A Phase I/II Study of FCX-007 (Genetically-Modified Autologous Human Dermal Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Phase: PHASE1
Conditions: Epidermolysis Bullosa Dystrophica, Recessive
Sponsor: Castle Creek Biosciences, LLC.

DocuSign Envelope ID: B18B051E-C873-4B3E-B8A5-9C3620464707 
 
 
 
 
 
 
 
 
 
 
 
FI-EB-001 
Fibrocell RDEB Phase I/II Protocol 
 
A Phase I/II Study of FCX-007 (Genetically-Modified Autologous Human Dermal 
Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa (RDEB) 
 
 
Status: 
Final 
 
Protocol Version: 
Version 8.0, 29 Oct 2019 
IND Number: 
16582 
 
Investigational Product: 
FCX-007 
 
Phase of Development: 
Phase I/II 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL MATERIAL 
This material is the property of Fibrocell Technologies and it must not be disclosed or used without written 
authorization from Fibrocell Technologies 

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Fibrocell Technologies 
 
Table of Contents 
1 
Background 12 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
1.1 
Disease Background ..........................................................................................12 
1.2 
FCX-007 Background ........................................................................................13 
2 
Rationale and Objectives ............................................................................................16 
2.1 
Rationale ...........................................................................................................16 
2.2 
Objectives ..........................................................................................................16 
3 
Experimental Plan .......................................................................................................17 
3.1 
Study Design .....................................................................................................17 
3.2 
Number of Investigative Sites .............................................................................19 
3.3 
Number and Source of Subjects ........................................................................19 
3.4 
Estimated Study Duration ..................................................................................19 
4 
Subject Eligibility.........................................................................................................20 
4.1 
Inclusion Criteria ................................................................................................20 
4.2 
Exclusion Criteria ...............................................................................................21 
5 
Subject Enrollment and Withdrawal ...........................................................................22 
5.1 
Subject Identification and Number Assignment ..................................................22 
5.2 
Concomitant Therapy and Skin Care .................................................................22 
5.3 
Withdrawal of Subjects.......................................................................................22 
6 
Investigational Product ...............................................................................................23 
6.1 
Manufacturing ....................................................................................................23 
6.2 
Labeling, Packaging, Storage and Handling.......................................................24 
7 
Study Visits 25 
7.1 
Screening Period ...............................................................................................28 
7.2 
Wound Monitoring Period ...................................................................................30 
7.3 
Visits 2 through 10 .............................................................................................31 
7.4 
Unscheduled Visits ............................................................................................37 
7.5 
Long-Term Follow-Up Period .............................................................................37 
8 
Procedures: FCX-007 Administration to Intact Skin .................................................39 
8.1 
Skin Selection ....................................................................................................39 
8.2 
Determination of the Number of Administrations ................................................39 
8.3 
Skin Markings ....................................................................................................39 
8.4 
Imaging ..............................................................................................................40 
8.5 
FCX-007 Administration to Intact Skin ................................................................40 
9 
Procedures: FCX-007 Administration to Wound(s) ...................................................41 
9.1 
Selection ............................................................................................................41 
9.2 
Treatment Assignment of Paired Wounds ..........................................................42 
9.3 
Imaging / Wound Measurement .........................................................................43 
9.4 
FCX-007 Administration .....................................................................................43 
10 
Procedures: Collection and Evaluation of Biopsies .................................................46 

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Fibrocell Technologies 
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RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
10.1 
Collection ...........................................................................................................46 
10.2 
Evaluation ..........................................................................................................47 
11 
Procedures: Safety Assessments ..............................................................................48 
11.1 
Data Safety Monitoring Board ............................................................................48 
11.2 
Medical and Medication History .........................................................................50 
11.3 
Physical Examination .........................................................................................51 
11.4 
Skin Examination ...............................................................................................51 
11.5 
Vital Signs ..........................................................................................................51 
11.6 
Laboratory Evaluations ......................................................................................52 
12 
Procedures: Optional Diagnostic Assessments .......................................................54 
12.1 
Evaluation of Diagnostic Biopsies ......................................................................54 
12.2 
Genetic Testing ..................................................................................................54 
12.3 
Autoimmune Assay ............................................................................................54 
13 
Adverse Experiences ..................................................................................................55 
13.1 
Definitions ..........................................................................................................55 
13.2 
Reporting Procedures ........................................................................................56 
14 
Statistical Considerations ...........................................................................................59 
14.1 
Number of Subjects ...........................................................................................59 
14.2 
General considerations ......................................................................................59 
14.3 
Data Management .............................................................................................59 
14.4 
Study Populations ..............................................................................................59 
14.5 
Demographic and Baseline Characteristics ........................................................60 
14.6 
Proof of Mechanism Analyses ............................................................................60 
14.7 
Safety Analyses .................................................................................................62 
14.8 
Interim Analysis..................................................................................................63 
14.9 
Handling of Missing and Incomplete Data ..........................................................63 
15 
Regulatory Obligations ...............................................................................................64 
15.1 
Informed Consent ..............................................................................................64 
15.2 
Institutional Review Board ..................................................................................64 
15.3 
Pre-Study Documentation Requirements ...........................................................65 
15.4 
Subject Confidentiality........................................................................................65 
16 
Administrative and Legal Obligations ........................................................................66 
16.1 
Protocol Amendments and Study Termination ...................................................66 
16.2 
Study Documentation and Storage ....................................................................66 
16.3 
Study Monitoring and Data Collection ................................................................67 
16.4 
Publication Policy ...............................................................................................67 
17 
Bibliography 68 
18 
Summary of Changes ..................................................................................................69 
Appendix A: 
Investigational Product Administration Instructions .........................72 
Appendix B: 
Biopsy Collection Procedures .............................................................74 

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Fibrocell Technologies 
Figures 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
Figure 1 – INXN-2004 Vector Map ............................................................................................14 
Figure 2 - High-Level Study Design ...........................................................................................17 
Figure 3 - Intact Skin Grid .........................................................................................................39 
Figure 4 - Wound Pairing and Selection Calculations Example .................................................42 
Figure 5 – Sample Drug Administration Preparation Wound Markings ......................................44 
Figure 6 – Example Target Wound, Injection Sites and Biopsy Locations .................................45 
Figure 7 - Photographs of Intradermally Administered Fibroblasts Cells ....................................73 
 
 
Tables 
Table 1 – FCX-007 Cell Count and Injections per Administration ..............................................23 
Table 2 - Schedule of Events ....................................................................................................26 

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Fibrocell Technologies 
 
Abbreviations 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
AEs ........................ adverse events 
ALT (SGPT) ........... alanine aminotransferase, included in metabolic panel 
AST (SGOT) .......... aspartate aminotransferase, included in metabolic panel 
BMZ ....................... basement membrane zone 
BP .......................... base pair 
C7 .......................... type VII collagen 
CBC ....................... complete blood count 
cDNA ..................... complementary deoxyribonucleic acid 
CFR ....................... Code of Federal Regulations 
CLIA ....................... Clinical Laboratory Improvement Amendments 
CM ......................... centimeter 
CMV ....................... cytomegalovirus 
COL7A1 ................. Collagen 7 gene 
cPPT ...................... central polypurine tract 
CRF ....................... case report form 
CTC ....................... Common Toxicity Criteria 
DIF ......................... direct immunofluorescence 
DMEM .................... Dulbecco’s Modified Eagle Medium 
DNA ....................... deoxyribonucleic acid 
DSMB .................... data safety monitoring board 
EB .......................... epidermolysis bullosa 
EDTA ..................... ethylenediamine tetraacetic acid 
ELISA..................... enzyme-linked immunosorbent assay 
EM ......................... electron microscopy 
FAS .......................... Full analysis set 
FACS ..................... Fluorescence-activated cell sorting 
FDA ....................... Food and Drug Administration 
GCP ....................... Good Clinical Practice 
HA .......................... hemaglutinin tag 
HDF ....................... Human Dermal Fibroblasts 
HEENT ................... head, ears, eyes, nose, throat 
Hep ........................ hepatitis 
HIPAA .................... Health Insurance Portability and Accountability Act 
HIV ......................... human immunodeficiency virus 
ICF ......................... informed consent form 
I/E .......................... inclusion / exclusion 
IEM ........................ immunoelectron microscopy 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
IF ........................... immunofluorescence 
Ig ............................ immunoglobulin 
IND ........................ Investigational New Drug application 
IP ........................... Investigational Product 
IRB ......................... Institutional Review Board 
KANr....................... kanamycin resistance 
LLN ........................ lower limit of normal 
LTFU ...................... long-term follow-up 
LTR ........................ long terminal repeat 
mAb ....................... monoclonal antibody 
MCH....................... mean corpuscular hemoglobin 
MCHC .................... mean corpuscular hemoglobin concentration 
MCV ....................... mean cell volume 
MCS ....................... multiple cloning site 
mRNA .................... messenger ribonucleic acid 
NC1 ....................... non-collagenous region 1 of the collagen 7 molecule 
NC2 ....................... non-collagenous region 2 of the collagen 7 molecule 
NCI ........................ National Cancer Institute 
NIH ........................ National Institute of Health 
OCT ....................... optimum cutting temperature compound 
PCR ....................... polymerase chain reaction 
PHI ......................... protected health information 
PI ........................... Principal Investigator 
PP .......................... per protocol 
qPCR ..................... quantitative polymerase chain reaction 
qRT-PCR ............... quantitative real time polymerase chain reaction 
RBC ....................... red blood cell count 
RCL ....................... replication competent lentivirus 
RDEB ..................... recessive dystrophic epidermolysis bullosa 
RDW ...................... red blood cell distribution width 
RNA ....................... ribonucleic acid 
SAE ....................... serious adverse event 
SAP ....................... statistical analysis plan 
SCC ....................... squamous cell carcinoma 
SIN-LV ................... self-inactivating lentivirus 
VSV-G.................... Vesicular Stomatitis Virus-G 
WBC ...................... white blood cell 
WPRE .................... Woodchuck Hepatitis Posttranscriptional Regulatory Element 
WT ......................... wild type 

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Fibrocell Technologies 
 
Protocol Synopsis 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
Title 
A Phase I/II Study of FCX-007 (Genetically-Modified Autologous Human Dermal 
Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa (RDEB) 
Statement of 
Purpose 
The purpose of this study is threefold: 
- 
To evaluate the safety of FCX-007 
- 
To evaluate C7 expression and the presence of anchoring fibrils resulting 
from FCX-007 
- 
To analyze wound healing as a result of FCX-007 administration 
 
 
Objectives 
Primary 
1) The primary objective of this protocol is to evaluate the safety of FCX-007. 
Secondary 
1) To evaluate mechanism of action of FCX-007 at visits 5 (Week 4), 6 (Week 
12), 8 (Week 25), 10 (Week 52), and unscheduled visits through the 
evaluation of skin biopsies for C7 expression and the presence of anchoring 
fibrils. 
2) To evaluate the efficacy of FCX-007 through an intra-subject paired 
analysis of target wound area at visits 5 (Week 4), 6 (Week 12), 8 (Week 
25),10 (Week 52), and unscheduled visits, comparing FCX-007 treated 
wounds to untreated wounds through investigator assessment of wound 
healing based on the digital images of wounds. 
 
Study Drugs 
Test Product: 
FCX-007 (Genetically Modified Autologous Human Dermal 
Fibroblasts) 
# of Subjects 
Up to 12 
Study Design 
This is a Phase I/II Study of FCX-007 (Genetically-Modified Autologous Human 
Dermal Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa (RDEB) being 
conducted by Fibrocell to evaluate FCX-007 in subjects with RDEB. Up to twelve 
subjects will be enrolled, up to six (6) in Phase I, and up to six (6) in Phase II. Phase 
I will enroll adult subjects only; Phase II can enroll adults and pediatric subjects 
(aged seven (7) or older). Within Phase I, subjects will be assigned to one of two 
arms: subjects with NC1+ status will be enrolled into Arm A and subjects with NC1- 
status will be enrolled into Arm B. The arms will enroll independently. 
In Phase I, the study may enroll an equivalent number of subjects to Arm A and Arm 
B (n=3 each arm). 
One administration of FCX-007 will consist of a maximum of 15 mL of FCX-007 
administered in sixty (60) 0.25 mL intradermal injections. The majority of the 
injections will be administered around the margin of target wounds and at least 6 
injections will be administered to intact skin. The Investigator will attempt to 
administer all of the 15mL of FCX-007. This will be accomplished by selecting target 
wounds that are as close as possible to 54 linear cm, leaving at least 6 
administrations for intact skin, for a total of 60 injections. 
For the wound administrations, subjects will receive FCX-007 administered 
intradermally to one, two or three paired target wounds at Visit 3 (Day 0). Subjects 
receive a second administration to wounded and/or intact skin at Visit 5 (Week 4). 
In this study, one wound in each target wound pair will be used as a control for 
efficacy and safety evaluations. FCX-007 administered wounds will be compared 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
within paired target wounds to untreated wounds. 
As there is no previous human experience with FCX-007, treatment administration 
will be staggered in two places: 
1. Between the first and second enrolled subjects in each arm. 
2. Between the third and fourth enrolled subjects in each arm. 
Proceeding to administration of FCX-007 after a stagger requires that the previous 
subject complete Week 4 evaluations and the Investigator must have received 
approval from the Data Safety Monitoring Board (DSMB) to continue the study prior 
to the next adult subject’s FCX-007 administration. 
At a minimum, FDA and DSMB approvals are required for enrollment of pediatric 
subjects. Local oversight committees may also require approval. 
Each phase of the study is divided into four (4) periods: Screening, Wound 
Monitoring, Treatment, and Long-Term Follow-Up. The Screening Period consists of 
entry criteria evaluations, the collection of one set of three 3-4 mm biopsies for FCX- 
007 manufacturing, and the identification and photography of potential target 
wounds. FCX-007 manufacturing requires about 4 months. This period is the 
Wound Monitoring Period. Subject target wounds may be imaged a minimum of two 
times (at least 4 weeks apart) during this period. The purpose of the imaging is to 
identify wounds with the most consistent wound areas that meet criteria, and to 
establish a baseline area that takes into account natural wound area variation. The 
Wound Monitoring Period is expected to have a duration of approximately four 
months; however, this period can extend beyond four months to accommodate 
patient scheduling, variations in manufacturing duration and protocol mandated 
delays (i.e. pauses due to staggered treatment). 
After FCX-007 manufacturing is complete, Fibrocell (the Sponsor) and the 
Investigator will mutually agree on the date of receipt of FCX-007. The duration of 
the Treatment Period may fluctuate between two and four days to accommodate 
subject safety and scheduling. The Treatment Period visits (Day -2 to Day 2) will be 
scheduled so that the day of dosing (Day 0) is the day of receipt of FCX-007. Prior 
to dosing, wounds are identified that meet treatment criteria based on imaging 
results obtained. Up to three pairs of target wounds may be identified for each 
subject and the Investigator will pair the target wounds according to similarity in 
wound area. 
One wound in each pair will receive FCX-007 and the other wound no treatment. 
Safety and proof of mechanism evaluations are conducted during site visits at Visits 
5 (Week 4), 6 (Week 12), 8 (Week 25) and 10 (Week 52), and unscheduled visits. 
Proof of mechanism will be monitored through assays conducted on biopsies taken 
from target wounds and areas of intact skin in which FCX-007 was administered. 
Safety is monitored throughout the study, captured during on-site visits and while 
the subject is off-site through adverse event diaries. The following assessments in 
each subject will be assessed: adverse events (AEs), physical examinations, vital 
signs, clinical laboratory evaluations (including C7 antibodies, and RCL), medical 
history, and prior/concomitant medications, as appropriate. A DSMB will periodically 
review subject safety data. 
The Long-Term Follow-Up is a 15-year period following Week 52/ET in which safety 
is monitored (including RCL testing yearly and any new malignancies to 15-years) 
at a minimum annually. If all post-treatment RCL assays are negative during the first 
year (e.g., Weeks 4, 12, 16, 25, 32, and 52), collection of the yearly follow-up 
samples will be discontinued. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
Population 
Inclusion Criteria 
1. Age 
a. Phase I: Eighteen (18) years old or older. 
b. Phase II: Seven (7) years old and older. 
2. Diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) (inclusive) 
by: 
a. Clinical diagnosis 
b. Immunofluorescence (IF) evaluation 
c. Electron microscopy (EM/IEM) evaluation 
d. Confirmation of RDEB C7 mutations in the subject 
3. NC1 Status 
a. Arm A: Positive for the NC1 domain of C7 (NC1+) as determined by 
results of genetic testing showing one or no loss of function 
mutations in exons 1-28 
b. Arm B: Negative for the NC1 domain of C7 (NC1-) as determined 
by results of genetic testing showing two loss of function mutations 
in exons 1-28) 
4. NC2 Status: negative or weakly positive for LH24 antibody staining as 
determined by immunoelectron microscopy (IEM). 
5. Subjects and guardians, who are, in the opinion of the Investigator, able to 
understand the study, co-operate with the study procedures and are willing to 
return to the clinic for all the required follow-up visits. 
Exclusion Criteria 
1. Medical instability limiting ability to travel to the investigative center. 
2. Active infection with HIV, hepatitis B or hepatitis C, as determined by 
hepatitis B surface antigen screening, detection of hepatitis C antibodies, or 
positive result of hepatitis C PCR analysis. 
3. The presence of antibodies to the basement membrane of monkey 
esophagus by indirect immunofluorescence using the subject’s serum. 
4. Evidence of systemic infection. 
5. Current evidence of metastatic squamous cell carcinoma at the site to be 
injected. 
6. Known allergy to any of the constituents of the product. 
7. Active drug or alcohol addiction. 
8. Hypersensitivity to anesthesia chosen (lidocaine/prilocaine cream, moderate 
sedation, general anesthesia). 
9. Receipt of a chemical or biological study product for the specific treatment of 
RDEB in the past six months 
10. Women who are pregnant or breast-feeding. 
11. Any clinically significant abnormal laboratory result from Day -2 (Grade 2 or 
higher on the National Cancer Institute [NCI] toxicity scale), except for the 
following: 
a. Albumin < 2.5 g/dL, 
b. Leukocytes > 20K/uL, 
c. Hemoglobin < 7.5 g/dL 
12. Clinically significant abnormalities (Grade 2 or higher on the NCI toxicity 
scale) identified through medical history and physical examination at Day 0, 
with the following exceptions: 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
 
