Corporate Presentation October 205
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 forward-looking 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 5 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 0 years experience in cell therapy companies; specialized 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
Investment Highlights Positive Phase III And Advanced EU Regulatory Strategy: Cx60 Clear US Regulatory and Clinical Strategy: Cx60 Valuable Pipeline Opportunities: AlloCSC-0 and Cx6 Complex 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) Results met primary endpoint Statistically superior to placebo in achieving combined remission at week 24 (p<0.025) Filing for MAA expected in Q6 and launch expected 2H7 Fully-owned asset Consistent and robust manufacturing process Management team has valuable experience in regulatory approval / commercialization process; first ever ATMP approved by EMA Use of data from positive pivotal Phase III trial in EU to support a BLA in the US FDA s endorsement through SPA obtained for pivotal phase III trial in the US Same primary endpoint as positive EU Phase III trial Phase III to start Q7 Fully-owned asset Lonza selected as contract manufacturing organization for Cx60 in the US AlloCSC-0: allogeneic cardiac stem cells, a new platform acquired through the acquisition of Coretherapix, being developed for cardiovascular indications Randomized, double blind, placebo controlled Phase II trial in acute myocardial infarction ongoing Interim data expected 2H6 Final one year follow up data expected H7 Cx6: Intravenously-administered allogeneic stem cell product for severe sepsis (Phase I study completed) Severe sepsis Phase ll trial design has been finalized; expected to enroll first patient in 4Q5 Advanced Therapy Medicinal Product 4
Multiple Product Candidates Product Indication Preclinical Phase I Phase II Phase III Market Allogeneic Adipose-Derived Stem Cells Cx60 (local) Complex Perianal Fistulas in Crohn s disease EMA-granted Orphan Drug FDA-endorsed SPA Cx6 (intravenous) Severe Sepsis Allogeneic Cardiac Stem Cells AlloCSC-0 (intracoronary) Acute Myocardial Infarction AlloCSC-02 (intramyocardial) Cardiology Characterized Autologous Chondrocytes ChondroCelect Knee Cartilage Lesions Partnered 2 Covered by 27 patent families 2 Distributed through Swedish Orphan Biovitrum ( Sobi ) and the Finnish Red Cross Blood Service 5
Cx60: Positive Phase lll Data Local injection of eascs for the treatment of complex perianal fistulas in Crohn s disease patients 6
Mechanism of Action: Adipose-Derived Stem Cells Inhibition of pro-inflammatory cytokines IFN-γ (ng/ml) 0 5 0 5 20 TNF-α (ng/ml) 0 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 Increase % of Tregs 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 20 5 0 5 0 ACTIVATED PBMCs * ACTIVATED PBMCs + ASCs * p<0.05 relative to activated PBMCs without ASCs Source: Tigenix data MSCs: Mesenchymal Stem Cells 7
Manufacturing Consistent and Robust Process Liposuction Cell isolation and expansion Up to 360 billion cells can be obtained from donor Quality control parameters defined: Master cell bank (cryo) Identity Purity Potency Frozen Drug Substance (FDS) Approximately 2,400 finished products of Cx60 Finished Product 8
Perianal Fistulas A Common Severe Complication of Crohn s Disease Fistulas: sores or ulcers that tunnel through the affected area into surrounding tissues Around % of adult Crohn s disease patients are affected by perianal fistulas 70% 80% of these are complex Affect anal sphincters Present multiple tracts Are recurrent Are often associated with perianal abscess Fistula Almost 20,000 adult Crohn s disease patients suffer from complex perianal fistulas in Europe and the US alone => compromised QoL, pain, depression and risk of anal epithelial carcinoma 9
