Fibrocell Science, Inc. - FORM 8-K - EX-3.1

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8-K - FORM 8-K - Fibrocell Science, Inc.	d578216d8k.htm

August 5, 2013

Fibrocell Science

Exhibit 3.1

This

presentation

includes

statements

that

are

“forward-looking

statements.”

Forward-looking

statements

include,

without limitation, our ability (i) to timely commence our clinical programs in 2013 to treat patients with restrictive

burn scars and vocal cord scars, and a timely completion of these trial (ii) to successfully genetically modify the

fibroblast cell to treat patients who have collagen deficient diseases, (iii) to successfully leverage our relationships

with

UCLA

and

MIT

develop

new

applications,

and

(iv)

adopt

technologies

that

will

dramatically

reduce

manufacturing time, complexity, and labor costs for our cell therapies. While management has based any forward-

looking statements contained in the presentation on its current expectations, the information on which such

expectations were based may change. These forward-looking statements rely on a number of assumptions concerning

future events and are subject to a number of risks, uncertainties, and other factors, many of which are outside of

Fibrocell Science’s control, that could cause actual results to materially differ from such statements. Such risks,

uncertainties, and other factors include, but are not necessarily limited to, those set forth under the caption “Item 1A.

Risk

Factors”

Fibrocell

Science’s

most

recent

Form

10-K

filing,

updated

“Item

1A.

Risk

Factors”

Fibrocell

Science’s most recent Form 10-Q filing. In addition, Fibrocell Science operates in a highly competitive and rapidly

changing environment, and new risks may arise. Accordingly, you should not place any reliance on forward-looking

statements as a prediction of actual results. Fibrocell Science disclaims any intention to, and undertakes no obligation

to, update or revise any forward-looking statement. You are also urged to carefully review and consider the various

disclosures in Fibrocell Science’s most recent annual report on Form 10-K, our most recent Form 10-Q as well as other

public filings with the SEC since the filing of Fibrocell Science’s most recent annual report.

Forward Looking Statement

Strategic Focus: Unlocking the Potential

of the Autologous Fibroblast Cell

•

Restrictive Burn Scarring

•

Vocal Cord Scarring

•

Acne Scarring

•

Recessive Dystrophic

Epidermolysis Bullosa (RDEB)

•

Morphea

•

Cutaneous Eosinophilias

•

Localized Treatment for

moderate to severe

Psoriasis

•

Focused on skin-derived

MSCs and more efficient

conversion of skin cells

to IPSCs

Autologous

Fibroblasts

Label Extension

for LAVIV®

(azficel-T)

Genetically-

Modified HDFs

for rare skin

diseases

Genetically-

Modified HDFs

for serious skin

diseases

UCLA/MIT

Collaboration

Aesthetics

•

Positioned

premium

aesthetic

–

First

New

Class

–

Personalized

Aesthetics

–

Replaces

person’s

own

fibroblast

cells

•

LAVIV

has

received

national

recognition

–

Allure

magazine

‘Breakthrough

Award’

–

Wall

Street

Journal

Technology

Innovation

Awards

–

Edison

Awards

Silver

Winner

Aesthetics

Science/Medical

Category

LAVIV®

(azficel-T)

Please

refer

the

end

this

presentation

for

Important

Safety

Information

about

LAVIV®

(azficel-T).

The Only Crème of Its Kind

•

Personalized

autologous

cream

•

Conditioned

complete

growth

media

from

the

azficel-T

production

process

collected,

concentrated

and

used

formulate

personalized

topical

cosmetic

Autologous Crème™

Product Pipeline

Restrictive Burn Scurring

Vocal Cord Scurring

Acne Scurring

Genetically Modified

Autologous Fibroblasts

Skin-derived MSC/IPSCs

•

Phase II study initiated

•

Efficacy data expected mid-2014

•

Positive pilot study published in Laryngoscope; abstract online:

http://www.ncbi.nlm.nih.gov/pubmed/21287562

•

Phase II protocol cleared by FDA

•

Estimated initiation of trial 2H 2013, once IRB approval is received

•

In end of Phase II discussions with FDA, regarding potential pathway forward

•

Results of Phase II study published in Dermatologic Surgery;

available online: http://onlinelibrary.wiley.com/doi/10.1111/dsu.12204/pdf

•

Pre-clinical activity advancing in genetically modified fibroblasts for the treatment of

recessive dystrophic epidermolysis bullosa (RDEB); Orphan Indication

•

Pre-clinical activity advancing in genetically modified fibroblasts transfected ex vivo with

therapeutic

gene(s)

interest

under

the

control

the

RheoSwitch™

Gene

Expression

System for the localized treatment of:

