Corporate Presentation. April 2015

Corporate Presentation April 2015

Forward-looking statements This document does not constitute or form part of any offer or invitation to sell or issue, or any solicitation of any offer to purchase or subscribe for, any shares in the Company, nor shall any part of it nor the fact of its distribution form part of or be relied on in connection with any contract or investment decision relating thereto, nor does it constitute a recommendation regarding the securities of the Company. This document may contain forward-looking statements and estimates made by the Company, including with respect to the anticipated future performance of TiGenix and the market in which it operates. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Forward-looking statements, forecasts and estimates only speak as of the date of this document and no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. TiGenix disclaims any obligation to update any such forwardlooking statement, forecast or estimates to reflect any change in the Company s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based. 2

Management team with proven track record of success Managing Director and CEO: Eduardo Bravo, MBA More than 25 years experience in the pharma and biotech industries at Sanofi-Aventis, Recordati, Cephalon and SmithKline Beecham CFO: Claudia D Augusta, PhD More than 15 years experience in equity and debt financing at Aquanima (Santander Group), Apax Corporate Finance and Deloitte Corporate Finance CTO: Wilfried Dalemans, PhD More than 25 years experience in the pharma and biotech industries; previous engagements at GSK Biologicals and Transgène CMO: Marie Paule Richard, MD More than 25 years experience in the global pharma and biotech industries at Bristol- Myers Squibb, Sanofi Aventis, GSK, Sanofi Pasteur, Crucell and AiCuris VP Regulatory Affairs & Corporate Quality: María Pascual, PhD More than 10 years experience in cell therapy companies; specialised in regulatory affairs for advanced therapies; external adviser to EMA VP Medical Affairs & New Product Commercialisation: Mary Carmen Diez, MD More than 20 years experience in the biopharmaceutical industry at Meda Pharma, Asta Médica, Pfizer and Dupont Pharma 3

Key facts about TiGenix Headquarters Operations Employees Stock exchange Leuven, Belgium Madrid, Spain Around 50 employees Euronext Brussels. Ticker: TIG Market capitalisation Euro 120 million on 8 March 2015 Reference shareholders Liquidity Analyst coverage Funds available 26% held by Grifols and Novartis 74% free-float of which 30% held by institutional investors 6 analysts covering the stock, of which four are independent Euro 13.5M at year-end 2014, plus Euro 25M from convertible bond issue in March 2015 4

Investment highlights Pivotal Phase III Orphan Asset: Cx601 Clear US Approval Strategy: Cx601 Valuable Pipeline Opportunity: Cx611 Proprietary Technology Platform Established Uniform Manufacturing Commercialised Product: ChondroCelect Perianal fistulas in Crohn s disease patients in the US & EU represents a multi-billion dollar market opportunity Pivotal Phase III allogeneic stem cell asset (local administration of a single dose) with data expected in 3Q2015 Phase I/II: 56% of patients achieved remission Use of data from pivotal Phase III trial in EU to support a BLA Application for SPA filed Q4 2014 for pivotal phase III trial in the US Lonza selected as contract manufacturing organisation for Cx601 in the US IND 2 to be filed as soon as technology transfer finalised Intravenously-administered allogeneic stem cell product for rheumatoid arthritis (Phase II) and severe sepsis (Phase I initiated) Positive phase I/IIa data in refractory RA Expanded allogeneic adipose-derived stem cells (eascs) Act mainly by controlling inflammation Well-defined and fully-characterised products Consistent and robust manufacturing process Up to 360 billion cells can be obtained from one donor 2,400 doses of Cx601 and 4,000 doses of Cx611 First ever ATMP 1 approved by EMA; valuable experience in regulatory approval / commercialisation process Indicated for the repair of cartilage defects in the knee Established national reimbursement and partnered with Swedish Orphan Biovitrum 1 Advanced Therapy Medicinal Product 2 Investigational New Drug 5

Multiple product candidates in clinical development Product 1 Cell Type Indication Preclinical Phase I Phase II Phase III Market Cx601 (local) allogeneic adipose-derived stem cells complex perianal fistulas in Crohn s disease Orphan Drug (EU) Cx611 (intravenous) allogeneic adipose-derived stem cells rheumatoid arthritis severe sepsis Cx621 (intralymphatic) allogeneic adipose-derived stem cells autoimmune disorders ChondroCelect characterised autologous chondrocytes knee cartilage lesions Partnered 2 1 Covered by 24 patent families 2 Distributed through Swedish Orphan Biovitrum ( Sobi ) and the Finnish Red Cross Blood Service 6

