Corporate Presentation

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1 Corporate Presentation December 205 Corporate Presentation 3 April 208

2 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 statements 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

3 Compelling Investment Case Lead product approved in Europe, strong partner First allogeneic stem cell product to receive MA in Europe ü First indication: treatment of complex perianal fistulas in adult Crohn s disease patients => high unmet medical need ü Global pivotal phase III trial for BLA registration started in 207. Expedited pathway to market in the US being explored ü US Orphan Drug Designation granted in October 207 Commercial launch expected in 208: ü Ex-US rights licensed to Takeda, leading company in the GI field ü Up to EUR 380M in potential milestones plus double-digit royalties Pipeline: ü Cx6 in phase II for the treatment of severe sepsis ü Follow-on indications for Cx60 identified ü Seasoned management team with deep experience in drug development ü Cash position at December 3, 207: EUR 34. million ü Traded on the Nasdaq and Euronext (TIG) Label in EU: treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used after conditioning of fistula 3

4 Key milestones reached in A period of significant achievements culminating in the EC approval of Alofisel First patient recruited into the SEPCELL study with Cx6 January 207 Positive 04 week data for Cx60 in Admire-CD March 207 Top line results of CAREMI trial for AlloCSC-0 March 207 Launch of Cx60 global phase III trial to support BLA with FDA June 207 Opening of US offices in Cambridge, MA June 207 Granting of commercial production license for expanded facility September 207 Orphan Drug designation of Cx60 in the US October 207 Approval of trade name (Alofisel ) and INN (darvadstrocel) for Cx60 November 207 Positive CHMP opinion for Cx60 December 207 Review of the safety and efficacy data from the first 20 randomized patients in SEPCELL study and clearance by the idmc* to continue with no changes in the protocol Positive EC decision for Alofisel (Cx60) March 208 * independent Data Monitoring Commiee 4

5 Alofisel (Cx60): Novel, locally administered therapy for the treatment of complex perianal fistulas in Crohn s disease patients EC approval received in March 208 Label in EU: treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used after conditioning of fistula 5

6 Adipose-Derived Stem Cells are Potent Anti-inflammatory Agents Mechanism of Action (MoA) is IDO -mediated eascs are well suited to treat inflammatory-mediated diseases by simultaneously interacting with many players in the immune system and thereby reverting an uncontrolled inflammatory response of the body This reversion occurs through activation of the function of the IDO enzyme By degrading tryptophan 2 into kynurenine and other products, IDO: inhibits T cell proliferation and proinflammatory cytokine secretion induces anti-inflammatory cytokines induces an increased number of Tregs controls monocyte and B cell maturation Image representation of the proprietary research that supports the mechanism of action of eascs The full video representing this mechanism of action can be found under IDO: Indoleamine 2,3-dioxygenase 2 Tryptophan is an essential amino acid required for cell proliferation from the inflamed tissue 6

7 Complex Perianal Fistulas A chronic, common and severe complication of Crohn s disease ü Chronic, abnormal communication between the epithelialized surface of the anal canal and the perianal skin Fistula ü Complication of Crohn s disease for 30 50% of patients ü Perianal fistulas in Crohn s disease are difficult to treat with currently available therapies and often lead to pain, swelling, infection, incontinence and social, sexual and employment restrictions Fistula ü Current treatments for perianal fistulas lack long term efficacy and present safety issues Infliximab- Remicade and Adalimumab - Humira 7

8 Over 25,000 Adult Crohn s Patients Suffer Perianal Fistulas More than 55,000 patients fit the expected label; 40% of these in the US Estimation of prevalence of Crohn s disease patients with perianal fistulas 49,993 Average of US published data,2,3 and US real world data (claims database) 4 Adult Crohn s disease patients with perianal fistulas: 75,90 European published data 5,6 37,495 24,746 With complex perianal fistulas: With complex perianal fistulas and controlled luminal disease: 56,392 37,29 With refractory complex perianal fistulas and controlled luminal disease: 22,272 Expected label 33,497 In ~75% CD patients perianal fistulas are complex 7- In ~66% CD patients with perianal fistulas luminal disease is controlled in ~90% CD patients perianal fistulas are treatment refractory 2-4 Schwartz et al Gastroenterology 22: Kappelman et al 203. Dig Dis Sci, 58: Khalili et al 202. Gut : Study commissioned to Vencore Health Analytics Inc based on Truven MarketScan database 5 Göttgens et al 207. Eur J Gastroenterol Hepatol [Epub ahead of print] 6 Burisch et al 203. J Crohn s Colitis 7: Bell et al Aliment Pharmacol Ther 7: Eglinton et al 202. Dis Colon Rectum 55: Riss et al 203. Tech Coloproctol 7: Molendijk et al 204. Inflamm Bowel Dis 20: Molendijk et al 205. Gastroenterology 49: Sands et al N Engl J Med 350: Domenech et al Aliment Pharmacol Ther 22: Rayen et al 207. Tech Coloproctol 2:9-24 8

