Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis
Phase: PHASE2
Conditions: Actinic Keratosis
Sponsor: DFB Soria, LLC

Phase 2 Dose-Rising Study of SOR007 Ointment for 
Actinic Keratosis 
 
Protocol Identifying Number: SOR007-2017-04 
Principal Investigator: Reginold Simmons, MD 
IND Number: 126915 
IND Sponsor: DFB Soria, LLC 
Version Number:  2.0 
Date: 20 April 2017 
 
 
 
 
 
 
 

ii 
 
Table of Contents 
LIST OF ABBREVIATIONS ....................................................................................................................................... v 
SPONSOR SIGNATURE PAGE .............................................................................................................................. vi 
STATEMENT OF COMPLIANCE ........................................................................................................................... vii 
PROTOCOL SUMMARY ........................................................................................................................................ viii 
SCHEMATIC OF STUDY DESIGN ......................................................................................................................... xi 
1 
KEY ROLES .................................................................................................................................................... 1 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ........................ 1 
2.1 
Background Information ...................................................................................................................... 1 
2.2 
Rationale ............................................................................................................................................... 3 
2.3 
Potential Risks and Benefits .............................................................................................................. 3 
2.3.1 
Known Potential Risks ..................................................................................................... 3 
2.3.2 
Known Potential Benefits ................................................................................................ 3 
3 
OBJECTIVES AND PURPOSE .................................................................................................................... 3 
4 
STUDY DESIGN AND ENDPOINTS ........................................................................................................... 3 
4.1 
Description of the Study Design ........................................................................................................ 3 
4.2.1 
Primary Endpoint .............................................................................................................. 4 
4.2.2 
Secondary Endpoints ...................................................................................................... 4 
4.2.3 
Exploratory Endpoints ..................................................................................................... 4 
5 
STUDY ENROLLMENT AND WITHDRAWAL ........................................................................................... 4 
5.1 
Participant Inclusion Criteria .............................................................................................................. 4 
5.2 
Participant Exclusion Criteria ............................................................................................................. 5 
5.3 
Strategies for Recruitment and Retention ........................................................................................ 6 
5.4 
Participant Withdrawal or termination ............................................................................................... 6 
5.4.1 
Reasons for Withdrawal or Termination ....................................................................... 6 
5.4.2 
Handling of Participant Withdrawals or termination .................................................... 7 
5.5 
Premature Termination or Suspension of Study ............................................................................. 7 
6 
STUDY AGENT .............................................................................................................................................. 8 
6.1 
Study Agent(s) and Control Description ........................................................................................... 8 
6.1.1 
Acquisition ......................................................................................................................... 8 
6.1.2 
Formulation, Appearance, Packaging, and Labeling .................................................. 8 
6.1.3 
Product Storage and Stability ......................................................................................... 8 
6.1.4 
Preparation ........................................................................................................................ 8 
6.1.5 
Dosing and Administration .............................................................................................. 8 
6.1.6 
Route of Administration ................................................................................................... 8 
6.1.7 
Starting Dose and Dose Escalation Schedule ............................................................. 9 
6.1.8 
Dose Adjustments/Modifications/Delays ...................................................................... 9 
6.1.9 
Duration of Therapy ......................................................................................................... 9 
6.1.10 
Tracking of Dose .............................................................................................................. 9 
6.1.11 
Device Specific Considerations ..................................................................................... 9 
6.2 
Study agent Accountability Procedures ............................................................................................ 9 
7 
STUDY PROCEDURES AND SCHEDULE .............................................................................................. 10 
7.1 
Study Procedures/Evaluations ......................................................................................................... 10 
7.1.1 
Study specific procedures ............................................................................................. 10 
7.1.2 
Standard of care study procedures ............................................................................. 11 
7.2 
Laboratory Procedures/Evaluations ................................................................................................ 11 

iii 
 
7.2.1 
Clinical Laboratory Evaluations .................................................................................... 11 
7.2.2 
Other Assays or Procedures ........................................................................................ 11 
7.2.3 
Specimen Preparation, Handling, and Storage ......................................................... 11 
7.2.4 
Specimen Shipment ....................................................................................................... 11 
7.3 
Study Schedule .................................................................................................................................. 11 
7.3.1 
Visit 1/Screening ............................................................................................................ 11 
7.3.2 
Enrollment/Baseline ....................................................................................................... 13 
7.3.3 
Follow-up ......................................................................................................................... 16 
7.3.4 
Final Study Visit .............................................................................................................. 16 
7.3.5 
Early Termination Visit .................................................................................................. 17 
7.3.6 
Unscheduled visits ......................................................................................................... 17 
7.3.7 
Schedule of Events Table ............................................................................................. 18 
7.4 
Justification for Sensitive Procedures ............................................................................................. 19 
7.5 
Concomitant Medications, Treatments, and Procedures ............................................................. 19 
7.6 
precautionary medications, treatments, and procedures ............................................................. 19 
7.7 
Prohibited Medications, Treatments, and Procedures ................................................................. 19 
7.8 
Prophylactic Medications, Treatments, and Procedures ............................................................. 19 
7.9 
Rescue Medications, Treatments, and Procedures ..................................................................... 19 
7.10 
Participant Access to Study Agent At Study Closure ................................................................... 19 
8 
ASSESSMENT OF SAFETY ...................................................................................................................... 19 
8.1 
Specification of Safety Parameters ................................................................................................. 20 
8.1.1 
Definition of Adverse Events (AE) ............................................................................... 20 
8.1.2 
Definition of Serious Adverse Events (SAE) .............................................................. 20 
8.1.3 
Definition of Unanticipated Problems (UP) ................................................................. 20 
8.2 
Classification of an Adverse Event ................................................................................................. 21 
8.2.1 
Severity of Event ............................................................................................................ 21 
8.2.2 
Relationship to Study Agent ......................................................................................... 21 
8.2.3 
Expectedness ................................................................................................................. 21 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up .......................................... 22 
8.4 
Reporting Procedures ....................................................................................................................... 22 
8.4.1 
Adverse Event Reporting .............................................................................................. 22 
8.4.2 
Serious Adverse Event Reporting ............................................................................... 22 
8.4.3 
Unanticipated Problem Reporting ................................................................................ 23 
8.4.4 
Events of Special Interest ............................................................................................. 23 
8.4.5 
Reporting of Pregnancy ................................................................................................ 23 
8.5 
Study Halting Rules ........................................................................................................................... 23 
8.6 
Safety Oversight ................................................................................................................................ 24 
9 
CLINICAL MONITORING ............................................................................................................................ 24 
10 
STATISTICAL CONSIDERATIONS .......................................................................................................... 24 
10.1 
Statistical and Analytical Plans ........................................................................................................ 24 
10.2 
Statistical Hypotheses ....................................................................................................................... 25 
10.3 
Analysis Datasets .............................................................................................................................. 25 
10.4 
Description of Statistical Methods ................................................................................................... 25 
10.4.1 
General Approach .......................................................................................................... 25 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 25 
10.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 25 

iv 
 
10.4.4 
Safety Analyses .............................................................................................................. 26 
10.4.5 
Adherence and Retention Analyses ............................................................................ 26 
10.4.6  
Baseline Descriptive Statistics ..................................................................................... 26 
10.4.7 
Planned Interim Analyses ............................................................................................. 26 
10.4.7 
additional sub-group analyses ..................................................................................... 26 
10.4.9 
Multiple Comparison/Multiplicity................................................................................... 26 
10.4.10 
Tabulation of Individual Response Data ..................................................................... 26 
10.4.11 
Exploratory Analyses ..................................................................................................... 26 
10.4.12 
concomitant medication ................................................................................................ 27 
10.5 
Sample Size ....................................................................................................................................... 27 
10.6 
Measures to Minimize Bias .............................................................................................................. 27 
10.6.1 
Enrollment/ Randomization/ Masking Procedures .................................................... 27 
10.6.2 
Evaluation of Success of Blinding ............................................................................... 27 
10.6.3 
Breaking the Study Blind/Participant Code ................................................................ 27 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................... 27 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................................. 28 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 28 
13.1 
Ethical Standard ................................................................................................................................. 28 
13.2 
Institutional Review Board ................................................................................................................ 28 
13.3 
Informed Consent Process ............................................................................................................... 28 
13.3.1 
Consent/assent and Other Informational Documents Provided to Participants.... 28 
13.3.2 
Consent Procedures and Documentation .................................................................. 29 
13.4 
Participant and data Confidentiality ................................................................................................ 29 
13.4.1 
Research Use of Stored Human Samples, Specimens or Data ............................. 29 
13.5 
Future Use of Stored Specimens .................................................................................................... 30 
14 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 30 
14.1 
Data Collection and Management Responsibilities ...................................................................... 30 
14.2 
Study Records Retention .................................................................................................................. 31 
14.3 
Protocol Deviations............................................................................................................................ 31 
14.4 
Publication and Data Sharing Policy ............................................................................................... 31 
15 
STUDY ADMINISTRATION ........................................................................................................................ 32 
15.1 
Study Leadership ............................................................................................................................... 32 
16 
CONFLICT OF INTEREST POLICY .......................................................................................................... 32 
17  
LIABILITY AND INSURANCE .................................................................................................................... 32 
18  
LITERATURE REFERENCES.................................................................................................................... 33 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
Version 2.0 
Protocol SOR007-2017-04 
 
 
20 April 2017 
 
 
 
v 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
AK 
Actinic Keratosis 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BUN 
Blood urea nitrogen 
CTCAE 
Common Terminology Criteria for Adverse Events 
EDC 
Electronic Data Capture System 
eCRF 
Electronic Case Report Form 
FDA 
The U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
ICMJE 
International Committee of Medical Journal Editors 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
LSR 
Local Skin Reaction 
NCI 
National Cancer Institute 
NDA 
New Drug Application 
PCA 
Precipitation with Compressed Antisolvents 
PK 
Pharmacokinetics 
SAE 
Serious Adverse Event 
SOC 
System Organ Class 
UP 
Unanticipated Problem 
WBC 
White blood cell 
 
 
 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
Version 2.0 
Protocol SOR007-2017-04 
 
 
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 vii 
STATEMENT OF COMPLIANCE 
I have read the attached protocol number SOR007-2017-04 entitled, Phase 2 Dose-Rising Study of SOR007 
Ointment for Actinic Keratosis, Version 2.0 dated 20 April 2017 and agree to comply with the contents of this 
document. 
I agree to comply with applicable FDA regulations and guidelines set forth in 21 CFR Parts 11, 50, 54, 56, and 312. 
This document is a confidential communication of DFB Soria, LLC. The recipient agrees that no unpublished 
information contained herein will be published or disclosed without prior written permission of DFB Soria, LLC. 
However, this document may be disclosed to appropriate institutional review boards, ethics review committees, or 
authorized representatives of the Investigator or of boards of health under the condition that they are requested 
to respect the confidentiality of the document. 
The signature of the Principal Investigator below constitutes his/her agreement. 
 