MSCs 1 interact closely with the immune system IFN-γ (ng/ml) 0 5 10 15 20 TNF-α (ng/ml) 0 1 2 3 4 5 ASCs PBMCs Activated PBMCs PBMCs+ASCs activated PBMCs+ASCs * * * p<0.05 relative to supernatant from activated PBMCs Source: De la Rosa et al. Tissue Engineering 2009 20 * The ability to interact with many players in the immune system qualify MSCs (including ASCs) as a potent anti-inflammatory agent % OF CD4+CD25+++ ON TOTAL CD4 15 10 5 0 ACTIVATED PBMCs ACTIVATED PBMCs + ASCs * p<0.05 relative to activated PBMCs without ASCs Source: Tigenix data 1 MSCs: Mesenchymal Stem Cells 7

eascs as a preferred source of MSCs Easily accessible (liposuction) Source and expansion Considerably higher yield than bone marrow Cell stability during expansion Low immunogenicity, no tissue matching needed Pharmacological profile Enables allogeneic use Demonstrated anti-inflammatory capabilities 8

Validated easc platform Quality Consistent and robust manufacturing process Quality control parameters defined: Identity, Purity, Potency Safety No signs of toxicity, tumorgenicity, or ectopic tissue growth in preclinical safety studies No clinical safety concern so far Efficacy Demonstrated control of inflammation in 5 different preclinical models, including different routes of administration Clinical efficacy demonstrated 9

Manufacturing process scheme Uniform manufacturing scheme for all products Liposuction Cell isolation and expansion Up to 360 billion cells can be obtained from 1 donor Finished product units at current doses (clinical trials): Master cell bank (cryo) 2,400 doses of Cx601 1 Frozen Drug Substance (FDS) 4,000 doses of Cx611 2 Finished Product 1 Based on ongoing Phase III trial in perianal fistula (120M cells per patient) 2 Assumes 1 million eascs/kg, average weight 80Kgs 10

A growing patent portfolio in cell therapy 24 patent families related to cell therapy products Pending & granted patents in over 20 jurisdictions including the US; expiry dates 2024 onwards Patent covering easc population and therapeutic uses granted in EU recently Key patent for Cx601 (PCX007) granted in US, AU, RU, MX, IL and NZ Patent protects use of ASCs in treatment of fistula Complementary protection possible through additional patents under review Portfolio covers key features of TiGenix s chondrocyte and stem cell platforms Expanded cell compositions and preparations Use of expanded cells in treatment of broad range of indications Cell preparation methods & delivery systems FTO for indications in clinical development confirmed by external counsels US: Morrison & Foerster Europe: Carpmaels & Ransford 11

Cx601 Local injection of eascs for the treatment of complex perianal fistulas in Crohn s disease patients 12

Perianal fistulas A common severe complication of Crohn s disease Fistulas: sores or ulcers that tunnel through the affected area into surrounding tissues Around 11% of Crohn s disease patients are affected by perianal fistulas 70-80% of these are complex affect anal sphincters present multiple tracts are recurrent Fistula are often associated with perianal abscess Almost 100,000 Crohn s disease patients suffer from complex perianal fistulas every year in European G5 and the US alone => compromised QoL, pain, depression, risk of anal epithelial carcinoma 13

