Comparisons Between OrCel and Apligraf

Comparative Histological ProfilesComparative Histological Profiles

Apligraf OrCel

Fully Differentiated andStratified Keratinocytes

Partially Differentiated, Non-Stratified “Wound Healing”

(Migrating & Replicating) Keratinocytes

Low Density Dermal Fibroblasts, Many Undergoing Apoptosis

Medium Density, Vigorously Growing Dermal Fibroblasts

(15% “Dividing” Cells)

In Vitro expression of KGF and GMCSF by cultured LSE and ORCEL

1

1000

1000000

KGF GM-CSF

Cyt

oki

ne

Ou

tpu

t P

er u

nit

Are

a, p

g/c

m2/

day LSE

ORCEL

Living Skin Equivalent (LSE) is a generic name for Apligraf

Output, OrCel vs. Apligraf

10

100

1000

10000

100000

bFGF GM-CSF HGF KGF-1 VEGF IL-1a MMP-9 PGE-2

Cyt

oki

ne

Pro

du

ctiv

ity,

pg

/cm

2 /d

ay

OrCel Apligraf

Pro-mitotic Pro-Inflammatory

OrCel in Donor Site Healing(Independent Physician Evaluation:

Donor Site Treated with both OrCel & Apligraf)

OrCel

ApligrafOrCel: Faster healing, less inflammation

Days to100% Healing

(Median)

OrCel

Standard of Care

DONOR SITESDONOR SITES

Pivotal: 2/01

Based on Photography

0

2

4

6

8

10

12

14

16

18

20

2222 Days

15 Days

PMA Claims

•Accelerated healing

•Less Scarring

•Reduced time to recropping

OrCel OrCel ™™ Heals Heals Wounds FasterWounds Faster

47%

23%

0

10

20

30

40

50

60

Diabetic Foot Ulcers Pilot Trial

% of Patients Achieving 100% Wound Closure

By 12 Weeks

OrCel

OrCel

Standard of Care

Standard Of Care

Summary of OrCel® vs. Apligraf® FeaturesFeature OrCel® Apligraf®

Shape/Size Square 6.5 x 6.5 x 0.09 cm (42 cm2) Round 75mm diam x 0.75mm (44cm2)

Matrix Preformed porous cross-linked bovine collagen sponge, very pliant

Contracted, dense, stiff bovine collagen gel

Keratinocytes (K) Immature mono-/bilayer (submerged culture condition)

Stratified multilayer (air interface culture condition)

Fibroblasts (F) Healthy vigorously dividing Dormant or apoptotic

Cell type ratio Nominal ~90% F ~10% K Nominal ~30% F ~70% K

Cytokine profile F (& F/K co-culture) dominated; activated “wound healing” profile

K (& F/K co-culture) dominated; normal skin steady state dormant profile

Ease of use Semi-auto thaw/rinse (~20 min) & direct application

Remove from dish, cut to size, fenestrate (~20 min)

Shelf life 7 mo (clin. trial); expect 12 – 18 mo 10 days in sealed pkg.

Current reimbursement

$1,100./42 cm2 $1,200/44 cm2

Summary: OrCel® vs. Apligraf® Data

• Pilot ORCEL (fresh) VLU trial data achieved closure in 12 weeks (59% vs. 36%) comparable to adjusted (Cox) Apligraf results at 6 months (56.8% vs. 39.8%); pivotal ORCEL (cryopreserved) clinical data are similar (50% vs. 31%).

• Pilot ORCEL DFU trial data achieve results within 12 weeks (47% vs. 23%) comparable to Apligraf (56% vs. 39%) at 12 weeks (SOC differed)

• ORCEL is easier to apply• ORCEL, since cryopreserved, has far superior shelf life (7-

12 months+ (projected) vs. 10 days) and can also be stored at the clinical site for “off-the-shelf” availability