Moderate to Severe Psoriasis

Cutaneous Eosinophilias (Orphan Indication)

Morphea (Orphan Indication)

•

Reprogramming skin cells into induced pluripotent stem cells (IPSCs)

•

Identifying, purifying, and cultivating MSCs from human adult skin

Status

What is a Fibroblast?

•

Most

common

cells

connective

tissue

•

Produce

collagen

and

extracellular

matrix

proteins,

which

form

infrastructure

tissue

•

Produce

growth

factors

and

other

cytokines

that

aid

cell

signaling

and

wound

repair

Fibroblast Cells

Dermal Fibroblasts

Dermal fibroblasts produce

•

Collagen type I

•

Collagen type III

•

Collagen type VII

•

Elastin

•

Hyaluronic acid (hyaluronin)

•

Matrix metalloproteinases

(MMPs)

(1)

Artist’s interpretation

Dermal Fibroblasts

(1) Matrix metalloproteinases refers to a group of proteins that play an important role in tissue remodeling associated with various physiological

and pathological processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis, and metastasis. There is considerable recent

research on MMPs and their potential role in future therapeutics.

Addressable Markets

Scarring: Burn, Vocal Cord, Acne

Fibrocell Scarring Pipeline:

Annual Addressable Market Opportunity

•

Restrictive Burn Scarring (U.S. only):

140,000 2 and 3 degree burn victims / year

(1)

Total excludes military burn injuries

20-30%

experience

restrictive

scarring

(2)

Assumption of 30% treated

Assumption of pool of patients available includes the

previous 3 years

(1)

American Burn Association http://www.ameriburn.org/

(2)

Fibrocell estimate based on discussion with key opinion leader

(3)

Fibrocell estimates based on current pricing and estimated average volumes of azficel-T used to treat patients with these conditions; prices are subjected to change and variation

(4)

Cohen, (2010); Dailey et al. (2007); Roy et al. (2005); Poels et

al. (2003); Koufman and Isaacson (1991); Painter (1990); Bouchayer et al. (1985); Laguaite (1972)

(5)

Acne Resource Center. www.acne-resource.org

•

Vocal Cord Scarring (U.S. only):

200,000-700,000

patients

with

VCS

(4)

Assumption of 10% treated

•

Acne Scarring (U.S. only):

million

patients

with

severe

acne

that

could

cause

scarring

(5)

Every 50,000 patients represents $750 million addressable market

Vocal Cord Scarring

$240

–

$840 M

Acne Scarring

$750 M

Restrictive Burn Scarring

$815 M

(3)

Restrictive Burn

Scarring

•

No FDA approved therapeutics

•

Azficel-T

treatment:

potential

improvement

range

motion,

reduction

pain and aesthetic improvement

•

Potential indication for unmet medical need:

Pre-

Treatment

12 Months Post-

Treatment

•

Full range-clench

14 Months Post-

Treatment

•

Fine finger movement

(1)

www.ameriburn.org; Goodis. J and E.d. Schraga. Burns, thermal. eMedicine Journal

Restrictive Burn Scarring Overview

Before After

Six Months Post Treatment:

•

Full range of neck rotation, and pain

free

•

Patient has stopped all analgesics

•

Discarded cervical collar

Feb 1, 2006 August 11, 2006

–

45,000 yearly hospitalizations for severe burns

(1) (excluding military and existing victims)

–

Promising results in open-label case studies

•

Phase II Trial: Single site, double-blind, randomized, placebo-controlled,

21 subjects

•

Subjects:

Unilateral restrictive burn scars of a jointed area

20-50 percent restriction in normal range of motion

•

Measurement Scales:

Range of Motion Measurement

Brief Pain Index

Scar Appearance

•

Phase II Clinical Study initiated in 2Q 2013; efficacy data expected

mid-2014

Restrictive Burn Scarring Status

Vocal Cord Scarring

•

FDA

approved

therapeutics

(1)

Chhetri, Dinesh, Injection of Cultured Autologous Fibroblasts for Human Vocal Fold Scars. The Laryngoscope 121(4) : 785-792, 2011.

