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. 3 
Date: 01-APR-2021 
 
 
Page 1 of 5 
 
 
Supersedes: NEW 
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: 01-APR-2021 
Amendment No.: 3 
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document constitutes agreement by the recipient that no previously unpublished information contained herein 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. 3 
Date: 01-APR-2021 
 
 
Page 2 of 5 
 
 
Supersedes: NEW 
PROTOCOL AMENDMENT INVESTIGATOR SIGNATURE PAGE 
Protocol Number: NFX-179-NF1-201 
Amendment Number: 3 
 
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 
 
 
 

PROTOCOL AMENDMENT APPROVAL PAGE
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Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 3 
Date: 01-APR-2021 
 
 
Page 4 of 5 
 
 
Supersedes: NEW 
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............................................................................................... 5 
 
 
 
 
 
 
 
 
 
 
 

Proprietary and Confidential 
Protocol No. NFX-179-NF1-201; Amendment No. 3 
Date: 01-APR-2021 
 
 
Page 5 of 5 
 
 
Supersedes: NEW 
1 
AMENDMENT HISTORY 
Revised protocol 1 footer date: 24-JUL-2020 
Previous amendments: Amendment 2, footer date 25-MAR-2021 
 
2 
AMENDMENT SUMMARY 
The following section of the NFX-179-NF1-201 revised protocol (footer date 24-JUL-2020) as 
modified by amendment 2 (footer date 25-MAR-2021) and with a final NFlection Therapeutics 
approval signature date of 27-JUL-2020 is amended: 
 Section 8.3.3 Efficacy analyses. 
 
3 
AMENDMENT RATIONALE 
This protocol change is made to allow for Target cNF Tumors that are found not to be qualifying 
neurofibromas to be excluded from sensitivity analyses of efficacy results. 
 
4 
PROTOCOL CHANGES 
Section 8.3.3 Efficacy analyses: 
Previous paragraph 1: 
“…Tumor volume is the primary measurement of interest; however, the ruler measurements of 
tumor length and height will also be analyzed as described below.” 
 
Changed paragraph 1: 
“…Tumor volume is the primary measurement of interest; however, the ruler measurements of 
tumor length and height will also be analyzed as described below. Any Target cNF Tumors 
confirmed not to be qualifying neurofibromas based on histological evaluation of the excised 
tissue may be excluded from sensitivity analyses of efficacy results.”