Perianal fistulas: treatment options and shortfalls Treatment options Efficacy Safety antibiotics immunossuppressants High rate of relapse on drug cessation: 72% 1 Low remission rate: 33% after 6 months of treatment 2 High rate of relapse: 66% 2 Safety concerns with prolonged use High risk of infectious complications infliximab (Remicade) Low remission rate: 23% after 54 weeks of treatment 3 High rate of relapse: 54% after 54 weeks of treatment 3, and 67% one year after drug cessation 4 adalimumab (Humira) Low remission rate: 33% after 56 weeks of treatment 5 Safety remains a concern with long term use of biologics Safety remains a concern with long term use of biologics surgery High rate of relapse: 50% 6 High risk of anal incontinence 7 1 L.J. Brandt et al. Metronidazole Therapy for Perineal Crohn s Disease: a Follow-Up Study, 83 GASTROENTEROLOGY 383-7 (1982) 2 E.S. Goldstein et al., 6 Mercaptopurine Is Effective in Crohn s Disease Without Concomitant Steroids, 10 INFLAMM BOWEL DIS 79 84 3 B.E. Sands et al., Infliximab Maintenance Therapy for Fistulizing Crohn s Disease, 350 N ENGL J MED 876 85 (2004) 4 E. Domenech et al., Clinical Evolution of Luminal and Perianal Crohn s Disease after Inducing Remission with Infliximab:22 ALIMENT PHARMACOL THER 1107-13 (2005) 5 J.F. Colombel et al., Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn s Disease: The CHARM Trial, 132 GASTROENTEROLOGY 52-65 (2007) 6 T. Sonoda et al., Outcomes of Primary Repair of Anorectal and Rectovaginal Fistulas Using the Endorectal Advancement Flap, 45 DIS COLON RECTUM 1622 28 (2002) 7 A. Soltani and A. Kaiser, Endorectal Advancement Flap for Crypto Glandular or Crohn s Fistula in Ano, 53 DIS COLON RECTUM 486 495 14

Cx601: developing a new treatment paradigm >10 years of experience, consistent efficacy and safety Cx401 (autologous) 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Phase I Phase II Phase III (FATT 1) 3 5 I patients 1 center Crohn s fistulas: 75% efficacy; open 1 50 patients 3 centers Crohn s and non-crohn s perianal fistulas: 71% efficacy vs 16% control; p<0,001 2 214 patients 19 centers Non-Crohn s perianal fistulas: 41% efficacy; p (n.s.) 4 Cx601 (allogeneic) Phase I/II Phase III (ADMIRE-CD) 6 34 patients 6 centers Crohn s perianal fistulas: 56% efficacy; open 5 289 patients 52 centers 1 García Olmo, et al., 2005. Diseases of the Colon & Rectum 2 García Olmo, et al., 2009. Diseases of the Colon & Rectum 3 Fistula Advanced Therapy Trial 4 Herreros, et al., 2012. Diseases of the Colon & Rectum 5 de la Portilla, F. et al., 2012. Int. Journal of Colorectal Disease 6 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn s Disease Note: Patient data refers to number of patients recruited 15

Cx601: Phase I/II Proof of concept for an allogeneic therapy TRIAL SUMMARY Start June 2009 Completion September 2010 Conditions Study design Enrolment complex perianal fistula in Crohn s disease patients single arm non-controlled safety/efficacy study one fistula/tract treated maximum of 2 doses 1 34 patients recruited; 24 treated # of centers 6 sites Primary endpoint Secondary endpoints Efficacy incidence of treatment emergent adverse-events closure of external openings (clinically and MRI) reduce number of draining fistulas 56% (closure external openings) PATIENT SELECTION Older than 18 years: both genders Complex perianal fistula fulfilling some of the following conditions: associated fecal incontinence risk factors of anal incontinence at least 1 previous treatment for a fistulous disorder Crohn s disease (CDAI 200) less than 3 fistulous tracts Wash out of anti-tnf of at least 8 weeks prior to inclusion No concomitant administration of anti- TNF allowed during the duration of the trial Efficacy confirmed by second gastroenterologist not involved in the direct care of the patient 1 First dose of 20M cells; Second dose of 40M cells injected if fistula has not closed after 12 weeks 16

Cx601: Phase I/II results Safety of allogeneic cells confirmed Repeated treatment with allogeneic eascs well tolerated Favorable side-effect profile Overview of adverse events. Full analysis set (n=24) Patients with at least one TEAE 1 during the study: 13 (54.2%) Patients with at least one TEAE possibly related to eascs during the study 5 (20.8%) Serious adverse events reported leading to withdrawal 1 2 (4.2%) (Events considered to be possibly related to the study treatment; no clinically relevant abnormalities found during physical examination or in vital signs) 1 Treatment Emergent Adverse Event 2 Local abscess and pyrexia 17