 
__________________________________________ __________________________ 
Signature of Principal Investigator  
 
Date 
 
 
_ Reginold Simmons, MD _________________________________________ 
Printed Name of Principal Investigator 
 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
Version 2.0 
Protocol SOR007-2017-04 
 
 
20 April 2017 
 
 
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PROTOCOL SUMMARY 
Title: 
Phase 2 Dose-Rising Study of SOR007 for Actinic Keratosis 
 
Précis: 
This is a Phase 2, randomized, double-blind, dose rising study to determine the safety, 
tolerability, and preliminary efficacy of four concentrations of SOR007 (Uncoated 
Nanoparticle Paclitaxel) Ointment (SOR007) applied to actinic keratosis (AK) lesions twice 
daily for up to 28 days, compared to SOR007 Ointment Vehicle.  
 
Subjects with AK will be enrolled in four dose-escalating cohorts of eight subjects assigned 
consecutively. Each cohort will be randomized to SOR007 or Ointment Vehicle in a ratio of 
3:1. Dose escalation will be as follows: 
 
• 
Cohort 1: Six subjects with 0.15% SOR007 Ointment topically applied to lesions; 
                  Two subjects with Ointment Vehicle topically applied to lesions; 
• 
Cohort 2: Six subjects with 0.3% SOR007 Ointment topically applied to lesions; 
                  Two subjects with Ointment Vehicle topically applied to lesions; 
• 
Cohort 3: Six subjects with 1% SOR007 Ointment topically applied to lesions; 
                  Two subjects with Ointment Vehicle topically applied to lesions; 
• 
Cohort 4: Six subjects with 2% SOR007 Ointment topically applied to lesions; 
                  Two subjects with Ointment Vehicle topically applied to lesions; 
 
Investigational product will be applied topically to a target AK lesion test field, a 25 cm2 area 
on the face which contains 4-8 AK lesions, twice daily for up to 28 days, or until all lesions 
resolve. Investigational product will be applied with a gloved finger. The maximum total 
amount of investigational product that will be applied daily will be 1 finger-tip unit (FTU), 
approximately 0.5g. No more than 25cm2, approximately 0.15% of the total body surface 
area, will be treated. 
 
Safety will be assessed in an ongoing manner and formal safety reviews will be conducted 
four times for each cohort: at Day 8, at Day 15, at Day 21 and at Day 28 for the last subject 
enrolled in each cohort. The next dose level cohort will enroll upon a finding of safety and 
tolerability at the previous cohort’s second safety review.  
 
Visit Schedule: 
 
Screening visit: Within 14 days prior to the first application of investigational product the 
subject will have hematology and biochemistry laboratory samples taken and be assessed 
against enrollment criteria. 
 
Day 1: Target AK lesion test field will be identified, assessed by the physician, and 
documented photographically. Suitability for enrollment will be confirmed. Study area will be 
photographed and mapped on a transparency. The subject will be randomized to treatment 
and have first application of investigational product. The tube of IP will be weighed prior to 
dispensing. Blood samples for pharmacokinetic (PK) analysis of paclitaxel plasma levels will 
be collected at 1 h, 2 h, 4 h, and 6 h post-first daily application. The subject will receive 
training on application and handling of investigational product which they will take home for 
self-application later that day and on subsequent days. The subject will maintain an 
application diary throughout the treatment period of the study. 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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Days 8, 15, 21: The subject will return to the clinic for assessment and documentation of 
target AK lesion test field and a single PK sample collection prior to first daily application of 
investigational product. A photograph will be taken and any changes on the transparency 
mappings will be recorded. The tubes of IP will be weighed.  
 
Day 28: The subject will return to the clinic for assessment and documentation of the target 
AK lesion test field, PK sample collection, and application of investigational product. PK 
samples will be collected prior to first daily application and 1 h, 2 h, 4 h, 6 h, and 12 h post-
first daily application. Hematology and biochemistry laboratory samples will be collected.  A 
photograph will be taken and any changes on the transparency mappings will be recorded. 
The last application will occur following the 12 h PK sample collection. The tubes of IP will be 
weighed. 
 
Day 43: The subject will return to the clinic for assessment and documentation of target AK 
lesion test field and a single PK sample collection. Hematology and biochemistry laboratory 
samples will be collected. A photograph will be taken and any changes on the transparency 
mappings will be recorded. 
 
Day 56: The subject will return to the clinic for assessment and documentation of target AK 
lesion test field and a single PK sample collection. A photograph will be taken and any 
changes on the transparency mappings will be recorded. 
 
Once the last cohort has completed the study, all available data, including safety, PK, and 
preliminary efficacy, will be analyzed. The PK blood samples will be analyzed per cohort when 
the last subject of each cohort completes Day 28.  
 
Objectives: 
 
Primary objective: 
• 
To determine the safety and tolerability of topical SOR007 Ointment applied to AK 
lesions 
 
 
Secondary objectives:  
• 
To obtain preliminary determination of the efficacy of topical SOR007 Ointment 
applied to AK lesions 
• 
To describe the pharmacokinetics of topical SOR007 Ointment applied to AK lesions 
 
Endpoints: 
Primary endpoint: Safety and tolerability as demonstrated by: 
• 
Local toxicity 
• 
Adverse events 
• 
Laboratory assessments 
• 
Vital signs 
• 
Local skin reactions (LSR) 
 
Secondary endpoints: 
• 
Preliminary Efficacy: reduction in number of AK lesions and lesion size 
• 
Systemic Exposure as determined by: Tmax, Cmax, AUC 
 
Population: 
Up to 32 subjects with AK lesions. 
Phase: 
Phase 2 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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Protocol SOR007-2017-04 
 
 
20 April 2017 
 
 
 
x 
Number of 
Sites enrolling 
participants: 
1 
Description of 
Study Agent: 
SOR007 Ointment Vehicle (active ingredient-free) 
 
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment 0.15 % (1.5 mg/g, 1.23 mg/mL 
paclitaxel, USP) 
 
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment 0.3 % (3 mg/g, 2.47 mg/mL paclitaxel, 
USP) 
 
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment 1.0 % (10 mg/g, 8.23 mg/mL paclitaxel, 
USP) 
 
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment 2.0 % (20 mg/g, 16.46 mg/mL 
paclitaxel, USP) 
 
Study Duration: 
The study duration will be up to approximately 10 months. 
 
Participant 
Duration: 
The participant duration is estimated to be 8 weeks for each subject.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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SCHEMATIC OF STUDY DESIGN 
 
Week -2 to Day 0 
Visit 1 
Day 1 
Visit 2 
1% SOR007 N = 6 
SOR007 Placebo N = 2 
0.3% SOR007 N = 6 
SOR007 Placebo N = 2 
0.15% SOR007 N = 6 
SOR007 Placebo N = 2 
  Day 8 
Visit 3 
 Day 15 
Visit 4 
  Day 21 
Visit 5 
  Day 28 
Visit 6 
    Day 43 
Visit 7 
1 week after the last 
subject in a cohort has 
received the first dose 
Safety Analysis 1 
Safety Analysis 2 
Safety Analysis 3 
Subject Timeline 
Safety Timeline 
2% SOR007 N = 6 
SOR007 Placebo N =2 
    Day 56 
Visit 8 
Safety Analysis 4 
2 weeks after the last 
subject in a cohort has 
received the first dose 
3 weeks after the last 
subject in a cohort has 
received the first dose 
4 week after the last 
subject in a cohort has 
received the first dose 
Review to consider escalation to next dose to happen 2 weeks 
after the last subject in a cohort has received the first dose 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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1 
1 
KEY ROLES 
Medical Director 
Gere diZerega, MD 
Professor, USC Keck School of Medicine 
President & CEO, US Biotest, Inc. 
231 Bonetti Dr., Suite 240, San Luis Obispo, CA 93401 
805-630-2800 
gere.dizerega@usbiotest.com 
Study Manager 
Leanne Drummond 
US Biotest, Inc.  
231 Bonetti Dr., Suite 240, San Luis Obispo, CA 93401 
805-595-1300 
leanne.drummond@usbiotest.com 
 
Principal Investigator 
Reginold Simmons, MD 
Moore Clinical Research 
4257 West Kennedy Blvd, Tampa, FL 33609 
813-948-7550 
rsimmons@moorecr.com 
Medical Monitor 
Antony Verco, MD 
231 Bonetti Dr., Suite 240, San Luis Obispo, CA 93401 
805-762-4615 
tony.verco@usbiotest.com 
Laboratory – PK Samples 
Covance Salt Lake City Laboratories 
Bioanalytical (BA) Group 
1121 East 3900 South, Suite C-110, Salt Lake City, UT 
84124, U.S.A. 
 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
 
The Sponsor for IND 126915, DFB Soria, LLC, has transferred responsibility for all obligations set forth in 21 CFR 
Part 312 to US Biotest, Inc., with regard to the IND. In accordance with 21 CFR Part 312, US Biotest, Inc., shall be 
considered the sponsor with regard to all activities related to the IND. Therefore, references to “Sponsor” 
hereafter in this protocol refer to US Biotest, Inc.  
 
2.1 
BACKGROUND INFORMATION  

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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Protocol SOR007-2017-04 
 
 
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2 
Name and description of study agent: 
Investigational drug product SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (SOR007) is being developed by 
US Biotest, Inc. (“US Biotest”) for the topical treatment of actinic keratosis (AK). SOR007 is also being investigated 
for the topical treatment of moderate to severe plaque psoriasis in a Phase I clinical trial under IND 126915, 
Protocol SOR007-2016-01.  
SOR007 contains a nanoparticularized uncoated paclitaxel powder (NanoPac®) created using a Precipitation with 
Compressed Antisolvent (PCA) technique that employs supercritical carbon dioxide and acetone to generate 
paclitaxel nanoparticles within a well-characterized particle-size distribution. SOR007 consists of this NanoPac 
suspended in an ointment vehicle (13% cyclomethicone 5, 5% mineral oil, and 5% paraffin wax in a white 
petrolatum base) that facilitates dermal absorption from topical application while maintaining particle size 
stability. All excipients are compendial grade (USP/NF) and approved for topical route of administration at 
concentrations equal to or less than the Maximum Potency detailed in the FDA Inactive Ingredients Database. 
Nonclinical Summary: 
Nonclinical studies of SOR007 in animal models of AK have not yet been completed. The safety of NanoPac and 
SOR007 have been investigated in other nonclinical models and are presented in the SOR007 Investigator’s 
Brochure. Numerous nonclinical studies were performed to establish the safety of paclitaxel formulated as Taxol® 
(see Taxol Package Insert). 
Daily topical administration of SOR007 to Göttingen minipigs for 28 days applied at the maximal feasible volume of 
2 mL/kg, at dose concentrations of 0.0, 0.3, 1.0, and 3% (0, 4.9, 16.5, and 49.9 mg/kg/day, respectively) was well 
tolerated (S07-TP-02-2015). There were no SOR007-related effects on survival, clinical signs, dermal irritation, 
body weights, body weight gains, food consumption, ophthalmic findings, or cardiology parameters. Dermal 
irritation was observed in all groups during the dosing phase and was considered vehicle or procedurally related as 
the frequency and severity of the findings were comparable between the placebo controls and SOR007-treated 
groups. SOR007-related effects on hematology parameters were limited to nonadverse, minimally to mildly lower 
RBC mass parameters, and reticulocytes on Day 29/30 that showed recovery during the 2-week reversal period. 
There were no SOR007-related changes in coagulation, clinical chemistry, or urinalysis parameters in main study 
phase or recovery animals. There were no gross or microscopic findings or differences in organ weights in the 
terminal or recovery groups that were attributed to administration of SOR007. Exposure to paclitaxel increased 
with increasing SOR007 dose; however, the increases in mean Cmax and AUC0-24 values were less than dose 
proportional. Day 28 combined-sex AUC0-24 values were 36.0, 85.5, and 149 ng·hr/mL at 4.9, 16.5, and 
49.9 mg/kg/day, respectively. Based on these findings, the NOAEL was the high dose of 49.9 mg/kg/day. 
Clinical Summary: 
SOR007 has not been administered to humans for topical treatment of AK. A Phase 1 clinical trial, Protocol 
SOR007-2016-01, in plaque psoriasis has recently completed subject participation with no treatment related 
adverse events (AE) reported by the 13 subjects who had SOR007 applied topically under occlusion for up to 10 
applications. The Phase I psoriasis plaque clinical trial is evaluating the anti-inflammatory efficacy of SOR007 in 
subjects with psoriasis vulgaris. Thirteen subjects with chronic plaque type psoriasis received occlusive application 
of six topical formulations:  SOR007 at 0.15%, 0.3%, 1.0%, and 2.0%, vehicle, and an active comparator 
approximately daily for up to 10 treatments over a 12-day period Approximately 200 µL of each formulation was 
be applied on each dosing day. The total body surface area exposed to SOR007 was 4.52 cm2, or 0.03% total body 
surface area of a 1.6 m2 human. The daily dose was approximately 5.7 mg per day, for a total of approximately 57 
mg of Uncoated Nanoparticle Paclitaxel per subject. Calculated on a mg/kg or mg/m2 basis, the paclitaxel applied 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
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20 April 2017 
 