 
 
 
 
 
Test Product, 
Dose, Mode of 
Administration 
 
 
 
 
 
 
Duration of 
Treatment 
Safety 
Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Proof of 
Mechanism 
Evaluations 
a. Anorexia, can enroll up to Grade 4 (inclusive) 
b. Constipation, can enroll up to Grade 2 (inclusive) 
c. Dysphagia, can enroll up to Grade 4 (inclusive) 
d. Keratitis, can enroll up to Grade 4 (inclusive) 
e. Bone pain, can enroll up to Grade 2 (inclusive) 
One set of three 3-4 mm biopsies obtained at Screening from non-blistered skin will 
be used to manufacture up to 20 mL of FCX-007 for use in this protocol. A 
maximum of fifteen (15) mL of FCX-007 will be administered intradermally on at visit 
3 (Day 0) in up to sixty (60) 0.25 mL injections. The maximum total administered 
dose will consist of up to 
 genetically modified fibroblast cells. Up to an 
additional 15 mL will be administered on Visit 5 (Week 4). 
FCX-007 will be packaged in 2 mL cryovials, each containing 1.2 mL for withdrawal 
of 1 mL. After a 21-gauge needle is used to withdraw FCX-007 from the vial, the 
needle is replaced with a 30-gauge needle prior to injection. 
Treatment is administered once at Day 0 (Visit 3) and again at Visit 5 (Week 4). 
 
Safety will be monitored throughout the study. The following assessments in each 
subject will be assessed: adverse events (AEs), physical examinations, vital signs, 
clinical laboratory evaluations, medical history, and prior/concomitant medications. 
Specifically, the following will be assessed for adverse events: 
- 
Changes in laboratory values, including: 
• 
C7 Antibodies as assayed by linear basement membrane zone 
(BMZ) staining for IgM, IgG, IgA or serum IgG antibodies binding to 
the epithelium of monkey esophagus with a basement membrane 
or superficial dermal pattern by indirect immunofluorescence (IIF) 
microscopy 
• 
Direct immunofluorescence (DIF) of subject’s skin biopsy staining 
for IgM, IgG, IgA or complement staining in a linear BMZ 
distribution localizing to the dermal-epidermal junction 
• 
Replication Competent Lentivirus (RCL) 
• 
Complete Blood Count with Differential 
- 
Changes in vital signs: blood pressure, heart rate, respiratory rate, 
temperature 
- 
Change in physical exam 
- 
Long-term safety follow-up including: 
• 
Delayed adverse events for at least 15 years in which safety is 
monitored at a minimum annually. 
• 
Replication Competent Lentivirus evaluation yearly for up to 15 
years. If all post-treatment assays are negative during the first year 
(e.g., Weeks 4, 12, 16, 25, 32, and 52), collection of the yearly 
follow-up samples will be discontinued. 
• 
Any new malignancies to Year 15 
The following will be investigated to evaluate proof of mechanism: 
- 
Expression of C7 as determined by immunofluorescence (IF). 
- 
The presence of mature anchoring fibrils as determined by immunoelectron 
microscopy (IEM). 
- 
The change in the treated target and control wounds area from baseline 
(Day 0) based on investigator assessment of wound healing. 

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Fibrocell Technologies 
 
1 
Background 
 
1.1 
Disease Background 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive, inherited skin 
disease caused by null mutations within the C7 gene (COL7A1). Mutations in COL7A1 have been 
shown conclusively to underlie dystrophic epidermolysis bullosa (Dang, 2008). The mutations 
cause an absence or reduction of functional C7 and anchoring fibrils. Anchoring fibrils may be 
reduced in number and show abnormal morphology (loss of fan-shaped appearance and central 
cross-banding) or, in the clinically most severe cases, the anchoring fibrils are barely detectable; 
where only a few thin structures can be seen (Tidman, 1985). 
Subtypes of RDEB share in common a deficiency of C7 (Intong, 2012) and this deficiency is the 
basis upon which diagnosis is made. The disease is characterized by a mechanical fragility and 
repeated blister formation, potentially occurring on all epithelial-surfaced or lined structures. 
Blister formation occurs in the basal laminal layer, specifically in the sub-lamina densa, at the 
level of the structurally defective anchoring fibrils (Dunnill, 1996). They can be long-term, large 
and severely painful blisters that result from minor skin trauma. COL7A1 contains 118 exons 
composed of a noncollagenous domain 1 (NC1) (exons 1-28), a central collagenous domain with 
Gly-X-Y region (exons 29-111), and a noncollagenous domain 2 (NC2) (exons 112 – 118) that 
catalyzes the anchoring fibril assembly. RDEB patients may either express the NC1 amino- 
terminal fragment of type VII collagen NC1[+] or lack it (NC1[-]). Epitope mapping of 
autoantibodies in patients with acquired autoimmunity to type VII collagen (epidermolysis bullosa 
acquisita) demonstrates that NC1 is the predominant domain targeted by patient autoantibodies 
These studies suggest that NC1 is likely the most antigenic portion of the type VII collagen 
molecule. Subjects whose fibroblasts demonstrate expression of the NC1 domain by Western blot 
analysis should have a reduced chance of an immune response to the therapeutic gene product, 
type VII collagen. These subjects’ immune systems will have recognized the most antigenic 
portion of the type VII collagen molecule, the NC1 domain, as self, thus reducing potential immune 
reactions. 
Persistent blistering begins at birth and contributes to the high mortality risk due to bacterial 
infection. In a study of 41 RDEB patients, the infectious causes of pneumonia and sepsis resulted 
in death in 14.6% and 9.8% respectively (Fine, 2010). Patients who survive bacterial sepsis during 
early infancy are at a high risk of later developing more severe complications such as growth 
retardation due to gastrointestinal involvement (Fine, 2008), multifactorial anemia, esophageal 
strictures, corneal scarring and/or progressive blindness (Fine, 2004), post streptococcal 
glomerulonephritis, renal failure, progressive hand and foot deformities such as pseudosyndactyly 
(Fine, 2005), muscle contractures that restrict movement, anemia, esophageal strictures (Fine, 
2008), microstomia, obliteration of the oral vestibule, dysphagia, rapid tooth decay, nail 
deformities, and hair loss. In addition, patients with the severe generalized subtype have an 
increased lifetime risk (over 90%) (RAC, 2007) of developing aggressive squamous cell 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
carcinoma. 87% die by the age of 45 due to metastatic squamous cell carcinoma (Fine, 2010). 
Currently there is no effective therapy for this disease. Nearly 10% of RDEB patients die before 
the age of 10, almost 40% by the age of 20, and 72% before the age of 30. Death is usually the 
result of aggressive squamous cell carcinoma, sepsis, or of malnutrition due to an inability or 
unwillingness to eat due to mouth or esophagus involvement (RAC, 2007). 
 
1.2 
FCX-007 Background 
 
1.2.1 Cell Manufacturing 
 
FCX-007 is an autologous cell product manufactured by ex vivo gene modification and expansion 
of dermal fibroblasts obtained from one set of three 3-4 mm biopsies of the patient’s skin. The 
biopsies are shipped in a sterile buffer solution to a central manufacturing facility, where they are 
digested with enzymes to release the fibroblast cells, which are then seeded into a tissue culture 
vessel. The cells are expanded, transduced with INXN-2004 (a lentiviral vector encoding the 
functional COL7A1 gene), and expanded further to obtain a sufficient quantity for study treatment. 
Cells undergo Drug Substance release testing. The Drug Product for patient injection is shipped 
same day or overnight prior to each scheduled day of investigational treatment. FCX-007 Drug 
Substance is evaluated against Drug Product release specifications. FCX-007 Drug Product is 
shipped refrigerated for overnight delivery to the clinic and is to be administered prior to the 
expiration date and time indicated on the product label. FCX-007 cells are injected intradermally 
at the periphery of RDEB wounds as well as into intact skin. 
 
1.2.2 INXN-2004 (LV-COL7 Lentivirus) Construction and Characterization 
 
The COL7A1 gene is introduced to the cultured Fibroblast cells using INXN-2004 (a recombinant 
Lentiviral Vector (LV) encoding the COL7A1 gene). The LV is a replication incompetent, Vesicular 
Stomatitis Virus-G (VSV-G) pseudotyped, self-inactivating lentivirus (SIN-LV) that expresses 
human COL7A1 gene under the CMV promoter. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
Figure 1 – INXN-2004 Vector Map 
 
 
 
1.2.2.1 
COL7A1 Gene 
The full length human COL7A1 gene (8835 base pairs (bp)) was assembled at Intrexon 
Corporation from fragments sourced from reverse transcription of human RNA, commercial 
plasmid (Origene plasmid SC300011), and DNA synthesis. The full length human COL7A1 gene 
was cloned into an expression vector at Intrexon. The COL7A1 gene was subsequently cloned 
into an LV vector to produce INXN-2004. 
 
1.2.3 Preclinical 
 
In vitro and in vivo studies were conducted to assess FCX-007 safety as well as the ability to 
confer formation of anchoring fibrils and correction of the RDEB phenotype in human organ 
cultures and human skin grafted onto immunodeficient mice. 
 
1.2.3.1 
In vitro Assessment of FCX-007 
In vitro pharmacology analyses were conducted on FCX-007 cells to evaluate copy number of 
integrated LV-COL7, mRNA and protein expression of C7, and functionality of the C7 expressed 
by FCX-007. In vitro pharmacology analysis of FCX-007 demonstrated that the COL7A1 gene 
integrated into RDEB cells (transduced) using INXN-2004. Following cell passaging and 
amplification post-transduction, integration of INXN-2004 in FCX-007 cells averaged 0.41 to 0.74 
copies per cell. The resulting transduced RDEB cells (FCX-007) expressed C7 protein. The 
expression of C7 was demonstrated through: 
- 
Indirect immunofluorescence (IIF) showing C7 staining on FCX-007 cells, 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
- 
Flow cytometry demonstrating that up to 30% of the FCX-007 cells are positive 
for C7 expression, and, 
- 
An enzyme-linked immunosorbent assay (ELISA) demonstrating C7 expression 
from FCX-007 cells at 1966 to 2313 ng/day/million cells. 
Additional assays demonstrated that FCX-007 C7 was predominantly trimeric, specifically bound 
to Laminin332, and reversed an RDEB hypermotility phenotype. 
 
1.2.3.2 
In vivo Toxicology Assessment of FCX-007 
The safety and biodistribution of FCX-007 was evaluated in a 6-month toxicology/toxicokinetics 
study in NSG mice injected subcutaneously with six doses of FCX-007. FCX-007 was well 
tolerated throughout the 3 and 6-month timepoints. GM-HDF did not result in cell-related mortality, 
adverse clinical observations or changes in body weights. There were no toxicologically important 
differences in organ weights or clinical pathology parameters and no GM-HDF-related gross 
pathology or histopathology findings in the male and female mice throughout the study. No 
adverse palpable masses related to administration of GM-HDF or tumorigenic potential was 
observed. PCR evaluation detected presence of low levels of vector DNA and/or RNA expression 
in skin in the male and female animals at 3 months confirming exposure to GM-HDF. PCR 
evaluation revealed a general lack of persistence of the cells and expression in the NSG mice to 
the 6-month timepoint. No test article-related findings were observed. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
2 
Rationale and Objectives 
 
2.1 
Rationale 
Fibrocell is developing FCX-007 in anticipation of improving skin function in RDEB patients 
through restoration of type VII collagen and anchoring fibril levels. 
 
2.2 
Objectives 
 
2.2.1 Primary 
 
1) 
The primary objective of this protocol is to evaluate the safety of FCX-007. 
 
