 and TMB-380 levels, 
immunogenicity, CD4+ T-cell counts, and CD4 receptor density/occupancy assessments. 
Complete and focused physical examinations will be performed throughout the study. 
In addition to general safety parameters assessed by physical exam and review of clinical 
laboratory data, all participants will be closely monitored for infusion-related AEs during 
and after administration of TMB-365. 
10.3.3 
Pharmacokinetic and Pharmacodynamic Analyses 
PK and PD profiles will be assessed. The serum concentration-time profile of TMB-365 and 
TMB-380 will be measured in all participants at time points chosen to determine minimum 
and maximum concentrations.  
PD end points will include CD4+ T-cell counts, CD4 receptor density (on CD4+ T-cells), 
CD4 receptor occupancy (by TMB-365, on CD4+ T-cells), and plasma HIV-1 RNA. 
The PK data will be used to determine levels of monoclonal antibodies that may be 
associated with maintenance of suppression of antiviral response. 
The PD data will be evaluated to determine the relationship among TMB-365 and TMB-
380 serum concentrations, CD4 receptor number, and CD4 receptor occupancy and 
maintenance of virologic suppression. TMB-365 binds to CD4 receptors where clearance is 
mediated, in part, by receptor turnover. The overall number of CD4 receptors in the body 
has not been accurately determined and the rate of receptor turnover is unknown, but is 
thought to be highly variable. TMB-380 does not bind to cellular receptors and is directed 
against the CD4 receptor binding domain of the viral envelope.  
10.3.4 
Safety Endpoints 
Safety endpoints include the following: 
• 
Incidence of TEAEs; 
• 
Incidence of TEAEs by severity; 

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• 
Incidence of TEAEs by relationship to study drug; 
• 
Incidence of SAEs; 
• 
Incidence of SAEs by severity; 
• 
Incidence of SAEs by relationship to study drug; 
• 
Discontinuation of participants from the study due to AEs; 
• 
Discontinuation of participants from the study due to deaths; 
• 
Clinical laboratory results; 
• 
Vital sign measurements; and 
• 
Physical examination results. 
10.4 Statistical Analyses 
All data collected at each visit will be summarized. Continuous variables (e.g., age, weight) 
will be summarized using descriptive statistics consisting of number of participants, mean, 
standard deviation, minimum, median, and maximum values. Categorical variables (e.g., 
gender) will be summarized using the number and percentage of participants in each 
category. If there are unscheduled assessments between visits or repeat assessments at a visit, 
the one closest to the scheduled time of the visit will be used in the summaries. The 
association of data collected with a visit (i.e., whether it is scheduled, unscheduled, or a 
repeat) will be unambiguous in the CRF. All data collected will be included in the data 
listings. 
All statistical analyses and data summaries will be performed using SAS® Version 9.1 or 
higher. A Statistical Analysis Plan (SAP) detailing the analyses described below, which may 
include mock table and listing shells. 
10.4.1 
Participant Accountability 
Participants who are screened but not eligible will not be included in the statistical analyses. 
These participants will be summarized in the participant accountability table only. 
Participants who are screened, eligible, but do not receive TMB-365 and TMB-380 will not 
be included in the statistical analysis but will be summarized in the participant 
accountability table only. 
Participants who receive at least one dose of TMB-365 and TMB-380 will be included in 
the safety analysis. 
Sentinel group subjects who complete the required clinic visits will be included in the PK 
analysis. Subjects failing to complete the required visits within prescribed windows may be 
replaced as the determination PK targets required to signal the enrollment of the Core 
participants must be met.   
Efficacy analysis will include an <intent to treat= which includes all participants who receive 
one dose of TMB-365 and TMB-380 as well as an <as treated= analysis which includes all 
participants who complete through Day 168 / Week 24. 
The number of participants discontinuing and the reasons for discontinuing will also be 
summarized. The number of participants included in the FAS and PK analysis sets will be 
presented. A list of participants excluded from any analysis set and the reason for exclusion 

