A Multicenter, Randomized, Double-Blind, Vehicle-Controlled Phase 1B Study of the Safety, Short-Term Engraftment and Action of NB01 in Adults With Moderate Acne
Phase: PHASE1
Conditions: Acne Vulgaris
Sponsor: Naked Biome, Inc.

 
 
 
 
CLINICAL STUDY PROTOCOL 
 
 
Study Title: 
A Multicenter, Randomized, Double-Blind, Vehicle-Controlled 
Phase 1B Study of the Safety, Short-Term Engraftment and Action 
of NB01 in Adults with Moderate Acne  
 
 
Sponsor: 
Naked Biome, Inc. 
 
IND Number: 
EudraCT Number: 
NCT Number: 
17552  
Not Applicable 
 NCT03709654   
 
 
Indication: 
Acne Vulgaris 
 
 
Protocol ID: 
NB01-P1BMA 
 
 
Therapeutics, Inc. 
Clinical Project 
Manager: 
 
Name: 
Russell Smiley 
Telephone: 
(858) 571-1800 
 
Sponsor Medical 
Monitor: 
Name: 
Emma Taylor, MD 
Telephone: 
(626) 260-1230 
 
 
 
Protocol 
Version/Date: 
Amendment 2: 
15 July 2019 
Amendment 1: 
01 October 2018 
Original:                      28 August 2018 
 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or 
under control of Naked Biome, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The information is only to be 
used by you in connection with authorized clinical studies of the investigational drug 
described in the protocol. You will not disclose any of the information to others without 
written authorization from Naked Biome, Inc., except to the extent necessary to obtain 
informed consent from those persons to whom the drug may be administered. 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................................... 2 
PROTOCOL SYNOPSIS ............................................................................................................................................... 5 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 17 
1. 
INTRODUCTION ............................................................................................................................................... 19 
1.1. 
Background ............................................................................................................................................. 19 
1.2. 
Investigational Medicinal Product Name ............................................................................................... 20 
1.2.1. 
General Information .............................................................................................................. 20 
1.2.2. 
Preclinical Pharmacology and Toxicology ........................................................................... 20 
1.2.3. 
Clinical Studies of NB01 ...................................................................................................... 21 
1.3. 
Rationale for This Study ......................................................................................................................... 21 
1.4. 
Risk/Benefit Assessment for the Study .................................................................................................. 22 
1.5. 
Compliance ............................................................................................................................................. 22 
2. 
OBJECTIVES ...................................................................................................................................................... 23 
3. 
STUDY DESIGN ................................................................................................................................................ 24 
3.1. 
Study Measurements ............................................................................................................................... 24 
3.1.1. 
Dosing Compliance .............................................................................................................. 24 
3.1.2. 
Safety .................................................................................................................................... 24 
3.1.3. 
Engraftment .......................................................................................................................... 25 
3.1.4. 
Efficacy ................................................................................................................................. 25 
3.1.5. 
Exploratory ........................................................................................................................... 25 
3.2. 
Endpoints ................................................................................................................................................ 25 
3.2.1. 
Safety Endpoints ................................................................................................................... 25 
3.2.2. 
Engraftment Endpoint ........................................................................................................... 26 
3.2.3. 
Efficacy Endpoints ................................................................................................................ 26 
3.2.4. 
Exploratory Endpoint ............................................................................................................ 26 
3.3. 
Study Design ........................................................................................................................................... 26 
3.4. 
Study Treatments .................................................................................................................................... 27 
3.5. 
Duration of Treatment ............................................................................................................................ 27 
3.6. 
End of Study ........................................................................................................................................... 27 
3.7. 
Biomarker Testing .................................................................................................................................. 28 
3.7.1. 
Biomarker Samples to Address the Study Objectives .......................................................... 28 
3.7.2. 
Biomarker Samples for Optional Future Research ............................................................... 28 
4. 
SUBJECT POPULATION .................................................................................................................................. 29 
4.1. 
Number of Subjects and Subject Selection ............................................................................................. 29 
4.2. 
Inclusion Criteria .................................................................................................................................... 29 
4.3. 
Exclusion Criteria ................................................................................................................................... 29 
5. 
STUDY DRUG PRODUCT ................................................................................................................................ 33 
5.1. 
Randomization, Blinding and Treatment Codes ..................................................................................... 33 
5.1.1. 
Procedure for Subject Randomization .................................................................................. 33 
5.1.2. 
Procedures for Breaking Treatment Codes ........................................................................... 33 
5.2. 
Description and Handling of Study Drug ............................................................................................... 33 
5.2.1. 
Formulation ........................................................................................................................... 33 
5.2.2. 
Packaging and Labeling ........................................................................................................ 34 
5.2.3. 
Storage and Handling ........................................................................................................... 35 
5.3. 
Application of Study Drug ...................................................................................................................... 36 
5.4. 
Prior and Concomitant Medications & Therapies .................................................................................. 36 

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5.4.1. 
Prohibited Medications or Therapies .................................................................................... 36 
5.4.2. 
Allowed Medications or Therapies ....................................................................................... 37 
5.4.3. 
Use of Other Moisturizers, Sunscreens and Makeup ............................................................ 37 
5.4.4. 
Use of Other Cleansers ......................................................................................................... 37 
5.4.5. 
Facial Shaving ...................................................................................................................... 38 
5.5. 
Accountability for NB01 ........................................................................................................................ 38 
5.6. 
Study Drug Product Return or Disposal ................................................................................................. 38 
5.7. 
Study Drug Product Complaints ............................................................................................................. 38 
6. 
STUDY PROCEDURES ..................................................................................................................................... 39 
6.1. 
Subject Enrollment and Treatment Assignment ..................................................................................... 39 
6.1.1. 
Subject Re-Screening ............................................................................................................ 39 
6.1.2. 
Subject Replacement ............................................................................................................ 39 
6.2. 
Pretreatment Assessments ...................................................................................................................... 39 
6.2.1. 
Screening Visit – Visit 1 ....................................................................................................... 39 
6.2.2. 
Baseline Assessments – Visit 2 (Day 1) ............................................................................... 40 
6.2.3. 
Treatment Assessments - Visit 3 (Week 2/Day 8), Visit 4 (Week 7/Day 
43) and Visit 5 (Week 12/End of Treatment/Day 80) .......................................................... 41 
6.2.4. 
Follow-up Assessment – Visit 6 (Week 16/End of Study/Day 106) .................................... 41 
6.2.5. 
Unscheduled Visit ................................................................................................................. 42 
6.3. 
Assessments for Premature Discontinuation from Study ....................................................................... 42 
7. 
ADVERSE EVENT REPORTING AND TOXICITY MANAGEMENT .......................................................... 43 
7.1. 
Adverse Event Definitions ...................................................................................................................... 43 
7.2. 
Adverse Event Details ............................................................................................................................ 44 
7.2.1. 
Dose Limiting Toxicity and Stopping Rules ........................................................................ 46 
7.2.2. 
Serious Adverse Events ........................................................................................................ 47 
7.2.3. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events ......................................................................... 49 
7.3. 
Pregnancy ............................................................................................................................................... 49 
7.4. 
Toxicity Management ............................................................................................................................. 50 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................................ 51 
8.1. 
Sample Size ............................................................................................................................................ 51 
8.2. 
Analysis Populations .............................................................................................................................. 51 
8.2.1. 
Safety Population .................................................................................................................. 51 
8.2.2. 
Intent-to-Treat Population .................................................................................................... 51 
8.2.3. 
Per-Protocol Population ........................................................................................................ 51 
8.3. 
Endpoints ................................................................................................................................................ 51 
8.3.1. 
Safety Endpoints ................................................................................................................... 51 
8.3.2. 
Engraftment Endpoint ........................................................................................................... 51 
8.3.3. 
Efficacy Endpoints ................................................................................................................ 51 
8.3.4. 
Exploratory Endpoint ............................................................................................................ 52 
8.4. 
Statistical Methods .................................................................................................................................. 52 
8.4.1. 
Dosing Compliance .............................................................................................................. 52 
8.4.2. 
Safety Analyses .................................................................................................................... 52 
8.4.3. 
Engraftment Analyses ........................................................................................................... 53 
8.4.4. 
Efficacy Analyses ................................................................................................................. 53 
8.5. 
Interim Analyses ..................................................................................................................................... 54 
9. 
RESPONSIBILITIES .......................................................................................................................................... 55 
9.1. 
Investigator Responsibilities ................................................................................................................... 55 
9.1.1. 
Good Clinical Practice .......................................................................................................... 55 
9.1.2. 
Institutional Review Board Review and Approval ............................................................... 55 

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9.1.3. 
Informed Consent ................................................................................................................. 55 
9.1.4. 
Confidentiality ...................................................................................................................... 55 
9.1.5. 
Study Files and Retention of Records .................................................................................. 56 
9.1.6. 
Case Report Forms ............................................................................................................... 56 
9.1.7. 
Inspections ............................................................................................................................ 57 
9.1.8. 
Protocol Compliance ............................................................................................................ 57 
9.2. 
Sponsor Responsibilities ......................................................................................................................... 57 
9.2.1. 
Protocol Modifications ......................................................................................................... 57 
9.2.2. 
Access to Information for Monitoring, Auditing or Inspections .......................................... 57 
9.2.3. 
Study Report and Publications .............................................................................................. 57 
10. END OF STUDY CRITERIA ............................................................................................................................. 59 
10.1. 
Completion of the Study ......................................................................................................................... 59 
10.2. 
Subject Discontinuation .......................................................................................................................... 59 
10.3. 
Study Termination .................................................................................................................................. 59 
11. REFERENCES .................................................................................................................................................... 61 
12. APPENDICES ..................................................................................................................................................... 63 
Appendix 1. 
Sponsor-Investigator Signature Page .................................................................................... 64 
Appendix 2. 
Schedule of Events Table ..................................................................................................... 65 
Appendix 3. 
Investigator’s Global Assessment (IGA) .............................................................................. 68 
Appendix 4. 
Common Terminology Criteria for Adverse Events (CTCAE) V. 5.0 ................................. 69 
Appendix 5. 
Acne Specific Quality of Life (QoL) Questionnaire ............................................................ 70 
  
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
Naked Biome, Inc. 
953 Indiana Street 
San Francisco, CA 94107 
 
 
Study Title:  
A Multicenter, Randomized, Double-Blind, Vehicle-Controlled 
Phase 1B Study of the Safety, Short-Term Engraftment and Action 
of NB01 in Adults with Moderate Acne  
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
17552 
Not Applicable 
NCT03709654 
  
Study Centers 
Planned: 
Approximately three study centers in the US. 
Objectives: 
The objectives of this study are as follows: 
1. Primary 
1. To determine the safety and tolerability of a multiple 
application of topical Propionibacterium acnes (P. 
acnes) microbiome transplant (“NB01”). 
2. Exploratory 
1. To define engraftment duration of NB01. 
2. To evaluate preliminary clinical efficacy using Acne 
Lesion Counts (total, inflammatory, and non-
inflammatory), Investigator Global Assessment (IGA) 
and subjective improvement on acne based on subject 
reported outcomes (Acne QoL Questionnaire). 
3. To evaluate treatment effects, based sebum production in 
a subpopulation from sites 02 and 03. 
Study Design: 
Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Phase 
1B Study  
No. of Subjects: 
36  
Target Population: 
Adult Male and Female Subjects with Moderate Facial Acne 
Vulgaris 

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Duration of Subject 
Participation: 
Subject participation will be approximately four months. Study 
duration will be approximately one year. 
Diagnosis and Main 
Eligibility Criteria: 
Inclusion Criteria 
1. Subject has provided written informed consent. 
2. Subject is male or non-pregnant female, 18-40 years of age, 
inclusive at Screening. 
3. Subject has a clinical diagnosis of moderate facial acne 
vulgaris defined as Grade 3 on the IGA (see Appendix 3, 
IGA Grading). 
4. Subject meets all of the following: 
• A minimum of 20 but not more than 50 facial 
inflammatory lesions (papules plus pustules), including 
nasal lesions, and no more than 1 facial nodular lesion 
(<5 mm)  
• No cystic lesions  
• A minimum of 20 but not more than 125 facial 
noninflammatory lesions (open and closed comedones), 
including nasal lesions 
5. Female subject with non-cyclical acne. 
6. Women of childbearing potential (WOCBP) willing to use 
adequate contraception (e.g., total abstinence, intrauterine 
device [IUD], barrier method with spermicide, surgical 
sterilization or surgically sterilized partner, Depo-Provera®, 
Nexplanon®, or NuvaRing®) for the duration of the 
Screening Period and during study participation. All oral 
contraceptive and hormonal implants will need to have been 
initiated and on a stable dose for at least 3 months prior to 
the screening period. WOCBP are defined as any female who 
has experienced menarche and who is NOT permanently 
sterile (hysterectomy, status-post 6 month or more, a bilateral 
tubal ligation or bilateral oophorectomy) or postmenopausal; 
postmenopausal is defined as 12 consecutive months with no 
menses without an alternative medical cause. 
7. Male subjects willing to use an acceptable method of 
contraception (e.g., total abstinence, barrier methods with 
spermicide) during study participation. 
8. Subject has the ability to personally apply benzoyl peroxide 
(BPO) and study drug, as per protocol. 