2.2.2 Secondary 
 
1) 
To evaluate mechanism of action of FCX-007 at visits 5 (Week 4), 6 (Week 12), 
8 (Week 25), 10 (Week 52), and unscheduled visits through the evaluation of 
skin biopsies for C7 expression and the presence of anchoring fibrils. 
2) 
To evaluate the efficacy of FCX-007 through an intra-subject paired analysis of 
target wound area at visits 5 (Week 4), 6 (Week 12), 8 (Week 25), 10 (Week 52), 
and unscheduled visits, comparing FCX-007 treated wounds to untreated 
wounds through investigator assessment of wound healing based on the digital 
images of wounds. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
As there is no previous human experience with FCX-007, treatment administration will be 
staggered in two places: 
1. 
Between the first and second enrolled subjects in each arm. 
2. 
Between the third and fourth enrolled subjects in each arm. 
Proceeding to administration of FCX-007 after a stagger requires that the previous subject 
complete Week 4 evaluations and the Investigator must have received approval from the Data 
Safety Monitoring Board (DSMB) to continue the study prior to the next subject’s FCX-007 
administration. 
At a minimum, FDA and DSMB approvals are required for enrollment of pediatric subjects. Local 
oversight committees may also require approval. 
Each phase of the study is divided into four (4) periods: Screening, Wound Monitoring, Treatment, 
and Long-Term Follow-Up. The Screening Period consists of entry criteria evaluations, the 
collection of one set of three 3-4 mm biopsies for FCX-007 manufacturing, and the identification 
and photography of potential target wounds. FCX-007 manufacturing requires about 4 months. 
This period is the Wound Monitoring Period. Subject target wounds may be imaged a minimum 
of two times (at least 4 weeks apart) during this period. The purpose of the imaging is to identify 
wounds with the most consistent wound areas that meet criteria, and to establish a baseline area 
that takes into account natural wound area variation. The Wound Monitoring Period is expected 
to have a duration of approximately four months; however, this period can extend beyond four 
months to accommodate patient scheduling, variations in manufacturing duration and protocol 
mandated delays (i.e. pauses due to staggered treatment). 
After FCX-007 manufacturing is complete, Fibrocell (the Sponsor) and the Investigator will 
mutually agree on the date of receipt of FCX-007. The duration of the Treatment Period may 
fluctuate between two and four days. The Treatment Period visits (Day -2 to Day 2) will be 
scheduled so that the day of dosing (Day 0) is the day of receipt of FCX-007. Prior to dosing, 
wounds are identified that meet treatment criteria based on imaging results obtained. Up to three 
pairs of target wounds may be identified for each subject and the Investigator will pair the target 
wounds according to similarity in wound area. 
One wound in each pair will receive FCX-007 and the other wound no treatment. 
Safety and proof of mechanism evaluations are conducted during site visits at Visits 5, 6, 8 and 
10 (weeks 4, 12, 25, 52), and unscheduled visits. Proof of mechanism will be monitored through 
assays conducted on biopsies taken from target wounds and areas of intact skin in which FCX- 
007 was administered. 
Safety is monitored throughout the study, captured during on-site visits and while the subject is 
off-site through adverse event diaries. The following assessments in each subject will be 
assessed: adverse events (AEs), physical examinations, vital signs, clinical laboratory 
evaluations (including C7 antibodies, and RCL), medical history, and prior/concomitant 
medications, as appropriate. A DSMB will periodically review subject safety data. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
The Long-Term Follow-Up is a 15-year period following Week 52/ET in which safety is monitored 
(including RCL testing yearly and any new malignancies to 15-years) at a minimum annually. If 
all post-treatment RCL assays are negative during the first year (e.g., Weeks 4, 12, 16, 25, 32, 
and 52), collection of the yearly follow-up samples will be discontinued. 
 
3.2 
Number of Investigative Sites 
One (1) to three (3) investigative sites will participate in the study. 
 
3.3 
Number and Source of Subjects 
The enrollment target is up to twelve (12) subjects: Up to six subjects in Phase I and up to six (6) 
subjects in Phase II. A seventh subject may be enrolled into Phase II at the discretion of the 
sponsor. 
In Phase I, 3 NC1+ subjects may be enrolled to Arm A and 3 NC1- subjects may be enrolled to 
Arm B. In Phase II, the study will target enrolling 3 subjects to each arm, but will allow a 
disproportionate distribution of subjects between Arm A and Arm B to equal 6 total subjects. All 
potential subjects must be properly consented, meet all inclusion/exclusion criteria, and undergo 
all screening procedures to be eligible for participation in this study. 
 
3.4 
Estimated Study Duration 
The duration is about 20 months per subject, including the Screening, Wound Monitoring and 
Treatment Periods. Recruitment is anticipated to take approximately 8 months, resulting in total 
study duration of approximately 28 months. The end of Treatment Period Visit is scheduled to 
occur at the end of the 12-month treatment phase. Safety data will continue to be collected by 
clinic visit or telephone contact approximately every 1 year for at least 15 years after the treatment 
phase. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
4 
Subject Eligibility 
 
Investigators will be expected to maintain a screening log of all potential study candidates that 
includes limited information about the potential candidate (e.g. gender, age, race) and outcome 
of the screening process (e.g. enrolled into study, reason for ineligibility, or refused to participate). 
 
4.1 
Inclusion Criteria 
To be eligible for inclusion, each subject must fulfill each of the following criteria: 
1. 
Age 
a. Phase I: Eighteen (18) years old or older. 
b. Phase II:  Seven (7) and older. 
2. 
Diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) (inclusive) by: 
a. Clinical diagnosis 
b. Immunofluorescence (IF) evaluation 
c. Electron microscopy (EM/IEM) evaluation 
d. Confirmation of RDEB C7 mutations in the subject 
3. 
NC1 Status 
a. Arm A: Positive for the NC1 domain of C7 (NC1+) as determined by 
genetic testing results showing one or no loss of function mutations in 
exons 1-28. 
b. Arm B: Negative for the NC1 domain of C7 (NC1-) as determined by 
genetic testing results showing two loss of function mutations in exons 1- 
28. 
4. 
NC2 Status: negative or weakly positive for LH24 antibody staining as 
determined by immunoelectron microscopy (IEM). 
5. 
Subjects and guardians, who are, in the opinion of the Investigator, able to 
understand the study, co-operate with the study procedures and are willing to 
return to the clinic for all the required follow-up visits. 

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Fibrocell Technologies 
 
4.2 
Exclusion Criteria 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
Subjects will be excluded from the study if any of the following criteria are met: 
1. 
Medical instability limiting ability to travel to the investigative center. 
2. 
Active infection with HIV, hepatitis B or hepatitis C, as determined by hepatitis 
B surface antigen screening, detection of hepatitis C antibodies, or positive 
result of hepatitis C PCR analysis. 
3. 
The presence of antibodies to the basement membrane of monkey esophagus 
by indirect immunofluorescence using the subject’s serum. 
4. 
Evidence of systemic infection. 
5. 
Current evidence of metastatic squamous cell carcinoma at the site to be 
injected. 
6. 
Known allergy to any of the constituents of the product. 
7. 
Active drug or alcohol addiction. 
8. 
Hypersensitivity to anesthesia chosen (lidocaine/prilocaine cream, moderate 
sedation, or general anesthesia). 
9. 
Receipt of a chemical or biological study product for the specific treatment of 
RDEB in the past six months 
10. 
Women who are pregnant or breast-feeding. 
11. 
Any clinically significant abnormal laboratory result from Day -2 (Grade 2 or 
higher on the National Cancer Institute [NCI] toxicity scale), except for the 
following: 
a. Albumin < 2.5 g/dL, 
b. Leukocytes > 20K/uL, 
c. Hemoglobin < 7.5 g/dL 
12. 
Clinically significant abnormalities (Grade 2 or higher on the NCI toxicity scale) 
identified through medical history and physical examination at Day 0, with the 
following exceptions: 
a. Anorexia, can enroll up to Grade 4 (inclusive) 
b. Constipation, can enroll up to Grade 2 (inclusive) 
c. Dysphagia, can enroll up to Grade 4 (inclusive) 
d. Keratitis, can enroll up to Grade 4 (inclusive) 
e. Bone pain, can enroll up to Grade 2 (inclusive) 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
5 
Subject Enrollment and Withdrawal 
Written protocol and informed consent approval are required from the IRB prior to enrollment. 
Assent form approval is required from the IRB prior to enrolling subjects below the age of consent. 
All subjects or their respective legal guardians must personally sign and date the relevant consent 
and/or assent form before enrollment. 
 
5.1 
Subject Identification and Number Assignment 
Subjects who sign the informed consent form will be assigned a 4-digit subject identification 
number. Subject identification numbers will begin with “XX” = pre-defined site number, and end 
with “XX” = subject number (sequential, starting with 01). This number will identify the subject 
throughout the study and must be used on all study documentation related to that subject. 
 
5.2 
Concomitant Therapy and Skin Care 
There are no restrictions on concomitant therapies and skin care. Throughout the study, any 
concomitant medications or treatments deemed necessary to provide adequate supportive care 
may be prescribed. In particular, medication should be considered during and after the injections 
to treat pain and/or anxiety (i.e. lorazepam). Routine skin care for RDEB patients will continue 
throughout the study. 
 
5.3 
Withdrawal of Subjects 
A subject is free to withdraw from the study at any time for any reason without prejudice to their 
future medical care by the physician or at the institution. The Investigator or Sponsor may also 
withdraw the subject at any time in the interest of subject safety or for other reasons. Criteria for 
withdrawal include: 
1. 
Consent/assent is withdrawn 
2. 
The subject refuses treatment and/or procedures/observations. 
3. 
Occurrence of unmanageable adverse events, or pregnancy. 
4. 
For other reasons (e.g., significant protocol violation, non-compliance). 
5. 
The Sponsor may be contacted if clarification is required. 
The primary reason for withdrawal must be recorded on the CRF. Comments or complaints made 
by the subject must also be recorded on the CRF. Withdrawal information will be communicated 
to the DSMB at each meeting. Withdrawal should be discussed with the medical monitor prior to 
withdrawal when possible. Subjects who wish to discontinue treatment or study procedures after 
receipt of FCX-007 will be asked to continue in the Long-Term Follow-Up Period (Section 7.5). 
Subjects who withdraw prior to FCX-007 administration will be considered a screen failure and 
will be replaced. The Sponsor reserves the right to terminate the study. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
6 
Investigational Product 
 
Investigational product (IP) utilized in this protocol is FCX-007 (genetically modified autologous 
human dermal fibroblasts suspended in DMEM). 
One administration of FCX-007 is up to 15 mL of cell suspension administered as sixty (60) 0.25 
mL intradermal injections. Table 1 provides details regarding the number of cells, vials and 
injections per administration. 
Table 1 – FCX-007 Cell Count and Injections per Administration 
FCX-007 Cells 
 
 
Concentration of FCX-007 Suspension 
 
 
# Vials 
 
Injections per Vial 
 
Cells per Injection 
 
Number of Injections 
 
 
6.1 
Manufacturing 
 
6.1.1 FCX-007 Manufacturing 
 
FCX-007 will be manufactured from one set of three 3-4 mm biopsies obtained at the Screening 
Visit. The biopsies will be placed into sterile phosphate buffered saline (PBS), and shipped at 2- 
8oC immediately to the manufacturing facility. Upon receipt of the biopsies, FCX-007 will be 
manufactured by gene modification and expansion of dermal fibroblasts obtained from the biopsy. 
The tissue will be digested with enzymes to release the fibroblasts, which will then be seeded into 
a tissue culture vessel. The cells will be expanded, transduced with INXN-2004 (a lentiviral vector 
encoding the functional COL7A1 gene), and expanded further. If the manufacturing process does 
not yield an FCX-007 cell count sufficient for at least one administration, or does not meet 
manufacturing release specifications, an additional set of biopsies may be requested from the 
subject. 
For each subject, approximately 
 FCX-007 cells will be manufactured for use in this 
study. Up to 
 will be administered at each dose administration. Cells undergo 
release testing and sent to the Investigative Site for administration on Day 0. The duration 
between biopsy collection and completion of manufacturing is approximately 120 days (4 months) 
but can vary due to capacity, technical manufacturing reasons, or clinical protocol required pauses 
between subjects. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
6.2 
Labeling, Packaging, Storage and Handling 
 
6.2.1 Packaging and Labeling 
 
6.2.1.1 
Packaging 
Investigational product will be provided to the Investigative Site as an opaque cell suspension in 
2.0 mL cryovials containing approximately 1.2 mL of FCX-007 per vial with a recoverable volume 
of 1.0 mL per vial. 
Up to thirty (30) vials of FCX-007 will be provided per subject; 15 vials for Day 0, and 15 vials for 
week 4. 
 
6.2.1.2 
Labeling 
The vials will be labeled with a minimum of the subject number and the date of manufacture. The 
secondary container in which the vials are shipped will include the following information: 
- 
IP Name: FCX-007 
- 
Lot Number 
- 
Fill Date and Time 
- 
Expiration Date and Time 
- 
Nominal Conc./Vol.: xe7 cells/mL in 1.0 mL 
- 
Manufactured by Fibrocell Technologies Inc. 
- 
CAUTION: NEW DRUG – Limited by US Federal Law to Investigational Use 
- 
NOT EVALUATED FOR INFECTIOUS SUBSTANCES 
The cells will be transported to the investigative site as a suspension and the vial will be packaged 
in a temperature controlled and monitored shipper and delivered by overnight courier. 
 
6.2.2 Storage and Handling 
 
After receipt of the shipped vials, they must be kept sealed in the shipper until ready for use. The 
Investigator will be responsible for accurate, written records of all FCX-007 received. The Sponsor 
or designee will be permitted upon request to audit the administration procedures and records. 
FCX-007 Drug Product will be shipped same day or overnight delivery to the clinic and must be 
administered prior to the expiration date and time indicated on the product label. 

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Fibrocell Technologies 
 
7 
Study Visits 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
This section outlines activities by visit. Additional information about specific procedures and 
evaluations can be found in Section 8 (Procedures: FCX-007 Administration to Intact Skin), 
Section 9 (Procedures: FCX-007 Administration to Wound(s)), and Section 10 (Procedures: 
Collection and Evaluation of Biopsies). Study tests and procedures will be performed only after 
a signed informed consent is obtained. 
During the study, every effort should be made to adhere to the visit schedule and visit windows 
provided in the Schedule of Events (Table 2). 
Subject Companions 
Subjects will be permitted to bring a companion to study visits. Cost associated with travel to the 
Investigative Site, including those of a companion, will be paid for by the sponsor with prior 
approval from the sponsor. 
Time Frame Between Subjects 
The second subject in each arm will not be treated until after the first subject has completed the 
4-week evaluation. The DSMB will meet after the first subject has completed visit 5 (Week 4) to 
review data and determine whether the second subject in each arm can be treated. Likewise, the 
fourth subject (and first potential pediatric subject) in each arm will not be treated until after the 
third subject has completed the 4-week evaluation and the DSMB has reviewed the data. DSMB 
and FDA approval will be required prior to enrollment of any pediatric subject. 

