A science-based organization dedicated to curing disease through the development and manufacture of cell-based therapeutics and regenerative medicine.

1. OTCQB:ORGS
A science-based organization dedicated to
curing disease through the development
and manufacture of cell-based
therapeutics and regenerative medicine
Corporate
Presenta4on
May
2014

2. Forward
Looking
Statements
Forward
Looking
Statements/
Offer
of
Securi4es
This
presenta,on
does
not
cons,tute
an
offer
for
the
purchase
or
sale
of
any
securi,es
of
Orgenesis.
You
should
not
make
any
investment
decisions
based
on
this
presenta,on.
The
informa,on
in
this
presenta,on
is
not
a
subs,tute
for
independent
professional
advice
before
making
any
investment
decisions.
No
securi,es
regulatory
authority
has
in
any
way
passed
on
any
of
the
informa,on
contained
in
the
presenta,on.
Much
of
this
presenta,on
includes
projec,ons
and
plans.
Our
stated
plans
are
subject
to
known
and
unknown
risks,
uncertain,es
and
other
factors
that
may
cause
the
actual
results
of
Orgenesis
to
be
materially
different
from
those
expressed
or
implied
in
this
presenta,on.
Our
products
may
never
develop
into
useful
products
and
even
if
they
do,
they
may
not
be
approved
for
sale
to
the
public;
we
have
substan,al
hurdles
to
face
in
proving
our
technology,
showing
it
can
be
safe
for
medical
use
and
obtaining
regulatory
approval
in
each
country
in
which
our
technology
may
be
sold.
We
may
not
be
able
to
fund
our
plans
or
keep
key
employees.
We
may
not
be
able
to
protect
our
intellectual
property.
Sales
projec,ons
may
not
come
to
frui,on,
and
our
compe,tors
may
provide
beFer
or
cheaper
products
or
services.
Addi,onal
informa,on
about
these
and
other
assump,ons,
risks
and
uncertain,es
are
set
out
in
the
"Risk
Factors"
sec,on
in
Orgenesis'
most
recent
10-­‐K
filed
on
EDGAR
with
the
Securi,es
and
Exchange
Commission.
Bernard
(OTCQB:ORGS)

3. § Company
Overview
§ Business
Model
§ Product
Development
Plan
§ Recent
Corporate
Developments

4. Orgenesis
Inc.
is
a
biotechnology
company
dedicated
to
curing
Type
1
diabetes
through
a
novel
technology,
cellular
trans-­‐
differen0a0on,
that
combines
cellular
therapy
and
regenera4ve
medicine.
§
Cellular
trans-­‐differen,a,on
is
a
proven
technology
that
converts
autologous
liver
cells
into
fully
func,onal
and
physiologically
glucose-­‐sensi,ve
insulin-­‐producing
cells.
§
Phase
1
ready
with
“Fast-­‐to-­‐Market”
clinical
development
strategy
focusing
on
Ultra-­‐Orphan
indica,on
–
leading
to
accelerated
approval
§
Technology
supported
with
strong
IP,
and
broad
patent
estate
§
Recent
acquisi,on
of
MaSTherCell
forms
a
ver,cally
integrated,
revenue-­‐genera,ng
business
model
with
focus
on
rapidly
growing
cell-­‐based
therapeu,cs
market
Company
Snapshot:
Symbol:
OTCQB:OGRS
Headquarters:
Gaithersburg,
MD
Industry:
Biotechnology
Market
cap.:
$38.5M
Share
Price:
$0.70
52
wk
High
/Low:
$1.00
/
$0.34
Shares
Out./Float:
55.2M
/
23.5M
Insider
Holdings:
~40%
Ins,tu,onal
Holdings:
<10%
Financings
YTD:
~$7.5M
Available
Funds:
~$3.5M
September
16th
,
2014
Company
Overview
(OTCQB:ORGS)

5. (OTCQB:ORGS)
A
Science-­‐based,
Innova4ve
and
Ver4cally
Integrated
Business
Model
Pioneer
and
leader
in
the
emerging
fields
of
cell-­‐based
therapy,
regenera,ve
medicine
and
cGMP
capabili,es
to
support
each.
A
science-­‐based
and
innova,ve
company
with
a
ver,cally
integrated
business
model:
1.
Clinical
development
of
proprietary
technology
planorm
(cellular
‘trans-­‐differen,a,on’)
–
ini,ally
targe,ng
insulin-­‐dependent
disorders
2.
Revenue
genera,on
through
innova,ve
cell-­‐based
manufacturing
capabili,es
–
cost-­‐efficient
clinical
development
of
Orgenesis
technology
while
independently
posi,oned
as
CDMO
industry
partner
of
choice
Over
next
18-­‐24
months,
main
goal
is
to
ensure
rapid
increase
in
value
by
establishing
clinical
PoC
with
P1b
clinical
results
in
key
indica,ons,
and
securing
long-­‐term
manufacturing
service
agreements
with
targeted
biotech
companies

