Conditions: Acne Vulgaris
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
This is an exploratory Phase 2 trial of BMX-010 in patients with Acne Vulgaris which will be conducted in two parts.

Detailed description:
Part A is designed to confirm the optimal formulation, strength, and dosing frequency of the study drug in patients with Acne. Up to 60 subjects will be enrolled in this part.

Part B is designed to be a randomized, double-blind trial studying the optimal formulation, strength, and dosing frequency of BMX-010 as determined in Part A, compared to Placebo in patients with Acne. Up to 150 subjects will be enrolled in this part. In both parts, adult subjects with Acne will be enrolled.

Arms:
arm 1: Approximately 30 subjects will receive BMX-010 0.03% for 7-28 days to be applied topically to Acne of the face.

Interventions: intervention 1: BMX-010 0.3%
Intervention descriptions: intervention 1: Safety and efficacy of BMX-010 in topical treatment of acne.

Protocol document:
Prot_000.pdf: 
BioMimetix JV, LLC 
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Protocol: BMX-DERM-203 Acne 
Version 1.0, October 30, 2018 
 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
An Exploratory Trial to Evaluate the Clinical Effectiveness 
of a Topical Application of BMX-010 in Subjects with Acne 
Vulgaris 
 
Sponsor: 
BioMimetix JV, LLC  
5340 South Quebec Street 
Suite 345N 
Greenwood Village, CO 80111 
Funding Source: 
BioMimetix JV, LLC 
Protocol Number: 
BMX-DERM-203 
Version: 
1.0 
Investigational Product: 
BMX-010  
Indication: 
Acne Vulgaris 
Development Phase: 
2 
Sponsor’s Responsible 
Medical Officer: 
Elizabeth A. Regan, MD, PhD 
303-921-1880 (cell) 
Elizabeth.regan@bmxpharma.com 
Clinical Trial Manager 
Adverse Event, Serious 
Adverse Event and 
Pregnancy Reporting 
Sara Penchev 
720-613-4872 
sara.penchev@bmxpharma.com 
Clinicaltrials.gov 
NCT03752242 
 
 
 
Date: 
October 30, 2018 
 


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CONFIDENTIAL 
1 
APPROVALS 
SPONSOR SIGNATURE PAGE 
 
Protocol Number: 
BMX-DERM-203 
Version: 
1.0 
Protocol Title: 
An Exploratory Trial to Evaluate the Clinical Effectiveness of a Topical 
Application of BMX-010 in Subjects with Acne Vulgaris 
 
Version Date: 
30 Oct 2018 
 
Approved by: 
 
 
 
James D. Crapo, MD 
Manager, BioMimetix JV, LLC 
 
Date 
 
 
 
 


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CONFIDENTIAL 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
BMX-DERM-203 
Version: 
1.0 
Protocol Title: 
An Exploratory Trial to Evaluate the Clinical Effectiveness of a Topical 
Application of BMX-010 in Subjects with Acne Vulgaris 
 
Version Date: 
30 Oct 2018 
 
I acknowledge that I have read and understand the protocol named above and agree to carry out 
all of its terms in accordance with applicable regulations and laws. 
I assure that the study drug supplied by the sponsor will be used only as described in the protocol 
named above. 
 
 
 
Principal Investigator Name Signed 
 
 
 
Date 
Principal Investigator Name Printed 
 
 
 
 
Clinical Center 
 
 
 
 
Address 
 
 
 
 
 
 
 
 
 
 


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CONFIDENTIAL 
2 
TABLE OF CONTENTS 
1 APPROVALS ....................................................................................................................... 2 
2 TABLE OF CONTENTS ...................................................................................................... 4 
3 LIST OF ABBREVIATIONS................................................................................................ 7 
4 SYNOPSIS ........................................................................................................................... 8 
5 BACKGROUND ................................................................................................................ 15 
6 STUDY OBJECTIVES ....................................................................................................... 17 
6.1 
Primary Objectives .................................................................................................. 17 
6.2 
Secondary Objectives .............................................................................................. 17 
7 STUDY DESIGN ................................................................................................................ 18 
7.1 
Part A Study Design ................................................................................................ 18 
7.2 
Part B Study Design ................................................................................................ 18 
7.2.1 
Stopping Rules .................................................................................................... 19 
8 SELECTION AND WITHDRAWAL OF SUBJECTS ........................................................ 21 
8.1 
Inclusion Criteria ..................................................................................................... 21 
8.2 
Exclusion Criteria: ................................................................................................... 21 
8.3 
Criteria for Discontinuation or Withdrawal of a Subject ........................................... 22 
9 TREATMENT OF SUBJECTS ........................................................................................... 24 
9.1 
Treatments Administered ......................................................................................... 24 
9.1.1 
Phase 1/Phase 2 Cohorts ...................................................................................... 24 
9.1.2 
Blinding in Part B ................................................................................................ 24 
9.2 
Identity of Investigational Products.......................................................................... 25 
9.2.1 
BMX-010 Drug Substance ................................................................................... 25 
9.2.1.1 
Structure ....................................................................................................... 25 
9.2.1.2 
General Properties ........................................................................................ 25 
9.2.1.3 
Manufacturer ................................................................................................ 25 
9.2.2 
BMX-010 Gel Drug Product ................................................................................ 25 
9.2.2.1 
Description and Composition ........................................................................ 25 
9.2.3 
BMX-010 Cream Drug Product ........................................................................... 26 
9.2.3.1 
Description and Composition ........................................................................ 26 
9.2.4 
Manufacturer ....................................................................................................... 27 
9.2.5 
Labeling .............................................................................................................. 27 
9.2.6 
Placebo ................................................................................................................ 28 
9.3 
Handling of Drug and Placebo at Clinical Centers ................................................... 28 
9.3.1 
Supply, Receipt and Storage ................................................................................ 28 
9.3.2 
Compliance and Accountability ........................................................................... 28 
9.3.3 
Final Accountability of Clinical Center Drug Supply ........................................... 28 
9.4 
Randomization Schedule ......................................................................................... 28 
9.5 
Treatment Compliance ............................................................................................. 29 


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9.6 
Excluded Medications and Treatments ..................................................................... 29 
9.7 
Diet ......................................................................................................................... 29 
10 RISK/BENEFIT ASSESSMENT ........................................................................................ 30 
10.1 
Potential Benefits of BMX-010................................................................................ 30 
10.2 
Risks of BMX-010 .................................................................................................. 30 
10.3 
Risks of Phlebotomy ................................................................................................ 31 
10.4 
Unknown Risks ....................................................................................................... 31 
11 ASSESSMENT OF EFFICACY ......................................................................................... 32 
11.1 
IGA ......................................................................................................................... 32 
11.2 
Patient Reported Outcomes (PRO) ........................................................................... 32 
11.3 
Follow- Up Phone questions .................................................................................... 34 
12 ASSESSMENTS FOR ALL SUBJECTS............................................................................. 35 
12.1 
Physical Examination, Vital Signs, Weight, and Height ........................................... 35 
12.2 
Medical History ....................................................................................................... 35 
12.3 
Medication History/Demographics and Concomitant Medications ........................... 35 
12.4 
Lesion Counts .......................................................................................................... 35 
12.5 
Discoloration Review .............................................................................................. 35 
12.6 
Photographs ............................................................................................................. 36 
12.7 
Clinical Safety Laboratory Variables ....................................................................... 36 
12.7.1 
Blood Tests.......................................................................................................... 36 
12.7.2 
Urine Tests .......................................................................................................... 36 
13 SAFETY ............................................................................................................................. 37 
13.1 
Adverse Events ........................................................................................................ 37 
13.1.1 
Reporting of AEs ................................................................................................. 37 
13.2 
Serious Adverse Events ........................................................................................... 37 
13.2.1 
Reporting of SAEs ............................................................................................... 38 
14 STATISTICS ...................................................................................................................... 39 
14.1 
Analysis Sets ........................................................................................................... 39 
14.2 
Demographics and Other Baseline Characteristics ................................................... 39 
14.3 
Treatments ............................................................................................................... 39 
14.4 
Safety Analysis ........................................................................................................ 39 
14.5 
Interim Analysis ...................................................................................................... 39 
14.6 
Determination of Sample Size ................................................................................. 39 
15 QUALITY CONTROL AND QUALITY ASSURANCE .................................................... 41 
15.1 
Monitoring .............................................................................................................. 41 
15.2 
Audits ...................................................................................................................... 41 
15.3 
Data Management and Processing ........................................................................... 41 
15.3.1 
Study Documentation .......................................................................................... 41 


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CONFIDENTIAL 
15.3.2 
Case Report Forms .............................................................................................. 41 
16 DATA MANAGEMENT PROCEDURES AND DATA VERIFICATION ......................... 42 
16.1 
Study Closure .......................................................................................................... 42 
17 ADMINISTRATIVE AND ETHICAL CONSIDERATIONS.............................................. 43 
17.1 
Regulatory and Ethical Compliance ......................................................................... 43 
17.2 
Institutional Review Board ...................................................................................... 43 
17.3 
Informed Consent .................................................................................................... 43 
17.4 
Privacy, Confidentiality, and Data Storage............................................................... 43 
17.5 
Records Retention ................................................................................................... 44 
17.6 
Conflict of Interest ................................................................................................... 44 
18 REFERENCES ................................................................................................................... 45 
19 Appendix A: Patient Reported Outcome (PRO) Questions .................................................. 47 
20 Appendix B: Phone Follow-up Questions ............................................................................. 50 
 


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CONFIDENTIAL 
3 
LIST OF ABBREVIATIONS 
AE 
Adverse Event 
BID 
Twice Daily 
CBC 
Complete Blood Count 
CMP 
Comprehensive Metabolic Panel 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ET 
Early Termination 
FDA 
Food and Drug Administration 
HCG 
Human Chorionic Gonadotropin 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment Scale 
IL 
Interleukin 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
Intravenous 
Mn 
Manganese 
NOAEL 
No Adverse Effect Level 
PK 
Pharmacokinetic 
PRN 
Pro re nata, When Necessary 
PRO 
Patient Recorded Outcome 
QD 
Once Daily 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
UV 
Ultraviolet 
WIRB 
Western Institutional Review Board 
 


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4 
SYNOPSIS 
Protocol Title: 
An Exploratory Trial to Evaluate the Clinical Effectiveness of a Topical Application of BMX-010 in 
Subjects with Acne Vulgaris 
Protocol Number: BMX-DERM-203 
Phase: 2 
Protocol Version: 1.0 
Test Drug: BMX-010  
Indication: Acne Vulgaris 
Number and Country of Study Sites: Up to 20 study centers in the United States. 
Objectives: 
Part A 
Primary Objectives 
1. Determine whether the optimum frequency of topical application of BMX-010 0.03% is once per 
day or twice per day for a treatment interval of 7 to 28 days. 
2. Determine whether the optimum frequency of topical application of BMX-010 0.1% is once per 
day or twice per day for a treatment interval of 7 to 28 days. 
3. Determine if BMX-010 cream or gel provides better efficacy.   
4. Evaluate the efficacy of BMX-010 0.03% in treatment of Acne Vulgaris. 
5. Evaluate the efficacy of BMX-010 0.1% in treatment of Acne Vulgaris. 
Secondary Objectives 
1. Document, as possible, the clinical effects of BMX-010 in subjects with Acne Vulgaris through 
clinical photography. 
2. Assess the mean percent reduction change in inflammatory and noninflammatory lesion counts 
from baseline to end of study. 
Part B 
Primary Objectives 
1. Evaluate the efficacy of BMX-010 compared to placebo in a randomized, double-blind trial.   
2. Determine the percent of subjects showing a 2 grade improvement in IGA score after treatment 
with BMX-010 compared to Placebo. 
3. Determine the percent of subjects showing a 2 grade improvement in IGA score with full or 
partial clearing (final IGA score of 1 or 0) after treatment with BMX-010 compared to Placebo. 
4. Determine the time to full clearing of Acne Vulgaris after initiation of treatment with BMX-010.   
Secondary Objectives: 
1. Determine the percent of subjects showing a 1 grade improvement in the IGA score. 
2. Document, as possible, the clinical effects of BMX-010 in subjects with Acne Vulgaris through 
clinical photography. 
3. Assess the mean percent reduction change in inflammatory and noninflammatory lesion counts 
from baseline to end of study.   
 