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Exclusion Criteria  
1. Subject has active bacterial, viral, or fungal skin infections. 
2. Subject has used any of the following topical anti-acne 
preparations or procedures on the face: 
• Topical anti-acne treatments including, but not limited to, 
over-the-counter (OTC) acne cleansers or treatments, BPO 
(other than the BPO required during Screening), 
antibiotics, azelaic acid, dapsone, sulfa based products, 
corticosteroids, and salicylic acid within two weeks of 
Screening; 
• Topical retinoids (e.g., prescription tazarotene, 
adapalene, and tretinoin including OTC adapalene) 
within four weeks of Screening; 
• Light treatments, microdermabrasion, or chemical peels 
within eight weeks of Screening; 
• Other topical therapy, which may materially affect the 
subject’s acne, in the opinion of the Principal Investigator 
(PI). 
3. Subject has used any of the following systemic anti-acne 
medications: 
• Corticosteroids (including intramuscular, intra-articular 
and intralesional injections) within four weeks of 
Screening. Inhaled, intranasal, or ocular corticosteroids 
are allowed if use is stable (stable use is defined as dose 
and frequency unchanged for at least four weeks prior to 
Screening); 
• Antibiotics or other systemic anti-acne medications 
within four weeks of Screening, with the exception of 
five days or less of antibiotic therapy during this period, 
but not within one week of Screening; 
• Androgen receptor blockers (i.e., spironolactone or 
flutamide) within eight weeks of Screening; with the 
exception of five days or less of spironolactone therapy 
during this period, but not within one week of Screening; 
• Retinoid therapy (e.g., isotretinoin) within six months of 
Screening; 
• Vitamin A supplements (greater than 10,000 units per 
day) within six months of Screening; 

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• Other systemic therapy, which may materially affect the 
subject’s acne, in the opinion of the PI. 
4. Subject has received any light-based therapies including 
photodynamic therapy (PDT), blue light, red light lasers, 
artificial tanning devices within four weeks of Screening, and 
is planning to be exposed to excessive sunlight during the 
study period; 
5. Subject has active nodulocystic acne or acne conglobate, 
acne fulminans, or other forms of acne (e.g., acne 
mechanica). 
6. Subject has any skin diseases with compromised skin barrier 
function (e.g. atopic dermatitis, etc.) such as noticeable 
breaks or cracks in the skin on the face, including severely 
excoriated skin or skin with open or weeping wounds 
suggestive of an active infection or increased susceptibility to 
infection in the treatment area (i.e., face). 
7. Subject has facial hair, scarring or other clinical conditions in 
the treatment area that could interfere with study 
assessments, in the PI’s opinion. 
8. Subject has active clinically significant periodontal disease in 
the opinion of the PI, or ongoing procedures (e.g., gum 
grafting). 
9. Subject has history/current ocular infections/surgeries within 
six months of enrollment at Baseline (Day 1), with the 
exception of any history of cataracts. 
10. Subject has a history of septic joints/endocarditis. 
11. Subject has sensitivity to or difficulty tolerating any 
ingredients in the study drug including glycerin, polyethylene 
glycol. 
12. Subject demonstrates non-compliance with BPO pre-
treatment during the Screening period.  Non-compliance is 
defined as BPO application for less than 5 days the week 
prior to Day 1, failure to apply BPO 24-48 hours prior to Day 
1, and BPO application within approximately 24 hours of the 
Day 1 visit. 
13. Subject is currently participating in an investigational drug, 
device, or biologic study or has used an investigational drug, 
biologic or device treatment within 30 days prior to first 
application of the study drug. 

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14. Subjects with prosthetic heart valves, pacemakers, 
intravascular catheters, or other foreign or prosthetic 
devices/implantable devices/hardware. 
15. Subject has a history of chronic human immunodeficiency 
virus (HIV), hepatitis C virus (HCV), or hepatitis B virus 
(HBV) infections. 
16. Subject has a history of malignancy (with the exception of 
non-melanoma skin cancer). 
17. Subject is immunosuppressed (such as resulting from 
transplantation, immunosuppressive therapy, active HIV 
infection/acquired immune deficiency syndrome [AIDS], 
neutropenia). 
18. Subject had a major surgical procedure, open biopsy, or 
significant traumatic injury within 14 days of initiating study 
drug (unless the wound has healed), or anticipation of the 
need for major surgery during the study. 
19. Subject has a medical or psychiatric condition and/or history 
of drug or alcohol abuse that, in the opinion of the PI, makes 
the subject inappropriate for study inclusion. 
20. Subjects with close contacts (e.g., spouses, children, or 
members in the same household) that have severe skin 
barrier defects or are immunocompromised. 
21. Subject is unable or unwilling to comply with study protocol 
procedures. 
22. Female subject is pregnant or lactating or is planning to 
become pregnant and/or breast feed within the duration of 
study participation. 
Study Procedures/ 
Frequency: 
Subjects will complete the following clinical site visits during the 
study: Screening, Day 1/Baseline, Week 2, Week 7, Week 12 End 
of Treatment (EOT), and Week 16/End of Study (EOS). The 
following procedures will be completed at all study visits, unless 
otherwise indicated: 
 
• Review of medical history (Screening only) 
• Limited physical examination (Screening, Day 1, and Week 
12/EOT only) 
• Vital signs, which include blood pressure, heart rate, and 
temperature (Screening, Day 1, and Week 12/EOT only) 
• Local complete blood count (CBC) (Screening and Week 
12/EOT only)  

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• Local urine pregnancy test (Screening, Day 1, and Week 
12/EOT only) 
• Twice daily facial washing  
• BPO pre-treatment of at least 5, but no more than 7, consecutive 
days (Screening). Should a subject require a modified Screening 
period schedule, BPO may be applied for more than 7 days with 
prior approval of the Sponsor Medical Monitor.  
• Subject Diary completion for pre-treatment period BPO and 
facial washing (Screening) 
• Subject Diary completion for study drug application (Day 1 
through Week 12/EOT), facial washing (Day 1 through Week 
12/EOT), and LSRs (Day 1 through Week 16/EOS)  
• Assessment of adverse events (AEs) and local skin reactions 
(LSRs) 
• Review of concomitant medications  
• IGA (Day 1 through Week 12/EOT) 
• Acne lesion counts, including inflammatory and non-
inflammatory lesion counts (Day 1 through Week 12/EOT) 
• Optional photography (Day 1 through Week 12/EOT) 
• Sebum production measurements (Day 1 through Week 
12/EOT) 
• Acne Quality of Life (QoL) questionnaire (Day 1 through Week 
12/EOT) 
• Obtain facial samples for TaqManÒ engraftment assay 
o Cheek Swab, skin surface (Day 1 through Week 
12/EOT) 
o Biore® Strip, follicular (Screening, and Week 12/EOT 
only)  
• Study drug application (Day 1 through end of Week 11*) 
*Subjects must complete application of study drug at least 3 days 
prior to, but no more than 7 days from, the Week 12 visit. 
See Appendix 2 for additional details in the Schedule of Events 
table.  
Test Product, Dose, 
and Mode of 
Administration: 
NB01 is a topical live biologic.  The active pharmaceutical 
ingredient consists of a single strain of health-associated P. acnes 
bacterium in a cryopreservative (glycerol), water and phosphate 
buffered saline (PBS).  Vehicle-control consists of glycerol, water 
and PBS.  Both NB01 and vehicle-control are delivered topically in 
single-dosed vacuum-sealed pads. 
Study Measurements: 
The following assessments will be completed for each subject 
according to the Schedule of Events (see Appendix 2). 

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Dosing Compliance: Measures of study drug compliance will include the duration (days) 
of treatment (defined as last dose date – first dose date +1), the total 
number of applications (determined from the doses reported in the 
Subject Diary), and the percent of expected doses applied. Subjects 
who apply at least 80% of the expected total number of applications 
and have no other evidence of material dosing non-compliance will 
be considered to be compliant with study drug dosing. 
Primary Safety: 
Adverse Events 
All reported or observed AEs will be recorded. At each visit, 
subjects will also be questioned specifically about the status of any 
ongoing AEs. Untoward events that occur prior to the first dose of 
study drug will be captured in the medical history section of the 
electronic case report form (eCRF) unless they are related to a 
study-specific procedure. Optional photographs may be obtained for 
areas outside of the face, as clinically indicated for the classification 
and management of AEs. 
Local Skin Reactions 
At each visit, LSRs will be assessed. Erythema, edema, 
erosion/ulceration, scaling/dryness, and scabbing/crusting in the 
treatment area will be assessed by the PI and itching and pain in the 
treatment area will be assessed by the subject using a 4-point 
ordinal scale where 0=absent, 1=mild (slight, barely perceptible), 
2=moderate (distinct presence), and 3=severe (marked, intense). 
Only LSRs that require medical intervention (e.g., prescription 
medication), require withholding or discontinuation of the 
application of the study drug, or extend 2 cm beyond the treatment 
area will be documented as AEs. Any LSRs that are not listed above 
will be recorded as an AE. 
LSRs will also be assessed by subjects weekly during the Screening 
Period, Treatment Period, and Follow-up Period using a subject 
diary to assess redness, swelling, erosions/ulceration, 
scaling/dryness, scabbing/crusting, itching and pain by the same 4-
point scale used during clinic visits.  Subjects will be asked to report 
the greatest severity of each LSR experienced during the previous 7 
days.  
Limited Physical Examination 
The limited physical examination will include examination of the 
face, chest, arms, and back (i.e., relevant acne regions). 
Abnormalities at Screening/Baseline will be recorded as medical 
history. Any new or worsening abnormalities at Visit 5/EOT will be 
recorded as AEs. 
Vital Signs 

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Vital signs including blood pressure, heart rate, and temperature 
will be measured at Screening/Baseline and Visit 5/EOT. 
Assessments will be made after the subject has rested in a seated 
position for at least five minutes.  
Complete Blood Count 
CBC will be assessed locally at Screening and Visit 5/EOT and 
must include Differential. 
Urine Pregnancy Test (UPT) 
A UPT will be performed at Screening/Baseline and Visit 5/EOT 
for WOCBP. 
Exploratory 
Engraftment: 
Engraftment Assay 
Follicular engraftment sampling will be completed via use of 
Biore® Strips applied across the bridge of the nose extending to 
either cheek. Skin surface engraftment sampling will be completed 
via cheek swab. 
Exploratory 
Efficacy: 
Investigator’s Global Assessment (IGA) 
Overall severity of acne will be assessed using a five-point scale 
where 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 
4=Severe. This is a static morphological scale that refers to a point 
in time and not a comparison to Baseline (see Appendix 3). 
Acne Lesion Counts 
The number of total lesions, inflammatory lesions (papules and 
pustules), and non-inflammatory lesions (open and closed 
comedones) on the face (including those present on the nose) will 
be counted. Counts of nodules and cysts will be reported separately 
and are not to be included in the inflammatory or non-inflammatory 
lesion counts.  
Acne Quality of Life (QoL) Questionnaire 
At each visit, subjects will be asked to complete the Acne QoL 
Questionnaire to assess subjective improvement of acne (see 
Appendix 5). 
Exploratory Sebum:  Sebum Production 
At each visit, sebum levels will be assessed for any changes from 
Screening, Baseline to Weeks 2, 7, and 12 at sites 02 and 03. Sebum 
production data will not be available for all subjects. Site 04 did not 
have a Sebumeter, therefore, sebum production was not assessed for 
any subject. Site 03 received a Sebumeter after having started 
enrollment of subjects. Some of the site’s subjects will not have any 
sebum data while others may have only partial data with the 
Screening values missing.  Subjects without any sebum data will be 
excluded from the summaries and analyses. Subjects with partial 

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data will be included in the summaries for observed values where 
data is available, but will be excluded from summaries and analyses 
for absolute change and percent change from Screening. 
Study Endpoints: 
 
Primary Safety: 
 
 
 
 
 
 
• Incidence (severity and causality) of any local and systemic 
AEs. 
• Number of subjects with presence (and severity) of each LSR 
and each time point. 
• Changes from Screening/Baseline in physical examination 
findings at Visit 5/EOT. 
• Changes from Screening/Baseline in vital signs at Visit 5/EOT. 
Changes from Screening in local CBC at Visit 5/EOT. 
Exploratory 
Engraftment: 
• For skin engraftment assay, absolute and percent change from 
Screening to follow-ups in Cas5/PanBac and for follicular 
engraftment assay, the proportion of subjects with “success” at 
EOT where “success” is defined as a Follicular Biore® with 
“yes” outcome for presence of live NB01. 
Exploratory 
Efficacy: 
 
• Absolute change in IGA score from Screening at each follow up 
visit. Percentage of subjects with (a) at least a one-point change 
in IGA score and (b) percentage of subjects with at least a two-
point change in IGA score from Screening at each follow-up 
visit. 
• Absolute and percent change from Screening at each follow-up 
visit in total, inflammatory, and non-inflammatory lesions. 
• Absolute and percent change from Screening to follow-up in 
each of the four Acne QoL domain scores. 
Exploratory 
Sebum: 
• Absolute and percent change from Screening to follow-up in 
sebum production in a subpopulation from sites 02 and 03. 
Sample Size 
Calculations: 
No formal sample size calculations were performed for this study 
given it is an initial proof of concept study. 
Statistical Methods: 
All statistical processing will be performed using SAS®. Summary 
tables (descriptive statistics and/or frequency tables) will be 
provided for screening and/or baseline variables, efficacy variables, 
and safety variables. Summaries will be provided for each treatment 
group. In general, continuous variables will be summarized by 
descriptive statistics including sample size, mean, Standard 

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Deviation (SD), median, minimum, and maximum. Categorical 
variables will be summarized by frequency and percentage. 
 
The Safety population will include all randomized subjects who 
received and applied study drug. The intent-to-treat (ITT) 
population will include all randomized subjects who were dispensed 
the study drug. The Per-Protocol (PP) population will include a 
subset of the ITT population who completed the study without 
significant protocol deviations (as will be determined prior to 
unblinding the randomization). 
Dosing 
Compliance: 
Descriptive statistics will be used to summarize for each treatment 
group the duration of treatment (defined as last dose date – first 
dose date +1), the total number of applications (determined from the 
doses reported in the Subject Diary), and the percent of expected 
doses applied for the ITT and PP populations. Subjects who apply at 
least 80% of the expected total number of applications and have no 
other evidence of material dosing non-compliance will be 
considered to be compliant with study drug dosing. 
Primary Safety: 
All safety analyses will be performed on the Safety population. 
 
Extent of Exposure 
Descriptive statistics will be used to summarize the extent of 
exposure in the Safety population. The total amount of study drug 
used by each subject will be calculated based on the number of days 
the study drug was applied (according to the subject’s diary entries).  
 
Physical Examinations 
Findings from the physical exam will be recorded in medical history 
(from assessment at Visit 1/Screening) or as AEs (from assessment 
at Visit 5/EOT). 
 
Vital Signs 
Descriptive statistics of vital signs (temperature, blood pressure, and 
heart rate) will be provided by treatment group.  
 
Clinical Laboratory Tests 
Local CBC tests will be evaluated for any material changes during 
the study period. All laboratory data will be listed and reported in 
the units received by the laboratory. Shift tables by analyte and by 
out-of-range flag will be presented. 
 
Local Skin Reactions 
The frequency of the individual LSRs (PI: erythema, edema, 
erosion/ulceration, scaling/dryness, and scabbing/crusting; Subject: 

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itching and pain) will be tabulated by severity and treatment group 
at each visit. The frequency of the individual LSRs recorded by 
subjects in weekly diaries (redness, swelling, erosion/ulceration, 
scaling/dryness, and scabbing/crusting, itching, and pain) will be 
tabulated by severity and treatment group for each study week.  
 
Adverse Events 
All AEs reported during the study will be listed, documenting 
course, severity, PI assessment of the relationship to the study drug, 
and outcome. Verbatim terms on the eCRFs will be linked to 
preferred terms (PTs) and system organ class (SOC) using the 
Medical Dictionary for Regulatory Activities (MedDRA) mapping 
system. The PTs and SOC will then be tabulated. All reported AEs 
will be summarized by the number of subjects reporting AEs, SOC, 
PT, severity, and relationship to study drug by treatment group.  
 
Urine Pregnancy Tests (UPT) 
Results from UPTs will be provided in a listing. 
Exploratory 
Engraftment: 
 
 
 
 
 
 
 
 
 
 
 
 
 
The engraftment assay analyses will be conducted on the ITT and 
PP populations. 
 