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Treatment Period 
Wound 
V2 
Event 
Information Letter and Phone Screen 
ICF/ Assent/ HIPAA 
Inclusion / Exclusion Criteria 
Demographics 
Medical / Medication History 
Concomitant Medications 
Adverse Events 
Physical Exam 
Skin Exam5 
Vital Signs 
Digital Imaging of Wounds 
Target Wound Selection 
Investigator Assessment of Wound 
Healing 
Bacterial Culture6 
FCX-007 Administration 
Urine Pregnancy Test 
Hematology & Chemistry 
HIV, Hep B, Hep C Testing 
RCL evaluation 
C7 Antibody Assay 
Genetic Testing 
Pre- 
Visit 1 Monitoring Day 
screen Screen1 
Period2 
-24 
X 
X 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
Day 
Day 
Wk 4 
Wk 12   Wk   Wk 25    Wk   Wk 52 
0 
2 
± 2d 
± 1wk   163 
± 2wk 
323 
± 2wk LTFU 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X12 
Blood and Urine
Tests 
 
 
Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
Table 2 - Schedule of Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Continues on next page 
 
 
1 Visit 1 protocol events may take up to 4 days. Screening assays for RDEB diagnosis will not be repeated unless 
warranted by the Investigator if the subject medical records contain these results. 
2 At least two visits to the site for imaging during the approximate 4 month period in which FCX-007 is being 
manufactured may occur. The last wound monitoring visit should occur no more than 60 days prior to the injection 
of FCX-007. 
3 Visits 7 and 9 can be performed in the office or via telephone consult. If visit is conducted via telephone consult, 
only concomitant medication and adverse event reporting from subject will be recorded. 
4 Subjects can remain at or near the Investigative Site between Visits 2 and 4. 
5 Skin exam on potential target wounds only during wound monitoring visits. 
6 To be performed at Visit 2 and as needed throughout the study if clinical evaluation is indicative of infection. 
7 A blood sample must be collected for RCL baseline assessment either at screening or wound monitoring visits, 
results must be available prior to Visit 3 (Day 0). 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
7.1 
Screening Period 
 
7.1.1 Prescreening 
 
An Investigator or designee will prescreen medical histories of RDEB patients for potential 
inclusion into this study. Medical information reviewed may include the following and is dependent 
upon the Investigative Site’s receipt of prior authorizations to access the data: 
- 
NC1 status 
- 
NC2 status as determined through LH24 antibody staining 
- 
COL7A1 genotype of the subject 
- 
C7 antibody history 
- 
RDEB diagnosis results as determined by IF and EM/IEM 
- 
Medical history 
- 
Negative direct immunofluorescence (DIF) 
The Investigator may request additional PHI disclosure authorizations from the potential subject 
to assist with Pre-Screening. 
Potentially eligible subjects over the age of 18 are mailed an IRB-approved information letter 
which includes a study overview, key inclusion/exclusion criteria, information about the 
recruitment process, and contact information. For the Phase II portion of the study, parents of 
potentially eligible minors will be mailed the IRB-approved information letter. 
If a potential subject or parent or guardian contacts the Investigative Site indicating interest in the 
study, they will be contacted by phone. An Investigator or designee reviews the letter with the 
subject or parent or guardian, and addresses questions. At this time the Investigator or designee 
can verbally review the inclusion / exclusion criteria. If the potential subject remains interested in 
participating in the study, a copy of the informed consent is sent to the potential subject to review. 
 
7.1.2 Informed Consent 
 
The Investigator will be responsible for obtaining from every subject prior to his/her participation 
in the study an ICF signed by the subject or legally authorized representative, in accordance with 
the Code of Federal Regulations, Title 21, Part 50.20. For subjects between the ages of 7 and 
17 (inclusive), the Investigator is responsible for obtaining assent from the subject and consent 
from both parents or legal guardians. The ICF/Assent that is used must be the current version 
and must be approved by both the reviewing IRB and by the Sponsor. Informed consent/assent 
will be obtained from the subject after a full explanation of the purpose of the study, risks and 
discomforts involved, potential benefits, etc. have been provided by the Investigator both verbally 
and in writing. The original signed copy of the informed consent/assent must be maintained in 
the institution’s records and is subject to inspection by a Sponsor representative. 

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Page 29 of 75 
 
 
 
 
Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
7.1.3 Screening (Visit 1) 
 
Screening evaluations may be conducted over the course of up to 3 days. 
To minimize travel requirements in this patient population, manufacturing biopsies can be 
collected before the subject leaves the clinic on the last day of the screening visit if the subject 
meets all of the entry criteria for which results are available and has a clinical RDEB diagnosis. It 
is possible that the following results will not be available at the time that the manufacturing 
biopsies are taken: 
- 
Diagnosis of RDEB by Immunofluorescence (IF) 
- 
Diagnosis of RDEB by Electron microscopy (EM/IEM) 
- 
Diagnosis of RDEB by Confirmation of RDEB C7 mutations in the subject 
- 
Infectious disease panel (HIV, hepatitis B, hepatitis C) results 
- 
NC1 status 
- 
NC2 status 
 
If manufacturing biopsies are not taken at the Screening visit, they may be taken at Wound 
Monitoring Visit 1. 
 
The following evaluations are conducted as part of the screening visit: 
- 
Review and signing of informed consent/assent. 
- 
Collection of demographic data (e.g. sex, age, race, and ethnicity) 
- 
Inclusion/exclusion criteria 
- 
Medical history including respiratory, cardiovascular, renal, gastrointestinal, 
hepatic, endocrine, hematological, neurological, psychiatric and other diseases. 
- 
Medication history 
- 
Physical and Skin Exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 22.5 mL) for clinical laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
HIV, Hep B, Hep C 
• 
RCL (this baseline blood sample may be collected at a wound monitoring 
visit. Results must be available prior to Day 0) 
• 
C7 antibody assay 
- 
Collection of urine for pregnancy test, if applicable 
- 
Digital imaging of wounds 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
- 
Identification of potential target wounds and labeling the selected wounds with 
sequential number of P01 through Pnn. 
- 
Collection of one set of three (3) 3-4 mm biopsies for the manufacturing of 
FCX-007 
- 
The following evaluations are required only if RDEB diagnosis documentation is 
not available to support entry into this protocol: 
• 
Collection of biopsy for EM/IEM 
• 
Collection of biopsy for IF and DIF 
• 
Collection of blood for genetic testing and determination of NC1 status 
- 
Once all screening data is available, the PI will complete screening assessment. 
The subject will not be scheduled for or receive treatment until the Investigator 
confirms all inclusion/exclusion criteria have been met. If screening tests results 
received after manufacturing biopsies have been taken show the subject does 
not meet study criteria, the subject will be withdrawn and all material obtained for 
manufacturing will be destroyed unless consent has been obtained to use the 
tissue for future research. 
 
7.2 
Wound Monitoring Period 
The Wound Monitoring Period may consist of 2 or more visits during the 4-month period in which 
FCX-007 is being manufactured. The purpose of the visits is to image potential target wounds. 
Potential target wounds will also undergo a skin examination during these visits. The overall 
length of the Wound Monitoring Period may vary due to manufacturing or data analysis. The first 
visit may be scheduled at least 30 days after the Screening visit and subsequent visits may be 
scheduled at least 30 days apart. If possible, the last wound monitoring visit may occur no more 
than 60 days prior to the injection of FCX-007. 
Because the length of the manufacturing period may vary, the wound monitoring visits should be 
based on the best available estimates of when the first injection will be available. 
If insufficient cell growth occurs and FCX-007 cannot be manufactured, subjects will be asked for 
additional manufacturing biopsies. 
Collection of blood for RCL analysis can be obtained at a wound monitoring visit if not taken at 
screening. Results must be available prior to Day 0. 
Manufacturing biopsies can be taken at Wound Monitoring Visit 1 if not obtained at the Screening 
Visit. 

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Fibrocell Technologies 
 
7.3 
Visits 2 through 10 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
Study procedures are scheduled at Visits 2 (Day -2), 3 (Day 0), 4 (Day 2), 5 (Week 4), 6 (Week 
12), 7 (Week 16), 8 (Week 25), 9 (Week 32), and 10 (Week 52). The Investigator may extend the 
subject’s stay for any visit at his/her discretion based on any adverse events experienced. 
Unscheduled procedures may occur during this period and resulting data should be captured on 
Unscheduled Visit case report forms. If deemed necessary, Investigators may attend to the 
subject at the hotel to check on their progress. Nursing support for bandage changes will be 
provided as needed. 
 
7.3.1 Visit 2 (Wound Selection/Run-In) 
 
Visit 2 procedures may occur up to 2 days (±1 day) prior to the day of FCX-007 administration. 
The following procedures will be performed during Visit 2: 
- 
Re-evaluation of inclusion/exclusion criteria 
- 
Review of medical and medication history 
- 
Skin Exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 12.5 mL) for laboratory tests 
• 
Serum chemistry 
• 
Hematology 
- 
Collection of urine for pregnancy test, if applicable 
- 
Bacterial culturing of target wounds 
- 
Final target wound selections of up to 3 pairs from the selected potential target 
wounds (See Section 9.1 for details) 
- 
Label the selected target wound pairs as T1A and T1B for the 1st pair, T2A and 
T2B for the 2nd pair, and T3A and T3B for the 3rd pair. 
- 
Digital imaging of wounds. 
 
7.3.2 Visit 3 (Day 0; Day of Injection) 
 
Visit 3 procedures are scheduled to occur on the day of receipt of FCX-007. The following 
procedures will be performed during this visit: 
- 
Re-evaluation of inclusion/exclusion criteria 
- 
Review of medical and medication history 
- 
Physical and Skin Exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 

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Fibrocell Technologies 
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RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
indicative of infection) 
- 
Surgical marking around the target wounds and on the intact skin 
- 
Digital imaging of injection sites 
- 
Tattoos will be placed on non-blistered skin near the target wounds for the 
purpose of calibrating the post-dose imaging. 
- 
Tattoos will also be placed next to the intact skin injection sites for the purpose of 
precisely locating the biopsy sites at follow-up visits. 
- 
Randomly assign each wound of a target wound pair to either active treatment or 
control (Visit 3 only). 
- 
Biopsy collection to be used as IF/DIF and IEM. 
• 
Biopsy location markings must be imaged prior to collection. 
• 
Biopsy collection must occur prior to administration 
- 
FCX-007 administration to target wounds 
- 
FCX-007 administration to the intact skin. 
- 
Post-dose digital imaging 
- 
Post-dose assessment of concomitant medications and adverse events 
As noted above, the subject may remain at the Investigative Site or in a nearby hotel for up to 2 
days following FCX-007 administration. During this period, the subject will be monitored for 
autoimmune reactions to FCX-007. At a minimum, subjects will be contacted once per day on 
days in which there are no scheduled procedures. 
 
7.3.3 Visit 4 (Day 2) 
 
Visit 4 procedures are scheduled to occur up to 2 days (±1 day) after Visit 3. The following 
procedures will be performed during this visit: 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Skin Exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Digital imaging of wounds 
Following Visit 4, the subject may return home. 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
7.3.4 Visit 5 (Week 4) 
 
The visit window for the Week 4 visit is ±2 days. The following procedures will be performed during 
this visit: 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging of wounds 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 
indicative of infection). 
- 
Skin biopsies will be collected for IEM, genomic DNA/mRNA and/or IF/DIF 
evaluation at the site of Investigational Product/placebo administration as 
outlined in Table 2. Biopsy location markings must be imaged prior to collection. 
- 
Skin biopsies will be collected from intact skin administration sites for IEM, 
genomic DNA/mRNA and/or IF/DIF evaluation as outlined in Table 2. 
- 
Surgical marking around the target wounds and on the intact skin 
- 
Tattoos will be placed on non-blistered skin near the target wounds for the 
purpose of calibrating the post-dose imaging. 
- 
Tattoos will also be placed next to the intact skin injection sites for the purpose of 
precisely locating the biopsy sites at follow-up visits. 
- 
FCX-007 administration to target wounds 
- 
FCX-007 administration to the intact skin. 
- 
Post-dose digital imaging 
- 
Post-dose assessment of concomitant medications and adverse events 

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Final Version 8.0, 29 Oct 2019 
 
 
7.3.5 Visit 6 (Week 12) 
 
The visit window for Week 12 is ±1 week. The following procedures will be performed during these 
visits: 
- 
Re-evaluation of inclusion/exclusion criteria 
- 
Review of medical history 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Physical and Skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging of wounds 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 
indicative of infection). 
- 
Skin biopsies will be collected for IEM, genomic DNA/mRNA and/or IF/DIF 
evaluation at the site of Investigational Product/placebo administration as 
outlined in Table 2. Biopsy location markings must be imaged prior to collection. 
- 
Skin biopsies will be collected from intact skin administration sites for IEM, 
genomic DNA/mRNA and/or IF/DIF evaluation as outlined in Table 2. 
 
7.3.6 Visit 7 (Week 16) 
 
Based on the subject’s availability to travel, this visit may be performed via a telephone consult 
or in the office. If the visit is performed via telephone consult, the investigator and 
subject/guardian will review adverse events and concomitant medications. If the visit is 
performed in the office, the following procedures will be performed: 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 

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• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging of wounds 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 
indicative of infection). 
 
7.3.7 Visit 8 (Week 25) 
 
The visit window for Week 25 is ±2 weeks. 
The following procedures will be performed: 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging of wounds 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is indicative of 
infection) 
- 
Skin biopsies will be collected for IEM, genomic DNA/mRNA and/or IF/DIF as outlined in 
Table 2. Biopsy location markings must be imaged prior to collection. 
- 
Skin biopsies will be collected from intact skin administration sites for IEM, genomic 
DNA/mRNA and/or IF/DIF evaluation as outlined in Table 2. 
 
7.3.8 Visit 9 (Week 32) 
 
Based on the subject’s availability to travel, this visit may be performed via a telephone consult 
or in the office. If the visit is performed via telephone consult, the investigator and 
subject/guardian will review adverse events and concomitant medications. If the visit is 
performed in the office, the following procedures will be performed: 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 

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Fibrocell Technologies 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging of wounds 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 
indicative of infection). 
 
7.3.9 Visit 10 (Week 52) / Early Termination (ET) 
 
Week 52 is the final visit of the Treatment Period. The visit window for Week 52 is ±2 weeks. The 
procedures below are the same to be performed for subjects who terminate early from the study. 
If a subject refuses or is unable to return for an Early Termination Visit, a local physician may be 
requested to evaluate the subject. At least 3 documented attempts should be made to contact 
subjects prior to making a determination of lost to follow-up. 
- 
Assessment of adverse events 
- 
Assessment of concomitant medications 
- 
Physical and skin exam 
- 
Vital signs: blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of blood (approximately 19 mL) for laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Analysis for C7 antibodies 
• 
RCL analysis 
- 
Digital imaging 
- 
Investigator Assessment of Wound Healing. 
- 
Bacterial culturing of target wounds (may be done if clinical evaluation is 
indicative of infection). 
- 
Skin biopsies will be collected for IEM, genomic DNA/mRNA and/or IF/DIF 
evaluation at the site of Investigational Product/placebo administration as 
outlined in Table 2. 
- 
Skin biopsies will be collected from intact skin administration sites for IEM, 
genomic DNA/mRNA and/or IF/DIF evaluation as outlined in Table 2. 