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will be prepared. 
10.4.2 
Demographic and Background Characteristics 
Demographic and background characteristics will be summarized. 
10.4.3 
Concomitant Medications 
All concomitant medications (prescriptions or over-the-counter medications) continued at 
the start of the trial or started during the trial and different from the study drug must be 
documented in the Concomitant Therapy section of the CRF. Reported information will 
include a description of the type of the drug, treatment period, dosage group, route of 
administration, and its indication. Any change in dosage of any non-investigational 
medication must also be reported in the Concomitant Therapy section. 
Female participants of childbearing potential and sexually active male participants with 
partners of childbearing potential must use birth control methods as outlined previously and 
must be willing to continue practicing these birth control methods throughout the trial and 
for at least 30 days after the last administered dose. The use of oral, injectable, and 
implantable hormonal contraceptives is to be recorded in the CRF. 
10.4.4 
Treatment Emergent Adverse Events  
The incidence (n and %) of TEAEs, SAEs, and early termination of study medication or 
study participation due to an AE will be presented. Additionally, TEAEs will be tabulated 
according to severity and relatedness categories as reported by the investigator. TEAEs will 
be presented in tables organized alphabetically by Preferred Term within System Organ 
Class. Each patient will be counted only once for each TEAE reporting level.  
10.4.5 
Vital Signs  
Actual values and change from Baseline values for vital signs and weight will be 
summarized descriptively by dose group at all scheduled study visits. Potentially clinically 
significant (PCS) criteria may be applied to vital signs as clinically indicated. If applied, the 
overall incidence of participants having met any of the PCS criteria will be presented. The 
number and percentage of participants with each individual PCS criteria will also be 
presented. Listings of participants with PCS vital signs will be provided.  
10.4.6 
Laboratory Determinations  
Actual values and change from Baseline values for continuous data from laboratory 
determinations will be summarized descriptively at relevant study visits including HIV-1 
RNA and CD4+ T cell determinations. Categorical data from clinical laboratory tests will 
be similarly summarized for the actual values. Clinical laboratory tests categorized as in or 
out of normal range will be summarized using worst-case shift tables. Worst-case shift tables 
will be the cross tabulation of the Baseline result category (high, normal, low) with the 
worst-case result during the treatment period.  
PCS criteria may also be applied to laboratory determinations as clinically indicated, and if 
applied, will be summarized as described above. 

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10.4.7 
Physical Examinations  
Physical examination findings will be summarized by dose group at each visit collected 
according to the number (%) of participants with abnormal findings.  
10.4.8 
Immunogenicity Testing  
Anti-TMB-365 and anti-TMB-380 antibody levels will be summarized in a separate report 
issued by the study virologist.  
10.4.9 
Pharmacokinetic Variables  
All blood samples collected for TMB-365 and TMB-380 serum concentration analysis in 
Sentinel group will be used to assess the PK profile (total drug exposure and drug 
elimination profile). PK parameters, such as half-life, AUC, and clearance, will be estimated 
for all participants by non-compartmental analysis. Missing plasma concentration data will 
not be imputed. Exploratory data analysis will include graphical and descriptive statistical 
evaluations. 
Blood samples collected from all participants in Core group will be used to summarize peak 
(maximum) and trough (minimum) TMB-365 and TMB-380 concentrations. 
10.4.10 
Other Information  
All other information recorded in the CRF (e.g., inclusion and exclusion criteria, results of 
serum pregnancy tests, screens for drugs of abuse) will be listed by dose 
group/investigator/participant. No summaries will be presented.  
11 DATA HANDLING AND QUALITY ASSURANCE 
11.1 Case Report Forms 
All data must be entered in English. The CRF should always reflect the latest observations 
on the participants in the trial. Therefore, the data are to be entered into the CRF as soon as 
possible during, or within seven days of the participant’s visit. To avoid inter-observer 
variability, every effort should be made to ensure that the same individual who made the 
initial Day 0 determinations completes all safety evaluations. The study monitor will verify 
that all data entries in the CRF are accurate and correct. If some assessments have not been 
done, or if certain information is not available, or not applicable, or is unknown, the 
investigator should indicate this in the CRF. The investigator will be required to sign off on 
the clinical data. 
The Sponsor or designee will review the CRF and evaluate the entries for completeness and 
consistency. The data captured in the CRF will be compared with the source documents to 
ensure no discrepancies between critical data recorded in the CRF and the source documents. 
All entries, corrections, and alterations are to be made by the responsible investigator or 
his/her designee.  
The study monitor cannot enter data in the CRF. Corrections to the data fields in the CRF 
should be tracked by an audit trail, meaning that the reason for the change and the name of 
the person who performed the change, together with the time and date the change was made 