6. Product
Development
Overview
Orgenesis
has
performed
pre-­‐clinical
safety
and
efficacy
studies
and
is
moving
to:
§
Ini,ate
regulatory
ac,vi,es
in
Asia,
Europe
and
U.S.
§
Finalize
GMP
and
complete
product
scale-­‐up
(MaSTherCell
–
Belgium)
§
Transfer
technology
to
US
affiliate
(Maryland)
§
Move
to
clinical
trials
and
collaborate
with
clinical
centers.
Product
Development
Timeline
2011
2012
2013
2014
2015
Proof
of
Principle
Pre-­‐clinical
studies
Phase
1b
Trials
Regulatory
Plan
(Paul
Erlich
Ins,tute
and
FDA
Engagement)
Develop
Produc,on
Process
Produc,on
Scale
up
Under
cGMP
(OTCQB:ORGS)

7. Recent
Corporate
Developments
§ Awarded
Maryland
Stem
Cell
Research
Fund
Grant
to
help
fund
pre-­‐clinical
§ Orgenesis
acquires
MaSTherCell,
crea,ng
a
ver,cally
integrated
business
focusing
on
the
research,
development
and
manufacture
of
cell-­‐based
therapeu,cs
Nov
2014
§ ScoF
Carmer
joins
as
CEO
of
Orgenesis
North
America
— led
the
U.S
Specialty
Care
Division
of
AstraZeneca
Jul
2014
PLC
(LSE:AZN)
May
2014
work
in
prepara,on
for
Phase
I
&
II
clinical
trials
in
the
U.S.
(OTCQB:ORGS)
Over
last
12
months,
ORGS
has
had
very
exci4ng
developments.
§ Funding
/
Awards
&
Recogni,on
§ New
Corporate
Partnerships
/
Key
Personnel
Moves
§ Awarded
$3.9M
grant
from
Belgium’s
DG06
to
complete
commercial
scale
Nov
2014
cGMP
facility

8. § T1D
Market
Opportunity
§ Compe,,ve
Landscape
§ Pre-­‐clinical
data
§ Differen,a,ng
liver-­‐derived
from
stem-­‐cell
derived
IPCs
§ AIP
cells
§ GMP
–
Using
Advanced
Technology
&
Systems

9. T1D
Market
Opportunity
Life-­‐threatening
and
life-­‐long
disease
.
§ Es,mated
1.5M
–
3.0M
people
with
T1D
(US)(1);
§ ~30,000+
new
diagnosis
per
year
(US)(2)
Significant
economic
burden
to
society.
§ Accounts
for
$14.9
billion
in
healthcare
costs
in
the
U.S.
each
year.(3)
US
insulin
market
~$8.9B
in
2013,
with
forecast
6
Yr.
CAGR
of
12.4%(4)
Daily
management
includes
mul4ple
insulin
injec4ons,
strict
blood
glucose
monitoring,
“carb
coun4ng”
and
significant
impact
on
QoL.
Despite
recent
‘advances’,
significant
clinical
risks
remain:
§ Hypoglycemic
episodes:
Hypoglycemic
unawareness,
Diabe,c
coma.
§ Hyperglycemic
consequences:
Ketoacidosis,
diabe,c
re,nopathy,
diabe,c
nephropathy,
stroke,
CV
disease.
Currently,
no
approved
therapy
for
a
“Prac4cal
Cure”.
(OTCQB:ORGS)
(1) Type
1
Diabetes,
2010:
Prime
Group
for
JDRF,
Mar
2011
(2) NIDDK:
diabetes.niddk.nih.gov/dm/pubs/sta,s,cs/index.htm#i_youngpeople
(3) The
United
States
of
Diabetes:
Challenges
and
Opportuni,es
in
the
Decade
Ahead,
2010:
United
Health
Group
(4) Grand
View
Research,
2014

10. Compe44ve
Landscape
Paucity
of
R&D
investment
dedicated
to
“Cure”.
Disease
Management
§ Increase
effec,veness
of
glucose
control
— Improved
insulin
— Ar,ficial
pancreas
Disease
Progression
§ Maintain
beta
cell
func,on
/
insulin
produc,on
— Autoimmune
tolerance
— T-­‐cell
abla,on
Clinical
Cure
§ Long
term
insulin
independence
— Islet
cell
transplanta,on
Prac4cal
Cure
(OTCQB:ORGS)
§ Long
term
insulin
independence
/
no
concomitant
immunosuppression
/
normal
quality
of
life
— Encapsula,on
of
insulin
producing
cells
(Directed
Differen,a,on)
— Autologous
Insulin
Producing
Cells
(Cellular
Trans-­‐
differen4a4on)

11. Cellular
Trans-­‐Differen4a4on
–
A
Prac4cal
Cure
A
unique,
proprietary
technology
that
transforms
a
pa4ent’s
liver
cells
into
glucose-­‐
responsive
and
func4onally
mature
Autologous
Insulin
Producing
cells
(AIPc).
(OTCQB:ORGS)
Liver
and
Pancreas:
1).
Derived
from
same
embryonic
lineage
(endoderm)
2.
Share
a
common
progenitor
and
many
transcrip,on
factors
3).
Both
have
a
built-­‐in
glucose-­‐sensing
system
.
.
.
Developmentally
related
cells
show
a
higher
suscep,bility
to
trans-­‐differen,a,on