Cx601: Phase I/II results Allogeneic eascs confirmed efficacy of autologous cells Reduction in number of draining fistulas Closure of external openings of treated fistula tracts 70% 60% 50% 40% 50,0% Nº fistulas: 61,5% 1 2 70% 60% 50% 40% 38,1% 56,3% 30% 30% 20% 10% 10,0% 7,7% 20% 10% 0% -10% 12 weeks (N=20) 24 weeks (N=13) 0% -10% 12 weeks (N=21) 24 weeks (N=16) N= Patients with available information. Missing data not included in percentage calculations Reduction of drainage in fistulas that have not achieved complete closure Substantial efficacy in complete closure of treated fistula tracts No spontaneous healing of non-treated fistula tracts Note: Patients who received only one dose were evaluated at weeks 12 and 24; Patients who received 2 doses were evaluated at weeks 12 and 26 18

Cx601: Phase III ADMIRE-CD 1 trial Robust Phase III designed to qualify as a single pivotal study TRIAL SUMMARY Start July 2012 Completion Condition Study design Enrolment ongoing complex perianal fistula in Crohn s disease patients randomized, double blind, placebo controlled trial all tracts treated. Fixed single dose 2 289 patients recruited # of centers 51 sites in 8 countries Primary endpoint Secondary endpoints at weeks 24 and 52 Combined Remission 3 at week 24 clinical Remission 4 response 5 time to remission / to response PDAI 6 score and Quality of Life assessment (IBDQ 7 ) PATIENT SELECTION Older than 18 years: both genders Non active luminal Crohn s disease (CDAI 8 220) diagnosed for 6 months Patients with perianal fistulizing Crohn s disease refractory to antibiotics, immunosuppressants and/or anti-tnf 2 internal openings (fistulas) and 3 external openings (tracts) Fistula draining < 6 weeks prior to inclusion Exclusion of naïve patients Concomitant treatments allowed without modification of treatment dose or regimen Limit of patients refractory to antibiotics to < 25% of total recruited patients 1 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn s Disease 2 120 million cells 3 Closure of all treated external openings draining at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm) 4 Closure of all treated external openings draining at baseline despite gentle finger compression 5 Closure of 50% of all treated external openings draining at baseline despite gentle finger compression 6 Perianal Disease Activity Index 19 7 Inflammatory Bowel Disease Questionnaire 8 Crohn's Disease Activity Index

Cx601: Phase III ADMIRE-CD 1 trial Six month read-out expected in Q3 2015 Patient enrolment: completed in November 2014 Statistical plan: Evaluations at Weeks 6, 12, 18, 24, 36 and 52 (after dosing) Primary efficacy analysis at Week 24 Efficacy and safety evaluations at Week 52 Blind clinical and MRI assessment Power: designed for finding at least 25% difference between study groups Cx601 could be approved and launched by H1 2017 1 Adipose-Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn s Disease 20

Clear US strategy defined for Cx601 Capturing the value of the biggest market Positive Type B meeting held with FDA in December 2013 adequacy of the existing non-clinical package to support an IND 1 filing for a US-based pivotal Phase III trial acceptability of using data from the ongoing ADMIRE-CD 2 Phase III study in Europe to support a biologic license application (BLA) agreement on key parameters of future US pivotal Phase III trial Development plan for the US being implemented Lonza selected as contract manufacturing organisation for Cx601 in the US Special Protocol Assessment (SPA) application submitted to FDA Q4 2014 IND 1 to be filed as soon as technology transfer finalised US Phase III protocol confirmation expected by the time of the European Phase III results read-out 1 Investigational New Drug 2 Adipose-Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn s Disease 21

Market potential: perianal fistula in Crohn s disease Estimated peak year sales Assumptions: Population EU28 + US: 824 million Prevalence of Crohn s disease: 0.105% (865,200 patients) 1 Launch EU: 2017 Launch US: 2020 $ Milllion 0 250 500 750 1.000 1.250 1.500 % CD patients with fistula 2 (approximately 121,100 patients) 12% 14% 16% % Complex fistula all fistula 3 (approximately 97,000 patients) 60% 80% 100% % Patients failing biologic 4 (approximately 77,500 patients) 70% 80% 90% % Market share (approximately 27,100 patients) 20% 35% 50% Average selling price $34k Note: Patient numbers refer to mid-point of the range given $21k $48k 1 TiGenix epidemiology report based on multiple publications 2 Schwartz et al, 2002, Vavricka et al., 2010, Pittet et al., 2010, KOL Interviews 3 Pittet et al., 2010, KOL Interviews 4 Sands et al., 2004, Lichtiger et al., 2010, KOL Interviews 22