 
 
3 
topically over the 12-day study would be approximately 0.1 mg/kg (3.8 mg/m2) per day, or 1.0 mg/kg (38 mg/m2) 
total exposure for a 60-kg subject. The primary endpoint will be change from baseline in psoriatic skin thickness 
(assessed by measurement of the thickness of the echolucent band (ELB) of the psoriatic infiltrate using 22 MHz 
sonography). Clinical assessment, photo documentation, and PK analysis were also performed.  No treatment 
related AEs were reported by the subjects who had up to 10 daily topical applications of SOR007.   
Importance of the study: 
AK is a pre-cancerous skin disease that affecting approximately 58 million Americans (Lewin Group 2005). The 
progression of AKs occurs due to chronic sun exposure. Most AKs are found on places of the body that experience 
the most sun exposure (i.e. face, neck, back of hands). If left untreated, an estimated 10% of AKs will develop into 
squamous cell carcinoma (Fuchs 2007). SOR007 is being developed as an alternative to existing treatments for AK. 
2.2 
RATIONALE  
This Phase 2 study will include subjects with AK. The study design allows for a safety evaluation of topical 
application of SOR007 onto the face as topical therapy for AK. We hypothesize that topical application of SOR007 
onto the face will result in limited, if any, systemic exposure to paclitaxel and should therefore result in only low-
grade and transitory AEs. Birth control and abstinence from sexual contact requirements in the proposed study will 
protect participants and their partners.  
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
There is no known risk of SOR007 applied topically to AK. 
2.3.2 KNOWN POTENTIAL BENEFITS  
There is no known benefit of SOR007 applied topically to AK. 
3 
OBJECTIVES AND PURPOSE 
The primary objective of this study is to evaluate the safety and tolerability of topical SOR007 ointment applied to 
the face in subjects with actinic keratosis (AK). Secondary objectives are (a) to determine preliminary efficacy of 
topical SOR007 ointment applied to AK; and (b) to determine the concentration of paclitaxel in the systemic 
circulation post-topical application. 
4 
STUDY DESIGN AND ENDPOINTS 
 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
The proposed study is a Phase 2, dose-rising, safety, and preliminary efficacy study. Subjects will have SOR007 
topically applied to AK lesions.  
Subjects will enroll in four dose-escalating cohorts of eight subjects each. Each cohort will be randomized to 
SOR007 or Ointment Vehicle in a ratio of 3:1. Safety will be assessed in an ongoing manner and formal safety 

Phase 2 Dose-Rising Study of SOR007 Ointment for Actinic Keratosis 
Version 2.0 
Protocol SOR007-2017-04 
 
 
20 April 2017 
 
 
 
4 
reviews will be conducted four times for each cohort: at Day 8, at Day 15, at Day 21 and at Day 28 for the last 
subject enrolled in each cohort. The next dose level cohort will enroll upon a finding of safety and tolerability at 
the previous cohort’s second safety review. Any symptoms of systemic toxicity will be reviewed along with the 
routine safety assessments. In addition, special attention will be given to the onset of ulceration within the AK test 
field. Significant ulceration in more than 33% of the subjects in a cohort will be considered a dose limiting toxicity 
(DLT) and dose escalation will not be permitted.  
 
• 
Cohort 1: Six subjects with 0.15% SOR007 ointment topically applied to lesions 
 
  Two subjects with SOR007 vehicle topically applied to lesions 
• 
Cohort 2: Six subjects with 0.3% SOR007 ointment topically applied to lesions 
 
  Two subjects with SOR007 vehicle topically applied to lesions 
• 
Cohort 3: Six subjects with 1% SOR007 ointment topically applied to lesions  
 
  Two subjects with SOR007 vehicle topically applied to lesions 
• 
Cohort 4: Six subjects with 2% SOR007 ointment topically applied to lesions 
 
  Two subjects with SOR007 vehicle topically applied to lesions 
 
Once the last cohort has completed the study, all available data, including safety, PK, and preliminary efficacy, will 
be analyzed. The PK blood samples will be analyzed per cohort when the last subject of each cohort completes Day 
28. 
 
4.2.1 PRIMARY ENDPOINT 
The primary endpoint will be safety and tolerability, as assessed by adverse events, changes in vital signs, 
laboratory results, and physical examination of the test field for local skin reactions (LSR). 
4.2.2 SECONDARY ENDPOINTS 
The secondary endpoints will be: 
• 
Preliminary efficacy of topical SOR007 ointment applied to AK by change in number and size of AK lesions. 
• 
Concentration of paclitaxel in the systemic circulation post-topical application. 
 
4.2.3 EXPLORATORY ENDPOINTS 
Not applicable. 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1 
PARTICIPANT INCLUSION CRITERIA 
Subjects who meet the following criteria will be considered eligible for participation in the study: 
• 
Signed informed consent. 

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• 
Men and women with presence of actinic keratosis. 
• 
Age 45-85 years, inclusive. 
• 
Women who have had surgical sterilization or are post-menopausal (absence of menses for at least one 
year) are eligible. Women of child-bearing potential who are non-pregnant and non-nursing, and willing to 
avoid pregnancy during the course of the study and during the menstrual cycle following completion of 
their participation in the study are eligible. (Adequate contraception is defined as regular use of 
diaphragm with condoms, IUD with condoms, or systemic contraceptives – if used for at least three 
months prior to enrollment in the study). A negative pregnancy test is required as an entry criteria. 
Women must continue to use the method of contraceptive for 30 days after the last study drug 
administration.  
• 
Male subjects must agree to sexual abstinence or use adequate contraception when sexually active in 
combination with their female partners, if they are of childbearing potential. That means the volunteer 
must be vasectomized or use a condom and his female partner must either be surgically sterile 
(hysterectomy or tubal ligation) or agree to use a reliable method of contraception with a failure rate of 
less than 1 % per year when used consistently and correctly such as implants, injectables, combined oral 
contraceptives, or non-DalKon Shield intra uterine devices [IUDs]. This applies from signing of the 
informed consent form until 90 days after the last study drug administration. Methods of contraception 
must have been effective for at least 30 days on the day of signing the informed consent form. Male 
volunteers must also refrain from sperm donation from signing of the informed consent form until 90 
days after the last study drug administration.  
• 
Presence of 4-8 AK lesions total in a 25 cm2 area identified on the face through transparency mapping and 
photographs. The face area will be defined from hair line to jaw line. The scalp will not be included. An 
imaginary normal hair line will be the upper boundary for bald men. Lesions that are thicker than 1 mm (a 
piece of paper) or larger than 9 mm will not be included in lesion counts. Lesions suspicious for squamous 
cell carcinoma, basal cell carcinoma, or melanoma will not be included in lesion counts and cannot be in 
the 25 cm2 area of treatment. 
• 
Able to refrain from the use of all other topical medications to the facial area during the treatment period. 
• 
Considered reliable and capable of understanding their responsibility and role in the study. 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
If a subject meets any of the following criteria, they must be excluded from the study: 
• 
History of allergy or hypersensitivity to paclitaxel. 
• 
Abnormal pre-existing dermatologic condition which might affect the normal course of the disease (e.g., 
albinism, or chronic vesiculobullous disorders). 
• 
Positive urine pregnancy test in women of child-bearing potential. 
• 
Inability to use adequate birth control measures for men or women of child-bearing potential, as defined 
above. 
• 
Serious psychological illness. 
• 
Significant history (within the past year) of alcohol or drug abuse. 
• 
During the 30 day period preceding study entry: 
o 
Participating in any clinical research 
o 
Using topical paclitaxel as treatment for AK 

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o 
Using any other topical agents including but not limited to actinex, glycolic acid products, alpha-
hydroxy acid products, and chemical peeling agents for treatment of AK 
o 
Using any systemic steroids or topical corticosteroids 
o 
Having cryosurgery (cryotherapy on extremities is acceptable) 
• 
Use of sun lamps or sun tanning beds or booths during the 2 weeks prior to first application until final 
visit. 
• 
Prior treatment with systemic paclitaxel or systemic cancer therapy within 6 months of study entry. 
• 
Medical history which, based on the clinical judgement of the Investigator, implies an unlikelihood of 
successful completion of the study. 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Sufficient subjects will be screened to allow for up to 32 subjects to be enrolled in the Phase 2 study. Subjects will 
be recruited from the Principal Investigator’s clinic. Advertising may be required for recruiting to the study. 
Subjects will be recruited and screened for eligibility and will proceed to treatment.  
Following successful screening, the eight subjects of the first cohort will be treated (at the lowest dose or vehicle) 
daily for a total of 56 treatments (twice daily for 28 days) per subject. Subjects will be followed for four weeks after 
their last application. During the study, the subjects will be monitored for safety and tolerability. Safety will be 
assessed in an ongoing manner and formal safety reviews will be conducted four times for each cohort: at Day 8, at 
Day 15, at Day 21 and at Day 28 for the last subject enrolled in each cohort. 
• 
If the Medical Monitor concludes it is acceptable to proceed to the next cohort, the next cohort will begin 
screening. 
• 
If the preceding dose elicits an unfavorable safety and/or tolerability profile in a subject, as determined by 
the Medical Monitor, the escalation to the next dose is not permitted at that time.  
Escalation of dosing to the highest concentration in the study (2% SOR007) will proceed as described above in 
groups of eight subjects. Once the last cohort has completed the study, all available data, including safety, PK, and 
preliminary efficacy, will be reviewed.  
Accrual of subjects will occur over a period of 10 months. 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
Participants are free to withdraw from participation in the study at any time upon request. Their reason for 
wanting to withdraw will be documented in the source notes and in the Electronic Data Capture system (EDC). 
A subject who is not suitable to be treated will be withdrawn prior to Day 1 (Baseline/Treatment), and therefore in 
all study documentation this subject would be considered a Screenfail Subject. 
• 
Clinical AE, laboratory abnormalities, or other medical conditions/situations may occur which would 
usually require withdrawal from a study. In this instance it is very important that all of these events be 