Perianal fistulas: treatment options and shortfalls Treatment options Efficacy Safety Antibiotics Immunossuppressants Infliximab (Remicade ) Adalimumab (Humira ) Surgery Poor quality of evidence on fistulas remission High rate of fistula relapse on drug cessation: 72% Poor quality of evidence on fistulas remission High rate of fistula relapse on drug cessation : 67-7% 2,3 Low remission rate of perianal fistulas: 23% after 54 weeks of treatment 4 High rate of relapse: 54% after 54 weeks of treatment 4, and 66% one year after drug cessation 5 Low remission rate: 33% after 56 weeks of treatment 6 Risk of recurrence remains (up to ~50-70%, depending on the type of surgery) 7,8 unless radical, mutilating surgery is performed Safety concerns with prolonged use High risk of infectious complications Safety remains a concern with long term use of biologics Safety remains a concern with long term use of biologics Risk of complications (eg. incontinence, abscesses formation, non-healing wounds 7,9 ) L.J. Brandt et al. Metronidazole Therapy for Perineal Crohn s Disease: a Follow-Up Study, 83 GASTROENTEROLOGY 383-7 (982) 2 E.S. Goldstein et al., 6 Mercaptopurine Is Effective in Crohn s Disease Without Concomitant Steroids, 0 INFLAMM BOWEL DIS 79 84 (2004) 3 B.I. Korelitz et al., Favorable Effect of 6-Mercaptopurine on Fistulae of Crohn s Disease, 30 DIGEST DIS SCI 58-64 (985) 4 B.E. Sands et al., Infliximab Maintenance Therapy for Fistulizing Crohn s Disease, 350 N ENGL J MED 876 85 (2004) 5 E. Domenech et al., Clinical Evolution of Luminal and Perianal Crohn s Disease after Inducing Remission with Infliximab, 22 ALIMENT PHARMACOL THER 07-3 (2005) 6 J.F. Colombel et al., Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn s Disease: The CHARM Trial, 32 GASTROENTEROLOGY 52-65 (2007) 7 C.B. Geltzeiler et al., Recent Developments in the Surgical Management of Perianal Fistula for Crohn s Disease, 27 ANN GASTROENTEROL - (204) 8 T. Sonoda et al., Outcomes of Primary Repair of Anorectal and Rectovaginal Fistulas Using the Endorectal Advancement Flap, 45 DIS COLON RECTUM 622 28 (2002) 0 9 A. Soltani and A. Kaiser, Endorectal Advancement Flap for Crypto Glandular or Crohn s Fistula in Ano, 53 DIS COLON RECTUM 486 495 (200)
Cx60: Product Description and Mode of Administration Product description o o Expanded adipose-derived stem cells (eascs) for the treatment of complex perianal fistulas in Crohn s disease 4 vials containing 30 million cells in 6 ml suspension each (total dose 20 million cells) Mode of administration. Fistula curettage and closure of internal opening (sutured) 2. Half of Cx60 dose (2 vials) is injected in the tissue around the internal opening, making several small blebs 3. The other half (2 vials) is injected along the walls of the fistula tracts, also making several small blebs a. Fistula internal opening b. Fistula tract Injection sites: Injection sites:
Cx60 Phase III ADMIRE-CD Trial Robust Phase III Study Designed to Qualify as a Single Pivotal Study TRIAL SUMMARY Condition Study design Status Enrollment Number of sites Primary endpoint Secondary endpoints at Weeks 24 and 52 Complex perianal fistulas in Crohn s disease patients Randomized, double-blind, placebo-controlled trial All tracts treated. Single injection 2 24 weeks primary analysis finalized. Follow up ongoing 289 patients recruited 50 active sites in 8 countries Combined Remission 3 at week 24 with α<0.025 Clinical Remission 4 Response 5 Time to Clinical Remission / to Response PDAI 6 and other scores Safety and tolerability Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn s Disease 2 20 million cells 3 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI 4 Closure of all treated external openings draining at baseline despite gentle finger compression 5 Closure of at least 50% of all treated external openings draining at baseline despite gentle finger compression 6 Perianal Disease Activity Index 2
Patients Selection: Key Eligibility Criteria Men and women aged 8 years or older Non active or mildly active luminal Crohn s disease (CDAI 220) diagnosed for 6 months Patients with complex perianal fistulas with 2 internal openings and 3 external openings Fistula draining 6 weeks prior to inclusion Patients with inadequate response to at least one of the following: antibiotics, immunosuppressants or anti-tnfs Medical standard of care was allowed to continue without modification of treatment dose or regimen 3
Design: Double-Blind, Placebo-Controlled Screening Preparation Treatment Primary Endpoint Follow-Up W-5 W-3 D0 W6 W2 W8 W24 W36 W52 W04 week Randomization Clinical Assessment Baseline MRI W24 MRI W52 MRI MRI: Magnetic Resonance Imaging 4
