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| 8-K - FORM 8-K - Fibrocell Science, Inc. | fcsc100516form8-k.htm |
Corporate Presentation
October 5, 2016
This presentation and our accompanying remarks contain “forward-looking statements” within the meaning of the
U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified
as forward-looking statements for this purpose and include, among others, statements relating to: the potential
advantages of our product candidates; the initiation, design and timing of pre-clinical and clinical studies and
activities and the reporting of the results thereof; the timing of regulatory submissions and actions; expected
milestones; and all other statements relating to our future operations, future financial performance, future financial
condition, prospects or other future events.
Forward-looking statements are based upon our current expectations and assumptions and are subject to a number
of known and unknown risks, uncertainties and other factors that could cause actual results to differ materially and
adversely from those expressed or implied by such statements. Factors that could cause or contribute to such
differences include, among others: our ability to obtain additional capital to fund our operations; FDA allowance to
treat pediatric subjects in the Phase II portion of our Phase I/II clinical trial of FCX-007; uncertainties relating to the
initiation, enrollment and completion of clinical trials and whether the results will validate and support the safety
and efficacy of our product candidates; the risk that results seen in pre-clinical studies may not be replicated in
humans; varying interpretation of pre-clinical and clinical data; our ability to maintain our collaborations with
Intrexon; and the other factors discussed under the caption “Item 1A. Risk Factors” in our most recent Form 10-K
and Form 10-Q filings which are available through the “Investors—SEC Filings” page of our website at
www.fibrocell.com. As a result, you should not place undue reliance on forward-looking statements.
The forward-looking statements made in connection with this presentation represent our views only as of the date
of this presentation (or any earlier date indicated in such statement). While we may update certain forward-looking
statements from time to time, we specifically disclaim any obligation to do so, even if new information becomes
available in the future.
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Forward-Looking Statements
Company Highlights
•Autologous cell and gene therapy company translating personalized
biologics into medical breakthroughs for diseases of the skin and
connective tissue
•FCX-007 — Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Actively recruiting adult subjects; first human clinical data expected in 3Q17
Granted pediatric rare disease designation by FDA
• FCX-013 — Linear Scleroderma
Proof-of-concept completed January 2016; IND planned 4Q17
Granted orphan drug designation by FDA for localized scleroderma
• Arthritis and related conditions
Deliver therapeutic protein locally to the joint providing sustained efficacy while
avoiding key side effects typically associated with systemic therapy
•Portfolio being developed in collaboration with Intrexon
3
Key Advantages of Our Autologous Fibroblast
Gene Therapy Platform
• Fibroblasts are the most common cell in skin and connective tissue, and are an ideal
delivery vehicle to administer protein of interest locally
Localized administration avoids side effects typically associated with systemic therapy
Reduced rejection and immunogenicity concerns because autologous fibroblasts are compatible
with the unique biology of each patient
• Use of a 3rd generation, self-inactivating (SIN) lentivirus:
Accommodates large gene constructs due to packaging size
Allows for target gene integration, ideal for long-term expression of the protein
• Fibroblasts are genetically modified ex vivo, providing distinct safety and efficacy
advantages:
Enables testing for safety and confirmation of transduction rates and protein expression prior to
administration
Reduces potential for host immune response upon retreatment as live virus is not administered
directly into the patient
•We are using our proprietary technology to create personalized biologics
Expertise in commercial-scale manufacturing of an autologous cell therapy
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Personalized Biologics Approach
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Development Pipeline
6
Personalized
Biologic Indication Research
Pre-Clinical
Development
Human Clinical
Trials
FCX-007
Recessive Dystrophic
Epidermolysis Bullosa (RDEB)
FCX-013 Linear Scleroderma
Research
Program
Arthritis
Recessive Dystrophic Epidermolysis Bullosa
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Disease Current Treatments Epidemiology
• Cause: A mutation in the
COL7A1 gene that encodes
for COL7
• Devastating, progressive,
painful blistering disease
that often leads to death
• Diagnosed at infancy
• High mortality rate
• Current treatments only
address symptoms
Bandaging & antibiotics –
bandaging alone can
exceed $10,000 per
month1
Feeding tubes
Surgery, including hand
and esophageal
Dystrophic EB (DEB)
~5,500 – 12,500 US2
• RDEB
~1,100 – 2,500 US3
FCX-007 Providing Hope for RDEB Patients
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RDEB patients do not produce
type VII collagen (COL7) due to
mutation in COL7A1 gene
Main component of anchoring
fibrils that connect skin layers
FCX-007 is an autologous human
dermal fibroblast transduced with
a lentiviral (LV) vector encoded for
COL7A1
Simple, local injection to the
papillary dermis
COL7 Expression Confirmation
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Culture supernatant evaluated for in vitro COL7 expression
• ELISA assay indicates virus dose-dependent protein expression
• Trimeric form of COL7 produced by RDEB patient fibroblasts
transduced with LV-COL7
•Must be trimeric to be functional
Reference: Bruckner-Tuderman, Leena. Can Type VII Collagen Injections Cure Dystrophic
Epidermolysis Bullosa? Molecular Therapy (2008) 17 1, 6–7.
