Attached files
| file | filename |
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| 8-K - 8-K - Fibrocell Science, Inc. | fcsc080917form8-k1.htm |
| EX-99.1 - EXHIBIT 99.1 - Fibrocell Science, Inc. | exhibit991pressrelease0809.htm |
Corporate Presentation
August 9, 2017
Forward-Looking Statements
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 studies and clinical trials 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 patients in the Phase 2 portion of our Phase 1/2 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-Qs 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.
2
Proprietary
autologous fibroblast
cell capabilities
+
Ex vivo genetic
modification of
patients’ own
fibroblast cells
FCX-007
Recessive Dystrophic
Epidermolysis Bullosa
(RDEB)
FCX-013
Moderate to Severe
Localized Scleroderma
Arthritis and related
conditions
3
Fibrocell at a Glance
Personalized medical breakthroughs for
diseases of the skin and connective tissue
• Three patients dosed; human clinical data expected
in 3Q17
Orphan Drug Designation
Rare Pediatric Disease Designation
Fast Track Designation
• IND filing expected in 4Q17
• Next step: Conduct GLP biodistribution/toxicology
study
Orphan Drug Designation
Rare Pediatric Disease Designation
• 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
Autologous fibroblasts
harvested from patients
• Readily sourced, as
fibroblasts are the most
common cell type in skin
and connective tissue
• Reduced rejection and
immunogenicity concerns
because the donor is the
patient
• Established manufacturing
process and regulatory
pathway for autologous
fibroblasts
Lentiviral vector gene
transfer
• 3rd generation and self-
inactivating for additional
safety
• Accommodates large gene
constructs
• Transduces both dividing
and non-dividing cells
• Target gene integration for
long-term expression of the
protein
Ex vivo gene
modified cells
• Confirmation vector
copy number and
protein expression
levels prior to dosing
• Live virus is not
administered directly
into patients
4
Our Autologous Fibroblast Gene Therapy Platform
Delivery Vehicle Vector
Ex vivo
Modification
Personalized Biologics Approach
5
Development Pipeline
6
Personalized
Biologic Condition Research
Pre-Clinical
Development
Human Clinical
Trials
FCX-007
Recessive
Dystrophic
Epidermolysis
Bullosa (RDEB)
FCX-013
Moderate to
Severe
Localized
Scleroderma
Research
Program
Arthritis
Human data
expected 3Q17
IND filing
expected
4Q17
FCX-007 Providing Hope for RDEB Patients
7
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
• Local injection to the papillary dermis
Estimated that 30-50% of normal COL7
expression could provide significant
improvement1
• Parents of RDEB patients are
heterozygous carriers of mutated
COL7A1; therefore, they only produce
about 50% of normal COL7 levels, yet
present no indications of RDEB
About RDEB
8
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 – 76% of
RDEB suffers do not live
past their 30’s2
• Current treatments only
address symptoms
Bandaging & antibiotics –
bandaging alone can
exceed $10,000 per
month3
Feeding tubes
Surgery, including hand
and esophageal
Dystrophic EB (DEB)
~5,500 – 12,500 US4
• RDEB
~1,100 – 2,500 US5
Functional COL7 Expression Confirmation
9
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.
COL7 Formation
Trimeric Form
(900kDa)
RD
EB
+
C
o
n
tr
o
l
P
u
ri
fi
ed
C
OL
7
FC
X
-0
0
7
-0
1
FC
X
-0
0
7
-0
2
COL7 IP
Immunoprecipitation (IP)/Western Blot
Trimeric COL7
(900kDa)
In vitro studies show FCX-007 results in
expression of COL7 in functional trimeric form
10
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 Replicate 1 FCX-007 Replicate 2 FCX-007
In Vivo Expression*In Vitro Expression
NHDF RDEB+ NHDF RDEB+
• RDEB xenograft on immunodeficient mouse sampled 17 days
post-FCX-007 treatment
• COL7 detected at the basement membrane zone (BMZ; refer to
arrow) and underlying dermis (green)
• NHDF expresses COL7 normally resulting in mature anchoring
fibrils at the BMZ as depicted by a brighter signal (green)
• No expression of COL7 in RDEB-positive fibroblasts
COL7 expression at
BMZ only 17 days
after injection of
FCX-007
*Images courtesy of Peter Marinkovich, MD laboratory, Stanford University
Phase 1:
1st patient
dosed Feb.
2017
• Continue follow-up at
4- and 12-weeks
• Respond to FDA with
benefit and safety
data in multiple adults
and toxicology study
Phase 1: Dose
additional adult
patients
Phase 2
Pediatrics
FCX-007 Phase 1/2 Clinical Trial Design
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Title A Phase 1/2 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 4, 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-patient 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 1 and to
wounds administered sterile saline in Phase 2 through the evaluation of digital imaging of wounds
Number of
Patients
Twelve patients consisting of six adults in the Phase 1 portion of the trial and, subject to FDA allowance, six
pediatrics in the Phase 2 portion of the trial
Status Actively recruiting adult patients in Phase 1 portion of trial; three patients dosed.
Path to Phase 2:
• DSMB reviewed
4-week post-
administration
safety data May
2017
FCX-013 Development Progressing
12
• Product profile
Autologous fibroblasts genetically modified using lentivirus and encoded for matrix
metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen
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,
and Rare Pediatric Disease Designation for treatment of moderate to severe
localized scleroderma
•Next step: Conduct GLP toxicology/biodistribution study
• IND filing expected 4Q17
• 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
13
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
Localized Scleroderma
14
Disease Epidemiology
• Excess production of collagen
characterized by skin fibrosis
and scars
• Focus on moderate to severe
subtypes, including linear
• Thickening may extend to
underlying tissue and muscle
in children which may impair
growth in affected limbs or
forehead
• Lesions appearing across
joints impair motion and may
be permanent
• Localized Scleroderma
~160,000 sufferers US6
comprised of different sub-
types
~90,000 patients are
considered severe7
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 Proof-of-Concept Study
15
• 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
Research Program for Arthritis
16
• 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 and Financials
17
Milestones Anticipated Timing
FCX-007 1st Adult Patient Dosed February 2017
FCX-007 DSMB Recommendation May 2017
FCX-007 Phase 1/2 Trial First human clinical data 3Q17
FCX-013 IND Filing 4Q17
Financials
• Cash = $15.9 million at June 30, 2017
• Current cash estimated to fund operations into 2Q18
References
1 Fritsch A., et. al. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanism
of disease and response to fibroblast therapy. J Clin Invest.2008; 118:1669–1679.
2 Fine, J. et. al. (ed.). Epidermolysis Bullosa: Clinical, Epidemiologic, and Laboratory Advances and the
Findings of the National Epidermolysis Bullosa Registry. The John Hopkins University Press, Baltimore,
MD, 1999.
3 The Dystrophic Epidermolysis Research Association of America (DebRA). EB brochure, page 6:
http://www.debra.org/DebraBrochure; accessed 07/20/15.
4 DEBRA International. What is EB Infographic: http://www.debra-international.org/epidermolysis-
bullosa.html.; accessed 10/06/2014.
5 Petrof 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.
6 Peterson LS et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-
1993. J Rheumatol. 1997; 24:73-80.
7Leitenberger, 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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