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Fibrocell Technologies 
 
7.4 
Unscheduled Visits 
FI-EB-001 
RDEB Phase I/II Protocol 
Final Version 8.0, 29 Oct 2019 
 
Unscheduled procedures will be conducted at the discretion of the Investigator. Procedures may 
include, but are not limited to physical exam, photographs, skin assessment, investigator 
assessment of wound healing, skin biopsies, wound cultures, and/or blood draws for lab 
procedures. 
 
7.5 
Long-Term Follow-Up Period 
Upon completion of the End of Study / Early Termination Visit, subjects will enter into the Long- 
Term Follow-Up Period. 
 
7.5.1 Years 1 - 5 
 
At a minimum, subjects will be contacted yearly for at least 5 years. Subjects will be contacted by 
phone. In addition, the subject’s primary care provider will be asked to contact the Investigator 
regarding any unexpected or serious adverse events. Telephone contact reports will document 
the discussions and the information obtained will be captured on case report forms. The following 
activities will occur at the one-year follow-up intervals: 
- 
Collection and analysis of blood sample for RCL testing (can be done remotely). 
 
If all post-treatment assays are negative during the first year (e.g., Weeks 
4, 12, 16, 25, 32, and 52), collection of the yearly follow-up samples will 
be discontinued. 
- 
Recording of exposures to mutagenic agents and other medicinal products 
- 
Recording of any new serious adverse events, hospitalizations, or illnesses 
(including new malignancies, new incidence or exacerbation of a pre-existing 
neurologic disorder, new incidence or exacerbation of a prior rheumatologic or 
other autoimmune disorder, new incidence of a hematologic disorder). 
- 
Discussion with primary care provider regarding medication and medical history. 
- 
If a skin cancer occurs in the region of the FCX-007 administration, attempts will 
be made to collect samples of the skin cancer to evaluate cells for the presence 
of viral vector. 
 
7.5.2 Years 6 – 15 
 
Subjects will continue to be followed-up on an annual basis for at least 15 years following FCX-007 
administration. Follow-ups from years 6 to 15 include: 
- 
Collection and analysis of blood sample for RCL testing (can be done remotely). 
 
If all post-treatment assays are negative during the first year (e.g., Weeks 
4, 12, 16, 25, 32, and 52), collection of the yearly follow-up samples will 
be discontinued. 

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Final Version 8.0, 29 Oct 2019 
CONFIDENTIAL 
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- 
Recording of exposures to mutagenic agents and other medicinal products 
- 
Recording of any new adverse events, hospitalizations, or illnesses (including 
new malignancies, new incidence or exacerbation of a pre-existing neurologic 
disorder, new incidence or exacerbation of a prior rheumatologic or other 
autoimmune disorder, new incidence of a hematologic disorder). 
- 
Discussion with primary care provider regarding medication and medical history. 

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8.4 
Imaging 
The intact skin grid will be imaged at baseline after the skin markings have been applied. This 
image will be used as a reference for biopsies at follow-up visits. The images will be captured by 
a Canfield VECTRA H1XP (the “Canfield”). 
 
8.5 
FCX-007 Administration to Intact Skin 
On Visit 3 (Day 0) and Visit 5 (Week 4), intradermally administer at least 6 0.25 mL injections of 
FCX-007 to the intact skin per the administration instructions in Appendix A:Investigational 
Product Administration Instructions. 

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9 
Procedures: FCX-007 Administration to Wound(s) 
 
9.1 
Selection 
A preliminary evaluation of target wounds will occur at the Screening Visit. Potential wounds that 
meet criteria will be identified at Screening and followed throughout the Wound Monitoring Period. 
New wounds may also be identified during the Wound Monitoring Period. Final target wound and 
wound pair selection will occur on Visit 2 based on meeting the following criteria: 
1. The total injection area (circumference plus the lengths of the axes) is a maximum 
of approximately 54 linear cm (see Figure 4 for more details). 
2. If more than one pair of wounds is identified, the sum of the injection areas a 
maximum of approximately 54 linear cm. 
3. If multiple pairs of wounds are identified that meet criteria, wounds with the most 
consistent wound areas throughout the Wound Monitoring Period are to be 
selected for the study. 
If no wound meets criteria 1 and 2 above, a smaller region of a larger wound may be selected for 
treatment if it can be matched to a similar area of a larger wound as the control. When selecting 
a smaller region appropriate for treatment, every effort should be made to minimize the border 
between the treated and the untreated regions of the wound (See Figure 6B). Ideally, a narrow 
peninsula off the main portion of the wound should be selected for administration of FCX-007. 
 
9.1.1 Location and Condition of Wounds 
 
Wounds located on a mucous membrane or covering facial areas are not permitted and wounds 
with active infection are not permitted. There are no restrictions regarding proximity of paired 
wounds. 
Wounds should appear clean with adequate granulation tissue, excellent vascularization, and not 
appear infected. Wounds with evidence of active infection are not eligible. Wounds may be 
debrided, at the discretion of the Investigator, if there is significant crusting or fibrinous debris. 
Bacterial cultures will be obtained from potential target wounds on Visit 2 and as needed based 
upon standard of care and medical judgment of the Investigator. 
 
9.1.2 Pairing and Labeling of Selected Wound Pairs 
 
Potential target wounds will be identified by a continuous sequential numbering of Pair 01 (P01) 
through Pnn. Depending on the size of the largest wound in the pair, the investigator may select 
up to three pairs of wounds for inclusion in the study. Because the Investigator will not know which 
of the two paired wounds will be randomly assigned to receive FCX-007, it should be assumed 
that the largest of the two wounds will receive FCX-007 when calculations are made to determine 

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9.3 
Imaging / Wound Measurement 
Target and control wounds will be measured at each indicated visit using the images captured by 
a Canfield VECTRA H1XP (the “Canfield”). This Canfield handheld imaging system allows for 3D 
imaging of skin surfaces. The Canfield software offers a comprehensive set of viewing and 
measurement tools which allow stitching of multiple images into a 3D image as well as allowing 
calculation of wound perimeter, linear distances and surface area. Investigators will use a 
restricted set of tools from the software to define both the perimeter and the wound axes for 
measurement. The software will provide calculations for investigator evaluation of wounds to 
select for inclusion in the study. 
Prior to the first administration of IP, small tattoos will be placed on non-blistered skin near target 
wounds for the purpose of calibrating the images. 
 
9.3.1 
Investigator Assessment of Wound Healing 
 
The investigator will assess wound healing of target wounds (treated and control/untreated) based 
on the digital images of the target wounds. The investigator will assess wound healing of target 
wounds from 0% to 100% healed on a categorical scale. The wound healing assessment will be 
captured in the following categories. 
 
- 
0% 
- 
1-9% 
- 
10-24% 
- 
25-49% 
- 
50-74% 
- 
75-89% 
- 
90-99% 
- 
100% 
9.4 
FCX-007 Administration 
9.4.1 Preparation 
 
A surgical marker will be used to make the following marks: 
- 
Dots at the injection sites around the periphery of the wound at 1 cm intervals 
- 
Two lines, 1 cm apart, perpendicular from the wound margin, indicating the path 
of injections across the axes. 
- 
Two circles indicating the location of the IF/DIF and IEM biopsies 

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Inject in the middle of 
the first square cm 
from the edge of the 
wound margin 
border 
Border between treated and 
untreated regions 
 
9.4.2.1 
Treatment of Partial Wounds 
It is preferable to inject whole wounds and not partial wounds; however, partial wounds should be 
used if whole wounds that meet criteria are not available. 
 
 
Figure 6 – Example Target Wound, Injection Sites and Biopsy Locations 
A: Treatment of an Entire Wound 
 
 
B: Treatment of a Partial Wound 
 
 
Small tattoos to mark the 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-dose IF and IEM 
Biopsies 
1 cm 
 
9.4.3 Visit 5 Administration 
 
Target wounds are administered investigational product up to two times throughout the treatment 
period; once at Visit 3 (Day 0) and again at Visit 5 (Week 4). 
Circumference: 
17.9 cm 
Long Axis Width: 
7 cm 
Short Axis Width: 
4 cm 
Injection Area: 
28.9 cm 
Inject in the 
middle of the first 
square cm from 
the edge of the 
wound margin. 
1 cm 
Post-dose IF and 
IEM Biopsies 

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10 Procedures: Collection and Evaluation of Biopsies 
 
10.1 Collection 
Biopsies are collected according to Table 2 - Schedule of Events. Biopsy handling and shipping 
instructions are provided in Appendix B: Biopsy Collection Procedures. Unscheduled biopsies 
or laboratory tests may be performed as necessary to evaluate inflammation, possible SCC 
growths, or suspected presence of C7/anchoring fibrils (wound healing). 
At Visits 5 (Week 4), 6 (Week 12), 8 (Week 25) and 10 (Week 52), up to four (4) and a minimum 
of three (3) biopsies will be collected: 
- 
Two (2) biopsies from intact skin 
• 
One for IF and DIF analysis to evaluate 
 C7 expression (IF) 
 C7 antibodies (DIF) 
• 
One to evaluate C7 mRNA and DNA 
- 
One (1) from the target wound to evaluate C7 mRNA and DNA 
At other Visits the Investigator may collect up to six (6) biopsies per visit. 
The number and type of biopsies obtained will ultimately depend on the judgment of the 
Investigator and Sponsor. 
 
10.1.1 Collection Location 
 
At all follow-up visits, biopsies are to be collected as closely to the injection sites as possible. To 
aid in locating the injection sites, a transparent overlay of the injection sites can be generated 
from imaging which can be placed over the subject’s wound / intact skin. Through use of the 
transparent overlay, aligned with the wound /intact skin according to the tattoos, biopsy sites are 
chosen that are in alignment with the injection sites. If more than one pair of wounds is included 
in the study, the target wound from which a biopsy is obtained may vary from visit to visit, at the 
discretion of the Investigator, to minimize subject discomfort. 
 
10.1.2 Biopsy Photographs and Markings 
 
Biopsy locations around wounds are to be marked with a small circle. The markings will be 
photographed prior to collection (reference Figure 5 for a depiction of biopsy wound markings). 
Biopsy location and purpose will be recorded in the source documentation. 

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10.2 Evaluation 
 
10.2.1 Immunofluorescence (IF) 
 
Expression of C7 is analyzed at Visits 3 (Day 0), 5 (Week 4), 6 (Week 12), 8 (Week 25) and 10 
(Week 52). Skin biopsies may also be obtained at unscheduled visits to evaluate C7 per 
investigator discretion. A qualified reader will evaluate production of C7. 
 
10.2.2 Immunoelectron Microscopy (IEM) 
 
Expression of C7, both NC1 and NC2 epitopes, and the formation of anchoring fibrils are analyzed 
through IEM at Visits 3 (Day 0), 8 (Week 25), and 10 (Week 52). Skin biopsies may also be 
obtained at unscheduled visits.  A qualified reader will score the presence of anchoring fibrils. as 
+ (presence of mature anchoring fibrils) or – (absence of mature anchoring fibrils). 
 
10.2.3 DNA Retention and mRNA Expression 
 
At least one skin biopsy is obtained at Visits 5 (Week 4), 6 (Week 12), 8 (Week 25), and 10 (Week 
52) to evaluated for genomic retention of C7 proviral vector sequences (DNA retention) as well 
as mRNA expression. 
 
10.2.4 Autoimmune Assays 
 
C7 Antibodies will be assayed by direct immunofluorescence (DIF) at Visits 3 (Day 0), 5 (Week 
4), 6 (Week 12), 8 (Week 25) and 10 (Week 52). Skin biopsies may also be obtained at 
unscheduled visits per investigator discretion. If there is an autoimmune reaction to C7 then 
injected fibroblasts may also stain positive for immune reactants. In addition, a Western Blot assay 
may be performed to complement the indirect and direct IF assays. 
The overall assessment of anti-C7 product immune response will be based on each of these 
assays. 

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11 Procedures: Safety Assessments 
 
Timing of safety assessments must be performed in accordance with Table 2 - Schedule of 
Events. Safety assessments include evaluation of medical and medication history, physical / skin 
examination, vital signs, AEs, and laboratory evaluations. AEs will be captured between visits 
through use of an Adverse Event Diary. Post-administration changes in these assessments that 
are deemed to be clinically significant by an Investigator or Sub-Investigator will be assessed as 
AEs. 
 
11.1 Data Safety Monitoring Board 
A DSMB comprised of the Medical Monitor, enrolling PIs, and Sponsor representatives and/or 
designee(s) will hold periodic teleconferences to evaluate the safety and treatment status of all 
subjects available during the study at these stages: 
- 
After the first subject, prior to the treatment of a second subject in each arm 
- 
After Visit 5 (Week 4) for the third subject, prior to treatment of the first Phase II 
subject, to make a recommendation as to whether: 1) treatment of adult patients 
in Phase II of the protocol should continue; and 2) the study should proceed with 
the enrollment and treatment of children in Phase II of the protocol. 
 
- 
At any other time as needed 
The DSMB has the authority to recommend dose or regimen modifications for safety concerns. 
A written summary documenting the results and recommendations of each review will be provided 
to the investigator(s) and maintained on file with the Sponsor. Additional sub-investigators and 
scientific personnel may participate in reviews, as appropriate. 
The DSMB will provide recommendations about stopping or continuing the trial. To contribute to 
enhancing the integrity of the trial, the DSMB may also formulate recommendations relating to 
the selection/recruitment/retention of participants, their management, improving adherence to 
protocol-specified regimens and retention of participants, and the procedures for data 
management and quality control. 
A DSMB charter will dictate procedures, responsibilities, membership, data requirements and 
meeting timing. 

