A Phase I/II Study of KB103, a Non-Integrating, Replication-Incompetent HSV Vector Expressing the Human Collagen VII Protein, for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
Phase: PHASE1
Conditions: Dystrophic Epidermolysis Bullosa
Sponsor: Krystal Biotech, Inc.

 
 
 
The GEM-1 Study 
 
KB103-001 
A Phase II Study of KB103, a Non-Integrating, Replication-Incompetent HSV Vector 
Expressing the Human Collagen VII Protein, for the Treatment of Dystrophic 
Epidermolysis Bullosa (DEB) 
 
 
 
 
Status:   
 
 
Final 
 
 
 
 
 
Protocol Version:  
 
Version 4.0 
 
 
 
 
 
 
 
 
 
Version Date:  
 
01-Aug-2019 
 
 
 
 
 
IND Number:  
 
18100 
 
Investigational Product: 
KB103 
 
 
 
 
 
Phase of Development: 
Phase II 
 
 
 
 
 
 
 
CONFIDENTIAL MATERIAL 
This material is the property of Krystal Biotech, Inc. and it must not be disclosed or used without written 
authorization from Krystal Biotech, Inc.
 

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Protocol Signature Page 
Sponsor Endorsement 
This protocol has been approved by Krystal Biotech, Inc. 
Sponsor’s Authorized Officer:  
 
Suma Krishnan, M.S., M.B.A. 
 
Chief Operating Officer 
 
Krystal Biotech, Inc. 
 
2100 Wharton Street, Suite 701 
 
Pittsburgh, PA  15203 
 
_____________________________________  
 
_______________ 
Signature 
 
 
 
 
 
 
Date  
 
Principal Investigator’s Agreement 
I have read the Phase II Protocol: 
A Phase II Study of KB103, a Non-Integrating, Replication-Incompetent HSV Vector Expressing 
the Human Collagen VII Protein, for the Treatment of Dystrophic Epidermolysis Bullosa (DEB) 
I have fully discussed the objectives of this trial and the contents of this protocol with the Sponsor’s 
representative. 
I agree to conduct the study as outlined herein and in accordance with International Conference on 
Harmonization (ICH) guidelines on Good Clinical Practice (GCP), with applicable Food and Drug 
Administration (FDA) regulations set forth in 21 CFR Parts 50,54, and 312, and all other applicable 
regulatory requirements. 
Principal Investigator Name: ____________________________________ 
____________________________________ 
 
 
_____________________ 
Signature 
 
 
 
 
 
 
Date  
 
 
 

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Table of Contents 
1 
Background ................................................................................................................... 10 
1.1 
Disease Background ........................................................................................... 10 
1.2 
Collagen VII ......................................................................................................... 10 
1.3 
COL7A1 Gene Delivery for DEB ......................................................................... 12 
1.4 
KB103 Background ............................................................................................. 13 
1.5 
KB103-001, Results from Subjects 01 and 02..................................................... 14 
1.6 
Rationale for Protocol Amendments .................................................................... 15 
2 
Objectives ...................................................................................................................... 16 
2.1 
Primary ................................................................................................................ 16 
2.2 
Secondary ........................................................................................................... 16 
2.3 
Other ................................................................................................................... 16 
3 
Selection of Patients ..................................................................................................... 17 
3.1 
Inclusion Criteria .................................................................................................. 17 
3.2 
Exclusion Criteria ................................................................................................ 17 
4 
Study Design ................................................................................................................. 19 
4.1 
Study Overview ................................................................................................... 19 
4.2 
Sites and Trial Duration ....................................................................................... 19 
4.3 
Concomitant Therapy and Skin Care .................................................................. 20 
4.4 
Subject Enrollment and Withdrawal .................................................................... 20 
4.5 
Safety Monitoring Committee .............................................................................. 21 
4.6 
Subject Companions ........................................................................................... 21 
5 
Study Procedures ......................................................................................................... 22 
5.1 
Stopping Criteria .................................................................................................. 22 
5.2 
Study Schedule ................................................................................................... 22 
5.3 
Screening and Baseline ...................................................................................... 24 
5.4 
Cycle 1 ................................................................................................................ 26 
5.5 
Observation Period (OP) 1 .................................................................................. 27 
5.6 
Cycle 2 ................................................................................................................ 27 
5.7 
Observation Period (OP) 2 .................................................................................. 28 
5.8 
Unscheduled Visits .............................................................................................. 28 
5.9 
Long-Term Follow-Up Period .............................................................................. 28 
6 
Investigational Product ................................................................................................ 30 
6.1 
At-Home Topical Administrations ........................................................................ 30 
6.2 
Dose Level .......................................................................................................... 30 
6.3 
Wound Area Selection ......................................................................................... 30 
6.4 
KB103 Administration .......................................................................................... 31 
6.5 
Placebo Administration ........................................................................................ 32 
6.6 
Peri- and Post-procedural Safety Monitoring ....................................................... 32 
6.7 
Post-Dose Procedures ........................................................................................ 32 

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7 
Efficacy Evaluations ..................................................................................................... 33 
7.1 
Wound Measurement .......................................................................................... 33 
7.2 
Biopsy Evaluation ................................................................................................ 33 
7.3 
Investigator’s Global Assessment Score ............................................................. 34 
7.4 
Patient-Reported Outcome Measures ................................................................. 34 
7.5 
Voice Memo Qualitative Data .............................................................................. 34 
8 
Safety Assessments ..................................................................................................... 35 
8.1 
Viral Shedding ..................................................................................................... 35 
8.2 
Medical and Medication History........................................................................... 35 
8.3 
Physical / Skin Examination ................................................................................ 35 
8.4 
Vital Signs ........................................................................................................... 35 
8.5 
Laboratory Evaluations ........................................................................................ 36 
9 
Adverse Events ............................................................................................................. 37 
9.1 
Definitions ............................................................................................................ 37 
9.2 
Severity ............................................................................................................... 38 
9.3 
Relationship ......................................................................................................... 39 
9.4 
Reporting Procedures ......................................................................................... 39 
10 
Statistical Considerations ............................................................................................ 41 
10.1 
Number of Subjects ............................................................................................. 41 
10.2 
Data Management ............................................................................................... 41 
10.3 
Study Populations ............................................................................................... 41 
10.4 
Demographic and Baseline Characteristics......................................................... 42 
10.5 
Proof of Mechanism Analyses ............................................................................. 42 
10.6 
Safety Analyses ................................................................................................... 43 
10.7 
Handling of Missing and Incomplete Data ........................................................... 43 
11 
Regulatory Obligations ................................................................................................. 44 
11.1 
Informed Consent ................................................................................................ 44 
11.2 
Institutional Review Board ................................................................................... 44 
11.3 
Pre-Study Documentation Requirements ............................................................ 45 
11.4 
Subject Confidentiality ......................................................................................... 45 
12 
Administrative and Legal Obligations ......................................................................... 46 
12.1 
Protocol Amendments and Study Termination .................................................... 46 
12.2 
Study Documentation and Storage ..................................................................... 46 
12.3 
Study Monitoring and Data Collection ................................................................. 47 
12.4 
Publication Policy ................................................................................................ 47 
13 
References ..................................................................................................................... 48 
14 
Appendix 1 – KB103 Administration and Removal Instructions .............................. 51 
15 
Appendix 2 – PRO Scale ............................................................................................... 54 
 
 
 

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Figures 
Figure 1 - Anchoring Fibril Formation ......................................................................................... 11 
Figure 2 - KB103 Vector Map ..................................................................................................... 13 
 
 
Tables 
Table 1 - KB103-001 Stopping Criteria ....................................................................................... 22 
Table 2 - Schedule of Events ...................................................................................................... 23 
 
 

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Abbreviations 
Abs ......................... antibodies 
AEs ........................ adverse events  
AF .......................... anchoring fibrils 
ALT (SGPT) ........... alanine aminotransferase, included in metabolic panel 
AST (SGOT) .......... aspartate aminotransferase, included in metabolic panel 
BMZ ....................... basement membrane zone 
CBC ....................... complete blood count 
CFR ........................ Code of Federal Regulations 
CLIA ....................... Clinical Laboratory Improvement Amendments 
CM ......................... centimetre 
COL7 ...................... collagen VII 
COL7A1 ................. collagen 7 gene 
CRF ........................ case report form 
CTC  ....................... Common Toxicity Criteria 
DEB ........................ dystrophic epidermolysis bullosa 
DNA ....................... deoxyribonucleic acid 
EB .......................... epidermolysis bullosa 
eGFP ...................... enhanced green fluorescent protein 
ELISA ..................... enzyme-linked immunosorbent assay 
ELISPOT ................ enzyme-linked immunospot 
EM .......................... electron microscopy 
ET .......................... early termination 
FDA ........................ Food and Drug Administration 
GCP ....................... Good Clinical Practice 
GFP ........................ green fluorescent protein 
GMP ....................... Good Manufacturing Practice 
GRAS ..................... Generally Regarded As Safe 
HCMV .................... human cytomegalovirus 
HDF ........................ Human Dermal Fibroblasts 
HEENT ................... head, ears, eyes, nose, throat 
Hep ........................ hepatitis 
HIPAA .................... Health Insurance Portability and Accountability Act 
HIV ......................... human immunodeficiency virus 
HK .......................... human keratinocytes 
HSV ........................ herpes simplex virus 