RDE
B
+
C
o
n
tr
o
l
P
u
ri
fi
e
d
C
OL
7
FC
X
-0
0
7
-0
1
FC
X
-0
0
7
-0
2
Trimeric
COL7
(900kDa)
COL7 IP
Immunoprecipitation (IP)/Western Blot
COL7 Formation
Trimeric Form
(900kDa)
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Detection of COL7 Expression by
Immunofluorescence (Magnification 20x)
• In vitro COL7 expression noted from FCX-007 replicates (red)
• FCX-007 expresses higher levels of COL7 than normal human
dermal fibroblasts (NHDF) as depicted by a brighter signal
• No expression of COL7 in RDEB-positive fibroblasts
FCX-007 Rep 1 FCX-007 Rep 2 FCX-007
In Vivo Expression*In Vitro Expression
NHDF RDEB+ NHDF RDEB+
• RDEB xenograft on immunodeficient mouse sampled 17 days
post-injection
• COL7 detected at the basement membrane zone (BMZ; refer to
arrow) and underlying dermis (green)
• NDHF slide expresses COL7 normally resulting in mature
anchoring fibrils
• No expression of COL7 in RDEB-positive fibroblasts*Image courtesy of Peter Marinkovich, MD lab, Stanford University
COL7 expression at
BMZ only 17 days
after injection of
FCX-007
• Autologous cells minimize rejection risk
• Direct administration of FCX-007 to the upper dermis ensures COL7
is expressed in the basement membrane zone where anchoring
fibrils are formed
• The integrative nature of the lentivirus allows the COL7A1 gene to
be passed to daughter cells as FCX-007 cells divide
• Academic research suggests that in vivo COL7 expression persists for
at least one year in RDEB skin tissue regenerated on
immunodeficient mice4
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Long-lasting COL7 Persistence Expected
FCX-007 Phase I/II Clinical Trial Design
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Title A Phase I/II Trial of FCX-007 (Genetically-Modified Autologous Human Dermal Fibroblasts) for
Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Objectives Primary
1) To evaluate the safety of FCX-007
Secondary
1) To evaluate mechanism of action of FCX-007 at weeks 12, 25, 52 and unscheduled visits through
the evaluation of skin biopsies for COL7 expression and the presence of anchoring fibrils
2) To evaluate the efficacy of FCX-007 through an intra-subject paired analysis of target wound area
at weeks 4, 12, 25, 52 and unscheduled visits, comparing FCX-007 treated wounds to untreated
wounds in Phase I and to wounds administered sterile saline in Phase II through the evaluation
of digital imaging of wounds
Number of
Subjects
Twelve subjects consisting of six adults in the Phase I portion of the trial and, subject to FDA
allowance, six pediatrics in the Phase II portion of the trial
Status Actively recruiting adult subjects in Phase I portion of trial
Linear Scleroderma
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Disease Epidemiology
• Excess production of collagen
I and III characterized by skin
fibrosis and linear scars
• The linear areas of skin
thickening may extend to
underlying tissue and muscle
in children which may impair
growth in affected legs and
arms or forehead
• Lesions appearing across
joints impair motion and may
be permanent
• Localized Scleroderma
~160,000 sufferers US5
comprised of many different
sub-types
Linear Scleroderma
Initial target for FCX-013 is
a group of ~40,000
patients6
Current Treatments
Current treatments only
address symptoms:
• Systemic or topical
corticosteroids
• UVA light therapy
• Physical therapy
Photo: Reprinted from the Journal of the American Academy of Dermatology, Volume 59, Issue 3, Stéphanie Christen-Zaech, Miriam D. Hakim, F. Sule Afsar, Amy S. Paller.
Pediatric morphea (localized scleroderma): Review of 136 patients, Figure 1, pp. 385-396. Copyright Sept 2008. Used with permission from Elsevier Ltd.