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captured, followed, and documented, and therefore a subject would be withdrawn from treatment but 
would continue through the follow up period and completion. 
Should the Investigator feel it to be in the best interest of the subject for them to be withdrawn from the study, 
the Investigator will immediately contact the Medical Monitor to discuss the reasons for withdrawal. 
Subjects that miss more than 2 consecutive days of ointment application should be considered non-compliant and 
be withdrawn from the study. 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
The sponsor should be notified immediately when a subject is removed or withdrawn from the study after 
treatment with investigational agent, as every attempt should be made to capture as much information following 
treatment as possible.  
In the event a subject is withdrawn they would undergo final study visit evaluations (End-of-Study evaluations) 
which include vital signs, AE collection and concomitant medication updates.  
In the event a subject does not attend a visit/visits and is unable to be contacted, then they should be considered 
lost-to-follow-up. Reasonable and diligent attempts such as dates and content of phone calls, emails and 
registered mail should be recorded in the subject’s record. 
If a subject repeatedly misses study visits or remains non-compliant between the time of topical SOR007 ointment 
application and the end of study visit, and where the majority of data is not available, the option to replace that 
subject in the cohort exists, however the data that is collected from the non-compliant subject will still be used in 
the safety evaluations in this study. A new subject will be enrolled into the study and the withdrawn subject will 
not be included in the cohort number count.  
Treatment compliance will be verified by use of the subject diaries and by IP tube weights pre- and post-dose. 
Subjects must apply SOR007 for at least 75% (11 doses) and not more than 125% (17 doses) of expected doses per 
week to be considered compliant with the treatment regimen. Anyone who missed the prescribed applications for 
more than 2 consecutive days should be considered non-compliant and withdrawn. 
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for the study suspension or termination, will be provided by the 
suspending or terminating party to sponsor. If the study is prematurely terminated or suspended, the PI will 
promptly inform the IRB and will provide the reasons for the termination or suspension. 
Circumstances that may warrant termination include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants; 
• 
Insufficient compliance with protocol requirements; 
• 
Data that are not sufficiently complete and/or evaluable; 
• 
Determination of futility. 

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Study may resume once concerns about safety, protocol compliance, and data quality are addressed and satisfy 
the sponsor, IRB, and/or Food and Drug Administration (FDA).  
6 
STUDY AGENT 
 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
 
6.1.1 ACQUISITION 
SOR007 will be manufactured by Dow Development Laboratories (DDL) and provided for use in this study. Study 
agent will not be shipped to the study site until all Regulatory Documentation has been provided by the site, at 
which time the study agent will be released for shipment. Shipment will be via courier, temperature controlled 68˚ 
to 77˚F (20˚ to 25˚C), and will occur prior to Site Initiation. Study Agent will be shipped to the on-site Pharmacy 
where it will be stored according to the conditions required (see 6.1.3) 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
SOR007 is presented as an off-white ointment, provided in a sealed, 15 g laminate tube. 
The tube label will at a minimum include: 
Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F). 
For Topical Dermatological Use Only. Keep out of the reach of children. 
Caution: New Drug – Limited by Federal (or United States) Law to investigational use. 
DFB Soria, LLC, US Biotest, 231 Bonetti, Suite 240, San Luis Obispo, CA 93401 
 
6.1.3 PRODUCT STORAGE AND STABILITY 
Prior to administration at the hospital/clinic, the SOR007 tubes will be stored at the Pharmacy, temperature 
controlled at 68˚ to 77˚F (20˚ to 25˚C). 
6.1.4 PREPARATION 
Not applicable. 
6.1.5 DOSING AND ADMINISTRATION 
Treatment will be applied to the lesions twice daily for up to 28 days. A maximum of 1/2 finger-tip unit (FTU) of 
ointment will be applied for each application. A FTU is defined as the amount of ointment expressed from a tube 
with a 5-mm diameter nozzle, applied from the distal skin-crease to the tip of the index finger of an adult. The 
“distal skin-crease” is the skin crease over the joint nearest the end of the finger. A FTU will cover up to 50 cm2 of 
body surface area.  
6.1.6 ROUTE OF ADMINISTRATION 
SOR007 will be applied topically to the target AK lesion test field. 

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6.1.7 STARTING DOSE AND DOSE ESCALATION SCHEDULE 
SOR007 concentrations of 0.15% (1.23 mg/mL), 0.3% (2.47 mg/mL), 1% (8.23 mg/mL), and 2% (16.46 mg/mL), or 
ointment vehicle will be administered. Each application will be 0.5 g (1/2 FTU).  Cohorts will be enrolled 
sequentially starting at the lowest concentration. Each cohort will start with a planned minimum of eight subjects, 
each receiving the SOR007 or vehicle ointment. Dose escalation to the next cohort will proceed following review of 
data by the Medical Monitor as appropriate. Special attention will be given to the onset of ulceration within the AK 
test field. Significant ulceration in more than 33% of the subjects in a cohort will be considered a DLT and dose 
escalation will not be permitted. 
6.1.8 DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS 
The decision to make dose adjustments to a subject’s treatment schedule will only be made after consultation with 
the medical monitor and as agreed upon with the medical monitor. Any symptoms of systemic toxicity will be 
reviewed along with the routine safety assessments.  
6.1.9 DURATION OF THERAPY 
Fifty-six applications of SOR007 will be administered over four weeks. Subjects will then be followed for four weeks 
after last application. 
6.1.10 TRACKING OF DOSE 
The subject will maintain an application diary and ointment tubes will be weighed at each applicable visit. 
On Day 1, the subject will receive two tubes of ointment. The tubes will be weighed before being dispensed. One 
tube will be opened and used for the first application and the subject will be instructed to continue using the open 
tube for the ointment applications. If the open tube is finished prior to the next visit, the subject can use the 
second (back up) tube until the next visit. The subject will bring in both tubes for the next visit and both tubes will 
be weighed. 
• 
If only one tube has been used it will be replaced with a new tube (weighed prior to dispensing) for the 
following week, and the first application from the new tube will be made at the site.  The subject will still 
have the back-up tube to take home again in case the first tube is emptied prior to the next visit. 
• 
If one tube was emptied and the second tube opened and used during the week, the empty tube will be 
retained at the site.  The subject will be dispensed a replacement back-up tube (weighed prior to 
dispensing) and instructed to continue using the tube which has already been opened and used before 
using the newly provided back-up tube. 
This process will be repeated at each study visit until the visit on Day 28. 
6.1.11 DEVICE SPECIFIC CONSIDERATIONS 
Not applicable. 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 

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The Investigator will maintain adequate records showing the receipt, dispensing, return, or other disposition of the 
investigational drug, including the date, quantity, batch or code number, and identification of subjects (number, 
initials) who received study medication. 
Accountability will be conducted on the individual tubes. 
The used tubes will be retained in the Pharmacy for accountability purposes, and will not be disposed of until 
confirmation is received from the Sponsor that accountability is completed. Tubes will be weighed pre- and post-
dose at each visit. 
Under no circumstances will the Investigator supply clinical material to other Investigators or clinicians or allow the 
supplies to be used other than as directed by this protocol without the consent of the sponsor. 
7 
STUDY PROCEDURES AND SCHEDULE 
 
7.1 
STUDY PROCEDURES/EVALUATIONS 
 
 
7.1.1 STUDY SPECIFIC PROCEDURES  
The following procedures and evaluations will be done as part of this study.         
• 
Complete medical history to be completed, documented, and reviewed by the Investigator within 14 days 
prior to SOR007 administration, including review of previous medical records, demographics, and parity; 
• 
Review and documentation of concomitant prescription and non-prescription medications; 
• 
Review and documentation of diagnosis of AK and previous treatments;  
• 
Female subjects will be required to taken a pregnancy test at screening and on Days 1, 28, and 56; 
• 
Comprehensive physical examination and vital signs (blood pressure, heart rate, temperature); 
• 
Blood samples will be taken during the Screening Visit and on Days 28 and 43 to measure white blood cell 
(WBC), hemoglobin, platelet count, liver function (total bilirubin, aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and prothrombin; 
• 
PK blood samples will be taken on Days 1, 8, 15, 21, 28, 43, and 56. For Day 1, blood will be taken at 1 h, 2 
h, 4h, and 6 h post initial application of SOR007. For Days 8, 15, and 21, blood will be taken prior to first 
daily application of SOR007. For Day 28, blood will be taken prior to first daily application and 1 h, 2 h, 4 h, 
6 h and 12 h post first daily application of SOR007. For Days 43 and 56, blood will be taken at the 
beginning of the follow-up visit. PK samples within the first 4 hours on days 1 and 28 will allow for a 10-
minute window around the samples. The remaining samples within the first 24 hours will allow for a 30-
minute window; 
• 
LSR evaluation will be performed by the evaluator. LSR will be performed to monitor the AK lesions in the 
test field as a whole through the evaluation of erythema, crusting, swelling, vesiculation/postulation, 
erosion/ulceration, hyperpigmentation, and hypopigmentation; 
• 
SOR007 or vehicle ointment to be applied topically to the target AK lesion test field. twice daily for up to 
28 days. Subjects will be assessed using a 25 cm2 treatment area containing 4-8 AK lesions. AK lesions will 
be notated on a transparency along with landmarks to help the investigator distinguish old and new AK’s 
throughout the subject’s participation in the trial. Photographs of the treatment area will also be used to 
help the investigator in distinguishing between different AK lesions and the status of these lesions 

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throughout the study subjects’ participation. The investigator will monitor the status of these AK lesions 
to ensure that the subject is safe to continue participation in the trial. 
 