Vocal Cord Scarring Overview

•

Most

commonly

encountered

finding

loss

voice

Due

surgery,

radiation

therapy,

vocal

cord

trauma

and

idiopathic

causes

•

Positive

pilot

study

results

published

peer-reviewed

journal

The

Laryngoscope,

2011

(1)

Azficel-T

well-tolerated

when

injected

into

vocal

folds

Improvements

lasted

one

year

Findings

supported

mucosal

wave

grade,

voice

handicap

index,

and

voice

quality

questionnaire

•

Phase

protocol

cleared

FDA

•

Estimated

initiation

trial

2013,

once

IRB

approval

received

•

Efficacy

data

expected

2014

•

Proposed

Endpoints:

Absolute

change

from

baseline

mucosal

wave

grade

using

videostroboscopy

Absolute

and

percentage

change

from

baseline

the

Voice

Handicap

Index

(VHI)

Perceptual

analysis

using

the

GRBAS

scale

(Grade

dysphonia,

•

Proposed

trial

design:

Two-site,

double-blind,

randomized,

placebo-

controlled,

subjects

Vocal Cord Scarring Status

oughnes,

reathiness,

sthenia,

train)

Acne Scarring

Acne Scarring Overview

•

No FDA approved therapeutics

•

Permanent discoloration and/or indentation of the skin as a result

of moderate to severe acne

•

Completed one Phase II study

Results published in peer-reviewed journal Dermatologic Surgery, available

online: http://onlinelibrary.wiley.com/doi/10.1111/dsu.12204/pdf

•

Currently in discussions with FDA on path forward

•

Efficacy

Statistically

significant

number

responders

subject

and

evaluator

assessments

four

months

•

Safety

Most

common

adverse

events:

erythema

(11.1%),

swelling

(10.1%);

all

were

mild

moderate

severity

Acne Scarring Phase II Study Results

Includes

initial

treatment

only.

Note:

Photos

from

Fibrocell

clinical

studies.

Before

After

Acne Scarring

25 Month Photos Anecdotally Demonstrate Potential Long-Lasting Effect

Potential Long-Lasting Effect:

Reports anecdotally suggest >75% of patients demonstrate treatment benefit 9 and

12 months following treatment

Photos anecdotally demonstrate sustained improvement 25 months following last

treatment

Photos provided by Gilly S. Munavalli, MD, MHS, FACMS, Dermatology, Laser & Vein Specialists of the Carolinas, Charlotte, NC

Intrexon Collaboration:

Genetically Modified Fibroblasts

Intrexon Collaboration:

Executive Summary

Based on market analyses, the annual market potential

for each indication is as follows:

•

$1.7-$3.4 billion for a treatment for moderate to

severe psoriasis

(1,2,3,4)

•

$120-$140 million for a treatment for cutaneous

eosinophilias

(5,6)

•

$300-$350 million for a treatment for morphea

(localized scleroderma)

(7,8)

•

$560 million-$2.2 billion for a treatment for

Recessive Dystrophic Epidermolysis Bullosa

(RDEB)

(9,10,11, 12)

Cutaneous

Eosinophilias

$120-$140

million

Moderate to

Severe

Psoriasis

$1.7-$3.4 Billion

RDEB

$560million-

$2.2 billion

Morphea

$300-$500

million

(1)

National Psoriasis Foundation, “About Psoriasis” Available at: http://www.psoriasis.org/about-psoriasis. Accessed June 27, 2013.

(2)

PhotoMedex, Inc., “Severity of Psoriasis” Available at: http://xtracnow.com/physicians/psoriasis_stats.htm/ Accessed June 27, 2013.

(3)

Beyer et al. “Recent Trends in Systemic Psoriasis Treatment Costs” Arch Dermatol2010;146(1):46-54.

(4)

Stern et al. “Psoriasis Is Common, Carries a Substantial Burden Even When Not Extensive, and Is Associated with Widespread Treatment Satisfaction” J InvestigDermatolzzz

Symp2004;9:136-139.

