European Regenerative Medicine Firms & Their Strategic Approaches Michael Morrison University of York

OVERVIEW Creating the European RM ‘Universe’ of firms Characterizing the European RM Universe Strategic Analysis

CREATING THE EUROPEAN REGENERATIVE MEDICINE ‘UNIVERSE’

DEFINING REGENERATIVE MEDICINE Regenerative medicine is a heterogeneous domain, incorporating multiple technological avenues of investigation. United by a shared goal of stimulating, directing or augmenting the body’s capacity for self-repair and regeneration. Our approach concentrates on technologies using novel biomaterials – living cells, genes and bioscaffolds.

DEFINING REGENERATIVE MEDICINE Excludes small molecules and biologicals (e.g. antibodies) that aim to stimulate in vivo regenerative action. Large pharmaceutical companies with an interest in aspects of regenerative medicine such as Pfizer, Sanofi-Aventis, Smith and Nephew etc not included on the list Basic cell culture tools/media suppliers not included unless have specialist focus.

DEFINING REGENERATIVE MEDICINE ‘European’ companies must be based entirely in a European state, or have their headquarters there. Subsidiaries of non-European firms are not included. Company must have some publicly available details (usually in the form of a website).

CHARACTERIZING THE EUROPEAN REGENERATIVE MEDICINE FIRM UNIVERSE

FIRM TYPE BY PRIMARY ORIENTATION N = 59

GEOGRAPHIC DISTRIBUTION OF FIRMS N =59

FIRMS BY SIZE (EMPLOYEE NOS)

FIRMS BY AGE (YEAR FOUNDED)

SUMMARY OF FIRM CHARACTERISTICS Cell therapy is the largest single sector Significant no. of bioscaffold and service firms Most firms are small (< 99 employees) Wide range of company ages – many remaining from 1990s and pre 2002 ‘crash’ UK and Germany are the main geographic hubs of commercial RM activity

STRATEGIC ANALYSIS OF EUROPEAN REGENERATIVE MEDICINE FIRMS

AUTOLOGOUS VS ALLOGENIC CELL THERAPY

STEM CELL VS SOMATIC CELL THERAPY

THERAPEUTIC FOCUS OF CELL THERAPY FIRMS

SALEABLE THERAPEUTIC PRODUCTS

RM PRODUCTS IN DEVELOPMENT

GENE THERAPY COMPANIES NameLocati on SizeFound’dDisease focus Notes Amsterdam Molecular Therapeutics (AMT) NLSmall1998Metabolic disorderLead product Glybera submitted for EMA MAA in 2009 Ark TherapeuticsUKMedium1997Vascular occlusion. Cancer Cerepro submitted to EMA for MAA in 2008, received rejection Trinam in phase III trials Arthrogen BVNLSmall2005Rheumatoid Arthritis Lead product still at preclinical stage Diamyd Medical AB SwedenSmall1976Chronic pain, cancer Main therapeutic programme is therapeutic vaccines for diabetes. Oxford BioMedicaUKSmall1996Neurodegenera- tive, Ocular Lead product in phase I/II TransgeneFranceSmall1979CancerSeveral cancer vaccines in development Mol MedItalySmall1996Graft vs. Host disease Lead product in Phase III trials MologenGermanySmall1998CancerDeveloping non- RM anti-cancer therapeutics

GENE THERAPY LANDSCAPE Engagement with Advanced Therapy Medicinal Products regulation: Ark’s Cerepro rejected in 2009 but has named-patient approval in France and Finland Amsterdam Molecular Therapeutics’ Glybera submitted for MAA in 2010 MolMed (Italy) have cell-based ex-vivo gene therapy in phase III trials

ServiceTotalStem cell? Cell and tissue based drug discovery / screening services / toxicity testing 42 Cell and tissue supply including research and clinical grade material 42 Contract manufacture of cells / cell line expansion, cell culturing and scale up 1- Specialist tools and reagents3- Distribution of bioscaffolds for tissue repair, wound healing etc 1- TOTAL134 FOCUS OF DEDICATED SERVICE PROVISION FIRMS

CONCLUSIONS

Companies pursuing newer regenerative medicine models appear to co-exist with older tissue engineering and gene therapy firms. Strong industry preference for less risky technologies – autologous cell therapy with somatic cells or adult stem cells. Little commercial investment in iPS and embryonic stem cell technologies.

CONCLUSIONS Commercial development concentrated in Western Europe, and concentrated in hubs. Importance of biotechnology infrastructure and financial support. Regulatory environment is also an important shaping factor – as with hESCs Can be illustrated by Germany – UK RM firm breakdown

CONCLUSIONS RM Sub-sectorGermanyUK Cell Therapy96 Gene Therapy12 Bioscaffolds24 Service/ other39 TOTAL1521