Study Design: 
This is a Phase 2 clinical trial of BMX-010 in adult men and women with Acne Vulgaris which will be 
studied in two parts (Part A and Part B). Part A will involve up to 60 subjects treated with either BMX-


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CONFIDENTIAL 
010 0.03% or 0.1% given QD or BID for a minimum of 7 days and a maximum of 28 days.  Information 
learned from Part A will be used to design Part B.   
Part B is a randomized, double-blind, multi-center, placebo-controlled study of adult men and women 
with Acne Vulgaris. Subjects will be randomized and dosed with BMX-010 0.03% or 0.1% with the 
frequency of dosing (either QD or BID) for each dose of the study drug as determined optimal in Part A 
of this trial. Dosing will occur for a minimum of 7 days and a maximum of  28 days. An overview of the 
study design is presented in the schematics below, and details of study activities are provided in Table 4a. 
In the Part A study, up to a total of up to 60 evaluable subjects with Acne Vulgaris will be dosed with 
BMX-010 (0.03% or 0.1%) topically applied either QD or BID. All subjects will dose for a minimum of 7 
days and a maximum of 28 days.  The dosing strength, formulation, frequency, and time frame will be at 
the discretion of the local clinician.   
The sponsor may close enrollment once enough data has been obtained to determine the optimal dosing 
frequency and duration of dosing for each concentration (0.03% or 0.1%) of BMX-010 cream or gel to be 
studied in Part B. 
In the Part B study, up to 150 evaluable subjects with Acne Vulgaris will be dosed with the concentration  
and formulation of BMX-010 determined optimal in Part A or Placebo given at the frequency determined 
optimal in Part A. The randomization scheme is 2:1, study drug : Placebo. All subjects will dose for a 
minimum of 7 days and a maximum of 28 days.    
The sponsor may close enrollment once enough data has been obtained to assess the expected efficacy of 
0.03% BMX-010 and 0.1% BMX-010. This data will be used to plan future studies. 
The Investigator Global Assessment (IGA) is a five scale (0 to 4) static evaluation of overall Acne 
Vulgaris severity (as described below).   
Investigator Global Assessment (IGA) Scale 
Grade 
Description 
0 = Clear 
Clear skin with no inflammatory of 
noninflammatory lesion 
1 = Minimal 
Almost clear, rare noninflammatory 
lesions with no more than one small 
inflammatory lesion 
2 = Mild 
Mild, some noninflammatory lesions, no 
more than a few inflammatory lesions 
3 = Moderate 
Moderate, up to many noninflammatory 
lesions and may have some inflammatory 
lesions, but no more than one small 
nodular lesion 
4 = Severe 
Severe, up to many noninflammatory and 
inflammatory lesions, but no more than a 
few nodular lesions 
Although acne occurs on the face and trunk, efficacy assessment by IGA will be limited to the face as that 
is the most frequent site of involvement.  However, the study product may be applied to all affected areas 
during this clinical trial.   
Inflammatory and noninflammatory lesions on the face will be counted and reported separately. All 
lesions on the face, including the nose should be counted.  


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CONFIDENTIAL 
Subjects will also be asked a series of patient-reported outcome questions and will be asked to consent to 
optional photographs of the treated lesions.  
Throughout both phases, subjects will be queried regarding adverse events (AEs), concurrent medical 
history and concomitant medication usage. 
 
Subject Population: 
Male or female at least 18 years of age with a clinical diagnosis of mild to severe facial Acne Vulgaris. 
Inclusion Criteria: 
1. Male or female, at least 18 years of age; 
2. A clinical diagnosis of mild to severe facial Acne Vulgaris; Subjects may also have acne at other 
body sites; 
3. Screening and Baseline IGA score > 2 (greater than or equal to 2); 
4. Willing to refrain from using any topical or systemic treatments for inflammatory skin disease, other 
than the investigational product; 
5. Candidate for topical treatment of Acne;  
6. If a cleanser, moisturizer or sunscreen is needed during the study, Subjects must be willing to use 
only allowed cleansers, moisturizers, sunscreens, or moisturizer/sunscreen combination products.  If 
the subject wears makeup they must agree to use non-comedogenic makeup. 
7. Females of child-bearing potential must have a negative urine pregnancy test within 48 hours prior to 
the first drug administration; 
8. Females of child-bearing potential must be willing to use 2 methods of contraception deemed 
adequate by the investigator (for example, oral contraceptive pills plus a barrier method) through the 
trial and for 1 month thereafter to be eligible for, and continue participation in, the study; 
9. Ability to complete the study in compliance with the protocol, including agreement in writing to 
apply study product only to the assigned areas; and 
10. Ability to understand and provide written informed consent. 
Exclusion Criteria: 
1. Any underlying disease(s) or some other dermatological condition of the face that requires the use of 
interfering topical or systemic therapy or makes evaluations and lesion count inconclusive; 
2. Use of androgen receptor blockers (such as spironolactone or flutamide); 
3. Severe cystic acne, acne conglobate, acne fulminans, or secondary acne; 
4. Use of phototherapy devices, energy-based devices, adhesive cleansing strips, or cosmetic procedures 
(e.g., facials, peeling, comedo extraction) in the past week; 
5. Presence of beard or excessive facial hair at Screening which would interfere with the study 
treatments or study assessments and refusal to remove for duration of study; 
6. Prior or current concomitant therapies that would interfere with assessments in the study; 
7. Subjects with any underlying disease that the Investigator deems uncontrolled, and poses a concern 
for the subject’s safety while participating in the study; 
8. Use of anti-inflammatory medications, salicylic acid; corticosteroids, antibiotics, antibacterials 
(including benzoyl peroxide-containing products [e.g., benzamycin]), retinoids; other topical acne 
treatments (e.g., photodynamic therapy, medicated soaps such as those containing benzoyl peroxide, 
salicylic acid, sulfur, or sodium sulfacetamide) in the past 2 weeks; 


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9. Oral retinoid use (e.g., isotretinoin) within 6 months prior to baseline or vitamin A supplements 
greater than 10,000 units/day within 6 months of baseline; 
10. Concomitant skin disease that could confound clinical evaluations or increase risk to the subject;  
11. Use of medicated make-up (including anti-aging make-up) throughout the study; 
12. Use during the study of 1) systemic steroids, 2) topical retinoids to the face, 3) antibiotics known to 
impact acne, 4) immunosuppressive agents, or immunomodulators; 
13. Facial use of 1) topical steroids, 2) topical anti-inflammatory agents, 3) topical antimycotics, 4) any 
topical acne treatments or 4) topical antibiotics; 
14. Use of medicated cleansers on the face (throughout the study); 
15. Use of topical astringents or abrasives, medical topical preparations (prescription and OTC products) 
within 2 days prior to Baseline and throughout the study; 
16. Systemic or skin infection requiring antimicrobial therapy;  
17. Systemic chemotherapy or radiotherapy within 4 weeks of the Baseline Visit; 
18. Immunocompromise of any cause, known human immunodeficiency virus infection, or acquired 
immunodeficiency syndrome; 
19. Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the investigator;  
20. Active drug or alcohol dependence;  
21. Significant acute or chronic medical, neurological, or psychiatric illness that, in the judgment of the 
investigator, could compromise subject safety, limit the subject’s ability to complete the study, and/or 
compromise the objectives of the study;  
22. Previous clinical trial participation for the indication being treated in this protocol.  
Dose Regimen/Route- Duration of Treatment and Follow up: 
Part A 
Subjects will be assigned by the local clinician to receive topical administration of either 0.03% BMX-
010 or 0.1% BMX-010, to apply to Acne Vulgaris on the face. Topical therapy with BMX-010 will be 
either QD or BID as assigned by the local clinician. The planned treatment duration is a minimum of 7 
days and a maximum of 28 days. Completion of 28 days of treatment will be recommended to all 
subjects; however, subjects who have full clearing of the Acne Vulgaris, as determined by the clinical 
center investigator, may stop study drug therapy and remain in the study with a final evaluation at Day 29 
or Day 43 (at the discretion of the investigator). 
 
Part B 
Subjects will be randomized 2:1 to receive topical administration of BMX-010 or Placebo which will be 
dosed at the concentration, formulation, and frequency as defined by Part A.  Study product will be 
applied liberally to Acne Vulgaris on the face. The planned treatment duration is a minimum of 7 days 
and a maximum of 28 days. Completion of 28 days of treatment will be recommended to all subjects; 
however, subjects who have full clearing of the Acne Vulgaris, as determined by the clinical center 
investigator, may stop therapy and remain in the study with a final evaluation at Day 29 or Day 43 at the 
discretion of the investigator. There will be weekly visits with follow-up done at approximately Days 8, 
15, 22, 29 and 43.  
 


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CONFIDENTIAL 
Dosage Form and Strength Formulation: 
BMX-010  
BMX-010 will be supplied at concentrations of 0.03% and 0.1%. BMX-010 will be manufactured by 
Albany Molecular Research, Inc. (AMRI), and formulation and packaging is done by Velesco 
Pharmaceutical Services, LLC. BMX-010 is yellow/brown in color and transient (up to 7 days) of yellow 
discoloration of skin can occur. BMX-010 is dispensed in approximately 10 mL tubes. 
Placebo  
The Placebo will consist of a formulation containing the same excipients as the active drug product. The 
Placebo will be color-matched to the active study drug. Placebo will be supplied in 10 mL tubes. 
Formulation and packaging of the Placebo is done by Velesco Pharmaceutical Services, LLC. 
Criteria for Evaluation: 
Clinical Efficacy 
Clinical effectiveness will be evaluated using the Five-scale IGA for Acne Vulgaris at baseline and end of 
study, Patient-reported outcomes, and counts of inflammatory and noninflammatory lesions.   
Safety Assessments 
Safety will be assessed via AE monitoring, concomitant medication monitoring, physical examinations, 
vital signs, clinical safety laboratory evaluations (complete blood count and chemistry), and pregnancy 
testing (if applicable). 