(5)

Cutaneous eosinophilias represent a family of more than 30 different conditions ranging from eosinophilic cellulitis (Wells’ syndrome) to eosinophilicdermatosis and

eosinophilic fasciitis. The prevalence varies based on which conditions are targeted for treatment. It could be as low as a few hundred patients (Wells’ syndrome and

eosinophilic fasciitis) to thousands of patients (Duhring disease, which affects 15% to 25% of celiac patients). We chose 4,000 patients based on the Fibrocell press release

dated July 1, 2013.

(6)

Beyer et al. “Recent Trends in Systemic Psoriasis Treatment Costs” Arch Dermatol 2010;146(1):46-54. We assume that the cutaneous eosinophiliasindication will command

a higher price than the psoriasis indication due to the need for new treatment options, the frequency of treatment, and the severity of the condition.

(7)

Kaplan et al. “Localized Fibrosing Disorders – Linear Scleroderma, Morphea, and Regional Fibrosis” eMedicine March 6, 2013.

(8)

Beyer et al. “Recent Trends in Systemic Psoriasis Treatment Costs” Arch Dermatol2010;146(1):46-54. We assume that the morpheaindication will command a higher price

than the psoriasis indication due to the need for new treatment options, the frequency of treatment, and the severity of the condition.

(9)

Stanford School of Medicine, “EpidermolysisBullosa Clinic Frequently Asked Questions” Available at: http://dermatology.stanford.edu/gsdc/eb_clinic/eb-faqs.html.

Accessed July 11, 2013.

(10)

The Dystrophic EpidermolysisBullosa Research Association of America (DEBRA), “About EB” http://www.debra.org/abouteb. Accessed July 11, 2013.

(11)

Herper, Matthew. “How A $440,000 Drug Is Turning Alexion Into Biotech‘s New Innovation Powerhouse.” Forbes. 5 September 2012

(12)

The price range represents the price potential for a new therapy for a severe ultra rare disease based on currently marketed rare disease therapies such as Soliris®

(eculizumab - ~$400,000/year), Elaprase® (idursulfase - ~$375,000/year), Naglazyme® (galsulfase - ~$365,000/year), Myozyme® (alglucosidasealfa - ~$300,000/year), and

Fabrazyme® (agalsidase beta - ~$200,000/year).

Intrexon Collaborations:

Genetically Modified Fibroblasts

for Recessive Dystrophic Epidermolysis

Bullosa (RDEB), Cutaneous Eosinophilias,

Morphea, and Psoriasis

•

Leverage

Fibrocell’s

fibroblast

technology

with

Intrexon’s

synthetic

biology

platforms

genetically-modify

(GM)

the

patient’s

own

fibroblast

cells

•

fibroblasts

for

recessive

dystrophic

epidermolysis

bullosa

(RDEB),

debilitating

rare

genetic

blistering

disease

•

fibroblasts

transfected

vivo

with

therapeutic

gene(s)

interest

under

the

control

the

RheoSwitch™

Gene

Expression

System

for

localized

treatment

Psoriasis,

Cutaneous

Eosinophilias,

and

Morphea,

which

are

serious

skin

diseases

Collaboration Approach

•

Initial target: recessive dystrophic epidermolysis bullosa

(RDEB) –

devastating orphan disease, which in its most

severe form, blisters are present over the entire body

•

Developing a protein replacement therapy –

mutations

in COL7A1 gene cause this rare genetic disease

RDEB Overview

Stanford

School

Medicine,

“EpidermolysisBullosa

Clinic

Frequently

Asked

Questions”

Available

at:

http://dermatology.stanford.edu/gsdc/eb_clinic/eb-faqs.html.

The

Dystrophic

EpidermolysisBullosa

Research

Association

America

(DEBRA),

“About

EB”

Herper,

Matthew.

“How

$440,000

Drug

Turning

Alexion

Into

Biotech‘s

New

Innovation

Powerhouse.”

Forbes.

September

2012

The

price

range

represents

the

price

potential

for

new

therapy

for

severe

ultra

rare

disease

based

currently

marketed

rare

disease

therapies

such

Soliris®

(eculizumab

~$400,000/year),

Elaprase®

(idursulfase

~$375,000/year), Naglazyme®

(galsulfase -

~$365,000/year), Myozyme®

(alglucosidasealfa -

~$300,000/year), and Fabrazyme®

(agalsidase beta -

~$200,000/year).