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ICF ......................... informed consent form 
ICP ......................... infected cell polypeptide 
ID ........................... intradermal 
IEM ......................... immunoelectron microscopy 
IF ............................ immunofluorescence 
Ig ............................ immunoglobulin 
IIF ........................... indirect immunofluorescence 
IND ......................... Investigational New Drug application 
IP ............................ Investigational Product 
IRB ......................... Institutional Review Board 
ITT .......................... Intent-to-treat 
LTFU ...................... long-term follow-up 
MCH ....................... mean corpuscular hemoglobin 
MCHC .................... mean corpuscular hemoglobin concentration 
MCV ....................... mean cell volume 
mRNA .................... messenger ribonucleic acid 
NC1 ........................ noncollagenous 1 domain 
NC2 ........................ noncollagenous 2 domain 
NCI  ........................ National Cancer Institute 
ORF ....................... open reading frame 
PCR ....................... polymerase chain reaction 
PFU ........................ plaque-forming units 
PHI ......................... protected health information 
PP .......................... per protocol 
RBC ....................... red blood cell count 
RCV ....................... replication competent virus 
RDEB ..................... recessive dystrophic epidermolysis bullosa 
RDW ...................... red blood cell distribution width 
SAE ........................ serious adverse event 
SD .......................... standard deviation 
SMC ....................... safety monitoring committee 
SOPs ...................... standard operating procedures 
WBC ....................... white blood cell 
 
 

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Protocol Synopsis 
Title 
A Phase II Study of KB103, a Non-Integrating, Replication-Incompetent HSV 
Vector Expressing the Human Collagen VII Protein, for the Treatment of 
Dystrophic Epidermolysis Bullosa (DEB) 
Objectives 
Primary 
1) 
To assess wound closure through post-administration imaging: 
a. Change in surface area of a KB103-administered wound 
relative to the same wound at baseline and a placebo-
administered wound 
b. Time to wound closure of a KB103-administered wound relative 
to a placebo-administered wound 
c. Duration of wound closure of a KB103-administered wound 
relative to a placebo-administered wound 
Secondary 
1) To assess change from baseline in the Investigator’s Global Assessment 
score 
2) To assess change from baseline in PRO scales of severity and pain 
Other 
1) To evaluate the expression of human collagen VII as determined by 
immunofluorescence (IF). 
2) To evaluate the presence of anchoring fibrils as determined by 
immunoelectron microscopy (IEM) post-administration. 
Test Product 
KB103  
# of Subjects  
Up to 14 including Phase 1 and Phase 2. This version of the protocol intends to 
enroll 3 subjects. 
Study Design 
This study is an intrasubject comparison of KB103-administered and placebo-
administered wounds. Up to three 50 cm2 areas will be selected for entry: one or 
two will be selected to receive topical KB103, and one to receive topical placebo.  
The primary objective of this study is to evaluate clinical efficacy through digital 
imaging of wounds. Secondary objectives include an evaluation of change in an 
Investigator’s global assessment and change in patient reported outcomes.  
Patients will be administered Investigation Product (IP) in two cycles. Cycle 1 
starts on Day 1. Up to three 50 cm2 areas are administered IP (one or two KB103 
and one placebo) every 2 to 3 days (to correspond with bandage changes) until 
wound closure, or up to 3 months. IP is administered to the entire areas, on the 
wound(s) and on intact skin.  
Following this initial dosing period, patients will enter into an observation period 
in which wounds are monitored at home using a phone imaging app. Upon re-
opening and/or expansion of a wound in the KB103 treatment area, patients will 
be asked to return to clinic or will be treated at home to begin the 2nd cycle of 
dosing. 
The 2nd cycle mimics the first. The same 50 cm2 areas are administered IP (one 
or two KB103 and one placebo) every 2 to 3 days until wound closure or up to 3 
months. IP is administered to the entire areas, on the wound(s) and on intact 
skin. 

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After the 2nd cycle of IP administration, patients enter a second observation 
period. Patients image their wounds at home using a phone app, and return to 
the clinic at monthly intervals. 
Time to wound closure and duration of wound closure will be evaluated after 
both the 1st and 2nd cycles.  Safety will be monitored throughout the study. 
 
Population 
Inclusion Criteria 
1. Clinical diagnosis of the recessive form of dystrophic epidermolysis 
bullosa. 
2. Age:  3 subjects age 2 and older 
3. Willing and able to give consent/assent. 
4. Confirmation of RDEB diagnosis by genetic testing, IF and EM. 
5. Confirmed RDEB COL7A1 mutations in subject. 
6. Two areas of skin up to 50 cm2, with at least 1 wound in each area. 
7. Subjects who, in the opinion of the Investigator, are 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. The presence of medical illness expected to complicate participation 
and/or compromise the safety of this technique, such as 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. Active infection in the area that will undergo administration 
4. Evidence of systemic infection. 
5. Known allergy to any of the constituents of the product. 
6. Current evidence or a history of squamous cell carcinoma in the area 
that will undergo treatment. 
7. Active drug or alcohol addiction. 
8. Hypersensitivity to local anesthesia (lidocaine/prilocaine cream). 
9. Receipt of chemical or biological study product for the specific treatment 
of RDEB in the past three months, except for KB103. 
10. Specific wounds that have previously been administered investigational 
gene or cell therapy. Wounds previously administered KB103 are not 
excluded. 
11. Positive pregnancy test or breast-feeding. 
12. Clinically significant abnormalities as determined by the investigator. 
Test Product 
and Route of 
Administration 
Topical KB103 (KB103 formulated with a carrier gel) 

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1 
Background 
1.1 
Disease Background 
Dystrophic epidermolysis bullosa (DEB) is a group of heritable skin diseases characterized by 
skin fragility, blister formation, milia, and scarring (Intong, 2012). Epidermolysis bullosa (EB) 
affects 1 in 20,000 live births and causes the skin and mucous membranes to blister and erode 
in response to minor injury or friction, such as scraping, rubbing, or scratching (Varki, et al., 2007). 
Dystrophic epidermolysis bullosa (DEB) is one of the major forms of EB and is the result of 
mutations to the COL7A1 gene encoding collagen VII (Varki, et al., 2007), (Uitto & Christiano, 
1994). 
Severe generalized recessive dystrophic epidermolysis bullosa (RDEB), formerly termed 
Hallipeau-Siemens, is characterized by extensive blistering and scarring of the skin and mucosal 
membranes. Blisters and erosions affect skin as well as certain mucosa exposed to disruptive 
external environment, including oropharynx, esophagus, rectum, genitourinary system and eye. 
Healing of erosions results in debilitating scarring. Damage to the mouth and esophagus can 
make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. 
Complications from extensive scarring can include fusion of the fingers and toes, joint deformities, 
and vision impairment. Additionally, patients suffering from RDEB have a high risk of developing 
squamous cell carcinoma, which is highly aggressive and life-threatening. There is significant 
mortality associated with RDEB with nearly 10% of the patients dying before age 10, almost 40% 
by age 20, and 72% die before the age of 30 (Varki, et al., 2007). There is no cure for EB and 
treatment options are limited. Current care focuses on managing the disease symptoms, including 
pain/itch medications, antibiotics and surgical treatments of scarring deformities (Fine, 2010).  
 
Given the severity of this disorder and the lack of effective treatment options, there exists a clear 
need for alternative treatment options that focus on the root cause of the debilitating symptoms 
and can be administered in a minimally invasive way. 
1.1.1 
RDEB Pain and Patient Reported Outcomes 
Pain is clinically meaningful as it is documented as one of the top symptoms affecting quality of 
life reported by EB patients (van Scheppingen, et al., 2008). As such, this protocol will evaluate 
pain through the use of pain scales. The pain scales (Wong-Baker  Faces  Pain Rating Scale, 
Appendix 2) are well established existing questionnaires from the medical literature that have 
been shown to be both valid and reliable measures of pain in children and adults for a wide range 
of dermatologic conditions (Morris, et al., 2012) (Garra, et al., 2010). The same scale has been 
used previously in a Phase 3 EB study (Browning, et al., 2017). 
1.2 
Collagen VII 
The mutations cause an absence or reduction of functional COL7 and anchoring fibrils. Anchoring 
fibrils may be reduced in number and show abnormal morphology (loss of fan-shaped appearance 

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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). 
Skin integrity is achieved by interactions between the basal keratinocyte cytoskeleton, 
hemidesmosome complexes at the dermal-epidermal junction and the underlying anchoring 
fibrils. Anchoring fibrils are supramolecular structures primarily composed of collagen VII 
(Jonkman, et al., 2003) that originate and terminate within the basement membrane (Burgeson, 
1993) and tether this superstructure to collagen bundles within the dermis (Leigh, et al., 1988). 
1.2.1 
COL7A1 Gene 
The COL7A1 gene encodes a 290-kDa alpha chain (Christiano, et al., 1994) and three of the 
chains form a triple helix (trimer). The trimers form antiparallel dimers, which aggregate laterally 
to form anchoring fibrils (AFs) within the extracellular space (Burgeson, 1993).  
The trimers are characterized by repeating Gly-X-Y amino acid sequences, flanked by a large 
145kDa amino-terminal, non-collagenous domain (NC1) and a small 34-kDa carboxyl-terminal 
non-collagenous domain (NC2). The tail-to-tail dimers that aggregate laterally to form the 
anchoring fibrils have NC1 domains at both ends. Figure 1 below schematically represents 
anchoring fibril formation.  
Figure 1 - Anchoring Fibril Formation 
 
(Bruckner-Tudorman, 2009) 
The NC1 domains interact with various proteins of the extracellular matrix, including fibronectin, 
laminin-5, type I and IV collagen. This interaction mediates attachment of the basement 
membrane to the dermis (Burgeson, 1993).  
1.2.2 
NC1 Domains 
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 