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Table 4.a 
Schedule of Observations and Procedures  
 
Assessment  
Screening7 
Treatment Period 
Follow-up 
Day -14 to  
Day -1 
Baseline 
Day 1 
Day 
8 (+/- 
2 
days) 
Day 
15 (+/- 
2 
days) 
Day 
22 (+/- 
2 
days) 
Day 28 
8 
Day 
29 
(+/- 2 
days) 
Day 43 
(+/- 2 
days) 
Follow-
Up 
9 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
Medical 
history/demographics 
X 
 
 
 
 
 
 
 
 
Concurrent medical 
conditions 
X 
X 
X 
X 
X 
 
X 
X 
 
Medication history 
X 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
 
X 
X 
 
Physical examination,  
including vital signs 
and weight1 
X 
X 
X 
X 
X 
 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
IGA2 
X 
X 
X 
X 
X 
 
X 
X 
 
Lesion Counts (Face) 
 
X 
X 
X 
X 
 
X 
X 
 
PRO questions 3 
 
 
X 
X 
X 
 
X 
X 
 
Clinical safety 
laboratory 
assessments4 
 
X 
 
 
 
 
 
X 
 
Urine pregnancy test5 
X 
 
 
 
 
 
 
X 
 
Randomization 
*Part B only 
 
X 
 
 
 
 
 
 
 
Dosing6 
 
X 
X 
X 
X 
X 
 
 
 
Discoloration Review 
 
 
X 
X 
X 
 
X 
X 
 
Photographs (optional) 
 
X 
X 
X 
X 
 
X 
X 
 
Pre- and post-
treatment  
AE monitoring 
X 
X 
X 
X 
X 
 
X 
X 
 
 
1 Includes sitting blood pressure, pulse rate and temperature. 
2 IGA is the 5-point scale as defined in this protocol. 
3  All subjects will be asked questions regarding the study drug, clearing and color, these are the Patient Reported 
Outcome (PRO) questions (see Appendix A). 
4 Clinical safety laboratory assessments will include CBC with differential and CMP. 
5 Females of child-bearing potential must have negative results within 48 hours prior to start of drug treatment for 
inclusion. The Day 43 test is performed for females of child-bearing potential who receive at least one 
application of study drug.  
6 In Part A, subjects who meet the inclusion/exclusion criteria will be dispensed BMX-010 gel or cream 
(concentration and formulation provided to be at the discretion of the local clinical investigator).  In Part B, 
subjects will be randomized to BMX-010 (0.03% or 0.1%) or Placebo (2:1 active:placebo); In Part A, study drug 
will be applied topically QD or BID at the discretion of the local clinical investigator.  In Part B, the dosing 
frequency will be set as defined from Part A.  Dosing will be applied to all active lesions for a minimum of 7 
days and up to Day 28. 
7 The screening and baseline visits may be combined. 
8 
Day 28 is not a clinic day.  The subject should stop dosing on Actual Day 28 of the study.     


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9      After the Day 43 final clinic visit, the clinical center may call or mail the subject at approximately 1, 2, and/or 3 
months later to ask the questions listed in Appendix B.   
 


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5 
BACKGROUND 
Acne is a very common chronic inflammatory disease.  Acne ranging from moderate to severe 
affects around 20% of young people.  Acne continues to persist into the 20s for 64% of 
individuals and 30s for 43% of individuals [1].     
There are systemic and topical treatments currently on the market for the treatment of acne.   
These products can cause severe side effects, thus new and innovative therapies are needed.  
Additionally, acne is known to cause significant psychological morbidity in patients [2].   
Acne lesions are either noninflammatory (open and closed comedones, called whiteheads and 
blackheads) or inflammatory (papules and pustules) [2].   
BioMimetix JV, LLC, has developed a topical gel and a topical cream formulation of BMX-010 
for the treatment of inflammatory skin diseases, such as Acne. BMX-010 (MnTE-2-PyP) is a 
manganese (Mn) porphyrin drug; porphyrins are made up of 4 pyrrole rings connected by 
methine bridges. These molecules often form complexes with metals by incorporating them into 
the nucleus of the porphyrin structure, situated between the interiorly-located vertices of the 
pyrrole rings. Such Mn-porphyrin-based compounds are potent anti-inflammatory agents that can 
catalytically inactivate a range of reactive oxygen species, including peroxynitrite and 
superoxide anion [3,4]. 
BMX-010 (MnTE-2-PyP) exhibits extremely high enzymatic redox activity for a broad range of 
oxidant species including O2-, H2O2, and ONOO- (ROS). The drug has catalytic antioxidant 
activity capable of scavenging ROS as well as the mimicking of superoxide dismutase. Unlike 
other antioxidants, this class of agents is catalytic and can repetitively eliminate ROS. BMX-010 
acts as a scavenger in the cell cytoplasm, as in the context of reduced TACE oxidation [5] and 
yet functions as an oxidizer in the nucleus, inhibiting the reduction of the p50 subunit of NF-κB 
and effectively blocking DNA binding [6]. As a result of the complex mechanism of action, 
BMX-010 and other metalloporphyrin compounds exhibit an unexpected potency in 
inflammatory injury models at doses 100 to 1000 times less than would be expected if they were 
acting primarily as stochiometric antioxidants [7,8]. BMX-010 and related compounds 
mechanism of action is reflected in diverse preclinical models.  
T cells become hypo-responsive after BMX-010 treatment [5,9]. BMX-010 treatment promotes 
metabolic quiescence, impedes diabetogenic autoimmune responses by restricting the metabolic 
pathways for energy production and affects anabolic processes necessary for cell proliferation 
[10]. This metabolic reduction decreases T cell differentiation, returning T cells to stasis or 
quiescence, all while retaining viability [7,11,12]. A lowered aerobic glycolysis in T cells 
suggests the potential for treating chronic inflammatory dermatologic conditions, such as atopic 
dermatitis or psoriasis.  
In pancreatic islet cells, oxidative stress develops during organ harvesting, during the isolation 
process, and during storage and transport. Isolation insults result in osmotic, mechanic ischemic, 
and oxidative stress for the islet cells. These events lead to increased production of pro-
inflammatory cytokines and free radicals by pancreatic acinar cells, passenger leukocytes, and 
islet cells themselves, leading ultimately to β cell dysfunction and death. Therefore, the ability to 


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reduce these early nonspecific proinflammatory events (i.e., free radical generation and cytokine 
production) during islet cell isolation should afford increased β cell mass as well as improved 
and more stable metabolic function [13,14]. Experiments in such models show that BMX-010 
modulates Th1 cells and effector cytokine production [5,8,9] and protects islets during isolation 
for transplantation [9,13]. 
In models of acute central nervous system injury and ischemic stroke, BMX-010 treatment 
reduces NF-κB activation [6] and CD8 T cell effector function [12] enhancing neurologic 
function [16,17]. In cancer models, BMX-010 blocks HIF-1 activation, decreases hypoxia, 
reduces tumor-protective cytokine release and ultimately suppresses tumor growth [18]. HIF-1 is 
critical for facilitating glycolysis in times of low oxygen, and tumor cells depend heavily on 
glycolysis to survive.  
In order to evaluate toxicity of the MnTE-2-PyP drug substance, a full good laboratory practice 
nonclinical safety assessment was conducted. BMX-010 was evaluated in in vitro genotoxicity 
studies, local tissue tolerance evaluation, safety pharmacology core battery studies, and single- 
and repeat-dose intravenous (IV) toxicity studies in mice and monkeys [13]. BMX-010 was 
determined not to be genotoxic or hemolytic, did not demonstrate flocculation or elicit adverse 
pharmacologic effects on respiration and the central nervous system, and had limited transitory 
effects on the cardiovascular system only at levels well above the therapeutic target dose. The IV 
clinical solution did not cause venous irritation in rabbits. The no observed adverse effect level 
(NOAEL) in mice was determined to be 10 mg/kg/day after 18 consecutive days of bolus IV 
dosing once daily (QD) in the morning. The NOAEL in monkeys after 14 days of bolus IV 
dosing in the morning was determined to be 5 mg/kg/day. At doses relevant to clinical use in 
humans, neither study revealed any indication of any specific target organ toxicity, including the 
classic heme porphyrin kidney, liver, CNS, or cardiac toxicities, or manganese toxicity. 
Mortality seen shortly after dosing in individual animals at higher doses was not accompanied by 
any organ or clinical pathology indications, suggesting a functional pharmacological-mediated 
effect. 
Based on the demonstrated activity of BMX-010 to reverse persistent dermal inflammation, we 
believe adding BMX-001 as a topical therapy for patients with Rosacea, may be a relevant 
contribution to this disease model either as monotherapy or as combination therapy.  
Completed Phase 1 safety studies on BMX-010 have indicated no identifiable toxicities.  
 
 


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6 
STUDY OBJECTIVES 
6.1 
Primary Objectives 
Part A 
1. Determine whether the optimum frequency of topical application of BMX-010 
0.03% is once per day or twice per day for a treatment interval of 7 to 28 days. 
2. Determine whether the optimum frequency of topical application of BMX-010 
0.1% is once per day or twice per day for a treatment interval of 7 to 28 days. 
3. Determine if BMX-010 cream or gel provides better efficacy.   
4. Evaluate the efficacy of BMX-010 0.03% in treatment of Acne Vulgaris. 
5. Evaluate the efficacy of BMX-010 0.1% in treatment of Acne Vulgaris. 
Part B 
1. Evaluate the efficacy of BMX-010 compared to placebo in a randomized, double-
blind trial.   
2. Determine the percent of subjects showing a 2 grade improvement in IGA score 
after treatment with BMX-010 compared to Placebo. 
3. Determine the percent of subjects showing a 2 grade improvement in IGA score 
with full or partial clearing (final IGA score of 1 or 0) after treatment with BMX-
010 compared to Placebo. 
4. Determine the time to full clearing of Acne Vulgaris after initiation of treatment 
with BMX-010.   
 
6.2 
Secondary Objectives 
Part A 
1. Document, as possible, the clinical effects of BMX-010 in subjects with Acne 
Vulgaris through clinical photography. 
2. Assess the mean percent reduction change in inflammatory and noninflammatory 
lesion counts from baseline to end of study. 
Part B 
1. Determine the percent of subjects showing a 1 grade improvement in the IGA 
score. 
2. Document, as possible, the clinical effects of BMX-010 in subjects with Acne 
Vulgaris through clinical photography. 
3. Assess the mean percent reduction change in inflammatory and noninflammatory 
lesion counts from baseline to end of study.   


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7 
STUDY DESIGN 
The purpose of this study is to first explore the optimum formulation (gel vs. cream), 
concentration (0.03% vs. 0.1%), and dosing frequency (QD vs. BID) of BMX-010 in subjects 
with Acne Vulgaris in Part A.  In Part B, the optimal formulation, concentration, and frequency 
will be used to study the efficacy of BMX-010, as determined by IGA scores and PROs.   
7.1 
Part A Study Design 
Subjects will be dispensed either 0.03% BMX-010 or 0.1% BMX-010 (gel or cream), at the 
discretion of the clinical center investigator, to apply to Acne Vulgaris on the face. Topical 
therapy with BMX-010 will be either QD or BID, also at the discretion of the clinical center 
invsetigator. The planned treatment duration is a minimum of 7 days and a maximum of 28 days. 
Completion of 28 days of treatment will be recommended to all subjects; however, subjects who 
have full clearing of the Acne Vulgaris, as determined by the clinical center investigator, may 
stop study drug therapy and remain in the study with a final evaluation at Day 29 or Day 43 (at 
the discretion of the investigator). 
 
7.2 
Part B Study Design 
Subjects will be randomized 2:1 to receive topical administration of BMX-010 or Placebo which 
will be dosed at the concentration, formulation, and frequency as defined by Part A.  Study 
product will be applied liberally to Acne Vulgaris on the face. The planned treatment duration is 
a minimum of 7 days and a maximum of 28 days. Completion of 28 days of treatment will be 
recommended to all subjects; however, subjects who have full clearing of the Acne Vulgaris, as 
determined by the clinical center investigator, may stop therapy and remain in the study with a 
final evaluation at Day 29 or Day 43 at the discretion of the investigator. There will be weekly 
visits with follow-up done at approximately Days 8, 15, 22, 29 and 43.  
 
