A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2a Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of NFX-179 Gel in Subjects With Cutaneous Neurofibromas
Phase: PHASE2
Conditions: Neurofibromatosis 1, Cutaneous Neurofibroma
Sponsor: NFlection Therapeutics, Inc.

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
Page 1 of 7 
 
 
Supersedes: 17-JUL-2020 
CLINICAL STUDY PROTOCOL AMENDMENT 
 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2a 
Study to Determine Safety, Tolerability, Pharmacokinetics, and 
Pharmacodynamic Activity of NFX-179 Gel in Subjects with Cutaneous 
Neurofibromas 
 
Protocol No. NFX-179-NF1-201 
Protocol/Amendment Date: 20-JUL-2020 
Amendment No.: 1 
Supersedes: N/A 
Sponsor: NFlection Therapeutics  
714 Woodcrest Road,  
Wayne, PA 19087  
United States 
Medical Monitor: Guy Webster, M.D. Ph.D. 
24-hour telephone: (302) 559-8684 
Email: GWebster@Nflectionrx.com 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document contains proprietary and confidential information of NFlection Therapeutics. Acceptance of this 
document constitutes agreement by the recipient that no previously unpublished information contained herein 
will be published or disclosed without the prior written approval of NFlection Therapeutics with the exception 
that this document may be disclosed to study staff under your supervision who need to know the contents for 
conducting the study and to appropriate Institutional Review Boards /Ethics Committees under the condition that 
the staff have agreed to keep this information confidential. The foregoing shall not apply to disclosure required 
by governmental regulations or laws, however, NFlection Therapeutics shall be promptly notified of any such 
disclosure.
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
Page 2 of 7 
 
 
Supersedes: 17-JUL-2020 
PROTOCOL AMENDMENT INVESTIGATOR SIGNATURE PAGE 
Protocol Number: NFX-179-NF1-201 
Amendment Number: 1 
 
INVESTIGATOR COMMITMENT: 
I will provide copies of the protocol, any subsequent protocol amendments and access to all 
information provided by NFlection to the investigational center staff under my supervision. I 
will discuss this material with them to ensure that they are fully informed about the 
Investigational Medicinal Product and the study protocol. 
I agree to conduct this clinical study according to the attached protocol, except when mutually 
agreed to with NFlection in writing. I also agree to conduct this study in compliance with all 
local regulatory requirements, Good Clinical Practices, as well as with the requirements of the 
appropriate Institutional Review Board(s) /Ethics Committee(s) and any other Institutional 
requirements. 
 
 
 
Printed Name of Investigator 
 
 
 
Signature of Investigator 
 
 
 
Date 
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
Page 4 of 7 
 
 
Supersedes: 17-JUL-2020 
TABLE OF CONTENTS 
 
PROTOCOL AMENDMENT INVESTIGATOR SIGNATURE PAGE .............................. 2 
PROTOCOL Amendment APPROVAL PAGE ...................................................................... 3 
TABLE OF CONTENTS ........................................................................................................... 4 
1 
AMENDMENT HISTORY ............................................................................................ 5 
2 
AMENDMENT SUMMARY ......................................................................................... 5 
3 
AMENDMENT RATIONALE ...................................................................................... 5 
4 
PROTOCOL CHANGES............................................................................................... 6 
 
 
 
 
 
 
 
 
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
Page 5 of 7 
 
 
Supersedes: 17-JUL-2020 
1 
AMENDMENT HISTORY 
Protocol footer date: 25-MAY-2020 
Previous amendments: None 
 
 
2 
AMENDMENT SUMMARY 
The following sections of the NFX-179-NF1-201 protocol with footer date 15-MAY-2020 and 
with a final NFlection Therapeutics approval signature date of 27-MAY-2020 are amended: 
 PROTOCOL APPROVAL PAGE (page 3 of 77) 
 Section 4.8 Subject discontinuation from the study 
 Section 5.2.3 Visits 3 and 4/Days 8 and 15 (QD treatment) 
 Section 5.3 Study cNF tumor identification 
 Section 6.2.2 Target cNF ultrasounds 
 Section 6.3.1 Demographics. 
 
