Organogenesis

• Canton, MA• Since 1985• First company to gain FDA approval

for a “living skin” product: Apligraf®• Approved for treatment of diabetic

foot ulcers and venous leg ulcers• Corporate partnership with Novartis

for sales and marketing of Apligraf®

Corporate Woes• 9/13/02: Temporary halt to sales of

Apligraf®. 110 employees on furlough.

• 9/25/02: Filed for bankruptcy• 12/02: Delisted by AMEX• 12/18/02: Shipment of Apligraf® to

Novartis resumed• Sales and marketing rights being

gradually returned to ORG

Apligraf®

• Human keratinocytes and fibroblasts from neonatal foreskin

• Mothers of donors screened• Proprietary cell culturing processes• Matrix of bovine Type I collagen

BOTH EPIDERMIS AND DERMIS

Approved Uses

• Partial and full-thickness venous leg ulcers (VLU)- >6 mos. for treatment

- Apligraf® saves $7500/patient

• Full-thickness diabetic foot ulcers (DFU)- 800,000 patients per year in U.S.

- 80,000 amputations per year

Diabetic Foot Ulcerwk 0 wk 1

wk 5 wk 16

Clinical Studies: VLU• 240 patients age 18-89• Non-infected partial or full-thickness

skin loss ulcer >1 month duration• Not responding to conventional

therapy• Repeated applications sometimes

necessary (no more than 5 allowed)• Control: pressure dressing and zinc

impregnated gauze

Clinical Studies: VLU results

• 24 weeks- Apligraf®: 55.4% full closure

- Control: 49.1% full closure• Recurrence

- Apligraf®: 8.3% (6/72) @ 6 mos.

- Control: 7.4% (4/54) @ 6 mos.

- Apligraf®: 18.1% (13/72) @ 12 mos.

- Control: 22.2% (12/54) @ 12 mos.

Clinical Studies: DFU

• 208 patients 18-80 years old• 112 received Apligraf®, 96 control• 0.4 cm2 – 16.3 cm2 full-thickness DFU• Multiple applications of Apligraf® if

<50% take (up to 5X)

Clinical Studies: DFU results

• 12 weeks- Apligraf®: 56% full closure

- Control: 38% full closure• Recurrence

- Apligraf®: 40% (25/63) 80% (20/25) close at 6

mos.

- Control: 44% (16/36) 63% (10/16) close at 6 mos.

Other Products

• FortaPerm and FortaGen• Highly purified collagen for soft tissue

repair/reinforcement- incontinence

- hernia repair

- breast reconstruction

- Biomet: orthopedic and periodontal (rotator cuff repair patch)

Pipeline (or former pipeline)

• Vascular graft (publication by Huynh et al. with an acellular collagen tube)

• Liver assist device

• Other uses of Apligraf® (e.g. burns)

Advanced Tissue Sciences

• La Jolla, CA

• Founded 1987; public offering 1988

• Strategic alliance with Smith & Nephew for sales and marketing of Dermagraft® and Transcyte®

• Filed for bankruptcy 2/7/03

Transcyte®

• Human fibroblast-derived temporary skin substitute

• FDA approved as temporary wound cover for full thickness burns in March 1997

• FDA approved as a temporary wound cover for partial thickness burns in October 1997

• Currently available from Smith & Nephew

Transcyte®

• Bilayer graft• Outer silicone polymer (epidermis)• Inner dermal layer

- nylon mesh

- human fibroblasts

- collagen matrix

- growth factors

Transcyte®

• Storage:- Cassette containing two 5” x 7.5” pieces

- Stored at -20°C; thawed at 37°C

- Are fibroblasts viable?

• Cost: $1350 per cassette

Dermagraft®• Cryopreserved human fibroblast-derived

dermal substitute• Human fibroblasts are seeded onto a

bioabsorbable polyglactin (PLGA) mesh scaffold• FB secrete human dermal collagen, matrix

proteins, growth factors and cytokines, to create a three-dimensional human dermal substitute containing metabolically active, living cells

• Does not contain macrophages, lymphocytes, blood vessels or hair follicles.

• FDA approved for diabetic foot ulcers (10/01)

Clinical Trial: DFU

• 12 weeks- Dermagraft®: 38.5% complete healing

- Control: 31.7% complete healing• 32 weeks

- Dermagraft®: 57.5% complete healing

- Control: 42.4% complete healing• Multiple applications of Dermagraft®

often necessary (1/week)

Pipeline (or former pipeline)

• Huge number of patents• Orthopedics

- cartilage (NeoCyte), ligament, tendon• Aesthetic and Reconstructive Surgery

- injectable collagen, LaserDerm, NouriCell• Cardiovascular

- angiogenesis patch, vascular grafts, heart valves, stents