For endpoint of Engraftment Assay of the Cas5/PanBac, the 
absolute and percent change from Screening at each follow-up visit, 
the comparison between NB01 and vehicle-control will be analyzed 
using ANCOVA with the dependent variable being absolute or 
percent change values and the factor treatment and the Screening 
value as a covariate in the model, with and without LOCF 
imputation. 
 
For the endpoint of Follicular Biore®, treatment groups will be 
compared with respect to the proportions of subjects with “success” 
at EOT Week 12 using the CMH test with and without stratification 
on study center, where “success” is defined as a Follicular Biore® 
with “yes” outcome based on recovery of live NB01. 
 
Exploratory 
Efficacy: 
The efficacy analyses will be conducted on the ITT and PP 
populations. 
 
Investigator’s Global Assessment 
The observed and change from Screening scores at each follow-up 
visit will be tabulated. For the endpoint of IGA, the treatment 
groups will be compared with respect to the proportions of subjects 
with (a) at least a one-point improvement and (b) at least a two-
point improvement in IGA score relative to Screening at each 

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follow-up visit using the CMH test with and without stratification 
on study center. 
 
Acne Lesion Counts 
For the endpoint of Acne Lesion Counts, absolute and percent 
change from Screening at each follow-up visit in total, 
inflammatory, and non-inflammatory lesions, the comparison 
between NB01 and vehicle-control will be analyzed using Analysis 
of Covariance (ANCOVA) model with the factor treatment and the  
Screening counts as a covariate in the model, with and without Last 
Observation Carried Forward (LOCF) imputation. 
 
Acne Quality of Life 
For endpoint of Acne-QoL, the absolute and percent change from 
Screening at each follow-up visit on four domains separately and 
total, the comparison between NB01 and vehicle-control will be 
analyzed using ANCOVA model with the factor treatment and the 
Screening score as a covariate in the model, with and without LOCF 
imputation. 
Exploratory 
Sebum: 
Sebum Production 
For endpoint of sebum production, the absolute and percent change 
from Screening at each follow-up visit, the comparison between 
NB01 and vehicle-control will be analyzed using ANCOVA model 
with the factor treatment and the Screening value as a covariate in 
the model, with and without LOCF imputation. 
 
 
This study will be conducted in accordance with the guidelines of Good Clinical Practice 
including archiving of essential documents.  
 

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse Event 
AIDS 
acquired immune deficiency syndrome 
ANCOVA 
Analysis of Covariance 
BID 
Twice Daily 
BPO 
5.0% Benzoyl Peroxide 
CAMP  
Christie, Atkins, and Munch-Peterson  
CBC 
Complete Blood Count 
CFR 
Code of Federal Regulations 
CMH 
Cochran-Mantel-Haenszel 
CoNS 
coagulase-negative Staphylococcus 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
deoR 
Deoxyribose operon repressor 
DLT 
Dose Limiting Toxicity 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EOS 
End of Study 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IGA 
Investigator Global Assessment 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine device 
LOCF 
Last Observation Carried Forward 
LSR 
Local Skin Reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
NB01 
P. acnes microbiome transplant 
OTC 
Over-the-Counter 
P. acnes 
Propionibacterium acnes 
pIMPLE 
P. acnes plasmid 
PBS 
Phosphate Buffered Saline 
PDT 
Photodynamic Therapy 
PI 
Principal Investigator 
PP 
Per-Protocol 

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PT 
Preferred Term 
QD 
Once Daily 
QoL 
Quality of Life 
SAE 
Serious Adverse Event 
S. aureus 
Staphylococcus aureus 
SD 
Standard Deviation 
SOC 
System Organ Class 
UPT 
Urine Pregnancy Test 
US 
United States 
WHO 
World Health Organization 
WOCBP 
Women of Childbearing Potential 

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1. 
INTRODUCTION 
1.1. 
Background 
Naked Biome hypothesizes that eliminating resident disease-associated bacterial strains and 
replacing them with a health-associated Propionibacterium acnes (P. acnes) transplant may 
help to improve, mitigate, treat, or prevent acne flares. In a Phase I single application study 
of NB01 conducted by the Sponsor, all 10 subjects completed the study without any drug-
related adverse events (AEs).   
 
Genotypic and phenotypic work performed by the Sponsor has identified candidate strains 
sourced from healthy subjects that match all our criteria for health as defined by the 
literature. Genotypically, the Sponsor’s candidate strain is a P. acnes ribotype 2, deoR+ 
(Johnson et al. 2016), lipase type II+ (Tomida et al. 2013) which contains a complete 
CRISPR system (Johnson et al. 2016), does not contain the pIMPLE plasmid (Kasimatis et 
al. 2013), and has no identifiable genomic evidence of antibiotic resistance. Phenotypically, 
the candidate strain produces low levels of porphyrin, comparable to other healthy 
associated ribotype 2’s in the literature and is sensitive to all five antibiotics tested internally 
(Clindamycin, Doxycycline, Erythromycin, Minocycline, Tetracycline as was measured 
with Etest [bioMérieux]). 
 
Additional safety assessments were performed by CHR-Hansen, Naked Biome’s GMP 
manufacturer, who confirmed that no genomic antibiotic resistance genes were present and 
that the candidate strain was sensitive to 13 out of 14 tested antibiotics, resistant only to 
metronidazole which P. acnes has known natural resistance to and was additionally non-
hemolytic and non-cytotoxic. 
 
Outside of known association of P. acnes with acne vulgaris, below is an accrued list of 
rare opportunistic infections associated with P. acnes. P. acnes has been observed in other 
infections such as implant-associated, soft tissue, periodontal, periocular, cardiovascular 
system, and deep-organ tissues infections, and may also have a role in relation to 
pulmonary infection as the bacteria can be isolated from lungs and lymph nodes. Routes of 
infection are often from the subject’s own commensal flora (normal skin or oral tract) 
(Kwon and Suh 2016). The expanded multi-locus sequence typing scheme based on 7 
housekeeping genes and 2 putative virulence genes developed by McDowell et al gives a 
good resolution and revealed strains which seem to have an increased capacity to cause 
infections and others that are rarer or found mainly among healthy individuals (McDowell 
et al. 2012, McDowell et al. 2013). 
 
Strain HP4G1 has a deoR repressor gene just upstream of the porphyrin operon suggesting a 
mechanism for reduced porphyrin synthesis and thus may not be associated with acne 
vulgaris. Further, the strain has a PAp60/PAmce allele combination found in non-invasive 
P. acnes strains and lacks 2 of 4 genes involved in iron uptake, which is of importance for 
growth in the human body at conditions with low iron access. Notably, regarding CAMP 
factors 1-4, which are expected to be involved in pathogenicity and are involved in co-
hemolysin with Staphylococcus aureus (S. aureus), HP4G1 had a mutation in the CAMP 2 

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gene leading to an extension of the gene as the stop codon was interrupted. This variant 
has not been observed before and as CAMP factor 2 is described as having properties for 
co-hemolysin and exotoxin, this may lower the pathogenic potential of the strain. 
Moreover, the strains belong to the CC72 clonal complex which, compared to CC5, 
contains strains less commonly isolated from healthy humans or individuals with 
infections. HP4G1 was found to be a ST100-like type not previously reported and most 
likely has a non-functional CAMP2 gene due to a mutation in the stop codon. Therefore, 
HP4G1 is most likely less virulent than P. acnes in general with a low risk of causing 
infections. 
 
Porphyrin is a known inflammatory metabolite involved in the pathogenesis of acne. 
Porphyrin is produced by the P. acnes bacterium and is a photosensitizing agent. 
Dermatologists routinely use blue and red-light therapies to selectively target P. acnes-
produced coproporphyrin III and protoporphyrin IX, respectively, thereby eliminating P. 
acnes and improving disease. As stated above, HP4G1 has a repressor of porphyrin 
production, called deoR. In vivo, the HP4G1 strain produces less porphyrin than acne-
associated strains that lack the deoR repressor operon. Despite that, the HP4G1 strain is a 
low porphyrin producer; the fact that it is applied in significant quantities (105 CFU/cm2) 
could lead to a temporary increase in porphyrin upon application. This hypothetical increase 
could be photosensitizing to subjects, as such, photosensitivity has been included as a 
theoretical side effect of HP4G1 application. 
 
The Sponsor intends to address the risk of these opportunistic infections through the 
selection of genotypic and phenotypic characteristics most associated with health and with 
the implementation of appropriate exclusion criteria to eliminate subjects that may have 
increased risk of a P. acnes infection. 
 
P. acnes is most specific to facial pilosebaceous region which is the natural niche for P. 
acnes, and therefore the best region for application to appropriate the sensitivity and 
therapeutic impact of a topical P. acnes transplant (McGinley et al. 1980). 
1.2. 
Investigational Medicinal Product Name  
1.2.1. 
General Information 
For further information on NB01, refer to the current investigator’s brochure (IB) for NB01. 
1.2.2. 
Preclinical Pharmacology and Toxicology 
There is no animal in vivo data to date on the safety or clinical efficacy of a topical live P. 
acnes microbiome transplant. There are no well substantiated animal models for 
inflammatory acne and Naked Biome is investigating human-specific bacteria. Therefore, 
in vivo animal clinical and toxicology studies will not yield clinically relevant results that 
would be applicable for human use. Animal clinical and toxicology studies are not 
relevant or useful when using human-specific bacteria absent well-substantiated animal 
models for inflammatory acne for pre-human efficacy testing (Mirshahpanah and Maibach 
2007). The best, most relevant, and only useful model to test NB01 is first in humans 

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(Mirshahpanah P, Howard Maibach 2007; Achermann et al. 2014). Additional literature 
on previous human studies for probiotics and acne are referenced (Baquerizo et al. 2014; 
Wei et al. 2016; Thiboutot et al. 2009). 
1.2.3. 
Clinical Studies of NB01 
The first clinical study of NB01, NB01-P1BSA, is a Phase Ib single-center open-label 
dose-escalation study using a single dose application with monitoring over 28 days on 10 
subjects at two different concentrations (lower bound (104 CFU/cm2) and upper bound 
(105 CFU/cm2)). This study is ongoing, however, in meeting the safety criteria of this 
initial study, Naked Biome plans to expand the IND research to a Phase Ib multi-dosed 
study under this protocol. All subjects will have been pre-treated with a daily 5.0% BPO 
gel (Perrigo 5% Benzoyl Peroxide Aqueous Gel) to decrease their resident microbiome 
bacterial load in preparation for transplantation and successful repopulation with a healthy 
microbiome. 
 
1.3. 
Rationale for This Study 
Acne vulgaris is a multifactorial disease affecting 85% of the global population over a lifetime 
and 40-50 million people in the US currently. It impacts individuals over a large timespan 
ranging from 13-40 years and has a large psychosocial impact on an individual’s self-esteem. 
The majority of those afflicted (50%-75%) are now resistant to conventional antibiotic therapy 
(Walsh et al. 2016). Acne is caused by overgrowth of P. acnes, impaction of hair follicles, 
excessive sebum production and hormonal dysregulation. Current standard of care includes 
treatment with 5.0% BPO, retinoids, and antibiotics.  However, there are significant side effects 
of the above medications, limiting subject compliance and leading to suboptimal long-term 
efficacy. The heavy dependence on long treatment courses of antibiotics combined with 
antibiotic resistance rising upwards of 50%-75%, is resulting in treatment failures and 
contributing to overall global antibiotic resistance. There has been little innovation in acne 
therapy in the past several decades and a significant current need to develop antibiotic 
alternatives. 
 
Current therapeutic options include: 
• 
Topical antibiotics-erythromycin/clindamycin 
• 
Oral Antibiotics-tetracycline, doxycycline, minocycline 
• 
Topical 5.0% BPO products 
• 
Topical retinoids 
• 
Oral Retinoids 
• 
Topical acids-salicylic acid, glycolic acid 
• 
Peels 
• 
Blue and red-light therapies 
• 
Dapsone (Aczone®) 
• 
Azelaic acid (Finacea®) 
 
Recent literature from the Human Microbiome Project has shown there are unique microbial 
signatures specific to healthy and acne disease states (Fitz-Gibbon et al. 2013; Tomida et al. 

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2013). Subsequent literature discovered a repressor in the porphyrin pathway in health-
associated strains resulting in significantly lower porphyrin production (Johnson et al. 
2016). Porphyrin is a known inflammatory mediator in acne pathogenesis (Kang et al. 
2015). Porphyrin levels inversely correlate with therapeutic improvement in acne (Richter et 
al. 2016). Additional papers have highlighted other virulent factors such as the pIMPLE 
plasmid that may be associated with acne pathogenesis and were found to be more common 
in disease-associated strains (Kasimatis et al. 2013). 
 
From this data, the Sponsor believes that by eliminating resident disease-associated bacterial 
strains and replacing them with a health-associated P. acnes transplant, there is the potential 
to improve, mitigate, treat, or prevent acne flares. Naked Biome is currently testing this in 
an initial Phase I study evaluating the safety, tolerability, and clinical impact that a single 
dose application of NB01 has on adult subjects with moderate acne. Naked Biome aims to 
test this further in multiple dosing with NB01 on subjects under this protocol. 
 
1.4. 
Risk/Benefit Assessment for the Study 
The risks of this study are that the applied study drug may contribute to worsening of disease 
and/or subjects may experience side effects including but not limited to unlikely opportunistic 
infections, irritation, dryness, or redness.  The benefits are that individual subjects may have 
improvement of their disease.  Overall benefits to society include development of novel 
therapeutics for the treatment of acne.  
1.5. 
Compliance 
This study will be conducted in compliance with this protocol, Good Clinical Practice, and all 
applicable regulatory requirements. 

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2. 
OBJECTIVES 
The objectives of this study are: 
1. Primary: To determine the safety and tolerability of a multiple application of topical P. acnes 
microbiome transplant ("NB01"). 
2. Exploratory: 
1. To define engraftment duration of NB01. 
2. To evaluate preliminary clinical efficacy using Acne Lesion Counts (total, inflammatory, 
and non-inflammatory), IGA, and subjective improvement of acne based on subject 
reported outcomes (Acne QoL Questionnaire). 
3. To evaluate treatment effects, based on sebum production in a subpopulation from sites 
02 and 03. 