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11.1.1 Stopping Criteria 
 
An objective of this study is to generate a safety profile of FCX-007 in subjects with RDEB. 
Subjects with RDEB have a significantly increased risk of experiencing SAEs such as serious 
infections relative to the general population; therefore, in most cases, possible discontinuation of 
the study will be reviewed on a case-by-case basis. Events which will not be reviewed case-by- 
case that will result in immediate enrollment discontinuation and treatment discontinuation for all 
subjects are a positive RCL assay and histologically confirmed cancer in combination with the 
presence of viral vector in the tumor. In addition, the Medical Monitor may interrupt study dosing 
and/or study entry at any time if medically indicated. To minimize risk, cumulative safety data will 
be reviewed by the Medical Monitor and DSMB, as outlined in Section 11.1. 
Occurrence of any of these observations will trigger a temporary suspension of FCX-007 
administration pending a safety investigation: 
1. 
A treatment emergent serious adverse event or suspected serious adverse event 
related to FCX-007, the FCX-007 administration procedure, or any other protocol 
procedure. 
2. 
A positive RCL qPCR assay result. A positive RCL qPCR assay will result in 
suspension of FCX-007 administration. The result will be confirmed by 
conducting a biological-based assay. If both assays are positive, FCX-007 
administration will be discontinued and no further enrollment into the study will 
be allowed. 
3. 
An autoimmune response determined by the Investigator to be possibly, 
probably or definitely related to treatment. 
4. 
Any systemic infection designated as suspected to be related to FCX-007. 
5. 
A treatment emergent uncontrolled bacterial, viral, or fungal infection in a wound 
that was administered by investigational product where product sterility testing 
results reported post injection were positive for contamination. 
6. 
Any subject diagnosed with a histologically proven skin cancer (including 
sarcomas) will be biopsied and assayed for viral vector by qPCR. A positive 
result for viral vector will cause product administration to be suspended. 
For subject safety, investigators should continue to follow patients in accordance with study visits 
and procedures as outlined in the protocol. An occurrence of any of these safety observations will 
be shared with all study Investigators, DSMB and the appropriate authorities. The DSMB will 
review the results of the safety investigation and may request any additional data needed to 
assess the safety of restarting product administration. The DSMB will determine if the suspension 
can be lifted or if the trial will need to terminate based on their review of the safety investigation. 
 
11.1.2 Transition from Phase I to Phase II 
 
The DSMB will review all data through Visit 5 (Week 4) for the first three subjects in each arm of 

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Phase I of the protocol and make a recommendation as to whether: 1) treatment of adult (≥ 18 
years old) patients in Phase II of the protocol should continue; and 2) the study should proceed 
with enrollment and treatment of children in Phase II of the protocol. The DSMB will consider 
cumulative safety data, including adverse events, pertinent laboratory and clinical data in making 
its recommendation to proceed with treatment of adult subjects in Phase II of the protocol. In 
addition, the DSMB will also consider evidence of direct benefit (see Section 10.1.2.1) in making 
its recommendation to proceed with for enrollment of pediatric (aged 7 to 17 years old) subjects 
in Phase II. Adult subjects will be allowed treatment in Phase II of the protocol upon obtaining 
the DSMB recommendation to proceed with their treatment. Pediatric patients will only be allowed 
to enroll into Phase II of the protocol if the DSMB recommends proceeding with enrollment of 
pediatric subjects into Phase II of the protocol and the FDA provides approval for proceeding to 
pediatric subjects. 
 
11.1.2.1 
Criteria for the Evidence of Benefit 
Evidence of benefit is defined as having any one or more of the following three criteria in a single 
FCX-007 treated wound: 
- 
An increased presence of C7, defined as an increase of 1 or more, relative to 
baseline, on a biopsy evaluated by immunofluorescence (IF), as measured by a 
qualified reader. 
- 
The presence of mature anchoring fibrils as designated by a qualified reader. 
- 
Increase in wound healing based on investigator assessment relative to baseline 
(Day 0) in any wound administered FCX-007. 
 
11.2 Medical and Medication History 
The Investigator or delegated staff performs a complete medical history at Screening, including a 
medication history. The Investigator or staff must record all clinically or medically relevant 
information. Medical and medication history are reviewed and updated at visit 2 and visit 3. 
Select medical history is also reviewed during Prescreening per the process outlined in Section 
7.1.1 (Prescreening) above. The medical history will include respiratory, cardiovascular, renal, 
gastrointestinal, hepatic, endocrine, hematological, neurological, psychiatric and other diseases. 

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11.3 Physical Examination 
A qualified individual will perform a full physical examination Visit 1, 3, and Visit 10. Body systems 
evaluated will include: 
- 
General appearance 
- 
HEENT (Head, Ears, Eyes, Nose, Throat) 
- 
Spine/Neck/Thyroid 
- 
Respiratory 
- 
Cardiovascular 
- 
Abdomen 
- 
Nervous System 
- 
Musculoskeletal 
Abnormalities or changes in severity noted during the exam should be reported in the source 
document and on the appropriate CRF page. If a new clinically relevant finding occurs (not noted 
prior to FCX-007 administration), an adverse event form must be completed. In addition, 
resolution of any abnormal findings during the study will be noted in the source document and 
appropriate CRF if clinically significant. 
 
11.4 Skin Examination 
A qualified individual will perform a skin examination at all visits to the Investigative Site. If at any 
point in the study a skin cancer occurs in the region of the FCX-007 administration, attempts will 
be made to collect samples of the skin cancer to evaluate cells for the presence of viral vector. 
 
11.5 Vital Signs 
Vital sign measurements include systolic and diastolic blood pressure, pulse, and respiratory rate 
as well as temperature. Blood pressure, pulse, and respiratory rate are taken after subjects are 
in a rested state. Blood pressure determined by cuff (manual or automated) is acceptable 
although the same method should be used throughout the study. Temperature, oral or tympanic, 
is acceptable although the same method should be used throughout the study. 

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11.6 Laboratory Evaluations 
 
11.6.1 Serum Chemistry and Hematology 
 
Whenever possible, the amount of blood collected should be minimized. Serum chemistry and 
hematology laboratory analyses will occur locally. Reference ranges will be supplied by the 
laboratory and used to assess the laboratory data for clinical significance and out-of-range 
pathological changes. Abnormal laboratory values which are unexpected or not explained by the 
subject’s clinical condition should be repeated until confirmed, explained or resolved. Changes 
from the Day -2 lab results will be recorded as an AE if deemed clinically relevant by the 
Investigator or medically qualified designee. The following evaluations will be conducted: 
Serum Chemistry / Metabolic Panel 
- Albumin 
- Alkaline Phosphatase Total 
- Anion Gap 
- ALT (SGPT) 
- AST (SGOT) 
- Urea Nitrogen 
- Calcium 
- Chloride 
- Bilirubin, direct & indirect 
- CO2 
- Creatinine 
- Glucose 
- Globulin 
- Potassium 
- Sodium 
- Total Bilirubin 
- Total Protein 
Hematology / Complete Blood Count with Differential 
- WBC 
- Hemoglobin 
- Hematocrit 
- Platelet Count 
- MCV RDW 
- RBC MCH 
- MCHC 
- Neutrophils, % and abs 
- Lymphocytes, % and abs 
- Monocytes, % and abs 
- Eosinophils, % and abs 
- Basophils, % and abs 
 
11.6.2 Urine Pregnancy Test 
 
A urine pregnancy test will be performed at the Visit 1 and Visit 2 for women of childbearing 
potential. 
 
11.6.3 Replication Competent Lentivirus Analysis 
 
A replication competent lentiviral (RCL) assay will be performed on 5 mL of blood collected at 
Visit 1 (at any time up until 4 weeks prior to the scheduled administration date) and Visits 5, 6, 8, 
and 10, (collected at Visit 7 and 9 if visit is conducted in office) and then yearly thereafter for up 
to 15 years (as described in the Long-Term Follow-Up Section 7.5). If all post-treatment RCL 
assays are negative during the first year (e.g., Weeks 4, 12, 16, 25, 32, and 52), collection of the 
yearly follow-up samples will be discontinued. The Long-Term Follow-Up blood samples can be 
collected remotely by the Subject’s primary EB care physician. A positive RCL assay result must 
be recorded as an adverse event. 
 
11.6.4 C7 Antibody Assay 
 
Subject serum will be collected at Screening and Visits 5, 6, 8, and 10 (collected at Visit 7 and 9 
if visit is conducted in office) for the purpose of conducting a C7 antibody assay. Subject serum 
will be evaluated by indirect IF using monkey esophagus as a substrate. Western blot analysis 

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can be performed as needed. A positive C7 antibody assay result must be recorded as an adverse 
event. 

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12 Procedures: Optional Diagnostic Assessments 
 
The following procedures, specific to confirming a subject’s diagnosis of RDEB, are performed 
only under the condition that they have not been conducted and documented previously as 
determined during Prescreening. If needed, the following procedures are conducted during the 
Screening Visit. 
 
12.1 Evaluation of Diagnostic Biopsies 
If not conducted previously, two biopsies are obtained during the Screening Visit for the purpose 
of conducting IF and IEM evaluations as outlined in Sections 10.1 and 10.2.2. 
 
12.2 Genetic Testing 
This process is only applicable to potential subjects which are eligible for the study but do not 
have genotype information. Genetic testing is conducted on the subject to confirm that the subject 
has RDEB as well as for determination of NC1 status. 
The subject is asked to have a blood sample drawn in a laboratory that is convenient for them. 
This blood sample will be sent to an outside lab for genetic testing. All fees associated with this 
genetic testing are reimbursed. 
 
12.3 Autoimmune Assay 
If not conducted previously, a biopsy is obtained during the Screening Visit for the purpose of 
performing DIF. Reference Section 10.2.4 Autoimmune Assays. 

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13 Adverse Experiences 
 
13.1 Definitions 
 
13.1.1 Adverse Events 
 
An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, disease or exacerbation of a pre-existing condition 
temporally associated with the use of a medicinal (investigational) product. 
Subjects should be asked a non-leading question in order to avoid bias in eliciting AEs; such as 
“How are you feeling?” It is important to question the subject in a non-leading way about changes 
in their health or concomitant medication usage since their last visit. Where possible, a diagnosis 
rather than a list of symptoms should be recorded. If a diagnosis has not been made then each 
symptom should be listed individually. 
Each AE requires a complete description including date of onset and corrective actions taken. 
The intensity of the AE and its relationship to the investigational product, as well as its outcome, 
must be recorded in the CRF. 
Symptoms of the disease under study/lack of efficacy should not be considered as AEs, as long 
as they are within the normal day-to-day fluctuation or expected progression of the disease. 
However, significant worsening of the symptoms should be recorded as an AE. 
A change in the value of a safety laboratory evaluation can represent an AE if the change is 
clinically relevant (as determined by the Investigator) or if, during treatment with the investigational 
product, a shift of a parameter is observed from a normal value to a pathological value, or a further 
worsening of an already pathological value. When evaluating such changes, the extent of 
deviation from the reference range, the duration until return to the reference range, either while 
continuing treatment or after the end of treatment with the investigational product, and the range 
of variation of the respective parameter within its reference range, should be taken into 
consideration. The Investigator should decide, based on the above criteria and the clinical 
condition of a subject, whether a change in a laboratory parameter represents an AE. For 
pathological laboratory values that were not present at baseline, follow-up laboratory evaluations 
should be performed until the values return to within reference range or until a plausible 
explanation is found. 
AEs should be recorded, starting from subject enrollment (date of signature on informed consent) 
per the Schedule of Events, until the end of the Long Term Follow-Up Period, and are to be 
recorded on the appropriate AE pages in the CRF and in source documents. Where possible, all 
AEs should be followed to resolution, or an outcome is reached. Medical tests and examinations 
will be performed, as appropriate, to document resolution of event(s). 

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NOTE: Blistering MUST be noted as an AE if it is seen proximal to a product-treated wound. 
 
13.1.2 Serious Adverse Events 
 
A Serious Adverse Event (SAE) is any untoward medical occurrence (whether considered to be 
related to investigational product or not) that at any dose: 
- 
Is fatal. 
- 
Is life-threatening (places the subject at immediate risk of death) 
- 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
- 
Is a persistent or significant disability/incapacity, or 
- 
Is a congenital abnormality/birth defect. 
A hospitalization meeting the regulatory requirement for the “serious” criteria is any inpatient 
hospital admission that includes a minimum of an overnight stay in a health care facility. 
Any event that does not exactly meet this definition yet, in the investigator’s opinion represents a 
significant hazard can be assigned the “other significant hazard” regulatory reporting serious 
criteria. 
Additionally, important medical events that may not be immediately life threatening or result in 
death or hospitalization but that may jeopardize the subject or require intervention to prevent one 
of the outcomes listed above, or result in urgent investigation, may be considered serious. 
Examples include allergic bronchospasm, convulsions, and blood dyscrasias. 
SAEs will be collected and reported throughout the study duration beginning with enrollment 
through the end of the Long-Term Follow-Up period. If early termination of study treatment occurs, 
SAEs will continue to be collected until the event resolves. 
 
13.2 Reporting Procedures 
All adverse events occurring after FCX-007 administration observed by the investigator or 
reported by the subject (whether or not attributed to investigational product), will be reported on 
the case report form. 
Medically significant adverse events considered related to the investigational product by the 
investigator or the sponsor will be followed until resolved or considered stable. The investigator 
must assign the following attributes: description; dates of onset and resolution; severity; 
assessment of relatedness to investigational product, and action taken. The investigator may be 
asked to provide follow-up information. 
All deaths occurring on study must be reported to Fibrocell. These include deaths during the Long- 
Term Follow-Up period. For all deaths, available autopsy reports and relevant medical reports 
should be provided to the Medical Monitor. 
The investigator should notify the IRB of serious adverse events occurring at the site and other 

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adverse event reports received from Fibrocell, in accordance with local procedures. 
It will be left to the investigator’s clinical judgment whether or not an adverse event is of sufficient 
severity to require the subject’s removal from study. A subject may also voluntarily withdraw from 
study due to what he or she perceives as an intolerable adverse event. If either of these occurs, 
the subject will be asked to undergo an early termination assessment and be given appropriate 
care under medical supervision until symptoms cease or the condition becomes stable. If the 
subject was permanently withdrawn from the study due to a serious adverse event, this 
information must be included in either the initial or follow-up Serious Adverse Event Report Form, 
and in the End of Study Case Report Form. 
The severity of toxicities will be assessed on the following scale with appropriate clinical 
definitions: Grade1 = mild adverse event, Grade 2 = moderate adverse event, Grade 3 = severe 
adverse event, Grade 4 = immediate life threatening adverse event, and Grade 5 = fatal adverse 
event. 
The relationship of adverse events to the investigational product will be assessed by the 
investigator using good clinical judgment according to the following definitions: 
• 
Unrelated: no temporal association or the cause of the event has been identified, or the study 
drug cannot be implicated based upon available information. 
• 
Unlikely (related): a potential relationship between study drug and the event could exist (i.e., 
the possibility cannot be excluded), but the event is most likely explained by causes other 
than the study drug. 
• 
Possible/Possibly (related): temporal association, but other etiologies are likely to be the 
cause. However, involvement of the study drug cannot be excluded based upon available 
information. 
• 
Probable/Probably (related): the event and use of study drug are temporally related, and the 
event is more likely explained by study drug than by other causes. 
• 
Definite/Definitely (related): established temporal or other association (e.g., re-challenge) and 
event is not reasonably explained by the subject’s known clinical state or any other factor, 
based on available information. 
 
13.2.1 Post-FCX-007 Administration Adverse Event Monitoring 
 
The Investigator must monitor the subject’s wounds closely for additional blister formation and 
expansion of the border of the wound during injections and immediately post-administration up to 
the 2 day follow up visit. Additional blister formation and/or expansion of the border of the wound 
must be recorded as an adverse event. 

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13.2.2 SAE Reporting Procedures 
 
All serious adverse events must be reported to Fibrocell or designee within 1 working day of the 
earlier of discovery or notification of the event throughout the duration of the study. Initial serious 
adverse event information and all amendments or additions must be recorded on a Serious 
Adverse Event Report Form and faxed or emailed to Fibrocell or designee. 