–

Gene encodes the alpha chain of type VII collagen

–

Type VII collagen forms the major anchoring fibril that

anchors the epidermis to the dermis

–

The incidence of RDEB is estimated to be about 1 to 2

per 1,000,000 people

(1)

with an estimated 2,800-5,600

RDEB patients in the U.S.

(2)

–

Rare disease price/patient estimate of >$200 to $400K

(3)

and estimated $560million-$2.2 billion addressable

market

(1,2,4)

(1)

(2)

(3)

(4)

http://www.debra.org/abouteb.

Accessed

July

11,

2013.

Accessed

July

11,

2013.

Cutaneous Eosinophilias

Overview

The goal is to treat these systemic diseases locally using the autologous

fibroblast as a delivery vehicle

Cutaneous eosinophilias are a family of more than 30 diseases

characterized by inflammation due to the accumulation of eosinophils

(a form of white blood cell) in the layers of the skin

The total prevalence of cutaneous eosinophilias is estimated to be

approximately 4,000 patients in the U.S.

(1,2)

Treatment for cutaneous eosinophilias depends

on the exact nature of the disease and the

severity, but it typically includes topical therapies,

corticosteroids (including prednisone),

antimalarial drugs (including hydroxychloroquine),

and immunosuppressive medications

Cutaneous

eosinophilias

represent

family

than

different

conditions

ranging

from

eosinophilic

cellulitis

(Wells’

syndrome)

eosinophilicdermatosis

and

eosinophilic

fasciitis.

The

prevalence

varies

based

which

conditions

are

targeted

for

treatment.

could

low

few

hundred

patients

(Wells’

syndrome

and

eosinophilic

fasciitis)

thousands

patients

(Duhring

disease,

which

affects

15%

25%

celiac

patients).

chose

4,000

patients

based

the

Fibrocell

press

release

dated

July

2013.

Beyer

al.

“Recent

Trends

Systemic

Psoriasis

Treatment

Costs”

Arch

Dermatol

2010;146(1):46-54.

assume

that

the

cutaneous

eosinophiliasindication

will

command

higher

price

than

the

psoriasis indication

due to the need for new treatment options, the frequency of treatment, and the severity of the condition.

(2)

•

(1)

Morphea

Overview

•

The

goal

treat

these

systemic

diseases

locally

using

the

autologous

fibroblast

delivery

vehicle

•

Morphea

rare

form

localized

scleroderma

characterized

the

thickening

and

hardening

the

skin

due

excessive

collagen

production;

other

organs

beyond

the

skin

are

typically

not

involved

•

The

total

prevalence

all

forms

morphea

thought

less

than

10,000

patients

the

U.S.

(1)

•

Morphea

treatment

typically

focuses

controlling

symptoms

and

slowing

disease

progression;

treatment

options

include

photo

(light)

therapy,

corticosteroids,

calcipotriene

cream,

antimalarial

drugs,

and

immunosuppressive

medications

(1)

Kaplan

al.

“Localized

Fibrosing

Disorders

–

Linear

Scleroderma,

Morphea,

and

Regional

Fibrosis”

eMedicine

March

2013.

Psoriasis Overview

The goal is to treat these systemic diseases locally using the autologous

fibroblast as a delivery vehicle

Chronic skin disease characterized by the overproduction of new skin cells,

which results in the formation of scaly patches

Believed to be an immune-mediated disease caused by a malfunction in the

immune system

No cure for Psoriasis: symptoms managed with topical agents, phototherapy,

and systemic therapies

U.S. prevalence approximately 4.5 million (25% with moderate to severe

disease, 10-20% also develop psoriatic arthritis)

(1,2,3)

U.S. psoriasis therapeutic market nearly $2

billion in 2012

Total direct and indirect healthcare costs

over $11 billion in 2008

(1) Stern

al.

“Psoriasis

Common,

Carries

Substantial

Burden

Even

When

Not

Extensive,

and

Associated

with

Widespread

Treatment

Satisfaction”

InvestigDermatolSymp2004;9:136 -139.

(2)

National

Psoriasis

Foundation,

“About

Psoriasis”

Available

at:

(3)

PhotoMedex,

Inc.,

“Severity

Psoriasis”

Available

at:

•

Accessed

June

27,

2013.