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(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. 
1.3 
COL7A1 Gene Delivery for DEB 
Published studies in animal models have shown that expression of COL7 results in DEB disease 
correction. Immunodeficient mice grafted with RDEB skin were intradermally injected fibroblasts 
modified to over-express COL7. The injection normalized RDEB disease features, including 
blistering and anchoring fibril defects (Ortiz-Urda, et al., 2003). In addition, a lentiviral vector 
expressing COL7 was administered intradermally into immunodeficient mice grafted with RDEB 
skin. The vector transduced dermal cells, which expressed COL7 into the extracellular space. The 
COL7 incorporated into the basement membrane zone (BMZ), formed anchoring fibril structures, 
and reversed the DEB phenotype (Woodley, et al., 2004). Recently, genetically modified 
fibroblasts were administered to human RDEB skin xenografts on NOD-scid mice and were 
shown to deposit COL7 and generate anchoring fibrils at the BMZ (Georgiadis, et al., 2016). 
This mechanism of action, whereby DEB cells are transduced to express COL7, has also 
demonstrated efficacy in a clinical trial at Stanford where patients were administered genetically 
modified keratinocytes via epidermal xenografts. The autologous keratinocyte grafts were 
modified with a Moloney leukemia virus–derived retroviral vector (LZRSE-COL7A1) (Siprashvili, 
et al., 2010). Analysis of the modified keratinocytes showed a transduction efficiency of 65 – 80% 
and demonstrated the COL7 to be functionally indistinguishable from the endogenous wild-type 
protein. Following administration of the grafts, COL7 expression was detected in 9 of 10 biopsy 
samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (40%) 
at 12 months.  At 3 months, 5 of 7 biopsy samples (71%) showed a morphologically normal 
appearance and had anchoring fibrils (Siprashvili, et al., 2016).  These observations of efficacy 
validate preclinical evidence suggesting that replacing as little as 30% of normal COL7 levels is 
sufficient for restoring proper skin function (Fritsch, et al., 2008) (South & Uitto, 2016). 
Although successful in achieving durable correction of key disease features, and well-tolerated 
from a safety perspective, ex vivo gene delivery is expensive, time-consuming (3 to 6 months to 
manufacture an autologous therapy), and invasive. Manufacturing requires harvesting skin cells 
from the DEB patient by skin biopsy, growing the cells in tissue culture, correcting the gene defect, 
expanding the gene-corrected cells, and then transplanting them back onto the patient through 
surgery or several injections.  Drawbacks include high cost, poor graft takes, surgical 
debridement, complex bandaging and wound care, and potential postsurgical infection. There is 
a need for a less invasive, non-autologous therapy. 

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1.4 
KB103 Background 
The vector delivery system, KB103, is a non-integrating, replication-deficient recombinant strain 
of herpes simplex virus (HSV)-1 engineered to express the COL7A1 transgene encoding COL7 
which strengthens and stabilizes the skin. Direct dermal delivery of this vector has the capability 
of enhancing COL7 expression in target cells including fibroblasts and keratinocytes, thereby 
strengthening the skin and reducing blistering. It can infect both dividing and non-dividing cells 
without integrating into the DNA, making it safer relative to integrating vectors. It also provides 
high transduction efficiency in skin cells in both fibroblasts and keratinocytes.   
KB103 is a replication defective HSV-1 modified as follows: 1) complete deletions of the viral ICP4 
and ICP22, and (2) insertion of a human cytomegalovirus (HCMV) immediate early promoter that 
drives human collagen VII expression cassette within both copies of the deleted ICP4 loci. HSV 
genes are expressed in a sequential, interdependent lytic cycle cascade and the removal of these 
essential immediate early genes renders the virus replication defective. The KB103 vector is 
represented schematically in Figure 2.  
Figure 2 - KB103 Vector Map 
 
 
To summarize the construction strategy, the collagen VII open reading frame (ORF), flanked by 
the HCMV promoter and a bovine growth hormone polyadenylation sequence, was cloned into a 
targeting plasmid that contains ICP4 flanking sequences to facilitate recombination with the ICP4 
loci within a replication-deficient HSV virus deleted for both copies of ICP4. Both copies of the 
ICP4 gene within the HSV virus have been replaced by a fluorescent reporter (eGFP). 
Transfection of the collagen VII targeting plasmid into complementing Vero cells followed by 
infection with the replication-deficient HSV virus allows for recombination at the ICP4 locus and 
replacement of eGFP with collagen VII. Positive isolates were selected based on loss of GFP 
expression and confirmed by quantitative PCR (not shown) and Western blot analysis. 
Following selection of positive isolates, a small-scale virus stock was prepared and purified in-
house using nine T-175 tissue culture flasks and 1 mL purification columns following established 
SOPs for HSV production. The final purified product showed good yield (> 1x1010pfu) and titer 
(3.4x109pfu/mL) based on an infectious titer plaque assay, confirmed positive for collagen VII 
expression by Western Blot analysis, and negative in a Replication-Competent Virus (RCV) 
screen. Purified KB103 was evaluated for expression and functionality in 2-D and 3-D cell-based 
assays using normal and RDEB patient-derived fibroblasts (HDF) and keratinocytes (HK).  
∆ICP4
∆ICP4
∆ICP22
UL
US
KB103
= heterologous promoter
= COL7A1
= regulatory elements

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1.5 
KB103-001, Results from Subjects 01 and 02 
KB103 (HSV-COL7) was evaluated in two adult subjects taking part in this protocol.  The therapy 
was well-tolerated and there were no serious or KB103-related adverse events. Wound images 
demonstrate wound closure post-administration and immunofluorescence and immune electron 
microscopy data demonstrate molecular and structural correction. 
The primary objectives of Version 1.0 of the study were to evaluate safety through the incidence 
of adverse events (AEs) associated with KB103 post-administration, to evaluate the expression 
of human collagen VII as determined by immunofluorescence (IF), and to evaluate the presence 
of anchoring fibrils as determined by immunoelectron microscopy (IEM) post-administration. 
Secondary objectives included an assessment of change in surface area of a treated wound area 
through imaging, and safety through an evaluation of laboratory values and physical exam. 
Eligible subjects were at least 18 years old, had the recessive form of DEB, and were NC1+.  
Each subject was on-study for approximately three months. Prior to administration, two wounds 
per subject < 10cm2 in surface area were selected to be randomized to receive either KB103 or 
placebo. KB103 was administered at least 4 times between Day 0 and Day 30, both topically and 
intradermally. 
1.5.1 
Safety 
Prior to the study, real-time qPCR assays for the detection of viral vector were validated at Charles 
River Laboratories for the purpose of analyzing viral shedding study samples. Blood and urine 
were collected during the study per protocol. All of the samples were either negative or below the 
limit of detection. No treatment-related adverse events were observed or reported. No patient 
showed systemic autoimmune symptoms or increased blistering around the sites of 
administration. There were no abnormal laboratory findings. 
1.5.2 
Efficacy 
Analysis of biopsies by immunofluorescence from KB103-treated intact skin and wounds revealed 
clearly detectable and correctly localized (at the BMZ) COL7 expression. Analysis of biopsies by 
immunoelectron microscopy showed initiation of anchoring fibril (AF) formation along the BMZ 
with closely localized COL7 staining at Weeks 2 and 4. By Day 80 mature NC2-positive AFs were 
observed demonstrating the presence of functional full-length COL7. The biopsy analyses 
correlated to an observed efficacy signal of wound closure. Relative to baseline, wound imaging 
for both subjects revealed complete wound closure for KB103-treated wounds by Week 4 and 
sustained closure through the End of Study visit and beyond (about 5 months of closure for 
Subject 01 and 4 months for Subject 02 as of the date of this protocol). 
1.5.3 
Summary 
In summary, the clinical data obtained from the first two subjects showed that KB103 has a 
favorable benefit-to-risk profile, having demonstrated wound healing associated with molecular 
and structural correction, and no drug-related adverse events. 

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1.6 
Rationale for Protocol Amendments 
Four subjects were enrolled onto version 2 of the Phase 2 portion of the protocol. Three subjects 
(1 adult and 2 children) were administered 3e8 per wound daily for 5 days. One adult was 
administered 6e8 daily for 5 days. There were no signs of immunogenicity, no KB103-related 
adverse events and the data indicate that 3e8 per wound per administration was an effective dose 
for wounds 20 cm2 or less. 
Post-dose imaging from these patients clearly indicated that wound morphology and size is a 
major factor in wound healing as a result of KB103 administration. Wounds that were chronic but 
recurring based on natural history tended to heal and close completely within 7 to 10 days of 
KB103 administration. Chronic wounds that were open for a few years showed signs of healing 
following an initial five consecutive applications but the wound healing process appears to 
stagnate. These wounds would likely benefit from additional administrations to obtain full closure. 
Caregivers of the patients currently on trial have requested additional administrations to wounds 
that have clearly benefited but have not achieved complete wound closure.   
Therefore, version 3.1 of the protocol incorporated dosing every 2 to 3 days for two weeks at 2e8 
PFU with the option of at-home KB103 administrations, at the discretion of the Investigator. 
Five patients were enrolled onto version 3.1 of the protocol. KB103 continues to be well tolerated 
and wound healing is observed in KB103 administered wounds. Wound healing results of the 
KB103 treated wounds evaluated to-date continues to show improvement.  There is also empirical 
evidence that repeat administration on the chronic wounds that were retreated in patients that 
rolled over from the previous portion of the study showed improved healing with complete closure 
of the wound observed.  Therefore, version 4.0 incorporates a 2-cycle approach to KB103 
administration with greater flexibility given regarding the number of administrations within each 
cycle to understand the duration of treatment prior to moving into the Phase 3 Clinical trial. 
  
 
 

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2 
Objectives 
2.1 
Primary 
1) To assess wound closure through post-administration imaging: 
a. Change in surface area of a KB103-administered wound relative to the 
same wound at baseline and the placebo administered wound 
b. Time to wound closure of a KB103-administered wound relative to a 
placebo-administered wound 
c. Duration of wound closure of a KB103-administered wound relative to a 
placebo-administered wound 
2.2 
Secondary 
1) 
To assess change from baseline in the Investigator’s Global Assessment score 
2) 
To assess change from baseline in PRO scales of severity and pain 
2.3 
Other 
1) 
To evaluate the expression of human collagen VII as determined by 
immunofluorescence (IF). 
2) 
To evaluate the presence of anchoring fibrils as determined by immunoelectron 
microscopy (IEM) post-administration. 
 