Largest Study in Complex Perianal Fistulas Screened n= 289 Screening Failures n= 77 Randomized n= 22 ITT set n= 22 Cx60 Placebo n= 07 n= 05 Not Treated n= 4 Treated n= 03 Safety set n= 205 Treated n= 02 Not Treated n= 3 Treated & post baseline assessment n= 03 Treated & post baseline assessment n= 0 ITT: Intention To Treat i.e. patients randomized 2 mitt: modified ITT i.e. patients randomized and treated, and with at least one post-baseline efficacy value mitt 2 set n= 204 5
Demographics, PDAI and Fistula Topography Demographics (ITT) Cx60 n= 07 Placebo n= 05 Age (years) mean (SD) 39.0 (3.) 37.6 (3.) Men (%) 60 (56.) 56 (53.3) Caucasian (%) 00 (93.5) 96 (9.4) Weight (kg) mean (SD) 73.9 (5.0) 7.3 (4.9) PDAI (ITT) Mean (SD) 6.5 6.7 Topography of Internal & External Openings (%) (Safety set) Cx60 n= 03 Placebo n= 02 One-tract fistula 53.4 68.6 Multiple-tract fistula 46.6 3.4 Similar demographics and PDAI score between arms Higher proportion of multiple-tract fistulas in Cx60 group Perianal Disease Activity Index 6
Cx60: A Major Breakthrough Primary Endpoint Met (ITT Population n= 22) p < 0.025 (mitt 2 Population n= 204) p < 0.025 % 60 % 60 50 40 49.5% 50 40 5.5 % 30 34.3% 30 35.6 % 20 20 0 0 0 0 Cx60 Placebo Cx60 Placebo Cx60 significantly superior to placebo in achieving Combined Remission Patients receiving Cx60 have 44% more chances to achieve Combined Remission than placebo patients Efficacy results consistent across all statistical populations ITT: Intention To Treat i.e. patients randomized 2 mitt: modified ITT i.e. patients randomized and treated, and with at least one post-baseline efficacy value 7
Overview of TEAEs up to W24 (Safety Population n=205) Number of Patients with (%) Cx60 Placebo n= 03 n=02 TEAEs 68 (66.0) 66 (64.7) Related TEAEs 6 (5.5) 26 (25.5) Withdrawn due to a TEAEs 4 (3.9) 4 (3.9) TESAEs 7 (6.5) 3 (2.7) Related TESAEs 5 (4.9) 6 (5.9) Withdrawn due to TESAEs 3 (2.9) 2 (2.0) TE(S)AE: Treatment-Emergent (Serious) Adverse Events If a patient has multiple events of the same severity, relationship or outcome, then they are counted only once in that severity, relationship or outcome. However, patients can be counted more than once overall. Favorable safety and tolerability profile of Cx60 and comparable to placebo 8
Cx60: A Regulatory De-Risked and Fully-Owned Asset Preparing for the European Launch in 207 Clear and fast pathway to the market built on a solid regulatory strategy Letter of intent submitted to the EMA and MAA 2 filing planned for Q 206 5 Scientific Advice Meetings held with EMA (2 pre-clinical, 2 CMC, clinical) Team with previous experience in obtaining MAA of cell therapy product Major commercial opportunity More than 70,000 adult patients in Europe with high medical need Protection obtained through EU patent and orphan designation Fully-owned commercial rights Commercialization strategy Partner in certain EU countries EMA: European Medicines Agency 2 MAA: Marketing Authorisation Application 9
Cx60: Capturing the Value of the Biggest Market Preparing for the US launch in 2020 Clear and fast pathway to the market built on a solid regulatory and clinical development strategy Type B meeting with FDA confirmed: Adequacy of existing non-clinical package to support an IND 2 filing Acceptability of using data from the ADMIRE-CD trial to support BLA 3 FDA endorsement through SPA 4 of US Phase III protocol: Primary end-point identical to ADMIRE-CD trial p-value < 0.05 (vs. p-value <0.025 in ADMIRE-CD trial) US Phase III trial scheduled to start by Q 207 Lonza selected as US contract manufacturing organization for Cx60 in the US Major commercial opportunity More than 40,000 adult patients in the US with high medical need Protection obtained through US patent until 2030 Retain US rights to develop and commercialize FDA: Food and Drug Administration 2 IND: Investigational New Drug 3 BLA: Biological License Application 4 SPA: Special Protocol Assessment 20