 
3 
AMENDMENT RATIONALE 
These protocol changes are made to: 
 Correct a typographic error to the protocol number on the PROTOCOL APPROAL PAGE 
 Respond to recommendations from the Food and Drug Administration; changes to section 
4.8 
 Correct an error which instructs the investigator to take standardized photographs at Visits 
3 and 4; changes to protocol section 5.2.3 
 Add the requirement that for each subject Target cNF Tumor number 5 be on the face; 
changes to protocol section 5.3 
 Update the description of the high frequency ultrasound equipment that may be used; 
changes to section 6.2.2 
 Correct a typographic error; changes to section 6.3.1. 
 
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
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Supersedes: 17-JUL-2020 
4 
PROTOCOL CHANGES 
PROTOCOL APPROVAL PAGE (page 3 of 77): 
Previous protocol number: 
NFX-179-NF-201. 
 
Changed protocol number: 
NFX-179-NF1-201. 
 
 
Section 4.8 Subject discontinuation from the study: 
Previous paragraph 2: 
The investigator may remove a subject from the study if, in the investigator's opinion, it is not in 
the best interest of the subject to continue the study. Examples of other reasons subjects may be 
discontinued from the study are a change in compliance with an inclusion or exclusion criterion, 
occurrence of AEs, occurrence of pregnancy or use of a prohibited therapy. Notification of 
discontinuation will immediately (within 24 hours) be made to the NFlection study monitor.  
 
Changed paragraph 2: 
The investigator will remove a subject from the study if, in the investigator's opinion, it is not in 
the best interest of the subject to continue the study. The investigator must remove a subject from 
the study if the subject experiences: 
 A Serious Adverse Event the investigator defines as related to the study medication, 
regardless of the intensity of the event 
 A non-serious adverse event the investigator defines as related to study medication that 
has a severity of severe and requires treatment to resolve.  
 
Examples of other reasons subjects may be discontinued from the study are a change in 
compliance with an inclusion or exclusion criterion, occurrence of AEs, occurrence of pregnancy 
or use of a prohibited therapy. Notification of discontinuation will immediately (within 24 hours) 
be made to the NFlection study monitor. 
 
 
Section 5.2.3 Visits 3 and 4/Days 8 and 15 (QD treatment): 
Previous procedure 7: 
Take standardized color photographs of each Target cNF Tumor. 
 
Changed procedure 7: 
Procedure 7 is deleted. 
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 1 
Date: 20-JUL-2020 
 
 
Page 7 of 7 
 
 
Supersedes: 17-JUL-2020 
Section 5.3 Study cNF tumor identification: 
Previous paragraph 3 major bullet 3: 
 Face: 
o Vertically from the mandibular ridge to the hairline (for subjects with a receding 
hair the hairline is defined by a vertical lie drawn coronally from tragus to tragus) 
o Horizontally from tragus to tragus, excluding the eyelids and areas within 5mm of 
the orbital rim. 
Changed paragraph 3 major bullet 3: 
 Face (Target cNF Tumor #5 must be on the face): 
o Vertically from the mandibular ridge to the hairline (for subjects with a receding 
hair the hairline is defined by a vertical lie drawn coronally from tragus to tragus) 
o Horizontally from tragus to tragus, excluding the eyelids and areas within 5mm of 
the orbital rim. 
  
Previous paragraph 5 bullet 5: 
 Target cNF Tumor #5/green ID stickers 
  
Changed paragraph 5 bullet 5: 
 Target cNF Tumor #5/green ID stickers (Target cNF Tumor #5 must be on the face). 
 
 
Section 6.2.2 Target cNF ultrasounds: 
Previous paragraph 2: 
The HFUS results will be used to determine the volume of the Target cNF. HFUS imaging 
will be performed using the Vevo3100 System.  
 
Changed paragraph 2: 
The HFUS results will be used to determine the volume of the Target cNF. HFUS imaging 
will be performed using an appropriate HFUS system (e.g., Vevo3100, GE Logiq E, etc.).  
 
 
Section 6.3.1 Demographics: 
Previous paragraph 1 sentence 3: 
In addition, medical and surgical history, EN history, and concomitant illness(es) will be 
recorded.  
 
Changed paragraph 1 sentence 3: 
In addition, medical and surgical history, NF1 history, and concomitant illness(es) will be 
recorded.