Figure 7.a 
Study Design for both parts 
 


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Following written informed consent, subjects will undergo screening evaluations within 14 days 
prior to the first application of study drug. The screening evaluations will include complete 
medical history, complete physical examination (including vital signs, weight, and height), 
clinical laboratory evaluations, urine pregnancy test for females of child-bearing potential (a 
negative pregnancy test is required within 48 hours prior to the start of drug treatment), 
concurrent medical conditions, and concomitant medication assessments.  
Subjects will be scored by the clinician for IGA.  The clinician will also obtain counts of the 
inflammatory and noninflammatory lesions on the face.    
The subject will be asked a series of Patient Reported Outcomes (Appendix A).   
In Part A, all eligible Subjects enrolled will receive the active study drug, BMX-010.  Subjects 
will treat their Acne Vulgaris on the face with the study product.  This will be demonstrated at 
the Baseline visit.  Subjects will be instructed by the clinical center staff and informed how often 
they should dose each day (QD or BID). 
In Part B, all eligible Subjects enrolled will be randomized to the study drug (BMX-010) or 
Placebo.  Subjects will treat their Acne Vulgaris on the face with the study product.  This will be 
demonstrated at the Baseline visit.  Subjects will be instructed by the clinical center staff and 
informed how often they should dose each day, which will have been confirmed by Part A of the 
study.   
Randomization will occur after completion of all screening assessments, once the subject is 
determined to be eligible. At Baseline, subjects will undergo confirmation study eligibility 
assessments as specified in Table 4.a. The first dose of study drug will be administered in the 
clinic under the supervision and direction of study staff and subjects will be trained on the 
amount of study product to use and where to apply it. 
Subjects will be instructed to bring all study drug (including empty tubes) with them when they 
return to the clinic each week for assessment of study drug use by the clinical center. 
Subjects will be asked a series of questions (Appendix A) during in-clinic study visit days. 
Subjects will be able to consent to optional photographs the treated lesions.  Since the Acne 
Vulgaris to be treated is on the face, the photos may include the face.    
Throughout both phases, subjects will be queried regarding adverse events (AEs), concurrent 
medical history, and concomitant medication usage.  
7.2.1 Stopping Rules  
The following stopping criteria will be implemented:   
1. Subject stopping criteria: If a subject experiences an AE that is deemed by the clinical 
center Principal Investigator to be at least “possibly” drug-related and is Grade ≥2 in 
severity (using the Common Terminology Criteria for Adverse Events (CTCAE v 5), that 
subject will be withdrawn from dosing, return for all scheduled evaluation visits, and be 
followed until the AE resolves or stabilizes.  


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2. Cohort stopping criteria: If 1 subject in a cohort experiences an AE that is deemed by the 
clinical center Principal Investigator to be probably or definitely drug-related and is 
Grade ≥3 in severity by CTCAE, or if 2 subjects in a cohort experience AEs that are 
deemed by the clinical center Principal Investigator(s) to be at least “possibly” drug-
related and are Grade >/= 3 in severity by CTCAE, dosing further subjects will be 
suspended until data is reviewed by the sponsor.    
3. Dose stopping criteria: If the Acne Vulgaris is deemed as cleared by the study 
investigator (IGA=0),  the subject will be instructed to stop dosing or continue based on 
the discretion of the clinical center investigator. Acne Vulgaris should be considered 
clear if it is not showing any inflammatory signs of disease. If it is decided by the local 
investigator to stop drug treatment, the clinical center investigator will determine which 
of the following scenarios will be implemented : 
- 
The subject should return to the clinical center weekly for further assessment.  
- 
The subject should return the following week to complete the end of study 
(Day 43) follow up visit. 
If the subject is still in the study, and the Acne Vulgaris returns,  the subject should 
contact the clinical center and resume treatment (through Day 28) and weekly visits until 
the planned Day 43.  


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8 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1 
Inclusion Criteria 
1. Male or female, at least 18 years of age; 
2. A clinical diagnosis of mild to severe facial Acne Vulgaris; Subjects may also have 
acne at other body sites; 
3. Screening and Baseline IGA score > 2 (greater than or equal to 2);\ 
4. Willing to refrain from using any topical or systemic treatments for inflammatory 
skin disease, other than the investigational product; 
5. Candidate for topical treatment of Acne;  
6. If a cleanser, moisturizer or sunscreen is needed during the study, Subjects must be 
willing to use only allowed cleansers, moisturizers, sunscreens, or 
moisturizer/sunscreen combination products.  If the subject wears makeup they must 
agree to use non-comedogenic makeup. 
7. Females of child-bearing potential must have a negative urine pregnancy test within 
48 hours prior to the first drug administration; 
8. Females of child-bearing potential must be willing to use 2 methods of contraception 
deemed adequate by the investigator (for example, oral contraceptive pills plus a 
barrier method) through the trial and for 1 month thereafter to be eligible for, and 
continue participation in, the study; 
9. Ability to complete the study in compliance with the protocol, including agreement in 
writing to apply study product only to the assigned areas; and 
10. Ability to understand and provide written informed consent. 
8.2 
Exclusion Criteria: 
1. Any underlying disease(s) or some other dermatological condition of the face that 
requires the use of interfering topical or systemic therapy or makes evaluations and 
lesion count inconclusive; 
2. Use of androgen receptor blockers (such as spironolactone or flutamide); 
3. Severe cystic acne, acne conglobate, acne fulminans, or secondary acne; 
4. Use of phototherapy devices, energy-based devices, adhesive cleansing strips, or 
cosmetic procedures (e.g., facials, peeling, comedo extraction) in the past week; 
5. Presence of beard or excessive facial hair at Screening which would interfere with the 
study treatments or study assessments and refusal to remove for duration of study; 
6. Prior or current concomitant therapies that would interfere with assessments in the 
study; 
7. Subjects with any underlying disease that the Investigator deems uncontrolled, and 
poses a concern for the subject’s safety while participating in the study; 
8. Use of anti-inflammatory medications, salicylic acid; corticosteroids, antibiotics, 
antibacterials (including benzoyl peroxide-containing products [e.g., benzamycin]), 
retinoids; other topical acne treatments (e.g., photodynamic therapy, medicated soaps 
such as those containing benzoyl peroxide, salicylic acid, sulfur, or sodium 
sulfacetamide) in the past 2 weeks; 


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9. Oral retinoid use (e.g., isotretinoin) within 6 months prior to baseline or vitamin A 
supplements greater than 10,000 units/day within 6 months of baseline; 
10. Concomitant skin disease that could confound clinical evaluations or increase risk to 
the subject;  
11. Use of medicated make-up (including anti-aging make-up) throughout the study; 
12. Use during the study of 1) systemic steroids, 2) topical retinoids to the face, 3) 
antibiotics known to impact acne, 4) immunosuppressive agents, or 
immunomodulators; 
13. Facial use of 1) topical steroids, 2) topical anti-inflammatory agents, 3) topical 
antimycotics, 4) any topical acne treatments or 4) topical antibiotics; 
14. Use of medicated cleansers on the face (throughout the study); 
15. Use of topical astringents or abrasives, medical topical preparations (prescription and 
OTC products) within 2 days prior to Baseline and throughout the study; 
16. Systemic or skin infection requiring antimicrobial therapy;  
17. Systemic chemotherapy or radiotherapy within 4 weeks of the Baseline Visit; 
18. Immunocompromise of any cause, known human immunodeficiency virus infection, 
or acquired immunodeficiency syndrome; 
19. Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by 
the investigator;  
20. Active drug or alcohol dependence;  
21. Significant acute or chronic medical, neurological, or psychiatric illness that, in the 
judgment of the investigator, could compromise subject safety, limit the subject’s 
ability to complete the study, and/or compromise the objectives of the study;  
22. Previous clinical trial participation for the indication being treated in this protocol.  
8.3 
Criteria for Discontinuation or Withdrawal of a Subject 
All subjects are free to withdraw from study participation at any time, for any reason, and 
without prejudice to their further medical care. In addition, the investigator may terminate a 
subject from the study at any time. The primary reason for discontinuation should be recorded on 
the case report form (CRF) using one of the following categories: 
1. Adverse event. The subject experiences an AE that imposes an unacceptable risk to the 
subject’s health, or the subject is unwilling to continue because of an AE. 
2. Lack of therapeutic effect. The investigator has determined that study drug administration 
is not benefitting the subject, and continued participation poses an unacceptable risk to 
the subject. 
3. Inclusion/exclusion criteria violation. The investigator discovers that the subject did not 
meet all of the inclusion/exclusion criteria after study enrollment. 
4. Protocol noncompliance. The subject has a significant protocol deviation, does not 
comply with study drug administration schedule, or fails to adhere to other study 
requirements as stated in the protocol. 
5. Lost to follow-up. The subject does not return to the clinic for scheduled assessments, 
and does not respond to the site’s attempts to contact the subject. 
6. Voluntary withdrawal. The subject wishes to withdraw from the study. The clinical center 
should attempt to determine the underlying reason for the voluntary withdrawal and 
document it on the CRF; if the underlying reason is documented as an AE or lack of 


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efficacy, the category of withdrawal should be marked in the corresponding category and 
not as voluntary withdrawal. 
7. Study termination. The sponsor, Institutional Review Board (IRB), or regulatory agency 
terminates the study. 
8. Pregnancy. 
9. Other. Any reason that does not fall into 1 of the above categories. The specific reason 
should be recorded on the CRF. 
Following early discontinuation from the study, the subject will be informed regarding the 
additional study evaluations that are necessary to monitor his/her safety. These subjects will be 
encouraged to participate in the final follow up study visit. 
In order to meet the number of specified evaluable subjects, a discontinued or withdrawn subject 
may be replaced and the newly enrolled subject will be assigned the identical treatment of the 
withdrawn subject. 


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9 
TREATMENT OF SUBJECTS 
9.1 
Treatments Administered 
9.1.1 Phase 1/Phase 2 Cohorts 
Part A 
 
Cream or gel:  BMX-010 0.03% or BMX-010 0.1% or Placebo QD 
Cream or gel:  BMX-010 0.03% or BMX-010 0.1% or Placebo BID  
 
Part B 
 
BMX-010 dose & formulation determined in Part A vs Placebo.  QD or 
BID frequency as determined in Part A will be conducted.   
 
  
In this study, up to 210 subjects will be enrolled.  
In Part A, up to 60 subjects will be enrolled.  Subjects will not be randomized and treatment 
concentration, formulation, and dosing frequency will be at the discretion of the clinical center 
investigator. All subjects will receive study drug at either 0.03% or 0.1% concentration.  They 
will dose either QD or BID as indicated by the clinical center investigator during the baseline 
and other weekly visits throughout the study.   
In Part B, up to 150 subjects will be enrolled.  This will be a double-blind study, where the 
investigator and subject both will not know whether study drug or Placebo has been dispensed.  
Subjects will be randomized to BMX-010 or Placebo (2:1) in accordance with the randomization 
schedule.  The Placebo cream is color-matched to the study drug, the Placebo gel is not.   Up to 
100 subjects will be randomized to BMX-010 and up to 50 subjects will be randomized to 
Placebo.   
 
Although acne occurs on the face and trunk, efficacy assessment by IGA will be limited to the 
face as that is the most frequent site of involvement.  However, the study product may be applied 
to all affected areas during this clinical trial.   
 
When subjects apply QD, it can be applied any time of the day.  When it is applied BID it should 
generally be applied 12 hours apart.   
 
9.1.2 Blinding in Part B 
The sponsor has a standard operating procedure regarding randomization and blinding. The 
sponsor also will have a designated list of personnel who have un-blinded access. The sites will 
be provided with a key to use if un-blinding is required during the trial.  
 