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should be logged. Roles and rights of the site personnel responsible for entering the clinical 
data into the CRF will be determined in advance and documented on the appropriate form. 
If additional corrections are needed, the responsible study monitor or project manager will 
issue a query. The appropriate investigational staff will answer queries sent to the 
investigator.  
11.2 Monitoring of the Study 
The clinical monitor, as a representative of the Sponsor, has the obligation to follow the 
study closely. In doing so, the monitor will visit the principal investigator and study facility 
periodically, or, remotely monitor if travel is restricted due to the COVID-19 pandemic or 
other unforeseen circumstances, in addition to maintaining necessary telephone and letter 
contact. The monitor will maintain current personal knowledge of the study through 
observation, review of study records and source documentation, and discussion of the 
conduct of the study with the principal investigator and staff. 
All aspects of the study will be carefully monitored by the Sponsor or designee for 
compliance with applicable government regulations with respect to the International 
Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (ICH) guideline E6(R2): Guideline for Good Clinical Practice and current standard 
operating procedures. 
Each investigator is expected to make a reasonable effort to accommodate the clinical 
monitor when site visits are necessary.  
11.3 Inspection of Records 
Principal investigators and institutions involved in the study will permit trial-related 
monitoring, audits, IRB/ERC review, and regulatory inspection(s), by providing direct 
access to all study records. In the event of an audit, the principal investigator will agree to 
allow the Sponsor, representatives of the Sponsor, or other relevant regulatory authorities 
access to all study records. 
The principal investigator should promptly notify the Sponsor or designee of any audits 
scheduled by any regulatory authorities and promptly forward copies of any audit reports 
received to the Sponsor or designee. 
11.4 Study Record Retention 
Essential documents including clinical records, laboratory results, and regulatory documents 
should be retained at least 15 years after the end of the study.  
12 ADMINISTRATIVE CONSIDERATIONS 
12.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in 
a manner designed to maintain participant confidentiality. All records will be kept in a 
secure storage area with limited access. Clinical information will not be released without 
the written permission of the participant (or the participant’s guardian), except as necessary 
for monitoring and auditing by the Sponsor, its designee, the applicable regulatory 
authorities, or the IRB/ERC. 

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The principal investigator and all employees and coworkers involved with this study may 
not disclose or use for any purpose other than performance of the study, any data, records, 
or other unpublished confidential information disclosed to those individuals for the purpose 
of the study. Prior written agreement from the Sponsor or designee must be obtained for the 
disclosure of any said confidential information to other parties. 
12.2 Ethics Review Committee 
The ICH guidelines require that approval be obtained from an IRB/ERC before participation 
of human participants in research studies. Before the study onset, the protocol, informed 
consent, advertisements to be used for participant recruitment, and any other written 
information regarding this study to be provided to the participant or the participant’s legal 
guardian must be approved by the IRB/ERC. Documentation of all IRB/ERC approvals and 
of the IRB/ERC compliance with ICH E6(R2) will be maintained by the site and will be 
available for review by the Sponsor or designee. 
All IRB/ERC approvals should be signed by the IRB/ERC chairperson or designee, and they 
must identify the IRB/ERC by name and address, the clinical protocol by title with or 
without the protocol number, and the date approval and/or favorable opinion was granted. 
The principal investigator is responsible for obtaining continued review of the clinical 
research at intervals specified by the IRB/ERC, but not exceeding one year. The principal 
investigator must supply the Sponsor or designee with written documentation of continued 
review of the clinical research. 
12.3 Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent 
immediate hazard to the participant, must be reviewed and approved by the Sponsor or 
designee. Amendments to the protocol must be submitted in writing to the principal 
investigator’s IRB/ERC for approval and the applicable regulatory authorities, as necessary, 
before participants can be enrolled into an amended protocol. 
12.4 Informed Consent 
A signed informed consent form, in compliance with applicable regulatory requirements, 
will be obtained from each participant before the participant enters the study or any unusual 
or non-routine procedure is performed that involves risk to the participant. An informed 
consent template may be provided by the Sponsor or designee to investigative sites. If any 
institution-specific modifications to study-related procedures are proposed or made by the 
site, the consent must be reviewed by the Sponsor or designee before IRB/ERC submission. 
Once reviewed, the consent will be submitted by the principal investigator to his/her 
IRB/ERC for review and approval before the start of the study. If the informed consent form 
is revised during the course of the study, all active participating participants must sign the 
revised IRB/ERC-approved consent form. 
Before enrollment, each prospective participant and/or his/her legal guardian will be given 
a full explanation of the study and be allowed to read the approved informed consent form. 
Once the principal investigator is assured that the participant/legal guardian understands the 
implications of participating in the study, the participant/legal guardian will be asked to give 
consent to participate in the study by signing the approved informed consent form. The 
principal investigator will also sign the form at that time. 