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14 Statistical Considerations 
 
The objectives of this protocol are outlined in Section 2.2 (Objectives). 
Treatment visits in this study will include Visits 3 through 10, and unscheduled visits. For efficacy 
evaluation, the end-of-treatment (or treatment endpoint) will also be defined as a post-treatment 
assessment time point for efficacy evaluations in order to handle the issue of missing data that is 
caused by incomplete data collection or early terminations. 
 
14.1 Number of Subjects 
A formal sample size calculation was not performed for this study. The sample size is based on 
what was considered an adequate number of subjects for a pilot study to obtain sufficient 
information on the safety and effectiveness of FCX-007. 
 
14.2 
General considerations 
Data will be summarized by treatment regimen and, when applicable, by study visit. Descriptive 
statistics (number and percentage for categorical data, mean, median, range, standard deviation 
and N for continuous data) will be presented for each evaluable parameter for change from 
baseline as well as the value at each timepoint. For discrete variables, descriptive analyses will 
be based on numbers of subjects (or wounds) and related percentages. 
All listings, summaries, figures, and statistical analyses will be generated using SAS version 9.1 
or other validated software. When applicable, statistical comparisons between treatments will 
account for correlated and/or paired data since the data are comprised of multiple wounds on the 
same individual. Statistical analyses will be exploratory and performed using 2-sided tests at a 
Type I error rate of 0.05. 
 
14.3 Data Management 
Pre-designed CRFs will be used to collect information for safety and proof of mechanism 
analyses. A clinical database will be managed by a sponsor’s representative for this study. The 
database will be constructed based on the CRF data entry plus laboratory data information. Data 
queries will be generated and resolved. In addition, range checks of the CRF fields, plausibility 
and consistency checks across CRF pages will be performed to assess consistency, accuracy 
and completeness of the data collected and entered into the CRF. Standard SAS datasets will be 
generated and provided for analysis. 
 
14.4 Study Populations 
The primary population for an analysis of the proof of mechanism is the Full Analysis Set (FAS) 

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population. Study populations are defined in the following sections. 
 
14.4.1 Safety Population 
 
This population is defined as all subjects who were administered FCX-007. 
 
14.4.2 Full Analysis Set Population 
 
TheFull Analysis Set (FAS) population includes subjects who were administered FCX-007 who 
have had at least one paired assessment of the target wound area post-administration. 
 
14.4.3 Per-Protocol Population 
 
The per-protocol (PP) population is defined as all subjects in the FAS population who have had 
at least one paired assessment of the target wound area post-administration, and completed the 
protocol as planned. 
 
14.5 Demographic and Baseline Characteristics 
The descriptive summaries of subjects’ demographic and baseline characteristics will be 
presented by treatment group for the safety, FAS, and PP populations. A detailed description of 
subject disposition will be provided. 
Subject characteristics will include a summary of the following: 
- 
Subject demographics. 
- 
Baseline disease characteristics as determined at screening. 
- 
Pre-existing medical conditions. 
Continuous variables will be summarized using number of observations, mean and standard 
deviation, median and minimum and maximum values. Categorical values will be summarized 
using number of observations and percentages. 
 
14.6 Proof of Mechanism Analyses 
 
14.6.1 Expression of Collagen VII 
 
Biopsies collected for the purpose of IF will be evaluated for expression of C7. Each biopsy will 
be scored by a qualified reader. Scores will be evaluated and C7 will be considered to be 
expressed if an increase from baseline is observed. 
Change in score from baseline will be evaluated and reported for each post-treatment visit and 
treatment endpoint by treatment and study phase and will be compared between treatments for 
each study phase. These analyses will be performed for both FAS and PP populations. 

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14.6.2 Immunoelectron Microscopy / Production of Anchoring Fibrils 
 
Biopsies collected for the purpose of IEM will be evaluated for the presence of anchoring fibrils, 
LH24 and mAb185 antibody staining and C7 expression. Evaluation of each item from each 
biopsy will be scored by a qualified reader. LH24 and mAb185 antibody staining and anchoring 
fibrils will be evaluated and considered to be present if a score of + is observed. 
The percent of target wounds with a + score for each item evaluated will be reported at each post- 
treatment visit by treatment for each study phase. For quantitative analysis, the obtained results 
will be assigned a numeric value of 0 and 1, respectively, for – and +. Change in score from 
baseline will be evaluated and reported for each post-treatment visit by treatment and study phase 
and compared between treatments for each study phase. These analyses will be performed for 
both FAS and PP populations. 
 
14.6.3 Target Wound Area 
 
Dimensions of target wounds (treated and control)/ partial wounds will be obtained using the 
Canfield VECTRA H1-270 System. Dimensions obtained will include length, width, and area (in 
cm2). Change in area and other dimensions from baseline initial target wound identification and 
between visits will be evaluated. 
The healed skin area of the target wounds (treated and control)/ partial wound will be evaluated 
using photographs by the investigator at each post-treatment visit and by treatment and study 
phase, and will be compared between treatments for each study phase. 
The percent of change in the target wound (treated and control) / partial wound area from baseline 
will be assessed by the investigator at each post-treatment visit and by treatment and study 
phase, and will be compared between treatments for each study phase. 
The proportion of target wounds (treated and control) / partial wounds achieving complete wound 
closure (≥ 90%) will be reported at each post-treatment visit by treatment and study phase and 
compared between treatments for each study phase. 
These analyses will be performed for both FAS and PP populations. 
 
14.6.3.1 
Investigator Assessment of Wound Healing 
The investigator will assess wound healing of target wounds (treated and control/untreated) based 
on the digital images of the target wounds. The investigator will assess wound healing of target 
wounds from 0% to 100% healed on a categorical scale. The wound healing assessment will be 
captured in the following categories. 
 
- 
0% 
- 
1-9% 
- 
10-24% 

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- 
25-49% 
- 
50-74% 
- 
75-89% 
- 
90-99% 
- 
100% 
 
14.7 Safety Analyses 
All continuous parameters will be summarized using standard summary statistics as appropriate 
(n, mean, standard deviation, median, minimum, maximum, 25th percentile, and 75th percentile). 
Summary statistics for categorical variables will include frequency counts and percentages. 
Patient demographics and relevant baseline data will be analyzed descriptively. Inclusion and 
exclusion criteria ensure that participants are suitable for the study. Premature termination will be 
tabulated and summarized. 
 
14.7.1 Adverse Events 
 
Adverse events will be coded using the MedDRA adverse event dictionary. Safety evaluations 
will be based on occurred adverse events, laboratory values, vital signs and appearance of C7 
antibodies, and RCL. Severities of toxicities will be described using the NCI Common Toxicity 
Criteria (CTC) grades. 
Adverse events will be grouped into pre-treatment adverse events and treatment-emergent 
adverse events and will be tabulated by preferred terminology and by body system for each study 
phase. The number of adverse event entries, as well as the number of patients will be reported. 
Analyses will include tabulation of adverse event type, relationship to FCX-007, seriousness, and 
severity of adverse events according to CTCAE. 
 
14.7.2 Physical Examinations 
 
Physical examinations at screening and subsequent follow-up visits will be displayed in tabular 
format displaying number of subjects examined and number and percentage of subjects with 
abnormalities by physical examination category. 
 
14.7.3 Vital Signs 
 
Vital signs will be listed and summarized by means and SD. 
 
14.7.4 Laboratory Tests 
 
Laboratory test values will be presented in shift tables and by display of changes to baseline. 

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Evaluations of C7 antibodies and RCL will be done descriptively. 
 
14.8 Interim Analysis 
There will be no formal interim analysis. The DSMB will evaluate safety following the first subject 
of each arm, prior to the fourth subject of each arm, and thereafter annually for the duration of the 
study. 
 
14.9 Handling of Missing and Incomplete Data 
Missing values will be captured as such in the CRF database. No imputation for missing data is 
planned for efficacy analyses, although different assumptions depending on the analysis, may be 
explored. Standard clinical monitoring and data management practices will be used to ensure the 
integrity of data. 

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15 Regulatory Obligations 
 
15.1 Informed Consent 
Before a subject’s participation in the trial, the investigator (or designee) is responsible for 
obtaining written informed consent from the subject or legally acceptable representative (see note 
below) after adequate explanation of the aims, methods, anticipated benefits, and potential 
hazards of the study and before any protocol-specific screening procedures or any investigational 
products are administered. A legally acceptable representative is an individual or other body 
authorized under applicable law to consent, on behalf of a prospective subject, to the subject’s 
participation in the clinical trial. 
The acquisition of informed consent should be documented in the subject’s medical records, and 
the informed consent form should be signed and personally dated by the subject or a legally 
acceptable representative and by the person who conducted the informed consent discussion 
(not necessarily an investigator). The original signed informed consent form must be retained in 
accordance with institutional policy, and a copy of the signed consent form must be provided to 
the subject or legally acceptable representative. 
If a potential subject is illiterate or visually impaired and does not have a legally acceptable 
representative, the investigator must provide an impartial witness to read the informed consent 
form to the subject and must allow for questions. Thereafter, both the subject or legally acceptable 
representative and the witness must sign the informed consent form to attest that informed 
consent was freely given and understood. 
 
15.2 Institutional Review Board 
A copy of the protocol, proposed informed consent form, other written subject information, and 
any proposed advertising material including the information letters must be submitted to the IRB 
for written approval. A copy of the written approval of the protocol, informed consent form, and 
advertising material must be received by Fibrocell before recruitment of subjects into the study 
and shipment of investigational product. 
The investigator must submit and, where necessary, obtain approval from the IRB for all 
subsequent changes to the above named documents. The investigator should notify the IRB of 
important deviations from the protocol or serious adverse events occurring at the site and other 
adverse event reports received from Fibrocell, in accordance with IRB procedures. 
The investigator will be responsible for obtaining IRB approval/renewal throughout the duration of 
the study at the frequency specified by the IRB. Copies of the investigator’s reports and the IRB’s 
written continuance of approval must be sent to Fibrocell. 

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15.3 Pre-Study Documentation Requirements 
The investigator is responsible for forwarding the following documents to Fibrocell for review 
before study initiation from Fibrocell can occur: 
- 
Signed and dated protocol signature page (Investigator’s Agreement) 
- 
Copy of approved informed consent form and assent form (for phase II) 
- 
Copy of the IRB approval of the protocol, information letter, consent form, and 
assent form 
- 
Up-to-date curricula vitae of principal investigator and all co/subinvestigators 
- 
The IRB composition and/or written statement that IRB is in compliance with 
regulations 
- 
Laboratory normal ranges and documentation of laboratory certification (or 
equivalent) 
- 
Current subject/investigator indemnity insurance 
- 
Signed study contract 
- 
Completed FDA form 1572. Laboratories providing primary and secondary 
endpoint data and any central laboratories for the study must be listed on the 
form. 
- 
For studies covered under 21 CFR Part 54.2(e), “Financial Disclosure,” 
completed Financial Disclosure statements for the principal investigator, all 
subinvestigators, and their spouses (legal partners) and dependent children. 
 
15.4 Subject Confidentiality 
The investigator must take all reasonable measures to ensure that the subject’s confidentiality is 
maintained. On the case report forms or other documents submitted to the study sponsor and 
those working with the study sponsor, subjects should be identified by their initials and a subject 
study number only. Documents that are not for submission to the study sponsor and those working 
with the study sponsor should be kept in strict confidence by the Investigator. 
In compliance with Federal regulations/ICH GCP Guidelines, the Investigator and Institution shall 
permit authorized representatives of Fibrocell and companies that work with Fibrocell, of the 
regulatory agency(s), and the IRB direct access to review the subject’s original medical records 
for verification of study-related procedures and data. Direct access includes examining, analyzing, 
verifying, and reproducing any records and reports that are important to the evaluation of the 
study. The investigator is obligated to inform and obtain the consent of the subject to permit such 
named representatives to have access to his/her study-related records without violating the 
confidentiality of the subject. 

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16 Administrative and Legal Obligations 
 
16.1 Protocol Amendments and Study Termination 
Protocol amendments must be made only with the prior approval of Fibrocell. Agreement from 
Fibrocell must be obtained for all protocol amendments and amendments to the informed consent 
document. The IRB must be informed of all amendments and give approval for any amendments 
likely to affect the safety of the subjects or the conduct of the trial. The investigator must send a 
copy of the approval letter from the IRB to Fibrocell. 
Fibrocell reserves the right to terminate the study, according to the study contract. The 
investigator should notify the IRB in writing of the trial’s completion or early termination and send 
a copy of the notification to Fibrocell. 
 
16.2 Study Documentation and Storage 
 
16.2.1 Delegation Log 
 
The investigator should maintain a list of appropriately qualified persons to whom he/she has 
delegated trial duties. All persons authorized to make entries and/or corrections on case report 
forms will be included on the Delegation of Authority Form. 
 
16.2.2 Source Documents 
 
Source documents are original documents, data, and records from which the subject’s case report 
form data are obtained. These include but are not limited to hospital records, clinical and office 
charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
 
16.2.3 Study File 
 
The investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system of all study-related (essential) documentation, in a complete, accurate, and legible 
manner, suitable for inspection at any time by representatives from Fibrocell, companies that work 
for and with Fibrocell, and/or applicable regulatory authorities. Elements should include: 
- 
Subject files containing completed case report forms, informed consents, and 
supporting copies of source documentation 
- 
Study files containing the protocol with all amendments, investigator’s brochure, 
copies of prestudy documentation, and all correspondence to and from the IRB 
and Fibrocell 
- 
Proof of receipt, Investigational Product Accountability Record, Return of 
Investigational Product for Destruction, Final Investigational Product 

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Reconciliation Statement, and all drug-related correspondence 
In addition, all original source documents supporting entries in the case report forms must be 
maintained and be readily available. 
No study document should be destroyed, moved to another location, or assigned to another party 
without prior written consent of Fibrocell. 
 
16.3 Study Monitoring and Data Collection 
The Fibrocell monitor is responsible for inspecting the case report forms at regular intervals to 
verify adherence to the protocol; completeness, accuracy, and consistency of the data; and 
adherence to local regulations on the conduct of clinical research. The monitor should have 
access to subject medical records and other study-related records needed to verify the entries on 
the case report forms. 
The Investigator agrees to cooperate with the monitor to ensure that any problems detected in 
the course of these monitoring visits, including delays in completing case report forms, are timely 
resolved. 
 
16.4 Publication Policy 
The information provided in support of or generated as a result of this study is confidential. Any 
use or reproduction thereof, including but not limited to publications or presentations by the 
Investigator or his associates, must be submitted to the Sponsor for review and approval prior to 
publication or presentation in any form. All publications must acknowledge the sponsorship. 