Cx60: Phase III US Trial Trial Design Endorsed by FDA through SPA Procedure in August 205 TRIAL SUMMARY Condition Study design Status Enrollment Number of sites Primary endpoint Secondary endpoints at Weeks 24 and 52 Complex perianal fistulas in Crohn s disease patients Randomized, double-blind, placebo-controlled trial All draining tracts treated. Single injection 2 In preparation 224 patients screened to allow for 68 randomized patients At least 50 60 active sites in 2 countries (USA & Canada) Combined Remission 3 at week 24 4 with α<0.05 Clinical Remission 5 Response 6 Time to Clinical Remission / to Response PDAI 7 and other scores Safety and tolerability Special Protocol Assessment 2 20 million cells 3 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI 4 The primary efficacy analysis, which has a week 24 endpoint, will be conducted at the time of the week 52 final analysis 5 Closure of all treated external openings draining at baseline despite gentle finger compression 6 Closure of at least 50% of all treated external openings draining at baseline despite gentle finger compression 7 Perianal Disease Activity Index 2
Cx60: Estimated Patients Population (EU & USA) An Attractive Commercial Opportunity Crohn s disease:,540,70 * -6 Adults:,432,860 (93%) 5-6 Perianal fistulas: 57,65 (%) 7-8 Complex: 8,2 (75%) 9-2 Controlled luminal CD: 78,09 (66%) 3 Refractory fistulas: 70,27 (90%) 3-5 * Estimated average prevalence in EU: 80/00,000-4 Estimated prevalence in US: 90/00,000 3,6 Stone MA et al. 203 2 Hein R et al. 204 3 Molodecky NA et al. 202 4 Lucendo AJ et al. 204 5 Kappelman MD et al. 2007 6 Kappelman MD et al. 203 7 SEESGCD.999 8 Gibson PR et al. 2007 9 Eglinton TW et al. 202 0 Bell SJ et al. 2003 Lahat A et al. 202 2 Molendijk I et al. 204 3 Sands BE et al. 2004 4 Present DH et al. 999 5 Domènech E et al. 2005 22
Cx60: Estimated Sales Potential (EU & USA) Assumptions: Estimated patients population to be treated with Cx60: ~70,000 patients Estimated first launch date in Europe: 2H7 Estimated launch dated in US: 2020 Estimated Market Share 20% 35% 50% Estimated Selling Price 25 K$ 33 K$ 50 K$ Estimated Sales Potential 350 Mio $ 809 Mio $,750 Mio $ 23
Cx6: Phase ll Ready Intravenous injection of eascs for the treatment of severe sepsis 24
Severe Sepsis: A High Unmet Medical Need Systemic illness due to an attack of host proinflammatory cytokines and other humoral substances commonly induced by a bacterial infection Incidence forecasted to grow at.5% p.a. 4 An estimated 5 9M sepsis cases occur worldwide each year Incidence has dramatically increased over the last decade (CAGR of 8-3%) 2 Sepsis mortality was estimated at 36% in a recent major European study 2 In the case of septic shock, mortality can reach up to 80% (28 50% of patients die within the first month of diagnosis) 3 Current molecular approaches to the treatment of sepsis have inadequately addressed the complex immuno-modulatory pathways involved in sepsis pathogenesis The Lancet Infectious Diseases; Volume 2; issue 2; page 89; February 202 2 Vincent JL et al Sepsis in European intensive care units. Critical Care Medicine 2006; 34: 344-353 3 University Hospital of Valme & Biomedical Research Institute of Seville: Presentation at Farmaindustria meeting July 204 25
eascs Can Protect In Severe Sepsis LPS Model CLP 2 Model Source: Gonzalez-Rey, 2009 * p < 0.00 Cx6 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 LPS: lipopolysaccharide. LPS model is based on endotoxemia induced by high-dose of endotoxin 2 CLP: cecal ligation and puncture. This model mimics the clinical situation of patients with colonic leakage following surgical procedures or diffused peritonitis 26
easc Effect at the Cytokine and Cellular Level * p<0.00 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 27
Cx6: Phase I results and Next Steps Phase II In Severe Sepsis Expected to Start 4Q 205 CELLULA Phase I trial results 250k, M, 4M easc/kg and placebo administered to 32 healthy volunteers (8 per group) Favorable safety and tolerability profile of Cx6, consistent with Phase I/IIa in refractory RA patients SEPCELL Phase Ib/IIa study in severe sepsis to start 4Q 205 Randomized, double blind, parallel groups, placebo controlled, multicenter study 80 patients (90 per group) with scabp requiring mechanical ventilation and/or vasopressors, admitted to the ICU. At least 50 centers in at least 4 countries 80M easc or placebo on days and 3 (60M in total) in addition to standard of care therapy. 90 days follow up Primary endpoint: Adverse event and potential immunological host responses against the administered cells Secondary endpoint: reduction in the duration of mechanical ventilation and/or vasopressors needed and/or improved survival, and/or clinical cure of the CAPB, and other infectionrelated endpoints Severe community-acquired bacterial pneumonia 28