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3 
Selection of Patients 
Investigators are 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). 
3.1 
Inclusion Criteria 
To be eligible for inclusion, each subject must fulfill each of the following criteria: 
1. 
Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa. 
2. 
Age:  3 subjects age 2 and older 
3. 
Willing and able to give consent/assent. 
4. 
Confirmation of RDEB diagnosis by genetic testing, IF and EM. 
5. 
Confirmed RDEB COL7A1 mutations in subject. 
6. 
Two areas of skin up to 50 cm2, with at least 1 wound in each area. 
7. 
Subjects who, in the opinion of the Investigator, are 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. 
3.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria are met: 
1. 
Medical instability limiting ability to travel to the investigative center. 
2. 
The presence of medical illness expected to complicate participation and/or 
compromise the safety of this technique, such as 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. 
Active infection in the area that will undergo administration 
4. 
Evidence of systemic infection. 
5. 
Known allergy to any of the constituents of the product. 
6. 
Current evidence or a history of squamous cell carcinoma in the area that will 
undergo treatment. 
7. 
Active drug or alcohol addiction. 
8. 
Hypersensitivity to local anesthesia (lidocaine/prilocaine cream). 
9. 
Receipt of chemical or biological study product for the specific treatment of 
RDEB in the past three months, except for KB103. 

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10. Specific wounds that have previously been administered investigational gene 
or cell therapy. Wounds previously administered KB103 are not excluded. 
11. Positive pregnancy test or breast-feeding. 
12. Clinically significant abnormalities as determined by the investigator.  
 
 

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4 
Study Design 
4.1 
Study Overview 
This study is an intrasubject comparison of KB103-administered and placebo-administered 
wounds. Up to three 50 cm2 areas will be selected for entry: one or two will be selected to receive 
topical KB103, and one to receive topical placebo.  
The primary objective of this study is to evaluate clinical efficacy through digital imaging of 
wounds. Secondary objectives include an evaluation of change in an Investigator’s global 
assessment and change in patient reported outcomes.  
Patients will be administered Investigation Product (IP) in two cycles. Cycle 1 starts on Day 1. Up 
to three 50 cm2 areas are administered IP (one or two KB103 and one placebo) every 2 to 3 days 
(to correspond with bandage changes) until wound closure, or up to 3 months. IP is administered 
to the entire areas, on the wound(s) and on intact skin.  
Following this initial dosing period, patients will enter into an observation period in which wounds 
are monitored at home using a phone imaging app. Upon re-opening and/or expansion of a wound 
in the KB103 treatment area, patients will be asked to return to clinic or will be treated at home to 
begin the 2nd cycle of dosing. 
The 2nd cycle mimics the first. The same 50 cm2 areas are administered IP (one or two KB103 
and one placebo) every 2 to 3 days until wound closure or up to 3 months. IP is administered to 
the entire areas, on the wound(s) and on intact skin. 
After the 2nd cycle of IP administration, patients enter a second observation period. Patients image 
their wounds at home using a phone app, and return to the clinic at monthly intervals. 
Time to wound closure and duration of wound closure will be evaluated after both the 1st and 2nd 
cycles.  Safety will be monitored throughout the study. 
Cycle 1 
Up to 3 months 
2-3 days apart 
→ 
Observation 1 
Variable duration → 
Cycle 2 
Up to 3 months 
2-3 days apart 
→ 
Observation 2 
Variable duration 
Three additional new patients age 2 and older will be enrolled under this version.  Patients from 
this protocol will be allowed to roll over into Phase 3 study of KB103. 
4.2 
Sites and Trial Duration 
One (1) investigative site is planned for this study.  
The trial duration is variable depending on the duration of response following the first and second 
administration cycles. It is estimated that trial participants will be on study for 6 months to a year. 
Additional time for recruitment and screening is anticipated to take 1 month. Safety data is to be 

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collected by clinic visit or telephone contact approximately every 1 year for up to 5 years after the 
subject completes the final on-site or at-home visit as part of this protocol.  
4.3 
Concomitant Therapy and Skin Care 
Stanford is a major epidermolysis bullosa center and has an established multidisciplinary 
epidermolysis bullosa team.  Subjects will have full access to the care provided by this team 
throughout participation in this study.  
The Investigator is encouraged to restrict topical administration of any EB therapy to a wound that 
receives KB103 or placebo for a minimum of 72 hours following administration. Any therapy 
administered to the target wound should also be applied to the control wound. 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 any biopsies to treat pain and/or anxiety (i.e. lidocaine, lorazepam, etc.).  Routine skin care 
for DEB patients continues throughout the study. Though not anticipated due to the non-
replicating nature of KB103, active herpes should be treated with an antiviral at the discretion of 
the Investigator. 
Conscious sedation to anesthetize pain associated with biopsies is acceptable at the discretion 
of the Investigator. 
4.4 
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.  
4.4.1 
Subject Identification and Number Assignment 
Subjects who sign the informed consent form are assigned a 3-digit subject identification number. 
Subject identification numbers begin with 001. This number identifies the subject throughout the 
study and must be used on all study documentation related to that subject. 
4.4.2 
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). 

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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 should be discussed with the medical monitor prior to withdrawal when 
possible.  Subjects who wish to discontinue treatment or study procedures after receipt of KB103 
are asked to continue in the Long-Term Follow-Up Period. Subjects who withdraw prior to the first 
KB103 administration are considered a screen failure and are replaced. The Sponsor reserves 
the right to terminate the study. 
4.5 
Safety Monitoring Committee 
A Safety Monitoring Committee (SMC) comprised of an independent DEB specialist, enrolling PIs, 
and Sponsor representatives and/or designee(s) hold periodic teleconferences to evaluate 
subject safety and treatment status. An SMC charter dictates procedure, responsibilities, 
membership, data requirements and meeting timing. A written summary documenting the results 
and recommendations of each review is 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 SMC provides recommendations about stopping or continuing the trial and has 
the authority to recommend dose or regimen modifications for safety concerns. The SMC may 
also make recommendations regarding the selection or retention of participants, their 
management, improving adherence to protocol-specified regimens, and the procedures for data 
management and quality control. 
4.6 
Subject Companions 
Subjects are permitted to bring a companion to study visits. Costs associated with travel to the 
Investigative Site, including those of a companion, are reimbursed by the sponsor. 
 
 
 
 
 

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5 
Study Procedures 
5.1 
Stopping Criteria 
Table 1 provides the stopping criteria. Occurrence of any of these observations triggers a 
temporary suspension of KB103 administration pending a safety investigation. 
Table 1 - KB103-001 Stopping Criteria 
Event 
Severity 
Number of 
Events 
A treatment emergent serious adverse event that is definitely or 
suspected to be related to KB103. 
Any 
1 
An AE associated with HSV infection in combination with a positive 
RCV qPCR assay result.  
Any 
1 
An immune response determined by the Investigator to be possibly, 
probably or definitely related to investigational product or a procedure. 
Severe 
1 
Any treatment emergent systemic infection designated as possibly, 
probably or definitely related to investigational product or a procedure. 
Moderate or 
higher 
2 or more 
A treatment emergent uncontrolled bacterial, viral, or fungal infection in 
an area administered investigational product where product sterility 
testing results reported post injection were positive for contamination. 
Mild or 
higher 
1 
For subject safety, subjects should be followed in accordance with the study visits and procedures 
as outlined in the protocol. An occurrence of any of these safety observations is shared with the 
SMC and the appropriate authorities. The SMC reviews the results of the safety investigation and 
may request any additional data needed to assess the safety of restarting product administration.  
The SMC determines if the suspension can be lifted or if the trial terminates based on their review 
of the safety investigation. 
5.2 
Study Schedule 
Study visit procedures are performed only after a signed informed consent / assent is obtained. 
During the study, every effort should be made to adhere to the visit schedule provided in the 
Schedule of Events (Table 2). Visit windows for each visit are described below. 
Patients visit the clinic at baseline and as needed after baseline for the Cycle 1 and Cycle 2 dose 
administrations. After the first dose administration of each cycle, patients can either return to the 
clinic for additional administrations or the administrations can occur at home by a trained 
professional. During the on-site dose administration periods, patients will stay in lodging near the 
clinical site. Following the 2nd cycle, patients will return home and visit the clinic at least monthly 
for 3 months. Interim unscheduled visits may occur in between the monthly visits depending on 
the patient’s ability and willingness to travel. 

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Table 2 - Schedule of Events 
 
 
Cycle #1 
OP1 #1 
Cycle #2 
OP #2 
 
Dosing every 
2-3 days 
Home 
images 
Dosing every 
2-3 days 
At-home monitoring and 
monthly on-site visits 
 
 
 
≤ 3 months 
Variable 
≤ 3 months 
3 months after C22 
 
Procedures 
Screen/ 
BL 
Dose 
days 
Last 
dose 
OP 1 
Dose 
days 
Last 
dose 
C2 
+1mo 
C2 
+2mo 
C2 
+3mo 
LTFU 
Urine Pregnancy 
Test 
X 
 
 
 
 
 
 
 
 
 
HIV, Hep B, Hep C 
Testing 
X 
 
 
 
 
 
 
 
 
 
Hematology & 
Chemistry3 
X 
 
X 
 
 
X 
X 
X 
X 
 
COL7 Antibody 
Assay 
X 
 
X 
 
 
X 
X 
X 
X 
 
HSV Antibody Assay 
X 
 
X 
 
 
X 
X 
X 
X 
 
Wound Area 
Assignment 
X 
 
 
 
 
 
 
 
 
 
Pre-dose Tattoos 
X 
 
 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Viral shedding (skin 
swab) 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Viral shedding (blood 
and urine) 
X 
 
X 
 
 
X 
X 
X 
X 
 
Physical Exam 
X 
 
 
 
 
 
 
 
X 
 
PRO Assessment 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Global Wound 
Assessment 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Vital Signs 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
At-home wound 
imaging4 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
On-site wound 
imaging 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Wound stenciling 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
IP Administration 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Wound biopsy5 
X 
 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
                                                
1 OP = Observation Period 
2 Visit windows for the OP2 visits are +/- 1 week 
3 After screening/baseline, performed only as clinically indicated to minimize blood draws 
4 At-home wound imaging occurs throughout the study during bandage changes 
5 Biopsies are performed at the discretion of the Investigator and Sponsor.  

