Cx601 ADMIRE-CD Top-Line Results Webcast. 24 August 2015

Transcription

1 Cx601 ADMIRE-CD Top-Line Results Webcast 24 August

2 Cx601 ADMIRE-CD Top-Line Results Webcast Speakers Mr Eduardo Bravo, Chief Executive Officer Dr Julián Panés, Head of Gastroenterology Department, Head of IBD Unit Associate Professor of Medicine, Hospital Clínic of Barcelona President-Elect of ECCO and Chairman of TiGenix ADMIRE-CD Scientific Advisory Board Dr Marie Paule Richard, Chief Medical Officer 2 2

3 Forward Looking Statement 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. 3 3

4 Eduardo Bravo Chief Executive Officer Introduction 4 4

5 TiGenix Pipeline 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 EMA granted Orphan Drug FDA endorsed SPA AlloCSC-01 (intracoronary) Allogeneic cardiac stem cells Acute myocardial infarction Cx611 (intravenous) Allogeneic adipose-derived stem cells Rheumatoid arthritis Severe sepsis Cx621 (intralymphatic) Allogeneic adipose-derived stem cells Autoimmune disorders AlloCSC-02 (intramyocardial) Allogeneic cardiac stem cells Cardiology ChondroCelect Characterised autologous chondrocytes Knee cartilage lesions Partnered 2 1 Covered by 25 patent families 2 Distributed through Swedish Orphan Biovitrum ( Sobi ) and the Finnish Red Cross Blood Service 5 5

6 Dr Julián Panés Head of Gastroenterology Department, Head of IBD Unit and Associate Professor of Medicine at Hospital Clínic Barcelona President-Elect of ECCO Chairman of TiGenix ADMIRE-CD Scientific Advisory Board Complex Perianal Fistulas in Crohn s Disease 6 6

7 Perianal Fistulas A common severe complication of Crohn s disease Fistulas: sores or ulcers that tunnel through the affected area into surrounding tissues Around 40% of Crohn s disease patients are affected by perianal fistulas 70-80% of these are complex affect anal sphincters present multiple tracts Fistula are recurrent are often associated with perianal abscess Almost 100,000 Crohn s disease patients suffer from complex perianal fistulas every year in Europe and the US alone => compromised QoL, pain, depression and risk of anal epithelial carcinoma 7 7

8 Perianal Fistulas: Treatment Options and Shortfalls Treatment options Efficacy Safety Antibiotics Immunossuppressants Infliximab / Adalimumab 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 concern with prolonged use High risk of infectious complications and cancer Low remission rate: 23% after 54 weeks of treatment 3 Safety remains a concern High rate of relapse: 54% after with long term use of 54 weeks of treatment 3, and biologics 67% one year after drug discontinuation 4,5 Surgery High rate of relapse: 50% 6 High risk of anal incontinence 7 1 Brandt et al. Metronidazole Therapy for Perineal Crohn s Disease: a Follow-Up Study, 83 GASTROENTEROLOGY (1982) 2 Goldstein et al. 6 - Mercaptopurine Is Effective in Crohn s Disease Without Concomitant Steroids, 10 INFLAMM BOWEL DIS (2004) 3 Sands et al. Infliximab Maintenance Therapy for Fistulizing Crohn s Disease, 350 N ENGL J MED (2004) 4 Domenech et al. Clinical Evolution of Luminal and Perianal Crohn s Disease after Inducing Remission with Infliximab:22 ALIMENT PHARMACOL THER (2005) 5 Colombel et al. Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn s Disease: The CHARM Trial, 132 GASTROENTEROLOGY (2007) 6 Sonoda et al. Outcomes of Primary Repair of Anorectal and Rectovaginal Fistulas Using the Endorectal Advancement Flap, 45 DIS COLON RECTUM (2002) 7 Soltani and Kaiser, Endorectal Advancement Flap for Crypto Glandular or Crohn s Fistula-in-Ano, 53 DIS COLON RECTUM (2010) 8 8