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3. 
STUDY DESIGN 
3.1. 
Study Measurements 
3.1.1. 
Dosing Compliance 
Measures of study drug compliance will include the duration (days) of treatment (defined as last 
dose date – first dose date +1), the total number of applications (determined from the doses 
reported in the Subject Diary), and the percent of expected doses applied. Subjects who apply at 
least 80% of the expected total number of applications and have no other evidence of material 
dosing non-compliance will be considered to be compliant with study drug dosing. 
3.1.2. 
Primary Safety 
Adverse Events 
All reported or observed AEs will be recorded. At each visit, subjects will also be questioned 
specifically about the status of any ongoing AEs. Untoward events that occur prior to the first 
dose of study drug will be captured in the medical history section of the electronic case report 
form (eCRF) unless they are related to a study-specific procedure. 
Local Skin Reactions 
At each visit, LSRs will be assessed. Erythema, edema, erosion/ulceration, scaling/dryness, and 
scabbing/crusting in the treatment area will be assessed by the PI and itching and pain in the 
treatment area will be assessed by the subject using a 4-point ordinal scale where 0=absent, 
1=mild (slight, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, 
intense). Only LSRs that require medical intervention (e.g., prescription medication), require 
withholding or discontinuation of the application of the study drug, or extend 2 cm beyond the 
treatment area will be documented as AEs. Any LSRs that are not listed above will be recorded 
as an AE. 
LSRs will also be assessed by subjects weekly during the Screening, Treatment and Follow-up 
periods using a subject diary to assess redness, swelling, erosion/ulceration, scaling/dryness, 
scabbing/crusting, itching and pain by the same 4-point scale used during clinic visits. Subjects 
will be asked to record the greatest severity of each LSR experienced during the previous 7 days. 
Limited Physical Examination 
The limited physical examination will include examination of the face, chest, arms, and back 
(i.e., relevant acne regions) Abnormalities at Screening/Baseline will be recorded as medical 
history. Any new or worsening abnormalities at Visit 5/EOT will be recorded as AEs. 
Vital Signs 
Vital signs including blood pressure, heart rate, and temperature will be measured at 
Screening/Baseline and Visit 5/EOT. Assessments will be made after the subject has rested in a 
seated position for at least five minutes.  

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Complete Blood Count 
CBC will be assessed locally at Screening and Visit 5/EOT and must include Differential. 
Urine Pregnancy Test 
A UPT will be performed at Screening/Baseline and Visit 5/EOT for WOCBP. 
3.1.3. 
Exploratory Engraftment 
Engraftment Assay 
Follicular engraftment sampling will be completed via use of Biore® Strips applied across the 
bridge of the nose extending to either cheek. Skin surface engraftment sampling will be 
completed via cheek swab. 
 
3.1.4. 
Exploratory Efficacy 
Investigator’s Global Assessment 
Overall severity of acne will be assessed using a five-point scale where 0=Clear, 1=Almost 
Clear, 2=Mild, 3=Moderate, and 4=Severe. This is a static morphological scale that refers to a 
point in time and not a comparison to Baseline (see Appendix 3). 
 
Acne Lesion Counts 
The number of total lesions, inflammatory lesions (papules and pustules), and non-inflammatory 
lesions (open and closed comedones) on the face (including those present on the nose) will be 
counted. Counts of nodules and cysts will be reported separately and are not to be included in the 
inflammatory or non-inflammatory lesion counts.  
 
Acne Quality of Life (QoL) Questionnaire 
At each visit, subjects will be asked to complete the Acne QoL Questionnaire to assess 
subjective improvement of acne (see Appendix 5). 
3.1.5. 
Exploratory Sebum 
At each visit, sebum levels will be assessed for any changes from Screening/Baseline to Weeks 
2, 7, and 12. 
3.2. 
Endpoints 
3.2.1. 
Pimary Safety Endpoints 
The safety endpoints of this study are: 
• Incidence (severity and causality) of any local and systemic AEs. 
• Number of subjects with presence (and severity) of each LSR and each time point. 
• Changes from Screening/Baseline in physical examination findings at Visit 5/EOT. 

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• Changes from Screening/Baseline in vital signs at Visit 5/EOT. 
• Changes from Screening in local CBC at Visit 5/EOT. 
3.2.2. 
Exploratory Engraftment Endpoint 
The engraftment endpoint for this study is: 
• For skin engraftment assay, absolute and percent change from Screening to follow-ups in 
Cas5/PanBac and for follicular engraftment assay, the proportion of subjects with 
“success” at EOT where “success” is defined as a Follicular Biore® sample with “yes” 
outcome based on recovery of live NB01. 
3.2.3. 
Exploratory Efficacy Endpoints 
The efficacy endpoints of this study are: 
• Absolute change from Screening at each follow-up visit in IGA score. Percentage of 
subjects with (a) at least a one-point change in IGA score and (b) percentage of subjects 
with at least a two-point change in IGA score from Screening at each follow-up visit. 
• Absolute and percent change from Screening at each follow-up visit in total, 
inflammatory, and non-inflammatory lesions. 
• Absolute and percent change from Screening to follow-up in Acne QoL. 
3.2.4. 
Exploratory Endpoint 
The exploratory endpoint of this study is: 
• Absolute and percent change from Screening to follow-up in sebum production. 
3.3. 
Study Design 
This is a multicenter, randomized, double-blind, vehicle-controlled Phase 1B study of daily 
doses of topically-delivered NB01 or vehicle-control in subjects with moderate, non-cyclical 
facial acne. 
Subjects who consent to participate in the study will initiate Screening procedures, during which 
they will be pre-treated with 5% topical BPO gel once daily (QD) for 5 to 7 days before 
randomizing into the study.  Subjects with modified screening period schedules may be able to 
apply BPO for more than 7 days; however, this must be pre-approved by the Sponsor’s Medical 
Monitor. 
Thirty six subjects were randomized into the study to receive high-dose NB01 (105 CFU/cm2) or 
vehicle-control.   
Subjects will be stratified according to these variables: 

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- 
Sex (male/female) 
- 
Age (18-25 years old/26-40 years old) 
The study will comprise of subjects with moderate facial acne who will be randomized to one of 
two treatment arms, either vehicle-control or high-dose NB01. 
The study arms consist of vehicle-control control and daily high-dose (105CFU/cm2) NB01, with 
subjects enrolled at a 2:1 ratio (treatment arm to vehicle-control arm). The PI may employ a dose 
reduction strategy with approval from the Sponsor’s Medical Monitor to reduce/modify dosing 
based on individual subject’s tolerability.  Such changes, however, shall not be made without the 
written approval of the Medical Monitor, see Section 7.4. 
Subjects will remain on study through 11 weeks of study treatment.  
3.4. 
Study Treatments 
On Day 1, the first study drug dose will be PI-applied approximately 24 hours after the subject 
has completed their final BPO dose. After Day 1, subjects will continue to apply study drug to 
the whole face at approximately the same time every evening, for 11 weeks. Subjects will hold 
all at-home facial washing, shaving, and/or product application on study visit clinic days; once 
pre-wash procedures have been completed at the study visit, subjects may wash their face at the 
study clinic. 
 
3.5. 
Duration of Treatment 
Subject participation in the study will be approximately 4 months. 
• 
Screening Period: 1-14 days which includes BPO Pre-Treatment Period: 5 days (up to 7 
days)  
• 
On-Study Treatment Period: 11 weeks of daily study drug treatment. 
• 
Follow-Up Period: 4 weeks.  
The overall study is expected to last approximately one year 
3.6. 
End of Study  
Subjects who complete all study visits through Week 12/Visit 5 will follow up via a telephone 
visit at Week 16/Visit 6 in order to complete safety follow-up. Subjects who discontinue early 
(before Week 12) should still have the EOT procedures performed in order to terminate the 
subject’s participation in the study. If the subject will not return to the clinic, efforts to contact 
the subject must be documented and the subject will be considered lost to follow-up. 
 

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3.7. 
Biomarker Testing 
3.7.1. 
Biomarker Samples to Address the Study Objectives 
The following biological specimens may be collected in this study and will be used to evaluate 
the association of exploratory biomarkers with study drug response, including engraftment, 
efficacy and/or AEs and to increase knowledge and understanding of the biology of acne or 
related diseases, and/or the validation of a companion diagnostic for acne. The specific analyses 
may include but will not be limited to the following biomarkers and assays: cheek swab and 
Biore® strip TaqManÒ and microbial sequencing laboratory analysis.  Because biomarker 
science is a rapidly evolving area of investigation, and AEs in particular are difficult to predict, it 
is not possible to specify prospectively all tests that will be done on the specimens provided.  The 
testing outlined below is based upon the current state of scientific knowledge. It may be modified 
during or after the end of the study to remove tests no longer indicated and/or to add new tests 
based upon the growing state of art knowledge. Any future testing must be approved by local 
authorities, as applicable, according to specific local regulations.  
3.7.2. 
Biomarker Samples for Optional Future Research 
In addition to the study-specific informed consent to be signed by each subject participating in 
the study, a separate, specific signature will be required to document a subject's agreement to 
allow the use of the remainder of their already collected microbial biomarker specimens for 
optional future research, once approved by local authorities, as applicable, according to specific 
local regulations.  
The specimens collected for optional future research will be used to increase our knowledge and 
understanding of the biology of the study disease and related diseases and to study the 
association of biomarkers with disease pathogenesis, progression and/or treatment outcomes, 
including efficacy, AEs, and the processes of drug absorption and disposition. These specimens 
may be used also to develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays. The collection and analysis of optional future research specimens 
will facilitate the rational design of new pharmaceutical agents and the development of 
diagnostic tests, which may allow for individualized drug therapy for patients in the future. 

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4. 
SUBJECT POPULATION 
4.1. 
Number of Subjects and Subject Selection 
4.2. 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study. 
1. Subject has provided written informed consent. 
2. Subject is male or non-pregnant female, 18-40 years of age, inclusive at Screening. 
3. Subject has a clinical diagnosis of moderate facial acne vulgaris defined as Grade 3 on 
the IGA (see Appendix 3, IGA Grading). 
4. Subject meets all of the following: 
• A minimum of 20 but not more than 50 facial inflammatory lesions (papules plus 
pustules), including nasal lesions, and no more than 1 facial nodular lesion (<5 mm)  
• No cystic lesions  
• A minimum of 20 but not more than 125 facial noninflammatory lesions (open and 
closed comedones), including nasal lesions 
5. Female subject with non-cyclical acne. 
6. WOCBP willing to use adequate contraception (e.g., total abstinence, IUD, barrier 
method with spermicide, surgical sterilization or surgically sterilized partner, Depo-
Provera®, Nexplanon®, or NuvaRing® for the duration of the Screening Period and 
during study participation. All oral contraceptive and hormonal implants will need to 
have been initiated and on a stable dose for at least 3 months prior to the Screening 
Period. WOCBP are defined as any female who has experienced menarche and who is 
NOT permanently sterile (hysterectomy, status-post 6 month or more a bilateral tubal 
ligation or bilateral oophorectomy) or postmenopausal; postmenopausal is defined as 12 
consecutive months with no menses without an alternative medical cause. 
7. Male subjects willing to use an acceptable method of contraception (e.g., total abstinence, 
barrier methods with spermicide) during study participation. 
8. Subject has the ability to personally apply BPO and study drug, as per protocol.  
4.3. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria are not eligible for participation in this 
study. 
1. Subject has active bacterial, viral, or fungal skin infections. 

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2. Subject has used any of the following topical anti-acne preparations or procedures on the 
face: 
• Topical anti-acne treatments including, but not limited to, OTC acne cleansers or 
treatments, BPO (other than the BPO pre-treatment required during Screening), 
antibiotics, azelaic acid, dapsone, sulfa based products, corticosteroids, and salicylic 
acid, within two weeks of Screening; 
• Topical retinoids (e.g., prescription tazarotene, adapalene, and tretinoin, including 
OTC adapalene) within four weeks of Screening; 
• Light treatments, microdermabrasion, or chemical peels within eight weeks of 
Screening; 
• Other topical therapy, which may materially affect the subject’s acne, in the opinion 
of the PI. 
3. Subject has used any of the following systemic anti-acne medications: 
• Corticosteroids (including intramuscular, intraarticular and intralesional injections) 
within four weeks of Screening. Inhaled, intranasal, or ocular corticosteroids are 
allowed if use is stable (stable use is defined as dose and frequency unchanged for at 
least four weeks prior to Screening); 
• Antibiotics or other systemic anti-acne medications within four weeks of Screening, 
with the exception of five days or less of antibiotic therapy during this period, but not 
within one week of Screening; 
• Androgen receptor blockers (i.e., spironolactone or flutamide) within eight weeks of 
Screening, with the exception of five days or less of spironolactone therapy during 
this period, but not within one week of Screening; 
• Retinoid therapy (e.g., isotretinoin) within six months of Screening; 
• Vitamin A supplements (greater than 10,000 units per day) within six months of 
Screening; 
• Other systemic therapy, which may materially affect the subject’s acne, in the opinion 
of the PI. 
4. Subject has received any light-based therapies including PDT, blue light, red light lasers, 
artificial tanning devices within four weeks of Screening and is planning to be exposed to 
excessive sunlight during the study period. 
5. Subject has active nodulocystic acne or acne conglobate, acne fulminans, or other forms 
of acne (e.g., acne mechanica). 

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6. Subject has any skin diseases with compromised skin barrier function (e.g. atopic 
dermatitis, etc.), such as noticeable breaks or cracks in the skin on the face, including 
severely excoriated skin or skin with open or weeping wounds suggestive of an active 
infection or increased susceptibility to infection in the treatment area (i.e., face). 
7. Subject has facial hair, scarring or other clinical conditions in the treatment area that 
could interfere with study assessments, in the opinion of the PI. 
8. Subject has active clinically significant periodontal disease in the opinion of the PI, or 
ongoing procedures (e.g., gum grafting). 
9. Subject has history/current ocular infections/surgeries within six months of enrollment, 
with the exception of any history of cataracts. 
10. Subject has a history of septic joints/endocarditis. 
11. Subject has sensitivity to or difficulty tolerating any ingredients in the study drug, 
including glycerin, polyethylene glycol. 
12. Subject demonstrates non-compliance with BPO pre-treatment during the Screening 
period.  Non-compliance is defined as BPO application for less than 5 days the week 
prior to Day 1, failure to apply BPO 24-48 hours prior to Day 1, and BPO application 
within approximately 24 hours of the Day 1 visit. 
13. Subject is currently participating in an investigational drug, device, or biologic study or 
has used an investigational drug, biologic or device treatment within 30 days prior to first 
application of the study drug. 
14. Subjects with prosthetic heart valves, pacemakers, intravascular catheters, or other 
foreign or prosthetic devices/implantable devices/hardware. 
15. Subject has a history of chronic HIV, HCV, or HBV infections. 
16. Subject has a history of malignancy (with the exception of non-melanoma skin cancer). 
17. Subject is immunosuppressed (such as resulting from transplantation, 
immunosuppressive therapy, active HIV infection/ AIDS, neutropenia). 
18. Subject had a major surgical procedure, open biopsy, or significant traumatic injury 
within 14 days of initiating study drug (unless the wound has healed), or anticipation of 
the need for major surgery during the study. 
19. Subject has a medical or psychiatric condition and/or history of drug or alcohol abuse 
that, in the opinion of the PI, makes the subject inappropriate for study inclusion. 
20. Subjects with close contacts (e.g., spouses, children, or members in the same household) 
that have severe barrier defects or are immunocompromised. 