12. Pre-­‐Clinical
Proof-­‐of-­‐Principal
(OTCQB:ORGS)
The
pre-­‐clinical
proof-­‐of-­‐principal
has
been
well
established
and
externally
validated.
Ectopic
PDX-­‐1
expression
ac,vates
insulin
produc,on
in
mice
in-­‐vivo
(Ferber
et
al
Nature
Med)
Ectopic
PDX-­‐1
-­‐
short
term
trigger
to
an
irreversible
reprogramming
process
(Ber
et
al
JBC)
Induc,on
of
pancrea,c
lineage
in
human
liver
cells
in-­‐vitro,
fetal
and
adult
and
the
promo,ng
effects
of
soluble
factors
(Sapir
et
al
PNAS)
PDX-­‐1
treatment
in-­‐vivo
induces
an
immune
modula,on,
and
ameliorates
hyperglycemia
in
diabe,c
NOD
mice
(Shternhall-­‐Ron
et
al
JAI)
The
role
of
hepa,c
dedifferen,a,on
in
the
ac,va,on
of
the
alternate
pancrea,c
repertoire
(Meivar-­‐Levy
et
al
Hepatology)
The
role
of
Exndin-­‐4
in
prolifera,on
and
transdifferen,a,on
process
(Aviv
et
al
JBC)
Methods
of
human
liver
cell
reprogramming
(Meivar-­‐Levy
et
al
Methods
Mol
Biol)
NKX6.1
ac,vates
PDX-­‐1-­‐Induced
Liver
to
Pancrea,c
Reprogramming
(Gefen-­‐Halevi
et
al
Cellular
Reprograming)
Characteriza,on
of
adult
liver
cells
reprogramming
towards
the
pancrea,c
lineage
(Meivar-­‐Levy
et
al
J.
Transplanta,on)
ORGENESIS
5/9/2014
-­‐
CONFIDENTIAL
2000
2003
2005
2007
2007
2009
2010
2010
2011
The
temporal
and
hierarchical
control
of
transcrip,on
factors-­‐induced
liver
to
pancreas
2014
transdifferen,a,on
(Berneman-­‐Zeitouni
D,
et
al
PlosOne)

13. First
Valida4on
of
Trans-­‐Differen4a4on
Hypothesis
PDX-­‐1
ac4vates
a
func4onal
β-­‐cell
lineage
in
liver,
in-­‐vivo.
(OTCQB:ORGS)
Ad-CMV-PDX-1
Ectopic
PDX-­‐1
expression
ac,vates
insulin
produc,on
in
mice
in-­‐vivo
(Ferber
et
al
Nature
Med)

14. with Con A, and were not stimulated antigen GST. However, mice that manifested showed a significant decrease 250
200
150
groups did not show significant differences in their prolifera-tive
responses to Con A.
Blun4ng
the
Auto-­‐Immune
Response
3.4. Reversal of CAD is associated with a Th1 to Th2
shift of the autoimmune T-cell cytokine response
700
a
The T cells that mediate the 600
destruction of the insulin-pro-ducing
In
Pre-­‐clinical
model
of
T1D,
PDX-­‐pancreatic 1
cells
b-drive
cells in shiCAD p
secrete Th1 cytokines, such
500
from
from
Th1
to
Th2
immune
response
.
.
.
as IFNg [33]. Moreover, immunomodulatory therapies that
arrest the diabetogenic autoimmune process usually lead to
Resul4ng
in
a
state
of
“tolerance”
vs
“aqack”
(OTCQB:ORGS)
1
Spleens
removed
2
S,mulated
with
T1D
an,gens
3
Studied
for
cytokine
secre,on
Ø Th1
-­‐
IFNg
(a)
Ø Th2
–
IL-­‐10
(d)
Shternhall
Ron
K
et
al,
Ectopic
PDX-­‐1
expression
in
liver
meliorates
T1D;
Journal
of
AutoImmunity
(2007)
doi:
10.1016
a Th2 shift in the autoimmune T-cell the increased production of IL-10 [27]. To the autoimmune response in mice treated 1, we studied IFNg and IL-10 secretion by with insulin, GAD, p34, p35, HSP60, splenocytes taken from the different experimental not differ in the amounts of IFNg or IL-with Con A, and were not stimulated antigen GST. However, mice that manifested showed a significant decrease 600
* * * * * *
1800
1200
p277
c
* * * * * *
1800
1200
GST ConA
400
300
200
700
100
600
500
800
400
600
300
200
400
100
200
0
Insulin HSP60 p12 p34 p35
INF (pg/ml)
INF (pg/ml)
INF (pg/ml)
800
700
600
600
500
400
400
200
300
0
GAD
b
d
c
a
Untreated
Ad-RIP-b-gal
Ad-CMV-PDX-1
200
100
700
600
500
1000
400
800
300
IL-10 (pg/ml)
p277
*
*
*
pancreatic b-cells in CAD secrete Th1 cytokines, such
as IFNg [33]. Moreover, immunomodulatory therapies that
arrest the diabetogenic autoimmune process usually lead to
600
GST ConA
0
Insulin HSP60 p12 p34 p35
INF (pg/ml)
INF (pg/ml)
INF (pg/ml)
0
GAD
b
d
e f
Untreated
Ad-RIP-b-gal
Ad-CMV-PDX-1
0
Insulin HSP60 p277 p12 p34 p35
600
pg/ml) IL-10 (pg/ml)
pg/ml)
*
*
*
*
*
*