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5.3 
Screening and Baseline 
For well-characterized subjects that meet criteria, the procedures for screening and baseline will 
be conducted during the same visit to the investigative site as the first day of Cycle 1. Subjects 
that are not well-characterized may be screened well in advance (about 2 months) of the planned 
baseline to allow time for genetic testing.  
5.3.1 
Informed Consent 
The Investigator is responsible for obtaining an ICF signed by the subject or legally authorized 
representative from every subject prior to his/her participation in the study, in accordance with the 
Code of Federal Regulations (CFR), 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. For subjects that are 5 or 6 years old, the Investigator is 
responsible for obtaining parental/legal guardian consent (no assent is required).  
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 is 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. 
5.3.2 
Phone Screening 
A phone screen is utilized to minimize subject travel. An Investigator or designee will prescreen 
medical histories of RDEB patients for potential inclusion into this study.  Potential subjects or 
parent or guardian are contacted by phone. An Investigator or designee provides a study 
overview, key inclusion/exclusion criteria, information about the recruitment process, and 
addresses questions. 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. 
Medical information reviewed may include the following and is dependent upon the Investigative 
Site’s receipt of prior authorizations to access the data: 
- 
NC1 and LH24 antibody results 
- 
Genetic testing results, including COL7A1 genotype of the subject 
- 
COL7 antibody history 
- 
IF and EM/IEM results 
- 
Medical history 
The Investigator may request additional personal health information disclosure authorizations 
from the potential subject to assist with Screening. 

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5.3.3 
Screening and Baseline Procedures 
The following procedures are performed on or the day before the first planned administration day.  
- 
Review and signature of informed consent form 
- 
The following evaluations are required only if RDEB diagnosis documentation is 
not available to support entry into this protocol. If these are needed, the 
screening visit may occur several weeks prior to the baseline visit: 
• 
Collection of a biopsy for EM/IEM 
• 
Collection of a biopsy for IF 
• 
Collection of blood for genetic testing 
- 
Collection of demographic data (e.g. sex, age, race, and ethnicity) 
- 
Inclusion/exclusion criteria 
- 
Medical history and medication history 
- 
Collection of blood (approximately 15 mL) for clinical laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
HIV, Hep B, Hep C 
• 
Baseline viral shedding 
• 
Baseline HSV and COLVII autoantibodies 
- 
Collection of urine 
• 
For a pregnancy test, if applicable 
• 
For baseline viral shedding  
- 
Physical and skin exam 
- 
Vital signs:  blood pressure, heart rate, respiratory rate, temperature 
- 
Collection of a baseline skin swab for viral shedding analysis 
- 
Bacterial culturing of target wounds (if clinical evaluation is indicative of infection) 
- 
Digital imaging of target areas 
- 
Collection of a biopsy from intact skin for IF and IEM analyses. This collection 
can occur at a later visit at the discretion of the Investigator. 
- 
Patient reported outcomes (PRO) questionnaire 
- 
Investigator’s global assessment 
 
 

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5.4 
Cycle 1 
The patient will visit the Investigative site for the first dose of Cycle 1. Additional Cycle 1 doses 
can occur on-site or at-home at the discretion of the Investigator. Unless the patient requires 
disease characterization, Day 1 of Cycle 1 is the same day as the Screening/Baseline visit. For 
Cycle 1, KB103 and placebo are administered topically every 2 to 3 days to correspond with 
bandage changes, up to 3 months. 
5.4.1 
On-Site Dosing Day Procedures 
For visits that occur at the clinic, the following procedures may be performed: 
- 
Adverse events 
- 
Concomitant medications 
- 
Vital signs 
- 
Viral shedding skin swab collection 
- 
Digital imaging of target wound areas 
- 
PRO assessment 
- 
Investigator’s global assessment 
- 
Wound stenciling 
- 
Topical administration of KB103 and placebo to the target areas 
5.4.2 
At-home Procedures 
After the first administration of each cycle, KB103 may be administered at home by a caretaker 
every 2 to 3 days until wound closure, a stopping criterion is met, 3 months have elapsed, or until 
directed to discontinue by the Investigator.  
Appendix 1 provides administration instructions. Wound closure is monitored through remote 
imaging. 
5.4.3 
Last Dosing Day of Cycle 1 
The patient will visit the Investigative site on or near the final Cycle 1 administration day, in 
which the following procedures will be performed: 
- 
Collection of blood (approximately 10 mL) for clinical laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Viral shedding 
• 
HSV and COLVII autoantibodies 
- 
Collection of urine for viral shedding 
- 
Optional: biopsy collection from a wound area 
- 
Wound stenciling 
- 
Topical administration of KB103 and placebo to the target areas 

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5.5 
Observation Period (OP) 1 
Following Cycle 1 wound closure and/or 3 months, the patient returns home. Wound areas are 
imaged every 2 to 3 days at home with a phone app.  
The duration of OP 1 varies. If complete wound closure is obtained during Cycle 1, OP 1 ends 
when the wound(s) re-open. If complete closure is not obtained during Cycle 1, OP 1 ends when 
the wound surface area increases relative to size of the wound at the last Cycle 1 administration.   
5.6 
Cycle 2 
The patient will visit the Investigative site for the first dose of Cycle 2. Additional Cycle 2 doses 
can occur on-site or at-home at the discretion of the Investigator. For Cycle 2, KB103 and 
placebo are administered topically every 2 to 3 days to correspond with bandage changes, up to 
3 months. 
5.6.1 
On-site Dosing Day Procedures 
For visits that occur at the clinic, the following procedures may be performed: 
- 
Adverse events 
- 
Concomitant medications 
- 
Vital signs 
- 
Viral shedding skin swab collection 
- 
Digital imaging of target wound areas 
- 
PRO assessment 
- 
Investigator’s global assessment 
- 
Wound stenciling 
- 
Topical administration of KB103 and placebo to the target areas 
5.6.2 
At-home Procedures 
After the first administration of each cycle, KB103 may be administered at home by a caretaker 
every 2 to 3 days until wound closure, a stopping criterion is met, 3 months have elapsed, or until 
directed to discontinue by the Investigator.  
Appendix 1 provides administration instructions. Wound closure is monitored through remote 
imaging. 
5.6.3 
Last Dosing Day of Cycle 2 
In addition to the procedures above, the following additional procedures should occur on or near 
the final Cycle 1 administration day: 
- 
Collection of blood (approximately 10 mL) for clinical laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Viral shedding 
• 
HSV and COLVII autoantibodies 

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- 
Collection of urine for viral shedding 
- 
Optional: biopsy collection from a wound area 
- 
Wound stenciling 
- 
Topical administration of KB103 and placebo to the target areas 
5.7 
Observation Period (OP) 2 
Following Cycle 2 wound closure and/or 3 months, wound areas are imaged remotely every 2 to 
3 days at home with a phone app.  
OP 2 also consists of monthly visits to the clinic.  
5.7.1 
OP 2 Monthly Visits 
At 30-day intervals (+/- 7 days) after the last administration of Cycle 2, the patient returns to the 
clinic for follow-up procedures: 
- 
Adverse events 
- 
Concomitant medications 
- 
Vital signs 
- 
Digital imaging of wounds 
- 
PRO assessment 
- 
Investigator’s global assessment 
- 
Collection of blood (approximately 10 mL) for clinical laboratory tests: 
• 
Serum chemistry 
• 
Hematology 
• 
Viral shedding 
• 
HSV and COLVII autoantibodies 
- 
Collection of a skin swab for viral shedding analysis 
- 
Collection of urine for viral shedding 
- 
Month 3 only: physical exam 
- 
Optional: Biopsy from a wound administered KB103 or placebo 
- 
Wound stenciling 
- 
If a target wound is open: Topical administration of KB103 and placebo to the 
target areas. 
5.8 
Unscheduled Visits 
Subjects may visit the clinic for unscheduled visits as deemed appropriate by the Investigator. 
Any or all of the monthly visit procedures may be performed during unscheduled visits. 
5.9 
Long-Term Follow-Up Period 
Upon completion of the End of Study / Early Termination Visit, subjects will enter into a Long-
Term Follow-Up Period. 

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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: 
- 
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 KB103 administration, attempts will be 
made to collect samples of the skin cancer to evaluate cells for the presence of 
viral vector. 
 

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6 
Investigational Product 
Subjects are administered topical KB103 to one or two wound areas, and topical placebo to a 
second wound area. Wound areas have a surface area of up to 50 cm2.  
During Cycles 1 and 2, topical KB103 and placebo are administered every two to three days to 
coincide with bandage changes. Administrations continue until the wound closes, a stopping 
criterion occurs or at the discretion of the Investigator, not to exceed 3 months per cycle. After the 
first administration of each cycle, administrations can be administered at home by a trained 
caretaker at the discretion of the Investigator. These are referred to as “At-Home Topical 
Administrations” below. During visits to the Investigative site, KB103 may be administered 
topically by the Investigator. KB103 is prepared according to the pharmacy manual prior to 
administration. 
6.1 
At-Home Topical Administrations 
At the discretion of the Investigator, KB103 may be administered at home. The Investigator will 
use at-home imaging to make remote dosing decisions, for example, if at-home dosing should 
discontinue due to wound closure.  
Trained caretakers may administer KB103 or trained personnel may travel to the subject to 
administer KB103. Training will be documented and will consist of administration, containment, 
and disposal procedures. At-home administration and disposal instructions are provided to the 
subjects and are in Appendix 1. 
6.2 
Dose Level 
Each topical KB103 dose is 6e8 PFU per wound area per day.  
6.3 
Wound Area Selection 
Up to three wound areas are selected to be part of the study: one or two to receive KB103, and 
one to receive placebo. Final selection of the wound areas occurs at baseline. The following is 
considered when selecting target wound areas: 
- 
Wound areas can consist of one wound, or multiple wounds, and can 
include intact skin. 
- 
The size of the wound area. Target wound areas have a surface area up to 
50 cm2. 
- 
The location of the wound area.  Appropriate sites are on the anterior and/or 
lateral trunk and/or upper and/or lower extremities in areas protected from 
frequent trauma or injury. Excluded areas include the face, and areas close to 
mucous membranes (genitourinary, oral or anal mucosa). 