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21. Subject is unable or unwilling to comply with study protocol procedures. 
22. Female subject is pregnant or lactating or is planning to become pregnant and/or breast 
feed within the duration of study participation. 

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5. 
STUDY DRUG PRODUCT 
5.1. 
Randomization, Blinding and Treatment Codes 
5.1.1. 
Procedure for Subject Randomization 
Subjects will be randomized to one of the two Treatment Groups on a 2:1 basis (NB01 or 
vehicle-control) using a central randomization scheme.  Randomization will be stratified by sex 
(male/female) and age (18-25 years old/26-40 years old).   
 
Subjects will be randomized on Day 1 after the subject has arrived at the site and eligibility has 
been confirmed.  To randomize a subject the PI or designee will call the contract research 
organization (CRO) and provide the required subject information.  The CRO will have a 
designated unblinded staff member available to assign a study drug kit number to the subject, 
which contains the treatment specified by the randomization schedule.  A subject randomization 
form documenting study drug kit number assignment will be provided to the site by the CRO. 
 
5.1.2. 
Procedures for Breaking Treatment Codes 
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the PI may obtain treatment assignment by opening the unblinding envelope for 
the subject kit. Sponsor recommends but does not require that the PI contact the Medical Monitor 
before breaking the blind. Treatment assignment should remain blinded unless that knowledge is 
necessary to determine subject emergency medical care. The rationale for unblinding must be 
clearly explained in source documentation and on the CRF/eCRF, along with the date on which 
the treatment assignment was obtained. The PI is requested to contact the Medical Monitor 
promptly in case of any treatment unblinding. 
Blinding of study treatment is critical to the integrity of this clinical study and therefore, if a 
subject’s treatment assignment is disclosed to the PI, the subject will have study treatment 
discontinued. All subjects will be followed until study completion unless consent to do so is 
specifically withdrawn by the subject. 
Sponsor may independently unblind cases for expedited reporting of suspected unexpected 
serious adverse reactions. 
5.2. 
Description and Handling of Study Drug 
5.2.1. 
Formulation 
“Study drug” for this study refers to the blinded NB01 or vehicle-control that will be 
administered to the study subjects as described in the procedures in Section 6. 

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NB01 Formulation: 
• Live culture of a single strain of P. acnes  
• Purified water 
• Glycerol 
• Phosphate buffered saline 
Vehicle-control Formulation: 
• Purified water 
• Glycerol 
• Phosphate buffered saline 
All excipients are generally regarded as safe and present in concentrations found on the FDA 
Inactive Ingredient Guide https://www.fda.gov/drugs/informationondrugs/ucm113978.htm.   
5.2.2. 
Packaging and Labeling 
NB01 and vehicle-control will be packaged, labeled, and supplied in a blinded fashion for this 
study.  The clinical study formulation comes as a clear solution dispensed using individual 
vacuum-sealed cotton pads.   
The packaging for NB01 and vehicle-control will be identical and supplied frozen to the PI by 
the Sponsor in single aliquot dosages delivered as a clear, topical solution in a cotton applicator 
pad packaged in a vacuum-sealed plastic pouch. A sample image of the study drug and label are 
as follows: 

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5.2.3. 
Storage and Handling 
At clinical site: Study drug will be stored at the clinical site in a -80° Celsius lab freezer before 
application to study subjects at Day 1, with the exception that Site 04 will maintain drug at -70° 
Celsius. A range of ± 10 degree Celsius is acceptable for storage.  Please contact the Sponsor in 
the event of temperature departure from that range.  Subjects will be provided with study drug at 
their study visit, with adequate supply to apply until their subsequent visit.   
 
At home: Subjects will take the study drug home from the site in temperature-conserving travel-
packs containing ice packs to maintain temperature until their arrival at home, at which time the 
entire travel-pack (with two different types of freezer blocks) will be stored in the subject’s 
residential freezer.   
 
Study drug should be removed from the freezer 5 minutes prior to application to allow it to thaw 
to room temperature. The study drug must be used within 5 to 30 minutes of removal from 
freezer storage. If for any reason application is not able to occur at the planned time within 30 
minutes, the site/subject will be instructed to dispose of the study drug in a standard waste 
receptacle at either the clinical site or at the subject’s home. The instructions for application 
glove and study drug pad disposal are discussed in Section 5.3.  
 
 

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5.3. 
Application of Study Drug 
Administerers of study drug should wash their hands and wear non-powdered nitrile gloves for 
application.  
 
At clinic: Subjects will wash their face with Cetaphil® right before in-office application on Day 
1. Subject’s dose will be administered by the PI (or sub-investigator designee) at the Day 1 visit 
after swab samples have been procured. 
 
At home: From Day 2 and thereafter, subjects will apply study drug every evening after their 
Cetaphil® wash. Subjects will be instructed to stop study drug application 3-7 days before Visit 
5. 
 
Used study drug pads, shrink-wrap packaging (bags) and application gloves will be discarded in 
a standard waste receptacle at either the clinical site or at the subject’s home.  Once the study 
drug has been applied, the administerer will dispose of the used pad and bag by pinching the pad 
and bag together with the gloved hand and, using the ungloved hand, peel off the glove inside-
out thereby containing the pad and bag within the glove. The subject will discard the glove (with 
pad and bag contained inside) in a standard waste receptacle and wash hands thoroughly with 
soap and water.   
 
5.4. 
Prior and Concomitant Medications & Therapies 
Current medications and any medications taken within 30 days prior to the start of the study 
(Baseline) will be recorded as prior/concomitant medications with the dose and corresponding 
indication. The medications to be recorded include prescription, OTC medications, and all 
vitamins, minerals, and dietary supplements being taken by the subject. All concomitant 
medications will be coded with the current version of the WHO Drug Dictionary. 
 
Any changes in concomitant medications and/or procedures/therapies during the study must be 
recorded. The reason for any changes in concomitant medications and/or procedures/therapies 
should be reported and should reflect either a baseline medical condition documented in the 
medical history or in conjunction with an AE. 
5.4.1. 
Prohibited Medications or Therapies 
Subjects are excluded from the study if taking any other acne medication: 
• Topical anti-acne treatments including, but not limited to, OTC acne cleansers or 
treatments, BPO (other than the BPO pre-treatment required during Screening), 
antibiotics, azelaic acid, dapsone, sulfa based products, corticosteroids, and salicylic acid 
• Topical retinoids (e.g., prescription tazarotene, adapalene, and tretinoin, including OTC 
adapalene) 

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BPO use is only allowed once subjects have been consented to participate in the study and only 
as part of the Screening period. Subjects are to wait until the end of the study before initiating 
any other therapy or investigational agent for the treatment of acne.  
5.4.2. 
Allowed Medications or Therapies 
Contraception for WOCBP is required per Inclusion Criterion #6 (see Section 4.2). Vitamins and 
mineral supplements are permitted at dosages considered by the PI as reasonable for maintaining 
good health and will be recorded in the eCRFs. 
 
Therapies (medication and non-medication therapies) not restricted by the protocol may be used 
during the study for the treatment or prevention of disease or to maintain good health.  
 
Non-prohibited chronic therapies being used at Screening/Baseline may be continued but must be 
recorded. 
 
Reasonable use of OTC medications such as acetaminophen or acetylsalicylic acid for relief of 
headache, muscle ache, etc. is allowed during the study and must be recorded.  
5.4.3. 
Use of Other Moisturizers, Sunscreens and Makeup 
Once subjects have completed the evening Cetaphil® wash, they are prohibited from using 
moisturizers, sunscreens (including moisturizers containing sunscreens), face makeup or other 
facial products, until the morning Cetaphil® wash throughout the study treatment period.  
The PI (or designee) will review the subject’s current topical facial product use during the 
Screening Period to ensure they do not contain prohibited medications such as benzoyl peroxide, 
retinol, salicylic acid, or glycolic acid.  The site will let the subjects know which of their 
products are acceptable for use during the trial.  
Once use of topical facial products (e.g. moisturizers, sunscreens, face make-up) has been 
approved by the PI (or designee), subjects may continue using them after completion of the Day 
1 Visit, during the daytime hours only (after the morning Cetaphil® wash and before the evening 
Cetaphil® wash). 
Subjects will be instructed to contact the PI or study staff for approval prior to the use of any 
new facial products.  Site staff will query the subjects regarding use of topical facial products at 
each study visit.     
5.4.4. 
Use of Other Cleansers 
The use of cleansers, other than the study-provided Cetaphil®, is prohibited throughout the 
subject’s participation in the study, from the Screening Visit through the Week 16/EOS visit. 

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5.4.5. 
Facial Shaving 
Shaving of the face is allowed during the study, with these exceptions: 
- 
Subjects may not shave in the morning prior to study clinic visits 
- 
Subjects are not to shave in the evening after the application of study drug. 
5.5. 
Accountability for NB01  
The PI is responsible for ensuring adequate accountability of all used and unused study drug. 
This includes acknowledgement of receipt of each shipment of study drug (quantity and 
condition). All unused study drug dispensed to subjects must be returned to the site at the 
following clinic visit for accountability and compliance assessments.   
NB01/vehicle-control study drug accountability records will be provided to each study site to: 
• Record the date and quantity of study drug kits received from the Sponsor 
• Record the date, subject number, subject initials, the study drug kit dispensed 
• Record the date, quantity of any unused study drug returned 
5.6. 
Study Drug Product Return or Disposal 
Unused study drug packages may be returned to the Sponsor by the site, upon Sponsor request, 
after the completion of the study.  Details on the return process are provided in the Study 
Reference Manual for this trial. 
5.7. 
Study Drug Product Complaints 
The Sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies to ensure the safety of study subjects, monitor quality, and facilitate process and 
product improvements. 
All product complaints associated with material packaged, labeled, and released by the Sponsor 
or its designee will be reported to the Sponsor. All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The PI or his/her designee is responsible for reporting a complete description of the product 
complaint via email or other written communication to the Sponsor contact or respective 
manufacturer as noted in the packaging information. Any AE associated with a product 
complaint should be reported to Sponsor. 
If the PI is asked to return the product for investigation, he/she will return a copy of the product 
complaint communication with the product.   

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6. 
STUDY PROCEDURES 
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows.  
The PI must document any deviation from protocol procedures and notify the Sponsor or CRO. 
6.1. 
Subject Enrollment and Treatment Assignment 
Subjects will be assigned a subject number once written informed consent has been obtained.  
Subjects who qualify for the study will be enrolled at Visit 2 when they are randomized to a 
treatment assignment. 
6.1.1. 
Subject Re-Screening 
Subjects who screen fail may be considered for enrollment at a later date, with prior Sponsor 
approval, but must re-consent and repeat necessary screening procedures. 
 
6.1.2. 
Subject Replacement 
If a subject is discontinued from the study for any reason other than a dose-limiting toxicity 
(DLT; see Section 7.2.1) prior to the completion of Week 2/Visit 3, that subject will be replaced. 
6.2. 
Pretreatment Assessments 
6.2.1. 
Screening Visit – Visit 1 
Subjects will be screened (Day -14 to Day -1) before randomization to determine eligibility for 
participation in the study. The following will be performed and documented at the Screening 
Visit: 
• Obtain a signed, written informed consent. 
• Review inclusion/exclusion criteria and confirm subject eligibility. 
• Record medical history. 
• Record prior and/or concomitant medications, topical facial products and 
procedures/therapies. 
• Have subject complete washout from any prohibited medications, if necessary. 
• Limited physical examination. 
• Vital signs. 
• UPT. 
• Local CBC.  
• Pre-Treatment with BPO of at least 5, but no more than 7, consecutive days (Screening) 
• Dispense Subject Diary (for completion of at-home Cetaphil® BID washes and BPO QD 
application). 

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• Sebum levels, measured at the mid-glabellar region of the forehead using a Sebumeter SM – 
815 (COURAGE + KHAZAKA electronic GmbH, Köln, Germany).  
• Assess AEs. 
• Assess LSRs. 
• IGA. 
• Acne Lesion Counts (total, inflammatory, and non-inflammatory lesion counts). 
• Quality of life assessment (Acne QoL Questionnaire). 
• Optional facial photography. 
• Cheek swab skin engraftment sample. 
• Face wash with Cetaphil®. 
• 
Biore® strip follicular engraftment sample. 
• Schedule the Visit 2/Baseline visit. 
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic after screening for randomization into the study on Day 1. 
From the time of obtaining informed consent through the first administration of study drug, 
record all serious adverse events (SAEs), as well as any AEs related to protocol-mandated 
procedures on the AE eCRF.  All other untoward medical occurrences observed during the 
screening period, including exacerbation or changes in medical history are to be captured on the 
medical history CRF/eCRF.  See Section 7 (Adverse Event Reporting and Toxicity 
Management) for additional details. 
6.2.2. 
Baseline Assessments – Visit 2 (Day 1) 
The following will be performed and documented at the Day 1 visit: 
• Reconfirm inclusion/exclusion criteria and subject eligibility. 
• Review of Screening Subject Diary.  
• Limited physical examination. 
• Vital signs. 
• UPT. 
• Sebum levels, measured at the mid-glabellar region of the forehead using a Sebumeter SM – 
815 (COURAGE + KHAZAKA electronic GmbH, Köln, Germany). 
• Assess AEs. 
• Assess LSRs. 
• Review concomitant medications, topical facial products and procedures/therapies. 
• IGA. 
• Acne Lesion Counts (total, inflammatory, and non-inflammatory lesion counts). 
• Quality of life assessment (Acne QoL Questionnaire). 
• Optional facial photography. 
• Cheek swab skin engraftment sample. 
• Randomize the subject (see Section 5.1.1). 
• PI or designee shall apply the first dose of study drug and review application instructions 
with the subject. 