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17 Bibliography 
 
Cell Biolabs, I., 2014. Product Data Sheet: pSMPUW universal lentiviral expression vector 
(promoterless). 
Dang, N., 2008. Mutation analysis and characterization of COL7A1 mutations in dystrophic 
epidermolysis bullosa. Experimental Dermatology, pp. 553-568. 
Dunnill, M., 1996. Clinicopathological correlations of compound heterozygous COL7A1 
mutations in recessive dystrophic epidermolysis bullosa. Journal of Investigative Dermatology, 
pp. 171-177. 
Falabella, A., Valencia, I., Eaglstein, W. & Schachner, L., 2000. Tissue-engineered skin 
(Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol, Volume 
136, pp. 1225-1230. 
Fine, J., 2004. Eye involvement in inherited epidermolysis bullosa: experience of the National 
Epidermolyis Bullosa Registry. Am J Ophthalmol, Volume 138, pp. 254-262. 
Fine, J., 2005. Pseudosyndactyly and musculoskeletal deformities in inherited epidermolysis 
bullosa (EB): experience of the National EB Registry. J Hand Surg, Volume 30B, pp. 14-22. 
Fine, J., 2008. Gastrointestinal complications of inherited epidermolysis bullosa - cumulative 
experience of the National EB Registry. J Pediatr Gastroenterol Nutr, pp. 147-158. 
Fine, J., 2010. Inherited epidermolysis bullosa. Orphanet J Rare Dis, pp. 5-12. 
Hsu, C.-K., Wang, S.-P., Lee, J. Y.-Y. & McGrath, J., 2014. Treatment of Hereditary 
Epidermolysis Bullosa: Updates and Future Prospects. Am J Clin Dermatol, Volume 15, pp. 1-6. 
Intong, R., 2012. Inherited epidermolysis bullosa: A new diagnostic criteria and classification. 
Clinics in Dermatology, pp. 70-77. 
Ortiz-Urda, S. et al., 2003. Injection of genetically engineered fibroblasts corrects regenerated 
human epidermolysis bullosa skin tissue. J. Clin. Invest., Volume 111, p. 251–255. 
Petrof, G. et al., 2013. Fibroblast cell therapy enhances initial healing in recessive dystrophic 
epidermolysis bullosa wounds: results of a randomised, vehicle-controlled trial. British Journal of 
Dermatology, Volume 169(5), pp. 1025-1033. 
RAC, N., 2007. Recombinant DNA ADvisory Committee Minutes of Meeting and Webcast. 
http://osp.od.nih.gov/sites/default/files/RAC_minutes_03-07.pdf, pp. 14-21. 
Siprashvili, Z. et al., 2010. Long-term type VII collagen restoration to human epidermylosis 
bullosa skin tissue. Hum Gene Ther, 21(10), p. 1299–1310. 
Tidman, M., 1985. Evaluation of anchoring fibrils and other components of hte dermal-epidermal 
junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique. J Invest 
Dermatol, pp. 374-377. 
Venugopal, S. et al., 2013. A phase II randomized vehicle-controlled trial of intradermal 
allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J AM ACAD DERMATOL, 
69(6), pp. 898-908. 
Woodley, D. et al., 2004. Injection of recombinant human type VII collagen restores collagen 
function in dystrophic epidermolysis bullosa. Nat. Med., Volume 10, p. 693–695. 

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18 Summary of Changes 
 
 
Version 
Section 
Original 
Amendment 
8.0 
Throughout 
Visit numbers detailed 
Visit numbers with associated timing of 
study visits in days/weeks, as applicable, 
specified. 
Throughout 
Visit number inconsistencies 
(Visit 5, Visit 6) when second 
FCX-007 administration to occur 
Visit 5 (Week 4) specified where 
applicable. 
Background; 
Investigational Product 
FCX-007 to be administered 
within 40 hours of vial fill time. 
FCX-007 to be administered prior to the 
expiration date and time indicated on the 
product label. 
Rationale and Objectives 
Fibrocell and Intrexon are co- 
developing FCX-007. 
Removed Intrexon as co-developer. 
Rationale and Objectives; 
Study Design 
Efficacy evaluation based on 
digital imaging system 
dimensions/calculations. 
Efficacy evaluation based on investigator 
assessment of wound healing based on 
digital images of wounds. 
Study Design 
Assignment of subjects into two 
arms based on NC1 status in 
each phase of the study. 
Assignment of subjects into two arms 
based on NC1 status in Phase 1 
Study Design 
Enrollment specifications in 
each arm and phase of the 
study prior to moving into next 
phase. 
Removed 
Study Design; 
Investigational Product; 
FCX-007 Administration 
FCX-007 administered around 
the margins and across the axes 
of wounds 
Removed across the axes of wounds. 
Study Design; Study Visits Subject target wounds will be 
imaged during the Wound 
Monitoring Period. 
Subject target wounds may be imaged 
during the Wound Monitoring Period. 
Study Design; Study 
Visits; Safety 
Assessments; 
RCL testing to occur annually in 
Years 1-5 in the LTFU period. 
RCL testing to occur yearly in the LTFU 
period for up to 15 years, however if 
subject’s RCL test results are negative in 
the first year, further yearly RCL testing will 
be discontinued. 
Investigational Product; 
FCX-007 Administration 
Sterile saline as investigational 
product/comparator. 
Removed 
Study Design; Study 
Visits; 
FCX-007 Administration; 
Statistical Considerations 
N/A 
Added investigator assessment of wound 
healing 
Study Visits 
One biopsy from intact skin and 
wounds for IF 
One biopsy from intact skin and wounds for 
IF and DIF 
FCX-007 Administration 
Target wounds measured 
Target and control wounds measured 
FCX-007 Administration 
Injecting across the bed of 
target wounds, the injection 
should be placed midway across 
the first square cm from the 
wound margin. 
Removed 
Collection/ Evaluation of 
Biopsies; 
Biopsy for IF analysis to 
evaluate C7 expression 
Biopsy for IF/DIF analysis to evaluate C7 
expression (IF) and C7 antibodies (DIF) 
Collection/ Evaluation of 
Biopsies; 
N/A 
Direct immunofluorescence (DIF) testing 
also performed on the biopsy collected for 
immunofluorescence (IF) testing. 
Collection/ Evaluation of 
Biopsies; 
Safety Assessments; 
Statistical Considerations 
IF evaluation result details, e.g., 
Each target wound biopsy is 
rated as -, +, ++, or +++. 
Removed 

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Version 
Section 
Original 
Amendment 
8.0 
(continued) 
Collection/ Evaluation of 
Biopsies; 
Safety Assessments 
C7 antibodies by will be 
assayed by DIF. 
Specified visits when expected. 
Collection/ Evaluation of 
Biopsies; 
DIF detailed testing 
specifications 
Removed 
Safety Assessments 
DSMB teleconference timing to 
occur after visit 5 (Week 4) for 
the third subject, prior to 
treatment of the first Phase II 
subject in each arm; and 
annually from the date of the 
first subject, first administration. 
Removed “in each arm” and annual 
meeting from the date of first subject, first 
administration. 
Safety Assessments 
Reduction in wound size relative 
to average area of the wound 
observed during the Wound 
Monitoring Period 
Increase in wound healing based on 
investigator assessment 
AE 
AE relationship option of yes or 
no. 
AE relationship options revised to 
unrelated, unlikely, possible/possibly, 
probable/probably, or definite/definitely 
related. 
AE 
SAE reporting to Fibrocell. 
SAE reporting to Fibrocell or designee. 
Statistical Considerations N/A 
Added general considerations section 
Statistical Considerations Intent-to treat population 
Revised to Full Analysis Set population 
Statistical Considerations 
Updated to reflect revisions to data being 
collected and evaluated. 
7.0 
Study Design 
At Week 12 visit, subjects 
receive second administration in 
wounded and intact skin. 
At Week 4 visit, subjects receive second 
administration in wounded and intact skin. 
6.0 
Study Design 
Visits are described in Weeks 
Aligned Visit numbers to Weeks 
Study Design 
12 subjects 
Up to 12 subjects 
Study Design 
Subjects will receive a second 
administration at Week 25 if 
unhealed portions of the target 
wound remain, and if there is 
evidence of function (an 
increase in C7, an increase in 
anchoring fibrils, or a presence 
of viral vector or mRNA) at the 
target wound or in a site of intact 
skin as determined through 
biopsy results. A subject may 
also receive an FCX-007 
administration to intact skin at 
Week 25 if there was evidence 
of function at the site of intact 
skin at Day 0. 
At Week 12 visit, subjects receive second 
administration in wounded and intact skin. 
Study Design 
The first three (3) visits of the 
Treatment Period (Day -2 to Day 
2) will be scheduled so that the 
day of dosing (Day 0) is the day 
of receipt of FCX-007. 
The Treatment Period can occur in as few 
as 2 days and up to 4 days, as safety and 
schedules permit. 
Number of Injections 
Up to 40 
Up to 60 
FCX-007 Administration 
Inject 0.25cm away from the 
wound margin 
Inject up to 1cm away from the wound 
margin 
Dose volume 
 
 
FCX-007 Administration 
Target wound size of 34cm 
Increase to 54cm 
Study Design 
In Phase II, control wounds 
treated with saline 
In Phase II, control wounds remain 
untreated 

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Version 
Section 
Original 
Amendment 
6.0 
(continued) 
FCX-007 Background 
The safety and biodistribution of 
FCX-007 was evaluated in a 3- 
month toxicology/toxicokinetics 
study in NSG mice injected 
subcutaneously with six doses 
of FCX-007. FCX-007 was well 
tolerated throughout the 3- 
month timepoints. 
The safety and biodistribution of FCX-007 
was evaluated in a 6-month 
toxicology/toxicokinetics study in NSG mice 
injected subcutaneously with six doses of 
FCX-007. FCX-007 was well tolerated 
throughout the 3 and 6-month timepoints. 
Study Visit 
Based on subject safety and scheduling, 
Visits 7 and 9 may be conducted with the 
investigator and subject via telephone. 
Study Design 
Paired wounds will be 
randomized via DataTrak to be 
randomized to treatment or no 
treatment 
Paired wounds will be randomly assigned 
to treatment or no treatment 

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Appendix A: Investigational Product Administration 
Instructions 
 
1. Intradermal injections are to be administered by the Investigator or an appropriately trained 
delegated health care professional. 
2. Administer anesthesia. Subjects will be administered anesthesia per standard of care at the 
Investigative Site. To minimize pain and discomfort during the investigational product 
administration, the Investigator should determine the most appropriate anesthetic for each 
subject, including the use of topical anesthetic cream, local anesthesia, conscious (moderate) 
sedation, general anesthesia (if undergoing another procedure at time of injection) or a 
combination thereof. In addition, medication should be considered during and after the 
injections to treat pain and/or anxiety (i.e. lorazepam). 
3. Mark the skin as indicated in Section 8.2 (intact skin) and Section 9.4.1 (wounds). 
4. Approximately 15 minutes prior to the administration of FCX-007, remove the subject’s 
treatment vials from the shipper. 
5. Resuspend the cells by gently inverting the injection vial three times. 
6. Tap the top of each vial to release any fluid in the cap prior to opening the vials. Do not dilute 
the product. 
7. Unscrew the cap and, using a detachable bore (21-gauge needle), aseptically draw 1.0 mL 
from one vial. 
8. Once the product is in the syringe, remove the 21-gauge needle and replace it with the 30- 
gauge needle for injection of the product. Do not use a 21-gauge needle for injection of the 
product. Follow sterile technique during this process. Note: Living cells are fragile and should 
be handled gently, especially when being aspirated into a syringe. Go slowly and use care 
during this process. 
9. Hold the syringe using the proper technique: the bevel facing upwards and the arms of the 
syringe are vertical. Some clinicians may prefer to bend the needle upwards at about a 15- 
degree angle to facilitate staying in a superficial plane — but use of this technique is optional. 
Grip the syringe with the middle and index finger below the arms, placing the thumb on the 
upper arm. Do not place the thumb on the plunger while directing the needle into the skin to 
avoid premature discharge of the product. 
10. Insert the 30-gauge needle at the first mark. 
11. Introduce the needle into the superficial papillary dermis at 0.25 mL per linear centimeter and 
bring the needle along a line parallel to the wound margin. The shadow of the needle under 
the skin must be visible if the injector is in the correct plane. If it is not, replace the needle just 
adjacent to the initial area of insertion in a more superficial plane. 

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12. The graduated markings on the syringe should be visible to ensure that the correct amount is 
being injected. 
13. Once the needle is inserted, apply light pressure to the plunger and inject very slowly, injecting 
very tiny boluses into the treatment area as the needle is withdrawn (the cells must be injected 
as delicately as possible). Keep a close eye on the amount and the skin to ensure only 0.25 
mL is injected into each centimeter, and a wheal is formed with each bolus. Stop injecting 
before withdrawing the needle and remove your thumb from the plunger. 
14. Immediate blanching of the skin or a small wheal must be seen as the product is injected. If 
the needle is in the superficial (papillary) dermis it will be difficult to inject too much volume. If 
you see no blanching or wheal when the product is initially injected, reposition the needle in a 
more superficial plane and inject additional product. 
15. Record any seepage of product or immediate impact to overall wound size. 
Figure 7 - Photographs of Intradermally Administered Fibroblasts Cells 
 

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Appendix B: Biopsy Collection Procedures 
 
Biopsy Supplies 
The following biopsy supplies will be supplied to the site as needed: 
- 
Punch biopsy instruments 
- 
Biopsy Transport Vials containing sterile phosphate buffered saline or sterile 
culture medium such as DMEM 
- 
Associated documentation 
- 
Shipping materials 
Prior to the procedure, the surgeon will need to assemble other items required as follows: 
- 
Syringe and local anesthetic and topical anesthetic cream 
- 
Scalpel (optional) for excision of sample from base 
- 
Suture needle (optional) 
- 
Scissors and/or forceps without teeth as desired 
- 
Wound dressing 
 
Collection Procedure 
Biopsies for the purpose of manufacturing are to be obtained from normal or unaffected skin with 
the specific location varying on a case-by-case basis according to the judgment of the 
Investigator. The neck, head (with the exception of post-auricular), groin, hands, feet and axilla 
are excluded areas. Based on previous experience with collecting biopsies from RDEB subjects 
under IRB approved protocol for product development purposes, the anatomical locations 
including upper leg, calf, trunk and upper arms (in descending order of frequency) are 
recommended areas. 
- 
Anesthetize the area by topical anesthetic, local perfusion. 
- 
Prepare the area. 
- 
Excise a sample of tissue using the appropriate supplied biopsy punch. The use 
of forceps and a scalpel may be necessary to remove the biopsy from its base. 
- 
Gently place excised tissue into cryovial using forceps. 
- 
Close donor site as appropriate. 
- 
Complete associated biopsy inventory form with appropriate subject information. 
- 
Package and ship biopsy as described in the Study Procedures Manual. 

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Local Anesthesia 
All biopsies are obtained after anesthesia. All anesthesia medication must be recorded on the 
concomitant medication source documents and CRF pages. Investigative sites should employ 
standard practice to locally anesthetize the biopsy areas. It is anticipated that a topical lidocaine 
or lidocaine / prilocaine cream will be followed by a 1% lidocaine with epinephrine (10 mg/mL with 
epinephrine) injection.