15. AIP
cells
are
“physiologically”
glucose-­‐sensi4ve:
They
produce,
store
and
secrete
processed
insulin
in
response
to
elevated
glucose
concentra4ons
PDX-1 is delivered using recombinant adenovirus
A
B
Insulin
/
Pdx-­‐1
/
DAPI
InsulCin
production and storage in
PDX-1 treated liver cells-EM, immuno-gold
IMC
Glucose metabolism is needed
for regulated C-peptide
secretion
15
C-pepeptide secretion
ng/m
Sapir
et
al
PNAS
2005
&
Berneman-­‐Zeituni,
PlosOne
2014

16. Sequen4al
Gene
Transduc4on
is
Cri4cal
to
Process
3
pTFs
results
in
40%-­‐60%
increased
insulin
produc4on
per
IPC,
sequen4al
administra4on
of
3pTFs
induces
matura4on
of
the
generated
IPC
cells.
The
Temporal
and
Hierarchical
Control
of
Transcrip4on
Factors-­‐Induced
Liver
to
Pancreas
Transdifferen4a4on
Berneman-­‐Zeitouni
et
al.
PLOS
One
9(2):
e87812.
doi:10.1371/journal.pone.0087812
35 2mM glucose
30
25
20
15
10
5
Insulin
(and
or
pro-­‐insulin)
secre,on
was
measured
by
sta,c
incuba,on
of
the
cells
for
15
min
at
2
and
17.5
mM
glucose
in
KRB.
n
>12
in
5
independent
experiments
preformed
in
cells
isolated
from
different
donors,
*p
<
0.05
comparing
between
triple
infec,on
and
all
other
treatments.
(OTCQB:ORGS)
0
17.5mM glucose
C-peptide secretion
ng/mg/h
**

17. Stem
Cell-­‐Driven
Differen4a4on
ES
and
iPS
cells
giver
rise
to
fetal
islets
that
are
not
glucose-­‐responsive.
(OTCQB:ORGS)
Differen,ated
human
stem
cells
resemble
fetal,
not
adult,
β
cells
Hrva,n
et
al.
PNAS
online
www.pnas.org/cgi/doi/10.1073/pnas.1400709111
*hPSC
refers
to
human
pluripotent
stem
cells
derived
from
embryonic
stem
cell
or
reprogrammed
(iPS)
cells