7.1.2 STANDARD OF CARE STUDY PROCEDURES  
 
For any treatment of AK outside the treatment field, the subject will be referred to their primary care provider. 
Should a lesion in the treatment field progress to a more serious lesion, i.e. squamous cell carcinoma or basal cell 
carcinoma, the subject will be withdrawn from the study and referred to their primary care provider for course of 
treatment. All attempts will be made to follow-up with the subject and to get a resolution for the lesion. 
 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
 
7.2.1 CLINICAL LABORATORY EVALUATIONS  
Clinical laboratory assessments performed at screening/baseline, Day 28, and Day 43 are noted in Section 7.1.1 
and all of these tests will be conducted at the local CLIA certified laboratory routinely used by the Investigator. 
7.2.2 OTHER ASSAYS OR PROCEDURES 
PK samples will be taken on Days 1, 8, 15, 21, 28, 43, and 56. For Day 1, blood will be taken at 1 h, 2 h, 4 h, and 6 h 
post initial application of SOR007. For Days 8, 15, and 21, blood will be taken prior to daily application of SOR007. 
For Day 28, blood will be taken prior to daily application and 1 h, 2 h, 4 h, 6 h, and 12 h post first initial application 
of SOR007. For Days 43 and 56, blood will be taken at the beginning of the follow-up visit. Subjects will return for a 
final visit on Day 56. PK samples within the first 4 hours on days 1 and 28 will allow for a 10-minute window around 
the samples. The remaining samples within the first 24 hours will allow for a 30-minute window.  
7.2.3 SPECIMEN PREPARATION, HANDLING, AND STORAGE 
PK samples will be drawn at the specified time/visit and stored frozen on-site until a cohort has completed all day 
28 draws for analysis, at which time each cohort blood samples will be batch-shipped to Covance Laboratories for 
analysis. Procedures for processing for storage will be provided prior to study initiation. PK samples from days 43 
and 56 will be sent with the next cohort PK samples.  For the last cohort all samples will be shipped after the day 
56 samples are collected. 
7.2.4 SPECIMEN SHIPMENT 
Not applicable. 
7.3 
STUDY SCHEDULE 
 
7.3.1 VISIT 1/SCREENING 
The following procedures and assessments must be completed, documented and reviewed by the Investigator 
during the screening period, within 14 days prior to the application of investigational product: 

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• 
Written informed consent including comprehensive discussion of the study schedule, procedures and 
subject protocol requirements. 
• 
Complete medical history, including review of previous medical records, demographics and parity. 
• 
Complete physical examination. 
• 
Vitals will be collected. 
• 
Review and documentation of AK diagnosis and previous treatments. If the site is unable to retrieve the 
past medical records containing a confirmed diagnosis for facial AK, it is acceptable for the site to 
document patient self-reporting with the Investigator making the diagnosis for facial AK at screening.  
• 
LSR performed by the evaluator. LSRs will be performed to monitor the AK lesions in the test field as a 
whole through the evaluation of erythema, crusting, swelling, vesiculation/postulation, 
erosion/ulceration, hyperpigmentation, and hypopigmentation as seen in the table below: 
Local Skin 
Response 
Grading Criteria 
0 
1 
2 
3 
4 
Erythema 
Not present 
Slightly pink 
< 50% 
Pink or light 
red > 50% 
Red, restricted 
to treatment 
area 
Red extending 
outside 
treatment area 
Flaking / Scaling 
Not present 
Isolated scale, 
specific to 
lesion 
Scale < 50% 
Scale > 50% 
Scaling 
extending 
outside 
treatment area 
Crusting 
Not present 
Isolated 
crusting 
Crusting 
< 50% 
Crusting  
> 50% 
Crusting 
extending 
outside 
treatment area 
Swelling 
Not present 
Slight, lesion 
specific 
edema 
Palpable 
edema 
extending 
beyond 
individual 
lesions 
Confluent 
and/or visible 
edema 
Marked 
swelling 
extending 
outside 
treatment area 
Vesiculation / 
Pustulation 
Not present 
Vesicles only 
Transudate or 
pustules, with 
or without 
vesicles < 
50% 
Transudate or 
pustules, with 
or without 
vesicles > 
50% 
Transudate or 
pustules with 
or without 
vesicles 
extending 
outside 
treatment area 
Erosion / 
Ulceration 
Not present 
Lesion 
specific 
erosion 
Erosion 
extending 
beyond 
individual 
lesions 
Erosion > 
50% 
Black eschar 
or ulceration 
Hyperpigmentation 
 
Present 
Not Present 
 
 
Hypopigmentation 
 
Present 
Not Present 
 
 

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• 
If applicable, a copy of the histology report confirming the diagnosis must be filed in the subject’s study 
record. 
• 
Blood samples for WBC, hemoglobin, platelet count, total bilirubin, AST, ALT, BUN, creatinine, and 
prothrombin. 
• 
Review and documentation of all concomitant prescription and non-prescription medications. 
• 
Female subjects of child bearing potential will take a urine pregnancy test. 
• 
Review of inclusion and exclusion criteria and determination of eligibility. 
 
7.3.2 ENROLLMENT/BASELINE 
Day 1/Visit 2 – Baseline and Treatment – Day of 1st SOR007 Ointment Treatment 
Following review of all test results from the Screening Visit, the following will be conducted: 
• 
Review of inclusion and exclusion criteria and determination of eligibility to proceed to treatment.  
• 
Female subjects of child bearing potential will take a urine pregnancy test prior to treatment. 
• 
The target AK lesion test field on the face will be identified. A 25 cm2 area of skin mapped by transparency 
tracing and photos with 4-8 AK lesions will be the application field. A copy of the photograph will be given 
to the subject to help identify where to apply the medication as instructed by the Investigator. The 
baseline photograph will be used at the final visit to allow the Investigator to accurately compare exactly 
all the keratosis recorded if they are clear, or still present. The transparency will be photocopied for 
records. 
• 
All AKs in the application field will be counted by the Investigator at baseline. 
• 
LSR performed by the evaluator.  
• 
Vitals will be collected. 
• 
The subject will be randomized to treatment and have first daily application of investigational product.  
• 
Two tubes will be weighed before being dispensed. One tube will be opened and used for the first 
application and the subject will be instructed to continue using the open tube for the ointment 
applications.  
• 
PK samples will be collected at 1 h, 2 h, 4 h, and 6 h after initial application.  
• 
Concomitant medication will be reviewed and updated as necessary. 
• 
AEs prior to this visit will be considered as medical history; from this visit forward will be collected and 
recorded in the AE forms. 
• 
Subjects will be given the following instructions for investigational product application: 
o 
Subject will wash their application test field every morning and night, wait 10 minutes and then 
lightly apply the given test medication to the application field for 28 days. 
o 
Subject will continue to use the open tube for ointment applications. If the open tube is finished 
prior to the next visit, the subject can use the second (back-up) tube until the next visit. The 
subject will bring both tubes for the next visit. 
o 
Subject will apply the medication cream with a gloved finger and must wash their hands 
thoroughly after each application. The gloves can be discarded in regular trash. 
o 
Subject will be instructed to apply a maximum of 1/2 finger-tip unit (FTU) of ointment for each 
application. A FTU is defined as the amount of ointment expressed from a tube with a 5-mm 

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diameter nozzle, applied from the distal skin-crease to the tip of the index finger of an adult. The 
“distal skin-crease” is the skin crease over the joint nearest the end of the finger. A FTU will cover 
up to 50 cm2 of body surface area (Finlay 1989; Long 1992). 
o 
Subject will avoid contact with the eyes, eyelids, nostrils, and mouth. If there is contact with the 
specified areas, the subject should wash the area of contact with cold water.  
o 
Subjects may use their own moisturizer to areas not treated and use make-up on areas not 
treated. 
o 
Subject will be advised that some subjects using active ingredient may develop skin reactions 
where the medicine is used. These reactions include redness, dryness, burning, pain, erosion 
(loss of the upper layer of the skin), and swelling. If irritation occurs at the application site, it may 
persist for two or more weeks after therapy is discontinued. Treated areas may be unsightly 
during and after therapy. The subject is allowed to cover the area with loose, light dressing while 
in public.  
o 
Subject will be instructed to not apply any other prescription medication or moisturizer to the 
treatment area during the study. 
o 
Subject will be instructed to keep a careful diary of the number of applications during the study. 
o 
Subject will be advised that if at any point the lesion begins to ulcerate to stop application of 
SOR007 on that lesion and to schedule a visit with the Investigator immediately. 
• 
Subjects will be given the following instructions for storage and handling of SOR007: 
o 
Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F). 
o 
For Topical Dermatological Use Only. Keep out of the reach of children. 
Day 8/Visit 3; Day 15/Visit 4; Day 21/Visit 5 
Subjects will return to the clinic for the following evaluations and procedures: 
• 
All AKs in the application field will be counted by the Investigator. 
• 
LSR performed by the evaluator. 
• 
Vitals will be collected. 
• 
Treatment compliance will be verified by use of the subject diaries. Subjects must apply SOR007 for at 
least 75% (11 doses) and not more than 125% (17 doses) of expected doses per week to be considered 
compliant with the treatment regimen. Anyone who missed the prescribed application for more than 2 
consecutive days should be considered non-compliant and withdrawn. 
• 
A photograph will be taken and any changes on the transparency mappings will be recorded. The 
transparency will be photocopied for records. 
• 
Both tubes will be collected and weighed. If only one tube has been used it will be replaced with a new 
tube (weighed prior to dispensing) for the following week, and the first application from the new tube will 
be made at the site. The subject will still have the back-up tube to take home again in case the in use tube 
is emptied prior to the next visit. If one tube was emptied and the second tube opened and used during 
the week, the empty tube will be retained at the site. The subject will be dispensed a replacement back-
up tube (weighed prior to dispensing) and instructed to continue using the tube which has already been 
opened and used before using the newly provided back-up tube. A tube can be reissued if sufficient 
ointment remains to treat for 1 week, approximately 4 g of ointment. 
• 
Concomitant medication will be reviewed and updated as necessary. 
• 
A single PK sample will be collected prior to first daily application of investigational product. 

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• 
Subject will receive first daily application of investigational product. 
• 
AEs will be reviewed and updated as necessary. 
The subject will undergo any other evaluations determined necessary by the Investigator to ensure the subject 
well-being. 
Day 28/Visit 6 – End of Treatment 
Subjects will return to the clinic for the following evaluations and procedures: 
• 
Female subjects of child bearing potential will take a urine pregnancy test prior to treatment. 
• 
All AKs in the application field will be counted by the Investigator. 
• 
LSR performed by the evaluator.  
• 
Vitals will be collected. 
• 
Treatment compliance will be verified by use of the subject diaries. Subjects must apply SOR007 for at 
least 75% (11 doses) and not more than 125% (17 doses) of expected doses per week to be considered 
compliant with the treatment regimen. Anyone who missed the prescribed application for more than 2 
consecutive days should be considered non-compliant and excluded from analysis. 
• 
A photograph will be taken and any changes on the transparency mappings will be recorded. The 
transparency will be photocopied for records. 
• 
The tubes of investigational product will be weighed and collected. 
• 
Concomitant medication will be reviewed and updated as necessary. 
• 
Subject will receive application of investigational product. 
• 
PK samples will be collected prior to first daily application and 1 h, 2 h, 4 h, 6 h, and 12 h post first daily 
application of investigational product. 
• 
The last application will occur following the 12 h PK sample collection. 
• 
Blood samples for WBC, hemoglobin, platelet count, total bilirubin, AST, ALT, BUN, creatinine, and 
prothrombin. 
• 
AEs will be reviewed and updated as necessary.  
The subject will undergo any other evaluations determined necessary by the Investigator to ensure the subject 
well-being. 
Day 43/Visit 7 
Subjects will return to the clinic for the following evaluations and procedures: 
• 
A single PK sample will be collected at the beginning of the visit.  
• 
All AKs in the application field will be counted by the Investigator. 
• 
LSR performed by the evaluator.  
• 
Vitals will be collected. 
• 
The baseline photograph will be used at the visit to allow the Investigator to accurately compare all the 
keratosis recorded if they are clear, or still present. 
• 
A photograph will be taken and any changes on the transparency mappings will be recorded. The 
transparency will be photocopied for records. 

