Regulation of Advanced Therapies A Biotech SME Perspective May 11, 2006 Gil Beyen CEO - TiGenix N.V. Member of the EuropaBio Advanced Therapies Working Group

EuropaBio EuropaBio is the voice of the biotechnology industry in Europe EuropaBio represents: + around 1500 SMEs + 68 large companies + 25 national biotechnology associations across Europe + 5 bio-regions EuropaBio champions the responsible use of biotechnology to ensure that its potential is fully used to the benefit of people and their environment in all fields, including healthcare.

TiGenix – an SME profile Founded :2000, spin-off of Universies of Leuven & Ghent Financing:Private - Venture backed (29 M) Team:45 people Focus:Regenerative medicine for joint surface repair Science: Biology of stable hyaline cartilage Approach:Evidence Based Medicine « From procedure to validated medicinal product » Lead product: ChondroCelect, autologous cell therapy product for cartilage repair in Phase III clinical trial SME

More than 2 million patients per year with cartilage damage (US + EU) Cartilage damage known to be one of the main causes for OA OA affecting over 10% of the population; one of leading cause of disability at older age; fast growing; no effective treatments today Need for biological solutions leading to durable repair (JRC report: market potential cartilage regeneration 2011: 25 bn ) Major unmet medical need Age Overweight Cartilage damage Genetics Osteoarthritis

Autologous Chondrocyte Implantation (ACI) 3. Implantation Articular surface Subchondral bone 1. Biopsy 2. Cell culture 4. Rehab Full thickness cartilage defect ?

To produce cells that can build stable cartilage in vivo To develop a consistent, reliable product with proven efficacy To position the product in the treatment algorithm of joint surface defects To obtain approval & reimbursement ChondroCelect Goal: validated therapeutic product for durable repair ChondroCelect cell technology Proprietary potency assay Extensive preclinical validation GMP with batch release criteria Prospective randomised GCP controlled clinical trials Health economics studies Key challenges Key responses

Condition: Harmonised and Equitable Regulatory Framework High standards patient & public confidence Harmonised requirements Adapted to specific needs Data exclusivity & IP protection Possibility for branding & pricing Equitable for all parties The bar can (and should) be high as long as at same level for all parties... achievable economic return; condition for innovation

The proposed ATP Regulation provides important step forward (1) Main positive points: Single legislation for all Advanced Therapy Medicinal Products... as a regulation... utilizing an existing product framework... tailor made to ATP Centralised procedure ensuring harmonised standards Data exclusivity & IP protection foreseen Financial incentives & administrative help

The proposed ATP Regulation provides important step forward (2) Remaining concerns: Equal requirements for all parties (also for hospital-based)...without hindering academic research Will there be sufficient expertise and what role? Composition of the CAT and role of CAT advice Implementation specifics (definitions, adaptation of the Clinical trials and GMP Directives) Speed of implementation

Conclusions Cell therapies and tissue engineering will change medical practices profoundly Harmonized and equitable regulatory framework, conditio sine qua non for the necessary innovation and to ensure patients access to valuable new therapies TiGenix (SME) and EuropaBio welcome the draft proposal and look forward to contributing to a speedy adoption process

Thank you! More info: Gil Beyen EuropaBio