18. Resource
Generation of Functional Human
Pancreatic b Cells In Vitro
Generation of Functional Human
Pancreatic b Cells In Vitro
Felicia W. Pagliuca,1,3 Jeffrey R. Millman,1,3 Mads Gu¨ rtler,1,3 Michael Segel,1 Alana Van Dervort,1 Jennifer Hyoje Ryu,1
Quinn P. Peterson,1 Dale Greiner,2 and Douglas A. Melton1,*
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge,
MA 02138, USA
2Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, AS7-2051, Worcester, MA 01605, USA
3Co-first author
*Correspondence: dmelton@harvard.edu
http://dx.doi.org/10.1016/j.cell.2014.09.040
Felicia W. Pagliuca,1,3 Jeffrey R. Millman,1,3 Mads Gu¨ rtler,1,3 Michael Segel,1 Alana Van Dervort,1 Jennifer Hyoje Ryu,1
Quinn P. Peterson,1 Dale Greiner,2 and Douglas A. Melton1,*
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge,
MA 02138, USA
2Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, AS7-2051, Worcester, MA 01605, USA
3Co-first author
*Correspondence: dmelton@harvard.edu
http://dx.doi.org/10.1016/j.cell.2014.09.040
11/17/14 Confidential Internal
Document
Resource
18
Figure 1. SC-b Cells Generated In Vitro
Secrete Insulin in Response to Multiple
Sequential High-Glucose Challenges like
Primary Human b Cells
(A) Schematic of directed differentiation from
hPSC into INS+ cells via new or previously pub-lished
control differentiations.
(B–D) Representative ELISA measurements of
secreted human insulin from HUES8 SC-b cells
(B), PH cells (C), and primary b (1"b) cells (D)
challenged sequentially with 2, 20, 2, 20, 2, and
20 mM glucose, with a 30 min incubation for each
concentration (see Experimental Procedures). Af-ter
sequential low/high-glucose challenges, cells
were depolarized with 30 mM KCl.
(E–G) Box and whisker plots of secreted human
insulin from different biological batches of HUES8
(open circles) and hiPSC SC-b (black circles) cells
(E; n = 12), biological batches of PH cells (F; n = 5),
and primary b cells (G; n = 4). Each circle is the
average value for all sequential challenges with
2 mM or 20 mM glucose in a batch. Insulin
secretion at 20 mM ranged 0.23–2.7 mIU/103 cells
for SC-b cells and 1.5–4.5 mIU/103 cells for human
islets, and the stimulation index ranged 0.4–4.1 for
SC-b cells and 0.6–4.8 for primary adult. The thick
horizontal line indicates the median.
See also FiguresS1and S2Aand Table S1. *p< 0.05
when comparing insulin secretion at 20 mM versus
SUMMARY
The generation of insulin-producing pancreatic b
cells from stem cells in vitro would provide an un-precedented
cell source for drug discovery and cell
transplantation therapy in diabetes. However, insu-lin-
producing cells previously generated from human
pluripotent stem cells (hPSC) lack many functional
characteristics of bona fide b cells. Here, we report
a scalable differentiation protocol that can generate
hundreds of millions of glucose-responsive b cells
from hPSC in vitro. These stem-cell-derived b cells
(SC-b) express markers found in mature b cells, flux
Ca2+ in response to glucose, package insulin into
secretory granules, and secrete quantities of insulin
comparable to adult b cells in response to multiple
sequential glucose challenges in vitro. Furthermore,
these cells secrete human insulin into the serum of
mice shortly after transplantation in a glucose-regu-lated
Type 1 diabetes results from autoimmune destruction of b
cells in the pancreatic islet, whereas themore common type 2 dia-betes
results from peripheral tissue insulin resistance and b cell
dysfunction. Diabetic patients, particularly those suffering from
type 1 diabetes, could potentially be cured through transplanta-tion
of newb cells. Patients transplanted with cadaveric human is-lets
can be made insulin independent for 5 years or longer via this
strategy, but this approach is limited because of the scarcity and
quality of donor islets (Bellin et al., 2012). The generation of an
unlimited supply of human b cells from stem cells could extend
this therapy to millions of new patients and could be an important
test case for translating stem cell biology into the clinic. This is
because only a single cell type, the b cell, likely needs to be gener-ated,
and the mode of delivery is understood: transplantation to a
vascularized location within the body with immunoprotection.
Pharmaceutical screening to identify new drugs that improve b
cell function, survival, or proliferation is also hindered by limited
supplies of islets and high variability due to differential causes
of death, donor genetic background, and other factors in their
isolation. A consistent, uniform supply of stem-cell-derived b cells
SUMMARY
The generation of insulin-producing pancreatic b
cells from stem cells in vitro would provide an un-precedented
cell source for drug discovery and cell
transplantation therapy in diabetes. However, insu-lin-
producing cells previously generated from human
pluripotent stem cells (hPSC) lack many functional
characteristics of bona fide b cells. Here, we report
a scalable differentiation protocol that can generate
hundreds of millions of glucose-responsive b cells
from hPSC in vitro. These stem-cell-derived b cells
(SC-b) express markers found in mature b cells, flux
Ca2+ in response to glucose, package insulin into
secretory granules, and secrete quantities of insulin
comparable to adult b cells in response to multiple
sequential glucose challenges in vitro. Furthermore,
these cells secrete human insulin into the serum of
mice shortly after transplantation in a glucose-regu-lated
manner, and transplantation of these cells ame-liorates
hyperglycemia in diabetic mice.
Type 1 diabetes results from autoimmune destruction of b
cells in the pancreatic islet, whereas themore common type 2 dia-betes
results from peripheral tissue insulin resistance and b cell
dysfunction. Diabetic patients, particularly those suffering from
type 1 diabetes, could potentially be cured through transplanta-tion
of newb cells. Patients transplanted with cadaveric human is-lets
can be made insulin independent for 5 years or longer via this
strategy, but this approach is limited because of the scarcity and
quality of donor islets (Bellin et al., 2012). The generation of an
unlimited supply of human b cells from stem cells could extend
this therapy to millions of new patients and could be an important
test case for translating stem cell biology into the clinic. This is
because only a single cell type, the b cell, likely needs to be gener-ated,
and the mode of delivery is understood: transplantation to a
vascularized location within the body with immunoprotection.
Pharmaceutical screening to identify new drugs that improve b
cell function, survival, or proliferation is also hindered by limited
supplies of islets and high variability due to differential causes
of death, donor genetic background, and other factors in their
isolation. A consistent, uniform supply of stem-cell-derived b cells
would provide a unique and valuable drug discovery platform for
diabetes. Additionally, genetically diverse stem-cell-derived b
(SC-b) express markers found in mature b cells, flux
Ca2+ in response to glucose, package insulin into
secretory granules, and secrete quantities of insulin
comparable to adult b cells in response to multiple
sequential glucose challenges in vitro. Furthermore,
these cells secrete human insulin into the serum of
mice shortly after transplantation in a glucose-regu-lated
manner, and transplantation of these cells ame-liorates
hyperglycemia in diabetic mice.
INTRODUCTION
The discovery of human pluripotent stem cells (hPSC) opened
the possibility of generating replacement cells and tissues
in the laboratory that could be used for disease treatment and
drug screening. Recent research has moved the stem cell field
closer to that goal through development of strategies to generate
cells that would otherwise be difficult to obtain, like neurons or
cardiomyocytes (Kriks et al., 2011; Shiba et al., 2012; Son
et al., 2011). These cells have also been transplanted into animal
models, in some cases with a beneficial effect like suppression of
arrhythmias with stem-cell-derived cardiomyocytes (Shiba et al.,
2012), restoration of locomotion after spinal injury with oligoden-drocyte
progenitors (Keirstead et al., 2005), or improved vision
after transplantation of retinal epithelial cells into rodent models
of blindness (Lu et al., 2009).
One of the rapidly growing diseases that may be treatable by
stem-cell-derived tissues is diabetes, affecting >300 million peo-ple
worldwide, according to the International Diabetes Federa-tion.
and the mode of delivery is understood: transplantation to a
vascularized location within the body with immunoprotection.
Pharmaceutical screening to identify new drugs that improve b
cell function, survival, or proliferation is also hindered by limited
supplies of islets and high variability due to differential causes
of death, donor genetic background, and other factors in their
isolation. A consistent, uniform supply of stem-cell-derived b cells
would provide a unique and valuable drug discovery platform for
diabetes. Additionally, genetically diverse stem-cell-derived b
cells could be used for disease modeling in vitro or in vivo.
Studies on pancreatic development in model organisms
(Gamer and Wright, 1995; Henry and Melton, 1998; Ninomiya
et al., 1999; Apelqvist et al., 1999; Kim et al., 2000; Hebrok
et al., 2000; Murtaugh et al., 2003) identified genes and signals
important for the pancreatic lineage, and these have been effec-tively
used to form cells in the b cell lineage in vitro from hPSC.
Definitive endoderm and subsequent pancreatic progenitors
can now be differentiated with high efficiencies (Kroon et al.,
2008; D’Amour et al., 2005, 2006; Rezania et al., 2012). These
cells can differentiate into functional b cells within 3–4 months
following transplantation into rodents (Kroon et al., 2008; Rezania
et al., 2012), indicating that some cells in the preparation contain
the developmental potential to develop into b cells if provided
enough time and appropriate cues. Unfortunately, the months-long
process the cells undergo in vivo is not understood, and it
is unclear whether this process of in vivo differentiation would
also occur in human patients. Attempts to date at generating
insulin-producing (INS+) cells from human pancreatic progeni-tors
in vitro have generated cells with immature or abnormal
phenotypes. These cells either fail to perform glucose-stimulated
428 Cell 159, 428–439, October 9, 2014 ª2014 Elsevier Inc.