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9.2 
Identity of Investigational Products 
9.2.1 BMX-010 Drug Substance 
9.2.1.1 Structure 
Figure 9.1: Structure of BMX-010 
9.2.1.2 General Properties 
Formula Weight: 965.12 
Chemical Name: Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin pentachloride 
Empirical Formula: C48H44Cl5MnN8 
CAS RN: 219818-60-7 
Appearance: Dark brown or purple solid 
9.2.1.3 Manufacturer 
Drug substance Lot #9739-C-R0-01-21-01, which will be used to manufacture the clinical trial 
material for the presently proposed trials, was manufactured, tested and released under cGMP by 
Albany Molecular Research, Inc., Albany, NY (AMRI). A 3-year stability study is being 
performed by AMRI according to ICH guidelines. 
9.2.2 BMX-010 Gel Drug Product 
9.2.2.1 Description and Composition 
The gel drug product is a preserved aqueous gel comprising 0.03%  or 0.1% BMX-010 and 
having the batch composition indicated in Table 9.a. The gel is filled at 10 g/tube into 0.5 ounce 
white LDPE squeeze tubes with screw caps. BMX-010 is yellow/brown in color and transient 
(up to 7 days) of yellow discoloration of skin is not considered to be an AE. 
 
 
 
 
 
 


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Table 9a: Batch Composition of BMX-010 Gel 
 
Quantity per batch, g 
(wt%) 
Component, Quality 
(Function) 
Placebo 
0.03% 
BMX-010 
0.1% 
BMX-010 
BMX-010, AMRI 
(API) 
___ 
3 
(0.03%) 
10 
(0.10%) 
NatrosolTM 250 Hydroxyethylcellulose HX, 
Pharm, NF 
(gelling agent) 
300 
(3.00%) 
300 
(3.00%) 
300 
(3.00%) 
Propylene Glycol, USP 
(gelling agent) 
500 
(5.00%) 
500 
(5.00%) 
500 
(5.00%) 
Potassium Sorbate Powder, NF 
(preservative) 
15 
(0.15%) 
15 
(0.15%) 
15 
(0.15%) 
Sodium Benzoate, NF 
(preservative) 
30 
(0.30%) 
30 
(0.30%) 
30 
(0.30%) 
Titanium Dioxide, USP 
(colorant) 
200 
(2.00%) 
200 
(2.00%) 
200 
(2.00%) 
Glacial Acetic Acid, USP 
(buffer) 
15.2 
(0.15%) 
15.2 
(0.15%) 
15.2 
(0.15%) 
Sodium Hydroxide 1N solution, USP 
(buffer) 
164.4 
(1.64%) 
164.4 
(1.64%) 
164.4 
(1.64%) 
Sterile Purified Water, USP 
(solvent) 
8775.4 
(87.75%) 
8772.4 
(87.72%) 
8765.4 
(87.65%) 
Medical Air, USP 
(blowing agent) 
0 
0 
0 
Total batch weight 
10000 
10000 
10000 
 
9.2.3 BMX-010 Cream Drug Product 
9.2.3.1 Description and Composition 
The cream drug product is a preserved oil-in-water emulsion cream comprising 0.03% or 0.1% 
BMX-010 and having the batch composition indicated in Table 9.a. The cream is filled at 10 
g/tube into 0.5 ounce white LDPE squeeze tubes with screw caps. BMX-010 is yellow/brown in 
color and transient (up to 7 days) of yellow discoloration of skin is not considered to be an AE. 
Table 9a: Batch Composition of BMX-010 Cream 
  
Quantity per batch, g 
(wt%) 
Component, Quality 
(Function) 
Placebo 
0.03% 
BMX-010 
0.1% 
BMX-010 


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BMX-010, AMRI 
(API) 
___ 
1.8 
(0.03%) 
6 
(0.10%) 
Mineral Oil, NF 
(emollient) 
720 
(12.00%) 
720 
(12.00%) 
720 
(12.00%) 
Petrolatum, USP 
(emollient) 
540 
(9.00%) 
540 
(9.00%) 
540 
(9.00%) 
Cetostearyl alcohol, NF 
 (emollient, viscosity increasing agent) 
720 
(12.00%) 
720 
(12.00%) 
720 
(12.00%) 
Propylene glycol, USP 
 (humectant) 
480 
(8.00%) 
480 
(8.00%) 
480 
(8.00%) 
Glacial Acetic Acid, USP 
(buffer) 
9 
(0.15%) 
9 
(0.15%) 
9 
(0.15%) 
Sodium Hydroxide 1N solution, NF 
(buffer) 
102.6 
(1.71%) 
102.6 
(1.71%) 
102.6 
(1.71%) 
Sterile Purified Water, USP 
(solvent) 
3,236.4 
(53.94%) 
3276.6 
(54.61%) 
3272.4 
(54.54%) 
Tween 20-LQ-(AP) 
(emulsifier) 
60 
(1.00%) 
60 
(1.00%) 
60 
(1.00%) 
Isopropyl palmitate, NF 
(emollient, viscosity increasing agent) 
60 
(1.00%) 
60 
(1.00%) 
60 
(1.00%) 
Imidazolidinyl urea, NF 
(preservative) 
12 
(0.20%) 
12 
(0.20%) 
12 
(0.20%) 
Methylparaben, NF 
(preservative) 
12 
(0.20%) 
12 
(0.20%) 
12 
(0.20%) 
Propylparaben, NF 
(preservative) 
6 
(0.10%) 
6 
(0.10%) 
6 
(0.10%) 
Iron Oxides, NF 
(colorant) 
42 
(0.7%) 
___ 
 
___ 
Medical Air, USP 
(blowing agent) 
0 
0 
0 
Total batch weight 
6000 
6000 
6000 
 
9.2.4 Manufacturer 
The drug product will be manufactured, tested and released under cGMP by Velesco 
Pharmaceutical Services, LLC, Kalamazoo, MI (Velesco). Stability adequate to support the 
proposed clinical study of the BMX-010 gel and cream will be demonstrated by Velesco. 
Stability studies will be conducted in accordance with ICH Q1A (R2) using a cGMP qualified 
stability indicating analytical method. 
9.2.5 Labeling  
The drug product labels will include a brief description of the drug product, the sponsor, lot 
number, storage information, emergency contact, and the statement, “Caution: New Drug – 
Limited by Federal Law to Investigational Use.”  Lot numbers are not listed in the protocol as 
Phase 2 studies using the cream will be double-blinded. 


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BMX-010 Gel or Cream –Lot X 
BioMimetix JV, LLC 
Caution: New Drug – Limited by Federal 
Law to Investigational Use 
Emergency contact: Dr. Elizabeth Regan, 
cell 303-921-1880 
Store at RT or 
Refrigeration 
Exemplary Label BMX-010 – Depending if the study product is a cream or gel, this will dictate the storage 
instructions.  The gel is stored at room temperature and the cream is stored under refrigerated conditions.   
9.2.6 Placebo 
Placebo (vehicle) will consist of the same excipients as the active drug product, but without the 
API. The placebo gel is white in color and does not match the color of the active drug. The 
placebo cream is color-matched to facilitate blinding. Placebo will be supplied in 10 mL tubes.  
9.3 
Handling of Drug and Placebo at Clinical Centers 
Both BMX-010 and Placebo will be delivered to the clinical centers in bags containing 20 or 10 
tubes. Each bag will contain tubes of only one concentration of drug or the placebo. Both the 
bags and the tubes will be labeled as to the lot number but not the strength. 
9.3.1 Supply, Receipt and Storage 
The drug supplies described in Section 9.3 will be shipped to each clinical center. The drugs will 
be refrigerated or kept at room temperature as indicated on the label.  The product should be 
stored in a locked, physically secure environment according to the clinical center or sponsor 
standard procedures for storage of investigational drug products. Drug accountability records 
will be maintained by each clinical center for all clinical trial products. 
9.3.2 Compliance and Accountability 
Drug accountability records will be maintained for all clinical trial products. 
9.3.3 Final Accountability of Clinical Center Drug Supply 
Subjects will be instructed to bring all study drug tubes (even if empty) back to the clinical 
centers during their weekly visit for review. Empty tubes will be collected from the subject and 
disposed once final drug accountability is performed by BioMimetix. They will be destroyed 
according to the clinical center or sponsor policy after final accountability by BioMimetix has 
been performed. At the end of the study all remaining un-used investigative product and placebo 
will be returned to the sponsor, BioMimetix JV, LLC, after drug accountability is performed, 
according to instructions which will be provided by sponsor. The clinical center will maintain 
documentation of the number and identification of BMX-010 and Placebo tubes that are returned 
to the sponsor and which are destroyed by the clinical center. Copies of these documents will be 
provided to BioMimetix JV, LLC. 
9.4 
Randomization Schedule 
The sponsor or designee will generate the randomization schedules. Randomization will occur 
once final eligibility is confirmed after completion of the screening procedures. 


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Part A of the study is not blinded.  All subjects will receive BMX-010.   
Part B of the study is double-blind, where both the subject and the clinical center staff will be 
blinded to the treatment assigned.  BMX-010 and Placebo will be dispensed 2:1 (study drug: 
placebo). 
9.5 
Treatment Compliance  
During the weekly visit during the treatment period a question will be asked of the subject to 
monitor treatment compliance (see Appendix A). 
At the baseline visit, the clinical staff will instruct the subjects to apply the study drug to the face 
and this will be demonstrated the first time it is applied. Appropriate application should be 
discussed with the subject at each weekly visit.  Assessment of drug use will take place at each 
weekly visit by clinical center staff. 
9.6 
Excluded Medications and Treatments 
Period of Exclusion 
Excluded Medication/Treatment 
≤ 4 weeks prior to Baseline Visit 
Systemic chemotherapy or radiotherapy 
≤ 4 weeks prior to Baseline and throughout study 
Systemic retinoids, corticosteroids, or 
immunosuppressive agents (e.g., methotrexate, 
cyclosporine) 
UV or Dead Sea therapy 
≤ 30 days prior to Screening Visit and throughout study 
Investigational drug or vaccine trial 
≤ 2 weeks prior to Baseline and throughout study 
High potency topical corticosteroids (Class I-III), 
Vitamin D analogs, keratolytics, coal tar (other than 
on the scalp, palms, groin, and/or soles), 
phototherapy, calcineurin inhibitors, antihistamines 
or any other therapeutic agents besides bland 
emollients 
5 times its circulating half-life, or 30 days, whichever is 
longer, prior to the Baseline Visit or throughout study 
Biological agent (such as a monoclonal antibody) 
9.7 
Diet 
Subjects will be asked to fast overnight (8 hour fast prior to the blood draw) prior to collection of 
blood samples for clinical laboratory safety testing; otherwise, there are no dietary restrictions 
for this study. 


