Noyes, F. R., Barber-Westin, S. D., (2002) Arthroscopic repair of meniscal tears extending into the avascular zone in patients youngerthan twenty years of age, Am J Sports Med. Jul-Aug;30(4):589-600.Panés, Gomollón, Taxonera et al. “Crohn’s Disease. A Review of Current Treatment with a Focus on Biologics Drugs”. 2007; 67 (17): 2511-2537.Peterson, L., Minas, T., Brittberg, M., Nilsson, A., Sjogren-Jansson, E., and Lindahl, A. (2000) Two- to 9-year outcome after autologouschondrocyte transplantation of the knee. Clin.Orthop. 212-234Peterson, L., Brittberg, M., Kiviranta, I., Akerlund, E. L., and Lindahl, A. (2002) Autologous chondrocyte transplantation. Biomechanicsand long-term durability. Am.J.Sports Med. 30: 2-12Psoriasis Drugs: A Global Strategic Business Report. Global Industry Analysts.“Rheumatoid Arthritis – Drug Pipeline Analysis аnd Market Forecasts tο 2015”. Global Industry Analysts.Rosenzweig, A. (2006) Cardiac cell therapy--mixed results from mixed cells. N.Engl.J.Med. 355: 1274-1277Salaffi, F., De, Angelis R., Stancati, A., and Grassi, W. (2005) Health-related quality of life in multiple musculoskeletal conditions: a crosssectionalpopulation based epidemiological study. II. The MAPPING study. Clin.Exp.Rheumatol. 23: 829-839Saris, D. B., Vanlauwe, J., Victor, J., Haspl, M., Bohnsack, M., Fortems, Y., Vandekerckhove, B., Almqvist, K. F., Claes, T., Handelberg, F., Lagae,K., van der, Bauwhede J., Vandenneucker, H., Yang, K. G., Jelic, M., Verdonk, R., Veulemans, N., Bellemans, J., and Luyten, F. P. (2008)Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee ina randomized controlled trial versus microfracture. Am J Sports Med 36: 235-246Saris, D. B., Vanlauwe, J. (2009) A prospective, randomized controlled trial of ChondroCelect versus microfracture in the repair ofsymptomatic cartilage defects of the knee, follow up at 36 months. Am J Sports Med., Nov 2009;37 Suppl 1:10S-19S.Steinwachs M., (2009) New technique for cell-seeded collagen matrix-supported autologous chondrocyte transplantation. Arthroscopy,25: 208-11Stem Cells Dev. 2008 Aug;17(4):681-93.”Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derivedmesenchymal stem cells.” Kang JW, Kang KS, Koo HC, Park JR, Choi EW, Park YH.Stürmer, K. M., Eulert, J., Weise, K., and Niethard, F. U. (2006) Gemeinsame Stellungnahme der AG ‘Geweberegeneration, Gewebeersatz’der Deutschen Gesellschaft für Unfallchirurgie und der Deutschen Gesellschaft für Orthopädie und Orhtopädische Chirurgie. EU-Kommissionsentwurf ‘Advanced therapies’Systemic Lupus Erythematosus - Pipeline Assessment and Market Forecasts to 2017 Aarkstore.Tanna, S. (2004) Osteoarthritis - Opportunities to address pharmaceutical gaps.The Bone and Joint Decade, The Global Economic and Healthcare Burden of Musculoskeletal Disease;http://www.boneandjointdecade.orgThe Future of Autoimmune Diseases Therapeutics – Market Forecasts to 2015, Competitive Benchmarking, Product Pipeline and DealAnalysis. GBI Research Dec 2009.US Department of Health and Human Services (2006) A new vision - A future for regenerative medicine. US Department of Health andHuman ServicesVander CB, 2006.Verdonk, R. Steinwachs M. Vanlauwe J. Engebretese L. (2006) Trends in cartilage repair. Current opinion of orthopaedic surgeons oncartilage repair: the results of a global web-based survey. ESSKA245 •