19. AIP
Cells
AIP
cells
are
meaningfully
differen4ated
from
any
other
current
(or
future)
compe4tor.
(OTCQB:ORGS)
Insulin
Independence
Therapy
&
Quality
of
Life
Tissue
Availability
Quality
Control
§ Glucose-­‐responsive
insulin
produc,on
within
one
week
of
AIP
cell
transplanta,on
§ Insulin-­‐independence
within
one
month
§ Single
course
of
therapy
(5-­‐10
years
insulin
independence)
§ No
need
for
concomitant
immunosuppressive
therapy
§ Return
to
(near)
normal
quality
of
life
for
pa,ents
§ Single
liver
biopsy
supplies
unlimited
source
of
therapeu,c
,ssue
(bio-­‐banking
of
,ssue
for
future
use
if
needed)
§ Highly
controlled
and
,ghtly
closed
GMP
systems
§ QC
of
final
product
upon
release
and
distribu,on
Ini4a4ng
clinical
trials
within
12
–
15
months

20. GMP
–
Using
Advanced
Technology
&
Systems
Orgenesis’
GMP
systems
improve
quality
and
speed
while
decreasing
costs.
(OTCQB:ORGS)
Liver
biopsy
Cell
Culturing Propaga4on Trans-­‐differen4a4on Packaging
Transplanta4on
Liver
Biopsy
Mechanic
&
enzyma,c
Isola,on
Cell
expansion
–
Single
use
bioreactors
Trans
-­‐
differen,a,on
via
pTFs
Washing,
QA/QC,
Packaging,
Release
and
distribu,on
AIP
cells
transplanted
into
liver
via
infusion
5-6 weeks

21. MaSTherCell
.
.
.
The
Perfect
Fit
§ Cell
Therapy
Market
§ Cell
Therapy
CDMO
Market
§ Business
and
Expansion
Strategies
§ Ra,onale
suppor,ng
acquisi,on

22. The
Cell
Therapy
Market
–
Clinical
Trials
10
Source:
Culme-­‐Seymour
EJ,
Davie
NL,
Brindley
DA,
Edwards-­‐Parton
S,
Mason
C:
A
decade
of
cell
therapy
clinical
trials
(2000-­‐2010).
Regenera4ve
medicine
7,4
(2012);
ClinicalTrials.gov
(www.clinicaltrials.gov)
• 22,500+ Clinical Trials
• 2800 “new” Cell Therapies
• 560 in PIII/Pivotal Trials
• Most therapies developped in US &
EU

23. Global
Cell
Therapy
Market
-­‐
Value
&
Forecasts
• Cell
therapy
products
market
set
to
grow
to
nearly
32B$
by
2018.
• Global
cell
therapy
market
expected
to
grow
exponen,ally
• Organ
replacement/transplant
is
playing
an
increasingly
large
role1
• Key
Market
Drivers:
BeFer
treatment
outcomes
and
reduc,on
of
the
direct
costs
associated
with
chronic
diseases
(by
~250B$
annually
in
the
U.S.)²
1) MedMarket
Diligence,
Oct.
2012
2) Alliance
for
Regenera4ve
Medicine
Annual
Report
2012-­‐2013
11
2.5X

24. CDMO
Market
-­‐
Manufacturing
With
revenue
from
commercial
products
and
clinical
trials
combined
–
total
available
market
value
(TAM)
reaches
$900M
in
2018.
$1,000M
$900M
$800M
$700M
$600M
$500M
$400M
$300M
$200M
$100M
$0M
2014
2015
2016
2017
2018
TAM
Clinical
Trial
($M)
TAM
Produc4on
Lot
($M)
Note:
Assuming
30%
of
the
sales
in
the
cell
therapy
industry
is
linked
with
the
produc4on
costs
and
thus
the
CMO.
15