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10 RISK/BENEFIT ASSESSMENT 
10.1 Potential Benefits of BMX-010 
The potential benefits may include protection against skin inflammation such as that experienced 
in Acne Vulgaris. The benefits may be long lasting. Because this clinical protocol is 
experimental, it cannot be guaranteed that subjects will receive any benefit as a result of 
participating in this research study.  
10.2 Risks of BMX-010  
This study is designed to determine the effectiveness of this agent when administered topically to 
subjects having inflammatory skin conditions.  
Phase 1 studies in BMX-010 have completed and no toxicities have been identified.  We have 
studied pharmacokinetics already on BMX-010 in 14 subjects.  The data is summarized below. 
Phase 1 of BMX-DERM-01 on patients with diagnosed Atopic Dermatitis and Plaque Psoriasis: 
Eight subjects have been studied: 2 dosed with 0.01% BMX-010, 3 dosed with 0.03% BMX-010, 
and 3 dosed with 0.1% BMX-010 given once per day to one lesion, and testing has determined 
that there is no quantifiable systemic absorption for the Part 1a treatment protocol. There have 
been no toxicities identified in the 33 subjects enrolled at the time of writing this protocol 
amendment. In Part 1b, 3 subjects have been studied, dosed with 0.1% gel up to 4 times a day to 
all lesions on the body. The lesions occupied 2% BSA in two subjects and 10% BSA in one 
subject. Two of the three subjects had no quantifiable systemic absorption, one was found to 
have a plasma level of 1.95 ng/ml at 24 hours following topical administration. This patient had 
AD involving 10 percent BSA and administered 0.1% gel 2 times per day. 
Phase 2 of BMX-DERM-01 on patients with diagnosed Atopic Dermatitis: PK was done on 3 
subjects after application of BMX-010 cream twice per day for 8 days. There was no quantifiable 
plasma level of the drug in any of the three subjects on day 8 at pre-dose, 1, 2, 4 and 24 hours 
after applying BMX-010 0.03% cream topically. In one subject a detectable level of BMX-010 
of 0.04 ng/mL in plasma was found 1 hour after topical administration and in one of the 3 
subjects a level of 0.12 ng/mL was detected in the plasma at 24 hours (This patient had applied 
the drug topically at 12 hours on day 8 as part of bid dosing). The limit of detection (BLOD) for 
BMX-010 was 0.04 ng/mL and the limit of quantitation (BLOQ) for BMX-010 was 0.121 
ng/mL. 
Animal safety/toxicology studies have not demonstrated any significant adverse events for 
topical therapy other than skin discoloration and discoloration of materials coming into contact 
with the drug. 
Studies have been performed using intravenous infusions of BMX-010 in multiple models 
including rats, mice, dogs, guinea pigs, and baboons with the finding of dose-related hypotension 
[5,6]. Redox-active metalloporphyrin compounds (such as BMX-010) are potent, catalytic 
antioxidants and have the potential to scavenge superoxide within the vascular system and 
thereby change the balance of superoxide and nitric oxide in the microvasculature. This would 
augment the vasodilating activity of nitric oxide and lead to hypotension [5,6]. This has been 


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found in animal models, but only as a transient side effect related to intravenous administration 
of the drug in doses orders of magnitude higher than that being considered for topical 
administration. Hypotension has not been identified in any animal model treated with BMX-010 
by topical therapy or by subcutaneous injection.  
Mild photosensitization is a possible side effect of BMX-010. While native porphyrins have been 
shown to be photosensitizers, the redox-active metalloporphyrins are not expected to show 
significant photosensitization. When native porphyrins are exposed to white light, the molecule 
can enter an excited state and on return to ground state emit fluorescent light, which is the cause 
for photosensitization. Redox-active metalloporphyrins such as BMX-010 contain a metal atom 
chelated into the middle of the porphyrin ring. The presence of this metal atom allows the 
molecule to give and take electrons and thus do redox chemistry. In the presence of white light, 
these redox-active metalloporphyrins would not be expected to enter an excitation state and 
would not be expected to emit fluorescence. A phototoxicity test in rabbits with BMX-010 
demonstrated only weak phototoxicity with no test animals showing edema at any time point and 
1 out of 5 animals exhibiting erythema at 24 hours and only very slight erythema at 72 hours. 
A summary of the possible adverse side effects that could be associated with BMX-010 
administration is below. These possible side effects are dose-dependent, and the relatively low 
doses of this drug planned in this study have not been associated with side effects in animals 
other than those related to the color of the topically applied drug. 
The most common side effects (expected to occur in more than 30% of subjects) are: 
• Yellow to brown discoloration of the skin at the administration site which may take 
several days to resolve 
• Discoloration of clothing or materials coming into contact with the treated skin 
Less common side effects (expected to occur in less than 10% of subjects) are: 
• Skin irritation at the administration site 
Additional possible side effects are: 
• Light-activated skin rash in response to sun exposure (this has not been reported by any 
patients enrolled in the study at the time of writing this protocol). 
• It is also possible that previously unobserved and unexpected side effects could occur. 
10.3 Risks of Phlebotomy 
Drawing blood may result in bruising or swelling in the area of the needle insertion, bleeding at 
the site of the needle puncture, light headedness, fainting and very rarely, local infection. These 
risks are reduced by the fact that the blood will be drawn by a qualified physician, nurse or 
phlebotomist. 
10.4 Unknown Risks 
There may be risks which are unknown. 
 


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11 ASSESSMENT OF EFFICACY  
The schedules of observations and procedures are provided in Table 4.a.  Descriptions for the 
efficacy assessments are provided in this section. 
11.1 IGA 
The Investigator Global Assessment (IGA) is a five scale (0 to 4) static evaluation of overall 
Acne Vulgaris severity (as described below).   The change in IGA scores from Baseline through 
the final follow up visit will be assessed as endpoints in the study. 
 
Drug treatment and efficacy assessment by IGA will be limited to the face.    For a score of 
Clear, residual hyperpigmentation and erythema may be present.   
 
Grade 
Description 
0 = Clear 
No papules and/or pustules; no 
erythema 
1 = Minimal 
Rare papules and/or pustules; faint, 
up to but not including mild erythema 
2 = Mild 
Few papules and/or pustules; mild 
erythema 
3 = Moderate 
Pronounced number of papules 
and/or pustules, but less than 
numerous papules and/or pustules; 
moderate erythema 
4 = Severe 
Numerous papules and/or pustules, 
occasionally with confluent areas of 
inflamed lesions; moderate to severe 
erythema 
 
There is no single, standardized grading system for severity of acne [20].   
11.2 Patient Reported Outcomes (PRO) 
1. Questions (see Bhate K, Williams HC.  Epidemiology of acne vulgaris.  Br J 
Dermatol. 2013 Mar;168(3):474-85. doi: 10.1111/bjd.12149. 
2. Sparavigna A, Tenconi B, De Ponti I, La Penna L.  An innovation approach to topical 
treatment of acne.  Clin Cosmet Investig Dermatol. 2015; 8: 179–185.  PMC4399783 
3. Batinic-Haberle I, Rajic Z, Tovmasyan A, Reboucas JS, Ye X, Leong KW, Dewhirst 
MW, Vujaskovic Z, Benov L, Spasojevic I. Diverse functions of cationic Mn(III) N-
substituted pyridylporphyrins, recognized as SOD mimics. Free Radic Biol Med 2011 
Sep 1; 51(5):1035-53. PMC3178885. 
4. Batinic-Haberle I, Tovmasyan A, Roberts ER, Vujaskovic Z, Leong KW, Spasojevic I. 
SOD therapeutics: latest insights into their structure-activity relationships and impact on 
the cellular redox-based signaling pathways. Antioxid Redox Signal 2014 May 20; 
20(15):2372-415. PMC4005498. 


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5. Delmastro MM, Styche AJ, Trucco MM, Workman CJ, Vignali DA, Piganelli JD. 
Modulation of redox balance leaves murine diabetogenic TH1 T cells "LAG-3-ing" 
behind. Diabetes 2012 Jul; 61(7):1760-8. PMC3379669. 
6. Tse HM, Milton MJ, Piganelli JD. Mechanistic analysis of the immunomodulatory effects 
of a catalytic antioxidant on antigen-presenting cells: implication for their use in targeting 
oxidation-reduction reactions in innate immunity. Free Radic Biol Med 2004; 36(2):233-
47. PMID: 14744635. 
7. Batinic-Haberle I, Spasojevic I, Tse HM, Tovmasyan A, Rajic Z, St Clair DK, 
Vujaskovic Z, Dewhirst MW, Piganelli JD. Design of Mn porphyrins for treating 
oxidative stress injuries and their redox-based regulation of cellular transcriptional 
activities. Amino Acids 2012 Jan; 42(1):95-113. PMC3022969. 
8. Delmastro MM, Piganelli JD. Oxidative stress and redox modulation potential in type 1 
diabetes. Clin Dev Immunol 2011; 2011:593863. PMID: 21647409. 
9. Piganelli JD, Flores SC, Cruz C, Koepp J, Batinic-Haberle I, Crapo J, Day B, 
Kachadourian R, YoungR, Bradley B, Haskins K. A metalloporphyrin-based superoxide 
dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-
cell clone. Diabetes 2002 Feb; 51(2):347-55. PMID: 11812741. 
10. Delmastro-Greenwood MM, Votyakova T, Goetzman E, Marre ML, Previte DM, 
Tovmasyan A, Batinic-Haberle I, Trucco MM, Piganelli JD. Mn porphyrin regulation of 
aerobic glycolysis: implications on the activation of diabetogenic immune cells.. Antioxid 
Redox Signal 2013 Dec 1; 19(16):1902-15. PMC3931434. 
11. Bottino R, Balamurugan AN, Tse H, Thirunavukkarasu C, Ge X, Profozich J, Milton M, 
Ziegenfuss A, Trucco M, Piganelli JD. Response of human islets to isolation stress and 
the effect of antioxidant treatment. Diabetes 2004 Oct; 53(10):2559-68. PMID: 
15448084. 
12. Sklavos MM, Tse HM, Piganelli JD. Redox modulation inhibits CD8 T cell effector 
function. Free Radic Biol Med 2008 Nov; 45(10):1477-86. PMID: 18805480. 
13. Gad SC, Sullivan DW Jr, Crapo JD, Spainhour CB. A nonclinical safety assessment of 
MnTE-2-PyP, a manganese porphyrin. Int J Toxicol 2013 Jul; 32(4):274-87. PMID: 
23704100.  
14. Bottino R, Balamurugan AN, Bertera S, Pietropaolo M, Trucco M, Piganelli JD. 
Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD 
mimic compound. Diabetes 2002 Aug; 51(8):2561-7. PMID: 12145171. 
15. Sklavos MM, Bertera S, Tse HM, Bottino R, He J, Beilke JN, Coulombe MG, Gill RG, 
Crapo JD, Trucco M, Piganelli JD. Redox modulation protects islets from transplant-
related injury. Diabetes 2010; 59(7):1731-8. PMC2889773. 
16. Sheng H, Spasojevic I, Tse HM, Jung JY, Hong J, Zhang Z, Piganelli JD, Batinic-
Haberle I, Warner DS. Neuroprotective efficacy from a lipophilic redox-modulating 
Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke 
and subarachnoid hemorrhage. J Pharmacol Exp Ther 2011 Sep; 338(3):906-16. 
PMC3164343. 
17. Sheng H, Yang W, Fukuda S, Tse HM, Paschen W, Johnson K, Batinic-Haberle I, Crapo 
JD, Pearlstein RD, Piganelli J, Warner DS. Long-term neuroprotection from a potent 
redox-modulating metalloporphyrin in the rat. Free Radic Biol Med 2009 Oct; 47(7):917-
23. PMC2975018. 


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18. Rabbani ZN, Spasojevic I, Zhang X, Moeller BJ, Haberle S, Vasquez-Vivar J, Dewhirst 
MW, Vujaskovic Z, Batinic-Haberle I. Antiangiogenic action of redox-modulating 
Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via 
suppression of oxidative stress in a mouse model of breast tumor. Free Radic Biol Med 
2009 Oct 1; 47(7):992-1004. PMC2749298. 
19. Ross AD, et al. Hemodynamic effects of metalloporphyrin catalytic antioxidants: 
structure-activity relationships and species specificity. Free Radic Biol Med 2002; 
33(12):1657-69. 
20. US Department of Health and Human Services Food and Drug Administration Center for 
Drug Evaluation and Research (CDER). Acne Vulgaris: Establishing Effectiveness of 
Drugs Intended for Treatment Guidance for Industry.  Rockville, MD: Office of 
Communications, Division of Drug Information.  May 2018.  
https://www.fda.gov/downloads/Drugs/Guidances/UCM071292.pdf 
 
Appendix A: Patient Reported Outcome (PRO) Questions) to assess patient assessment of 
disease and clearing will be asked to the subjects at each clinic visit. We will also ask a treatment 
compliance question.  
11.3 Follow- Up Phone questions 
After the Day 43 final clinic visit, the clinical center may call or mail the subject at 
approximately 1, 2, and/or 3 months later to ask the questions listed in Appendix B.   
 