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• 
The percent of lesions cleared will be determined. (Change in lesion counts will be determined by 
subtracting the final counts from the initial counts i.e. 7(initial) – 4(final) = 3). Partially cleared lesions are 
counted as still present in final count. A cleared actinic keratosis lesion is defined as either no evidence of 
the lesion, or only residual smooth flat redness present without elevation above the skin.  
• 
Blood samples for WBC, hemoglobin, platelet count, total bilirubin, AST, ALT, BUN, creatinine, and 
prothrombin. 
• 
Concomitant medication will be reviewed and updated as necessary. 
• 
AEs will be reviewed and updated as necessary. 
The subject will undergo any other evaluations determined necessary by the Investigator to ensure the subject 
well-being. 
Day 56/Visit 8 – Final Visit 
Subjects will return to the clinic for the following evaluations and procedures: 
• 
Female subjects of child bearing potential will take a pregnancy test. 
• 
A single PK sample will be collected at the beginning of the visit.  
• 
All AKs in the application field will be counted by the Investigator at final visit. 
• 
LSR performed by the evaluator. 
• 
Vitals will be collected. 
• 
The baseline photograph will be used at the visit to allow the Investigator to accurately compare all the 
keratosis recorded if they are clear, or still present.  
• 
A photograph will be taken and any changes on the transparency mappings will be recorded. The 
transparency will be photocopied for records. 
• 
The percent of lesions cleared will be determined. (Change in lesion counts will be determined by 
subtracting the final counts from the initial counts i.e. 7(initial) – 4(final) = 3). Proportion of subjects who 
have 100% clearance will be the primary efficacy endpoint. Partially cleared lesions are counted as still 
present in final count. A cleared actinic keratosis lesion is defined as either no evidence of the lesion, or 
only residual smooth flat redness present without elevation above the skin.  
• 
Concomitant medication will be reviewed and updated as necessary 
• 
AEs will be reviewed and updated as necessary. 
The subject will undergo any other evaluations determined necessary by the Investigator to ensure the subject 
well-being. 
7.3.3 FOLLOW-UP  
 
The subject’s participation in the study will end following their final study visit. Subjects who have lesions that are 
still present at the last visit will be advised to see a dermatologist or their general medical doctor for further 
evaluation.  
 
7.3.4 FINAL STUDY VISIT 

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The final study visit will occur four weeks following the last application of SOR007. At this time the subject will exit 
the study with no further follow-up requirements unless there are ongoing and study related AEs (see Section 8.3). 
7.3.5 EARLY TERMINATION VISIT 
In the event a subject is withdrawn they would, at minimum, undergo End of Treatment visit evaluations, which 
include vital signs, AE collection, concomitant medication updates, LSR evaluations, and blood samples. If a subject 
is withdrawn at a routine study visit all evaluations that would have been done at that study visit should be 
completed, as far as possible, and the least amount of information that would be captured are the vitals, AEs, 
concomitant medications, LSR evaluations, and blood samples. Blood samples will be sent to the local laboratory to 
test for WBC, hemoglobin, platelet count, total bilirubin, AST, ALTL, BUN, creatinine, and prothrombin. 
7.3.6 UNSCHEDULED VISITS 
Any unscheduled visits will be documented in the source, and any assessments and/or evaluations performed will 
be noted and reviewed. If the unscheduled visit occurs between the time of dosing but prior to end of study, the 
following assessments should be conducted and entered into the EDC to monitor the ongoing safety of the subject:  
• 
Vital signs will be obtained; 
• 
AE will be recorded; 
• 
Concomitant medication will be reviewed and updated as necessary. 
The subject will undergo any other evaluations determined necessary by the Investigator to ensure the subject’s 
well-being. If the Investigator deems it necessary for blood work to be done this information will be filed in the 
source and be available if required at a later date, but laboratory results will not be transcribed into the EDC.  

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7.3.7 SCHEDULE OF EVENTS TABLE 
 
 
Screening Clinic 
Visit 
Day 1 
Day 8  
(±2 days) 
Day 15 
(±2 days) 
Day 21 
(±2 days) 
Day 28 
(±2 days) 
Day 43 
(±2 days) 
Day 56 
(±2 days) 
Informed Consent 
X 
 
 
 
 
 
 
 
History1 
X 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
Concomitant Therapy 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Samples 
X 
 
 
 
 
X 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of LSRs 
X 
X 
X 
X 
X 
X 
X 
X 
AK Lesion Count in Treatment Field 
 
X 
X 
X 
X 
X 
X 
X 
PK Samples2 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for Female Subjects 
X 
X 
 
 
 
X 
 
X 
Photographs 
X 
X 
X 
X 
X 
X 
X 
X 
Transparency Mapping 
 
X 
X 
X 
X 
X 
X 
X 
Examination of AK 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events3 
 
X 
X 
X 
X 
X 
X 
X 
End of Study 
 
 
 
 
 
 
 
 X4 
1 
History includes all events before initiation of SOR007 treatment. 
2 
For Day 1, PK samples will be collected at 1 h, 2 h, 4 h, and 6 h post application first daily application. For Days 8, 15, and 21, PK samples will be collected prior to daily application. For Day 28, PK 
samples will be collected prior to final application and 1 h, 2 h, 4 h, 6 h and 12 h post first daily application. For Days 43 and 56, PK samples will be collected at the beginning of the visit. PK 
samples within the first 4 hours will allow for a 10-minute window around the samples. The remaining samples within the first 24 hours will allow for a 30-minute window. 
3 
Adverse event determination will start immediately following initiation of study treatment.  
4 
AEs and concomitant medications at the Week 4 follow-up that are still active will be followed.

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7.4 
JUSTIFICATION FOR SENSITIVE PROCEDURES 
Not applicable. 
7.5 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES  
All concomitant prescription medications taken during study participation will be recorded on the case report 
forms (eCRFs). For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the eCRF are concomitant prescription 
medications, over-the-counter medications, and non-prescription medications. 
7.6 
PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES  
Not applicable. 
7.7 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
Use of concomitant chemotherapy (other than the protocol specified agents), immunotherapy, or radiation 
therapy, at any time prior to end of study is prohibited. 
Although no interaction studies have been conducted using SOR007, according to the Taxol Package Insert, 
paclitaxel is metabolized by cytochrome P450 isozymes CYP2C8 and CYP3A4. Thus, there is a potential for drug 
interactions with concomitantly administered substrates (e.g., repaglinide and rosiglitazone), inhibitors (e.g., 
gemfibrozil), and inducers (e.g., rifampin) of CYP2C8. There is also the potential for paclitaxel to interact 
pharmacokinetically with CYP3A4 substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, 
sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, 
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and 
carbamazepine). Use of prohibited medication is only of concern in the target AK lesion field.  
 
7.8 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES  
Not applicable. 
7.9 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES  
Not applicable. 
7.10 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE  
Not applicable. 
8 
ASSESSMENT OF SAFETY 
 

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8.1 
SPECIFICATION OF SAFETY PARAMETERS 
Safety assessments being conducted in this study include: 
• 
AE, collected at all study visits from the time of dosing 
• 
Laboratory findings 
• 
Changes in concomitant medications and 
• 
Findings from dermatological examinations. 
Safety will be reviewed by the Medical Monitor in an ongoing manner via the EDC system, and details will be 
confirmed at routine on-site monitoring visits. 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended change in structure, function, signs, or symptoms 
temporally associated with the use of a medicinal product, whether or not related to the product. Undesirable 
changes in laboratory values should not be considered AEs unless they are considered symptomatic of a clinical 
condition or diagnosis, are evaluated as clinically significant or require therapy. Worsening of a pre-existing 
condition is also considered an AE as is the discovery of an abnormal finding during physical exam that was not 
included in the medical history. Clinical conditions attributable to disease progression will be considered AEs and 
reported on the eCRF. 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
A Serious Adverse Event (SAE) is any adverse event that meets at least one of following criteria: 
• 
Is fatal; 
• 
Is life threatening, meaning the subject was, in the view of the Investigator, at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more serious 
form or progressed, might have caused death; 
• 
Is a persistent or significant disability or incapacity; 
• 
Requires or prolongs inpatient hospitalization. Inpatient hospitalization will be considered a 
hospitalization that is longer than 24 hours, or a hospitalization that requires an intervention to treat 
emergent symptomatology (non-diagnostic); 
• 
Is a congenital anomaly or birth defect; 
• 
Other important medical events may be considered a serious adverse experience when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes as listed in this definition. 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
As this is a Phase 2 study all unanticipated problems will be captured as either AEs or SAEs and will be defined and 
reported accordingly. 

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8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
Signs and symptoms will be graded by the Investigator as mild, moderate, severe, or life threatening according to 
the following definitions: 
• 
Mild:  Causing no limitation of usual activity 
• 
Moderate:  Causing some limitations of usual activities 
• 
Severe:  Causing inability to carry out usual activities 
• 
Life Threatening:  Subject was at immediate risk of death from the event 
• 
Fatal:  Death related to the event. 
Toxicities should be evaluated according to the NCI CTCAE, version 4.0. 
https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf    
Toxicity grades should be recorded as: 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Life Threatening, 5 = Fatal. 
8.2.2 RELATIONSHIP TO STUDY AGENT 
Events will be considered drug-related if classified by the Investigator as possible, probable, or definite.  
Association of events to the study drug will be made using the following definitions: 
• 
No relationship to study drug:  the event is not associated with study drug. 
• 
Possibly related to study drug:  the event follows a reasonable temporal association with the study drug 
administration, however could have been produced by the subject’s clinical condition or other therapy. 
• 
Probably related to study drug:  the event follows a) a reasonable temporal association with the study 
drug administration, but b) abates upon discontinuation of study drug and c) cannot be explained by the 
subject’s clinical condition or other therapy.  
• 
Definitely related to study drug:  the event: a) follows a reasonable temporal association with the study 
drug administration, but b) abates upon discontinuation of study drug, c) cannot be explained by the 
subject’s clinical condition or other therapy, and d) reappears on re-exposure to study drug. 
8.2.3 EXPECTEDNESS  
Sponsor will be responsible for determining whether an AE is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk information previously 
described for the study agent, in the protocol and within the Investigator’s Brochure. 