25. CoGs
/
Batch
Process
development
Tech
transfert
Business
Strategy:
Lock
IN
Early
Total
out
of
the
pocket
expense
for
customer
R&D
Phase
I
Phase
II
Phase
III
Commercial
Customer
acquired
in
phase
II/III
Year
1
Year
2
Year
3
Year
4
Year
5
Customer
acquired
in
R&D
/
phase
I
AFract
customers
during
early
stage
• to
minimize
tech
transfer
costs
• to
enable
process
development…
• to
provide
cost
efficient
manufacturing…
• throughout
en,re
product
lifecylce
Process
development
tools
&
exper,se
are
key
34
Total
out
of
pocket
customer
expense
Development
Manufacturing

26. Expansion
Strategy
–
US
Market
Entry
• Rental
of
exis,ng
US
cost-­‐efficient
clean
room
and
high
quality
infrastructure
o Hospital
o Cluster
o Local
incubators
/
cell
therapy
ecosystem
• Deploy
qualified
work
force
in
strategic
area(s)
o Washington,
DC
o Boston
• Final
stage
nego,a,ons
with
MAJOR
US
Cancer
Center
–
JV
partnership
o Late
stage
research
thru
P2
clnical
trials
o Companies
exit
to
MaSTherCell
for
P3
and
Commercial
scale
manufacture
o Leverage
JV
and
Brand
for
EU
expansion
/
compe,,ve
advantage
36

27. (OTCQB:ORGS)
Strategic
and
Financial
Ra4onale
for
Merger
Complimentary
management
teams
combine
to
strengthen
overall
company
leadership
Leverages
exis,ng
collabora,ons
(Orgenesis,
MaSTerCell,
ATMI)
to
realize
$25M
-­‐
$50M
in
opera,onal
synergies:
• Revenue
cycle
management
• Overhead
efficiencies
• Supply
chain
management
• 3rd
party
collabora,on
/
partnerships
Increase
scale,
expand
geographic
footprint,
and
enhance
technology
planorm
COGs
efficiencies
to
Orgenesis
make
acquisi,on
accre,ve
in
Yr
1
of
product
launch
Orgenesis
revenue
genera,on
expedites
MaSTherCell
,me
to
profitability
by
2
years
Individual
Corporate
Brands
retained
to
drive
diversified
business
strategy,
while
maximizing
technical
support
and
P&L
efficiencies

28. § Future
Growth
Drivers
/
Next
Steps

29. Future
Growth
Drivers
/
Next
Steps
Opera4ons
§ Complete
European
GMP
manufacturing
of
clinical
grade
cells
§ Expand
U.S.
opera,ons
(clinical,
manufacturing,
commercial)
§ Submit
IND
§ Ini,ate
Phase
1b
trials
in
U.S.
and
EU
Complete
near-­‐term
financing
§ Complete
$10M
financing
of
current
opera,ng
plan
-­‐
$3.5M
already
raised
Execute
medium-­‐term
Capital
Markets
plan
§ Ini,ate
roadshow
with
US
investment
bank
consor,um
to
raise
capital
for
P1
expansion
§ File
S-­‐1
§ Up-­‐list
to
NASDAQ
(OTCQB:ORGS)

30. Management
Team
(OTCQB:ORGS)
Vered
Caplan
–
Chairman
and
Interim
Chief
Execu4ve
Officer,
Orgenesis
Ltd
§ Formerly
served
as
CEO
of
GammaCan,
a
company
focused
on
the
use
of
immunoglobulins
for
the
treatment
of
cancer.
§ Serves
as
director
of
various
companies
including:
Op,cul
Ltd.,
a
company
involved
with
op,c
based
bacteria
classifica,on;
Inmo,on
Ltd.,
a
company
focused
on
self-­‐propelled
disposable
colonoscopies;
Nehora
Photonics
Ltd.,
a
company
involved
with
a
non-­‐invasive
blood
monitoring;
Ocure
Ltd.,
a
company
focused
with
wound
management;
Eve
Medical
Ltd.,
a
company
involved
with
hormone
therapy
for
Menopause
and
PMS;
and
Biotech
Investment
Corp.,
a
company
focused
on
prostate
cancer
diagnos,cs.
Scoq
Carmer
–
Chief
Execu4ve
Officer
(Orgenesis
Inc,
North
America)
§ Led
the
U.S
Specialty
Care
Division
of
AstraZeneca
PLC
(LSE:AZN),
a
$93
billion
pharmaceu,cals
company;
responsible
for
the
company’s
pornolio
of
specialty
care
biopharmaceu,cal
products.
§ Former
EVP,
Commercial
Opera,ons
of
MedImmune
-­‐
acquired
by
AstaZeneca
(LSE:AZN)
for
~$16
billion.
§ Served
as
VP,
Immunology
for
Genentech,
Inc.;
responsible
for
the
U.S.
launches
of
Rituxan
and
ACTEMRA
in
Rheumatoid
Arthri,s.
§ Served
as
Global
Therapeu,c
Area
Head
for
Bone
and
Metabolic
Disorders
at
Amgen,
Inc.;
responsible
for
global
development
and
commercializa,on
strategies
for
denosumab
(Xgeva
and
Prolia).
§ Began
his
career
at
GlaxoSmithKline
plc
(LSE:GSK),
where
he
held
various
posi,ons
of
increasing
responsibility
in
sales,
marke,ng,
strategic
pricing
and
business
development.

