Integra LifeSciences Holdings Corp.

1
Integra LifeSciences Holdings Corp.

• Plainsboro, NJ
• 860 employees
• 3 divisions
• Integra LifeSciences
• Integra NeuroSciences
• Integra Padgett Instruments
• INTEGRA Dermal Regeneration Template

2
Financials

• Publicly traded since 1995 on NASDAQ (IART)
• For FYE 12/03 revenues increased 58 to 185.6 M
• FY 2003 net income 26.8 M
• Stock price 31.87 on 4/12/04
• Web site www.integra-ls.com

3
IART, LIFC, and NASDAQ (1 yr)
4
INTEGRA Dermal Regeneration Template

• Bilayer skin replacement used for treating
  full-thickness or deep partial-thickness burns
• FDA approved
• Marketed by Ethicon, Inc. (JJ)
• Dermal layer and temporary epidermal layer
• Temporary epidermis replaced with ultra-thin
  autograft (0.003 0.005)

5
INTEGRA Dermal Regeneration Template
6
INTEGRA Dermal Regeneration Template Dermal
layer

• Porous matrix of fibers of cross-linked bovine
  tendon collagen and a glycosaminoglycan
  (chondroitin-6-sulfate)
• Manufactured with a controlled porosity and
  defined degradation rate
• Permits infiltration of fibroblasts, macrophages,
  lymphocytes, and capillaries derived from the
  wound bed.
• Endogenous collagen matrix is deposited by
  fibroblasts simultaneously, the dermal layer of
  INTEGRA Dermal Regeneration Template is degraded

7
INTEGRA Dermal Regeneration Template Epidermal
layer

• Temporary synthetic polysiloxane polymer
  (silicone)
• Upon adequate vascularization of the dermal layer
  and availability of donor autograft tissue
  (usually 7-14 days), the temporary silicone layer
  is removed and a thin, meshed layer of epidermal
  autograft is placed over the "neodermis."
• Cells from the epidermal autograft grow and form
  a confluent stratum corneum, thereby closing the
  wound reconstituting a functional dermis and
  epidermis.

8
Clinical Studies

• 149 burn patients
• Median take for INTEGRA 80
• conventional autograft 95
• Acceptable to investigators
• Epidermal autograft take 90 vs. 95 for
  conventional autograft
• Wounds with INTEGRA and meshed epidermal
  autograft less likely to show meshed and spread
  pattern than meshed conventional autograft

9
Clinical Studies

• No significant difference in healing time between
  INTEGRA and temporary wound covers
• Healing time with thin autograft comparable to
  conventional autograft
• Donor sites of thin autografts healed faster and
  allowed more cycles for reharvesting than
  conventional donor sites

10
Clinical Studies

• Physician and patient assessment of cosmetic and
  functional outcome
• Patients preferred INTEGRA over control
• Physicians favor INTEGRA in terms of scarring
  and cosmesis
• Donor sites _at_ 12 months favored thin epidermal
  autograft over conventional

11
Integra NeuroSciences

• NeuraGen? Peripheral Nerve Guide
• Absorbable collagen tube
• Conduit for axonal growth across a nerve gap
• Axons of severed peripheral nerves regenerate
  spontaneously, but will not establish functional
  connections unless the nerve stumps are
  surgically reconnected
• Rapid method for rejoining severed peripheral
  nerves, in contrast to conventional microsurgical
  techniques

12
NeuraGen? Peripheral Nerve Guide
13
(No Transcript)
14
Cartilage Regeneration Template

• Damaged cartilage on the knee
• The site is debrided and prepared for the
  cartilage matrix implant
• The cartilage matrix is implanted into the
  damaged area of the knee
• Cartilage begins to regenerate
• Healthy, completely regenerated cartilage

15
Integra Collagen Products

• Bone regeneration
• Resorbable sponge used with BMP-2
• Medtronic Sofamor Danek spinal applications
• Dental
• Guided tissue regeneration in periodontal surgery
• Hemostasis in dental surgery
• Sulzer Dental
• Neurosurgical
• DuraGen Dural Graft Matrix

16
Genzyme Biosurgery

• Cambridge, MA
• One of 3 divisions of Genzyme Corporation
• Epicel cultured epidermal autografts
• Carticel autologous cultured chondrocytes
• www.genzymebiosurgery.com

17
Financials

• Publicly traded on NASDAQ since 2001 (was GZBX
  now GENZ)
• FYE 12/02 revenues increased 2 to 240.1 M
• FY 2002 operating loss 24.5 M
• For Q1-03 revenue 65.6 M
• Stock price (GZBX) 1.96 on 4/30/03
• GENZ 47.49 on 4/12/04

18
GZBX, IART, LIFC, NASDAQ (1 yr)
19
Epicel

• First introduced in 1987
• Used in treatment of burns
• From postage-stamp sized biopsy to entire body
  surface area in 16 days
• 75 patients per year
• 600 patients worldwide
• Ship product to U.S., Europe or Japan

20
Epicel

• Autologous keratinocytes co-cultured with
  irradiated murine cells to form cultured
  epidermal autografts (CEA)
• 2 to 8 cell layers thick
• Each sheet attached to a petrolatum gauze backing
  with stainless steel surgical clips.
• Each autograft is approximately 50 cm2 and is
  individually packaged in sterile, buffered, serum
  free Dulbecco's Modified Eagles Medium (DMEM).
• The murine cells used in the culture process have
  been extensively tested for the presence of
  infectious agents.

21
Epicel Clinical DatabaseSurvival displayed by
TBSA burned (n478)
22
Carticel

• Autologous cultured chondrocytes
• Began marketing in 1995
• Used to repair symptomatic cartilage defects of
  the femoral condyle caused by acute or repetitive
  trauma in patients who have had an inadequate
  response to a prior arthroscopic or other
  surgical repair procedure
• Not for patients with osteoarthritis
• Covered by most insurance plans

23
Carticel

• Raisin-sized biopsy during arthroscopic
  procedure shipped to Genzyme
• Chondrocytes expanded in culture to millions of
  cells shipped back to surgeon
• Periosteum from lower leg sutured over the defect
  like a patch to hold the cells in place
• Patients back to full weight bearing in 6-8
  weeks resume physical activity within one year
• Over 6000 patients treated since 1995

24
Carticel Clinical Experience
25
Carticel II (in development)

• Three-dimensional autologous cartilage graft that
  may be delivered arthroscopically
• Treat larger defects, permit early weightbearing
  and allow for significantly quicker return to
  function than the current product.