AlloCSC-0: Phase ll interim data in <2 months Intracoronary administration of allogeneic cardiac stem cells for the treatment of acute ischaemic heart disease 29
AlloCSC-0: Preventing Congestive Heart Failure Myocardial Repair may be the only Feasible Alternative,9M Acute Myocardial Infarctions (US+EU) occur annually, mostly treated by PCI 2 and stent implantation Successful treatment of AMI has contributed to a Chronic Heart Failure epidemic (26M patients worldwide 3 ) CHF post-ami is a terminal disease with an annual mortality rate of ~5% after the first episode, for which no curative treatment exists with the exception of heart transplantation In 205, the AHA estimated that the direct and indirect cost of coronary heart disease, the main cause of myocardial infarction, was $82 billion and is expected to reach $322 billion in 2030. Similarly the cost of heart failure in the United States was estimated at $24 billion for 205, reaching $47 billion in 2030 4 An attractive market for a treatment able to mitigate or delay the onset of CHF Datamonitor: Stakeholder Insight: Acute coronary syndromes, DMHC2347, 2007 2 PCI: Percutaneous Coronary Intervention 3 Ambrosy PA et al., J Am Coll Cardiol. 204;63:23-33. 4 Circulation. 205 Jan 27;3(4):e29-322. 30
AlloCSC-0: A Regenerative Treatment Post-AMI Preventing the Onset of Chronic Disease The formation of a non-functional scar tissue gives rise to a process of ventricular remodeling whereby the myocardium tries to compensate the effect of the injury Over time the heart dilates losing its contractile capacity causing the onset of CHF. This is a terminal condition with no treatment other than transplantation The severity of this process is related to the size of the scar resulting from the AMI. Smaller scars are related to better outcomes Myocardial repair seems to be the only feasible treatment to address the post-acute phase of the disease and prevent the onset of chronic heart failure (CHF) Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 20;4:98 08. 3
AlloCSC-0: Efficacy Demonstrated in Pig Model Efficacy Data from MRI Histological Analysis CARDIAC REMODELING 50# 00# EDVi#2 40# 90# 30# 80# 20# 70# CARDIAC FUNCTION 60# ESVi#3 4 EF### 55# CONTROL * 50#! 45# 50# # 50 M # CO 25 M L# # O O NT R CO 50 M # 50 M 25 M O CO NT R 30# # 30# AlloCSC- 0 40# 35# L# 80# # 40# L# 90# 25 M 00# * NT R * 0# 60# * p-value < 0.05! AlloCSC-0 prevents cardiac remodelling after infarction preserving heart function AlloCSC-0 reduces scar size promoting formation of new contractile tissue Significant dose effect observed MRI: Magnetic Resonance Imaging EDVi: End-Diastolic Volume Index ESVi: End-Systolic Volume Index 4 EF: Ejection Fraction 2 3 32
CAREMI Phase I/II Trial Finalizing Recruitment Safety and Efficacy of Intracoronary Infusion of Allogeneic Cardiac Stem Cells in Patients with Acute Myocardial Infarction (AMI) PATIENT SELECTION Initial clinical pre-screening: Males, females 8 years and 80 years Patients who present a STEMI Killip 2 on admission Successful revascularization by PCI (TIMI 2 = 3) within 2h after the onset of symptoms EF 50% by echocardiography (day 2 after infarct symptoms) EF 45% by MRI on D3-5 post-stemi Infarct size ( st MRI) >25% in LV 3 Bare-metal stents or second generation drug eluting stent at PCI The infarct culprit coronary artery is adequate for treatment administration and the procedure is technically feasible The patient is stable and in adequate clinical condition to undergo the procedure Condition Study design Recruitment TRIAL SUMMARY Acute Myocardial Infarction AlloCSC-0 administered 5-7 days after PCI 4 Phase. Open label dose escalation in 6 patients Phase 2: Placebo controlled, 49 patients randomized 2: (35M cell dose in active arm) Phase : Completed Phase 2: 36 of 49 treated, set to complete recruitment in 4Q 205 # of centers 8 sites Primary endpoint Secondary endpoints (6 and 2 months) Mortality and MACE 5 from any cause at 30 days Safety: Mortality and MACE Efficacy: evolution of infarct size, biomechanical parameters by MRI Clinical parameters: 6m walk test, NYHA 6 scale Completion H7 (Interim data 2H6) STEMI: ST-Segment-Elevation Myocardial Infarction 2 TIMI: Thrombolysis In Myocardial Infarction 3 LV: Left Ventricle 4 PCI: Percutaneous Coronary Intervention 5 MACE: Major Adverse Cardiac Events 6 NYHA: New York Heart Association 33