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• Dispense Subject Diary (for documentation of at-home Cetaphil® BID washes and evening 
study drug application). 
• Dispense Study Drug and gloves, reminding the subject that study drug is to be stored in the 
freezer 
• Schedule the next visit. 
6.2.3. 
Treatment Assessments - Visit 3 (Week 2/Day 8), Visit 4 (Week 7/Day 43) and 
Visit 5 (Week 12/End of Treatment/Day 80) 
The following will be performed and documented at each visit during the treatment phase: 
• Collect, review, and dispense Subject Diary. NOTE: In review of the Subject Diary, the PI 
should question the subject to gauge understanding of application instructions, and re-
instruct, at each visit except Visit 5, EOS. 
• Sebum levels, measured at the mid-glabellar region of the forehead using a Sebumeter SM – 
815 (COURAGE + KHAZAKA electronic GmbH, Köln, Germany). 
• Assess AEs. 
• Assess LSRs. 
• Review concomitant medications, topical facial products and procedures/therapies. 
• Limited physical examination (Visit 5/EOT only). 
• Vital signs (Visit 5/EOT only). 
• UPT (Visit 5/EOT only). 
• Local CBC (Visit 5/EOT only).  
• IGA. 
• Acne Lesion Counts (total, inflammatory, and non-inflammatory lesion counts). 
• Quality of life assessment (Acne QoL Questionnaire). 
• Optional facial photography. 
• Cheek swab skin engraftment sample. 
• Face wash with Cetaphil® (only at Visit 5/EOT prior to Biore® strip sampling). 
• Biore® strip follicular engraftment sample (Visit 5/EOT only). 
• Dispense Study Drug (only at Visit 3 and Visit 4). 
• Schedule the next visit. 
6.2.4. 
Follow-up Assessment – Visit 6 (Week 16/End of Study/Day 106) 
The following will be performed and documented during a telephone follow-up call with the 
subject: 
• Assess AEs and LSRs.  If the subject reports any worsening ongoing AEs or material new 
AEs, especially those that may potentially be related to the study drug, the subject will be 
scheduled for an office visit if, in the opinion of the PI, a clinical evaluation is warranted 
(e.g., a significant safety concern). 
• Counsel the subject regarding the need for post study follow up with their primary care 
physician for any ongoing medical needs if indicated. 
• Review concomitant medications, topical facial products and procedures/therapies. 

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6.2.5. 
Unscheduled Visit 
The following will be performed and documented at unscheduled visits: 
• Review Subject Diary. NOTE: In review of the Subject Diary, the PI should question the 
subject to gauge understanding of application instructions, and re-instruct, as needed. 
• Sebum levels, measured at the mid-glabellar region of the forehead using a Sebumeter SM – 
815 (COURAGE + KHAZAKA electronic GmbH, Köln, Germany). 
• Assess AEs. 
• Assess LSRs. 
• Review concomitant medications, topical facial products and procedures/therapies. 
• Limited physical examination. 
• Vital signs. 
• UPT. 
• Local CBC.  
• IGA. 
• Acne Lesion Counts (total, inflammatory, and non-inflammatory lesion counts). 
• Quality of life assessment (Acne QoL Questionnaire). 
• Optional facial photography. 
• Cheek swab skin engraftment sample. 
• Biore® strip follicular engraftment sample. 
• Confirm next scheduled visit. 
6.3. 
Assessments for Premature Discontinuation from Study 
If a subject discontinues the study prior to Week 12/Visit 5 (for example, as a result of an AE), 
every attempt should be made to schedule the subject to complete EOT visit procedures (see 
Section 10.2, Subject Discontinuation).  

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7. 
ADVERSE EVENT REPORTING AND TOXICITY 
MANAGEMENT 
7.1. 
Adverse Event Definitions 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related.  
An AE (also referred to as an adverse experience) can therefore be any unfavorable and 
unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a drug, without any judgment about causality. An AE can arise from 
any use of the drug (e.g., off-label use, use in combination with any drug) and from any route of 
administration, formulation, or dose, including an overdose. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug 
caused the event. “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the AE. 
 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all suspected 
adverse reactions for which there is reason to conclude that the drug caused the event. A 
suspected adverse reaction implies a lesser degree of certainty about causality than adverse 
reaction, which means any AE caused by a drug. For the purposes of prescription drug labeling, 
the term adverse reaction means an undesirable effect, reasonably associated with the use of a 
drug that may occur as part of its pharmacological action or may be unpredictable in its 
occurrence.  
 
An AE does not include the following: 
Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an AE and must be reported. 
Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen. 
Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions). 
Overdose without clinical sequelae.  
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is not an AE. It is 
considered to be pre-existing and should be documented on the medical history CRF. 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the IB or is 
not listed at the specificity or severity that has been observed; or, if an IB is not required or 

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available, the event is considered “unexpected” if it is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. For 
example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the IB listed only cerebral vascular accidents. "Unexpected," as used in this definition, also 
refers to AEs or suspected adverse reactions that are mentioned in the IB as occurring with a 
class of drugs or as anticipated from the pharmacological properties of the drug but are not 
specifically mentioned as occurring with the particular drug under investigation. 
 
Timely and complete reporting of all AEs assists the Sponsor and/or their designee in identifying 
any untoward medical occurrence, thereby allowing:  
1) protection of the safety of study subjects;  
2) a greater understanding of the overall safety profile of the study drug;  
3) recognition of dose-related study drug toxicity; 
4) appropriate modification of study protocols;  
5) improvements in study design or procedures; and  
6) adherence to worldwide regulatory requirements.  
7.2. 
Adverse Event Details 
AEs may be either spontaneously reported or elicited during questioning and examination of a 
subject. All AEs must be recorded on the AE CRF. If known, the PI should report the diagnosis 
of the underlying illness or disorder, rather than its individual symptoms. Subjects experiencing 
AEs that cause interruption or discontinuation of study drug or those experiencing AEs that are 
present at the end of their participation in the study should receive follow-up as appropriate. AEs 
should be followed to resolution or stabilization (if possible) and, if they become serious, 
reported as SAEs. If possible, the outcome of any AEs that caused permanent discontinuation or 
that were present at the end of the study, especially those considered by the PI to be related to the 
study drug, should be reported. 
 
Information on the medical condition of subjects should begin following the subject’s written 
informed consent to participate in the study and a medical history should be taken at screening. 
During any wash out and baseline periods, any changes in the health of subjects should be 
recorded as changes in medical history unless an event occurred as a result of a study-related 
procedure and is unanticipated; in such cases, the event should be recorded as an AE and 
reported to the Institutional Review Board (IRB) as an “unanticipated problem” in accordance 
with local procedures. Other changes in subject health information becomes AE data when the 
subject begins dosing with the study drug; therefore, AE data should be collected from the date 
of the first dose of study drug until the date of the final study visit. These data are considered 
treatment-emergent AEs. 
 
The PI will instruct the subject to report any AEs that may occur during the study. At each visit, 
the PI should ask the subject, in non-directive fashion, about any change in the subject’s overall 

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health status since the previous visit. Optional photographs may be obtained for areas outside of 
the face, as clinically indicated for the classification and management of AEs. 
 
The PI will assign a CTCAE grade to all AEs (CTCAE Version 5.0, Appendix 4). The severity 
of each AE, as judged by the PI, will be recorded on the appropriate AE CRF and will be graded 
according to the following scale: 
 
Mild - The AE is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
 
Moderate - The AE is usually alleviated with additional specific therapeutic intervention. 
The event interferes with usual activities of daily living, causing discomfort, but poses no 
significant or permanent risk of harm to the research participant. 
 
Severe - The AE interrupts usual activities of daily living or significantly affects clinical 
status or may require intensive therapeutic intervention. 
 
The PI must determine the relationship of the AE to the study drug according to the following 
categories: 
 
Definitely related - An event that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
study drug; and that is confirmed by improvement on stopping or reducing the dosage, 
and reappearance of the event on repeated exposure (re-challenge). 
 
Probably related - An event that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
study drug; and that is confirmed by improvement on stopping or reducing the dosage of 
the study drug; and that is unlikely to have been caused by concurrent/underlying illness 
or other drugs, procedures, or other causes. 
 
Possibly related - An event that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
study drug; but may have been caused by concurrent/underlying illness, other drug, 
procedure, or other causes. 
 
Unlikely related - An event that does not follow a reasonable temporal sequence from 
administration of the study drug; that does not follow a known or expected response 
pattern to the study drug, or most likely was caused by concurrent/underlying illness, 
other drug, procedure, or other causes, because of their known effects.  
 
Not Related - An event almost certainly caused by concurrent/underlying illness, other 
drug, procedure, or other causes. 
 
The PI should categorize the outcome of the AE according to the following categories: 

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Fatal - Termination of life as a result of an AE. 
 
Not Recovered/Not Resolved - AE has not improved or the subject has not recuperated. 
 
Recovered/Resolved - AE has improved or the subject has recuperated. 
 
Recovered/Resolved with Sequelae - subject recuperated but retained the pathological 
conditions resulting from the prior disease or injury. 
 
Recovering/Resolving - AE is improving or the subject is recuperating. 
 
Unknown - Not known, not observed, not recorded or subject refused. 
 
7.2.1. 
Dose Limiting Toxicity and Stopping Rules 
The Medical Monitor will consider DLT when reviewing the safety data and making 
recommendations for discontinuing a subject from the study per Section 10.2. A DLT is defined 
as a new onset systemic Grade 2 or higher (CTCAE Version 5.0, Appendix 4) AE for which 
there is no clear alternative explanation of the cause of the AE.  In the event a subject is enrolled 
in the study with a baseline medical condition that would not exclude the subject from entering 
the study, but meets the classification criteria for a systemic Grade 2 (or higher) or non-systemic 
(local) Grade 3 (or higher) event, a worsening of the baseline condition during the study that 
results in an increase in one grade above their Baseline grade shall warrant assessment as a 
potential DLT. 
 
Non-systemic (local) AEs Grade 3 or higher for which there is no clear alternative explanation of 
the cause of the AE will also be considered DLTs.  Any subject who experiences a DLT, as 
described above, must discontinue treatment and be scheduled for a final visit. Any DLTs that 
are Grade 2 or greater systemic AEs must be reported by the PI immediately. If three or more 
subjects experience DLTs in the study, enrollment in the study will be halted, and a safety review 
will occur using an independent medical reviewer who will have access to the subject’s treatment 
allocation. This review shall be completed promptly within 10 business days. Subjects who are 
active in the study will be instructed to withhold study drug applications during the safety review 
period. If all of the subjects experiencing DLTs (i.e. three or more) are found to be subjects 
receiving the active NB01 study drug, the independent medical reviewer will provide a written 
recommendation to the Sponsor to continue the study, discontinue the study or modify the study 
protocol. The Sponsor is responsible for promptly reviewing the independent medical reviewer’s 
recommendations, accepting or rejecting these recommendations, and determining whether 
amendments to the protocol or changes in study conduct will be required. The Sponsor will 
provide the final written decision regarding the study status. In the event this is not the case, the 
independent medical reviewer will notify the Sponsor and Medical Monitor of how many 
subject’s DLTs were in subjects receiving vehicle (e.g. Y subjects). In the event Y new subjects 
experience DLTs, the independent medical reviewer review process outlined above will be 
repeated. This process will be repeated throughout the entire study until the study is complete or 

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the stopping rule has been met. In the event that a total of three (3) or more subjects experience 
DLTs related to NB01 study drug, the study will be discontinued.  
 
If an SAE occurs during the study and is determined by the Sponsor to be at least possibly 
related to the study drug, enrollment of new subjects and dosing of active subjects will be halted. 
A safety review will occur using an independent medical reviewer who will have access to the 
subject’s treatment allocation.  This review shall be completed promptly within 5 business days.   
The independent medical reviewer will provide a written recommendation to the Sponsor to 
continue the study, discontinue the study or modify the study protocol. The Sponsor is 
responsible for promptly reviewing the independent medical reviewer’s recommendations, 
accepting or rejecting these recommendations, and determining whether amendments to the 
protocol or changes in study conduct will be required. The Sponsor will provide the final written 
decision regarding the study status. A summary of the event should also be reported to FDA as 
part of an IND Safety Report in accordance with Section 7.2.2.  FDA should also be notified 
within 48 hours of the final decision and provided an IND Safety Follow-up Report as necessary 
(if new information was collected since the initial Safety Report).   
7.2.2. 
Serious Adverse Events 
An event that is serious must be recorded on the CRF/eCRF and requires expeditious handling to 
comply with regulatory requirements. 
 
An AE or suspected adverse reaction is considered “serious” if, in the opinion of either the PI or 
Sponsor, it results in any of the following outcomes: 
• Death; the event must be the cause of death for the SAE to meet this serious criterion. 
• Life-threatening event; an event in which the subject was at risk of death at the time of the 
event and not an event that hypothetically might have caused death if it had been more 
severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization (for ≥24 
hours). 
• Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions. 
• Congenital anomaly/birth defect. 
• Important medical events; a medical event(s) that may not result in death, be life-
threatening, or require hospitalization but, based upon appropriate medical judgment, may 
jeopardize the subject and may require medical or surgical intervention to prevent one of 
the outcomes listed in the definition above. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.  
 
Events NOT considered to be SAEs are: 
• Hospitalizations for the treatment, which was elective or pre-planned, of a pre-existing 
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• Treatment on an emergency, outpatient basis, for an event not fulfilling any of the 
definitions of “serious” given above and not resulting in hospital admission. 
 
AEs classified as “serious” by either the PI or the Sponsor require expeditious handling and 
reporting to the Sponsor or designee to comply with regulatory requirements. All SAEs, 
whether related or unrelated to study drug, must be immediately reported by telephone to 
the Medical Monitor listed on the first page of the protocol. In the event that he/she is 
unavailable, contact the back-up Medical Monitor listed in the study reference manual. 
Written notification of all SAEs should be sent to the Trial Manager by email or confirmed 
facsimile transmission. These include those SAEs listed in the protocol or IB and must include 
an assessment of whether there is a reasonable possibility that the study drug caused the event.  
 
Any suspected adverse reactions that are serious and unexpected represent especially important 
safety information that must be reported more rapidly to Health Authorities; therefore, it is 
important that the PI submit any information requested by the Sponsor or designee as soon as it 
becomes available. 
 
If only limited information is initially available, follow-up reports are required. Should the PI 
become aware of an SAE (regardless of its relationship to study drug) that occurs within 30 days 
after stopping the study drug, the SAE must be reported in accordance with procedures specified 
in this protocol. In the event of death, if an autopsy is performed, a copy of the report should be 
sent to the Sponsor or designee, if available. 
 
As required, the Sponsor or designee will notify participating PIs of all suspected adverse 
reactions that are serious and unexpected. This notification will be in the form of an IND safety 
report of potential serious risks as soon as possible but no later than 15 calendar days after the 
Sponsor determines that the information is “reportable” according to the criteria listed in 21 CFR 
Section 312.32. These are: 
 
i) Serious and unexpected suspected adverse reactions; 
ii) Findings from other studies including epidemiological studies, pooled analyses, 
or other clinical studies that suggest a significant risk in humans exposed to the 
study drugs; 
iii) Findings from animal or in vitro tests that suggest a significant risk to humans 
exposed to the study drugs, or reports of significant organ toxicity at or near the 
expected human exposure; and 
iv) Clinically important increases in the rate of occurrence of serious suspected adverse 
reactions. 
 