31. Management
Team
(con0nued)
Hugues
Bultot
–
Chief
Execu4ve
Officer
(MaSTherCell);
Member,
Orgenesis
BoD
Serial
life
sciences
entrepreneur,
‘from
science
to
business’.
• Former
CEO
of
Artelis,
a
company
focused
on
disposable
bioreactors
and
now
integrated
into
Pall
Life
Sciences.
Co-­‐founded
company
in
2005,
developed
the
business
model,
helped
acquire
ini,al
customer
base,
ini,ated
diversifica,on
in
Cell
Therapy
area,
and
eventually
nego,ated
trade
sale
in
2010.
• Successfully
developed
a
global
network
in
the
bio-­‐process
industry
–
big
pharma,
academic
ins,tu,ons,
equipment
supplier,
NGO…
• Recently
co-­‐founded
Univercells,
a
company
focused
on
low-­‐cost
biopharmaceu,cals
–
vaccines,
mAbs
and
recombinant
proteins
–
bringing
further
depth
to
his
industry-­‐leading
knowledge
and
exper,se
in
low-­‐cost
manufacturing
to
the
benefit
of
MaSTherCell.
• Served
as
Director
of
various
companies
during
his
career
as
a
private
equity
manager,
as
a
tech
transfer
manager
and
as
a
corporate
finance
specialist.
Sarah
Ferber,
Ph.D.
–
Chief
Scien4fic
Officer
&
Founder
• Studied
biochemistry
at
the
Technion
under
the
supervision
of
Professor
Avram
Hershko
and
Professor
Aaron
Ciechanover,
winners
of
the
Nobel
Prize
in
Chemistry
in
2004.
• Completed
a
post-­‐doctoral
fellowship
at
the
Joslin
Diabetes
Center
at
Harvard
Medical
School.
Her
breakthrough
discovery
suggested
that
humans
carry
their
own
'stem-­‐cells'
throughout
adulthood,
thus
obvia,ng
the
need
for
embryonic
stem
cells
for
genera,ng
an
organ
in
need.
• Most
of
the
research
was
conducted
in
Prof.
Ferber’s
lab,
in
the
Endocrine
Research
Lab
at
the
Sheba
Medical
Center,
and
currently
employs
11
scien,sts.
• Received
TEVA,
LINDNER,
RUBIN
and
WOLFSON
awards
for
this
research.
• Research
work
has
been
funded
over
the
past
10
years
by
the
Juvenile
Diabetes
Research
Founda,on
(JDRF),
the
Israel
Academy
of
Science
founda,on
(ISF)
and
D-­‐Cure,
a
non-­‐profit
organiza,on.
(OTCQB:ORGS)

32. OTCQB:ORGS
|
Company
Presenta4on
–
October
2014
Company
Contact:
ScoF
Carmer
Chief
Execu,ve
Officer
Orgenesis
Maryland,
Inc.
Headquarters:
Orgenesis,
Inc.
Germantown
Innova,on
Center
20271
Goldenrod
Lane
Germantown,
MD
20876
Telephone:
301.204.1983
Email:
ScoF.C@orgenesis.com
Corporate
Website:
(www.orgenesis.com)
Investor
Rela4ons:
Tobin
Smith
NBT
Capital
Markets
240-­‐483-­‐4629
(office)
Email:
tsmith@nbtgroupinc.com

33. Appendix

34. Extensive
Patent
Porvolio
(OTCQB:ORGS)
IP
Pornolio
Patent
Title
Pub.
Date
US
2012/0329710
A1
patent
applica,on
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Islet
Tissues
December
27,
2012
US
8119405
granted
patent
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Islet
Tissues
February
21,
2012
AU
2004/236573
B2
grandet
patent
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Islet
Tissues
October
22,
2009
EP
1354942
B1
granted
patent
Induc,on
of
insulin-­‐producing
cells
January
30,
2008
EP
1180143
B1
granted
patent
IN
Vitro
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Islet
Tissues,
Pharmaceu,cal
Composi,ons
Related
Thereto
May
9,
2007
US
2005/0090465
A1
patent
applica,on
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Tissues
April
28,
2005
AU
779619
B2
grandet
patent
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Tissues
February
3,
2005
AU
2004/236573
A1
patent
applica,on
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Tissues
November
18,
2004
WO
2004/098646
A1
patent
applica,on
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
Produc,on
in
Non-­‐Pancrea,c
Islet
Tissues
November
18,
2004
WO
2004/098646
A1R1
patent
applica,on
Methods
of
Inducing
Regulated
Pancrea,c
Hormone
November
18,
2004
“Methods
Of
Inducing
Regulated
Pancrea4c
Hormone
Produc4on
In
Non-­‐Pancrea4c
Islet
Tissues”
§ Patent
granted
in
U.S.
&
Australia
§ Published
in
Europe
&
Japan
“Methods
Of
Inducing
Regulated
Pancrea4c
Hormone
Produc4on”
§ Patent
granted
in
Australia
&
Europe
§ Published
in
Japan
&
Canada
Currently
filing
third
family
of
patents
protec4ng
produc4on
process