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The principal investigator will provide a copy of the signed informed consent form to the 
participant and/or legal guardian. The original form will be maintained in the participant’s 
medical records at the site. 
12.5 Protocol Violations and Deviations 
A deviation from the protocol is an unintended and/or unanticipated departure from the 
procedures and/or processes that were approved by the Sponsor and the IRB/ERC and were 
agreed to by the principal investigator. Deviations usually have an impact on an individual 
participant or a small group of participants, and do not involve inclusion/exclusion or 
primary endpoint criteria. A protocol violation occurs: (a) when there is a non-adherence to 
the protocol that results in significant additional risk to the participant; (b) when the 
participant or principal investigator has failed to adhere to significant protocol requirements 
(e.g., inclusion/exclusion criteria); (c) when the participant was enrolled without prior 
Sponsor approval; or (d) when there is non-adherence to applicable regulations and/or ICH 
E6(R2) guidelines.  
All departures from the protocol (e.g., missed visit windows, laboratory samples not 
collected on the required day) will be documented as protocol deviations. The principal 
investigator or designee must document and explain any protocol deviation or violation in 
the participant’s source documentation. The IRB/ERC should be notified of all protocol 
violations in a timely manner by the investigator. Protocol deviations and violations will be 
documented by the responsible clinical monitor during monitoring visits, and those 
observations will be reviewed with the investigator.  
The principal investigator may implement a change from the protocol without prior Sponsor 
and IRB/ERC approval only to eliminate an immediate hazard to a participant. If the 
investigator believes that an exception to the protocol is justified for an individual 
participant, the investigator may present the facts and rationale to the Medical Monitor and 
request a one-time exception. This request will be submitted in writing on a protocol inquiry 
form, which will be emailed to the Medical Monitor for review and disposition. The Medical 
Monitor will then email the decision to the investigator regarding approval or denial of the 
request. This written documentation must be filed in the investigator’s study file.  
This process will apply if the investigator believes that a participant should receive an 
excluded concomitant medication and remain in the study, or if the investigator believes 
that a participant should remain in the study when the protocol dictates that the participant 
should be discontinued. The implemented change should be submitted to the IRB/ERC for 
review as soon as possible. However, it is the policy of the Sponsor that there will be no 
exceptions granted concerning the inclusion and exclusion criteria. Laboratory support of 
inclusion and exclusion criteria may be repeated once during the Screening period. 
12.6 Study Reporting Requirements 
By participating in this study, the principal investigator agrees to submit reports of SAEs 
according to the time line and method outlined in the protocol. In addition, the principal 
investigator agrees to submit periodic reports to his/her IRB/ERC as appropriate.  
12.7 Financial Disclosure and Obligations 
Principal investigators and sub-investigators are required to provide financial disclosure 
information to allow the Sponsor or designee to submit the complete and accurate 
certification or disclosure statements under regulatory requirements. In addition, the 
principal investigator and sub-investigators must provide the Sponsor or designee with a 