Upon receiving such notices, the PI must review and retain the notice with the IB and promptly 
submit a copy of this information to the responsible IRB according to local regulations. The PI 
and IRB will determine if the informed consent requires revision. The PI should also comply 
with the IRB procedures for reporting any other safety information. Where required, submission 
of safety updates by the PI to Health Authorities should be handled according to local 
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The Sponsor or designee may be required to report certain SAEs to regulatory authorities (e.g., 
United States FDA) within seven calendar days of being notified about the event; therefore, it is 
important that PIs submit any information requested by the Sponsor or designee as soon as it 
becomes available. 
7.2.3. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
The PI will evaluate clinical laboratory results, physical exam findings and vital signs to 
determine if any findings are clinically significant.  Any clinically significant results that 
represent and new or worsening change from Baseline should be recorded as an AE.  
7.3. 
Pregnancy 
Male subjects who are not surgically sterile, and are sexually active with a female partner must 
agree to use an effective method of birth control from the first administration of the study drug 
until 30 days after the last study drug application. Female subjects who are WOCBP, and are 
sexually active with a male partner must agree to use an effective method of birth control from 
the first administration of the study drug until 30 days after the last study drug application.  
Protocol Section 4.2, Inclusion Criteria #6, provides definitions of sterility and methods of 
acceptable birth control. 
 
Prior to study enrollment, subjects must be advised of the importance of avoiding pregnancy 
during study participation and the potential risk factors for an unintentional pregnancy. The 
subject must sign an informed consent form documenting this discussion. 
 
WOCBP should be instructed to contact the investigator immediately if they suspect they might 
be pregnant (e.g., missed or late menstrual period) during the study and for 30 days after she has 
completed her last test article application. If a subject or investigator suspects that a subject may 
be pregnant at any time during the study, the test article must be withheld until the results of 
laboratory pregnancy testing are available. If pregnancy is confirmed, the subject must not 
receive or apply further test article. 
 
If following initiation of study treatment, it is subsequently discovered that a subject was 
pregnant or may have been pregnant at the time of test article exposure, the investigator must 
immediately notify the Medical Monitor of this event and record the pregnancy on the 
appropriate pregnancy surveillance form. The form will be sent to the Sponsor or designee. The 
investigator must notify the IRB of any pregnancy associated with the study treatment and keep 
careful source documentation of the event, including abortion (accidental, therapeutic, or 
spontaneous) and birth of offspring. Offspring should be followed for a minimum of eight weeks 
and any congenital anomaly/birth defect in a child born to a subject or a male subject’s sexual 
partner that was exposed to the study drug should be documented on the pregnancy surveillance 
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During the study, all male subjects should be instructed to contact the PI immediately if they 
suspect that their sexual partner might be pregnant (e.g., female sexual partner has missed or late 
menstrual period).  
 
7.4. 
Toxicity Management  
A dose mitigation strategy will be employed whereby, with Medical Monitor approval, the dose 
may be reduced/modified according to the individual subject’s tolerance.  Typical modification 
may include short drug holiday periods off therapy, every other day dosing, etc.  Such changes 
however shall not be made without the written approval of the Medical Monitor. 
 
 

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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Sample Size 
No formal sample size calculations were performed for this study given it is an initial proof of 
concept study. 
8.2. 
Analysis Populations 
8.2.1. 
Safety Population 
The Safety population will include all randomized subjects who received and applied study drug.  
8.2.2. 
Intent-to-Treat Population 
The ITT population will include all randomized subjects who were dispensed the study drug.  
8.2.3. 
Per-Protocol Population 
The PP population will include a subset of the ITT population who completed the study without 
significant protocol deviations (as will be determined prior to unblinding the randomization). 
8.3. 
Endpoints 
8.3.1. Primary Safety Endpoints 
• Incidence (severity and causality) of any local and systemic AEs. 
• Number of subjects with presence (and severity) of each LSR and each time point. 
• Changes from Screening/Baseline in physical examination findings at Visit 5/EOT. 
• Changes from Screening/Baseline in vital signs at Visit 5/EOT. 
• Changes from Screening in local CBC at Visit 5/EOT. 
8.3.2. Exploratory Engraftment Endpoint 
• For skin engraftment assay, absolute and percent change from Screening to follow-ups in 
Cas5/PanBac and for follicular engraftment assay, the proportion of subjects with “success” 
at EOT where “success” is defined as a Follicular Biore® with “yes” outcome based on 
recovery of live NB01. 
8.3.3. Exploratory Efficacy Endpoints 
• Absolute change from Screening at each follow-up visit in IGA score. 
• Absolute and percent change from Screening at each follow-up visit in total, inflammatory, 
and non-inflammatory lesions. 

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• Absolute and percent change from Screening to follow-up in Acne QoL. 
8.3.4. 
Exploratory Sebum Endpoint 
• Absolute and percent change from Screening to follow-up in sebum production. 
8.4. 
Statistical Methods 
All statistical processing will be performed using SAS®. Summary tables (descriptive statistics 
and/or frequency tables) will be provided for screening and/or baseline variables, efficacy 
variables, and safety variables. Summaries will be provided for each treatment group. In general, 
continuous variables will be summarized by descriptive statistics including sample size, mean, 
SD, median, minimum, and maximum. Categorical variables will be summarized by frequency 
and percentage. 
8.4.1. 
Dosing Compliance 
Descriptive statistics will be used to summarize for each treatment group the duration of 
treatment (defined as last dose date – first dose date +1), the total number of applications 
(determined from the doses reported in the Subject Diary), and the percent of expected doses 
applied for the ITT and PP populations. Subjects who apply at least 80% of the expected total 
number of applications and have no other evidence of material dosing non-compliance will be 
considered to be compliant with study drug dosing. 
8.4.2. Pimary Safety Analyses 
All safety analyses will be performed on the Safety population. 
 
Extent of Exposure 
Descriptive statistics will be used to summarize the extent of exposure in the Safety population. 
The total amount of study drug used by each subject will be calculated based on the number of 
days the study drug was applied (according to the subject’s diary entries).  
 
Physical Examinations 
Findings from the physical exam will be recorded in medical history (from assessment at Visit 
1/Screening) or as AEs (from assessment at Visit 5/EOT. 
 
Vital Signs 
Descriptive statistics of vital signs (temperature, blood pressure, and heart rate) will be provided 
by treatment group.  
 
Clinical Laboratory Tests 
Local CBC tests will be evaluated for any material changes during the study period. All 
laboratory data will be listed and reported in the units received by the laboratory. Shift tables by 
analyte and by out of range flag will be presented. 
 

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Local Skin Reactions 
The frequency of the individual LSRs (PI: erythema, edema, erosion/ulceration, scaling/dryness, 
and scabbing/crusting; Subject: itching and pain) will be tabulated by severity and treatment 
group at each visit. The frequency of the individual LSRs recorded by subjects in weekly diaries 
(redness, swelling, erosion/ulceration, scaling/dryness, and scabbing/crusting, itching, and pain) 
will be tabulated by severity and treatment group for each study week. 
 
Adverse Events 
All AEs reported during the study will be listed, documenting course, severity, PI assessment of 
the relationship to the study drug, and outcome. Verbatim terms on the eCRFs will be linked to 
preferred terms (PTs) and system organ class (SOC) using the Medical Dictionary for Regulatory 
Activities (MedDRA) mapping system. The PTs and SOC will then be tabulated. All reported 
AEs will be summarized by the number of subjects reporting AEs, SOC, PT, severity, and 
relationship to study drug by treatment group.  
 
Urine Pregnancy Tests 
Results from UPTs will be provided in a listing. 
8.4.3. Exploratory Engraftment Analyses 
The engraftment analyses will be conducted on the ITT and PP populations. 
 
Engraftment Assay 
For endpoint of Engraftment Assay of Cas5/PanBac, the absolute and percent change from 
Screening at each follow-up visit, the comparison between NB01 and vehicle-control will be 
analyzed using ANCOVA model with the dependent variable being absolute or percent change 
values and the factor treatment and the Screening value as a covariate in the model, with and 
without LOCF imputation. 
 
For endpoint of Follicular Biore®, the treatment groups will be compared with respect to the 
proportions of subjects with “success” at Week 12 using the CMH test with and without 
stratification on study center, where “success” is defined as a Follicular Biore® with “yes” 
outcome based on the recovery of live NB01. 
 
8.4.4. Exploratory Efficacy Analyses 
The efficacy analyses will be conducted on the ITT and PP populations. 
 
Investigator’s Global Assessment 
The observed and change from Screening scores at each follow-up visit will be tabulated. For 
endpoint of IGA, the treatment groups will be compared with respect to the proportions of 
subjects with (a) at least a one-point improvement and (b) at least a two-point improvement in 
IGA score relative to Screening at each follow-up visit using the CMH test with and without 
stratification on study center. 

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Acne Lesion Counts 
For endpoint of Acne Lesion Counts, the absolute and percent change from Screening at each 
follow-up visit in total, inflammatory, and non-inflammatory lesions, the comparison between 
NB01 and vehicle-control will be analyzed using Analysis of Covariance (ANCOVA) model 
with the factor treatment and the Screening counts as a covariate in the model, with and without 
Last Observation Carried Forward (LOCF) imputation. 
 
 
Acne Quality of Life 
For endpoint of Acne-QoL, the absolute and percent change from Screening at each follow-up 
visit on four domains separately and total, the comparison between NB01 and vehicle-control 
will be analyzed using ANCOVA model with the factor treatment and the Screening score as a 
covariate in the model, with and without LOCF imputation. 
8.5. 
Exploratory Sebum Analyses 
Sebum Production 
For endpoint of sebum production, the absolute and percent change from Screening at each 
follow-up visit, the comparison between NB01 and vehicle-control will be analyzed using 
ANCOVA model with the factor treatment and the Screening value as a covariate in the model, 
with and without LOCF imputation. 
8.6. 
Interim Analyses 
No interim analyses are planned for this study. 
 

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9. 
RESPONSIBILITIES 
9.1. 
Investigator Responsibilities 
9.1.1. 
Good Clinical Practice 
This study will be conducted in compliance with the principles of the Declaration of Helsinki, 
with the current Good Clinical Practice guidelines and with other applicable regulations. The PI 
and all study staff will conduct the study in compliance with this protocol. The protocol, 
informed consent documents, recruitment advertisements, and any amendments to these items 
will have IRB approval prior to study initiation. Voluntary informed consent will be given by 
every subject prior to the initiation of any study-related procedures. The rights, safety and well-
being of the study subjects are the most important considerations and prevail over the interests of 
science and society. All personnel involved in the conduct of this study must be qualified by 
education, training, and experience to perform their assigned responsibilities. Contact 
information for each site and any clinical laboratories used in the study will be maintained up to 
date in a separate reference document. 
9.1.2. 
Institutional Review Board Review and Approval 
Before study initiation, the PI must have written and dated approval from the IRB for the 
protocol, consent form, subject recruitment materials/process (e.g., advertisements), and any 
other written information to be provided to the subject. The PI should also provide the IRB with 
a copy of the product labeling, information to be provided to the subject and any updates. The PI 
will submit documentation of the IRB approval to the Sponsor.  
 
The IRB approved consent form must include all elements required by FDA, state, and local 
regulations, and may include appropriate additional elements. 
9.1.3. 
Informed Consent 
The PI/designee will explain the study to each potential subject and the subject must indicate 
voluntary consent by signing and dating the approved informed consent form. The PI must 
provide the subject with a copy of the consent form, in a language the subject understands.  
 
The PI will maintain documentation that informed consent was obtained prior to the initiation of 
any study-specific procedures. 
9.1.4. 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure storage 
area with limited access.  
 

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The study Sponsor, and its representatives, may review optional photographs taken during the 
study, but will not have access to other personal identifying information during review of these 
photographs.  In order to protect subject privacy, a rectangular bar will be placed over subjects’ 
eyes in the photographs, to help de-identify any photo(s) to be used in any of the publication or 
presentation materials described in Section 9.2.3.  Additionally, any features that could be used 
to identify subjects, such as a scars or tattoos, will also be covered in the photographs. 
Clinical information will not otherwise be released (with the exception of de-identified data 
described in Section 9.2.3) without the written permission of the subject, except as necessary for 
monitoring by TI or the Sponsor, the FDA or other regulatory authority, or the IRB. 
 
The PI and all employees and coworkers involved with this study shall 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 TI or the Sponsor must be obtained for the disclosure of any said confidential 
information to other parties. 
9.1.5. 
Study Files and Retention of Records 
The PI must maintain all study records (including study drug disposition, informed consents, 
CRFs, source documents, correspondence, regulatory documents, contracts, etc.) for the 
maximum period required by the Sponsor or the institution where the study is conducted, 
whichever is longer. Study drug Accountability Logs and original Label Pages (if applicable) 
must be kept with study records at the site. 
 
The PI must contact the Sponsor prior to destroying any records associated with this study. 
 
If the PI withdraws from the study, the records shall be transferred to a mutually agreed upon 
designee. Written notification of such a transfer must be given to the Sponsor. 
9.1.6. 
Case Report Forms 
This study utilizes eCRFs; validated 21 CFR Part 11 compliant electronic data capture (EDC) 
software will be used to collect data. All requested information must be entered on the eCRFs in 
the areas provided in a timely manner. When changes or corrections are made in the eCRF, the 
EDC system will maintain a complete audit trail of the person making the changes, the date and 
time of the change, and the reason for the change. Only individuals who have completed EDC 
training and are listed on the Delegation of Responsibilities Log with responsibility for eCRF 
completion will be provided usernames and passwords in order to access the system and make 
entries on the eCRF. 
 
The PI or physician sub-investigator must electronically sign and date each subject’s eCRF. 
Individuals who will be providing electronic signatures must first submit documentation with a 
handwritten signature acknowledging that their electronic signature is a legally binding 
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9.1.7. 
Inspections 
Representatives from TI and/or the Sponsor or a third party selected by the Sponsor may conduct 
a quality assurance audit of this study. During the audit, the PI must provide the auditor with 
direct access to all relevant documents and discuss any findings with the auditor. 
 
In the event of an inspection by the FDA or other regulatory authorities, the PI must give the 
inspector direct access to relevant documents and to discuss any findings with the inspector. The 
PI must notify TI in the event of an FDA site audit. 
 
9.1.8. 
Protocol Compliance 
The IRB approved protocol must be followed except in the case of a change that is intended to 
eliminate an immediate risk to subjects. All protocol deviations must be documented.  
 
9.2. 
Sponsor Responsibilities 
9.2.1. 
Protocol Modifications 
The Sponsor will prepare all protocol revisions. All protocol amendments must receive IRB 
approval prior to implementation. All administrative letters must be submitted to the IRB for 
their information. Copies of all correspondence with the IRB regarding this study must be sent to 
TI. 
 
New or altered consent forms required by the IRB due to a protocol change must be signed by all 
subjects currently enrolled in the study and must be used for any subsequent subject enrollment. 
 
9.2.2. 
Access to Information for Monitoring, Auditing or Inspections 
Representatives of the Sponsor and the Sponsor’s CRO must be allowed to visit all study sites, to 
review study records, and to directly compare them with source documents (including, but not 
limited to patient and hospital records), to discuss the study conduct with the PI and study staff, 
and to verify that the PI, study staff, and facilities remain acceptable for the conduct of the study. 
 