FCX-013 Development Progressing
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•Product profile
Autologous fibroblasts genetically modified using lentivirus and encoded for a
protein responsible for breaking down excess collagen I and III
Target protein known to breakdown collagens
Incorporates Intrexon’s RheoSwitch Therapeutic System® (RTS®) to control protein
expression
• RTS® has previous human clinical trial experience
•Proof-of-concept animal study data demonstrated protein expression,
reduced thickness of fibrotic tissue
• Scale-up manufacturing in process
•Received FDA orphan drug designation for treatment of localized
scleroderma
•Next steps include dose-ranging and toxicology/biodistribution studies
•IND submission expected 4Q17
FCX-013 Proof-of-Concept Study
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• Study Design
Bleomycin treated SCID mouse model
N=30 mice over test and control groups
Assessed histologically for reduction of dermal
thickness and sub-dermal muscle in the presence
of FCX-013 and oral ligand
• Result
Bleomycin treatment resulted in skin fibrosis, measured by a significant increase in dermal thickness
Demonstrated that FCX-013 with ligand reduced the dermal thickness of fibrotic tissue to levels
similar to non-bleomycin (saline) with ligand treated skin
Further reduced the thickness of the sub-dermal muscle layer
Blecomycin treatments Ligand Treatment
D0 D28 D29 D39
Cell
injection
Harvest skin
samples
CONTROL:
Saline (no Bleo)
No Cells
TEST:
Bleomycin
FCX-013
CONTROL:
Bleomycin
Non-Modified Cells
• FCX-013 employs Intrexon’s RheoSwitch
Therapeutic System® (RTS®)
The RTS® biologic switch is activated by an orally-
administered activator ligand (AL) that provides the
ability to control level and timing of protein
expression
• Enhances the safety profile of FCX-013 by
providing control over the expression of the
protein
• In vitro studies support RTS® control over FCX-
013 protein expression:
Significant increase in expression of the target
protein in the presence of the AL
In the absence of the AL, the expression is reduced
to normal cellular production of the target protein
Cells transduced with RTS® and off-target gene
construct (RTS-GFP) and non-transduced fibroblasts
(mock) express normal cellular production levels
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RheoSwitch® Control
RTS-GFP Control FCX-013 Mock Control
FCX-013 RTS® Control
no AL
+ AL
Ta
rg
et P
ro
tein
Conce
n
tr
ati
o
n
Research Program for Arthritis
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•Deliver therapeutic protein locally to the joint providing sustained
efficacy while avoiding key side effects typically associated with
systemic therapy
•Combines Fibrocell’s autologous fibroblast technology with
Intrexon’s cellular engineering to develop localized gene therapies
•Focused on addressing chronic inflammation and degenerative
diseases of the joint, including arthritis
Milestones
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Milestones Anticipated Timing
FCX-007 1st Adult Subject Dosed Yearend 2016
FCX-007 Phase I/II Trial First human clinical data 3Q17
FCX-013 IND Submission 4Q17
Company Highlights
•Autologous cell and gene therapy company translating personalized
biologics into medical breakthroughs for diseases of the skin and
connective tissue
•FCX-007 — Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Actively recruiting adult subjects; first human clinical data expected in 3Q17
Granted pediatric rare disease designation by FDA
• FCX-013 — Linear Scleroderma
Proof-of-concept completed January 2016; IND planned 4Q17
Granted orphan drug designation by FDA for localized scleroderma
• Arthritis and related conditions
Deliver therapeutic protein locally to the joint providing sustained efficacy while
avoiding key side effects typically associated with systemic therapy
•Portfolio being developed in collaboration with Intrexon
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References
1The Dystrophic Epidermolysis Research Association of America (DebRA). DEB
brochure, page 6: http://www.debra.org/pdfs/Debra-of-America-Brochure.pdf;
accessed 07/20/15.
2DEBRA International. What is EB Infographic: http://www.debra-
international.org/epidermolysis-bullosa.html.; accessed 10/06/2014.
3Petrof G., et al. Fibroblast cell therapy enhances initial healing in recessive
dystrophic epidermolysis bullosa wounds: results of a randomised, vehicle-
controlled trial. Brit J Dermatol. 2013 Nov;169(5):1025-33.
4Siprashvili Z., et al. Long-term type VII collagen restoration to human
epidermolysis bullosa skin tissue. Human Gene Therapy. 2010 Oct;21(10): 1299-
1310.
5Data on file, Fibrocell Science.
6Leitenberger, et. al. Distinct autoimmune syndromes in morphea: a case study
of 245 adult and pediatric cases. Arch Dermatol. 2009 May;145(5):545-550.
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