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commitment to update this information promptly, if any relevant changes occur during the 
course of the investigation and for one year following the completion of the study. 
The Sponsor or designee is not financially responsible for further testing/treatment of any 
medical condition that may be detected during the Screening process. In addition, in the 
absence of specific arrangements, the Sponsor or designee is not financially responsible for 
treatment of the participant’s disease. 
12.8 Investigator Documentation 
Before beginning the study, the principal investigator will be asked to comply with ICH 
E6(R2) and applicable regulatory requirements by providing the essential documents to the 
Sponsor or designee, which include but are not limited to the following: 
• An original investigator-signed investigator agreement page of the protocol.  
• The IRB/ERC approval of the protocol and informed consent. 
• The IRB/ERC-approved informed consent, samples of site advertisements for 
recruitment for this study, and any other written information regarding this study that is 
to be provided to the participant or legal guardian. 
• Curriculum vitae for the principal investigator and each sub-investigator. Current 
licensure must be noted on the curriculum vitae or a copy of the license provided. The 
curriculum vitae must be signed and dated by the principal investigator and sub-
investigators within two years before study start-up to indicate the documents are 
accurate and current. 
• Completed financial disclosure forms to allow the Sponsor or designee to submit 
complete and accurate certification or disclosure statements under applicable regulatory 
requirements. In addition, the investigators must provide to the Sponsor or designee a 
commitment to update this information promptly if any relevant changes occur during 
the course of the investigation and for one year following the completion of the study 
(Section 12.7). 
• Laboratory certifications and normal ranges for any local laboratories used by the site, 
in accordance with applicable regulatory requirements. 
12.9 Study Conduct 
The principal investigator agrees that the study will be conducted according to the principles 
of ICH E6(R2) and the principles of the World Medical Association Declaration of Helsinki. 
The principal investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. 
12.10 Publications 
Following completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the Sponsor or designee 
will be responsible for these activities and will work with the investigators to determine how 
the manuscript is written and edited, the number and order of authors, the publication to 
which it will be submitted, and other related issues. The Sponsor has final approval authority 
over all such issues.  
Data are the property of the Sponsor and cannot be published without prior authorization 
from the Sponsor.  

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13 REFERENCES 
 
1 UNAIDS/WHO. UNAIDS DATA 2017 
2 McPherson TD, Sobieszczyk ME, Markowitz M. Cabotegravir in the treatment and 
prevention of Human Immunodeficiency Virus-1. Expert Opin Investig Drugs. 
Apr;27(4):413-20 (2018) 
3 Caskey M, Klein F, Nussenzweig MC. Broadly neutralizing anti-HIV-1 monoclonal 
antibodies in the clinic. Nat Med. 25(4):547-53 (2019) 
4 Pace C, Markowitz M. Monoclonal antibodies to host cellular receptors for the 
treatment and prevention of HIV-1 infection. Curr Opin HIV AIDS. 10(3):144-50 
(2015) 
5 Clinicaltrials.gov 
6 Wuxi Apptec. Dose range finding study of TMB-365 and TMB-355 following single 
intramuscular injection to naïve cynomolgus monkeys. (Study number: 400026-
2016112302-CPK) (2018) 
7 Song R, Oren DA, Franco D, Seaman MS, Ho DD. Strategic addition of an N-linked 
glycan to a monoclonal antibody improves its HIV-1-neutralizing activity. Nat 
Biotechnol. 31(11):1047-52 (2013) 
8 TaiMed Biologics USA. Study Report for TMB-365 In Vitro Antiviral Activity. 
(Report number: TMB-RD-R2018007) (2018) 
9 TaiMed Biologics, Inc. Study Report for the Assessments of Anti-Human CD4 
Antibodies TMB-355 and TMB-365 on CD4 and FcRn Binding Affinity. (Report 
number: TMB-RD-R2018008) (2018) 
10 Freeman M, Seaman M, Rits-Volloch S, Hong X, Kao C, Ho D, Chen B. Crystal 
Structure of HIV-1 Primary Receptor CD4 in Complex with a Potent Antiviral 
Antibody. Structure. 18:1632-41 (2010) 
11 Burkly LC, Olson D, Shapiro R, Winkler G, Rosa JJ, Thomas DW, Williams C, 
Chisholm P. Inhibition of HIV infection by a novel CD4 domain 2-specific 
monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced 
cell fusion. J Immunol. 149:1779-87 (1992) 
12 TaiMed Biologics, Inc. Study Report for Assessments of Anti-human CD4 
Antibodies TMB-355 and TMB-365 on FcγR3a, FcγR2a and C1q Binding Affinity. 
(Report number: TMB-RD-R2018006) (2018) 
13 Wuxi Apptec. TMB-365: 28-day intramuscular injection toxicity and toxicokinetics 
study in cynomolgus monkeys with 56-day recovery. (Study number: 535-0001-
TX) (2018) 
14 Pharmaron. A pharmacokinetics, pharmacodynamics and dose range finding Study 
of TMB365 given via intravenous injection in cynomolgus monkeys. (Study 
number: 52503-18-261) (2019) 
15 Wuxi Apptec. Pharmacokinetics study of TMB-365 and TMB-355 following single 