9 A Real Need for New Treatment Options Available treatments lack long term efficacy and present safety issues Currently approved biologic Only one medical treatment approved for fistulas in Crohn s disease in Europe (infliximab) Only ~/5 patients see a response after year of continued treatment (IV infusion every 8 weeks),2 Risk of relapse on withdrawal higher than in luminal disease 3 ; 2/3 of healed fistulas recur within year after discontinuation 4 Rarely achieves complete healing in the long-term (3% of patients) 5 Efficacy does not increase in combination with immunosuppressants 6 Treatment does not abolish the need for surgery 7 Associated with serious infections in 9% of patients and to infusion reactions in % of patients 8 Surgery Complex fistulas require surgical intervention 8 An average of 4 surgeries over a period of years 9,0 with only half of patients healed 9 Fistula surgery is linked to risk of sphincter damage leading to faecal incontinence,2 30% and 54% of patients report post-operative incontinence to solid and liquid stools 3 High rate of recurrences and failures % and 3% of patients with complex anal fistulas require ostomy and proctectomy 7, with no guarantee of healing 8,9 Sands et al N Engl J Med 350: Grimaud et al 200. Gastroenterology 38: Doherty et al 207. J Crohn s Colitis [Epub] 4 Domenech et al Aliment Pharmacol Ther 22: Rayen et al 207. Tech Coloproctol 2: Present et al 999. N Engl J Med 349: Poritz et al Dis Colon Rectum 45: D Haens et al 206. J Crohn s Colitis : Graf et al 205. Colorectal Dis 8: Galandiuk et al Ann Surg 24: Norton et al 203. J Crohn s Colitis 7:e Geltzeiler et al 204. Ann Gastro 27: Riss et al 203. Tech Coloproctol 7: Schwartz et al 205. Inflamm Bowel Dis 2: Herman et al 206. Abz J Surg 86: Senejoux et al 206. J Crohn s Colitis 0: Molendijk et al 204. Inflamm Bowel Dis 20: Figg et al Dis Colon Rectum 52: Lee et al 207. Colorectal Dis 9:48-429

10 A Completely Different and Simple Approach A single administration with sustained efficacy (ADMIRE-CD trial) Method of administration of Cx60: Injection 0

11 Pivotal Phase III Design Validated by EMA and FDA Complex fistulas refractory to best available standard of care Randomized, double-blind, placebo controlled 22 patients randomized : Patients with non-active or mildly-active Crohn s disease 40% of patients with multiple tract fistulas Draining fistulas despite active treatment (majority anti-tnf) All patients stayed on their best standard of care treatment All draining tracts treated Efficacy defined as combined remission : clinical remission and lack of abscesses on magnetic resonance imaging => Highly stringent endpoint vs. other studies targeting closing of external opening(s) and cessation of drainage Efficacy measured at 24 and 52 weeks. Safety follow up to 04 weeks Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI (Magnetic Resonance Imaging)

12 Primary Endpoint Met at Week 24 Results published in The Lancet in July 206 % Patients 60 Combined Remission at W24 (mitt 2 Population n= 204) p = % % 20 0 Alofisel Control Alofisel -treated patients had a 44% greater probability of achieving Combined Remission than placebo patients Shorter median time to Clinical Remission (6.7 weeks for Cx60 vs. 4.6 weeks in the control group) Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI (Magnetic Resonance Imaging) 2 mitt: modified Intention To Treat i.e. patients randomized, treated and with post-baseline assessment. Efficacy results are consistent across all statistical populations 2