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- 
The appearance of the wound. Wounds should appear clean with adequate 
granulation tissue, excellent vascularization, and not appear infected. 
- 
Historical consistency in size of the wound. A wound with a historically more 
consistent surface area is chosen over a less consistently sized wound. 
- 
The similarity of the wounds. To the extent possible, similarity in location on 
the body should be considered. 
- 
Wounds that have previously been administered investigational gene or cell 
therapy (except for previous KB103 administration) are not eligible for KB103 and 
placebo administration. 
The Investigator will first selection two areas; one for KB103 and one for placebo. If another 
area meets the criteria above, it will be considered for inclusion in the study to receive KB103.     
6.4 
KB103 Administration 
At-home topical administration of KB103 and placebo is performed as outlined in Appendix 1. 
KB103 will be administered only if a target wound is visibly open. An opening as the result of 
biopsy will be considered visibly open wound.  KB103 is compounded into a gel per the pharmacy 
manual. 
On-site administration is performed as follows: 
1. 
Unpackage the Mepitel One, Mepiform, Vaseline, and Kerlix Gauze dressings and 
place them nearby. Prepare the wound for KB103 administration by unbandaging the 
area. Cut a hole in the Mepitel One to the size of the wound to be treated and place the 
cut Mepitel on the patient’s skin around the wound surface. 
2. 
To apply KB103, while wearing gloves, apply the compounded product directly to the 
patient’s skin by depressing the syringe plunger very slowly to cover the surface of the 
wound with KB103.  Ensure that the KB103 is contained to the wound without any 
spillage.  
3. 
If necessary, open a new syringe, connect the spreader and use it to spread the product 
on the patient’s skin. 
a. 
Any spillage on hard surfaces should be immediately wiped up with 10% bleach 
wipes, and any used wipes should be disposed of as a  biohazard per standard 
operating procedure of the clinical site.  
4. 
Let the KB103 sit for 5 minutes prior to placing any covering over the wound. Keep the 
area clean and do not touch the wound during the 5-minute period. 
5. 
After applying KB103, remove the gloves, discard them in the biohazard container, and 
put on a new pair of gloves.  
6. 
Cover the wound using the non-adherent side of the Mepiform above the wound and 
then cut to the full size of Mepitel dressings. 

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7. 
Thoroughly wrap the dressing in Vaseline Kerlix Gauze and further dress per standard 
of care. 
6.5 
Placebo Administration 
A wound area is selected to serve as the control at baseline.  Topical placebo is administered on 
the days in which KB103 is administered. If KB103 is not administered to both of the KB103-
selected wound areas on any dosing day, then placebo will not be administered.  The dressings 
applied to the wound area that is administered the placebo gel mimic those applied to wound area 
administered KB103. 
6.6 
Peri- and Post-procedural Safety Monitoring 
Throughout the study, subjects will have full access to the care provided by Stanford’s EB team. 
During visits to the clinic, subjects will be within 3 miles of the site. Throughout the study, subjects 
will have direct access to the PI via the PI’s cell phone. 
6.7 
Post-Dose Procedures 
Following dosing, all empty or partially used vials will be destroyed per Stanford standard 
operating procedures. During the period in which KB103 and placebo is administered to the skin, 
patients should avoid touching, scratching, or tampering with the administration sites or their 
dressings. Following removal of KB103 and placebo, patients should minimize contact with the 
area. Bandages removed at home should be disposed of as outlined in Appendix 1. 

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7 
Efficacy Evaluations 
7.1 
Wound Measurement 
Prior to the first administration of IP, small tattoos are placed on non-blistered skin near the target 
wound for the purpose of locating the wound areas at subsequent visits. 
7.1.1 
Imaging 
Target wounds are measured at each visit to the clinic using a phone camera app. Investigators 
use the camera’s software to define wound surface area and other measurements.  
Target wounds are also monitored at home using the phone camera app. Subjects are instructed 
to image the target wounds during bandage changes (approximately twice per week).  
7.1.2 
Stenciling 
Stencils are used to trace wound areas at each visit.  
1. 
Place the stencil directly over the wound area 
2. 
Trace all wounds within the 50 cm2 area 
3. 
After the tracing, place the stencil dirty-side down on a flat, disposal surface 
4. 
Use a clean, pre-labeled stencil to re-trace the wounds 
5. 
Dispose of the dirty stencil 
6. 
Make a photocopy of the clean stencil and place the photocopy in the study file 
7. 
Place the clean stencil inside of an envelope in the study file   
7.2 
Biopsy Evaluation 
There are 2 evaluations that require a tissue sample on this study: COL7 analysis by IF and AF 
analysis by IEM.  
Throughout the study, the collection of biopsies is optional, and performed at the discretion of the 
Investigator and Sponsor. If a biopsy is not collected it will not be considered a protocol deviation. 
The biopsy schedule is outlined in Table 2 - Schedule of Events.  
IF biopsies are processed at Stanford per Stanford standard operating procedures. 
IEM biopsies are to be collected on Monday or Tuesday and shipped to Shriners Hospital to the 
address below for overnight or same-day delivery. Collection on Thursday or Friday should be 
avoided.  
Douglas R. Keene 
Assistant Investigator 
Micro-Imaging Center 

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Shriners Hospital for Children 
3101 SW Sam Jackson Park Road 
Portland, Oregon  97239 
7.3 
Investigator’s Global Assessment Score 
Areas administered topical KB103 and placebo will be clinically evaluated at baseline and at Days 
15, 30, 45, 60, 90, and unscheduled visits with an IGA score of: 1) complete closure (i.e., 100% 
healed), 2) <100% to 75% healed, 3) 74% to 50% healed, 4) 49% to 0% healed, 5) unable to 
determine, or 6) not assessed. The IGA score is used to provide a snapshot of overall disease 
severity in dermatologic clinical studies, (Langley, et al., 2015) including EB (Tabolli, et al., 2009).  
Results to date in a Phase 1/2a keratinocyte graft study suggest that wound measurements from 
imaging and IGA score are supportive and well correlated (Dutt-Singkh, et al., 2018). 
7.4 
Patient-Reported Outcome Measures 
A PRO instrument will be used to evaluate secondary endpoints of change in pain and severity at 
individual wound areas treated with KB103 compared to intra-subject placebo wound areas. At 
each time point, subjects will be instructed to rate pain symptoms within the last 24 hours for each 
wound area. Subject global impression of change will be assessed at baseline, and at Days 15, 
30, 45, 60 (for adults only), and 90 and unscheduled visits. All study personnel will be trained to 
on how to administer PROs. 
The PRO instrument will be paper-based and collected in person by the treating EB or Principal 
Investigator. If the EB physician or the Principal Investigator administer the PROs, they will not 
be able to perform the IGA.  
7.5 
Voice Memo Qualitative Data 
Assistive technology is of utility in the RDEB patient population due to the debilitating nature of 
the disease. During this study, voice memos will be used to capture qualitative data. Throughout 
the study subjects and caretakers will be encouraged to record voice memos while at home in 
between the site visits.  
Patients and caretakers are encouraged to record: 
- 
Wound observations, positive and negative 
- 
Questions that they want to ask their doctor at their next visit 
- 
Observations about at-home procedures, including imaging and at-home KB103 
administration (if applicable)  
Adverse events should be reported immediately by phone as stated in the Adverse Event section 
below.  
Recordings will be downloaded and transcribed for inclusion in the source documentation. 

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8 
Safety Assessments 
Timing of safety assessments must be performed per the Schedule of Events. Safety 
assessments include evaluation of medical and medication history, physical / skin examination, 
vital signs, AEs, and laboratory evaluations. AEs are captured between visits through verbal 
communication with the site staff. Post-administration changes in these assessments that are 
deemed to be clinically significant by an Investigator or Sub-Investigator are assessed as AEs. 
8.1 
Viral Shedding 
Viral shedding will be analyzed through the collection of blood, urine and skin swabs at a wound 
areas administered KB103. Swabs will be collected per the schedule of events.  
8.2 
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 baseline. The medical 
history includes respiratory, cardiovascular, renal, gastrointestinal, hepatic, endocrine, 
hematological, neurological, psychiatric and other diseases. 
8.3 
Physical / Skin Examination 
A qualified individual performs a full physical examination. Body systems evaluated include: 
- 
General appearance 
- 
Skin 
- 
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 in the eCRF. If a new clinically relevant finding occurs (not noted prior to KB103 
administration), an adverse event form must be completed. In addition, resolution of any abnormal 
findings during the study are noted in the source document and appropriate CRF if clinically 
significant. If at any point in the study a skin cancer occurs in the region of the KB103 
administration, attempts are made to collect samples of the skin cancer to evaluate cells for the 
presence of viral vector. 
8.4 
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 

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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.    
8.5 
Laboratory Evaluations 
8.5.1 
Serum Chemistry and Hematology 
The amount of blood collected should be minimized. Reference ranges are used to assess the 
laboratory data for clinical significance. Abnormal laboratory values which are unexpected or not 
explained by the subject’s clinical condition should be repeated as feasible until confirmed, 
explained or resolved. Changes from baseline are recorded as an AE if deemed clinically relevant 
by the Investigator or qualified designee. The following evaluations are 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 
8.5.2 
Urine Pregnancy Test 
A urine pregnancy test is performed at baseline for women of childbearing potential. 
8.5.3 
HSV Antibody Assay 
Collect serum at baseline and Day 30 for the purpose of conducting an HSV antibody assay.   
8.5.4 
Collagen VII Antibody Assay 
Collect serum at baseline and Day 30 for the purpose of conducting a collagen VII antibody assay.  
Using the subject’s serum, COL7 antibodies are assayed by linear 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. A non-
CLIA western blot assay is also used to assay for COL7 antibodies as a confirmatory assay. 