Cx611 Intravenous injection of eascs for the treatment of early rheumatoid arthritis 23

Rheumatoid arthritis: a huge market opportunity The overall RA market is expected to grow at a CAGR of slightly above 7% to approximately $23.4Bn in 2016 On a dollar basis, the market is dominated by biologic drugs (>80% of the market), and especially by antibodies which block tumor necrosis factor TNF 1 (5 out of the 9 currently approved biologicals 2 ) with average annual cost of ~$19k Despite a wide variety of therapeutic options, a high level of unmet patient need exists Early Rheumatoid Arthritis target acute & inflammatory disease state induce and maintain low disease activity after failure of high dose MTX +/- corticosteroids avoid patients entering into long-term biologics use for symptomatic control indication of Cx611 activity evidenced in refractory patients in Phase IIa trial 1 Wiki Analysis: Arthritis Drug market 2 Humira, Enbrel, Remicade, Simponi and Cimzia 24

eascs are functional in RA models Arthritic score after three i.v. doses of eascs TNF - alpha IL - 10 % cytokine-secreting T cells % cytokine-secreting T cells * p<0.001 * p<0.001 Days after treatment Source: TiGenix data on file Source: González-Rey et al. Ann. Rheum. Dis. 2009 Intravenous administration of eascs protects animals from rapid progress to arthritic joints (CIA model) T cells from RA patients reduce their inflammatory profile upon contact with eascs (in vitro experiment) 25

Phase I/IIa trial First randomised trial with eascs in refractory RA patients TRIAL SUMMARY Start March 2011 Completion January 2013 Condition Study design Enrolment Patients with RA refractory to at least two biologics Dose escalation, single blind, placebo-controlled (Cx611+ DMARD 1 vs. placebo + DMARD) 53 patients # of centers 23 sites Primary endpoint Secondary endpoints Safety (tolerability and treatmentemergent adverse events) Efficacy measured by: ACR 2 remission (ACR 20, ACR50, ACR 70) EULAR 3 (DAS 4 28, VSG 5 ) Imaging (RAMRIS) Quality of life (SF-36) PATIENT SELECTION Heterogeneous patient population: Median range of diagnoses 5 69 years Patients with severe grade of RA: Median DAS 28 score: 3.2 7.9 Patients refractory to at least two biologics Mean number of previous DMARDs: 3.38 => 74% of patients received 3 or more DMARDs Mean number of previous biologics: 2.92 => 45% of patients received 3 or more biologics 66% of patients had received Enbrel 64% of patients had received Humira 51% of patients had received Infliximab 1 DMARD: Disease-modifying anti-rheumatic drugs 2 American College of Rheumatology 3 European League Against Rheumatism 4 Disease Activity Score 5 Variable Surface Glycoprotein 26

Phase I/IIa trial Favorable safety profile of all three doses of Cx611 Safety profile Cx611+DMARD (N=46) Placebo+DMARD (N=7) Patients with any adverse events (AE) 38 (83%) 4 (57%) Patients with any related AE 22 (48%) 1 (14%) Patients with any grade 3-4 related AE 1 (2%) 1 (14%) Patients with any AE leading to discontinuation 1 (2%) 0 (0%) Only one patient experienced a serious adverse event leading to discontinuation of the treatment 1 All other side effects were mild and transient: most common related adverse events in the Cx611+DMARD group: fever (15%), headache (9%), asthenia (6%) 1 Lacunar infarction, which is defined as a type of stroke in the brain's deep structures 27

Phase I/IIa results Encouraging therapeutic activity EULAR criteria EULAR response Good + Moderate DAS 28 (CRP) <3.2 37 43 39 40 35 29 25 20 20 30 24 20 15 15 15 13 20 % 20 % 15 % 15 10 10 10 0 0 5 0 0 5 0 0 0 M1 M2 M3 FV M1 M2 M3 FV DAS 28 (CRP) <2.6 (remission) 7 11 11 9 0 0 0 0 M1 M2 M3 FV M6 (FV) M6 (FV) M6 (FV) Cx611 + DMARD (N=46) Placebo + DMARD (N=7) M1, M2, M3 and M6 (FV) refers to month 1, 2, 3 and 6 (Final Visit) respectively 28

