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 Ulcer wk 0wk 1 wk 5wk 16

Clinical Studies: VLU 240 patients age 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 mos. - Control: 7.4% 6 mos. - Apligraf®: 18.1% 12 mos. - Control: 22.2% 12 mos.

Clinical Studies: DFU 208 patients years old 112 received Apligraf®, 96 control 0.4 cm 2 – 16.3 cm 2 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