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8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
AE should be followed until resolved, stabilized or, if ongoing at End-of-Study (study-related AEs only), for a 
minimum of 30 days following the termination of the subject’s participation from the study for any reason. 
Subjects will be required to spontaneously report any AE. Study personnel will ask open-ended questions to obtain 
information about AEs at every visit. Date and time of onset and resolution (if applicable) of the AE will be 
documented. 
All AEs and SAEs must be followed until the event resolves or, in the opinion of the Investigator, becomes stable.  
The sponsor will report any serious, unexpected and drug-related AE to applicable regulatory agencies and make 
these reports available to the investigative sites. The Investigator must promptly inform the IRB of such events and 
retain a copy of the notification in the site’s regulatory binder. 
8.4 
REPORTING PROCEDURES 
 
8.4.1 ADVERSE EVENT REPORTING  
All AE (whether or not attributable to the investigational agent) occurring during the study observed by the 
Investigator or reported by the subject will be recorded on the eCRF. The following information will be recorded 
for all AE: 
• 
Name of condition/diagnosis/description 
• 
Onset and resolution dates 
• 
Severity 
• 
Relationship to Investigational Agent 
• 
Action taken 
• 
Seriousness  
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
All SAEs, including death, due to any cause which occurs during this study between the period of dose 
administration and end of study (occurring 28 days after last application), whether or not expected and regardless 
of relationship to study drug, must be reported to the Medical Monitor immediately upon discovery of the event, 
using the SAE reporting form, by fax and, if necessary, by phone to: 
Antony Verco, MD 
Medical Monitor 
Email: tony.verco@usbiotest.com 
Phone: 805-762-4615 
Fax: 805-980-4196 
 
24-hour Emergency Contacts: 
Gere diZerega, MD 
or 
Antony Verco, MD 
 
Medical Director 
 
Medical Monitor 
 
805-630-2800  
 
805-762-4615 
The sponsor will advise the Investigator regarding the nature of any further information or documentation that is 
required. The Investigator should provide the following documentation at the time of notification if available: 

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• 
SAE Report Form; 
• 
Concomitant and support medication pages; 
• 
Relevant diagnostic reports; 
• 
Relevant laboratory reports; 
• 
Admission Notes; 
• 
Hospital discharge summary (when available). 
8.4.3 UNANTICIPATED PROBLEM REPORTING  
 
Incidents or events that occur during the conduct of the study, meeting the criteria for an AE or SAE, will be 
captured in the source documents and in the EDC, and in the case of an SAE also on the formal reporting form 
designed to capture the required information. Reporting of these events will be in accordance with the rules 
around AE and SAE reporting described in the protocol, including notification of the IRB and/or the FDA as 
required. 
 
8.4.4 EVENTS OF SPECIAL INTEREST  
Of particular interest will be signs of local toxicity; persistent erythema, ulceration, excessive pruritus. Additionally, 
systemic toxicity (i.e. peripheral neuropathy, neutropenic fever, excessive bleeding) due to paclitaxel exposure will 
be monitored; this is not expected and is unlikely due to the mode of administration and dose levels. 
8.4.5 REPORTING OF PREGNANCY  
Any pregnancy occurring in a subject during the study duration must be reported to US Biotest as soon as the 
Investigator is aware of it. The pregnancy will not be considered an SAE; however, information on these 
pregnancies will be collected and followed for the outcome of the pregnancy and the health of the newborn. 
Any pregnancy complication or premature terminations including miscarriage, spontaneous abortion, or elective 
termination of a pregnancy for medical reasons will be reported as an SAE, as described in Section 8.4.2. Should 
the pregnancy result in a congenital anomaly or birth defect, a separate SAE report must be submitted. 
Furthermore, all neonatal deaths that occur within 30 days of the birth should be reported as SAEs, without regard 
to causality. In addition, any infant death that occurs after the 30-day reporting period that the Investigator 
suspects is related to the exposure to the study treatment should also be reported. 
8.5 
STUDY HALTING RULES  
This study is a dose escalation study, and dose escalation will be determined following review of all safety and 
tolerability data of a cohort by the Medical Monitor. Following review, the study may be terminated. 
The Medical Monitor may determine if it is acceptable to proceed with an increased dose in the eight subjects of 
the next cohort; or they may determine that the safety and tolerability profiles are not acceptable and may stop 
the study. 
The sponsor is responsible for notifying the FDA of any temporary halts to the study or when a study is terminated; 
the Investigator will be required to notify the IRB accordingly.  

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8.6 
SAFETY OVERSIGHT 
Safety will be overseen by the Medical Monitor.  
All subject study data will be captured in an EDC system, allowing real-time access to ongoing safety and 
tolerability data. Summary tables of safety information will be reviewed by the Medical Monitor prior to dose 
escalation in a new cohort. A report will be generated outlining any safety concerns from the data available for 
review in the EDC. 
In the event the Medical Monitor has any concerns or sees any safety trends emerging during his ongoing reviews 
he will bring it to the immediate attention of the Medical Director and the Principal Investigator.  
9 
CLINICAL MONITORING 
US Biotest monitors, or monitors designated by US Biotest, will conduct scheduled site visits to the investigational 
centers for the purposes of monitoring the study. The Investigator agrees to allow these monitors, and other 
authorized sponsor personnel or designees, access to the subject’s medical records, regulatory binder, study 
binder, eCRFs, and source documents as needed to assure the conduct of the study was within compliance. In 
addition, the FDA or other government agencies may request an inspection following notification to the site. In 
such an event, the Investigator agrees to notify the sponsor immediately of the request, and will allow sponsor and 
inspectors to review records. 
US Biotest will conduct a Site Initiation Visit to provide the Investigator and their staff with a comprehensive 
overview of the protocol and study procedures and to review mutual obligations and requirements of regulatory 
authorities. A regulatory file or binder containing required documentation will be kept at the site for reference and 
inspection. 
Routine monitoring visits will be made to assure compliance with the study protocol, to review and collect the 
subject’s eCRF and compare with source documents, to ensure adequate records of clinical supplies are 
maintained, and to assess the continued suitability of the investigational site. On completion of the study, the 
monitor will make a final assessment of the conduct of the study and inventory all clinical supplies to be returned 
to US Biotest. 
 
10 
STATISTICAL CONSIDERATIONS   
 
10.1 
STATISTICAL AND ANALYTICAL PLANS 
A formal Statistical Analysis Plan (SAP) will be prepared for this trial, and the SAP will be signed off prior to study 
database lock. 
 
 

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10.2 
STATISTICAL HYPOTHESES 
 No inferential analyses are proposed; thus, no hypotheses are stated. 
10.3 
ANALYSIS DATASETS 
All subjects who receive treatment will be included in the outcome presentations. 
10.4 
DESCRIPTION OF STATISTICAL METHODS 
 
10.4.1 GENERAL APPROACH 
In this Phase 2 dose escalation trial, the focus will be on providing descriptive statistical summaries including tables 
and graphs for each of the dose groups. The clinical/medical review of these data will determine if there are any 
issues with toxicity that could be associated with dose and if there is any effect of the treatments on the AK 
lesions.  
10.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
The primary objective of this study is to evaluate the safety and tolerability of four doses of topical SOR007 
ointment (concentrations of 1.23, 2.47, 8.23, and 16.46 mg/mL) applied to target AK lesion test field on subjects 
diagnosed with AK. 
The adverse events reported will be coded in MedDRA and summarized by System Organ Class (SOC) and Preferred 
Term (PT) for each of the dose groups. Where possible and relevant, these will also be subset temporally by date 
and time of onset (e.g. first 24 hours, up to Day 7); the details of the timeframes will be established medically and 
presented in the SAP. Events reported as Grade 3 or greater on the CTCAE v4.0 (Appendix A) and those that lead to 
trial discontinuation will be noted. Any serious AEs and any deaths will be summarized separately. 
The laboratory analyses will be presented in summary tables with changes from screening. By applying the normal 
ranges (high, normal and low) shift tables will be generated. Values which are noted by the investigator to be 
abnormal and clinically relevant will be summarized separately as will any analytes where the shift in category is 
greater than two (e.g. high to low or low to high). The SAP may capture medically relevant changes (e.g. 3 x the 
normal range) and analytes which meet this criterion will also be presented separately. 
Vital signs (blood pressure, heart rate, temperature), as well as changes from screening, will be summarized for 
each visit. Graphical displays may be generated to illustrate the changes. 
LSR results (Grade 0-4, or Present/Not Present) will be summarized and presented by visit for each evaluation 
category (erythema, crusting, swelling, vesiculation/postulation, erosion/ulceration, hyperpigmentation, and 
hypopigmentation).  
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
To evaluate the preliminary efficacy of SOR007 on AK lesions. This will be reported from data collected from the 
number and sizes of AK lesions, and will be summarized by visit and dose group 

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To address the secondary objective of the concentration of paclitaxel in the systemic circulation post-topical 
application, the pharmacokinetic (PK) samples taken on Days 1, 8, 15, 21, 28, 43, and 56. If some concentration 
data is above the detectable limit and can be reported numerically, this data will be tabulated and graphed for 
individuals and by dose group.  
10.4.4 SAFETY ANALYSES 
 
All safety analyses will be presented as part of the primary endpoint analysis. 
10.4.5 ADHERENCE AND RETENTION ANALYSES 
 All subjects who are enrolled and treated in the trial will be accounted for. Subjects terminating early will be noted 
and the reasons provided. 
10.4.6  BASELINE DESCRIPTIVE STATISTICS 
Complete demographic, medical history (coded in MedDRA) and disease history will be summarized for each of the 
dose groups. 
10.4.7 PLANNED INTERIM ANALYSES  
An interim analysis is not planned 
10.4.7.1 
SAFETY REVIEW 
Not applicable. 
10.4.7.2 
EFFICACY REVIEW 
Assessment will be conducted to provide preliminary determination of the efficacy of topical SOR007 Ointment 
applied to AK lesions. Details are included in 10.4.3 above. 
10.4.7 ADDITIONAL SUB-GROUP ANALYSES 
Not applicable. 
10.4.9 MULTIPLE COMPARISON/MULTIPLICITY 
Not applicable. 
10.4.10 
TABULATION OF INDIVIDUAL RESPONSE DATA 
All data collected in the trial and any calculated outcomes derived from this data will, at a minimum, be listed with 
the dose group, subject identifier and a timepoint, if relevant. The organization of the listings will support the 
writing of the Clinical Study Report (CSR) as outlined in the ICH E3 guidelines. 
10.4.11 
EXPLORATORY ANALYSES 
Not applicable.  