Cx611 Intravenous injection of eascs for the treatment of severe sepsis 29

Severe sepsis: a high unmet medical need Systemic illness due to an attack of host pro-inflammatory cytokines and other humoral substances commonly induced by a bacterial infection Incidence forecasted to grow at 1.5% p.a. 4 An estimated 15 19M sepsis cases occur worldwide each year 1 Incidence is estimated at approx. 300 cases per 100,000 population p.a. 2 Incidence has dramatically increased over the last decade (CAGR of 8-13%) 3 Sepsis mortality was estimated at 36% in a recent major European study 3 In the case of septic shock, mortality can reach up to 80% (28 50% of patients die within the first month of diagnosis) 4 1 The Lancet Infectious Diseases; Volume 12; issue 2; page 89; February 2012 2 Hall MJ et al. Inpatient care for septicemia or sepsis: NCHS data brief, no 62. Hyattsville, MD: National Center for Health Statistics. 2011 3 Vincent JL et al Sepsis in European intensive care units. Critical Care Medicine 2006; 34: 344-353 4 University Hospital of Valme & Biomedical Research Institute of Seville: Presentation at Farmaindustria meeting July 2014 30

The Challenge: a disease-modifying agent that targets the underlying immune dysfunction Current molecular approaches to the treatment of sepsis have inadequately addressed the complex immuno-modulatory pathways involved in sepsis pathogenesis. Cellular therapies offer a novel multifaceted mechanism of action that is potentially able to address the underlying immune dysregulation through multiple pathways. Editor's summary A Swiss Army knife for treating sepsis 31

eascs can protect in severe sepsis LPS Model CLP Model Source: Gonzalez-Rey, 2009 * p<0.001 Cx611 reduces mortality in animal models of sepsis This effect is due to a combination of reducing pro-inflammatory and increasing antiinflammatory mediators, production of anti-microbial effectors, and increased phagocytosis 32

easc effect at the cytokine and cellular level * p<0.001 LPS model of pro-inflammatory mediators # of anti-inflammatory mediator of inflammatory cells CLP model Source: Gonzalez-Rey et al. Gut. 2009 Jul;58(7):929-39 33

Phase I trial synopsis and rationale: CELLULA 1 study Evaluation of the therapeutic effect of eascs on the inflammatory response to LPS 2 in healthy volunteers TRIAL SUMMARY Start Q4 2014 Expected completion Objective Study design Enrolment # of centres Primary endpoint Q2 2015 effect of eascs on inflammatory response to LPS parallel groups: 0,250M, 1M and 4M eascs/kg and placebo randomisation scheme: 3:1 32 healthy volunteers 1 (Academic Medical Center, University of Amsterdam) vital signs and symptoms laboratory measures and functional assays of innate immunity Rationale Model mimics clinical signs of sepsis fever, chills headache, myalgia nausea mild tachycardia insignificant change in blood pressure Genomic response similar as in sepsis (not the case for animal studies) Provides proof-of-principle: essential information on the mechanism of action of eascs to counteract the consequences of an LPS exposure Results will guide for a proposed phase II study in severe sepsis 1 The effect of expanded human allogeneic adipose-derived mesenchymal adult stem cells on the human response to lipopolysaccharide in human volunteers 2 lipopolysaccharide 34

Key milestones 35

Key milestones Product 2014 2015 2016 2017 Cx601 (local) Europe US 4Q14 Phase 3 enrolment completed 3Q14 CMO selection ü ü ü 3Q15 primary endpoint results (24 weeks) 3Q15 Positive SPA 4Q14 SPA submission 1Q16 study results (1 year follow-up) 1H16 EMA filing 1H17 EU launch 1H16 tech transfer finalized 2H16 pivotal Phase 3 initiated Cx611 (IV) RA severe sepsis ü 4Q15 Phase 2 enrolment initiated 4Q14 Phase 1 initiated 2Q15 Phase 1 study results 4Q15 Phase 2 enrolment initiated 1Q17 Phase 2 enrolment completed YE17 Phase 2 study results YE17 Phase 2 study results 2Q17 Phase 2 enrolment completed ChondroCelect ü 1Q14 manufacturing facility sold ü 2Q14 CC licensed to SOBI increase market penetration in existing countries expand geographic reach through new market entry 36

Corporate Presentation April 2015 37