CAREMI Phase I/II Trial Positive Preliminary Results from Phase I Presented at ESC In the dose-escalation open-label phase, 6 patients were treated and 5 of them were followed up for 6 months Patients received a single injection of million (M), 22M or 35M cells of AlloCSC-0 (n=2 each) by intracoronary infusion 5 to 7 days after Percutaneous Coronary Intervention (PCI) Data presented at the European Society of Cardiology meeting in London, showed that AlloCSC-0 has a good safety profile as no adverse events or Major Adverse Cardiac Events (MACE) were observed during the 6 month follow-up period * p-value < 0. ** p-value < 0.05 Preliminary efficacy data showed a reduction in the infarct size, and a LVEF improvement on MRI, over the 6-month follow-up period (n=5; p<0.05 for both parameters) 3 2 LVEF (%): Left Ventricular Ejection Fraction % change versus screening MRI 2 IS (ml): Infarct Size 3 IS (% of LV): Infarct Size as % of Left Ventricular mass 34
Key Milestones, IP, Facts and Investment Highlights 35
Key Milestones Product 204 205 206 207 Cx60 (local) AlloCSC-0 (IC) Cx6 (IV) Europe US acute myocardial infarction severe sepsis ChondroCelect 4Q4 Phase 3 enrollment completed 3Q4 CMO selection ü 4Q4 SPA submission ü ü 4Q4 Phase initiated ü ü ü Q4 manufacturing facility sold 2Q4 licensed to SOBI 3Q5 Phase 3 primary endpoint met (24 weeks) 3Q5 positive SPA ü Q5 Phase 2 enrollment initiated 4Q5 Phase 2 enrollment completed 2Q5 Phase study results ü ü ü 4Q5 Phase 2 enrollment initiated 2Q6 study results ( year follow-up) Q6 EMA filing 2H6 tech transfer finalized 2H6 Phase 2 interim analysis 2Q7 Phase 2 enrollment completed YE6 IND filing Increase market penetration in existing countries Expand geographic reach through new market entry 2H7 EU launch Q7 pivotal Phase 3 initiated H7 Phase 2 study results YE7 Phase 2 study results 36
Key Intellectual Property Patent Portfolio in Cell Therapy 27 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 Cx60 (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 37
Key Facts About TiGenix Headquarters / Operations Employees Leuven, Belgium / Madrid, Spain Approximately 70 employees Stock Exchange Euronext Brussels. Ticker: TIG Market Capitalization Approx. EUR 55M October 4, 205 Reference Shareholders 28% held by Grifols, Genetrix and Novartis Liquidity ~72% free-float, of which ~30% held by institutional investors Analyst Coverage 6 analysts covering the stock, of which four are independent Cash and Cash Equiv. EUR 22.7M at June 30, 205 Convertible Bond Principal amount for EUR 25M due in 208 Note: Numbers reflect EUR/USD =.2432 as of 09/30/5 38
Investment Highlights Positive Phase III And Advanced EU Regulatory Strategy: Cx60 Clear US Regulatory and Clinical Strategy: Cx60 Valuable Pipeline Opportunities: AlloCSC-0 and Cx6 Complex 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) Results met primary endpoint Statistically superior to placebo in achieving combined remission at week 24 (p<0.025) Filing for MAA expected in Q6 and launch expected 2H7 Fully-owned asset Consistent and robust manufacturing process Management team has valuable experience in regulatory approval / commercialization process; first ever ATMP approved by EMA Use of data from positive pivotal Phase III trial in EU to support a BLA in the US FDA s endorsement through SPA obtained for pivotal phase III trial in the US Same primary endpoint as positive EU Phase III trial Phase III to start Q7 Fully-owned asset Lonza selected as contract manufacturing organization for Cx60 in the US AlloCSC-0: allogeneic cardiac stem cells, a new platform acquired through the acquisition of Coretherapix, being developed for cardiovascular indications Randomized, double blind, placebo controlled Phase II trial in acute myocardial infarction ongoing Interim data expected 2H6 Final one year follow up data expected H7 Cx6: Intravenously-administered allogeneic stem cell product for severe sepsis (Phase I study completed) Severe sepsis Phase ll trial design has been finalized; expected to enroll first patient in 4Q5 Advanced Therapy Medicinal Product 39
Corporate Presentation October 205 40