 


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12 ASSESSMENTS FOR ALL SUBJECTS 
The schedules of observations and procedures are provided in Table 4.a.  Descriptions for the 
study assessments are provided in this section. 
12.1 Physical Examination, Vital Signs, Weight, and Height 
A general physical examination of major body systems will be performed on the visits as shown 
in Table 4.a. The delegated investigator will need to indicate for each system if abnormal or 
normal and whether if abnormal is clinically significant or not.  
Height will be measured and documented at Screening only. Weight will be measured during the 
physical examinations. 
Vital signs (temperature, respiratory rate, blood pressure, and heart rate) will be measured during 
the physical examinations. Blood pressure and heart rate measurements will be taken while 
subjects are in a seated position after resting for 5 minutes.  
12.2 Medical History 
Standard medical history assessments will be conducted at Screening. Clinical centers should 
make every effort possible to obtain medical records to document the diagnosis of the applicable 
indication. At the screening visit, we will also ask about participation in previous investigational 
trials for the indication being treated in the study and the number of previous trials participated. 
12.3 Medication History/Demographics and Concomitant Medications 
At the screening visit subjects will be queried regarding concomitant medication use and 
medication history. Restricted medications were previously described in Section 9.6. 
Demographic information will consist of items such as age, race, gender, education, 
employment, smoking status. 
12.4 Lesion Counts 
All inflammatory and noninflammatory lesions will be counted by a clinical center investigator 
at each weekly visit. 
 
12.5 Discoloration Review 
Discoloration is an assessment of skin color change related to the study product color remaining 
on the skin. It will be reviewed by delegated clinical center staff at the weekly visits as reflected 
in Table 4.a and one of the options below will be selected. 
 
Discoloration 
None 
Minimal 
Moderate 
Marked 
 


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12.6 Photographs  
Photographs of the Acne Vulgaris optional based on subject consent and selection of specific 
clinical center participation by the sponsor. Photographs will be offered at each clinic visit.  
12.7 Clinical Safety Laboratory Variables 
12.7.1 Blood Tests 
Fasting blood samples (following an at least 8-hour fast) will be collected during as shown in 
Table 4.a. Clinical safety laboratory tests will include complete blood count with differential and 
comprehensive metabolic panel. 
12.7.2 Urine Tests 
Urine pregnancy tests (beta-human chorionic gonadotropin [HCG]) will be performed for 
women of childbearing potential within 48 hours prior to the start of drug treatment and repeated 
on the last visit. 
 


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13 SAFETY 
13.1 Adverse Events 
An AE is any untoward medical occurrence in a subject receiving study drug and which does not 
necessarily have a causal relationship with this treatment. For this protocol, the definition of AE 
also includes worsening of any pre-existing medical condition. An AE can therefore be any 
unfavorable and unintended or worsening sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of BMX-010, whether or not related to 
use of the BMX-010. Abnormal laboratory findings without clinical significance (based on the 
Principal Investigator’s judgment) should not be recorded as AEs. But laboratory value changes 
that require therapy or adjustment in prior therapy are considered AEs. 
From the time the subject signs the informed consent form through the Follow-Up Visit all AEs 
must be recorded in the subject medical record and CRF. 
AEs will be assessed according to the CTCAE version 5, which has been harmonized to 
MedDRA (Medical Dictionary for Regulatory Activities) coding. If CTCAE grading does not 
exist for an AE, the severity of the AE will be graded as mild (1), moderate (2), severe (3), life-
threatening (4), or fatal (5). 
Attribution of AEs will be indicated as follows: 
• 
Definite: The AE is clearly related to the BMX-010 
• 
Probably: The AE is likely related to the BMX-010 
• 
Possible: The AE may be related to the BMX-010 
• 
Unlikely: The AE is doubtfully related to the BMX-010 
• 
Unrelated: The AE is clearly NOT related to the BMX-010 
13.1.1 Reporting of AEs 
BioMimetix JV, LLC, should be notified of all treatment-related AEs on a regular basis (to be 
agreed upon by the study team and BioMimetix JV, LLC). Reports of these should be made to 
Elizabeth Regan, MD, PhD, at 303-921-1880 (cell). 
13.2 Serious Adverse Events 
An AE is considered “serious” if in the opinion of the investigator it is one of the following 
outcomes: 
• 
Fatal 
• 
Life-threatening 
• 
Constitutes a congenital anomaly or birth defect 
• 
A medically significant condition (defined as an event that compromises subject safety or 
may require medical or surgical intervention to prevent one of the three outcomes above). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant incapacity or substantial disruption to conduct normal 
life functions. 


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13.2.1 Reporting of SAEs 
Only AEs that the sponsor and/or Principal Investigator determines to be serious, unanticipated, 
and related or possibly/probably (i.e., more likely than not) related to the research must be 
reported to the IRB. Those AEs will be submitted, according the following guidelines: 
• 
Report within 24 hours of learning about any subject’s death that was unanticipated and 
more likely related to the research than unrelated; 
• 
Report within 5 business days of learning about any serious, unanticipated, and related or 
possibly/probably related AE; 
• 
Report within 10 business day of learning about any other unanticipated problem or event 
that was more likely related to the research than unrelated. 
The Principal Investigator is responsible for compliance with all applicable regulations 
pertaining to the reporting of AEs to the IRB. To ensure patient safety, each study treatment-
related serious adverse event (SAE) will also be reported to the sponsor, BioMimetix JV, LLC, 
within 24 hours by the Principal Investigator. Follow-up information on these events shall also 
be reported to BioMimetix JV, LLC, within 24 hours of receipt. Follow-up information may 
include hospital admission records, discharge summaries and autopsy reports, where applicable.  
The sponsor must report to the Food and Drug Administration (FDA), in an Investigational New 
Drug (IND) safety report, any suspected adverse reaction that is both serious and unexpected. 
Before submitting this report, the sponsor needs to ensure that the event meets all three of the 
definitions contained in the requirement:  
• 
Suspected adverse reaction (i.e., there is a reasonable possibility that the drug caused the 
AE) 
• 
Serious  
• 
Unexpected  
If the AE does not meet all three of the definitions, it should not be submitted as an expedited 
IND safety report. 
The sponsor is required to report to the FDA all IND Safety reports in writing within 15 days (7 
days for unexpected fatal or life-threatening suspected adverse reaction). The FDA Form 3500A 
can be found on the FDA website, www.fda.gov. All other AEs will be reported to the FDA in 
the IND Annual Report. 
In addition to the above mentioned reporting responsibilities, after discontinuation of the study, 
all SAEs considered to be drug related will be reported to BioMimetix JV, LLC, by the Principal 
Investigator. 


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14 STATISTICS 
A statistical analysis plan (SAP) will be prepared and finalized prior to data analysis. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. 
14.1 Analysis Sets 
All subjects who have received at least one dose of study medication will be included in the 
Safety Population. All analyses of safety will be performed for the Safety Population.  
The Intent-To-Treat (ITT) evaluable population will consist of all subjects in the Safety 
Population with CEA and IGA (when available) component scores recorded at screening and/or 
baseline and at least 1 post-baseline visit. The ITT population will be used to assess clinical 
activity data. 
14.2 Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics will be summarized by dose using descriptive statistics 
(e.g., means/standard deviations, percentiles, frequencies).  
14.3 Treatments 
The number of subjects treated at each dose level will be summarized using descriptive statistics. 
14.4 Safety Analysis 
All treatment-emergent AEs will be summarized by dose group and indication (AD or PS). 
Counts and percents will be presented by treatment group for each observed system organ class 
(SOC) and preferred medical diagnosis.  
The preferred terms and SOCs will be summarized in the following set of tables: 
• 
All AEs;  
• 
All AEs by maximum level of intensity;  
• 
All AEs by closest relationship to the study medication. 
Laboratory test variables will be summarized by dose group and study visit using descriptive 
statistics. Laboratory data collected from baseline and up to 7 days after a subject’s last dose of 
study drug (or the date of the final follow up visit) will be included in the analysis. 
Descriptive statistics will be used to summarize vital signs by dose group and study visit. Vital 
sign data collected from baseline and up to 7 days after a subject’s last dose of study drug (or the 
date of the final follow up visit) will be included in the analysis. 
14.5 Interim Analysis 
No interim analysis is planned.  
14.6 Determination of Sample Size 
The sample sizes will provide sufficient data for clinical interpretation of safety and efficacy 
assessments. Sample sizes are not based on statistical considerations. The proposed enrollment 


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counts will provide validation of the safety objectives and a basis to estimate potential efficacy 
for future studies.  
 
 


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15 QUALITY CONTROL AND QUALITY ASSURANCE 
15.1 Monitoring 
BioMimetix JV, LLC, will monitor this study. The Principal Investigator at each clinical center 
should be available to the clinical trial monitor during monitoring visits and ensure that access to 
all documents and records is provided. The Principal Investigator agrees to cooperate with the 
clinical trial monitor to ensure that any problems detected in the course of these monitoring visits 
are resolved. All study documents must be made available upon request to the clinical trial 
monitor and other authorized regulatory authorities, including but not limited to the National 
Institute of Health and the FDA. Every reasonable effort will be made to maintain confidentiality 
during study monitoring. 
15.2 Audits 
The study may be audited by an audit team originating from the sponsor or its designee, or 
outside regulatory agencies. The investigator agrees to cooperate with the auditor to ensure than 
any problems detected in the course of the audit visits are resolved. 
15.3 Data Management and Processing 
15.3.1 Study Documentation 
BioMimetix JV, LLC, will have access to the electronic database, with edit rights, for this 
clinical trial and will provide monitoring to confirm the accuracy of data entered into this 
database. 
15.3.2 Case Report Forms 
Data generated per protocol will be provided in paper or entered into an eCRF database provided 
by BioMimetix JV, LLC. When the CRFs have been completed, the clinical trial monitor will 
work with the study site coordinator or data management team to verify all source 
documentations and review data. Copies of the photographs will be filed as source documents 
and provided to the sponsor.  


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16 DATA MANAGEMENT PROCEDURES AND DATA VERIFICATION 
The Principal Investigator at each clinical center is responsible for maintaining adequate records 
to enable the conduct of the study to be fully documented. Subsequent electronic review of the 
data may result in queries being generated that will be forwarded simultaneously to the 
investigator or designee for resolution. All data modifications resulting from review or querying 
of the data will be electronically tracked. 
Any errors detected by either the monitor or the investigator should be communicated to the 
sponsor.  
Copies of all regulatory documents such as the protocol, study approval letters, all CRFs, drug 
dispensing and accountability logs, all original patient consent forms, and all correspondence 
pertaining to the conduct of the study should be kept by the investigator for the maximum period 
of time permitted by local regulations. 
16.1 Study Closure 
Following completion of the study, the Principal Investigator at each clinical center will be 
responsible for ensuring the following activities for all subjects enrolled from his/her clinical 
center: 
1. Data clarification and/or resolution of queries 
2. Accounting, reconciliation, and destruction/return of used and unused study drugs 
3. Review of site study records for completeness 
4. Shipment of all remaining laboratory samples to the designated laboratories 
5. Final report to the IRB 