9 Dr Marie Paule Richard Chief Medical Officer Cx601 ADMIRE-CD Top-Line Results 9 9

10 Cx601Phase III ADMIRE-CD 1 Trial Robust Phase III study designed to qualify as a single pivotal study TRIAL SUMMARY Condition Study design Status Enrolment Number of sites Primary endpoint Secondary endpoints at Weeks 24 and 52 Complex perianal fistulas in Crohn s disease patients Randomised, 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 1 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn s Disease 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 10 10

11 Patients Selection: Key Eligibility Criteria Men and women aged 18 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 11 11

12 Design: Double-Blind, Placebo-Controlled Screening Preparation Treatment Primary Endpoint Follow-Up W-5 W-3 D0 W6 W12 W18 W24 W36 W52 week Randomisation Clinical Assessment Baseline MRI W24 MRI W52 MRI MRI: Magnetic Resonance Imaging 12 12

13 Largest Study in Complex Perianal Fistulas Screened n= 289 Screening Failures n= 77 Randomised n= 212 ITT set n= 212 Cx601 n= 107 Placebo n= 105 Not Treated Treated Treated Not Treated n= 4 n= 103 n= 102 n= 3 Safety set n=

14 Demographics, PDAI and Fistula Topography Cx601 Placebo Demographics (ITT) n= 107 n= 105 Age (years) mean (SD) 39.0 (13.1) 37.6 (13.1) Men (%) 60 (56.1) 56 (53.3) Caucasian (%) 100 (93.5) 96 (91.4) Weight (kg) mean (SD) 73.9 (15.0) 71.3 (14.9) PDAI (ITT) Mean (SD) Topography of Internal & Cx601 Placebo External Openings (%) (Safety set) n= 103 n= 102 One-tract fistula Multiple-tract fistula Similar demographics and PDAI score between arms Higher proportion of multiple-tract fistulas in Cx601 group 14 14

15 Primary Endpoint: Combined Remission at W24 (ITT Population n= 212) % 60 p < % 34.3% Observed Relative Risk: 1.44 Patients receiving Cx601 have 44% more chances to achieve Combined Remission than placebo patients 10 0 Cx601 Placebo Primary endpoint met Cx601 significantly superior to placebo in achieving Combined Remission Efficacy results consistent across all statistical populations 15 15

16 Combined Remission at W24 (mitt Population n= 204) % p < % % 20 Observed Relative Risk: Cx601 Placebo Cx601 also significantly superior to placebo in mitt population 16 16

17 Overview of TEAEs Up To W24 (Safety Population n= 205) Number of Patients with (%) Cx601 Placebo n= 103 n=102 TEAEs 68 (66.0) 66 (64.7) Related TEAEs 16 (15.5) 26 (25.5) Withdrawn due to a TEAEs 4 (3.9) 4 (3.9) TESAEs 17 (16.5) 13 (12.7) 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. Favourable safety and tolerability profile of Cx601 and comparable to placebo 17 17

18 Summary and Key Conclusions Largest RCT in complex perianal fistulas in Crohn s disease adult patients Primary endpoint, Combined Remission at week 24, met (p<0.025) More than 50% of the patients treated with Cx601 achieved Combined Remission at week 24 With Cx601, patients have 44% more chances to achieve Combined Remission Favourable safety and tolerability profile of Cx601 and comparable to placebo Full efficacy and safety results will be presented at the 11 th Congress of ECCO Cx601 represents a major breakthrough for the treatment of complex perianal fistulas in Crohn s disease patients RCT: Randomised Controlled Trial 18 18

19 Eduardo Bravo Chief Executive Officer Next Steps 19 19

20 Next Steps Cx601 - EUROPE Regulatory filing in Europe - 1Q2016 Anticipated approval and launch in Europe - 2H2017 Cx601 - US Finalize tech transfer to our US CMO (Lonza) - 2H2016 File IND - 2H2016 Initiate Phase III in the US, endorsed by the FDA under SPA - 2H2016 Anticipated approval and launch in the US CMO: Contract Manufacturing Organization; IND: Investigational New Drug Application 20 20

21 Thank you! Patients Investigators Team 21 21

22 Any questions? 22 22

23 Thank you for your attention!