13 Benefit Sustained, Lower Relapse Rate at Week 52 % Patients % % Patients 40 Combined Remission at W52 (mitt 2 Population n= 204) p = % No Relapse Rate at W % 55.9% Alofisel Control 0 Alofisel Control More than 50% of the patients receiving Alofisel had all treated fistulas in Combined Remission 3 one year after a single administration of the product 75.0% of the patients treated with Cx60 who were in combined remission at W24 did not relapse, compared to 55.9% for patients in the placebo arm Safety profile: rate of (serious) adverse reaction comparable to that of the control group Relapse: reopening of any of the treated external openings with active drainage as clinically assessed, or development of perianal collection 2cm of the treated perianal fistula confirmed by centrally blinded MRI assessment in patients with clinical remission at any previous visit 2 mitt: modified Intention To Treat i.e. patients randomized, treated and with post-baseline assessment. Efficacy results are consistent across all statistical populations 3 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI (Magnetic Resonance Imaging) 3

14 EC Approval Received March 208 Clear and fast pathway to the market built on a solid regulatory strategy Positive CHMP opinion received in December 207 Approved PIP 4 with 20 patients to be started not before 2020 GMP license for commercial manufacturing granted Orphan Designation received 2009; Ratification post MA in January 208 Positive EU decision (MA) received March 208 D D80 D20 þ þ þ þ MAA 5 Submitted Q206 Start of the procedure st Clock Stop D2 þ D50 þ D80 þ 2nd Clock Stop D8 AR 6 LoQ 7 Responses Joint AR LoOI 8 Responses þ D20 þ CHMP 9 Opinion D277 EU Decision MA: Marketing Authorization 2 EMA: European Medicines Agency 3 CMC: Chemistry Manufacturing and Controls 4 PIP: Pediatric Investigational Plan 5 MAA: Marketing Authorization Application 6 AR: Assessment Report 7 LoQ: List of Questions 8 LoOI: List of Outstanding Issues 9 CHMP: Committee of Human Medicinal Products (within EMA) 4

15 Leading experts discuss Cx60 s potential as a new treatment for complex perianal fistulas in Crohn s disease This drug is going to make a significant contribution to patients in need for this debilitating condition. Dr. Isabelle Lugan, PhD, VP, Global Program Lead at Takeda we as surgeons are so excited by the prospect of a therapy which will both cure the fistula and spare the patient having any loss of control of their bowels. This combination is critically important we are thrilled that we have something that s finally an alternative where we can ideally get these fistulas cured without disturbing the muscle. The last drug approved for fistulas was approved in 998 so [there has been] no incremental progress in the last 20 years. There remains a considerable number of patients whose fistula tracks don t close there is a lot of room to improve the outcomes for these patients. Pr. William J. Sandborn, MD, PhD Pr. Steven D. Wexner, MD, PhD Cx60 demonstrated significantly greater efficacy compared to control in achieving the primary endpoint, combined remission at week 24, which is a very tough endpoint, in modified ITT populations Of those patients who achieved combined remission at week 24, numerically a greater proportion of patients receiving Cx60 vs control had non relapse. Pr. Jean-Frederic Colombel, MD, PhD Analyst and Investor event webcast: 5

16 Ex-US Rights of Cx60 Licensed to Takeda Exclusive ex-us development and commercialization rights to Cx60 for the treatment of complex perianal fistulas in Crohn s disease patients EUR 25M up front plus EUR 0M equity investment TiGenix eligible to receive potentially up to EUR 355M in regulatory and sales milestones, including the EUR 5M EU marketing approval milestone Double-digit royalties on net sales, tiered to reimbursement price Takeda will assume manufacturing responsibilities for Cx60 after an initial period of product supply by TiGenix for the EU TiGenix retains full rights to the US market TiGenix retains full rights to develop Cx60 in new indications 6

17 Takeda is the Best Partner for Cx60 Alofisel (Cx60) is the perfect fit for Takeda s existing IBD portfolio Source: Takeda presentation (JPM event 207) 7