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17 ADMINISTRATIVE AND ETHICAL CONSIDERATIONS 
17.1 Regulatory and Ethical Compliance 
This protocol was designed and will be conducted and reported in accordance with the 
International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good 
Clinical Practice, the Declaration of Helsinki, and applicable federal, state, and local regulations. 
17.2 Institutional Review Board 
The primary IRB for this study will be Western Institutional Review Board (WIRB). The 
protocol, informed consent form, advertising material, and additional protocol-related documents 
must be submitted to the IRB for review. The study may be initiated only after the Principal 
Investigator has received written and dated approval from the IRB. 
All subsequent protocol amendments and changes to the informed consent form will be required 
to be approved by WIRB. 
17.3 Informed Consent 
The informed consent form must be written in a manner that is understandable to the subject 
population. Prior to its use, the informed consent form must be approved by the IRB. 
The Principal Investigator or authorized key personnel will discuss with the potential subject the 
purpose of the research, methods, potential risks and benefits, subject concerns, and other study-
related matters. This discussion will occur in a location that ensures subject privacy and in a 
manner that minimizes the possibility of coercion. Appropriate accommodations will be made 
available for potential subjects who cannot read or understand English or are visually or audibly 
impaired. Potential subjects will have the opportunity to contact the Principal Investigator or 
authorized key personnel with questions and will be given as much time as needed to make an 
informed decision about participation in the study. 
Before conducting any study-specific procedures, the Principal Investigator must obtain written 
informed consent from the subject or a legally acceptable representative. The original informed 
consent form will be stored in a study-specific informed consent binder, and a copy of the 
informed consent form will be provided to the subject. The Principal Investigator and the study 
team are responsible for asking the subject whether the subject wishes to notify his/her primary 
care physician about participation in the study. If the subject agrees to such notification, the 
Principal Investigator will inform the subject’s primary care physician about the subject’s 
participation in the clinical study. 
17.4 Privacy, Confidentiality, and Data Storage 
The Principal Investigator will ensure that subject privacy and confidentiality of the subject’s 
data will be maintained.  
To protect privacy, every reasonable effort will be made to prevent undue access to subjects 
during the course of the study. Prospective participants will be consented in an exam room where 
it is just the research staff, the patient and his family, if desired. For all future visits, interactions 


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with research staff (study doctor and study coordinators) regarding research activities will take 
place in a private exam room. All research related interactions with the participant will be 
conducted by qualified research staff who are directly involved in the conduct of the research 
study. 
To protect confidentiality, subject files in paper format will be stored in secure cabinets under 
lock and key. Subjects will be identified only by a unique study number and subject initials. 
Electronic records of subject data will be maintained using a dedicated compliant database, 
which is housed in an encrypted and password-protected file on a secure network drive. Access 
to electronic databases (without edit rights) will be limited to the Principal Investigator, the study 
coordinator, and the statistical team. The only personnel with both access and edit rights to the 
electronic databases are the data management team, including the clinical trials manager.  
Upon completion of the study, research records will be archived. Subject names or identifiers 
will not be used in reports, presentations at scientific meetings, or publications in scientific 
journals. 
17.5 Records Retention 
The Principal Investigator will maintain study-related records for the longer of a period of: 
1. at least 2 years after the date on which a New Drug Application is approved by the FDA, 
if an IND is involved 
2. at least 2 years after formal withdrawal of the IND associated with this protocol, if an 
IND is involved 
17.6 Conflict of Interest 
The Principal Investigator and Sub-Investigators must comply with applicable federal, state, and 
local regulations regarding reporting and disclosure of conflict of interest. Conflicts of interest 
may arise from situations in which financial or other personal considerations have the potential 
to compromise or bias professional judgment and objectivity. Conflicts of interest include but are 
not limited to royalty or consulting fees, speaking honoraria, advisory board appointments, 
publicly-traded or privately-held equities, stock options, intellectual property, and gifts. 
 


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18 REFERENCES 
21. Bhate K, Williams HC.  Epidemiology of acne vulgaris.  Br J Dermatol. 2013 
Mar;168(3):474-85. doi: 10.1111/bjd.12149. 
22. Sparavigna A, Tenconi B, De Ponti I, La Penna L.  An innovation approach to topical 
treatment of acne.  Clin Cosmet Investig Dermatol. 2015; 8: 179–185.  PMC4399783 
23. Batinic-Haberle I, Rajic Z, Tovmasyan A, Reboucas JS, Ye X, Leong KW, Dewhirst 
MW, Vujaskovic Z, Benov L, Spasojevic I. Diverse functions of cationic Mn(III) N-
substituted pyridylporphyrins, recognized as SOD mimics. Free Radic Biol Med 2011 
Sep 1; 51(5):1035-53. PMC3178885. 
24. Batinic-Haberle I, Tovmasyan A, Roberts ER, Vujaskovic Z, Leong KW, Spasojevic I. 
SOD therapeutics: latest insights into their structure-activity relationships and impact on 
the cellular redox-based signaling pathways. Antioxid Redox Signal 2014 May 20; 
20(15):2372-415. PMC4005498. 
25. Delmastro MM, Styche AJ, Trucco MM, Workman CJ, Vignali DA, Piganelli JD. 
Modulation of redox balance leaves murine diabetogenic TH1 T cells "LAG-3-ing" 
behind. Diabetes 2012 Jul; 61(7):1760-8. PMC3379669. 
26. Tse HM, Milton MJ, Piganelli JD. Mechanistic analysis of the immunomodulatory effects 
of a catalytic antioxidant on antigen-presenting cells: implication for their use in targeting 
oxidation-reduction reactions in innate immunity. Free Radic Biol Med 2004; 36(2):233-
47. PMID: 14744635. 
27. Batinic-Haberle I, Spasojevic I, Tse HM, Tovmasyan A, Rajic Z, St Clair DK, 
Vujaskovic Z, Dewhirst MW, Piganelli JD. Design of Mn porphyrins for treating 
oxidative stress injuries and their redox-based regulation of cellular transcriptional 
activities. Amino Acids 2012 Jan; 42(1):95-113. PMC3022969. 
28. Delmastro MM, Piganelli JD. Oxidative stress and redox modulation potential in type 1 
diabetes. Clin Dev Immunol 2011; 2011:593863. PMID: 21647409. 
29. Piganelli JD, Flores SC, Cruz C, Koepp J, Batinic-Haberle I, Crapo J, Day B, 
Kachadourian R, YoungR, Bradley B, Haskins K. A metalloporphyrin-based superoxide 
dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-
cell clone. Diabetes 2002 Feb; 51(2):347-55. PMID: 11812741. 
30. Delmastro-Greenwood MM, Votyakova T, Goetzman E, Marre ML, Previte DM, 
Tovmasyan A, Batinic-Haberle I, Trucco MM, Piganelli JD. Mn porphyrin regulation of 
aerobic glycolysis: implications on the activation of diabetogenic immune cells.. Antioxid 
Redox Signal 2013 Dec 1; 19(16):1902-15. PMC3931434. 
31. Bottino R, Balamurugan AN, Tse H, Thirunavukkarasu C, Ge X, Profozich J, Milton M, 
Ziegenfuss A, Trucco M, Piganelli JD. Response of human islets to isolation stress and 
the effect of antioxidant treatment. Diabetes 2004 Oct; 53(10):2559-68. PMID: 
15448084. 
32. Sklavos MM, Tse HM, Piganelli JD. Redox modulation inhibits CD8 T cell effector 
function. Free Radic Biol Med 2008 Nov; 45(10):1477-86. PMID: 18805480. 
33. Gad SC, Sullivan DW Jr, Crapo JD, Spainhour CB. A nonclinical safety assessment of 
MnTE-2-PyP, a manganese porphyrin. Int J Toxicol 2013 Jul; 32(4):274-87. PMID: 
23704100.  
34. Bottino R, Balamurugan AN, Bertera S, Pietropaolo M, Trucco M, Piganelli JD. 
Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD 
mimic compound. Diabetes 2002 Aug; 51(8):2561-7. PMID: 12145171. 


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35. Sklavos MM, Bertera S, Tse HM, Bottino R, He J, Beilke JN, Coulombe MG, Gill RG, 
Crapo JD, Trucco M, Piganelli JD. Redox modulation protects islets from transplant-
related injury. Diabetes 2010; 59(7):1731-8. PMC2889773. 
36. Sheng H, Spasojevic I, Tse HM, Jung JY, Hong J, Zhang Z, Piganelli JD, Batinic-
Haberle I, Warner DS. Neuroprotective efficacy from a lipophilic redox-modulating 
Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke 
and subarachnoid hemorrhage. J Pharmacol Exp Ther 2011 Sep; 338(3):906-16. 
PMC3164343. 
37. Sheng H, Yang W, Fukuda S, Tse HM, Paschen W, Johnson K, Batinic-Haberle I, Crapo 
JD, Pearlstein RD, Piganelli J, Warner DS. Long-term neuroprotection from a potent 
redox-modulating metalloporphyrin in the rat. Free Radic Biol Med 2009 Oct; 47(7):917-
23. PMC2975018. 
38. Rabbani ZN, Spasojevic I, Zhang X, Moeller BJ, Haberle S, Vasquez-Vivar J, Dewhirst 
MW, Vujaskovic Z, Batinic-Haberle I. Antiangiogenic action of redox-modulating 
Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via 
suppression of oxidative stress in a mouse model of breast tumor. Free Radic Biol Med 
2009 Oct 1; 47(7):992-1004. PMC2749298. 
39. Ross AD, et al. Hemodynamic effects of metalloporphyrin catalytic antioxidants: 
structure-activity relationships and species specificity. Free Radic Biol Med 2002; 
33(12):1657-69. 
40. US Department of Health and Human Services Food and Drug Administration Center for 
Drug Evaluation and Research (CDER). Acne Vulgaris: Establishing Effectiveness of 
Drugs Intended for Treatment Guidance for Industry.  Rockville, MD: Office of 
Communications, Division of Drug Information.  May 2018.  
https://www.fda.gov/downloads/Drugs/Guidances/UCM071292.pdf 
 


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19 Appendix A: Patient Reported Outcome (PRO) Questions 
Weekly Visit 
1. How often are you applying the study drug? 
o Once a Day 
o Twice A Day 
2. Did you apply the study product as instructed? 
o Yes  
o No 
o If no: clarify with comments 
3. Would you like to apply the study drug more often?  
o Yes 
o No 
4. Do you feel that your quality of life has improved from using the study drug?  
o Yes 
o No 
 
5.  How would you assess the change in your rash since your previous visit? 
o Worse 
o No change 
o A little better  
o Definitely better  
o Drastically better  
o Clear  
 
Clearing Questions- only to be asked if the Acne Vulgaris has cleared or partially cleared.  
Indicate [  ] N/A if no clearing has occurred 
1. 
 On approximately what date did the Acne Vulgaris clear? 
2. Have any of your previously cleared lesion(s) come back? Yes/No 
a. If Yes, on what date did it come back?  
b. If Yes, where did it come back? 
i. Same area as before 
ii. New area, specify: 


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The following questions are for the last visit only 
 
1. Do you feel that your quality of life has improved from using the study drug?  
o Yes 
o No 
 
2. How would you assess the change in your rash since your previous visit? 
o Worse 
o No change 
o A little better  
o Definitely better  
o Drastically better  
o Clear  
 
 
Clearing Questions- only to be asked if the rosacea has cleared or partially cleared.  
Indicate [  ] N/A if no clearing has occurred 
 
 
1. On approximately what date did the rosacea clear? 
 
 
2. Have any of your previously cleared lesion(s) come back?  
o Yes 
o No 
 
If Yes, on what date did it come back?  
 
If Yes, where did it come back? 
 
o Same area as before 
 
o New area, specify: 
 
 
 
Color Questions 
1. Do you have any concerns about the color of the study product? 
o No concerns 


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o Mild concerns 
o Major concerns 
2. Did the study product stain (meaning the color stayed on after washing) your 
clothing/bedsheets, etc? Yes/No 
  
 
 


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20 Appendix B: Phone Follow-up Questions  
 
 
1. What is the current status of your Acne? 
 
2. Are you currently on any medications or treatments for controlling your Acne?  If 
yes, obtain list.   
 
3. Would you like to continue to use the study drug?  Yes/No, Comments.