Von Der, Mark K., Gauss, V., von der, Mark H., and Muller, P. (1977) Relationship between cell shape and type of collagen synthesised aschondrocytes lose their cartilage phenotype in culture. Nature 267: 531-5322003, www.who.int/bulletinWHO Report “The global burden of rheumatoid arthritis in the year 2000”. Deborah Symmons Colin Mathers, Bruce Pfleger.Widuchowski W., Widuchowski, J., Trzaska, T, (2007), Articular cartilage defects: Study of 25,124 knee arthroscopies. Knee Vol 14: 177-182Widuchowski, W., Lukasik, P., Kwiatkowski, G., Faltus, R., Szyluk, K., Widuchowski, J., Koczy, B. (2008) Isolated full thickness chondralinjuries. Prevalence and outcome of treatment. A retrospective study of 5233 knee arthroscopies. Acta Chir Orthop Traumatol Cech. Vol75: 382-386Woolf, A. D. and Pfleger, B. (2003) Burden of major musculoskeletal conditions. Bull.World Health Organ 81: 646-656DelaRosa O, Lombardo E, Beraza A, Mancheño-Corvo P, Ramirez C, Menta R, Rico L, Camarillo E, García L, Abad JL, Trigueros C, DelgadoM, Büscher D. “Requirement of IFN-gamma-mediated indoleamine 2,3-dioxygenase expression in the modulation of lymphocyteproliferation by human adipose-derived stem cells.” Tissue Eng Part A. 2009 Oct;15(10):2795-806.DelaRosa O, Lombardo E. “Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeuticpotential.” Mediators Inflamm. <strong>2010</strong>;<strong>2010</strong>:865601. Epub <strong>2010</strong> Jun 14.García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA.” A phase I clinical trial of the treatment of Crohn’sfistula by adipose mesenchymal stem cell transplantation.” Dis Colon Rectum. 2005 Jul;48(7):1416-23.Garcia-Olmo D, Garcia-Arranz M, Herreros D. Expanded adipose-derived stem cells for the treatment of complex perianal fistulaincluding Crohn’s disease. Expert Opin Biol Ther. 2008 Sep;8(9):1417-23.Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. “Expandedadipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial.” Dis Colon Rectum. 2009 Jan;52(1):79-86.González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. “Adipose-derived mesenchymal stem cells alleviate experimental colitisby inhibiting inflammatory and autoimmune responses.” Gastroenterology. 2009 Mar;136(3):978-89. Epub 2008 Nov 27.González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. “Treatment of experimental arthritis by inducing immune tolerance withhuman adipose-derived mesenchymal stem cells.” Arthritis Rheum. 2009 Apr;60(4):1006-19.Gonzalez-Rey E, Gonzalez MA, Varela N, O’Valle F, Hernandez-Cortes P, Rico L, Büscher D, Delgado M. “Human adipose-derivedmesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis.” AnnRheum Dis. <strong>2010</strong> Jan;69(1):241-8.Lombardo E, DelaRosa O, Mancheño-Corvo P, Menta R, Ramírez C, Büscher D. “Toll-like receptor-mediated signaling in human adiposederivedstem cells: implications for immunogenicity and immunosuppressive potential.” Tissue Eng Part A. 2009 Jul;15(7):1579-89.Panés, Gomollón, Taxonera et al. “Crohn’s Disease. A Review of Current Treatment with a Focus on Biologics Drugs”. 2007; 67 (17): 2511-2537Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s Disease. N Engl J Med. 2004;350:876-885.Yoo KH, Jang IK, Lee MW, Kim HE, Yang MS, Eom Y, Lee JE, Kim YJ, Yang SK, Jung HL, Sung KW, Kim CW, Koo HH. “Comparison ofimmunomodulatory properties of mesenchymal stem cells derived from adult human tissues.” Cell Immunol. 2009;259(2):150-6. Epub2009 Jun 23.Zanotti C, Martinez-Puente C, Pascual I, Pascual M, Herreros D, García-Olmo D. “An assessment of the incidence of fistula-in-ano in fourcountries of the European Union.” Int J Colorectal Dis. 2007 Dec;22(12):1459-62. Epub 2007 Jun 7.246 • <strong>TiGenix</strong> • Rights Offering
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TiGenix NV(Public limited liability
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Table of ContentsSummary ..........