Accessed

June

27,

2013.

http://www.psoriasis.org/about-psoriasis.

http://xtracnow.com/physicians/psoriasis_stats.htm/

UCLA Collaboration:

Skin-derived Stem Cell

and Skin-derived IPSCs

Identified a rare mesenchymal stem cell (MSC) population from adult

human skin

Published data -

“Vega-Crespo et al 2013, BioResearch Open Access, 1:25”

(http://online.liebertpub.com/doi/pdf/10.1089/biores.2012.0204)

Identified a small molecule BAY11 that can stabilize expression of OCT4

synthetic mRNA, key programming factor for generating induced

pluripotent stem cells

Published results -

“Awe et al 2013, Stem Cell Res Ther; 4:15”

(http://stemcellres.com/content/pdf/scrt163.pdf)

Exclusive license to both patent applications

Skin-derived Stem Cell and IPSC

Collaboration

•

Growing Momentum of IPSCs

(Induced Pluripotent Stem Cells)

Source: PubMed.gov

Growing Momentum of MSCs

(Mesenchymal Stem Cells)

Source: PubMed.gov

Financials

•

Cash position of $26.1 million as of March 31, 2013

•

Large private capital raise completed in October 2012; institutional

investors include, among others, an affiliated fund of Third Security, LLC,

an investment firm founded by R.J. Kirk

•

No debt

•

Company’s capital structure greatly simplified

–

Outstanding preferred stock converted into common stock

–

Approximately 99% of warrants conceded anti-dilution provisions

Financial Information

Commenced trading on NYSE MKT on May 17, 2013

Capitalization Table

Common shares (post reverse split)

Warrants

Options

Fully diluted shares outstanding

Shareholder breakdown: Institutional vs. Retail

27.5M

6.3M

0.6M

34.4M

60% / 40%

Summary

Summary

•

Cutting edge autologous cell therapy company developing first-in-class medical applications

using fibroblasts

•

Advancing

robust

pipeline

for

medical

applications

LAVIV®

(azficel-T):

–

Restrictive burn scarring, vocal cord scarring and acne scarring

•

Strategic collaboration with Intrexon focusing on genetically-modified autologous fibroblast

cells:

–

Developing therapeutic options for the localized treatment of moderate to severe psoriasis

and for rare skin diseases

•

Developing skin-derived MSCs and more efficient conversion of skin cells to IPSCs through

MIT/UCLA collaboration

•

LAVIV®

lead product

–

Indicated for improvement of the appearance of moderate to severe nasolabial fold

wrinkles in adults

–

One of only three FDA approved cell based products

–

LAVIV®

is positioned as a premium aesthetic

•

Strong cash position with $26.1 million at March 31, 2013

–

No debt

Indication

LAVIV®

(azficel-T)

autologous

cellular

product

indicated

for

improvement

the

appearance

moderate

severe

nasolabial

fold

wrinkles

adults.

The

safety

and

efficacy

LAVIV

for

areas

other

than

the

nasolabial

folds

have

not

been

established.

The

efficacy

LAVIV

beyond

six

months

has

not

been

established.

Important Safety Information

LAVIV®(azficel-T) is an autologous cellular product for intradermal injection only.

LAVIV is contraindicated for allogeneic use, in patients with allergy to gentamicin,

amphotericin, dimethylsulfoxide (DMSO) or material of bovine origin and in

patients with active infection in the facial area. The following

reactions have been

reported following treatment with LAVIV: hypersensitivity reactions, bleeding and

bruising at the treatment site, vasculitis, herpes labialis, basal cell cancer; keloid

and hypertrophic scarring may occur following post-auricular skin biopsies or LAVIV

injections.

Additional

warnings

and

precautions

considered

include

the

use

LAVIV in patients with genetic disorders or formation of normal collagen matrices

and in immunosuppressed patients, or those patients undergoing chemotherapy

for malignancies or receive immunomodulatory therapies for autoimmune

diseases.

The most common adverse reactions, occurring in

1% of patients who receive

LAVIV, were injection-site redness, bruising, swelling, pain, hemorrhage, edema,

nodules, papules, irritation, dermatitis and pruritus.

For more information about LAVIV, please see the full Prescribing Information,

Attached files

Fibrocell Science, Inc. Reports

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