TAIMED BIOLOGICS 
 
CONFIDENTIAL 
PROTOCOL: TMB-a21 
DATE: 23 JAN 2024      
71 
 
 
intravenous bolus injection and intramuscular injection to naïve cynomolgus 
monkeys. (Study number: 400026-2016112301-CPK) (2018) 
16 Pharmaron. A 4-week toxicity and toxicokinetics GLP Study of TMB365 given via 
intravenous injection with a 8-week recovery in cynomolgus monkeys. (Study 
number: 52503-18-262) (2019) 
17 Wu, X., et al., (2012) Selection pressure on HIV-1 envelope by broadly neutralizing 
antibodies to the conserved CD4-binding site. J Virol, 86(10): 5844-56. 
18 Rudicell, R.S., et al., (2014) Enhanced Potency of a Broadly Neutralizing HIV-1 
Antibody In vitro Improves Protection against Lentiviral Infection In vivo. J Virol, 
88(21): 12669-82. 
19 IIT Research Institute (2016) Repeat dose intravenous and subcutaneous toxicity 
and pharmacokinetic study of monoclonal antibody VRC-HIVMAB075-00-AB 
(VRC07 523LS) in male and female Sprague-Dawley rats. Final report amendment 
No.1 (Study number: 2517-001-002) 
20 Charles River Laboratories, Inc. (2015) A tissue cross-reactivity study of VRC07-
523LS in normal human and Sprague-Dawley rat tissues (Study number: 
20072713) 
21 Miglietta et al., Synergy in monoclonal antibody neutralization of HIV-1 
pseudoviruses and infectious molecular clones. Journal of Translational Medicine 
2014 Dec 13;12:346. 
22 Chou TC, Theoretical Basis, Experimental Design, and Computerized Simulation 
of Synergism and Antagonism in Drug Combination Studies. Pharmacol Rev. 2006 
Sep;58(3):621-81. 
23 Gaudinski, M.R., et al., (2019) Safety and pharmacokinetics of broadly neutralising 
human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-
escalation clinical trial. Lancet HIV, 6:e667-79. 
24 TMB-RD-R2021005. In Vitro Activity of TMB-365 Cell Clones Against 
Ibalizumab Resistant Pseudotyped HIV-1 Viruses. TaiMed Biologics. 
25 BLA761065 clinical pharmacology and biopharmaceutics review 
26 Dillman RO. Infusion reactions associated with the therapeutic use of monoclonal 
antibodies in the treatment of malignancy. Cancer Metastasis Rev. 18(4):465-71 
(1999) 
27 Dalakas MC. The use of intravenous immunoglobulin in the treatment of 
autoimmune neuromuscular diseases: evidence-based indications and safety 
profile. Pharmacol Ther. Jun;102(3):177-93 (2004) 
28 Schwartzberg LS, Stepanski EJ, Fortner BV, Houts AC. Retrospective chart review 
of severe infusion reactions with rituximab, cetuximab, and bevacizumab in 
community oncology practices: assessment of clinical consequences. Support Care 
Cancer. 16:393-8 (2008)