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10.4.12 
CONCOMITANT MEDICATION 
All medication taken during the trial will be, at a minimum, listed with the study date start and stop. For this small 
clinical trial, the medications will not be coded using the WHO Drug Dictionary. 
10.5 
SAMPLE SIZE 
Up to 32 subjects 
10.6 
MEASURES TO MINIMIZE BIAS 
 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
Within each cohort (dose group), subjects will be randomized to receive either SOR007 or vehicle, in a 3:1 ratio.  
SOR007 is presented as an off-white ointment, provided in a sealed, 15 g laminate tube.  The SOR007  and vehicle 
tubes will be identical in appearance. 
10.6.2 EVALUATION OF SUCCESS OF BLINDING  
Not applicable. 
10.6.3 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
Study blind will not be broken until the database has been locked for final data analysis, unless in the case of 
medical emergency.  Tamper evident sealed envelopes with code break information will be included with the 
product shipment.  These envelopes should be filed securely and only accessed in an emergency situation.   
 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
An eCRF is required and must be completed for each consenting and enrolled subject by qualified and authorized 
personnel. Subjects who fail the Screening assessments will not have an eCRF. All data in the eCRF must reflect the 
corresponding source document. Any corrections to entries made on the eCRF must be documented in a valid 
audit trail. Only data required by the protocol for the purposes of the study should be collected within the EDC. 
The Investigator must maintain adequate and accurate source documents on which the eCRFs for each subject are 
based. They will be separate and distinct from the eCRFs. These records should include detailed notes on: 
• 
The medical history prior to the subject’s involvement in the study; 
• 
Date of informed consent; 
• 
The basic identifying information that links the subject’s medical record with the eCRFs; 
• 
The results of all diagnostic tests performed, diagnoses made, therapy provided, and any other data on 
the condition of the subject; 
• 
The medical condition during the subject’s involvement in the study; 
• 
All AEs; 

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• 
The subject’s exposure to the study medication; 
• 
The subject’s exposure to any concomitant therapy; 
• 
All relevant observations and data on the condition of the subject throughout the trial; 
• 
Justification for all entries in the subject’s eCRF.  
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
Data required by the protocol will be collected and entered into a validated data management system that is 
compliant with all regulatory requirements. The eCRF is an electronic document designed to record all of the 
protocol-required information to be reported to the Sponsor on each study subject. 
Data recording must follow the instructions described in the CRF Completion Guidelines. The PI has ultimate 
responsibility for the collection and reporting of all clinical data entered on the eCRF. The PI or designee, as 
identified on Form FDA 1572, must electronically sign the completed eCRF for each participating subject to attest 
to their accuracy, authenticity, and completeness. 
All software applications used in the collection of data will be properly validated following standard computer 
system validation that is compliant with all regulatory requirements. 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
 
13.1 
ETHICAL STANDARD  
The study will be conducted in accordance with the ethical principles of the Declaration of Helsinki. Sponsor and 
Investigator will comply with their responsibilities as defined in 21 CFR 312.50-312.70. 
13.2 
INSTITUTIONAL REVIEW BOARD  
Before the start of the study, the study protocol, informed consent form and/or other appropriate documents will 
be submitted to the IRB and/or the authorities, in accordance with local legal requirements. It is the responsibility 
of the Investigator to assure that all aspects of the IRB review are conducted in accordance with current 
regulations. US Biotest and the Investigator must inform each other in writing that all ethical and legal 
requirements have been met before the first subject is enrolled in the study. 
Amendments to the protocol will be subject to the same requirements as the original protocol. All changes to the 
consent form will be IRB approved; a determination will be made regarding whether previously consented 
participants need to be re-consented. 
13.3 
INFORMED CONSENT PROCESS  
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Subjects being considered for participation in this study will be provided an Informed Consent Form (ICF) to read 
and sign before being permitted to participate. The ICF will describe the study agent and any prior findings from 

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previous studies, it will describe the study procedures including the timing of study clinic visits and their 
responsibilities to  adhere to those timelines, any risks which may be associated with the study agent or the 
procedures being carried out in the study, and all other items required under 21 CFR part 50.25.  
Subjects will be required to provide signed consent prior to any study-related procedures are carried out. The 
Investigator is required to document the process for obtaining informed consent in the source notes. 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
The Investigator will obtain informed consent from each subject enrolled in the study, in accordance with the U.S. 
Food and Drug Administration (FDA) regulations 21 CFR 50.20 - 50.27 and the laws and regulations of the state in 
which the investigation is being conducted. The IRB must approve ICF to be used by the Investigator. The 
Investigator will provide the sponsor with a copy of the written approval generated by the IRB or Ethics Committee 
before the Investigator will be permitted to enroll subjects into the study. 
It is the responsibility of the Investigator to ensure that informed consent is obtained from the subject or his/her 
guardian or legal representative before any activity or treatment is undertaken which is not part of routine care. 
This includes, but is not limited to, the performance of diagnostic or therapeutic procedures and the 
administration of the first dose of study medication. The draft version of the informed consent document will be 
modified by each site and reviewed and approved in writing by US Biotest prior to submission to the IRB. 
Should a protocol amendment be made, the subject consent form may be revised to reflect the changes of the 
protocol. If the consent form is revised, it is the responsibility of the Investigator to ensure that an amended 
consent is approved by the IRB and signed by all subjects currently on study as well as those subsequently entered 
in the study. 
The Investigator will not undertake any investigation specifically required only for the clinical study until valid 
consent has been obtained. The terms of the consent and when it was obtained must also be documented in the 
eCRF. The original, signed informed consent document must be maintained on file at the study site and be made 
available for review during monitoring visits and site audits. 
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY  
All local legal requirements regarding data protection will be enforced. All study findings and documents will be 
regarded as confidential. The Investigator and members of his/her research team must not disclose such 
information without prior written approval from US Biotest.  
The anonymity of participating subjects must be maintained to the extent required by law. Throughout 
documentation and evaluation, the subjects will be identified on eCRFs and other documents submitted to US 
Biotest by their initials, birth date, and their subject number. The subjects will be told that all study findings will be 
stored and handled in strictest confidence, according to legal requirements, but will be informed that authorized 
research Investigators and agents of the FDA, the NCI, and authorized personnel of US Biotest have the right to 
inspect their medical records. 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS OR DATA 

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Samples and data collected under this protocol are specifically for use in the evaluation and analyses being 
conducted in the study. Samples will not be available for purposes other than indicated within this protocol, and 
no genetic testing will be performed. 
Access to stored samples will be limited to personal authorized to have access at the site prior to shipping to the 
laboratories for analysis/assessment. Samples will be stored using codes assigned by the Sponsor or as required by 
the clinical laboratories.  
Samples will only be retained until analysis is complete, following which samples will be disposed of according to 
the laboratory SOPs. No samples will be retained for any future use. 
Data will be kept in password-protected computers. Only Investigators and those delegated responsibility on the 
Delegation of Authority Log will have access to the samples and data. 
13.5 
FUTURE USE OF STORED SPECIMENS  
 
Not applicable. 
14 
DATA HANDLING AND RECORD KEEPING  
 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. The 
Investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported.  
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of data. 
Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, cross out the 
original entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION 
FLUID OR TAPE ON THE ORIGINAL. 
Source documents will be maintained for recording data for each participant enrolled in the study. Data reported 
in the eCRF derived from source documents should be consistent with the source documents, or the discrepancies 
should be explained and captured in a progress note and maintained in the participant’s official electronic study 
record. 
Data recording must follow the instructions described in the eCRF Completion Guidelines. The PI has ultimate 
responsibility for the collection and reporting of all clinical data entered on the eCRF. The PI or designee, as 
identified on the Delegation of Responsibilities Log (and included on Form FDA 1572), must electronically sign the 
completed eCRF to attest to their accuracy, authenticity, and completeness. 
The database will be locked when all outstanding queries have been addressed, all agreed to data is marked as 
source verified, and the PI has signed off on the eCRF contents. 

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14.2 
STUDY RECORDS RETENTION  
The Investigator must retain a copy of all study documents in accordance with the FDA or local regulations, 
whichever are the more stringent. 
The Investigator must maintain study documents: 
• 
For a minimum of two years following the date the marketing application (NDA) is approved for the 
indication for which the drug was investigated for;  
• 
For a minimum of two years following the release date of the final report, if no marketing application is 
to be filed, or if the marketing application is not approved for the indication of which the drug was 
investigated or is discontinued and the FDA has been notified; or, 
• 
For a minimum of 15 years after the completion or discontinuation of the study to be filed in support of 
the registration in the European Union. 
If the Investigator relocates, retires or withdraws from the study for any reason, the study records may be 
transferred to an acceptable designee, such as another Investigator, another institution, or the sponsor. The 
Investigator must obtain the sponsor’s written permission before transferring or disposing of any records. 
14.3 
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, Good Clinical Practice (GCP), FDA or IRB 
requirements. The noncompliance may be either on the part of the participant, the Investigator, or the study site 
staff. As a result of deviations, corrective actions are to be developed by the site and implemented promptly. 
These practices are consistent with ICH E6:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
It is the responsibility of the site to use continuous vigilance to identify and report deviations as soon as possible 
after occurrence and identification of the protocol deviation. All deviations must be addressed in study source 
documents, reported to the Sponsor and to the data Management group.  
The noncompliance may be either on the part of the participant, the Investigator, or the study site staff. As a result 
of deviations, corrective actions are to be developed by the site and implemented promptly.  
Protocol deviations must be sent to the local IRB per their guidelines. The site PI/study staff is responsible for 
knowing and adhering to their IRB requirements.  
Serious non-compliance on the part of the site, and an inability of the Sponsor to bring the site back into 
compliance, will be reported to the FDA in accordance with their requirements.  
14.4 
PUBLICATION AND DATA SHARING POLICY 
By signing the study protocol, the Investigator agrees with the use of results of the study for the purposes of 
national and international registration, publication, and information for medical and pharmaceutical professionals. 

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If necessary, the authorities will be notified of the Investigator's name, address, qualifications, and extent of 
involvement. The sponsor will prepare an integrated clinical/statistical report. Publication/presentation of data is 
not allowed without explicit permission from US Biotest. Submission of data for publication/presentation will be 
coordinated and approved by US Biotest in collaboration with the Investigator. 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical trials 
registration policy as a condition for publication. The ICMJE defines a clinical trial as any research project that 
prospectively assigns human subjects to intervention or concurrent comparison or control groups to study the 
cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include 
drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. Health outcomes 
include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic 
measures and AE. The ICMJE policy, and the Section 801 of the Food and Drug Administration Amendments Act of 
2007, requires that all clinical trials be registered in a public trials registry such as ClinicalTrials.gov, which is 
sponsored by the National Library of Medicine. Data entered to the ClinicalTrials.gov website will be in accordance 
with the FDA requirements for this registration and for publication of study results on that site. 
15 
STUDY ADMINISTRATION 
 
15.1 
STUDY LEADERSHIP 
The study will be overseen by the Study Manager who will be responsible, together with the Investigator, for 
tracking enrolment, timelines, and deliverables, and other study-related performance. 
All questions regarding the enrollment of subjects, regulatory requirements for the conduct of the study, safety 
reporting, or study conduct should be addressed to the Study Manager or Site Monitor designated by the sponsor. 
Contact information for the sponsor is provided near the beginning of this protocol and will be provided to the 
Investigator in separate study documents. 
 
16 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is 
critical and therefore any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the trial. As required by the FDA, a Financial Disclosure Form will be completed by each person 
noted on the FDA Form 1572 for this study at the site, the original will be filed in the TMF and a copy will remain in 
the site’s regulatory binder. 
17  
LIABILITY AND INSURANCE  
The sponsor will take out reasonable third-party liability insurance coverage in accordance with all local legal 
requirements. This insurance will cover all parties involved in the trial including, but not necessarily limited to, the 
principal Investigator, clinical trial site, and subjects.  

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18  
LITERATURE REFERENCES  
Finlay, A. Y., Edwards, P. H., Harding, K. G. (1989) “Fingertip unit” in dermatology. Lancet, 15(8655), 155. 
Fuchs, A., Marmur, E. (2007) The kinetics of skin cancer: progression of actinic keratosis to squamous cell 
carcinoma. Journal of Dermatologic Surgery and Oncology, 33(9), 1099-1101. 
Lewin Group, Inc. (2005) The burden of skin diseases. The Society for Investigative Dermatology and The American 
Academy of Dermatology Association. 
Long, C. C., Finlay, A. Y., Averill, R. W. (1992) The rule of hand: 4 hand areas = 2 FTU = 1 g. Archives of Dermatology, 
128, 1129-1130.