Representatives of government regulatory authorities may also evaluate the study records, source 
documents, PI, study staff, and facilities. 
 
The PI should immediately notify the Sponsor of any audits of this study by any regulatory 
agency and must promptly provide copies of any audit reports. 
 
9.2.3. 
Study Report and Publications 
A clinical study report will be prepared and provided to the regulatory agency. Naked Biome will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 

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of Clinical Study Reports (ICH E3). NOTE: An abbreviated report may be prepared in certain 
cases. 
 
The trial Sponsor may use de-identified data (including de-identified photographs) obtained 
during the study in scientific journals or magazines and as part of other presentations for 
corporate, research, medical, scientific, or educational purposes. 
 
PIs in this study may communicate, orally present, or publish in scientific journals or other 
scholarly media only after the following conditions have been met: 
1. The results of the study in their entirety have been publicly disclosed by or with the 
consent of Naked Biome in an abstract, manuscript, or presentation form or the study has 
been completed at the study site for at least two years. 
2. The PI will submit to Naked Biome any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission 
of the publication or presentation. 
3. No such communication, presentation, or publication will include Naked Biome’s 
confidential information. 
4. The PI will comply with Naked Biome’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to 
withhold publication or presentation for an additional 60 days to obtain patent protection 
if deemed necessary. 

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10. 
END OF STUDY CRITERIA 
At the end of each subject’s participation in the study, the PI will complete an End of Study form 
for all completed and discontinued subjects.  
10.1. Completion of the Study 
Each subject who completes all study visits, as specified in this protocol will have completed the 
study. 
10.2. Subject Discontinuation 
A subject may be withdrawn from the study prior to completion for any of the following reasons: 
• Adverse event 
• Death 
• Lost to follow-up 
• Subject non-compliance  
• PI decision 
• Pregnancy 
• Progressive disease 
• Significant protocol deviation 
• Study terminated by Sponsor 
• Withdrawal of consent by subject*  
 
*If the subject decides to withdraw from the study due to an AE it should be classified as 
withdrawal due to an AE.  
 
If a subject withdraws prior to the Week 12 visit, every attempt should be made to complete final 
study procedures prior to discharge from the study. If a subject withdraws prematurely during the 
treatment period for any reason, the Week 12/EOT procedures will be completed. When a 
subject is withdrawn from the study for a treatment-related AE (i.e., possibly, probably or 
definitely related as defined in Section 7.2), when possible, the subject should be followed until 
resolution of the AE. 
10.3. Study Termination 
The study may be terminated by the PI or the Sponsor. If, in the opinion of the PI, clinical 
observations made during the study suggest that it may be unwise to continue, he or she may stop 
the study. A study termination by the PI will be reported to the Sponsor. 
 
In addition, a written statement fully documenting the reasons for this action will be submitted to 
the Sponsor by the PI within five working days. 
 

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In the event that the Sponsor chooses to discontinue or terminate the study, appropriate 
notification will be given to the PI and an orderly discontinuation of all subjects per Section 10.2 
will occur. 
 

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11. 
REFERENCES 
Achermann Y, Goldstein EJ, Coenye T, et al. Propionibacterium acnes: from commensal to 
opportunistic biofilm-associated implant pathogen. Clin Microbiol Rev. 
2014;27(3):419-440. 
Baquerizo Nole KL, Yim E, Keri JE. Probiotics and prebiotics in dermatology. J Am Acad 
Dermatol. 2014;71(4):814-821. 
Fitz-Gibbon S, Tomida S, Chiu B-H, et al. Propionibacterium acnes strain populations in the in 
the human skin microbiome associated with acne. J Invest Dermatol. 
2013;133(9):2152-2160. 
Johnson T, Kang D, Barnard E, et al. Strain-level differences in porphyrin production and 
regulation in propionibacterium acnes elucidate disease associations. mSphere. 
2016;1(1):e00023-15. 
Kang D, Shi B, Erfe M, Craft N, Li H. Vitamin B12 modulates the transcriptome of the skin 
microbiota in acne pathogenesis. Sci Transl Med. 2015:7(293): 293ra103. 
Kasimatis G, Fitz-Gibbon S, Tomida S. Analysis of complete genomes of Propionibacterium 
acnes reveals a novel plasmid and increased pseudogenes in an acne associated 
strain. Biomed Res Int. 2013:918320. 
Kwon HH, Suh DH. Recent progress in the research about Propionibacterium acnes strain 
diversity and acne: pathogen or bystander? Int J Dermatol. 2016;55(11):1196-
1204. 
McDowell A, Barnard E, Nagy I, et al. An expanded multilocus sequence typing scheme for 
Propionibacterium acnes: investigation of ‘pathogenic’, ‘commensal’ and 
antibiotic resistant strains. PLoS One. 2012;7(7):e41480. 
McDowell A, Nagy I, Magyari M, et al. The opportunistic pathogen Propionibacterium acnes: 
insights into typing, human disease, clonal diversification and CAMP factor 
evolution. PLoS One. 2013;8(9):e70897. 
McGinley KJ, Webster GF, Ruggieri MR. Regional variations in density of cutaneous 
propionibacteria: correlation of Propionibacterium acnes populations with 
sebaceous secretion. J Clin Microbiol. 1980;12(5):672-675. 
Mirshahpanah P, Maibach HI. Models in Acnegenesis. Cutan Ocul Toxicol. 2007;26(3):195-202. 
Richter C, Trojahn C, Dobos G, et al. Follicular fluorescence quantity to characterize acne 
severity: a validation study. Skin Res Technol. 2016;22(4):451-459. 

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Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update 
from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad 
Dermatol. 2009;60(5 Suppl):S1-S50. 
Tomida S, Nguyen L, Chiu BH, et al. Pan-genome and comparative genome analyses of 
propionibacterium acnes reveal its genomic diversity in the healthy and diseased 
human skin microbiome. mBio. 2013;4(3):e00003-13. 
Walsh TR, Efthimiou J, Dréno B. Systematic review of antibiotic resistance in acne: an 
increasing topical and oral threat. Lancet Infect Dis. 2016;16(3):e23-e33. 
Wei EX, Kirsner RS, Eaglstein WH. End points in dermatologic clinical trials: a review for 
clinicians. J Am Acad Dermatol. 2016;75(1):203-209. 
 

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APPENDICES 

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APPENDIX 1. 
SPONSOR-INVESTIGATOR SIGNATURE PAGE 
NAKED BIOME, INC. 
 
STUDY ACKNOWLEDGEMENT 
 
This protocol has been approved by Naked Biome, Inc. The following signature documents this 
approval. 
 
Emma Taylor 
 
 
Name (Printed) 
 
 
Signature 
 
 
 
 
Date 
 
 
 
 
INVESTIGATOR STATEMENT 
 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Naked Biome, Inc. I will discuss this material with them to ensure that 
they are fully informed about the drugs and the study. 
 
 
 
Principal Investigator Name (Printed) 
 
Signature 
 
 
 
 
Date 
 
Site Number 
 

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Appendix 2. Schedule of Events Table 
STUDY PERIOD ► 
Pre-
Treatment  
Treatment 
Follow-Up 
 
STUDY VISIT (± visit window)► 
 
Visit 1 
Screening 
Visit 2b 
Baseline 
Visit 3 
(±2 days) 
Visit 4 
(±7 days) 
Visit 5p 
End of 
Treatment  
(+3 to +7 
days) 
Unscheduled 
Visits 
(n/a) 
Visit 6  
(End of 
Study)x 
(±3 days) 
 
 
 
 
 
 
PROCEDURE▼TREATMENT DAY► Day -14 to -1 
Day 1 
 
Day 8 
(Week 2) 
Day 43 
(Week 7) 
Day 80 
(Week 
12/EOT) 
n/a 
Day 106 
(Week 
16/EOSt) 
Eligibility Criteria Reviewa 
X 
X 
 
 
 
 
 
Informed Consent Process 
X 
 
 
 
 
 
 
Limited Physical Examinationc 
X 
X 
 
 
X 
X 
 
Medical History Review 
X 
 
 
 
 
 
 
Concomitant Medication Review 
X 
X 
X 
X 
X 
X 
 
Adverse Event Assessment 
Xd 
Xe 
X 
X 
X 
X 
X 
Vital Signsf 
X 
X 
 
 
X 
X 
 
Laboratory Assessment – CBCg 
X 
 
 
 
X 
X 
 
Urine Pregnancy Testh 
X 
X 
 
 
X 
X 
 
BPO Pre-Treatment 
Xi 
 
 
 
 
 
 
Subject Diaryj & Compliance Review 
Xu 
Xu, v, w 
Xu, v, w 
 Xu, v, w  
 Xu, v, w 
 
Xv, w 
Twice Daily Facial Washingl 
Xk 
Xk, m  
Xk 
Xk 
Xk 
 
 
Randomization 
 
X 
 
 
 
 
 
Quality of Life Questionnaire 
X 
X 
X 
X 
X 
X 
 
Sebum productiony 
X 
X 
X 
X 
X 
X 
 

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STUDY PERIOD ► 
Pre-
Treatment  
Treatment 
Follow-Up 
 
STUDY VISIT (± visit window)► 
 
Visit 1 
Screening 
Visit 2b 
Baseline 
Visit 3 
(±2 days) 
Visit 4 
(±7 days) 
Visit 5p 
End of 
Treatment  
(+3 to +7 
days) 
Unscheduled 
Visits 
(n/a) 
Visit 6  
(End of 
Study)x 
(±3 days) 
 
 
 
 
 
 
PROCEDURE▼TREATMENT DAY► Day -14 to -1 
Day 1 
 
Day 8 
(Week 2) 
Day 43 
(Week 7) 
Day 80 
(Week 
12/EOT) 
n/a 
Day 106 
(Week 
16/EOSt) 
Facial Photography (optional) 
X 
X 
X 
X 
X 
X 
 
Engraftment Sampling – follicular0 
Xn 
 
 
 
Xq 
X 
 
Engraftment Sampling - skin surface 
Xn 
X 
X 
X 
X 
X 
 
Investigator Global Assessment (IGA) 
X 
X 
X 
X 
X 
X 
 
Acne Lesion Counts 
X 
X 
X 
X 
X 
X 
 
Dispense Study Drug to Subjects 
 
X 
X 
X 
 
 
 
Local Skin Reactions 
X 
X 
X 
X 
X 
X 
X 
Study Drug Applicationr 
 
Xb, m 
 
X 
 
X 
 
 
 
 
Abbreviations: BPO = Benzoyl Peroxide; CBC = Complete Blood Counts; EOS = End of Study 
Footnotes: 
a Includes confirmation of contraception use for the duration of Screening prior to first application and through study participation.  
b Day 1 procedures must be completed prior to the application of study drug. Day 1 study drug is applied by the PI or sub-investigator designee at the site. 
c Limited physical examination of face, chest, arms, back (relevant acne regions).  
d Adverse Events are assessed from the time of consent. 
e Subjects will remain at the clinic for at least 30 minutes after the initial (Day 1) study drug application to be assessed for AEs. 
f Blood pressure, heart rate, temperature. 
g CBC is assessed locally and must include Differential.  
h Urine dipstick test assessed locally. 

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i All screening visit procedures will be completed prior to initiating BPO pre-treatment. BPO gel should be applied for at least 5 days, in the AM immediately 
after the AM Cetaphil® wash. Final BPO pre-treatment should be approximately 24 hours prior to application of study drug. 
j Study subjects will note date and time of each BPO pre-treatment and Cetaphil® wash for the Screening period, and date and time for each Cetaphil® wash and 
study drug application during the study treatment period. 
k Subjects must not wash, shave, apply make-up or other products to their face, and subjects must hold their application of study drug, on clinic visit days. 
l Subjects will wash their face with Cetaphil® cleanser twice daily beginning at the Screening visit throughout the Week 12/EOT visit. No other face wash 
products may be used during the Subject's participation in the study.    
m Subjects will wash with Cetaphil® at the clinic after all other Day 1 procedures have been completed and immediately prior to study drug 
application by the PI. 
n Screening samples are obtained prior to initiation of BPO pre-treatment. 
o Follicular engraftment sampling is completed via use of Biore® Strips applied across the bridge of the nose extending to either cheek.  
p The Week 12/EOT visit will take place between 3 to 7 days following the Subject's final study drug application. The PI should inquire regarding the 
subjects understanding of and compliance with study drug application procedures and re-instruct, as necessary. 
q Week 12/EOT follicular engraftment sampling will be obtained after facial washing via Biore® strip at the clinic and should be completed 3 to 7 days 
following the last study drug application. 
r Study drug is applied by the PI (or sub-I designee) on Day 1; study drug is applied by the Subject daily thereafter in the evenings.  
s Study procedures are completed as is clinically indicated for vital signs, physical exam, urine pregnancy, and CBC for unscheduled study visits. 
t EOT procedures should be completed at the Week 12 visit. Should the subject discontinue the study prior to Week 12 (Visit 5), the EOT procedures should 
be scheduled and completed as soon as possible. 
u Dispense Subject Diary to the subject. 
v Review the Subject Diary to calculate study drug compliance. 
w Collect the Subject Diary from the subject. 
x The Week 16 telephone visit is to determine the outcome of on any AEs or LSRs that were ongoing at the Week 12 Visit and to determine if any new AEs 
or LSRs occurred during the follow-up period. The Week 16 visit will become a clinic visit if the subject reports any new AEs, especially those (in the 
opinion of the PI) that may be potentially be related to the study (e.g., a significant safety concern).  
y Measured at the mid-glabellar region of the forehead using a Sebumeter SM – 815 (COURAGE + KHAZAKA electronic GmbH, Köln, Germany). 
 
 

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Appendix 3. Investigator’s Global Assessment (IGA)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Global Assessment 
Score 
Definition 
Guideline 
0 
Clear 
Absence of active disease with no inflammatory or non-
inflammatory lesions. 
1 
Almost Clear 
Few non-inflammatory lesions are present; few 
inflammatory lesions may be present. 
2 
Mild 
Some non-inflammatory lesions and some inflammatory 
lesions (papules/pustules only; no nodular lesions) are 
present. 
3 
Moderate 
Many non-inflammatory lesions and many inflammatory 
lesions are present, but no more than one nodular lesion. 
4 
Severe 
Significant degree of inflammatory disease; 
inflammatory lesions are a predominant feature, with a 
few nodular lesions present; non-inflammatory lesions 
may be present. 

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Appendix 4. Common Terminology Criteria for Adverse Events (CTCAE) V. 5.0 
 
For the current CTCAE Criteria for use in evaluating Dose Limiting Toxicities for this trial, 
please refer to: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf 
 
 
 
 
 
 

 
 
Appendix 5. Acne Specific Quality of Life (QoL) Questionnaire