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9 
Adverse Events 
Throughout the course of the study (from the date of informed consent), all adverse events (AEs) 
will be monitored and reported on the AE case report form. If an adverse event occurs, the first 
concern will be the safety of the study participants. All AEs occurring after administration will be 
followed throughout the study. All AEs related to study treatments or procedures will be followed 
until resolved or stabilized or until follow-up is no longer possible. 
In general, even when not participating in a clinical trial, the study subjects and their caretakers 
communicate with their EB doctor on a regular basis via phone. Study subjects and their 
caretakers will be instructed to report via phone any adverse events that occur during the study 
while off-site. The events will then be transcribed to the AE CRF.   
9.1 
Definitions 
9.1.1 
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 

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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 
are performed, as appropriate, to document resolution of event(s).   
9.1.2 
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 are 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 
continue to be collected until the event resolves. 
9.1.3 
Immune Response Adverse Events 
Observation of a severe immune response determined by the Investigator to be possibly, probably 
or definitely related to investigational product or a procedure is a stopping criterion.  
9.2 
Severity 
Definitions for classification of severity appear below. The Investigator will review these definitions 
with the Subject. The Investigator will determine the severity classification based on these 
definitions, his/her clinical experience with DEB patients, and/or the Subject’s description of the 
event.  

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[Note: A “severe” AE is not the same as an “SAE” (serious adverse event), which is defined 
above.] 
Mild: Symptoms are barely noticeable or do not make the Subject uncomfortable. The 
AE does not influence performance or functioning. Prescription drugs are not ordinarily 
needed for relief of symptom(s). 
Moderate: Symptoms are of sufficient severity to make the Subject uncomfortable. 
Performance of daily activities is influenced. Treatment of symptom(s) with 
prescription drugs or therapies may be needed. 
Severe: Symptoms are of sufficient severity to cause the Subject severe discomfort. 
Performance of daily activities is compromised. Treatment for symptom(s) with 
prescription drugs or therapies may be needed. 
9.3 
Relationship 
The Investigator will determine whether the Subject’s symptom or problem is most likely unrelated 
to the study treatment or is possibly/probably related to the anesthesia employed, the study 
device, or the injection procedure. 
9.4 
Reporting Procedures 
All adverse events occurring after KB103 administration observed by the investigator or reported 
by the subject (whether or not attributed to investigational product), are reported on the case 
report form.  
Medically significant adverse events considered related to the investigational product by the 
investigator or the sponsor are 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 Krystal. These include deaths during the Long-
Term Follow-Up period. For all deaths, available autopsy reports and relevant medical reports 
may be requested. 
The investigator should notify the IRB of serious adverse events occurring at the site and other 
adverse event reports received from the sponsor, in accordance with local procedures.  
It is 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 is 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.  

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9.4.1 
Post-KB103 Administration Adverse Event Monitoring 
The Investigator must monitor the subject’s treated and paired, non-treated wounds closely for 
additional blister formation and expansion of the border. 
9.4.2 
SAE Reporting Procedures 
All Serious Adverse Events (SAEs) that occur after the time of informed consent must be reported 
to Krystal and the IRB. All subjects with an SAE must be followed and the outcomes reported. 
The Investigator should supply the Sponsor and the IRB with any additional requested information 
(e.g., hospital discharge summary, autopsy reports and terminal medical reports). The Sponsor 
shall evaluate all SAEs and determine if they meet FDA reporting requirements. In the event of 
an SAE, the Investigator must: 
1. 
Notify Krystal within 24 hours of the Investigator’s awareness of the event. 
2. 
Obtain and maintain all pertinent medical records, information, and medical judgments 
from colleagues who assisted in the treatment and follow-up of the subject. 
3. 
Provide Krystal with a complete, written case history, including copies of supporting 
reports (e.g., progress notes, laboratory reports) and a statement from the Investigator as 
to whether or not the event was related to the use of the investigational product. 
4. 
Promptly inform the governing IRB of the event, if it is related. For other SAEs, notify the 
governing IRB as required by the IRB, local regulations, and the governing health 
authorities. 
 
 

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10 
Statistical Considerations 
Post-screening procedures occur as outlined in the Schedule of Events. The end-of-treatment (or 
treatment endpoint) is also defined as the last 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. 
10.1 
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 KB103. 
10.2 
Data Management 
An electronic case report form (eCRF) is used to collect information for safety and proof of 
mechanism analyses.  A clinical database is managed by a sponsor’s representative for this 
study. The database is constructed based on the CRF data entry plus laboratory data information.  
Data queries are 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 are 
generated and provided for analysis. 
10.3 
Study Populations 
The primary population for an analysis of the proof of mechanism is the intent-to-treat (ITT) 
population. Study populations are defined in the following sections.  
10.3.1 
Safety Population 
This population is defined as all subjects who were administered KB103. 
10.3.2 
Intent-to-Treat Population 
The intent-to-treat (ITT) population includes subjects who were administered KB103 who have 
had at least one paired assessment of the target wound area post-administration, i.e., at least 
one KB103 target wound and one placebo target wound.  
10.3.3 
Per-Protocol Population 
The per-protocol (PP) population is defined as all subjects in the ITT population who have had at 
least one paired assessment of the target wound area post-administration, and completed the 
protocol as planned.  

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10.4 
Demographic and Baseline Characteristics 
The descriptive summaries of subjects’ demographic and baseline characteristics are presented 
by treatment group for the safety, ITT, and PP populations. A detailed description of subject 
disposition is provided.   
Subject characteristics include a summary of the following: 
- 
Subject demographics. 
- 
Baseline disease characteristics as determined at screening. 
- 
Pre-existing medical conditions. 
Continuous variables are summarized using number of observations, mean and standard 
deviation, median, and minimum and maximum values. Categorical values are summarized using 
number of observations and percentages. 
10.5 
Proof of Mechanism Analyses 
10.5.1 
Expression of Collagen VII 
Biopsies collected for the purpose of IF are evaluated for expression of collagen VII by a qualified 
reader.   
10.5.2 
Production of Anchoring Fibrils 
Biopsies collected for the purpose of IEM are evaluated for the presence of anchoring fibrils by a 
qualified reader. 
10.5.3 
Target Wound Area 
Target wound surface area is obtained through on-site and at-home imaging of target areas. 
Change in area from baseline is evaluated for using a paired t-test for each KB103 target wound 
vs. control wound. 
Time to closure and durability of closure will be assessed after each cycle of administrations. 
10.5.4 
Investigator’s Global Assessment 
Investigator’s Global Assessment (IGA) score on the target wound is obtained at baseline and 
post-baseline visits as outlined in the schedule of events.  IGA scores will be evaluated at baseline 
and for post-baseline visits, using a paired t-test for each KB103 target wound vs. control wound. 
10.5.5 
Patient Reported Outcome 
Patient reported outcome (PRO) in terms of pain and severity of the target wound is obtained at 
baseline and post-baseline visits as outlined in the schedule of events, using Wong-Baker Faces 
Pain Rating scale.  Change in the pain ratings will be evaluated at baseline and at post-baseline 
visits, using a paired t-test for each KB103 target wound vs. control wound. 

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10.6 
Safety Analyses 
All continuous parameters are summarized using standard summary statistics as appropriate (n, 
mean, standard deviation (SD), median, minimum, maximum, 25th percentile, and 75th 
percentile). Summary statistics for categorical variables include frequency counts and 
percentages.  
Patient demographics and relevant baseline data is analyzed descriptively. Inclusion and 
exclusion criteria ensure that participants are suitable for the study. Premature termination data 
is tabulated and summarized.  
10.6.1 
Adverse Events 
Adverse events are coded using the MedDRA adverse event dictionary.  Safety evaluations are 
based on occurred adverse events, laboratory values, vital signs and appearance of collagen VII 
antibodies, and RCV. Severities of toxicities is described using the NCI Common Toxicity Criteria 
(CTC) grades.  
Adverse events are grouped into pre-treatment adverse events and treatment-emergent adverse 
events and are 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 are reported. Analyses include 
tabulation of adverse event type, relationship to KB103, seriousness, and severity of adverse 
events according to CTCAE.  
10.6.2 
Physical Examinations 
Physical examinations at screening and subsequent follow-up visits are displayed in tabular 
format displaying number of subjects examined and number and percentage of subjects with 
abnormalities by physical examination category.  
10.6.3 
Vital Signs 
Vital signs are listed and summarized by mean and SD. 
10.6.4 
Laboratory Tests 
Laboratory test values are presented in shift tables and by display of changes to baseline. 
Evaluations of collagen VII antibodies and RCV will be done descriptively.  
10.7 
Handling of Missing and Incomplete Data 
For efficacy evaluation, the treatment endpoint is defined as one assessment time point, which 
includes the last measurement obtained during the study for a variable. No other imputation of 
values for missing data is performed. Standard clinical monitoring and data management 
practices are used to ensure the integrity of data. 
 
 

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11 
Regulatory Obligations 
11.1 
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. 
11.2 
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 the sponsor 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 the sponsor, in accordance with IRB procedures.  
The investigator is 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 the sponsor. 

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11.3 
Pre-Study Documentation Requirements 
The investigator is responsible for forwarding the following documents to the sponsor for review 
before study initiation from the sponsor 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 sub-
investigators, and their spouses (legal partners) and dependent children. 
11.4 
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 the sponsor and companies that work with the sponsor, 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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12 
Administrative and Legal Obligations 
12.1 
Protocol Amendments and Study Termination 
Protocol amendments must be made only with the prior approval of the sponsor. Agreement from 
the sponsor 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 the sponsor.  
The sponsor 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 the sponsor. 
12.2 
Study Documentation and Storage 
12.2.1 
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 are included on the Delegation of Authority Form.  
12.2.2 
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.  
12.2.3 
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 the sponsor, companies that 
work for and with the sponsor, 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 pre-study documentation, and all correspondence to and from the IRB 
and the sponsor.  
- 
Proof of receipt, Investigational Product Accountability Record, Return of 
Investigational Product for Destruction, Final Investigational Product 
Reconciliation Statement, and all drug-related correspondence.  