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3.7.1 Categories of potential inves
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5.7.1 Shares and warrants held by i
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7.5.2 Taxation.....................
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SummaryThe words written in capital
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Activities and strategy of the Comp
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• Two allogeneic adult stem cell
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• TiGenix’ success depends on i
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Unaudited pro forma income statemen
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Recent developmentsAcquisition of C
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In this context, we would like to s
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Announcement of the results of theO
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After the Contribution andafter the
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ContributionContribution AgreementC
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Risk factorsAny investment in the P
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commercialisation of ChondroCelect,
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in delays in bringing products to t
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The Company cannot predict what eff
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y each of its patents and patent ap
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to exercise preferential subscripti
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this prospectus which is capable of
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• investment professionals fallin
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1. General information and informat
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1.4.2 Company documents and otherin
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• the granting of discharge of li
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• in case of registered Shares, t
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cast at the meeting. If the amount
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No one may cast a greater number of
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If a Belgian resident individual ne
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Belgium has concluded tax treaties
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3. Information on the Contributiona
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In this context, we would like to s
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TiGenix has a limited financial deb
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Thousands of Euro (€) TiGenix Cel
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3.5.2 Issuance Price and RatioThe i
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(c)Rules for subscriptionSubject to
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The Scrips Private Placement will o
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to comply with any of its obligatio
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3.11.2 Scenario 1: Existing Shareho
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• a pledge of Locked Shares to a
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4. General information about THECOM
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DateINCORPORATIONFebruary 21,2000Tr
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Upon completion of the IPO of TiGen
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Issue dateMay 14,2004April 20,2005T
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4.7.2 Voting rightsAs further descr
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can be obtained free of charge at t
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5.2.4 Composition of the Board of D
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Amonis. Mr. Duron has been CEO of K
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5.3.4 Nomination and remunerationco
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• investor relations: nurturing c
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The remuneration of the members of
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5.7.2 Shares and warrants held by e
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Cellerix EBIP 2010An EBIP for senio
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The minutes must also contain a jus
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6. Activities of Tigenix andits sub
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• Clinical stage pipeline. TiGeni
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6.3.3 Acquisition of CellerixAs a r
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Full thickness articular cartilage
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Fig. 6.2: Autologous Chondrocyte Im
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Preclinical work in a meniscus repa
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The Company is also ensuring high q
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Recognising the importance of pre-l
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In Spain, since the passage of Orde
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Fig. 6.6: ChondroMimetic procedure
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6.5.3 Commercial strategyBuilding o
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6.7 Manufacturing & logisticsEffici
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The international application WO06/
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ChondroMimetic competitionThe main
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in Cellerix’ GMP facility in Madr
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6.14.3 History and development of C
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The table below gives an overview o
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Prevalence No. of cases (2010) Esti
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Fig. 6.9: Platform development stra
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In developing Cx601, Cellerix has b
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6.14.6 Manufacturing & logisticsCel
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population, methods for the isolati
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• Cimzia (certolizumab) - UCB: Al
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Spanish Ministry of Education and S
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7.2 Consolidated income statementTw
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7.3.1.2 Research and development ex
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7.3.2.3 Selling, general and admini
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7.4.1 Cash flows from operating act
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Cash & cash equivalents and intangi
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As of December 31, 2010, the Group
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8. Consolidated Financial informati
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8.1.3 Consolidated cash flow statem
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8.1.5 Notes to consolidated financi
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operating results and operating pla
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The Group does not account for work
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8.1.5.4 Operating result (EBIT)Resu
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8.1.5.7 TaxesThere is no current ta
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8.1.5.10 Tangible assetsThousands o
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8.1.5.14 Deferred charges & accrued
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8.1.5.18 Finance lease obligations
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Business combination Cellerix SADes
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Weighted averageexercise priceTOTAL
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the respective issue date of the wa
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Transactions with non-executive dir
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8.1.5.28 Subsequent eventsAcquisiti
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