18 Exploring Expedited Pathways to US Market Orphan Drug + RMAT designation could significantly reduce time to market Global pivotal Phase III clinical trial launched in June 207 intended to support a future regulatory filing for Cx60 in the U.S As of March 3, 208, patients have been recruited into the trial across 37 sites in seven European countries including Spain, Italy, France, Poland, Belgium, Hungary and the Czech Republic Cx60 was designated Orphan Drug (ODD) by FDA in October 207 IND clearance for the start of US recruitment is expected by end of 208 TiGenix aims to file for RMAT Designation in parallel to the filing of the US IND TiGenix believes that, building on the ODD of Cx60, there is a case for the FDA to grant conditional approval of Cx60 in the US based on European ADMIRE-CD data while the Global Study is being completed This accelerated pathway with RMAT designation could significantly reduce time to market RMAT: Regenerative Medicine Advanced Therapy 8

19 ADMIRE-CD Global Design Study design Number of sites Targeted Enrolment Primary endpoint Key Secondary endpoints at Week 24 & relevant at W52 Trial Summary Randomized, double-blind, placebocontrolled trial All tracts treated. Single administration >20 sites in EU/ISR and Canada/ US (~60% of all sites) 326 patients to be randomized (>436 to be screened) Combined Remission at W24 with α<0.05 for all treated fistulas Clinical Remission at W24 Response at W24 Combined Remission, Clinical Remission/Response at W52 Time to Clinical Remission / Response at W24, W52 Safety and tolerability up to W52 epros and QOL assessments Key Inclusion Criteria Men and women aged 8-75 years Documented clinically controlled asymptomatic or mild symptomatic CD: by PRO-2 and endoscopically Patients with complex perianal fistulas with 2 internal openings and 3 external openings Absence of collection on MRI not properly drained during preparation Fistula draining 6 weeks prior to inclusion Patients with fistula and inadequate response to prior treatment, at least one of the following: immunosuppressants or biologics Cx60 as Add-on therapy: Medical SoC to be continued without modification of treatment dose or regimen if ongoing at baseline either as single agent or combinations 9

20 Cx60 Product Profile is Extremely Competitive Prescribing expected to include around 2/3 of all patients in the expected label in the US Pa'ent subgroups within expected label in US Group A Controlled luminal disease Antib. / Immuno. Not responding Group B Controlled luminal disease Infliximab Not responding Group C Controlled luminal disease Second biologic Not responding Group D Controlled luminal disease After failure of repair surgery Non-controlled luminal disease Infliximab Not responding % of pa'ents in US within each subgroup 2% 38% 7% 24% 54% pa@ents upside % pa'ents in US within each group treated with Cx60 50% 45% 85% 90% 60% % pa'ents in US treated with Cx60 (from total within expected label) Sources: Simon-Kucher & Partners; Expert discussions in June 206 with 5 medical directors, 2 ex-medicare carriers, 2 hospital pharmacy directors, 5 KOLs and 6 HVPs (gastroenterologists and colorectal surgeons) in the US % 7% 4% 2% 5% pa@ents upside 63% pa@ents within expected label in US 20 2

21 Favorable Coverage and Coding Expected for Cx60 in the US Expected coverage by Medicare Part B and commercial medical benefit Hospital / ASC visit: Diagnosis and treatment decision If there is an abscess Preparation: Incision, drainage and seton placement (Current SoC) Existing CPT codes expected to be used Current existing bill for preparation procedure: CPT and Conditioning of fistula 2 : Bill for procedure Intra-lesional injection of Cx60 Bill for drug 3 Cx60 reimbursement will consist of separate bills: one for the drug and another for the administration procedure Preparation surgery and conditioning of fistula expected to be billed as independent procedures under currently existing codes Expected reimbursement of Cx60 through miscellaneous codes during first year likely not a hurdle for targeted centers of excellence Sources: Simon-Kucher & Partners; expert discussions June 206 ASC: Ambulatory Surgical Center 2 Removal of seton, curettage and suturing of internal opening 3 Physicians may receive an administration fee 2