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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 the sponsor.  
12.3 
Study Monitoring and Data Collection 
The sponsor 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. 
12.4 
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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13 
References 
Browning, J. et al., 2017. Characteristics of patients (pts) with epidermolysis bullosa (EB) in the 
phase 3 ESSENCE study of SD-101. J Invest Dermatol, 137(5), p. S120. 
Bruckner-Tudorman, L., 2009. Can Type VII Collagen Injections Cure Dystrophic Epidermolysis 
Bullosa?. Cell, 17(1), pp. 6-7. 
Burgeson, R., 1993. Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest 
Dermatol, pp. 252-255. 
Cell Biolabs, I., 2014. Product Data Sheet: pSMPUW universal lentiviral expression vector 
(promoterless).  
Christiano, A. et al., 1994. Premature termination codons in the type VII collagen gene 
(COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa,. Genomics, 
21(1), pp. 160-168. 
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. 
Dutt-Singkh, Y. et al., 2018. 50% wound healing correlates with RDEB patient reported 
outcomes in pain, itch and skin durability. J Invest Dermatol, 138(5), p. S56. 
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. 
Fritsch, A. et al., 2008. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals 
mechanisms of disease and response to fibroblast therapy. The Journal of Clinical Investigation, 
Volume 118, p. 1669–1679. 
Garra, G. et al., 2010. Validation of the Wong-Baker FACES Pain Rating Scale in pediatric 
emergency department patients.. Acad Emerg Med, 17(1), pp. 50-4. 
Georgiadis, C., Syed, F. P. A., Abdul-Wahab, A. & Lwin, S., 2016. Lentiviral Engineered 
Fibroblasts ExpressingCodon-Optimized COL7A1RestoreAnchoring Fibrils in RDEB Codon-

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OptimizedCOL7A1Restore Anchoring Fibrils in RDEB. Journal of Investigative Dermatology, 
Volume 136, pp. 284-292. 
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. 
Jonkman, M., Rulo, H. & Duipmans, J., 2003. From gene to disease; epidermolysis bullosa due 
to mutations in proteins in or around the hemidesmosome.. Ned Tijdschr Geneeskd, 147(23), 
pp. 1108-13. 
Langley, R. et al., 2015. The 5-point Investigator's Global Assessment (IGA) Scale: A modified 
tool for evaluating plaque psoriasis severity in clinical trials.. J Dermatolog Treat, 26(1), pp. 23-
31. 
Leigh, I. et al., 1988. Type VII collagen is a normal component of epidermal basement 
membrane, which shows altered expression in recessive dystrophic epidermolysis bullosa. J. 
Invest. Dermatol., Volume 90, pp. 639-642. 
Morris, V. et al., 2012. Itch assessment scale for the pediatric burn survivor. J Burn Care Res, 
33(3), pp. 419-24. 
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., 2016. Safety andWound Outcomes Following Genetically Corrected 
Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. 
JAMA, 316(17), pp. 1808-1817. 
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. 
South, A. & Uitto, J., 2016. Type VII Collagen Replacement Therapy in RDEB - How Much, How 
Often?. Journal of Investigative Dermatology, Volume 136, pp. 1079-1081. 
Tabolli, S. et al., 2009. Quality of life in patients with epidermolysis bullosa.. Br J Dermatol, 
161(4), pp. 869-77. 
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. 
Uitto, J. & Christiano, A. M., 1994. Molecular basis for the dystrophic forms of epidermolysis 
bullosa: Mutations in the type VII collagen gene.. Arch. Dermatol. Res., Volume 287, p. 16–22. 
van Scheppingen, C. et al., 2008. Main problems experienced by children with epidermolysis 
bullosa: a qualitative study with semi-structured interviews.. Acta Derm Venereol, 88(2), pp. 
143-50. 

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Varki, R., Sadowski, S., Uitto, J. & Pfendner, E., 2007. Epidermolysis bullosa. II. Type VII 
collagen mutations and phenotype-genotype correlations in the dystrophic subtypes.. J. Med. 
Genet., Volume 44, pp. 181-92. 
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. 
Woodley, D., Keene, D. A. T. & Huang, Y., 2004. Intradermal Injection of Lentiviral Vectors 
Corrects Regenerated Human Dystrophic Epidermolysis Bullosa Skin Tissue in Vivo. Molecular 
Therapy, 10(2), pp. 318-326. 
 
 

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Appendix 1 – KB103 Administration and Removal 
Instructions 
At-Home Administration Instructions 
1. 
Open the compounding, dressing, cleaning and handling kits.  
2. 
Put on the gloves provided with the cleaning and handling kit.  
3. 
You will receive two KB103 vials for each wound to be treated. The vials are shipped 
on dry ice and stored in an ultra-low temperature freezer at the patient’s home. Open 
the ultra-low temperature freezer and remove four KB103 vials. Inspect the vials for 
signs of leakage. If leakage as occurred, take a picture of the leakage and dispose of 
the vial in the provided red biohazard bag. 
4. 
Place the KB103 vials on the blue towel provided in the cleaning and handling kit and 
let them sit for 20 to 30 minutes to allow the KB103 to warm to room temperature. Do 
not let the vials sit for more than 40 minutes prior to use. 
5. 
The study team will tell you which of the wounds should be given KB103. If you are 
unsure, contact your study doctor or study coordinator. 
6. 
Unpackage Mepitel One, Mepiform, Vaseline, and Kerlix Gauze dressings that were 
provided with the dressing kit and place them nearby. Prepare the wound for KB103 
administration by unbandaging the area. Cut a hole in Mepitel One to the size of the 
wound to be treated and place the cut Mepitel on the patient’s skin around the wound 
surface. 
7. 
To compound KB103 with the gel, take one syringe and attached an 18G needle to it. 
Open a vial of KB103 and draw the product entirely into the syringe (each vial contains 
200uL of KB103). Repeat the same procedure to draw the same volume of gel into a 
second syringe. 
8. 
Activate safety cover of the needles and removes needles from syringes. Discard the 
needles in the sharp needle’s container. 
9. 
Join the two syringes using the guarded Luer lock connector. 
10. 
To mix KB103 and gel (1:1 dilution), place the syringes in a vertical position and keep 
the syringe containing KB103 on top. Slowly dispense the syringe containing KB103 
while drawing on the syringe containing the gel until all KB103 is mixed with the gel. 
Invert the syringes and repeat this operation twice.  

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11. 
Disconnect the syringes, keep the syringe containing the compounded product and 
apply directly to the patient’s skin depressing the syringe plunger 
very slowly to cover the surface of the wound with KB103.  
Ensure that the KB103 is contained to the wound without any 
spillage.  
12. 
If necessary, open a new syringe, connect the spreader and use 
it to spread the product on the patient’s skin. 
a. 
Any spillage on hard surfaces should be immediately wiped up with the provided 
10% bleach wipes, and any used wipes should be placed in the provided 
biohazard container.  
b. 
If KB103 spills on an absorbent material such as carpet, while wearing gloves, 
use a paper towel to absorb any visible KB103. Discard the towel. Spray with 
Lysol and use a provided 10% bleach wipe to vigorously blot the area.  
13. 
Let the KB103 sit for 5 minutes prior to placing any covering over the wound. Keep the 
area clean and do not touch the wound during the 5-minute period. 
14. 
After applying KB103, remove the gloves, discard them in the 
biohazard container, and put on a new pair of gloves.  
15. 
Cover the wound using the non-adherent side of Mepiform on 
above the wound and then cut to the full size of Mepitel 
dressings. 
16. 
Thoroughly wrap the dressing in Vaseline Kerlix Gauze and further dress as normally 
done. 
17. 
All used materials are to be discarded into a biohazard container.  Prior to disposal, 
thoroughly spray the material (bandages, gloves, syringe, etc) with the provided Lysol 
spray.  Store the biohazard container in a safe place out of reach of pets and children 
until the day of bandage removal and dressing change. 
18. 
Leave KB103 on the wound for at least 24 to 72 hours. 
14.1.2 
Bandage Removal and Disposal 
When removing bandages: 
• 
Avoid direct contact between the treatment site and dressings. 
• 
Wear gloves while removing dressings. 
• 
Keep the treatment sites covered with the bandages until the time of removal.  
• 
When it is time to remove the dressings, place the used dressings and cleaning 
materials in the provided biohazard container. Thoroughly spray the bandages with 
Lysol and securely close the container. 

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• 
Following removal of the dressing, while wearing gloves, clean the area with the 
subject’s standard mild cleanser solution (saline, or mild soap and water). 
• 
Avoid touching or scratching the treatment sites following removal of the bandages. 
• 
Dress the wound as per the usual routine. 
14.1.3 
Dry Ice Disposal 
Leave the dry ice in the container in which it was shipped and set it outside, out of reach of pets 
and children. Do not seal the container. Allow the dry ice to sublimate (convert to carbon dioxide 
gas), then dispose of the container. 
DO NOT: 
- 
Place the dry ice in the red biohazard bucket or attempt to ship it for any other reason. 
- 
Attempt to dump dry ice in a sink, tub or toilet. The extreme cold will harm plumbing 
parts and pipes. 
- 
Dispose of dry ice in garbage receptacles or garbage chutes. 
- 
Leave dry ice in an unventilated room to evaporate. It will release a build-up of carbon 
dioxide into the air that can cause rapid suffocation. 
- 
Place dry ice on a tile or laminate countertop. Instead, use a solid surface - a wood 
cutting board or piece of plywood is best. Dry ice is sometimes used in tile removal and 
may destroy the bonding agent holding the tile or laminated material in place. 
- 
Store dry ice in a glass or air-tight container. Pressure will build up inside and could 
cause the container to explode. 

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Appendix 2 – PRO Scale