22 US Commercial Model Accounts across US can be covered with a targeted headcount Account distribution with procedure volumetric data LEGEND ASCs (48) CoEs (7) Non CoE Hospitals (330) Bulk of procedures to be performed in hospitals and ASCs located near or at CoEs 2 7 CoEs, 330 Hospitals and 48 ASCs account for 84% of complex perianal fistula procedures Full coverage with targeted field headcount of approx. 60 people including MSLs, Field Reimbursement Specialists, KAMs and Hospital Account Managers Sources: HPD Data; Validated target account list from physician surveys; QuintilesIMS Consulting Services Analysis ASC: Ambulatory Surgical Center 2 CoE: Centre of Excellence 22

23 Cx60 Peak Year Sales Analysts Consensus for US market Several variables kept today on the conservative side provide future upside 70,000 37,000 Addressable patient population 0% - 30% Penetration rate USD 40,000 50,000 Price per dose USD 270M 663M Peak Year Sales USD 205M 300M A commercial opportunity assessment including extensive payer and physician research conducted by Simon-Kucher & Partners in 206 revealed that potential feasible prices for Cx60 in the US may be significantly above the price range indicated by the analyst reports quoted on this slide. This slide does not represent a recommendation or endorsement of a particular pricing strategy for Cx60 on behalf of TiGenix Sources: Analyst research reports from Bank of America Merrill Lynch, Cowen & Co., Canaccord Genuity, BTIG 23

24 Cx60 Pipeline Expansion Potential developments for Cx60 beyond complex perianal fistulas in Crohn s disease Other gastrointestinal fistulas Gastrointestinal indications other than fistulas Other indications 24

25 Significant Potential in Other Gastrointestinal Fistulas Addressable population could be four times larger Estimated Patient Populations in US (204) Crohn s disease Non-Crohn s disease 42,756 * Complex perianal fistulas 23,69 25,892 6,064 5,797 Other hard to treat fistulas with external access Indication 3,88 Indication 2 Indication 3 4,742 Indication 2 Patients under expected label Cx60 Patients with other fistulas Source: Truven MarketScan database * Complex perianal fistulas out of the expected label include those in patients with non-controlled luminal symptoms, those that are not refractory to currently available therapies, and those affecting children Study Commissioned to Vencore Health Analytics Inc,

26 Pipeline Cx6 Novel Treatment for Severe Sepsis 26

27 Severe Sepsis: Leading cause of mortality in the developed world Life-threatening complication of infection leading to systemic inflammation and potentially organ failure Between 5M to 9M sepsis cases occur worldwide each year. Mortality reaches 50% for severe sepsis raising to 80% in septic shock 2 Efficacy in in vivo models indicate that Cx6 s novel MoA may offer an innovative alternative to the treatment of severe sepsis The CELULLA Phase I study demonstrated the favorable safety and tolerability profile of Cx6 in the treatment of sepsis TiGenix Phase II trial (SEPCELL) is supported by the Horizon 2020 European Commission Program and endorsed by top European Key Opinion Leaders Diagnosed cases and mortality of Sepsis vs. Breast Cancer, Prostate Cancer & AIDS Diagnosis Discharges thousands Sepsis Breast, Prostate Cancer & AIDS Trend in U.S. hospital stays with septicemia % CAGR The Lancet Infectious Diseases; Volume 2; issue 2; page 89; February Martin GS Expert Rev Anti Infect Ther. 202 June ; 0(6): Adapted from Lagu, T., et al. Critical Care Medicine, 40(3):754-76; Adapted from: Elixhauser et al. Septicemia in U.S. Hospitals 2009, AHRQ, Healthcare Cost Brief No. 22 October 20 27

28 Cx6: Phase I/II SEPCELL Trial Design ICU patients with scabp requiring mechanical ventilation and/or vasopressors RANDOMIZATION : Cx6 N=90 (60 Million) Cx6 or placebo (day and day 3) Placebo N=90 4 days 29 days 90 days 365 days 720 days Secondary efficacy clinical endpoints: Survival; mechanical ventilator and/or vasopressor treatment/free days; scabp clinical response; other efficacy endpoints, such as time to discharge from ICU Exploratory Safety Endpoint: Long-term safety follow-up (through phone calls) Primary safety endpoints: Safety measured throughout 90 days by the incidence of treatment emergent adverse events (TEAEs) judged related or not to study treatment Secondary safety endpoints: potential host immune response to administered cells. Side effects: frequency, duration, severity, relatedness to study treatment Severe Community-Acquired Bacterial Pneumonia 28 28

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